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WO2024051843A1 - Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof - Google Patents

Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof Download PDF

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Publication number
WO2024051843A1
WO2024051843A1 PCT/CN2023/117894 CN2023117894W WO2024051843A1 WO 2024051843 A1 WO2024051843 A1 WO 2024051843A1 CN 2023117894 W CN2023117894 W CN 2023117894W WO 2024051843 A1 WO2024051843 A1 WO 2024051843A1
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Prior art keywords
pharmaceutical composition
combination
preventing
present
technical solution
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PCT/CN2023/117894
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French (fr)
Chinese (zh)
Inventor
陈琳
王宇
高文勇
李建军
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Beijing Darwin Cell Biotechnology Co Ltd
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Beijing Darwin Cell Biotechnology Co Ltd
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
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    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H39/00—Devices for locating or stimulating specific reflex points of the body for physical therapy, e.g. acupuncture
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    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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Definitions

  • the invention belongs to the technical field of biomedicine, and specifically relates to a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period and its application.
  • Facial nerve palsy (also known as facial paralysis) is a common facial nerve disease (accounting for 60%-75%), with an incidence rate of 11.5-53.3 people/100,000 people, a recurrence rate of 2.6%-15.2%, and the majority of patients are 20-40 years old.
  • the main clinical manifestations include reduction or loss of facial voluntary movement, expression function, facial nerve and facial expression muscle tissue dystrophy, etc., and affect the patient's appearance, personal dignity and social image, and in severe cases, even lead to psychological disorders, depression and anxiety in patients. disease.
  • facial nerve paralysis is divided into acute phase (within 15 days of onset), recovery phase (within 16 days to 6 months of onset), and sequelae phase (more than 6 months of onset) according to the duration of onset of the disease.
  • Familial facial palsy may be secondary to an autoimmune disorder involving inherited human leukocyte antigens.
  • Abnormal anatomy of the facial nerve canal, stenosis of the facial nerve canal, and rapid changes in climate and temperature may all be risk factors for facial nerve paralysis. Damage to different parts of the facial nerve (including preganglionic damage to the geniculate ganglion, damage to the geniculate ganglion, lesions near the stylomastoid foramen, etc.) causes different clinical symptoms.
  • Patent applications disclose technical content related to nerve repair protein extracts and nerve repair protein compositions with repair effects.
  • the aforementioned applications and contents are essential to this application. Few technical references and components.
  • the object of the present invention is to provide a pharmaceutical composition for use in preparing drugs for preventing and treating facial nerve paralysis in the recovery period, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains dehydrating drugs, antiviral drugs, and anti-inflammatory drugs. Any one or combination of drugs, nerve repair drugs and/or blood circulation improving drugs, traditional Chinese medicine preparations.
  • the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
  • the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination
  • the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
  • the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.
  • GM1 monosialoganglioside
  • cerebrospinalis carnosine methylcobalamin
  • adenosylcobalamin Vitamin B complex
  • butylphthalide cinpazide maleate
  • edaravone edar
  • the traditional Chinese medicine preparation is selected from the group consisting of facial palsy pills, ginseng reconstituted pills, ginkgo leaves or ginkgo leaf extracts, Jacob Decoction and Qianzheng Powder or their modifications, Daqin Genji Decoction or their modifications.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
  • the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazole, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, and Ginkgo biloba. 0.2-0.6g of leaves and 3-6g of ginseng reconstituted pills.
  • the dosage regimen of the oral pharmaceutical composition is:
  • Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;
  • Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month.
  • the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
  • the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
  • the pharmaceutical composition for single acupoint injection consists of mouse nerve growth factor 30ug-90ug, methylcobalamin 0.5mg-1.0mg, adenosylcobalamin 0.5mg-1.0mg, dexamethasone 2mg- It consists of 5 mg and 1 ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection is composed of mouse nerve growth factor It is composed of 30ug, methylcobalamin 0.5mg, adenosylcobalamin 1.0mg, dexamethasone 5mg and lidocaine hydrochloride 1ml, wherein the concentration of lidocaine hydrochloride is selected from any of 0.8%, 1%, 1.5% and 2%. A sort of.
  • the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
  • the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
  • the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
  • the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
  • each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
  • the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
  • the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.
  • the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
  • the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
  • the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
  • the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
  • the object of the present invention is to provide a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period.
  • the pharmaceutical composition contains dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs, and traditional Chinese medicine preparations. any one or combination thereof.
  • the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
  • the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination
  • the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
  • the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.
  • GM1 monosialoganglioside
  • cerebrospinalis carnosine methylcobalamin
  • adenosylcobalamin Vitamin B complex
  • butylphthalide cinpazide maleate
  • edaravone edar
  • the traditional Chinese medicine preparation is selected from the group consisting of facial palsy pills, ginseng reconstituted pills, ginkgo leaves or ginkgo leaf extracts, Jacob Decoction and Qianzheng Powder or their modifications, Daqin Genji Decoction or their modifications.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
  • the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazole, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, and Ginkgo biloba. 0.2-0.6g of leaves and 3-6g of ginseng reconstituted pills.
  • the dosage regimen of the oral pharmaceutical composition is:
  • Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;
  • Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month.
  • the oral pharmaceutical composition is selected from any one of simultaneous administration or sequential administration or a combination thereof.
  • the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
  • the pharmaceutical composition for single acupoint injection consists of mouse nerve growth factor 30ug-90ug, methylcobalamin 0.5mg-1.0mg, adenosylcobalamin 0.5mg-1.0mg, dexamethasone 2mg- It consists of 5 mg and 1 ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
  • the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
  • the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
  • the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
  • each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period can be any It can be optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises or their combination.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
  • the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
  • the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.
  • the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
  • the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
  • the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
  • the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
  • Another object of the present invention is to provide a treatment plan for preventing and treating facial nerve paralysis in the recovery stage.
  • the treatment plan includes a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery stage, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or Use in combination.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains any one of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs, and traditional Chinese medicine preparations. or combination thereof.
  • the dehydrating drug is selected from the group consisting of mannitol, sorbitol, aescin, Any one of sodium aescinate, 50% hypertonic glucose solution, or a combination thereof.
  • the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination
  • the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
  • the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.
  • GM1 monosialoganglioside
  • cerebrospinalis carnosine methylcobalamin
  • adenosylcobalamin Vitamin B complex
  • butylphthalide cinpazide maleate
  • edaravone edar
  • the traditional Chinese medicine preparation is selected from the group consisting of facial palsy pills, ginseng reconstituted pills, ginkgo leaves or ginkgo leaf extracts, Jacob Decoction and Qianzheng Powder or their modifications, Daqin Genji Decoction or their modifications.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.
  • the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
  • the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazole, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, and Ginkgo biloba. 0.2-0.6g of leaves and 3-6g of ginseng reconstituted pills.
  • the dosage regimen of the oral pharmaceutical composition is:
  • Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;
  • Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month.
  • the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
  • the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
  • the pharmaceutical composition for single acupoint injection consists of mouse nerve growth factor 30ug-90ug, methylcobalamin 0.5mg-1.0mg, adenosylcobalamin 0.5mg-1.0mg, dexamethasone 2mg- It consists of 5 mg and 1 ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for single acupoint injection is composed of mouse nerve growth factor It consists of 60ug, methylcobalamin 1.0mg, adenosylcobalamin 0.5mg, dexamethasone 3mg and lidocaine hydrochloride 1ml, wherein the concentration of lidocaine hydrochloride is selected from any of 0.8%, 1%, 1.5% and 2%. A sort of.
  • the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
  • the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
  • the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
  • the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
  • each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
  • the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
  • the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.
  • the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
  • the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
  • the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
  • the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
  • the nerve repair cell protein extract or nerve repair cell protein composition with repair effect described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582). have to.
  • the preparation method of the nerve repair cell protein extract with nerve repair effect includes the following steps:
