CN105497975A - Preparation method and application of medical composite hydrogel dressing - Google Patents
Preparation method and application of medical composite hydrogel dressing Download PDFInfo
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- CN105497975A CN105497975A CN201510955042.5A CN201510955042A CN105497975A CN 105497975 A CN105497975 A CN 105497975A CN 201510955042 A CN201510955042 A CN 201510955042A CN 105497975 A CN105497975 A CN 105497975A
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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
- A61L26/0023—Polysaccharides
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- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- 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
-
- 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
-
- 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
- A61L26/008—Hydrogels or hydrocolloids
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/60—Materials for use in artificial skin
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- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/04—Contact lenses for the eyes
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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
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
Abstract
The invention provides medical composite hydrogel dressing which is prepared from hyaluronic acid, sodium citrate, a cross-linking agent, an aloe solution, a vitamin E solution and an alkaline solution. The medical composite hydrogel dressing contains sodium citrate which can make the medical composite hydrogel dressing have good mechanical properties. By means of cooperation of sodium citrate and other preparation raw materials, the obtained medical composite hydrogel dressing has good tensile properties and gel strength. Besides, the medical composite hydrogel dressing also contains hyaluronic acid which can make the medical composite hydrogel dressing have good medical properties such as adhesion, moisture retention, lubricity, anti-inflammatory performance and wound healing promotion. The invention further provides a preparation method and application of the medical composite hydrogel dressing.
Description
Technical field
The present invention relates to gel technique field, particularly relate to a kind of preparation method and application thereof of medical composite aquogel dressing.
Background technology
The biogel of occurring in nature is vulnerable to External Force Acting makes the network structure of its inside be destroyed, develop into fluid, after external force stops, reverting to semisolid gel structure again, this phenomenon is called as thixotropy, and the thixotropy of Native Gel is unfavorable for its extensive use.Hydrogel (hyfrogel) utilizes chemical means that high molecular crosslink is become tridimensional network, and liquid medium is filled with in cancellated hole, liquid medium and macromolecule network structure have affinity, the inside is enclosed in by macromolecule network structure, lose mobility, therefore hydrogel can utilize slow release sealing liquid to realize some function.Hydrogels is similar to natural Native Gel tissue, but it can keep original form under external force, has certain resistance and elasticity, and the liquid medium in energy effective sealing gel, make it obtain and apply widely.
Application number be 201510262702.1 Chinese patent disclose a kind of preparation method of medical aquogel, comprise the following steps: (1) is removed ionized water 20 ~ 30 weight portion and poured in reactor, reactor is heated, then in reactor, slowly add pectin from lemon peel 13 ~ 15 weight portion, gelatin 5 ~ 8 weight portion, while adding pectin from lemon peel and gelatin, carry out mechanical agitation; (2) after adding pectin from lemon peel and gelatin, continue stirring 10 ~ 15min, chitosan 10 ~ 14 weight portion, soybean oligo saccharide 3 ~ 6 weight portion, polycaprolactone 4 ~ 8 weight portion, chlorhexidine acetate 6 ~ 9 weight portion is added again in reactor, also carry out mechanical agitation while adding even, churned mechanically rotating speed is 100 ~ 150 revs/min; (3) after above-mentioned material has mixed, hydrogel is cooled to room temperature, namely obtains medical aquogel.This medical aquogel that prior art provides has good breathability and biocompatibility; Have no side effect in medical and there is higher swelling ratio.But tensile strength and the gel strength of this medical aquogel are poor, in transport and use procedure, fracture and fragmentation easily occur, application is inconvenience comparatively.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of preparation method and application thereof of medical composite aquogel dressing, medical composite aquogel dressing provided by the invention has good tensile property and gel strength.
The invention provides a kind of medical composite aquogel dressing, prepared by the material comprising hyaluronic acid, sodium citrate, cross-linking agent, aloe solution, vitamin E solution and alkaline solution.
Preferably, the mass ratio of described hyaluronic acid and sodium citrate is 78:(1 ~ 5);
The mass ratio of described hyaluronic acid and cross-linking agent is 1000:(1 ~ 20).
Preferably, described cross-linking agent is BDDE.
Preferably, in described aloe solution, the mass concentration of Aloe is 0.5% ~ 2%;
In described vitamin E solution, the mass concentration of vitamin E is 1% ~ 3%.
