CN111481463A - Oligopeptide alcohol gel or water alcohol gel and preparation method and application thereof - Google Patents

Oligopeptide alcohol gel or water alcohol gel and preparation method and application thereof Download PDF

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CN111481463A
CN111481463A CN202010399123.2A CN202010399123A CN111481463A CN 111481463 A CN111481463 A CN 111481463A CN 202010399123 A CN202010399123 A CN 202010399123A CN 111481463 A CN111481463 A CN 111481463A
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gel
oligopeptide
alcohol
alcogel
palmitoyl
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闫学海
沈桂芝
邢蕊蕊
袁成前
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Institute of Process Engineering of CAS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04Dispersions; Emulsions
    • A61K8/042Gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • 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
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • 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
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0028Polypeptides; Proteins; Degradation products thereof
    • A61L26/0047Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/008Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin

Abstract

The invention discloses an oligopeptide alcohol gel or water alcohol gel, a preparation method and application thereof, wherein (a) at least one oligopeptide and a derivative thereof; and (b) at least one lower alcohol and/or polyol. The oligopeptide alcohol gel/water alcohol gel provided by the invention is used as a repairing functional component of a wash-free antibacterial gel, can promote skin fibroblast proliferation, has the functions of wound healing and inhibiting inflammatory reaction and injury, thereby maintaining skin barrier balance from the deep layer of skin and repairing irritation and injury caused by long-term use of ethanol antibacterial products to the skin.

Description

Oligopeptide alcohol gel or water alcohol gel and preparation method and application thereof
Technical Field
The invention belongs to the field of biological materials and daily chemical products, and particularly relates to oligopeptide alcohol gel or water alcohol gel, a preparation method thereof, and application of the oligopeptide alcohol gel or water alcohol gel as a repairing functional component in a wash-free antibacterial gel.
Background
Hydroalcoholic gels are a class of gel materials having a three-dimensional structure formed in a water and lower alcohol or polyol blending system. When the water content therein is zero and only an alcohol-based solvent is contained, the formed gel is called an alcogel. Due to the unique hydrophilicity, high alcohol permeability and special skin feel of the hydroalcoholic gel, the hydroalcoholic gel has wide application in the fields of biomedical dressings, pharmacy and beauty and skin care.
At present, the common hydroalcoholic gel is mostly obtained by blending a water-soluble high-molecular polymer and a hydroalcoholic solvent. Such as polyacrylic acid copolymers of carbomer, polyvinyl alcohol and its derivatives, etc. For example, patent CN109069393A provides an alcogel which retains a water-soluble polymer containing carboxyl groups, a polyhydric alcohol and an acid, and is suitable for use in cosmetic gel films in the cosmetic field and the medical field. The cosmetic has the advantages of no need of adding preservatives, capability of improving the stability of valuable components of the cosmetic, comfort of skin and the like. Patent CN101081203B provides a use of a hydroalcoholic gel for the treatment, prevention or reduction of the risk of testosterone deficiency. The hydrogel matrix mainly comprises carbomer 980, ethanol and water, and can stably release the testosterone drug in a controlled slow release manner.
Or inorganic materials such as silicates, etc. Patent CN106999366A discloses Mg3Si4O10(OH)2The hydroalcoholic gel of synthetic phyllosilicates of (a), which is applied in skin care as a viscosity-enhancing agent, a matte-effect agent and/or an application-evening agent.
At present, in the further understanding of the microstructure and mechanism of skin, it is found that the processes of proliferation, renewal, metabolism and inflammation of skin cells are all regulated and controlled by specific sequence of oligopeptides, so that the introduction of specific bioactive peptides into skin care can fundamentally prevent and repair various skin problems. However, direct application of oligopeptide compounds still has some drawbacks. The oligopeptide compounds need to enter the stratum corneum of the skin to play a role in repairing the stratum corneum, and the stratum corneum which is the outermost layer of normal skin and the skin secrete grease to prevent the penetration of the oligopeptide compounds. Therefore, the oligopeptide alcohol gel or the hydro-alcohol gel is developed, and can reduce the entry resistance by virtue of the oil removal effect of a hydro-alcohol system, so that the functional oligopeptides can penetrate through the stratum corneum to play a repairing role. Secondly, oligopeptide alcohol gel or water alcohol gel is used as a three-dimensional gel material, compared with the water alcohol gel of hydrophilic high molecular polymer, the network formed by non-covalent interaction between molecules has faster reversible response characteristic, so that the oligopeptide alcohol gel or water alcohol gel has reversible sol/gel characteristic, and the application in the aspects of biomedicine and beauty care is very significant.