  • S-1 Mesenchymal passaged stem cells with a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 ⁇ mol/L stress medium, and then culture it at 37.0°C ⁇ 0.5°C, 5% ⁇ 1.0% CO2 for 2h-6h, separate, wash, and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;
  • BSA bovine serum albumin
  • S-2 Disperse the collected cells in the solvent at a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL, and then place them at 2°C-8°C for ultrasonic treatment to prepare a cell lysis solution , wherein the solvent is selected from any one selected from physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof;
  • PBS phosphate buffered saline
  • TBPS buffer TBST buffer
  • Tris buffer Tris buffer
  • step S-3 After separating the cell lysate prepared in step S-2, the obtained separation liquid is filtered through 0.45um and 0.22um filters in sequence.
  • the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI1640 42-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal growth factor (EGF) 5 -10ug/mL, fibroblast growth factor (FGF) 5-10ug/mL, insulin transferrin 5-10ug/mL, Compound amino acid (18AA) 0.02-0.05% and 3-8 ⁇ mol/L stressor.
  • BSA bovine serum albumin
  • the culture medium of step S-1 contains DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblasts Growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6 ⁇ mol/L stressors.
  • BSA bovine serum albumin
  • the density of mesenchymal passage stem cells in step S-1 is 8.0 ⁇ 10 6 -2.0 ⁇ 10 7 cells/mL, preferably 8.0 ⁇ 10 6 -1.0 ⁇ 10 7 cells/mL.
  • the mesenchymal passage stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.
  • the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. Or a combination thereof, the number of cell washings is 2-5 times, preferably 3-4 times.
  • the separation described in step S-1 is selected from any one of centrifugation, filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm* 5-10min.
  • the ultrasonic conditions of step S-2 are: working at 2°C-8°C, 25kHZ, 360W for 3 seconds, followed by a gap of 1 second, and ultrasonic treatment for 1-5 minutes.
  • the separation described in step S-3 is selected from any one of 2000-8000rpm*10-30min centrifugation, multi-stage centrifugation, multi-stage filtration or a combination thereof, preferably 3000-7000rpm*15-25min .
  • the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min.
  • the filter membrane pore size of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
  • the cell protein extract prepared in step S-3 is frozen and stored, preferably at -40°C to -20°C.
  • the cell protein extract prepared in step S-3 is enzymatically hydrolyzed by either a nuclease or a totipotent nuclease and then separated and purified.
  • the culture of mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts the culture methods in this field.
  • the culture of mesenchymal passage stem cells includes the following steps: adding primary mesenchymal stem cells to the passage medium at an initial density of 5.0 ⁇ 10 5 -5.0 ⁇ 10 6 /ml. , and then place it in the culture medium at 37.0°C ⁇ 0.5°C and 5% ⁇ 1.0% CO2 for 10-15 days. Every 2-3 days, after observing that the subculture medium turns yellow, replace half of the subculture medium. , the subculture medium contains DMEM/F12 medium with 10% FBS, 100 U/ml penicillin and 100ug/ml streptomycin.
  • the culture of primary mesenchymal stem cells includes the following steps:
  • the percentage when the present invention relates to the percentage between liquid and liquid, the percentage is volume/volume percentage; when the present invention relates to the percentage between liquid and solid, the percentage is volume/weight percentage; the present invention When referring to percentages between solids and liquids, the percentages are weight/volume; the remainder are weight/weight.
  • Acupoint selection Position the acupoints in accordance with the National Standard of the People's Republic of China "Acupoint Names and Positioning" (GB/T 12345-2006) issued by the State Bureau of Technical Supervision.
  • the present invention has the following beneficial effects:
  • the scientifically formulated pharmaceutical composition of the present invention is used to treat facial paralysis in the recovery period, and uses simultaneous administration and/or sequential administration to treat the affected side, which is beneficial to reducing facial paralysis edema, eliminating inflammation in the facial paralysis area, nourishing and repairing nerves damaged by facial paralysis. Damage myelin and axons.
  • the dehydrating drugs in the pharmaceutical composition are used to eliminate facial paralysis edema, reduce or even eliminate facial nerve damage caused by edema;
  • the antiviral drugs are used to fight viruses, eliminate the causes of facial paralysis, and promote nerve regeneration;
  • the anti-inflammatory drugs are used to eliminate facial paralysis inflammatory factors, which is beneficial to Clear facial paralysis inflammation and edema;
  • Nerve repair drugs and/or blood circulation improving drugs are used to improve blood circulation disorders caused by facial paralysis edema, viruses, inflammation, etc., repair facial nerve damage caused by facial paralysis edema, viruses, inflammation, etc., promote nerve nutrition, promote myelin and axis Surge repair, etc.;
  • Chinese medicine preparations are used to dispel wind and reduce phlegm, activate blood circulation and unblock meridians, which is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the recovery period.
  • the pharmaceutical composition of the present invention combined with radiofrequency surgery and rehabilitation exercises has the advantages of synergy, fast onset, high efficiency, high cure rate, basically no side effects and basically no recurrence rate, and significantly improves the treatment of patients. Prognosis and quality of life.
  • the culture of primary mesenchymal stem cells includes the following steps:
  • Passage culture of primary mesenchymal stem cells (culture of mesenchymal stem cells): Add primary mesenchymal stem cells at an initial density of 5.0 ⁇ 10 5 -5.0 ⁇ 10 6 /ml into a solution containing 10% FBS and 100U /ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it at 37.0°C ⁇ 0.5°C, 5% ⁇ 1.0% CO2 for 10-15 days, with an interval of 2-3 days , after observing that the culture medium turns yellow, replace it with half the amount. culture medium.
  • step (2) Disperse the cells collected in step (1) in physiological saline at a density of 1.0 ⁇ 10 7 cells/mL, ultrasonicate for 3s, 1s gap, and 2min under the conditions of 2-8°C, 25kHz, 360W to obtain cells. Lysis solution;
  • step (3) Centrifuge the cell lysate prepared in step (2) at 7000rpm*20min, and filter the obtained centrifuge through 0.45um and 0.22um filters in sequence to obtain the cell protein extract;
  • step (3) Add the required amount of mannitol to the cell protein extract prepared in step (3), stir, mix evenly, and freeze-dry.
  • the resulting freeze-dried preparation contains 5% mannitol (m/m).
  • Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention for facial paralysis in the recovery period
  • Group 1 10 patients
  • Group 2 40 patients
  • Group 3 20 patients
  • Patient inclusion criteria meet the diagnostic criteria of facial neuritis in traditional Chinese medicine and Western medicine, and the onset of the disease exceeds 15 days to 6 months; age is 20-70 years old; H-B classification is above level II; informed consent to accept this trial; good compliance.
  • Patient exclusion criteria patients with complete rupture or loss of the facial nerve; patients with infection or skin damage at the puncture site; patients with local tumors or other space-occupying lesions involving the facial nerve; patients with coagulation dysfunction, which may increase the risk of bleeding or hematoma; patients with pacemaker implants Those who enter may interfere with the normal work of the pacemaker; those who are pregnant or lactating may affect the health of the fetus or baby; those who are allergic to electrode needles or local anesthetics may cause allergic reactions or other adverse reactions; those with mental disorders or inability to Those who cooperate with rehabilitation or corrective training.
  • the pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B 1 .
  • the treatment plan for the 2 groups includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.
  • Pulsed radiofrequency surgery Using a radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical), based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology, nerve activation, repair, regulation and micro-correction surgery are performed on the lesion. (Pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42°C, 90-140V, 2-5Hz; during the operation, two groups of eyes were kept open , facial movements that repeatedly show teeth and puff;
  • Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;
  • Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month
  • the pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride.
  • Acupoint injection is performed at Yangbai point, Taiyang point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point, once a day.
  • the first set of rehabilitation exercises first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements.
  • Three groups are trained every day, each group is trained 30 times; the second set of rehabilitation exercises: the first is to look in the mirror; the second is to open the eyes and try to keep the silent nerve branches; the third is to pout, gnash the teeth and puff out the cheeks around the mouth. Train three groups a day, each group training 10 times.
  • the treatment plan of the 3 groups includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.
  • Pulsed radiofrequency surgery A radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical) is used to perform nerve activation and repair adjustment on the lesion based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology. Controlled micro-correction surgery (pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42°C, 90-140V, 2-5Hz; during the operation, 2 groups were used Facial movements of keeping eyes open, repeatedly showing teeth, and repeating air puffing;
  • Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;
  • Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month;
  • the pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride.
  • Acupoint injections are performed at the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the side face, once a day;
  • the first set of rehabilitation exercises first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements.
  • Three groups are trained every day, each group is trained 30 times; the second set of rehabilitation exercises: first, look in the mirror; second, try to keep the silent nerve branches open with eyes open; third, pout, clenched teeth and puffed cheeks around the mouth. Train three groups a day, each group training 10 times.
  • Group 1 After 3 days of treatment, about 50% of patients improved their facial muscles; after 28 days of treatment, the effective rate was 70%.
  • Group 2 After 3 days of treatment, about 60% of patients improved their facial muscles; after 7 days of treatment, the effective rate was 80%. The recovery rate after 28 days of treatment is about 90%. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.
  • Group 3 After 3 days of treatment, about 80% of the patients' facial muscles improved, and the effective rate of 7 days of treatment was 90%. The recovery rate after 28 days of treatment is about 95%. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.

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Abstract

A pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and a use thereof. The pharmaceutical composition contains any one among or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, bendazol, dexamethasone, prednisone, citicoline sodium, ginkgo leaves, mouse nerve growth factor, mecobalamine, and cobamamide.

Description

用于防治恢复期面神经麻痹的药物组合物及其应用Pharmaceutical composition for preventing and treating facial nerve paralysis in recovery period and its application 技术领域Technical field

本发明属于生物医药技术领域，具体涉及一种防治恢复期面神经麻痹的药物组合物及其应用。The invention belongs to the technical field of biomedicine, and specifically relates to a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period and its application.

