CN107362386A - A kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel and application - Google Patents
A kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel and application Download PDFInfo
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- A—HUMAN NECESSITIES
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- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L24/0031—Hydrogels or hydrocolloids
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- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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- 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
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Abstract
The invention belongs to medicine and health technology field, and in particular to a kind of preparation and its application of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel, comprise the following steps：One is purified chitosan crude product；Two chitosan will be handled through strong base solution after purification, alkylated reaction, and washing is dried to obtain hydroxyl butyl chitosan；Three prepare hydroxyl butyl chitosan Trostin M glue, and through coating-dividing sealing, the process such as sterilizing produces product of the present invention.Product of the present invention has the following advantages that：One gained hydroxyl butyl chitosan is water soluble chitosan, has temperature sensitivity and good biocompatibility.Two can be used for body surface hemostasis, stop blooding in and can body with cavity, are also had broad application prospects in tissue filling, covering and support field of porous materials in addition.
Description
Technical field
The invention belongs to medical and health technology field and gel technique field, and in particular to a kind of preparation and its application of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel.
Background technology
In recent years, many researchs show, the wound hemostasis in emergency treatment, surgical procedure in sudden accident, locally effectively quick-acting haemostatic powder seems extremely important to patient, in particularly performing the operation, stop blooding and reduction is lost blood, keeps that visual area is clear, prevents vital tissue damage, guarantee operation safety and postoperative Wound healing etc. to be respectively provided with significance.
According to the mechanism of hemostasis, people are typically stopped blooding by four kinds of modes at present：First, it is to promote vessel retraction, reduces capillary permeability, reduces CBF, promotes the coagulation process at damaged blood vessels, for example hemostasis is blocked using clamp, ligation.2nd, it is by increasing platelet counts, strengthening its aggregation adhesion, promote intra platelet free calcium blood coagulation activity material, reach hemostasis purpose.3rd, coagulation system activation is promoted, activation factor forms fibrin ferment, and catalyzed by thrombin fibrinogen forms fibrin.4th, stopped blooding by suppressing fibrinolysis.And Hemostasis specifically conventional in surgical procedure have it is following several：First, clamp, hemostasis by ligation；2nd, hemostasis is blocked；3rd, hemostasis by compression；4th, low temperature stops blooding；5th, Hemostatics；6th, heat setting is stopped blooding；7th, decompression hemostasis.
Traditional hemostatic material General Principle is that charge effect is enriched with blood platelet or tissue adhesion's hemostasis, because the defects of apparent be present in such material, as bleeding stopping period is grown, liquid absorption deficiency, dosage is big, and is easy to tissue adhesion, easily causes the secondary bleeding of wound in actual use, in the presence of some tissue exclusiveness, still there is the characteristics of certain physiological-toxicity.Therefore there is more preferable biocompatibility, the new hemostatic material efficiently to stop blooding turns into study hotspot.Then the improvement for hemostatic material is always that a kind of of industry research and development pursues.
Many researchs have confirmed, chitosan is as unique alkaline polysaccharide in nature, chitosan has excellent gel characteristic, pass through the special electrostatic force of group, hydrophobe effect and hydrogen bond action in chitosan molecule chain, it can be produced with some gelling agents compound, the colloidal materials of large quantity of moisture can be kept by being formed, with very strong moisture absorption, performance of keeping humidity, enough viscosity can also be provided simultaneously, mucous membrane, skin etc. can be affixed on and do not fallen off, pessimal stimulation and allergic reaction etc. will not be produced to human body skin.And developing the chitosan gel rubber with specific function turns into study hotspot recently, there are many researchs to concentrate at present and develop various chitose gels and apply biomedical engineering.
