Traditional Chinese medicine composition for treating acne and seborrheic dermatitis as well as preparation method and quality detection method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a traditional Chinese medicine composition for treating acne and seborrheic dermatitis as well as a preparation method and a quality detection method. The invention discloses a traditional Chinese medicine composition for treating acne and seborrheic dermatitis. The traditional Chinese medicine composition is prepared from the following medicinal raw materials: herba artemisiae scopariae, radix salviae miltiorrhizae, fructus forsythiae, radix scutellariae, radix angelicae sinensis and radix sanguisorbae. The prescription follows the principle of monarch, minister, assistant and guide, the proportion of all the medicines is scientifically blended, the components are simple, the structure is rigorous, quality control is facilitated, excessive toxic and side effects of the raw material medicines are reduced, the preparation method of the traditional Chinese medicine composition and the preparation combines a traditional brief method with a modern equipment technology, a standardized quality standard is established, and the traditional Chinese medicine composition is mild in medicine property and free of toxic and side effects. The traditional Chinese medicine has the effects of eliminating dampness and heat and cooling and activating blood, and is used for treating acne and seborrheic dermatitis caused by dampness and heat accumulation. According to the technical scheme, the technical problem that in the prior art, medicines for treating acne and / or seborrheic dermatitis are complex in component or prone to drug resistance can be solved, and the traditional Chinese medicine composition has ideal application and popularization prospects.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine preparations, and in particular to a traditional Chinese medicine composition for treating acne and seborrheic dermatitis, a preparation method and a quality detection method. Background Art

[0002] Acne is a common skin disease that occurs in the sebaceous glands of the hair follicles during adolescence. According to the Global Burden of Disease statistics, the global incidence rate is about 9.4%, ranking it as the eighth most common disease in the world. The incidence rate of the closely related seborrheic dermatitis is 2% to 8%. The pathogenesis of the two is complex, mostly caused by chronic inflammation of the sebaceous glands of the hair follicles, and they often occur on the head and face, affecting the appearance and can cause a serious psychological burden on the patient.

[0003] Acne is similar to the "lung wind acne" recorded in Chinese medical literature. For example, the "Essentials of Surgery in the Golden Mirror of the Medical Ancestral Sutra" records that "this syndrome is caused by heat in the blood of the lung meridian, and it often occurs on the face and nose, with broken lumps, shaped like paint chips, red and swollen, and painful, and white powdery juice is broken out." It is an inflammatory lesion of the hair follicles and sebaceous glands, often accompanied by sebum overflow. Chinese medicine believes that this disease is mostly caused by improper diet, excessive consumption of fatty and sweet foods, damp heat in the lungs and stomach, and wind evil.

[0004] Seborrheic dermatitis is similar to "facial edema" and "white scales" recorded in Chinese medical literature. For example, in the "Essentials of Surgery in the Golden Mirror of the Medical Ancestral Sutra", "facial edema" is recorded as follows: "This symptom occurs on the face. At the beginning, the face is swollen and itchy like a worm, the skin is dry, and white scales appear. After a while, it is very itchy and scratched. If the heat and dampness are strong, the body fluid will be yellow and water, and if the wind and dryness are strong, the body fluid will be blood, and the pain is unbearable." Another example is the record of "white scales": "This symptom initially extends to the face, ears and neck, and it is dry and itchy. After a long time, white scales fly up, which fall off and grow again." This disease is mostly caused by internal damp heat, external wind evil, blocking the skin, and damp heat steaming up (oily seborrheic); or due to damp heat damaging yin and consuming blood, blood deficiency and wind dryness, and skin malnutrition (dry seborrheic).

[0005] Since acne and seborrheic dermatitis are related to endocrine disorders and require long-term treatment, a combination of Chinese and Western medicine is currently used. Chinese medicine treatments for acne and seborrheic dermatitis include oral Chinese medicine therapy (such as Runzao Zhiyang Capsules, Danggui Kushen Pills, Danshen Capsules), skin application, medicinal baths, acupuncture, and other methods. Western medicine is based on the principle of "degreasing, anti-inflammatory, sterilizing, and relieving itching", oral anti-inflammatory and antifungal drugs, and topical use such as compound sulfur lotion and compound chloramphenicol tincture, in order to achieve the effect of treating both the symptoms and the root cause. However, most of the Chinese medicine prescriptions currently used have complex ingredients, and the pharmacological mechanism is difficult to explore, which is not conducive to quality control; Western medicine treatment is prone to drug resistance, and the effect is reduced after long-term use, and it needs to be used in increased doses or even fails.

[0006] In summary, there is an urgent need to study Chinese medicine preparations for the treatment of acne and / or seborrheic dermatitis in order to develop a Chinese medicine preparation with simple ingredients and ideal therapeutic effects, so as to overcome the problems of complex ingredients of existing Chinese medicine prescriptions and the easy occurrence of drug resistance in Western medicine preparations. Summary of the invention

[0007] The purpose of the present invention is to provide a Chinese medicine composition for treating acne and seborrheic dermatitis, so as to solve the technical problems of the existing drugs for treating acne and / or seborrheic dermatitis, such as complex ingredients or easy drug resistance.

[0008] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0009] A traditional Chinese medicine composition for treating acne and seborrheic dermatitis comprises, by weight, 2-6 parts of Artemisia capillaris, 2-5 parts of Salvia miltiorrhiza, 1-4 parts of Forsythia suspensa, 1-3 parts of Scutellaria baicalensis, 1-2 parts of Angelica sinensis, and 1-2 parts of Sanguisorba officinalis.

