CN110464869A - A kind of preparation method and applications from thickening bone surface of a wound hemostasis gel - Google Patents
A kind of preparation method and applications from thickening bone surface of a wound hemostasis gel Download PDFInfo
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- CN110464869A CN110464869A CN201910688734.6A CN201910688734A CN110464869A CN 110464869 A CN110464869 A CN 110464869A CN 201910688734 A CN201910688734 A CN 201910688734A CN 110464869 A CN110464869 A CN 110464869A
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/108—Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
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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
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2301/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
- C08J2301/08—Cellulose derivatives
- C08J2301/26—Cellulose ethers
- C08J2301/28—Alkyl ethers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
Abstract
The invention discloses a kind of from thickening bone surface of a wound hemostasis gel and preparation method and application, the gel includes amphoteric ion-polysaccharide polymer brush, solvent substrate, coagulation factor component, first, prepare amphoteric ion-polysaccharide polymer brush, then, the amphoteric ion-polysaccharide polymer brush is mixed with solvent substrate, stir to get pregel, finally, coagulation factor is added into the pregel, it stirs to get from thickening bone surface of a wound hemostasis gel, bone surface of a wound hemostasis gel component in the present invention is simple, it does not need additionally to add thickener, the components such as excipient, haemostatic effect is good simultaneously, it is easy to absorb, do not influence wound healing.
Description
Technical field
The present invention relates to biomedical materials fields, and in particular to a kind of from the preparation method for thickening bone surface of a wound hemostasis gel
And its application.
Background technique
The hemostasis problem of the bone surface of a wound in bone surgery, the hemostasis of the especially cancellous bone surface of a wound always are puzzlement orthopedist
Problem, the bleeding of the cancellous bone surface of a wound is often oozing of blood, see that no angiorrhoxis amount of bleeding is big, bleeding is fast on surface, but stop blooding
Not in time, the amount of bleeding of oozing of blood can also jeopardize patient vitals.
It is difficult to play the role of quick-acting haemostatic powder in the hemostatic fashion short time of the routine such as coagulation, styptic sponge filling, gauze,
Currently, mostly blocking the oozing of blood surface of a wound in clinical practice by bone wound surface smearing bone wax, haemostatic effect is reached, common bone wax ingredient is
Beeswax, vaseline etc., this bone wax have good plasticity, but the poor biocompatibility of this kind of material and not by human body institute
It absorbs, in the aggregation of the residue platelet that the bone surface of a wound leaves etc., has delayed bone wound healing.
Currently, absorbable bone wax is domestic and international research hotspot, the materials such as poloxamer, collagen, chitosan, oxycellulose
Because the materials such as good biocompatibility and degradability poloxamer, collagen, chitosan, oxycellulose are because of good biology
Compatibility and degradability, the application in terms of bone surface of a wound hemostasis are concerned.But these high molecular materials and surface of a wound adhesiveness
Difference washes away lower easy slide in blood.
107158452 A of Chinese patent literature CN discloses a kind of bone surface of a wound hemostatic composition and preparation method thereof and answers
With the composition is made of solvent substrate, thickener, excipient and ion salt, and thickener is big point of cellulose family, carbomer etc.
Son, excipient are the polysaccharose substances such as modified starch, sodium alginate.The invention haemostatic effect is good, plasticity is good, biocompatibility
It is good, but composition component is complicated, proposes high requirement to the control of raw material, and anthemorrhagic speed is to be improved.
Summary of the invention
For this purpose, it is to be solved by this invention be existing bone wound hemostatic material can not have good adhesiveness simultaneously, can
Plasticity, haemostatic effect, anthemorrhagic speed and ingredient simply easily absorb the problem of these advantages, to provide a kind of from thickening bone
The preparation method of surface of a wound hemostasis gel.
In order to solve the above technical problems, The technical solution adopted by the invention is as follows:
A kind of bone surface of a wound Trostin M sizing material of thickening certainly provided by the present invention includes the component of following weight percentage:
Amphoteric ion-polysaccharide polymer brush 10%-60%
Solvent substrate 40%-90%
Coagulation factor 0.01%-0.5%.
