CN107033258A - A kind of hydroxyl butyl chitosan medical sponge and preparation method thereof - Google Patents
A kind of hydroxyl butyl chitosan medical sponge and preparation method thereof Download PDFInfo
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- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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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- 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
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
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Abstract
The invention belongs to medicine and health technology field, and in particular to a kind of hydroxyl butyl chitosan sponge and preparation method thereof.The sponge is made up of hydroxyl butyl chitosan, sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, plastic agent (one or more in glycerine, polyethylene glycol).Crosslinking agent need not be added, there is temperature-sensing property after absorptive tissue liquid or blood, gel state can be converted into when reaching normal body temperature, it is firmly combined with tissue, with stopping blooding, prevent adhesion, the effect that promotion organization is repaired, it can also be used in combination with bactericide, growth factor and other drugs, can also be applied to organizational project and artificial organs field.
Description
Technical field
The invention belongs to medicine and health technology field, and in particular to a kind of hydroxyl butyl chitosan sponge and preparation method thereof.
Background technology
At present, on China medical market, a variety of medical sponge products are widely used in surgical hemostasis, cavity hemostasis and wound healing treatment.
The home and overseas styptic sponge product registered in state food pharmaceuticals administration general bureau of China, main species include：Polyvinyl alcohol medical sponge,
Polyvinyl alcohol and glycerine, collagen protein sponge, polyvinyl formal sponge, chitosan styptic sponge, absorbable gelatin sponge, carboxymethyl shell
Glycan sponge.Wherein, the medical sponge that gelatin, collagen material are prepared from, because its raw material is foreign protei, using in human body,
Easily immunogene is caused to be reacted；Polyvinyl alcohol sponge has formaldehyde etc. to participate in reaction when preparing, it, which is remained, to bring ill-effect to human body.It is poly- including shell
The sponge that the above material such as sugar, carboxymethyl chitosan is made, although its water imbibition, hemostatic effect are preferable, but presence is insecure with tissue adhension,
It is easily separated from the shortcoming of the surface of a wound.And the hydroxyl butyl chitosan sponge for preparing of the present invention overcomes disadvantages mentioned above, at the same can also play prevent adhesion, promotion group
Knit healing and other effects.
The content of the invention
The present invention provides a kind of hydroxyl butyl chitosan medical sponge and preparation method thereof.
To achieve the above object, the present invention provides following preparation method：
Step one：Chitosan purifying products
A certain amount of chitosan crude product is weighed, 1% hydrochloric acid is dissolved in 1g: 50mL ratio, insoluble matter is filtered to remove, 1mol/L hydrogen-oxygens are added dropwise
Change sodium solution to meta-alkalescence, precipitated, with purifying water washing to neutrality, use ethanol solution desalting and dewatering, the chitosan purified after drying.
Step 2：The preparation of hydroxyl butyl chitosan
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 25 DEG C -80 DEG C.Unnecessary alkali lye is filtered out, remaining solid content is distributed to isopropyl in 1g: 20mL ratio
In alcohol solution, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are 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, centrifugation after ethanol is added, dries, obtain hydroxyl butyl chitosan product.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, hydroxyl butyl chitosan solution is prepared, according to hydroxyl butyl 0.1~200.0mg/mL of chitosan content, sodium chloride content
0~9.0mg/mL, disodium hydrogen phosphate 0~2.0mg/ml of content, biphosphate 0~2.0mg/ml of sodium content, plastic agent is (one in glycerine, polyethylene glycol
Kind or more than one) 0~100.0mg/ml ratio weighs above-mentioned article and is dissolved in purified water or water for injection, stirring is until be completely dissolved.
Non-final sterilising prods, filtration sterilization is carried out with filtration sterilization device in this step continuation, and deaeration thereafter and lyophilized, cutting packaging etc.
Step, is operated using sterile processing, it is ensured that the sterile level of product.Final sterilized prod is then sterilized in step 6.
