CN110960583A - Pharmaceutical composition for treating acne and application thereof - Google Patents

Pharmaceutical composition for treating acne and application thereof Download PDF

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Publication number
CN110960583A
CN110960583A CN201811150040.9A CN201811150040A CN110960583A CN 110960583 A CN110960583 A CN 110960583A CN 201811150040 A CN201811150040 A CN 201811150040A CN 110960583 A CN110960583 A CN 110960583A
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extract
parts
pharmaceutical composition
extracting
solution
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叶小利
李学刚
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Southwest University
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Southwest University
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    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718Coptis (goldthread)
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    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
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    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • A61K35/618Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
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    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537Salvia (sage)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/70Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/708Rheum (rhubarb)
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    • A61K8/00Cosmetics or similar toiletry preparations
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    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
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    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365Hydroxycarboxylic acids; Ketocarboxylic acids
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    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
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    • A61K8/67Vitamins
    • A61K8/671Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
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    • A61K8/67Vitamins
    • A61K8/678Tocopherol, i.e. vitamin E
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    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
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Abstract

A pharmaceutical composition for treating acne and application thereof belong to Chinese herbal medicine compound, in particular to a pharmaceutical composition for treating acne and application thereof. The paint comprises the following components in parts by weight: the composition is a compound preparation, and the medicine has a synergistic effect, does not have stress tolerance and can effectively treat acne.

Description

Pharmaceutical composition for treating acne and application thereof
Technical Field
The invention belongs to a Chinese herbal medicine compound, and particularly relates to a pharmaceutical composition for treating acne and application thereof.
Background
Acne is an infectious disease of the skin caused primarily by propionibacterium acnes, and is associated with, in addition to propionibacterium, increased androgens and sebum, hyperkeratosis at the opening of the pilosebaceous glands, and secondary inflammation. At present, the treatment is mostly carried out by adopting external bactericidal medicines such as bactericidal tretinoin, azelaic acid, sulfur lotion and the like and assisting oral antibiotics, but because of the abuse of the existing medicines, particularly the abuse of antibiotics, the proportion of drug-resistant propionibacterium is promoted year by year, and great inconvenience is brought to the clinical treatment of acne.
Research shows that the Chinese medicinal materials coptis root and rhubarb have excellent antibacterial activity, especially the activity of inhibiting propionibacterium acnes. In essence, there are a lot of researches on the development of Chinese medicines for treating acne. In 2006, patent CN1840070A discloses an application of a pharmaceutical composition in preparing a medicine for treating acne, the medicine comprises traditional Chinese medicinal materials such as coptis chinensis, rheum officinale, dandelion, salvia miltiorrhiza, fritillaria and the like, the pharmaceutical composition only comprises pure traditional Chinese medicines, western medicine components are not contained, propionibacterium is not easy to generate drug resistance, and the curative effect on acne is obvious; 2011, patent CN102370759A discloses a compound zhiji for treating acne and a preparation method thereof, which is prepared by decocting and concentrating traditional Chinese medicinal materials such as coptis chinensis, salvia miltiorrhiza, rheum officinale, scutellaria baicalensis, fructus forsythiae and cortex mori radicis, and the composition overcomes the defect that western medicines have tolerance and can effectively treat acne.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for treating acne, the composition is a compound preparation, and the medicine has synergistic effect, has no intolerance and can effectively treat acne.
The pharmaceutical composition for treating acne comprises the following components in parts by weight: 0.1-5 parts of coptis chinensis extract, 0.1-5 parts of rhubarb extract, 0.1-5 parts of salvia miltiorrhiza extract, 1-10 parts of pearl powder, 1-20 parts of linoleic acid, 0.1-5 parts of vitamin A, 0.1-5 parts of vitamin E and 0.01-1 part of trimethoprim.
Preferably, the pharmaceutical composition for treating acne comprises, by weight, 1-3 parts of coptis extract, 1-3 parts of rheum officinale extract, 1-3 parts of salvia miltiorrhiza extract, 2-5 parts of pearl powder, 5-10 parts of linoleic acid, 0.5-2 parts of vitamin A, 0.5-2 parts of vitamin E and 0.05-0.1 part of trimethoprim.
Preferably, the pharmaceutical composition for treating acne further comprises 5-10% by weight of glycolic acid.