Particularly, aiming at the urgent need of the wash-free antibacterial gel which is quick, dry, efficient in sterilization and bacteriostasis and has the skin repairing and maintaining effects in the industry, the application potential of the oligopeptide hydroalcoholic gel type wash-free antibacterial gel is shown.
Disclosure of Invention
Therefore, the invention provides oligopeptide alcohol gel or water alcohol gel, a preparation method and application thereof. Surprisingly, the applicants have found that by dissolving the oligopeptide in an alcoholic or hydroalcoholic solvent, an alcogel/hydroalcoholic gel can be formed with the oligopeptide as a fibrous structure by increasing the concentration of the oligopeptide, after dissolution, standing and aging. The preparation method is green, efficient and simple, and the prepared oligopeptide alcohol gel/water alcohol gel can be used as an effective component to be applied to wash-free antibacterial gel.
In order to achieve the purpose of the invention, the invention adopts the following technical scheme:
in a first aspect, the present invention provides an oligopeptide alcogel or hydroalcoholic gel comprising:
(a) at least one oligopeptide and derivatives thereof; and
(b) at least one hydroalcoholic solvent of a lower alcohol and/or a polyol, and/or a polyol derivative;
the oligopeptide is selected from one or more of copper peptide, palmitoyl tripeptide-1, palmitoyl tripeptide-5, palmitoyl tripeptide-8, palmitoyl tetrapeptide-5, palmitoyl tetrapeptide-7, palmitoyl tetrapeptide-10, palmitoyl penta-4, palmitoyl penta-5, palmitoyl hexapeptide-9, palmitoyl hexapeptide-12, palmitoyl hexapeptide-14, palmitoyl hexapeptide-15, dipeptide-4, carnosine, tripeptide-6, peptide-10 citrulline, tetrapeptide-1 and acetyl dipeptide-1 cetyl wax ester; the alcogel is a gel taking alcohol as a dispersion system; the hydroalcoholic gel refers to a gel which takes a hydroalcoholic solvent as a dispersion system. Since the above-mentioned oligopeptides have limited solubility in water, it is difficult to form a gel structure in water. The inventors of the present application have surprisingly found that by dissolving the oligopeptide in an alcoholic or hydroalcoholic solvent, an alcogel/hydroalcoholic gel with the oligopeptide as a fibrous structure can be formed after dissolving, standing and aging by increasing the concentration of the oligopeptide.
In a preferred embodiment of the invention, the hydroalcoholic solvent is a mixture of water and a dermatologically acceptable lower alcohol or polyol. In the hydroalcoholic solvent, the mass fraction of water is 0-90%; preferably 0 to 55%; for example, it may be 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or 55%.
The term "lower alcohol", as used herein, alone or in combination, means a straight or branched chain alcohol molecule containing from 1 to 6 carbon atoms. Such alcohol molecules include, but are not limited to, ethanol, propanol, isopropanol, n-butanol, hexanol, tert-butanol, and the like.
As used herein, "ethanol" refers to C2H5And (5) OH. It may refer to absolute ethanol, edible alcohol in pharmacopoeia or any common form incorporating various amounts of water.
