Traditional Chinese medicine composition for treating acne and preparation method thereof

Abstract

The invention relates to the technical field of medicines, in particular to a traditional Chinese medicine composition for treating acne and a preparation method thereof. The traditional Chinese medicine composition comprises the following components in parts by weight: 270 parts of humifuse euphorbia herb, 90 parts of chinaroot greenbrier, 63 parts of aloe, 45 parts of fructus chebulae, 45 parts of fructus chebulae immaturus, 45 parts of tamarind, 45 parts of ziziphus jujube, 45 parts of polypody yunnanensis and 25 parts of scammonia resina. The traditional Chinese medicine composition provided by the invention has a remarkable inhibition effect on acne inflammatory response induced by propionibacterium acnes.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a Chinese medicine composition for treating acne and a preparation method thereof. Background Art

[0002] Acne is the most common type of inflammatory skin disease and is a chronic inflammatory skin disease of the hair follicles and sebum. It usually occurs during adolescence and is prone to occur in areas rich in sebaceous glands such as the face, chest and back. It is easy to cause skin pathological changes such as acne, pustules, and nodules. It often causes itching or pain, and it is very easy to relapse and difficult to cure fundamentally. In contemporary society, people pay more and more attention to skin management. Although skin problems will not endanger life, they will affect the aesthetic effect of facial skin to varying degrees, have a certain negative impact on the patient's mental health and social life, and are prone to inferiority and depression.

[0003] The limitations of acne drug treatment are mainly reflected in the differences in drug efficacy, drug side effects and safety issues, the emergence of drug resistance, long treatment cycles and high recurrence rates, and limitations in drug use. In order to overcome these limitations, it is necessary to select appropriate model animals and modeling methods for the development of acne intervention products of different degrees and mechanisms. Acne treatment is in line with the development needs of the era of great health and is of great significance in health care and improving the quality of life. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a Chinese medicine composition for treating acne and a preparation method thereof. The present invention explores the inhibitory effect and possible mechanism of the Chinese medicine composition on acne inflammatory response through a Propionibacterium acnes induced acne inflammation model, provides a basis for the application of the Chinese medicine composition in treating acne inflammatory response, and solves the problems raised in the above background technology.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] The present invention provides a traditional Chinese medicine composition for treating acne, comprising the following components in parts by weight:

[0007] 270 parts of Herba Euphorbiae Ichthyophthirius, 90 parts of Smilax Chinensis, 63 parts of Aloe Vera, 45 parts of Myrobalan, 45 parts of Cibotium Officinale, 45 parts of Tamarindus Indica, 45 parts of Kashikapu Ziziphus, 45 parts of Polypodium Vulgare and 25 parts of Scamonia Resin.

[0008] The present invention also provides a method for preparing the Chinese medicine composition described in the above technical solution, comprising the following steps:

[0009] 1) mixing the herb of euphorbia pulex, sarsaparilla, terminalia chebula, citronella, tamarind, jujube, polypodium vulgare and water and decocting the mixture to obtain a decoction;

[0010] 2) concentrating and drying the decoction obtained in step 1) to obtain Chinese medicine powder;

[0011] 3) The Chinese medicine powder obtained in step 2) is mixed with aloe vera and scabraxan to obtain a Chinese medicine composition.

[0012] Preferably, the conditions for decocting in step 1) include: a decocting time of 0.5 to 2 hours, a number of times of 1 to 4 times, and an amount of water added of 10 to 14 times.

[0013] Preferably, the decoction conditions include: the decoction time is 1 hour, the number of times is 3 times, and the amount of water added is 12 times.

[0014] Preferably, the aloe vera and scabrax are crushed, passed through a 100-mesh sieve, and then mixed with the traditional Chinese medicine powder.

[0015] The present invention also provides the use of the traditional Chinese medicine composition described in the above technical solution in preparing a drug for treating acne.

[0016] The present invention also provides the use of the traditional Chinese medicine composition described in the above technical solution in the preparation of acne medicine induced by Propionibacterium acnes.

[0017] The present invention also provides the use of the traditional Chinese medicine composition described in the above technical solution in the preparation of a drug for treating acne by reducing the content of serum inflammatory factors.

[0018] Preferably, the inflammatory factors include one or more of TNF-α, IL-6 and IL-1.

[0019] Beneficial effects:

[0020] The invention provides a traditional Chinese medicine composition for treating acne. The traditional Chinese medicine composition comprises herba euphorbiae, smilax china, reed, chebula chinensis, citron orange, tamarind, jujube, polypodium vulgare and scamonia; wherein the herba euphorbiae has an inhibitory effect on multiple bacteria, can effectively kill or inhibit the growth and reproduction of pathogens, prevent them from further damaging the body, and thus indirectly reduce the inflammatory response.

[0021] The invention adopts pure natural Chinese medicinal plant raw materials, and the formula is strictly formulated in accordance with the basic theory of traditional Chinese medicine and modern medicine. The whole formula is reasonable and rigorous, and can be prepared into medical and health products in various dosage forms. The raw materials are easy to obtain, the preparation process is relatively simple, and it is suitable for factory industrial production.

[0022] The present invention uses Propionibacterium acnes to induce an acne inflammation model, and intends to conduct a preliminary study on the anti-inflammatory mechanism of the Chinese medicine composition. The results of the present invention show that the isotretinoin soft capsule group and the medium and high dose groups of the Chinese medicine composition can significantly reduce the auricle swelling rate of acne mice.

