CN112603993A - Gel for treating inflammatory acne based on chitosan and preparation method thereof - Google Patents

Gel for treating inflammatory acne based on chitosan and preparation method thereof Download PDF

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Publication number
CN112603993A
CN112603993A CN202011512100.4A CN202011512100A CN112603993A CN 112603993 A CN112603993 A CN 112603993A CN 202011512100 A CN202011512100 A CN 202011512100A CN 112603993 A CN112603993 A CN 112603993A
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chitosan
parts
gel
inflammatory acne
stirring
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龚祖光
梅琳
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Shanghai New Valve Medical Devices Co ltd
Jiangsu Newvalue Medical Products Co ltd
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Shanghai New Valve Medical Devices Co ltd
Jiangsu Newvalue Medical Products Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
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    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22—Cysteine endopeptidases (3.4.22)
    • C12Y304/22002—Papain (3.4.22.2)

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Abstract

The invention discloses a gel for treating inflammatory acne based on chitosan and a preparation method thereof, wherein the gel comprises the following components in parts by weight: water, ethanol, humectant, film forming agent, quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan, anti-inflammatory agent, papain and chelating agent. Adding quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan and papain into water and ethanol, adding the humectant and the anti-inflammatory agent into the solution, continuously stirring, adding the film forming agent and the chelating agent, and continuously stirring until the mixture is uniform to obtain the gel. The gel has antibacterial, anti-inflammatory and antioxidant effects, and can be used for treating inflammatory acne wound, promoting wound healing, and preventing and reducing scar formation.

