Compound traditional Chinese medicine acne gel preparation as well as preparation method and application thereof

Abstract

The invention discloses a compound traditional Chinese medicine acne gel preparation as well as a preparation method and application thereof, the traditional Chinese medicine raw materials comprise nine traditional Chinese medicines such as salvia miltiorrhiza, scutellaria baicalensis, oldenlandia diffusa, centella asiatica, wild chrysanthemum flower, safflower, honeysuckle, mangnolia officinalis and liquorice, and the gel preparation is prepared. The acne treatment effect is achieved through the effects of clearing away heat and toxic materials, promoting blood circulation to remove blood stasis, promoting qi circulation to remove dampness and the like.

Description

Technical Field

[0001] The invention relates to the field of medicine, and in particular to a traditional Chinese medicine gel preparation and a preparation method and application thereof. Background Art

[0002] Acne is a chronic inflammatory skin disease of the hair follicles and sebaceous glands, characterized by the presence of non-inflammatory (open and closed comedones) and inflammatory (papules, pustules and nodules) lesions, which mainly occur in areas with dense sebaceous glands, such as the cheeks, forehead, and mandible, and can also be seen on the chest, upper back and shoulders. The course of acne is slow, often lasting until middle age before gradually alleviating and healing, causing many inconveniences to patients' lives and social life. The pathogenesis of acne is relatively complex and has not yet been fully understood. The current mainstream view is that it mainly includes four aspects: excessive skin oil secretion, abnormal keratinization of cells around hair follicles, abnormal microbial flora and inflammatory response.

[0003] At present, Western medicine mostly uses oral, topical drugs or physical therapy to treat acne. Commonly used drugs include retinoic acid drugs, antibiotics, and hormones. Although Western medicine treatment has certain efficacy, there are still problems of contraindications and toxic side effects. For example, oral isotretinoin has toxic side effects such as teratogenicity and increased blood lipids, and topical hormone chemicals may cause side effects such as chronic skin damage. The external methods for treating acne include acid brushing treatment or using acne removal products containing acids, but acids can cause obvious burning sensations on the face of acne patients, aggravating the degree of skin damage. There are also some Chinese medicine products for treating acne in the prior art, such as the previously applied CN201310527422.X patent application, which uses Salvia miltiorrhiza, Scutellaria baicalensis, Hedyotis diffusa, Chrysanthemum indica, Carthamus tinctorius, White Wei, and Licorice as the main raw materials and Carbomer as the matrix to prepare the gel, which can play a certain improvement role after rabbit ear acne test verification, but compared with the mainstream drugs for treating acne on the market, there is still a certain gap. Therefore, based on the theory of traditional Chinese medicine and the principle of Chinese medicine compatibility, this patent adds three Chinese medicines such as Centella asiatica, Honeysuckle and Magnolia officinalis to take advantage of their detoxification and qi-promoting functions, so that the whole prescription has both ascending and descending effects, and purgative and tonifying effects, which can jointly achieve the effects of clearing away heat, detoxifying, promoting blood circulation and removing blood stasis. Moreover, it has been verified by efficacy tests that the present invention has an inhibitory effect on the abnormal increase of TNF-α, IL-6 and IL-1β levels in rabbits caused by acne, and exhibits a stronger anti-inflammatory effect; at the same time, Centella asiatica has the effect of reducing swelling and promoting tissue regeneration, can promote the formation of granulation tissue, activate epithelial cells, accelerate wound healing, and is beneficial to the repair of scars caused by acne; in addition, in order to avoid the occurrence of side effects such as headaches and nausea, the white violet that may contain cardiac glycosides is removed to improve the safety of the medication. The patent application CN201910577209.7 discloses an acne gel, which is prepared by extracting a traditional Chinese medicine compound. The raw materials include scutellaria baicalensis, coptis chinensis, phellodendron chinense, sophora flavescens, angelica dahurica, bletilla striata, poria, salvia miltiorrhiza, urea, salicylic acid, carbomer, laurocapron, and triethylamide in appropriate amounts. It can treat various types of acne, surgical surface infections such as carbuncles, swellings, and burns, and reduce swelling. However, the addition of salicylic acid may cause a burning sensation to the skin and cause certain damage to the skin; the patent application CN202211368180.X provides a traditional Chinese medicine composition for treating acne, and its preparation method and application, wherein the traditional Chinese medicine composition includes five traditional Chinese medicines such as sophora flavescens, salvia miltiorrhiza, wild chrysanthemum, white peony root, and liquorice, but its active ingredient contains potassium azelayl diglycinate, and there is a lack of safety information on this ingredient, which poses certain safety risks.

[0004] Traditional Chinese medicine has accumulated rich experience in the treatment of acne. The diagnosis and treatment methods of acne have long been recorded in the history of traditional Chinese medicine, such as "Xizhu of the Origin of Miscellaneous Diseases·Origin of Nose Diseases": "The nose is red and swollen... and some people do not drink alcohol but the nose is red. This is called lung wind sore, which is caused by blood heat stagnation in the lungs. It is suitable to use Qingfei Yinzi, or use Siwu and Wuling together, and add Huangqin and Huangbai." There is also "Lei Zheng Zhi Cai·Nose and Mouth Disease": "Some people do not drink alcohol but the nose is red. This is called lung wind, which is caused by blood heat stagnation in the lungs. Qingfei Yinzi is suitable." Traditional Chinese medicine treats acne with the principle of "promoting lung, clearing heat, and removing dampness", which mainly includes clearing heat and detoxification, dispersing wind and heat, clearing dampness and heat, promoting blood circulation and removing blood stasis, removing blood stasis and dispersing nodules, and removing phlegm and unblocking collaterals. Among them, external treatment with traditional Chinese medicine is a commonly used treatment method in clinical practice, but because acne is self-limiting and prone to fluctuations in the course of the disease, new compound drugs still need to be developed in external treatment of traditional Chinese medicine to improve the efficacy. Summary of the invention

[0005] In view of the many limitations of current drugs on the market, the present invention aims to provide a Chinese medicine compound composition and preparation thereof for preventing or treating acne, so as to help acne patients get out of trouble. The pharmaceutical composition of the present invention is composed of Chinese medicinal materials as the main raw materials; the Chinese medicinal extract is obtained by extracting the raw medicinal materials with ethanol or water as the extraction solvent; the pharmaceutical preparation is obtained by conventional preparation methods with the Chinese medicinal extract and conventional excipients acceptable in pharmacy; the specific dosage forms include gels, solutions, ointments, powders, tinctures, lotions, sprays, creams, pastes, and film coatings. The medicine of the present application is simple to use, has significant efficacy, and is used for the prevention or treatment of acne on acne-like skin and oily skin.

[0006] In the first aspect, the present invention provides a Chinese medicine compound composition, whose raw medicinal materials are composed of nine Chinese medicinal materials, namely, Salvia miltiorrhiza, Scutellaria baicalensis, Oldenlandia diffusa, Centella asiatica, Chrysanthemum indica, Carthamus tinctorius, Honeysuckle, Magnolia officinalis, and Licorice, with 5-30 parts of Salvia miltiorrhiza, 10-40 parts of Scutellaria baicalensis, 10-40 parts of Oldenlandia diffusa, 10-40 parts of Centella asiatica, 10-40 parts of Chrysanthemum indica, 5-25 parts of Carthamus tinctorius, 5-30 parts of Honeysuckle, 5-30 parts of Magnolia officinalis, and 5-25 parts of Licorice.

[0007] Preferably, the raw medicinal materials are as follows: 5-30 parts of Salvia miltiorrhiza, 10-40 parts of Scutellaria baicalensis, 10-40 parts of Oldenlandia diffusa, 10-40 parts of Centella asiatica, 10-40 parts of Chrysanthemum indica, 5-25 parts of Carthamus tinctorius, 5-30 parts of Honeysuckle, 5-30 parts of Magnolia officinalis, and 5-25 parts of Licorice.

[0008] Preferably, the raw medicinal materials are as follows: 10-20 parts of Salvia miltiorrhiza, 15-30 parts of Scutellaria baicalensis, 15-30 parts of Oldenlandia diffusa, 15-30 parts of Centella asiatica, 15-30 parts of Chrysanthemum indica, 5-15 parts of Carthamus tinctorius, 10-20 parts of Honeysuckle, 10-20 parts of Magnolia officinalis, and 5-15 parts of Licorice.

[0009] Preferably, the raw medicinal materials are as follows: 12-18 parts of Salvia miltiorrhiza, 18-25 parts of Scutellaria baicalensis, 18-25 parts of Oldenlandia diffusa, 18-25 parts of Centella asiatica, 18-25 parts of Chrysanthemum indica, 8-12 parts of Carthamus tinctorius, 12-18 parts of Honeysuckle, 12-18 parts of Magnolia officinalis, and 8-12 parts of Licorice.

[0010] Most preferably, the raw medicinal materials are as follows: 15 parts of Salvia miltiorrhiza, 20 parts of Scutellaria baicalensis, 20 parts of Oldenlandia diffusa, 20 parts of Centella asiatica, 20 parts of Chrysanthemum indici, 10 parts of Carthamus tinctorius, 15 parts of Honeysuckle, 15 parts of Magnolia officinalis, and 10 parts of Licorice.

[0011] In a second aspect, the present invention provides a Chinese medicine extract prepared from the raw medicinal materials of the above Chinese medicine compound composition, wherein the extraction solvent can be selected from an ethanol aqueous solution or water with a volume fraction of 30% to 80%.

[0012] The medicinal material extraction process is selected from the following two methods:

[0013] (1) Alcohol extraction process: Weigh the prescribed medicinal materials, add 6 to 20 times the volume of 30% to 80% ethanol aqueous solution for reflux extraction, and extract 1 to 4 times, each time for 1 to 3 hours;

[0014] (2) Water extraction process: Weigh the prescribed medicinal materials, add 6 to 20 times the amount of water for reflux extraction, and extract 1 to 4 times, each time for 1 to 3 hours;

[0015] After the extraction is completed, the extracts are combined and centrifuged at 3000-8000rpm for 3-20min. The supernatant is spray-dried with an inlet air temperature of 120-140°C, an outlet air temperature of 60-80°C, and a peristaltic pump flow rate of 5-15ml / min to obtain a spray-dried powder of the Chinese medicine extract.

[0016] In a third aspect, the present invention provides a Chinese medicine compound preparation, which is prepared by conventional methods from the above Chinese medicine extracts and pharmaceutically acceptable excipients. The gel preparation uses an aqueous gel as a matrix, and the gel matrix includes the following components: carbomer, hydroxyethyl cellulose, xanthan gum, pullulan, glycerin, propylene glycol, phenoxyethanol, and distilled water.

[0017] The preparation method of the Chinese medicine compound gel comprises the following steps: Step 1) Preparation of Chinese medicine extract: weighing the prescribed medicinal materials, adding the extraction solvent for reflux extraction, centrifuging the extract, taking the supernatant for spray drying, and obtaining the spray-dried powder of the Chinese medicine extract;

[0018] Step 2) Preparation of gel: Take the spray-dried powder of the Chinese herbal extract obtained in step 1), add part of the distilled water to dissolve it, add carbomer, hydroxyethyl cellulose, xanthan gum and pullulan, stir, and after swelling is complete and mixed evenly, continue to add glycerol, propylene glycol and phenoxyethanol, adjust the pH value, add the remaining distilled water, stir, and mix the gel evenly to obtain; the weight ratio of the spray-dried powder of the Chinese herbal extract to the total amount of distilled water is 5-30:200-1000.

[0019] Step 1) Preparation of Chinese herbal medicine extract

[0020] The extraction solvent may be an ethanol aqueous solution or water with a volume fraction of 30% to 80%.

[0021] The medicinal material extraction process is selected from the following two methods:

[0022] (1) Alcohol extraction process: Weigh the prescribed medicinal materials, add 6 to 20 times the volume of 30% to 80% ethanol aqueous solution for reflux extraction, and extract 1 to 4 times, each time for 1 to 3 hours;

[0023] (2) Water extraction process: Weigh the prescribed medicinal materials, add 6 to 20 times the amount of water for reflux extraction, and extract 1 to 4 times, each time for 1 to 3 hours;

[0024] After the extraction is completed, the extracts are combined, centrifuged at 3000-8000 rpm for 3-20 min, and the supernatant is spray-dried at an air inlet temperature of 120-140°C, an air outlet temperature of 60-80°C, and a peristaltic pump flow rate of 5-15 ml / min to obtain a spray-dried powder of the Chinese medicine extract;

[0025] Step 2) Preparation of gel

[0026] Take 5 to 30 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1), add an appropriate amount of distilled water to dissolve it, and after dissolution, add 1 to 5 parts of carbomer, 1 to 5 parts of hydroxyethyl cellulose, 0.5 to 3 parts of xanthan gum and 0.5 to 3 parts of pullulan, stir at 300 to 700 rpm, and after swelling is complete and mixed evenly, continue to add 15 to 60 parts of glycerol, 30 to 120 parts of propylene glycol and 2 to 8 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 5-7, add the remaining distilled water, and add a total of 200 to 1000 parts of distilled water, increase the speed to 350 to 750 rpm, mix the gel evenly, and fill it after sterilization.

