CN119970814B - A pain relief preparation and its preparation method and application - Google Patents
A pain relief preparation and its preparation method and applicationInfo
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- CN119970814B CN119970814B CN202510480045.1A CN202510480045A CN119970814B CN 119970814 B CN119970814 B CN 119970814B CN 202510480045 A CN202510480045 A CN 202510480045A CN 119970814 B CN119970814 B CN 119970814B
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Abstract
本发明属于疼痛缓解制剂技术领域，具体涉及一种疼痛缓解制剂及其制备方法和应用。所述疼痛缓解制剂由右莰醇、柴胡的丙二醇提取物与药剂学可接受的辅料组成，其中，右莰醇与柴胡的丙二醇提取物的质量比为1~2.5:1，柴胡的丙二醇提取物通过以下方法制备而成：将柴胡研磨成粉后与丙二醇混合，超声提取，过滤，收集滤液，干燥，得到柴胡的丙二醇提取物。本发明还提供了所述疼痛缓解制剂的制备方法，并证实了所述疼痛缓解制剂在缓解急性疼痛和带状疱疹后神经痛中的应用，拓展了疼痛缓解制剂的种类。The present invention belongs to the technical field of pain relief preparations, and specifically relates to a pain relief preparation, a preparation method and an application thereof. The pain relief preparation is composed of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients, wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 1-2.5:1, and the propylene glycol extract of bupleurum is prepared by the following method: grinding bupleurum into powder and mixing with propylene glycol, ultrasonic extraction, filtering, collecting the filtrate, and drying to obtain the propylene glycol extract of bupleurum. The present invention also provides a preparation method of the pain relief preparation, and confirms the application of the pain relief preparation in relieving acute pain and postherpetic neuralgia, expanding the types of pain relief preparations.
Description
Technical Field
The invention belongs to the technical field of pain relieving preparations, and particularly relates to a pain relieving preparation, a preparation method and application thereof.
Background
Many diseases are accompanied by painful symptoms such as bacterial infections, viral infections, etc. Pain affects the normal life of the patient, and thus, relief of pain is necessary.
In the prior art, the means for relieving pain mainly comprise taking preparations such as ibuprofen, acetaminophen and the like, adopting lidocaine patches and the like for local anesthesia, pulse radio frequency treatment and short-time spinal cord electrical stimulation. The preparation has higher convenience and wider application, for example, the preparation can be applied to relieving pain symptoms at present and comprises (1) antiviral preparations such as acyclovir tablets, valacyclovir tablets and the like, which can help kill viruses in the body and relieve pain symptoms, (2) nonsteroidal anti-inflammatory preparations such as ibuprofen tablets, indomethacin tablets, diclofenac sodium slow-release capsules and the like, which can help relieve fever and pain, (3) central nervous system preparations such as gabapentin capsules, pregabalin capsules and the like, which can slightly inhibit central nervous system and relieve uncomfortable symptoms such as pruritus, and (4) tricyclic antidepressant preparations such as amitriptyline hydrochloride tablets, promethazine hydrochloride and the like, which can cause symptoms such as anxiety and depression and the like to increase pain after herpes zoster, which can be treated by using the preparations at the moment, (5) blood circulation promoting and qi-flowing traditional Chinese medicine preparations such as bupleurum, peach liver soothing decoction, blood stasis dispelling decoction and the like, which can help relieve blood circulation and blood stasis dispelling symptoms. However, due to the difference in physique among different patients, their sensitivity to the analgesic preparations of the prior art is different, so that the development of pain relieving preparations is required to be continued.
Disclosure of Invention
In order to solve the technical problems, the invention provides a pain relieving preparation, a preparation method and application thereof. The pain relieving preparation can relieve acute pain and also relieve postherpetic neuralgia.
The invention aims to provide a pain relieving preparation which consists of propylene glycol extracts of right borneol and bupleurum and pharmaceutically acceptable auxiliary materials, wherein the mass ratio of the propylene glycol extracts of right borneol and bupleurum is 1-2.5:1, and the propylene glycol extract of bupleurum is prepared by grinding bupleurum into powder, mixing with propylene glycol, carrying out ultrasonic extraction, filtering, collecting filtrate and drying to obtain the propylene glycol extract of bupleurum.
