CN121015814A - A traditional Chinese medicine composition for promoting blood circulation and removing blood stasis, an external preparation and its uses. - Google Patents

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology, specifically to a TCM composition for promoting blood circulation and removing blood stasis, a topical preparation, and its uses. The TCM composition comprises Dipsacus asper, Lycopodium clavatum, Frankincense, Myrrh, Saposhnikovia divaricata, Panax notoginseng, Curcuma longa, Cinnamomum cassia, Ligusticum striatum, Ligusticum chuanxiong, Gardenia jasminoides, Morus alba twigs, Nelumbo nucifera leaf, Rheum palmatum, Daemonorops draco, Salvia miltiorrhiza, Carthamus tinctorius, Artemisia argyi leaf, and Mentha haplocalyx. This invention's TCM composition for promoting blood circulation and removing blood stasis is rationally formulated and has excellent therapeutic effects on wind-cold-dampness syndrome. It is suitable for patients with symptoms such as frozen shoulder, cervical spondylosis, lower back and leg pain, muscle and joint pain, as well as rheumatoid arthritis, gouty arthritis, etc. By selecting a specific combination of natural penetrants and the TCM composition to prepare a topical dosage form, it can promote the drug's penetration through physiological barriers into target organs or tissues, allowing it to directly act on the lesion. It has a rapid onset of action, long-lasting efficacy, is convenient to use, has good patient compliance, and has no toxic side effects, providing a new option for topical transdermal agents in the clinical treatment of chronic pain.

Description

Traditional Chinese medicine composition for promoting menstruation and removing blood stasis, external preparation and application

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for menstruation and stasis removal, an external preparation and application.

Background

Muscle joint pain refers to muscle joint pain caused by systemic and/or local diseases,

Pain can be divided into two types, acute pain and chronic pain. Acute pain is usually transient, resulting from injury, surgery, disease or inflammation, and is often seen in trauma, muscle strain, acute febrile disease, and the like. Chronic pain refers to pain that persists for more than 3 months, which is usually due to chronic disease or injury, is commonly seen in trauma, chronic muscle strain, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, etc., and can persist for a long period of time, severely affecting the daily life and mind of the patient.

For chronic pain, western medicine often adopts symptomatic treatment, such as taking nonsteroidal anti-inflammatory drugs and the like, and although pain symptoms can be relieved to a certain extent, symptoms and root causes are often cured, the chronic pain is easy to repeat after taking the drugs, and serious side effects such as digestive tract ulcers, osteoporosis and the like are often caused in the treatment process due to the large side effects of western medicine. In the theory of traditional Chinese medicine, the arthralgia-syndrome belongs to the category of arthralgia-syndrome, wherein the arthralgia-syndrome belongs to the concept of traditional Chinese medicine, and refers to symptoms such as closed channel and blocked channel and unsmooth qi and blood circulation, and further pain, numbness, difficulty in flexing and stretching of muscles, bones and joints and the like caused by deficiency of skin and muscle, deficiency of qi and blood, deficiency of liver and kidney and invasion of exogenous evil such as wind, cold, dampness and heat into human body.

The traditional Chinese medicine is based on syndrome differentiation treatment, and is mainly used for dispelling wind, dispelling cold and promoting diuresis, and is also used for promoting qi and activating blood circulation, and is mainly used for warming channels and dispelling cold, dispelling wind and removing dampness, so that blood coagulation is caused by cold in blood, and is usually used for promoting blood circulation and removing blood stasis, and is mainly used for promoting diuresis, and is also used for dispelling wind, dispelling cold and activating blood circulation.

The classic formula "Duhuosheng decoction" in the "Qianjin Fang Ji" is composed of radix Angelicae Pubescentis, herba Taxilli, cortex Eucommiae, radix Achyranthis bidentatae, herba asari, radix Gentianae Macrophyllae, poria, cortex Cinnamomi, radix Saposhnikoviae, rhizoma Chuanxiong, radix Ginseng, radix Glycyrrhizae, radix Angelicae sinensis, radix Paeoniae, and dried radix rehmanniae. Has the effects of dispelling wind-damp, relieving arthralgia, tonifying liver and kidney, and invigorating qi and blood. It is suitable for arthralgia syndrome due to deficiency of both liver and kidney and deficiency of qi and blood, manifested as cold pain in waist and knee, aversion to cold, cold limbs, pale tongue with white coating, and deep and thready pulse.

The classic formula of the typhoid fever theory is Chinese angelica four-reverse decoction, which comprises angelica sinensis, cassia twig, peony, asarum, liquorice, ricepaperplant pith and jujube. Has the effects of warming channel, dispelling cold, nourishing blood and dredging collaterals. It is indicated for the syndrome of blood deficiency and cold congealing in the channels and collaterals, manifested as cold extremities, cold pain in joints, thready and absolute pulse.

Compared with the oral administration of traditional Chinese medicine, the external treatment method of the medicine has a plurality of advantages, can locate the medicine, directly acts on focus, and the potency of the medicine can directly reach the focus, so the medicine has quicker effect, avoids the oral administration of the traditional Chinese medicine, has small toxic and side effects, is safer to use, can avoid the first pass effect of liver and the interference and inactivation of gastrointestinal factors, and can reduce the difference among individuals of patients, thus developing the percutaneous administration preparation with important theoretical and practical significance for the effective treatment of rheumatic arthralgia and the multi-target synergistic effect, and can fill the clinical use requirement.

Disclosure of Invention

In order to overcome the technical defects, the invention provides a traditional Chinese medicine composition for promoting menstruation and removing blood stasis, an external preparation and application thereof, and the composition is matched with various components to cooperatively promote, plays roles of percutaneous permeation promotion and heart channel permeation, and achieves the effects of relieving symptoms such as ache, stiffness, numbness, stasis and blockage of neck, shoulder, waist, leg, joint, tendon, muscle and bone parts caused by wind cold, stasis and damp evil, and has remarkable effect of treating rheumatic arthralgia and high cure rate.

The invention aims at providing a traditional Chinese medicine composition for promoting menstruation and removing blood stasis, which is prepared from the following raw materials of teasel root, lycopodium clavatum, frankincense, myrrh, radix sileris, pseudo-ginseng, turmeric, cinnamon, rhizoma zingiberis, ligusticum wallichii, gardenia, mulberry twig, lotus leaf, rheum officinale, dragon's blood, red sage root, safflower, mugwort leaf and peppermint.

The inventor takes the basic theory of traditional Chinese medicine as guidance, combines modern pharmacological research, selects teasel root, lycopodium clavatum, frankincense, myrrh, divaricate saposhnikovia root, pseudo-ginseng, turmeric, cinnamon, wood ginger, szechuan lovage rhizome, gardenia, mulberry twig, lotus leaf, rhubarb, dragon's blood, red sage root and safflower to carry out reasonable compatibility, promotes synergy, directly acts on focus by multi-target synergistic effect, and can directly reach the disease focus by the potency of medicine to effectively treat the rheumatic arthralgia.