[0010] Furthermore, in parts by weight, the medicinal raw materials include: 4 parts of Artemisia Capillaris, 3 parts of Salvia miltiorrhiza, 2 parts of Forsythia suspensa, 2 parts of Scutellaria baicalensis, 1 part of Angelica sinensis, and 1 part of Sanguisorba officinalis.

[0011] The technical solution also provides a method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis, comprising the following steps performed in sequence:

[0012] S1: soaking the raw materials of medicinal materials;

[0013] S2: adding water to the soaked medicinal material, boiling and extracting, and combining the filtrate to obtain a water extract;

[0014] S3: the water extract is concentrated under reduced pressure and then allowed to stand to obtain a supernatant and a precipitate; the precipitate is filtered to obtain a filtrate, and the filtrate and the supernatant are combined; and then the water extract is concentrated under reduced pressure to obtain a thick paste;

[0015] S4: using part of the thick paste for wet granulation with soluble starch to obtain wet granules; spray-drying granulation of the remaining thick paste and the wet granules to obtain Chinese medicine granules.

[0016] Furthermore, in S1, the temperature condition of the immersion treatment is room temperature, and the duration of the immersion treatment is 0-30 minutes; the duration of the immersion treatment is preferably 30 minutes.

[0017] Further, in S2, the decoction extraction method is: decoction extraction is performed for 1 hour using 10 times the volume of water as the solvent of the medicinal material, and then decoction extraction is performed for 45 minutes using 8 times the volume of water as the solvent of the medicinal material.

[0018] Further, in S3, the water extract is concentrated under reduced pressure to 10 degrees Baume (relative density of about 1.074) and the standing time is 12 hours.

[0019] Further, in S3, the relative density of the thick paste is 1.10-1.30, preferably 1.20.

[0020] Further, in S4, the mass ratio of the thick paste used for wet granulation and spray drying granulation is 1:1.

[0021] Further, in S4, the wet granulation method is: mixing the thick paste and the soluble starch in a mass ratio of 1:4, and using 75% ethanol for wet granulation; preferably, the mass ratio of the soluble starch to 75% ethanol is 5:1;

[0022] The spray drying granulation method is: keep the wet granules in a boiling state in a 70°C environment, spray the thick paste, and then dry the granules to obtain the Chinese medicine granules; preferably, the parameters of the boiling drying granulator are set as: inlet air temperature 70°C, air pressure adjusted to 0.6Mpa, and spray speed 5mL / min.

[0023] The technical scheme also provides a method for detecting the Chinese medicine granules obtained according to the preparation method, wherein thin layer chromatography detection is performed on Salvia miltiorrhiza, Scutellaria baicalensis and Sanguisorba officinalis, and the developing agents used are: 3:5:0.3 chloroform-acetone-formic acid, 5:3:1:1 ethyl acetate-butanone-formic acid-water, and 5:2:0.5 dichloromethane-acetone-formic acid;

[0024] Gallic acid in Chinese medicine granules was detected by high performance liquid chromatography; the parameters of high performance liquid chromatography detection were set as follows: octadecylsilane bonded silica gel was used as filler; 0.4% formic acid solution-methanol with a volume ratio of 95:5 was used as mobile phase; the detection wavelength was 270nm;

[0025] Each 10g of Chinese medicine granules contains ≥9.0mg of gallic acid.

[0026] The technical principle and beneficial effects of this technical solution are:

[0027] (1) The prescription of the present invention follows the principle of monarch, minister, assistant and envoy and scientifically adjusts the proportions of various drugs. It has simple components and rigorous structure, is easy to control quality and reduces excessive toxic and side effects of raw materials. The preparation method of the Chinese medicine composition and preparation combines traditional simple methods with modern equipment technology. It has mild medicinal properties, has the effects of clearing dampness and heat, cooling blood and activating blood circulation, and is used for acne and seborrheic dermatitis caused by internal dampness and heat accumulation.

[0028] (2) The appropriate type of auxiliary materials was selected during the granulation process, which reduced the difficulty of granulation. The properties of the obtained particles met the requirements, with a high particle forming rate, ideal particle solubility, and low particle moisture absorption rate.

[0029] (3) In the granulation process, pre-granulation is first performed and then spray drying granulation is performed. This is different from the traditional granulation method, which reduces the difficulty of granulation. The properties of the obtained particles meet the requirements, the particle forming rate is high, the particle solubility is ideal, and the particle moisture absorption rate is low.

[0030] (4) This plan establishes standardized quality standards. Based on the previous process research and pharmacodynamic experiments, a relatively complete quality standard is established for the active ingredients and preparation-related inspection items of the Chinese medicine composition. Thin layer chromatography and liquid chromatography are used to determine the content of salvia miltiorrhiza, baicalin, and gallic acid in the Chinese medicine composition. Standards are formulated for the preferred granules, which is conducive to ensuring the safety and effectiveness of the drug.

[0031] In summary, acne and seborrheic dermatitis are characterized by vigorous secretion of sebaceous glands and local skin lesions during the occurrence and development of the disease. According to TCM syndrome differentiation, dampness and heat are accumulated inside the body. The Chinese medicine composition of this scheme can effectively treat the above diseases. The present invention has a simple structure, rigorous prescription, and is in line with medical theory. The ingredients in the prescription are all commonly used Chinese medicines, with mild medicinal properties and definite therapeutic effects. DETAILED DESCRIPTION

[0032] The present invention is further described in detail below in conjunction with the examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following examples and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial sources. The standards for the excipients used in this scheme refer to the 2020 edition of the Chinese Pharmacopoeia, Part IV, Pharmaceutical Excipients; the standards for the use of Chinese medicinal materials and decoction pieces refer to the 2020 edition of the Chinese Pharmacopoeia, Part I, Medicinal Materials and Decoction Pieces.