Preferably, the coptis chinensis extract is prepared by the following method:
1) coarse extraction: pretreating Coptidis rhizoma, soaking in sulfuric acid, percolating, neutralizing percolate, concentrating, and filtering to obtain clear Coptidis rhizoma extract concentrate;
2) salting out: adding concentrated hydrochloric acid into the concentrated coptis extract, adding 0.5-1% of concentrated hydrochloric acid and the concentrated coptis extract by volume, then adding sodium chloride accounting for 5-10% of the concentrated coptis extract by weight, precipitating for 1-24 hours, and carrying out solid-liquid separation to obtain a clear mother solution;
3) preparing a coptis extract: extracting the clarified mother liquor by using a solvent I, separating an organic phase I, continuously extracting a water phase by using a solvent II, discarding the water phase, collecting the organic phase II, and concentrating the organic phase II to obtain a coptis chinensis extract; wherein the solvent I is ethyl acetate, dichloromethane, chloroform or/and diethyl ether, and the solvent II is ethyl acetate-butanol or butanol.
Preferably, the concentration of the coptis chinensis extract concentrated solution is 0.1-5 g of coptis chinensis crude drug/mL of solution.
Preferably, the extraction with solvent I and the extraction with solvent II are performed 2 times with equal volumes of solvent.
More preferably, the volume ratio of the concentrated hydrochloric acid to the coptis chinensis extract concentrated solution added in the step (2) is 0.5%, and the weight of the added sodium chloride is 5% of the weight of the coptis chinensis extract concentrated solution;
preferably, the rhubarb extract is prepared by the following method:
(a) coarse extraction: pulverizing radix et rhizoma Rhei, adding 1mol/L ammonia water solution 10 times of the volume of crude drug, stirring and extracting at 40 deg.C for 12 hr, centrifuging, extracting the residue under the same conditions for 8 hr, and mixing the extractive solutions;
(b) refining: adding ethanol with the amount of 30 times of the crude rhubarb into the extracting solution, uniformly stirring, putting the extracting solution into a refrigerator for refrigeration, centrifuging, and concentrating the supernatant to obtain a rhubarb extracting concentrated solution with the concentration of 1-2 g crude rhubarb/mL;
(c) and (3) extracting and preparing rhubarb: adding 2mol/L HCl solution into the concentrated rhubarb extracting solution to adjust the pH value to 2-3, carrying out acid hydrolysis at 70 ℃ for 3h, filtering and recovering the precipitate, and drying the precipitate in an oven at 40 ℃ to obtain the rhubarb extract.
Preferably, the salvia miltiorrhiza extract is prepared by the following method:
① percolating with powder of radix Salviae Miltiorrhizae, soaking in 95% ethanol overnight, percolating, collecting percolate 1 times the volume of radix Salviae Miltiorrhizae each day, collecting 5 times the volume of the percolate, stopping percolating, mixing percolates, and concentrating to obtain total extract;
② extracting, dissolving 1 part of radix Salviae Miltiorrhizae extract in 20 parts (W/V) mixed solvent, extracting, separating organic phase, adding 5% anhydrous sodium sulfate, drying, standing at 4 deg.C for 6h, separating solid and liquid, and concentrating to obtain radix Salviae Miltiorrhizae extract, wherein the mixed solvent is a mixture of 35 parts of ethyl acetate and 50 parts of 5% sodium bicarbonate solution (V/V).
The application of the pharmaceutical composition in the preparation of the medicine, the skin care product or the cosmetic for treating and/or preventing the acne also belongs to the protection scope of the invention.
The medicinal composition can be directly used for external application as a medicament after being ground, or can be used as an active ingredient to be further prepared into external medicaments of different formulations, including paste, medical dressing, liquid preparation, patch, spray and the like.
When the ointment is applied, vaseline, lanolin, dimethicone, polyethylene glycol and the like are preferably selected as the ointment matrix.
More preferably, simethicone and polyethylene glycol are used.
The pharmaceutical composition can also be added into skin care products as an active ingredient, is applied after being mixed by an aqueous solvent or/and an alcoholic solvent, and comprises the steps of preparing a facial cleanser, a facial mask, a cream product or essence with the skin care effect and the like, and the pharmaceutical composition is preferably added into a hydrogel matrix/polyethylene glycol matrix to prepare the facial cleanser, the facial mask, the cream product or essence with the skin care effect and the like. Further, polyhydroxy acid and/or aldobionic acid can be added to make into the product.