Containing sodium citrate in medical composite aquogel dressing provided by the invention, sodium citrate can make medical composite aquogel dressing have good mechanical property, the present invention by sodium citrate and other raw materials with the use of, make the medical composite aquogel dressing obtained have good tensile property and gel strength.In addition, also containing hyaluronic acid in medical composite aquogel dressing provided by the invention, hyaluronic acid can make medical composite aquogel dressing have good medical performance, as performances such as viscoelasticity, moisture retention, lubricity, anti-inflammatory, wound healings.
The invention provides the preparation method of the medical composite aquogel dressing described in a kind of technique scheme, comprising:
Hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution are reacted, obtains product;
Described product soaked in mixed solution, obtain medical composite aquogel dressing, described mixed solution comprises aloe solution and vitamin E solution.
Preferably, the temperature of described reaction is 50 DEG C ~ 70 DEG C.
Preferably, the preparation method of described product is:
By hyaluronic acid and alkaline solution mixing, obtain mixed liquor;
By described mixed liquor and sodium citrate mixing, obtain mixture;
Described mixture and cross-linking agent are reacted, obtains product.
Preferably, after described hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution have reacted, also comprised:
The reaction solution obtained is carried out successively evaporate, dry, washing and after drying, obtain product.
Preferably, the mass ratio of described product and mixed solution is 5:(0.5 ~ 2.5).
Method provided by the invention have employed sodium citrate in the process of the medical composite aquogel dressing of preparation, and the preparation of medical composite aquogel dressing is carried out with the use of other raw materials, make the medical composite aquogel dressing prepared have good tensile property and gel strength.Experimental result shows, the gel strength of the medical composite aquogel dressing that method provided by the invention prepares is 270g ~ 392g.
In addition, method provided by the invention additionally uses hyaluronic acid in the process of the medical composite aquogel dressing of preparation, and hyaluronic use can make medical composite aquogel dressing have good medical performance.
The invention provides a kind of medical composite aquogel dressing and prepare the application in tissue filling agent, medicinal slow release agent, the embedding medium of enzyme, contact lenses, artificial blood plasma, artificial skin or tissue engineering bracket material, described medical composite aquogel dressing is the medical composite aquogel dressing described in technique scheme, or the medical composite aquogel dressing that the method described in technique scheme prepares.
Containing hyaluronic acid and sodium citrate in medical composite aquogel dressing provided by the invention, and also can carry out biodegradation containing other composition also inanimate object toxicity in medical composite aquogel dressing, make this medical composite aquogel dressing while having good tensile property, gel strength, also have certain medical performance, can be applicable to biologic medical field.
Accompanying drawing explanation
In order to be illustrated more clearly in the embodiment of the present invention or technical scheme of the prior art, be briefly described to the accompanying drawing used required in embodiment or description of the prior art below, apparently, accompanying drawing in the following describes is only embodiments of the invention, for those of ordinary skill in the art, under the prerequisite not paying creative work, other accompanying drawing can also be obtained according to the accompanying drawing provided.
Fig. 1 is the tensile property test collection of illustrative plates of the medical composite aquogel dressing that the embodiment of the present invention 1 prepares.
Detailed description of the invention
Be clearly and completely described to the technical scheme in the embodiment of the present invention below, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
The invention provides a kind of medical composite aquogel dressing, prepared by the material comprising hyaluronic acid, sodium citrate, cross-linking agent, aloe solution, vitamin E solution and alkaline solution.
The raw materials of medical composite aquogel dressing provided by the invention comprises hyaluronic acid, and described hyaluronic acid can make medical composite aquogel dressing provided by the invention have the performance of good viscoelasticity, moisture retention, lubricity, anti-inflammatory and wound healing.The present invention does not have special restriction to described hyaluronic source, adopts hyaluronic acid well known to those skilled in the art, can be bought and obtain, the hyaluronic acid of the Hylaform series provided as adopted Genzyme company of the U.S. by market.
The raw materials of medical composite aquogel dressing provided by the invention comprises sodium citrate, described sodium citrate is natural pH adjusting agent, be easy to obtain, stable performance, there is good water solublity, biodegradable, the medical composite aquogel dressing that the present invention can be made to prepare has good corrosion resistance and stability, but also medical composite aquogel dressing provided by the invention can be made to have good tensile property and gel strength.The source of the present invention to described sodium citrate does not have special restriction, can be bought and obtain, the sodium citrate of the DL series provided as adopted SIGMA company by market.
