CN109568652A - Promote the dressing composition of wound healing - Google Patents
Promote the dressing composition of wound healing Download PDFInfo
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- CN109568652A CN109568652A CN201811600195.8A CN201811600195A CN109568652A CN 109568652 A CN109568652 A CN 109568652A CN 201811600195 A CN201811600195 A CN 201811600195A CN 109568652 A CN109568652 A CN 109568652A
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- carbomer
- wound healing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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Abstract
The present invention is a kind of dressing composition for promoting wound healing, belongs to medical configuration product field.The present invention includes preservative, filmogen and solvent, the solvent is glycerol and/or water, and the filmogen includes component A and/or component B composition, and the component A includes carbomer and triethanolamine, the component B includes polyvinyl alcohol, and the preservative is p-hydroxybenzoate.The present invention can also include cell repair agent.The present invention is not only with good stability, and there are also the ability for promoting wound healing well, 14 days wound healing rates reach as high as 75.4% in rat experiment.
Description
Technical field
Medical configuration product field of the present invention, especially a kind of adjuvant composition for promoting wound healing.
Background technique
It is well known that if the four limbs and organ of people would not grow again departing from body.Mammal generally all without
Method accomplishes this point, and only in amphibian, such as newt or the animal of even lower level such as turbellarian worm, this limb regeneration phenomenon is just more
It is common.
In fact, there are two types of the modes of healing for injured limbs.One is the healings of already mentioned regenerative, are exactly human body weight
It is new longer with original structure almost.Another kind is exactly to form a scab in wound, and collagen is disorderly filled in wound
Mouth position forms a scar without what systemic institutional framework, and substantially there is no hair follicles and sweat gland for the inside.Lactation is dynamic
The healing mode of object is mainly the latter.
In the prior art, the material base of cell repair system includes at least following three classes: (1) growth factor group.At present
Have been found that such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor
(FGF), hepatocyte growth factor (HGF), insulin like growth factor-1 (IGF-1), IGF- II, LIF ELISA
(LIF), nerve growth factor (NGF), oncostatinM (OSM), platelet-derived endothelial growth factor (PDECGF), turn
Change Transforming Growth Factor Alpha (TGF- α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain source nerve battalion
Support the factor (PDGF) etc. more than 40.
(2) with the protein group of repair function.Synthesis is relevant the study found that damaging according in different cells and cell
The difference at the position of wound, by different special reparation protein responsibles for rehabilitation.At present, it has been found that and the reparation protein reported
There are the protein s IRT6 efficiently repaired for promoting DNA of researcher's discovery of University of Rochester, North Carolina, USA university
Researcher studies the protein etc. for being known as Ku of discovery.
(3) basic substance of other supply synthesis repair function protein, such as amino acid, peptide, nucleic acid.
About the specific repair mechanism of cell repair system, mankind's face this further investigate.Meanwhile with research
Deeply, more protein of repairing will be found.
The principle of liquid dressing forms liquid dressing substantially by there is a material of film-forming quality, and when use is coated on
The surface of a wound forms protective film after dry, plays physical barriers, protection, wound healing to the surface of a wound.Common filmogen has:
Polyvinyl alcohol, sodium carboxymethylcellulose, PVP K30, carbomer, hydroxypropyl methyl cellulose etc..
Consult the correlative study of filmogen, such as " the property research of several aqueous solution type plastics filmogens and sieve
Choosing " (- 2009 years 12 phases of volume 29 of Pan Xiaojuan, Shen Li, Ruan Jia " Journal of Chinese Hospital Pharmacy ").And we constantly test,
Make from solution dry film formation time, the thickness of film, intensity, toughness, the safety of viscosity etc. and filmogen itself afterwards
Maturity etc. is comprehensive, we have selected carbomer as the core component of wound fluid casting product.
It is comprehensive to consult liquid wound-dressing clinical research, as " liquid wound-dressing is for treating skin superficial for pertinent literature
The efficacy and safety clinical research of damage " (drug research mechanism, No.1 Hospital, Shanxi Medical Univ；Mountain Western Medicine S University second
Hospital department of plastic surgery Yan Xin, Liu Zhongguo etc., " Chinese drug and clinic " the 01st phase in 2014), the results showed that, using carbomer as core
The wound fluid casting product of ingredient is safe, reliable and effective.
Lack in the prior art however, lacking in the prior art by composition and liquid dressing with cell repair function
Material effectively combines technology convenient to use.
Summary of the invention
Since above-mentioned deficiency exists in the prior art, the present invention provides a kind of the auxiliary of completely new promotion wound healing
Feed composition, the composition are mainly made of preservative, filmogen and solvent, can also include having cell repair function
Composition, the composition not only have the function of promoting wound healing also have very excellent stability, can be in conventional ring
It is saved for a long time in border, it can be made to use in wide range.
Specifically, the present invention is achieved through the following technical solutions:
A kind of dressing composition promoting wound healing, including preservative, filmogen and solvent；
The solvent is glycerol and/or water；
The filmogen includes component A and/or component B composition；
The component A includes carbomer and triethanolamine；
The component B includes polyvinyl alcohol.
Preferably, the preservative is p-hydroxybenzoate.
Preferably, the dressing composition further includes cell repair agent.
Preferably, promote the dressing composition of wound healing by 0.3-5% by weight percentage at membrane material
The solvent of material, the cell repair agent of the preservative of 0.05-0.15%, 0-3% and 91.85-99.65% forms.
Preferably, the preparation method of the carbomer is that the positive fourth of macromole evocating agent, acrylic acid is sequentially added into container
Ester, solvent, divalent copper catalyst and organic base replace inert gas, and liquid nitrogen cool down-vacuumizes-thaw cycles 1-5 times, heat up
To 60-90 DEG C, react 24-36 hour, rapid column chromatography, methanol be added, there is Precipitation, filter, take solid, dry to get
Carbomer；
Any one or more of the solvent in DMF, DME, MTBE and methyl phenyl ethers anisole；
The organic base appointing in triethylamine, diisopropylamine, tert-butylmethylamine, three (2- methylaminoethyl) amine
It anticipates one or more；
The divalent copper catalyst is selected from copper fluoride, copper chloride, copper bromide, cupric iodide, copper acetate, copper citrate, quinoline
One of copper, cupric tartrate, copper tetrafluoroborate, Cupric salicylate, 2 ethyl hexanoic acid copper, terephthalic acid (TPA) copper are a variety of；
The quality of the solvent is 3-8 times of n-butyl acrylate；
The additive amount of the macromole evocating agent is the 0.02-0.05% of n-butyl acrylate quality；
The additive amount of the divalent copper catalyst is the 1-15% of macromole evocating agent quality；
The additive amount of the organic base is the 8-15% of macromole evocating agent quality.