[0027] Preferably, in step 2, the pH value is adjusted to 6; sterilization can be performed at 120° C. for 30 min.

[0028] Specifically, the preparation method of the Chinese medicine compound gel preparation using the alcohol extraction process is as follows:

[0029] Step 1): weigh the prescribed medicinal materials, add 6 to 20 times the volume fraction of 30% to 80% ethanol aqueous solution for reflux extraction, extract 1 to 4 times, each time for 1 to 3 hours; after the extraction is completed, combine the extracts, centrifuge at 3000 to 8000 rpm for 3 to 20 minutes, take the supernatant for spray drying, the inlet air temperature is 120 to 140°C, the outlet air temperature is 60 to 80°C, and the peristaltic pump flow rate is 5 to 15 ml / min to obtain the spray-dried powder of the Chinese medicine extract;

[0030] Step 2): Take 5 to 30 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 1 to 5 parts of carbomer, 1 to 5 parts of hydroxyethyl cellulose, 0.5 to 3 parts of xanthan gum and 0.5 to 3 parts of pullulan, stir at 300 to 700 rpm, and after swelling is complete and mixed evenly, continue to add 15 to 60 parts of glycerol, 30 to 120 parts of propylene glycol and 2 to 8 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 5-7, add the remaining distilled water, and add a total of 200 to 1000 parts of distilled water, increase the speed to 350 to 750 rpm, mix the gel evenly, and fill it after sterilization.

[0031] Preferably, the preparation method of the Chinese medicine compound gel preparation using the alcohol extraction process is as follows:

[0032] Step 1): weigh the prescribed medicinal materials, add 8 to 16 times the volume fraction of 50% to 75% ethanol aqueous solution for reflux extraction, extract 1 to 3 times, each time for 1.5 to 2.5 hours, combine the extracts, centrifuge at 4000 to 6000 rpm for 5 to 15 minutes, take the supernatant for spray drying, the inlet air temperature is 125 to 135° C., the outlet air temperature is 65 to 75° C., and the peristaltic pump flow rate is 7 to 12 ml / min to obtain the spray-dried powder of the Chinese medicine extract;

[0033] Step 2): Take 10-20 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, add 2-4 parts of carbomer, 2-4 parts of hydroxyethyl cellulose, 1-2 parts of xanthan gum and 1-2 parts of pullulan after dissolution, stir at 350-550 rpm, and after swelling is complete and mixed evenly, continue to add 25-50 parts of glycerol, 50-100 parts of propylene glycol and 3-6 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 400-800 parts of distilled water, increase the rotation speed to 400-600 rpm, mix the gel evenly, and fill it after sterilization.

[0034] Specifically, the preparation method of the Chinese medicine compound gel preparation using the water extraction process is as follows:

[0035] Step 1): weigh the prescribed medicinal materials, add 6 to 20 times the amount of water for reflux extraction, extract 1 to 4 times, each time for 1 to 3 hours; after the extraction is completed, combine the extracts, centrifuge at 3000 to 8000 rpm for 3 to 20 minutes, take the supernatant for spray drying, the inlet air temperature is 120 to 140°C, the outlet air temperature is 60 to 80°C, and the peristaltic pump flow rate is 5 to 15 ml / min to obtain the spray-dried powder of the Chinese medicine extract;

[0036] Step 2): Take 5 to 30 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 1 to 5 parts of carbomer, 1 to 5 parts of hydroxyethyl cellulose, 0.5 to 3 parts of xanthan gum and 0.5 to 3 parts of pullulan, stir at 300 to 700 rpm, and after swelling is complete and mixed evenly, continue to add 15 to 60 parts of glycerol, 30 to 120 parts of propylene glycol and 2 to 8 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 5-7, add the remaining distilled water, and add a total of 200 to 1000 parts of distilled water, increase the speed to 350 to 750 rpm, mix the gel evenly, and fill it after sterilization.

[0037] Preferably, the preparation method of the Chinese medicine compound gel preparation using the water extraction process is as follows:

[0038] Step 1): weigh the prescribed medicinal materials, add 8 to 16 times the amount of water for reflux extraction, extract 1 to 3 times, each time for 1.5 to 2.5 hours, combine the extracts, centrifuge at 4000 to 6000 rpm for 5 to 15 minutes, take the supernatant for spray drying, the inlet air temperature is 125 to 135°C, the outlet air temperature is 65 to 75°C, and the peristaltic pump flow rate is 7 to 12 ml / min to obtain the spray-dried powder of the Chinese medicine extract;

[0039] Step 2): Take 10-20 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, add 2-4 parts of carbomer, 2-4 parts of hydroxyethyl cellulose, 1-2 parts of xanthan gum and 1-2 parts of pullulan after dissolution, stir at 350-550 rpm, and after swelling is complete and mixed evenly, continue to add 25-50 parts of glycerol, 50-100 parts of propylene glycol and 3-6 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 400-800 parts of distilled water, increase the rotation speed to 400-600 rpm, mix the gel evenly, and fill it after sterilization. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 Blank rabbit ears and acne model rabbit ears, where A is the blank rabbit ear observed with the naked eye; B is the model rabbit ear observed with the naked eye; C is the blank rabbit ear under an electron microscope (200X); D is the model rabbit ear under an electron microscope (200X).

[0041] Figure 2The apparent morphology of each group was compared after two weeks of ear treatment, including A blank group; B model group; C positive drug group; D alcohol extraction best low dose group; E alcohol extraction best medium dose group; F alcohol extraction best high dose group; G alcohol extraction suitable low dose group; H alcohol extraction suitable medium dose group; I alcohol extraction suitable high dose group; J water extraction best low dose group; K water extraction best medium dose group; L water extraction best high dose group; M water extraction suitable low dose group; N water extraction suitable medium dose group; O water extraction suitable high dose group; P patent CN201310527422.X group; Q Centella asiatica, Magnolia officinalis and Honeysuckle group.

[0042] Figure 3 HE staining results (200X), among which, A blank group; B model group; C positive drug group; D alcohol extraction best low dose group; E alcohol extraction best medium dose group; F alcohol extraction best high dose group; G alcohol extraction suitable low dose group; H alcohol extraction suitable medium dose group; I alcohol extraction suitable high dose group; J water extraction best low dose group; K water extraction best medium dose group; L water extraction best high dose group; M water extraction suitable low dose group; N water extraction suitable medium dose group; O water extraction suitable high dose group; P patent CN201310527422.X group; Q Centella asiatica, Magnolia officinalis and Honeysuckle group.

[0043] Figure 4 Serum TNF-α levels.

[0044] Note: Different lowercase letters in each column indicate statistically significant differences among the groups (p<0.05).

[0045] Figure 5 Serum IL-6 levels.

[0046] Note: Different lowercase letters in each column indicate statistically significant differences among the groups (p<0.05).

[0047] Figure 6 Serum IL-1β levels.

[0048] Note: Different lowercase letters in each column indicate statistically significant differences among the groups (p<0.05).

[0049] Figure 7 Single-dose irritation results.

[0050] Figure 8 Repeated dosing results in irritation. DETAILED DESCRIPTION

[0051] Experimental Example 1: Study on the Extraction Process of Traditional Chinese Medicine of the Present Invention

[0052] 1.1 Instruments and reagents

[0053] Constant temperature electric heating mantle (ZDHW, Beijing Zhongxing Weiye Instrument Co., Ltd.); water bath (HH-8, Changzhou Yuexin Instrument Manufacturing Co., Ltd.); rotary evaporator (N-1100, Shanghai Ailang Instrument Co., Ltd.); ultrasonic cleaning machine (KQ-400KDE, Kunshan Ultrasonic Instrument Co., Ltd.); high performance liquid chromatograph (Agilent-1260, Agilent Technologies Co., Ltd.); one millionth balance (XPR6UD50, Mettler-Toledo); one ten-thousandth balance (AX224ZH, Ohaus Instrument (Changzhou) Co., Ltd.)

[0054] Danshen (2310183, Beijing Shengshilong Pharmaceutical Co., Ltd.); Scutellaria baicalensis (2402035, Beijing Shengshilong Pharmaceutical Co., Ltd.); Hedyotis diffusa (2312052, Beijing Shengshilong Pharmaceutical Co., Ltd.); Centella asiatica (20220905, Beijing Tongrentang Health Pharmaceutical Co., Ltd.); Chrysanthemum indica (220806001, Darentang (Tianjin) Chinese Medicine Pieces Co., Ltd.); Carthamus tinctorius (2311144, Beijing Shengshilong Pharmaceutical Co., Ltd.); Honeysuckle (221210103, Darentang (Tianjin) Chinese Medicine Pieces Co., Ltd.); Magnolia officinalis (9220801312, Darentang (Tianjin) Chinese Medicine Pieces Co., Ltd.); Licorice ( 2312185, Beijing Shengshilong Pharmaceutical Co., Ltd.); baicalin reference substance (N15GB167969, ≥98%, Shanghai Yuanye Biotechnology Co., Ltd.); salvianolic acid B reference substance (BN23HB202048, ≥98%, Shanghai Yuanye Biotechnology Co., Ltd.); montanol reference substance (A11IB222723, ≥98%, Shanghai Yuanye Biotechnology Co., Ltd.); methanol (chromatographic grade, Tianjin Concord Reagent Co., Ltd.); acetonitrile (chromatographic grade, Tianjin Concord Reagent Co., Ltd.); ethanol (analytical grade, Tianjin Concord Reagent Co., Ltd.); phosphoric acid (218128, Thermo Fisher Scientific (China) Co., Ltd.)

[0055] 1.2 Extraction process investigation

[0056] By consulting the literature, the main active ingredients and pharmacological effects of the prescription drugs were analyzed (see Table 1). Taking into account the appropriate extraction conditions of each Chinese medicine, based on the principle of simple and feasible operation, the basic process was proposed as follows: reflux extraction with 10 times the volume (V / W) of 60% ethanol aqueous solution, each time for 1.5 hours, for 2 consecutive extractions, and the extracts were combined.

[0057] Table 1 Efficacy and pharmacological effects of prescription drugs

[0058]

[0059] 1.2.1 Single factor-orthogonal test to optimize the extraction process

[0060] In order to ensure the exact efficacy of the gel and the full utilization of the prescription medicinal materials, a single factor combined with orthogonal test is proposed to investigate the optimal process. At the same time, by consulting the literature and the Pharmacopoeia, the types and pharmacological effects of the chemical components contained in each medicinal flavor are preliminarily determined. For acne and other diseases, it is found that the three components of salvianolic acid B, baicalin, and montana glycosides are effective, easy to extract and relatively stable. Therefore, the above three components are proposed as evaluation indicators, and the results are comprehensively scored (score = 25*(content of salvianolic acid B / maximum content of salvianolic acid B) + 25*(content of baicalin / maximum content of baicalin) + 25*(content of montana glycoside / maximum content of montana glycoside) + 25*(rate of ointment / maximum rate of ointment).

[0061] First, the soaking time, extraction time, solvent volume fraction, and solid-liquid ratio were explored through single-factor experiments. The number of extractions was fixed at 2, and the corresponding parameters of each factor were determined one by one (see Table 2 for the experimental plan). Then, the optimal conditions for the extraction process were determined through orthogonal experiments. Finally, 3 batches of samples were prepared to verify the optimal conditions and determine an extraction process that meets the preparation requirements and has stable and controllable results.

[0062] Table 2 Single factor investigation scheme for extraction process

[0063]

[0064] 1.2.2 Determination of paste yield

[0065] Place the extract at room temperature, stir well, and accurately transfer 50 mL to a constant-weight evaporating dish. After evaporation in a 100°C water bath, place in a blast drying oven, dry at 105°C for 6 hours, cool in a desiccator for 30 minutes, and quickly and accurately weigh. Record the data and calculate the paste rate.

[0066] 1.2.3 Content determination

[0067] Referring to the requirements for content determination of salvianolic acid B, baicalin and baicalin in Part 1 of the 2020 edition of the Pharmacopoeia, the results are summarized in Table 3.

[0068] Table 3 Requirements for determination of index component content

[0069]

[0070] According to the determination conditions of the content of each index component, the proposed content determination method is:

[0071] Chromatographic conditions and system suitability test: Octadecylsilane bonded silica gel was used as filler; acetonitrile-0.1% phosphoric acid aqueous solution was used as mobile phase; column temperature was 20°C; detection wavelength was 280nm (baicalin, salvianolic acid B), 331nm (monoside). Elution gradient is shown in Table 4.

