AU2019101673A4

AU2019101673A4 - Coptis chinensis acne-removing composition and its application

Info

Publication number: AU2019101673A4
Application number: AU2019101673A
Authority: AU
Inventors: Xuegang LI; Xiaoli Ye; Baoshun ZHANG
Original assignee: Southwest University
Current assignee: Southwest University
Priority date: 2019-12-20
Filing date: 2019-12-20
Publication date: 2020-02-06
Anticipated expiration: 2027-12-20

Abstract

Abstract A Coptis chinensis acne-removing composition comprising of the following components in units by weight: 0.01 to 10 units of Coptis chinensis extract, 0.01 to 10 units of Rhubarb extract, 0.01 to 10 units of Salvia miltiorrhizaextract,0 to 10 units of supramolecular salicylic acid, to 10 units of glycolic acid, 0.1 to 5 units of linoleic acid, 0.01 to 5 units of vitamin A, and 0.01 to 5 units of vitamin E. Compared with other pure TCM prescriptions, the Coptis chinensis acne-removing composition is simpler and more effective, and has low dependence of pure TCM prescriptions, which can effectively remove acnes, accompanied by antibacterial, anti-inflammatory, anti-itching, whitening and other effects. - 1-

Description

COPTIS CHINENSIS ACNE-REMOVING COMPOSITION AND ITS APPLICATION

Technical Field

The present disclosurerelates to natural cosmetic compound of Chinese herbal medicine, in particular to a Coptis chinensis acne-removing composition.

Background Technology

Acne (also known as pimple) is a kind of skin infectious disease mainly caused by Propionibacterium acnes, which is not only related to Propionibacterium, but also related to the increase of androgen and sebum, excessive keratosis at the opening of follicle sebaceous gland, and secondary inflammation. At present, acne is mainly treated with tretinoins, azelaic acid, sulfur lotion and other topical bactericidal drugs supplemented by oral antibiotics. However, due to the current drug abuse, especially the abuse of antibiotics, the proportion of drug-resistant Propionibacterium is increasing year by year, which brings great inconvenience to the clinical treatment of acne.

Studies have shown that Coptis chinensis and Rhubarb, two kinds of traditional Chinese medicines (TCMs), have good antibacterial activity, especially the activity of inhibiting Propionibacterium acnes. In effect, a large number of researches are focusing onthe development of TCMs for treatment of acne. In 2006, patent CN1840070A disclosed application of a drug composition in preparation of drugs for treatment of acne, only comprising of Coptis chinensis, Rhubarb, Taraxacum, Salvia miltiorrhiza, Fritillaria and other natural Chinese medicinal materials, without western medicinal ingredients, which is not prone to generation of drug-resistant Propionibacterium, and has a remarkable efficacy on acne.In 2011, patent CN102370759A disclosed a TCM compound and its preparation method, generating from decoction and concentration of Coptis chinensis, Salvia miltiorrhiza, Rhubarb, Radix Scutellariae, Forsythia suspensa, White Mulberry

-1 Description

2019101673 20 Dec 2019

Root-bark and other Chinese medicinal materials,which overcomes western medicines'dependence and has a remarkable efficacy on acne.

Invention Summary

The present disclosure aims at a kind of Coptis chinensis acne-removing composition, in which each component has synergistic effect, no dependence, and has a remarkable efficacy on acne and pimple.

A Coptis chinensis acne-removing composition comprising of the following components in units by weight: 0.01 to 10 units of Coptis chinensis extract, 0.01 to 10 units of Rhubarb extract, 0.01 to 10 units of Salvia miltiorrhiza extract, 0 to 10 units of supramolecular salicylic acid,0 to 10 units of glycolic acid, 0.1 to 5 units of linoleic acid, 0.01 to 5 units of vitamin A, and 0.01 to 5 units of vitamin E.

Preferably, the Coptis chinensis acne-removing composition described above comprising of the following components in units by weight: 0.1 to 3 units of Coptis chinensis extract, 0.1 to 3 units of Rhubarb extract, 0.1 to 3 units of Salvia miltiorrhiza extract, 1 to 5 part of supramolecular salicylic acid, 0.2 to 1 units of linoleic acid, 0.1 to 1 units of vitamin A, and 0.1 to 1 units of vitamin E.