Further, the amphoteric ion-polysaccharide polymer brush is prepared by zwitterionic monomer and water；
The zwitterionic monomer is one of carboxylic acid glycine betaine, phosphocholine, sulfobetaines；
The solvent substrate is vegetable oil, polyethylene glycol 400, glycerine, one or two kinds of in Macrogol 600；
The coagulation factor be factor I, prothrombin, thromboplastin, factor IV, labile factor,
Labile factor I, proconvertin, blood coagulation factor VIII, plasma thromboplastin component, Stuart factor, plasma thromboplastin antecedent, coagulation factor
One or both of XII, factor XIII.
The present invention also provides a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, includes the following steps:
1) amphoteric ion-polysaccharide polymer brush is prepared；
2) amphoteric ion-polysaccharide polymer brush mixed with solvent substrate, stir to get pregel；
3) coagulation factor is added in Xiang Suoshu pregel, stirs to get from thickening bone surface of a wound hemostasis gel.
Further, amphoteric ion described in step 1)-polysaccharide polymer brush preparation process are as follows:
(1) zwitterionic monomer, reagent one and organic solvent are mixed, obtains mixture；
(2) under an inert gas, water-soluble polysaccharide is added in Xiang Suoshu mixture, is reacted, obtains reactant；
(3) it by after reactant cooling, is added in solvent one, is reacted, obtain sediment；
(4) sediment is filtered and is washed, obtain polymer；
(5) polymer is subjected to frozen dried, obtains amphoteric ion-polysaccharide polymer brush
Further, the reagent one is cuprous bromide or azodiisobutyronitrile；
The organic solvent is N,N-dimethylformamide, toluene, dimethyl sulfoxide；
The inert gas is at least one of nitrogen, helium, argon gas, neon；
The water-soluble polysaccharide is one of hyaluronic acid, carboxymethyl cellulose, chitosan；
The solvent one is one of ethanol solution, anhydrous methanol, ethyl acetate.
Further, the molar ratio that the amphoteric ion-polysaccharide polymer brush is mixed with solvent substrate is (1-6): (4-
9)；
The zwitterionic monomer reagent one and the molar ratio of organic solvent mixing are (1-10): (0.01-3):
100；
The molar ratio of the water-soluble polysaccharide and the mixture is 1:(100-8)；
The molar ratio of the reactant and solvent one is (1-50): 100；
Described two coagulation factor ratios are 1:(0.1-10) IU；
Described two solvent substrate molar ratios are (0.1-2): 1.
Further, zwitterionic monomer described in step (1), reagent one and organic solvent mixing temperature are 15 DEG C；
The temperature of reaction described in step (2) is 40-75 DEG C, time 24-48h；
Cooling temperature described in step (3) is 20-30 DEG C, and the reaction temperature is 20-30 DEG C, and the reaction time is
24-48h；
The vacuum degree of suction filtration described in step (4) is 1-100Pa, and the time filtered every time is 5-45min, number 2-4
It is secondary；
The temperature of the washing is 20-30 DEG C, time 5-10min, and number is 2-4 times, and washing reagent is dehydrated alcohol
Or acetone；
The temperature of freeze-drying described in step (5) is -20-35 DEG C, time 48-72h.
Further, the speed of stirring described in step 2) is 100-2000r/min, and temperature is 20-30 DEG C, is stirred every time
Time be 2-30min；
The speed of stirring described in step 3) is 100-2000r/min, and temperature is 20-30 DEG C, and the time stirred every time is
1-20min。
Compared with prior art, the invention has the following beneficial effects:
1, provided by the invention a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, this method uses amphoteric ion list
Body polymerize with water-soluble polysaccharide, generates amphoteric ion-polysaccharide polymer brush, and addition coagulation factor obtains bone surface of a wound gel, the party
Method raw material composition is few, and preparation process is simple, and can be coagulated by designing amphoteric ion-polysaccharide polymer brush of different molecular weight and adjusting
The degradation speed of glue in vivo, to adapt to needs different in clinical treatment.
