CN111991417A - Hypochlorous acid gel with physiological responsiveness and application thereof in skin wound surface - Google Patents
Hypochlorous acid gel with physiological responsiveness and application thereof in skin wound surface Download PDFInfo
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- CN111991417A CN111991417A CN202011070468.XA CN202011070468A CN111991417A CN 111991417 A CN111991417 A CN 111991417A CN 202011070468 A CN202011070468 A CN 202011070468A CN 111991417 A CN111991417 A CN 111991417A
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- Prior art keywords
- hypochlorous acid
- acid gel
- gel
- physiologically responsive
- poloxamer
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- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 230000004043 responsiveness Effects 0.000 title claims abstract description 12
- 206010072170 Skin wound Diseases 0.000 title claims abstract description 9
- 239000011159 matrix material Substances 0.000 claims abstract description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 8
- 230000003385 bacteriostatic effect Effects 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 229920002385 Sodium hyaluronate Polymers 0.000 claims description 6
- 229940010747 sodium hyaluronate Drugs 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 229920001993 poloxamer 188 Polymers 0.000 claims description 5
- 229940044519 poloxamer 188 Drugs 0.000 claims description 5
- 229920001992 poloxamer 407 Polymers 0.000 claims description 5
- 229940044476 poloxamer 407 Drugs 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical class CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 3
- 229920002674 hyaluronan Polymers 0.000 claims description 3
- 229960003160 hyaluronic acid Drugs 0.000 claims description 3
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 3
- 239000002504 physiological saline solution Substances 0.000 claims description 3
- 239000008215 water for injection Substances 0.000 claims description 3
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 229920006037 cross link polymer Polymers 0.000 claims description 2
- 239000003906 humectant Substances 0.000 claims description 2
- 229940014041 hyaluronate Drugs 0.000 claims description 2
- -1 hyaluronic acid ester Chemical class 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000006174 pH buffer Substances 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000000375 suspending agent Substances 0.000 claims description 2
- 230000037314 wound repair Effects 0.000 claims description 2
- 239000004034 viscosity adjusting agent Substances 0.000 claims 1
- 239000000499 gel Substances 0.000 abstract description 18
- 230000029663 wound healing Effects 0.000 abstract description 6
- 241000894006 Bacteria Species 0.000 abstract description 5
- 239000000017 hydrogel Substances 0.000 abstract description 3
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- 239000011149 active material Substances 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000002955 isolation Methods 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 description 22
- 208000027418 Wounds and injury Diseases 0.000 description 22
- 241000700159 Rattus Species 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 5
- 206010040943 Skin Ulcer Diseases 0.000 description 4
- 239000000645 desinfectant Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 231100000019 skin ulcer Toxicity 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 206010062255 Soft tissue infection Diseases 0.000 description 2
- 206010048038 Wound infection Diseases 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000035617 depilation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 206010007247 Carbuncle Diseases 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010016936 Folliculitis Diseases 0.000 description 1
- 206010017553 Furuncle Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000011557 critical solution Substances 0.000 description 1
- ZXJXZNDDNMQXFV-UHFFFAOYSA-M crystal violet Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1[C+](C=1C=CC(=CC=1)N(C)C)C1=CC=C(N(C)C)C=C1 ZXJXZNDDNMQXFV-UHFFFAOYSA-M 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229960001235 gentian violet Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 206010025226 lymphangitis Diseases 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses hypochlorous acid gel with physiological responsiveness and application thereof in skin wound surfaces, and belongs to the technical field of medical instruments. The active ingredients with the functions of inhibiting bacteria and promoting wound healing and the like are added into the temperature-sensitive sterile hydrogel matrix, are in a sol state with good fluidity at room temperature, are quickly gelled and solidified at physiological temperature, complete physical isolation on skin wounds, simultaneously play the function of a physiological active material and promote the wound healing.
Description
Technical Field
The invention belongs to the field of medical instruments, and relates to hypochlorous acid gel with physiological responsiveness and application thereof in skin wound surfaces.
Skin and soft tissue infection is one of the clinically common infection types, is a local inflammatory disease caused by invasion of epidermis, dermis and subcutaneous tissues by conditional pathogenic bacteria, is clinically common and comprises folliculitis, furuncle, carbuncle, lymphangitis, acute cellulitis, burn wound infection, operation incision infection, bedsore infection, diabetic foot and the like. In addition, early and timely prevention and control of infection are also important targets for the standardized treatment of wounds. At present, antibiotic medicines or disinfection preservatives such as iodophor and the like are mainly applied clinically for treating skin soft tissue or wound infection, but the effect of applying the iodophor is not ideal, and the local administration of the antibacterial medicines can promote wound healing and prevent infection spreading. Antibiotic drugs have great side effects, and more bacteria have drug resistance to traditional bactericidal drugs. The temperature-sensitive hydrogel dressing has a temperature-sensitive group which has the Lowest Critical Solution Temperature (LCST), and the volume of the temperature-sensitive hydrogel dressing is suddenly shrunk or expanded near the LCST, so that the volume transformation from a sol phase to a shrunk phase, namely the transformation from a liquid state to a solid state, is generated. The liquid state is at low temperature, and when the liquid state is acted on the wound surface of a human body, the liquid state is converted into a gel state to cover the wound surface, so that the wound surface is kept moist, and the wound surface healing is accelerated. Therefore, compared with the traditional dressing, the temperature-sensitive gel has the following characteristics: providing a humid environment, maintaining electrolyte balance and accelerating wound healing; secondly, antibacterial components are loaded to inhibit microbial infection of the wound surface; and thirdly, external stimulation is resisted, and secondary infection of the wound is prevented.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide hypochlorous acid gel with physiological responsiveness and application thereof in skin wounds, wherein the physiological responsiveness temperature-sensitive hypochlorous acid gel is non-toxic and has good safety.