According to the research result of the invention, after the combination of the right camphol and the propylene glycol extract of the bupleurum, the mixture preparation is formed by matching with pharmaceutically acceptable auxiliary materials, and the right camphol and the propylene glycol extract of the bupleurum have the synergistic analgesic effect in relieving acute pain or postherpetic neuralgia. In addition, in the pain relieving preparation, the right borneol is mainly used for relieving pain related to nerve injury, can regulate organism immunity and inhibit pain conduction, and the propylene glycol extract of the bupleurum contains saikosaponin, volatile oil and sterol, so that the pain signal conduction can be activated and reduced, therefore, after the right borneol is combined with the propylene glycol extract of the bupleurum, the effect of reducing the pain signal conduction is enhanced, the acute pain can be relieved, and the pain relieving effect on postherpetic neuralgia is obvious.
In addition, according to the research result of the present invention, right borneol has weak analgesic effect in relieving acute pain or postherpetic neuralgia when acting alone, and Bupleurum chinense has weak analgesic effect in relieving acute pain or postherpetic neuralgia when acting alone.
In addition, after the bupleurum is ground into powder, the particle size is reduced, the surface area is increased, the contact with the solvent of the propanediol is more sufficient, the saikosaponin, the volatile oil and the sterol can be dissolved in the propanediol with the aid of ultrasonic extraction, and then the operations of filtering, collecting filtrate and drying are carried out, so that the saikosaponin, the volatile oil and the sterol-enriched propanediol extract of the bupleurum can be obtained.
Preferably, the mass ratio of the right camphol to the propylene glycol extract of the bupleurum is 2:1, and the pain relieving effect is better.
Preferably, the pain relieving formulation, the condition of the ultrasonic extraction is ultrasonic extraction at 400W power for 30min. Under the ultrasonic condition, the solubility of saikosaponin, volatile oil and sterol in propylene glycol is high.
Preferably, the preparation method of the propylene glycol extract of the bupleurum comprises the steps of grinding the bupleurum into 40-mesh powder, mixing the powder with the propylene glycol according to the proportion of 1kg to 8L, carrying out ultrasonic extraction for 30min under 400W power, filtering by a 50-mesh screen, and drying the collected filtrate to obtain the propylene glycol extract of the bupleurum.
Preferably, the pain relieving preparation, the pharmaceutically acceptable auxiliary materials at least comprise any one of the following conditions:
(a) Pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water;
(b) The pharmaceutically acceptable auxiliary material is propylene glycol;
(c) Pharmaceutically acceptable adjuvants including hydroxypropyl beta cyclodextrin, propylene glycol and water.
The "combination" of pharmaceutically acceptable auxiliary materials refers to a raw material using a plurality of pharmaceutically acceptable auxiliary materials, and these raw materials may be used after being mixed or may be used separately.
Preferably, the concentration of the right camphol in the pain relieving preparation is 60 ng/mL-80 ng/mL.
Preferably, the pain relief formulation has a concentration of about 75ng/mL of right-hand kaempferol.
The invention provides a preparation method of a pain relieving preparation, which is characterized in that the propylene glycol extracts of dextroamphetamine and bupleurum and pharmaceutically acceptable auxiliary materials are mixed to obtain a mixture which is the pain relieving preparation.
Preferably, when the pharmaceutically acceptable auxiliary material is a combination of propylene glycol and water, the preparation method of the pain relieving preparation comprises the steps of dissolving right camphol in propylene glycol to obtain right camphol liquid, dissolving the propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, and mixing the right camphol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the pain relieving preparation is suitable for intramuscular injection.
Preferably, when the pharmaceutically acceptable auxiliary material is propylene glycol, the preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into propylene glycol to obtain propylene glycol extract liquid of bupleurum, and mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation which is suitable for nasal drops.