Application publication number CN104189941A（Application number 201410444308.5）Chinese patent literature disclose a kind of chitosan gel rubber hemostatic material and preparation method thereof, it is by chitosan, crosslinking agent and fibrin ferment is compound obtains.The invention product adhesion wound, good biocompatibility, it is good to absorb strong haemostatic effect, promotes wound healing, reduces postoperative complications.But because it adds crosslinking agent and fibrin ferment, the use of crosslinking agent easily causes human body uncomfortable, and its preparation process is complicated.Application publication number
CN103665400A（Application number 201310559897.7）Chinese patent literature disclose a kind of preparation method and application of hyacinth bletilla hemostatic gel, use using the bletilla striata and hyaluronic acid as raw material, make hydrogel that there is stronger retractility and certain mechanical strength, be easy to the release of hyaluronic acid again, can be as the use of injection-type hydrogel.Absorbability gelfoam and natural polymer hydrogel are clinically the most frequently used hemostatic materials, but Clinical practice absorbability gelfoam has the shortcomings that secondary infection rate is high, tissue foreign body reaction is big at present.Hydrogel can absorb substantial amounts of water and be swelled while keep solid forms.Its own possessed superior function, but it is poor with the adhesive of wound, the low practical application that also limit it of mechanical strength.
Due to chitosan, carboxymethyl chitosan or hyaluronic acid are primary raw material, in prepared gel products, except unexpected the shortcomings that being previously mentioned, crosslinking agent and substantial amounts of plasticizer are added in various degree, otherwise it is used for the gel products of such use, existing can flow after being applied to human body in tissue, it is not easy to retain, adding a large amount of plasticizer and crosslinking agent not only increases outside cost and the wasting of resources, and conventional crosslinking agent is all different degrees of that human body and environment are impacted, especially in the huge China of current environmental protection pressure, the more aobvious protrusion of contradiction, hydroxyl butyl chitosan gel rubber in the present invention not only overcomes disadvantages mentioned above, also more be advantageous to the effect of human body.In the present invention thermo-responsive hydro gel remove with quick-acting haemostatic powder, wound healing, mitigate patient suffering, the performance such as antibacterial in addition, also with 37 DEG C or so（Body temperature）When quick-gelatinizing characteristic so that it need not add poisonous and hazardous crosslinking agent and a large amount of plasticizer etc..Energy-conserving and environment-protective, prepare and use simple and fast.
The content of the invention
The present invention is directed to the deficiency of existing market hemostasis gel material, there is provided one kind has Thermo-sensitive hydroxyl butyl chitosan hemostasis gel.Products obtained therefrom of the present invention is easy to use, and use range is wide, has good biocompatibility, nontoxic to human body, invention product degradable can absorb in vivo.With quick-acting haemostatic powder, analgesic, detumescence, anti-inflammation and other effects.Shorten operating time, prevent post-operation adhesion, reduce infection rate after abortion operation and the incidence of disease, can effectively mitigate patient pain, accelerating wound healing etc..Specific preparation method is as follows：
Step 1：Chitosan purifying crude
A certain amount of chitosan crude product is weighed, by 1g:50mL ratio is dissolved in 1% hydrochloric acid, is filtered to remove insoluble matter, and 1mol/L sodium hydroxide solutions are added dropwise to meta-alkalescence, are precipitated, with purifying water washing to neutrality, with ethanol solution desalting and dewatering, the chitosan purified after drying.
Step 2：The preparation of Thermo-sensitive hydroxyl butyl chitosan
The Chitosan powder of purifying is pressed into 1g：10mL ratio is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution, and nitrogen protection is lower to heat 24 hours, and temperature is 25 DEG C -80 DEG C.Unnecessary alkali lye is filtered out, remaining solid content is pressed into 1g：20mL ratio is distributed in isopropanol water solution, then adds 1, the 2- epoxy butanes of certain volume, is reacted 1 hour, is heated 24 hours to 72 hours at 25 DEG C -80 DEG C.PH value is adjusted after cooling to neutrality, insoluble matter is filtered out, centrifuges, dries after addition ethanol, obtain with temperature sensitivity hydroxyl butyl chitosan product.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, prepare hydroxyl butyl chitosan gel rubber solution, under room temperature condition, a certain amount of hydroxyl butyl Chitosan powder is weighed, reduces speed of agitator, is added in preprepared water, stirring is opened to being completely dissolved, it is separately added into beta-schardinger dextrin, antioxidant and preservative again, stirring is to being completely dissolved.Then measure appropriate plasticizer to add in above-mentioned solution, continue to stir, until mixing completely.Correlative addition：By weight percentage, wherein hydroxyl butyl chitosan concentration is 0.5% ~ 20%, the concentration of beta-schardinger dextrin be 0.1% ~ 10%, the concentration of antioxidant be 0.001% ~ 0.5% and 0.001% ~ 1% preservative, be 1% ~ 50% by the concentration of percent by volume plasticizer.