The polyhydric alcohol is selected from ethylene glycol, propylene glycol, isoprene glycol, 1, 3-propylene glycol, 1, 2-butanediol, 2, 3-butanediol, 1, 4-butanediol, 1, 2-pentanediol, 1, 6-hexanediol, 1, 5-pentanediol, 1, 2-hexanediol, dipropylene glycol, glycerol, diglycerol, erythritol, pentaerythritol, arabitol, ribitol, sorbitol, galactitol, maltitol, panthenol, 1, 2-octanediol; preferably glycerol, propylene glycol, pentylene glycol and butylene glycol, more preferably butylene glycol, pentylene glycol and mixtures thereof.
The concentration of the oligopeptide in the alcogel/hydroalcoholic gel is 0.1-100mg/m, and may be, for example, 0.1mg/m, 0.2mg/m 0, 0.3mg/m 1, 0.5mg/m 2, 0.6mg/m 3, 0.8mg/m 4, 1mg/m 5, 2mg/m 6, 3mg/m 7, 4mg/m 8, 6mg/m 9, 8mg/m, 10mg/m 0, 12mg/m 1, 15mg/m 2, 16mg/m 3, 18mg/m 4, 20mg/m 5, 22mg/m 6, 25mg/m 7, 28mg/m 8, 30mg/m 9, 35mg/m, 40mg/m 0, 45mg/m 1, 50mg/m 2, 55mg/m 3, 60mg/m 4, 65mg/m 5, 70mg/m 6, 75mg/m 7, 80mg/m 0, 45mg/m 1, 50mg/m 2, 55mg/m 3, 60mg/m 4, 65mg/m 5, 90mg/m, 85mg/m, or more, and may be stabilized by a solvent, such that the oligopeptide is dissolved in water or more than 1mg/m, and more preferably, and more than 1, and more preferably, and more than 1.
The oligopeptide hydrogel gel provided by the invention is a transparent or semitransparent uniform gel.
The oligopeptide alcogel/hydroalcoholic gel of the present invention has reversible shear-thinning rheological properties.
In a preferred embodiment of the present invention, the reversible shear-thinning rheology is intended to mean that the oligopeptide alcogel/hydroalcoholic gel becomes flowable in the sol state upon high shear or ultrasonic cavitation, and can recover the gel state after standing and aging. Can reversibly exhibit sol/gel state changes.
In a preferred embodiment of the invention, the alcogel/hydroalcoholic gel is free of other gel-forming ingredients. In other words, in a preferred embodiment of the present invention, the gel is an oligopeptide as a framework material.
In a second aspect, the present invention provides a method for preparing an oligopeptide alcogel/hydroalcoholic gel according to the first aspect, comprising the steps of:
mixing oligopeptide with alcohol or water alcohol solvent, stirring and/or heating to dissolve, standing at a certain temperature, and aging to obtain oligopeptide alcohol gel/water alcohol gel. According to the preparation method disclosed by the invention, the preparation method is green, efficient and simple.
Preferably, the temperature rise range is 30-80 ℃; preferably 40-60 ℃;
the certain temperature range is-20-50 ℃; preferably-20-30 deg.C, such as-20 deg.C, -10 deg.C, 0 deg.C, 4 deg.C, 10 deg.C, 15 deg.C, 18 deg.C, 20 deg.C, 22 deg.C, 23 deg.C, 25 deg.C, 26 deg.C, 28 deg.C, 30 deg.C, 32 deg.C, 35 deg.C, 36 deg.C, 38 deg.C, 40 deg.C, 42 deg.C, 44 deg;
the standing and aging time range is 0.5-120 h; preferably 1-12 h; for example, 1h, 1.2h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h or 12 h;
in a third aspect, the present invention provides the use of an oligopeptide alcogel/hydroalcoholic gel as described in the first aspect or prepared in the second aspect. The oligopeptide alcohol gel or the water alcohol gel is applied to biological materials, tissue repair, pharmaceutic adjuvants, daily chemicals and medicines.
Wherein the oligopeptide alcogel or hydroalcoholic gel is used as a skin repair agent;
wherein the oligopeptide alcohol gel or water alcohol gel is used as a transdermal penetrating agent;
wherein the oligopeptide alcohol gel or water alcohol gel is used as a controlled release sustained release agent;
in a fourth aspect, the invention provides a wash-free bacteriostatic gel based on oligopeptide alcohol gel/hydroalcoholic gel, which comprises the oligopeptide alcohol hydrogel described in the first aspect or prepared in the second aspect, a bacteriostatic effective component, a thickening agent and a pH neutralizing agent.