The raw materials of medical composite aquogel dressing provided by the invention comprises cross-linking agent.In an embodiment of the present invention, described cross-linking agent can be BDDE (BDDE).In an embodiment of the present invention, described BDDE is safer, avirulence, has no side effect.
The raw materials of medical composite aquogel dressing provided by the invention comprises aloe solution.In an embodiment of the present invention, described aloe solution is Aloe vulgaris solution.In an embodiment of the present invention, in described aloe solution, the mass concentration of Aloe is 0.5% ~ 2%; In other examples, in described aloe solution, the mass concentration of Aloe is 1% ~ 1.5%.In an embodiment of the present invention, the solvent in described aloe solution is ethanol; In other examples, the solvent in described aloe solution is dehydrated alcohol.In an embodiment of the present invention, the preparation method of described aloe solution is:
Hot water extraction is adopted to prepare Aloe extract;
By described Aloe extract and solvent mixing, obtain aloe solution.
In an embodiment of the present invention, described Aloe is Aloe vulgaris.In an embodiment of the present invention, processed can be carried out to Aloe by before described Aloe extraction.In an embodiment of the present invention, described processed temperature is 50 DEG C ~ 70 DEG C; In other examples, the temperature of described processed is 55 DEG C ~ 65 DEG C; In a further embodiment, the temperature of described processed is 60 DEG C.In an embodiment of the present invention, the time of described processed is 3 hours ~ 5 hours; In other examples, the time of described processed is 3.5 hours ~ 4.5 hours; In a further embodiment, the time of described processed is 4 hours.
The present invention does not have special restriction to the concrete grammar that described Hot water extraction prepares Aloe extract, adopts the effective ingredient in the technical scheme extraction Aloe of Hot water extraction well known to those skilled in the art.In an embodiment of the present invention, the concrete operation step of described Hot water extraction is:
Carry out reflux, extract, by behind Flos Aloe footpath and water mixing, obtain extracting solution;
Filter after described extracting solution centrifugalize, obtain Aloe extract.
In an embodiment of the present invention, processed can be carried out before the reflux, extract, of described Flos Aloe footpath according to the method described in technique scheme.The source of the present invention to described Flos Aloe footpath does not have special restriction, can be bought and obtain, the Aloe Barbadensis Miller flower footpath provided as used Sanya, Hainan scientific research and production base by market.
In an embodiment of the present invention, reflux, extract, can be carried out by behind Flos Aloe footpath and distilled water mixing.In an embodiment of the present invention, the temperature of described reflux, extract, is 90 DEG C ~ 110 DEG C; In other examples, the temperature of described reflux, extract, is 95 DEG C ~ 105 DEG C; In a further embodiment, the temperature of described reflux, extract, is 100 DEG C.
In an embodiment of the present invention, after obtaining extracting solution, filter after described extracting solution centrifugalize, obtain Aloe extract.In an embodiment of the present invention, the centrifugal rotational speed in described centrifugal separation processes is 4500 revs/min ~ 5500 revs/min; In other examples, the centrifugal rotational speed in described centrifugal separation processes is 4800 revs/min ~ 5200 revs/min; In a further embodiment, the centrifugal rotational speed in described centrifugal separation processes is 5000 revs/min.In an embodiment of the present invention, the time of described centrifugalize is 5 minutes ~ 15 minutes; In other examples, the time of described centrifugalize is 8 minutes ~ 12 minutes; In a further embodiment, the time of described centrifugalize is 10 minutes.
In an embodiment of the present invention, the product after described extracting solution centrifugalize is filtered, remove supernatant Flos Aloe in the product after centrifugalize.In an embodiment of the present invention, filter cloth can be adopted to filter.In an embodiment of the present invention, the order number of described filter cloth is 350 order ~ 450 orders; In other examples, the order number of described filter cloth is 380 order ~ 420 orders; In a further embodiment, the order number of described filter cloth is 400 orders.
In an embodiment of the present invention, the operation of above-mentioned reflux, extract, centrifugalize and filtration can be repeated, filter after the Aloe extract at every turn obtained is merged, then carry out centrifugal treating with after the residue in water cleaning amalgamation liquid, use filtered through gauze again, obtain Aloe extract.