Step 4：Deaeration
The hydroxyl butyl chitosan solution completed will be prepared, connect vacuum equipped, carry out standing and defoaming, deaeration surging is that deaeration pressure is -8 × 105~-3 × 105Pa, inclined heated plate are 5~30min.After the completion of deaeration, dried and clean turnover barrel good seal is transferred to, is transferred to packing workshop.
Step 5：Coating-dividing sealing
According to production ordering, prepare relevant device and material, open filling apparatus in advance, after debugging meets the requirements, the hydroxyl butyl chitosan gel rubber liquid that deaeration is completed is taken out from turnover barrel, started filling.The product of filling amount, as needed filling different capabilities is adjusted, sealed through automatic sealing, be put into dedicated box and prepare sterilizing.
Step 6：Sterilizing
The product for producing completion is sterilized：
Sterilizing parameter is 121 DEG C of moist heat sterilization, 5min ~ 30min or send Radiation Center to be irradiated, and irradiation dose is 15KGy ~ 40KGy.
Product provided by the invention has the following advantages that：
First, this product hydroxyl butyl chitosan gel rubber; it is the high-molecular compound chitin purified from shrimp shell; by deacetylated processing; the chitosan of certain deacetylation is obtained, then by a kind of hydroxyl butylamino glucose made of hydroxyl butylation and deep processing, there is good hemostasis, prevent adhesion, the effect of antibacterial and tissue repair; inflammatory reaction to wound tissue is small; quick-acting haemostatic powder, accelerate wound healing, repair, and there is good histocompatbility.
2nd, hydroxyl butyl chitosan has Thermo-sensitive, and it is in 37 degrees centigrades（Human body temperature）Can rapid gellation, and be liquid in normal temperature, therefore applied very convenient in human body, can be used at various positions, including body surface, internal and cavity etc., play its exclusive advantage.And good with contact site stickiness after its gelation, deformation difficult for drop-off.Thermo-sensitive is shown in Fig. 1.
3rd, hydroxyl butyl chitosan is water soluble chitosan of new generation, compared to other chitosan class products, directly can prepare slurry with deionized water, avoid using acid solution, environment friendliness.
4th, crosslinking agent is not used in product of the present invention, avoids using organic crosslinking agents such as formaldehyde, overcomes the security for easily in human body the shortcomings that residual toxicity, improving product.
Five, this products can be used as slow controlled-release material be mixed with medicine, for the use at position in non-vascular, increase the action time of medicine.
Six, this products can be applied in organization bracket field of porous materials.
The content of the invention
Illustrate technical scheme, but protection domain not limited to this with reference to embodiment and experimental example.
Embodiment one
Step 1：Chitosan purifying crude
1000g chitosan crude product is weighed, by 1g:50mL ratio is dissolved in 1% hydrochloric acid, is filtered to remove insoluble matter, and 1mol/L sodium hydroxide solutions are added dropwise to meta-alkalescence, are precipitated, with purifying water washing to neutrality, with ethanol solution desalting and dewatering, the chitosan purified after drying.