The variety of hydrogel matrices is numerous: for example, the cross-linked water-based acrylic acid copolymer, namely carbomer resin, namely water-based thickening resin, can also adopt hydrogel formed by dissolving sodium alginate, agar and gelatin. The prepared hydrogel dressing is a clean, convenient and self-dissolving and hydrating water-based dressing. The hydrogel dressing releases the drug and is sterilized at the same time, and has a slow release function. The polymer hydrogel is generally prepared by adding a hydrophilic polymerization monomer (such as hydroxyethyl methacrylate and the like) into a suspension, adding an initiator, and rapidly catalyzing polymerization. Or polymerizing non-hydrophilic monomer such as butyl methacrylate, etc. and making into composite with hydrogel.
The pharmaceutical composition can also be added into cosmetics as an effective component to prevent acne, relieve the problems of acne or acne stuffiness and the like caused by air impermeability and long makeup time of facial cosmetics, and is particularly applied to cream and cream products, such as foundation liquid, isolation cream, BB cream, CC cream or pre-makeup milk.
Based on the review of a large amount of documents, more than 100 Chinese medicinal materials and Chinese medicinal material prescriptions with the function of treating acne are combed, 20 commonly used Chinese medicinal materials for treating acne are finally selected as research materials, and after a plurality of experimental researches, the Chinese goldthread extract, the rhubarb extract and the salvia miltiorrhiza extract are finally obtained to be compounded, which can obviously inhibit epidermal cell androgen and androgen receptors in a synergistic manner, and then the medicinal composition is prepared by adding functional components such as trimethoprim, pearl powder, linolenic acid and the like.
Compared with other pure traditional Chinese medicine formulas, the medicinal composition is simpler and more effective, has the characteristics of low dependence and the like of the pure traditional Chinese medicine formula, can effectively treat and prevent acne, and has the functions of antibiosis, antiphlogosis, itching relieving and the like.
The pharmaceutical composition used in the invention has good effects on keeping skin white, tender, smooth, fine and the like, and is also a curative effect type cosmetic and application thereof. The composition can be used as an oral Chinese medicine composition, and is free from toxicity and harm when being externally used.
Detailed Description
The salvia miltiorrhiza extract and the rhubarb extract can also be purchased from commercial salvia miltiorrhiza extracts and rhubarb extracts, and the finally obtained pharmaceutical composition still has excellent treatment effect.
Example 1
5Kg of coptis extract, 5Kg of salvia extract, 2Kg of rhubarb extract, 1Kg of pearl, 1Kg of linoleic acid, 0.1Kg of vitamin A, 0.1Kg of vitamin E, 0.01Kg of trimethoprim and 87.69Kg of ointment substrate.
Wherein the Coptidis rhizoma extract is prepared by slicing 40kg Coptidis rhizoma, soaking in 0.5% sulfuric acid for 24 hr, percolating, and collecting 40L percolate every day; neutralizing the collected percolate with lime to the pH of 2, and filtering; washing the residue with appropriate amount of water for 1 time, and mixing the filtrate and washing solution; concentrating the combined neutralized solution under reduced pressure to concentration of 0.1g original drug/mL, cooling, filtering, and centrifuging to obtain clear concentrated Coptidis rhizoma extractive solution; adding concentrated hydrochloric acid with the volume ratio of 0.5% into the concentrated extracting solution, adding sodium chloride with the weight ratio of 5% of the solution, precipitating overnight, and filtering to obtain a clear solution; extracting the solution with 400L ethyl acetate to obtain refined solution; extracting the refined solution with 400L ethyl acetate-butanol mixed solvent, recovering solvent to obtain Coptidis rhizoma active site 5Kg for treating acne.
The red sage root extract and the rhubarb extract are both products sold in the market, the main active component of the red sage root extract sold in the market is the tanshinone, and the main active component of the rhubarb is the rhein.
The Chinese goldthread extract, the red sage extract, the rhubarb extract, the pearl powder of 500 meshes and other materials are mixed according to a certain proportion to prepare the ointment. The product has antibacterial, antiinflammatory, and antipruritic effects, and can be used for treating dermatoses such as acne caused by Propionibacterium acnes.