Preferably, the macromole evocating agent the preparation method is as follows:
(1) by 2- isobutyl ethyl bromide, 3- (trimethoxysilyl) propyl acrylate, dinonyl -2 4,4'-,
2'- dithiazole, cupric salt, methyl phenyl ethers anisole are added in reactor, replace inert gas, and liquid nitrogen cool down-vacuumizes-thaw cycles 1-
5 times, it is warming up to 60-90 DEG C, is reacted 24-36 hours, rapid column chromatography, vacuum distillation removes solvent, obtains intermediate；
Any one of the cupric salt in copper chloride, copper bromide, copper fluoride, cupric iodide；
The 2- isobutyl ethyl bromide: 4,4'- dinonyl -2,2'- dithiazole: cupric salt: 3- (trimethyoxysilane
Base) the ratio between the mole of propyl acrylate is 1:(1-1.2): (0.2-0.5): (15-25)；
The additive amount of the methyl phenyl ethers anisole is the 10-15% of 3- (trimethoxysilyl) propyl acrylate quality；
(2) by intermediate, potassium fluoride, 3- (trimethoxysilyl) propyl acrylate, tert-butyl phenol and solvent
It is added in reactor, replaces inert gas, the tetrahydrofuran solution and 2- bromine of tetrabutyl ammonium fluoride are sequentially added under ice-water bath
Isobutyl acylbromide, is back to room temperature naturally, is stirred to react 12-24 hours, filters out solid, rapid column chromatography, and vacuum distillation removes solvent,
Methylene chloride/petroleum ether system recrystallization, filters out liquid, obtained solid is macromole evocating agent；
The solvent is tetrahydrofuran or ether；
The potassium fluoride: 3- (trimethoxysilyl) propyl acrylate: the molar ratio of tert-butyl phenol is (15-
20): (8-12): 1；
The additive amount of the solvent is 10-15 times of intermediate weight；
The additive amount of 3- (trimethoxysilyl) propyl acrylate is the 8-15% of solvent quality；
The concentration of the tetrahydrofuran solution of the tetrabutyl ammonium fluoride is 0.8-1.2mol/L；
The additive amount of the tetrabutyl ammonium fluoride is the 5- of 3- (trimethoxysilyl) propyl acrylate mole
12%；
The additive amount of the 2- bromine isobutyl acylbromide is the 1- of 3- (trimethoxysilyl) propyl acrylate mole
1.2 again.
Preferably, the tert-butyl phenol is selected from 2,3- DI-tert-butylphenol compounds, 2,4-DTBP, the tertiary fourth of 2,5- bis-
Base phenol, 2,6 DI-tert-butylphenol compounds, 3,4- DI-tert-butylphenol compounds, 3,5- DI-tert-butylphenol compounds, 2-TBP, the tertiary fourth of 3-
Any one in base phenol, 4-TBP.
Preferably, the liquid nitrogen cool down-vacuumize-thaw cycles step be a. by reaction vessel immerse liquid nitrogen bath in and protect
It holds 3-5 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is less than or equal to 10Pa and is kept for 1-3 minutes；It c. will be anti-
It answers container to immerse in 20-30 DEG C of water-bath, inert gas is passed through after bottle internal solvent liquefies again until air pressure is arrived in reaction vessel
Normal pressure, every a-c step 1 that executed is all over as one circulation of completion.
Preferably, the alcoholysis degree of the polyvinyl alcohol is 98.0-99.0mol% and viscosity is 3.2-3.8mPas.
Preferably, the cell repair agent includes the composition with cell repair function.
Preferably, the cell repair agent further includes 3- hydroxyl -4- pyridinone derivatives, the 3- hydroxyl -4- pyrrole
Pyridine ketones derivant general structure is as follows:
Wherein, R1For H or methyl；R2In methyl, ethyl, n-propyl, isopropyl any one；R3Selected from H, methyl,
Ethyl, n-propyl, any one in isopropyl.
Composition with cell repair function according to described in Chinese patent CN 103405751B have cell repair function
The preparation method preparation of the composition of energy.
When cell repair agent contains 3- hydroxyl -4- pyridinone derivatives, the preparation method of cell repair agent is will have
There is the composition of cell repair function to mix to obtain the final product with 3- hydroxyl -4- pyridinone derivatives, wherein 3- hydroxyl -4- pyridinone
The additive amount of derivative is the 0.2-1% of the composition quality with cell repair function.
When being made of in solvent water and glycerol and when filmogen is made of carbomer and triethanolamine and without containing thin
When born of the same parents' renovation agent, promote the method and step of the dressing composition quickly to heal as follows:
(1) carbomer is weighed, is dispersed in glycerol, is stirred in dispersion, dispersion is made sufficiently, uniformly to stand, must block
Wave nurse glycerol dispersion liquid；
(2) carbomer glycerol dispersion liquid is slowly added into water, is sufficiently stirred and is uniformly dissolved, it is water-soluble to obtain carbomer glycerol
Liquid；
(3) preservative is weighed, stirring and dissolving adds water in carbomer glycerine water solution, and constant volume weighs three ethyl alcohol
Amine is added in carbomer glycerine water solution, stirring while adding, obtains carbomer solution；
(4) by carbomer solution with it is filling, jump a queue, roll lid, obtain Medical-use cold compress dressing solution；
(5) by Medical-use cold compress dressing solution at a temperature of 100-115 DEG C, moist heat sterilization 20-60min promotees to obtain the final product after cooling
Into the dressing composition quickly to heal.
When being made of in solvent water and glycerol and when filmogen is made of carbomer and triethanolamine and contain cell
When renovation agent, promote the method and step of the dressing composition quickly to heal as follows:
(1) carbomer is weighed, is dispersed in glycerol, is stirred in dispersion, dispersion is made sufficiently, uniformly to stand, must block
Wave nurse glycerol dispersion liquid；
(2) carbomer glycerol dispersion liquid is slowly added into water, is sufficiently stirred and is uniformly dissolved, it is water-soluble to obtain carbomer glycerol
Liquid；
(3) preservative and cell repair agent are weighed, stirring and dissolving adds water in carbomer glycerine water solution, constant volume,
Triethanolamine is weighed, is added in carbomer glycerine water solution, it is stirring while adding, obtain carbomer solution；
(4) by carbomer solution with it is filling, jump a queue, roll lid, obtain Medical-use cold compress dressing solution；
(5) by Medical-use cold compress dressing solution at a temperature of 100-115 DEG C, moist heat sterilization 20-60min promotees to obtain the final product after cooling
Into the dressing composition quickly to heal.