Preferably, the Coptis chinensis acne-removing composition described above comprising of the following components in units by weight: 0.1 to 3 units of Coptis chinensis extract, 0.1 to 3 units of Rhubarb extract, 0.1 to 3 units of Salvia miltiorrhiza extract, 1 to 5 part of supramolecular salicylic acid, 0.2 to 1 units of linoleic acid, 0.1 to 1 units of vitamin A, 0.1 to 1 units of vitamin E, and residual matrixes and excipients.

-2Description

2019101673 20 Dec 2019

Preferably, the Coptis chinensis acne-removing composition described above further includes 5% to 10% glycolic acid by weight.

Preferably, the Coptis chinensis extract is prepared by the following method:

1) Rough extraction: a clear Coptis chinensis concentrated extract is obtained from pretreatment and sulfuric acid immersion of Coptis chinensis, followed by percolation, neutralization of percolate, concentration, and final filtration;

2) Salting out: a concentrated hydrochloric acid with a volume of 0.5% - 1% of the Coptis chinensis concentrated extract is added to the Coptis chinensis concentrated extract, and then a sodium chloride with a weight of 5% - 10% of the Coptis chinensis concentrated extract is added and precipitated for 1 to 24 h to obtain a clear mother solution after solid-liquid separation;

3) Preparation of Coptis chinensis extract: the clear mother solution is extracted with a solvent I to separate organic phase I, the aqueous phase is then extracted with a solvent II and discarded, organic phase II is collected and concentrated to obtain a Coptis chinensis extract; in which the solvent I is ethyl acetate, dichloromethane, trichloromethane or/and ether, and the solvent II is ethyl acetate-butanol or butanol.

Preferably, the Coptis chinensis concentrated extract is a solution with a concentration of 0.1 to 5 g of Coptis chinensis crude drug/mL.

Preferably, the extraction with solvent I and the extraction with solvent II refer to two times of solvent extraction at equal volume.

More preferably, the concentrated hydrochloric acid added in the step (2) is 0.5% of the Coptis chinensis concentrated extract by volume, and the sodium chloride added is 5% of the Coptis chinensis concentrated extract by weight.

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2019101673 20 Dec 2019

Preferably, the Rhubarb extract is prepared by the following method:

(a) Rough extraction: Rhubarb is crushed and added with 0.5-2mol/L ammonia solution by 5-to 20-fold volume of crude drug, stirred at 10 -60 °C for 12 h, and centrifuged to obtainfirst extract solution and residue, residue isthen extracted under the same conditions for 8 h to obtain second extract solution, and finallytwo extractsolutions are mixed together;

(b) Refining: the extract is added with ethanol by 20- to 40-fold weight of Rhubarb crude drug, stirred evenly, stored in refrigerator, and centrifuged to obtain supernatant, which is then concentrated for a rhubarb concentrated extract with a concentration of 0.1 to 3 g Rhubarb crude drug/mL.

(c) Preparation of Rhubarb extract: the rhubarb concentrated extract is added with 1-3 mol/L HC1 solution to adjust pH of 1-4, acid-hydrolyzed at 70°C for 3 h, and filtered to obtain precipitate, which is then recovered and dried at 40°C in oven to obtain a rhubarb extract.

Preferably, the Salvia miltiorrhiza extract is prepared by the following method:

(1) Percolation: Salvia miltiorrhiza is crushed, soaked with 70% - 100% ethanol overnight, percolated and collected 1-fold volume of Salvia miltiorrhiza percolate every day, which is stopped after collection of 4- to 8-fold volume, followed by mixing and concentrating percolate to obtain total concrete;

(2) Extraction: 1 part of Salvia miltiorrhiza extract is dissolved in 20 units (W7V) mixed solvent, extracted, separated organic phase, added with 1% - 10% anhydrous sodium sulfate, dried at 0 - 8 °C for 2 - 10 h, and concentrated to obtain Salvia miltiorrhiza extract after solid-liquid separation. The mixed solvent is a solvent mixed with 25 to 45 units of ethyl acetate and 50 units of sodium hydrogen carbonate solution with a mass concentration of 5%.