Radix Dipsaci, bitter and pungent in flavor, slightly warm in nature, good in liver and kidney meridian, capable of tonifying liver and kidney, strengthening tendons and bones, continuously breaking and stopping metrorrhagia, and can be used for treating soreness and weakness of waist and knees, fracture due to injury of tendons, metrorrhagia, bleeding on fetus, and restlessness;

Herba Lycopodii, slightly bitter and pungent in taste, warm in nature, and capable of invigorating liver, spleen and kidney channels, dispelling wind and removing dampness, relaxing tendons and activating collaterals, and can be used for treating rheumatalgia, joint discomfort and traumatic injury;

olibanum, pungent and bitter in taste, warm in nature, inducing heart, liver and spleen meridians, activating blood and relieving pain, detumescence and promoting granulation, mainly treating traumatic injury, rheumatalgia, pyocutaneous disease and swelling toxin, dysmenorrhea;

Myrrh, bitter taste, peace, heart, liver and spleen meridian, stasis dispelling, pain relieving, swelling eliminating, tissue regeneration promoting, and the main treatment of traumatic injury, stasis and swelling, pain in chest and abdomen, carbuncle, swelling and sore;

notoginseng radix has sweet and slightly bitter taste, and is effective in warming, nourishing liver and stomach channel, dispelling blood stasis, stopping bleeding, promoting blood circulation, and relieving pain, and can be used for treating internal and external hemorrhage (such as hemoptysis and hematochezia), blood stasis swelling and pain, and traumatic injury;

Turmeric, curcuma rhizome, pungent and bitter in taste, warm in nature, has effects of invigorating liver and spleen meridian, breaking blood and promoting qi circulation, and dredging meridian and relieving pain, and can be used for treating rheumatalgia, chest and hypochondrium stabbing pain, and traumatic injury swelling and pain;

ligusticum wallichii, pungent and warm, entering liver, gall and pericardium meridian, activating blood and promoting qi circulation, dispelling wind and relieving pain, and mainly treating blood stasis and qi stagnation pain syndromes (such as headache and dysmenorrhea) and rheumatalgia;

Radix Salviae Miltiorrhizae, bitter in taste, slightly cold, has effects in restoring heart and liver meridian, promoting blood circulation, removing blood stasis, dredging meridian, relieving pain, clearing away heart-fire, and relieving restlessness, and can be used for treating thoracic obstruction, heart pain, menoxenia, abdominal mass, pyocutaneous disease, and toxic swelling;

safflower, pungent and warm in taste, heart and liver meridian return, blood circulation promoting, meridian dredging, stasis dispelling and pain relieving, and mainly treats amenorrhea due to blood stasis, dysmenorrhea, traumatic injury and mass;

Radix Saposhnikoviae, pungent and sweet in taste, slightly warm in nature, entering bladder, liver and spleen meridians, dispelling pathogenic wind, relieving exterior syndrome, eliminating dampness, relieving pain, and relieving spasm, and can be used for treating exogenous exterior syndrome (wind-cold/wind-heat), rheumatalgia, tetanus, and rubella pruritus;

ramulus Mori, slightly bitter in taste, has effects in calming liver meridian, dispelling pathogenic wind and dampness, and benefiting joint, and can be used for treating rheumatalgia and joint flexion and extension disorder;

the wooden ginger is pungent in taste and warm in nature, enters spleen and stomach channels, warms middle-jiao and dispels cold, regulates qi and relieves pain, and is mainly used for treating cold-dampness arthralgia and epigastralgia;

lotus leaf, bitter in taste, and capable of calming, and can be used for treating liver, spleen and stomach channels, clearing summer-heat, resolving dampness, rising clear yang, and treating summer-heat, damp diarrhea, hematemesis, epistaxis and hyperlipidemia;

Gardenia, bitter and cold taste, heart, lung and triple energizer meridian, fire purging and restlessness relieving, heat clearing and dampness removing, blood cooling and toxin removing, and is mainly used for treating febrile vexation, damp-heat jaundice, blood heat hematemesis and epistaxis and conjunctival congestion and swelling and pain;

dragon's blood, sweet and salty, calm, restore heart and liver meridian, activate blood and relieve pain, remove blood stasis and stop bleeding, and is mainly used for treating traumatic injury, swelling and pain due to blood stasis, traumatic hemorrhage and unhealed ulcer;

cinnamon, cortex Cinnamomi, sweet and bitter in flavor, has the effects of invigorating kidney, spleen, heart and liver channels, tonifying fire and yang, dispelling cold and relieving pain, warming and dredging channels and collaterals, and is mainly used for treating kidney-yang deficiency and cold coagulation and stasis pain;

Rhubarb, bitter and cold taste, spleen, stomach, large intestine, liver and pericardium meridian, purgation and accumulation, heat clearing and blood cooling, blood stasis expelling and meridian dredging, and is mainly used for treating constipation due to excessive heat, hematemesis and epistaxis, blood stasis and amenorrhea, carbuncle and furuncle;

rhizoma Cyperi, pungent, slightly bitter and slightly sweet, and has effects of regulating liver, spleen and triple energizer channels, dispersing stagnated liver qi for relieving qi stagnation, regulating qi-flowing for regulating menstruation and relieving pain, and can be used for treating hypochondriac pain due to stagnation of liver-qi, spleen-stomach qi stagnation, abdominal distention and pain, and menoxenia.

The traditional Chinese medicine composition formula of the invention inherits the overall dialectical concept of traditional Chinese medicine, starts with the regulation of viscera functions, achieves the effects of harmonizing the five medicines, regulating the middle warmer and regulating the balance, and plays the roles of relaxing tendons and activating collaterals, and regulating qi and strengthening spleen together. The recipe is applied clinically to dialectical medicine and modified with symptoms, and is mainly used for treating the symptoms of muscle and skin striae, deficiency of qi and blood, deficiency of liver and kidney, invasion of exogenous evils such as wind, cold, dampness, heat and the like into human bodies, blockage of channels and collaterals, unsmooth qi and blood running, and further symptoms such as ache, numbness, difficulty in flexing and stretching of muscles, bones and joints and the like, including rheumatic arthritis, rheumatoid arthritis, hyperosteogeny, spondylitis, scapulohumeral periarthritis, osteoarthritis and the like.

The preparation is prepared from common clubmoss herb and himalayan teasel root serving as principal drugs, is compatible for treating main symptoms of wind-damp blockage and muscle and bone malnutrition, and is used as ministerial drugs, wherein the frankincense, the myrrh, the szechuan lovage rhizome, the red sage root, the safflower and the sanchi are used as adjuvant drugs for synergistically enhancing the effects of activating blood and removing obstruction in collaterals, and is used as a menstruation inducing drug for treating the concurrent symptoms of blood stasis and qi and blood obstruction, wherein the frankincense and the myrrh are used for activating qi and activating blood, detumescence and promoting granulation, enhancing the effects of activating collaterals and relieving pain, the szechuan lovage rhizome is used for dispelling heat, improving microcirculation, relieving limb numbness caused by wind-cold and dampness evil, the red sage root, the safflower and the sanchi are used for cooling blood and removing stasis, and relieving menstruation and improving blood stasis syndrome synergistically, the divaricate saposhnikovia root, the cinnamon, the turmeric, the rhubarb and the cape jasmine are used as adjuvant drugs for dispelling wind and removing dampness, warming and dredging channels and collaterals and clearing stasis heat, assisting the principal drugs to expel exogenous evil, and the mulberry twig and the lotus leaf are used as a menstruation inducing drug for promoting the medicine to promote the flow and clear yang and clearing summer heat and harmonizing middle-warmer. The whole formula has the effects of warming kidney, dispelling cold, eliminating dampness, dredging collaterals, removing blood stasis and relieving pain. The medicines are combined together, the monarch and minister medicines are combined, the assistant and guide directions are clear, the cold and heat are regulated, the effects of eliminating pathogenic factors without hurting the healthy energy, activating blood without consuming blood, dispelling wind and warming channels, inducing menstruation and dredging collaterals are achieved, and the effects of eliminating pathogenic factors and strengthening healthy energy are reflected.