When filmogen is made of polyvinyl alcohol and when not containing cell repair agent, promote the dressing quickly to heal combination
The method and step of object is as follows:
(1) polyvinyl alcohol is weighed, solvent is added, heating sufficiently leaches into poly-vinyl alcohol solution；
(2) preservative is weighed, is added in poly-vinyl alcohol solution, sufficiently dissolution is stirred, adds solvent, constant volume stirs equal
It is even, obtain polyvinyl alcohol dressing solution；
(3) polyvinyl alcohol dressing solution is filling, jump a queue, roll lid, obtain Medical-use cold compress dressing solution；
(4) Medical-use cold compress dressing solution is at a temperature of 100-115 DEG C, moist heat sterilization 20-60min, promotes to obtain the final product after cooling
The dressing composition quickly to heal.
When filmogen is made of polyvinyl alcohol and when containing cell repair agent, promote the dressing composition quickly to heal
Method and step it is as follows:
(1) polyvinyl alcohol is weighed, solvent is added, heating sufficiently leaches into poly-vinyl alcohol solution；
(2) preservative and cell repair agent are weighed, is added in poly-vinyl alcohol solution, sufficiently dissolution is stirred, adds solvent,
Constant volume stirs evenly, and obtains polyvinyl alcohol dressing solution；
(3) polyvinyl alcohol dressing solution is filling, jump a queue, roll lid, obtain Medical-use cold compress dressing solution；
(4) Medical-use cold compress dressing solution is at a temperature of 100-115 DEG C, moist heat sterilization 20-60min, promotes to obtain the final product after cooling
The dressing composition quickly to heal.
When being made of in solvent water and filmogen is made of carbomer and triethanolamine and cell repair agent is not contained
When, promote the method and step of the dressing composition quickly to heal as follows:
(1) preservative is weighed, is added to the water, stirring and dissolving obtains anticorrosion aqueous solution；
(2) carbomer is weighed, is well dispersed in anticorrosion aqueous solution, after swelling 12-36 hours, stirring dissolves it sufficiently
Homogeneous system is formed, water constant volume is added, obtains carbomer solution；
(3) triethanolamine is weighed, carbomer solution is stirred, triethanolamine is added while stirring, is stirred into carbomer
Liquid dressing solution；
(4) carbomer liquid dressing solution is filling, jump a queue, roll lid after Medical-use cold compress dressing solution；
(5) Medical-use cold compress dressing solution is at a temperature of 100-115 DEG C, moist heat sterilization 20-60min, promotes to obtain the final product after cooling
The dressing composition quickly to heal.
When being made of in solvent water and filmogen is made of carbomer and triethanolamine and contains cell repair agent, promote
Method and step into the dressing composition quickly to heal is as follows:
(1) preservative and cell repair agent are weighed, is added to the water, stirring and dissolving obtains anticorrosion aqueous solution；
(2) carbomer is weighed, is well dispersed in anticorrosion aqueous solution, after swelling 12-36 hours, stirring dissolves it sufficiently
Homogeneous system is formed, water constant volume is added, obtains carbomer solution；
(3) triethanolamine is weighed, carbomer solution is stirred, triethanolamine is added while stirring, it is stirred into carbomer
Liquid dressing solution；
(4) carbomer liquid dressing solution is filling, jump a queue, roll lid after Medical-use cold compress dressing solution；
(5) Medical-use cold compress dressing solution is at a temperature of 100-115 DEG C, moist heat sterilization 20-60min, promotes to obtain the final product after cooling
The dressing composition quickly to heal.
The invention has the beneficial effects that: the principle of liquid dressing is formed substantially by there is the material of film-forming quality
Liquid dressing, the surface of a wound is coated on when use, forms protective film after dry, plays physical barriers to the surface of a wound, is protected, the promotion surface of a wound is cured
It closes.
After the swelling of the liquid such as carbomer and water, glycerol, macromolecule space net structure is formed after neutralizing with antalkali
Colloidal materials are filled with the water as decentralized medium, glycerol liquids in structural void, build a stabilising system.When this
After heated, body surface heat is taken away in the evaporation of the moisture in structural void to colloidal materials, to reach the mesh of partial cooling
's.Simultaneously by hypoxia-inducible factor-1 alpha in the composition lifting body with cell repair function (HIF-1 α) level, promote wound
Mouth healing.
Specific embodiment
The present invention is further elaborated below with reference to specific embodiment, following embodiments are only used to explain
The present invention can not be used to limit the present invention.
Specifically, following embodiments use raw material sources or No. CAS it is as follows:
Polyvinyl alcohol, No. CAS: 9002-89-5, alcoholysis degree 98.0mol%, viscosity 3.3mPas are purchased from Shanghai Ah
Latin.
Ethyl-para-hydroxybenzoate, No. CAS: 120-47-8.
Triethanolamine, No. CAS: 102-71-6.
Carbomer A type, No. CAS: 9062-04-8,0.5% carbomer liquid viscosity value range: 5Pas, purchased from Shanghai Ah
Latin.
Carbomer Type B, No. CAS: 9062-04-8,0.5% carbomer liquid viscosity: 30Pas is purchased from Shanghai Aladdin.
Composition with cell repair function, the method recorded according to 103405751 B embodiment 2 of Chinese patent CN
It is prepared.
Glycerol, No. CAS: 56-81-5.
N-butyl acrylate, No. CAS: 141-32-2.
Methyl phenyl ethers anisole, No. CAS: 100-66-3.
DMF, No. CAS: 68-12-2.
Copper fluoride, No. CAS: 7789-19-7.
Cupric tartrate, No. CAS: 815-82-7.
Triethylamine, No. CAS: 121-44-8.
Methanol, No. CAS: 67-56-1.
2- isobutyl ethyl bromide, No. CAS: 600-00-0.
3- (trimethoxysilyl) propyl acrylate, No. CAS: 2530-85-0.
4,4'- dinonyl -2,2'- dithiazole, No. CAS: 180729-91-3.
Copper chloride, No. CAS: 10125-13-0.
Potassium fluoride, No. CAS: 7789-23-3.