Example 2
0.1Kg of coptis extract, 0.1Kg of salvia extract, 5Kg of rhubarb extract, 10Kg of pearl, 20Kg of linoleic acid, 5Kg of vitamin A, 0.1Kg of vitamin E, 0.1Kg of glycolic acid, 0.01Kg of trimethoprim and 59.59Kg of ointment substrate.
Slicing 1Kg of coptis, then immersing for 24 hours in 0.5% sulfuric acid, percolating, and collecting 1L of percolate every day; neutralizing the collected percolate with lime to the pH of 10, and filtering; washing the residue with appropriate amount of water for 3 times, and mixing the filtrate and washing solution; concentrating the combined neutralized solution under reduced pressure to a concentration of 5g original drug/mL, cooling, filtering, and centrifuging to obtain clear concentrated Coptidis rhizoma extractive solution; adding concentrated hydrochloric acid with the volume ratio of 0.5% into the concentrated extract of the coptis chinensis, adding sodium chloride with the weight ratio of 5% of the solution, precipitating overnight, and filtering to obtain clear mother liquor; extracting the mother liquor with 0.8L dichloromethane, separating organic phase, adding 0.8L butanol mixed solvent to extract water phase, separating butanol solution containing Coptidis rhizoma extract, and concentrating to obtain Coptidis rhizoma extract 0.1 Kg.
Pulverizing 1Kg of Saviae Miltiorrhizae radix, soaking in 95% ethanol overnight, and percolating to extract; collecting 1 liter of percolate every day, and stopping percolation after collecting 5 liters of percolate; concentrating the percolate under reduced pressure to obtain 0.2Kg of total extract; dissolving 0.2Kg of radix salviae miltiorrhizae extract in 1L of mixed solvent (solvent mixed by 35 parts of ethyl acetate and 50 parts of sodium bicarbonate solution (5 percent)), sufficiently shaking and extracting for 1 hour, standing and layering to obtain an ethyl acetate layer; adding 5% anhydrous sodium sulfate into ethyl acetate solution, drying, standing in refrigerator at 4 deg.C for 6 hr, filtering to remove anhydrous sodium sulfate, and recovering ethyl acetate to obtain 0.1Kg of Saviae Miltiorrhizae radix extract.
Pulverizing 40Kg of radix et rhizoma Rhei, extracting with 400L of 1mol/L ammonia water solution at 40 deg.C under stirring for 12 hr; centrifuging, and extracting the residue with 400L of 1mol/L ammonia water solution at 40 deg.C for 8 hr; mixing extractive solutions, adding 1200L ethanol into the extractive solution, and refrigerating in refrigerator overnight; centrifuging, and concentrating the supernatant to 1g crude rhubarb/mL; adding 2mol/L HCl solution to adjust the pH value to 2-3, hydrolyzing with acid at 70 ℃ for 3h, filtering and recovering the precipitate, and drying the precipitate in an oven at 40 ℃ to obtain 5Kg of rhubarb extract.
Pulverizing Coptidis rhizoma extract, Saviae Miltiorrhizae radix extract, radix et rhizoma Rhei extract and Margarita, sieving with 500 mesh sieve, mixing the other materials at a certain proportion, and making into unguent. The product has antibacterial, antiinflammatory, and antipruritic effects, and can be used for treating dermatoses such as acne caused by Propionibacterium acnes.
Example 3
5Kg of coptis extract, 5Kg of salvia extract, 5Kg of rhubarb extract, 5Kg of pearl, 5Kg of linoleic acid, 5Kg of vitamin A5Kg, 5Kg of vitamin E, 20Kg of glycolic acid, 1Kg of trimethoprim and 44Kg of ointment matrix.
The preparation method of the coptis extract comprises the following steps: pulverizing 40Kg Coptidis rhizoma, soaking in 0.5% sulfuric acid for 24 hr, percolating, and collecting 40L percolate every day; neutralizing the collected percolate with lime to the pH of 5, and filtering; washing the residue with appropriate amount of water for 2 times, and mixing the filtrate and washing solution; concentrating the combined neutralized solution under reduced pressure to a concentration of 1g original drug/mL, cooling, filtering, and centrifuging to obtain a clear concentrated solution; adding concentrated hydrochloric acid with the volume ratio of 0.5% into the concentrated clear solution, adding sodium chloride with the weight ratio of 5% of the solution, precipitating overnight, and filtering to obtain clear solution; extracting the solution with 10L of chloroform to obtain a refined solution; extracting the refined solution with 10L butanol mixed solvent, and recovering solvent to obtain 5Kg Coptidis rhizoma active site for treating acne.