Preferably, the oligopeptide alcohol gel or water alcohol gel is contained in the wash-free antibacterial gel in an amount of 0.05-50%, preferably 0.5-20%.
As a preferred embodiment, the no-clean bacteriostatic gel comprises the following components in percentage by weight: oligopeptide alcohol hydrogel 0.5-20.0%, thickener 0.05-2.0%, pH neutralizer 0.01-1.0%, and ethanol water solution in balance.
The viscosity of the wash-free bacteriostatic gel is any amount between about 1000-;
the thickening agent includes Carbomer (Carbomer), crosslinked sulfonic acid copolymer and mixtures thereof, the Carbomer includes an acrylic acid addition polymer crosslinked with an unsaturated polyfunctional agent, such as the polyallyl ether of sucrose, preferably Carbomer, especially L ubizol
Figure BDA0002488690520000051
940、
Figure BDA0002488690520000052
940、
Figure BDA0002488690520000053
980、
Figure BDA0002488690520000054
Ultrez 10、
Figure BDA0002488690520000055
Ultrez 20, and the like;
the pH neutralizing agent includes an organic amine, such as may be selected from the group consisting of triethanolamine, triethylamine, isopropylamine, diisopropylamine, and the like. Inorganic bases such as sodium hydroxide, potassium hydroxide, and the like;
the ethanol water solution has a volume fraction of more than 65 percent, and meets the requirement of a disinfection product on the ethanol content;
the no-wash bacteriostatic gel of the invention can also comprise one or more other active ingredients used in skin care. Such active ingredients may include one or more of the following:
for example, a member selected from the group consisting of polyvinylpyrrolidone/iodine, chlorhexidine digluconate (CHG), Parachlorometaxylenol (PCMX), hexachlorobenzene, triclosan, L auricidin, hydrogen peroxide, silver chloride, silver oxide, and silver sulfadiazine;
emollients, which are commonly added to hand products, increase the moisture content of the stratum corneum by forming a closed barrier to prevent water evaporation from or penetration into the stratum corneum and physically binding water to prevent evaporation. For example selected from the following: one or more of glycerin, lanolin, allantoin, jojoba oil, tea tree oil, sodium hyaluronate, dimethicone, vaseline, isopropyl myristate, betaine, olive oil, isopropyl myristate, and grease wax.
A fragrance for masking the pungent odor of ethanol. For example selected from the following: chamomile essence, lavender essence, apple essence, aloe essence, jasmine essence, mint essence, sweet orange essence, lemon essence and the like.
Suitable preservatives may also be added to the above gels. For example, it may be selected from phenoxyethanol, formaldehyde solution, parabens, pentanediol or sorbic acid
The preparation method of the no-clean antibacterial gel comprises the following steps: dissolving the thickening agent in distilled water, standing, fully swelling, and stirring until the thickening agent is completely dissolved; adding the ethanol solution into the solution step by step in batches, and stirring uniformly. Sequentially oligopeptide hydroalcoholic gel, emollient and aromatic under stirring, and finally adjusting pH to 6.0-7.0 with pH neutralizer.
Compared with the prior art, the invention has the following beneficial effects:
(1) the oligopeptide alcohol gel/water alcohol gel has good reversible response characteristic. The alcohol gel/water alcohol gel is changed into sol state from gel state by shearing or ultrasonic action, the sol can be restored to gel state after standing, and the conversion process can be repeated for many times. The characteristic is beneficial to the uniform application of the biological dressing gel and the controlled release and slow release of the active ingredients.
(2) The washing-free disinfection containing oligopeptide alcohol gel/hydroalcoholic gel can be used for cleaning, disinfecting and nursing hand mucous membranes, and particularly can promote skin fibroblast proliferation, has the effects of wound healing and inhibiting inflammatory reaction and injury, so that skin barrier balance is maintained from the deep layer of the skin, and the skin is stimulated and damaged by long-term use of ethanol antibacterial products.