Step 4：Deaeration is with freezing
The hydroxyl butyl chitosan solution completed will be prepared, connect vacuum equipped, carried out standing and defoaming, hydroxyl butyl chitosan solution is poured into mould after finishing
In tool, pre-freeze 1h~24h in -80 DEG C~-20 DEG C of fast freezing case is placed in, then freeze-drying obtains bulk sponge.
Step 5：Cutting packaging
Hydroxyl butyl chitosan sponge after will be lyophilized, is removed from the molds, and selective thickness reduction is carried out as requested.Cutting equipment is adjusted, according to
Need to cut into different size, be put into packaging bag, sealed through automatic sealing, it is packaged after be put into sterilizing dedicated box.
Step 6：Sterilizing
The product completed will be produced, carry out ethylene oxide sterilizing or radiation sterilization.Non-final sterilising prods are without this step.
The product that the present invention is provided has the following advantages that：
1. the main component hydroxyl butyl chitosan of this product, is the high-molecular compound chitin purified from shrimp shell, by deacetylated processing, obtains
To the chitosan of certain deacetylation, then a kind of hydroxyl butylamino glucose being made by hydroxyl butylation and deep processing, stop blooding, prevent with good
Adhesion and tissue repair effect, the inflammatory reaction to wound tissue are small, accelerate wound healing, repair, and with good histocompatbility.
2. this product also has temperature-sensing property.Sponge is after water suction or blood, less than being liquid condition under gelling temp, but when temperature is higher than solidifying
During glue temperature (can change preparation parameter to be designed as being less than 37 DEG C), its energy rapid curing is gel state, and both states are reversible.Can
To adjust the gelling temp of gel by the molecular weight for adjusting hydroxyl butyl chitosan, hydroxyl butyl substitution value and concentration, body temperature is made it below, because
And when acting on human body (body surface is internal), this product absorptive tissue liquid or blood, it will be changed into gel state from solution state are fixed on
Tissue, the surface of a wound or other tissue surfaces, are firmly combined with, will not because of adhesion loosely, displacement etc. cause product the surface of a wound can not be played hemostasis, prevent adhesion,
The protective effects such as promotion organization healing.
3. this product is without using crosslinking agent, it is to avoid residual cross-linker retains and produces toxic side effect in the tissue.
4. the product in the present invention can be combined with bactericide, growth factor and other drugs, targetedly tissue is treated.
5. this product can apply to organizational project and artificial organs field.
The product preparation method that the present invention is provided has the following advantages that：
1. the preparation of hydroxyl butyl chitosan and the preparation process cycle of sponge are shorter, efficiency high, so that large-scale production is possibly realized.
2. the main material of this product belongs to animal derived material, according to domestic and international laws and regulations requirement, it is both needed to carry out the inactivation of virus of product and removes immune
Originality.And the product preparation method that the present invention is provided can effectively remove virus and immunogene, substantially increase the security of product.
Brief description of the drawings
Macrograph when Fig. 1 is not packed for the product prepared in embodiment 2.
Macrograph when Fig. 2 is not packed for the product prepared in embodiment 5.
Embodiment
Embodiment 1
Step one：Chitosan purifying products
A certain amount of chitosan crude product is weighed, 1% hydrochloric acid is dissolved in 1g: 50mL ratio, insoluble matter is filtered to remove, 1mol/L hydrogen-oxygens are added dropwise
Change sodium solution to meta-alkalescence, precipitated, with purifying water washing to neutrality, use ethanol solution desalting and dewatering, the chitosan purified after drying.
Step 2：The preparation of hydroxyl butyl chitosan
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 50 DEG C.Unnecessary alkali lye is filtered out, it is water-soluble that in 1g: 20mL ratio remaining solid content is distributed into isopropanol
In liquid, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are heated 18 hours at 70 DEG C.PH value is adjusted after cooling into
Property, insoluble matter is filtered out, centrifugation after ethanol is added, dries, hydroxyl butyl chitosan product is obtained.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, prepare hydroxyl butyl chitosan solution, according to hydroxyl butyl chitosan content 150.0mg/mL, glycerine 50.0mg/mL,
Polyethylene glycol 50.0mg/ml ratio weighs above-mentioned article and is dissolved in purified water, and stirring is until be completely dissolved.