[0072] Preparation of reference solution: Take appropriate amounts of baicalin, salvianolic acid B, and montanaglycoside reference substances, weigh accurately, and dissolve in methanol (heat if necessary) to prepare a solution containing 0.4 mg of baicalin, 0.2 mg of salvianolic acid B, and 0.08 mg of montanaglycoside per 1 ml.

[0073] Preparation of the test solution: Take 10 mL of the concentrated solution, accurately add 20 mL of methanol, ultrasonicate for 40 min, filter, and take the filtrate to obtain the test solution.

[0074] Table 4 Elution gradient

[0075]

[0076] 1.3 Results of extraction process investigation

[0077] 1.3.1 Single Factor Experiment

[0078] 1.3.1.1 Investigation of soaking time

[0079] Weigh 7.5g of Salvia miltiorrhiza, 10g of Scutellaria baicalensis, 10g of Hedyotis diffusa, 10g of Centella asiatica, 10g of Chrysanthemum indici, 5g of Carthamus tinctorius, 7.5g of Honeysuckle, 7.5g of Magnolia officinalis, and 5g of Licorice (n=2), add 725ml of 60% ethanol, soak for 0min, 30min, and 60min respectively, reflux extraction twice, each time for 1.5 hours, combine the extracts, determine the paste yield and the content of index components, and score them.

[0080] Table 5 Soaking time - single factor investigation results

[0081]

[0082] The results showed that the soaking time had little effect on the extraction results. From the perspective of efficient and energy-saving production, no soaking or soaking for 30 minutes was considered sufficient.

[0083] 1.3.1.2 Investigation of material-liquid ratio

[0084] Weigh 7.5 g of Salvia miltiorrhiza, 10 g of Scutellaria baicalensis, 10 g of Hedyotis diffusa, 10 g of Centella asiatica, 10 g of Chrysanthemum indici, 5 g of Carthamus tinctorius, 7.5 g of Honeysuckle, 7.5 g of Magnolia officinalis, and 5 g of Licorice (n=2), add 8, 10, and 12 times the amount of 60% ethanol, respectively, without soaking, reflux extraction twice, each time for 1.5 hours, combine the extracts, determine the paste yield and the content of index components, and score them.

[0085] Table 6 Material-liquid ratio - single factor investigation results

[0086]

[0087] The results showed that there were small differences among the three. It can be considered that under the current extraction conditions, 8 times, 10 times, and 12 times the solvent can all be used for sufficient extraction. However, during the experiment, it was found that during the extraction process with a solid-liquid ratio of 1:8, the medicinal materials were easily exposed above the liquid surface. Therefore, in order to ensure sufficient extraction and save energy, a solid-liquid ratio of 1:10 was considered for extraction.

[0088] 1.3.1.3 Extraction time investigation

[0089] Weigh 7.5g of Salvia miltiorrhiza, 10g of Scutellaria baicalensis, 10g of Hedyotis diffusa, 10g of Centella asiatica, 10g of Chrysanthemum indici, 5g of Carthamus tinctorius, 7.5g of Honeysuckle, 7.5g of Magnolia officinalis, and 5g of Licorice (n=2), add 725ml of 60% ethanol, without soaking, reflux extraction twice, each time for 1, 1.5, and 2 hours respectively, combine the extracts, determine the paste yield and the content of index components, and score them.

[0090] Table 7 Extraction time-single factor investigation results

[0091]

[0092] The results show that the scoring results of extraction time of 1.5 hours are close to that of extraction time of 2 hours. It can be considered that under the current conditions, each extraction time of 1.5 hours is sufficient.

[0093] 1.3.1.4 Investigation of extraction solvent

[0094] Weigh 7.5 g of Salvia miltiorrhiza, 10 g of Scutellaria baicalensis, 10 g of Hedyotis diffusa, 10 g of Centella asiatica, 10 g of Chrysanthemum indici, 5 g of Carthamus tinctorius, 7.5 g of Honeysuckle, 7.5 g of Magnolia officinalis, and 5 g of Licorice (n=2), add 725 ml of water, 30% ethanol, 60% ethanol, and 80% ethanol respectively, without soaking, reflux extraction twice, each time for 1.5 hours, combine the extracts, determine the paste yield and the content of index components, and score them.

[0095] Table 8 Extraction solvent-single factor investigation results

[0096]

[0097] The results showed that the content of each index component corresponding to 60% ethanol extraction was the highest and the comprehensive score was the highest. The content of index components corresponding to water extraction was medium, but the paste yield was higher than that of the other three groups. Therefore, to ensure the adequacy of the research, subsequent orthogonal experiments will examine the above two parameters separately.

[0098] 1.3.2 Alcohol extraction orthogonal test

[0099] On the basis of single factor experiment, the scope of investigation was expanded and L9(3 4 ) orthogonal table, and investigated A solid-liquid ratio, B ethanol volume fraction, C extraction times, and D extraction time respectively.

[0100] Weigh 7.5g of Salvia miltiorrhiza, 10g of Scutellaria baicalensis, 10g of Hedyotis diffusa, 10g of Centella asiatica, 10g of Chrysanthemum indici, 5g of Carthamus tinctorius, 7.5g of Honeysuckle, 7.5g of Magnolia officinalis, and 5g of Licorice (n=2) for extraction, and use the extract yield, baicalin content, salvianolic acid B content, and montanol content as indicators for comprehensive scoring to determine the best extraction process. Orthogonal experimental design and results are shown in Tables 9-11.

[0101] Table 9 Alcohol extraction orthogonal test design

[0102]

[0103] Table 10 Alcohol extraction orthogonal test results-1

[0104]

[0105]

[0106] Table 11 Alcohol extraction orthogonal test results-2

[0107]

[0108] The orthogonal experimental results were analyzed by comprehensive scoring method. The results showed that the influence of each factor on the extraction process was C>D>A>B, that is, the number of extractions>extraction time>solid-liquid ratio>ethanol volume fraction; the optimal extraction process obtained by intuitive analysis was A3B3C3D3, that is, adding 12 times the amount of 70% ethanol, reflux extraction 3 times, each time for 2 hours. After 3 batches of verification, the best process yield was 35.57%, baicalin content was 125.66mg / g, salvianolic acid B content was 61.33mg / g, and montanol content was 24.93mg / g, which was in line with expectations. However, since this condition is more time-consuming and has a high production cost, the "No. 4 process" (see Table 11 No. 4, that is, adding 10 times the amount of 50% ethanol, reflux extraction 2 times, each time for 2 hours) with a relatively close comprehensive score was considered as the appropriate process for alcohol extraction for efficacy investigation.

[0109] 1.3.3 Orthogonal test of water extraction

[0110] Using L9(3 4 ) orthogonal table, respectively, A extraction times, B material-liquid ratio, C extraction time were investigated. 7.5g of Salvia miltiorrhiza, 10g of Scutellaria baicalensis, 10g of Hedyotis diffusa, 10g of Centella asiatica, 10g of Chrysanthemum indici, 5g of Carthamus tinctorius, 7.5g of Honeysuckle, 7.5g of Magnolia officinalis, 5g of Licorice (n=2) were weighed for extraction, and the yield of paste, baicalin content, salvianolic acid B content, and montanin content were used as indicators for comprehensive scoring to determine the best extraction process. Orthogonal experimental design and results are shown in Tables 12-15.

[0111] Table 12 Orthogonal experimental design of water extraction

[0112]

[0113]

[0114] Table 13 Water extraction orthogonal test results-1

[0115]

[0116] Table 14 Water extraction orthogonal test results-2

[0117]

[0118] Table 15 ANOVA results of water extraction orthogonal test

[0119]

[0120] The results of variance analysis showed that the influence of each factor on the extraction process was A>B>C, that is, the number of extractions>solid-liquid ratio>extraction time, and only the number of extractions had a significant effect on the results (p<0.05), while the solid-liquid ratio and extraction time had no significant effect (p>0.05). The best extraction process was A3B3C3, that is, adding 12 times of water to extract 3 times, each time for 2 hours. After 3 batches of verification, the best process had an ointment yield of 41.01%, a baicalin content of 130.19 mg / g, a tannic acid B content of 30.19 mg / g, and a montmorillonin content of 16.71 mg / g, which was in line with expectations. Since this condition is more time-consuming and has a high production cost, the "No. 6 process" (see Table 14, No. 6, that is, adding 12 times of water, reflux extraction 2 times, each time for 1 hour) with a relatively close comprehensive score was considered as a suitable water extraction process, and the efficacy was investigated together with the best water extraction process, the best alcohol extraction process, and the best alcohol extraction process.

[0121] 1.4 Preparation method

[0122] (1) Alcohol extraction is the best: weigh the prescribed medicinal materials, add 12 times the volume fraction of 70% ethanol aqueous solution for reflux extraction, extract 3 times, each time for 2 hours, combine the 3 extracts, centrifuge at 5000rpm for 10min, take the supernatant for spray drying, the inlet air temperature is 130℃, the outlet air temperature is 70℃, and the peristaltic pump flow rate is 10ml / min to prepare spray-dried powder; take a certain amount of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add carbomer, hydroxyethyl cellulose, xanthan gum and pullulan, stir at 400rpm, after swelling is complete and mixed evenly, continue to add glycerol, propylene glycol and phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, increase the speed to 450rpm, and mix the gel evenly. Sterilize at 120℃ for 30min and then fill.

[0123] (2) Suitable alcohol extraction: Weigh the prescribed medicinal materials, add 10 times the volume fraction of 50% ethanol aqueous solution for reflux extraction, extract twice, each time for 2 hours, combine the two extracts, centrifuge at 5000rpm for 10min, take the supernatant for spray drying, inlet air temperature 130℃, outlet air temperature 70℃, peristaltic pump flow rate 10ml / min, prepare spray-dried powder; take a certain amount of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add carbomer, hydroxyethyl cellulose, xanthan gum and pullulan, stir at 400rpm, after swelling is complete and mixed evenly, continue to add glycerol, propylene glycol and phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, increase the speed to 450rpm, mix the gel evenly. Sterilize at 120℃ for 30min and then fill.

[0124] (3) Water extraction is the best: Weigh the prescribed medicinal materials, add 12 times the amount of water for reflux extraction, extract 3 times, each time for 2 hours, combine the 3 extracts, centrifuge at 5000rpm for 10min, take the supernatant for spray drying, the inlet air temperature is 130℃, the outlet air temperature is 70℃, and the peristaltic pump flow rate is 10ml / min to prepare spray-dried powder; take a certain amount of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add carbomer, hydroxyethyl cellulose, xanthan gum and pullulan, stir at 400rpm, after swelling is complete and mixed evenly, continue to add glycerol, propylene glycol and phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, increase the speed to 450rpm, mix the gel evenly. Sterilize at 120℃ for 30min and then fill.

[0125] (4) Water extraction: Weigh the prescribed medicinal materials, add 12 times the amount of water for reflux extraction, extract twice, each time for 1 hour, combine the two extracts, centrifuge at 5000rpm for 10min, take the supernatant for spray drying, inlet air temperature 130℃, outlet air temperature 70℃, peristaltic pump flow rate 10ml / min, prepare spray-dried powder; take a certain amount of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add carbomer, hydroxyethyl cellulose, xanthan gum and pullulan, stir at 400rpm, after swelling is complete and mixed evenly, continue to add glycerol, propylene glycol and phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, increase the speed to 450rpm, mix the gel evenly. Sterilize at 120℃ for 30min and then fill.

[0126] According to the process determined by the above extraction process investigation results, the Chinese medicine extract and Chinese medicine compound gel preparation of the present application are prepared. The following are examples of representative preparation embodiments.

[0127] Embodiment 1 Chinese medicine compound gel preparation (optimum embodiment of alcohol extraction)

[0128] Chinese herbal medicine prescription: 15 parts of salvia miltiorrhiza, 20 parts of scutellaria baicalensis, 20 parts of oldenlandia diffusa, 20 parts of centella asiatica, 20 parts of wild chrysanthemum, 10 parts of safflower, 15 parts of honeysuckle, 15 parts of magnolia bark, 10 parts of licorice; weigh the prescribed herbs, add 12 times the total weight of the herbs and a volume fraction of 70% ethanol aqueous solution for reflux extraction, extract 3 times, each time for 2 hours, combine the 3 extracts, centrifuge at 5000rpm for 10 minutes, take the supernatant for spray drying, the inlet air temperature is 130℃, the outlet air temperature is 70℃, the peristaltic pump flow rate is 10ml / min, and prepare the Chinese herbal medicine extract. Take the spray-dried powder; take 15 parts of the spray-dried powder of the Chinese herbal medicine extract, add an appropriate amount of distilled water to dissolve it, after dissolution, add 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan, stir at 400 rpm, and after swelling is complete and mixed evenly, continue to add 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 600 parts of distilled water, increase the rotation speed to 450 rpm, and mix the gel evenly; sterilize at 120°C for 30 minutes and then fill.

