A traditional Chinese medicine composition, a traditional Chinese medicine extract and application thereof in preparation of a medicine for treating pain

Abstract

The application discloses a traditional Chinese medicine composition, a traditional Chinese medicine extract and application of the traditional Chinese medicine composition and the traditional Chinese medicine extract in preparation of a medicine for treating pain. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 4-8 parts of Radix et Rhizoma Aconiti, 14-18 parts of Impatiens balfourii, 20-24 parts of Radix et Rhizoma Bistortae, 20-24 parts of Radix et Rhizoma Rhei and 14-18 parts of Phellodendri Cortex. The application provides a new traditional Chinese medicine composition for treating pain, and an external traditional Chinese medicine preparation prepared based on the traditional Chinese medicine composition, which has excellent effects of good analgesic effect, strong skin permeability and good safety, is convenient to use and meets the clinical drug requirement.

Description

Technical Field

[0001] This invention relates to the pharmaceutical field, specifically to a traditional Chinese medicine composition, a traditional Chinese medicine extract, and its application in the preparation of a medicament for treating pain. Background Technology

[0002] Pain is a complex process in which the body, after being subjected to noxious stimuli, acts on pain receptors, and then transmits pain signals to the central nervous system via primary afferent fibers. Many diseases can cause pain, such as sprains and strains, rheumatoid arthritis, and cancer, affecting patients' work and reducing their quality of life. Currently, clinical treatment of pain mainly relies on Western medicines such as opioids or nonsteroidal anti-inflammatory drugs (NSAIDs). However, long-term use often brings numerous side effects, causing damage to the gastrointestinal tract, skin, cardiovascular system, liver, and kidneys, and even leading to dependence and addiction. Therefore, developing analgesics with low addictive potential and fewer adverse reactions has significant clinical value.

[0003] In pain management, traditional Chinese medicine (TCM) has attracted increasing attention from researchers due to its unique pharmacological effects and holistic regulatory advantages. TCM gels, as a form of TCM preparation, are convenient to use, have direct effects, and few side effects, making them particularly suitable for treating skin and soft tissue pain. However, currently available TCM gels still have certain limitations in pain management. Some gels have poor permeability, making it difficult to reach deep tissues, resulting in poor therapeutic effects. Improper preparation processes lead to unstable efficacy and are prone to adverse reactions such as allergies. Therefore, developing topical TCM gels with good analgesic effects, strong permeability, and high safety is of great significance for improving the effectiveness of pain management. Summary of the Invention

[0004] To address the aforementioned problems in the existing technology, this invention combines the pharmacological effects of traditional Chinese medicine with modern pharmaceutical technology to provide a traditional Chinese medicine composition, a traditional Chinese medicine extract, and its application in the preparation of drugs for treating pain.

[0005] The first objective of this invention is to provide a traditional Chinese medicine composition.

[0006] The second objective of this invention is to provide a traditional Chinese medicine extract.

[0007] A third objective of this invention is to provide the use of the traditional Chinese medicine composition and / or the traditional Chinese medicine extract in the preparation of products for treating pain.

[0008] The fourth objective of this invention is to provide a topical medicine for treating pain.

[0009] The fifth objective of this invention is to provide a method for preparing a topical medicine for treating pain.

[0010] To achieve the above objectives, the present invention is implemented through the following solution:

[0011] Aconitum carmichaelii, pungent and bitter in taste, and hot in nature, has the effects of dispelling wind and dampness, warming the meridians and relieving pain. It is mainly used for wind-cold-dampness arthralgia, joint pain, cold pain in the heart and abdomen, cold hernia pain, and anesthesia and analgesia. Rhododendron molle, pungent and warm in taste, and highly toxic, has the effects of dispelling wind and dampness, relaxing muscles and promoting blood circulation, and relieving pain. It is often used to treat stubborn rheumatism, fracture pain, toothache, and stubborn skin diseases. Cynanchum paniculatum, pungent and warm in taste, has the effects of dispelling wind and cold, removing dampness and relieving pain. It is often used for various pain syndromes such as rheumatic arthralgia, back pain, pain from falls and injuries, abdominal pain, and toothache. Rheum palmatum, bitter in taste and cold in nature, has the effects of purging and promoting bowel movement, clearing heat and cooling blood, promoting blood circulation and breaking up accumulations, and clearing heat and detoxifying. It treats abdominal pain due to stagnation, damp-heat diarrhea, abdominal masses, and injuries from falls and injuries. Phellodendron amurense, bitter in taste and cold in nature, has the effects of clearing heat and drying dampness, purging fire and eliminating steaming, and detoxifying and healing sores. It is mainly used to treat sores, carbuncles, eczema, and damp ulcers. This invention combines the above-mentioned drugs to achieve the effects of warming the meridians and relieving pain, dispelling wind and dampness, cooling the blood and detoxifying. It is used for external treatment of pain and has a good curative effect.

[0012] A traditional Chinese medicine composition is made from the following components: by weight, 4-8 parts of Aconitum carmichaelii, 14-18 parts of Rhododendron molle, 20-24 parts of Cynanchum paniculatum, 20-24 parts of Rheum palmatum, and 14-18 parts of Phellodendron chinense.

[0013] Preferably, the components used to prepare the traditional Chinese medicine composition further include, by weight, 10-12 parts of Glauber's salt.

[0014] More preferably, the components used to make the traditional Chinese medicine composition further include, by weight, 2 to 4 parts of borneol.

[0015] More preferably, the traditional Chinese medicine composition is made from the following components: by weight, 6.8 parts of Aconitum carmichaelii, 16.8 parts of Rhododendron molle, 22.5 parts of Cynanchum paniculatum, 22.5 parts of Rheum palmatum, 16.8 parts of Phellodendron chinense, 11.2 parts of Glauber's salt, and 3.4 parts of Borneol.

[0016] More preferably, the traditional Chinese medicine composition is made from the following components: by weight, 4 parts Aconitum carmichaelii, 14 parts Rhododendron molle, 20 parts Cynanchum paniculatum, 20 parts Rheum palmatum, 14 parts Phellodendron chinense, 10 parts Glauber's salt and 2 parts Borneol.

[0017] More preferably, the traditional Chinese medicine composition is made from the following components: by weight, 8 parts of Aconitum carmichaelii, 18 parts of Rhododendron molle, 24 parts of Cynanchum paniculatum, 24 parts of Rheum palmatum, 18 parts of Phellodendron chinense, 12 parts of Glauber's salt and 4 parts of borneol.

[0018] The use of any of the aforementioned traditional Chinese medicine compositions in the preparation of products for treating pain should also be within the scope of protection of this invention.

[0019] A traditional Chinese medicine extract, which is an aqueous extract and / or alcoholic extract of a traditional Chinese medicine composition, wherein the traditional Chinese medicine composition is made of the following components: by weight, 4-8 parts of Aconitum carmichaelii, 14-18 parts of Rhododendron molle, 20-24 parts of Cynanchum paniculatum, 20-24 parts of Rheum palmatum and 14-18 parts of Phellodendron chinense.

[0020] Preferably, the components used to prepare the traditional Chinese medicine composition further include, by weight, 10-12 parts of Glauber's salt.

[0021] More preferably, the components used to make the traditional Chinese medicine composition further include, by weight, 2 to 4 parts of borneol.

[0022] More preferably, the traditional Chinese medicine composition is made from the following components: by weight, 6.8 parts of Aconitum carmichaelii, 16.8 parts of Rhododendron molle, 22.5 parts of Cynanchum paniculatum, 22.5 parts of Rheum palmatum, 16.8 parts of Phellodendron chinense, 11.2 parts of Glauber's salt, and 3.4 parts of Borneol.

[0023] More preferably, the traditional Chinese medicine composition is made from the following components: by weight, 4 parts Aconitum carmichaelii, 14 parts Rhododendron molle, 20 parts Cynanchum paniculatum, 20 parts Rheum palmatum, 14 parts Phellodendron chinense, 10 parts Glauber's salt and 2 parts Borneol.

[0024] More preferably, the traditional Chinese medicine composition is made from the following components: by weight, 8 parts of Aconitum carmichaelii, 18 parts of Rhododendron molle, 24 parts of Cynanchum paniculatum, 24 parts of Rheum palmatum, 18 parts of Phellodendron chinense, 12 parts of Glauber's salt and 4 parts of borneol.

[0025] Preferably, the herbal extract is an aqueous extract and an alcoholic extract of the herbal composition.

[0026] Different extraction processes significantly impact efficacy and the retention of active pharmaceutical ingredients. Traditional Chinese medicine compound preparations often contain numerous and complex components, and research on the fundamental properties of their active pharmaceutical ingredients is relatively weak, posing a challenge to pretreatment. To avoid the low sensitivity and inability to determine process quality when optimizing extraction processes solely based on pharmacodynamic indicators, this invention combines high-performance liquid chromatography (HPLC) characteristic chromatographic detection technology with the retention rates of various components to evaluate and determine extraction processes, resulting in more sensitive and reliable results.

[0027] Preferably, the method for preparing the herbal extract includes decoction and / or percolation.

[0028] More preferably, the decoction method includes the following steps: thoroughly decocting the traditional Chinese medicine composition with water, separating the solid and liquid, and collecting the liquid.

[0029] More preferably, the decoction method includes the following steps: first, decoct the Aconitum carmichaelii in water, and then decoct the resulting decoction with Rhododendron molle, Cynanchum paniculatum, Rheum palmatum and Phellodendron chinense, separate the solid and liquid, and collect the liquid.

[0030] More preferably, the decoction method includes the following steps: first, decoct the aconite root in 6 to 9 times its weight in water for 1 to 3 hours; then, decoct the resulting mixture with the rhododendron flower, the cynanchum paniculatum, the rhubarb, the phellodendron bark, and 6 to 20 times the total weight of the medicinal materials in water, and then separate the solid and liquid, collecting the liquid.

[0031] More preferably, the decoction method includes the following steps: first, decoct the aconite root with 6 to 8 times its weight in water for 1 to 2 hours; then combine the resulting decoction with the rhododendron flower, the cynanchum paniculatum, the rhubarb, and the phellodendron bark, and decoct twice, adding water in 6 to 8 times its total weight each time, and decoct for 1 to 2 hours each time; filter and combine the filtrates.