The preparation method of the salvia miltiorrhiza extract comprises the following steps: pulverizing 50Kg of Salvia miltiorrhiza, soaking in 95% ethanol overnight, and percolating to extract; collecting 50 liters of percolate every day, and stopping percolation after collecting 250 liters of percolate; concentrating the percolate under reduced pressure to obtain 10Kg of total extract; dissolving 10Kg of radix salviae miltiorrhizae extract in 200L of mixed solvent (solvent mixed by 35 parts of ethyl acetate and 50 parts of sodium bicarbonate solution (5 percent)), sufficiently shaking and extracting for 1 hour, standing and layering to obtain an ethyl acetate layer; adding 5% anhydrous sodium sulfate into ethyl acetate solution, drying, standing in a refrigerator at 4 deg.C for 6 hr, filtering to remove anhydrous sodium sulfate, and recovering ethyl acetate to obtain 5Kg active site of Saviae Miltiorrhizae radix for treating acne.
The preparation method of the rhubarb extract comprises the following steps: pulverizing 40Kg of radix et rhizoma Rhei, extracting with 400L of 1mol/L ammonia water solution at 40 deg.C under stirring for 12 hr; centrifuging, and extracting the residue with 400L of 1mol/L ammonia water solution at 40 deg.C for 8 hr; mixing extractive solutions, adding 1200L ethanol into the extractive solution, and refrigerating in refrigerator overnight; centrifuging, and concentrating the supernatant to 1g crude rhubarb/mL; adding 2mol/L HCl solution to adjust the pH value to 2-3, hydrolyzing with acid at 70 ℃ for 3h, filtering and recovering the precipitate, and drying the precipitate in an oven at 40 ℃ to obtain 5Kg of active site of rhubarb for treating acne.
Pulverizing Coptidis rhizoma extract, Saviae Miltiorrhizae radix extract, radix et rhizoma Rhei extract and Margarita, sieving with 500 mesh sieve, mixing the other materials at a certain proportion, and making into unguent. The product has antibacterial, antiinflammatory, and antipruritic effects, and can be used for treating dermatoses such as acne caused by Propionibacterium acnes.
Example 4
5Kg of coptis extract, 5Kg of salvia extract, 2Kg of rhubarb extract, 5Kg of pearl, 5Kg of linoleic acid, 2Kg of vitamin A, 2Kg of vitamin E, 10Kg of glycolic acid, 0.1Kg of trimethoprim and 63.9Kg of ointment substrate.
Slicing 40Kg of coptis, then immersing for 24 hours in 0.5% sulfuric acid, percolating, and collecting 20L of percolate every day; neutralizing the collected percolate with lime to the pH of 7, and filtering; washing the residue with appropriate amount of water for 2 times, and mixing the filtrate and washing solution; concentrating the combined neutralized solution under reduced pressure to concentration of 0.5g original drug/mL, cooling, filtering, and centrifuging to obtain clear concentrated Coptidis rhizoma extractive solution; adding concentrated hydrochloric acid with the volume ratio of 0.5% into the concentrated extracting solution, adding sodium chloride with the weight ratio of 5% of the solution, precipitating overnight, and filtering to obtain a clear solution; the solution was extracted with 40 liters of ether and the organic phase was discarded; extracting the water phase with 40L ethyl acetate-butanol (1:4)) mixed solvent, recovering butanol solution containing Coptidis rhizoma extract, and concentrating to obtain Coptidis rhizoma extract 5 Kg.
Pulverizing 50Kg of Salvia miltiorrhiza, soaking in 95% ethanol overnight, and percolating to extract; collecting 20L of percolate every day, and stopping percolation after collecting 100L of percolate; concentrating the percolate under reduced pressure to obtain 6Kg of total extract; dissolving 6Kg of radix salviae miltiorrhizae extract in 100L of mixed solvent (solvent mixed by 35 parts of ethyl acetate and 50 parts of sodium bicarbonate solution (5 percent)), sufficiently shaking and extracting for 1 hour, standing and layering to obtain an ethyl acetate layer; adding 5% anhydrous sodium sulfate into ethyl acetate solution, drying, standing in refrigerator at 4 deg.C for 6 hr, filtering to remove anhydrous sodium sulfate, and recovering ethyl acetate to obtain 5Kg of Saviae Miltiorrhizae radix extract.
