Tibetan medicine formula, Tibetan medicine emplastrum and preparation method thereof

Abstract

The invention relates to the technical field of Tibetan medicines, and discloses a Tibetan medicine formula, a Tibetan medicine emplastrum and a preparation method of the Tibetan medicine emplastrum. The formula comprises 30 to 50 parts of Tibetan cat milk, 30 to 50 parts of aconitum pendulum, 15 to 30 parts of acorus calamus, 8 to 15 parts of Muslim myrrh, 8 to 15 parts of frankincense, 8 to 15 parts of cassia seed, 8 to 15 parts of abelmoschus esculentus seed, 20 to 40 parts of myristica fragrans, 8 to 15 parts of delphinium delphinium, 30 to 50 parts of common vladimiria root and 30 to 50 parts of fructus chebulae, and an ointment-containing body layer of the emplastrum comprises the Tibetan medicine formula provided by the invention. The prescription provided by the invention is guided by a prescription solution of a Tibetan medicine classic famous prescription 'Ruyi treasure prescription', simplifies the medicinal composition, neutralizes the toxicity of medicinal materials, not only improves the safety, but also expands the range of indications and improves the curative effect, and the Tibetan medicine prescription external dosage form emplastrum provided by the invention has the characteristics of simplicity, portability, convenience in use, high patient compliance and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of Tibetan medicine, in particular to a Tibetan medicine prescription, a Tibetan medicine plaster and a preparation method thereof. BACKGROUND

[0002] Tibetan medicine is a traditional medicine developed by the Tibetan people in the special natural environment of the Qinghai-Tibet Plateau, relying on the unique "five sources and three causes" theoretical system. It has a history of more than 3800 years. Tibetan medicine is mainly composed of medicinal materials (plants, animals and minerals) unique to the Qinghai-Tibet Plateau. Under the guidance of the theory of "Four Medical Classics", it is made into a substance for preventing and treating diseases through traditional processing technology. Ruyi Zhenbao Prescription is a classic prescription of Tibetan medicine, which is the first choice for treating white vein disease in Tibetan medicine. It is currently included in "Ministry of Health of the People's Republic of China Drug Standards (Tibetan Medicine Volume)". According to records, the prescription has the effects of clearing heat, refreshing the brain and opening the orifices, relaxing the tendons and dredging the collaterals, and drying yellow water. It is used for treating pestilence, old heat, white vein disease, numbness of limbs, paralysis, facial asymmetry, confusion, arthralgia, gout, and limb stiffness. It has good effect on white vein disease. It shows therapeutic effect on a variety of diseases in clinical application, including cerebrovascular disease, nervous system disease (such as white vein disease), migraine, sciatica, trigeminal neuralgia, supraorbital neuralgia, diabetic neuropathy, retinal vein occlusion, acute and chronic contusion, motor system chronic disease, rheumatism and rheumatoid arthralgia, etc.

[0003] According to the literature of Tibetan medical classics, the mother prescription of Ruyi Zhenbao Prescription was first recorded in "Four Medical Classics". It is composed of pearl mother, mace, white mace, cardamom, safflower, clove, ox gall, sandalwood, eaglewood, rhinoceros horn, musk, costus, piper longum, cassia, acacia catechu, Terminalia chebula, Phyllanthus emblica, crab, sea gold sand, winter holly flower, cumin, black seed, short spike rabbit ear grass, etc. It is named Twenty-five Pearl Mother Powder. There are many medicinal ingredients in the prescription, and the combined use of each medicinal ingredient can harmonize the three causes, refresh the brain and open the orifices, dredge the collaterals, dry yellow water, clear old heat, and cure white vein disease.

[0004] At present, the main dosage form developed based on Ruyi Zhenbao Prescription is internal use powder or pill, and there is no related report on external use dosage form. Compared with internal use dosage form, the core advantage of external use dosage form of traditional Chinese medicine is strong targeting, small side effects and high compliance, which is particularly outstanding in the treatment of specific diseases and patient compliance. Ruyi Zhenbao Prescription has remarkable curative effect on trigeminal neuralgia, sciatica, multiple neuritis, arthritis, acute and chronic contusion, gout and diabetic peripheral neuritis, etc. Therefore, it is necessary to develop the external use dosage form of Ruyi Zhenbao Prescription. SUMMARY

[0005] Therefore, the present application aims to provide a Tibetan medicine formula, a Tibetan medicine plaster and a preparation method thereof.

[0006] In order to achieve the above technical effects, the present application adopts the following technical solutions:

[0007] In a first aspect, the present application provides a Tibetan medicine formula, which comprises raw medicinal materials in the following proportions: 30-50 parts of Tibetan cat milk, 30-50 parts of iron club hammer, 15-30 parts of Tibetan aconite, 8-15 parts of Mukul myrrh, 8-15 parts of frankincense, 8-15 parts of cassia seed, 8-15 parts of yellow crowfoot, 20-40 parts of mace, 8-15 parts of yellow hair delphinium, 30-50 parts of Sichuan costus, and 30-50 parts of Terminalia chebula.

[0008] Further, the preferred scheme of the Tibetan medicine formula comprises raw medicinal materials in the following proportions: 40 parts of Tibetan cat milk, 40 parts of iron club hammer, 20 parts of Tibetan aconite, 10 parts of Mukul myrrh, 10 parts of frankincense, 10 parts of cassia seed, 10 parts of yellow crowfoot, 30 parts of mace, 10 parts of yellow hair delphinium, 40 parts of Sichuan costus, and 40 parts of Terminalia chebula.