背景技术Background technique

面神经麻痹(又称面瘫)为常见的面神经疾病(占比60％-75％)，发病率为11.5-53.3人/10万人，复发率为2.6％-15.2％，患者集中为20-40岁的男性，其主要临床表现包括面部自主运动、表情功能减退或丧失，面神经和面部表情肌组织营养障碍等，并影响患者容貌、个人尊严和社会形象，严重者甚至导致患者心理障碍、抑郁焦虑等病症。临床按照患者发病时长，将面神经麻痹其分为急性期(发病15天以内)、恢复期(发病16天至6个月内)和后遗症期(发病超过6个月)。Facial nerve palsy (also known as facial paralysis) is a common facial nerve disease (accounting for 60%-75%), with an incidence rate of 11.5-53.3 people/100,000 people, a recurrence rate of 2.6%-15.2%, and the majority of patients are 20-40 years old. In men, the main clinical manifestations include reduction or loss of facial voluntary movement, expression function, facial nerve and facial expression muscle tissue dystrophy, etc., and affect the patient's appearance, personal dignity and social image, and in severe cases, even lead to psychological disorders, depression and anxiety in patients. disease. Clinically, facial nerve paralysis is divided into acute phase (within 15 days of onset), recovery phase (within 16 days to 6 months of onset), and sequelae phase (more than 6 months of onset) according to the duration of onset of the disease.

面神经麻痹的致病病因尚不明确。病毒感染(如潜伏的I型单纯疱疹病毒感染和带状疱疹病毒感染)及病毒感染后的重新激活等，所导致的面神经麻痹的致病机制被广泛接受。家族性面神经麻痹可能继发于遗传性人类白细胞抗原的自身免疫性疾病。面神经管解剖结构异常、面神经管狭窄、气候及温度的急剧变化等，均可能成为导致面神经麻痹的危险因素。面神经的不同部位损害(包括膝状神经节前损害、膝状神经节损害、茎乳孔附近病变等)而表现不同的临床症状。面神经麻痹患者若治疗不及时、恢复不彻底，则常伴发瘫痪肌的萎缩、眼睑痉挛、连带运动、患侧面部牵拉感，且可能呈现病损后导致再生的神经纤维向邻近其他神经纤维通路生长，而支配原来属于其他神经纤维效应器所致的其他症状。目前，尚缺乏有效治疗恢复期面神经麻痹的药物及治疗方案。The cause of facial nerve palsy is unknown. The pathogenic mechanisms of facial nerve paralysis caused by viral infection (such as latent herpes simplex virus type I infection and herpes zoster virus infection) and reactivation after viral infection are widely accepted. Familial facial palsy may be secondary to an autoimmune disorder involving inherited human leukocyte antigens. Abnormal anatomy of the facial nerve canal, stenosis of the facial nerve canal, and rapid changes in climate and temperature may all be risk factors for facial nerve paralysis. Damage to different parts of the facial nerve (including preganglionic damage to the geniculate ganglion, damage to the geniculate ganglion, lesions near the stylomastoid foramen, etc.) causes different clinical symptoms. If patients with facial nerve paralysis are not treated in time and the recovery is not complete, they are often accompanied by atrophy of the paralyzed muscles, blepharospasm, joint movements, and a pulling sensation on the affected side of the face. In addition, the damaged nerve fibers may cause the regenerated nerve fibers to move toward other nearby nerve fibers. The pathways grow and innervate other symptoms caused by effectors originally belonging to other nerve fibers. Currently, there is a lack of effective drugs and treatment options for facial nerve paralysis in the recovery period.

专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)公开了有关具有修复功效的神经修复蛋白提取物及神经修复蛋白组合物的技术内容，前述申请及内容作为本申请必不可少的技术参考和组成部分。 Patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582) disclose technical content related to nerve repair protein extracts and nerve repair protein compositions with repair effects. The aforementioned applications and contents are essential to this application. Few technical references and components.

发明内容Contents of the invention

本发明的目的在于提供一种药物组合物用于制备防治恢复期面神经麻痹的药物中的应用，其中，所述用于防治恢复期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物、中药制剂的任一种或其组合。The object of the present invention is to provide a pharmaceutical composition for use in preparing drugs for preventing and treating facial nerve paralysis in the recovery period, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains dehydrating drugs, antiviral drugs, and anti-inflammatory drugs. Any one or combination of drugs, nerve repair drugs and/or blood circulation improving drugs, traditional Chinese medicine preparations.

本发明的优选技术方案中，所述脱水类药物选自甘露醇、山梨醇、七叶皂苷、七叶皂苷钠、50％的高渗葡萄糖溶液的任一种或其组合。In the preferred technical solution of the present invention, the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.

本发明的优选技术方案中，所述抗病毒药物选自阿昔洛韦、伐昔洛韦、地巴唑、犀羚解毒、病毒灵、法匹拉韦(favipiravir)、Paxlovid、莫诺拉韦(Molnupiravir)、奥司他韦、雷米迪维、伦地西韦(Remdesivir，GS-5734)、茚地那韦、沙奎那韦、洛匹那韦、利托那韦(Ritonavir)、阿扎那韦、达芦那韦、替拉那韦、氟沙那韦、恩扎托韦、普瑞托韦、阿巴卡韦、埃替格韦、马立巴韦、雷特格韦、利巴韦林、金刚烷乙胺、奥司他韦、扎那米韦、帕拉米韦、拉尼米韦、更昔洛韦、巴洛沙韦(Baloxavir)、奈非那韦的任一种或其组合。In the preferred technical solution of the present invention, the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination thereof.

本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.

本发明的优选技术方案中，所述神经修复药物和/改善血液循环药物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。In the preferred technical solution of the present invention, the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.

本发明的优选技术方案中，所述中药制剂选自面瘫丸、人参再造丸、银杏叶片或银杏叶提取物、葛根汤合牵正散或其加减方组合物、大秦艽汤或其加减方组合物、龙胆泻肝汤合瓜蒌红花汤或其加减方组合物、涤痰汤合牵正散或其加减方组合物、补阳还五汤合牵正散或其加减方组合物、伤湿止痛膏、麝香虎骨膏，或者由鲜姜、人参、莲藕、山药、甘草、菊苣、玫瑰、当归制成的中药膏剂的任一种或其组合。 In the preferred technical solution of the present invention, the traditional Chinese medicine preparation is selected from the group consisting of facial palsy pills, ginseng reconstituted pills, ginkgo leaves or ginkgo leaf extracts, Gegen Decoction and Qianzheng Powder or their modifications, Daqin Genji Decoction or their modifications. Recipe composition, Longdan Xiegan Decoction combined with Gualou Honghua Decoction or a modified combination thereof, Ditan Decoction combined with Qianzheng Powder or a modified combination thereof, Buyang Huanwu Decoction combined with Qianzheng Powder or a modified combination thereof, Any one or combination of traditional Chinese medicine ointments made from fresh ginger, ginseng, lotus root, yam, licorice, chicory, rose, and angelica.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物由单次口服用的药物组合物和和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.

本发明的优选技术方案中，单次口服用的药物组合物含有七叶皂苷钠20-40mg、地巴唑10-30mg、甲钴胺0.5-1.5mg、腺苷钴胺0.5-1.5mg，银杏叶片0.2-0.6g和人参再造丸3-6g。In the preferred technical solution of the present invention, the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazole, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, and Ginkgo biloba. 0.2-0.6g of leaves and 3-6g of ginseng reconstituted pills.

本发明的优选技术方案中，口服用药物组合物的给药方案为：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:

(1)口服七叶皂苷钠20mg/次，2次/天，用药1个月；(1) Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;

(2)口服地巴唑10mg/次，3次/天，用药1个月；(2) Oral dibazole 10 mg/time, 3 times/day, for 1 month;

(3)口服甲钴胺0.5mg/次和腺苷钴胺0.5mg/次，3次/天，用药1个月；(3) Oral methylcobalamin 0.5 mg/time and adenosylcobalamin 0.5 mg/time, 3 times/day, for 1 month;

(4)口服银杏叶片0.2g/次，3次/天，用药1个月；(4) Take 0.2g/time of ginkgo leaves orally, 3 times/day, for 1 month;

(5)口服人参再造丸3g/次，2次/天，用药1个月。(5) Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month.

本发明的优选技术方案中，所述口服用药物组合物选自同时给药或序贯给药的任一种或其组合。In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.

本发明的优选技术方案中，单次穴位注射用的药物组合物含有鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺0.5mg-1.0mg、地塞米松2mg-5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of mouse nerve growth factor 30ug-90ug, methylcobalamin 0.5mg-1.0mg, adenosylcobalamin 0.5mg-1.0mg, dexamethasone 2mg- It consists of 5 mg and 1 ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子 30ug、甲钴胺0.5mg、腺苷钴胺1.0mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is composed of mouse nerve growth factor It is composed of 30ug, methylcobalamin 0.5mg, adenosylcobalamin 1.0mg, dexamethasone 5mg and lidocaine hydrochloride 1ml, wherein the concentration of lidocaine hydrochloride is selected from any of 0.8%, 1%, 1.5% and 2%. A sort of.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.