[0032] Specifically, the decoction method includes the following steps: weighing aconite root slices, rhododendron flower slices, cynanchum paniculatum slices, rhubarb slices, and phellodendron bark slices; first decoct aconite root for 2 hours, then add water three times, with the amount of water added being 8, 6, and 6 times the total weight of the medicinal materials respectively, for a total of three decoctions, each lasting 1 hour, then filter and combine the filtrates.

[0033] More preferably, the percolation method includes the following steps: immersing the traditional Chinese medicine composition, fully percolating with a solvent, and collecting the percolate.

[0034] More preferably, the traditional Chinese medicine composition is a fine powder, medium powder, or coarse powder.

[0035] More preferably, the traditional Chinese medicine composition is a powder.

[0036] More preferably, the soaking time is 0h to 24h.

[0037] More preferably, the immersion time is 0 hours.

[0038] More preferably, the amount of solvent used is 3 to 9 times the total weight of the medicinal materials by volume.

[0039] More preferably, the amount of solvent used is 4 to 8 times the volume of the total weight of the medicinal materials.

[0040] More preferably, the amount of solvent used is 6 times the volume of the total weight of the medicinal materials.

[0041] More preferably, the solvent is ethanol.

[0042] More preferably, the solvent is 30 v / v% to 90 v / v% ethanol.

[0043] More preferably, the solvent is 40 v / v% to 80 v / v% ethanol.

[0044] Most preferably, the solvent is 80 v / v ethanol.

[0045] More preferably, the percolation rate is 3 ml / min / kg to 9 ml / min / kg.

[0046] More preferably, the percolation rate is 9 ml / min / kg.

[0047] Specifically, the method for preparing the Chinese herbal extract by percolation includes the following steps: according to the prescription, weigh out the powders of Aconitum carmichaelii, Rhododendron molle, Cynanchum paniculatum, Rheum palmatum, and Phellodendron chinense; percolate with 80% ethanol at a rate of 9 ml / min / kg at a volume of 6 times the total weight of the herbs, and collect the percolate.

[0048] The use of any of the Chinese herbal extracts in the preparation of products for treating pain should also be within the scope of protection of this invention.

[0049] A topical medicine for treating pain comprises a traditional Chinese medicine composition and / or a traditional Chinese medicine extract; the traditional Chinese medicine composition is made of the following components: by weight, 4-8 parts of Aconitum carmichaelii, 14-18 parts of Rhododendron molle, 20-24 parts of Cynanchum paniculatum, 20-24 parts of Rheum palmatum, and 14-18 parts of Phellodendron chinense; the traditional Chinese medicine extract is an aqueous extract and / or an alcoholic extract of the traditional Chinese medicine composition.

[0050] Preferably, the components used to prepare the traditional Chinese medicine composition further include, by weight, 10-12 parts of Glauber's salt.

[0051] Preferably, the herbal extract is an aqueous extract and an alcoholic extract of the herbal composition.

[0052] Preferably, the method for preparing the herbal extract includes decoction and / or percolation.

[0053] More preferably, the decoction method includes the following steps: fully decocting the Aconitum carmichaelii, Rhododendron molle, Cynanchum paniculatum, Rheum palmatum and Phellodendron chinense with water, separating the solid and liquid, and collecting the liquid.

[0054] More preferably, the decoction method includes the following steps: first, decoct the Aconitum carmichaelii in water, and then decoct the resulting decoction with Rhododendron molle, Cynanchum paniculatum, Rheum palmatum and Phellodendron chinense, separate the solid and liquid, and collect the liquid.

[0055] More preferably, the decoction method includes the following steps: first, decoct the Aconitum carmichaelii in 6 to 9 times the amount of water for 1 to 3 hours, and then decoct the resulting decoction with Rhododendron molle, Cynanchum paniculatum, Rheum palmatum, Phellodendron chinense, and 4 to 8 times the amount of water, and then separate the solid and liquid, and collect the liquid.

[0056] More preferably, the decoction method includes the following steps: first, decoct the Aconitum carmichaelii in 6 to 8 times the amount of water for 1 to 2 hours; then combine the decoction with Rhododendron molle, Cynanchum paniculatum, Rheum palmatum and Phellodendron chinense and continue to decoct for 1 to 2 hours; then decoct twice more in 6 to 8 times the amount of water, each time for 1 to 2 hours; filter and combine the filtrates.

[0057] Specifically, the decoction method includes the following steps: weighing aconite root slices, rhododendron flower slices, cynanchum paniculatum slices, rhubarb slices, and phellodendron bark slices; first, decoct the aconite root slices in 8 times the volume of water of the above five medicinal materials for 2 hours, then combine the resulting decoction with the rhododendron flower slices, the cynanchum paniculatum slices, the rhubarb slices, and the phellodendron bark slices, and decoct them in 8 times, 6 times, and 6 times the volume of water respectively, for 1 hour each time, filter, and combine the filtrates.

[0058] More preferably, the percolation method includes the following steps: immersing the traditional Chinese medicine composition, fully percolating with a solvent, and collecting the percolate.

[0059] More preferably, the traditional Chinese medicine composition is a fine powder, medium powder, or coarse powder.

[0060] More preferably, the traditional Chinese medicine composition is a powder.

[0061] More preferably, the soaking time is 0h to 24h.

[0062] More preferably, the immersion time is 0 hours.

[0063] More preferably, the amount of solvent used is 3 to 9 times the amount.

[0064] More preferably, the amount of solvent used is 4 to 8 times the amount of solvent used.

[0065] More preferably, the amount of solvent used is 6 times the normal amount.

[0066] More preferably, the solvent is ethanol.

[0067] More preferably, the solvent is 30 v / v% to 90 v / v% ethanol.

[0068] More preferably, the solvent is 40 v / v% to 80 v / v% ethanol.

[0069] Most preferably, the solvent is 80 v / v ethanol.

[0070] More preferably, the percolation rate is 3 ml / min / kg to 9 ml / min / kg.

[0071] More preferably, the percolation rate is 9 ml / min / kg.

[0072] Specifically, the method for preparing the Chinese herbal extract by percolation includes the following steps: according to the prescription, weigh out the powders of Aconitum carmichaelii, Rhododendron molle, Cynanchum paniculatum, Rheum palmatum, and Phellodendron chinense; percolate with 6 times the amount of 80v / v% ethanol at a rate of 9ml / min / kg, and collect the percolate.

[0073] Preferably, the topical medication is a semi-solid or liquid preparation. The liquid preparation includes, but is not limited to, ointments, pour-over solutions, lotions, tinctures, and liniments. The semi-solid preparation includes, but is not limited to, ointments, creams, pastes, eye ointments, gels, and suppositories.

[0074] More preferably, the liquid preparation is a tincture or liniment.

[0075] More preferably, the semi-solid formulation is a gel.

[0076] The matrix is ​​not only an excipient for gels, but also has a significant impact on the quality and efficacy of gels.

[0077] More preferably, the matrix of the semi-solid formulation is a water-soluble matrix.

[0078] More preferably, the water-soluble matrix is ​​hydroxyethyl cellulose.

[0079] More preferably, the final concentration of the hydroxyethyl cellulose is 0.5 wt% to 2 wt%.

[0080] More preferably, the final concentration of the hydroxyethyl cellulose is 1.5 wt%.

[0081] More preferably, the semi-solid formulation is a transdermal penetration enhancer.

[0082] More preferably, the transdermal penetration enhancer is any one of azone, oleic acid, isopropyl myristate, and propylene glycol.

[0083] More preferably, the transdermal penetration enhancer is propylene glycol.

[0084] More preferably, the final concentration of the propylene glycol is 2wt% to 7wt%.

[0085] Most preferably, the final concentration of the propylene glycol is 5 wt%.

[0086] A method for preparing a topical medication for treating pain includes the following steps:

[0087] S1. The traditional Chinese medicine composition is processed by decoction or percolation; the traditional Chinese medicine composition is made from the following components: by weight, Aconitum carmichaelii 4-8 parts, Rhododendron molle 14-18 parts, Cynanchum paniculatum 20-24 parts, Rheum palmatum 20-24 parts and Phellodendron chinense 14-18 parts;

[0088] S2. Mix Glauber's salt and borneol thoroughly with the product obtained in step S1 to obtain the product; the amount of crude drug per 1g or 1ml of the product obtained in step S1 is 0.1g / ml to 1.5g / ml.

[0089] Preferably, in step S1, the components used to prepare the traditional Chinese medicine composition further include, by weight, 10-12 parts of Glauber's salt.

[0090] More preferably, in step S1, the components used to make the traditional Chinese medicine composition further include, by weight, 2 to 4 parts of borneol.

[0091] More preferably, in step S1, the traditional Chinese medicine composition is made from the following components: by weight, 6.8 parts of Aconitum carmichaelii, 16.8 parts of Rhododendron molle, 22.5 parts of Cynanchum paniculatum, 22.5 parts of Rheum palmatum, 16.8 parts of Phellodendron chinense, 11.2 parts of Glauber's salt, and 3.4 parts of Borneol.

[0092] More preferably, in step S1, the traditional Chinese medicine composition is made from the following components: by weight, 4 parts of Aconitum carmichaelii, 14 parts of Rhododendron molle, 20 parts of Cynanchum paniculatum, 20 parts of Rheum palmatum, 14 parts of Phellodendron chinense, 10 parts of Glauber's salt and 2 parts of borneol.

[0093] More preferably, in step S1, the traditional Chinese medicine composition is made from the following components: by weight, 8 parts of Aconitum carmichaelii, 18 parts of Rhododendron molle, 24 parts of Cynanchum paniculatum, 24 parts of Rheum palmatum, 18 parts of Phellodendron chinense, 12 parts of Glauber's salt and 4 parts of borneol.

[0094] Preferably, in step S1, the decoction method includes the following steps: fully decocting the traditional Chinese medicine composition with water, separating the solid and liquid, and collecting the liquid.

[0095] More preferably, in step S1, the decoction method includes the following steps: first, decoct the Aconitum carmichaelii in water, and then decoct the resulting decoction with Rhododendron molle, Cynanchum paniculatum, Rheum palmatum and Phellodendron chinense, separate the solid and liquid, and collect the liquid.