-4Description

2019101673 20 Dec 2019

Application of the Coptis chinensis acne-removing composition in the present disclosure in preparation of drugs, skin care products or cosmetics for treatment and/or prevention of acne also falls within the protection scope of the present disclosure.

The Coptis chinensis acne-removing composition inthe present disclosurecan be used as a drug for direct topical application after grinding, or as effective components for preparation oftopical drugs in different forms, such as pastes, medical dressings, liquid, patches and sprays, preferably pastes, which mainly refer to pastes prepared by traditional paste preparation process.

When the composition is applied in pastes, it is preferable to select white vaseline, glycerol monostearate, span 60, tween 80, triethanolamine, glycerol, poloxamer andfatty alcohol polyoxyethylene ether ammonium sulfate as matrixes and excipients of paste.

It is more preferable to select poloxamer and fatty alcohol polyoxyethylene ether ammonium sulfate.

The Coptis chinensis acne-removing composition inthe present disclosurecan also be usedas active ingredients for skin care productsby mixing with aqueous solventsand/oralcoholic solvents for application, such as facial cleansers, masks, skin care ointments, creams or essences, and preferably added into hydrogel matrix/polyethylene glycol matrix forfacial cleansers, masks, skin care ointments, creams or essences, etc. The composition can be further added with poly hydroxy acid and/oraldobionic acid and the liketo form the above-described product.

There are many kinds of hydrogel matrix: such as cross-linked waterborne acrylic acid copolymer (Carbomer resin), that is, waterborne thickened resin, orhydrogel from dissolvedsodium alginate, agar and gelatin.Prepared hydrogel dressing is a kind of clean, convenient, self-soluble and hydrating waterborne dressing,which can release drugs and

- 5 Description

2019101673 20 Dec 2019 sterilizes at the same time, and has slow releasefunction. Polymer hydrogel is usually prepared by rapid catalytic polymerization of hydrophilic polymeric monomers (such as hydroxyethyl methacrylate) with evocators in suspension, or by preparation of compound using non-hydrophilic monomers (such as butylmethacrylate) afterpolymerizationand hydrogel.

The Coptis chinensis acne-removing composition inthe present disclosure can also be used as active ingredientsfor cosmetics to prevent acne and to reduce air-proof caused by facial cosmetics and acne or pimple caused by long-term makeup, especially applied in ointments and creams, such as foundation liquids,make-up bases, BB creams, CC creams or make-up primers.

The present disclosure combs out more than 100 kinds of Chinese medicinal materials and Chinese medicinal prescriptions that have effect of acne treatment based on a large number of literature, finally selects 20 kinds of commonly used Chinese medicinal materials for acne treatment as study materials, and performs many experimental studies to ultimately obtain complex comprising of Coptis chinensis extract, Rhubarb extract and Salvia miltiorrhiza extract, which can significantly inhibit androgens and androgen receptors in epidermis cells and simultaneously has a significant anti-Propionibacterium acne effect, and then supplements with supramolecular salicylic acid and glycolic acid and other whitening and resurfacing components to allocate the composition described in the present disclosure.

Compared with other pure TCM prescriptions, the Coptis chinensis acne-removing composition in the present disclosure is simpler and more effective, and has low dependence of pure TCM prescriptions, which can effectively remove acnes,accompanied by antibacterial, anti-inflammatory, anti-itching, whitening and so on effects.

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Detailed Description of the Presently Preferred Embodiments

Salvia miltiorrhiza extract and Rhubarb extract in the present disclosure can also be purchased directly from market.

Embodiment 1

A total of 10 kg of Coptis chinensis extract, 0.01 kg of Salvia miltiorrhiza extract, 0.01 kg of Rhubarb extract, 5 kg of supramolecular salicylic acid, 0.1 kg of linoleic acid, 0.01 kg of vitamin A, 5 kg of vitamin E, and 79.87 kgof residual matrixes and excipients.