Description

Gel for treating inflammatory acne based on chitosan and preparation method thereof
Technical Field
The invention belongs to the technical field of acne treatment, and particularly relates to a gel for treating inflammatory acne based on chitosan.
Background
Carboxymethyl chitosan is a water-soluble chitosan derivative, has many characteristics, such as strong antibacterial property and fresh-keeping effect, and is an amphoteric polyelectrolyte. The chitosan derivative has various applications in the aspects of cosmetics, fresh keeping, medicines and the like, and is one of the chitosan derivatives which are researched more recently.
The carboxymethyl chitin is substituted on C6-OH of sugar residue, and a small amount of carboxymethyl is substituted on C3-OH to generate O-carboxymethyl chitin. In chitosan, the carboxymethyl group can be substituted on-OH and-NH to generate O-carboxymethyl and N-carboxymethyl chitosan, and the actual substitution conditions are as follows: C6-O-carboxymethyl, C2-N-carboxymethyl, C3-O-carboxymethyl, C6-O, C2-N-carboxymethyl and the like. Carboxymethylation at the C3 position is difficult due to steric hindrance at C3 and intramolecular hydrogen bonds between C2 and C3, so that carboxymethyl substitution on hydroxyl groups is less, C3-O carboxymethyl is less, and C6-O carboxymethyl is mainly used. For C6-OH and C2-NH, the substitution activity of carboxymethyl on hydroxyl is higher than that of amino under alkaline conditions, so that when the substitution degree is less than 1, the substitution of carboxymethyl is mainly on hydroxyl rather than on amino, and only when the substitution degree is close to 1 and higher than 1, the carboxymethyl substitution on amino can be simultaneously carried out to form O, N-carboxymethyl chitosan. The water solubility of carboxymethyl chitosan is not only soluble in water because it is a sodium carboxylate, but also because the introduction of carboxymethyl group destroys the secondary structure of chitosan molecule, greatly reducing its crystallinity, and becoming almost amorphous.
The prior art discloses the application of carboxymethyl chitosan in moisture absorption, moisture retention and bacteriostasis, but does not disclose the application of carboxymethyl chitosan in antianaphylaxis.
Use of carboxymethyl chitosan with application number CN201610946257.5 in the preparation or screening of products for the treatment of allergy. Cell and human body tests show that the carboxymethyl chitosan has an anti-allergic effect, can be used as an anti-allergic active ingredient to be added into a product, has a practical application value, and has the following defects:
has poor antibacterial and anti-inflammatory effects, does not have an antioxidant function, has poor treatment effect on inflammatory acne wounds and has poor wound healing effect.
Disclosure of Invention
The object of the present invention is to provide a gel for treating inflammatory acne based on chitosan, which solves the problems set forth in the background art mentioned above.
In order to achieve the purpose, the invention provides the following technical scheme: the gel for treating inflammatory acne based on chitosan is characterized by comprising the following components in percentage by weight: water, ethanol, humectant, film forming agent, quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan, anti-inflammatory agent, papain and chelating agent.
Preferably, the chitosan also comprises carboxymethyl chitosan and carboxyethyl chitosan, and the weight part of the chitosan is 3-5 parts, and the molecular weight is less than 3.0x104Dalton, the deacetylation degree is 60-70%, and the substitution degree of carboxymethyl or carboxyethyl is more than 60%;
the chitosan has the effects of inhibiting bacteria and promoting wound healing.
Preferably, the weight part of the ethanol is 2-4 parts.
The ethanol has antibacterial and astringent effects, and is beneficial for mixing of various components.
Preferably, the humectant comprises 2-4 parts by weight of propylene glycol, 3-7 parts by weight of glycerin and 2-5 parts by weight of butanediol.
The propylene glycol has moisturizing and thickening effects, the glycerin has moisturizing effects, and the butylene glycol has moisturizing and antibacterial effects.
Preferably, the film forming agent is acryloyl dimethyl ammonium taurate/VP copolymer, and the weight part of the acryloyl dimethyl ammonium taurate/VP copolymer is 10-16 parts.
The ammonium acryloyldimethyltaurate/VP copolymer provided in this way has an exfoliating function, and also has anti-inflammatory and antibacterial effects, and makes the mixture opaque.
Preferably, the anti-inflammatory agent is salicylic acid, and the weight part of the salicylic acid is 1-2 parts.
The salicylic acid has antiinflammatory effect.
Preferably, the chelating agent is disodium EDTA, the weight part of the disodium EDTA is 20-30 parts, the weight part of the papain is 2-3 parts, the papain has a cutin removing function, the weight part of the o-cymene-5-alcohol is 1-4 parts, the o-cymene-5-alcohol has an antioxidant effect, the quaternary ammonium salt-73 is 3-6 parts, and the quaternary ammonium salt-73 has bacteriostatic and antibacterial effects.
The invention also provides a preparation method of the gel for treating inflammatory acne based on chitosan, which comprises the following steps:
s1, adding quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan and papain into 10-15 parts of water, and uniformly stirring to obtain a solution;
s2, adding the humectant anti-inflammatory agent into the mixed solution, continuously stirring, gradually vacuumizing in the stirring process, and removing bubbles generated by stirring;
s3, adding the film forming agent and the chelating agent, continuously stirring until the mixture is uniform, filtering by using an ultrasonic vibration sieve, filtering to remove large particles in the mixture, and continuously stirring until the mixture becomes gel.
Preferably, the stirring device adopts a closed clean stirrer for stirring, the stirrer is operated at a constant speed of 300-.
The invention has the technical effects and advantages that: the gel for treating inflammatory acne based on chitosan has the advantages of inhibiting bacteria, diminishing inflammation and resisting oxidation, can treat inflammatory acne wound, promote wound healing, prevent and reduce scar formation, and filter out larger particles through ultrasonic vibration screening, so that the gel is uniform and fine, and the coating effect is better.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
Example one