In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:
a) wound repair materials, sodium hyaluronate and/or hyaluronic acid derivatives;
b) bacteriostatic components, hypochlorous acid and/or hypochlorite;
c) a temperature sensitive matrix material consisting of poloxamer 407 and/or poloxamer 188;
d) the pH buffer comprises sodium chloride, potassium chloride, sulfuric acid, hydrochloric acid, phosphoric acid, phosphate or other soluble salts;
e) solvent, purified water.
In the hypochlorous acid gel with physiological responsiveness, the mass concentration (w/v) of sodium hyaluronate is less than or equal to 1%, the mass concentration (w/v) of poloxamer 407 is 17% -21%, the mass concentration (w/v) of poloxamer 188 is 1% -3%, and the mass concentration (w/v) of hypochlorous acid is 0.01% -0-2.00%.
Preferably, pharmaceutically acceptable pharmaceutical excipients are further added into the chitosan gel with physiological responsiveness.
Further preferably, the pharmaceutical excipients comprise one or more of a viscosity regulator, a suspending agent, an antioxidant, a stabilizer and a humectant.
Preferably, the water is water for injection, physiological saline or purified water.
Preferably, the sodium hyaluronate derivative is a sodium hyaluronate cross-linked polymer, a hyaluronic acid ester or a metal hyaluronate.
Preferably, the gelling temperature of the hypochlorous acid gel with physiological responsiveness is between 30 and 37 ℃.
The preparation method of the hypochlorous acid gel with physiological responsiveness comprises the following steps:
putting poloxamer 407 and/or poloxamer 188 into normal saline, water for injection or purified water in a clean environment at a temperature of lower than 28 ℃, and stirring until the poloxamer is completely swelled; adding hyaluronic acid and/or its derivative, and mixing; adding hypochlorous acid and/or sodium hypochlorite, and regulating the pH value of the system by hydrochloric acid to obtain the hypochlorous acid gel with physiological responsiveness.
The temperature-sensitive gel system for the skin wound is uniformly sprayed on the wound in a sol state at room temperature (lower than 28 ℃) through the spray bottle, and the sol rapidly completes phase transformation to form gel under the action of body temperature, so that the proliferation of pathogenic microorganisms of the wound can be effectively inhibited, the invasion of external pathogens is resisted, a moist wound environment is formed, and the healing of the wound is promoted.
Detailed Description
The present invention will now be described in detail with reference to examples, which are illustrative, not restrictive, and are not to be construed as limiting the scope of the invention.
Example 1:
this example demonstrates the following materials contained in the present invention:
component concentration (mass percentage)
After the solution is prepared by the formula, the pH value is 3-7; the available chlorine should be 90-200 mg/L.
Example 2:
this example demonstrates the following materials contained in the present invention:
component concentration (mass percentage)
After the solution is prepared by the formula, the pH value is 3-7; the available chlorine should be 90-200 mg/L.
Example 3:
this example demonstrates the following materials contained in the present invention:
component concentration (mass percentage)
After the solution is prepared by the formula, the pH value is 3-7; the available chlorine should be 90-200 mg/L.
Example 4:
experiment for testing bacteriostatic effect
The culture broth of Staphylococcus aureus (9 h) was suspended, and 3 tubes of each of the test solutions (examples 1, 2, and 3, and a commercially available hypochlorous acid disinfectant) and PBS (5mL) were prepared. 100. mu.L of the above bacterial suspension was dropped into each of the test sample solution and the control sample solution, and mixed well. Timing, acting for 20min, respectively putting sample solutions (0.5mL) into test tubes containing 5mL of PBS, fully and uniformly mixing, appropriately diluting, then taking 2-3 dilutions, respectively absorbing 1mL, placing in 3 plates, pouring 15mL of nutrient agar culture medium cooled to 40-45 ℃, rotating the plates to fully and uniformly mix the agar, turning the plates after agar solidification, culturing for 48h at 37 ℃, counting viable bacteria colonies, repeating the test for 3 times, and calculating the bacteriostasis rate, wherein the bacteria inhibition rate is shown in Table 1:
table 1 comparison of bacteriostatic rates of examples 1, 2 and 3
| Sample type | Bacteriostatic ratio (%) |
| 5mL PBS | 0 |
| Example 1 | 90.8 |
| Example 2 | 91.0 |
| Example 3 | 93.0 |
| Commercial hypochlorous acid disinfectant | 85.0 |
The results in table 1 show that the bacteriostatic levels of examples 1, 2 and 3 are higher than those of the commercial hypochlorous acid disinfectant, so that the disinfectant has a stronger bacteriostatic effect and stronger killing capability on bacteria at wounds.