[0129] Example 2 Chinese medicine compound gel preparation

[0130] Chinese medicinal material prescription: 30 parts of salvia miltiorrhiza, 35 parts of scutellaria baicalensis, 15 parts of oldenlandia diffusa, 20 parts of centella asiatica, 40 parts of wild chrysanthemum, 15 parts of safflower, 10 parts of honeysuckle, 25 parts of magnolia bark, 15 parts of licorice; weigh the prescribed medicinal materials, add 20 times the total weight of the medicinal materials and a volume fraction of 30% ethanol aqueous solution for reflux extraction, extract twice, each time for 1.5 hours, combine the two extracts, centrifuge at 3000rpm for 20 minutes, take the supernatant for spray drying, the inlet air temperature is 140℃, the outlet air temperature is 75℃, the peristaltic pump flow rate is 15ml / min, and the preparation is in progress. Spray-dried powder of Chinese herbal extract; take 5 parts of spray-dried powder of Chinese herbal extract, add appropriate amount of distilled water to dissolve, add 1 part of carbomer, 5 parts of hydroxyethyl cellulose, 0.5 parts of xanthan gum and 2.5 parts of pullulan after dissolution, stir at 300rpm, after swelling is complete and mixed evenly, continue to add 50 parts of glycerol, 100 parts of propylene glycol and 2 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 200 parts of distilled water, increase the speed to 350rpm, mix the gel evenly; sterilize at 120℃ for 30min and then fill.

[0131] Example 3 Chinese medicine compound gel preparation

[0132] Chinese herbal medicine prescription: 10 parts of salvia miltiorrhiza, 40 parts of scutellaria baicalensis, 10 parts of white flower oldenlandia tongue, 35 parts of centella asiatica, 30 parts of wild chrysanthemum, 20 parts of safflower, 5 parts of honeysuckle, 30 parts of magnolia bark, 5 parts of licorice; weigh the prescribed herbs, add 16 times the total weight of the herbs and a 50% ethanol aqueous solution with a volume fraction for reflux extraction, extract once, 3h, centrifuge at 7000rpm for 8min, take the supernatant for spray drying, the inlet air temperature is 125℃, the outlet air temperature is 75℃, the peristaltic pump flow rate is 12ml / min, and prepare Chinese herbal medicine extract spray-dried powder: Take 8 parts of Chinese herbal medicine extract spray-dried powder, add appropriate amount of distilled water to dissolve, add 2 parts of carbomer, 2 parts of hydroxyethyl cellulose, 3 parts of xanthan gum and 1 part of pullulan after dissolution, stir at 500rpm, and after swelling is complete and mixed evenly, continue to add 60 parts of glycerol, 120 parts of propylene glycol and 8 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 600rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0133] Example 4 Chinese medicine compound gel preparation

[0134] Chinese medicinal material prescription: 25 parts of salvia miltiorrhiza, 10 parts of scutellaria baicalensis, 40 parts of white flower oldenlandia tongue, 10 parts of centella asiatica, 10 parts of wild chrysanthemum, 5 parts of safflower, 25 parts of honeysuckle, 5 parts of magnolia bark, 25 parts of liquorice; weigh the prescribed medicinal materials, add 60% ethanol aqueous solution with a volume fraction of 6 times the total weight of the medicinal materials for reflux extraction, extract 4 times, each time for 1 hour, combine the 4 extracts, centrifuge at 8000rpm for 3min, take the supernatant for spray drying, the inlet air temperature is 120℃, the outlet air temperature is 80℃, and the peristaltic pump flow rate is 5m l / min, prepare spray-dried powder; take 30 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add 5 parts of carbomer, 1 part of hydroxyethyl cellulose, 1 part of xanthan gum and 0.5 parts of pullulan, stir at 700rpm, after swelling is complete and mixed evenly, continue to add 30 parts of glycerol, 60 parts of propylene glycol and 6 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 750rpm, and mix the gel evenly. Sterilize at 120℃ for 30 minutes before filling.

[0135] Example 5 Chinese medicine compound gel preparation

[0136] Chinese medicinal material prescription: 5 parts of salvia miltiorrhiza, 25 parts of scutellaria baicalensis, 30 parts of oldenlandia diffusa, 40 parts of centella asiatica, 15 parts of wild chrysanthemum, 25 parts of safflower, 30 parts of honeysuckle, 10 parts of magnolia bark, 20 parts of licorice; weigh the prescribed medicinal materials, add 10 times the total weight of the medicinal materials and a volume fraction of 80% ethanol aqueous solution for reflux extraction, extract 3 times, each time for 2.5 hours, combine the 3 extracts, centrifuge at 4000rpm for 15 minutes, take the supernatant for spray drying, the inlet air temperature is 135℃, the outlet air temperature is 60℃, and the peristaltic pump is used. The flow rate is 8ml / min, and the spray-dried powder is prepared; 25 parts of the spray-dried powder are taken, and an appropriate amount of distilled water is added to dissolve it. After dissolution, 4 parts of carbomer, 2 parts of hydroxyethyl cellulose, 0.5 parts of xanthan gum and 3 parts of pullulan are added, and stirred at 600rpm. After swelling is complete and mixed evenly, 15 parts of glycerol, 30 parts of propylene glycol and 4 parts of phenoxyethanol are added, and triethanolamine is added to adjust the pH value to 6, and the remaining distilled water is added, and a total of 800 parts of distilled water are added, and the rotation speed is increased to 700rpm to mix the gel evenly. Sterilize at 120℃ for 30 minutes before filling.

[0137] Example 6 Chinese medicine compound gel preparation (alcohol extraction suitable example)

[0138] Chinese medicinal material prescription: 15 parts of salvia miltiorrhiza, 20 parts of scutellaria baicalensis, 20 parts of oldenlandia diffusa, 20 parts of centella asiatica, 20 parts of wild chrysanthemum, 10 parts of safflower, 15 parts of honeysuckle, 15 parts of magnolia bark, 10 parts of licorice; weigh the prescribed medicinal materials, add 10 times the total weight of the medicinal materials and a volume fraction of 50% ethanol aqueous solution for reflux extraction, extract twice, each time for 2 hours, combine the two extracts, centrifuge at 5000rpm for 10 minutes, take the supernatant for spray drying, the inlet air temperature is 130℃, the outlet air temperature is 70℃, the peristaltic pump flow rate is 10ml / min, and prepare the Chinese medicinal extract spray-dried powder of the material; take 15 parts of the spray-dried powder of the Chinese herbal medicine extract, add an appropriate amount of distilled water to dissolve it, after dissolution, add 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan, stir at 400rpm, after swelling is complete and mixed evenly, continue to add 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 600 parts of distilled water, increase the speed to 450rpm, and mix the gel evenly; high-temperature sterilization at 120℃ for 30min and then fill.

[0139] Example 7 Chinese medicine compound gel preparation

[0140] Chinese herbal medicine prescription: 30 parts of salvia miltiorrhiza, 35 parts of scutellaria baicalensis, 15 parts of oldenlandia diffusa, 20 parts of centella asiatica, 40 parts of wild chrysanthemum, 15 parts of safflower, 10 parts of honeysuckle, 25 parts of magnolia bark, 15 parts of licorice; weigh the prescribed herbs, add 20 times the total weight of the herbs and a 30% ethanol aqueous solution with a volume fraction for reflux extraction, extract twice, each time for 1.5 hours, combine the two extracts, centrifuge at 3000rpm for 20 minutes, take the supernatant for spray drying, and the inlet air temperature is 140℃ , outlet temperature 75℃, peristaltic pump flow rate 15ml / min, prepare spray-dried powder; take 5 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add 5 parts of carbomer, stir at 300rpm, after swelling completely and mixing evenly, continue to add 50 parts of glycerol, 100 parts of propylene glycol and 2 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 200 parts of distilled water, increase the speed to 350rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0141] Example 8 Chinese medicine compound gel preparation

[0142] Chinese herbal medicine prescription: 10 parts of salvia miltiorrhiza, 40 parts of scutellaria baicalensis, 10 parts of white flower oldenlandia, 35 parts of centella asiatica, 30 parts of wild chrysanthemum, 20 parts of safflower, 5 parts of honeysuckle, 30 parts of magnolia bark, 5 parts of liquorice; weigh the prescribed herbs, add 16 times the total weight of the herbs and a 50% ethanol aqueous solution with a volume fraction for reflux extraction, extract once, 3 hours, centrifuge at 7000rpm for 8 minutes, take the supernatant for spray drying, the inlet air temperature is 125℃, the outlet air temperature is 75℃, and the peristaltic pump flow Speed ​​12ml / min, prepare spray-dried powder; take 8 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add 4 parts of carbomer and 1 part of hydroxyethyl cellulose, stir at 500rpm, after swelling is complete and mixed evenly, continue to add 60 parts of glycerol, 120 parts of propylene glycol and 8 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 600rpm, mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0143] Example 9 Chinese medicine compound gel preparation

[0144] Chinese herbal medicine prescription: 25 parts of salvia miltiorrhiza, 10 parts of scutellaria baicalensis, 40 parts of white flower oldenlandia tongue, 10 parts of centella asiatica, 10 parts of wild chrysanthemum, 5 parts of safflower, 25 parts of honeysuckle, 5 parts of magnolia bark, 25 parts of liquorice; weigh the prescribed herbs, add 60% ethanol aqueous solution with a volume fraction of 6 times the total weight of the herbs for reflux extraction, extract 4 times, each time for 1 hour, combine the 4 extracts, centrifuge at 8000rpm for 3min, take the supernatant for spray drying, the inlet air temperature is 120℃, the outlet air temperature is 80℃, and the peristaltic pump is used. The flow rate is 5ml / min, and the spray-dried powder is prepared; 30 parts of the spray-dried powder are taken, and an appropriate amount of distilled water is added to dissolve it. After dissolution, 3 parts of carbomer, 2 parts of hydroxyethyl cellulose, and 0.5 parts of xanthan gum are added, and stirred at 700rpm. After swelling is complete and mixed evenly, 30 parts of glycerol, 60 parts of propylene glycol, and 6 parts of phenoxyethanol are added, and triethanolamine is added to adjust the pH value to 6, and the remaining distilled water is added, and a total of 1000 parts of distilled water is added, and the rotation speed is increased to 750rpm to mix the gel evenly. Sterilize at 120℃ for 30 minutes before filling.

[0145] Example 10 Chinese medicine compound gel preparation

[0146] Chinese medicinal material prescription: 5 parts of salvia miltiorrhiza, 25 parts of scutellaria baicalensis, 30 parts of oldenlandia diffusa, 40 parts of centella asiatica, 15 parts of wild chrysanthemum, 25 parts of safflower, 30 parts of honeysuckle, 10 parts of magnolia bark, 20 parts of liquorice; weigh the prescribed medicinal materials, add 10 times the total weight of the medicinal materials and a volume fraction of 80% ethanol aqueous solution for reflux extraction, extract 3 times, each time for 2.5 hours, combine the 3 extracts, centrifuge at 4000rpm for 15 minutes, take the supernatant for spray drying, the inlet air temperature is 135℃, the outlet air temperature is 60℃, and the peristaltic The pump flow rate is 8ml / min, and the spray-dried powder is prepared; 25 parts of the spray-dried powder are taken, and an appropriate amount of distilled water is added to dissolve it. After dissolution, 1 part of carbomer, 3 parts of hydroxyethyl cellulose, 2 parts of xanthan gum and 2 parts of pullulan are added, and stirred at 600rpm. After swelling is complete and mixed evenly, 15 parts of glycerol, 30 parts of propylene glycol and 4 parts of phenoxyethanol are added, and triethanolamine is added to adjust the pH value to 6, and the remaining distilled water is added, and a total of 800 parts of distilled water are added, and the rotation speed is increased to 700rpm to mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0147] Example 11 Chinese medicine compound gel preparation (best embodiment of water extraction)

[0148] Chinese medicinal material prescription: 15 parts of salvia miltiorrhiza, 20 parts of scutellaria baicalensis, 20 parts of oldenlandia diffusa, 20 parts of centella asiatica, 20 parts of wild chrysanthemum, 10 parts of safflower, 15 parts of honeysuckle, 15 parts of magnolia bark, and 10 parts of licorice; weigh the prescribed medicinal materials, add 12 times the total weight of the medicinal materials for reflux extraction, extract 3 times, each time for 2 hours, combine the 3 extracts, centrifuge at 5000rpm for 10 minutes, take the supernatant for spray drying, the inlet air temperature is 130℃, the outlet air temperature is 70℃, and the peristaltic pump flow rate is 10ml / min to prepare the Chinese medicine extract spray-dried powder; take 15 parts of spray-dried powder of Chinese herbal medicine extract are dissolved by adding appropriate amount of distilled water. After dissolution, 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan are added, and stirred at 400 rpm. After swelling is complete and mixed evenly, 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol are added, and triethanolamine is added to adjust the pH value to 6. The remaining distilled water is added, and a total of 600 parts of distilled water are added. The rotation speed is increased to 450 rpm to mix the gel evenly; and the mixture is sterilized at 120°C for 30 min and then filled.

