CN106267328B - A kind of preparation method of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel - Google Patents

A kind of preparation method of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel Download PDF

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CN106267328B
CN106267328B CN201610835998.6A CN201610835998A CN106267328B CN 106267328 B CN106267328 B CN 106267328B CN 201610835998 A CN201610835998 A CN 201610835998A CN 106267328 B CN106267328 B CN 106267328B
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collagenous fibres
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polycaprolactone
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CN106267328A (en
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姜谱
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Anhui Special Biological Technology Co Ltd
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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
    • A61L24/102—Collagen
    • 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
    • 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
    • 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
    • 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
    • A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L89/00—Compositions of proteins; Compositions of derivatives thereof
    • C08L89/04—Products derived from waste materials, e.g. horn, hoof or hair
    • C08L89/06—Products derived from waste materials, e.g. horn, hoof or hair derived from leather or skin, e.g. gelatin
    • 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

Abstract

The invention discloses a kind of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel preparation methods, it is related to hemostasis gel technical field, include the following steps: that (1) abortive calfskin pre-processes, (2) preparation of collagenous fibres Extraction solvent, (3) preparation of collagenous fibres solution, (4) preparation of modified collagen fiber solution, the preparation of (5) hemostasis gel.Hemostasis gel of the present invention can directly overlie bleed site, play haemostatic effect, and stop blooding rapidly, promote the reparation of the surface of a wound while effectively reducing amount of bleeding；There is excellent biocompatibility and biological degradability simultaneously, it is safe to use, using rear without any side effects.

