CN105497975B - A kind of preparation method and applications of medical composite hydrogel dressing - Google Patents
A kind of preparation method and applications of medical composite hydrogel dressing Download PDFInfo
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- CN105497975B CN105497975B CN201510955042.5A CN201510955042A CN105497975B CN 105497975 B CN105497975 B CN 105497975B CN 201510955042 A CN201510955042 A CN 201510955042A CN 105497975 B CN105497975 B CN 105497975B
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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
-
- 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
-
- 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 present invention provides a kind of medical composite hydrogel dressing, are prepared by the material including hyaluronic acid, sodium citrate, crosslinking agent, aloe solution, vitamin E solution and alkaline solution.Contain sodium citrate in medical composite hydrogel dressing provided by the invention, sodium citrate can make medical composite hydrogel dressing have preferable mechanical property, the present invention by sodium citrate and other prepare being used cooperatively for raw material, so as to get medical composite hydrogel dressing have preferable tensile property and gel strength.In addition, also containing hyaluronic acid in medical composite hydrogel dressing provided by the invention, hyaluronic acid can make medical composite hydrogel dressing have preferable medical performance, such as viscoplasticity, moisture retention, lubricity, anti-inflammatory, wound healing performance.The present invention also provides a kind of preparation method and applications of medical composite hydrogel dressing.
Description
Technical field
The present invention relates to the preparation method of gel technique field more particularly to a kind of medical composite hydrogel dressing and its answer
With.
Background technology
Biogel in nature, which is vulnerable to the reticular structure that outer force effect keeps it internal, to be destroyed, and stream is evolved into
Body can revert to semisolid gel structure again after external force stops, and this phenomenon is referred to as thixotropy, and Native Gel touches
Denaturation is unfavorable for its extensive use.Hydrogel (hyfrogel) using chemical means by high molecular crosslink at tridimensional network,
And liquid medium is filled in the hole of reticular structure, liquid medium and macromolecule reticular structure are affinity, by high score
Sub- reticular structure is enclosed in the inside, loses mobility, therefore hydrogel can utilize sustained release sealing liquid to realize certain functions.Water
Gel is similar to the Native Gel tissue of nature, but it can keep original form under external force, has certain resistance
And elasticity, and the liquid medium in gel can be effectively sealed, so that it has been obtained wider application.
A kind of preparation method of medical aquogel is disclosed application No. is 201510262702.1 Chinese patent, including with
Lower step：(1) 20~30 parts by weight of ionized water are removed to pour into reactor, reactor is heated, then slowly into reactor
13~15 parts by weight of pectin from lemon peel, 5~8 parts by weight of gelatin are added, machinery is carried out while pectin from lemon peel and gelatin is added
Stirring；(2) after adding pectin from lemon peel and gelatin, continue 10~15min of stirring, then chitosan 10~14 is added into reactor
Parts by weight, 3~6 parts by weight of soyabean oligosaccharides, 4~8 parts by weight of polycaprolactone, 6~9 parts by weight of acetic acid chlorhexidine, addition it is same
When also to carry out mechanical agitation uniform, churned mechanically rotating speed is 100~150 revs/min；(3) after the completion of above-mentioned material mixing, by water
Gel is cooled to room temperature to get to medical aquogel.This medical aquogel that the prior art provides has good gas permeability
And biocompatibility；In medical it is without side-effects and have higher swelling ratio.But the tension of this medical aquogel is strong
Degree and gel strength are poor, and fracture is easy to happen during transport and use and is crushed, application is more inconvenient.
Invention content
In view of this, the purpose of the present invention is to provide a kind of preparation method of medical composite hydrogel dressing and its answering
With medical composite hydrogel dressing provided by the invention has preferable tensile property and gel strength.
The present invention provides a kind of medical composite hydrogel dressing, by including hyaluronic acid, sodium citrate, crosslinking agent, reed
The material of luxuriant growth solution, vitamin E solution and alkaline solution is prepared.
Preferably, the mass ratio of the hyaluronic acid and sodium citrate is 78：(1~5)；
The mass ratio of the hyaluronic acid and crosslinking agent is 1000：(1~20).
Preferably, the crosslinking agent is 1,4-butanediol diglycidyl ether.
Preferably, the mass concentration of aloe is 0.5%~2% in the aloe solution；
The mass concentration of vitamin E is 1%~3% in the vitamin E solution.