[0023] The ELISA test results of the present invention indicate that isotretinoin soft capsules and medium- and high-dose Chinese medicine compositions can significantly reduce the levels of serum TNF-α, IL-6, and IL-1 in acne mice.

[0024] The HE staining results of the present invention show that the isotretinoin soft capsule and the medium and high doses of the Chinese medicine composition can effectively improve the pathological damage of the ears of acne mice. The above results all indicate that the Chinese medicine composition has a significant inhibitory effect on the acne inflammatory reaction induced by Propionibacterium acnes. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required to be used in the embodiments are briefly introduced below.

[0026] Figure 1 is the linear relationship diagram of quercetin;

[0027] Figure 2 The effect of the Chinese medicine composition on the auricle morphology of acne model mice, A. normal control group B. model group C. low-dose group of the Chinese medicine composition D. medium-dose group of the Chinese medicine composition E. high-dose group of the Chinese medicine composition F. isotretinoin soft capsule group;

[0028] Figure 3 The effect of the Chinese medicine composition on the auricle tissue pathology of acne model mice (×400), A. normal control group B. model group C. low-dose group of the Chinese medicine composition D. medium-dose group of the Chinese medicine composition E. high-dose group of the Chinese medicine composition F. isotretinoin soft capsule group. DETAILED DESCRIPTION

[0029] The invention provides a Chinese medicine composition for treating acne, comprising the following components in parts by weight: 270 parts of Herba Euphorbiae Ichthyophthirius, 90 parts of Smilax Chinensis, 63 parts of Aloe Vera, 45 parts of Terminalia Chebula, 45 parts of Cibotium Officinale, 45 parts of Tamarindus Indica, 45 parts of Kashikapu Ziziphi Spinosae, 45 parts of Polypodium Vulgare and 25 parts of Scamonia Reticulata. The invention has no special limitation on the sources of the above drugs, and conventional commercially available ones can be used.

[0030] The present invention also provides a method for preparing the Chinese medicine composition described in the above technical solution, comprising the following steps:

[0031] 1) mixing the herb of euphorbia pulex, sarsaparilla, terminalia chebula, citronella, tamarind, jujube, polypodium vulgare and water and decocting the mixture to obtain a decoction;

[0032] 2) concentrating and drying the decoction obtained in step 1) to obtain Chinese medicine powder;

[0033] 3) The Chinese medicine powder obtained in step 2) is mixed with aloe vera and scabraxan to obtain a Chinese medicine composition.

[0034] The present invention mixes the herb of euphorbia, sarsaparilla, terminalia chebula, citron, tamarind, jujube, radix polypodium and water and then decocts to obtain a decoction. In the present invention, the decoction conditions preferably include: a time of 0.5 to 2 hours, a number of times of 1 to 4 times, and an amount of water added of 10 to 14 times. In the present invention, the decoction conditions more preferably include: a time of 1 hour, a number of times of 3 times, and an amount of water added of 12 times. The decoction method provided by the present invention can improve the paste yield and quercetin content.

[0035] The present invention concentrates and dries the obtained decoction to obtain a Chinese medicine powder. The present invention does not specifically limit the steps of concentration and drying, and those skilled in the art can perform conventional operations. In the present invention, the relative density after concentration is preferably 1.08 to 1.12. In the present invention, the drying temperature is preferably 50 to 80° C., more preferably 60° C.

[0036] The present invention mixes the obtained Chinese medicine powder with aloe vera and scamonia resin to obtain a Chinese medicine composition. In the present invention, the aloe vera and scamonia resin are preferably crushed and passed through a 100-mesh sieve before being mixed with the Chinese medicine powder. The present invention preferably mixes the sieved material with the Chinese medicine powder.

[0037] The present invention also provides the use of the Chinese medicine composition described in the above technical solution in the preparation of a drug for treating acne. The present invention has no special limitation on the dosage form and preparation method of the drug, and those skilled in the art can use conventional methods.

[0038] The present invention also provides the use of the Chinese medicine composition described in the above technical solution in the preparation of acne drugs induced by Propionibacterium acnes. The present invention has no special restrictions on the dosage form and preparation method of the drug, and those skilled in the art can use conventional methods.

[0039] The present invention also provides the use of the Chinese medicine composition described in the above technical solution in the preparation of a drug for treating acne by reducing the content of serum inflammatory factors. The present invention does not specifically limit the dosage form and preparation method of the drug, and those skilled in the art can use conventional methods. In the present invention, the inflammatory factors include one or more of TNF-α, IL-6 and IL-1.

[0040] In order to further illustrate the present invention, the present invention is described in detail below in conjunction with embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0041] Example 1

[0042] 1. Materials and Instruments

[0043] 1. Standard substance: Quercetin reference substance (China Food and Drug Inspection Institute, batch number 100081-201610).

[0044] 2. Test materials: Microcrystalline cellulose, lactose, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, magnesium stearate, all of which are domestically produced pharmaceutical specifications; methanol and acetonitrile are of chromatographic grade; phosphoric acid reagents are of analytical grade, and water is purified water.

[0045] 3. Instruments: Shimadzu high performance liquid chromatograph (LC-2030C Shimadzu Corporation, Japan), electronic balance (YP10002), electronic balance (SOP), ultrasonic cleaner (SK8210HP), DZTW temperature-adjustable electric heating jacket, cooling water circulation device (CA-1116A), vacuum drying oven (gzx-9070MBE), rotary evaporator (RE-501), electric constant temperature water bath (DZKW), etc.