2, provided by the invention a kind of from thickening bone surface of a wound hemostasis gel, the gel is by reacting to each other between raw material, no
Need addn of thickener and excipient that there can be good plasticity and from thickening capabilities, have on bone surface of a wound surface good viscous
Attached property, contains coagulation factor in the gel, after gel and contacting blood, absorbs the water release coagulation factor in blood, hemostasis
Effect is prominent, meanwhile, which has excellent degradability, and can control degradation speed.
Specific embodiment
Technical solution of the present invention is clearly and completely described below, it is clear that described embodiment is the present invention
A part of the embodiment, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not having
Every other embodiment obtained under the premise of creative work is made, shall fall within the protection scope of the present invention.
Embodiment 1
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 30%
Solvent substrate 70%
Coagulation factor 0.15%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 2mol carboxylic acid glycine betaine, 0.2mol cuprous bromide and 100mol toluene are mixed under conditions of 15 DEG C, is obtained
Mixture；
2) 200mol hyaluronic acid in a nitrogen environment, is added into mixture obtained in step 1), in 45 DEG C of temperature
Lower reaction 48h, obtains reactant；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 600mol ethanol solution, at 25 DEG C
Under the conditions of, reaction for 24 hours, obtains sediment；
4) by sediment made from step 3) at a temperature of 25 DEG C with the vacuum degree of 15Pa, filter 3 times, filter every time
10min is washed 3 times using dehydrated alcohol then under the conditions of 25 DEG C, is washed 5min every time, obtain polymer；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 48h obtains amphoteric ion-polysaccharide polymer brush；
6) vegetable oil is mixed with Macrogol 600 with the molar ratio of 1:0.8, then by both sexes made from step 5) from
Son-polysaccharide polymer brush is mixed with the mixture of vegetable oil and Macrogol 600 with the molar ratio of 1:9, and mixture is existed
Under the conditions of 25 DEG C, 5min is stirred with the speed of 1500r/min, then adds factor I, additive amount is gel quality
0.15%, finally under the conditions of 25 DEG C, finally obtained with the speed stirring 2min of 1500r/min from thickening bone surface of a wound Trostin M
Glue.
Embodiment 2
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 35%
Solvent substrate 65%
Coagulation factor 0.15%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 5mol carboxylic acid glycine betaine, 0.8mol cuprous bromide and 100mol toluene are mixed under conditions of 25 DEG C, is obtained
Mixture；
2) 100mol hyaluronic acid in a nitrogen environment, is added into mixture obtained in step 1), in 60 DEG C of conditions
Lower reaction 48h, obtains reactant；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 1000mol ethanol solution, at 25 DEG C
Under the conditions of, 48h is reacted, sediment is obtained；
4) sediment made from step 3) is filtered 3 times at a temperature of 25 DEG C with the vacuum degree of 12Pa, is filtered every time
15min, using acetone washing 3 times, washs 10min every time, obtains polymer then at a temperature of 25 DEG C；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 72h obtains amphoteric ion-polysaccharide polymer brush；
6) then by amphoteric ion made from step 5)-polysaccharide polymer brush and the mixture of polyethylene glycol 400 with 2:8's
Molar ratio is mixed, and by mixture under the conditions of 25 DEG C, stirs 10min with the speed of 1200r/min, then add blood coagulation because
Son I and prothrombin mixture, coagulation factor mixture additive amount are the 0.15% of gel quality, factor I and blood coagulation
The mixing ratio of factor II is 1:1IU, finally under the conditions of 25 DEG C, is finally obtained with the speed stirring 8min of 1200r/min from increasing
Thick bone surface of a wound hemostasis gel.