[0033] The following is further described in detail through specific implementation methods:

[0034] A Chinese medicinal compound granule for treating chronic gastritis, which comprises, by weight, 2-6 parts of Artemisia capillaris, 2-5 parts of Salvia miltiorrhiza, 1-4 parts of Forsythia suspensa, 1-3 parts of Scutellaria baicalensis, 1-2 parts of Angelica sinensis, and 1-2 parts of Sanguisorba officinalis.

[0035] The preferred formula is: 4 parts of Artemisia capillaris, 3 parts of Salvia miltiorrhiza, 2 parts of Forsythia suspensa, 2 parts of Scutellaria baicalensis, 1 part of Angelica sinensis, and 1 part of Sanguisorba officinalis.

[0036] The Chinese medicine compound granules are prepared according to the following process (overall process):

[0037] Extraction of medicinal materials: According to the weight ratio of the prescription, six kinds of medicinal materials, including Artemisia capillaris, Salvia miltiorrhiza, Forsythia suspensa, Scutellaria baicalensis, Angelica sinensis and Sanguisorba officinalis, are weighed, put into a thermal cycle multifunctional extraction tank, rinsed with normal water for 1 minute, and dust is washed off. Then, purified water is added to the extraction tank to immerse the medicinal materials, and the medicinal materials are decocted and extracted after immersion at room temperature (25-35°C) for 30 minutes, and extracted twice in total. After the first immersion, purified water is added to 10 times the amount of medicinal materials (volume) and boiled for 1 hour, and 8 times the amount of water is added for the second time, and boiled for 45 minutes. After decoction, the combined extract is filtered and concentrated under reduced pressure at 90°C to 10 degrees Baume (relative density of about 1.074), moved into a precipitation tank, and left to stand at room temperature for 12 hours. The precipitate is released from the precipitation tank and filtered, and the filtrate is combined with the supernatant, and concentrated under reduced pressure at 90°C (vacuum degree is -0.04Mpa) to form a thick paste (relative density 1.10-1.30, preferably 1.20).

[0038] Preparation: The obtained thick paste is prepared into tablets, powders, capsules, extracts, oral solutions, capsules or granules.

[0039] Preferably, the thick paste is prepared as granules, and the thick paste is divided into two parts, one for preparing wet granules and the other for spray granulation. The thick paste and soluble starch are weighed according to the material mass ratio of 1:4-1:2 (preferably 1:4), and 75% anhydrous ethanol is used to pre-granulate to obtain wet granules. The specific process of wet granulation is: the soluble starch in the prescription is slowly mixed with 75% ethanol in a ratio of 5:1 for multiple times, and then added to the thick paste, the stirring paddle of the wet granulator is turned on (100 rpm), the high-speed cutter is turned on (2000 rpm), and it runs for 10 minutes, the material is discharged, and the granulation is performed by shaking with a 20-mesh sieve, and the moisture is ventilated and dried in an oven at 60°C until the moisture is less than 8.0%, and the wet granules are obtained by granulating with a 30-mesh sieve.

[0040] The wet granules are fed into a boiling drying granulator, and another portion of thick paste is sprayed into the granules while the granules are kept boiling (i.e., the mass ratio of the thick paste used to prepare the wet granules, the thick paste used for spraying, and the soluble starch used to prepare the wet granules is 1:1:4.), and the granules are mixed and granulated after drying. The temperature in the boiling chamber is controlled at 70°C. The parameters of the boiling drying granulator are set as follows: the air inlet temperature is 70°C, the air pressure is adjusted to 0.6Mpa, and the injection speed is 5mL / min. After cooling, granulation and unloading, the drug granules of this scheme are obtained.

[0041] Example 1

[0042] This embodiment is carried out according to the above-mentioned optimal process, specifically: according to the prescription weight ratio, 200g of Artemisia capillaris, 150g of Salvia miltiorrhiza, 100g of Forsythia suspensa, 100g of Scutellaria baicalensis, 50g of Angelica sinensis, and 50g of Sanguisorba officinalis are weighed, put into a thermal cycle multifunctional extraction tank, rinse with normal water for 1 minute, and wash away dust. Add purified water to the extraction tank to immerse the medicinal materials, immerse at room temperature for 30 minutes, and then decoct and extract. Extract twice in total. After the first immersion, add purified water to 10 times the amount of medicinal materials (volume) and boil for 1 hour. The second time, add 8 times the amount of water and boil for 45 minutes. After decoction, filter and combine the extracts, concentrate under reduced pressure at 90°C, move into a precipitation tank, and let stand for 12 hours; release the precipitate from the precipitation tank and filter, combine the filtrate with the supernatant, and concentrate under reduced pressure at 90°C to a thick paste with a relative density of 1.10, weigh, and obtain the Chinese medicine composition of the present invention.

[0043] For the preferred granules, the preparation method further comprises the following steps:

[0044] After the thick paste as described above is obtained, the thick paste and soluble starch are weighed in a material mass ratio of 1:2 and spray granulated using a boiling drying granulator.

[0045] Example 2

[0046] This embodiment is basically the same as Embodiment 1, except that the density of the thick paste is 1.20.