[0046] 2. Dosage Form Selection

[0047] Tablets have accurate dosage, uniform content, good stability, and are easy to carry, transport, and take: the production is mechanized and automated at a high level, so tablets are selected as the dosage form of this Chinese medicine combination.

[0048] 3. Study on preparation process conditions

[0049] (I) Inspection of medicinal materials All medicinal materials were inspected in accordance with relevant statutory standards and all were found to be qualified.

[0050] 2. Design of extraction process route

[0051] Process route design: The process route of this product is designed based on the traditional preparation method, active ingredients and physical and chemical properties of the prescription.

[0052] 1. Study on the water extraction technology of seven medicinal materials including Herba Dijincao

[0053] 1.1 Test methods

[0054] The single factor test method was used to investigate the number of extractions, amount of water added, and extraction time that affect the extraction efficiency. The orthogonal test method was used to investigate the number of extractions, extraction time, and amount of water added. The water extraction rate and quercetin content were used as indicators for comprehensive evaluation to screen the best extraction conditions. Comprehensive score = (extraction rate / maximum extraction rate) × 20% + (quercetin content / maximum quercetin content) × 80%.

[0055] 1.2 Determination of index components

[0056] The quercetin content was determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 edition, Volume 1, page 131).

[0057] The chromatographic conditions and system suitability experiments used octadecylsilane bonded silica gel as filler; acetonitrile-0.4% phosphoric acid solution (48:52) as mobile phase; detection wavelength was 360nm; and the theoretical plate number calculated based on the quercetin peak should be no less than 5000.

[0058] Preparation of reference solution Accurately weigh an appropriate amount of quercetin reference substance and add 80% methanol to prepare a quercetin reference substance solution containing 15 μg per 1 mL.

[0059] Preparation of the test solution: Accurately take 10 mL of the extract concentrate, place it in a 50 mL volumetric flask, add methanol to the mark, shake well, filter, accurately measure 20 mL of the filtrate (weighed), add 7 mL of 25% hydrochloric acid solution, place it in a 85°C water bath for hydrolysis for 30 minutes, take it out, cool it quickly, transfer it to a 50 mL volumetric flask, add methanol to dilute to the mark, shake well, filter, and take the filtrate.

[0060] Determination method: Accurately pipette 10 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0061] 1.3 Test content and results

[0062] 1.3.1 Establishment of quercetin measurement standards

[0063] 1.3.1.1 Investigation of linear range

[0064] Preparation of reference stock solution Accurately weigh 51.8 mg of quercetin reference substance (batch number: 100081-201610), place it in a 50 mL brown volumetric flask, add 80% methanol to make up to volume, accurately pipette 18 mL, place it in a 25 mL brown volumetric flask, add 80% methanol to make up to volume, as the quercetin reference stock solution (739.206 μg / mL).

[0065] Linear relationship investigation: 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 mL of the above reference stock solution was accurately pipetted and placed in 50 brown volumetric flasks respectively. 80% methanol was added to make up the volume, injected into the liquid chromatograph, and the peak area was recorded. The standard curve equation was obtained by regression with the reference concentration (μL / mL) as the horizontal axis and the peak area as the vertical axis: Quercetin y=38467x-18723, R=0.9997. The results are shown in Table 1 Figure 1 .

[0066] Table 1 Results of the linear relationship experiment of quercetin

[0067]

[0068] 1.3.1.2 Methodological Examination

[0069] In the precision test, a reference solution of quercetin with a mass concentration of 14.78 μg / mL was injected 6 times in succession, 10 μL each time, and the peak area RSD% of quercetin in 6 injections was 0.152%. The results are shown in Table 2.

[0070] Table 2 Precision test results (n=6)

[0071]

[0072] The test results show that the instrument has good precision during operation.

[0073] Repeatability test: Seven medicinal materials were weighed according to the prescription, and the extraction process was performed in the same way. According to the preparation method of the test solution in 1.2, 6 test solutions were prepared respectively, and the quercetin content was measured. The average quercetin content was 41.71 μg / g, and the RSD was 1.500%. The results are shown in Table 3.

[0074] Table 3 Repeatability test results (n=6)

[0075]

[0076] Stability test Take the same extract and prepare the test solution according to the preparation method of the test solution. The peak area is measured under the above chromatographic conditions at 0, 1, 2, 4, 6, 12, 24, and 36 hours, and the RSD value is 1.660%. The results show that the test solution is stable within 36 hours at room temperature. The test results are shown in Table 4.

[0077] Table 4 Stability test results

[0078]

[0079] The recovery rate was determined by the standard addition method. Take 20 ml of the same extract, a total of 10 portions, the first portion was recovered as a blank, and the remaining 9 portions were divided into three groups, and 0.5, 1.0, and 1.5 mL of quercetin reference solution with a concentration of 739.206 μg / mL were added respectively, prepared according to the preparation method of the test solution, filtered with a microporous filter membrane (0.45 μm), and detected. The determination was carried out under the chromatographic conditions of the content determination. The average recovery of 9 determinations was 101.2491% (n=9) for quercetin, RSD%=2.026%, and the results are shown in Table 5.