[0009] According to Tibetan medicine, the occurrence of diseases is caused by the imbalance of three factors, i.e., "lung" (wind / nerve), "chiba" (gallbladder / fire / heat), and "peigen" (saliva / water / earth). The formula of the present application restores the balance of the three factors by dispelling wind, removing dampness, promoting blood circulation, detoxifying, and regulating qi and blood. In the formula, the iron club hammer and the Tibetan cat milk are the monarch drugs, the iron club hammer has the effects of dispelling wind and removing dampness, promoting blood circulation and relieving pain, removing blood stasis and swelling, killing insects and detoxifying, the Tibetan cat milk has the effects of clearing heat and detoxifying, dispelling wind and removing dampness, promoting blood circulation and relieving pain, and strengthening bones, and can neutralize the intense nature of the iron club hammer and nourish the damaged "white vein" (nerve and bone). The Sichuan costus, the Terminalia chebula, the Tibetan aconite, and the mace are the minister drugs, the Sichuan costus has the effect of regulating qi and relieving pain, the Terminalia chebula has the effects of regulating the three factors, detoxifying, and balancing the overall drug nature, the Tibetan aconite has the effects of promoting blood circulation, relieving pain, and reducing inflammation, and the mace has the effect of promoting blood circulation and dredging collaterals, and the four drugs assist the monarch drug and enhance the main effect. The Mukul myrrh, the frankincense, the yellow hair delphinium, the cassia seed, and the yellow crowfoot are the auxiliary drugs, which assist the monarch and the minister and eliminate the accompanying symptoms. The Terminalia chebula and the Tibetan aconite are the minister drugs, which regulate the drugs and guide the drugs to the meridians. In the formula, the iron club hammer and the Tibetan cat milk are the monarch drugs, the Sichuan costus, the Terminalia chebula, the Tibetan aconite, and the mace are the minister drugs, the Mukul myrrh, the frankincense, the yellow hair delphinium, the cassia seed, and the yellow crowfoot are the auxiliary drugs, and the Terminalia chebula and the Tibetan aconite are the minister drugs, which together have the effects of dispelling wind and removing dampness, promoting blood circulation and dredging collaterals, relieving swelling and pain, detoxifying and removing blood stasis, and drying yellow water.

[0010] In a second aspect, the present application provides the use of the Tibetan medicine composition in the preparation of a medicament for treating neuropathic pain, rheumatism and rheumatoid arthritis, vasculitis, eczema, and contusion.

[0011] In a third aspect, the present application provides a Tibetan medicine plaster, comprising a backing layer, a drug-containing ointment layer, and an anti-adhesion layer, wherein the drug-containing ointment layer is composed of an effective component and a matrix carrying the effective component, and the effective component is the Tibetan medicine composition provided by the present application, and the matrix is a mixture of beeswax and vegetable oil. The Tibetan medicine plaster is an innovative form of external use of traditional Chinese medicine, which combines the convenience of a patch and the high drug loading characteristics of an ointment.

[0012] In a fourth aspect, the present application provides a preparation method of the Tibetan medicine plaster, comprising the following steps:

[0013] Step 1: According to the weight ratio of each raw material in the above-mentioned Tibetan medicine composition, each raw material is weighed and pretreated to a decocting form. The treated raw materials, Tibetan cat milk, iron club hammer, Tibetan aconite, Sichuan costus, Terminalia chebula, nutmeg, Cassia seed, and Abelmoschus esculentus are mixed to obtain a mixed medicine. The mixed medicine is added to vegetable oil (such as sesame oil, rapeseed oil, camellia oil, etc.) and decocted at 100-130℃ for 1.5-2.5 hours. The amount of vegetable oil is 3-5 times the weight of the mixed medicine. 15-30 minutes before the decoction is completed, raw materials of Mukul myrrh and frankincense are added, and then the decoction is continued for 15-30 minutes. After filtering the residue, a medicinal oil is obtained.

[0014] Step 2: Add beeswax to the medicinal oil of step 1 and heat it until the beeswax melts and mixes evenly with the medicinal oil to obtain a drug-containing ointment. The amount of beeswax added is 1 / 4 to 1 / 3 of the mass of the medicinal oil.

[0015] Step 3: The drug-containing ointment of step 2 is coated on the backing layer (non-woven fabric, elastic cloth, etc.) to obtain a drug-containing ointment layer. An anti-adhesion layer (silicone oil paper) is covered on the surface of the drug-containing ointment layer to obtain the Tibetan medicine plaster.

[0016] Further, the decocting forms of each raw material are as follows: the raw materials of Tibetan cat milk, iron club hammer, Tibetan aconite, Sichuan costus, Terminalia chebula, and nutmeg are powders passing through a 20-40 mesh sieve, the raw material of yellow hair delphinium is small pieces of 5-10 cm, and the raw materials of Cassia seed, Abelmoschus esculentus, Mukul myrrh, and frankincense are not treated and kept in their original form. By pretreating the raw materials to a decocting form, the dissolution efficiency of the effective components in each raw material is improved, and the decoction time is saved.

[0017] Further, the thickness of the drug-containing ointment layer is 0.5-2 mm.

[0018] The preparation method provided by the present application reduces the high-temperature decomposition of active ingredients (such as polysaccharides in Tibetan cat milk, aconitine in iron club, volatile oil in resinous medicinal materials, etc.) by low-temperature decoction and segmented feeding, while ensuring the dissolution of effective components. The retention rate of aconitine in the medicine-containing paste prepared by the method of the present application is 92% by high performance liquid chromatography detection; the retention rate of polysaccharides is 88.5% by phenol-sulfuric acid detection; and the retention rate of volatile oil is 94.2% by the determination method of volatile oil in the fourth part of Chinese Pharmacopoeia (2020 edition).

[0019] The effective components of the prescription provided by the present application contain fat-soluble ingredients. The present application can improve the release of ingredients in raw medicinal materials by selecting a complex matrix of beeswax-plant oil as a matrix for carrying effective components, and the ductility of the paste is also optimized. The volatile oil components of Acorus calamus in the prescription of the present application are natural penetration enhancers. By reasonably proportioning Acorus calamus, the prescription can not only blend various drugs, but also improve the transdermal absorption rate of the plaster and enhance the therapeutic effect.

[0020] Compared with the prior art, the present application has the following beneficial effects:

[0021] (1) Scientific compatibility reduces toxicity and significantly improves drug safety;

[0022] The prescription of the present application uses a pure plant formula and does not contain mineral drugs, avoiding the risk of heavy metals. In the prescription of the present application, iron club is used in combination with Tibetan cat milk. Tibetan cat milk can neutralize the toxicity of iron club and reduce skin allergic reactions. Compared with the plaster of the comparative example without Tibetan cat milk, the clinical test shows that the irritability is reduced by 60%. In the prescription of the present application, the tannins contained in Terminalia chebula combine with the alkaloids of iron club to form a low-toxicity complex, which can reduce the toxicity of iron club and greatly improve the safety of the drug.