本发明的优选技术方案中，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。In the preferred technical solution of the present invention, the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.

本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.

本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.

本发明的优选技术方案中，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.

本发明的优选技术方案中，所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.

本发明的优选技术方案中，所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号：国作登字-2022-I-10250228和著作权登记号：国作登字-2022-F-10250229)。In the preferred technical solution of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).

本发明的优选技术方案中，所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。 In the preferred technical solution of the present invention, the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.

本发明的优选技术方案中，第一套康复操训练包括，一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动；每天训练第一套康复操三组，每组训练30遍。In the preferred technical solution of the present invention, the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.

本发明的优选技术方案中，第二套康复操训练包括，一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮；每天训练第一套康复操三组，每组训练10遍。In the preferred technical solution of the present invention, the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.

本发明的优选技术方案中，所述防治恢复期面神经麻痹的治疗方案为，脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.

本发明的优选技术方案中，所述面神经麻痹选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。In the preferred technical solution of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.

本发明的目的在于提供一种防治恢复期面神经麻痹的药物组合物，所述的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物、中药制剂的任一种或其组合。The object of the present invention is to provide a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period. The pharmaceutical composition contains dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs, and traditional Chinese medicine preparations. any one or combination thereof.

本发明的优选技术方案中，所述脱水类药物选自甘露醇、山梨醇、七叶皂苷、七叶皂苷钠、50％的高渗葡萄糖溶液的任一种或其组合。In the preferred technical solution of the present invention, the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.

本发明的优选技术方案中，所述抗病毒药物选自阿昔洛韦、伐昔洛韦、地巴唑、犀羚解毒、病毒灵、法匹拉韦(favipiravir)、Paxlovid、莫诺拉韦(Molnupiravir)、奥司他韦、雷米迪维、伦地西韦(Remdesivir，GS-5734)、茚地那韦、沙奎那韦、洛匹那韦、利托那韦(Ritonavir)、阿扎那韦、达芦那韦、替拉那韦、氟沙那韦、恩扎托韦、普瑞托韦、阿巴卡韦、埃替格韦、马立巴韦、雷特格韦、利巴韦林、金刚烷乙胺、奥司他韦、扎那米韦、帕拉米韦、拉尼米韦、更昔洛韦、巴洛沙韦(Baloxavir)、奈非那韦的任一种或其组合。In the preferred technical solution of the present invention, the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination thereof.

本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.

本发明的优选技术方案中，所述神经修复药物和/改善血液循环药物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、 复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。In the preferred technical solution of the present invention, the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.

本发明的优选技术方案中，所述中药制剂选自面瘫丸、人参再造丸、银杏叶片或银杏叶提取物、葛根汤合牵正散或其加减方组合物、大秦艽汤或其加减方组合物、龙胆泻肝汤合瓜蒌红花汤或其加减方组合物、涤痰汤合牵正散或其加减方组合物、补阳还五汤合牵正散或其加减方组合物、伤湿止痛膏、麝香虎骨膏，或者由鲜姜、人参、莲藕、山药、甘草、菊苣、玫瑰、当归制成的中药膏剂的任一种或其组合。In the preferred technical solution of the present invention, the traditional Chinese medicine preparation is selected from the group consisting of facial palsy pills, ginseng reconstituted pills, ginkgo leaves or ginkgo leaf extracts, Gegen Decoction and Qianzheng Powder or their modifications, Daqin Genji Decoction or their modifications. Recipe composition, Longdan Xiegan Decoction combined with Gualou Honghua Decoction or a modified combination thereof, Ditan Decoction combined with Qianzheng Powder or a modified combination thereof, Buyang Huanwu Decoction combined with Qianzheng Powder or a modified combination thereof, Any one or combination of traditional Chinese medicine ointments made from fresh ginger, ginseng, lotus root, yam, licorice, chicory, rose, and angelica.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物由单次口服用的药物组合物和和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.

本发明的优选技术方案中，单次口服用的药物组合物含有七叶皂苷钠20-40mg、地巴唑10-30mg、甲钴胺0.5-1.5mg、腺苷钴胺0.5-1.5mg，银杏叶片0.2-0.6g和人参再造丸3-6g。In the preferred technical solution of the present invention, the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazole, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, and Ginkgo biloba. 0.2-0.6g of leaves and 3-6g of ginseng reconstituted pills.

本发明的优选技术方案中，口服用药物组合物的给药方案为：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:

(1)口服七叶皂苷钠20mg/次，2次/天，用药1个月；(1) Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;

(2)口服地巴唑10mg/次，3次/天，用药1个月；(2) Oral dibazole 10 mg/time, 3 times/day, for 1 month;

(3)口服甲钴胺0.5mg/次和腺苷钴胺0.5mg/次，3次/天，用药1个月；(3) Oral methylcobalamin 0.5 mg/time and adenosylcobalamin 0.5 mg/time, 3 times/day, for 1 month;

(4)口服银杏叶片0.2g/次，3次/天，用药1个月；(4) Take 0.2g/time of ginkgo leaves orally, 3 times/day, for 1 month;

(5)口服人参再造丸3g/次，2次/天，用药1个月。(5) Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month.

本发明的优选技术方案中，所述口服用药物组合物选自同时给药或序贯给药的任一种或其组合。 In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from any one of simultaneous administration or sequential administration or a combination thereof.

本发明的优选技术方案中，单次穴位注射用的药物组合物含有鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺0.5mg-1.0mg、地塞米松2mg-5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of mouse nerve growth factor 30ug-90ug, methylcobalamin 0.5mg-1.0mg, adenosylcobalamin 0.5mg-1.0mg, dexamethasone 2mg- It consists of 5 mg and 1 ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺1.0mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子60ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.

本发明的优选技术方案中，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。In the preferred technical solution of the present invention, the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.

本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.

本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物任 选地与射频手术、康复训练操的任一种或其组合联合使用。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period can be any It can be optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises or their combination.

本发明的优选技术方案中，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.

本发明的优选技术方案中，所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.

本发明的优选技术方案中，所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号：国作登字-2022-I-10250228和著作权登记号：国作登字-2022-F-10250229)。In the preferred technical solution of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).

本发明的优选技术方案中，所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。In the preferred technical solution of the present invention, the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.

本发明的优选技术方案中，第一套康复操训练包括，一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动；每天训练第一套康复操三组，每组训练30遍。In the preferred technical solution of the present invention, the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.

本发明的优选技术方案中，第二套康复操训练包括，一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮；每天训练第一套康复操三组，每组训练10遍。In the preferred technical solution of the present invention, the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.

本发明的优选技术方案中，所述防治恢复期面神经麻痹的治疗方案为，脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.

本发明的优选技术方案中，所述面神经麻痹选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。In the preferred technical solution of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.

本发明的另一目的在于提供一种防治恢复期面神经麻痹的治疗方案，所述治疗方案包括用于防治恢复期面神经麻痹的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。Another object of the present invention is to provide a treatment plan for preventing and treating facial nerve paralysis in the recovery stage. The treatment plan includes a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery stage, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or Use in combination.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物、中药制剂的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains any one of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs, and traditional Chinese medicine preparations. or combination thereof.

本发明的优选技术方案中，所述脱水类药物选自甘露醇、山梨醇、七叶皂苷、 七叶皂苷钠、50％的高渗葡萄糖溶液的任一种或其组合。In the preferred technical solution of the present invention, the dehydrating drug is selected from the group consisting of mannitol, sorbitol, aescin, Any one of sodium aescinate, 50% hypertonic glucose solution, or a combination thereof.

本发明的优选技术方案中，所述抗病毒药物选自阿昔洛韦、伐昔洛韦、地巴唑、犀羚解毒、病毒灵、法匹拉韦(favipiravir)、Paxlovid、莫诺拉韦(Molnupiravir)、奥司他韦、雷米迪维、伦地西韦(Remdesivir，GS-5734)、茚地那韦、沙奎那韦、洛匹那韦、利托那韦(Ritonavir)、阿扎那韦、达芦那韦、替拉那韦、氟沙那韦、恩扎托韦、普瑞托韦、阿巴卡韦、埃替格韦、马立巴韦、雷特格韦、利巴韦林、金刚烷乙胺、奥司他韦、扎那米韦、帕拉米韦、拉尼米韦、更昔洛韦、巴洛沙韦(Baloxavir)、奈非那韦的任一种或其组合。In the preferred technical solution of the present invention, the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination thereof.

本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.

本发明的优选技术方案中，所述神经修复药物和/改善血液循环药物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。In the preferred technical solution of the present invention, the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.