[0149] Example 12 Chinese medicine compound gel preparation

[0150] Chinese herbal medicine prescription: 30 parts of salvia miltiorrhiza, 35 parts of scutellaria baicalensis, 15 parts of oldenlandia diffusa, 20 parts of centella asiatica, 40 parts of wild chrysanthemum, 15 parts of safflower, 10 parts of honeysuckle, 25 parts of magnolia bark, 15 parts of liquorice; weigh the prescribed herbs, add 20 times the total weight of the herbs for reflux extraction, extract twice, each time for 1.5 hours, combine the two extracts, centrifuge at 3000rpm for 20 minutes, take the supernatant for spray drying, the inlet air temperature is 140℃, the outlet air temperature is 75℃, and the peristaltic pump flow rate is 15ml / m in, prepare spray-dried powder; take 5 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, after dissolution, add 1 part of carbomer, 5 parts of hydroxyethyl cellulose, 0.5 parts of xanthan gum and 2.5 parts of pullulan, stir at 300rpm, after swelling is complete and mixed evenly, continue to add 50 parts of glycerol, 100 parts of propylene glycol and 2 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 200 parts of distilled water, increase the speed to 350rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0151] Example 13 Chinese medicine compound gel preparation

[0152] Chinese herbal medicine prescription: 10 parts of salvia miltiorrhiza, 40 parts of scutellaria baicalensis, 10 parts of white flower oldenlandia tongue, 35 parts of centella asiatica, 30 parts of wild chrysanthemum, 20 parts of safflower, 5 parts of honeysuckle, 30 parts of magnolia bark, 5 parts of liquorice; weigh the prescribed herbs, add 16 times the total weight of the herbs for reflux extraction, extract once, 3h, centrifuge at 7000rpm for 8min, take the supernatant for spray drying, the inlet air temperature is 125℃, the outlet air temperature is 75℃, the peristaltic pump flow rate is 12ml / min, prepare the spray Dry powder: Take 8 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 2 parts of carbomer, 2 parts of hydroxyethyl cellulose, 3 parts of xanthan gum and 1 part of pullulan after dissolution, stir at 500rpm, and after swelling is complete and mixed evenly, continue to add 60 parts of glycerol, 120 parts of propylene glycol and 8 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 600rpm, and mix the gel evenly. Sterilize at 120℃ for 30 minutes before filling.

[0153] Example 14 Chinese medicine compound gel preparation

[0154] Chinese medicinal material prescription: 25 parts of salvia miltiorrhiza, 10 parts of scutellaria baicalensis, 40 parts of white flower oldenlandia tongue, 10 parts of centella asiatica, 10 parts of wild chrysanthemum, 5 parts of safflower, 25 parts of honeysuckle, 5 parts of magnolia bark, 25 parts of liquorice; weigh the prescribed medicinal materials, add 6 times the total weight of the medicinal materials for reflux extraction, extract 4 times, each time for 1 hour, combine the 4 extracts, centrifuge at 8000rpm for 3min, take the supernatant for spray drying, the inlet air temperature is 120℃, the outlet air temperature is 80℃, the peristaltic pump flow rate is 5ml / min, Prepare spray-dried powder; take 30 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 5 parts of carbomer, 1 part of hydroxyethyl cellulose, 1 part of xanthan gum and 0.5 parts of pullulan after dissolution, stir at 700rpm, add 30 parts of glycerol, 60 parts of propylene glycol and 6 parts of phenoxyethanol after swelling is complete and mixed evenly, add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 750rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0155] Example 15 Chinese medicine compound gel preparation

[0156] Chinese herbal medicine prescription: 5 parts of salvia miltiorrhiza, 25 parts of scutellaria baicalensis, 30 parts of oldenlandia diffusa, 40 parts of centella asiatica, 15 parts of wild chrysanthemum, 25 parts of safflower, 30 parts of honeysuckle, 10 parts of magnolia bark, 20 parts of liquorice; weigh the prescribed herbs, add 10 times the total weight of the herbs for reflux extraction, extract 3 times, each time for 2.5 hours, combine the 3 extracts, centrifuge at 4000rpm for 15 minutes, take the supernatant for spray drying, the inlet air temperature is 135℃, the outlet air temperature is 60℃, and the peristaltic pump flow rate is 8ml / m in, prepare spray-dried powder; take 25 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 4 parts of carbomer, 2 parts of hydroxyethyl cellulose, 0.5 parts of xanthan gum and 3 parts of pullulan after dissolution, stir at 600rpm, after swelling is complete and mixed evenly, continue to add 15 parts of glycerol, 30 parts of propylene glycol and 4 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 800 parts of distilled water, increase the speed to 700rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0157] Example 16 Chinese medicine compound gel preparation (water extraction suitable example)

[0158] Chinese medicinal material prescription: 15 parts of salvia miltiorrhiza, 20 parts of scutellaria baicalensis, 20 parts of oldenlandia diffusa, 20 parts of centella asiatica, 20 parts of wild chrysanthemum, 10 parts of safflower, 15 parts of honeysuckle, 15 parts of magnolia bark, and 10 parts of licorice; weigh the prescribed medicinal materials, add 12 times the total weight of the medicinal materials for reflux extraction, extract twice, each time for 1 hour, combine the two extracts, centrifuge at 5000rpm for 10min, take the supernatant for spray drying, the inlet air temperature is 130℃, the outlet air temperature is 70℃, and the peristaltic pump flow rate is 10ml / min to prepare the Chinese medicine extract spray-dried powder; take 15 parts of spray-dried powder of Chinese herbal medicine extract are dissolved by adding appropriate amount of distilled water. After dissolution, 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan are added, and stirred at 400 rpm. After swelling is complete and mixed evenly, 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol are added, and triethanolamine is added to adjust the pH value to 6. The remaining distilled water is added, and a total of 600 parts of distilled water are added. The rotation speed is increased to 450 rpm to mix the gel evenly; and the mixture is sterilized at 120°C for 30 min and then filled.

[0159] Example 17 Chinese medicine compound gel preparation

[0160] Chinese herbal medicine prescription: 30 parts of salvia miltiorrhiza, 35 parts of scutellaria baicalensis, 15 parts of oldenlandia diffusa, 20 parts of centella asiatica, 40 parts of wild chrysanthemum, 15 parts of safflower, 10 parts of honeysuckle, 25 parts of magnolia bark, 15 parts of licorice; weigh the prescribed herbs, add 20 times the total weight of the herbs for reflux extraction, extract twice, each time for 1.5 hours, combine the two extracts, centrifuge at 3000rpm for 20 minutes, take the supernatant for spray drying, the inlet air temperature is 140℃, the outlet air temperature is 7 5℃, peristaltic pump flow rate 15ml / min, prepare spray-dried powder; take 5 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 5 parts of carbomer after dissolution, stir at 300rpm, after swelling completely and mixing evenly, continue to add 50 parts of glycerol, 100 parts of propylene glycol and 2 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 200 parts of distilled water, increase the speed to 350rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0161] Example 18 Chinese medicine compound gel preparation

[0162] Chinese herbal medicine prescription: 10 parts of salvia miltiorrhiza, 40 parts of scutellaria baicalensis, 10 parts of white flower oldenlandia, 35 parts of centella asiatica, 30 parts of wild chrysanthemum, 20 parts of safflower, 5 parts of honeysuckle, 30 parts of magnolia bark, 5 parts of liquorice; weigh the prescribed herbs, add 16 times the total weight of the herbs for reflux extraction, extract once, 3h, centrifuge at 7000rpm for 8min, take the supernatant for spray drying, inlet air temperature 125℃, outlet air temperature 75℃, peristaltic pump flow rate 12ml / min, prepare spray-dried powder; take 8 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 4 parts of carbomer and 1 part of hydroxyethyl cellulose, stir at 500rpm, and continue to add 60 parts of glycerol, 120 parts of propylene glycol and 8 parts of phenoxyethanol after swelling is complete and mixed evenly, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 600rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0163] Example 19 Chinese medicine compound gel preparation

[0164] Chinese herbal medicine prescription: 25 parts of salvia miltiorrhiza, 10 parts of scutellaria baicalensis, 40 parts of white flower oldenlandia tongue, 10 parts of centella asiatica, 10 parts of wild chrysanthemum, 5 parts of safflower, 25 parts of honeysuckle, 5 parts of magnolia bark, 25 parts of liquorice; weigh the prescribed herbs, add 6 times the total weight of the herbs for reflux extraction, extract 4 times, each time for 1 hour, combine the 4 extracts, centrifuge at 8000rpm for 3min, take the supernatant for spray drying, the inlet air temperature is 120℃, the outlet air temperature is 80℃, and the peristaltic pump flow rate is 5ml / min, prepare spray-dried powder; take 30 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 3 parts of carbomer, 2 parts of hydroxyethyl cellulose, 0.5 parts of xanthan gum, stir at 700rpm, after swelling is complete and mixed evenly, continue to add 30 parts of glycerol, 60 parts of propylene glycol and 6 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 1000 parts of distilled water, increase the speed to 750rpm, and mix the gel evenly. Sterilize at 120℃ for 30 minutes before filling.

[0165] Example 20 Chinese medicine compound gel preparation

[0166] Chinese herbal medicine prescription: 5 parts of salvia miltiorrhiza, 25 parts of scutellaria baicalensis, 30 parts of oldenlandia diffusa, 40 parts of centella asiatica, 15 parts of wild chrysanthemum, 25 parts of safflower, 30 parts of honeysuckle, 10 parts of magnolia bark, 20 parts of liquorice; weigh the prescribed herbs, add 10 times the total weight of the herbs for reflux extraction, extract 3 times, each time for 2.5 hours, combine the 3 extracts, centrifuge at 4000rpm for 15 minutes, take the supernatant for spray drying, the inlet air temperature is 135℃, the outlet air temperature is 60℃, and the peristaltic pump flow rate is 8ml / min, prepare spray-dried powder; take 25 parts of spray-dried powder, add appropriate amount of distilled water to dissolve, add 1 part of carbomer, 3 parts of hydroxyethyl cellulose, 2 parts of xanthan gum and 2 parts of pullulan after dissolution, stir at 600rpm, after swelling is complete and mixed evenly, continue to add 15 parts of glycerol, 30 parts of propylene glycol and 4 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add 800 parts of distilled water in total, increase the speed to 700rpm, and mix the gel evenly. Sterilize at 120℃ for 30min before filling.

[0167] Experimental Example 2: Pharmacodynamics Study of Compound Chinese Medicine Acne Gel

[0168] 2.1 Experimental animals and test drugs

[0169] 2.1.1 Drug testing

[0170] Compound Chinese medicine acne gel - optimal alcohol extraction process (prepared by Tianjin University of Traditional Chinese Medicine Engineering Research Center); Compound Chinese medicine acne gel - suitable alcohol extraction process (prepared by Tianjin University of Traditional Chinese Medicine Engineering Research Center); Compound Chinese medicine acne gel - optimal water extraction process (prepared by Tianjin University of Traditional Chinese Medicine Engineering Research Center); Compound Chinese medicine acne gel - suitable water extraction process (prepared by Tianjin University of Traditional Chinese Medicine Engineering Research Center); Compound gel - CN201310527422.X (prepared by Tianjin University of Traditional Chinese Medicine Engineering Research Center); Compound gel - Centella asiatica, Magnolia officinalis, and Honeysuckle (Prepared by Tianjin University of Traditional Chinese Medicine Engineering Research Center Preparation); kecuoyinone gel (Hefei Cube Pharmaceutical Co., Ltd.); coal tar (Alfa Aesar (China) Chemical Co., Ltd.); ethanol (Tianjin Concord Reagent Co., Ltd.); rabbit tumor necrosis factor α (TNF-α) ELISA kit (MM-024001, Jiangsu Enzyme Immunity Industry Co., Ltd.); rabbit interleukin 6 (IL-6) ELISA kit (MM-030201, Jiangsu Enzyme Immunity Industry Co., Ltd.); rabbit interleukin 1β (IL-1β) ELISA kit (MM-030501, Jiangsu Enzyme Immunity Industry Co., Ltd.).