Further, the amount of lycopodium clavatum in the composition of the present invention may be 10 to 50 parts by weight, for example, 20 to 50 parts by weight, or 30 to 50 parts by weight, or 40 to 50 parts by weight, such as 45 parts by weight, and

The amount of radix Dipsaci may be 10-50 parts by weight, or 10-40 parts by weight, or 20-40 parts by weight, or 30-40 parts by weight, such as 35 parts by weight, and

The amount of Olibanum can be 5-30 weight parts, or 15-25 weight parts, or 18-23 weight parts, such as 20 weight parts, and

The amount of the myrrh can be 5-30 parts by weight, or 15-30 parts by weight, or 20-30 parts by weight, or 22-28 parts by weight, such as 25 parts by weight, and

The amount of radix Saposhnikoviae can be 10-20 parts by weight, or 12-20 parts by weight, or 15-20 parts by weight, or 10-15 parts by weight, such as 15 parts by weight, and

The amount of Notoginseng radix may be 5-30 parts by weight, or 10-25 parts by weight, or 10-20 parts by weight, or 15-20 parts by weight, such as 18 parts by weight, and

The amount of turmeric may be 10-20 parts by weight, or 12-20 parts by weight, or 15-20 parts by weight, or 10-15 parts by weight, such as 15 parts by weight, and

The amount of cinnamon can be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 12-15 parts by weight, such as 12 parts by weight, and

The amount of the wood ginger may be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 10-12 parts by weight, such as 10 parts by weight, and

The amount of rhizoma Ligustici Chuanxiong can be 5-30 parts by weight, or 15-30 parts by weight, or 20-25 parts by weight, such as 23 parts by weight, and

The amount of Gardenia jasminoides Ellis may be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 12-15 parts by weight, such as 12 parts by weight, and

The amount of ramulus Mori may be 1-10 parts by weight, or 1-8 parts by weight, or 3-5 parts by weight, such as 5 parts by weight, and

The amount of lotus leaf may be 1-10 parts by weight, or 3-10 parts by weight, or 5-10 parts by weight, or 8-10 parts by weight, such as 8 parts by weight, and

The amount of radix et rhizoma Rhei may be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 15-20 parts by weight, such as 15 parts by weight, and

The amount of sanguis Draxonis may be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 10-12 parts by weight, such as 10 parts by weight, and

The amount of Saviae Miltiorrhizae radix may be 5-30 parts by weight, or 15-30 parts by weight, or 20-30 parts by weight, or 23-28 parts by weight, such as 25 parts by weight, and

The amount of safflower may be 5 to 30 parts by weight, or 15 to 25 parts by weight, or 18 to 22 parts by weight, such as 20 parts by weight.

Further, the lycopodium clavatum comprises one or a combination of lycopodium clavatum powder and lycopodium clavatum extract, and/or,

The radix Dipsaci comprises one or a combination of radix Dipsaci powder and radix Dipsaci extract, and/or,

The Olibanum comprises one or a combination of milk powder and Olibanum extract, and/or,

The myrrh comprises one or a combination of myrrh powder and myrrh extract, and/or,

The radix Saposhnikoviae comprises one or a combination of radix Saposhnikoviae and radix Saposhnikoviae extract, and/or,

The Notoginseng radix comprises Notoginseng radix powder, notoginseng radix extract or their combination, and/or,

The turmeric comprises one or a combination of turmeric powder, turmeric extract, and/or,

The cinnamon comprises one or a combination of cinnamon powder and cinnamon extract, and/or,

One or a combination of the wooden Jiang Baokuo wooden ginger powder and the wooden ginger extract, and/or,

The rhizoma Ligustici Chuanxiong comprises one or more of rhizoma Ligustici Chuanxiong powder and rhizoma Ligustici Chuanxiong extract, and/or,

The fructus Gardeniae comprises one or a combination of fructus Gardeniae powder and fructus Gardeniae extract, and/or,

The mulberry twig comprises one or a combination of mulberry twig powder and mulberry twig extract, and/or,

The lotus leaf comprises one or a combination of lotus leaf powder and lotus leaf extract, and/or,

The radix et rhizoma Rhei comprises one or a combination of radix et rhizoma Rhei powder and radix et rhizoma Rhei extract, and/or,

The sanguis Draxonis comprises one or a combination of sanguis Draxonis powder and sanguis Draxonis extract, and/or,

The radix Salviae Miltiorrhizae comprises one or a combination of radix Salviae Miltiorrhizae powder and radix Salviae Miltiorrhizae extract, and/or,

The safflower comprises one or a combination of safflower powder and safflower extract, and/or,

The folium Artemisiae Argyi comprises one or a combination of folium Artemisiae Argyi powder and folium Artemisiae Argyi extract.

The second purpose of the invention is to provide the application of the traditional Chinese medicine composition in preparing external medicines for dispelling wind and cold, activating blood and removing obstruction in collaterals and easing pain, warming kidney yang and strengthening tendons and bones.

The invention also provides an external preparation, which is characterized by comprising the composition and pharmaceutically acceptable auxiliary materials in the field, wherein the addition amount of the composition is 5-30% of the total mass.

The pharmaceutical excipients may be selected from one or more of solvents, propellants, solubilizing agents, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure modifiers, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-binding agents, integration agents, permeation enhancers, pH modifiers, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, and release retarders.

Further, the preparation is any one of ointment, cream, gel and patch.

Further, the preparation is a gel, and comprises the composition, a gel matrix, a humectant and a penetration enhancer, wherein the addition amount of the composition is 5-30% by weight of the gel.

The gel matrix is one or more selected from methylcellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose, sodium carboxymethyl cellulose, carbomer 940, gelatin and sodium alginate;

The humectant is one or more selected from glycerol, 1, 3-butanediol, propylene glycol, polyethylene glycol 300, polyethylene glycol 400 and sorbitol;

the penetration enhancer is one or more of borneol, blumea oil or peppermint oil;

Further, the preparation is ointment, and comprises the composition, an oil phase matrix, water, an emulsifying agent and a penetration enhancer, wherein the addition amount of the composition is 5-30% by weight of the ointment.

The oil phase matrix is one or more selected from stearic acid, paraffin, beeswax, higher alcohol, liquid paraffin, vaseline or vegetable oil;

The emulsifier is preferably one or more of soaps, sodium laurylsulfate, fatty acid esters of polyalcohol (such as glyceryl monostearate), polysorbate, and polyethylene glycol ether;

the penetration enhancer is one or more of borneol, blumea oil or peppermint oil;

Further, the preparation is a patch, and the patch comprises a backing, a paste layer and an anti-adhesive film, wherein the paste layer comprises the composition, a cross-linking agent, a penetration enhancer, a plasticizer and a humectant, and the addition amount of the composition is 5-30% by weight of the paste layer;

the cross-linking agent is selected from one or more of ethyl oleate, triethyl citrate, diethyl phthalate, dimethyl phthalate or dibutyl phthalate, and preferably selected from one of triethyl citrate and diethyl phthalate;

The humectant is one or more selected from glycerol, 1, 3-butanediol, propylene glycol, polyethylene glycol 300, polyethylene glycol 400 and sorbitol, preferably glycerol;

The material of the pressure-sensitive adhesive is selected from ethylene/acrylic ester copolymer, polyisobutylene, polypentadiene, polyacrylate, silicone copolymer, styrene-isoprene-styrene triblock copolymer (SIS), ethylene-butadiene-styrene triblock copolymer (SBS), hydrogenated SBS (SEBS) and polyurethane;

the backing material is one or more selected from polyester, cotton, polyamide, polyolefin, polyurethane, silk and hemp;

the anti-sticking film material is selected from one or more of polyethylene, polypropylene, vinyl acetate, ethylene polymer and polyvinyl chloride.

The fourth purpose of the invention is to provide a preparation method of an external traditional Chinese medicine preparation, wherein the traditional Chinese medicine composition is prepared into a conventional dosage form according to a conventional method in the field;

when the conventional dosage form is a gel, the gel is prepared by mixing the traditional Chinese medicine composition with a gel matrix, a humectant and a penetration enhancer, wherein the addition amount of the traditional Chinese medicine composition is 5-30% by weight of the gel, the addition amount of the penetration enhancer is 1-10% by weight of the gel, the traditional Chinese medicine composition is a traditional Chinese medicine ethanol extract, and the penetration enhancer is one or more of borneol, blumea oil or peppermint oil;

When the conventional preparation is a paste, the paste is prepared by mixing the traditional Chinese medicine composition with an oil phase matrix, water, an emulsifying agent and a penetration enhancer, wherein the addition amount of the traditional Chinese medicine composition is 5-30% wt of the paste, and the addition amount of the penetration enhancer is 1-10% wt of the paste;

When the conventional preparation is a patch, the patch is prepared by uniformly mixing the traditional Chinese medicine composition, a cross-linking agent, a permeation promoter, a plasticizer and a humectant, coating the mixture on a backing material to form a paste layer, and finally covering a protective film, wherein the addition amount of the traditional Chinese medicine composition is 5-30% by weight of the paste layer, the addition amount of the permeation promoter is 1-10% by weight of the paste layer, the traditional Chinese medicine composition is a traditional Chinese medicine ethanol extract, and the permeation promoter is one or more of borneol, blumea oil or peppermint oil.