Step 2：The preparation of Thermo-sensitive hydroxyl butyl chitosan
The Chitosan powder 500g of purifying is pressed into 1g：10mL ratio is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution, and nitrogen protection is lower to heat 24 hours, and temperature is 40 DEG C.Unnecessary alkali lye is filtered out, remaining solid content is pressed into 1g：20mL ratio is distributed in isopropanol water solution, then adds 1, the 2- epoxy butanes of certain volume, is reacted 1 hour, is heated 36 hours at 50 DEG C.PH value is adjusted after cooling to neutrality, insoluble matter is filtered out, centrifuges, dries after addition ethanol, obtain with temperature sensitivity hydroxyl butyl chitosan product.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, hydroxyl butyl chitosan gel rubber solution is prepared, under room temperature condition, 200g hydroxyl butyl Chitosan powders is weighed, reduces speed of agitator, add in 10L water, opens stirring to being completely dissolved, adds beta-schardinger dextrin 50g, stirring is until complete dissolved clarification.Weigh 1g sodium hydrogensulfites and 2g poly-D-lysines respectively again, be added in solution and stir to being completely dissolved.Then 500mL polyethylene glycol 400s are measured to add in above-mentioned solution, continue to stir, until mixing completely.
Step 4：Deaeration
The hydroxyl butyl chitosan solution in step 3 is transferred in the good glass kettle of sealing, connects vacuum equipped, open vavuum pump, it is -5 × 10 to set deaeration pressure5Pa, start deaeration, inclined heated plate 15min.After the completion of deaeration, dried and clean turnover barrel good seal is transferred to, is transferred to packing workshop.
Step 5：Coating-dividing sealing
According to production ordering, prepare relevant device and material, open filling apparatus in advance, after debugging meets the requirements, the hydroxyl butyl chitosan gel rubber liquid that deaeration is completed is taken out from turnover barrel, started filling.Regulation filling amount is 15mL, and beginning is filling, is sealed through automatic sealing, is put into dedicated box and prepares sterilizing.
Step 6：Sterilizing
The product for producing completion is sterilized：
Radiation Center is sent to be irradiated, irradiation dose 25KGy.
After sterilizing, Quality Mgmt Dept's detection product, product of the present invention is obtained after detection is qualified.
Embodiment two
Step 1：Chitosan purifying crude
2000g chitosan crude products are weighed, by 1g:50mL ratio is dissolved in 1% hydrochloric acid, is filtered to remove insoluble matter, and 1mol/L sodium hydroxide solutions are added dropwise to meta-alkalescence, are precipitated, with purifying water washing to neutrality, with ethanol solution desalting and dewatering, the chitosan purified after drying.
Step 2：The preparation of Thermo-sensitive hydroxyl butyl chitosan
The Chitosan powder 1500g of purifying is pressed into 1g：10mL ratio is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution, and nitrogen protection is lower to heat 24 hours, and temperature is 80 DEG C.Unnecessary alkali lye is filtered out, remaining solid content is pressed into 1g：20mL ratio is distributed in isopropanol water solution, then adds 1, the 2- epoxy butanes of certain volume, is reacted 1 hour, is heated 36 hours at 80 DEG C.PH value is adjusted after cooling to neutrality, insoluble matter is filtered out, centrifuges, dries after addition ethanol, obtain with temperature sensitivity hydroxyl butyl chitosan product.
Step 3：Hydroxyl butyl chitosan solution is prepared
In dust proof workshop, hydroxyl butyl chitosan gel rubber solution is prepared, under room temperature condition, weigh 500g hydroxyl butyl Chitosan powders, reduce speed of agitator, add in 50L water, open stirring to being completely dissolved, add beta-schardinger dextrin 500g, stirring is until complete dissolved clarification.Weigh 10g cysteines and 10g glucolactones respectively again, be added in solution and stir to being completely dissolved.Then measure 1000mL glycerine to add in above-mentioned solution, continue to stir, until mixing completely.