Step 4：Deaeration is with freezing
The hydroxyl butyl chitosan solution completed will be prepared, connect vacuum equipped, carried out standing and defoaming, hydroxyl butyl chitosan solution is poured into mould after finishing
In tool, pre-freeze 24h in -80 DEG C of fast freezing case is placed in, then freeze-drying obtains bulk sponge.
Step 5：Cutting packaging
Hydroxyl butyl chitosan sponge after will be lyophilized, is removed from the molds.Cutting equipment is adjusted, 5cm × 5cm specification is cut into as needed,
Be put into packaging bag, sealed through automatic sealing, it is packaged after be put into sterilizing dedicated box.
Step 6：Sterilizing
The product completed will be produced, carry out ethylene oxide sterilizing.
After testing, this product is impregnated in the purified water of same volume, and its gelling temp is 31 DEG C.
Embodiment 2
Step one：Chitosan purifying products
Step one in be the same as Example 1.
Step 2：The preparation of hydroxyl butyl chitosan
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 40 DEG C.Unnecessary alkali lye is filtered out, it is water-soluble that in 1g: 20mL ratio remaining solid content is distributed into isopropanol
In liquid, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are heated 24 hours at 60 DEG C.PH value is adjusted after cooling into
Property, insoluble matter is filtered out, centrifugation after ethanol is added, dries, hydroxyl butyl chitosan product is obtained.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, prepare hydroxyl butyl chitosan solution, according to hydroxyl butyl chitosan content 100.0mg/mL, glycerine 20.0mg/mL,
Polyethylene glycol 20.0mg/ml ratio weighs above-mentioned article and is dissolved in purified water, and stirring is until be completely dissolved.
Step 4：Deaeration is with freezing
Step 4 in be the same as Example 1.
Step 5：Cutting packaging
Hydroxyl butyl chitosan sponge after will be lyophilized, is removed from the molds, thickness 6mm sponge is compressed into 3mm.Cutting equipment is adjusted, according to
Need to cut into 2.5cm × 5cm specification, be put into packaging bag, sealed through automatic sealing, it is packaged after be put into sterilizing dedicated box.
Step 6：Sterilizing
The product completed will be produced, carry out co-60 radiation sterilizing, sterilizing dose is 25KGy.
After testing, this product is impregnated in the purified water of same volume, and its gelling temp is 29 DEG C.
Embodiment 3
Step one：Chitosan purifying products
Step one in be the same as Example 1.
Step 2：The preparation of hydroxyl butyl chitosan
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 50 DEG C.Unnecessary alkali lye is filtered out, it is water-soluble that in 1g: 20mL ratio remaining solid content is distributed into isopropanol
In liquid, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are heated 24 hours at 55 DEG C.PH value is adjusted after cooling into
Property, insoluble matter is filtered out, centrifugation after ethanol is added, dries, hydroxyl butyl chitosan product is obtained.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, prepare hydroxyl butyl chitosan solution, according to hydroxyl butyl chitosan content 50.0mg/mL, glycerine 10.0mg/mL,
Polyethylene glycol 10.0mg/ml ratio weighs above-mentioned article and is dissolved in water for injection, and stirring is until be completely dissolved.
Step 4：Deaeration is with freezing
Step 4 in be the same as Example 1.
Step 5：Cutting packaging
Hydroxyl butyl chitosan sponge after will be lyophilized, is removed from the molds.Cutting equipment is adjusted, 2.5cm × 2.5cm rule are cut into as needed
Lattice, are put into packaging bag, are sealed through automatic sealing, it is packaged after be put into sterilizing dedicated box.