In addition, colorants, preservatives, flavors, flavoring agents, sweeteners, or other materials may also be added to the pharmaceutical formulation, if desired.

The dosage of the pharmaceutical composition of the present invention to be administered depends on many factors such as the nature and severity of allergic asthma to be prevented or treated, the sex, age, weight and individual response of the patient or animal, the administration route and the administration frequency, etc. The above-mentioned doses may be administered in a single dosage form or divided into several, for example two, three or four dosage forms. The dosage level will be selected based on the particular route of administration, the severity of the condition being treated, the condition and past medical history of the patient to be treated, and the like. However, it is common in the art to administer doses that begin at levels below that required to achieve the desired therapeutic effect and gradually increase until the desired effect is achieved.

The traditional Chinese medicine composition for promoting menstruation and removing blood stasis has reasonable compatibility, has excellent treatment effect on wind-cold-dampness arthralgia, and is suitable for scapulohumeral periarthritis, cervical spondylosis, lumbago and skelalgia, muscle and joint pain, and rheumatic arthritis, rheumatoid arthritis and gouty arthritis with the symptoms. The invention selects a specific natural penetrating agent combination and a traditional Chinese medicine composition to prepare an external preparation, can promote the medicine to enter target organs or tissues through various physiological barriers such as blood brain barriers, mucous membranes, skin and the like, can directly act on focus, has rapid effect, durable efficacy, convenient use, good patient compliance, convenient use, safety, no stimulation and no toxic or side effect, and provides a new choice of external transdermal agent for clinical treatment of chronic pain.

Detailed Description

The present invention will be described in detail with reference to specific embodiments thereof, so that those skilled in the art can better understand the technical solutions of the present invention. The experimental procedures, which do not address the specific conditions in the examples below, are generally carried out under conventional conditions or under conditions recommended by the manufacturer. Percentages and parts are by weight unless otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the present invention. The preferred methods and materials described herein are presented for illustrative purposes only.

The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.

The invention is based on the inventor's dialectical compatibility of traditional Chinese medicine and clinical experience, and aims at treating the symptoms of wind-damp arthralgia and blood stasis, such as joint swelling and pain, spasm of tendons and vessels, traumatic injury and swelling, limb numbness, or cold and heat evil, and the combination of the kidney-yang and wind-damp dispelling medicine is used for strengthening body resistance and eliminating evil.

According to the invention, on the one hand, a traditional Chinese medicine composition for promoting menstruation and removing blood stasis is provided, which is prepared from the following raw materials of teasel root, lycopodium clavatum, frankincense, myrrh, divaricate saposhnikovia root, pseudo-ginseng, turmeric, cinnamon, wood ginger, szechuan lovage rhizome, gardenia, mulberry twig, lotus leaf, rhubarb, dragon's blood, red sage root, safflower, mugwort leaf and peppermint.

In some specific embodiments, the lycopodium clavatum comprises one or a combination of lycopodium clavatum powder, lycopodium clavatum extract, and/or,

The radix Dipsaci comprises one or a combination of radix Dipsaci powder and radix Dipsaci extract, and/or,

The Olibanum comprises one or a combination of milk powder and Olibanum extract, and/or,

The myrrh comprises one or a combination of myrrh powder and myrrh extract, and/or,

The radix Saposhnikoviae comprises one or a combination of radix Saposhnikoviae and radix Saposhnikoviae extract, and/or,

The Notoginseng radix comprises Notoginseng radix powder, notoginseng radix extract or their combination, and/or,

The turmeric comprises one or a combination of turmeric powder, turmeric extract, and/or,

The cinnamon comprises one or a combination of cinnamon powder and cinnamon extract, and/or,

One or a combination of the wooden Jiang Baokuo wooden ginger powder and the wooden ginger extract, and/or,

The rhizoma Ligustici Chuanxiong comprises one or more of rhizoma Ligustici Chuanxiong powder and rhizoma Ligustici Chuanxiong extract, and/or,

The fructus Gardeniae comprises one or a combination of fructus Gardeniae powder and fructus Gardeniae extract, and/or,

The mulberry twig comprises one or a combination of mulberry twig powder and mulberry twig extract, and/or,

The lotus leaf comprises one or a combination of lotus leaf powder and lotus leaf extract, and/or,

The radix et rhizoma Rhei comprises one or a combination of radix et rhizoma Rhei powder and radix et rhizoma Rhei extract, and/or,

The sanguis Draxonis comprises one or a combination of sanguis Draxonis powder and sanguis Draxonis extract, and/or,

The radix Salviae Miltiorrhizae comprises one or a combination of radix Salviae Miltiorrhizae powder and radix Salviae Miltiorrhizae extract, and/or,

The safflower comprises one or a combination of safflower powder and safflower extract, and/or,

The folium Artemisiae Argyi comprises one or a combination of folium Artemisiae Argyi powder and folium Artemisiae Argyi extract.

In some specific embodiments, the Chinese medicinal composition comprises herba Lycopodii powder, radix Dipsaci powder, radix aucklandiae powder, rhizoma Dioscoreae powder, radix Saposhnikoviae powder, notoginseng radix powder, curcuma rhizome powder, cortex Cinnamomi powder, rhizoma Dioscoreae powder, rhizoma Ligustici Chuanxiong powder, fructus Gardeniae powder, ramulus Mori powder, folium Nelumbinis powder, radix et rhizoma Rhei powder, sanguis Draxonis powder, saviae Miltiorrhizae radix powder, carthami flos powder, and folium Artemisiae Argyi powder.

In some specific embodiments, the traditional Chinese medicine composition is prepared from one or a combination of lycopodium clavatum extract, dipsacus root extract, olibanum extract, myrrh extract, ledebouriella root extract, notoginseng extract, turmeric extract, cinnamon extract, katsumade galangal extract, ligusticum chuanxiong extract, gardenia extract, mulberry twig extract, lotus leaf extract, rheum officinale extract, dragon's blood extract, red sage extract, safflower extract, mugwort leaf extract.

In some specific embodiments, the traditional Chinese medicine composition can be applied to sub-healthy people with physical discomfort caused by wind cold, stasis and damp evil, such as neck, shoulder, waist, leg, joints, tendons, muscles, and skeletal part ache, stiffness, numbness, stasis and blockage, microcirculation disturbance and weight abnormality.

In some specific embodiments, the amount of lycopodium clavatum in the compositions of the invention may be 10-50 parts by weight, for example 20-50 parts by weight, or 30-50 parts by weight, or 40-50 parts by weight, such as 45 parts by weight;

In some embodiments, the amount of teasel root in the compositions of the present invention may be from 10 to 50 parts by weight, or from 10 to 40 parts by weight, or from 20 to 40 parts by weight, or from 30 to 40 parts by weight, such as 35 parts by weight;

in some embodiments, the amount of mastic gum in the compositions of the invention may be from 5 to 30 parts by weight, or from 15 to 25 parts by weight, or from 18 to 23 parts by weight, such as 20 parts by weight;

In some embodiments, the amount of myrrh in the composition of the invention may be 5-30 parts by weight, or 15-30 parts by weight, or 20-30 parts by weight, or 22-28 parts by weight, such as 25 parts by weight;

In some embodiments, the amount of wind-resistant in the compositions of the present invention may be 10 to 20 parts by weight, or 12 to 20 parts by weight, or 15 to 20 parts by weight, or 10 to 15 parts by weight, such as 15 parts by weight;

In some embodiments, the amount of pseudo-ginseng in the compositions of the present invention may be 5 to 30 parts by weight, or 10 to 25 parts by weight, or 10 to 20 parts by weight, or 15 to 20 parts by weight, such as 18 parts by weight;