[0080] Table 5 Results of quercetin recovery determination (n=9)

[0081]

[0082] 1.3.2 Single Factor Experiment

[0083] According to the prescription ratio, 7 kinds of medicinal materials including Herba Dijinzi were weighed, and the single factor investigation of extraction times, amount of water added and extraction time was carried out according to Tables 6, 7 and 8. The filtrate was fixed to 2000 ml and prepared according to the test sample processing method. The results are shown in Tables 9, 10 and 11.

[0084] Table 6 Single factor analysis of extraction times

[0085]

[0086] Table 7 Single factor investigation of water addition

[0087]

[0088] Table 8 Single factor investigation of extraction time

[0089]

[0090] Table 9 Single factor investigation results of extraction times

[0091]

[0092] From the experimental results, extraction twice has the highest extraction rate, followed by extraction three times, with the score above 90%, so we chose to extract one, two and three times for further orthogonal investigation.

[0093] Table 10 Results of single factor investigation on water addition

[0094]

[0095] Judging from the experimental results, the extraction rate of 12 times the amount is the highest, followed by 10 times and 14 times, and 8 times the amount is the lowest. After comprehensive consideration, the three levels of 10 times, 12 times, and 14 times the amount were finally selected for further orthogonal experimental investigation.

[0096] Table 11 Results of single factor investigation on extraction time

[0097]

[0098] From the experimental results, the extraction rate is the highest when the extraction time is 1 hour, followed by 1.5 hours and 2 hours, and the lowest is 0.5 hours. After comprehensive consideration, we finally selected 0.5 hours, 1 hour, and 1.5 hours as the three levels for further orthogonal test investigation.

[0099] Orthogonal test

[0100] Weigh 90g of 7 herbs including Herba Dijincao according to the prescription ratio, and perform L9 (3 4 ) Orthogonal test table test, the filtrate was fixed to 2000ml, and the quercetin and cream yield were determined respectively. The results are shown in Table 12 and Table 13.

[0101] Table 12 Experimental factor level table

[0102]

[0103] Table 13 L9 (3 4 ) Orthogonal test

[0104]

[0105] Table 14 Variance analysis table

[0106]

[0107] It can be seen from the intuitive analysis that the factors affecting the water extraction process are A>C>B, with the greatest influence of the number of extractions and extraction time, and the optimal water extraction process conditions are A2B2C3. According to the variance analysis, only factor A has a significant difference (P<0.05), and there is still no significant difference between factors B and C. The water extraction process is: 7 medicinal materials such as Herba Dijin, add 12 times the amount to extract three times, each time for 1 hour. Through the data analysis of the orthogonal experiment, factor C3 is adjusted to C2 or C1; factor B2 is adjusted to B1; by considering the water absorption rate of the medicinal materials and cost saving, the optimal extraction conditions for water extraction are: 7 medicinal materials such as Herba Dijin, extract 3 times, add 12 times the amount each time, each time for 1 hour, filter, and combine the filtrate. According to this condition, a verification experiment was carried out, and the results of the verification experiment were similar to those of the orthogonal experiment.

[0108] 2. Research on concentration and drying process

[0109] In order to prevent the effective ingredients from being destroyed by heat for a long time, the vacuum concentration equipment is used for concentration. According to the properties of the drug, the performance of the equipment and the operating conditions, the vacuum concentration conditions of the Tadu Qingxue Tablets extract are determined to be: 53.3~93.3Kpa.

[0110] According to the investigation and research of concentration and drying process, the relative density of water-extracted clear paste was finally determined to be 1.08-1.12, the concentration temperature was 60℃, and the drying temperature was 60℃. The results are shown in Tables 15, 16, and 17.

[0111] Table 15 Concentration temperature investigation results

[0112]

[0113] Table 16 Concentration density investigation results

[0114]

[0115] Table 17 Drying temperature investigation results

[0116]

[0117] 3. Research on crushing process

[0118] The original process of Tadu Qingxue Tablets: Aloe vera and scabrachoa resin in the prescription are crushed and used as medicine. Considering the properties of the medicinal materials, aloe vera is an extract and scabrachoa resin is a resin-based medicinal material. If there is no special requirement for the dosage form, they should be crushed and used as medicine. In addition, the prescription amount of these two medicinal materials is small, so extraction is not considered.

[0119] 3.1 Study on the grinding process of two medicinal materials separately

[0120] Three batches of aloe vera and scabraxan in the prescription were taken respectively, with three levels in each batch, and the particle size range was investigated between 80, 100 and 120 mesh sieves for grinding process research and the grinding particle size was investigated. The results are shown in Tables 18 and 19 below.

[0121] Table 18 Results of the study on the crushing of aloe vera

[0122]

[0123] Table 19 Results of the crushing test of the medicinal material of Scamonia

[0124]

[0125] The experimental results show that the powder yield of the above medicinal materials gradually decreases with the increase of the crushing particle size, and the difficulty of sieving increases. From the observation of crushing particle size, the powder is finer at 100 mesh, the crushed material is coarser at 80 mesh, and the crushing particle size of 120 mesh medicinal materials is better, but the crushing is more difficult, and there is more loss during the sieving process. In addition, aloe vera medicinal materials are easier to crush, while the medicinal material scamonia resin is more sensitive to heat, the crushing time increases, and the preheating process during the crushing process is sticky, and frozen crushing is required. The crushing rate of the mixed medicinal materials was investigated.