Embodiment 3
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 55%
Solvent substrate 45%
Coagulation factor 0.05%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 2mol sulphonic acid betaine, 1mol cuprous bromide and 100mol toluene are mixed under conditions of 10 DEG C, is mixed
Close object；
2) 50mol hyaluronic acid in a nitrogen environment, is added into mixture obtained in step 1), under the conditions of 45 DEG C
48h is reacted, reactant is obtained；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 450mol ethanol solution, at 25 DEG C
Under the conditions of, 36h is reacted, sediment is obtained；
4) sediment made from step 3) is filtered 3 times at a temperature of 25 DEG C with the vacuum degree of 15Pa, is filtered every time
15min is washed 3 times using dehydrated alcohol then at a temperature of 25 DEG C, is washed 5min every time, obtain polymer；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 48h obtains amphoteric ion-polysaccharide polymer brush；
6) vegetable oil is mixed with glycerine with the molar ratio of 1:1, it is then that amphoteric ion-polysaccharide made from step 5) is poly-
Object brush is closed to be mixed with vegetable oil with glycerol mixture with the molar ratio of 1:4, by mixture under the conditions of 25 DEG C, with
The speed of 1500r/min stirs 2min, then adds factor I, additive amount is the 0.05% of gel quality, finally at 25 DEG C
Under the conditions of, it is finally obtained with the speed stirring 5min of 1500r/min from thickening bone surface of a wound hemostasis gel.
Embodiment 4
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 60%
Solvent substrate 30%
Coagulation factor 0.12%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 4mol sulphonic acid betaine, 1mol azodiisobutyronitrile and 100mol dimethyl sulfoxide are mixed under conditions of 0 DEG C,
Obtain mixture；
2) 400mol chitosan in a nitrogen environment, is added into mixture obtained in step 1), under the conditions of 70 DEG C
48h is reacted, reactant is obtained；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 800mol ethanol solution, at 25 DEG C
Under the conditions of, reaction for 24 hours, obtains sediment；
4) sediment made from step 3) is filtered 3 times at a temperature of 25 DEG C with the vacuum degree of 18Pa, is filtered every time
25min is washed 3 times using dehydrated alcohol then at a temperature of 25 DEG C, is washed 5min every time, obtain polymer；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 72h obtains amphoteric ion-polysaccharide polymer brush；
6) vegetable oil is mixed with Macrogol 600 with the molar ratio of 2:1, then by amphoteric ion-made from step 5)
Polysaccharide polymer brush is mixed with vegetable oil with glycerol mixture with the molar ratio of 1:9, by mixture under the conditions of 25 DEG C,
5min is stirred with the speed of 600r/min, then adds factor I and thromboplastin mixture, coagulation factor mixture
Additive amount is the 0.12% of gel quality, and the mixing ratio of factor I and thromboplastin is 2:1IU, finally in 25 DEG C of conditions
Under, it is finally obtained with the speed stirring 18min of 600r/min from thickening bone surface of a wound hemostasis gel.
Embodiment 5
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 40%
Solvent substrate 60%
Coagulation factor 0.25%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) by 5mol carboxylic acid glycine betaine, 0.05mol azodiisobutyronitrile and 100mol dimethyl sulfoxide under conditions of 10 DEG C
Mixing, obtains mixture；
2) 250mol chitosan in a nitrogen environment, is added into mixture obtained in step 1), under the conditions of 75 DEG C
48h is reacted, reactant is obtained；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 1000mol ethanol solution, at 25 DEG C
Under the conditions of, reaction for 24 hours, obtains sediment；
4) sediment made from step 3) is filtered 3 times at a temperature of 25 DEG C with the vacuum degree of 98Pa, is filtered every time
35min, using acetone washing 3 times, washs 5min every time, obtains polymer then at a temperature of 25 DEG C；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 48h obtains amphoteric ion-polysaccharide polymer brush；
6) amphoteric ion made from step 5)-polysaccharide polymer brush and glycerol mixture are carried out with the molar ratio of 3:7
Mixing stirs 8min by mixture under the conditions of 25 DEG C with the speed of 200r/min, then add factor I and blood coagulation because
Sub- III mixture, coagulation factor mixture additive amount are the 0.25% of gel quality, factor I and thromboplastin it is mixed
Composition and division in a proportion is 1:2IU, finally under the conditions of 25 DEG C, is finally obtained with the speed stirring 20min of 200r/min from the thickening bone surface of a wound and is stopped
Blood clotting glue.