Preferably, the pharmaceutically acceptable auxiliary materials are the combination of auxiliary materials hydroxypropyl beta cyclodextrin, propylene glycol and water, and the preparation method of the pain relieving preparation comprises the steps of wrapping right borneol in the auxiliary materials hydroxypropyl beta cyclodextrin to obtain right borneol liquid, dissolving the propylene glycol extract of bupleurum into a water-propylene glycol mixed solution to obtain the propylene glycol extract liquid of bupleurum, and mixing the right borneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation which is suitable for intramuscular injection.
The present invention provides the use of a pain relieving formulation, said use being in the relief of acute pain, or in the relief of post-herpetic neuralgia.
Preferably, the use of the pain relieving formulation, the post-herpetic neuralgia is pain caused by varicella-zoster virus.
Compared with the prior art, the invention has the following beneficial effects:
The pain relieving preparation comprises the propylene glycol extract of the borneol and the bupleurum and pharmaceutically acceptable auxiliary materials, wherein the mass ratio of the propylene glycol extract of the borneol to the bupleurum is 1-2.5:1, and the preparation method of the propylene glycol extract of the bupleurum comprises the steps of grinding the bupleurum into powder, mixing with the propylene glycol, carrying out ultrasonic extraction, filtering, collecting filtrate, and drying to obtain the propylene glycol extract of the bupleurum. After the combination of the right camphol and the propylene glycol extract of the bupleurum, the mixture preparation is formed by matching with pharmaceutically acceptable auxiliary materials. The pain relieving preparation of the invention has the synergistic analgesic effect of the propylene glycol extract of the dextromethorphan and the bupleurum in relieving acute pain or postherpetic neuralgia.
Detailed Description
The present invention will be further described with reference to specific examples in order to enable those skilled in the art to better understand the technical aspects of the present invention.
In the description of the present invention, reagents are commercially available and methods are conventional in the art unless otherwise specified.
In the following examples and experimental procedures, right borneol is purchased from borneol technology Co.Ltd in Jiangxi Lin, and is prepared by extracting and processing fresh branches and leaves of camphor of Lauraceae, wherein the content of the right borneol is more than or equal to 96%, and the package specification is 500 g/bag. According to the medical research result, the right camphol has analgesic effect, anti-inflammatory effect and sleep improving effect.
Radix bupleuri is purchased from a traditional Chinese medicine store. According to the medical research results, the bupleurum has the functions of relieving fever, resisting inflammation, soothing liver, relieving depression, lifting yang qi and relieving exterior and interior.
In the pain relieving preparation, the substance with the pain relieving effect is propylene glycol extract of dextromethorphan and bupleurum, and after the propylene glycol extract and the pharmaceutically acceptable auxiliary materials are combined, the mixture can be prepared into intramuscular injection or nasal drops, and the pain relieving effect is achieved, and the pain relieving effect is that acute pain or postherpetic neuralgia is relieved.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving the propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain the propylene glycol extract liquid of bupleurum, and mixing the right borneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the pain relieving preparation is suitable for intramuscular injection. Wherein the volume ratio of water to propylene glycol in the water-propylene glycol mixed solution is 10:1.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into propylene glycol to obtain propylene glycol extract liquid of bupleurum, and mixing the right borneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation suitable for nasal drops.
The preparation method of the pain relieving preparation comprises the steps of wrapping right borneol in the auxiliary material hydroxypropyl beta cyclodextrin to obtain right borneol liquid, dissolving the propylene glycol extract of bupleurum into a water-propylene glycol mixed solution to obtain the propylene glycol extract liquid of bupleurum, and mixing the right borneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation which is suitable for intramuscular injection. Wherein the volume ratio of water to propylene glycol in the water-propylene glycol mixed solution is 10:1.
The following describes embodiments of the present invention and the corresponding pain relief effects in the form of intramuscular injections and related animal experiments.
Example 1
A pain relieving preparation comprises right camphol, propylene glycol extract of radix bupleuri and pharmaceutically acceptable adjuvants, wherein the mass ratio of right camphol to propylene glycol extract of radix bupleuri is 1:1.
The preparation method of the propylene glycol extract of radix bupleuri comprises grinding radix bupleuri into 40 mesh powder, mixing with propylene glycol at a ratio of 1 kg:8L, ultrasonic extracting under 400W power for 30min, filtering with 50 mesh screen, and lyophilizing the filtrate at-20deg.C to obtain the propylene glycol extract of radix bupleuri.
The pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, preparing right borneol liquid and propylene glycol extract liquid of bupleurum based on the mass ratio of the right borneol to the propylene glycol extract of bupleurum of 1:1, and then mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the concentration of the right borneol in the pain relieving preparation is 75ng/mL.
Example 2
A pain relieving preparation comprises right camphol, propylene glycol extract of radix bupleuri and pharmaceutically acceptable adjuvants, wherein the mass ratio of right camphol to propylene glycol extract of radix bupleuri is 1.5:1.
The preparation method of the propylene glycol extract of radix bupleuri comprises grinding radix bupleuri into 40 mesh powder, mixing with propylene glycol at a ratio of 1 kg:8L, ultrasonic extracting under 400W power for 30min, filtering with 50 mesh screen, and lyophilizing the filtrate at-20deg.C to obtain the propylene glycol extract of radix bupleuri.
The pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, preparing right borneol liquid and propylene glycol extract liquid of bupleurum according to the volume ratio of water to propylene glycol of 10:1 and the mass ratio of right borneol to propylene glycol extract of bupleurum of 1.5:1, and then mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the concentration of right borneol in the pain relieving preparation is 75ng/mL.
Example 3
A pain relieving preparation comprises right camphol, propylene glycol extract of radix bupleuri and pharmaceutically acceptable adjuvants, wherein the mass ratio of right camphol to propylene glycol extract of radix bupleuri is 2:1.
The preparation method of the propylene glycol extract of radix bupleuri comprises grinding radix bupleuri into 40 mesh powder, mixing with propylene glycol at a ratio of 1 kg:8L, ultrasonic extracting under 400W power for 30min, filtering with 50 mesh screen, and lyophilizing the filtrate at-20deg.C to obtain the propylene glycol extract of radix bupleuri.
The pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, preparing right borneol liquid and propylene glycol extract liquid of bupleurum based on the mass ratio of the right borneol to the propylene glycol extract of bupleurum of 2:1, and then mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the concentration of the right borneol in the pain relieving preparation is 75ng/mL.
Example 4
A pain relieving preparation comprises right camphol, propylene glycol extract of radix bupleuri and pharmaceutically acceptable adjuvants, wherein the mass ratio of right camphol to propylene glycol extract of radix bupleuri is 2.5:1.
The preparation method of the propylene glycol extract of radix bupleuri comprises grinding radix bupleuri into 40 mesh powder, mixing with propylene glycol at a ratio of 1 kg:8L, ultrasonic extracting under 400W power for 30min, filtering with 50 mesh screen, and lyophilizing the filtrate at-20deg.C to obtain the propylene glycol extract of radix bupleuri.
The pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, preparing right borneol liquid and propylene glycol extract liquid of bupleurum according to the volume ratio of water to propylene glycol of 10:1 and the mass ratio of the right borneol to the propylene glycol extract of bupleurum of 2.5:1, and then mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the concentration of the right borneol in the pain relieving preparation is 75ng/mL.
Example 5
A pain relieving preparation comprises right camphol, propylene glycol extract of radix bupleuri and pharmaceutically acceptable adjuvants, wherein the mass ratio of right camphol to propylene glycol extract of radix bupleuri is 2:1.
The preparation method of the propylene glycol extract of radix bupleuri comprises grinding radix bupleuri into 40 mesh powder, mixing with propylene glycol at a ratio of 1 kg:8L, ultrasonic extracting under 400W power for 30min, filtering with 50 mesh screen, and lyophilizing the filtrate at-20deg.C to obtain the propylene glycol extract of radix bupleuri.
The pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, preparing right borneol liquid and propylene glycol extract liquid of bupleurum based on the mass ratio of the right borneol to the propylene glycol extract of bupleurum of 2:1, and then mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the concentration of the right borneol in the pain relieving preparation is 60ng/mL.
Example 6
A pain relieving preparation comprises right camphol, propylene glycol extract of radix bupleuri and pharmaceutically acceptable adjuvants, wherein the mass ratio of right camphol to propylene glycol extract of radix bupleuri is 2:1.