[0171] 2.1.2 Experimental animals

[0172] One hundred and four male New Zealand White rabbits aged 8-10 weeks.

[0173] 2.2 Experimental methods

[0174] 2.2.1 Preparation of gel

[0175] Compound Chinese medicine acne gel - alcohol extraction optimal process low dose (hereinafter referred to as "alcohol extraction optimal low dose"): prepared according to "Example 1", only the amount of dry powder added was changed, so that the gel contained 0.1g / g of crude drug;

[0176] Compound Chinese medicine acne gel - optimal alcohol extraction process medium dose (hereinafter referred to as "optimal alcohol extraction medium dose"): prepared according to "Example 1", only the amount of dry powder added was changed, so that the gel contained 0.2g / g of crude drug;

[0177] Compound Chinese medicine acne gel - alcohol extraction optimal process high dose (hereinafter referred to as "alcohol extraction optimal high dose"): prepared according to "Example 1", only the amount of dry powder added was changed, so that the gel contained 0.4g / g of crude drug;

[0178] Compound Chinese medicine acne gel - alcohol extraction suitable process low dose (hereinafter referred to as "alcohol extraction suitable low dose"): prepared according to "Example 6", only the amount of dry powder added was changed, so that the gel contained 0.1g / g of crude drug;

[0179] Compound Chinese medicine acne gel - alcohol extraction suitable process medium dose (hereinafter referred to as "alcohol extraction suitable medium dose"): prepared according to "Example 6", only the amount of dry powder added was changed, so that the gel contained 0.2g / g of crude drug;

[0180] Compound Chinese medicine acne gel - alcohol extraction suitable process high dose (hereinafter referred to as "alcohol extraction suitable high dose"): prepared according to "Example 6", only the amount of dry powder added was changed, so that the gel contained 0.4g / g of crude drug;

[0181] Compound Chinese medicine acne gel - water extraction optimal process low dose (hereinafter referred to as "water extraction optimal low dose"): prepared according to "Example 11", only the amount of dry powder added was changed, so that the gel contained 0.1g / g of crude drug;

[0182] Compound Chinese medicine acne gel - water extraction optimal process medium dose (hereinafter referred to as "water extraction optimal medium dose"): prepared according to "Example 11", only the amount of dry powder added was changed, so that the gel contained 0.2g / g of crude drug;

[0183] Compound Chinese medicine acne gel - water extraction optimal process high dose (hereinafter referred to as "water extraction optimal high dose"): prepared according to "Example 11", only the amount of dry powder added was changed, so that the gel contained 0.4g / g of crude drug;

[0184] Compound Chinese medicine acne gel - low dose with suitable water extraction process (hereinafter referred to as "low dose with suitable water extraction"): prepared according to "Example 16", only the amount of dry powder added was changed, so that the gel contained 0.1 g / g of crude drug;

[0185] Compound Chinese medicine acne gel - water extraction suitable process medium dose (hereinafter referred to as "water extraction suitable medium dose"): prepared according to "Example 16", only the amount of dry powder added was changed, so that the gel contained 0.2g / g of crude drug;

[0186] Compound Chinese medicine acne gel - high dose by suitable water extraction process (hereinafter referred to as "suitable water extraction high dose"): prepared according to "Example 16", only the amount of dry powder added was changed, so that the gel contained 0.4g / g of crude drug;

[0187] Compound gel-CN201310527422.X (hereinafter referred to as "patent CN201310527422.X"): select medicinal materials according to "Example 1 of Chinese patent application CN201310527422.X", namely 1.0 kg of Salvia miltiorrhiza, 1.5 kg of Scutellaria baicalensis, 1.5 kg of Hedyotis diffusa, 2.5 kg of Chrysanthemum indici, 1.5 kg of Carthamus tinctorius, 2.0 kg of Psoralea corylifolia, and 1.5 kg of Licorice. Prepare the gel according to the same method and raw material / excipient ratio as the present invention (Example 1);

[0188] Compound gel - Centella asiatica, Magnolia officinalis and Honeysuckle (hereinafter referred to as "Centella asiatica, Magnolia officinalis and Honeysuckle"): Only Centella asiatica, Honeysuckle and Magnolia officinalis are added, and a gel is prepared according to the same method and raw material / auxiliary material ratio as the present invention (Example 1).

[0189] 2.2.2 Establishment of rabbit ear acne model

[0190] The model was established by Kligman method. Coal tar dilution (2% coal tar solution prepared with 95% ethanol) was applied once a day to the 2cm x 2cm area at the opening of the ear canal on the right ear of adult New Zealand white rabbits for 14 consecutive days. The left ear was not treated as a control.

[0191] After the model was established, the rabbit ear skin lesions and the presence of black horn plugs at the hair follicle openings were observed with the naked eye. After the model was established, two adult New Zealand white rabbits were randomly selected and killed by air embolism. The full-thickness skin at the opening of the bilateral ear ducts was removed, fixed with 4% paraformaldehyde, embedded in paraffin after dehydration, sliced ​​and dried. The rabbit ear tissue disease was observed after HE staining to verify whether the model was successful.

[0192] 2.2.3 Animal grouping and treatment

[0193] All 104 experimental rabbits survived after one week of adaptive feeding, and 6 rabbits were randomly selected as the blank group, and the remaining 98 experimental rabbits were used to model the rabbit ear acne model. After the modeling was completed, 2 rabbits were randomly selected to verify whether the modeling was successful. After the modeling was successful, the remaining 96 experimental rabbits were randomly divided into 16 groups, namely: the best low-dose group of alcohol extraction, the best medium-dose group of alcohol extraction, the best high-dose group of alcohol extraction, the appropriate low-dose group of alcohol extraction, the appropriate medium-dose group of alcohol extraction, the appropriate high-dose group of alcohol extraction, the best low-dose group of water extraction, the best medium-dose group of water extraction, the best high-dose group of water extraction, the appropriate low-dose group of water extraction, the appropriate medium-dose group of water extraction, the appropriate high-dose group of water extraction, the patent CN201310527422.X group, the Centella asiatica Magnolia officinalis honeysuckle group, the positive drug (kecuoyin ketone gel) group, and the model group, with 6 rabbits in each group.

[0194] The drug-treated group and the positive drug group were smeared with the corresponding drug at 1 g / animal / d for 14 consecutive days, while the blank group and the model group were not treated.

[0195] 2.2.4 Sample collection and storage

[0196] After the experiment, 5 ml of blood was collected from the ear vein of the New Zealand rabbit and left to coagulate at room temperature. The blood was centrifuged at 3000 rpm at 4°C for 20 min and the supernatant was collected and stored at -80°C. The rabbits were killed by air embolism, and the full-thickness skin at the opening of the ear tubes was removed by punching. The skin was fixed with 4% paraformaldehyde, embedded in paraffin after dehydration, sliced ​​and dried. The rabbit ear tissue lesions were observed after HE staining.

[0197] 2.2.5 Determination of serum TNF-α, IL-6, and IL-1β levels

[0198] Take the serum sample of "2.2.4" and use Elisa kit to measure the content of TNF-α, IL-1β and IL-6 in rabbit serum. The specific operation refers to the Elisa kit.

[0199] 2.2.6 Statistics and Plotting

[0200] The experimental data were analyzed by one-way ANOVA using SPSS27 software and plotted using Origin 2018.

[0201] 2.3 Experimental Results

[0202] 2.3.1 Validation of the rabbit ear acne model

[0203] Under naked eye observation, the surface of a normal rabbit ear without modeling is smooth, light pink and white, with good light transmittance (such as Figure 1 -A). Three days after modeling, the pores began to become coarser and the surrounding skin began to keratinize. After 14 days of modeling, the rabbit ears became significantly thicker and obvious fat plugs appeared on the surface. When squeezed by hand, white rice juice and black keratin plugs appeared, and the hair follicles were bulging (such as Figure 1 -B), the surface of the rabbit's ears feels rough and unpleasant when touched.

[0204] Observation under an electron microscope showed that the epidermis of normal rabbit ears without modeling was thin, the cells were neatly arranged, keratinization was normal, the transparent layer was not obvious, the hair follicle opening was not dilated, and the cortical junction was clearly visible (such as Figure 1 -C). After modeling, the stratum corneum of the rabbit ear was significantly thickened, and the openings of the sebaceous gland follicles were filled with keratinized embolic material. The follicle wall was thickened, with scattered lymphocyte infiltration. The spinous cell layer was significantly thickened and enlarged, and the number of lymphocytes increased (such as Figure 1 -D). It meets the successful criteria of acne modeling described in the literature.

[0205] 2.3.2 Visual Observation

[0206] After successful modeling and drug administration, the blank group ( Figure 2 -A) The surface of the rabbit ears was smooth and light pink, the hair follicles at the duct opening were tight, and there were no keratin plugs or acne; model group ( Figure 2 -B) Enlarged pores, severe keratinization, obvious thickening, more black keratin plugs blocking the hair follicles, and more acne-like particles. Compared with the model group, the swelling of the rabbit ears in each drug-treated group was reduced, and the thickening phenomenon was improved. Among them, the positive drug group ( Figure 2 -C) and the best medium dose group ( Figure 2 -E), the best high-dose alcohol extraction group ( Figure 2 -F), alcohol extraction appropriate medium dose group ( Figure 2-H), alcohol extraction suitable high dose group ( Figure 2 -I), water extraction best high dose group ( Figure 2 -L), water extraction appropriate medium dose group ( Figure 2 -N), water extraction suitable high dose group ( Figure 2 -O) Rabbit ears were soft and thin, acne-like particles disappeared, and the hair follicle openings were significantly reduced; the best low-dose alcohol extraction group ( Figure 2 -D), water extraction optimal low dose group ( Figure 2 -G), water extraction optimal medium dose group ( Figure 2 -K), water extraction suitable low dose group ( Figure 2 -M) and patent CN201310527422.X group ( Figure 2 -P) rabbit ear hardness decreased, but there were still scattered particles, and the expansion of the hair follicle opening was not effectively controlled; water extraction was suitable for the low-dose group ( Figure 2 -J) group, Centella asiatica Magnolia officinalis Lonicera group ( Figure 2 -Q) Compared with the model group, although the particulate matter was reduced, the hair follicle openings were generally raised and the keratinization phenomenon was more serious than that of other drug-administered groups.

[0207] 2.3.3 Rabbit ear section staining

[0208] HE-stained sections of rabbit ears were taken and observed under an optical microscope. The results showed that the overall structure of rabbit ear tissue in the blank group was basically normal, the fibrous tissue was arranged regularly and tightly, and the size was relatively uniform. No obvious inflammatory cell infiltration was observed in the tissue (such as Figure 3 -A). The overall structure of the tissue in the model group was abnormal, with widespread infiltration of inflammatory cells such as lymphocytes and eosinophils (such as Figure 3 -B as indicated by the red arrow), the cortex is significantly thickened (as shown in Figure 3 -B as indicated by the gray arrow), the cutaneous process is elongated, the lower end is widened and fused or intertwined with the adjacent cutaneous process, forming an irregular cavity in which keratinized material can be seen (such as Figure 3 -B as indicated by the blue arrow); the number of hair follicles and sebaceous glands in the dermis is small, and there is focal connective tissue hyperplasia (such as Figure 3 -B as indicated by the green arrow). In the positive drug group, the fibrous focal epidermis was slightly thickened (as shown in Figure 3 -C gray arrow), a small amount of lymphocyte infiltration can be seen in the tissue (as shown in Figure 3 -C (indicated by the red arrow).