[0126] 3.2 Research on the crushing process of mixed medicinal materials

[0127] According to the prescription ratio, 63g of aloe vera and 25g of scabrax were weighed in three batches, with three levels in each batch. The particle size range was between 80, 100, and 120 mesh sieves to conduct a crushing process study and investigate the crushing particle size. The results are shown in Table 20 below.

[0128] Table 20 Research results of mixed crushing process

[0129]

[0130] According to the results, the powder yield of mixed crushing is higher than 90% when the particle size is 100 mesh, but when the crushing particle size reaches 120 mesh, the crushing rate drops below 90%, so it is more reasonable to determine the crushing particle size at 100 mesh.

[0131] Through the study of the grinding process of the two medicinal materials in the prescription, it was determined that the grinding process is to grind aloe vera separately and freeze-grind scabraxan, and both are passed through a 100-mesh sieve.

[0132] 4. Molding process research

[0133] 4.1 Determination of dosage of excipients

[0134] According to the prescription and extraction process of Tadu Qingxue Tablets, the dosage of excipients was converted:

[0135] Take the prescribed amount of medicinal materials, extract, concentrate, dry and crush them using the ammonium extraction process to obtain about 200g of dry paste powder

[0136] Dry paste powder about 200 g

[0137] Aloe Vera Powder 63 g

[0138] 25 g scamonia fat

[0139] The total is about 57%, which means that the amount of auxiliary materials required is about 43%.

[0140] 4.2 Single factor test of tablet excipients

[0141] According to the physical and chemical properties of the active ingredients in the prescription and the characteristics of the extract tablets, this part takes the viscosity of the soft material, the appearance of the particles, the appearance of the tablet core, the compressibility, the hardness and the disintegration time as the evaluation indicators, and uses a single factor experiment to optimize the type and dosage of fillers, disintegrants and binders.

[0142] 4.2.1 Screening of hygroscopicity of excipients

[0143] The hygroscopicity of tablet particles determines the stability of the preparation in the later stage. The selection of appropriate excipients can reduce the hygroscopicity of tablet particles, which is conducive to the tablet molding and later stability. Therefore, we determined the hygroscopicity of raw dry extracts and common fillers, and selected dextrin, microcrystalline cellulose, lactose, starch, and sucrose, and mixed them with the raw dry extract in a main-excipient ratio of 1:1. Take 10 g of each of the raw dry extract and the above 4 excipients, mix them evenly to make granules, and accurately weigh 2 g of each. The excipients were screened based on the hygroscopicity, molding rate, moisture, granulation, whole granulation, granule condition, and appearance as indicators. The results are shown in Table 21.

[0144] Moisture absorption rate % = [particle weight after moisture absorption - particle weight before moisture absorption) / particle weight before moisture absorption] × 100%

[0145] Table 21 Investigation of moisture absorption rate of five fillers

[0146]

[0147] From the results, it can be seen that the granulation-whole grains of starch and sucrose are not suitable for mixing with the extract particles according to the appearance data. Dextrin, lactose and microcrystalline cellulose are suitable in terms of granulation-whole grains, appearance and forming rate, so the above excipients are further optimized. After the raw materials and excipients are mixed into particles, the hygroscopicity of the raw materials is reduced to a certain extent, and the hygroscopicity of the mixture gradually increases in the order of: lactose, microcrystalline cellulose, starch, dextrin, and sucrose. This shows that its moisture resistance is relatively good. The lower the moisture absorption rate, the less likely the particles are to absorb moisture, and the more stable the quality. The more fine powder, the more unstable the tablet weight.

[0148] 4.2.2 Investigation of filler types

[0149] According to the prescription ratio, the dry extract powder and crushed material were taken as the raw materials of the tablets. Based on the preliminary experiment, the fixed disintegrant was 5% low-substituted hydroxypropyl cellulose (L-HPC), 2% cross-linked polyvinylpyrrolidone (PVPP), the binder was 80% ethanol solution, and the lubricant was 1% magnesium stearate. Starch, lactose and microcrystalline cellulose (MCC) fillers were selected. The hardness, disintegration time and friability were measured according to the (Chinese Pharmacopoeia 2020 Edition). The results are shown in Tables 22 and 23.

[0150] Table 22 Investigation of filler types

[0151]

[0152] Table 23 Results of investigation on filler types

[0153]

[0154] The experimental results show that when starch or lactose is selected as a filler, the soft material has high viscosity, poor particle formability, rough tablet surface, low hardness, poor compressibility and long disintegration time. When microcrystalline cellulose is selected as a filler, the soft material has moderate viscosity, complete particles, smooth tablet appearance, appropriate hardness and short disintegration time, but the compressibility is average. When microcrystalline cellulose and lactose are used in combination, the compressibility is good and other indicators also meet the requirements. Therefore, microcrystalline cellulose and lactose are selected as fillers.

[0155] 4.2.2 Investigation of disintegrant types and dosage

[0156] 4.2.2.1 Investigation of disintegrant types

[0157] Take the raw material powder of the prescription ratio, mix it with the filler and disintegrant, add an appropriate amount of binder to make a soft material, pass through a 16-mesh sieve to granulate, dry the wet granules in a 60℃ oven for 2 h, take them out, sieve through a 14-mesh sieve, mix them evenly with the lubricant, and press them into tablets with a round punch. The best disintegrant was selected based on the core hardness, disintegration time, friability and compressibility. The experimental results are shown in Tables 24 and 25.