Contain sodium citrate in medical composite hydrogel dressing provided by the invention, sodium citrate can make medical Compound Water
Gel dressing have preferable mechanical property, the present invention by sodium citrate and other prepare being used cooperatively for raw material so that
The medical composite hydrogel dressing arrived has preferable tensile property and gel strength.In addition, provided by the invention medical compound
Also contain hyaluronic acid in aerogel dressing, hyaluronic acid can make medical composite hydrogel dressing have preferable medical property
Can, such as viscoplasticity, moisture retention, lubricity, anti-inflammatory, wound healing performance.
The present invention provides a kind of preparation methods of the medical composite hydrogel dressing described in above-mentioned technical proposal, including：
Hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution are reacted, reaction product is obtained；
The reaction product is impregnated in mixed solution, obtains medical composite hydrogel dressing, the mixed solution packet
Include aloe solution and vitamin E solution.
Preferably, the temperature of the reaction is 50 DEG C~70 DEG C.
Preferably, the preparation method of the reaction product is：
Hyaluronic acid and alkaline solution are mixed, mixed liquor is obtained；
The mixed liquor and sodium citrate are mixed, mixture is obtained；
The mixture and crosslinking agent are reacted, reaction product is obtained.
Preferably, after the completion of the hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution reaction, further include：
Obtained reaction solution is evaporated successively, is dried, is washed and is dried again, reaction product is obtained.
Preferably, the mass ratio of the reaction product and mixed solution is 5：(0.5~2.5).
Method provided by the invention uses sodium citrate during preparing medical composite hydrogel dressing, and coordinates
The preparation that raw material carries out medical composite hydrogel dressing is prepared using other, makes the medical composite hydrogel dressing being prepared
There are preferable tensile property and gel strength.The experimental results showed that the medical Compound Water that method provided by the invention is prepared
The gel strength of gel dressing is 270g~392g.
In addition, method provided by the invention additionally uses hyalomitome during preparing medical composite hydrogel dressing
The use of acid, hyaluronic acid can make medical composite hydrogel dressing have preferable medical performance.
The present invention provides a kind of medical composite hydrogel dressing in the packet for preparing tissue filling agent, medicinal slow release agent, enzyme
Bury the application in agent, contact lenses, artificial blood plasma, artificial skin or tissue engineering bracket material, the medical composite hydrogel
Dressing is that the medical composite hydrogel dressing described in above-mentioned technical proposal or the method described in above-mentioned technical proposal are prepared
Medical composite hydrogel dressing.
Contain hyaluronic acid and sodium citrate in medical composite hydrogel dressing provided by the invention, and medical compound
Containing other ingredients also no biotoxicity and biodegradation can be carried out in aerogel dressing, keep this medical composite hydrogel deposited
Expect to can be applied to biologic medical neck also with certain medical performance while with preferable tensile property, gel strength
Domain.
Description of the drawings
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technology description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The embodiment of invention for those of ordinary skill in the art without creative efforts, can also basis
The attached drawing of offer obtains other attached drawings.
Fig. 1 is the tensile property test map for the medical composite hydrogel dressing that the embodiment of the present invention 1 is prepared.
Specific implementation mode
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
The every other embodiment that technical staff is obtained without making creative work belongs to the model that the present invention protects
It encloses.
The present invention provides a kind of medical composite hydrogel dressing, by including hyaluronic acid, sodium citrate, crosslinking agent, reed
The material of luxuriant growth solution, vitamin E solution and alkaline solution is prepared.
The raw material for preparing of medical composite hydrogel dressing provided by the invention includes hyaluronic acid, and the hyaluronic acid can
Make medical composite hydrogel dressing provided by the invention that there is preferable viscoplasticity, moisture retention, lubricity, anti-inflammatory and promotion
The performance of wound healing.The present invention does not have the source of the hyaluronic acid special limitation, ripe using those skilled in the art
The hyaluronic acid known can be bought by market and be obtained, such as the Hylaform series that the offer of Genzyme companies of the U.S. can be used
Hyaluronic acid.
The raw material for preparing of medical composite hydrogel dressing provided by the invention includes sodium citrate, and the sodium citrate is day
Right pH adjusting agent, is easily obtained, and performance is stablized, and has preferable water solubility, biodegradable, the present invention can be made to be prepared
Medical composite hydrogel dressing there is preferable corrosion resistance and stability, but also can make provided by the invention medical multiple
Heshui gel dressing has preferable tensile property and gel strength.It is special that the present invention does not have the source of the sodium citrate
Limitation can be bought by market and be obtained, and the sodium citrate of the DL series of SIGMA companies offer such as can be used.
The raw material for preparing of medical composite hydrogel dressing provided by the invention includes crosslinking agent.In the embodiment of the present invention
In, the crosslinking agent can be 1,4-butanediol diglycidyl ether (BDDE).In an embodiment of the present invention, the BDDE compared with
It is non-toxic, without side-effects for safety.