Wherein, the preparation method of Coptis chinensis extract is as follows: slicing 40 kg of coptis chinensis, soaking for 24 h with 0.5% sulfuric acid, percolating,and collecting 40 L of percolate every day; adding collected percolate into lime for neutralization to pH of 2, and filtering to obtain filtrate and residue; washing residue with a proper amount of water for 1 time to obtain washing solution, and mixing filtrate and washing solution; concentrating mixed neutralization solution under reduced pressure to a concentration of 0.1 g of crude drug/mL, cooling, filtering, and centrifuging to obtain a clear Coptis chinensis concentrated extract; adding 0.5% concentrated hydrochloric acid by volume to concentrated extract, adding 5%sodium chloride by weight, precipitating overnight, and filtering to obtain a clear solution; extracting clear solution with 400 L of ethyl acetate to obtain a refined solution; extracting refined solution with 400 L of ethyl acetate-butanol solvent, and recovering solvent to obtain 10 kg of Coptis chinensis extract.

Salvia miltiorrhiza extract and Rhubarb extract are all marketed products. The main active component of Salvia miltiorrhiza extract is Salvia miltiorrhizacryptone, and of Rhubarb is Rhein.

Coptis chinensis extract, Salvia miltiorrhiza extract, rhubarb extract, supramolecular salicylic acid and other materials are mixed in proportion and prepared into ointment.

-7Description

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This product has antibacterial, anti-inflammatory, anti-itching, whitening and other functions, which can be used to treat acne and other skin diseases caused by Propionibacterium acnes.

Embodiment2

A total of 0.01 kg of Coptis chinensis extract, 10 kg of Salvia miltiorrhiza extract, 0.01 kg of Rhubarb extract, 5 kg of glycolic acid, 5 kg of linoleic acid, 5kg of vitamin A,0.01 kg of vitamin E, and 74.97 kgof residual matrixes and excipients.

Wherein, the preparation method of Coptis chinensis extract is as follows: slicing 40 kg of coptis chinensis, soaking for 24 h with 0.5% sulfuric acid, percolating,and collecting 40 L of percolate every day; adding collected percolate into lime for neutralization to pH of 2, and filtering to obtain filtrate and residue; washing residue with a proper amount of water for 1 time to obtain washing solution, and mixing filtrate and washing solution; concentrating mixed neutralization solution under reduced pressure to a concentration of 0.1 g of crude drug/mL, cooling, filtering, and centrifuging to obtain a clear Coptis chinensis concentrated extract; adding 0.5% concentrated hydrochloric acid by volume to concentrated extract, adding 5% sodium chloride by weight, precipitating overnight, and filtering to obtain a clear solution; extracting clear solution with 400 L of ethyl acetate to obtain a refined solution; extracting refined solution with 400 L of ethyl acetate-butanolsolvent, and recovering solvent to obtain 10 kg of Coptis chinensis extract.

- 8 Description

2019101673 20 Dec 2019

Coptis chinensis extract, Salvia miltiorrhiza extract, rhubarb extract, supramolecular salicylic acid and other materials are mixed in proportion and prepared into ointment. This product has antibacterial, anti-inflammatory, anti-itching, whitening and other functions, which can be used to treat acne and other skin diseases caused by Propionibacterium acnes.

Embodiment 3

A total of 1 kg of Coptis chinensis extract, 1 kg of Salvia miltiorrhiza extract, 10 kg of Rhubarb extract, 2 kg of supramolecular salicylic acid, 2 kg of glycolic acid, 1 kg of linoleic acid, 1kg of vitamin A, 1 kg of vitamin E, and 81 kg of residual matrixes and excipients.