Embodiment 6
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 45%
Solvent substrate 55%
Coagulation factor 0.1%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) by 4mol carboxylic acid glycine betaine, 2mol azodiisobutyronitrile and 100molN, item of the dinethylformamide at 35 DEG C
It is mixed under part, obtains mixture；
2) 400mol hyaluronic acid in a nitrogen environment, is added into mixture obtained in step 1), in 65 DEG C of conditions
Lower reaction 48h, obtains reactant；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 10000mol absolute methanol solution, 25
Under the conditions of DEG C, reaction for 24 hours, obtains sediment；
4) sediment made from step 3) is filtered 3 times at a temperature of 25 DEG C with the vacuum degree of 65Pa, is filtered every time
25min is washed 3 times using dehydrated alcohol then at a temperature of 25 DEG C, is washed 45min every time, obtain polymer；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 72h obtains amphoteric ion-polysaccharide polymer brush；
6) glycerine is mixed with polyethylene glycol 400 with the molar ratio of 1:2, then by amphoteric ion-made from step 5)
Polysaccharide polymer brush is mixed with glycerine and polyethylene glycol 400 with the molar ratio of 1:4, by mixture under the conditions of 25 DEG C,
15min is stirred with the speed of 1800r/min, then adds factor I and thromboplastin mixture, coagulation factor mixing
Object additive amount is the 0.1% of gel quality, and the mixing ratio of factor I and thromboplastin is 1:5IU, finally in 25 DEG C of items
Under part, finally obtained with the speed stirring 1min of 1800r/min from thickening bone surface of a wound hemostasis gel.
Embodiment 7
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 42%
Solvent substrate 58%
Coagulation factor 0.05%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 3mol sulfobetaines, 1mol cuprous bromide and 100mol dimethyl sulfoxide are mixed under conditions of 20 DEG C, is obtained
To mixture；
2) under helium environment, 400mol carboxymethyl cellulose is added into mixture obtained in step 1), at 75 DEG C
Under the conditions of react for 24 hours, obtain reactant；
3) reactant obtained in step 2) is cooled to 20 DEG C, be added in 10000mol absolute methanol solution, 20
Under the conditions of DEG C, 36h is reacted, sediment is obtained；
4) sediment made from step 3) is filtered 2 times at a temperature of 20 DEG C with the vacuum degree of 5Pa, filters 45min every time,
Then it at a temperature of 20 DEG C, is washed 4 times using dehydrated alcohol, washs 5min every time, obtain polymer；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 48h obtains amphoteric ion-polysaccharide polymer brush；
6) glycerine is mixed with polyethylene glycol 400 with the molar ratio of 0.2:1, then by both sexes made from step 5) from
Son-polysaccharide polymer brush is mixed with glycerine and polyethylene glycol 400 with the molar ratio of 6:4, by mixture in 20 DEG C of conditions
Under, 30min is stirred with the speed of 1500r/min, then adds factor I and thromboplastin mixture, coagulation factor is mixed
Closing object additive amount is the 0.05% of gel quality, and the mixing ratio of factor I and thromboplastin is 2:0.3IU, finally 20
Under the conditions of DEG C, finally obtained with the speed stirring 5min of 1500r/min from thickening bone surface of a wound hemostasis gel.
Embodiment 8
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 38%
Solvent substrate 62%
Coagulation factor 0.2%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 5mol phosphocholine, 1.5mol azodiisobutyronitrile and 100mo toluene are mixed under conditions of 4 DEG C, is obtained
Mixture；
2) under ar gas environment, 400mol chitosan is added into mixture obtained in step 1), under the conditions of 55 DEG C
48h is reacted, reactant is obtained；
3) reactant obtained in step 2) is cooled to 25 DEG C, be added in 10000mol ethyl acetate solution, 25
Under the conditions of DEG C, 48h is reacted, sediment is obtained；
4) sediment made from step 3) is filtered 3 times at a temperature of 25 DEG C with the vacuum degree of 20Pa, is filtered every time
20min, using acetone washing 3 times, washs 5min every time, obtains polymer then at a temperature of 25 DEG C；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 60h obtains amphoteric ion-polysaccharide polymer brush；
6) glycerine is mixed with Macrogol 600 with the molar ratio of 2:1, then by amphoteric ion-made from step 5)
Polysaccharide polymer brush is mixed with glycerine and Macrogol 600 with the molar ratio of 2:1, by mixture under the conditions of 25 DEG C,
10min is stirred with the speed of 600r/min, then adds proconvertin and blood coagulation factor VIII mixture, coagulation factor is mixed
Closing object additive amount is the 0.2% of gel quality, and the mixing ratio of proconvertin and blood coagulation factor VIII is 1:1IU, finally 25
Under the conditions of DEG C, finally obtained with the speed stirring 10min of 600r/min from thickening bone surface of a wound hemostasis gel.