In some specific embodiments, the amount of turmeric in the compositions of the present invention may be 10-20 parts by weight, or 12-20 parts by weight, or 15-20 parts by weight, or 10-15 parts by weight, or such as 15 parts by weight;

in some embodiments, the amount of cinnamon in the compositions of the present invention may be 10 to 20 parts by weight, or 10 to 18 parts by weight, or 10 to 15 parts by weight, or 12 to 15 parts by weight, such as 12 parts by weight;

In some specific embodiments, the amount of Mujiang in the compositions of the present invention may be 10-20 parts by weight, or

10-18 Parts by weight, or 10-15 parts by weight, or 10-12 parts by weight, such as 10 parts by weight;

In some embodiments, the amount of Ligusticum wallichii in the compositions of the present invention may be 5-30 parts by weight, or 15-30 parts by weight, or 20-25 parts by weight, such as 23 parts by weight;

in some embodiments, the amount of cape jasmine in the compositions of the present invention may be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 12-15 parts by weight, such as 12 parts by weight;

in some specific embodiments, the amount of ramulus Mori in the compositions of the present invention may be 1-10 parts by weight, or 1-8 parts by weight, or 3-5 parts by weight, such as 5 parts by weight;

In some embodiments, the amount of lotus leaf in the compositions of the present invention may be 1 to 10 parts by weight, or 3 to 10 parts by weight, or 5 to 10 parts by weight, or 8 to 10 parts by weight, such as 8 parts by weight;

In some specific embodiments, the amount of rhubarb in the compositions of the present invention may be from 10 to 20 parts by weight, or from 10 to 18 parts by weight, or from 10 to 15 parts by weight, or from 15 to 20 parts by weight, such as 15 parts by weight;

in some embodiments, the amount of sanguis Draxonis in the compositions of the present invention may be 10-20 parts by weight, or 10-18 parts by weight, or 10-15 parts by weight, or 10-12 parts by weight, such as 10 parts by weight;

In some embodiments, the amount of Salvia Miltiorrhiza in the composition of the present invention may be 5-30 parts by weight, or 15-30 parts by weight, or 20-30 parts by weight, or 23-28 parts by weight, such as 25 parts by weight;

in some specific embodiments, the amount of safflower in the compositions of the present invention may be from 5 to 30 parts by weight, or from 15 to 25 parts by weight, or from 18 to 22 parts by weight, such as 20 parts by weight.

It is understood by those skilled in the art that "parts by weight" of each of the Chinese medicinal materials means the ratio relationship of the amounts of the Chinese medicinal materials, and not the actual mass unit. The unit weight part may be any mass, for example, 1 part by weight may be 1g, 500g or 1kg, and may even be 15g, 30g, etc., according to actual circumstances.

In a second aspect, the invention provides an external preparation which is characterized by comprising the composition and pharmaceutically acceptable auxiliary materials in the field, wherein the addition amount of the composition is 5-30% of the total mass.

In some specific embodiments, the addition amount of the composition may be selected to be 5%, 10%, 15%, 20%, 25%, 30% relative to the total weight of the medicament, and other specific values within the numerical range may be selected, which will not be described in detail herein;

It is well understood by those skilled in the art that such pharmaceutically acceptable excipients are generally recognized for this purpose and as inactive ingredients of the medicament.

The auxiliary materials comprise solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integration agents, permeation promoters, pH value regulators, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, inclusion agents, moisturizers, absorbents, diluents, flocculating agents and deflocculants, filter aids, and release retarders.

Wherein the diluent can be one or more of mannitol, sucrose, lactose, sorbitol, xylitol, polyethylene glycol, propylene glycol, vegetable oil and mineral oil; the disintegrating agent can be one or more of croscarmellose sodium, colloidal silicon dioxide and citric acid; the binder can be one or more of starch slurry, ethanol, water and povidone alcohol solution, the preservative can be one or more of ethyl parahydroxybenzoate, propyl parahydroxybenzoate, sorbic acid, potassium sorbate, calcium propionate, sodium dehydroacetate, sodium diacetate and sodium lactate, the antioxidant can be one or more of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetate, dibutyl hydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid and sodium metabisulfite, the flavoring agent can be one or more of aspartame, sucrose, xylitol, stevioside, cyclamate, sorbitol, cocoa, pure vanilla, vanillin, ethyl vanillin, chocolate, malt and peppermint, the suspending agent can be one or more of xanthan gum, polyvinylpyrrolidone, sodium alginate, aluminum stearate and hydrogenated vegetable oil, and the emulsifying agent can be one or more of alkyl sulfate, soap, dodecyl benzene sulfonate, lactic acid ester and sulfosalt

One or more of sulfosuccinate, monoglyceride sulfonate, phosphate, siloxane and taurine salt.

The preparation of the invention is any one of ointment, cream, gel and patch.

In some specific embodiments, the preparation is a gel, and comprises the composition, a gel matrix, a humectant and a penetration enhancer, wherein the addition amount of the composition is 5-30% wt of the gel, the addition amount of the composition can be selected to be 5%, 10%, 15%, 20%, 25% and 30% relative to the total weight of the gel, and other specific point values in the numerical range can be selected, so that the details are not repeated;

The adding amount of the penetrating agent is 1-10% wt of the gel, the adding amount of the penetrating agent can be 1%, 3%, 5%, 7% and 10% relative to the total weight of the gel, and other specific point values in the numerical range can be selected, so that the detailed description is omitted;

In some examples of the embodiment, the gel is prepared by mixing the traditional Chinese medicine composition with a gel matrix, a humectant and a penetration enhancer, wherein the traditional Chinese medicine composition is a traditional Chinese medicine ethanol extract;

Wherein, neutralizing agent, perfume, penetration enhancer, antiseptic, antioxidant, crosslinking agent, and humectant can also be added into the gel.

The gel matrix is one or more selected from methylcellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose, sodium carboxymethyl cellulose, carbomer 940, gelatin and sodium alginate;

The humectant is one or more selected from glycerol, 1, 3-butanediol, propylene glycol, polyethylene glycol 300, polyethylene glycol 400 and sorbitol;

the penetration enhancer is one or more of borneol, blumea oil or peppermint oil;

In some specific embodiments, the preparation is a paste, and comprises the composition, an oil phase matrix, water, an emulsifying agent and a penetration enhancer, wherein the addition amount of the composition is 5-30% wt of the ointment, the addition amount of the composition can be selected to be 5%, 10%, 15%, 20%, 25% and 30% relative to the total weight of the ointment, and other specific point values in the numerical range can be selected and are not repeated herein;

the adding amount of the penetrating agent is 1-10% wt of the ointment, the adding amount of the penetrating agent can be 1%, 3%, 5%, 7% and 10% relative to the total weight of the ointment, and other specific point values in the numerical range can be selected, so that the detailed description is omitted;

In some examples of this embodiment, the paste is prepared by mixing the Chinese medicinal composition with an oil phase matrix, water, an emulsifier, and a penetration enhancer;

Wherein, the ointment can also be added with humectant, penetration enhancer, antiseptic and thickener.

The oil phase matrix is one or more selected from stearic acid, paraffin, beeswax, higher alcohol, liquid paraffin, vaseline or vegetable oil;

The emulsifier is preferably one or more of soaps, sodium laurylsulfate, fatty acid esters of polyalcohol (such as glyceryl monostearate), polysorbate, and polyethylene glycol ether;

the penetration enhancer is one or more of borneol, blumea oil or peppermint oil;

In some specific embodiments, the preparation is a patch, the patch comprises a backing, a paste layer and an anti-adhesive film, the paste layer comprises the composition, a cross-linking agent, a permeation enhancer, a plasticizer and a humectant, the addition amount of the composition is 5-30% wt of the paste layer, the addition amount of the composition can be selected to be 5%, 10%, 15%, 20%, 25% and 30% relative to the total weight of the paste layer, and other specific values in the numerical range can be selected and are not repeated here;

The adding amount of the penetrating agent is 1-10% wt of the paste layer, the adding amount of the penetrating agent can be 1%, 3%, 5%, 7% and 10% relative to the total weight of the paste layer, and other specific point values in the numerical range can be selected, so that the detailed description is omitted;

In some examples of the embodiment, the patch is prepared by uniformly mixing the traditional Chinese medicine composition, a cross-linking agent, a penetration enhancer, a plasticizer and a humectant, coating on a backing material to form a paste layer, and finally covering a protective film, wherein the addition amount of the traditional Chinese medicine composition is 5-30% by weight of the paste layer, the traditional Chinese medicine composition is a traditional Chinese medicine ethanol extract, and the penetration enhancer is one or more of borneol, blumea oil or peppermint oil.