[0047] Example 3

[0048] This embodiment is basically the same as Embodiment 1, except that the density of the thick paste is 1.30.

[0049] Example 4

[0050] This embodiment is basically the same as embodiment 2, except that the method for obtaining thick paste granulation is as follows: thick paste and soluble starch are weighed at a material ratio of 1:4. 75% anhydrous ethanol is used to pre-granulate to obtain wet granules. The wet granules are fed into a boiling drying granulator, and the thick paste (consistent with the amount of thick paste used for wet granulation) is sprayed into the granules while the granules are kept in a boiling state, and the granules are mixed and granulated after drying. The modified granulation method is the optimal method of this scheme, and more specifically, refer to the description of the optimal method above.

[0051] Example 5

[0052] This embodiment is basically the same as embodiment 4, except that during granulation, an equal amount of soluble starch is replaced with powdered sugar (fine sucrose powder).

[0053] Example 6

[0054] This embodiment is basically the same as embodiment 4, except that during granulation, an equal amount of soluble starch is replaced by dextrin.

[0055] Example 7

[0056] This embodiment is basically the same as embodiment 4, except that during granulation, an equal amount of soluble starch is replaced by mannitol.

[0057] Example 8

[0058] This embodiment is basically the same as embodiment 4, except that during granulation, an equal amount of soluble starch is replaced by microcrystalline cellulose.

[0059] Experimental Example 1: Extraction Process Research

[0060] With reference to the formula of Example 4, follow-up research was carried out. The medicinal materials were weighed and boiled according to the prescription ratio of 1 / 10 (see Table 1 for the decoction and extraction method), the extract was combined, filtered, the volume V was measured, 20 mL was accurately drawn into a dry and weighed evaporating dish and concentrated to a thick paste, moved into a 105°C oven for drying for 3 hours, taken out, cooled to room temperature in a desiccator, taken out and weighed W, and calculated. Extract amount (g) = W*V / 20×100%. The experimental results are shown in Table 2. The test results show that the extract amounts of Experiments 1 and 2 are not much different, but Experiment 3 is quite different. Considering the comprehensive consideration of cost and energy conservation, the extraction conditions of Experiment 2 can be selected. The extraction process conditions to be determined are that the six medicinal materials such as Artemisia capillaris and Salvia miltiorrhiza are soaked in water for 30 minutes, and then boiled twice. The first time, 10 times the amount of water is added and boiled for 1 hour, and the second time, 8 times the amount of water is added and boiled for 45 minutes.

[0061] Table 1: Extraction process parameter design

[0062]

[0063] Table 2: Extraction test results

[0064] experiment Extract amount (g) 1 25.24 2 24.97 3 22.59

[0065] Experimental Example 2: Concentration Process Research

[0066] The concentration of the extract will affect the granule forming effect. This product adopts vacuum concentration. The concentration conditions are: vacuum concentration using a thermal cycle multifunctional concentration tank, the temperature is 90°C, the vacuum degree is -0.04Mpa, and the granules are concentrated to a thick paste with a relative density of about 1.10-1.30, and then the granules are prepared according to the method of Examples 1-3 (conventional granulation method). Formability determination: The particles are first passed through a No. 1 sieve, and then through a No. 5 sieve. The particles that can pass through the No. 1 sieve but cannot pass through the No. 5 sieve are collected and weighed. Particle forming rate = particle mass after sieving / material weight × 100%. The particle forming results are shown in Table 3. The test results show that the particle forming degree obtained by granulating with an extract with a relative density of 1.20 is the highest, and too high or too low viscosity will affect the color and forming properties of the particles. With a relative density of 1.20, the particle forming rate can reach 88.6%, but if the relative density is slightly higher or lower by 0.1, it will result in a decrease in the forming rate by about 15-24%. The thick paste prepared from the medicinal raw materials of this solution is used to prepare the subsequent granules. The relative density of the thick paste has such a significant effect on the granule formability, which was not predicted by the inventor. Therefore, the selection of a thick paste density of 1.20 has achieved unexpected technical effects in the specific application environment of this technical solution.

[0067] Table 3: Formability of particles prepared from extracts of different concentrations (average results from 3 repeated experiments)

[0068]

[0069] Experimental Example 3: Granulation Process Study

[0070] This experimental example attempts to use two granulation methods, one is the method used in Example 2 (method 1), and the other is the method used in Example 4 (method 2). The operating method of the former is: weigh the thick paste and soluble starch according to the material ratio of 1:2, and directly use the boiling drying granulator for spray granulation. Specifically: the thick paste and soluble starch are added to the boiling drying granulator, and the 75% ethanol solution is atomized and sprayed directly on the fluidized material. After drying, cooling, granulation and unloading, the drug particles of this scheme are obtained; wherein, the parameters of the boiling drying granulator are set as: inlet air temperature 70°C, air pressure adjusted to 0.6Mpa, and injection speed 5mL / min. The operating method of the latter is the optimal operating method of this scheme, see Example 4 and the previous text, which will not be repeated here. The research results of the influence of different granulation methods on the properties of particles are shown in Table 4. The results show that the particles obtained by pre-granulation and then spray drying granulation are uniform in color and size, have better formability, and no precipitation after dissolution.