Drawings
FIG. 1 is a schematic representation of the oligopeptide hydroalcoholic gel of example 1 (gel state after standing)
FIG. 2 is a pictorial representation (in solution form after sonication) of the oligopeptide hydroalcoholic gel of example 1;
FIG. 3 is an inverted pictorial view of the oligopeptide alcohol gel of example 2;
FIG. 4 is an inverted pictorial view of the oligopeptide alcohol gels of examples 3 and 4;
FIG. 5 is an atomic force micrograph of an oligopeptide hydroalcoholic gel from example 7;
FIG. 6 is a scanning electron micrograph of an oligopeptide hydroalcoholic gel from example 8;
FIG. 7 is a transmission electron micrograph of the oligopeptide alcogel of example 9;
FIG. 8 is a photograph of a leave-on antiseptic gel of example 11 containing an oligopeptide hydroalcoholic gel.
Detailed Description
The principles and features of this invention are described below in conjunction with examples, which are set forth to illustrate, but are not to be construed to limit the scope of the invention.
The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications. The reagents or apparatus used are conventional products commercially available from normal sources, not indicated by the manufacturer. The indicated percentage concentrations, except where indicated, refer to volume fractions.
Example 1
Weighing 5mg of palmitoyl hexapeptide-12, adding into 75% ethanol water solution with volume fraction of 1m L, heating to 60 ℃ to obtain uniformly dispersed solution, placing at 4 ℃, standing and aging for 12h to finally obtain the palmitoyl hexapeptide-12 hydroalcoholic gel.
The actual image of the obtained hydroalcoholic gel is shown in FIG. 1, and the hydroalcoholic gel is uniform and transparent in appearance and does not flow after being poured. After being pushed and pulled before injection (simulating smearing effect), the gel can be converted into a sol state, as shown in figure 2.
Example 2
Weighing 1mg of palmitoyl pentapeptide-4, adding into propylene glycol aqueous solution with volume fraction of 1m L being 45%, stirring and dissolving to obtain uniformly dispersed solution, standing and aging for 2h at 4 ℃, and finally obtaining the palmitoyl hexapeptide-9 hydroalcoholic gel.
The actual picture of the obtained palmitoyl hexapeptide-9 hydroalcoholic gel is shown in FIG. 3.
Example 3
Weighing 5mg of palmitoyl hexapeptide-9, adding into 1m of L pentanediol solution, heating to 40 ℃ to dissolve to obtain uniformly dispersed solution, placing at 10 ℃, standing and aging for 6h to finally obtain palmitoyl hexapeptide-9 alcogel.
The resulting alcoholic gel was substantially as shown in FIG. 4 (left), and was uniform and translucent in appearance and was not flowable after being poured.
Example 4
Weighing 4mg of palmitoyl tetrapeptide-7, adding the palmitoyl tetrapeptide-7 into 1m of mixed solution of L ethanol and isopropanol (the volume ratio is 3:1), stirring and dissolving to obtain uniform dispersion solution, standing at 25 ℃, and aging for 12 hours to finally obtain the palmitoyl tetrapeptide-7 alcogel gel.
The resulting alcoholic gel was substantially as shown in FIG. 4 (right), and was uniform and translucent in appearance and was not flowable after being poured.
Example 5
Weighing 1mg of palmitoyl tripeptide-5, adding the palmitoyl tripeptide-5 into 75% ethanol aqueous solution with volume fraction of 1m L, stirring and dissolving to obtain a uniformly dispersed solution, standing and aging at 4 ℃ for 12 hours to finally obtain the alcohol gel/hydroalcoholic gel of palmitoyl hexapeptide-9, wherein the obtained alcohol gel/hydroalcoholic gel is in a uniform, clear and transparent gel state, and the atomic force microscope picture of the obtained hydroalcoholic gel is shown in figure 5, so that the microstructure of the hydroalcoholic gel presents a long fiber structure with uniform size.