2,4-DTBP, No. CAS: 96-76-4.
2,6- DI-tert-butylphenol compounds, No. CAS: 128-39-2.
Tetrabutyl ammonium fluoride, No. CAS: 429-41-4.
2- bromine isobutyl acylbromide, No. CAS: 20769-85-1.
Methylene chloride, No. CAS: 75-09-2.
Petroleum ether, No. CAS: 8032-32-4.
No. CAS: 50700-61-3.
No. CAS: 104764-53-6.
Embodiment 1
It is a kind of promote wound healing dressing composition, by 50g polyvinyl alcohol, 1.0g ethyl-para-hydroxybenzoate and
949g water is prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 50.0 grams of polyvinyl alcohol are weighed, 800 grams of purified waters are added, being heated to 70 DEG C, sufficiently to leach into polyvinyl alcohol molten
Liquid；
(2) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, is added in poly-vinyl alcohol solution, magnetic force 300rpm stirs 30min,
It adds purified water and is settled to 1000 grams of solution, 300rpm magnetic agitation 60min is at polyvinyl alcohol dressing solution；
(3) independence that is polyvinyl alcohol dressing solution cillin bottle is filling, jumping a queue, roll after covering as corresponding loading amount specification is western
Woods bottle packaging；
(4) the cillin bottle polyvinyl alcohol dressing solution of independent loading amount specification is at a temperature of 115 DEG C, moist heat sterilization 30min, cold
But promote the dressing composition of wound healing after.
Embodiment 2
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer Type B, 1.0g pairs
Nipagin A and 990g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, is added in 800 grams of purified waters, 300rpm magnetic stirring apparatus sufficiently stirs
30min dissolution is mixed, at anticorrosion aqueous solution；
(2) 4.0 grams of carbomer Type B are weighed, is well dispersed in anticorrosion aqueous solution, after swelling 24 hours, 300rpm magnetic force
Stirring sufficiently dissolution 60min obtains carbomer solution；It adds purified water and is settled to 995 grams of carbomer solutions.
(3) 5.0 grams of triethanolamine are weighed, triethanolamine is added while stirring, obtains for 250rpm magnetic agitation carbomer solution
Carbomer thick liquid, 300rpm magnetic agitation 60min is at carbomer liquid dressing solution；
(4) carbomer liquid dressing solution cillin bottle is filling, jump a queue, roll lid after become corresponding loading amount specification independence
Cillin bottle packs carbomer liquid dressing solution；
(5) the cillin bottle carbomer liquid dressing solution of independent loading amount specification is at a temperature of 115 DEG C, moist heat sterilization 30min,
Promote the dressing composition of wound healing after cooling.
Embodiment 3
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer A type, 1.0g pairs
Nipagin A and 990g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer A type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes, is made
Dispersion sufficiently, uniformly, stands 4 hours after stirring, obtains carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, magnetic stirring apparatus 300rpm stirring and dissolving is water-soluble in carbomer glycerol
In liquid, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
Embodiment 4
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer C-1 type, 1.0g
Ethyl-para-hydroxybenzoate and 990g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer C-1 type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes,
Dispersion is set sufficiently, uniformly to stand 4 hours after stirring, obtain carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, magnetic stirring apparatus 300rpm stirring and dissolving is water-soluble in carbomer glycerol
In liquid, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
Above-mentioned carbomer C-1 type the preparation method is as follows:
1.0g macromole evocating agent, 26g n-butyl acrylate, 82g methyl phenyl ethers anisole, 22g DMF are sequentially added into container,
15mg copper fluoride and 45mg triethylamine replace nitrogen, and liquid nitrogen cool down-vacuumizes-thaw cycles 3 times, are warming up to 75 DEG C, reaction 24
Hour, using neutral alumina chromatographic column rapid column chromatography, 50g methanol is added, there is Precipitation, crosses 200 meshes, takes solid,
24 hours are dried at 50 DEG C to get carbomer C-1 type.
Above-mentioned macromole evocating agent the preparation method is as follows:
(1) by 67.2mg 2- isobutyl ethyl bromide, 15g 3- (trimethoxysilyl) propyl acrylate, 0.17g
4,4'- dinonyl -2,2'- dithiazole, 12.9mg copper chloride, 1.7g methyl phenyl ethers anisole are added in reactor, replace nitrogen, and liquid nitrogen is cold
But-vacuumize-thaw cycles 3 times, 60 DEG C are warming up to, is reacted 24 hours, neutral alumina chromatographic column rapid column chromatography, 70 DEG C/
Vacuum distillation removes solvent under the conditions of 25Pa, obtains intermediate；
(2) by 3.0g intermediate, 1.1g potassium fluoride, 3.0g 3- (trimethoxysilyl) propyl acrylate, 0.3g
2,4-DTBP and 35g tetrahydrofuran are added in reactor, replace nitrogen, sequentially add 0.8mol/L under ice-water bath
Tetrahydrofuran solution 0.19mL and 4.2g the 2- bromine isobutyl acylbromide of tetrabutyl ammonium fluoride, is back to room temperature naturally, and 300rpm stirring is anti-
It answers 15 hours, 300 meshes filter out solid, alkali alumina chromatographic column rapid column chromatography, and 35 DEG C/25Pa vacuum distillation removes molten
Agent, methylene chloride/petroleum ether system recrystallization, 100 meshes filter out liquid, and obtained solid is macromole evocating agent.
The liquid nitrogen mentioned in above-mentioned steps cool down-vacuumizes-and reaction vessel immerses in liquid nitrogen bath and protected by thaw cycles a.
It holds 3 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is equal to 10Pa and is kept for 1 minute；C. reaction vessel is soaked
Enter in 25 DEG C of water-baths, be passed through after bottle internal solvent liquefies again nitrogen until reaction vessel in air pressure to normal pressure, it is every to have executed a-c
Step 1 is all over as one circulation of completion.
Embodiment 5
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer C-2 type, 1.0g
Ethyl-para-hydroxybenzoate and 990g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer C-2 type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes,
Dispersion is set sufficiently, uniformly to stand 4 hours after stirring, obtain carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, magnetic stirring apparatus 300rpm stirring and dissolving is water-soluble in carbomer glycerol
In liquid, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
Above-mentioned carbomer C-2 type the preparation method is as follows:
1.0g macromole evocating agent, 26g n-butyl acrylate, 82g methyl phenyl ethers anisole, 22g DMF are sequentially added into container,
15mg copper fluoride and 45mg triethylamine replace nitrogen, and liquid nitrogen cool down-vacuumizes-thaw cycles 3 times, are warming up to 75 DEG C, reaction 24
Hour, using neutral alumina chromatographic column rapid column chromatography, 50g methanol is added, there is Precipitation, crosses 200 meshes, takes solid,
24 hours are dried at 50 DEG C to get carbomer C-2 type.