Wherein, the preparation method of Salvia miltiorrhiza extract is as follows: crushing 1 kg of Salvia miltiorrhiza, soaking with 95% ethanol overnight, and then percolating; collecting 1 L of percolate every day, and stopping percolation after collection of 5 L ofpercolate; concentratingpercolateunder reduced pressure to obtain0.2 kgoftotal

-9Description

2019101673 20 Dec 2019 concrete;dissolving0.2 kg of Salvia miltiorrhiza concrete in 1 L of mixed solvent (mixed with 35 units of ethyl acetate and 50 units of sodium bicarbonate solution (5%)), fullyshaking and extractingfor 1 h, and standing for lamination to obtain ethyl acetate layer; adding 5% anhydrous sodium sulfate into ethyl acetate solution for drying, storing in refrigerator at 4 °C for 6 h, filtering and removing anhydrous sodium sulfate, and recovering ethyl acetate to obtainO.l kg of Salvia miltiorrhiza extract.

Wherein, the preparation method of Rhubarb extractisas follows:crushing 40 kg of rhubarb,and mixing with 400 L of Imo 1/L ammonia solution at 40 °C for 12 h; centrifuging to obtain first extract solution and residue, and mixing residue with 400 L of Imo 1/L ammonia solution at 40 °C for 8 h to obtain second extract solution; mixingtwo extract solutions, adding 1,200 L of ethanol into extract solution, and storing in refrigerator overnight; centrifuging, and concentrating to Ig of rhubarb crude drug/mL; adding 2 mol/L HC1 solution to adjust pH of 2 - 3, acid-hydrolyzing at 70 °C for 3 h, filtering and recovering precipitate, and drying precipitatein oven at 40 °C to obtain 10 kg of Rhubarb extract.

Embodiment 4

A total of 5 kg of Coptis chinensis extract, 5 kg of Salvia miltiorrhiza extract, 5 kg of Rhubarb extract, 2 kg of supramolecular salicylic acid, 2 kg of glycolic acid, 1 kg of linoleic acid, 1kg of vitamin A, 1 kg of vitamin E, and 78 kgof residual matrixes and excipients.

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2019101673 20 Dec 2019

Wherein, the preparation method of Coptis chinensis extract is as follows: slicing 40 kg of coptis chinensis, soaking for 24 h with 0.5% sulfuric acid, percolating,and collecting 40 L of percolate every day; adding collected percolate into lime for neutralization to pH of 5, and filtering to obtain filtrate and residue; washing residue with a proper amount of water for 2 times to obtain washing solution, and mixing filtrate and washing solution; concentrating mixed neutralization solution under reduced pressure to a concentration of 1 g of crude drug/mL, cooling, filtering, and centrifuging to obtain a clear Coptis chinensis concentrated extract; adding 0.5% concentrated hydrochloric acid by volume to concentrated extract, adding 5%sodium chloride by weight, precipitating overnight, and filtering to obtain a clear solution; extracting clear solution with 10 L of trichloromethane to obtain a refined solution; extracting refined solution with 10 L of butanol mixed solvent, and recovering solvent to obtain 10 kg of Coptis chinensis extract.

Wherein, the preparation method of Salvia miltiorrhiza extract is as follows:crushing50 kg of Salvia miltiorrhiza, soaking with 95% ethanol overnight, and then percolating; collecting50L of percolate every day, and stopping percolation after collection of250L of percolate; concentrating percolateunder reduced pressure to obtainlO kgoftotal concrete; dissolving 10 kg of Salvia miltiorrhiza concrete in 200L of mixed solvent (mixed with 35 units of ethyl acetate and 50 units of sodium bicarbonate solution (5%)), fullyshaking and extractingfor 1 h, and standing for lamination to obtain ethyl acetate layer; adding 5% anhydrous sodium sulfate into ethyl acetate solution for drying, storing in refrigerator at 4 °C for 6 h, filtering and removing anhydrous sodium sulfate, and recovering ethyl acetate to obtainlO kg of Salvia miltiorrhiza extract.