Example 6
Weighing 6mg of palmitoyl tripeptide-1, adding into 1m L of mixed solution of ethanol, glycerol and water (the volume ratio of ethanol to glycerol to water is 2:1:1), stirring and dissolving to obtain uniformly dispersed solution, standing and aging at 30 ℃ for 12h to finally obtain the hydro-alcoholic gel of the oligopeptide, wherein the obtained hydro-alcoholic gel of the oligopeptide is in a uniform clear transparent gel state.
Example 7
Weighing 4mg of palmitoyl hexapeptide-9 and 2mg of carnosine, adding the palmitoyl hexapeptide-9 and the carnosine into 75% ethanol solution with the concentration of 1m L, stirring and dissolving to obtain uniform dispersion solution, placing the solution at the temperature of 20 ℃, standing and aging for 12 hours to finally obtain the oligopeptide hydro-alcoholic gel, wherein the obtained oligopeptide hydro-alcoholic gel is in a uniform, clear and transparent gel state.
Example 8
Weighing 5mg of palmitoyl tetrapeptide-10 and 2mg of copper peptide, adding the palmitoyl tetrapeptide-10 and the copper peptide into a mixed solvent (volume ratio is 3:1) of ethanol and butanediol of 1m L, stirring and dissolving to obtain a uniformly dispersed solution, placing the solution at the temperature of minus 20 ℃, standing and aging for 12 hours to finally obtain the alcogel of oligopeptide, wherein the appearance of the obtained alcogel is in a uniform, clear and transparent state, the appearance of the obtained hydroalcoholic gel is in a uniform, clear and transparent gel state, and a scanning electron microscope picture of the obtained hydroalcoholic gel is shown in figure 6, and the result shows that the microstructure of the obtained hydroalcoholic gel is a three-dimensional.
Example 9
Weighing 5mg of palmitoyl pentapeptide-4, 5mg of palmitoyl tripeptide-1 and 10mg of acetyl hexapeptide-8, respectively adding the materials into a pentanediol aqueous solution with the volume fraction of 1m L percent of 80 percent, heating to 55 ℃ to dissolve the materials to obtain a uniformly dispersed solution, placing the uniformly dispersed solution at 0 ℃ and standing and aging for 0.5h to finally obtain the hydroalcoholic gel of the oligopeptide, wherein the obtained hydroalcoholic gel has a uniform appearance, a clear and transparent gel state, and a transmission electron microscope picture of the hydroalcoholic gel is shown in fig. 7, and the result shows that the obtained hydroalcoholic gel is a nano-scale elongated fiber structure.
Example 10
Weighing 5mg of palmitoyl tetrapeptide-7 and 2mg of carnosine, adding the palmitoyl tetrapeptide-7 and the carnosine into 1m L ethanol solution with the volume fraction of 65%, heating to 80 ℃ to dissolve the palmitoyl tetrapeptide-7 and the carnosine to obtain uniformly dispersed solution, placing the solution at 4 ℃, standing and aging for 2 hours to finally obtain the hydro-alcoholic gel of the oligopeptide, wherein the obtained hydro-alcoholic gel is in a uniform, clear and transparent gel state.
Example 11
The wash-free bacteriostatic gel containing oligopeptide alcohol gel/hydroalcoholic gel comprises the following raw materials in parts by weight: 5% oligopeptide alcohol gel/hydroalcoholic gel, 0.5%
Figure BDA0002488690520000101
Ultrez 20 (mass volume fraction), 0.1% triethanolamine (mass volume fraction), 75% ethanol, and the balance water.
The preparation method comprises the following steps: take 0.5g
Figure BDA0002488690520000102
Ultrez 20 was added to 10g of distilled water, and after standing and swelling, the mixture was stirred to homogeneity, 75g of ethanol solution was added in 5 portions, and after homogenization, 5m L of the oligopeptide hydroalcoholic gel of example 1, 0.05g of glycerol and the balance of water were added, and the pH was adjusted to 6.5 with triethanolamine, and the resulting leave-on antiseptic gel was homogeneous and transparent in appearance, as shown in FIG. 8.