Step 4：Deaeration
The hydroxyl butyl chitosan solution in step 3 is transferred in the good glass kettle of sealing, connects vacuum equipped, open vavuum pump, deaeration pressure is -8 × 105Pa, inclined heated plate 8min.After the completion of deaeration, dried and clean turnover barrel good seal is transferred to, is transferred to packing workshop.
Step 5：Coating-dividing sealing
According to production ordering, prepare relevant device and material, open filling apparatus in advance, after debugging meets the requirements, the hydroxyl butyl chitosan gel rubber liquid that deaeration is completed is taken out from turnover barrel, started filling.Regulation filling amount is 50mL, and beginning is filling, is sealed through automatic sealing, is put into dedicated box and prepares sterilizing.
Step 6：Sterilizing
The product for producing completion is sterilized：Sterilizing parameter is 121 DEG C of moist heat sterilization, 30min.
After sterilizing, Quality Mgmt Dept's detection product, product of the present invention is obtained after detection is qualified.
Embodiment three
Step 1：Chitosan purifying crude
500g chitosan crude products are weighed, by 1g:50mL ratio is dissolved in 1% hydrochloric acid, is filtered to remove insoluble matter, and 1mol/L sodium hydroxide solutions are added dropwise to meta-alkalescence, are precipitated, with purifying water washing to neutrality, with ethanol solution desalting and dewatering, the chitosan purified after drying.
Step 2：The preparation of Thermo-sensitive hydroxyl butyl chitosan
The Chitosan powder 400g of purifying is pressed into 1g：10mL ratio is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution, and nitrogen protection is lower to heat 24 hours, and temperature is 40 DEG C.Unnecessary alkali lye is filtered out, remaining solid content is pressed into 1g：20mL ratio is distributed in isopropanol water solution, then adds 1, the 2- epoxy butanes of certain volume, is reacted 1 hour, is heated 60 hours at 60 DEG C.PH value is adjusted after cooling to neutrality, insoluble matter is filtered out, centrifuges, dries after addition ethanol, obtain with temperature sensitivity hydroxyl butyl chitosan product.
Step 3：Hydroxyl butyl chitosan solution is prepared
In dust proof workshop, hydroxyl butyl chitosan gel rubber solution is prepared, under room temperature condition, weigh 200g hydroxyl butyl Chitosan powders, reduce speed of agitator, add in 2L water, open stirring to being completely dissolved, add beta-schardinger dextrin 4, stirring is until complete dissolved clarification.Weigh 1g potassium sorbates and 0.5g sodium benzoates respectively again, be added in solution and stir to being completely dissolved.Then measure 500mL glycerine to add in above-mentioned solution, continue to stir, until mixing completely.
Step 4：Deaeration
The hydroxyl butyl chitosan solution in step 3 is transferred in the good glass kettle of sealing, connects vacuum equipped, open vavuum pump, deaeration pressure is -4 × 105Pa, inclined heated plate 25min.After the completion of deaeration, dried and clean turnover barrel good seal is transferred to, is transferred to packing workshop.
Step 5：Coating-dividing sealing
According to production ordering, prepare relevant device and material, open filling apparatus in advance, after debugging meets the requirements, the hydroxyl butyl chitosan gel rubber liquid that deaeration is completed is taken out from turnover barrel, started filling.Regulation filling amount is 3mL, and beginning is filling, is sealed through automatic sealing, is put into dedicated box and prepares sterilizing.
Step 6：Sterilizing
The product for producing completion is sterilized：Radiation Center is sent to be irradiated, irradiation dose 30KGy.
After sterilizing, Quality Mgmt Dept's detection product, product of the present invention is obtained after detection is qualified.
Zoopery
To confirm that this product hemostasis, and adhesion inhibiting properties and histocompatbility, spy carry out zoopery, the rat chosen under an identical environment is tested as control experiment and product of the present invention.Make discovery from observation postoperative 14 days, control rats tissue adhesion is serious, is not easy to separate；And product of the present invention does not have adhesion, and product is degradable does not remain, and experimental animal indices are normal.Specific effect is shown in Fig. 2（Control group effect）And Fig. 3（Product group of the present invention）.