[0071] Table 4: Effects of different granulation methods on particle properties (average results of 3 repeated experiments)

[0072]

[0073] The inventors also considered whether the amount of soluble starch used in mode 1 was too low, resulting in an unsatisfactory particle forming rate. On the basis of mode 1, the amount of soluble starch was increased to 400g, but the particle forming rate still could not exceed 90% (three repeated experiments could not exceed 90%), and the solubility experiment showed that there was still a small amount of precipitation in the dissolved matter. Therefore, in order to improve the forming property of the particles, it is necessary to make a large adjustment on the basis of the original preparation process, and the amount of auxiliary materials cannot be adjusted only on the conventional method. In this technical solution, part of the thick paste and soluble starch are firstly used for wet granulation, and then the spray granulation method is adopted to add the remaining thick paste to form the final product. The operation mode of this technical solution has a significant improvement effect on the forming property and solubility of Chinese medicine particles. The granulation form adopted in this technical solution has not been tried in the prior art, and it is the first time that this technical solution is proposed, and the ideal effect is obtained. In addition, in this technical solution, the dosage ratio of the thick paste used for wet granulation and spray granulation is 1:1. If the amount of thick paste used for wet granulation is increased, the ratio becomes 2:1, and the other process is consistent with Example 4, the solubility of the granules is not ideal, and a small amount of precipitation exists after melting. If the amount of thick paste used for wet granulation is reduced, the ratio becomes 1:2, and the other process is consistent with Example 4, the formability of the granules is not ideal, and the forming rate is less than 90%.

[0074] Experimental Example 4: Study on excipient types

[0075] This experimental example investigates the effects of auxiliary materials such as powdered sugar, dextrin, mannitol, microcrystalline cellulose and soluble starch on the properties of particles. The specific method adopts the operating method of Example 4, and only replaces the auxiliary materials of wet granulation in equal amounts. The granulation, particle properties, formability, fluidity, solubility and moisture absorption rate of the particles obtained with different auxiliary materials are investigated. Moisture absorption rate determination method: Place the sample in a flat weighing bottle of known weight, accurately weigh it, store it in a constant temperature incubator at a temperature of 25°C and a relative humidity of 75% for 48 hours, and take it out and accurately weigh it. Moisture absorption rate = (hygroscopic particles-original particles) / original particles × 100%. See Table 5 for experimental results. The test results show that the properties of the particles prepared using auxiliary material soluble starch are significantly better than those of its auxiliary materials, the particles are more uniform, the formability is higher, and the solubility and moisture absorption are better. The granulation method of this technical solution is reported for the first time, and those skilled in the art do not know which granulation auxiliary material to use to ensure the ideal treatment effect under this process. The inventor screened a variety of auxiliary materials and found that soluble starch showed good performance in the granulation method of this scheme. The prior art generally believes that the anti-hygroscopic effect of soluble starch is not as good as other auxiliary materials. However, in the special process of this scheme, soluble starch actually showed a full range of advantages, which was not expected by the inventor before the experiment. In other conventional spray granulation methods, soluble starch did not show such a full range of advantages.

[0076] Table 5: Effects of different granulation methods on particle properties (average results of 3 repeated experiments)

[0077]

[0078] Experimental Example 5: Stability study of preparations

[0079] (1) Accelerated test

[0080] According to the relevant provisions under the accelerated test, the stability study of the granules (for the granules prepared in Example 4) was carried out at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5% for 6 months. The experimental results are shown in Table 6. The accelerated test was carried out at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5%. After 6 months, the results of various inspection indicators met the standard requirements.

[0081] Table 6: Long-term storage stability test results (average value of 3 repeated experiments)

[0082]

[0083]

[0084] (2) Long-term test

[0085] According to the relevant provisions under the long-term test, the stability study of the granules (for the granules prepared in Example 4) was carried out at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 10%. The experimental results are shown in Table 7. The long-term storage test was carried out at 25°C ± 2°C and a relative humidity of 60% ± 10%. After 12 months, the results of various inspection indicators met the standard requirements.

[0086] Table 7: Long-term storage stability test results (average value of 3 repeated experiments)

[0087]

[0088]

[0089] Experimental Example 6: Establishment of Quality Standards

[0090] In order to ensure that the efficacy of the Chinese medicine composition is stable and the quality is controllable, the quality standards of the system are as follows:

[0091] Test 1: Quality standards for active ingredients in traditional Chinese medicine compositions

[0092] (1) Salvia miltiorrhiza: Take an appropriate amount of this product, grind it into powder, weigh 2.0g, add 20mL of hot water to dissolve, adjust the pH to 2-3 with 1mol / L hydrochloric acid solution, extract with ethyl acetate twice, 20mL each time, combine the ethyl acetate extracts, evaporate to dryness, and dissolve the residue in 2mL of methanol as the test solution. Weigh 0.5g of Salvia miltiorrhiza control medicinal material, add water to decoct, and prepare the control medicinal material solution according to the preparation method of the test solution. According to the thin layer chromatography method (General 0502 of the fourth appendix of the 2020 edition of the Chinese Pharmacopoeia), take 2μl of each of the above solutions and spot them on the same high-efficiency silica gel G plate, use chloroform-acetone-formic acid (3:5:0.3) as the developing agent, develop, take out, dry, spray with 10% sulfuric acid ethanol solution, and heat at 105°C until the spots are clearly colored. In the chromatogram of the test product, spots of the same color appear at the corresponding position of the chromatogram of the reference product.