Wherein, the ointment-containing layer can be added with a dissolution penetration enhancer, an antioxidant, a filler, a tackifier and other pharmaceutically acceptable excipients.

The cross-linking agent is one or more selected from the group consisting of a cycloaliphatic saturated hydrocarbon resin, a hydrogenated rosin glyceride and a terpene resin, and the plasticizer is one or more selected from the group consisting of liquid paraffin, ethyl oleate, triethyl citrate, diethyl phthalate, dimethyl phthalate and dibutyl phthalate;

The humectant is one or more selected from glycerol, 1, 3-butanediol, propylene glycol, polyethylene glycol 300, polyethylene glycol 400 and sorbitol;

The material of the pressure-sensitive adhesive is selected from ethylene/acrylic ester copolymer, polyisobutylene, polypentadiene, polyacrylate, silicone copolymer, styrene-isoprene-styrene triblock copolymer (SIS), ethylene-butadiene-styrene triblock copolymer (SBS), hydrogenated SBS (SEBS) and polyurethane;

the backing material is one or more selected from polyester, cotton, polyamide, polyolefin, polyurethane, silk and hemp;

the anti-sticking film material is selected from one or more of polyethylene, polypropylene, vinyl acetate, ethylene polymer and polyvinyl chloride.

It will be appreciated by those skilled in the art that the above formulations may be prepared according to methods known in the art,

Is formulated into a suitable administration form or dosage form for human use.

In addition, if necessary, colorants, preservatives, fragrances, flavoring agents, and the like may be added to the pharmaceutical preparation,

Sweeteners or other materials.

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. Test used

The agent or instrument is not manufacturer specific and is a conventional product commercially available.

EXAMPLE 1 Chinese medicinal extract

The traditional Chinese medicine composition comprises 48 parts of lycopodium clavatum, 35 parts of teasel root, 20 parts of frankincense, 22 parts of myrrh, 12 parts of divaricate saposhnikovia root, 18 parts of pseudo-ginseng, 20 parts of turmeric, 12 parts of cinnamon, 10 parts of rhizoma zingiberis, 20 parts of szechuan lovage rhizome, 12 parts of cape jasmine, 5 parts of mulberry twig, 8 parts of lotus leaf, 18 parts of rheum officinale, 13 parts of dragon's blood, 25 parts of red-rooted salvia root and 25 parts of safflower.

The preparation method comprises the following steps:

the preparation method comprises the steps of performing diacolation extraction by taking 50% ethanol as an extraction solvent, soaking a traditional Chinese medicine composition with 1-3 times of the solvent before extraction, performing extraction with 8-9 times of the solvent, controlling the flow rate of diacolation extraction to be 4-5 ml/min, obtaining an extraction liquid after extraction is completed, and performing reduced pressure rotary evaporation on the decoction by a rotary evaporator to obtain an extract.

EXAMPLE 2 Chinese medicinal extract

The traditional Chinese medicine composition comprises the following raw materials of 50 parts of lycopodium clavatum, 35 parts of teasel root, 18 parts of frankincense, 25 parts of myrrh, 12 parts of divaricate saposhnikovia root, 18 parts of pseudo-ginseng, 15 parts of turmeric, 15 parts of cinnamon, 15 parts of rhizoma zingiberis, 30 parts of szechuan lovage rhizome, 12 parts of cape jasmine fruit, 5 parts of mulberry twig, 10 parts of lotus leaf, 20 parts of rheum officinale, 10 parts of dragon's blood, 25 parts of red-rooted salvia root and 20 parts of safflower.

The preparation method is the same as in example 1.

EXAMPLE 3 Chinese medicinal extractum

The traditional Chinese medicine composition comprises the following raw materials of 45 parts of lycopodium clavatum, 40 parts of teasel root, 23 parts of frankincense, 28 parts of myrrh, 15 parts of divaricate saposhnikovia root, 20 parts of pseudo-ginseng, 18 parts of turmeric, 12 parts of cinnamon, 12 parts of rhizoma zingiberis, 23 parts of szechuan lovage rhizome, 10 parts of cape jasmine fruit, 8 parts of mulberry twig, 5 parts of lotus leaf, 15 parts of rheum officinale, 15 parts of dragon's blood, 25 parts of red-rooted salvia root and 18 parts of safflower.

The preparation method is the same as in example 1.

EXAMPLE 4 Chinese medicinal extractum

The traditional Chinese medicine composition comprises the following raw materials of 40 parts of lycopodium clavatum, 30 parts of teasel root, 22 parts of frankincense, 25 parts of myrrh, 15 parts of divaricate saposhnikovia root, 10 parts of pseudo-ginseng, 15 parts of turmeric, 15 parts of cinnamon, 12 parts of rhizoma zingiberis, 23 parts of szechuan lovage rhizome, 15 parts of cape jasmine fruit, 3 parts of mulberry twig, 10 parts of lotus leaf, 15 parts of rheum officinale, 10 parts of dragon's blood, 28 parts of red-rooted salvia root and 20 parts of safflower.

The preparation method is the same as in example 1.

EXAMPLE 5 traditional Chinese medicine pressure-sensitive Patch

Taking 10 parts of polyisobutylene, 35 parts of liquid paraffin, 28 parts of styrene-isoprene-styrene segmented copolymer and 20 parts of terpene resin, heating and stirring uniformly, adding 5 parts of glycerin, 14 parts of extractum (example 1), 1 part of borneol, 3 parts of blumea oil and 3 parts of peppermint oil under heat preservation, mixing and stirring, cooling to prepare a patch paste, coating the paste on a backing material, covering an anti-sticking film, and preparing the patch.

EXAMPLE 6 Chinese medicinal pressure sensitive Patch

Mixing 10 parts of polyisobutylene, 30 parts of liquid paraffin, 25 parts of styrene-isoprene-styrene segmented copolymer and 25 parts of hydrogenated rosin glyceride, stirring uniformly under heating, adding 5 parts of propylene glycol, 15 parts of extract (example 3), 0.5 part of borneol, 1.5 parts of blumea oil and 3 parts of peppermint oil under heat preservation, stirring, cooling to obtain a patch paste, coating the paste on a backing material, covering a release film, and preparing the patch.

EXAMPLE 7 Chinese medicinal ointment

Heating 40 parts of white vaseline, 30 parts of glyceryl monostearate and 15 parts of hardened castor oil at 80 ℃ to melt, preserving heat for later use, dissolving 10 parts of extract (example 2) with a proper amount of propylene glycol, adding 1 part of borneol, 1 part of blumea oil and 2 parts of peppermint oil into the mixture, stirring uniformly, and cooling.

EXAMPLE 8 traditional Chinese medicine gel

Adding 15 parts of carbomer 940 into part of purified water, stirring and dissolving at room temperature, heating to 70-90 ℃, adding 80 parts of propylene glycol, 5 parts of dibutyl hydroxy toluene, 20 parts of diisopropyl adipate and 3 parts of benzyl alcohol, stirring evenly, dissolving 12 parts of extract (example 4) with ethanol, stirring with 1 part of borneol, 2 parts of blumea oil and 1 part of peppermint oil until the extract is completely dissolved, cooling to 40-60 ℃, supplementing the rest of water, regulating the pH to about 5.5, stirring fully until the extract is completely dissolved, and cooling to obtain the finished product.

The composition of the present invention was subjected to efficacy verification.