本发明的优选技术方案中，所述中药制剂选自面瘫丸、人参再造丸、银杏叶片或银杏叶提取物、葛根汤合牵正散或其加减方组合物、大秦艽汤或其加减方组合物、龙胆泻肝汤合瓜蒌红花汤或其加减方组合物、涤痰汤合牵正散或其加减方组合物、补阳还五汤合牵正散或其加减方组合物、伤湿止痛膏、麝香虎骨膏，或者由鲜姜、人参、莲藕、山药、甘草、菊苣、玫瑰、当归制成的中药膏剂的任一种或其组合。In the preferred technical solution of the present invention, the traditional Chinese medicine preparation is selected from the group consisting of facial palsy pills, ginseng reconstituted pills, ginkgo leaves or ginkgo leaf extracts, Gegen Decoction and Qianzheng Powder or their modifications, Daqin Genji Decoction or their modifications. Recipe composition, Longdan Xiegan Decoction combined with Gualou Honghua Decoction or a modified combination thereof, Ditan Decoction combined with Qianzheng Powder or a modified combination thereof, Buyang Huanwu Decoction combined with Qianzheng Powder or a modified combination thereof, Any one or combination of traditional Chinese medicine ointments made from fresh ginger, ginseng, lotus root, yam, licorice, chicory, rose, and angelica.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。 In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, and prednisolone. Any one or a combination of pine, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin.

本发明的优选技术方案中，所述用于防治恢复期面神经麻痹的药物组合物由单次口服用的药物组合物和和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.

本发明的优选技术方案中，单次口服用的药物组合物含有七叶皂苷钠20-40mg、地巴唑10-30mg、甲钴胺0.5-1.5mg、腺苷钴胺0.5-1.5mg，银杏叶片0.2-0.6g和人参再造丸3-6g。In the preferred technical solution of the present invention, the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazole, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, and Ginkgo biloba. 0.2-0.6g of leaves and 3-6g of ginseng reconstituted pills.

本发明的优选技术方案中，口服用药物组合物的给药方案为：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:

(1)口服七叶皂苷钠20mg/次，2次/天，用药1个月；(1) Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;

(2)口服地巴唑10mg/次，3次/天，用药1个月；(2) Oral dibazole 10 mg/time, 3 times/day, for 1 month;

(3)口服甲钴胺0.5mg/次和腺苷钴胺0.5mg/次，3次/天，用药1个月；(3) Oral administration of methylcobalamin 0.5 mg/time and adenosylcobalamin 0.5 mg/time, 3 times/day for 1 month;

(4)口服银杏叶片0.2g/次，3次/天，用药1个月；(4) Take 0.2g/time of ginkgo leaves orally, 3 times/day, for 1 month;

(5)口服人参再造丸3g/次，2次/天，用药1个月。(5) Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month.

本发明的优选技术方案中，所述口服用药物组合物选自同时给药或序贯给药的任一种或其组合。In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.

本发明的优选技术方案中，单次穴位注射用的药物组合物含有鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug-90ug、甲钴胺0.5mg-1.0mg、腺苷钴胺0.5mg-1.0mg、地塞米松2mg-5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of mouse nerve growth factor 30ug-90ug, methylcobalamin 0.5mg-1.0mg, adenosylcobalamin 0.5mg-1.0mg, dexamethasone 2mg- It consists of 5 mg and 1 ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺1.0mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein , the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子 60ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is composed of mouse nerve growth factor It consists of 60ug, methylcobalamin 1.0mg, adenosylcobalamin 0.5mg, dexamethasone 3mg and lidocaine hydrochloride 1ml, wherein the concentration of lidocaine hydrochloride is selected from any of 0.8%, 1%, 1.5% and 2%. A sort of.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.

本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.

本发明的优选技术方案中，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。In the preferred technical solution of the present invention, the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.

本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.

本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.

本发明的优选技术方案中，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.

本发明的优选技术方案中，所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.

本发明的优选技术方案中，所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号：国作登字-2022-I-10250228和著作权登记号：国作登字-2022-F-10250229)。In the preferred technical solution of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).

本发明的优选技术方案中，所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。In the preferred technical solution of the present invention, the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.

本发明的优选技术方案中，第一套康复操训练包括，一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动；每天训练第一套康复操三组，每组训练30遍。In the preferred technical solution of the present invention, the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.

本发明的优选技术方案中，第二套康复操训练包括，一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮；每天训练第一套康复操三组，每组训练10遍。In the preferred technical solution of the present invention, the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.

本发明的优选技术方案中，所述防治恢复期面神经麻痹的治疗方案为，脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。 In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.

本发明的优选技术方案中，所述面神经麻痹选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。In the preferred technical solution of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.

为了清楚地表述本发明，本发明所述的具有修复功效的神经修复细胞蛋白提取物或神经修复细胞蛋白组合物参照专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)制得。In order to clearly describe the present invention, the nerve repair cell protein extract or nerve repair cell protein composition with repair effect described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582). have to.

本发明的优选技术方案中，所述具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：In the preferred technical solution of the present invention, the preparation method of the nerve repair cell protein extract with nerve repair effect includes the following steps:

S-1:将密度为5.0×106个/mL-5.0×107个/mL的间充质传代干细胞置于含有DMEM/F12 40-50％、RPMI1640 40-50％、牛血清蛋白(BSA)0.1-2％、表皮细胞生长因子(EGF)1-15ug/mL、成纤维细胞生长因子(FGF)1-15ug/mL、胰岛素转铁蛋白1-15ug/mL、复方氨基酸(18AA)0.01-0.1％和2-10μmol/L应激物的培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养2h-6h后，分离，洗涤，收集细胞，其中，所述的应激物选自化合物1-16的任一种或其组合；

S-1: Mesenchymal passaged stem cells with a density of 5.0×10 6 /mL-5.0×10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 μmol/L stress medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 2h-6h, separate, wash, and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;

S-2：将收集细胞按照密度为5.0×106个/mL-5.0×107个/mL分散于溶剂中，再将其置于2℃-8℃条件下超声处理，制得细胞裂解液，其中，所述溶剂选自选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合；S-2: Disperse the collected cells in the solvent at a density of 5.0×10 6 /mL-5.0×10 7 /mL, and then place them at 2℃-8℃ for ultrasonic treatment to prepare a cell lysis solution , wherein the solvent is selected from any one selected from physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof;

S-3:将步骤S-2制得的细胞裂解液分离后，所得的分离液依次经0.45um、0.22um滤膜过滤，即得。S-3: After separating the cell lysate prepared in step S-2, the obtained separation liquid is filtered through 0.45um and 0.22um filters in sequence.

本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 42-45％、RPMI1640 42-45％、牛血清蛋白(BSA)0.5-1.5％、表皮细胞生长因子(EGF)5-10ug/mL、成纤维细胞生长因子(FGF)5-10ug/mL、胰岛素转铁蛋白5-10ug/mL、 复方氨基酸(18AA)0.02-0.05％和3-8μmol/L的应激物。In the preferred technical solution of the present invention, the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI1640 42-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal growth factor (EGF) 5 -10ug/mL, fibroblast growth factor (FGF) 5-10ug/mL, insulin transferrin 5-10ug/mL, Compound amino acid (18AA) 0.02-0.05% and 3-8μmol/L stressor.

本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 45％、RPMI1640 45％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL，胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和4-6μmol/L的应激物。In the preferred technical solution of the present invention, the culture medium of step S-1 contains DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblasts Growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6μmol/L stressors.

本发明的优选技术方案中，步骤S-1的间充质传代干细胞密度为8.0×106-2.0×107个/mL，优选为8.0×106-1.0×107个/mL。In the preferred technical solution of the present invention, the density of mesenchymal passage stem cells in step S-1 is 8.0×10 6 -2.0×10 7 cells/mL, preferably 8.0×10 6 -1.0×10 7 cells/mL.

本发明的优选技术方案中，步骤S-1的间充质传代干细胞在培养基中培养3h-5h，优选为3.5h-4.5h。In the preferred technical solution of the present invention, the mesenchymal passage stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.

本发明的优选技术方案中，步骤S-1中洗涤细胞的溶剂选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合,细胞洗涤次数为2-5次，优选为3-4次。In the preferred technical solution of the present invention, the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. Or a combination thereof, the number of cell washings is 2-5 times, preferably 3-4 times.

本发明的优选技术方案中，步骤S-1所述的分离选自离心、过滤的任一种或其组合，其中，所述离心条件为1000-2000rpm*3-15min，优选为1200rpm-1500rpm*5-10min。In the preferred technical solution of the present invention, the separation described in step S-1 is selected from any one of centrifugation, filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm* 5-10min.

本发明的优选技术方案中，步骤S-2的超声条件为：在2℃-8℃、25kHZ、360W条件下工作3s再间隙1s，超声处理1-5min。In the preferred technical solution of the present invention, the ultrasonic conditions of step S-2 are: working at 2°C-8°C, 25kHZ, 360W for 3 seconds, followed by a gap of 1 second, and ultrasonic treatment for 1-5 minutes.