Above-mentioned macromole evocating agent the preparation method is as follows:
(1) by 67.2mg 2- isobutyl ethyl bromide, 15g 3- (trimethoxysilyl) propyl acrylate, 0.17g
4,4'- dinonyl -2,2'- dithiazole, 12.9mg copper chloride, 1.7g methyl phenyl ethers anisole are added in reactor, replace nitrogen, and liquid nitrogen is cold
But-vacuumize-thaw cycles 3 times, 60 DEG C are warming up to, is reacted 24 hours, neutral alumina chromatographic column rapid column chromatography, 70 DEG C/
Vacuum distillation removes solvent under the conditions of 25Pa, obtains intermediate；
(2) by 3.0g intermediate, 1.1g potassium fluoride, 3.0g 3- (trimethoxysilyl) propyl acrylate, 0.3g
2,6- DI-tert-butylphenol compounds and 35g tetrahydrofuran are added in reactor, replace nitrogen, sequentially add 0.8mol/L under ice-water bath
Tetrahydrofuran solution 0.19mL and 4.2g the 2- bromine isobutyl acylbromide of tetrabutyl ammonium fluoride, is back to room temperature naturally, and 300rpm stirring is anti-
It answers 15 hours, 300 meshes filter out solid, alkali alumina chromatographic column rapid column chromatography, and 35 DEG C/25Pa vacuum distillation removes molten
Agent, methylene chloride/petroleum ether system recrystallization, 100 meshes filter out liquid, and obtained solid is macromole evocating agent.
The liquid nitrogen mentioned in above-mentioned steps cool down-vacuumizes-and reaction vessel immerses in liquid nitrogen bath and protected by thaw cycles a.
It holds 3 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is equal to 10Pa and is kept for 1 minute；C. reaction vessel is soaked
Enter in 25 DEG C of water-baths, be passed through after bottle internal solvent liquefies again nitrogen until reaction vessel in air pressure to normal pressure, it is every to have executed a-c
Step 1 is all over as one circulation of completion.
Embodiment 6
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer C-3 type, 1.0g
Ethyl-para-hydroxybenzoate and 990g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer C-3 type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes,
Dispersion is set sufficiently, uniformly to stand 4 hours after stirring, obtain carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, magnetic stirring apparatus 300rpm stirring and dissolving is water-soluble in carbomer glycerol
In liquid, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
Above-mentioned carbomer C-3 type the preparation method is as follows:
1.0g macromole evocating agent, 26g n-butyl acrylate, 82g methyl phenyl ethers anisole, 22g DMF are sequentially added into container,
39mg cupric tartrate and 45mg triethylamine replace nitrogen, and liquid nitrogen cool down-vacuumizes-thaw cycles 3 times, are warming up to 75 DEG C, reaction
24 hours, using neutral alumina chromatographic column rapid column chromatography, 50g methanol is added, there is Precipitation, crosses 200 meshes, takes solid
Body, at 50 DEG C dry 24 hours to get carbomer C-3 type.
Above-mentioned macromole evocating agent the preparation method is as follows:
(1) by 67.2mg 2- isobutyl ethyl bromide, 15g 3- (trimethoxysilyl) propyl acrylate, 0.17g
4,4'- dinonyl -2,2'- dithiazole, 12.9mg copper chloride, 1.7g methyl phenyl ethers anisole are added in reactor, replace nitrogen, and liquid nitrogen is cold
But-vacuumize-thaw cycles 3 times, 60 DEG C are warming up to, is reacted 24 hours, neutral alumina chromatographic column rapid column chromatography, 70 DEG C/
Vacuum distillation removes solvent under the conditions of 25Pa, obtains intermediate；
(2) by 3.0g intermediate, 1.1g potassium fluoride, 3.0g 3- (trimethoxysilyl) propyl acrylate, 0.3g
2,6- DI-tert-butylphenol compounds and 35g tetrahydrofuran are added in reactor, replace nitrogen, sequentially add 0.8mol/L under ice-water bath
Tetrahydrofuran solution 0.19mL and 4.2g the 2- bromine isobutyl acylbromide of tetrabutyl ammonium fluoride, is back to room temperature naturally, and 300rpm stirring is anti-
It answers 15 hours, 300 meshes filter out solid, alkali alumina chromatographic column rapid column chromatography, and 35 DEG C/25Pa vacuum distillation removes molten
Agent, methylene chloride/petroleum ether system recrystallization, 100 meshes filter out liquid, and obtained solid is macromole evocating agent.
The liquid nitrogen mentioned in above-mentioned steps cool down-vacuumizes-and reaction vessel immerses in liquid nitrogen bath and protected by thaw cycles a.
It holds 3 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is equal to 10Pa and is kept for 1 minute；C. reaction vessel is soaked
Enter in 25 DEG C of water-baths, be passed through after bottle internal solvent liquefies again nitrogen until reaction vessel in air pressure to normal pressure, it is every to have executed a-c
Step 1 is all over as one circulation of completion.
Embodiment 7
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer C-4 type, 1.0g
Ethyl-para-hydroxybenzoate and 990g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer C-4 type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes,
Dispersion is set sufficiently, uniformly to stand 4 hours after stirring, obtain carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate are weighed, magnetic stirring apparatus 300rpm stirring and dissolving is water-soluble in carbomer glycerol
In liquid, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
Above-mentioned carbomer C-4 type the preparation method is as follows:
1.0g macromole evocating agent, 26g n-butyl acrylate, 82g methyl phenyl ethers anisole, 22gDMF are sequentially added into container,
7.1mg copper fluoride, 21.3mg cupric tartrate and 45mg triethylamine replace nitrogen, and liquid nitrogen cool down-vacuumizes-thaw cycles 3 times,
75 DEG C are warming up to, is reacted 24 hours, using neutral alumina chromatographic column rapid column chromatography, 50g methanol is added, there is Precipitation,
200 meshes are crossed, solid is taken, 24 hours are dried at 50 DEG C to get carbomer C-4 type.