Claims (23)
1. a kind of preparation and its application of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel, it is characterized in that, hydroxyl butyl chitosan is water soluble chitosan, and it has temperature sensitivity, preparation process includes the preparation of hydroxyl butyl chitosan, the preparation of hydroxyl butyl chitosan gel rubber liquid, defoaming, different size is distributed into, sterilizing is made.
2. product of the present invention is mainly used in people's body surface, in vivo and cavity stops blooding.
3. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 1, it is characterised in that preparing for hydroxyl butyl chitosan gel rubber is as follows：A certain amount of chitosan crude product is weighed, by 1g:50mL ratio is dissolved in 1% hydrochloric acid, is filtered to remove insoluble matter, and 1mol/L sodium hydroxide solutions are added dropwise to meta-alkalescence, are precipitated, with purifying water washing to neutrality, with ethanol solution desalting and dewatering, the chitosan purified after drying.
4. Chitosan powder after purification is pressed into 1g：10mL ratio is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution, and nitrogen protection is lower to heat 24 hours, and temperature is 25 DEG C -80 DEG C.
5. filtering out unnecessary alkali lye, remaining solid content is pressed into 1g：20mL ratio is distributed in isopropanol water solution, then adds 1, the 2- epoxy butanes of certain volume, is reacted 1 hour, is heated 24 hours to 72 hours at 25 DEG C -80 DEG C.
6. adjusting pH value after cooling to neutrality, insoluble matter is filtered out, centrifuges, dry after addition ethanol, obtain hydroxyl butyl chitosan product.
7. under the conditions of clean environment, weigh the hydroxyl butyl Chitosan powder of constant weight, open stirring and at the uniform velocity add in preprepared water and dissolve, obtain certain density hydroxyl butyl chitosan solution, after hydroxyl butyl chitosan is completely dissolved, weighing a certain amount of beta-schardinger dextrin, antioxidant and preservative and being added in above-mentioned solution is completely dissolved it, reduces rotating speed.
8. the plasticizer for measuring certain volume is at the uniform velocity added thereto, mix, vacuum deaerator, stand, packaging, sterilizing just obtains the hydroxyl butyl chitosan gel rubber of the present invention with Thermo-sensitive.
9. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 2 ~ 8, it is characterised in that by weight percentage, it is 0.5 to have the ratio of Thermo-sensitive hydroxyl butyl chitosan and water:100~20：100.
10. the ratio preferably with Thermo-sensitive hydroxyl butyl chitosan and water is 5:100~15：100.
11. the ratio of Thermo-sensitive hydroxyl butyl chitosan and water that has for more having choosing is 6:100~8：100.
12. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 7, it is characterised in that by weight percentage, the ratio of beta-schardinger dextrin and water is 0.1:100~10:100.
13. the ratio of preferable beta-schardinger dextrin and water is 0.5:100~5:100.
14. the ratio of preferred beta-schardinger dextrin and water is:1:100~2:100.
15. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 7, it is characterised in that the species of antioxidant is：The ratio of sodium hydrogensulfite, cysteine or potassium sorbate, by weight percentage antioxidant and water is 0.001:100~0.5:100；Preferably the ratio of antioxidant and water is 0.05 by weight percentage:100~0.2:100.
16. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 7, it is characterised in that preservative is harmless preservative, and its species is：Polyaminopropyl biguanide, glucolactone, calcium gluconate, poly-D-lysine, propylparaben and sodium benzoate, therefrom choose any one kind of them, and by weight percentage, the mass ratio of each preservative and water is 0.001：100~1:100.
17. the mass ratio of each preferable preservative and water is 0.01：100~0.05:100.
18. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 8, it is characterised in that the species of plasticizer is：The ratio of polyethylene glycol, glycerine and sodium carboxymethylcellulose, by weight percentage thickener and water is 0.1:100~50:100；Wherein polyethylene glycol is PEG200, PEG400, PEG600.