[0096] More preferably, in step S1, the decoction method includes the following steps: first, decoct the aconite root with 6 to 9 times the volume of water (based on the weight of the five medicinal materials: aconite root, rhododendron flower, cynanchum paniculatum, rhubarb, and phellodendron bark) for 1 to 3 hours; then, fully decoct the resulting decoction with 6 to 20 times the volume of water (based on the total weight of the rhododendron flower, cynanchum paniculatum, rhubarb, and phellodendron bark) to separate the solid and liquid, and collect the liquid.

[0097] More preferably, in step S1, the decoction method includes the following steps: First, decoct the aconite root with water in an amount of 6 to 8 times the total weight of the five medicinal materials, namely, Rhodiola rosea, Cynanchum paniculatum, Rheum palmatum, and Phellodendron chinense, for 1 to 2 hours. Then, combine the decoction with the Rhodiola rosea, Cynanchum paniculatum, Rheum palmatum, and Phellodendron chinense, and decoct twice, adding water in an amount of 6 to 8 times the total weight of the five medicinal materials each time, and decoct for 1 to 2 hours each time. Filter and combine the filtrates.

[0098] Specifically, in step S1, the decoction method includes the following steps: weighing aconite root slices, rhododendron flower slices, cynanchum paniculatum slices, rhubarb slices, and phellodendron bark slices; first decoct the aconite root slices for 2 hours with water equal to 8 times the total weight of the five medicinal materials (aconite root, rhododendron flower, cynanchum paniculatum, rhubarb, and phellodendron bark), then add water three times, with the amount of water added being 8, 6, and 6 times the total weight of the five medicinal materials respectively, for a total of three decoctions, each lasting 1 hour, then filtering and combining the filtrates.

[0099] Preferably, in step S1, the percolation method includes the following steps: soaking the traditional Chinese medicine composition, fully percolating with a solvent, and collecting the percolate.

[0100] More preferably, in step S1, the traditional Chinese medicine composition is fine powder, medium powder, or coarse powder.

[0101] More preferably, in step S1, the traditional Chinese medicine composition is powder.

[0102] More preferably, in step S1, the soaking time is 0h to 24h.

[0103] More preferably, in step S1, the soaking time is 0h.

[0104] More preferably, in step S1, the amount of solvent used is 3 to 9 times the total weight of the medicinal materials by volume.

[0105] More preferably, in step S1, the amount of solvent used is 4 to 8 times the total weight of the medicinal materials by volume.

[0106] More preferably, in step S1, the amount of solvent used is 6 times the volume of the total weight of the medicinal materials.

[0107] More preferably, in step S1, the solvent is ethanol.

[0108] More preferably, in step S1, the solvent is 30 v / v% to 90 v / v% ethanol.

[0109] More preferably, in step S1, the solvent is 40 v / v% to 80 v / v% ethanol.

[0110] In a further preferred embodiment, in step S1, the solvent is 80 v / v ethanol.

[0111] More preferably, in step S1, the percolation rate is 3 ml / min / kg to 9 ml / min / kg.

[0112] More preferably, in step S1, the percolation rate is 9 ml / min / kg.

[0113] Specifically, in step S1, the method for preparing the Chinese herbal extract by percolation includes the following steps: according to the prescription amount, weigh the powders of Aconitum carmichaelii, Rhododendron molle, Cynanchum paniculatum, Rheum palmatum, and Phellodendron chinense; percolate with 80% ethanol at a rate of 9 ml / min / kg at a volume of 6 times the total weight of the herbs, and collect the percolate.

[0114] Preferably, in step S2, Glauber's salt and borneol are thoroughly mixed with the filtered product obtained in step S1.

[0115] More preferably, in step S2, the amount of crude drug per 1g or 1ml of the product obtained in step S1 is 0.1g / ml to 1.5g / ml.

[0116] More preferably, in step S2, the method for adjusting the amount of raw medicinal material in the product obtained in step S1 is concentration.

[0117] More preferably, in step S2, the concentration is reduced pressure concentration.

[0118] More preferably, in step S2, the temperature of the vacuum concentration is 50°C to 80°C.

[0119] In a further preferred embodiment, in step S2, the temperature of the vacuum concentration is 60°C to 80°C.

[0120] Most preferably, in step S2, the temperature of the vacuum concentration is 70°C.

[0121] More preferably, in step S2, the vacuum degree of the reduced pressure concentration is -0.08MPa to -0.04MPa.

[0122] More preferably, in step S2, the vacuum degree of the reduced pressure concentration is -0.06 MPa.

[0123] More preferably, in step S2, a rotary evaporator is used for vacuum concentration.

[0124] Preferably, if the external medicine is a semi-solid preparation, then in step S2, Glauber's salt is first thoroughly mixed with the product obtained in step S1, and the resulting mixture is then thoroughly mixed with borneol. The semi-solid preparation includes, but is not limited to, ointments, creams, pastes, eye ointments, gels, and suppositories.

[0125] More preferably, the semi-solid formulation is a gel.

[0126] More preferably, in step S2, the amount of crude drug per 1g or 1ml of the product obtained in step S1 is 0.25g / ml to 1.25g / ml.

[0127] More preferably, in step S2, the amount of crude drug in each 1g or 1ml of the product obtained in step S1 is 1.25g / ml.

[0128] More preferably, in step S2, Glauber's salt, the product obtained in step S1 and the matrix are first reacted thoroughly until they swell completely, and the resulting reactants are then thoroughly mixed with borneol.

[0129] More preferably, in step S2, the borneol microemulsion is obtained by fully reacting borneol powder, propylene glycol, polyoxyethylene 40 hydrogenated castor oil, isopropyl palmitate, 5 w / v % ethylparaben ethanol solution, and water in a mass-volume percentage ratio of (3-4) g: (3-4) ml: (6-7) g: (1-2) ml: (1-2) ml: (3-4) ml.

[0130] More preferably, in step S2, the borneol microemulsion is obtained by fully reacting borneol powder, propylene glycol, polyoxyethylene 40 hydrogenated castor oil, isopropyl palmitate, and 5 w / v % ethylparaben ethanol solution in a mass-volume percentage of 3.4 g: 3.4 ml: 6.7 g: 1.1 ml: 1.1 ml: 3.5 ml.

[0131] More preferably, in step S2, the matrix is ​​a water-soluble matrix.

[0132] More preferably, in step S2, the water-soluble matrix is ​​hydroxyethyl cellulose.

[0133] More preferably, in step S2, the final concentration of the hydroxyethyl cellulose is 0.5 wt% to 2 wt%.

[0134] Most preferably, in step S2, the final concentration of the hydroxyethyl cellulose is 1.5 wt%.

[0135] More preferably, the topical drug further includes a transdermal penetration enhancer, then the preparation method further includes the following step: S3. Thoroughly mix the product obtained in step S2 with the transdermal penetration enhancer.

[0136] More preferably, in step S3, the transdermal penetration enhancer is any one of azone, oleic acid, isopropyl myristate, and propylene glycol.

[0137] In a further preferred embodiment, in step S3, the transdermal penetration enhancer is propylene glycol.

[0138] More preferably, in step S3, the final concentration of propylene glycol is 2wt% to 7wt%.

[0139] Most preferably, in step S3, the final concentration of propylene glycol is 5 wt%.

[0140] Preferably, if the topical medication is a liquid preparation, then in step S1, the traditional Chinese medicine composition is treated by percolation. The liquid preparation includes, but is not limited to, ointments, pour-over solutions, lotions, tinctures, and liniments.

[0141] More preferably, the liquid preparation is a tincture or liniment.

[0142] More preferably, in step S2, the amount of crude drug per 1g or 1ml of the product obtained in step S1 is 0.1g / ml to 1.0g / ml.

[0143] More preferably, in step S2, the borneol is first thoroughly mixed with the product obtained in step S1, and the resulting mixture is then thoroughly mixed with the Glauber's salt.

[0144] More preferably, in step S2, the borneol powder is first thoroughly mixed with the product obtained in step S1, and the resulting mixture is then thoroughly mixed with the sodium sulfate powder.

[0145] More preferably, step S2 further includes: adjusting the alcohol content of the product obtained in step S2 to 40 v / v% to 60 v / v.

[0146] More preferably, step S2 further includes: adjusting the alcohol content of the product obtained in step S2 to 50 v / v.

[0147] Compared with the prior art, the present invention has the following beneficial effects:

[0148] This invention provides a novel traditional Chinese medicine formula for pain treatment, and a topical traditional Chinese medicine preparation based thereon, which has excellent effects such as good analgesia, strong skin penetration and good safety, is easy to use and meets the needs of clinical medication. Attached Figure Description

[0149] Figure 1 The results are characteristic chromatograms of the gel test solution detected by HPLC at a wavelength of 254 nm. S1 is sample I gel, and S2 is sample II gel. Peaks 1, 5, 10, 11, 12, 13, and 14 are the chromatographic peaks of berberine hydrochloride, paeonol, aloe-emodin, rhein, emodin, and chrysophanol, respectively. Peaks 2, 3, 4, 6, 7, 8, and 9 are characteristic peaks of unknown compounds.

[0150] Figure 2The results are characteristic chromatograms of the gel test solution detected by HPLC at a wavelength of 284 nm. S1 is sample I gel, and S2 is sample II gel. Peaks 1, 5, 10, 11, 12, 13, and 14 are the chromatographic peaks of berberine hydrochloride, paeonol, aloe-emodin, rhein, emodin, and chrysophanol, respectively. Peaks 2, 3, 4, 6, 7, 8, and 9 are characteristic peaks of unknown compounds.

[0151] Figure 3 Images of the appearance of Vicon gels prepared with different matrices; A is based on hydroxyethyl cellulose; B is based on carbomer.

[0152] Figure 4 Transdermal diffusion curves of paeonol in Vicon gels prepared with different penetration enhancers.

[0153] Figure 5 Transdermal diffusion curves of berberine hydrochloride in Vicon gels prepared with different penetration enhancers. Detailed Implementation

[0154] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available.

[0155] The instruments used in the following examples include: national standard test sieves (Zhejiang Tiantai Feida Metal Wire Mesh Factory), rotary evaporator (N-1100V, Tokyo Rikagi K.K., Japan), and high performance liquid chromatograph (Agilent 1260 Infinity II, Agilent Technologies, USA).