[0158] Table 24 Disintegrant Investigation

[0159]

[0160] Table 25 Disintegrant Investigation Results

[0161]

[0162] The results showed that when 10% PVPP was selected as the disintegrant, the tablets had good compressibility, smooth and beautiful cores, good hardness, and short disintegration time. Therefore, 10% PVPP was selected as the disintegrant in the prescription.

[0163] 4.2.3 Investigation of adhesives

[0164] The filler, disintegrant, and lubricant were fixed, and 50%, 60%, 70%, and 80% ethanol were selected as the binder. The optimal binder was screened out based on the soft material viscosity, granulation difficulty, particle appearance, tablet core hardness, brittleness, and disintegration time as the evaluation indicators. The experimental results are shown in Table 26.

[0165] Table 26 Investigation of adhesives

[0166]

[0167] The experimental results show that when 50% and 60% ethanol are used as binders, the soft material has high viscosity, poor particle forming properties, high difficulty in granulation, poor appearance, long disintegration time, and the tablet core hardness does not meet the requirements. The soft material obtained by using 70% ethanol has good viscosity, the particles are harder after forming, and the tablet core hardness is smaller, but the disintegration time is longer. When 80% ethanol solution is used as a binder, the soft material has moderate viscosity, the particles are complete and the hardness is appropriate, the tablet core is smooth and beautiful, and the hardness and disintegration time can meet the requirements, so 80% ethanol solution is selected as the binder in the prescription.

[0168]

Preparation method

[0169] Of the above nine ingredients, except for scamonia fat and aloe vera which are crushed into fine powder, the remaining seven ingredients are added with 12 times the amount of water and boiled for 3 times, each time for 1 hour, filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.08~1.12 (60℃), dried at 60℃, and crushed into fine powder. The scamonia fat and aloe vera fine powder (passed through a 100-mesh sieve) are mixed with microcrystalline cellulose and lactose (ratio: 1.3:1.9) and cross-linked polyvinylpyrrolidone (10%), and then granulated with 80% ethanol (16 mesh), dried (60℃), granulated (16 mesh), added with magnesium stearate (1%), mixed, and pressed into 1000 tablets (0.5 g / tablet).

[0170] Example 2

[0171] Selection and feeding of experimental animals: ICR mice, SPF grade, weight 18-20g, male, purchased from Xinjiang Experimental Animal Research Center, grade: SPF grade. License number: SCXK (new) 2023-0001. Animals were kept in plastic cages for mice, with no more than 6 animals of the same sex in each cage, free access to water and food, room temperature 20℃-26℃, relative humidity 40%-70%, light 12h, dark 12h; adaptive feeding for 3 days before the start of the experiment, and animals that met the requirements were selected as experimental animals after general behavioral observation.

[0172] Preparation method of Chinese medicine composition: 270g of Herba Dijin, 90g of Smilax, 63g of Aloe, 45g of Terminalia chebula, 45g of Cibotium barometz, 45g of Tamarind, 45g of Kashikafuju, 45g of Polypodium vulgare, 25g of Scamonia, among the above nine herbs, except for Scamonia and Aloe, which are ground into fine powder (passed through a 100-mesh sieve), the other seven herbs need to be added with 12% water, boiled for 3 times, each time for 1 hour, then filtered, concentrated, and fixed to 2000ml. Then put it on a water bath to dry until it is paste-like, then put it into a vacuum drying oven, and thoroughly dry it at 60°C for standby use.

[0173] Reagents and test bacteria required for the experiment: Propionibacterium acnes (BNCC330605), batch number: 231215, Beina Biotechnology Co., Ltd.; Isotretinoin soft capsules, batch number: 201505, Shanghai Xinyi Yan'an Pharmaceutical Co., Ltd.; Mouse interleukin 1 (IL-1) ELISA detection kit, batch number: YX-E20532, Mouse interleukin 6 (IL-6) ELISA detection kit, batch number: YX-E20012, Mouse tumor necrosis factor α (TNF-α) ELISA detection kit, batch number: YX-E20220, Shanghai Youxuan Biotechnology Co., Ltd.; Japanese MGC anaerobic gas production bag, Qingdao Green Valley Co., Ltd.; Thioglycollate fluid medium (FTM), batch number: 231227, Nantong Kaiheng Biotechnology Development Co., Ltd.; Columbia blood agar medium, Shanghai Chromagar Microbiology Technology Co., Ltd. Oleic acid and 4% paraformaldehyde universal tissue fixative.

[0174] Solvent: 0.5% sodium carboxymethyl cellulose CMC-Na solution, purchased from Tianjin Guangfu Fine Chemical Research Institute.

[0175] Instruments and equipment required for the experiment: SHZ-D (Ⅲ) circulating water vacuum pump, Shanghai Dongxi Refrigeration Instrument Equipment Co., Ltd.; RE-501 rotary evaporator, Gongyi Yuhua Instrument Co., Ltd.; DC-2015 low-temperature constant temperature bath, Shanghai Yarong Biochemical Instrument Factory; DZTW temperature-adjustable electric heating sleeve, Beijing Yongguangming Medical Instrument Factory; DHG-9140A electric heating blast drying oven, Shanghai Xingchuang Scientific Instrument Equipment Co., Ltd.; SW-CJ-1F clean bench, Suzhou Antai Air Technology Co., Ltd.; bsp-400 biochemical incubator, Shanghai Boxun Medical Biological Instrument Co., Ltd.; electric constant temperature water bath, Beijing Yongguangming Medical Instrument Co., Ltd.; 99E0214 ultrasonic cleaner, Shanghai Kedao Ultrasonic Instrument Co., Ltd.; gzx-9070MBE vacuum drying oven, Shanghai Jinghong Testing Equipment Co., Ltd.; digital caliper, Shanghai Jiuliang Hardware Tools Co., Ltd.