Pulverizing 16Kg of radix et rhizoma Rhei, extracting with 100L of 1mol/L ammonia water solution at 40 deg.C under stirring for 12 hr; centrifuging, and extracting the residue with 100L 1mol/L ammonia water solution at 40 deg.C for 8 hr under stirring; mixing extractive solutions, adding 300L ethanol into the extractive solution, and refrigerating in refrigerator overnight; centrifuging, and concentrating the supernatant to 1g crude rhubarb/mL; adding 2mol/L HCl solution to adjust the pH value to 2-3, hydrolyzing with acid at 70 ℃ for 3h, filtering and recovering the precipitate, and drying the precipitate in an oven at 40 ℃ to obtain 2Kg of rhubarb extract.
Pulverizing Coptidis rhizoma extract, Saviae Miltiorrhizae radix extract, radix et rhizoma Rhei extract and Margarita, sieving with 500 mesh sieve, mixing the other materials at a certain proportion, and making into unguent. The product has antibacterial, antiinflammatory, and antipruritic effects, and can be used for treating dermatoses such as acne caused by Propionibacterium acnes.
In order to further research the anti-propionibacterium acnes and the clinical treatment effect on acnes of the pharmaceutical composition, a plurality of groups of control groups are provided. The components and contents of the pharmaceutical composition in each control group are as follows:
control group 1: example 4 is a formulation with appropriate ratios, therefore, the reference of example 4 was selected and "coptis extract" was removed from this control group.
The medicine comprises the following components: 5Kg of salvia miltiorrhiza extract, 2Kg of rhubarb extract, 5Kg of pearl, 5Kg of linoleic acid and vitamin
A2Kg, vitamin E2 Kg, glycolic acid 10Kg, trimethoprim 0.1Kg, and ointment base 68.9 Kg. Pulverizing Coptidis rhizoma extract, Saviae Miltiorrhizae radix extract, radix et rhizoma Rhei extract and Margarita, sieving with 500 mesh sieve, mixing the above materials at a certain proportion, and making into unguent.
Control group 2: the medicine comprises the following components: 12.5Kg of coptis extract and 87.5Kg of ointment base. Mixing the above materials at a certain proportion, and making into unguent.
Control group 3: the medicine comprises the following components: 6.25Kg of coptis extract, 6.25Kg of rhubarb and 87.5Kg of ointment substrate. Mixing the above materials at a certain proportion, and making into unguent.
Control group 4: the medicine comprises the following components: 5Kg of coptis extract, 4Kg of salvia extract, 2.5Kg of rhubarb extract and 87.5Kg of ointment substrate. Mixing the above materials at a certain proportion, and making into unguent.
Control group 5: the medicine comprises the following components: 20Kg of coptis root, 20Kg of salvia miltiorrhiza, 10Kg of rhubarb and 50Kg of ointment substrate. Pulverizing Coptidis rhizoma, Saviae Miltiorrhizae radix, and radix et rhizoma Rhei, sieving with 500 mesh sieve, mixing the above materials at a certain proportion, and making into unguent.
Control group 6: the medicine comprises the following components: 5Kg of coptis extract, 4Kg of salvia extract, 2.5Kg of rhubarb extract, 5Kg of pearl, 5Kg of linoleic acid and 40Kg of ointment substrate. Pulverizing Coptidis rhizoma, Saviae Miltiorrhizae radix, radix et rhizoma Rhei, and Margarita, sieving with 500 mesh sieve, mixing the above materials at a certain proportion, and making into unguent.
Control group 7: the medicine comprises the following components: 5Kg of coptis extract, 4Kg of salvia extract, 2.5Kg of rhubarb extract, 5Kg of pearl, 5Kg of linoleic acid, 2Kg of vitamin A, 2Kg of vitamin E and 36Kg of ointment substrate. Pulverizing Coptidis rhizoma, Saviae Miltiorrhizae radix, radix et rhizoma Rhei, and Margarita, sieving with 500 mesh sieve, mixing the above materials at a certain proportion, and making into unguent.