本发明的优选技术方案中，步骤S-3所述分离选自2000-8000rpm*10-30min离心、多级离心、多级过滤的任一种或其组合，优选为3000-7000rpm*15-25min。In the preferred technical solution of the present invention, the separation described in step S-3 is selected from any one of 2000-8000rpm*10-30min centrifugation, multi-stage centrifugation, multi-stage filtration or a combination thereof, preferably 3000-7000rpm*15-25min .

本发明的优选技术方案中，步骤S-3的多级离心依次为3000-4000rpm*3-5min、5000-6000rpm*3-5min和7000rpm*5-8min。In the preferred technical solution of the present invention, the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min.

本发明的优选技术方案中，所述多级过滤的滤膜孔径选自80um、50um、30um、10um、5um的任一种。In the preferred technical solution of the present invention, the filter membrane pore size of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.

本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物冻存，优选冻存于-40℃至-20℃。In the preferred technical solution of the present invention, the cell protein extract prepared in step S-3 is frozen and stored, preferably at -40°C to -20°C.

本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物采用核酸酶或全能核酸酶的任一种酶解后再分离纯化。In the preferred technical solution of the present invention, the cell protein extract prepared in step S-3 is enzymatically hydrolyzed by either a nuclease or a totipotent nuclease and then separated and purified.

本发明的优选技术方案中，所述间充质传代干细胞的培养或原代间充质干细胞的培养采用本领域的培养方法。 In the preferred technical solution of the present invention, the culture of mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts the culture methods in this field.

本发明的优选技术方案中，所述间充质传代干细胞的培养包括下述步骤：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到传代培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每隔2-3天，观察传代培养基变黄后，半量更换传代培养基，其中，所述传代培养基含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基。In the preferred technical solution of the present invention, the culture of mesenchymal passage stem cells includes the following steps: adding primary mesenchymal stem cells to the passage medium at an initial density of 5.0×10 5 -5.0×10 6 /ml. , and then place it in the culture medium at 37.0℃±0.5℃ and 5%±1.0% CO2 for 10-15 days. Every 2-3 days, after observing that the subculture medium turns yellow, replace half of the subculture medium. , the subculture medium contains DMEM/F12 medium with 10% FBS, 100 U/ml penicillin and 100ug/ml streptomycin.

本发明的优选技术方案中，所述原代间充质干细胞的培养包括下述步骤：In the preferred technical solution of the present invention, the culture of primary mesenchymal stem cells includes the following steps:

1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养，每间隔2-3天半量更换培养基，培养至组织块爬出细胞；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Huatong glue layer tissue, cut it into small pieces of 3mm3 , centrifuge, clean, collect the tissue pieces, and place them in a solution containing 10% fetal bovine serum FBS, 100ug/ ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it under the conditions of 37.0℃±0.5℃, 5%±1.0% CO2 , and replace the medium with half the medium every 2-3 days. Culture until cells crawl out of the tissue block;

2)振摇，收集低层细胞用PBS清洗后，加入0.25％的胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打，1200-1500rpm/min*5-8min离心后，收集细胞，即得。2) Shake, collect the lower layer cells and wash with PBS, add 0.25% trypsin for digestion for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, gently pipette, and centrifuge at 1200-1500rpm/min*5-8min Afterwards, collect the cells and you are ready.

除非另有说明，本发明涉及液体与液体之间的百分比时，所述的百分比为体积/体积百分比；本发明涉及液体与固体之间的百分比时，所述百分比为体积/重量百分比；本发明涉及固体与液体之间的百分比时，所述百分比为重量/体积百分比；其余为重量/重量百分比。Unless otherwise stated, when the present invention relates to the percentage between liquid and liquid, the percentage is volume/volume percentage; when the present invention relates to the percentage between liquid and solid, the percentage is volume/weight percentage; the present invention When referring to percentages between solids and liquids, the percentages are weight/volume; the remainder are weight/weight.

除非另有说明，本发明采用如下方法进行评价：Unless otherwise stated, the present invention adopts the following methods for evaluation:

1.取穴：按照由国家技术监督局发布的中华人民共和国国家标准《腧穴名称与定位》(GB/T 12345-2006)的穴位以定位。1. Acupoint selection: Position the acupoints in accordance with the National Standard of the People's Republic of China "Acupoint Names and Positioning" (GB/T 12345-2006) issued by the State Bureau of Technical Supervision.

2.面瘫运动功能评价量表；2. Facial paralysis motor function evaluation scale;

3.面瘫生活质量评价量表。3. Facial paralysis quality of life evaluation scale.

与现有技术相比，本发明具有下述有益效果：Compared with the prior art, the present invention has the following beneficial effects:

1、本发明科学组配药物组合物用于治疗恢复期面瘫，并采用同时给药和/或序贯给药方式治疗患侧，利于减轻面瘫水肿，消除面瘫部位炎症，营养面瘫损伤神经并修复损伤髓鞘及轴突。药物组合物中的脱水药物用于消除面瘫水肿，减轻甚至清除水肿导致的面神经损伤；抗病毒药物用于抗病毒，清除引起面瘫的病因，促进神经再生；消炎药物用于清除面瘫炎症因子，利于清除面瘫炎症及其水肿； 神经修复药物和/或改善血液循环的药物用于改善面瘫水肿、病毒、炎症等导致的血液循环障碍，并修复面瘫水肿、病毒、炎症等导致的面神经损伤，促进营养神经、促进髓鞘及轴突修复等；中药制剂用于祛风化痰、活血通络，利于恢复期面瘫的治疗、康复和预后。1. The scientifically formulated pharmaceutical composition of the present invention is used to treat facial paralysis in the recovery period, and uses simultaneous administration and/or sequential administration to treat the affected side, which is beneficial to reducing facial paralysis edema, eliminating inflammation in the facial paralysis area, nourishing and repairing nerves damaged by facial paralysis. Damage myelin and axons. The dehydrating drugs in the pharmaceutical composition are used to eliminate facial paralysis edema, reduce or even eliminate facial nerve damage caused by edema; the antiviral drugs are used to fight viruses, eliminate the causes of facial paralysis, and promote nerve regeneration; the anti-inflammatory drugs are used to eliminate facial paralysis inflammatory factors, which is beneficial to Clear facial paralysis inflammation and edema; Nerve repair drugs and/or blood circulation improving drugs are used to improve blood circulation disorders caused by facial paralysis edema, viruses, inflammation, etc., repair facial nerve damage caused by facial paralysis edema, viruses, inflammation, etc., promote nerve nutrition, promote myelin and axis Surge repair, etc.; Chinese medicine preparations are used to dispel wind and reduce phlegm, activate blood circulation and unblock meridians, which is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the recovery period.

2、本发明的药物组组合物联用射频手术及康复操，具有协同增效、起效快、有效率高、治愈率高、基本无副作用和基本无复发率等优点，显著改善患者的治疗预后和生活质量。2. The pharmaceutical composition of the present invention combined with radiofrequency surgery and rehabilitation exercises has the advantages of synergy, fast onset, high efficiency, high cure rate, basically no side effects and basically no recurrence rate, and significantly improves the treatment of patients. Prognosis and quality of life.

具体实施方式Detailed ways

下面结合具体实施例对本发明的详细内容做进一步解释和描述，但并不以此限制本发明的保护范围。The details of the present invention will be further explained and described below in conjunction with specific embodiments, but this does not limit the scope of the present invention.

实施例1具有修复功效的神经修复细胞蛋白提取物的制备 Example 1 Preparation of nerve repair cell protein extract with repair effect

1、原代间充质干细胞的培养1. Culture of primary mesenchymal stem cells

原代间充质干细胞的培养包括下述步骤：The culture of primary mesenchymal stem cells includes the following steps:

1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于培养瓶中，加入含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基，再将其置于37℃、5％CO2条件下培养，促进其贴壁，每间隔2-3天,观察培养基变黄后，半量更换培养基，培养10-12天，至组织块边上可见细胞爬出；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Huatong glue layer tissue, cut it into 3mm3 small pieces, centrifuge, clean, collect the tissue pieces, place them in a culture bottle, add 10% fetal bovine DMEM/F12 culture medium with serum FBS, 100ug/ml penicillin, and 100ug/ml streptomycin, and then culture it at 37°C and 5% CO2 to promote adhesion. Observe every 2-3 days. After the medium turns yellow, replace half of the medium and culture for 10-12 days until cells can be seen crawling out from the edge of the tissue block;

2)轻轻摇晃，使组织块掉落，分别收集组织块和低层细胞，其中，将收集的组织块再贴壁培养；2) Shake gently to make the tissue blocks fall off, collect the tissue blocks and low-layer cells respectively, and culture the collected tissue blocks again;

3)将收集的低层细胞用PBS清洗后，加入适量0.25％胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打瓶底，1500rpm*5min离心后，收集细胞，即得。3) Wash the collected lower-layer cells with PBS, add an appropriate amount of 0.25% trypsin for digestion for 2 to 3 minutes, add an equal volume of trypsin stop solution to stop digestion, gently tap the bottom of the bottle with a pipette, and centrifuge at 1500 rpm for 5 minutes to collect the cells. That’s it.