A gel for treating inflammatory acne based on chitosan has the following formula: 10 parts of water, 2 parts of ethanol and 2 parts of propylene glycol, 3 parts of glycerol, 2 parts of butanediol, 10 parts of acryloyl dimethyl taurate/VP copolymer, 733 parts of quaternary ammonium salt, 1 part of o-cymene-5-alcohol, 3 parts of chitosan, 1 part of salicylic acid, 2 parts of papain and 20 parts of EDTA disodium.
The humectant comprises propylene glycol, glycerol and butanediol, the film forming agent is acryloyl dimethyl ammonium taurate/VP copolymer, the antiinflammatory agent is salicylic acid, the chelating agent is disodium EDTA, the chitosan is carboxymethyl chitosan, and the molecular weight is 2.9x104Dalton, degree of deacetylation 60%, degree of carboxymethyl substitution 60%.
The invention also provides a preparation method of the gel for treating inflammatory acne based on chitosan, which comprises the following steps:
s1, adding quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan and papain into 10-15 parts of water, and uniformly stirring to obtain a solution;
s2, adding the humectant and the anti-inflammatory agent into the mixed solution, continuously stirring, gradually vacuumizing in the stirring process, and removing bubbles generated by stirring;
s3, adding the film forming agent and the chelating agent, continuously stirring until the mixture is uniform, filtering by using an ultrasonic vibration sieve, filtering to remove large particles in the mixture, and continuously stirring until the mixture becomes gel.
The stirring equipment adopts a closed clean stirrer for stirring, the stirrer is operated at a constant speed of 300-400r/min, and the antioxidant is dropwise added while stirring.
Example two
A gel for treating inflammatory acne based on chitosan has the following formula: 12.5 parts of water, 3 parts of ethanol and 3.5 parts of propylene glycol, 5 parts of glycerol, 3.5 parts of butanediol, 13 parts of ammonium acryloyl dimethyl taurate/VP copolymer, 734.5 parts of quaternary ammonium salt, 2.5 parts of o-cymene-5-alcohol, 4 parts of chitosan, 1.5 parts of salicylic acid, 2.5 parts of papain and 26 parts of EDTA disodium.
The humectant comprises propylene glycol, glycerol and butanediol, the film forming agent is acryloyl dimethyl ammonium taurate/VP copolymer, the antiinflammatory agent is salicylic acid, the chelating agent is disodium EDTA, the chitosan is carboxymethyl chitosan, and the molecular weight is 2.0x104Dalton, degree of deacetylation 70% and degree of carboxymethyl substitution 90%.
The invention also provides a preparation method of the gel for treating inflammatory acne based on chitosan, which comprises the following steps:
s1, adding quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan and papain into 10-15 parts of water, and uniformly stirring to obtain a solution;
s2, adding the humectant and the anti-inflammatory agent into the mixed solution, continuously stirring, gradually vacuumizing in the stirring process, and removing bubbles generated by stirring;
s3, adding the film forming agent and the chelating agent, continuously stirring until the mixture is uniform, filtering by using an ultrasonic vibration sieve, filtering to remove large particles in the mixture, and continuously stirring until the mixture becomes gel.
The stirring equipment adopts a closed clean stirrer for stirring, the stirrer is operated at a constant speed of 300-400r/min, and the antioxidant is dropwise added while stirring.
EXAMPLE III
A gel for treating inflammatory acne based on chitosan has the following formula: 15 parts of water, 4 parts of ethanol and 4 parts of propylene glycol, 7 parts of glycerol, 5 parts of butanediol, 16 parts of acryloyl dimethyl taurate/VP copolymer, 4 parts of quaternary ammonium salt-736 parts of o-cymene-5-alcohol, 5 parts of chitosan, 2 parts of salicylic acid, 3 parts of papain and 30 parts of EDTA disodium.
The humectant comprises propylene glycol, glycerol and butanediol, the film forming agent is acryloyl dimethyl ammonium taurate/VP copolymer, the antiinflammatory agent is salicylic acid, the chelating agent is disodium EDTA, the chitosan is carboxyethyl chitosan, and the molecular weight is 1.0x104Dalton, degree of deacetylation 65% and degree of carboxyethyl substitution 70%.
The invention also provides a preparation method of the gel for treating inflammatory acne based on chitosan, which comprises the following steps:
s1, adding quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan and papain into 10-15 parts of water, and uniformly stirring to obtain a solution;
s2, adding the humectant and the anti-inflammatory agent into the mixed solution, continuously stirring, gradually vacuumizing in the stirring process, and removing bubbles generated by stirring;
s3, adding the film forming agent and the chelating agent, continuously stirring until the mixture is uniform, filtering by using an ultrasonic vibration sieve, filtering to remove large particles in the mixture, and continuously stirring until the mixture becomes gel.
The stirring equipment adopts a closed clean stirrer for stirring, the stirrer is operated at a constant speed of 300-400r/min, and the antioxidant is dropwise added while stirring.
The chitosan has antibacterial and wound healing promoting effects.
The ethanol has antibacterial and astringent effects, and is beneficial for mixing various components.
Propylene glycol has moisturizing and thickening effects, glycerin has moisturizing effects, and butylene glycol has moisturizing and antibacterial effects.
Acryloyldimethyl ammonium taurate/VP copolymer has effects of removing cutin, resisting inflammation and bacteria, and making the mixture opaque.
Salicylic acid has anti-inflammatory effect.
The papain has the function of removing cutin.
The o-cymene-5-ol has antioxidant effect.
The quaternary ammonium salt-73 has antibacterial and antibacterial effects.
The gel for treating inflammatory acne based on chitosan has proper consistency, stable property, luster, high transparency and long detention time, is sieved by ultrasonic vibration to filter out larger particles, so that the gel is uniform and fine, has better coating effect, can have better treatment effect on acne treatment, has less dosage and better curative effect, has more ideal moisturizing effect by using multiple humectants of propylene glycol, glycerol and butanediol, ensures that the prepared gel is not easy to lose water, and has more ideal treatment effect; and the acryloyl dimethyl ammonium taurate/VP copolymer is used as the film forming agent, so that the film forming effect is better, the gel coating is more uniform, the use effect is more ideal, and the dosage can be saved.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.