[0156] The reagents used in the following examples include: polyoxyethylene 40 hydrogenated castor oil (RH-40, CAS#: 23593-75-1, BASF GmbH, Germany), isopropyl palmitate (CAS#: 142-91-6, Shanghai Aladdin Biochemical Technology Co., Ltd.), ethylparaben (CAS#: 120-47-8, Tianjin Yongda Chemical Reagent Co., Ltd.), hydroxyethyl cellulose (HEC) (CAS#: 9004-62-0, ASHLAND INDUSTRIES NEDERLAND BV), carbomer-940 (CAS#: 9007-20-9, Shanghai Maclean Biochemical Technology Co., Ltd.), and diclofenac gel (GSK Consumer Healthcare S.A.).

[0157] The experimental animals used in the following examples were: SPF-grade KM mice, male, weighing 25-30 g, purchased from Zhuhai Bestone Biotechnology Co., Ltd., and the experimental animal quality license number: SCXK(Yue) 2020-0051.

[0158] Example 1 Prescription of Weikang Gel

[0159] The present invention provides a traditional Chinese medicine preparation for analgesia, named "Weikang Gel", and the prescription of its main active ingredients is: in parts by weight, 4-8 parts of Radix Aconiti, 14-18 parts of Flos Rhododendri Mollis, 20-24 parts of Radix Cynanchi Paniculati, 20-24 parts of Radix Et Rhizoma Rhei, 14-18 parts of Cortex Phellodendri, 10-12 parts of Natrii Sulfas, and 2-4 parts of Borneolum Syntheticum.

[0160] The following provides 3 specific prescriptions for the establishment of the extraction process and the forming process of Weikang Gel below:

[0161] Prescription 1: In parts by weight, 6.8 parts of Radix Aconiti, 16.8 parts of Flos Rhododendri Mollis, 22.5 parts of Radix Cynanchi Paniculati, 22.5 parts of Radix Et Rhizoma Rhei, 16.8 parts of Cortex Phellodendri, 11.2 parts of Natrii Sulfas, and 3.4 parts of Borneolum Syntheticum;

[0162] Prescription 2: In parts by weight, 4 parts of Radix Aconiti, 14 parts of Flos Rhododendri Mollis, 20 parts of Radix Cynanchi Paniculati, 20 parts of Radix Et Rhizoma Rhei, 14 parts of Cortex Phellodendri, 10 parts of Natrii Sulfas, and 2 parts of Borneolum Syntheticum;

[0163] Prescription 3: In parts by weight, 8 parts of Radix Aconiti, 18 parts of Flos Rhododendri Mollis, 24 parts of Radix Cynanchi Paniculati, 24 parts of Radix Et Rhizoma Rhei, 18 parts of Cortex Phellodendri, 12 parts of Natrii Sulfas, and 4 parts of Borneolum Syntheticum.

[0164] Example 2 Establishment of the Extraction Process of Weikang Gel

[0165] I. Determination of the Extraction Process Route

[0166] The Radix Aconiti, Flos Rhododendri Mollis, Radix Cynanchi Paniculati, Radix Et Rhizoma Rhei, and Cortex Phellodendri in the traditional Chinese medicine composition described in Example 1 were extracted by water decoction method and dilute ethanol percolation method respectively, and the extraction process route was determined by acetic acid writhing test combined with HPLC characteristic fingerprint and retention rate of index components.

[0167] (1) Water Decoction Method

[0168] 1. Weighing of medicinal materials: According to Prescription 1 in Example 1, weigh the prescribed amounts of Radix Aconiti slices, Flos Rhododendri Mollis slices, Radix Cynanchi Paniculati slices, Radix Et Rhizoma Rhei slices, and Cortex Phellodendri slices.

[0169] 2. Extraction (decoction with water): First, decoct Radix Aconiti with water for 2 hours, and the amount of water added is 8 times the total weight of the above five medicinal materials by volume. Then, decoct with Flos Rhododendri Mollis, Radix Cynanchi Paniculati, Radix Et Rhizoma Rhei, and Cortex Phellodendri three times, and the amounts of water added are 8, 6, and 6 times the total weight of the five medicinal materials by volume in sequence. Decoct three times in total, each time for 1 hour, filter, and combine the decoction.

[0170] 3. Concentration: The obtained medicinal liquid was placed in a rotary evaporator and concentrated under reduced pressure at 60℃ and a vacuum degree of -0.06MPa to obtain an extract with a crude drug content of 1g / ml.

[0171] 4. Molding: Filter the extract while hot, add the prescribed amount of fine Glauber's salt powder (which can pass through a No. 5 sieve and contains no less than 95% that can pass through a No. 6 sieve) and 5.6g of glycerol to the filtrate to dissolve it, add 1.5g of hydroxyethyl cellulose in small amounts several times, stir quickly and evenly, cool to room temperature to obtain a high dose of Sample I gel (crude drug amount is 1.0g / g).

[0172] The only difference in the above method is that in step 3, the extract with a crude drug content of 0.5 g / ml is obtained by vacuum concentration, which is to prepare a medium dose of sample I gel (crude drug content of 0.5 g / g); the extract with a crude drug content of 0.25 g / ml is obtained by vacuum concentration, which is to prepare a low dose of sample I gel (crude drug content of 0.25 g / g).

[0173] (2) Dilute ethanol percolation method

[0174] 1. Weighing of medicinal materials: The five herbs, namely Aconitum carmichaelii, Rhododendron molle, Cynanchum paniculatum, Rheum palmatum, and Phellodendron chinense, are crushed and passed through a No. 2 sieve to obtain powder of each herb; according to the prescription in Example 1, weigh the above five powders.

[0175] 2. Extraction (percolation): Soak the five-ingredient powder in 60 v / v% ethanol for 24 hours. The amount of 60 v / v% ethanol used is 1 volume of the total weight of the five-ingredient medicinal materials. Then, percolate with 8 volumes of 60 v / v% ethanol (percolation rate is 9 ml / min / kg) and collect the percolate.

[0176] 3. Concentration: The concentration method is the same as that of the "water decoction method".

[0177] 4. Shaping: The shaping method is the same as that of the "water decoction method".

[0178] High-dose Sample II gel (crude drug content of 1.0 g / g), medium-dose Sample II gel (crude drug content of 0.5 g / g), and low-dose Sample II gel (crude drug content of 0.25 g / g) were prepared.

[0179] (3) Acetic acid writhing test

[0180] 1. Feeding and grouping

[0181] Eighty KM mice were acclimatized for 5 days, and their abdominal hair was removed 12 hours before the experiment using an 8% sodium sulfide aqueous solution. The mice were then randomly divided into 8 groups based on body weight using a block randomization method (KM mice were sorted by weight from smallest to largest, assigned random numbers, and divided into blocks of 10 mice each; mice within each block were also randomly numbered, with mice of the same number in different blocks belonging to the same group). These groups were designated as the model group, positive drug group, high-dose sample I gel group, medium-dose sample I gel group, low-dose sample I gel group, high-dose sample II gel group, medium-dose sample II gel group, and low-dose sample II gel group.

[0182] Model group: Each mouse was given a blank matrix (i.e., HEC dissolved in distilled water and stirred until gelled, with a final HEC concentration of 1.5 wt%) at 0.2 g / 20 g (drug dosage / body weight); Positive drug group: Each mouse was given diclofenac gel at 5 mg / 20 g; High-dose sample I gel group: Each mouse was given a high dose of sample I gel (crude drug content of 1.0 g / g) at 0.2 g / 20 g; Medium-dose sample I gel group: Each mouse was given a medium dose of sample I gel (crude drug content of 0.5 g / g) at 0.2 g / 20 g; Sample Sample I gel low-dose group: Each mouse was given a low dose of Sample I gel (0.2g / 20g crude drug content 0.25g / g); Sample II gel high-dose group: Each mouse was given a high dose of Sample II gel (0.2g / 20g crude drug content 1.0g / g); Sample II gel medium-dose group: Each mouse was given a medium dose of Sample II gel (0.2g / 20g crude drug content 0.5g / g); Sample II gel low-dose group: Each mouse was given a low dose of Sample II gel (0.2g / 20g crude drug content 0.25g / g).

[0183] 2. Torsional response detection

[0184] Mice in each group were restrained using a self-made restraint device. One hour later, each mouse was intraperitoneally injected with 0.6v / v% acetic acid solution at a dose of 0.2ml / 20g (dose / body weight). The number of writhing responses in the mice within 30 minutes was recorded (one writhing response was defined as the appearance of abdominal concavity, trunk and hind limb extension, and hip elevation).

[0185] 3. Test Results

[0186] The test results are shown in Table 1. There were no statistically significant differences between the dosage groups of Sample I gel and Sample II gel. Compared with the model group, the difference in the number of writhing movements in mice in the medium and high dose groups of Sample I gel and Sample II gel was significantly reduced. There were no significant differences in the number of writhing movements in mice in the dosage groups of Sample I gel and Sample II gel compared with the positive drug group. This indicates that both extraction processes used to prepare the Vicon gel can alleviate the writhing response and reduce pain in mice, with efficacy comparable to existing analgesic gels. At the same dosage, the number of writhing movements in mice treated with Sample II gel was less than that treated with Sample I gel, indicating that Sample II gel has a better analgesic effect. This suggests that the dilute ethanol percolation method is more conducive to extracting the effective analgesic components of the medicinal materials.

[0187] Table 1. Effects of Sample I gel and Sample II gel on acetic acid-induced writhing response in mice. n=10)

[0188]

[0189] Note: * indicates a significant difference compared to the model group (P<0.05); · indicates no significant difference compared to the positive drug group (P>0.05).

[0190] (4) HPLC characteristic chromatograms and determination of the retention rate of index components

[0191] 1. Preparation of the test solution

[0192] Gel test solution: Accurately weigh 2.5g each of sample I gel (crude drug content 1.0g / g) and sample II gel (crude drug content 1.0g / g), place them in a 25ml volumetric flask, add methanol to dissolve and dilute to the mark, weigh, sonicate (power 250W frequency 40kHz) for 30 minutes, cool, weigh again, make up the lost weight with methanol, shake well, filter, and collect the filtrate to obtain the test solution.