Wherein, the preparation method of Rhubarb extractisas follows:crushing 40 kg of rhubarb,and mixing with 400 L of Imo 1/L ammonia solution at 40 °C for 12 h; centrifuging to obtain first extract solution and residue, and mixing residue with 400 L

-11 Description

2019101673 20 Dec 2019 of Imol/L ammonia solution at 40 °C for 8 h to obtain second extract solution; mixingtwo extract solutions, adding 1,200 L of ethanol into extract solution, and storing in refrigerator overnight; centrifuging, and concentrating to Ig of rhubarb crude drug/mL; adding 2 mol/L HC1 solution to adjust pH of 2 - 3, acid-hydrolyzing at 70 °C for 3 h, filtering and recovering precipitate, and drying precipitate in oven at 40 °C to obtain 10 kg of Rhubarb extract.

A number of control groups were set up in order to further study anti-Propionibacterium acne effect of the Coptis chinensis acne-removing composition in the present disclosure and its clinical efficacy on acne. Components and contents of the Coptis chinensis acne-removing composition in each control group were set up as follows:

Control Group 1: components: 12.5 kg of Coptis chinensis extract and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Control Group 2: components: 6.25 kg of Coptis chinensis extract, 6.25 kg of Rhubarb extract, and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Control Group 3: components: 4 kg of Coptis chinensis extract, 4 kg of Salvia miltiorrhiza extract, 4.5 kg of Rhubarb extract, and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Control Group 4: components: 3.5 kg of Coptis chinensis extract, 3.5 kg of Salvia miltiorrhiza extract, 3.5 kg of Rhubarb extract, 2 kg of supramolecular salicylic acid, and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

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Control Group 5: components: 3.5 kg of Coptis chinensis extract, 3.5 kg of Salvia miltiorrhiza extract, 3.5 kg of Rhubarb extract, 2 kg of glycolic acid, and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Control Group 6: components: 3 kg of Coptis chinensis extract, 3 kg of Salvia miltiorrhiza extract, 3 kg of Rhubarb extract, 2 kg of supramolecular salicylic acid, 1.5 kg of glycolic acid, and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Control Group 7: components: 3 kg of Coptis chinensis extract, 3 kg of Salvia miltiorrhiza extract, 3 kg of Rhubarb extract, 1.5 kg of supramolecular salicylic acid, 1 kg of glycolic acid, 1 kg of linoleic acid, and 87.5 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Control Group 8: components: 5 kg of Coptis chinensis extract, 5 kg of Salvia miltiorrhiza extract, 2 kg of Rhubarb extract, 5 kg of pearl, 5 kg of linoleic acid, 2 kg of vitamin A, 2 kg of vitamin E, 10 kg of glycolic acid, 0.1 kg of trimethoprim, and 63.9 kg of ointment matrix. All components were mixed by proportion and prepared to ointment.

Comparison on Anti-Propionibacterium Acne Effect

Propionium acnes are the main pathogen of acne. The antibacterial experiment method was carried out according to the Guiding Principles of New Drug Research of Natural Drugs (Traditional Chinese Medicine)', using Propionibacterium acnes as bacterial model, the antibacterial activity of the composition was studied by detecting MIC: after o

bacterial culture, the bacterial concentration was adjusted to 1 x 10 /mL,50 pL of bacteria were added to each well of 96-well plate, the composition indifferent concentrations were then added respectively to culture for 24 h,and the growth of bacteria was observed to judge the results of MIC, as shown in Table 1.

Table 1 Comparison on anti-Propionibacterium acne effect (MIC pg/mL)

Embodiment 1

8.0

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Embodiment 2	8.0
Embodiment 4	4.0
Control Group 1	500.0
Control Group 2	125
Control Group 3	32.2
Control Group 4	16.0
Control Group 5	16.0
Control Group 6	8.0
Control Group 7	8.0
Control Group 8	2.0

As can be seen from Table 1, the Coptis chinensis acne-removing composition in the present disclosurehas a good effect of inhibiting activity of Propionibacterium acnes, and the products prepared from commercial Rhubarb extract and Salvia miltiorrhiza extract also have the same efficacy.The antibacterial activity of the composition is enhanced with the increased number of components, in particular to the combinations of Coptis chinensis extract, Rhubarb extract and Salvia miltiorrhiza extract, namely, the antibacterial effect of the rest groups is obviously enhanced except for Control Groups 1 and 2. At the same time, it is found that the anti-Propionibacterium acne activity in Control Group 8 is the strongest, which may be related to the presence of antibiotic (trimethoprim) in Control Group 8.