2、原代间充质干细胞的传代培养(间充质传代干细胞的培养)2. Passage culture of primary mesenchymal stem cells (culture of mesenchymal stem cells)

原代间充质干细胞的传代培养(间充质传代干细胞的培养)：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每间隔2-3天，观察培养基变黄后，半量更换 培养基。Passage culture of primary mesenchymal stem cells (culture of mesenchymal stem cells): Add primary mesenchymal stem cells at an initial density of 5.0×10 5 -5.0×10 6 /ml into a solution containing 10% FBS and 100U /ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 10-15 days, with an interval of 2-3 days , after observing that the culture medium turns yellow, replace it with half the amount. culture medium.

3、化合物1-16的制备参照文献1(New limonophyllines A-C from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines，Arch.Pharm.Res.(2018)41:431–437)。3. For the preparation of compounds 1-16, refer to literature 1 (New limonophyllines A-C from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines, Arch.Pharm.Res. (2018) 41:431–437).

具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：The preparation method of nerve repair cell protein extract with nerve repair effect includes the following steps:

(1)将间充质传代细胞按照密度为8.0×106个/mL加入到含有DMEM/F12 45％、RPMI1640 45％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL、胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和5μmol/L的化合物16的培养基中，再将其置于37℃、5％CO2条件下培养4h后，将其置于1200rpm*5min离心，用PBS洗涤3次后，收集细胞；(1) Add mesenchymal passage cells at a density of 8.0×10 6 cells/mL into a solution containing DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, and epidermal growth factor (EGF) 10ug/ mL, fibroblast growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 5 μmol/L compound 16, and then placed at 37°C, 5 After culturing for 4 hours under % CO2 conditions, centrifuge at 1200rpm*5min, wash 3 times with PBS, and collect the cells;

(2)将步骤(1)收集的细胞按照密度为1.0×107个/mL分散于生理盐水中，在2-8℃、25kHz、360W条件下超声3s、间隙1s，超声2min，制得细胞裂解液；(2) Disperse the cells collected in step (1) in physiological saline at a density of 1.0 × 10 7 cells/mL, ultrasonicate for 3s, 1s gap, and 2min under the conditions of 2-8°C, 25kHz, 360W to obtain cells. Lysis solution;

(3)将步骤(2)制得的细胞裂解液置于7000rpm*20min离心，将所得的离心液依次经0.45um、0.22um滤膜过滤，即得细胞蛋白提取物；(3) Centrifuge the cell lysate prepared in step (2) at 7000rpm*20min, and filter the obtained centrifuge through 0.45um and 0.22um filters in sequence to obtain the cell protein extract;

(4)在步骤(3)制得的细胞蛋白提取物加入所需量的甘露醇，搅拌，混合均匀后，冻干，所得冻干制剂中含有5％的甘露醇(m/m)。(4) Add the required amount of mannitol to the cell protein extract prepared in step (3), stir, mix evenly, and freeze-dry. The resulting freeze-dried preparation contains 5% mannitol (m/m).

试验例1本发明药物组合物用于恢复期面瘫的治疗效果研究 Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention for facial paralysis in the recovery period

选取恢复期面瘫患者70名，分为1组(10名)、2组(40名)和3组(20名)。患者入组标准：符合面神经炎中医、西医诊断标准，患者发病超过在15天-6个月之内；年龄20-70岁；H-B分级在II级以上；知情同意接受本试验；依从性好。患者排除标准：面神经完全断裂或缺失者；穿刺部位感染或皮肤损伤者；累及面神经的局部肿瘤或其他占位性病变者；凝血功能障碍者，可能增加出血或血肿的风险；心脏起搏器植入者，可能干扰起搏器的正常工作；孕妇或哺乳期妇女者，可能影响胎儿或婴儿的健康；对电极针或局部麻醉药过敏者，可能引起过敏反应或其他不良反应；精神障碍或无法配合康复或矫正训练治疗者。70 patients with facial paralysis in the recovery period were selected and divided into Group 1 (10 patients), Group 2 (40 patients) and Group 3 (20 patients). Patient inclusion criteria: meet the diagnostic criteria of facial neuritis in traditional Chinese medicine and Western medicine, and the onset of the disease exceeds 15 days to 6 months; age is 20-70 years old; H-B classification is above level II; informed consent to accept this trial; good compliance. Patient exclusion criteria: patients with complete rupture or loss of the facial nerve; patients with infection or skin damage at the puncture site; patients with local tumors or other space-occupying lesions involving the facial nerve; patients with coagulation dysfunction, which may increase the risk of bleeding or hematoma; patients with pacemaker implants Those who enter may interfere with the normal work of the pacemaker; those who are pregnant or lactating may affect the health of the fetus or baby; those who are allergic to electrode needles or local anesthetics may cause allergic reactions or other adverse reactions; those with mental disorders or inability to Those who cooperate with rehabilitation or corrective training.

1组的治疗方案(每个疗程7天，治疗4个疗程)：单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组成，临配临 用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次。Treatment plan for Group 1 (7 days for each course, 4 courses of treatment): The pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B 1 . Use, select the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face for acupoint injection, once a day.

2组的治疗方案(每个疗程7天，治疗4个疗程)包括脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。The treatment plan for the 2 groups (each course is 7 days, 4 courses of treatment) includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.

1、脉冲射频手术：采用射频控温热凝器(型号R-2000B M1，购自北琪医疗)，基于长时程温控高电压变频脉冲射频技术对病变部位进行神经激活修复调控微纠偏手术(脉冲宽度20ms、静息期480ms、最大电压值100V、脉冲频率2HZ)，在41-42℃、90-140V、2-5Hz条件下脉冲射频1200秒；手术中，配合2组睁大眼保持、重复龇牙和重复鼓气的面部运动；1. Pulsed radiofrequency surgery: Using a radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical), based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology, nerve activation, repair, regulation and micro-correction surgery are performed on the lesion. (Pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42℃, 90-140V, 2-5Hz; during the operation, two groups of eyes were kept open , facial movements that repeatedly show teeth and puff;

2、术后口服药物的同时给药和/或序贯给药的方案：2. Simultaneous and/or sequential administration of oral medications after surgery:

(1)口服七叶皂苷钠20mg/次，2次/天，用药1个月；(1) Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;

(2)口服地巴唑10mg/次，3次/天，用药1个月；(2) Oral dibazole 10 mg/time, 3 times/day, for 1 month;

(3)口服甲钴胺0.5mg/次和腺苷钴胺0.5mg/次，3次/天，用药1个月；(3) Oral methylcobalamin 0.5 mg/time and adenosylcobalamin 0.5 mg/time, 3 times/day, for 1 month;

(4)口服银杏叶片0.2g/次，3次/天，用药1个月；(4) Take 0.2g/time of ginkgo leaves orally, 3 times/day, for 1 month;

(5)口服人参再造丸3g/次，2次/天，用药1个月(5) Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month

3、术后穴位注射给药方案：3. Postoperative acupoint injection medication regimen:

单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成，临配临用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次。The pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. Acupoint injection is performed at Yangbai point, Taiyang point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point, once a day.

4、术后康复操训练：4. Postoperative rehabilitation exercise training:

第一套康复操：一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动。每天训练三组，每组训练30遍；第二套康复操：一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮。每天训练三组，每组训练10遍。The first set of rehabilitation exercises: first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements. Three groups are trained every day, each group is trained 30 times; the second set of rehabilitation exercises: the first is to look in the mirror; the second is to open the eyes and try to keep the silent nerve branches; the third is to pout, gnash the teeth and puff out the cheeks around the mouth. Train three groups a day, each group training 10 times.

3组的治疗方案(每个疗程7天，治疗4个疗程)包括脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。The treatment plan of the 3 groups (each course is 7 days, 4 courses of treatment) includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.