(1) Investigation of the therapeutic Effect of the Chinese medicinal patch on type II collagen-induced arthritis rats

Experimental animals male Wistar rats, weight 120+ -10 g. Rats are fed in special IVC cages, the feeding environment temperature is 24-26 ℃, the humidity is 40-60%, the lighting time is 12h (8:00-20:00), normal SPF-grade feed and sterile water are given to the rats, padding and sterilizing cages are replaced regularly, and experiments are carried out after 7 days of adaptive feeding. Male Wistar rats were randomly assigned to 8 groups of blank (CON), model (MOD), high dose (GP-1-H) of example 5, medium dose (GP-1-M) of example 5, low dose (GP-1-L) of example 5, and high dose (GP-3-H) of example 6.

GP-1-L group, 2cm×2cm patch (administration amount 200 mg/kg);

GP-1-M group, 2cm×2cm patch (administration amount 400 mg/kg);

GP-1-H group, 2cm×2cm patch (dosage 800 mg/kg);

GP-3-H group, 2cm×2cm patch (dosage 800 mg/kg) was given.

Experimental drug is prepared by dissolving bovine type II collagen in 0.1mol/L acetic acid at concentration of 10mg/mL at 4deg.C

Stirring to dissolve thoroughly, standing overnight at 4deg.C, heating autoclaved liquid paraffin to 70deg.C, adding inactivated attenuated BCG vaccine into liquid paraffin at concentration of 10mg/mL, and grinding to dissolve completely to obtain adjuvant.

The experimental method comprises the steps of adopting bovine type II collagen to perform injection in the foot plantar pad skin of the right hind foot of a rat, and performing modeling on the rat with rheumatoid arthritis, wherein the method comprises the steps of mixing bovine type II collagen acetic acid solution with the concentration of 10mg/mL with a complete adjuvant in an equal volume, emulsifying to obtain a suspension, injecting the foot plantar pad of the right hind foot of each experimental group of the rat in the skin with the injection amount of 0.1mL for 7 days, and performing reinforced injection in the root of the rat tail once, wherein a blank group is injected with 0.1mL of autoclaved liquid paraffin. The traditional Chinese medicine patch is stuck to the right rear sole and joints of the rat 4 hours after the injection of the bovine type II collagen, a blank patch is used for a model group, and the blank group is normally fed. The administration was continued for 10 days 1 time per day. The left hind foot joint swelling rate and the suppression rate of the rat foot joint swelling were calculated, and the results are shown in table 1.

The left hind foot joint swelling ratio (%) = (post-inflammatory joint volume-pre-inflammatory joint volume)/pre-inflammatory joint volume×100% of the rat, and the foot joint swelling inhibition ratio (%) = (model group foot joint volume-experimental group foot joint volume)/model group foot joint volume×100% of the rat.

Statistical analysis data processing was performed using spss software, experimental data were expressed as mean ± standard deviation, P <0.05 was statistically different, and P <0.01 was statistically significant.

Experimental results show that after the administration of bovine type II collagen, the foot joint volume of rats in the model group is obviously increased (P < 0.01) compared with that of rats in the blank group, and compared with the model group, the degree of swelling of the right foot joint of rats in each group is obviously reduced (P < 0.01) after the administration of the medicament. The sequence of the swelling inhibition rate of each group of rats is GP-1-H > GP-3-H > GP-1-M > GP-1-L.

(2) Skin irritation test

The method comprises the steps of taking a plurality of rabbits for test, dehairing the breast parts on two sides of the chest of the animal by using 8% sodium sulfide solution 24 hours before administration, dividing the animal into a complete skin group and a broken skin group after dehairing, dividing the skin of the dehaired area into a groined break before administration, keeping the skin damage degree on the left side and the right side consistent by using the depth of the broken skin group based on blood seepage, comparing the left side and the right side of the dehaired area (medicament-coated area) with the traditional Chinese medicine patch of the embodiment 1 by using the self on the left side of the same body, feeding the right side of the dehaired area with a blank matrix cataplasm, sealing and fixing by using a tape after gauze covering, feeding by a separate cage for 24 hours, removing medicaments, observing whether red spots and edema appear on the administration parts after removing medicaments for 1 hour, 24 hours, 48 hours and 72 hours respectively, and recovering the change conditions and time, wherein the results show that the red spots and the edema do not appear in the left side and the right side of the administration area of all rabbits for test in the observation time.

(3) Drug screening experiments

The experimental method comprises the steps of selecting patients diagnosed as rheumatic arthritis patients by traditional Chinese medicine, wherein the average age is 56.2+/-2.7 years, the average course of disease is about 3.9+/-1.8 years, 30 cases are taken as each group, the diagnosis standard is ① joint swelling and pain, limb spasm, obvious aversion to cold and limb coldness, severe pain when cold occurs, ② symptoms are aggravated when people feel overcast and rainy days, strong wind, coldness, illness aggravated, ③, dark red tongue with blood stasis points, white and greasy tongue coating or yellow and white alternate pulse with floating or wiry pulse, and 1-3 cases can be distinguished as (yang deficiency and cold and dampness stagnation) excess symptoms.

Based on the traditional Chinese medicine composition of the example 1, a traditional Chinese medicine patch prepared from a plurality of traditional Chinese medicines or penetrating agents is selected as a tested object and is applied to an affected part 1 time a day for 28 days.

The first group comprises monarch drug and ministerial drug (herba Lycopodii, olibanum, myrrha, rhizoma Ligustici Chuanxiong, saviae Miltiorrhizae radix, carthami flos and Notoginseng radix);

the second group comprises monarch drug and ministerial drug (radix dipsaci, frankincense, myrrh, szechuan lovage rhizome, red sage root, safflower and pseudo-ginseng);

The third group is monarch drug and ministerial drug (lycopodium clavatum, teasel root, frankincense and myrrh);

a fourth group of monarch drug + ministerial drug (lycopodium clavatum + teasel root + ligusticum wallichii);

a fifth group of monarch drug and ministerial drug (lycopodium clavatum, teasel root, red sage root, safflower and pseudo-ginseng);

a sixth group of monarch drug and adjuvant drug (herba Lycopodii, radix Dipsaci, radix Saposhnikoviae, cortex Cinnamomi, rhizoma Curcumae Longae, radix et rhizoma Rhei and fructus Gardeniae);

Seventh group, monarch drug + leading menstruation drug (lycopodium clavatum + teasel root + mulberry twig + lotus leaf)

Eighth group, example 1 Chinese medicinal composition+borneol

Ninth group, example 1 Chinese medicinal composition+blumea oil+peppermint oil

Tenth group, example 1 Chinese medicinal composition+azone

Eleventh group, example 1

The clinical curative effect judging standard is that the clinical symptoms of the joint morning stiffness, pain, tenderness and the like of the patient are obviously improved after the treatment, the clinical symptoms of the joint morning stiffness, pain, tenderness and the like of the patient are effectively improved, and the clinical symptoms of the joint morning stiffness, pain, tenderness and the like of the patient are not improved. Total effective rate (%) =apparent rate (%) +effective rate (%). The results are shown in Table 2.

It can be seen that the medicines have synergistic effect, common clubmoss herb or teasel root with the effects of dispelling wind and cold are used as monarch medicines, ministerial medicines and adjuvant medicines, the medicine effect is obviously weakened, the effects of strengthening the body resistance and dispelling pathogenic factors can be achieved only by combining kidney yang with wind and dampness dispelling medicines, the monarch medicines have the most obvious effect, the ministerial medicines are secondarily used, the adjuvant effects are the weakest, and the whole formula has the effects of warming the kidney and dispelling cold, eliminating dampness and dredging collaterals, and removing blood stasis and relieving pain to be optimal.

The traditional Chinese medicine patch has the maximum relative bioavailability of percutaneous absorption compared with the eighth group and the ninth group, and the traditional Chinese medicine patch prepared by adopting azone as a penetrating agent in the tenth group has the same curative effect as the traditional Chinese medicine patch prepared by adopting borneol as the penetrating agent, and the chemical penetrating agent (azone) has the same penetrating effect as the traditional Chinese medicine composition prepared by adopting borneol as the penetrating agent.