Comparison on Clinical Efficacy

Treatment Method: patients in the voluntary test group were given facial topical drug and control drugfor 6 days, once respectively each morning and evening.

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Evaluation Criteria for Efficacy: the efficacy was evaluated according to the reduction of skin lesions (acnes, papules, pustules, etc.) before and after treatment. Complete response: the skin lesions resolved by 90%, and no new skin lesions appeared, with only a small amount of pigmentation left; Partial response: the skin lesions resolved by 60% 89%, and no new skin lesions appeared, with a small amount of pigmentation left; Improvement: the skin lesions resolved by 30% - 59%, and a few new lesions appeared, with a small amount of pigmentation left; No response: the skin lesions resolved by < 30%, and new lesions appeared, with pigmentation left. Response Rate = (Cases of Complete Response + Cases of PartialResponse) Total Cases x 100%. The results are shown in Table 2.

Table 2 Observation of clinical efficacy

	Complete Response (%)	Partial Response (%)	Improvement (%)	No Response (%)
Drug Group (Embodiment 4)	95	1	4	0
Control Group 1	35	5	5	55
Control Group 2	40	10	5	45
Control Group 3	50	15	10	25
Control Group 4	75	15	5	5
Control Group 5	70	15	5	10
Control Group 6	85	5	5	5
Control Group 7	90	5	5	0
Control Group 8	90	5	3	2

According to clinical statistics, response rate refers to the sum of complete response,

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2019101673 20 Dec 2019 partial response and improvement. As can be seen from Table 2, the complete response rate of Coptis chinensis acne-removing cream is as high as 95% and the response rate is 100%;Coptis chinensis extract alone also has an efficacy(response rate of 45%);the combination of Coptis chinensis extract and Rhubarb extract can improve the acne-removing efficacy (response rate of 55%); the combination of Coptis chinensis extract, Rhubarb extract and Salvia miltiorrhiza extract can further improve the efficacy (response rate of 75%); in particular, the addition of supramolecular salicylic acid and/or glycolic acid to Coptis chinensis extract, Rhubarb extract and Salvia miltiorrhiza extract can obviously improve the efficacy (response rate of more than 90%); and the further addition of linoleic acid and vitaminscan significantly improve the efficacy (response rate of 100%). At the same time, it is found that although the anti-Propionibacterium acne activity in Control Group 8 is superior to that of the Coptis chinensis acne-removing composition, the effect of the Coptis chinensis acne-removing composition of the present disclosure on acne treatment is superior to that of Control Group 8 (the complete response rate and the partial response rate of Drug Group are superior to those of Control Group 8).

Claims

Claims 2019101673 20 Dec 2019

(1) Percolation: Salvia miltiorrhiza is crushed, soaked with 70% -100% ethanol overnight, percolated and collected 1-fold volume of Salvia miltiorrhiza percolate every day, which is stopped aftercollection of 4- to 8-fold volume, followed by mixing and concentrating percolateto obtain total concrete;

1) Rough extraction: a clear Coptis chinensis concentrated extract is obtained from pretreatment and sulfuric acid immersion of Coptis chinensis, followed by percolation, neutralization of percolate, concentration, and final filtration;

1. A Coptis chinensis acne-removing composition comprising of the following components in units by weight: 0.01 to 10 units of Coptis chinensis extract, 0.01 to 10 units of Rhubarb extract, 0.01 to 10 units of Salvia miltiorrhiza extract, 0 to 10 units of supramolecular salicylic acid, 0 to 10 units of glycolic acid, 0.1 to 5 units of linoleic acid, 0.01 to 5 units of vitamin A, and 0.01 to 5 units of vitamin E.
(2) Extraction: 1 part of Salvia miltiorrhiza extract is dissolved in 20 units (W/V) mixed solvent, extracted, separated organic phase, added with 1% -10% anhydrous sodium sulfate, dried at 0-8 °C for 2-10 h, and concentrated to obtain Salvia miltiorrhiza extract after solid-liquid separation. The mixed solvent is a solvent mixed with 25 to 45 units of ethyl acetate and 50 units of sodium hydrogen carbonate solution with a mass concentration of 5%.