[0193] Xu Changqing test solution: Accurately weigh 0.5g of Xu Changqing slices, place them in a round-bottom flask, accurately add 50ml of methanol, weigh the solution, heat under reflux for 30 minutes, cool, weigh the solution again, replenish the lost weight with methanol, shake well, filter, and collect the filtrate.

[0194] Rhubarb test solution: Accurately weigh 1.0g of rhubarb slices, place them in a round-bottom flask, accurately add 50ml of methanol, weigh the solution, heat under reflux for 1 hour, cool, weigh the solution again, replenish the lost weight with methanol, shake well, filter, and collect the filtrate.

[0195] Phellodendron bark test solution: Accurately weigh 1.0g of Phellodendron bark slices, place them in a round-bottom flask, accurately add 50ml of methanol, weigh the solution, heat under reflux for 30 minutes, cool, weigh the solution again, replenish the lost weight with methanol, shake well, filter, and collect the filtrate.

[0196] 2. HPLC chromatographic detection

[0197] Chromatographic conditions: A Kromasil C18 column (4.6 mm inner diameter × 250 mm column length, 5 μm particle size) was used; acetonitrile was used as mobile phase A, and 0.1 v / v% phosphoric acid solution was used as mobile phase B. The gradient elution program is shown in Table 2. Detection wavelengths: 254 nm for paeonol, aloe-emodin, rhein, chrysophanol, and rhein; 284 nm for berberine hydrochloride and berberine hydrochloride. Flow rate: 1 ml / min; column temperature: 30 ℃; injection volume: 10 μl.

[0198] Table 2 HPLC gradient elution program

[0199]

[0200] The results of the methodological evaluations of linearity, specificity, precision, repeatability, stability, and spiking recovery have shown that the above chromatographic conditions and methods are stable and feasible, and the detection results are reliable.

[0201] The chromatographic conditions described above were used to determine the gel test solution and the test solutions of each medicinal material, and the retention rates of seven indicator components (paeonol in Cynanchum paniculatum, aloe-emodin, rhein, emodin, and chrysophanol in Rheum palmatum, and berberine hydrochloride and berberine hydrochloride in Phellodendron chinense) were calculated. The retention rate was calculated using the formula: Retention rate of indicator component = Content of indicator component in gel / Content of indicator component in medicinal material * 100%.

[0202] 3. Test Results

[0203] The measured feature maps are as follows Figures 1-2 As shown, the variety and peak area of ​​the indicator components in Sample II gel are superior to those in Sample I gel. Seven common peaks exist between Sample I and Sample II gels, namely peaks 1, 2, 3, 5, 6, 7, and 8. The peak areas of these common peaks in Sample I gel are all smaller than those in Sample II gel. In addition to the aforementioned common peaks, peaks 4, 9, 10, 11, 12, 13, and 14 are also visible in the characteristic chromatogram of Sample II gel. This indicates that the dilute ethanol percolation method extracts a richer variety of effective components compared to the water decoction method.

[0204] The retention rates of the indicator components in Sample I and Sample II gels are shown in Table 3. The retention rates of the indicator components differed significantly between the two gels. Sample II gel retained paeonol, aloe-emodin, rhein, emodin, chrysophanol, berberine hydrochloride, and berberine hydrochloride, with retention rates of 55.2%, 98.03%, 73.13%, 41.11%, 21.66%, 27.79%, and 76.56%, respectively. In contrast, Sample I gel only contained berberine hydrochloride and berberine hydrochloride, with retention rates of only 5.40% and 27.38%, respectively; the other five indicator components were not detected. This indicates that the dilute ethanol percolation method extracted more effective components than the water decoction method in Sample II gel.

[0205] Table 3 Retention rates of indicator components in Sample I gel and Sample II gel

[0206]

[0207]

[0208] In summary, the two extraction methods for preparing Vicon gel showed significant differences in the types of characteristic peaks, peak areas, and retention rates of key components. The dilute ethanol percolation method demonstrated significantly better extraction performance than the water decoction method. Therefore, the dilute ethanol percolation method will be used for subsequent preparation of Vicon gel.

[0209] II. Factors Affecting the Extraction Process

[0210] (1) The effect of the particle size of medicinal slices on the percolation effect

[0211] 1. Crushing of medicinal slices

[0212] Weigh out appropriate amounts of Aconitum carmichaelii slices, Rhododendron molle slices, Cynanchum paniculatum slices, Rheum palmatum slices, and Phellodendron chinense slices, and grind them into coarse powder (which can all pass through a No. 2 sieve, but contains no more than 40% that can pass through a No. 4 sieve), medium powder (which can all pass through a No. 4 sieve, but contains no more than 60% that can pass through a No. 5 sieve), and fine powder (which can all pass through a No. 5 sieve and contains no less than 95% that can pass through a No. 6 sieve).

[0213] 2. Preparation of percolate

[0214] Preparation of coarse powder percolate: Weigh out 6.8g (6.8072g) of coarse powder of Aconitum carmichaelii, 16.8g (16.8012g) of coarse powder of Rhododendron molle, 22.5g (22.5035g) of coarse powder of Cynanchum paniculatum, 22.5g (22.5079g) of coarse powder of Rheum palmatum, and 16.8g (16.8029g) of coarse powder of Phellodendron chinense, totaling 85.4g, according to the prescription ratio. The percolation method is as follows: Soak all the coarse powder of the five herbs in 60v / v% ethanol at room temperature for 12 hours. Then, percolate with 60v / v% ethanol as a solvent (percolation rate is 9ml / min / kg). Collect the percolate, put it in a 500ml volumetric flask, add 60v / v% ethanol to the mark, shake well, and set aside.

[0215] Preparation of the percolation solution of the medium-sized powder: Weigh out 6.8g (6.8094g) of fine powder of Aconitum carmichaelii, 16.8g (16.8024g) of fine powder of Rhododendron molle, 22.5g (22.5047g) of fine powder of Cynanchum paniculatum, 22.5g (22.5066g) of fine powder of Rheum palmatum, and 16.8g (16.8024g) of fine powder of Phellodendron chinense according to the prescription ratio, for a total of 85.4g; The percolation method is the same as that for the percolation solution of the coarse powder.

[0216] Preparation of the fine powder percolate: Weigh out 6.8g (6.8094g) of fine aconite powder, 16.8g (16.8024g) of fine rhododendron powder, 22.5g (22.5047g) of fine cynanchum powder, 22.5g (22.5066g) of fine rhubarb powder, and 16.8g (16.8024g) of fine phellodendron powder according to the prescription ratio, for a total of 85.4g; the percolation method is the same as that for the coarse powder percolate.

[0217] 3. Determination of ointment yield

[0218] Accurately pipette 30 ml each of the coarse powder percolate, the medium powder percolate, and the fine powder percolate (equivalent to 5.1240 g of raw medicinal material), place them in an evaporating dish that has been dried to constant weight, evaporate to dryness in a water bath, dry to constant weight in a hot air oven at 120°C, cool in a desiccator for 30 minutes, accurately weigh, and calculate the yield of the extract.

[0219] 4. Determination of the retention rate of indicator components

[0220] Preparation of percolate test solution: Accurately pipette 5 ml each of coarse powder percolate, medium powder percolate and fine powder percolate, make two parallel portions, place each portion in a 10 ml volumetric flask, add 60 v / v% ethanol to the mark, filter through a microporous membrane (0.22 μm) to obtain the test solution.

[0221] Accurately pipette 5 μl of coarse powder percolate test solution, 4 μl each of medium powder percolate test solution and fine powder percolate test solution, and perform detection according to the "HPLC chromatographic detection" method of this embodiment, and calculate the retention rate of the 7 index components.

[0222] 5. Test Results

[0223] Table 4. Statistical results of the yield of percolate from different particle sizes

[0224]

[0225] As shown in Table 4, the yield of extract from fine powdered medicinal slices is higher than that from coarse powdered and medium powdered medicinal slices.

[0226] Table 5. Statistical results of retention rates of percolate with different particle sizes

[0227]

[0228]

[0229] As shown in Table 5, the retention rates of most index components in medium-sized powder and fine powder are not significantly different. Considering the production efficiency and cost of the percolation process, medium-sized powder was selected as the particle size of medicinal slices with the best percolation effect for subsequent experiments.

[0230] (2) Effects of immersion time, ethanol concentration, ethanol dosage and percolation rate on percolation effect

[0231] 1. Experimental Design

[0232] Based on the medium particle size of the pulverized medicinal slices, the yield of the ointment and the retention rates of paeonol, rhein, berberine hydrochloride and berberine hydrochloride were used as evaluation indicators. An orthogonal experiment was conducted to evaluate four factors: soaking time (A, h), ethanol concentration (B, v / v%), ethanol dosage (C, times), and percolation rate (D, ml / min / kg). Nine experimental groups were designed as shown in Table 6.

[0233] Table 6. Four-Factor, Three-Level Design

[0234]

[0235] 2. Preparation of the test solution

[0236] Weigh out 3.4g of Aconitum carmichaelii powder, 8.4g of Rhododendron molle powder, 11.25g of Cynanchum paniculatum powder, 11.25g of Rheum palmatum powder, and 8.4g of Phellodendron chinense powder according to the prescription ratio, totaling 42.7g. Perform percolation according to the "Percolation Method" in "2. Preparation of Percolation Solution" of this embodiment, combined with the experimental groups shown in Table 7. Collect the percolation solution, place it in a 500ml volumetric flask, add the corresponding solvent to the mark, shake well, and refrigerate for later use.

[0237] Table 7 Experimental Groups

[0238]

[0239] 3. Determination of ointment yield

[0240] 59 ml of percolate from each of the nine experimental groups (equivalent to 5.0386 g of raw medicinal material) was precisely pipetted into an evaporating dish that had been dried to constant weight. The mixture was evaporated to dryness in a water bath, dried to constant weight in a hot air oven at 120°C, cooled in a desiccator for 30 minutes, and the weight was accurately measured. The yield of the extract was then calculated.

[0241] 4. Determination of the retention rate of indicator components

[0242] Preparation of test solutions for the experimental groups: Accurately pipette 5 ml of the percolate obtained from each of the 9 experimental groups, make 2 parallel portions, and filter them through a microporous membrane (0.22 μm) to obtain the test solutions.