The raw material for preparing of medical composite hydrogel dressing provided by the invention includes aloe solution.In the embodiment of the present invention
In, the aloe solution is aloe barbadensis Miller solution.In an embodiment of the present invention, the quality of aloe is dense in the aloe solution
Degree is 0.5%~2%；In other examples, the mass concentration of aloe is 1%~1.5% in the aloe solution.At this
In the embodiment of invention, the solvent in the aloe solution is ethyl alcohol；In other examples, molten in the aloe solution
Agent is absolute ethyl alcohol.In an embodiment of the present invention, the preparation method of the aloe solution is：
Aloe extract is prepared using Hot water extraction；
The aloe extract and solvent are mixed, aloe solution is obtained.
In an embodiment of the present invention, the aloe is aloe barbadensis Miller.In an embodiment of the present invention, by the aloe
Aloe can be carried out dehydrating before extraction.In an embodiment of the present invention, the dehydration temperature is 50 DEG C~70
℃；In other examples, the temperature of the dehydration is 55 DEG C~65 DEG C；In a further embodiment, the dehydration
The temperature of processing is 60 DEG C.In an embodiment of the present invention, the time of the dehydration is 3 hours~5 hours；In others
In embodiment, the time of the dehydration is 3.5 hours~4.5 hours；In a further embodiment, the dehydration
Time is 4 hours.
The specific method that the present invention prepares the Hot water extraction aloe extract does not have special limitation, using ability
Active ingredient in the technical solution extraction aloe of Hot water extraction known to field technique personnel.In the embodiment of the present invention
In, the concrete operation step of the Hot water extraction is：
Refluxing extraction is carried out after Chinese aloe flower diameter and water are mixed, obtains extracting solution；
It is filtered after the extracting solution is centrifuged, obtains aloe extract.
In an embodiment of the present invention, can by before the Chinese aloe flower diameter refluxing extraction according to described in above-mentioned technical proposal
Method is carried out dehydrating.The present invention does not have special limitation to the source of the Chinese aloe flower diameter, can be bought and be obtained by market, such as
The Aloe Barbadensis Miller flower diameter that Sanya, Hainan scientific research and production base can be used to provide.
In an embodiment of the present invention, refluxing extraction is carried out after Chinese aloe flower diameter and distilled water being mixed.In the present invention
Embodiment in, the temperature of the refluxing extraction is 90 DEG C~110 DEG C；In other examples, the temperature of the refluxing extraction
Degree is 95 DEG C~105 DEG C；In a further embodiment, the temperature of the refluxing extraction is 100 DEG C.
In an embodiment of the present invention, it after obtaining extracting solution, is filtered after the extracting solution is centrifuged, obtains aloe and carry
Take object.In an embodiment of the present invention, the centrifugal rotational speed in the centrifugal separation processes is 4500 revs/min~5500 revs/min；
In other embodiments, the centrifugal rotational speed in the centrifugal separation processes is 4800 revs/min~5200 revs/min；In other reality
It applies in example, the centrifugal rotational speed in the centrifugal separation processes is 5000 revs/min.In an embodiment of the present invention, the centrifugation point
From time be 5 minutes~15 minutes；In other examples, the time of the centrifugation is 8 minutes~12 minutes；
In other embodiment, the time of the centrifugation is 10 minutes.
In an embodiment of the present invention, the product after the extracting solution being centrifuged is filtered, and removal centrifuges
Supernatant Chinese aloe flower in product afterwards.In an embodiment of the present invention, filter cloth may be used to be filtered.The present invention's
In embodiment, the mesh number of the filter cloth is the mesh of 350 mesh~450；In other examples, the mesh number of the filter cloth is 380 mesh
~420 mesh；In a further embodiment, the mesh number of the filter cloth is 400 mesh.
In an embodiment of the present invention, above-mentioned refluxing extraction, centrifugation and the operation of filtering can be repeated, it will be every
Secondary obtained aloe extract filters after merging, and carries out centrifugal treating after then washing with water the residue in amalgamation liquid, then use yarn
Cloth filters, and obtains aloe extract.
In the present invention, the solvent is consistent with the solvent in aloe solution described in above-mentioned technical proposal, no longer superfluous herein
It states.In an embodiment of the present invention, the dosage of the solvent makes the mass concentration of aloe in the aloe solution being prepared be
0.5%~2%.