Above-mentioned macromole evocating agent the preparation method is as follows:
(1) by 67.2mg 2- isobutyl ethyl bromide, 15g 3- (trimethoxysilyl) propyl acrylate, 0.17g
4,4'- dinonyl -2,2'- dithiazole, 12.9mg copper chloride, 1.7g methyl phenyl ethers anisole are added in reactor, replace nitrogen, and liquid nitrogen is cold
But-vacuumize-thaw cycles 3 times, 60 DEG C are warming up to, is reacted 24 hours, neutral alumina chromatographic column rapid column chromatography, 70 DEG C/
Vacuum distillation removes solvent under the conditions of 25Pa, obtains intermediate；
(2) by 3.0g intermediate, 1.1g potassium fluoride, 3.0g 3- (trimethoxysilyl) propyl acrylate, 0.3g
2,6- DI-tert-butylphenol compounds and 35g tetrahydrofuran are added in reactor, replace nitrogen, sequentially add 0.8mol/L under ice-water bath
Tetrahydrofuran solution 0.19mL and 4.2g the 2- bromine isobutyl acylbromide of tetrabutyl ammonium fluoride, is back to room temperature naturally, and 300rpm stirring is anti-
It answers 15 hours, 300 meshes filter out solid, alkali alumina chromatographic column rapid column chromatography, and 35 DEG C/25Pa vacuum distillation removes molten
Agent, methylene chloride/petroleum ether system recrystallization, 100 meshes filter out liquid, and obtained solid is macromole evocating agent.
The liquid nitrogen mentioned in above-mentioned steps cool down-vacuumizes-and reaction vessel immerses in liquid nitrogen bath and protected by thaw cycles a.
It holds 3 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is equal to 10Pa and is kept for 1 minute；C. reaction vessel is soaked
Enter in 25 DEG C of water-baths, be passed through after bottle internal solvent liquefies again nitrogen until reaction vessel in air pressure to normal pressure, it is every to have executed a-c
Step 1 is all over as one circulation of completion.
Embodiment 8
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer C-4 type, 2.5g
Cell repair agent, 1.0g ethyl-para-hydroxybenzoate and 987.5g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer C-4 type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes,
Dispersion is set sufficiently, uniformly to stand 4 hours after stirring, obtain carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate and cell repair agent 2.5g, magnetic stirring apparatus 300rpm stirring and dissolving are weighed
In carbomer glycerine water solution, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
The cell repair agent is by composition and 3- hydroxyl -4- pyridinone derivatives system with cell repair function
, preparation method is the 3- hydroxyl -4- pyridinone derivatives by quality for the composition 0.45% with cell repair function
It is mixed with the composition with cell repair function to obtain the final product.
The structural formula of above-mentioned -4 pyridine derivatives of 3- hydroxyl is as follows:
Above-mentioned carbomer C-4 type the preparation method is as follows:
1.0g macromole evocating agent, 26g n-butyl acrylate, 82g methyl phenyl ethers anisole, 22gDMF are sequentially added into container,
7.1mg copper fluoride, 21.3mg cupric tartrate and 45mg triethylamine replace nitrogen, and liquid nitrogen cool down-vacuumizes-thaw cycles 3 times,
75 DEG C are warming up to, is reacted 24 hours, using neutral alumina chromatographic column rapid column chromatography, 50g methanol is added, there is Precipitation,
200 meshes are crossed, solid is taken, 24 hours are dried at 50 DEG C to get carbomer C-4 type.
Above-mentioned macromole evocating agent the preparation method is as follows:
(1) by 67.2mg 2- isobutyl ethyl bromide, 15g 3- (trimethoxysilyl) propyl acrylate, 0.17g
4,4'- dinonyl -2,2'- dithiazole, 12.9mg copper chloride, 1.7g methyl phenyl ethers anisole are added in reactor, replace nitrogen, and liquid nitrogen is cold
But-vacuumize-thaw cycles 3 times, 60 DEG C are warming up to, is reacted 24 hours, neutral alumina chromatographic column rapid column chromatography, 70 DEG C/
Vacuum distillation removes solvent under the conditions of 25Pa, obtains intermediate；
(2) by 3.0g intermediate, 1.1g potassium fluoride, 3.0g 3- (trimethoxysilyl) propyl acrylate, 0.3g
2,6- DI-tert-butylphenol compounds and 35g tetrahydrofuran are added in reactor, replace nitrogen, sequentially add 0.8mol/L under ice-water bath
Tetrahydrofuran solution 0.19mL and 4.2g the 2- bromine isobutyl acylbromide of tetrabutyl ammonium fluoride, is back to room temperature naturally, and 300rpm stirring is anti-
It answers 15 hours, 300 meshes filter out solid, alkali alumina chromatographic column rapid column chromatography, and 35 DEG C/25Pa vacuum distillation removes molten
Agent, methylene chloride/petroleum ether system recrystallization, 100 meshes filter out liquid, and obtained solid is macromole evocating agent.
The liquid nitrogen mentioned in above-mentioned steps cool down-vacuumizes-and reaction vessel immerses in liquid nitrogen bath and protected by thaw cycles a.
It holds 3 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is equal to 10Pa and is kept for 1 minute；C. reaction vessel is soaked
Enter in 25 DEG C of water-baths, be passed through after bottle internal solvent liquefies again nitrogen until reaction vessel in air pressure to normal pressure, it is every to have executed a-c
Step 1 is all over as one circulation of completion.
Embodiment 9
A kind of dressing composition promoting wound healing, by 5.0g triethanolamine, 4.0g carbomer C-4 type, 2.5g
Cell repair agent, 1.0g ethyl-para-hydroxybenzoate and 987.5g water are prepared.
The dressing composition of above-mentioned promotion wound healing the preparation method is as follows:
(1) 2.0 grams of carbomer C-4 type is weighed, is dispersed in 100 grams of glycerol, with 300rpm magnetic agitation 30 minutes,
Dispersion is set sufficiently, uniformly to stand 4 hours after stirring, obtain carbomer glycerol dispersion liquid.
(2) carbomer glycerol dispersion liquid is added in 800 grams of purified waters, magnetic stirring apparatus 300rpm stirring 30min makes it
It is uniformly dissolved, obtains carbomer glycerine water solution；
(3) 1.0 grams of ethyl-para-hydroxybenzoate and cell repair agent 2.5g, magnetic stirring apparatus 300rpm stirring and dissolving are weighed
In carbomer glycerine water solution, adds purified water and be settled to 997.5 grams；
(4) 2.5 grams of triethanolamine are weighed, is added in carbomer glycerine water solution, stirring while adding, mixing speed is
300rpm obtains carbomer solution；
(5) carbomer solution cillin bottle is filling, jump a queue, roll lid, become the Medical-use cold compress dressing of corresponding loading amount specification
Solution；
(6) by the Medical-use cold compress dressing solution of independent loading amount specification at a temperature of 115 DEG C, moist heat sterilization 30min, after cooling
Up to the dressing composition for promoting wound healing.