The preparation method of the propylene glycol extract of radix bupleuri comprises grinding radix bupleuri into 40 mesh powder, mixing with propylene glycol at a ratio of 1 kg:8L, ultrasonic extracting under 400W power for 30min, filtering with 50 mesh screen, and lyophilizing the filtrate at-20deg.C to obtain the propylene glycol extract of radix bupleuri.
The pharmaceutically acceptable auxiliary materials are the combination of propylene glycol and water.
The preparation method of the pain relieving preparation comprises the steps of dissolving right borneol in propylene glycol to obtain right borneol liquid, dissolving propylene glycol extract of bupleurum into water-propylene glycol mixed liquid to obtain propylene glycol extract liquid of bupleurum, preparing right borneol liquid and propylene glycol extract liquid of bupleurum based on the mass ratio of the right borneol to the propylene glycol extract of bupleurum of 2:1, and then mixing the right borneol liquid and the propylene glycol extract liquid of bupleurum to obtain the pain relieving preparation, wherein the concentration of the right borneol in the pain relieving preparation is 80ng/mL.
Examples 1 to 4 differ in the mass ratio of propylene glycol extracts of right borneol and bupleurum root. In example 1, the mass ratio of the propylene glycol extract of the right borneol to the propylene glycol extract of the bupleurum root was 1:1, in example 2, the mass ratio of the propylene glycol extract of the right borneol to the propylene glycol extract of the bupleurum root was 1.5:1, in example 3, the mass ratio of the propylene glycol extract of the right borneol to the propylene glycol extract of the bupleurum root was 2:1, and in example 4, the mass ratio of the propylene glycol extract of the right borneol to the propylene glycol extract of the bupleurum root was 2.5:1. The difference between examples 3,5 and 6 is that the concentrations of right camphene in the pain relieving formulation are 75ng/mL, 60ng/mL, 80ng/mL, respectively.
The dosage forms of examples 1-6 are all intramuscular injections, and the use method is intramuscular injection.
The analgesic effect of the pain relieving preparations of examples 1 to 6 is discussed below.
Experiment 1, intramuscular injection experiment of virus model
(1) Main experimental materials and animals
CV-1 cells purchased from Shanghai Gei Biotechnology Co., ltd. Under the brand name Gei organism.
Complete culture medium DMEM/F12.
Female mice weighing 30+ -0.2 g.
(2) Grouping and molding
Preparing a cell suspension from CV-1 cells in a complete culture medium, inoculating the cell suspension into a culture dish, inoculating the cell suspension to the culture dish at the concentration of 5X 10 5 cells/cm 2, infecting the cell suspension by varicella-zoster virus, collecting infected cells after 80% or more CV-1 cells are infected by varicella-zoster virus, washing the infected cells in a phosphate buffer solution with the concentration of 0.1mol/L, pH 7.2.2, and re-suspending the infected cells to finally obtain a virus inoculation liquid with the concentration of 10X 10 7 cells/100 mu L. Among them, varicella-zoster virus is specifically VZV-rOka, supplied by Xiamen university.
132 Female mice were randomly divided into 11 groups of 12, each, and the names of the 11 groups were blank group, model group, right borneol group, propylene glycol extract group of bupleurum, example 1 group, example 2 group, example 3 group, example 4 group, example 5 group, example 6 group, and drug control group, respectively.
The treatment mode of the blank female mice is that 50 mu L of physiological saline is injected into subcutaneous muscle at the left uncut portion of the toe.
The other groups were treated in such a manner that 50. Mu.L of the virus inoculation liquid was subcutaneously injected into the female mice at the left uncut portion of the toe, and the change of the paw withdrawal threshold of the female mice of the experimental group was observed from the day of intramuscular injection, and the paw withdrawal threshold was measured by a pressure pain tester. The paw withdrawal threshold of female mice began to decrease continuously at day 2 after intramuscular injection of the viral inoculum, and decreased to a lower level and stabilized at this pain threshold level at day 12 after intramuscular injection of the viral inoculum, indicating that the postherpetic neuralgia model was successfully modeled.
(3) Treatment of
The blank group served as a healthy control group, and physiological saline with the concentration of 0.9g/100mL was injected intramuscularly.