Comparison of the anti-Propionibacterium acnes effects of the Coptis acne cream
Propionibacterium acnes is the primary pathogen that causes acne. The antibacterial experimental method is carried out according to the research guiding principle of natural medicines (traditional Chinese medicines) and new medicines: propionibacterium acnes is used as a bacterial model, and the antibacterial activity of the Propionibacterium acnes is researched by detecting MIC: after the bacteria were cultured, the concentration of the bacteria was adjusted to 1X 108Per mL; 50 microliters of bacteria were added to each well of a 96-well plate, and then drugs at different concentrations were added, and the bacteria were cultured for 24 hours, and the growth of the bacteria was observed, and the MIC was determined, and the results are shown in Table 1.
TABLE 1 comparison of antibacterial (Propionibacterium acnes) effectiveness (μ g/mL)
Example 1 4.0
Example 4 4.0
Control group 1 16.0
Control group 2 500
Control group 3 250
Control group 4 125
Control group 5 250
Control group 6 32.2
Control group 7 16.0
As can be seen from table 1, the acne cream containing coptis chinensis has a very good effect of inhibiting the activity of propionibacterium acnes; the product prepared by rhubarb extract and salvia extract purchased from the market also has the same curative effect; with the increase of the number of the compatible medicines, the antibacterial activity of the medicine is increased; in the product, after the coptis chinensis extract is lacked, the antibacterial activity of the product is greatly reduced (compared with the control group 1 in example 4); the same formulation, used without extraction, showed a decrease in antibacterial activity (control 4 compared to 5).
Comparison of curative effects and treatment effects of the coptis acne ointment
The treatment method comprises the following steps: the patients in the volunteer test group were given topical facial drug and control drug once a day, in the morning and evening, and the patients were tested for 6 days.
The therapeutic effect judgment standard is as follows: the curative effect is judged according to the reduction of skin lesions (acne, pimple, pustule, etc.) before and after treatment. And (3) curing: the skin damage is reduced by more than or equal to 90 percent, no new skin damage appears, and only a small amount of pigmentation is left; the effect is shown: the skin damage is reduced by 60 to 89 percent, no new skin damage appears, and a small amount of pigmentation is left; improvement: the skin lesion is reduced by 30 to 59 percent, and a little pigmentation is left after new skin lesion appears occasionally; and (4) invalidation: the lesions subsided by less than 30%, new lesions still appeared, leaving behind pigmentation. Effective rate is (number of cure cases + number of effective cases) ÷ total number of cases × 100%. The results are shown in Table 2.
TABLE 2 Observation of clinical efficacy
Figure BDA0001817735710000081
Figure BDA0001817735710000091
As can be seen from the table 2, the cure rate of the coptis acne cream is as high as 95%, and the coptis acne cream is completely effective, which shows that the effect is extremely obvious; in the formula, after the coptis chinensis extract is removed, the curative effect is obviously reduced; the curative effect is increased along with the increase of the number of Chinese medicinal materials in the formula; the same formulation but unprocessed acne cream of coptis (coptis chinensis) showed a decrease in efficacy (controls 4 and 5).

Claims (10)

1. The pharmaceutical composition for treating acne comprises the following components in parts by weight: 0.1-5 parts of coptis chinensis extract, 0.1-5 parts of rhubarb extract, 0.1-5 parts of salvia miltiorrhiza extract, 1-10 parts of pearl powder, 1-20 parts of linoleic acid, 0.1-5 parts of vitamin A, 0.1-5 parts of vitamin E and 0.01-1 part of trimethoprim.
2. The pharmaceutical composition of claim 1, comprising the following components by weight: 1-3 parts of coptis chinensis extract, 1-3 parts of rheum officinale extract, 1-3 parts of salvia miltiorrhiza extract, 2-5 parts of pearl powder, 5-10 parts of linoleic acid, 0.5-2 parts of vitamin A, 0.5-2 parts of vitamin E and 0.05-0.1 part of trimethoprim.