In the present invention, described solvent is consistent with the solvent in aloe solution described in technique scheme, does not repeat them here.In an embodiment of the present invention, the consumption of described solvent makes the mass concentration of Aloe in the aloe solution prepared be 0.5% ~ 2%.
The raw materials of medical composite aquogel dressing provided by the invention comprises vitamin E solution.In an embodiment of the present invention, in described vitamin E solution, the mass concentration of vitamin E is 1% ~ 3%; In other examples, in described vitamin E solution, the mass concentration of vitamin E is 1.5% ~ 2.5%; In a further embodiment, in described vitamin E solution, the mass concentration of vitamin E is 2%.In an embodiment of the present invention, the solvent in described vitamin E solution is ethanol; In other examples, the solvent in described vitamin E solution is dehydrated alcohol.The source of the present invention to described vitamin E solution does not have special restriction, adopts solution preparation method well known to those skilled in the art, vitamin E is prepared into solution.The source of the present invention to described vitamin E does not have special restriction, and can be bought by market and obtain, the purity provided as adopted Beijing Chemical Plant is analytically pure vitamin E.
The raw materials of medical composite aquogel dressing provided by the invention comprises alkaline solution.In an embodiment of the present invention, the mass concentration of described alkaline solution neutral and alkali material is 0.1% ~ 6%; In other examples, the mass concentration of described alkaline solution neutral and alkali material is 0.5% ~ 5%; In a further embodiment, the mass concentration of described alkaline solution neutral and alkali material is 1% ~ 3%.In an embodiment of the present invention, the alkaline matter in described alkaline solution is alkali metal hydroxide; In other examples, the alkaline matter in described alkaline solution is sodium hydroxide.In an embodiment of the present invention, the solvent in described alkaline solution is water.
In an embodiment of the present invention, the mass ratio of described hyaluronic acid and sodium citrate is 78:(1 ~ 5); In other examples, the mass ratio of described hyaluronic acid and sodium citrate is 78:(2 ~ 4); In a further embodiment, the mass ratio of described hyaluronic acid and sodium citrate is 78:(2.5 ~ 3.5).
In an embodiment of the present invention, the mass ratio of described hyaluronic acid and cross-linking agent is 1000:(1 ~ 20); In other examples, the mass ratio of described hyaluronic acid and cross-linking agent is 1000:(5 ~ 15); In a further embodiment, the mass ratio of described hyaluronic acid and cross-linking agent is 1000:(8 ~ 12).
In an embodiment of the present invention, in described aloe solution, Aloe and hyaluronic mass ratio are (1 ~ 2): 64; In other examples, in described aloe solution, Aloe and hyaluronic mass ratio are (1.2 ~ 1.8): 64; In a further embodiment, in described aloe solution, Aloe and hyaluronic mass ratio are (1.4 ~ 1.6): 64.In an embodiment of the present invention, in described vitamin E solution, vitamin E and hyaluronic mass ratio are (1 ~ 1.5): 1280; In other examples, in described vitamin E solution, vitamin E and hyaluronic mass ratio are (1.1 ~ 1.4): 1280; In a further embodiment, in described vitamin E solution, vitamin E and hyaluronic mass ratio are (1.2 ~ 1.3): 1280.In an embodiment of the present invention, described alkaline solution neutral and alkali material and hyaluronic mass ratio are 1:(4 ~ 6); In other examples, described alkaline solution neutral and alkali material and hyaluronic mass ratio are 1:(4.5 ~ 5.5); In a further embodiment, described alkaline solution neutral and alkali material and hyaluronic mass ratio are 1:(4.8 ~ 5.2).
The invention provides a kind of preparation method of medical composite aquogel dressing, comprising:
Hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution are reacted, obtains product;
Described product soaked in mixed solution, obtain medical composite aquogel dressing, described mixed solution comprises aloe solution and vitamin E solution.
Hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution react by the present invention, obtain product.In the present invention, kind and the consumption of the kind of described hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution and consumption and hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution described in technique scheme are consistent, do not repeat them here.
In an embodiment of the present invention, the temperature of described reaction is 50 DEG C ~ 70 DEG C; In other examples, the temperature of described reaction is 55 DEG C ~ 65 DEG C; In a further embodiment, the temperature of described reaction is 60 DEG C.In an embodiment of the present invention, the time of described reaction is 5 hours ~ 7 hours; In other examples, the time of described reaction is 5.5 hours ~ 6.5 hours; In a further embodiment, the time of described reaction is 6 hours.In an embodiment of the present invention, can react under the condition stirred.