The model group was intramuscular injected with physiological saline at a concentration of 0.9g/100 mL.
The right kaempferol group was only intramuscular injected with a propylene glycol solution of 75ng/mL right kaempferol, and was used to observe pain relief in female mice under the action of right kaempferol alone.
The propylene glycol extract group of bupleurum was only intramuscular injected with 75ng/mL of propylene glycol extract liquid of bupleurum, to observe pain relief in female mice with propylene glycol extract of bupleurum alone.
Example 1 group intramuscular injection of the pain relieving formulation of example 1.
Example 2 groups the pain relieving formulation of example 2 was injected intramuscularly.
Example 3 groups the pain relieving formulation of example 3 was injected intramuscularly.
Example 4 groups the pain relieving formulation of example 4 was injected intramuscularly.
Example 5 groups the pain relieving formulation of example 5 was injected intramuscularly.
Example 6 groups the pain relieving formulation of example 6 was injected intramuscularly.
The drug control group was intramuscular injected with the pain relieving formulation of the drug control group.
Specific intramuscular injection amounts are referred to table 1.
In the course of the virus model intramuscular injection experiment, the propylene glycol solution of right-handed kaempferol was obtained by dissolving right-handed kaempferol in propylene glycol. The propylene glycol extract liquid of bupleurum is obtained by dissolving the propylene glycol extract of bupleurum into water-propylene glycol mixed solution, and the volume ratio of water to propylene glycol in the water-propylene glycol mixed solution is 10:1. The pain relieving preparation of the drug control group is prepared by changing the propylene glycol extract of Bupleurum chinensis of example 3 into the water extract of Bupleurum chinensis, grinding Bupleurum chinensis into 40 mesh powder, mixing with deionized water according to the ratio of 1kg to 8L, ultrasonic extracting for 30min under 400W power, filtering with 50 mesh screen, and lyophilizing the collected filtrate at-20deg.C.
TABLE 1 treatment of female mice of different groups
(4) Pain index test
The mechanical stimulation paw withdrawal threshold of the right hind limb of female mice was determined using a Von FREY FILAMENT tactile pain meter. Recording the stimulation intensity of female mice when the female mice take foot lifting, foot licking or avoiding actions, measuring each female mouse 5 times, and taking the average value of 3 times after the maximum value and the minimum value are removed to obtain the mechanical stimulation foot shrinking threshold value. The results are shown in Table 2.
TABLE 2 treatment results for female mice of different groups
Shingles is an infectious disease affecting nerves and skin, caused by varicella-zoster virus. Shingles often occurs in the trunk, including the chest, abdomen and back, and mainly causes pain and rash without accompanying other special symptoms, and generally without special sequelae after immediate treatment. Some patients with shingles may develop chronic pain, post-shingles neuralgia. Post-herpetic neuralgia patients often present with prolonged pain, which mainly includes neuralgia, tingling, numbness, etc., and has various pain properties, which may be cauterized, shocked, incised, needled, or torn. Post-herpetic neuralgia affects the normal life of the patient, and therefore, development of a formulation for alleviating post-herpetic neuralgia is necessary.
From the results shown in table 2, the group of examples 1 to 6 can significantly relieve postherpetic neuralgia. The effects of the drug control group, the right borneol group and the propylene glycol extract group of the bupleurum root for relieving the postherpetic neuralgia are obviously lower than those of the embodiment 1 group to the embodiment 6 group, and the P is less than 0.05.
Experiment 2, acute pain model intramuscular injection experiment
(1) Experimental animal
SD rats weighing 250+ -10.2 g.
(2) Moulding
132 SD rats were randomly divided into 11 groups of 12, each of which 11 groups were named blank, model, right borneol, propylene glycol extract of bupleurum, example 1, example 2, example 3, example 4, example 5, example 6 and drug control, respectively.