Embodiment 9
One kind is present embodiments provided from thickening bone surface of a wound hemostasis gel and preparation method thereof, which prepares raw material
Component including following weight percentage:
Amphoteric ion-polysaccharide polymer brush 33%
Solvent substrate 67%
Coagulation factor 0.3%.
The gel is made by following preparation method, the preparation method the following steps are included:
1) 5mol sulfobetaines, 0.05mol cuprous bromide and 100mol toluene are mixed under conditions of 0 DEG C, is obtained
Mixture；
2) under neon environment, 40mol chitosan is added into mixture obtained in step 1), it is anti-under the conditions of 40 DEG C
72h is answered, reactant is obtained；
3) reactant obtained in step 2) is cooled to 30 DEG C, be added in 800mol ethyl acetate solution, at 30 DEG C
Under the conditions of, 48h is reacted, sediment is obtained；
4) sediment made from step 3) is filtered 4 times at a temperature of 30 DEG C with the vacuum degree of 15Pa, is filtered every time
10min is washed 2 times using dehydrated alcohol then at a temperature of 30 DEG C, is washed 30min every time, obtain polymer；
5) polymer made from step 4) is subjected to freezing and lyophilization in freeze drier with -20 DEG C, with 35 DEG C
Parsing-desiccation is carried out, whole process 72h obtains amphoteric ion-polysaccharide polymer brush；
6) amphoteric ion made from step 5)-polysaccharide polymer brush and vegetable oil mixt are carried out with the molar ratio of 1:9
Mixing stirs 8min by mixture under the conditions of 30 DEG C with the speed of 200r/min, then add Stuart factor and blood coagulation because
Sub- III mixture, coagulation factor mixture additive amount are the 0.3% of gel quality, factor I and thromboplastin it is mixed
Composition and division in a proportion is 1:5IU, finally under the conditions of 30 DEG C, is finally obtained with the speed stirring 8min of 800r/min from thickening bone surface of a wound hemostasis
Gel.
Comparative example 1
This comparative example provides a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, with embodiment 1, unique difference
Be in: be not added with coagulation factor.
Comparative example 2
This comparative example provides a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, with embodiment 2, unique difference
Be in: be not added with coagulation factor.
Test example 1
Examples 1 to 9 is derived from thickening bone surface of a wound hemostasis gel to be distributed into closing paste box, is gone out through the irradiation of cobalt -60
It is stored refrigerated after bacterium, carry out following clinical test:
26 healthy adult rabbit are chosen as experimental subjects, pre- raising one week, male and female are unlimited；13 groups are equally divided into, often
Group 2, group number 1~11 are that experimental group uses gained hemostasis gel, group in the embodiment of the present invention 1~9 and comparative example 1~2 respectively
Numbers 12 be control group, using listing product, is selected at rabbit back leg tibiofibula as operative site.
After the anesthesia of 1% yellow Jackets posterior auricular vein, by operative site preserved skin, exposure tibiofibula front side skin, Iodophor disappears
Poison, takes longitudinal incision on front side of rabbit back leg tibiofibula, blunt separation musculature, and exposure tibiofibula leading edge stings bone using sharp mouth
Pincers bite the position broken, meeting fracture activity oozing of blood.It selects hemostasis gel to smear the surface of a wound, fractures after block reset, sew up a wound.
5 days after operation, 7 days every group put to death 1 animal, the results are shown in Table 1 for observation:
Table 1
It can be seen from the result of table 1 when water-soluble polysaccharide selects hyaluronic acid, degradation speed is very fast and anthemorrhagic speed
Also very fast.The haemostatic effect of gel used in Examples 1 to 9 is excellent compared with listing product.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or
It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or
It changes still within the protection scope of the invention.