1、脉冲射频手术：采用射频控温热凝器(型号R-2000B M1，购自北琪医疗)，基于长时程温控高电压变频脉冲射频技术对病变部位进行神经激活修复调 控微纠偏手术(脉冲宽度20ms、静息期480ms、最大电压值100V、脉冲频率2HZ)，在41-42℃、90-140V、2-5Hz条件下脉冲射频1200秒；手术中，配合2组睁大眼保持、重复龇牙和重复鼓气的面部运动；1. Pulsed radiofrequency surgery: A radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical) is used to perform nerve activation and repair adjustment on the lesion based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology. Controlled micro-correction surgery (pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42℃, 90-140V, 2-5Hz; during the operation, 2 groups were used Facial movements of keeping eyes open, repeatedly showing teeth, and repeating air puffing;

2、术后口服药物的同时给药和/或序贯给药的方案：2. Simultaneous and/or sequential administration of oral medications after surgery:

(1)口服七叶皂苷钠20mg/次，2次/天，用药1个月；(1) Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month;

(2)口服地巴唑10mg/次，3次/天，用药1个月；(2) Oral dibazole 10 mg/time, 3 times/day, for 1 month;

(3)口服甲钴胺0.5mg/次和腺苷钴胺0.5mg/次，3次/天，用药1个月；(3) Oral methylcobalamin 0.5 mg/time and adenosylcobalamin 0.5 mg/time, 3 times/day, for 1 month;

(4)口服银杏叶片0.2g/次，3次/天，用药1个月；(4) Take 0.2g/time of ginkgo leaves orally, 3 times/day, for 1 month;

(5)口服人参再造丸3g/次，2次/天，用药1个月；(5) Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month;

3、术后穴位注射给药方案：3. Postoperative acupoint injection medication regimen:

(1)单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成，临配临用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次；(1) The pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. Acupoint injections are performed at the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the side face, once a day;

(2)单次穴位注射实施例1制得的神经修复细胞蛋白提取物冻干制剂130ug，用2ml生理盐水溶解，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴、对侧太阳穴、地仓穴，双手合谷穴进行穴位注射，每天穴位注射1次。(2) A single acupoint injection of 130ug of the freeze-dried preparation of nerve repair cell protein extract prepared in Example 1 was dissolved in 2 ml of physiological saline. Select the Yangbai point, temple, Sibai point, Yingxiang point, and Ju on the affected side of the face Acupoint injections are performed at Liao, Dicang, Jieche, the temple on the opposite side, Dicang, and Hegu points on both hands, once a day.

4、康复操训练：4. Rehabilitation exercise training:

第一套康复操：一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动。每天训练三组，每组训练30遍；第二套康复操：一是照镜子；二是睁眼尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮。每天训练三组，每组训练10遍。The first set of rehabilitation exercises: first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements. Three groups are trained every day, each group is trained 30 times; the second set of rehabilitation exercises: first, look in the mirror; second, try to keep the silent nerve branches open with eyes open; third, pout, clenched teeth and puffed cheeks around the mouth. Train three groups a day, each group training 10 times.

疗效评定：满意度调查表和临床评分House-Brakmann面神经功能分级疗效评价表。

Efficacy evaluation: Satisfaction questionnaire and clinical rating House-Brakmann facial nerve function classification efficacy evaluation form.

1组：治疗3天，约50％的患者面部肌肉改善；治疗28天的有效率70％。Group 1: After 3 days of treatment, about 50% of patients improved their facial muscles; after 28 days of treatment, the effective rate was 70%.

2组：治疗3天，约60％的患者面部肌肉改善；治疗7天的有效率80％。治疗28天的痊愈率约90％。患者遵照医嘱，注意减少甚至避免熬夜、疲劳、外部感染、受凉等因素的影响，基本无复发，生活质量显著提高。Group 2: After 3 days of treatment, about 60% of patients improved their facial muscles; after 7 days of treatment, the effective rate was 80%. The recovery rate after 28 days of treatment is about 90%. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.

3组：治疗3天，约80％的患者面部肌肉改善，治疗7天的有效率90％。治疗28天的痊愈率约95％。患者遵照医嘱，注意减少甚至避免熬夜、疲劳、外部感染、受凉等因素的影响，基本无复发，生活质量显著提高。Group 3: After 3 days of treatment, about 80% of the patients' facial muscles improved, and the effective rate of 7 days of treatment was 90%. The recovery rate after 28 days of treatment is about 95%. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.

以上对本发明具体实施方式的描述并不限制本发明，本领域技术人员可以根据本发明作出各种改变或变形，只要不脱离本发明的精神，均应属于本发明权利要求保护的范围。 The above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art can make various changes or deformations according to the present invention. As long as they do not deviate from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims (10)

一种药物组合物用于制备防治恢复期面神经麻痹的药物中的应用，其中，所述用于防治恢复期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物、中药制剂的任一种或其组合；A pharmaceutical composition for use in the preparation of drugs for preventing and treating facial nerve paralysis in the recovery period, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and /or any one or combination of blood circulation-improving drugs, traditional Chinese medicine preparations; 如权利要求1所述的应用，所述用于防治恢复期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦、伐昔洛韦、地巴唑、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。The application as claimed in claim 1, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period contains mannitol, sodium aescin, acyclovir, valacyclovir, dibazole, dexamethasone, prednisolone, Any one or a combination of tisson, citicoline sodium, ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin. 如权利要求1-2任一项所述的应用，所述用于防治恢复期面神经麻痹的药物组合物由单次口服用的药物组合物和和单次穴位注射用的药物组合物组成。The application according to any one of claims 1 to 2, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection. 如权利要求1-3任一项所述的应用，单次口服用的药物组合物含有七叶皂苷钠20-40mg、地巴唑10-30mg、甲钴胺0.5-1.5mg、腺苷钴胺0.5-1.5mg，银杏叶片0.2-0.6g和人参再造丸3-6g。The application according to any one of claims 1 to 3, the pharmaceutical composition for single oral administration contains sodium aescinate 20-40 mg, dibazole 10-30 mg, methylcobalamin 0.5-1.5 mg, adenosylcobalamin 0.5-1.5mg, Ginkgo leaves 0.2-0.6g and Ginseng Zaozhao Pills 3-6g. 如权利要求1-4任一项所述的应用，口服用药物组合物的给药方案为：For the application according to any one of claims 1 to 4, the dosage regimen of the oral pharmaceutical composition is: (1)口服七叶皂苷钠20mg/次，2次/天，用药1个月；(1) Oral sodium aescinate 20 mg/time, 2 times/day, for 1 month; (2)口服地巴唑10mg/次，3次/天，用药1个月；(2) Oral dibazole 10 mg/time, 3 times/day, for 1 month; (3)口服甲钴胺0.5mg/次和腺苷钴胺0.5mg/次，3次/天，用药1个月；(3) Oral methylcobalamin 0.5 mg/time and adenosylcobalamin 0.5 mg/time, 3 times/day, for 1 month; (4)口服银杏叶片0.2g/次，3次/天，用药1个月；(4) Take 0.2g/time of ginkgo leaves orally, 3 times/day, for 1 month; (5)口服人参再造丸3g/次，2次/天，用药1个月。(5) Oral ginseng reconstituted pills 3g/time, 2 times/day, for 1 month. 如权利要求1-5任一项所述的应用，所述用于防治恢复期面神经麻痹的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。The application according to any one of claims 1 to 5, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof. 如权利要求1-6任一项所述的应用，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。The application according to any one of claims 1-6, the radiofrequency surgery is performed under the conditions of 41℃-42℃, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency 800 seconds-1400 Second. 一种防治恢复期面神经麻痹的药物组合物，所述的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物、中药制剂的任一种或其组合。A pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period. The pharmaceutical composition contains any one or a combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs, traditional Chinese medicine preparations. . 如权利要求8所述的药物组合物，所述用于防治恢复期面神经麻痹的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。The pharmaceutical composition according to claim 8, said pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery period, is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof. 一种防治恢复期面神经麻痹的治疗方案，所述治疗方案包括用于如权利要求8-9任一项所述的防治恢复期面神经麻痹的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。 A treatment plan for preventing and treating facial nerve paralysis in the recovery period, which treatment plan includes a pharmaceutical composition for preventing and treating facial nerve paralysis in the recovery stage as described in any one of claims 8-9, optionally combined with radiofrequency surgery and rehabilitation training exercises. Use any one or a combination thereof.
PCT/CN2023/117894 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof Ceased WO2024051843A1 (en)

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PCT/CN2023/117899 Ceased WO2024051847A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial nerve micro-entrapment syndrome and use thereof
PCT/CN2023/117898 Ceased WO2024051846A1 (en) 2022-09-09 2023-09-09 Use of radio frequency apparatus in treatment of facial paralysis synkinesis
PCT/CN2023/117896 Ceased WO2024051844A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating acute stage facial nerve paralysis and use thereof
PCT/CN2023/117900 Ceased WO2024051848A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating nervous system lesions and application thereof
PCT/CN2023/117897 Ceased WO2024051845A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating sequelae stage facial nerve paralysis, and use thereof

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PCT/CN2023/117898 Ceased WO2024051846A1 (en) 2022-09-09 2023-09-09 Use of radio frequency apparatus in treatment of facial paralysis synkinesis
PCT/CN2023/117896 Ceased WO2024051844A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating acute stage facial nerve paralysis and use thereof
PCT/CN2023/117900 Ceased WO2024051848A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating nervous system lesions and application thereof
PCT/CN2023/117897 Ceased WO2024051845A1 (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating sequelae stage facial nerve paralysis, and use thereof

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