In an embodiment of the present invention, the preparation method of described product is:
By hyaluronic acid and alkaline solution mixing, obtain mixed liquor;
By described mixed liquor and sodium citrate mixing, obtain mixture;
Described mixture and cross-linking agent are reacted, obtains product.
In an embodiment of the present invention, in described mixed liquor, hyaluronic mass concentration is 1% ~ 8%; In other examples, in described mixed liquor, hyaluronic mass concentration is 2% ~ 7%; In a further embodiment, in described mixed liquor, hyaluronic mass concentration is 3% ~ 6%.
In an embodiment of the present invention, sodium citrate can be added in described mixed liquor, obtain mixture.In an embodiment of the present invention, by described mixed liquor and sodium citrate mixing under the condition stirred, mixture can be obtained.
In an embodiment of the present invention, cross-linking agent can be joined in described mixture and react, obtain product.In an embodiment of the present invention, after hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution have reacted, the reaction solution obtained is carried out successively evaporate, dry, washing and after drying, obtain product.In an embodiment of the present invention, the method for described evaporation is rotary evaporation in vacuo.In an embodiment of the present invention, the temperature of described evaporation is 35 DEG C ~ 40 DEG C.In an embodiment of the present invention, the time of described evaporation makes the moisture in the evaporate obtained be 40% ~ 60%; In other examples, the time of described evaporation makes the moisture in the evaporate obtained be 45% ~ 55%; In a further embodiment, the time of described evaporation makes the moisture in the evaporate obtained be 50%.
In an embodiment of the present invention, after being evaporated by reaction solution, dry temperature is 35 DEG C ~ 40 DEG C.In an embodiment of the present invention, dry in vacuum drying oven after reaction solution can being evaporated.
In an embodiment of the present invention, dried product is washed, remove residual alkaline matter.In an embodiment of the present invention, the reagent of described washing is phosphate solution and water.In an embodiment of the present invention, the mass ratio of described phosphate solution and water is (2.5 ~ 5): 100; In other examples, the mass ratio of described phosphate solution and water is (3 ~ 4): 100.In an embodiment of the present invention, the mass concentration of described phosphate solution is 7% ~ 8%; In other examples, the mass concentration of described phosphate solution is 7.5%.In an embodiment of the present invention, described water is distilled water.In an embodiment of the present invention, the number of times of described washing makes the pH value of the washed product obtained be 6 ~ 7.5; In other examples, the number of times of described washing makes the pH value of the washed product obtained be 6.5 ~ 7.
In an embodiment of the present invention, the product after washing is carried out after drying, obtains product.In an embodiment of the present invention, the temperature of the product after washing being carried out after drying is 35 DEG C ~ 40 DEG C.In an embodiment of the present invention, the product after washing can be dried in vacuum drying oven.
After obtaining product, described product is soaked by the present invention in mixed solution, obtains medical composite aquogel dressing; Described mixed solution comprises aloe solution and vitamin E solution.In the present invention, the kind of the kind of described aloe solution and vitamin E solution and source and aloe solution described in technique scheme and vitamin E solution with originate consistent, do not repeat them here.In an embodiment of the present invention, the mass ratio of described aloe solution and vitamin E solution is (20 ~ 50): (1 ~ 1.5); In other examples, the mass ratio of described aloe solution and vitamin E solution is (25 ~ 45): (1.1 ~ 1.4); In a further embodiment, the mass ratio of described aloe solution and vitamin E solution is (30 ~ 40): (1.2 ~ 1.3).In an embodiment of the present invention, the mass ratio of described product and mixed solution is 5:(0.5 ~ 2.5); In other examples, the mass ratio of described product and mixed solution is 5:(1 ~ 2); In a further embodiment, the mass ratio of described product and mixed solution is 5:(1.4 ~ 1.6).
In an embodiment of the present invention, the temperature of described immersion is 20 DEG C ~ 30 DEG C; In other examples, the temperature of described immersion is 22 DEG C ~ 28 DEG C; In a further embodiment, the temperature of described immersion is 24 DEG C ~ 26 DEG C.In an embodiment of the present invention, the time of described immersion is 10 hours ~ 15 hours; In other examples, the time of described immersion is 12 hours ~ 13 hours.