Claims (8)
1. a kind of from thickening bone surface of a wound hemostasis gel, which is characterized in that it includes that following weight percent contains that the gel, which prepares raw material,
The component of amount:
Amphoteric ion-polysaccharide polymer brush 10%-60%
Solvent substrate 40%-90%
Coagulation factor 0.01%-0.5%.
2. according to claim 1 a kind of from thickening bone surface of a wound hemostasis gel, which is characterized in that the amphoteric ion-is more
Glycopolymers brush is prepared by zwitterionic monomer and water；
The zwitterionic monomer is one of carboxylic acid glycine betaine, phosphocholine, sulfobetaines；
The solvent substrate is vegetable oil, polyethylene glycol 400, glycerine, one or two kinds of in Macrogol 600；
The coagulation factor is factor I, prothrombin, thromboplastin, factor IV, labile factor, blood coagulation
Factor Ⅴ I, proconvertin, blood coagulation factor VIII, plasma thromboplastin component, Stuart factor, plasma thromboplastin antecedent, Hageman factor,
One or both of factor XIII.
3. a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, which comprises the steps of:
1) amphoteric ion-polysaccharide polymer brush is prepared；
2) amphoteric ion-polysaccharide polymer brush mixed with solvent substrate, stir to get pregel；
3) coagulation factor is added in Xiang Suoshu pregel, stirs to get from thickening bone surface of a wound hemostasis gel.
4. according to claim 3 a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, which is characterized in that step 1)
Described in amphoteric ion-polysaccharide polymer brush preparation process are as follows:
(1) zwitterionic monomer, reagent one and organic solvent are mixed, obtains mixture；
(2) under an inert gas, water-soluble polysaccharide is added in Xiang Suoshu mixture, is reacted, obtains reactant；
(3) it by after reactant cooling, is added in solvent one, is reacted, obtain sediment；
(4) sediment is filtered and is washed, obtain polymer；
(5) polymer is subjected to frozen dried, obtains amphoteric ion-polysaccharide polymer brush.
5. according to claim 4 a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, which is characterized in that the examination
Agent one is cuprous bromide or azodiisobutyronitrile；
The organic solvent is N,N-dimethylformamide, toluene, dimethyl sulfoxide；
The inert gas is at least one of nitrogen, helium, argon gas, neon；
The water-soluble polysaccharide is one of hyaluronic acid, carboxymethyl cellulose, chitosan；
The solvent one is one of ethanol solution, anhydrous methanol, ethyl acetate.
6. according to claim 3 or 4 a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, which is characterized in that institute
Stating the molar ratio that amphoteric ion-polysaccharide polymer brush is mixed with solvent substrate is (1-6): (4-9)；
The zwitterionic monomer reagent one and the molar ratio of organic solvent mixing are (1-10): (0.01-3): 100；
The molar ratio of the water-soluble polysaccharide and the mixture is 1:(100-8)；
The molar ratio of the reactant and solvent one is (1-50): 100；
Described two coagulation factor ratios are 1:(0.1-10) IU；
Described two solvent substrate molar ratios are (0.1-2): 1.
7. according to claim 4 a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, which is characterized in that step
(1) zwitterionic monomer described in, reagent one and organic solvent mixing temperature are 15 DEG C；
The temperature of reaction described in step (2) is 40-75 DEG C, time 24-48h；
Cooling temperature described in step (3) is 20-30 DEG C, and the reaction temperature is 20-30 DEG C, and the reaction time is 24-
48h；
The vacuum degree of suction filtration described in step (4) is 1-100Pa, and the time filtered every time is 5-45min, and number is 2-4 times；
The temperature of the washing is 20-30 DEG C, time 5-10min, and number is 2-4 times, and washing reagent is dehydrated alcohol or third
Ketone；
The temperature of freeze-drying described in step (5) is -20-35 DEG C, time 48-72h.
8. according to claim 3 a kind of from the preparation method for thickening bone surface of a wound hemostasis gel, which is characterized in that step 2)
Described in stirring speed be 100-2000r/min, temperature be 20-30 DEG C, the time stirred every time be 2-30min；
The speed of stirring described in step 3) is 100-2000r/min, and temperature is 20-30 DEG C, and the time stirred every time is 1-
20min。
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