The SD rat is fasted for the first 6 hours of molding and is forbidden for 1 hour of molding, the SD rat is placed in a 1L transparent glass container which is soaked with an isoflurane liquid cotton ball, so that the awareness of the SD rat disappears, an incision with the length of 1cm is made from the position of 0.5cm at the proximal end of the sole of the SD rat to the toe, the skin is incised, then the plantar muscles are lifted by using an ophthalmic forceps and are incised along the longitudinal direction, and meanwhile, the starting, stopping and attachment of the muscles are kept intact. After hemostasis by pressing, the skin is sutured with a fine needle to complete the modeling of the acute pain model.
(3) Treatment of
The blank group served as a healthy control group, and physiological saline with the concentration of 0.9g/100mL was injected intramuscularly.
The model group was intramuscular injected with physiological saline at a concentration of 0.9g/100 mL.
The right kaempferol group was only intramuscular injected with 75ng/mL of the propylene glycol solution of right kaempferol.
The right kaempferol group was only intramuscular injected with 75ng/mL of bupleurum glycol extract liquid.
Example 1 group intramuscular injection of the pain relieving formulation of example 1.
Example 2 groups the pain relieving formulation of example 2 was injected intramuscularly.
Example 3 groups the pain relieving formulation of example 3 was injected intramuscularly.
Example 4 groups the pain relieving formulation of example 4 was injected intramuscularly.
Example 5 groups the pain relieving formulation of example 5 was injected intramuscularly.
Example 6 groups the pain relieving formulation of example 6 was injected intramuscularly.
The drug control group was intramuscular injected with the pain relieving formulation of the drug control group.
Wherein, the propylene glycol solution of the right camphol is obtained by dissolving the right camphol in propylene glycol. The propylene glycol extract liquid of bupleurum is obtained by dissolving the propylene glycol extract of bupleurum into water-propylene glycol mixed solution, and the volume ratio of water to propylene glycol in the water-propylene glycol mixed solution is 10:1. The pain relieving preparation of the drug control group is prepared by changing the propylene glycol extract of Bupleurum chinensis of example 3 into the water extract of Bupleurum chinensis, grinding Bupleurum chinensis into 40 mesh powder, mixing with deionized water according to the ratio of 1kg to 8L, ultrasonic extracting for 30min under 400W power, filtering with 50 mesh screen, and lyophilizing the collected filtrate at-20deg.C.
Specific intramuscular injection amounts are referred to table 3.
TABLE 3 treatment of SD rats in different groups
(4) Pain index test
The mechanical stimulus pinch threshold was tested with reference to the method of experiment 1 above and the results are shown in table 4.
TABLE 4 treatment results for different groups of SD rats
The method has important significance in various aspects of relieving acute pain, and is characterized in multiple aspects of physiology, psychology, disease treatment, socioeconomic performance and the like, for example, the method can avoid physiological dysfunction, promote wound healing, relieve anxiety and fear, improve sleep quality, improve patient compliance, reduce medical resource occupation and the like.
From the results shown in table 4, the acute pain can be significantly relieved in the group of examples 1 to 6, and the effect of the drug control group, the right borneol group and the propylene glycol extract group of bupleurum root on relieving the acute pain is significantly lower than that in the group of examples 1 to 6, with P <0.05.
It should be noted that, when numerical ranges are referred to in the present invention, it should be understood that two endpoints of each numerical range and any numerical value between the two endpoints are optional, and because the adopted step method is the same as the embodiment, in order to prevent redundancy, the present invention describes a preferred embodiment. While the preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the inventive concepts, which are within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. The present invention is intended to include such modifications and alterations insofar as they come within the scope of the equivalent technology thereof.
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| US20080220084A1 (en) * | 2007-03-09 | 2008-09-11 | Pfantastic Medical Research Institute, Llc | Combination therapy for alleviating pain-related conditions |
| US20130252924A1 (en) * | 2010-11-11 | 2013-09-26 | Akron Molecules Gmbh | Compounds and Methods for Treating Pain |
| KR101917877B1 (en) * | 2017-06-29 | 2018-11-13 | 재단법인 경기도경제과학진흥원 | Composition for treating, alleviating or preventing peripheral neuropathic pain induced by anticancer agent |
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| (+)-Borneol alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice;Jiang J, Shen YY, Li J, Lin YH, Luo CX, Zhu DY;《Eur J Pharmacol.》;20150331(第757期);摘要 * |
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