2) Salting out: a concentrated hydrochloric acid witha volume of 0.5%- 1% of the Coptis chinensis concentrated extract is added to the Coptis chinensis concentrated extract, and then a sodium chloride with aweight of 5%- 10% of the Coptis chinensis concentrated extract is added and precipitatedfor 1 to 24 h to obtain aclear mother solutionafter solid-liquid separation;

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2. The Coptis chinensis acne-removing composition according to claim 1, characterized in that: The Coptis chinensis acne-removing composition comprises of the following components in units by weight: 0.1 to 3 units of Coptis chinensis extract, 0.1 to 3 units of Rhubarb extract, 0.1 to 3 units of Salvia miltiorrhiza extract, 1 to 5 part of supramolecular salicylic acid, 0.2 to 1 units of linoleic acid, 0.1 to 1 units of vitamin A, and 0.1 to 1 units of vitamin E; more preferably, the pharmaceutical compositionfurthercomprises residual matrixes and excipientsby weight.
3) Preparation of Coptis chinensis extract: the clear mother solutionis extracted witha solvent I to separate organic phase I, the aqueous phaseis thenextracted with a solvent II and discarded, organic phase II is collected and concentrated to obtain a Coptis chinensis extract; in which the solvent I is ethyl acetate, dichloromethane, trichloromethane or/and ether, and the solvent II is ethyl acetate-butanol or butanol.

3. The Coptis chinensis acne-removing composition according to claim 2, characterized in that:

The Coptis chinensis acne-removing composition further comprises 5% to 10% glycolic acid by weight.
4. The Coptis chinensis acne-removing composition according to any of claims 1-3, characterized in that:

The Coptis chinensis extract is prepared by the following method:
5. The Coptis chinensis acne-removing composition according to claim 4, characterized in that:

The Coptis chinensis concentrated extract is asolution with a concentration of 0.1 to 5 g of Coptis chinensis crude drug/mL.
6. The Coptis chinensis acne-removing composition according to claim 5, characterized in that:

The extraction with solvent I and the extraction with solvent II refer to two times of solvent extraction at equal volume.
7. The drug composition according to claim 5, characterized in that:

The concentrated hydrochloric acid addedin the step (2) is 0.5% of the Coptis chinensis concentrated extract by volume, and the sodium chloride added is 5% of the Coptis chinensis concentrated extract by weight.
8. The Coptis chinensis acne-removing composition according to any of claims 1 - 7, characterized in that:

The Rhubarb extract is prepared by the following method:

(a) Rough extraction: Rhubarb is crushed and added with0.5-2mol/L ammonia solution by 5-to 20-fold volume of crude drug, stirred at 10 - 60 °C for 12 h, and centrifuged to obtainfirst extract solution and residue, residue is then extracted under the same conditions for 8 h to obtain second extract solution, and finally two extract solutions are mixed together;

(b) Refining: the extract is added with ethanol by 20- to 40-fold weight of Rhubarb crude drug, stirred evenly, stored in refrigerator, and centrifuged to obtain

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2019101673 20 Dec 2019 supernatant, which is then concentrated for a rhubarb concentrated extract with a concentration of 0.1 to 3 g Rhubarb crude drug/mL.

(c) Preparation of Rhubarb extract: the rhubarb concentrated extract is added with 1-3 mol/L HC1 solution to adjust pH of 1-4, acid-hydrolyzed at 70°C for 3 h, and filteredto obtain precipitate, which is then recovered and dried at 40°C in oven to obtain a rhubarb extract.
9. The Coptis chinensis acne-removing composition according to any of claims 1 - 7, characterized in that:

The Salvia miltiorrhiza extract is prepared by the following method:
10. Application of the Coptis chinensis acne-removing composition according to any of claims 1 - 9 in preparation of drugs, skin care products or cosmetics for treatment and/or prevention of acne.