[0243] Accurately pipette 4 μl of the coarse powder percolate test solution, 4 μl each of the medium powder percolate test solution and the fine powder percolate test solution, and perform the detection according to the "HPLC chromatographic detection" method of this embodiment, and calculate the retention rate of the four index components.

[0244] 5. Test Results

[0245] Table 8 Statistical results of orthogonal experiments

[0246]

[0247] Note: Based on previous experiments, the extraction rate of rhein in experiments A1B1C1D1, A2B1C2D3, and A3B1C3D2 was too low to calculate the retention rate. Therefore, the extracts were concentrated. 20 ml of the percolate from experiments A1B1C1D1, A2B1C2D3, and A3B1C3D2 was taken, the solvent was recovered under reduced pressure until dry, the residue was dissolved in the corresponding solvent, transferred to a 5 ml volumetric flask, and then diluted to the mark with the corresponding solvent.

[0248] Based on the results in Table 8, intuitive analysis and analysis of variance were performed, and the results are as follows:

[0249] The results of the intuitive analysis show that, based on the range, with the yield rate as the evaluation index, the order of influence of each factor is B→C→A→D, and the differences between the levels of each factor are not significant; with the paeonol retention rate as the index, the order of influence of each factor on this index is B→A→C→D; with the rhein retention rate as the index, the order of influence of each factor on this index component is B→C→D→A; with the berberine hydrochloride retention rate as the index, the order of influence of each factor on this index component is B→C→D→A.

[0250] Analysis of variance showed that ethanol concentration was the most important factor affecting the percolation effect of paeonol, rhein, berberine hydrochloride, and berberine hydrochloride, followed by soaking time and ethanol dosage. For the percolation effect of paeonol, rhein, berberine hydrochloride, and berberine hydrochloride, level 3 > level 2 > level 1 for ethanol concentration, thus determining the optimal ethanol concentration as level 3 (80 v / v% ethanol). Level 2 > level 3 > level 1 for ethanol dosage, thus determining the optimal ethanol dosage as level 2 (6 times). Level 3 > level 2 > level 1 for soaking time. Repeated testing proved that no soaking and soaking for 24 hours had no significant effect on the retention rates of paeonol, rhein, berberine hydrochloride, and berberine hydrochloride, thus determining the optimal soaking time as 0 hours. There was no significant difference in percolation rate among levels 1, 2, and 3. Since a faster percolation rate is beneficial to improving production efficiency, the optimal percolation rate was determined to be 9 ml / min / kg.

[0251] In summary, the percolation conditions were determined as follows: without soaking the herbal powder, directly add 6 times the total weight of the five herbs by volume of 80% ethanol for percolation, and the percolation rate is 9 ml / min / kg.

[0252] (3) Effects of temperature and final volume on concentration effect

[0253] 1. Preparation of percolate

[0254] According to prescription 1 of Example 1, weigh out the following amounts: 6.8g (6.8072g) of Aconitum carmichaelii powder, 16.8g (16.8012g) of Rhododendron molle powder, 22.5g (22.5035g) of Cynanchum paniculatum powder, 22.5g (22.5079g) of Rheum palmatum powder, and 16.8g (16.8029g) of Phellodendron chinense powder, for a total of 85.4g.

[0255] According to the "Percolation Method" in "2. Preparation of Percolation Solution" of this embodiment, combined with the optimal percolation conditions for the optimal particle size of the medicinal slices determined in the previous step, the percolation solution is prepared.

[0256] 2. Reduced pressure concentration

[0257] Following the method described in "I. Determination of Extraction Process Route" of this embodiment, "3. Concentration", the 500ml percolate was concentrated under reduced pressure to a final volume of 80ml, then transferred to a 500ml volumetric flask, 80% ethanol was added to the mark, and the mixture was shaken well. The temperature was adjusted to 60℃, 70℃, or 80℃. When the temperature was 70℃, the final volume of the concentration was further adjusted to 40ml or 60ml, and the mixture was transferred to a 500ml volumetric flask, 80% ethanol was added to the mark, and the mixture was shaken well. The concentrated solutions obtained under different concentration conditions were collected.

[0258] 3. Determination of the retention rate of indicator components

[0259] Preparation of concentrated test solution: Accurately pipette 5 ml of the obtained concentrated solution into two parallel portions, place each portion into a 10 ml volumetric flask, add 80 v / v% ethanol to the mark, and filter through a microporous membrane (0.22 μm) to obtain the solution.

[0260] Accurately pipette 3 μl of the concentrated test solution and perform the detection according to the "HPLC chromatographic detection" method of this embodiment, and calculate the retention rate of the four indicator components.

[0261] 4. Test Results

[0262] Table 9. Statistical results of retention rates of various index components under different vacuum concentration conditions. (Paeonol)

[0263]

[0264] As shown in Table 9, at the same final volume, compared with 60℃ and 80℃, the retention rates of the four index components in the product obtained by vacuum concentration at 70℃ were all higher. Among them, rhein, berberine hydrochloride, and berberine hydrochloride showed almost no loss compared with those before concentration. When concentrating at 70℃, compared with a final volume of 80ml, the retention rates of the four index components in the product obtained by vacuum concentration at a final volume of 40ml or 60ml were similar, with berberine hydrochloride and berberine hydrochloride showing higher retention rates. Considering production efficiency, the optimal vacuum concentration condition was determined to be vacuum concentration at 70℃ to a final volume of 60ml, which yielded an extract with a crude drug content of 1.4g / ml.

[0265] Example 3: Effect of matrix on Vicon gel formation

[0266] Common water-soluble matrices include polyethylene glycol, carbomer, sodium alginate, sodium carboxymethyl cellulose, and hydroxyethyl cellulose (HEC). These matrices are easy to wash off, release drugs quickly, and are non-irritating to the skin and mucous membranes. However, gels prepared using carboxymethyl cellulose, polyethylene glycol, and sodium alginate as matrices generally suffer from poor spreadability, susceptibility to mold growth, and crusting. This invention selects hydroxyethyl cellulose and carbomer, which have relatively superior performance, as candidate matrices. The matrices used for preparing Vicon gel were determined based on molding feasibility, appearance, spreadability, and viscosity.

[0267] I. Gel Preparation

[0268] (1) Preparation of concentrated drug solution

[0269] 1. Weighing of medicinal materials: According to prescription 1 in Example 1, weigh 6.8g (6.8072g) of Aconitum carmichaelii powder, 16.8g (16.8012g) of Rhododendron molle powder, 22.5g (22.5035g) of Cynanchum paniculatum powder, 22.5g (22.5079g) of Rheum palmatum powder and 16.8g (16.8029g) of Phellodendron chinense powder, for a total of 85.4g.

[0270] 2. Extraction (percolation): Percolate with 80% ethanol at a rate of 9 ml / min / kg, using 6 times the total weight of the above five medicinal materials. Collect the percolate.

[0271] 3. Concentration: Place the percolate in a 500ml volumetric flask, add 80v / v% ethanol to the mark, shake well, and concentrate under reduced pressure in a rotary evaporator at 70℃ and a vacuum degree of 0.08MPa~0.09MPa to a final volume of 60ml, thus obtaining an extract with a crude drug content of 1.25g / ml.

[0272] 4. Dissolving Glauber's salt: Filter the extract while it is still hot; weigh 11.2g of the prescribed amount of fine Glauber's salt powder, add it to the filtrate of the extract, and dissolve it completely to obtain a concentrated medicinal solution.

[0273] Prepare two portions of concentrated medicine solution in parallel according to steps 1-4 above, and set aside for later use.

[0274] (2) Preparation of borneol microemulsion

[0275] Weigh 3.4g of the prescribed amount of borneol powder, add 3.4ml of propylene glycol (as a solvent for fat-soluble borneol), and dissolve thoroughly in a magnetic stirrer (40℃, 300r / min). Add 6.7g of polyoxyethylene 40 hydrogenated castor oil (RH-40) (as a co-solvent), 1.1ml of isopropyl palmitate (as a surfactant), and 1.1ml of 5w / v% ethylparaben ethanol solution (as a preservative). Stir until homogeneous, and while stirring, add 3.5ml of water until clear. Prepare two parallel borneol microemulsions for later use.

[0276] (3) Gel formation

[0277] 1. Using HEC as a matrix: Weigh 1.5g of HEC and add it to 1 part of concentrated drug solution in small amounts several times. Place the solution in a magnetic stirrer and stir rapidly (600r / min) until it swells completely. Then add 1 part of borneol microemulsion while stirring rapidly (600r / min) until it is mixed evenly. Add distilled water to bring the weight to 100g and continue stirring (600r / min) until homogeneous. This is the HEC gel (final HEC concentration is 1.5wt%).

[0278] 2. Using carbomer as a matrix: Weigh 1.5g of carbomer-940 and add it in portions to 20ml of distilled water. Place the mixture in a magnetic stirrer and stir rapidly until it is evenly dispersed. Let it stand to allow it to swell fully. Then add 2g of triethanolamine dropwise to make it into a gel state, thus obtaining carbomer gel. Slowly add 1 part of concentrated drug solution and stir rapidly (600r / min) until it is evenly mixed. Then add 1 part of borneol microemulsion while stirring rapidly (600r / min) until it is evenly mixed. Add distilled water to bring the weight to 100g and continue stirring (600r / min) until homogeneous. This is the carbomer gel.

[0279] II. Evaluation of Molding Effect

[0280] (1) Evaluation Method

[0281] The appearance of gels with two different matrices was observed visually to evaluate their molding feasibility, appearance, and spreadability. A rotational viscometer was used, with the rotor selected according to the required viscosity, at a temperature of 25°C and a rotation speed of 6–60 r / min. -1 The dynamic viscosity of each gel was measured three times for each gel sample.

[0282] (2) Evaluation Results

[0283] like Figure 3 As shown in A, the HEC gel is a brownish-yellow semi-solid with a uniform color, no bubbles, a glossy appearance, and can be molded and adhered to a stirring rod; as shown in Figure A. Figure 3 As shown in B, the carbomer gel is a brownish-yellow viscous liquid that cannot be formed and does not adhere to the stirring rod. Evaluation showed that the HEC gel exhibited good uniformity, a fine texture, was easy to spread, showed slight resistance, and had a moderate viscosity (4242.33 mPa·s); the HEC gel showed poor uniformity, exhibited stratification, was difficult to spread, and had a lower viscosity (1225.67 mPa·s). This indicates that HEC is more conducive to gel formation as a matrix.