[0023] (2) Multi-target treatment, wide indications;

[0024] In addition to being suitable for the treatment of white vein disease, the present application also has significant effects on rheumatism and rheumatoid arthritis, vasculitis, eczema, and contusion. In the prescription of the present application, “iron club + Chuanmuhong” expels wind and relieves pain, and “musk + myrrh” promotes blood circulation and unblocks collaterals, which can quickly relieve joint swelling and pain. “Huangmao Cuiquehua + Acorus calamus” disperses blood stasis and reduces swelling, which can accelerate tissue repair and is beneficial to the treatment of contusion.

[0025] (3) Fewer medicinal ingredients, lower drug cost, and easy quality control;

[0026] Compared with the prescription of the classic Tibetan medicine “Ruyi Zhenbao Prescription” which contains more than 25 medicinal ingredients, the prescription of the present application contains only 11 medicinal ingredients.

[0027] (4) The transdermal absorption rate of the plaster is high, the curative effect is strong, and side effects are few;

[0028] According to the Guiding Principle of Drug Transdermal Absorption Experiment Technology, the cumulative penetration amount of the plaster is (15.3±1.8) μg / cm 2 in 24 hours, which is 210% higher than the average cumulative penetration amount (4.9±0.7) μg / cm 2 of a commercially available rheumatism plaster product (Wushufang Rheumatism Pain Plaster, Chongqing Hillan Pharmaceutical Co., Ltd.).

[0029] No serious allergic reaction is found in clinical application, and the skin tolerance is good.

[0030] (5) The plaster has a long shelf life, and the preparation method is simple, which is conducive to standardized production.

[0031] According to the accelerated stability test (40±2℃, RH 75±5%, 6 months) and HPLC and GC content determination, the retention rate of the main active ingredients (aconitine, commiphora acid, olibanum acid and aconitum volatile oil) of the plaster is >90% after 12 months of simulated normal temperature preservation, and the plaster has a long shelf life; by controlling the addition amount and boiling temperature of the vegetable oil, it is ensured that the effective components are fully dissolved in a short time; by controlling the addition amount of beeswax, the hardness of the plaster body is controlled, and the stability of the plaster is ensured.

[0032] (6) The clinical verification effect is remarkable.

[0033] According to the feedback of patients, the plaster can obviously relieve pain in 15-30 minutes, and the continuous action time is 12-24 hours; according to the clinical test, for the treatment of rheumatism and rheumatoid arthritis, the effective rate of the plaster reaches 95%, the effective rate of vasculitis treatment is 85%, the effective rate of eczema treatment is 85%, the effective rate of contusion treatment is 90%, and the effective rate of neuropathic pain treatment is 85%. DETAILED DESCRIPTION

[0034] The embodiments of the present application will be described in detail below with reference to the examples, but those skilled in the art will understand that the following examples are only used to illustrate the present application, and should not be regarded as limiting the scope of the present application. The specific conditions are not indicated in the examples, and the conventional conditions or the conditions recommended by the manufacturer are used. The reagents or instruments used are not indicated by the manufacturer, and are conventional products that can be purchased on the market.

[0035] According to the first aspect of the present application, the present application provides a Tibetan medicine formula, which comprises raw medicinal materials in the following proportions by weight: 30-50 parts of Tibetan cat milk, 30-50 parts of iron club hammer, 15-30 parts of Acorus calamus, 8-15 parts of Mukul myrrh, 8-15 parts of frankincense, 8-15 parts of Cassia seed, 8-15 parts of Speranskia tuberculata, 20-40 parts of mace, 8-15 parts of Delphinium brunonianum, 30-50 parts of Saussurea lappa, and 30-50 parts of Terminalia chebula.

[0036] Further, the preferred scheme of the Tibetan medicine formula comprises raw medicinal materials in the following proportions by weight: 40 parts of Tibetan cat milk, 40 parts of iron club hammer, 20 parts of Acorus calamus, 10 parts of Mukul myrrh, 10 parts of frankincense, 10 parts of Cassia seed, 10 parts of Speranskia tuberculata, 30 parts of mace, 10 parts of Delphinium brunonianum, 40 parts of Saussurea lappa, and 40 parts of Terminalia chebula.

[0037] The main effects of the present application formula are: expelling wind and dampness, promoting blood circulation to remove meridian obstruction, removing swelling and pain, removing blood stasis, drying “yellow water”, and regulating three factors “lung, red pa, and begon”.

[0038] Indications: rheumatism and rheumatoid arthritis, white vein disease, vasculitis, eczema, contusion and injury, blood stasis and swelling pain.

[0039] The present application formula restores the balance of three factors by expelling wind and dampness, promoting blood circulation, removing blood stasis, and regulating qi and blood, which is explained as follows:

[0040] (I) Monarch drug (mainly for the main disease)

[0041] 1. Iron club hammer

[0042] Nature and taste: sweet, slightly bitter, hot, and analgesic.

[0043] Effect: strong expelling wind and dampness, promoting blood circulation to stop pain, removing blood stasis and swelling, killing insects and removing toxins, which is the core drug for treating rheumatism and rheumatoid arthritis, contusion and injury, and sore and toxic swelling in Tibetan medicine.

[0044] For: “Begon” dampness, “Lung” qi stagnation, and “Yellow water” stasis.

[0045] 2. Tibetan cat milk

[0046] Nature and taste: flat (slightly warm), sweet, astringent, and bitter, and effect of tonifying, regulating, and removing toxins.

[0047] Effect: clearing heat and removing toxins, expelling wind and dampness, promoting blood circulation to stop pain, and strengthening bones, which can neutralize the strong nature of iron club hammer, and tonify the damaged “white vein” (nerves and bones).

[0048] For: “Lung” imbalance, “Red pa” heat and toxins, and “Yellow water” accumulation.

[0049] (II) Minister drug (auxiliary monarch drug, enhancing main effect)

[0050] 1. Qianghao

[0051] Property: warm, pungent, bitter, and effect of moving qi, warming middle, and relieving pain.

[0052] Effect: moving qi and blood, unblocking collaterals and relieving pain, especially good at unblocking qi stagnation in collaterals and enhancing the effect of relieving pain of Tiebangchui.

[0053] Target: qi stagnation and blood stasis (pain wandering).

[0054] 2. Haritaki

[0055] Property: flat, astringent, sour, and sweet, and effect of regulating, detoxifying, and astringing.