The raw material for preparing of medical composite hydrogel dressing provided by the invention includes vitamin E solution.In the reality of the present invention
It applies in example, the mass concentration of vitamin E is 1%~3% in the vitamin E solution；In other examples, the dimension life
The mass concentration of vitamin E is 1.5%~2.5% in plain E solution；In a further embodiment, it is tieed up in the vitamin E solution
The mass concentration of raw element E is 2%.In an embodiment of the present invention, the solvent in the vitamin E solution is ethyl alcohol；At other
Embodiment in, solvent in the vitamin E solution is absolute ethyl alcohol.The present invention does not have the source of the vitamin E solution
There is special limitation, using solution preparation method well known to those skilled in the art, vitamin E is prepared into solution.This
Invention does not have the source of the vitamin E special limitation, can be bought and be obtained by market, and Beijing Chemical Plant's offer such as can be used
Purity be analytically pure vitamin E.
The raw material for preparing of medical composite hydrogel dressing provided by the invention includes alkaline solution.In the embodiment of the present invention
In, the mass concentration of the alkaline solution neutral and alkali substance is 0.1%~6%；In other examples, the alkaline solution
The mass concentration of neutral and alkali substance is 0.5%~5%；In a further embodiment, the matter of the alkaline solution neutral and alkali substance
Measure a concentration of 1%~3%.In an embodiment of the present invention, the alkaline matter in the alkaline solution is alkali metal hydroxide；
In other examples, the alkaline matter in the alkaline solution is sodium hydroxide.In an embodiment of the present invention, the alkali
Property solution in solvent be water.
In an embodiment of the present invention, the mass ratio of the hyaluronic acid and sodium citrate is 78：(1~5)；In others
In embodiment, the mass ratio of the hyaluronic acid and sodium citrate is 78：(2~4)；In a further embodiment, described transparent
The mass ratio of matter acid and sodium citrate is 78：(2.5~3.5).
In an embodiment of the present invention, the mass ratio of the hyaluronic acid and crosslinking agent is 1000：(1~20)；At other
Embodiment in, the mass ratio of the hyaluronic acid and crosslinking agent is 1000：(5~15)；In a further embodiment, described
The mass ratio of bright matter acid and crosslinking agent is 1000：(8~12).
In an embodiment of the present invention, the mass ratio of aloe and hyaluronic acid is (1~2) in the aloe solution：64；
In other embodiments, the mass ratio of aloe and hyaluronic acid is (1.2~1.8) in the aloe solution：64；In other reality
It applies in example, the mass ratio of aloe and hyaluronic acid is (1.4~1.6) in the aloe solution：64.In the embodiment of the present invention
In, the mass ratio of vitamin E and hyaluronic acid is (1~1.5) in the vitamin E solution：1280；In other embodiments
In, the mass ratio of vitamin E and hyaluronic acid is (1.1~1.4) in the vitamin E solution：1280；In other embodiment
In, the mass ratio of vitamin E and hyaluronic acid is (1.2~1.3) in the vitamin E solution：1280.In the implementation of the present invention
In example, the mass ratio of the alkaline solution neutral and alkali substance and hyaluronic acid is 1:(4~6)；In other examples, described
The mass ratio of alkaline solution neutral and alkali substance and hyaluronic acid is 1:(4.5~5.5)；In a further embodiment, the alkalinity
The mass ratio of solution neutral and alkali substance and hyaluronic acid is 1:(4.8~5.2).
The present invention provides a kind of preparation methods of medical composite hydrogel dressing, including：
Hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution are reacted, reaction product is obtained；
The reaction product is impregnated in mixed solution, obtains medical composite hydrogel dressing, the mixed solution packet
Include aloe solution and vitamin E solution.
The present invention reacts hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution, obtains reaction product.At this
In invention, the hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution type and dosage and above-mentioned technical proposal described in thoroughly
Bright matter acid, sodium citrate, crosslinking agent and the type of alkaline solution are consistent with dosage, and details are not described herein.
In an embodiment of the present invention, the temperature of the reaction is 50 DEG C~70 DEG C；In other examples, described anti-
The temperature answered is 55 DEG C~65 DEG C；In a further embodiment, the temperature of the reaction is 60 DEG C.In the embodiment of the present invention
In, the time of the reaction is 5 hours~7 hours；In other examples, the time of the reaction is 5.5 hours~6.5
Hour；In a further embodiment, the time of the reaction is 6 hours.It in an embodiment of the present invention, can be in the item of stirring
It is reacted under part.
In an embodiment of the present invention, the preparation method of the reaction product is：
Hyaluronic acid and alkaline solution are mixed, mixed liquor is obtained；
The mixed liquor and sodium citrate are mixed, mixture is obtained；
The mixture and crosslinking agent are reacted, reaction product is obtained.