[0284] The thickening mechanism of carbomer is usually achieved by neutralizing carbomer into a salt, causing the coiled molecules to unwind due to electrostatic repulsion. Therefore, carbomer gels are extremely sensitive to electrolytes, which can reduce their viscosity. However, the Glauber's salt in the Vicon gel formulation contains ionizable cations and quaternary ammonium cations. Experiments showed that omitting Glauber's salt improved the gel's forming effect, but it was still inferior to HEC gel. Therefore, HEC was chosen as the matrix for preparing Vicon gel.

[0285] Example 4: Effect of transdermal penetration enhancer on the efficacy of Vicon gel

[0286] I. Preparation of the medicinal solution

[0287] (1) Weighing of medicinal materials

[0288] According to prescription 1 in Example 1, weigh out 13.6g of Aconitum carmichaelii powder, 33.6g of Rhododendron molle powder, 45g of Cynanchum paniculatum powder, 45g of Rheum palmatum powder, and 33.6g of Phellodendron chinense powder, for a total of 170.8g.

[0289] (2) Extraction (percolation)

[0290] Percolation was performed using 6 times the total weight of the above five medicinal materials in 80% v / v ethanol at a rate of 9 ml / min / kg, and the percolate was collected.

[0291] (3) Concentration

[0292] The percolate was placed in a 1000ml volumetric flask, 80v / v% ethanol was added to the mark, and the mixture was shaken well. The mixture was then concentrated under reduced pressure in a rotary evaporator at 70℃ and a vacuum of -0.06MPa to a final volume of 60ml, thus obtaining an extract with a crude drug content of 2.85g / ml.

[0293] (4) Dissolving Glauber's salt

[0294] Filter the extract while it is still hot; weigh 22.4g of fine Glauber's salt powder and add it to the filtrate of the extract. After it is fully dissolved, a concentrated medicinal solution is obtained, which is the high-dose medicinal solution (crude drug weight 2.85g / ml).

[0295] (5) Dilution

[0296] Dilute the high-dose drug solution with water to obtain a reserve drug solution (raw drug amount 1g / ml) for preparing the gel.

[0297] II. Preparation of Vicon Gel

[0298] (1) Preparation of borneol microemulsion

[0299] Weigh 3.4g of borneol powder, add 3.4ml of propylene glycol, and dissolve it completely in a magnetic stirrer (40℃, 300r / min). Add 6.7g of polyoxyethylene 40 hydrogenated castor oil (RH-40), 1.1ml of isopropyl palmitate, and 1.1ml of 5w / v% ethylparaben ethanol solution. Stir well, and while stirring, add 3.5ml of water. Stir until clear.

[0300] (2) Gel formation

[0301] Weigh 1.5g of HEC and add it to the prepared drug solution (1g / ml of raw drug) in small amounts several times. Stir rapidly with a magnetic stirrer (600r / min) until it swells completely. Then add the borneol microemulsion while stirring rapidly (600r / min) until it is mixed evenly. Add distilled water to bring the weight to 100g and continue stirring (600r / min) until homogeneous.

[0302] III. Determination of the Acceptable Medium in Transdermal Absorption Tests

[0303] In the in vitro transdermal absorption test, the receiving medium simulates the body fluid under the skin and is required to meet the sink condition. The selection of the receiving medium affects the test results. In this example, the effects of normal saline, ethanol - normal saline (4:6) solution, PEG400 - ethanol - normal saline (1:3:6) solution, and PEG400 - ethanol - normal saline (2:2:6) solution as receiving media on the transdermal absorption of the target components in the gel were investigated.

[0304] (1) Experimental animals

[0305] 36 SPF - grade KM mice, weighing 18 - 22 g, were purchased from the Guangdong Provincial Medical Experimental Animal Center [Experimental Animal Quality License Number: SCXK(Yue)2022 - 0002].

[0306] (2) Preparation of excised mouse skin

[0307] The KM mice were sacrificed by cervical dislocation, and the hair on the abdominal skin was shaved off. Then, a thin layer of non - irritating depilatory ointment was applied, and the remaining hair was cleaned. The mice were placed on a clean transparent glass plate, and the abdominal skin was separated, and the subcutaneous blood vessels, fat layer, and residues were removed. After repeated rinsing with normal saline, the integrity of the skin was checked after washing. The intact excised mouse skin was obtained as the permeation barrier. After cutting the excised mouse skin into appropriate shapes and sizes, it was stored in a - 20°C refrigerator. The test should be carried out within one week. Before the experiment, the mouse skin was thawed, and the skin should be intact and undamaged.

[0308] (3) In vitro transdermal experiment

[0309] The in vitro transdermal experiment device used the LOGAN dry - heating fully automatic transdermal diffusion system SYSTEM 918 - 12. The capacity of the receiving cell was 5 ml, the diameter of the supply cell was 1.5 cm, and the effective diffusion area was 1.7671 cm 2 . During the experiment, the excised mouse skin was first thawed in a 4°C refrigerator, then taken out and placed at room temperature. The skin should be intact and undamaged, washed with normal saline, and the water was blotted dry with filter paper. 12 pieces of excised mouse skin were randomly taken out, and the excised mouse skin was fixed at the lower end of the supply cell with the stratum corneum facing the supply cell. After exhausting the air bubbles, 0.5 g of Weikang gel was applied to the stratum corneum respectively. Normal saline, ethanol - normal saline (4:6) solution, PEG400 - ethanol - normal saline (1:3:6) solution, or PEG400 - ethanol - normal saline (2:2:6) solution was added to the diffusion cell as the receiving medium. In a 37°C constant temperature water bath, it was stirred at a constant speed of 300 r / min. 2 ml of the receiving medium was taken at 2 h, 4 h, 8 h, and 12 h of stirring respectively, and at the same time, an equal amount of the same - temperature receiving medium was added to the receiving cell and the air bubbles were removed.

[0310] The collected receiving solution was filtered through a 0.22 μm microporous membrane, and the relative peak areas of the characteristic spectra of paeonol, rhein, and berberine hydrochloride were determined according to the "HPLC chromatographic detection" method in Example 3.

[0311] Table 10. Relative peak area results of characteristic spectra of different receiving media.

[0312]

[0313]

[0314] As shown in Table 10, under the same crude drug concentration (1.0 g crude drug / g), the same transdermal time (12 h), and the same injection volume (40 μl), among the 13 chromatographic peaks identified by the gel test solution, only peaks 10 and 11 were present in the physiological saline receiving solution. Adding different proportions of PEG400 and ethanol could promote the transdermal absorption of the components. For example, when PEG400-ethanol-physiological saline (2:2:6) was used as the receiving medium, the number of transdermal components increased to 6, with a total relative peak area of ​​0.3691; PEG400-ethanol-physiological saline... When water (1:3:6) was used as the transdermal medium, eight components were able to penetrate the skin, with a total relative peak area of ​​0.6718. When ethanol-saline (4:6) was used as the transdermal medium, ten components were able to penetrate the skin, increasing the total relative peak area to 1.3088. However, the ethanol content must be considered when selecting a suitable transdermal medium. Although the ethanol-saline (4:6) medium showed better transdermal component diversity and total relative peak area compared to other groups, its high ethanol content could severely disrupt the physiological state of the mouse skin. Therefore, considering all factors, PEG400-ethanol-saline (1:3:6) was chosen as the transdermal medium.

[0315] IV. The Influence of Transdermal Permeation Enhancers on Transdermal Absorption

[0316] (1) Gel preparation

[0317] HEC gel was prepared using carbomer as a matrix according to the method in Example 3.

[0318] (2) Addition of transdermal penetration enhancers

[0319] Using 1 wt% azone (CAS#:59227-89-3), 3 wt% oleic acid (CAS#:112-80-1), 3% isopropyl myristate (IPM, CAS#:110-27-0), or 5 wt% propylene glycol as transdermal penetration enhancers, 5 g of HEC gel was rapidly mixed with the transdermal penetration enhancer in small batches (600 rpm) until homogeneous. HEC gel without the penetration enhancer served as a blank control.

[0320] (3) In vitro transdermal test

[0321] Referring to the "In vitro transdermal experiment" in "III. Determination of the acceptor medium for transdermal absorption test" of this embodiment, 0.5 g of each of the above-mentioned gels containing different amounts of the permeation enhancer were administered to isolated mouse skin in triplicate. The supply cell was fixed on the acceptor cell, and a PEG400-ethanol-physiological saline (1:3:6) solution was added to the acceptor cell as the acceptor medium. The mixture was stirred at a constant speed of 300 r / min in a 37°C constant temperature water bath. At 2 h, 4 h, 8 h, and 12 h of stirring, 2 ml of the acceptor medium was collected, and an equal volume of acceptor medium at the same temperature was added to the acceptor cell while removing air bubbles. The collected acceptor solution was filtered through a 0.22 μm microporous membrane and analyzed by HPLC.

[0322] Table 11. Relative peak area results of characteristic spectra of the receiving solutions of Vicon gel containing different penetration enhancers.

[0323]

[0324]

[0325] As shown in Table 11, under the same concentration of crude drug (1.0 g crude drug / g), the same transdermal time (12 h), and the same injection volume (40 μl), a total of 13 chromatographic peaks were identified in the Vicon gel test solution. Six components could be detected through the skin, namely peaks 1, 7, 8, 9, 10, and 11. Different penetration enhancers did not affect the types of transdermal components, but the total relative peak areas of the characteristic peaks were different. The total relative peak areas of the transdermal components of Vicon gel containing 1 wt% azone, 3 wt% oleic acid, and 3 wt% isopropyl myristate were all lower than the total relative peak areas of the gel without penetration enhancers, while the total relative peak areas of the transdermal components of 5 wt% propylene glycol gel were greater than those of the gel without penetration enhancers.