[0056] Effect: regulating various drugs, detoxifying Tiebangchui, astringing yellow water, and promoting wound healing, which is the "King of Medicine" in Tibetan medicine, and can prevent the over-intense drug properties and promote wound healing.

[0057] Target: yellow water exudation and sore not closing.

[0058] 3. Tibetan Acorus

[0059] Property: warm, pungent, bitter, and aromatic, and effect of opening orifices, eliminating dampness, and dispelling wind.

[0060] Effect: warming and unblocking collaterals, opening orifices and refreshing the mind, eliminating dampness and turbidity, and can guide drugs directly to the disease site, especially suitable for dampness and turbidity blocking collaterals.

[0061] Target: dampness and turbidity blocking collaterals.

[0062] 4. Nutmeg

[0063] Property: warm, pungent, and slightly bitter, and effect of warming middle, moving qi, and calming the mind.

[0064] Effect: warming and dispelling cold, moving qi and relieving pain, and calming the "Long" heart (nerves), suitable for cold-damp arthralgia and nerve pain caused by "Long" imbalance.

[0065] Target: "Long" cold and "Peiguan" dampness.

[0066] (Three) Auxiliary drugs (assist the monarch and minister, eliminate the symptoms)

[0067] 1. Mucur Myrrh and Frankincense

[0068] Property: Myrrh (flat, bitter, and pungent), and Frankincense (warm, pungent, and bitter).

[0069] Effect: promoting blood circulation and removing blood stasis, unblocking collaterals and relieving pain, and promoting muscle regeneration, which is a classic drug pair for external injuries, sores, and rheumatic pain.

[0070] Target: blood stasis and swelling, and unhealed sores.

[0071] 2. Delphinium brunonianum

[0072] Properties: Cool, bitter, pungent, clear heat, activate blood, detoxify.

[0073] Effect: Clearing heat and toxic of "Akba", activating blood and relieving pain, suitable for redness, heat and pain caused by heat and toxic.

[0074] Target: Heat and toxic of "Akba" (inflammation, pus).

[0075] 3. Cassia seed

[0076] Properties: Cold, sweet, bitter, salty, clear liver, softening, and benefiting "yellow water".

[0077] Effect: Softening and resolving, clearing and benefiting damp heat, helping to dissipate nodules and joint effusion.

[0078] Target: Accumulation of "yellow water" and joint swelling.

[0079] 4. Yellow lotus seed

[0080] Properties: Cold, slightly sweet and bland, clearing heat, benefiting dampness and pus.

[0081] Effect: Clearing and benefiting "yellow water" heat and toxic, reducing swelling and pus, suitable for eczema and sore with yellow water.

[0082] Target: "Yellow water" heat syndrome (damp heat type skin disease and joint swelling and pain).

[0083] (Four) Medicines (harmonize various drugs, guide drugs to the meridian)

[0084] 1. Terminalia chebula (already has the function of harmonizing)

[0085] 2. Acorus calamus (already has the function of guiding the meridian)

[0086] In summary, the composition of the present application has the following compatibility characteristics:

[0087] (1) Attack and tonification: iron hammer (attack evil) + Tibetan cat milk (tonify).

[0088] (2) Cold and warm: Delphinium brunonianum, Cassia seed (cold) + nutmeg, Chuanmuhuang (warm).

[0089] (3) Multi-target treatment:

[0090] Expelling wind and dampness (iron hammer, Acorus calamus, Chuanmuhuang); activating blood and relieving pain (Mukul myrrh, frankincense, Delphinium brunonianum); detoxifying and removing blood stasis (Terminalia chebula, Tibetan cat milk, Cassia seed); drying "yellow water" (yellow lotus seed, frankincense, Cassia seed).

[0091] (4) Toxicity control: Terminalia chebula resolves the toxicity of iron hammer, and Tibetan cat milk adjusts the nature of the medicine.

[0092] According to the second aspect of the present application, the present application provides the use of the above-mentioned Tibetan medicine composition in the preparation of a medicament for treating white vein disease, rheumatism and rheumatoid arthritis, vasculitis, eczema, and contusion.

[0093] According to the third aspect of the present application, the present application provides a Tibetan medicine plaster, which comprises a backing layer, a drug-containing ointment layer, and an anti-sticking layer, wherein the drug-containing ointment layer is composed of an effective component and a matrix carrying the effective component, the effective component is the Tibetan medicine composition provided by the present application, and the matrix is a mixture of beeswax and vegetable oil. The matrix serves as a carrier of the effective component and has the effects of enhancing penetration and moisturizing and promoting skin regeneration. The backing layer refers to a layer of material that can coat the drug-containing ointment, such as cloth, film, paper, etc. The anti-sticking layer refers to a layer of material that covers the surface of the drug-containing ointment layer to protect, prevent dust, and prevent sticking, such as silicone oil paper.

[0094] According to the fourth aspect of the present application, the present application provides a preparation method of a Tibetan medicine plaster, which comprises the following steps:

[0095] Step 1. According to the weight ratio of each raw material in the above-mentioned Tibetan medicine composition, each raw material is weighed and pretreated to a decocting form. Specifically, the raw materials Tibetan cat milk, iron club hammer, Tibetan aconite, Sichuan costus, Terminalia chebula, and mace are washed, crushed, and passed through a 20-40 mesh sieve. The raw material of yellow hair delphinium is cut into small pieces of 5-10 cm. The raw materials of cassia seed, yellow lotus seed, Mukul myrrh, and frankincense are not treated and kept in their original form. The treated raw materials Tibetan cat milk, iron club hammer, Tibetan aconite, Sichuan costus, Terminalia chebula, mace, cassia seed, and yellow lotus seed are mixed to obtain a mixed medicine. The mixed medicine is added to vegetable oil (such as sesame oil, rapeseed oil, camellia oil, etc.) and decocted at 100-130°C for 1.5-2.5 hours. The amount of vegetable oil is 3-5 times the weight of the mixed medicine. The raw materials Mukul myrrh and frankincense are added 15-30 minutes before the completion of decoction, and then the decoction is filtered after 15-30 minutes of further decoction to obtain a medicinal oil.

[0096] Step 2. Beeswax is added to the medicinal oil of step 1, and heated until the beeswax is melted and uniformly mixed with the medicinal oil to obtain a drug-containing ointment. The amount of beeswax added is 1 / 4 to 1 / 3 of the mass of the medicinal oil.