[0209] The overall structure of the tissues in the three groups with the best alcohol extraction process was slightly abnormal, and some epidermis in the group with the best low-dose alcohol extraction was thickened (e.g. Figure 3 -D as indicated by the gray arrows), the sebaceous glands become larger and more numerous, clustering around the hair follicles (as shown in Figure 4A). Figure 3 -D as indicated by the yellow arrow); the epidermal structure of the skin in the best medium-dose alcohol extraction group was clear, with a small amount of granulocyte infiltration (as shown in Figure 2). Figure 3-E as indicated by the red arrow); a small amount of focal connective tissue hyperplasia in the best high-dose alcohol extraction group (as shown in Figure 3 -F as indicated by the green arrow), collagen fibers and fibroblasts are interlaced, and a small amount of granulocytes infiltrate (as shown in Figure 3 -F as indicated by the red arrow). The tissue structures of the three groups with suitable alcohol extraction process were slightly abnormal, among which the number of hair follicles and sebaceous glands in the dermis of the skin appendages of the suitable alcohol extraction low-dose group was small, and a small amount of focal connective tissue hyperplasia (such as Figure 3 -G green arrow), a small amount of lymphocyte infiltration (as shown in Figure 3 -G as indicated by the red arrow); focal hyperkeratosis in the alcohol extraction appropriate medium dose group (as shown in Figure 3 -H orange arrow), a small amount of lymphocyte infiltration (as shown in Figure 3 -H as indicated by the red arrow); keratinized material was occasionally seen in the high-dose alcohol extraction group (such as Figure 3 -I blue arrow), a small amount of lymphocyte infiltration (as shown in Figure 3 -I red arrow). The tissue structure of the three groups with the best water extraction process was slightly abnormal, and the best low-dose water extraction group had focal epidermal thickening (such as Figure 3 -J as indicated by gray arrows), a small amount of lymphocyte infiltration (as indicated by Figure 3 -J as indicated by the red arrow; small-scale hyperkeratosis in the best medium-dose water extract group (as shown in Figure 3 -K orange arrow), a small amount of focal connective tissue hyperplasia (as shown in Figure 3 -K as indicated by the green arrow); there was a small amount of lymphocyte infiltration in the optimal high-dose water extract group (as shown in Figure 3 -L as indicated by the red arrow). The tissue structures of the three groups with suitable water extraction process were slightly abnormal, among which a small number of cells in the spinous layer of the epidermis in the low-dose water extraction group had loose and lightly stained cytoplasm (such as Figure 3 -M as indicated by the purple arrow), accompanied by a small amount of lymphocyte infiltration (as shown in Figure 3 -M as indicated by the red arrow); Occasionally, hyperkeratosis was observed in the water extract medium dose group (such as Figure 3 -N orange arrow), a small amount of focal connective tissue hyperplasia (as shown in Figure 3 -N as indicated by the green arrow; water extraction is suitable for small-scale hyperkeratosis in the high-dose group (such as Figure 3 -O orange arrows). Patent CN201310527422.X group has multiple epidermal thickening (such as Figure 3 -P as indicated by the gray arrow), the cutaneous process is elongated to form an irregular cavity, in which keratinized material can be seen (e.g. Figure 3 -P as shown by the blue arrow), accompanied by some lymphocyte infiltration (as shown by Figure 3 -P as indicated by the red arrow). The Centella asiatica Magnolia officinalis and Honeysuckle group had extensive hyperkeratosis (as shown in Figure 3 -Q orange arrows), multiple epidermal thickening (such as Figure 3-Q gray arrow), the skin protrusions are elongated, and a small number of cells in the spinous layer of the epidermis have loose cytoplasm (as shown in Figure 2). Figure 3 -Q purple arrow), the number of dermal skin appendages, hair follicles and sebaceous glands is small, and a small amount of focal connective tissue hyperplasia (such as Figure 3 -Q green arrow), lymphocyte and granulocyte infiltration (as shown in Figure 3 -Q (indicated by the red arrow).

[0210] With the model group (such as Figure 3 -B), the inflammatory cell infiltration in each drug group was significantly improved, and the keratinization of hair follicle wall and squamous epithelial hyperplasia were all improved; compared with the positive drug group (such as Figure 3 -C) compared to the best alcohol extraction process (such as Figure 3 -E), high-dose group (such as Figure 3 -F), alcohol extraction suitable process high dose group (such as Figure 3 -I), water extraction best process (such as Figure 3 -H), high-dose group (such as Figure 3 -I) and water extraction suitable process high dose group (such as Figure 3 -L) has a similar effect; and the patent CN201310527422.X group (such as Figure 3 -P), Centella asiatica, Magnolia officinalis and Honeysuckle group (such as Figure 3 -Q), compared with the gel administration groups prepared by alcohol extraction or water extraction in this patent (such as Figure 3 -D~O) efficacy was greatly improved, the tissue lesions in each group were significantly improved, and the effects of inhibiting inflammatory cell infiltration and fibrous tissue atrophy were significantly enhanced; compared with the various gel administration groups prepared by alcohol extraction or water extraction in this patent, the therapeutic effects were equivalent under the same dosage. At the same time, the abnormal tissue structure in each group gradually alleviated with the increase of dosage.

[0211] 2.3.4 Serum levels of TNF-α, IL-6, and IL-1β

[0212] like Figures 4 to 6As shown in the figure, compared with the blank group, the levels of TNF-α, IL-1β and IL-6 in the model group were significantly increased. Compared with the model group, the levels of TNF-α, IL-1β and IL-6 in the serum of each drug group decreased, and the difference was significant (p<0.05), indicating that each group of drugs had a certain therapeutic effect on rabbit ear acne. Compared with the positive drug group, the levels of serum inflammatory factors IL-1β, IL-6 and TNF-α in the best medium dose of alcohol extraction group, the best high dose of alcohol extraction group, the appropriate low dose of alcohol extraction group, the appropriate high dose of alcohol extraction group, the best medium dose of water extraction group, the best high dose of water extraction group, the appropriate medium dose of water extraction group and the appropriate high dose of water extraction group were all lower, and there was no significant difference in the levels with the positive drug group, and the therapeutic effects were not much different; the levels of TNF-α and IL-1β in the patent CN201310527422.X group were significantly different from those in the positive drug group (p<0.05); the levels of various inflammatory factors in the Centella asiatica, Magnolia officinalis and Honeysuckle group were significantly different from those in the positive drug group (p<0.05), which shows that the patent CN201310527422.X group and the Centella asiatica, Magnolia officinalis and Honeysuckle group are both insufficient in efficacy against rabbit ear acne. Compared with the best medium dose group of alcohol extraction, the best low and high dose groups of alcohol extraction had little difference with the appropriate low, medium and high dose groups of alcohol extraction, the best low, medium and high dose groups of water extraction and the appropriate medium and high dose groups of water extraction in inhibiting the levels of TNF-α and IL-6 in serum (p>0.05); the appropriate medium dose group of alcohol extraction, the best low dose group of water extraction and the appropriate low dose group of water extraction were insufficient in reducing the level of IL-1β in serum (p<0.05).

[0213] The results showed that the rabbit ear acne model was successfully established, and the levels of various inflammatory factors were well reflected. Among the treatment groups, the positive drug kecuoyin ketone gel group had the best efficacy. In comparison, there was no significant difference in the levels of various inflammatory factors in the alcohol extraction best low, medium and high dose groups, alcohol extraction suitable low, medium and high dose groups, water extraction best low, medium and high dose groups and water extraction suitable medium and high dose groups corresponding to this patent. They can all significantly inhibit the abnormal increase of inflammatory factors in the serum caused by the rabbit ear acne model; the low dose group in the water extraction suitable process is slightly insufficient in inhibiting the IL-1β level, which can be improved by increasing the dosage. At the same time, compared with the prescription provided by patent CN201310527422.X and the combined extracts of Centella asiatica, Magnolia officinalis and honeysuckle, the gel prepared by this prescription has a stronger therapeutic effect on rabbit ear acne, which is reflected to varying degrees in the results of the three inflammatory factor determinations.

[0214] Study on the skin irritation of 3 compound Chinese medicine acne gel

[0215] 3.1 Experimental animals and test drugs

[0216] 3.1.1 Drug testing

[0217] Compound Chinese medicine acne gel (prepared by the Engineering Research Center of Tianjin University of Traditional Chinese Medicine), blank gel matrix (prepared by the Engineering Research Center of Tianjin University of Traditional Chinese Medicine)

[0218] 3.1.2 Experimental animals

[0219] Twenty-four healthy New Zealand white rabbits aged 8-10 weeks (half male and half female).

[0220] 3.2 Experimental methods

[0221] 3.2.1 Preparation of compound Chinese medicine acne gel

[0222] Prepare according to "Example 1".

[0223] 3.2.2 Irritation test

[0224] Single administration: 12 healthy New Zealand rabbits, half male and half female, were randomly divided into intact skin group and damaged skin group. Self-comparison method was used. The long hair on both sides of the rabbit's back was cut 24 hours before the test, and then the hair was removed with a depilatory cream (about 3cm×4cm). The skin of the intact skin group was not damaged in the depilatory area; the skin of the damaged skin group was scratched in the shape of "#" with a thin blade, and the wound was not damaged to the extent of bleeding without damaging the dermis. The skin of the self-control side was smeared with 0.5mL of blank gel matrix (as the intact skin blank group and the damaged skin blank group), and the other side was smeared with 0.5mL of compound Chinese medicine acne acne gel (as the intact skin administration group and the damaged skin administration group), covered with a single layer of sterile gauze and a single layer of wax paper, and then fixed with non-irritating rubber glue. After 4 hours, it was washed with warm water, and the skin irritation reaction of the application site was observed and recorded at 1, 24, 48, and 72 hours after washing.

[0225] Multiple administration: 12 healthy New Zealand rabbits were selected, half of which were male and half were female. The animal grouping, hair removal area, skin treatment and administration steps were the same as those for the single administration experiment. The drug was used continuously for 7 days. The skin irritation reaction at the application site was observed and recorded 1, 24, 48 and 72 hours after drug removal.

[0226] According to the Technical Guidelines for Drug Irritation, Allergy and Hemolysis Studies, the skin irritation intensity is scored according to Table 12. For multiple-dose skin irritation tests, the drug is administered once a day for 7 consecutive days, and the score is performed after the last administration. First, the mean score of each group at each observation time point (1, 24, 48, 72h) is calculated, and the mean score of each animal's stimulation score is calculated every day for 7 days, and the skin irritation intensity is judged according to Table 13.

[0227] Table 12 Skin irritation reaction scoring standard

[0228]

[0229] Table 13 Evaluation criteria for skin irritation intensity

[0230]

[0231] 3.3 Experimental Results

[0232] Table 14 Skin irritation rating results

[0233]

[0234] The results showed that at each observation time point, New Zealand rabbits had no abnormal reactions, no erythema, edema, and no death. Figure 7 , Figure 8 , Table 14. This shows that the gel is non-irritating.

Claims

1. A Chinese medicinal compound composition for preventing or treating acne, characterized in that: The medicinal raw materials are as follows: 5-30 parts of salvia miltiorrhiza, 10-40 parts of scutellaria baicalensis, 10-40 parts of oldenlandia diffusa, 10-40 parts of centella asiatica, 10-40 parts of wild chrysanthemum, 5-25 parts of safflower, 5-30 parts of honeysuckle, 5-30 parts of magnolia bark and 5-25 parts of liquorice.

2. The Chinese medicine compound composition according to claim 1, characterized in that: The medicinal raw materials are as follows: 10-20 parts of salvia miltiorrhiza, 15-30 parts of scutellaria baicalensis, 15-30 parts of oldenlandia diffusa, 15-30 parts of centella asiatica, 15-30 parts of wild chrysanthemum, 5-15 parts of safflower, 10-20 parts of honeysuckle, 10-20 parts of magnolia bark and 5-15 parts of liquorice.

3. The Chinese medicine compound composition according to claim 2, characterized in that: The medicinal material comprises the following raw materials: 12-18 parts of salvia miltiorrhiza, 18-25 parts of scutellaria baicalensis, 18-25 parts of oldenlandia diffusa, 18-25 parts of centella asiatica, 18-25 parts of wild chrysanthemum, 8-12 parts of safflower, 12-18 parts of honeysuckle, 12-18 parts of magnolia officinalis and 8-12 parts of liquorice.

4. The Chinese medicine compound composition according to claim 3, characterized in that: The medicinal material is composed of the following raw materials: 15 parts of salvia miltiorrhiza, 20 parts of scutellaria baicalensis, 20 parts of oldenlandia diffusa, 20 parts of centella asiatica, 20 parts of wild chrysanthemum, 10 parts of safflower, 15 parts of honeysuckle, 15 parts of magnolia bark and 10 parts of liquorice.

5. A Chinese medicine extract for preventing or treating acne, prepared by solvent extraction of the Chinese medicine compound composition according to any one of claims 1 to 4, characterized in that: The extraction solvent is selected from ethanol aqueous solution or water with a volume fraction of 30% to 80%.

6. The method for preparing the Chinese herbal medicine extract according to claim 5, comprising the following steps: weighing the prescribed medicinal materials, adding an extraction solvent for reflux extraction, centrifuging the extract, taking the supernatant for spray drying, and obtaining the spray-dried powder of the Chinese herbal medicine extract.

7. The method for preparing the Chinese medicine extract according to claim 6, characterized in that: Weigh the prescribed medicinal materials, add 6 to 20 times the volume fraction of 30% to 80% ethanol aqueous solution for reflux extraction, and extract 1 to 4 times, each time for 1 to 3 hours; after the extraction is completed, combine the extracts, centrifuge at 3000 to 8000 rpm for 3 to 20 minutes, take the supernatant for spray drying, the inlet air temperature is 120 to 140°C, the outlet air temperature is 60 to 80°C, and the peristaltic pump flow rate is 5 to 15 ml / min to obtain the spray-dried powder of the Chinese medicine extract.