The cell repair agent is by composition and 3- hydroxyl -4- pyridinone derivatives system with cell repair function
, preparation method is the 3- hydroxyl -4- pyridinone derivatives by quality for the composition 0.45% with cell repair function
It is mixed with the composition with cell repair function to obtain the final product.
The structural formula of above-mentioned -4 pyridine derivatives of 3- hydroxyl is as follows:
Above-mentioned carbomer C-4 type the preparation method is as follows:
1.0g macromole evocating agent, 26g n-butyl acrylate, 82g methyl phenyl ethers anisole, 22gDMF are sequentially added into container,
7.1mg copper fluoride, 21.3mg cupric tartrate and 45mg triethylamine replace nitrogen, and liquid nitrogen cool down-vacuumizes-thaw cycles 3 times,
75 DEG C are warming up to, is reacted 24 hours, using neutral alumina chromatographic column rapid column chromatography, 50g methanol is added, there is Precipitation,
200 meshes are crossed, solid is taken, 24 hours are dried at 50 DEG C to get carbomer C-4 type.
Above-mentioned macromole evocating agent the preparation method is as follows:
(1) by 67.2mg 2- isobutyl ethyl bromide, 15g 3- (trimethoxysilyl) propyl acrylate, 0.17g
4,4'- dinonyl -2,2'- dithiazole, 12.9mg copper chloride, 1.7g methyl phenyl ethers anisole are added in reactor, replace nitrogen, and liquid nitrogen is cold
But-vacuumize-thaw cycles 3 times, 60 DEG C are warming up to, is reacted 24 hours, neutral alumina chromatographic column rapid column chromatography, 70 DEG C/
Vacuum distillation removes solvent under the conditions of 25Pa, obtains intermediate；
(2) by 3.0g intermediate, 1.1g potassium fluoride, 3.0g 3- (trimethoxysilyl) propyl acrylate, 0.3g
2,6- DI-tert-butylphenol compounds and 35g tetrahydrofuran are added in reactor, replace nitrogen, sequentially add 0.8mol/L under ice-water bath
Tetrahydrofuran solution 0.19mL and 4.2g the 2- bromine isobutyl acylbromide of tetrabutyl ammonium fluoride, is back to room temperature naturally, and 300rpm stirring is anti-
It answers 15 hours, 300 meshes filter out solid, alkali alumina chromatographic column rapid column chromatography, and 35 DEG C/25Pa vacuum distillation removes molten
Agent, methylene chloride/petroleum ether system recrystallization, 100 meshes filter out liquid, and obtained solid is macromole evocating agent.
The liquid nitrogen mentioned in above-mentioned steps cool down-vacuumizes-and reaction vessel immerses in liquid nitrogen bath and protected by thaw cycles a.
It holds 3 minutes；B. reaction vessel vacuumizes, and so that reaction vessel interior air pressure is equal to 10Pa and is kept for 1 minute；C. reaction vessel is soaked
Enter in 25 DEG C of water-baths, be passed through after bottle internal solvent liquefies again nitrogen until reaction vessel in air pressure to normal pressure, it is every to have executed a-c
Step 1 is all over as one circulation of completion.
Test case 1
Stability test
The dressing composition of wound healing will be promoted to be stored in the ring of 5 DEG C and 25 DEG C made from embodiment 1-9 respectively
It under border, was sampled every 30 days, measures its centrifugation layering ratio.
Centrifugation layering ratio measurement method be weigh 1.0g promote wound healing dressing composition be placed in 1.5mL from
In heart pipe, with 6000rpm centrifugation 30 minutes, the height of upper oil phase and the total height ratio of sample were centrifugation layering ratio.
Test result is as shown in table 1.
1 dressing composition stability table of table
As seen from the above table, the dressing composition provided by the invention for promoting wound healing is under conventional preservation condition
There is fabulous stability, especially saved under the conditions of 5 DEG C, it is ensured that is stablized in its 90 days not stratified.There is cell in addition
Dressing composition stability under the conditions of being stored at room temperature after the composition of repair function has a little reduction, this is because having thin
The water solubility of the composition of born of the same parents' repair function is poor to will lead to layering.
Test case 2
Cell repair test
40 male GK rats are selected, weight is provided between 180-200g by Guangdong Province's Experimental Animal Center, correlation behaviour
Work is stringent sterile working.Machine temperature control scald apparatus is torn open using YLS-5Q is desk-top in back of mice side, with 85 DEG C/0.5kg
Under conditions of to mouse scald 10 minutes, generate diameter be 18mm second-degree burn, then press wound hemostasis, be randomly divided into 10
Group every group 4 handles wound using 0.2mL physiological saline daily, remaining each group is respectively with implementation wherein first group is control group
The example 1-9 dressing composition obtained for promoting wound healing handles wound, and daily dosage was 0.2mL, at the 0th, 7,14 day
Photo is shot, calculates wound area using 6.0 software of Image Pro plus, and calculate wound healing rate.
Test result is as shown in table 2.
2 wound healing rate of table
| 7 days wound healing rates | 14 days wound healing rates | |
| Embodiment 1 | 3.8% | 55.6% |
| Embodiment 2 | 5.2% | 62.3% |
| Embodiment 3 | 4.8% | 64.7% |
| Embodiment 4 | 5.4% | 64.2% |
| Embodiment 5 | 5.0% | 65.5% |
| Embodiment 6 | 5.6% | 65.3% |
| Embodiment 7 | 6.0% | 69.3% |
| Embodiment 8 | 8.0% | 71.2% |
| Embodiment 9 | 9.8% | 75.4% |
| Control group | 4.4% | 48.7% |
As seen from the above table, the dressing composition provided by the invention for promoting wound healing has promotes wound to be cured well
The ability of conjunction, although 7 days healing rates are not much different with control group, healing rate is obviously improved compared with control group within 14 days,
Highest healing rate is up to 75.4%.
Claims (10)
1. a kind of dressing composition for promoting wound healing, which is characterized in that including preservative, filmogen and solvent；
The solvent is glycerol and/or water；
The filmogen includes component A and/or component B composition；
The component A includes carbomer and triethanolamine；
The component B includes polyvinyl alcohol.