[0097] Step 3. The drug-containing ointment of step 2 is coated on the backing layer (non-woven fabric, elastic cloth, etc.) to obtain a drug-containing ointment layer. An anti-sticking layer (silicone oil paper) is covered on the surface of the drug-containing ointment layer to obtain the Tibetan medicine plaster.

[0098] The use method of the Tibetan medicine plaster of the present application is to apply the Tibetan medicine plaster to the corresponding acupoints, with each application lasting for 12-24 hours, and 7-14 days as a course of treatment. The Tibetan medicine plaster is continuously used, with the specification of each application being 5×14 cm, and the thickness of the drug-containing ointment layer being 0.5-2 mm.

[0099] To further illustrate the therapeutic effect of the plaster of the present application, the present application is described in detail below in combination with specific examples and comparative examples.

[0100] Example 1:

[0101] The raw medicinal materials are weighed as follows: 40 parts of Tibet cat milk, 40 parts of iron club, 20 parts of Acorus calamus, 10 parts of Mukul myrrh, 10 parts of frankincense, 10 parts of Cassia seed, 10 parts of Okra, 30 parts of nutmeg, 10 parts of yellow hair delphinium, 40 parts of wood of Sichuan, and 40 parts of Terminalia chebula.

[0102] The raw medicinal materials of Tibet cat milk, iron club, Acorus calamus, wood of Sichuan, Terminalia chebula, and nutmeg are crushed into coarse powder by a crusher or a mortar and passed through a 20-40 mesh sieve; Cassia seed and Okra are slightly crushed or kept intact; yellow hair delphinium is cut into 5-10 cm small pieces; Mukul myrrh and frankincense are kept in block or granular form.

[0103] First, the Tibet cat milk, iron club, Acorus calamus, wood of Sichuan, Terminalia chebula, nutmeg, Cassia seed, and Okra are mixed to obtain mixed medicine, 3 times the weight of sesame oil is poured into a sand pot, the mixed medicine is added, and the oil is heated on a low fire, keeping the oil temperature at 100-130°C (the oil surface is slightly boiling, with fine bubbles, and absolutely avoiding vigorous boiling, smoking, or burning), and the oil is boiled for 1.5-2.5 hours. During this period, the medicine needs to be stirred gently with a clean and dry wooden stick from time to time to prevent the medicine from sinking to the bottom and burning. The color of the medicine becomes dark and the texture becomes crisp (but not black).

[0104] When the boiling time is almost up (about 15-30 minutes left), add the granules of Mukul myrrh and frankincense. Continue to boil on a low fire for about 15-30 minutes until the Mukul myrrh and frankincense are completely melted and evenly dispersed in the oil.

[0105] Prepare a clean container and a fine filter screen or gauze (preferably multiple layers), and carefully pour the boiled medicine oil through the filter screen into the prepared container while it is hot. Squeeze the medicine residue in the filter screen hard to try to drain as much medicine oil as possible, and discard the medicine residue.

[0106] Pour the filtered pure medicine oil back into a clean pot (make sure there is no impurity and no water), heat the medicine oil again on a low fire, prepare beeswax, cut or shave the beeswax into fine shreds, and add it to the warm medicine oil in small amounts, continuously heat on a low fire and stir constantly until the beeswax is completely melted and evenly mixed with the medicine oil to obtain a medicine-containing paste.

[0107] The amount of beeswax is 1 / 4 to 1 / 3 of the mass of the filtered pure medicine oil, and the specific amount needs to be adjusted according to the season (less in winter and more in summer) and the desired hardness of the paste.

[0108] Test paste: Dip a small amount on a cold water or a cold plate with a pair of chopsticks or a glass rod, take it out after waiting for a few seconds to cool down, and pinch it with fingers to test its hardness and viscosity. The ideal state is that the paste is not sticky after cooling, has certain toughness, can be easily spread, but will not flow.

[0109] Adjustment: If the paste is too soft, continue to heat and add a small amount of beeswax; if it is too hard, you can add a small amount of hot medicinal oil (or clean vegetable oil) to dilute it.

[0110] After the paste reaches the desired consistency, turn off the heat. Cool it slightly (but still in liquid form, about 60-70°C), and while it is still hot, pour the plaster into a clean, dry, sealed container. Avoid overfilling. Let the plaster cool naturally in the container until it is completely solidified.

[0111] Take the solidified paste and spread it on a 5x14cm non-woven fabric with a thickness of 0.5-2mm, and then cover it with a layer of silicone oil paper to obtain a plaster.

[0112] Example 2:

[0113] The same as Example 1, except that the weight composition of raw materials is: 30 parts of Tibetan cat milk, 30 parts of iron club, 15 parts of Acorus calamus, 8 parts of Mukul myrrh, 8 parts of frankincense, 8 parts of Cassia seed, 8 parts of Okra seed, 20 parts of nutmeg, 8 parts of yellow hair delphinium, 30 parts of costus, and 30 parts of Terminalia chebula.

[0114] Example 3:

[0115] The same as Example 1, except that the weight composition of raw materials is: 50 parts of Tibetan cat milk, 50 parts of iron club, 30 parts of Acorus calamus, 15 parts of Mukul myrrh, 15 parts of frankincense, 15 parts of Cassia seed, 15 parts of Okra seed, 40 parts of nutmeg, 15 parts of yellow hair delphinium, 50 parts of costus, and 50 parts of Terminalia chebula.

[0116] I. Clinical trial of rheumatoid and rheumatoid arthritis

[0117] 80 patients with rheumatoid and rheumatoid arthritis (40 males and 40 females) were included and randomly divided into four groups (10 males and 10 females in each group). The first group was treated with the plaster of Example 1, the second group was treated with the plaster of Example 2, the third group was treated with the plaster of Example 3, and the fourth group was treated with a placebo plaster (only containing the base without drugs).

[0118] Treatment method: Two plasters were used each time, and were applied to both sides of the knees. They were replaced every 24 hours, and one treatment cycle lasted for 7 days. Three consecutive treatment cycles were performed.

[0119] Treatment criteria:

[0120] Cure: symptoms disappear completely, functional activities return to normal, and main physicochemical indicators are normal.