Claims (9)

1. The gel for treating inflammatory acne based on chitosan is characterized by comprising the following components in percentage by weight: water, ethanol, humectant, film forming agent, quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan, anti-inflammatory agent, papain and chelating agent.
2. A chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, wherein: the chitosan also comprises carboxymethyl chitosan and carboxyethyl chitosan, wherein the weight part of the chitosan is 3-5 parts, and the molecular weight is less than 3.0x104Dalton, deacetylation degree of 60-70%, and substitution degree of carboxymethyl or carboxyethyl of above 60%.
3. A chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, wherein: the weight portion of the ethanol is 2-4 portions.
4. A chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, wherein: the humectant comprises 2-4 parts of propylene glycol, 3-7 parts of glycerol and 2-5 parts of butanediol.
5. A chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, wherein: the film forming agent is acryloyl dimethyl ammonium taurate/VP copolymer, and the weight portion of the acryloyl dimethyl ammonium taurate/VP copolymer is 10-16 portions.
6. A chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, wherein: the anti-inflammatory agent is salicylic acid, and the weight part of the salicylic acid is 1-2 parts.
7. A chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, wherein: the chelating agent is disodium EDTA, the weight part of the disodium EDTA is 20-30 parts, the weight part of the papain is 2-3 parts, the weight part of the o-cymene-5-alcohol is 1-4 parts, and the weight part of the quaternary ammonium salt-73 is 3-6 parts.
8. A method of preparing a chitosan-based gel for the treatment of inflammatory acne as claimed in claim 1, comprising the steps of:
s1, adding quaternary ammonium salt-73, o-cymene-5-alcohol, chitosan and papain into 10-15 parts of water, and uniformly stirring to obtain a solution;
s2, adding the humectant and the anti-inflammatory agent into the mixed solution, continuously stirring, gradually vacuumizing in the stirring process, and removing bubbles generated by stirring;
s3, adding the film forming agent and the chelating agent, continuously stirring until the mixture is uniform, filtering by using an ultrasonic vibration sieve, filtering to remove large particles in the mixture, and continuously stirring until the mixture becomes gel.
9. The method of claim 8, wherein the gel for treating inflammatory acne is prepared from chitosan, and the gel comprises the following components: the stirring equipment adopts a closed clean stirrer for stirring, the stirrer is operated at a constant speed of 300-400r/min, and the antioxidant is dropwise added while stirring.
CN202011512100.4A 2020-12-19 2020-12-19 Gel for treating inflammatory acne based on chitosan and preparation method thereof Pending CN112603993A (en)

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