[0093] (2) Scutellaria baicalensis: Take an appropriate amount of this product, grind it into powder, weigh 6.0g, add 20mL of methanol, ultrasonically treat for 30min, filter, evaporate the filtrate to dryness, add 2mL of methanol to dissolve the residue, and use it as the test solution. Take 0.5g of Scutellaria baicalensis reference medicinal material powder, add water and boil for 30min, filter, recover the solvent from the filtrate until dry, add 2mL of methanol to the residue, and use it as the control medicinal material solution. Take another baicalin reference substance, add methanol to make a 1mg / mL solution, and use it as the reference solution. According to the thin layer chromatography method (General Rules 0502 of the 2020 Fourth Edition of the Chinese Pharmacopoeia), take 5μl of each of the above solutions and spot them on the same high-efficiency silica gel G plate, use ethyl acetate-butanone-formic acid-water (5:3:1:1) as the developing solvent, develop, take out, dry, and spray with 2% FeCl3 solution for color development. In the chromatogram of the test product, spots of the same color appear at the corresponding position of the chromatogram of the reference substance.

[0094] (3) Radix Sanguisorbae: Take an appropriate amount of this product, grind it into powder, weigh 2.0g, add 20mL of hot water to dissolve, adjust the pH to 2-3 with 1mol / L hydrochloric acid solution, extract with ethyl acetate twice, 20mL each time, combine the ethyl acetate extracts, recover the solvent to dryness, and dissolve the residue in 2mL of methanol as the test solution. Take another gallic acid reference substance, add methanol to make a solution with a concentration of 1mg per 1mL as the reference solution. According to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Four General Rules 0502), take 5μl of the above solution and spot it on the same high-efficiency silica gel G plate, use dichloromethane-acetone-formic acid (5:2:0.5) as the developing agent, develop, take out, dry, and spray with 2% FeCl3 ethanol solution for color development. In the test sample chromatogram, spots of the same color appear at the corresponding position of the reference chromatogram.

[0095] Test example 2: Granule inspection

[0096] It should comply with the relevant provisions under granules (General Rules 0104, Part IV, Chinese Pharmacopoeia 2020 Edition).

[0097] Test Example 3: Content Determination

[0098] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0099] Test Example 4: Chromatographic Conditions and System Suitability Test

[0100] Octadecylsilane bonded silica gel is used as filler; 0.4% formic acid solution-methanol (95:5) is used as mobile phase; detection wavelength is 270nm. The theoretical plate number should be no less than 2000 based on gallic acid peak.

[0101] Preparation of reference solution: Take gallic acid reference, weigh accurately, add methanol to make 1mL of solution containing 50μg, shake well, and obtain.

[0102] Preparation of test solution: Grind an appropriate amount of the product, take 1 g, weigh accurately, put it in a stoppered flask, add 25 mL of methanol accurately, weigh the weight, treat it with ultrasound (60 kHz) for 30 min, let it cool, wipe the outside dry, weigh it again, make up the lost weight with methanol, shake well, filter, take the filtrate and centrifuge it (13000 r / min, 5 min), and take the supernatant.

[0103] Determination method: Accurately pipette 5 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0104] Each bag (10g / bag) of this product contains gallic acid (C7H6O5), not less than 9.0mg.

[0105] Experimental Example 7: Evaluation of the treatment of rabbit acne model

[0106] (1) Experimental Materials

[0107] Test drug: granule extract of the Chinese medicine composition (content: 1.2 g crude drug / mL), the formula of which is shown in Example 4.

[0108] Positive control drug: Tanshinone capsules, produced by Hebei Xinglong Xili Pharmaceutical Co., Ltd.

[0109] Experimental animals: 65 healthy rabbits, half male and half female, weighing 2.0-2.5 kg.

[0110] (2) Experimental groups and drug dosage

[0111] See Table 8. Each data is expressed as mean ± standard deviation, and the comparison between the two groups was performed by t test, with P < 0.05 representing a significant difference.

[0112] Table 8: Dosage design of the Chinese medicine composition granules

[0113]

[0114]

[0115] (3) Methods and Results

[0116] 65 rabbits were randomly divided into 6 groups, with 10-12 rabbits in each group. Except for the normal control group, 0.2 mL of 50% oleic acid was applied to the left and right external auditory canals of the rabbits in the other groups with a pipette, once a day for 28 consecutive days. On the 12th day after the modeling, 30 μl of Staphylococcus epidermidis was injected intradermally into the external auditory canals of the rabbits modeled with oleic acid, and marks were made around the injection site to replicate the rabbit acne model. On the 29th day after the modeling, each group was given the corresponding drugs by gavage according to Table 20, and the normal control group and the model group were given an equal volume of normal saline once a day for 30 consecutive days. The body weight was weighed once a week during the modeling and drug administration period, and the dosage was adjusted according to the body weight. 18 hours after the last administration, the rabbits were killed by injecting 5 mL of air into the ear vein. The skin was taken from the right ear mark, and the tissue blocks were fixed with 10% formalin, embedded in paraffin, and sliced. Four consecutive slices were made for each specimen, and HE staining was performed. The histological changes were observed under a light microscope. The areas of the two hair follicles with the same position and the most complete structure and the diameters of the four sebaceous glands in the four slices were detected, and their respective average values ​​were calculated. The results are shown in Table 9.

[0117] Table 9: Effects of the Chinese medicine composition granules on hair follicles and sebaceous glands in the treatment of acne

[0118]

[0119] Note: △ indicates P<0.05 compared with the normal control group; ** indicates P<0.05 compared with the model group.