Comparative example 1
Comparative example 1 was obtained by replacing 5m L oligopeptide hydroalcoholic gel in example 11 with an equal amount of 75% ethanol (volume fraction) and preparing a leave-on bacteriostatic gel according to the method of example 11.
Comparative example 2
Comparative example 2 was obtained by replacing 5m L oligopeptide hydroalcoholic gel in example 11 with 25mg palmitoyl hexapeptide-12 and 5m L of 75% ethanol (volume fraction) and preparing a leave-on bacteriostatic gel according to the method of example 11.
Bacteriostatic effectiveness evaluation test 1
The washing-free bacteriostatic gel containing oligopeptide alcohol gel/hydroalcoholic gel in example 11 of the invention is subjected to bacteriostatic effect detection (bacteriostatic zone test measured by carrier method), each bacterium is respectively shake-cultured in the culture solution at 37 ℃ for 24h, and then the bacterium solution is diluted to the bacterium concentration of 1 × 108CFU/m L, which was spread on an agar plate, bacteria were spread uniformly, and 1m L of the wash-free bacteriostatic gel containing oligopeptide alcohol gel/hydroalcoholic gel obtained in example 11 was spread on a 6 mm-diameter round paper sheet, which was then placed in a culture plate after inoculation, and cultured at 37 ℃ for 24 hours, the results of which are shown in Table 1.
Wherein, the diameter of the inhibition zone is less than 10mm and is considered to be inactive, the diameter of the inhibition zone is 10-14mm and is considered to have medium activity, the diameter of the inhibition zone is 14-19mm and is considered to be high activity, and the diameter of the inhibition zone is not less than 20mm and is considered to be very strong activity.
Table 1:
test strains Example 11 Comparative example 1 Comparative example 2
Escherichia coli 20.5mm 20.5mm 20.5mm
Staphylococcus aureus 21.5mm 21.0mm 21.5mm
Candida albicans 21.0mm 21.5mm 21.0mm
The results show that the bacteriostatic effects of the example 11, the comparative example 1 and the comparative example 2 are equivalent, and the bacteriostatic effects are excellent.
Bacteriostatic effectiveness evaluation test 2
The washing-free bacteriostatic gel containing oligopeptide alcohol gel/hydroalcoholic gel in the example 11 of the invention is subjected to bacteriostatic effect detection. The method is carried out according to the steps of the quantitative bacteria killing test method of disinfection technical specification (2002 edition) 2.1.1.7. The test conditions are as follows: action concentration: stock solution, action time: for 30 s. The results of the experiment are as follows:
Figure BDA0002488690520000111
the above results show that example 11 of the present invention has excellent bacteriostatic effect, and meets the requirements of the national disinfection technical specifications.
Repair and maintenance performance evaluation test 3
45 trial subjects 30-50 years old were recruited and randomized into three groups of 15 subjects each. The leave-on antiseptic gels of example 11 and comparative examples 1 and 2, respectively, were subjected to a one week use experience. The average was applied 5 times daily and the hand skin condition was scored after one week. The using effect is 10 points in total, wherein 10 points indicate that the skin state is good; a score of 6 indicates general skin condition, a score of 4 or less indicates dry skin, and a score of 1 indicates severe conditions such as skin chapping and red swelling.
The results of the effect evaluation are shown in the following table:
wash-free gel Evaluation of Performance
Example 11 8.2±1.2
Comparative example 1 4.5±0.9
Comparative example 2 6.5±0.6
The results show that the performance evaluation of example 11 and comparative example 2 with the addition of the oligopeptide is obviously improved compared with comparative example 1 without the addition of the oligopeptide; the embodiment added in the form of the hydroalcoholic gel is further improved in performance compared with the comparative example 2 due to better absorption effect.