8. The method for preparing a Chinese medicine extract according to claim 6 comprises the following steps: weighing the prescribed medicinal materials, adding 6 to 20 times the amount of water for reflux extraction, extracting 1 to 4 times, each time for 1 to 3 hours; after the extraction is completed, combining the extracts, centrifuging at 3000 to 8000 rpm for 3 to 20 minutes, taking the supernatant for spray drying, with an inlet air temperature of 120 to 140°C, an outlet air temperature of 60 to 80°C, and a peristaltic pump flow rate of 5 to 15 ml / min to obtain a spray-dried powder of the Chinese medicine extract.

9. A Chinese medicinal compound preparation for preventing or treating acne, prepared from the Chinese medicinal extract according to any one of claims 5 to 8, the preparation being selected from the group consisting of gels, solutions, ointments, powders, tinctures, lotions, sprays, creams, pastes, and film coatings.

10. The Chinese medicinal compound preparation for preventing or treating acne according to claim 9, which is a gel preparation, wherein the gel matrix comprises the following ingredients: carbomer, hydroxyethyl cellulose, xanthan gum, pullulan, glycerin, propylene glycol, phenoxyethanol, and distilled water.

11. The method for preparing a Chinese medicine compound preparation for preventing or treating acne according to claim 10, comprising the following steps: adding an appropriate amount of distilled water to dissolve 5 to 30 parts of spray-dried powder of Chinese medicine extract, and after dissolution, adding 1 to 5 parts of carbomer, 1 to 5 parts of hydroxyethyl cellulose, 0.5 to 3 parts of xanthan gum and 0.5 to 3 parts of pullulan, stirring at 300 to 700 rpm, and after swelling is complete and mixed evenly, continuing to add 15 to 60 parts of glycerol, 30 to 120 parts of propylene glycol and 2 to 8 parts of phenoxyethanol, and then adding triethanolamine to adjust the pH value to 5-7, adding the remaining distilled water, adding a total of 200 to 1000 parts of distilled water, increasing the rotation speed to 350 to 750 rpm, mixing the gel evenly, and filling after sterilization.

12. A method for preparing a Chinese medicine compound gel preparation for preventing or treating acne, characterized in that: Step 1): weigh the prescribed medicinal materials, add 6 to 20 times the volume fraction of 30% to 80% ethanol aqueous solution for reflux extraction, extract 1 to 4 times, each time for 1 to 3 hours; after the extraction is completed, combine the extracts, centrifuge at 3000 to 8000 rpm for 3 to 20 minutes, take the supernatant for spray drying, the inlet air temperature is 120 to 140°C, the outlet air temperature is 60 to 80°C, and the peristaltic pump flow rate is 5 to 15 ml / min to obtain the spray-dried powder of the Chinese medicine extract; Step 2): Take 5 to 30 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 1 to 5 parts of carbomer, 1 to 5 parts of hydroxyethyl cellulose, 0.5 to 3 parts of xanthan gum and 0.5 to 3 parts of pullulan, stir at 300 to 700 rpm, and after swelling is complete and mixed evenly, continue to add 15 to 60 parts of glycerol, 30 to 120 parts of propylene glycol and 2 to 8 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 5-7, add the remaining distilled water, and add a total of 200 to 1000 parts of distilled water, increase the speed to 350 to 750 rpm, mix the gel evenly, and fill it after sterilization.

13. The method for preparing the Chinese medicine compound gel preparation according to claim 12, characterized in that: Step 1): weigh the prescribed medicinal materials, add 8 to 16 times the volume fraction of 50% to 75% ethanol aqueous solution for reflux extraction, extract 1 to 3 times, each time for 1.5 to 2.5 hours, combine the extracts, centrifuge at 4000 to 6000 rpm for 5 to 15 minutes, take the supernatant for spray drying, the inlet air temperature is 125 to 135° C., the outlet air temperature is 65 to 75° C., and the peristaltic pump flow rate is 7 to 12 ml / min to obtain the spray-dried powder of the Chinese medicine extract; Step 2): Take 10-20 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, add 2-4 parts of carbomer, 2-4 parts of hydroxyethyl cellulose, 1-2 parts of xanthan gum and 1-2 parts of pullulan after dissolution, stir at 350-550 rpm, and after swelling is complete and mixed evenly, continue to add 25-50 parts of glycerol, 50-100 parts of propylene glycol and 3-6 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 400-800 parts of distilled water, increase the rotation speed to 400-600 rpm, mix the gel evenly, and fill it after sterilization.

14. A method for preparing a Chinese medicine compound gel preparation for preventing or treating acne, characterized in that: Step 1): weigh the prescribed medicinal materials, add 6 to 20 times the amount of water for reflux extraction, extract 1 to 4 times, each time for 1 to 3 hours; after the extraction is completed, combine the extracts, centrifuge at 3000 to 8000 rpm for 3 to 20 minutes, take the supernatant for spray drying, the inlet air temperature is 120 to 140°C, the outlet air temperature is 60 to 80°C, and the peristaltic pump flow rate is 5 to 15 ml / min to obtain the spray-dried powder of the Chinese medicine extract; Step 2): Take 5 to 30 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 1 to 5 parts of carbomer, 1 to 5 parts of hydroxyethyl cellulose, 0.5 to 3 parts of xanthan gum and 0.5 to 3 parts of pullulan, stir at 300 to 700 rpm, and after swelling is complete and mixed evenly, continue to add 15 to 60 parts of glycerol, 30 to 120 parts of propylene glycol and 2 to 8 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 5-7, add the remaining distilled water, and add a total of 200 to 1000 parts of distilled water, increase the speed to 350 to 750 rpm, mix the gel evenly, and fill it after sterilization.

15. The method for preparing the Chinese medicine compound gel preparation according to claim 14, characterized in that: Step 1): weigh the prescribed medicinal materials, add 8 to 16 times the amount of water for reflux extraction, extract 1 to 3 times, each time for 1.5 to 2.5 hours, combine the extracts, centrifuge at 4000 to 6000 rpm for 5 to 15 minutes, take the supernatant for spray drying, the inlet air temperature is 125 to 135°C, the outlet air temperature is 65 to 75°C, and the peristaltic pump flow rate is 7 to 12 ml / min to obtain the spray-dried powder of the Chinese medicine extract; Step 2): Take 10-20 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, add 2-4 parts of carbomer, 2-4 parts of hydroxyethyl cellulose, 1-2 parts of xanthan gum and 1-2 parts of pullulan after dissolution, stir at 350-550 rpm, and after swelling is complete and mixed evenly, continue to add 25-50 parts of glycerol, 50-100 parts of propylene glycol and 3-6 parts of phenoxyethanol, then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 400-800 parts of distilled water, increase the rotation speed to 400-600 rpm, mix the gel evenly, and fill it after sterilization.

16. The method for preparing the Chinese medicine compound gel preparation according to any one of claims 12 to 15, characterized in that: In step 2), sterilization is performed at 120° C. for 30 min.

17. The method for preparing the Chinese medicine compound gel preparation according to claim 13, characterized in that: Step 1): weigh the prescribed medicinal materials, 15 parts of Salvia miltiorrhiza, 20 parts of Scutellaria baicalensis, 20 parts of Hedyotis diffusa, 20 parts of Centella asiatica, 20 parts of Chrysanthemum indici, 10 parts of Carthamus tinctorius, 15 parts of Honeysuckle, 15 parts of Magnolia officinalis, and 10 parts of Licorice; add 12 times the total weight of the medicinal materials and a volume fraction of 70% ethanol aqueous solution for reflux extraction, extract 3 times, each time for 2 hours, combine the 3 extracts, centrifuge at 5000rpm for 10 minutes, take the supernatant for spray drying, the inlet air temperature is 130°C, the outlet air temperature is 70°C, and the peristaltic pump flow rate is 10ml / min to prepare the Chinese medicine extract spray-dried powder; Step 2): Take 15 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan, stir at 400rpm, and after swelling is complete and mixed evenly, continue to add 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 600 parts of distilled water, increase the speed to 450rpm, and mix the gel evenly; sterilize at 120℃ for 30min and then fill.

18. The method for preparing the Chinese medicine compound gel preparation according to claim 13, characterized in that: Step 1): weigh the prescribed medicinal materials, 15 parts of Salvia miltiorrhiza, 20 parts of Scutellaria baicalensis, 20 parts of Hedyotis diffusa, 20 parts of Centella asiatica, 20 parts of Chrysanthemum indici, 10 parts of Carthamus tinctorius, 15 parts of Honeysuckle, 15 parts of Magnolia officinalis, and 10 parts of Licorice; add 10 times the total weight of the medicinal materials and a volume fraction of 50% ethanol aqueous solution for reflux extraction, extract twice, each time for 2 hours, combine the two extracts, centrifuge at 5000rpm for 10 minutes, take the supernatant for spray drying, the inlet air temperature is 130°C, the outlet air temperature is 70°C, and the peristaltic pump flow rate is 10ml / min to prepare the Chinese medicine extract spray-dried powder; Step 2): Take 15 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan, stir at 400rpm, and after swelling is complete and mixed evenly, continue to add 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 600 parts of distilled water, increase the speed to 450rpm, and mix the gel evenly; sterilize at 120℃ for 30min and then fill.

19. The method for preparing the Chinese medicine compound gel preparation according to claim 15, characterized in that: Step 1): weigh the prescribed medicinal materials, 15 parts of Salvia miltiorrhiza, 20 parts of Scutellaria baicalensis, 20 parts of Hedyotis diffusa, 20 parts of Centella asiatica, 20 parts of Chrysanthemum indici, 10 parts of Carthamus tinctorius, 15 parts of Honeysuckle, 15 parts of Magnolia officinalis, and 10 parts of Licorice; add 12 times the total weight of the medicinal materials of water for reflux extraction, extract 3 times, each time for 2 hours, combine the 3 extracts, centrifuge at 5000rpm for 10 minutes, take the supernatant for spray drying, the inlet air temperature is 130°C, the outlet air temperature is 70°C, and the peristaltic pump flow rate is 10ml / min to prepare the Chinese medicine extract spray-dried powder; Step 2): Take 15 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan, stir at 400rpm, and after swelling is complete and mixed evenly, continue to add 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 600 parts of distilled water, increase the speed to 450rpm, and mix the gel evenly; sterilize at 120℃ for 30min and then fill.

20. The method for preparing the Chinese medicine compound gel preparation according to claim 15, characterized in that: Step 1): weigh the prescribed medicinal materials, 15 parts of Salvia miltiorrhiza, 20 parts of Scutellaria baicalensis, 20 parts of Hedyotis diffusa, 20 parts of Centella asiatica, 20 parts of Chrysanthemum indici, 10 parts of Carthamus tinctorius, 15 parts of Honeysuckle, 15 parts of Magnolia officinalis, and 10 parts of Licorice; add 12 times the total weight of the medicinal materials of water for reflux extraction, extract twice, each time for 1 hour, combine the two extracts, centrifuge at 5000rpm for 10min, take the supernatant for spray drying, the inlet air temperature is 130°C, the outlet air temperature is 70°C, and the peristaltic pump flow rate is 10ml / min to prepare the Chinese medicine extract spray-dried powder; Step 2): Take 15 parts of the spray-dried powder of the Chinese medicine extract obtained in step 1, add an appropriate amount of distilled water to dissolve it, and after dissolution, add 3 parts of carbomer, 3 parts of hydroxyethyl cellulose, 1.5 parts of xanthan gum and 1.5 parts of pullulan, stir at 400rpm, and after swelling is complete and mixed evenly, continue to add 37.5 parts of glycerol, 75 parts of propylene glycol and 4 parts of phenoxyethanol, and then add triethanolamine to adjust the pH value to 6, add the remaining distilled water, add a total of 600 parts of distilled water, increase the speed to 450rpm, and mix the gel evenly; sterilize at 120℃ for 30min and then fill.

21. Use of a Chinese herbal compound composition, a Chinese herbal extract or a Chinese herbal compound preparation in the preparation of a medicament for preventing or treating acne, wherein the Chinese herbal compound composition, the Chinese herbal extract or the Chinese herbal compound preparation is selected from the Chinese herbal compound composition of any one of claims 1 to 4, the Chinese herbal extract of claim 5, the Chinese herbal extract prepared by the method of any one of claims 6 to 8, the Chinese herbal compound preparation of any one of claims 9 to 10 or the Chinese herbal compound preparation prepared by the method of any one of claims 11 to 20.

22. The use according to claim 21, wherein the acne is acne vulgaris or acne in oily skin.

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