[0176] Animal grouping and administration: 72 ICR male mice were randomly divided into normal control group, model group, isotretinoin soft capsule (4.55 mg / kg) group and low (0.15 g / kg), medium (0.30 g / kg) and high (0.60 g / kg) dose groups of the Chinese medicine composition, with 12 mice in each group. Except for the normal control group, 2% oleic acid was applied to the right auricle of the mice in the other five groups every day, and 50uL Propionibacterium acnes (1×10 7 CFU / mL) for 14 consecutive days. If the modeling site showed obvious thickening of the auricle, redness, swelling, hardening and nodules, and sebum flakes on the skin surface, the modeling was successful. Two mice were randomly selected from the model group for ear pathological sections. If the epidermis was significantly thickened and the dermis was infiltrated with lymphocytes and neutrophils, the acne model was successfully established. According to the equivalent dose conversion method between humans and animals, each drug group was gavaged with the corresponding dose of drug, and the normal control group and model group were gavaged with the corresponding volume of normal saline for 21 consecutive days.

[0177] Apparent morphological changes of mouse auricle and auricle swelling rate: Before modeling, the thickness of the right auricle of each group of mice was measured with a vernier caliper, which was recorded as the auricle thickness before modeling. During the modeling period, the changes of the right auricle of the mice were observed with the naked eye to see whether the skin tissue of the ear was red, swollen, or thickened; whether papules or pustules appeared; whether sebaceous glands appeared in the modeling site, etc. After the modeling, the thickness of the right auricle of each group of mice was measured and recorded as the auricle thickness after modeling. The improvement of the ear skin of the mice in the observation group during the drug treatment. After the drug administration, the thickness of the right auricle of the rats in the treatment group was measured and recorded as the auricle thickness after injection in the treatment group, and the auricle swelling rate of the mice was calculated.

[0178] Mouse ear swelling rate = (ear thickness after injection - ear thickness before injection) / ear thickness before injection.

[0179] Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α, IL-6, and IL-1 in mouse serum

[0180] After the last administration, all mice were fasted but not watered for 24 h. Blood was collected from the mouse eyeballs, left at room temperature for more than 2 h, centrifuged at 3500 r / min, 4°C for 15 min, and the supernatant was kept. All reagents in the ELISA kit were left at room temperature for more than 30 min, and the operation was strictly in accordance with the instructions of the kit. The absorbance (OD value) was measured at a wavelength of 450 nm using an ELISA reader, and the content of TNF-α, IL-6, and IL-1 was calculated based on the drawn standard curve.

[0181] Determination of mouse thymus and spleen index: 2 hours after the last oral administration, the mice were weighed, killed by cervical dislocation, and immersed in 75% alcohol solution. The thymus and spleen were quickly removed aseptically in an ultra-clean workbench and weighed with an electronic balance. Thymus index = thymus mass (mg) / mouse mass (g), spleen index = spleen mass (mg) / mouse mass (g).

[0182] Observation of mouse auricle tissue pathological sections: The fresh tissue was fixed with 4% formaldehyde for more than 24 hours, and then embedded in paraffin and sectioned into about 3 μm sections. The paraffin blocks were routinely dewaxed in xylene, and then dehydrated with ethanol gradient, and stained with hematoxylin-eosin (HE) and photographed under a microscope.

[0183] SPSS22 software was used to perform statistical analysis on the experimental results, and one-way analysis of variance was used to compare the differences among multiple groups. The difference was considered statistically significant when P < 0.05.

[0184] Experimental Results

[0185] Observation of body weight changes in mice during drug administration: Compared with the normal control group, the body weight of mice in the model group and the high-dose Chinese medicine combination group decreased significantly on the 7th, 14th, and 21st days (P<0.01). Compared with the model group, except for the high-dose Chinese medicine combination group, the low and medium doses and isotretinoin groups increased significantly (P<0.01).

[0186] Observation of the changes in the apparent morphology of the auricle and the swelling rate of the auricle of mice: According to the experimental results, the auricle capillaries of the mice in the normal control group were very clear, soft in texture, and light pink, without any rash, inflammatory reaction, loss of subcutaneous fat secretion, pustules or papules; while the auricle skin surface of the mice in the model group was rough, and the auricle skin surface of the mice was severely greasy, atrophic, deformed, and thickened, and some papules or pustules were formed; Isotretinoin soft capsules reduced and thickened the capillaries of mice, and the redness and swelling of the auricle and skin wrinkles of the mice were completely relieved, and papules and pustules were completely eliminated, and the capillaries became more clearly visible; in the high-dose group of Tadu, although a few mice still had inflammation of the auricle, the rest of the mice were in the same situation as the isotretinoin soft capsule group; in addition, the low- and medium-dose groups of the Chinese medicine combination showed pathological reactions similar to those of the model group, but after careful observation, this situation was also significantly improved. After the experiment, it was found that, with a few exceptions, the auricles of most mice in the high-dose Chinese medicine composition and isotretinoin soft capsule groups were well treated. According to Table 2, it can be seen that compared with the normal group, the thickness and swelling rate of the auricles of the mice in the model group (71%) increased significantly (P<0.01); compared with the model group, the thickness and swelling rate of the auricles of the mice in the Chinese medicine composition and each administration group decreased significantly, among which the high-dose Chinese medicine composition group (29%) and the isotretinoin soft capsule group (21%) had extremely significant differences (P<0.01);