[0326] Calculate the cumulative infiltration (Q) at each time point using formulas (1) and (2). n and cumulative transdermal absorption percentage (W%):

[0327] Formula (1):

[0328] Formula (2): W=Q n *A / S;

[0329] In the above formula, C n Vn is the drug concentration in the receiving medium measured at the nth sampling (μg / ml); V0 is the volume of the receiving cell (ml); Cn is the concentration of the drug in the receiving medium. n-1 V represents the drug concentration (μg / ml) in the receiving medium measured during the (n-1)th sampling; i A represents the sampling volume (ml); A represents the effective diffusion area (cm²).2 S represents the mass of the drug in the sample (g).

[0330] Transdermal diffusion curves were plotted with the cumulative transdermal absorption percentage (w%) of paeonol and berberine hydrochloride on the Y-axis and time (h) on the X-axis, respectively. Figure 4 As shown, the cumulative transdermal absorption percentage of paeonol in the Vicon gel containing 5 wt% propylene glycol was higher than that in the Vicon gel containing 1 wt% azone, 3 wt% oleic acid, and 3 wt% IPM. Figure 5 As shown, the cumulative transdermal absorption percentage of berberine hydrochloride in Vicon gel containing 3 wt% IPM is higher than that in Vicon gel containing 5 wt% propylene glycol, 3 wt% oleic acid and 1 wt% azone.

[0331] (3) Determination of skin retention of Vicon gel containing different penetration enhancers

[0332] After the permeation experiment, the skin was removed, the matrix was removed, and the remaining sample was washed with physiological saline. The sample was cut along the edge of the diffusion cell imprint, the moisture was absorbed with filter paper, the sample was shredded, placed in a centrifuge tube, and 5 small steel balls were added. 1 ml of methanol was added, and the sample was sonicated for 5 min. The sample was then centrifuged at 5000 rpm for 10 min. The supernatant was collected and filtered through a 0.22 μm microporous membrane as the sample solution. The sample was then analyzed according to the "HPLC chromatographic detection" method in Example 3, with an injection volume of 25 μl.

[0333] Table 12. Relative peak area results of skin retention of Vicon gel containing different penetration enhancers.

[0334]

[0335]

[0336] As shown in Table 12, under the same concentration of crude drug (1.0 g crude drug / g), the same transdermal time (12 h), and the same injection volume (25 μl), the 13 peaks of the above-mentioned Vicon gel test solution could be detected in the skin residue of different permeation enhancers. The types of components retained in the skin were not significantly affected, but the total relative peak area of ​​the characteristic peaks was different.

[0337] Calculate the skin retention amount (Q) of components in the isolated skin layer. s / μg·cm -2 ):Q S =VC / A, where A is the effective diffusion area, V is the total volume of the skin extract, and C is the mass concentration of the drug in the skin extract. The results are shown in Table 13. The skin retention of different components varies, with berberine hydrochloride and paeonol being significantly higher than rhein.

[0338] Table 13 Results of skin retention of index components in Vicon gel containing different penetration enhancers (n=3)

[0339]

[0340]

[0341] The dermis contains sebaceous glands, hair follicles, and sweat glands, as well as abundant capillaries, lymphatic vessels, and nerves (for pain perception). Drugs penetrate the epidermis into the dermis and subcutaneous tissue to exert local therapeutic effects, such as analgesia; drugs also enter the systemic circulation through the skin's microcirculation to produce systemic effects. Therefore, the skin permeation rate and skin retention rate of paeonol, berberine hydrochloride, and rhein were summed to obtain the total permeation rate, as shown in Table 14. It can be seen that different penetration enhancers have varying effects on the permeation of each indicator component. Although none of the penetration enhancers significantly increased the permeation of paeonol, 3 wt% IPM promoted the transdermal absorption of berberine hydrochloride. The skin retention results showed that 1 wt% azone, 3 wt% IPM, and 5 wt% propylene glycol all increased the retention of the indicator components in the skin.

[0342] Table 14 Results of total permeability of gel index components containing different permeation enhancers ( n=3)

[0343]

[0344] Considering the total permeability of all components, the gel containing 5 wt% propylene glycol had a higher total permeability than the blank group and was superior to other groups. Therefore, propylene glycol was selected as the transdermal absorption enhancer.

[0345] The effect of different concentrations of propylene glycol on the permeability of Vicon gel was further investigated. The results showed that Vicon gel containing 2 wt%, 5 wt%, and 7 wt% propylene glycol could increase the permeability of paeonol and berberine hydrochloride. Among them, the promoting effect of 5 wt% propylene glycol was better than that of 2 wt% and 7 wt%. Therefore, 5 wt% propylene glycol was determined to be the best transdermal absorption promoter for Vicon gel.

[0346] Example 5: Safety evaluation of Vicon gel

[0347] I. Preparation of the medicinal solution

[0348] Same as Example 4.

[0349] II. Preparation of Vicon Gel

[0350] Same as Example 4.

[0351] III. Preparation of Blank Matrix

[0352] HEC was dissolved in distilled water and stirred until it reached a gel state, resulting in a blank matrix with a final HEC concentration of 1.5 wt%.

[0353] IV. Acute toxicity test for external application

[0354] (1) Feeding and grouping

[0355] Sixteen KM mice were fasted for 12 hours but allowed free access to water. They were weighed and then randomly divided into two groups according to their body weight using a block randomization method: the blank matrix group and the topical gel group.

[0356] Blank matrix group: Each mouse was given a blank matrix; Topical gel group: Each mouse was given Vicon gel (1g / g crude drug). Mice were fixed with a self-made fixator and administered the drug twice within 12 hours.

[0357] (2) Toxicity test

[0358] After the last administration, the toxicity of mice in each group was observed, and the signs (appearance, respiration, movement, muscle tone, reflexes, eyelids, feces and skin) of the mice were monitored for abnormalities within 72 hours. The mortality was recorded.

[0359] (3) Inspection Results

[0360] Observations showed no abnormal signs in mice in both the blank matrix group and the topical gel group within 72 hours of topical application. The mortality rates of the two groups are shown in Table 15, with a mortality rate of 0%, equivalent to 59 times the intended adult clinical dose. This indicates that the Vicon gel provided by this invention has good safety and no obvious acute topical toxicity.

[0361] Table 15 Records of Animal Mortality

[0362]

[0363] Example 6: Vicon Tincture

[0364] I. Preparation Method

[0365] (1) Weighing of medicinal materials

[0366] According to prescription 1 in Example 1, weigh out 6.8g of Aconitum carmichaelii powder, 16.8g of Rhododendron molle powder, 22.5g of Cynanchum paniculatum powder, 22.5g of Rheum palmatum powder, and 16.8g of Phellodendron chinense powder, for a total of 85.4g.

[0367] (2) Extraction (percolation)

[0368] Percolation was performed using 6 times the total weight of the medicinal materials in 80% v / v ethanol at a rate of 9 ml / min / kg, and the percolate was collected (the amount of crude medicinal material was approximately 0.17 g / ml).

[0369] (3) Add borneol

[0370] Weigh 3.4g of borneol powder and dissolve it in the above percolate. Add water to make the alcohol content reach 50v / v% (measured with an alcohol meter).

[0371] (4) Dissolving Glauber's salt

[0372] Weigh 11.2g of fine Glauber's salt powder, add it to the solution obtained in the previous step and dissolve it completely. Then add 50% v / v ethanol to 1000ml to obtain (crude drug amount 0.1g / ml).

[0373] II. Usage and Dosage

[0374] 2-3 sprays per person, 3-5 times daily, approximately 2ml per person per day.

[0375] Example 7: Vicon Liniment

[0376] I. Preparation Method

[0377] (1) Weighing of medicinal materials

[0378] According to prescription 1 in Example 1, weigh out 34g of Aconitum carmichaelii powder, 84g of Rhododendron molle powder, 112.5g of Cynanchum paniculatum powder, 112.5g of Rheum palmatum powder, and 84g of Phellodendron chinense powder, for a total of 427g.

[0379] (2) Extraction (percolation)

[0380] Percolation was performed using 6 times the total weight of the above five medicinal materials in 80% v / v ethanol at a rate of 9 ml / min / kg, and the percolate (approximately 2000 ml) was collected.

[0381] (3) Concentration

[0382] The percolate was placed in a rotary evaporator and concentrated under reduced pressure at 70°C and a vacuum of -0.06 MPa to a crude drug concentration of 1.0 g / ml. Ethanol was added to bring the alcohol content to 50 v / v% (measured by an alcohol meter) for later use.

[0383] (4) Dissolving borneol and Glauber's salt

[0384] Weigh 17g of borneol powder and dissolve it in the above concentrated solution. Then add 11.2g of Glauber's salt powder and dissolve it completely. Add 50% v / v ethanol to 1000ml, let it stand overnight, and filter to obtain (crude drug amount 0.5g / ml).

[0385] II. Usage and Dosage

[0386] 2-3 sprays per person, 3-5 times daily, approximately 2ml per person per day.

[0387] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description and ideas, and it is neither necessary nor possible to exhaustively describe all implementation methods here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A topical traditional Chinese medicine composition for treating pain, characterized in that, It is made from the following components: by weight, Aconitum carmichaelii 4-8 parts, Rhododendron molle 14-18 parts, Cynanchum paniculatum 20-24 parts, Rheum palmatum 20-24 parts, Phellodendron chinense 14-18 parts, Glauber's salt 10-12 parts and Borneol 2-4 parts.

2. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of products for treating pain.

3. A topical medication for treating pain, characterized in that, Made from the traditional Chinese medicine composition according to claim 1.

4. The topical medicine according to claim 3, characterized in that, The topical medication is a liquid or semi-solid preparation.

5. The topical medicine according to claim 4, characterized in that, The matrix of the semi-solid formulation is a water-soluble matrix.

6. The topical medicine according to claim 4, characterized in that, The semi-solid formulation also includes a transdermal penetration enhancer.

7. The topical medicine according to claim 6, characterized in that, The transdermal penetration enhancer is any one of azone, oleic acid, isopropyl myristate, and propylene glycol.

8. The method for preparing the topical pain medication according to claim 3, characterized in that, Includes the following steps: S1. Treat Aconitum carmichaelii, Rhododendron molle, Cynanchum paniculatum, Rheum palmatum and Phellodendron chinense by decoction or percolation; S2. Mix Glauber's salt and borneol thoroughly with the product obtained in step S1 to obtain the final product.

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