The invention provides a kind of medical composite aquogel dressing and prepare the application in tissue filling agent, medicinal slow release agent, the embedding medium of enzyme, contact lenses, artificial blood plasma, artificial skin or tissue engineering bracket material, described medical composite aquogel dressing is the medical composite aquogel dressing described in technique scheme, or the medical composite aquogel dressing that the method described in technique scheme prepares.
Containing hyaluronic acid and sodium citrate in medical composite aquogel dressing provided by the invention, and also can carry out biodegradation containing other composition also inanimate object toxicity in medical composite aquogel dressing, make this medical composite aquogel dressing while having good tensile property, gel strength, also have certain medical performance.According to the standard of People's Republic of China (PRC) pharmaceuticals industry standard YY0308-2004 " Medical sodium hyaluronate gel ", test the tensile property of medical composite aquogel dressing provided by the invention; Test result is, medical composite aquogel dressing provided by the invention has good tensile property.
The Texture instrument of the LFRA model adopting Brookfield company of the U.S. to provide, tests the gel strength of medical composite aquogel dressing provided by the invention; Test result is, the gel strength of medical composite aquogel dressing provided by the invention is 270g ~ 392g, has higher intensity.
Raw material used by following examples of the present invention is commercial goods, the Hylaform product that hyaluronic acid used provides for Genzyme company of the U.S., the DL product that sodium citrate used provides for SIGMA company, used 1, the 2425-79-8 product that 4-butanediol diglycidyl ether (BDDE) provides for Mike woods company, Aloe Barbadensis Miller flower footpath used provides for Sanya, Hainan scientific research and production base, and vitamin E solution used provides for Aladdin.
Embodiment 1
Prepare the Aloe vulgaris solution that mass concentration is 0.5% by the following method:
4h is dried in Aloe Barbadensis Miller flower footpath in the baking oven of 60 DEG C, determines, wherein without after moisture, Flos Aloe footpath to be put in drying baker for subsequent use; Dried Flos Aloe footpath is placed in round-bottomed flask, in flask, add distilled water carry out reflux, extract, at 100 DEG C, by the extracting solution centrifugalize 10min under the rotating speed of 4800r/min obtained, the filtrate obtained is removed supernatant Flos Aloe through filter-cloth filtering, obtains polysaccharide clear liquid; 3 polysaccharide clear liquids are prepared according to the method described in technique scheme; Carry out centrifugal treating with after distilled water cleaning residue after the polysaccharide clear liquid prepared 3 times merges, the filtrate after centrifugal treating is used 400 order filter-cloth filterings again, obtain Aloe extract.
By Aloe extract dilute with water obtained above, obtain the Aloe vulgaris solution that mass concentration is 0.5%.
The mass concentration that the hyaluronic acid taking 10g joins 990g is dissolve completely in the sodium hydrate aqueous solution of 1.5%, obtains mixed liquor;
The sodium citrate adding 0.64g in described mixed liquor is uniformly mixed, and obtains mixture;
The BDDE adding 0.2g in described mixture stirring reaction 5 hours at 60 DEG C, obtains reaction solution;
Described reaction solution is placed in vacuum rotary evaporator at 37 DEG C, carries out rotary evaporation, obtain the product that water content is 50%;
Dry in the vacuum drying box of the product after rotary evaporation at 37 DEG C, obtain drying product;
Adopt phosphate solution and distilled water repeatedly to clean described oven dry product, remove sodium hydroxide wherein, obtain the washed product that pH value is 7;
The washed product obtained is dried at 37 DEG C in vacuum drying box, obtains desciccate;
Under room-temperature sterile condition, described desciccate is soaked 12 hours in mixed solution, obtain medical composite aquogel dressing; The mass ratio of described desciccate and mixed solution is 5:2, in described mixed solution mass concentration be 0.5% Aloe vulgaris solution and mass concentration be the mass ratio of the vitamin E solution of 3% be 20:1.
According to the method described in technique scheme, the tensile property of the medical composite aquogel dressing that the test embodiment of the present invention 1 prepares, as shown in Figure 1, Fig. 1 is the tensile property test collection of illustrative plates of the medical composite aquogel dressing that the embodiment of the present invention 1 prepares to test result.The change in displacement of medical composite aquogel dressing after increasing according to pressure in Fig. 1, the medical composite aquogel dressing that the embodiment of the present invention 1 prepares has good tensile property.