Step 6：Sterilizing
The product completed will be produced, carry out electron beam radiation disinfection, sterilizing dose is 25KGy.
After testing, this product is impregnated in the purified water of same volume, and its gelling temp is 27 DEG C.
Embodiment 4
Step one：Chitosan purifying products
Step one in be the same as Example 1.
Step 2：The preparation of hydroxyl butyl chitosan
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 40 DEG C.Unnecessary alkali lye is filtered out, it is water-soluble that in 1g: 20mL ratio remaining solid content is distributed into isopropanol
In liquid, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are heated 48 hours at 50 DEG C.PH value is adjusted after cooling into
Property, insoluble matter is filtered out, centrifugation after ethanol is added, dries, hydroxyl butyl chitosan product is obtained.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, hydroxyl butyl chitosan solution is prepared, according to hydroxyl butyl chitosan content 50.0mg/mL, sodium chloride content 8.0mg/mL,
Disodium hydrogen phosphate content 0.5mg/ml, biphosphate sodium content 0.15mg/ml ratio weigh above-mentioned article and are dissolved in water for injection, stirring until
It is completely dissolved.
Step 4：Deaeration is with freezing
Step 4 in be the same as Example 1.
Step 5：Cutting packaging
Hydroxyl butyl chitosan sponge after will be lyophilized, is removed from the molds.Cutting equipment is adjusted, 5cm × 10cm specification is cut into as needed,
Be put into packaging bag, sealed through automatic sealing, it is packaged after be put into sterilizing dedicated box.
Step 6：Sterilizing
The product completed will be produced, carry out co-60 radiation sterilizing, sterilizing dose is 25KGy.
After testing, this product is impregnated in the purified water of same volume, and its gelling temp is 26 DEG C.
Embodiment 5
Step one：Chitosan purifying products
Step one in be the same as Example 1.
Step 2：The preparation of hydroxyl butyl chitosan
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 50 DEG C.Unnecessary alkali lye is filtered out, it is water-soluble that in 1g: 20mL ratio remaining solid content is distributed into isopropanol
In liquid, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are heated 12 hours at 55 DEG C.PH value is adjusted after cooling into
Property, insoluble matter is filtered out, centrifugation after ethanol is added, dries, hydroxyl butyl chitosan product is obtained.
Step 3：Hydroxyl butyl chitosan solution is prepared
Under the conditions of clean environment, hydroxyl butyl chitosan solution is prepared, hydroxyl butyl is weighed according to hydroxyl butyl chitosan content 200.0mg/mL ratio
Chitosan dissolution of raw material is in water for injection, and stirring is until be completely dissolved.Filtration sterilization is carried out with filtration sterilization device.
Step 4：Deaeration is with freezing
Under aseptic processing conditions, by the hydroxyl butyl chitosan solution of filtration sterilization, vacuum equipped is connected, standing and defoaming is carried out, by hydroxyl fourth after finishing
Base chitosan solution is poured into mould, is placed in pre-freeze 1h~24h in -80 DEG C~-20 DEG C of fast freezing case, and then freeze-drying obtains bulk sponge.
Step 5：Cutting packaging
Under aseptic processing conditions, the hydroxyl butyl chitosan sponge after freezing is removed from the molds.Cutting equipment is adjusted, is cut into as needed
Diameter 5cm specification, is put into packaging bag, is sealed through automatic sealing.
After testing, this product is impregnated in the sterilized water for injection of same volume, and its gelling temp is 24 DEG C.
Claims (6)
1. a kind of hydroxyl butyl chitosan sponge, it is characterised in that (sweet by hydroxyl butyl chitosan, sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, plastic agent
It is one or more kinds of in oil, polyethylene glycol) composition.