In an embodiment of the present invention, the mass concentration of hyaluronic acid is 1%~8% in the mixed liquor；In others
In embodiment, the mass concentration of hyaluronic acid is 2%~7% in the mixed liquor；In a further embodiment, the mixed liquor
The mass concentration of middle hyaluronic acid is 3%~6%.
In an embodiment of the present invention, sodium citrate can be added into the mixed liquor, obtains mixture.In the present invention
Embodiment in, the mixed liquor and sodium citrate can be mixed under stirring conditions, obtain mixture.
In an embodiment of the present invention, crosslinking agent can be added in the mixture and is reacted, obtain reaction production
Object.In an embodiment of the present invention, anti-by what is obtained after the completion of hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution reaction
It answers solution to be evaporated successively, dry, washing and drying again, obtaining reaction product.In an embodiment of the present invention, the steaming
The method of hair is rotary evaporation in vacuo.In an embodiment of the present invention, the temperature of the evaporation is 35 DEG C~40 DEG C.In the present invention
Embodiment in, the moisture in the evaporation product that time of the evaporation makes is 40%~60%；Other real
It applies in example, the moisture evaporated in product that the time of the evaporation makes is 45%~55%；In other embodiment
In, the moisture evaporated in product that the time of the evaporation makes is 50%.
In an embodiment of the present invention, dry temperature is 35 DEG C~40 DEG C after reaction solution being evaporated.The present invention's
In embodiment, dried in vacuum drying oven after reaction solution being evaporated.
In an embodiment of the present invention, the product after drying is washed, removes remaining alkaline matter.In the present invention
Embodiment in, the reagent of the washing is phosphate solution and water.In an embodiment of the present invention, the phosphate solution and
The mass ratio of water is (2.5~5)：100；In other examples, the mass ratio of the phosphate solution and water is (3~4)：
100.In an embodiment of the present invention, the mass concentration of the phosphate solution is 7%~8%；In other examples, institute
The mass concentration for stating phosphate solution is 7.5%.In an embodiment of the present invention, the water is distilled water.In the reality of the present invention
It applies in example, the pH value for the washed product that the number of the washing makes is 6~7.5；In other examples, the washing
The pH value of washed product that makes of number be 6.5~7.
In an embodiment of the present invention, the product after washing is dried again, obtains reaction product.The present invention's
In embodiment, it is 35 DEG C~40 DEG C that the product after washing, which is carried out temperature dry again,.It in an embodiment of the present invention, can be with
Product after washing is dried in vacuum drying oven.
After obtaining reaction product, the present invention impregnates the reaction product in mixed solution, obtains medical compound water congealing
Glue dressing；The mixed solution includes aloe solution and vitamin E solution.In the present invention, the aloe solution and vitamin E
The type of solution and source are consistent with the type and source of aloe solution described in above-mentioned technical proposal and vitamin E solution, herein
It repeats no more.In an embodiment of the present invention, the mass ratio of the aloe solution and vitamin E solution is (20~50):(1~
1.5)；In other examples, the mass ratio of the aloe solution and vitamin E solution is (25~45):(1.1~1.4)；
In a further embodiment, the mass ratio of the aloe solution and vitamin E solution is (30~40):(1.2~1.3).At this
In the embodiment of invention, the mass ratio of the reaction product and mixed solution is 5：(0.5~2.5)；In other examples,
The mass ratio of the reaction product and mixed solution is 5：(1~2)；In a further embodiment, the reaction product and mixing
The mass ratio of solution is 5：(1.4~1.6).
In an embodiment of the present invention, the temperature of the immersion is 20 DEG C~30 DEG C；In other examples, the leaching
The temperature of bubble is 22 DEG C~28 DEG C；In a further embodiment, the temperature of the immersion is 24 DEG C~26 DEG C.In the reality of the present invention
It applies in example, the time of the immersion is 10 hours~15 hours；In other examples, the time of the immersion is 12 hours
~13 hours.
The present invention provides a kind of medical composite hydrogel dressing in the packet for preparing tissue filling agent, medicinal slow release agent, enzyme
Bury the application in agent, contact lenses, artificial blood plasma, artificial skin or tissue engineering bracket material, the medical composite hydrogel
Dressing is that the medical composite hydrogel dressing described in above-mentioned technical proposal or the method described in above-mentioned technical proposal are prepared
Medical composite hydrogel dressing.
Contain hyaluronic acid and sodium citrate in medical composite hydrogel dressing provided by the invention, and medical compound
Containing other ingredients also no biotoxicity and biodegradation can be carried out in aerogel dressing, keep this medical composite hydrogel deposited
Expect while with preferable tensile property, gel strength also with certain medical performance.According to the People's Republic of China (PRC)
Pharmaceuticals industry standard YY0308-2004《Medical sodium hyaluronate gel》Standard, test medical Compound Water provided by the invention
The tensile property of gel dressing；Test result is that medical composite hydrogel dressing provided by the invention has preferable draftability
Energy.