2. the dressing composition according to claim 1 for promoting wound healing, which is characterized in that the preservative is
P-hydroxybenzoate.
3. the dressing composition according to claim 1 for promoting wound healing, which is characterized in that further include that cell is repaired
Multiple agent.
4. the dressing composition according to claim 1 for promoting wound healing, which is characterized in that by percentage by weight
The cell repair agent of the preservative, 0-3% of filmogen, 0.05-0.15% than the 0.3-5% of meter and 91.85-99.65%
Solvent composition.
5. the dressing composition according to claim 1 for promoting wound healing, which is characterized in that the carbomer
Preparation method is that macromole evocating agent, n-butyl acrylate, solvent, divalent copper catalyst and organic are sequentially added into container
Alkali replaces inert gas, and liquid nitrogen cool down-vacuumizes-thaw cycles 1-5 times, is warming up to 60-90 DEG C, reaction 24-36 hours, fastly
Fast column chromatography, is added methanol, there is Precipitation, filter, and takes solid, dry to get carbomer；
Any one or more of solvent in DMF, DME, MTBE and methyl phenyl ethers anisole described in the preparation method of the carbomer；
The organic base is any one in triethylamine, diisopropylamine, tert-butylmethylamine, three (2- methylaminoethyl) amine
Kind is a variety of；
The divalent copper catalyst is selected from copper fluoride, copper chloride, copper bromide, cupric iodide, copper acetate, copper citrate, copper 8-hydroxyquinolinate, wine
One of stone acid copper, copper tetrafluoroborate, Cupric salicylate, 2 ethyl hexanoic acid copper, terephthalic acid (TPA) copper are a variety of；
The quality of solvent described in the preparation method of the carbomer is 3-8 times of n-butyl acrylate；
The additive amount of the macromole evocating agent is the 0.02-0.05% of n-butyl acrylate quality；
The additive amount of the divalent copper catalyst is the 1-15% of macromole evocating agent quality；
The additive amount of the organic base is the 8-15% of macromole evocating agent quality.
6. the dressing composition according to claim 5 for promoting wound healing, which is characterized in that the macromolecular is drawn
Send out agent the preparation method is as follows:
(1) by 2- isobutyl ethyl bromide, 3- (trimethoxysilyl) propyl acrylate, 4,4'- dinonyl -2,2'- two
Thiazole, cupric salt, methyl phenyl ethers anisole are added in reactor, replace inert gas, and liquid nitrogen cool down-vacuumizes-thaw cycles 1-5 times,
It is warming up to 60-90 DEG C, is reacted 24-36 hours, rapid column chromatography, vacuum distillation removes solvent, obtains intermediate；
Any one of the cupric salt in copper chloride, copper bromide, copper fluoride, cupric iodide；
The 2- isobutyl ethyl bromide: 4,4'- dinonyl -2,2'- dithiazole: cupric salt: 3- (trimethoxysilyl)
The ratio between mole of propyl acrylate is 1:(1-1.2): (0.2-0.5): (15-25)；
The additive amount of the methyl phenyl ethers anisole is the 10-15% of 3- (trimethoxysilyl) propyl acrylate quality；
(2) intermediate, potassium fluoride, 3- (trimethoxysilyl) propyl acrylate, tert-butyl phenol and solvent are added
In reactor, inert gas is replaced, the tetrahydrofuran solution and 2- bromine isobutyl of tetrabutyl ammonium fluoride are sequentially added under ice-water bath
Acylbromide is back to room temperature naturally, is stirred to react 12-24 hours, filters out solid, rapid column chromatography, and vacuum distillation removes solvent, dichloro
Methane/petroleum ether system recrystallization, filters out liquid, obtained solid is macromole evocating agent；
Solvent described in the preparation method step (2) of the macromole evocating agent is tetrahydrofuran or ether；
The potassium fluoride: 3- (trimethoxysilyl) propyl acrylate: the molar ratio of tert-butyl phenol is (15-20):
(8-12): 1；
The additive amount of solvent described in the preparation method step (2) of the macromole evocating agent is 10-15 times of intermediate weight；
3- (trimethoxysilyl) propyl acrylate described in the preparation method step (2) of the macromole evocating agent
Additive amount is the 8-15% of solvent quality；
The concentration of the tetrahydrofuran solution of the tetrabutyl ammonium fluoride is 0.8-1.2mol/L；
The additive amount of the tetrabutyl ammonium fluoride is the 5-12% of 3- (trimethoxysilyl) propyl acrylate mole；
The additive amount of the 2- bromine isobutyl acylbromide is the 1-1.2 of 3- (trimethoxysilyl) propyl acrylate mole
Times.
7. the dressing composition according to claim 6 for promoting wound healing, which is characterized in that the tert-butyl benzene
Phenol is selected from 2,3- DI-tert-butylphenol compounds, 2,4- DI-tert-butylphenol compounds, 2,5- DI-tert-butylphenol compounds, 2,6 DI-tert-butylphenol compounds, 3,4-
It is DI-tert-butylphenol compounds, 3,5- DI-tert-butylphenol compounds, 2-TBP, 3- tert-butyl phenol, any in 4-TBP
It is a kind of.
8. the dressing composition according to claim 1 for promoting wound healing, which is characterized in that the polyvinyl alcohol
Alcoholysis degree be 98.0-99.0mol% and viscosity is 3.2-3.8mPas.
9. the dressing composition according to claim 3 for promoting wound healing, which is characterized in that the cell repair
Agent includes the composition with cell repair function.
10. the dressing composition according to claim 9 for promoting wound healing, which is characterized in that the cell
Renovation agent further includes 3- hydroxyl -4- pyridinone derivatives, and the 3- hydroxyl -4- pyridinone derivatives general structure is as follows:
Wherein, R1For H or methyl；R2In methyl, ethyl, n-propyl, isopropyl any one；R3Selected from H, methyl, second
Base, n-propyl, any one in isopropyl.
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| US11446256B1 (en) | 2021-08-20 | 2022-09-20 | Advantice Health, Llc | Aqueous wound healing formulation |
| CN117159782A (en) * | 2023-10-12 | 2023-12-05 | 湖南玉津医疗科技有限公司 | Porous sponge hemostatic dressing and preparation method thereof |
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| CN117159782B (en) * | 2023-10-12 | 2024-03-08 | 湖南玉津医疗科技有限公司 | Porous sponge hemostatic dressing and preparation method thereof |
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