2. in the product in claim 1, by quality apparent volume ratio, hydroxyl butyl chitosan content is 0.1~200.0mg/cm3, sodium chloride content is
0~9.0mg/cm3, disodium hydrogen phosphate content is 0~2.0mg/cm3, biphosphate sodium content is 0~2.0mg/ml, plastic agent (glycerine, polyethylene glycol
Middle one or more) content be 0~100.0mg/cm3Ratio.
3. the product preparation method in claim 1 is prepared including chitosan purifying products, the preparation of hydroxyl butyl chitosan, hydroxyl butyl chitosan solution, taken off
Bubble is with freezing, cutting the step such as packaging and sterilizing.Specially：
1) chitosan purifying products：
A certain amount of chitosan crude product is weighed, 1% hydrochloric acid is dissolved in 1g: 50mL ratio, insoluble matter is filtered to remove, 1mol/L hydrogen-oxygens are added dropwise
Change sodium solution to meta-alkalescence, precipitated, with purifying water washing to neutrality, use ethanol solution desalting and dewatering, the chitosan purified after drying.
2) preparation of hydroxyl butyl chitosan：
The Chitosan powder of purifying is scattered in basification in 50% sodium hydroxide or potassium hydroxide aqueous solution in 1g: 10mL ratio, nitrogen is protected
Shield is lower to be heated 24 hours, and temperature is 25 DEG C -80 DEG C.Unnecessary alkali lye is filtered out, remaining solid content is distributed to isopropyl in 1g: 20mL ratio
In alcohol solution, 1, the 2- epoxy butanes of certain volume are subsequently added, are reacted 1 hour, are 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, centrifugation after ethanol is added, dries, obtain hydroxyl butyl chitosan product.
3) hydroxyl butyl chitosan solution is prepared：
Under the conditions of clean environment, hydroxyl butyl chitosan solution is prepared, according to hydroxyl butyl 0.1~200.0mg/mL of chitosan content, sodium chloride content
0~9.0mg/mL, disodium hydrogen phosphate 0~2.0mg/ml of content, biphosphate 0~2.0mg/ml of sodium content, plastic agent is (one in glycerine, polyethylene glycol
Kind or more than one) 0~100.0mg/ml ratio weighs above-mentioned article and is dissolved in purified water or water for injection, stirring is until be completely dissolved.
Non-final sterilising prods, filtration sterilization is carried out with filtration sterilization device in this step continuation, and deaeration thereafter and lyophilized, cutting packaging etc.
Step, is operated using sterile processing, it is ensured that the sterile level of product.Final sterilized prod is then sterilized in step 6.
4) deaeration is with freezing：
The hydroxyl butyl chitosan solution completed will be prepared, connect vacuum equipped, carried out standing and defoaming, hydroxyl butyl chitosan solution is poured into mould after finishing
In tool, pre-freeze 1h~24h in -80 DEG C~-20 DEG C of fast freezing case is placed in, then freeze-drying obtains bulk sponge.
5) cutting packaging：
Hydroxyl butyl chitosan sponge after will be lyophilized, is removed from the molds, and selective thickness reduction is carried out as requested.Cutting equipment is adjusted, according to
Need to cut into different size, be put into packaging bag, sealed through automatic sealing, it is packaged after be put into sterilizing dedicated box.
6) sterilize：
The product completed will be produced, carry out ethylene oxide sterilizing or radiation sterilization.Non-final sterilising prods are without this step.
4. the application in the fields such as this product is stopped blooding, prevented adhesion in vivo and in vitro, promotion organization reparation.
5. application of this product after being combined with bactericide, growth factor and other drugs.
6. this product is in the application in organizational project and artificial organs field.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610072903.XA CN107033258A (en) | 2016-02-03 | 2016-02-03 | A kind of hydroxyl butyl chitosan medical sponge and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610072903.XA CN107033258A (en) | 2016-02-03 | 2016-02-03 | A kind of hydroxyl butyl chitosan medical sponge and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107033258A true CN107033258A (en) | 2017-08-11 |
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Cited By (1)
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| 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 |
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| 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 |
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