Using the Texture instrument for the LFRA models that Brookfield companies of the U.S. provide, test is provided by the invention medical compound
The gel strength of aerogel dressing；Test result is that the gel strength of medical composite hydrogel dressing provided by the invention is
270g~392g has higher intensity.
Raw material used in following embodiment of the present invention is commercial goods, and hyaluronic acid used is U.S. Genzyme
The Hylaform products that company provides, sodium citrate used are the DL products that SIGMA companies provide, 1,4-butanediol used
Diglycidyl ether (BDDE) is the 2425-79-8 products that Mike woods company provides, and Aloe Barbadensis Miller flower diameter used is Hainan
What Sanya scientific research and production base provided, vitamin E solution used is what Aladdin provided.
Embodiment 1
The aloe barbadensis Miller solution that mass concentration is 0.5% is prepared by the following method：
Aloe Barbadensis Miller flower diameter is dried into 4h in 60 DEG C of baking oven, after determining wherein no moisture, Chinese aloe flower diameter is set dry
It is spare in dry case；Chinese aloe flower diameter after drying is placed in round-bottomed flask, distilled water is added into flask and is returned at 100 DEG C
Stream extraction, centrifuges 10min, by obtained filtrate through filter-cloth filtering by obtained extracting solution under the rotating speed of 4800r/min
Supernatant Chinese aloe flower is removed, polysaccharide clear liquid is obtained；3 polysaccharide clear liquids are prepared according to the method described in above-mentioned technical proposal；
Centrifugal treating is carried out after residue wash with distilled water after the polysaccharide clear liquid that 3 times prepare is merged, again by the filtrate after centrifugal treating
With 400 mesh filter-cloth filterings, aloe extract is obtained.
Aloe extract obtained above is diluted with water, the aloe barbadensis Miller solution that mass concentration is 0.5% is obtained.
Weigh 10g hyaluronic acid be added to 990g mass concentration be 1.5% sodium hydrate aqueous solution in completely it is molten
Solution, obtains mixed liquor；
The sodium citrate that 0.64g is added into the mixed liquor is stirred mixing, obtains mixture；
The BDDE that 0.2g is added into the mixture is stirred to react 5 hours at 60 DEG C, obtains reaction solution；
The reaction solution is placed in vacuum rotary evaporator at 37 DEG C and carries out rotary evaporation, obtaining water content is
50% product；
It will be dried in vacuum drying box of the product after rotary evaporation at 37 DEG C, obtain drying product；
The drying product is cleaned repeatedly using phosphate solution and distilled water, sodium hydroxide therein is removed, obtains
The washed product that pH value is 7；
Obtained washed product is dried in vacuum drying box at 37 DEG C, desciccate is obtained；
Under the conditions of room-temperature sterile, the desciccate is impregnated 12 hours in mixed solution, obtains medical Compound Water
Gel dressing；The mass ratio of the desciccate and mixed solution is 5:2, mass concentration is 0.5% in the mixed solution
The mass ratio for the vitamin E solution that aloe barbadensis Miller solution and mass concentration are 3% is 20:1.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 1 is prepared is tested
The tensile property of dressing, test results are shown in figure 1, and Fig. 1 is that the medical composite hydrogel that the embodiment of the present invention 1 is prepared applies
The tensile property test map of material.According to the change in displacement of medical composite hydrogel dressing after pressure increase in Fig. 1 it is found that this hair
The medical composite hydrogel dressing that bright embodiment 1 is prepared has preferable tensile property.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 1 is prepared is tested
The gel strength of dressing；Test result is the gel strength for the medical composite hydrogel dressing that the embodiment of the present invention 1 is prepared
For 270g.
Embodiment 2
The aloe barbadensis Miller solution that mass concentration is 0.5% is prepared according to method described in embodiment 1.