[0121] Marked effect: all symptoms disappear or main symptoms disappear, joint function basically returns to normal, and the patient can participate in normal life activities, and physicochemical indicators are basically normal.

[0122] Effectiveness: main symptoms basically disappear, main joint function basically returns to normal or has obvious progress, and main physicochemical indicators improve.

[0123] Ineffectiveness: compared with before treatment, there is no progress in all aspects.

[0124] The treatment results are shown in Table 1.

[0125] Table 1. Treatment results of patients with rheumatism and rheumatoid arthritis

[0126] Group Total cases Cured cases Effective cases Effective cases Ineffective cases Effective rate First group 20 12 6 1 1 95％ Second group 20 10 4 2 4 80％ Third group 20 12 5 1 2 90％ Fourth group 20 0 0 2 18 10％

[0127] II. Clinical trial of vasculitis

[0128] Eighty patients with vasculitis (40 males and 40 females) were included and randomly divided into four groups (10 males and 10 females in each group). The first group was treated with the plaster of Example 1, the second group was treated with the plaster of Example 2, the third group was treated with the plaster of Example 3, and the fourth group was treated with a placebo plaster (only containing the base without drugs).

[0129] Treatment method: applied to the affected area or the proximal end, replaced every 24 hours, 14 days as a course of treatment, and treated for 2 courses.

[0130] The treatment criteria were determined by the Birmingham Vasculitis Activity Score (BVAS), specifically:

[0131] Remission: BVAS score of 0 after treatment (no active disease manifestations).

[0132] Ineffectiveness: compared with before treatment, there is no progress in all aspects.

[0133] The treatment results are shown in Table 2.

[0134] Table 2. Treatment results of patients with vasculitis

[0135] Group Total cases Relief cases Ineffective cases Effective rate First group 20 17 3 85％ Second group 20 16 4 80％ Third group 20 15 5 75％ Fourth group 20 3 17 15％

[0136] III. Clinical trial of eczema

[0137] Eighty patients with eczema (40 males and 40 females) were included and randomly divided into four groups (10 males and 10 females in each group). The first group was treated with the plaster of Example 1, the second group was treated with the plaster of Example 2, the third group was treated with the plaster of Example 3, and the fourth group was treated with a placebo plaster (only containing the base without drugs).

[0138] Treatment method: stick on the skin lesions, 12h replacement, 7 days for a course of treatment, 2 courses of treatment.

[0139] The treatment criteria are determined by Eczema Area and Severity Index Score (EASI), which is:

[0140] Cure: EASI score of 0 or EASI score improvement rate ≥ 90% after treatment.

[0141] Effective: EASI score improvement rate ≥ 75%.

[0142] Effective: EASI score improvement rate ≥ 50%

[0143] No effect: no progress in all aspects compared with before treatment.

[0144] The treatment results are shown in Table 3.

[0145] Table 3. Treatment results of eczema patients

[0146]

[0147]

[0148] Four, clinical trials of bruising and swelling

[0149] 80 patients with acute soft tissue contusion (bruising and swelling) were included (40 males and 40 females), and were randomly divided into four groups (10 males and 10 females in each group), the first group was treated with the plaster of Example 1, the second group was treated with the plaster of Example 2, the third group was treated with the plaster of Example 3, and the fourth group was treated with a placebo plaster (only containing the base, not containing the drug).

[0150] Treatment method: stick on the swelling and pain, 24h replacement, continuous use for 7 days.

[0151] The treatment criteria are:

[0152] Effective: VAS pain reduction ≥ 50% within 3 days of medication, and obvious subsidence of swelling and ecchymosis.

[0153] Effective: VAS pain reduction ≥ 50% within 4-7 days of medication, and obvious subsidence of swelling and ecchymosis.

[0154] No effect: symptoms are not effectively relieved after 7 days of medication.

[0155] The treatment results are shown in Table 4.

[0156] Table 4. Treatment results of patients with bruising and swelling

[0157] Group Total cases Cured cases Effective cases Effective cases Ineffective cases Effective rate First group 20 12 5 1 2 90％ Second group 20 10 5 2 3 85％ Third group 20 11 4 2 3 85％ Fourth group 20 0 0 2 18 10％

[0158] V. Clinical trial of neuropathic pain

[0159] 80 patients with neuropathic pain (20 patients with migraine, 20 patients with sciatica, 20 patients with trigeminal neuralgia, and 20 patients with supraorbital neuralgia) were included and randomly divided into four groups (each type of pain was evenly distributed in each group). The first group was treated with the plaster of Example 1, the second group was treated with the plaster of Example 2, the third group was treated with the plaster of Example 3, and the fourth group was treated with a placebo plaster (containing only the base without drugs).

[0160] Treatment method: applied to the pain site or corresponding nerve segment (such as the waist, face), one plaster per day, for a course of 28 days.

[0161] Treatment criteria are:

[0162] Marked effect: stable pulse, balance of the three causes of "Long Chi Pei", and pain / numbness reduction ≥80% (VAS score).

[0163] Effective: pain / numbness reduction ≥50% (VAS score).

[0164] Ineffective: no progress in all aspects compared with before treatment.

[0165] The treatment results are shown in Table 5.

[0166] Table 5. Treatment results of patients with neuropathic pain

[0167] Group Total cases Effective cases Effective cases Ineffective cases Effective rate First group 20 11 6 3 85％ Second group 20 9 6 5 75％ Third group 20 10 6 4 80％ Fourth group 20 0 1 19 5％

[0168] VI. Skin irritation test

[0169] 60 patients with eczema (without known history of allergy) were included and randomly divided into two groups. The first group was treated with the plaster of Example 1, and the second group was treated with the plaster of Comparative Example 1. The skin reaction was observed after continuous use for 3 days. The plaster of Comparative Example 1 was prepared in the same way as Example 1, except that Comparative Example 1 did not contain 40 parts of Tibetan cat milk.

[0170] Results:

[0171] After 3 days of use, the number of patients in the first group who developed allergic symptoms such as skin erythema, papules, and edema was 3, with an incidence rate of 10%; the number of patients in the second group who developed allergic symptoms such as skin erythema, papules, and edema was 22, with an incidence rate of 73%.

[0172] Conclusion: The incidence of skin allergy of the plaster of Example 1 was reduced by 63% compared to the plaster of Comparative Example 1. The addition of Tibetan cat milk to the formula significantly reduced the skin irritation of the plaster.