[0187] Effects on the content of inflammatory factors TNF-α, IL-6, and IL-1 in mouse serum: Compared with the normal control group, the content of TNF-α, IL-6, and IL-1 in the model group was significantly increased (P<0.01). Compared with the model group, the content of TNF-α, IL-6, and IL-1 in the serum of mice in each group treated with the Chinese medicine composition was significantly reduced (P<0.05 or P<0.01). Among them, the difference between the high-dose Chinese medicine composition group and the isotretinoin soft capsule group was extremely significant (P<0.01).

[0188] Determination of mouse thymus and spleen index: Compared with the normal control group, the spleen and thymus index of the model group mice was significantly reduced (P<0.01). Compared with the model group, the spleen and thymus index of the mice in each group of the Chinese medicine composition administration was significantly increased, among which the high-dose Chinese medicine composition group and the isotretinoin soft capsule group had extremely significant differences (P<0.01).

[0189] Observation of pathological sections of mouse auricle tissue: no obvious abnormality was found in the auricle of mice in the normal control group, the boundaries between the dermis, epidermis and subcutaneous tissue were clear, and there was no inflammatory cell infiltration; the epidermis of the auricle of mice in the model group was significantly thickened, the boundaries between the dermis, epidermis and subcutaneous tissue became blurred, a large number of inflammatory cells infiltrated the dermis, and the capillaries in the dermis were significantly dilated; the epidermal thickness of the auricle of mice in the isotretinoin soft capsule group and the high-dose group of the Chinese medicine composition was significantly reduced, the boundaries between the dermis, epidermis and subcutaneous tissue were basically clearly visible, and there was a small amount of inflammatory cell infiltration; compared with the model group, the epidermal thickness of the auricle of mice in the medium and low-dose groups of the Chinese medicine composition was slightly reduced, part of the epidermis was necrotic, the structure disappeared, the dermis, epidermis and subcutaneous tissue were slightly improved, and there was inflammatory cell infiltration.

[0190] Table 27 Effects of Chinese herbal compound on body weight of acne model mice (x±s, n=10)

[0191]

[0192] Note: Compared with the normal control group, ★P<0.05, ★★P<0.01; compared with the model group, #P<0.05, ##P<0.01

[0193] Table 28 Effects of Chinese herbal compound on auricle thickness and swelling rate in acne model mice (x±s, n=10)

[0194]

[0195] Note: Compared with the normal control group, ★P<0.05, ★★P<0.01; compared with the model group, #P<0.05, ##P<0.01

[0196] Table 29 Effects of Chinese herbal compound combination on serum inflammatory factors TNF-α, IL-6, and IL-1 levels in acne model mice (x±s, n=10)

[0197]

[0198] Note: Compared with the normal control group, ★P<0.05, ★★P<0.01; compared with the model group, #P<0.05, ##P<0.01

[0199] Table 30 Effects of compound Chinese medicine combination on thymus and spleen indexes of acne model mice (x±s, n=10)

[0200]

[0201] Note: Compared with the normal control group, ★P<0.05, ★★P<0.01; compared with the model group, #P<0.05, ##P<0.01

[0202] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating acne, characterized in that: The composition comprises the following components in parts by weight: 270 parts of Herba Euphorbiae Ichthyophthirius, 90 parts of Smilax Chinensis, 63 parts of Aloe Vera, 45 parts of Myrobalan, 45 parts of Cibotium Officinale, 45 parts of Tamarindus Indica, 45 parts of Kashikapu Ziziphus, 45 parts of Polypodium Vulgare and 25 parts of Scamonia Resin.

2. A method for preparing the Chinese medicine composition according to claim 1, characterized in that: The following steps are involved: 1) mixing the herb, smilax china, terminalia chebula, citron, tamarind, jujube, polypodium vulgare and water, and then boiling the mixture to obtain a decoction; 2) concentrating and drying the decoction obtained in step 1) to obtain Chinese medicine powder; 3) The Chinese medicine powder obtained in step 2) is mixed with aloe vera and scabraxan to obtain a Chinese medicine composition.

3. The preparation method according to claim 2, characterized in that: The conditions of decoction in step 1) include: time of 0.5-2 hours, number of times of 1-4 times, and amount of water added of 10-14 times.

4. The preparation method according to claim 2 or 3, characterized in that: The decoction conditions include: the decoction time is 1 hour, the number of times is 3 times, and the amount of water added is 12 times.

5. The preparation method according to claim 2, characterized in that: The aloe vera and scabrax are ground, passed through a 100-mesh sieve, and then mixed with the Chinese medicine powder.

6. Use of the Chinese medicine composition according to claim 1 in preparing a drug for treating acne.

7. Use of the Chinese medicine composition according to claim 1 in the preparation of acne medicine induced by Propionibacterium acnes.

8. Use of the Chinese medicine composition according to claim 1 in the preparation of a drug for treating acne by reducing the content of serum inflammatory factors.

9. The use according to claim 8, characterized in that: The inflammatory factors include one or more of TNF-α, IL-6 and IL-1.

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