[0120] As can be seen from the table above, compared with the normal group, the diameter of the sebaceous glands and the area of ​​the hair follicles in the model group were significantly increased, and there was a significant difference between the two groups, indicating that the acne model was successfully established. Compared with the model group, the positive drug group and the groups of granules of the Chinese medicine composition at various doses can significantly reduce the diameter of the sebaceous glands and the area of ​​the hair follicles. The above results show that the granules of the Chinese medicine composition have a good therapeutic effect on the rabbit ear acne model caused by oleic acid.

[0121] Experimental Example 8: Acute toxicity test of Chinese medicine composition on mice

[0122] The experiment was conducted using a Chinese medicine composite granule extract. The experimental animals were Kunming mice, 10 mice per group, half male and half female, 7-9 weeks old, provided by the Experimental Animal Center of the Third Military Medical University. A single oral administration experiment was conducted in accordance with the "Preclinical Safety Evaluation and Practice of New Drugs" and the "Compilation of Guiding Principles for Preclinical Research of New Drugs". The mice were fasted for 12 hours before administration, and data were collected continuously after administration. The Bliss method was used to calculate the LD 50 and 95% confidence limits.

[0123] A single-dose preliminary experiment was conducted on mice, and the results are shown in Table 10. Referring to the results in the table, 8 dose groups of 144.42, 129.97, 116.96, 105.28, 94.74, 85.28, 76.74, and 69.57 g crude drug / kg were set up according to a common ratio of 0.9 for testing, and the results are shown in Table 11.

[0124] Table 10: LD of a single oral dose of Chinese medicine composition granules in mice 50 Preliminary test

[0125] Dosage (g crude drug / kg) Number of animals Deaths Observation days 144.42 5 5 7 108.32 5 4 7 72.21 5 1 7 36.12 5 0 7

[0126] Table 11: Mortality of mice after a single oral administration of Chinese medicine composition granules

[0127]

[0128] This experiment selected a single oral administration method. According to the provisions of the "Compilation of Guiding Principles for Preclinical Research of New Drugs", the performance and death of Kunming mice after a single administration of a sample of a Chinese medicine composition granule were observed. The results showed that most experimental animals had brown loose stools 2 hours after medication. Except for dead animals, this symptom disappeared after 1 day; animal activity was slightly reduced at high doses; animal death may occur at high doses, and the time of death is basically within 18 hours. This experiment was observed for 14 consecutive days. No abnormal tissues and organs were found in animals that died after administration and survived at the end of the experiment after autopsy. The LDso calculated by the Bliss method was 97.89g crude drug Ikg, and the 95% confidence limit was 91.56-104.67g crude drug / kg. It indicates that the safety of oral contact of the Chinese medicine composition granule sample is very good.

[0129] Experimental Example 9: Clinical efficacy and safety evaluation of Chinese medicine composition

[0130] (1) Research objectives

[0131] This study used Wei'anzhi capsules as a control drug to evaluate the clinical efficacy and safety of the Chinese medicine composition in treating acne.

[0132] (2) Research design and methods

[0133] This study adopted a randomized parallel controlled design, and the indication was acne.

[0134] (2.1) Trial Drugs

[0135] Test drug: Granules of this Chinese medicine composition.

[0136] Control drug: Vianester capsules; specification: 25 mg; batch number: 030603; manufacturer: Chongqing Huabang Pharmaceutical Co., Ltd.

[0137] (2.2) Case selection

[0138] A total of 300 patients were included in this study, all of whom were outpatients. The patients were randomly divided into an experimental group and a control group, with 150 cases in the experimental group and 150 cases in the control group.

[0139] (2.3) Treatment options

[0140] The experimental group took Chinese medicine granules, one pack each time, three times a day; the control group took 50 mg of Wei'an ester capsules orally, three times a day. Two months was a course of treatment. The patients stopped taking other drugs during the treatment. The patients were observed every two weeks during the medication period, and the changes in symptoms and the occurrence of side effects were recorded.

[0141] (2.4) Criteria for determining efficacy

[0142] According to the clinical manifestations of each patient before and after treatment, the symptoms and signs of the subjects were recorded.

[0143] Recovery means that the rash disappears by more than 90%, the inflammation basically disappears, and no new rash appears;

[0144] Significant effect means that the rash disappears by 70%-89%, the inflammation is significantly alleviated, and new rashes occasionally appear;

[0145] Effective means that the rash subsides by 30%-69%, inflammation is reduced, and new rashes appear:

[0146] Ineffective: the rash subsides less than 30%, and the inflammation remains the same or worsens:

[0147] Total effective rate = cure rate + marked effective rate.

[0148] (3) Results

[0149] (3.1) Case data

[0150] There were 150 cases in the experimental group, including 88 males and 62 females, with an age range of 17-56 years, an average of 31±9.97 years, and a disease course of 8 weeks to 4.5 years, with an average of (0.8±0.54) years. There were 150 cases in the control group, including 76 males and 74 females, with an age range of 18-53 years, an average of 35±11.24 years, and a disease course of 7 weeks to 5 years, with an average of (0.9±0.82) years. There was no statistical difference in age, gender, and disease course between the two groups (P>0.05). They were comparable.

[0151] (3.2) Index decomposition and evaluation

[0152] The treatment effect of the experimental group on comedonal acne was better than that of the control group (P<0.05), and the difference was significant after statistical comparison. However, there was no significant difference in the treatment effect of nodular, cystic, papular, pustular and conglobate acne between the two groups, as shown in Table 12.