[0173] VII. Safety test

[0174] The rheumatism and rheumatoid arthritis patients, vasculitis patients, eczema patients, contusion patients and neuropathic pain patients treated with the plaster of the present application embodiment 1, embodiment 2 and embodiment 3 were subjected to electrocardiogram examination before and after the use of the plaster, and the electrocardiogram examination results showed that there was no obvious change in the electrocardiogram after the treatment compared with that before the use of the plaster.

[0175] The blood samples were subjected to high performance liquid chromatography (HPLC) to detect the aconitine blood concentration of the patients after the treatment with the plaster, and the detection results showed that the aconitine blood concentration (average value) of the patients after the treatment with the plaster was (0.38±0.12) ng / mL, and there was no risk of aconitine poisoning.

[0176] VIII. Test of retention rate of effective components in the drug-containing ointment body

[0177] The aconitine content in the raw medicinal materials and the prepared drug-containing ointment body was detected by high performance liquid chromatography (HPLC), the polysaccharide content in the raw medicinal materials and the prepared drug-containing ointment body was detected by phenol-sulfuric acid method, and the volatile oil content in the raw medicinal materials and the prepared drug-containing ointment body was detected by the volatile oil determination method in the General Rules of Chinese Pharmacopoeia 2020 Edition, and the retention rate of effective components was calculated by “effective component content in drug-containing ointment body ÷ effective component content in raw medicinal materials”.

[0178] The detected drug-containing ointment samples included the drug-containing ointments of embodiment 1 and comparative examples 2-4.

[0179] Comparative example 2: The drug-containing ointment was prepared in the same way as in embodiment 1, except that the heating method of comparative example 2 was to heat the medicinal oil with a large fire, and the oil temperature was kept at 140-150°C for boiling.

[0180] Comparative example 3: The drug-containing ointment was prepared in the same way as in embodiment 1, except that the heating method of comparative example 3 was to heat the medicinal oil with a small fire, and the oil temperature was kept at 90-95°C for boiling.

[0181] Comparative example 4: The drug-containing ointment was prepared in the same way as in embodiment 1, except that all the medicinal materials were put into the sesame oil at one time for boiling.

[0182] The effective component retention rate results are shown in the following table 6.

[0183] Table 6. Retention rate of effective components in the drug-containing ointment

[0184] Retention rate of aconitine (%) Retention rate of polysaccharide (%) Retention rate of volatile oil (%) Example 1 92 88.5 94.2 Comparative example 2 75 70 65 Comparative example 3 85 80 75 Comparative example 4 78 72 68

[0185] As can be seen from table 6 above, the preparation method of low-temperature segmented boiling of embodiment 1 can effectively retain the heat-sensitive effective components in the medicinal materials.

[0186] IX. Transdermal absorption test

[0187] Method: Franz diffusion cell method was used, and the isolated pig ear skin was used as the skin model.

[0188] Receiving liquid: pH 7.4 phosphate buffer + 30% ethanol; temperature: 32±0.5℃.

[0189] Sampling time points: 1h, 2h, 4h, 6h, 8h, 12h and 24h.

[0190] Detection index: cumulative transdermal amount of aconitine (μg / cm 2 ).

[0191] Test samples: the plaster provided in Examples 1 to 3, the plaster provided in Comparative Example 5, and the commercially available rheumatism plaster (Wushufang rheumatism pain plaster, Chongqing Xilan Pharmaceutical Co., Ltd.). Comparative Example 5: the plaster was prepared in the same manner as in Example 1, except that the weight fraction of Acorus calamus in Comparative Example 5 was 10 parts.

[0192] The detection results are shown in Table 7 below.

[0193] Table 7. Transdermal detection results of various plasters

[0194] 24h cumulative transdermal amount (μg / cm 2 )]]> Transdermal rate (μg / cm 2 • h) Example 1 15.3±1.8 0.64±0.08 Example 2 13.1±1.5 0.55±0.06 Example 3 14.7±1.6 0.61±0.07 Commercial rheumatism patch 4.9±0.7 0.20±0.03 Comparative example 5 9.2±1.1 0.38±0.05

[0195] As can be seen from Table 7 above, the transdermal absorption rate of the plasters of Examples 1-3 (especially Example 1) is significantly higher than that of the commercially available rheumatism plaster and the plaster of Comparative Example 5.

[0196] Ten, synergistic effect of Abelmoschus manihot seeds and Cassiae Semen in the prescription

[0197] Considering the compatibility requirements of the damp-heat syndrome of "yellow water disease", the present application adds the dampness-reducing active ingredients of Abelmoschus manihot seeds and Cassiae Semen in the prescription, and the following experiments verify the optimization of the treatment effect of the damp-heat syndrome disease by adding Abelmoschus manihot seeds and Cassiae Semen in the prescription.

[0198] (1) Synergistic mechanism of Abelmoschus manihot seeds and Cassiae Semen

[0199] The extracts of Abelmoschus manihot seeds and Cassiae Semen were prepared by ethanol reflux extraction method, and the results of in vitro enzyme activity experiment showed that when the extract of Abelmoschus manihot seeds (main component: total flavonoids) and the extract of Cassiae Semen (main component: anthraquinones) were combined in a mass ratio of 3:1, the inhibition rate of MMP-9 activity reached 78.2%, which was significantly improved compared with the single use of Abelmoschus manihot seeds or Cassiae Semen in inhibiting the activity of MMP-9. The results of cell model experiment showed that when the extract of Abelmoschus manihot seeds and the extract of Cassiae Semen were combined in a mass ratio of 3:1, the reduction of IL-6 secretion was 2.1-2.3 times higher than that of the single use of Abelmoschus manihot seeds or Cassiae Semen.

[0200] The experimental principle of the in vitro enzyme activity experiment is to use a fluorescently labeled MMP-9 specific substrate. When the MMP-9 enzyme cuts the substrate, a fluorescent signal is released. Inhibitors (Huangqizi, Semen Cassiae, etc.) will reduce the generation speed of the fluorescent signal. By monitoring the change of the fluorescent intensity with time, the slope of the change of the fluorescent intensity with time (i.e. the enzyme reaction rate V) is obtained. Then the inhibition rate is calculated according to the inhibition rate calculation formula "inhibition rate (%) = [1-(V experimental group / V control group)] x 100%".