Example 5: hypochlorous acid temperature-sensitive gel experiment for promoting wound healing
1. Rat wound model establishment
Feeding with common feed for 3 days before experiment, and freely taking food and drinking water at room temperature of (22 + -1) deg.C and relative humidity of 40-70%; after the rats are fasted for 12 hours (preferably 24 hours) without water prohibition and are successfully anesthetized by intraperitoneal injection with 10% chloral hydrate according to 0.4ml/100g of body weight, a 5% iodine tincture and 75% alcohol local sterilization operation area is used, the back of the rats is cut off with fur with the diameter of 4 x 4cm, sodium sulfide is used for depilation treatment, after gentian violet is marked on the depilation area, a circular full-thickness skin ulcer model with the diameter of about 2.0cm x 2.0cm is prepared on the back of the rats by taking the spine as a midline by a surgical method, the wound surface is coated once a day by glacial acetic acid, a 5cm x 7cm 4-layer gauze block is used for binding and fixing, and a defect skin rat model is formed after 1 week.
2. Grouping of laboratory animals
The 48 skin ulcer rats were randomly divided into:
(1) blank control group
(2) Hypochlorous acid temperature-sensitive gel group (experiment group)
(3) Skin ulcer model set (model set)
(4) Skin ulcer positive group (recovery new liquid)
3. Method of administration
The wound surface is evenly sprayed with hypochlorous acid temperature-sensitive gel after the local disinfection every day in the experimental group; the control group is sprayed with the new healing liquid after local disinfection on the wound surface, and the new healing liquid is applied once a day on the basis of soaking the wound surface. The wound surface was washed with normal saline daily in the model group. The blank control group was administered with physiological saline on the back daily
4. Observation index
Calculating the wound healing rate after molding and at the end of observation (according to the specified time of each group respectively),
shrinkage rate (original area-unhealed wound area)/original area of wound surface × 100%
5. Results of the experiment
TABLE 1 wound area and shrinkage before and after administration for each group of rats
The wound surface shrinkage of the model group is 38.81%, and compared with the model group, the skin wound surface shrinkage of the rat in the positive control group is 83.36%; the highest shrinkage rate of the hypochlorous acid temperature-sensitive gel group is 82.36 percent.
Claims (7)
1. A physiologically responsive hypochlorous acid gel, comprising:
a) wound repair materials, sodium hyaluronate and/or hyaluronic acid derivatives;
b) bacteriostatic components, hypochlorous acid and/or hypochlorite;
c) a temperature sensitive matrix material consisting of poloxamer 407 and/or poloxamer 188;
d) the pH buffer comprises sodium chloride, potassium chloride, sulfuric acid, hydrochloric acid, phosphoric acid, phosphate or other soluble salts;
e) solvent, purified water.
In the hypochlorous acid gel with physiological responsiveness, the mass concentration (w/v) of sodium hyaluronate is less than or equal to 1%, the mass concentration (w/v) of poloxamer 407 is 17% -21%, the mass concentration (w/v) of poloxamer 188 is 1% -3%, and the mass concentration (w/v) of hypochlorous acid is 0.01% -0-2.00%.
2. The physiologically responsive hypochlorous acid gel of claim 1, wherein a pharmaceutically acceptable excipient is further added to the physiologically responsive hypochlorous acid gel.
3. The physiologically responsive hypochlorous acid gel according to claim 2, wherein said pharmaceutical excipients comprise one or more of viscosity modifiers, suspending agents, antioxidants, stabilizers, and humectants.
4. The physiologically responsive hypochlorous acid gel according to claim 1, wherein said water is water for injection, physiological saline or purified water.
5. The physiologically responsive hypochlorous gel of claim 1, wherein said sodium hyaluronate derivative is a sodium hyaluronate cross-linked polymer, a hyaluronic acid ester, or a metal hyaluronate.
6. The physiologically responsive hypochlorous acid gel of claim 1, wherein said physiologically responsive hypochlorous acid gel has a gelling temperature between 30 ℃ and 37 ℃.
7. Use of the physiologically responsive hypochlorous acid gel of claim 1 in clinical trials for treating skin wounds.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111603399A (en) * | 2020-06-28 | 2020-09-01 | 南京东万生物技术有限公司 | Oral gargle and preparation method thereof |
| CN113082050A (en) * | 2021-04-26 | 2021-07-09 | 贵州扬生医用器材有限公司 | Temperature-sensitive gel for gynecology and preparation method thereof |
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2020
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111603399A (en) * | 2020-06-28 | 2020-09-01 | 南京东万生物技术有限公司 | Oral gargle and preparation method thereof |
| CN113082050A (en) * | 2021-04-26 | 2021-07-09 | 贵州扬生医用器材有限公司 | Temperature-sensitive gel for gynecology and preparation method thereof |
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Application publication date: 20201127 |