[0153] Table 12: Comparison of efficacy of two groups of acne vulgaris by indicator decomposition method

[0154]

[0155] (3.3) Comprehensive efficacy evaluation

[0156] The cure rate and total effective rate of the experimental group were significantly higher than those of the control group, and the difference between the two groups was significant. 95 cases (63.3%) in the experimental group began to see results after 2 weeks of treatment, while 61 cases (40.7%) in the control group saw results after 2 weeks of treatment. In the experimental group, 69 cases (46%) were cured, 44 cases (29.3%) were markedly effective, 24 cases (16.0%) were effective, and 13 cases (8.7%) were ineffective. The total effective rate was 75.3%. The results are shown in Table 13.

[0157] Table 13: Comparison of comprehensive efficacy of two groups for acne vulgaris

[0158]

[0159]

[0160] (3.4) Adverse reaction evaluation

[0161] No adverse reactions were observed in both groups in this study.

[0162] (4) Conclusion

[0163] In the present invention, Artemisia capillaris can clear away heat and dampness, and in vitro experimental studies have shown that it can effectively inhibit the reproduction of Staphylococcus aureus; the active ingredient tanshinone of Salvia miltiorrhiza can inhibit the secretion of androgen, and can also have a significant inhibitory effect on Propionibacterium acnes. The results of a clinical study on 300 patients with acne in a randomized parallel control manner showed that the present invention can effectively improve inflammation, reduce the formation of cysts and pustules, thereby reducing post-inflammatory pigmentation and scar formation, and the total clinical effective rate reached 75.3%, and no obvious adverse reactions were found. Therefore, the present invention is an effective and safe drug for treating common acne.

[0164] The above is only an embodiment of the present invention, and the common knowledge such as the known specific structure and characteristics in the scheme is not described in detail here. It should be pointed out that for those skilled in the art, several deformations and improvements can be made without departing from the structure of the present invention, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A Chinese medicine composition for treating acne and seborrheic dermatitis, characterized in that: Calculated by weight, the medicinal raw materials include: 2-6 parts of Artemisia capillaris, 2-5 parts of Salvia miltiorrhiza, 1-4 parts of Forsythia suspensa, 1-3 parts of Scutellaria baicalensis, 1-2 parts of Angelica sinensis, and 1-2 parts of Sanguisorba officinalis.

2. A Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 1, characterized in that: Calculated by weight, the medicinal raw materials include: 4 parts of Artemisia capillaris, 3 parts of Salvia miltiorrhiza, 2 parts of Forsythia suspensa, 2 parts of Scutellaria baicalensis, 1 part of Angelica sinensis, and 1 part of Sanguisorba officinalis.

3. A method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 1 or 2, characterized in that: The method includes the following steps in sequence: S1: soaking the raw materials of medicinal materials; S2: adding water to the soaked medicinal material, boiling and extracting, and combining the filtrate to obtain a water extract; S3: the water extract is concentrated under reduced pressure and then allowed to stand to obtain a supernatant and a precipitate; the precipitate is filtered to obtain a filtrate, and the filtrate is combined with the supernatant; and then concentrated under reduced pressure to obtain a thick paste; S4: using part of the thick paste for wet granulation with soluble starch to obtain wet granules; spray-drying granulation of the remaining thick paste and the wet granules to obtain Chinese medicine granules.

4. A method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 3, characterized in that: In S1, the temperature condition of the immersion treatment is room temperature, and the duration of the immersion treatment is 0-30 minutes; the duration of the immersion treatment is preferably 30 minutes.

5. A method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 3, characterized in that: In S2, the decoction extraction method is: decoction extraction is performed for 1 hour using 10 times the volume of water of the medicinal material as solvent, and then decoction extraction is performed for 45 minutes using 8 times the volume of water of the medicinal material as solvent.

6. A method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 3, characterized in that: In S3, the water extract is concentrated under reduced pressure to 10 degrees Baume (relative density of about 1.074) and allowed to stand for 12 hours.

7. A method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 6, characterized in that: In S3, the relative density of the thick paste is 1.10-1.30, preferably 1.

20.

8. The method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 3, characterized in that: In S4, the mass ratio of thick paste used for wet granulation and spray drying granulation was 1:

1.

9. A method for preparing a Chinese medicine composition for treating acne and seborrheic dermatitis according to claim 8, characterized in that: In S4, the wet granulation method is: mixing the thick paste and the soluble starch in a mass ratio of 1:4, and wet granulating with 75% ethanol; preferably, the mass ratio of the soluble starch to the 75% ethanol is 5:1; The spray drying granulation method is: keep the wet granules in a boiling state in a 70°C environment, spray the thick paste, and then dry the granules to obtain the Chinese medicine granules; preferably, the parameters of the boiling drying granulator are set as: inlet air temperature 70°C, air pressure adjusted to 0.6Mpa, and spray speed 5mL / min.

10. A method for detecting the Chinese medicine granules obtained by the preparation method according to any one of claims 3 to 9, characterized in that: Thin layer chromatography was performed on Salvia miltiorrhiza, Scutellaria baicalensis and Sanguisorba officinalis, and the developing solvents used were: 3:5:0.3 chloroform-acetone-formic acid, 5:3:1:1 ethyl acetate-butanone-formic acid-water, and 5:2:0.5 dichloromethane-acetone-formic acid; Gallic acid in Chinese medicine granules was detected by high performance liquid chromatography; the parameters of high performance liquid chromatography detection were set as follows: octadecylsilane bonded silica gel was used as filler; 0.4% formic acid solution-methanol with a volume ratio of 95:5 was used as mobile phase; the detection wavelength was 270nm; Each 10g of Chinese medicine granules contains ≥9.0mg of gallic acid.

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