19. preferably the ratio of plasticizer and water is 2 by weight percentage:100~20:100.
20. more preferably the ratio of plasticizer and water is 5 by weight percentage:100~10:100.
21. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 8, it is characterised in that need to carry out chitosan gel rubber solution vacuum deaerator in hydroxyl butyl chitosan gel rubber solution preparation process, deaeration pressure is -8 × 105~-3 × 105Pa, inclined heated plate are 5~30min.
22. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 8, it is characterised in that sterilization method is：Moist heat sterilization and irradiation sterilization；Sterilizing parameter is 121 DEG C, 5min ~ 30min of moist heat sterilization, and irradiation sterilization is that electron beam sterilization or cobalt -60 sterilize, and its sterilizing dose is 10kGy ~ 25KGy.
23. the preparation and its application of a kind of Thermo-sensitive hydroxyl butyl chitosan hemostasis gel according to claim 1, characterized in that, product specification is 1mL, 3mL, 5mL, 6mL, 8mL, 10mL, 15mL, 20mL, 25mL, 30mL, 35mL, 40mL, 45mL, 50mL, 100mL, 200mL, 300mL, 400mL, 500mL.
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| CN108342043A (en) * | 2017-12-29 | 2018-07-31 | 佛山市锦彤企业管理有限公司 | A kind of antibacterial thermosensitive polymer hydrogel |
| CN108440771A (en) * | 2017-12-29 | 2018-08-24 | 佛山市锦彤企业管理有限公司 | A kind of temperature-responsive polymer hydrogel |
| CN108653818A (en) * | 2018-05-24 | 2018-10-16 | 上海其胜生物制剂有限公司 | A kind of reversible collagen stimulation filler and preparation method thereof |
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| CN113908329A (en) * | 2021-09-29 | 2022-01-11 | 惠众国际医疗器械（北京）有限公司 | Implantable hydrogel dressing and preparation method thereof |
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| CN108440771A (en) * | 2017-12-29 | 2018-08-24 | 佛山市锦彤企业管理有限公司 | A kind of temperature-responsive polymer hydrogel |
| CN110386995A (en) * | 2018-04-19 | 2019-10-29 | 中国海洋大学 | A kind of homogeneous phase synthetic method of hydroxyl butyl chitosan |
| CN108653818A (en) * | 2018-05-24 | 2018-10-16 | 上海其胜生物制剂有限公司 | A kind of reversible collagen stimulation filler and preparation method thereof |
| CN109646393A (en) * | 2018-11-21 | 2019-04-19 | 惠众国际医疗器械（北京）有限公司 | A kind of temperature sensitive hydrogel and preparation method thereof for surface wound reparation |
| WO2022116385A1 (en) * | 2020-12-01 | 2022-06-09 | 爱美客技术发展股份有限公司 | Unsaturated hydroxybutyl chitosan and thermosensitive hydrogel, and preparation method therefor and use thereof |
| CN115252894A (en) * | 2021-04-29 | 2022-11-01 | 上海大学 | Composite hydrogel bracket and application thereof in preparation of product for repairing nerve injury |
| CN113174063A (en) * | 2021-04-30 | 2021-07-27 | 北京大学 | Preparation and application of bioadhesive enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel |
| CN113174063B (en) * | 2021-04-30 | 2022-03-18 | 北京大学 | Preparation and application of bioadhesive enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel |
| CN113908329A (en) * | 2021-09-29 | 2022-01-11 | 惠众国际医疗器械（北京）有限公司 | Implantable hydrogel dressing and preparation method thereof |
| CN113908329B (en) * | 2021-09-29 | 2022-07-08 | 惠众国际医疗器械（北京）有限公司 | Implantable hydrogel dressing and preparation method thereof |
| CN115337467A (en) * | 2022-08-16 | 2022-11-15 | 万瑞飞鸿(北京)医疗器材有限公司 | Drug coating, intravascular stent, and preparation method and application thereof |
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