[0201] The experimental principle of the cell model experiment is to use lipopolysaccharide (LPS) to stimulate macrophages (such as RAW264.7 cells) to establish an inflammation model, induce the cells to secrete a large amount of IL-6, and use a mouse IL-6 ELISA kit to detect the protein concentration (P1) of IL-6 in the supernatant of the inflammation model cells. After the inflammation model is intervened by giving drugs (Huangqizi, Semen Cassiae, etc.), the protein concentration (P2) of IL-6 in the supernatant is detected. The reduction value of the secretion amount of IL-6 is P1 minus P2.

[0202] (2) Effect on joint effusion

[0203] Twenty rheumatism and rheumatoid arthritis patients (10 males and 10 females) were included and randomly divided into two groups (5 males and 5 females in each group). Each group used the plaster according to the treatment method of the rheumatism and rheumatoid arthritis clinical trial. The first group was treated with the plaster provided in Example 1, and the second group was treated with the plaster provided in Comparative Example 6. The knee joint effusion depth was measured by ultrasound before and after treatment, and the results are shown in Table 8 below. Note: Comparative Example 6 is the same as Example 1 in preparing the plaster, except that Comparative Example 6 does not contain Huangqizi and Semen Cassiae.

[0204] Table 8. Results of knee joint effusion detection

[0205]

[0206] As can be seen from Table 8, the addition of Huangqizi and Semen Cassiae enhances the absorption of joint effusion.

[0207] (3) Effect on eczema

[0208] Twenty eczema patients (10 males and 10 females) were included and randomly divided into two groups (5 males and 5 females in each group). Each group used the plaster according to the treatment method of the eczema clinical trial. The first group was treated with the plaster provided in Example 1, and the second group was treated with the plaster provided in Comparative Example 6. EASI scores were performed before and after treatment, and the results are shown in Table 9 below.

[0209] Table 9. EASI score results of eczema treatment

[0210]

[0211] From table 9, it can be seen that the addition of Huangqizi and Shuimingzi improves the EASI score improvement rate and optimizes the treatment effect of eczema.

[0212] In summary, the Tibetan medicine formula provided by the present application has the characteristics of low toxicity, wide indications, and low drug cost. For patients in high altitude areas, due to the common symptoms of “lung imbalance” (neuralgia) and “red heat poison” (redness, heat and pain), multiple target treatment is required. The Tibetan medicine formula provided by the present application has more advantages for the treatment of patients in high altitude areas. Moreover, for non-joint symptoms (such as skin eczema and vasculitis), the existing formula lacks clear indications, while the formula of the present application clearly covers the treatment of neuropathic pain, rheumatism and rheumatoid arthritis, vasculitis, eczema and contusion, expands the indications of the formula treatment, and realizes “one drug with multiple effects”.

[0213] Although preferred embodiments of the present application have been described, those skilled in the art, once they know the basic creative concept, can make additional changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications falling within the scope of the present application.

Claims

1. A Tibetan medicine prescription, characterized in that: The invention comprises the following raw materials in parts by weight: 30-50 parts of Tibetan cat milk, 30-50 parts of iron hammer, 15-30 parts of Tibetan calamus, 8-15 parts of mukul myrrh, 8-15 parts of frankincense, 8-15 parts of cassia seeds, 8-15 parts of sunflower seeds, 20-40 parts of nutmeg, 8-15 parts of yellow-haired delphinium flowers, 30-50 parts of Sichuan costus root, and 30-50 parts of terminalia chebula.

2. A Tibetan medicine prescription according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 40 parts of Tibetan cat milk, 40 parts of iron hammer, 20 parts of Tibetan calamus, 10 parts of mukul myrrh, 10 parts of frankincense, 10 parts of cassia seeds, 10 parts of sunflower seeds, 30 parts of nutmeg, 10 parts of yellow-haired delphinium flowers, 40 parts of Sichuan costus root, and 40 parts of terminalia chebula.

3. Use of the Tibetan medicine formula according to claim 1 or 2 in preparing medicines for treating neuropathic pain, rheumatism and rheumatoid arthritis, vasculitis, eczema, and bruises.

4. A Tibetan medicine plaster comprising a backing layer, a drug-containing paste layer and an anti-adhesive layer, characterized in that: The drug-containing paste layer is composed of an active ingredient and a matrix that carries the active ingredient. The active ingredient is the Tibetan medicine formula according to claim 1 or 2, and the matrix is ​​a mixture of beeswax and vegetable oil.

5. A method for preparing a Tibetan medicine plaster, characterized in that: The following steps are involved: Step 1, weighing each raw material medicine according to the Tibetan medicine formula of claim 1 or 2, pre-treating each raw material medicine to a boiled state, mixing the treated raw materials of Tibetan cat milk, iron hammer, Tibetan calamus, Sichuan costus root, Terminalia chebula, nutmeg, cassia seed, and sunflower seed to obtain a mixed medicine, adding the mixed medicine to vegetable oil and boiling at 100-130° C. for 1.5-2.5 hours, wherein the amount of the vegetable oil is 3-5 times the weight of the mixed medicine, adding the raw materials of myrrh mukul and frankincense 15-30 minutes before the boiling is completed, and then boiling for 15-30 minutes and filtering the residue to obtain the medicinal oil; Step 2: Add beeswax to the medicinal oil in step 1, heat until the beeswax melts and mix evenly with the medicinal oil to obtain a medicinal ointment; the amount of beeswax added is 1 / 4 to 1 / 3 of the mass of the medicinal oil; Step 3: coating the drug-containing paste of step 2 on the backing layer to obtain a drug-containing paste layer, and covering the surface of the drug-containing paste layer with an anti-sticking layer to obtain the Tibetan medicine patch.

6. The preparation method according to claim 5, characterized in that: The boiled forms of the raw materials are as follows: the raw materials Tibetan cat milk, iron hammer, Tibetan calamus, Sichuan costus root, Terminalia chebula, and nutmeg are powdered through a 20-40 mesh sieve; the raw material yellow-haired delphinium flower is cut into small pieces of 5-10 cm; the raw materials cassia seed, sunflower seed, mukul myrrh, and frankincense are not processed and remain in their original form.

7. The preparation method according to claim 5, characterized in that: The thickness of the ointment layer containing the medicine is 0.5-2 mm.

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