3. The pharmaceutical composition of claim 2, further comprising 5-10% by weight glycolic acid.
4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the Coptidis rhizoma extract is prepared by the following method:
1) coarse extraction: pretreating Coptidis rhizoma, soaking in sulfuric acid, percolating, neutralizing percolate, concentrating, and filtering to obtain clear Coptidis rhizoma extract concentrate;
2) salting out: adding concentrated hydrochloric acid into the concentrated coptis extract, adding 0.5-1% of concentrated hydrochloric acid and the concentrated coptis extract by volume, then adding sodium chloride accounting for 5-10% of the concentrated coptis extract by weight, precipitating for 1-24 hours, and carrying out solid-liquid separation to obtain a clear mother solution;
3) preparing a coptis extract: extracting the clarified mother liquor by using a solvent I, separating an organic phase I, continuously extracting a water phase by using a solvent II, discarding the water phase, collecting the organic phase II, and concentrating the organic phase II to obtain a coptis chinensis extract; wherein the solvent I is ethyl acetate, dichloromethane, chloroform or/and diethyl ether, and the solvent II is ethyl acetate-butanol or butanol.
5. The pharmaceutical composition of claim 4, wherein the concentration of the concentrated solution of Coptidis rhizoma is 0.1-5 g Coptidis rhizoma crude drug/mL.
6. The pharmaceutical composition of claim 5, wherein the extraction with solvent I and the extraction with solvent II are for 2 times equal volumes of solvent.
7. The pharmaceutical composition according to claim 5, wherein the volume ratio of the concentrated hydrochloric acid to the concentrated Coptidis rhizoma extract added in step (2) is 0.5%, and the weight of the added sodium chloride is 5% of the weight of the concentrated Coptidis rhizoma extract.
8. The pharmaceutical composition according to any one of claims 1 to 7, wherein the rhubarb extract is prepared by the following method:
(a) coarse extraction: pulverizing radix et rhizoma Rhei, adding 1mol/L ammonia water solution 10 times of the volume of crude drug, stirring and extracting at 40 deg.C for 12 hr, centrifuging, extracting the residue under the same conditions for 8 hr, and mixing the extractive solutions;
(b) refining: adding ethanol with the amount of 30 times of the crude rhubarb into the extracting solution, uniformly stirring, putting the extracting solution into a refrigerator for refrigeration, centrifuging, and concentrating the supernatant to obtain a rhubarb extracting concentrated solution with the concentration of 1-2 g crude rhubarb/mL;
(c) and (3) extracting and preparing rhubarb: adding 2mol/L HCl solution into the concentrated rhubarb extracting solution to adjust the pH value to 2-3, carrying out acid hydrolysis at 70 ℃ for 3h, filtering and recovering the precipitate, and drying the precipitate in an oven at 40 ℃ to obtain the rhubarb extract.
9. The pharmaceutical composition of any one of claims 1 to 7, wherein the Salvia miltiorrhiza extract is prepared by the following method:
① percolating with powder of radix Salviae Miltiorrhizae, soaking in 95% ethanol overnight, percolating, collecting percolate 1 times the volume of radix Salviae Miltiorrhizae each day, collecting 5 times the volume of the percolate, stopping percolating, mixing percolates, and concentrating to obtain total extract;
② extracting, dissolving 1 part of radix Salviae Miltiorrhizae extract in 20 parts (W/V) mixed solvent, extracting, separating organic phase, adding 5% anhydrous sodium sulfate, drying, standing at 4 deg.C for 6h, separating solid and liquid, and concentrating to obtain radix Salviae Miltiorrhizae extract, wherein the mixed solvent is prepared by mixing 35 parts of ethyl acetate and 50 parts of 5% sodium bicarbonate solution.
10. Use of a pharmaceutical composition according to any one of claims 1 to 9 for the preparation of a medicament, a skin care product or a cosmetic product for the treatment and/or prevention of acne.
CN201811150040.9A 2018-09-29 2018-09-29 Pharmaceutical composition for treating acne and application thereof Pending CN110960583A (en)

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CN112569277A (en) * 2019-09-29 2021-03-30 重庆伊士腾生物科技有限公司 Coptis chinensis acne-removing composition and application thereof
CN113425787A (en) * 2021-06-18 2021-09-24 南方医科大学 Composition for preventing and treating acne and preparation method and application thereof

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Publication number Priority date Publication date Assignee Title
CN112569277A (en) * 2019-09-29 2021-03-30 重庆伊士腾生物科技有限公司 Coptis chinensis acne-removing composition and application thereof
CN113425787A (en) * 2021-06-18 2021-09-24 南方医科大学 Composition for preventing and treating acne and preparation method and application thereof

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