Weigh 80g hyaluronic acid be added to 920g mass concentration be 4.5% sodium hydrate aqueous solution in completely it is molten
Solution, obtains mixed liquor；
The sodium citrate that 1.03g is added into the mixed liquor is stirred mixing, obtains mixture；
The BDDE that 0.08g is added into the mixture is stirred to react 5 hours at 50 DEG C, obtains reaction solution；
The reaction solution is placed in vacuum rotary evaporator at 35 DEG C and carries out rotary evaporation, obtaining water content is
50% product；
It will be dried in vacuum drying box of the product after rotary evaporation at 35 DEG C, obtain drying product；
The drying product is cleaned repeatedly using phosphate solution and distilled water, sodium hydroxide therein is removed, obtains
The washed product that pH value is 6；
Obtained washed product is dried in vacuum drying box at 35 DEG C, desciccate is obtained；
Under the conditions of room-temperature sterile, the desciccate is impregnated 12 hours in mixed solution, obtains medical Compound Water
Gel dressing；The mass ratio of the desciccate and mixed solution is 5:2.5, mass concentration is 0.5% in the mixed solution
Aloe barbadensis Miller solution and mass concentration be 1% the mass ratio of vitamin E solution be 30:1.5.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 2 is prepared is tested
The tensile property of dressing, it is preferable that test result shows that the medical composite hydrogel dressing that the embodiment of the present invention 2 is prepared has
Tensile property.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 2 is prepared is tested
The gel strength of dressing；Test result is the gel strength for the medical composite hydrogel dressing that the embodiment of the present invention 2 is prepared
For 392g.
Embodiment 3
The aloe barbadensis Miller solution that mass concentration is 0.5% is prepared according to method described in embodiment 1.
Weigh 50g hyaluronic acid be added to 950g mass concentration be 6% sodium hydrate aqueous solution in be completely dissolved,
Obtain mixed liquor；
The sodium citrate that 0.8g is added into the mixed liquor is stirred mixing, obtains mixture；
The BDDE that 0.03g is added into the mixture is stirred to react 5 hours at 70 DEG C, obtains reaction solution；
The reaction solution is placed in vacuum rotary evaporator at 40 DEG C and carries out rotary evaporation, obtaining water content is
50% product；
It will be dried in vacuum drying box of the product after rotary evaporation at 40 DEG C, obtain drying product；
The drying product is cleaned repeatedly using phosphate solution and distilled water, sodium hydroxide therein is removed, obtains
The washed product that pH value is 7.5；
Obtained washed product is dried in vacuum drying box at 40 DEG C, desciccate is obtained；
Under the conditions of room-temperature sterile, the desciccate is impregnated 12 hours in mixed solution, obtains medical Compound Water
Gel dressing；The mass ratio of the desciccate and mixed solution is 5:3, mass concentration is 0.5% in the mixed solution
The mass ratio for the vitamin E solution that aloe barbadensis Miller solution and mass concentration are 1% is 25:1.2.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 3 is prepared is tested
The tensile property of dressing, it is preferable that test result shows that the medical composite hydrogel dressing that the embodiment of the present invention 3 is prepared has
Tensile property.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 3 is prepared is tested
The gel strength of dressing；Test result is the gel strength for the medical composite hydrogel dressing that the embodiment of the present invention 3 is prepared
For 296g.
Embodiment 4
The aloe barbadensis Miller solution that mass concentration is 2.5% is prepared according to method described in embodiment 1.
Weigh 60g hyaluronic acid be added to 940g mass concentration be 3.5% sodium hydrate aqueous solution in completely it is molten
Solution, obtains mixed liquor；
The sodium citrate that 0.8g is added into the mixed liquor is stirred mixing, obtains mixture；
The BDDE that 0.05g is added into the mixture is stirred to react 5 hours at 65 DEG C, obtains reaction solution；
The reaction solution is placed in vacuum rotary evaporator at 36 DEG C and carries out rotary evaporation, obtaining water content is
50% product；
It will be dried in vacuum drying box of the product after rotary evaporation at 36 DEG C, obtain drying product；
The drying product is cleaned repeatedly using phosphate solution and distilled water, sodium hydroxide therein is removed, obtains
The washed product that pH value is 6.5；
Obtained washed product is dried in vacuum drying box at 36 DEG C, desciccate is obtained；
Under the conditions of room-temperature sterile, the desciccate is impregnated 12 hours in mixed solution, obtains medical Compound Water
Gel dressing；The mass ratio of the desciccate and mixed solution is 5:2.5, mass concentration is 2.5% in the mixed solution
Aloe barbadensis Miller solution and mass concentration be 3% the mass ratio of vitamin E solution be 20:1.5.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 4 is prepared is tested
The tensile property of dressing, it is preferable that test result shows that the medical composite hydrogel dressing that the embodiment of the present invention 4 is prepared has
Tensile property.
According to the method described in above-mentioned technical proposal, the medical composite hydrogel that the embodiment of the present invention 4 is prepared is tested
The gel strength of dressing；Test result is the gel strength for the medical composite hydrogel dressing that the embodiment of the present invention 4 is prepared
For 387g.