The results show that the washing-free antibacterial gel added with the oligopeptide hydroalcoholic gel has double effects of high-efficiency bacteriostasis and damage repair.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims (10)

1. An oligopeptide alcogel or hydroalcoholic gel comprising:
(a) at least one oligopeptide and derivatives thereof; and
(b) at least one lower alcohol and/or polyol; the oligopeptide and the derivatives thereof are one or more of copper peptide, palmitoyl tripeptide-1, palmitoyl tripeptide-5, palmitoyl tripeptide-8, palmitoyl tetrapeptide-5, palmitoyl tetrapeptide-7, palmitoyl tetrapeptide-10, palmitoyl penta-4, palmitoyl penta-5, palmitoyl hexapeptide-9, palmitoyl hexapeptide-12, palmitoyl hexapeptide-14, palmitoyl hexapeptide-15, dipeptide-4, carnosine, tripeptide-6, peptide-10 citrulline, tetrapeptide-1 and acetyl dipeptide-1 cetyl wax ester; the alcogel is a gel taking alcohol as a dispersion system; the hydroalcoholic gel refers to a gel which takes a hydroalcoholic solvent as a dispersion system.
2. The oligopeptide alcogel or hydroalcoholic gel according to claim 1, wherein the hydroalcoholic solvent is a mixture of water and a dermatologically acceptable lower alcohol or polyol; in the hydroalcoholic solvent, the mass fraction of water is 0-90%; preferably 0 to 55%.
3. The oligopeptide alcogel or hydroalcogel according to claim 1 or 2, wherein the lower alcohol is a straight or branched chain alcohol molecule containing 1 to 6 carbon atoms; preferably, the lower alcohol is selected from one or more of ethanol, propanol, isopropanol, n-butanol, hexanol or tert-butanol;
the polyhydric alcohol is selected from one or more of ethylene glycol, propylene glycol, isoprene glycol, 1, 3-propylene glycol, 1, 2-butanediol, 2, 3-butanediol, 1, 4-butanediol, 1, 2-pentanediol, 1, 6-hexanediol, 1, 5-pentanediol, 1, 2-hexanediol, dipropylene glycol, glycerol, diglycerol, erythritol, pentaerythritol, arabitol, ribitol, sorbitol, galactitol, maltitol, panthenol and 1, 2-octanediol; preferably one or more selected from glycerol, propylene glycol, pentylene glycol and butylene glycol; more preferably one or more selected from the group consisting of pentanediol and butanediol.
4. The oligopeptide alcogel or hydroalcogel according to claims 1-3, wherein the oligopeptide alcogel or hydroalcogel is in the form of a transparent gel or a translucent gel.
5. The oligopeptide alcogel or hydroalcoholic gel according to any one of claims 1 to 4, wherein the alcogel/hydroalcoholic gel has reversible sol/gel transition characteristics.
6. The oligopeptide alcogel or hydroalcogel according to any one of claims 1-5, wherein the alcogel/hydroalcogel is free of other gel-forming ingredients.
7. The oligopeptide alcogel or hydroalcogel according to any one of claims 1 to 6, wherein the mass fraction of the oligopeptides in the alcogel/hydroalcogel is greater than or equal to 0.01%; preferably greater than or equal to 0.1%.
8. The process for the preparation of an alcogel/hydroalcoholic gel according to any one of claims 1 to 7, characterized in that it comprises the following steps: mixing oligopeptide with alcohol or water alcohol solvent, stirring and/or heating to dissolve, standing at a certain temperature, and aging to obtain oligopeptide alcohol gel/water alcohol gel.
9. The method of claim 8, wherein the oligopeptide-forming alcohol/hydro-alcohol gel is present in a concentration of 0.1-100mg/m L, preferably 1-20mg/m L.
Preferably, the temperature rise range is 30-80 ℃; preferably 40-60 ℃;
preferably, the certain temperature is in a temperature range of-20-50 ℃; preferably-20-30 ℃;
preferably, the standing and aging time range is 0.5-120 h; preferably 1-12 h.
10. Use of the oligopeptide alcohol gel or water alcohol gel according to any one of claims 1 to 7 in the preparation of biomaterials, tissue repair materials, adjuvants, skin care products, hand washing solutions, household chemicals and bacteriostatic drugs.
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