Finally, it should be noted that the above description is only a preferred embodiment of the present invention, and that many similar changes can be made by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (10)

1. A traditional Chinese medicine composition for promoting blood circulation and removing blood stasis, characterized in that it is composed of the following raw materials: *Lycopodium clavatum*, *Dipsacus asper*, frankincense, myrrh, *Saposhnikovia divaricata*, *Panax notoginseng*, turmeric, cinnamon, *Ligusticum striatum*, *Ligusticum chuanxiong*, gardenia, mulberry twig, lotus leaf, rhubarb, dragon's blood, salvia miltiorrhiza, and safflower. 2. The traditional Chinese medicine composition according to claim 1, characterized in that, by weight, the raw material composition is: 10-50 parts, or 20-50 parts, or 30-50 parts, or 40-50 parts, such as 45 parts of *Lycopodium clavatum*; and, Dipsacus asperoides, in doses of 10-50, 10-40, 20-40, or 30-40, such as 35 doses; and, Frankincense 5-30 parts, or 15-30 parts, or 15-25 parts, or 18-23 parts, such as 20 parts; and, Myrrh: 5-30 parts, or 15-30 parts, or 20-30 parts, or 22-28 parts, such as 25 parts; and, Windproofing: 10-20 parts, or 12-20 parts, or 15-20 parts, or 10-15 parts, such as 15 parts; and, Panax notoginseng 5-30 parts, or 10-25 parts, or 10-20 parts, or 15-20 parts, such as 18 parts; and, Turmeric 10-20 parts, or 12-20 parts, or 15-20 parts, or 10-15 parts, such as 15 parts; and, Cinnamon 10-20 parts, or 10-18 parts, or 10-15 parts, or 12-15 parts, such as 12 parts; and, Litsea cubeba 10-20 parts, or 10-18 parts, or 10-15 parts, or 10-12 parts, such as 10 parts; and, Chuanxiong (Ligusticum striatum) in doses of 5-30 parts, or 15-30 parts, or 20-30 parts, or 20-25 parts, such as 23 parts; and, Gardenia fruit, 10-20 parts, or 10-18 parts, or 10-15 parts, or 12-15 parts, such as 12 parts; and, Mulberry branches, 1-10 parts, or 1-8 parts, or 3-8 parts, or 3-5 parts, such as 5 parts; and, Lotus leaves, 1-10 parts, or 3-10 parts, or 5-10 parts, or 8-10 parts, such as 8 parts; and, Rhubarb, 10-20 parts, or 10-18 parts, or 10-15 parts, or 15-20 parts, such as 15 parts; and, Dragon's blood, 10-20 parts, or 10-18 parts, or 10-15 parts, or 10-12 parts, such as 10 parts; and, Salvia miltiorrhiza, 5-30 parts, or 15-30 parts, or 20-30 parts, or 23-28 parts, such as 25 parts; and, Safflower 5-30 parts, or 15-30 parts, or 15-25 parts, or 18-22 parts, such as 20 parts. 3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that: the *Lycopodium clavatum* comprises one or a combination of *Lycopodium clavatum* powder, *Lycopodium clavatum* extract, and/or the *Dipsacus asper* comprises one or a combination of *Dipsacus asper* powder, *Dipsacus asper* extract, and/or the frankincense comprises one or a combination of frankincense powder, frankincense extract, and/or the myrrh comprises one or a combination of myrrh powder, myrrh extract, and/or the saposhnikovia divaricata comprises one or a combination of saposhnikovia divaricata extract, and/or the notoginseng comprises one or a combination of notoginseng powder, notoginseng extract, and/or the turmeric comprises one or a combination of turmeric powder, turmeric extract, and/or the cinnamon comprises one or a combination of cinnamon powder, cinnamon extract, and/or the litsea cubeba comprises litsea cubeba powder, litsea cubeba extract, and litsea cubeba extract. The ingredients include one or a combination thereof; and/or, the Ligusticum chuanxiong includes one or a combination thereof of Ligusticum chuanxiong powder and Ligusticum chuanxiong extract; and/or, the Gardenia jasminoides includes one or a combination thereof of Gardenia jasminoides powder and Gardenia jasminoides extract; and/or, the Mulberry twig includes one or a combination thereof of Mulberry twig powder and Mulberry twig extract; and/or, the Lotus leaf includes one or a combination thereof of Lotus leaf powder and Lotus leaf extract; and/or, the Rhubarb includes one or a combination thereof of Rhubarb powder and Rhubarb extract; and/or, the Dragon's Blood includes one or a combination thereof of Dragon's Blood powder and Dragon's Blood extract; and/or, the Salvia miltiorrhiza includes one or a combination thereof of Salvia miltiorrhiza powder and Salvia miltiorrhiza extract; and/or, the Safflower includes one or a combination thereof of Safflower powder and Safflower extract; and/or, the Artemisia argyi includes one or a combination thereof of Artemisia argyi powder and Artemisia argyi extract. 4. The use of the traditional Chinese medicine composition according to claims 1-3 in the preparation of external medicines with the functions of dispelling wind and cold, promoting blood circulation and relieving pain, warming kidney yang, and strengthening tendons and bones. 5. A topical preparation, characterized in that it comprises the composition of claim 1 or 2 and pharmaceutical excipients acceptable in the art, wherein the amount of the composition added is 5-30% of the total mass. 6. The topical preparation according to claim 3, characterized in that the preparation is an ointment or cream. Any one of the following: agent, gel, patch. 7. The topical preparation according to claim 5, characterized in that the preparation is a gel, comprising the composition according to claim 1 or 2, a gel matrix, a humectant, and a penetration enhancer; the amount of the composition added is 5-30% wt of the gel. 8. The topical preparation according to claim 5, characterized in that the preparation is an ointment, comprising the composition according to claim 1 or 2, an oil phase matrix, water, an emulsifier, and a penetration enhancer; the amount of the composition added is 5-30% wt of the ointment. 9. The topical preparation according to claim 5, wherein the preparation is a patch, the patch comprising a backing, a paste layer and an anti-adhesive film; The ointment layer comprises the composition of claim 1 or 2, a crosslinking agent, a penetration enhancer, a plasticizer, and a humectant; the amount of the composition added is 5-30%wt of the ointment layer; The backing material is selected from one or more of polyester, cotton, polyamide, polyolefin, polyurethane, silk, and linen; The anti-sticking film material is selected from one or more of polyethylene, polypropylene, vinyl acetate and ethylene polymers, and polyvinyl chloride. 10. A method for preparing a topical traditional Chinese medicine preparation, characterized in that the traditional Chinese medicine composition according to any one of claims 1-3 is prepared into a conventional dosage form according to conventional methods in the art; When the conventional dosage form is a gel, the gel is prepared according to the following steps: the traditional Chinese medicine composition is mixed with a gel matrix, a moisturizer, and a penetration enhancer; the amount of the traditional Chinese medicine composition added is 5-30%wt of the gel, and the amount of the penetration enhancer added is 1-10%wt of the gel; the traditional Chinese medicine composition is an ethanol extract of traditional Chinese medicine; the penetration enhancer is one or more of borneol, artemisia oil, or peppermint oil; When the conventional formulation is an ointment, the ointment is prepared according to the following steps: the traditional Chinese medicine composition is mixed with an oil phase matrix, water, emulsifier, and penetration enhancer; the amount of the traditional Chinese medicine composition added is 5-30%wt of the ointment, and the amount of the penetration enhancer added is 1-10%wt of the ointment; the traditional Chinese medicine composition is an ethanol extract of traditional Chinese medicine; the penetration enhancer is one or more of borneol, artemisia oil, or peppermint oil; When the conventional preparation is a patch, the patch is prepared according to the following steps: the traditional Chinese medicine composition is mixed evenly with a crosslinking agent, a penetration enhancer, a plasticizer, and a moisturizer, coated onto a backing material to form a paste layer, and finally covered with a protective film; the amount of the traditional Chinese medicine composition added is 5-30%wt of the paste layer, and the amount of the penetration enhancer added is 1-10%wt of the paste layer; the traditional Chinese medicine composition is an ethanol extract of traditional Chinese medicine; the penetration enhancer is one or more of borneol, artemisia oil, or peppermint oil.