According to the method described in technique scheme, the gel strength of the medical composite aquogel dressing that the test embodiment of the present invention 1 prepares; Test result is, the gel strength of the medical composite aquogel dressing that the embodiment of the present invention 1 prepares is 270g.
Embodiment 2
The Aloe vulgaris solution that mass concentration is 0.5% is prepared according to the method described in embodiment 1.
The mass concentration that the hyaluronic acid taking 80g joins 920g is dissolve completely in the sodium hydrate aqueous solution of 4.5%, obtains mixed liquor;
The sodium citrate adding 1.03g in described mixed liquor is uniformly mixed, and obtains mixture;
The BDDE adding 0.08g in described mixture stirring reaction 5 hours at 50 DEG C, obtains reaction solution;
Described reaction solution is placed in vacuum rotary evaporator at 35 DEG C, carries out rotary evaporation, obtain the product that water content is 50%;
Dry in the vacuum drying box of the product after rotary evaporation at 35 DEG C, obtain drying product;
Adopt phosphate solution and distilled water repeatedly to clean described oven dry product, remove sodium hydroxide wherein, obtain the washed product that pH value is 6;
The washed product obtained is dried at 35 DEG C in vacuum drying box, obtains desciccate;
Under room-temperature sterile condition, described desciccate is soaked 12 hours in mixed solution, obtain medical composite aquogel dressing; The mass ratio of described desciccate and mixed solution is 5:2.5, in described mixed solution mass concentration be 0.5% Aloe vulgaris solution and mass concentration be the mass ratio of the vitamin E solution of 1% be 30:1.5.
According to the method described in technique scheme, the tensile property of the medical composite aquogel dressing that the test embodiment of the present invention 2 prepares, test result shows, the medical composite aquogel dressing that the embodiment of the present invention 2 prepares has good tensile property.
According to the method described in technique scheme, the gel strength of the medical composite aquogel dressing that the test embodiment of the present invention 2 prepares; Test result is, the gel strength of the medical composite aquogel dressing that the embodiment of the present invention 2 prepares is 392g.
Embodiment 3
The Aloe vulgaris solution that mass concentration is 0.5% is prepared according to the method described in embodiment 1.
The mass concentration that the hyaluronic acid taking 50g joins 950g is dissolve completely in the sodium hydrate aqueous solution of 6%, obtains mixed liquor;
The sodium citrate adding 0.8g in described mixed liquor is uniformly mixed, and obtains mixture;
The BDDE adding 0.03g in described mixture stirring reaction 5 hours at 70 DEG C, obtains reaction solution;
Described reaction solution is placed in vacuum rotary evaporator at 40 DEG C, carries out rotary evaporation, obtain the product that water content is 50%;
Dry in the vacuum drying box of the product after rotary evaporation at 40 DEG C, obtain drying product;
Adopt phosphate solution and distilled water repeatedly to clean described oven dry product, remove sodium hydroxide wherein, obtain the washed product that pH value is 7.5;
The washed product obtained is dried at 40 DEG C in vacuum drying box, obtains desciccate;
Under room-temperature sterile condition, described desciccate is soaked 12 hours in mixed solution, obtain medical composite aquogel dressing; The mass ratio of described desciccate and mixed solution is 5:3, in described mixed solution mass concentration be 0.5% Aloe vulgaris solution and mass concentration be the mass ratio of the vitamin E solution of 1% be 25:1.2.
According to the method described in technique scheme, the tensile property of the medical composite aquogel dressing that the test embodiment of the present invention 3 prepares, test result shows, the medical composite aquogel dressing that the embodiment of the present invention 3 prepares has good tensile property.
According to the method described in technique scheme, the gel strength of the medical composite aquogel dressing that the test embodiment of the present invention 3 prepares; Test result is, the gel strength of the medical composite aquogel dressing that the embodiment of the present invention 3 prepares is 296g.
Embodiment 4
The Aloe vulgaris solution that mass concentration is 2.5% is prepared according to the method described in embodiment 1.