As seen from the above embodiment, the present invention provides a kind of medical composite hydrogel dressing, by including hyaluronic acid, lemon
Lemon acid sodium, crosslinking agent, aloe solution, vitamin E solution and alkaline solution material be prepared.It is provided by the invention medical multiple
Contain sodium citrate in Heshui gel dressing, sodium citrate can make hydrogel that there is preferable mechanical property, the present invention to pass through
Sodium citrate and other prepare being used cooperatively for raw material, so as to get medical composite hydrogel dressing have preferable draftability
Energy and gel strength.In addition, also containing hyaluronic acid in medical composite hydrogel dressing provided by the invention, hyaluronic acid can
Make medical composite hydrogel dressing that there is preferable medical performance, such as viscoplasticity, moisture retention, lubricity, anti-inflammatory, promotes the surface of a wound
The performances such as healing.
Claims (9)
1. a kind of medical composite hydrogel dressing, by including hyaluronic acid, sodium citrate, crosslinking agent, aloe solution, vitamin E
The material of solution and alkaline solution is prepared；The mass ratio of the hyaluronic acid and sodium citrate is 78：(1~5)；
The mass ratio of the hyaluronic acid and crosslinking agent is 1000：(1~20).
2. medical composite hydrogel dressing according to claim 1, which is characterized in that the crosslinking agent is 1,4-butanediol
Diglycidyl ether.
3. medical composite hydrogel dressing according to claim 1, which is characterized in that the matter of aloe in the aloe solution
Measure a concentration of 0.5%~2%；
The mass concentration of vitamin E is 1%~3% in the vitamin E solution.
4. the preparation method of the medical composite hydrogel dressing described in a kind of any one of claims 1 to 3, including：
Hyaluronic acid, sodium citrate, crosslinking agent and alkaline solution are reacted, reaction product is obtained；
The reaction product is impregnated in mixed solution, obtains medical composite hydrogel dressing, the mixed solution includes reed
Luxuriant growth solution and vitamin E solution.
5. according to the method described in claim 4, it is characterized in that, the temperature of the reaction is 50 DEG C~70 DEG C.
6. according to the method described in claim 4, it is characterized in that, the preparation method of the reaction product is：
Hyaluronic acid and alkaline solution are mixed, mixed liquor is obtained；
The mixed liquor and sodium citrate are mixed, mixture is obtained；
The mixture and crosslinking agent are reacted, reaction product is obtained.
7. according to the method described in claim 4, it is characterized in that, the hyaluronic acid, sodium citrate, crosslinking agent and alkalinity are molten
After the completion of liquid reaction, further include：
Obtained reaction solution is evaporated successively, is dried, is washed and is dried again, reaction product is obtained.
8. according to the method described in claim 4, it is characterized in that, the mass ratio of the reaction product and mixed solution is 5：
(0.5~2.5).
9. a kind of medical composite hydrogel dressing prepare tissue filling agent, medicinal slow release agent, the embedding medium of enzyme, contact lenses,
Application in artificial blood plasma, artificial skin or tissue engineering bracket material, the medical composite hydrogel dressing are claim 1
Method system described in any one of medical composite hydrogel dressing or claim 4~8 described in any one of~3
Standby obtained medical composite hydrogel dressing.
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| CN108339149A (en) * | 2018-04-27 | 2018-07-31 | 泰州市榕兴医疗用品股份有限公司 | A kind of preparation method of the aerogel dressing containing vitamin e |
| CN111603441B (en) * | 2020-07-01 | 2022-11-25 | 瑞希(重庆)生物科技有限公司 | Amphiphilic polyamino acid copolymer/poloxamer thermo-sensitive gel and preparation method thereof |
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| CN101537195A (en) * | 2008-03-21 | 2009-09-23 | 上海昊海生物科技有限公司 | Method for improving final sterilization stability of hyaluronic acid gel |
| CN104151572A (en) * | 2013-05-16 | 2014-11-19 | 吴学森 | Method for preparing medical cross-linking sodium hyaluronate gel |
| CN104804199A (en) * | 2015-01-26 | 2015-07-29 | 岑莲 | Biomedical composite hydrogel, and preparation method and applications thereof |
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| CN1960736A (en) * | 2004-02-27 | 2007-05-09 | 海德罗默公司 | Anti-infectious hydrogel compositions |
| CN101537195A (en) * | 2008-03-21 | 2009-09-23 | 上海昊海生物科技有限公司 | Method for improving final sterilization stability of hyaluronic acid gel |
| CN104151572A (en) * | 2013-05-16 | 2014-11-19 | 吴学森 | Method for preparing medical cross-linking sodium hyaluronate gel |
| CN104804199A (en) * | 2015-01-26 | 2015-07-29 | 岑莲 | Biomedical composite hydrogel, and preparation method and applications thereof |
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