The mass concentration that the hyaluronic acid taking 60g joins 940g is dissolve completely in the sodium hydrate aqueous solution of 3.5%, obtains mixed liquor;
The sodium citrate adding 0.8g in described mixed liquor is uniformly mixed, and obtains mixture;
The BDDE adding 0.05g in described mixture stirring reaction 5 hours at 65 DEG C, obtains reaction solution;
Described reaction solution is placed in vacuum rotary evaporator at 36 DEG C, carries out rotary evaporation, obtain the product that water content is 50%;
Dry in the vacuum drying box of the product after rotary evaporation at 36 DEG C, obtain drying product;
Adopt phosphate solution and distilled water repeatedly to clean described oven dry product, remove sodium hydroxide wherein, obtain the washed product that pH value is 6.5;
The washed product obtained is dried at 36 DEG C in vacuum drying box, obtains desciccate;
Under room-temperature sterile condition, described desciccate is soaked 12 hours in mixed solution, obtain medical composite aquogel dressing; The mass ratio of described desciccate and mixed solution is 5:2.5, in described mixed solution mass concentration be 2.5% Aloe vulgaris solution and mass concentration be the mass ratio of the vitamin E solution of 3% be 20:1.5.
According to the method described in technique scheme, the tensile property of the medical composite aquogel dressing that the test embodiment of the present invention 4 prepares, test result shows, the medical composite aquogel dressing that the embodiment of the present invention 4 prepares has good tensile property.
According to the method described in technique scheme, the gel strength of the medical composite aquogel dressing that the test embodiment of the present invention 4 prepares; Test result is, the gel strength of the medical composite aquogel dressing that the embodiment of the present invention 4 prepares is 387g.
As seen from the above embodiment, the invention provides a kind of medical composite aquogel dressing, prepared by the material comprising hyaluronic acid, sodium citrate, cross-linking agent, aloe solution, vitamin E solution and alkaline solution.Containing sodium citrate in medical composite aquogel dressing provided by the invention, sodium citrate can make hydrogel have good mechanical property, the present invention by sodium citrate and other raw materials with the use of, make the medical composite aquogel dressing obtained have good tensile property and gel strength.In addition, also containing hyaluronic acid in medical composite aquogel dressing provided by the invention, hyaluronic acid can make medical composite aquogel dressing have good medical performance, as performances such as viscoelasticity, moisture retention, lubricity, anti-inflammatory, wound healings.
Claims (10)
1. a medical composite aquogel dressing, is prepared by the material comprising hyaluronic acid, sodium citrate, cross-linking agent, aloe solution, vitamin E solution and alkaline solution.
2. medical composite aquogel dressing according to claim 1, is characterized in that, the mass ratio of described hyaluronic acid and sodium citrate is 78:(1 ~ 5);
The mass ratio of described hyaluronic acid and cross-linking agent is 1000:(1 ~ 20).
3. medical composite aquogel dressing according to claim 1, is characterized in that, described cross-linking agent is BDDE.
4. medical composite aquogel dressing according to claim 1, is characterized in that, in described aloe solution, the mass concentration of Aloe is 0.5% ~ 2%;
In described vitamin E solution, the mass concentration of vitamin E is 1% ~ 3%.
5. a preparation method for the medical composite aquogel dressing in Claims 1 to 4 described in any one, comprising:
Hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution are reacted, obtains product;
Described product soaked in mixed solution, obtain medical composite aquogel dressing, described mixed solution comprises aloe solution and vitamin E solution.
6. method according to claim 5, is characterized in that, the temperature of described reaction is 50 DEG C ~ 70 DEG C.
7. method according to claim 5, is characterized in that, the preparation method of described product is:
By hyaluronic acid and alkaline solution mixing, obtain mixed liquor;
By described mixed liquor and sodium citrate mixing, obtain mixture;
Described mixture and cross-linking agent are reacted, obtains product.
8. method according to claim 5, is characterized in that, after described hyaluronic acid, sodium citrate, cross-linking agent and alkaline solution have reacted, also comprises:
The reaction solution obtained is carried out successively evaporate, dry, washing and after drying, obtain product.
9. method according to claim 5, is characterized in that, the mass ratio of described product and mixed solution is 5:(0.5 ~ 2.5).
10. the application in tissue filling agent, medicinal slow release agent, the embedding medium of enzyme, contact lenses, artificial blood plasma, artificial skin or tissue engineering bracket material is being prepared in a medical composite aquogel dressing, described medical composite aquogel dressing is the medical composite aquogel dressing in Claims 1 to 4 described in any one, or the medical composite aquogel dressing that the method in claim 5 ~ 9 described in any one prepares.
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