Description

A kind of preparation method of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel
Technical field:
The present invention relates to hemostasis gel technical fields, and in particular to a kind of polycaprolactone-abortive calfskin collagenous fibres are compound only The preparation method of blood clotting glue.
Background technique:
Often the bleeding profusely along with the surface of a wound in surgery and trauma operation, so that patient be made to face great life Danger, therefore prepare the research hotspot that quickly and effectively hemostatic material is used as always medical field.Traditional hemostatic material exists The shortcomings that not portable and disinfection saves, and stop blooding and almost lean on mechanism, haemostatic effect is bad.In recent years, people develop Biological absorbable hemostatic material, wherein Animal Skin Collagen sill is as a kind of good medical material of biological property, with human body It is biodegradable and have no toxic side effect with good histocompatbility, while adherency, proliferation and the wound of cell can be promoted It is compound；And by its distinctive microcellular structure and good adhesiveness, promotes the growth of biotic factor to spread, induce and promote Into fibroblastic growth, to promote the healing of wound.
Currently, it is sour enzyme combination extraction method that universal Animal Skin Collagen, which extracts preparation method, main includes the pre- place of raw material Reason, degreasing enzymolysis, digestion, are saltoutd, are centrifuged and purified, but there is gained collagen purity and low yield, at high cost etc. Problem, and collagen can be made to reduce or lose biomechanical property because dealing with improperly in extraction process, stop to influence it Blood effect.For this problem, our company starts with from the extracting method of collagen, and combines the modification to collagen is extracted And the addition of auxiliary agent prepares hemostasis gel material, improves haemostatic effect, biocompatibility, biology drop on a low-cost basis Solution property and safety in utilization.
Summary of the invention:
Technical problem to be solved by the present invention lies in providing, a kind of to prepare simple, haemostatic effect good and with superior bio The polycaprolactone of compatibility and biological degradability-abortive calfskin collagenous fibres compound hemostatic gel preparation method.
The following technical solution is employed for the technical problems to be solved by the invention to realize:
A kind of preparation method of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel, includes the following steps:
(1) abortive calfskin pre-processes: purifying abortive calfskin as raw material can trace to the source, is wrapped up after being fully deployed with preservative film It is good, it is placed in 5~8h of freezing in -5~0 DEG C of environment, then with 5-10 DEG C of temperature, the sodium bicarbonate and hexa metaphosphoric acid of mass fraction 5% Sodium mixed aqueous solution impregnates 10~15min, then uses sponge brush brushing surface 2~3 times under deionized water shower；
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of 1.2~1.5:1 of molar ratio by Cyclopropyl Bromide and 2- pyrrole Pyrrolidone is sufficiently mixed, prior to being ultrasonically treated 15~30min under supersonic frequency 40kHz, power 50W, then at microwave frequency 3~5min of microwave treatment under 2450MHz, power 700W is then heated to 30~60min of reflux state insulated and stirred, to be mixed 5-10 DEG C of deionized water of the weight such as addition, is sufficiently stirred rear stratification after solution naturally cools to 50-55 DEG C, phase of fetching water, Up to Extraction solvent；
(3) preparation of collagenous fibres solution: the abortive calfskin after above-mentioned scrub is sent into freeze drier, dry to aqueous Amount using onal machine is ground into the particle that granularity is 2-3mm after being 10-15%, adds in above-mentioned made Extraction solvent, sufficiently 10~15min is stood after dispersion, is transferred in ball mill after standing, is milled to fineness less than 50 μm, quality point is then added The PVP K30 of number 5% and hydrogenated castor oil polyoxyethylene ether mixed aqueous solution, after being sufficiently mixed using working frequency 40Hz, The Surface Treatment with Plasma machine of power 600W handles 10~15s to gained mixture, and after treatment is transferred in 0~5 DEG C of environment 3~5h is stood, polyacrylic acid and polyethylene glycol oxide is then added, and be heated to reflux state 15~30min of insulated and stirred, finally 270 meshes are crossed, gained filtrate is collagenous fibres solution；
(4) polycaprolactone, poly- second two preparation of modified collagen fiber solution: are added into above-mentioned made collagenous fibres solution Alcohol 4000 and methionine are sufficiently mixed, in 35~40 DEG C of 1~2h of sealing and standing after being uniformly dispersed then in microwave frequency 2~3min of microwave treatment under 2450MHz, power 700W, is sufficiently mixed again, and utilization working frequency 40Hz, power 600W Surface Treatment with Plasma machine handles 10~15s, and gained mixture is cooled under ice-water bath with the speed of 10~15 DEG C/min, 10~15min of insulated and stirred is after temperature is down to 0~5 DEG C to get modified collagen fiber solution；
(5) preparation of hemostasis gel: into above-mentioned made modified collagen fiber solution be added polyglycolic acid, Polycarbophil, Cystine and haemostatic medicament are distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays sterilization, after being finally packaged The cryo-conservation under the conditions of 0~5 DEG C.
The dosage mass ratio of sodium bicarbonate and calgon is 2~3:1 in the step (1).
Abortive calfskin, Extraction solvent, PVP K30, hydrogenated castor oil polyoxyethylene ether, polyacrylic acid in the step (3) With 10~15:40 of dosage mass ratio~50:2~3:1~2:0.5~1:0.5~1 of polyethylene glycol oxide.
Polyacrylic acid passes through chemical modification, method of modifying are as follows: by polyacrylic acid and junket ammonia using preceding in the step (3) Acid be added double weight part ethyl alcohol in, reflux state insulated and stirred 10min is heated to after being uniformly dispersed, add resveratrol and Disodium ethylene diamine tetraacetate continues at insulated and stirred 30min under reflux state, after gained mixture naturally cools to 35-40 DEG C It is transferred in 0-5 DEG C of environment immediately and stands 8h, be then fed into spray dryer, obtained solid is ground after drying is made powder.
The polyacrylic acid, tyrosine, resveratrol and disodium ethylene diamine tetraacetate dosage mass ratio be 10~15:1 ~2:3~6:0.5~1.
The dosage mass ratio of collagenous fibres solution, polycaprolactone, Macrogol 4000 and methionine in the step (4) 25~30:3~6:1~2:0.5~1.
The use of modified collagen fiber solution, polyglycolic acid, Polycarbophil, cystine and haemostatic medicament in the step (5) Measure 25~30:2 of mass ratio~3:1~2:0.5~1:0.5~1.
The haemostatic medicament is selected from chemicals or Chinese medical extract with hemostasia effect.
The beneficial effects of the present invention are: the present invention purifies abortive calfskin as raw material can trace to the source, it is molten that extraction prepares collagenous fibres Liquid, and the extracted collagenous fibres of polycaprolactone graft modification are utilized, and be aided with a variety of auxiliary agents and hemostasis gel, the hemostasis is made Gel can directly overlie bleed site, play haemostatic effect, and stop blooding rapidly, promote the surface of a wound while effectively reducing amount of bleeding Reparation；There is excellent biocompatibility and biological degradability simultaneously, it is safe to use, without the secondary work of any poison after use With.
Specific embodiment:
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below Specific embodiment is closed, the present invention is further explained.
Embodiment 1
(1) abortive calfskin pre-processes: purifying abortive calfskin as raw material can trace to the source, is wrapped up after being fully deployed with preservative film It is good, it is placed in -5~0 DEG C of environment and freezes 8h, then with 5-10 DEG C of temperature, the sodium bicarbonate and calgon of mass fraction 5% (the dosage mass ratio of sodium bicarbonate and calgon is 3:1) mixed aqueous solution impregnates 15min, then under deionized water shower With sponge brush brushing surface 2 times；
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of molar ratio 1.2:1 by Cyclopropyl Bromide and 2-Pyrrolidone It is sufficiently mixed, prior to being ultrasonically treated 30min under supersonic frequency 40kHz, power 50W, then at microwave frequency 2450MHz, power Microwave treatment 5min under 700W, is then heated to reflux state insulated and stirred 60min, and solution to be mixed naturally cools to 50-55 5-10 DEG C of deionized water of the weight such as addition after DEG C, is sufficiently stirred rear stratification, water intaking is mutually to get Extraction solvent；
(3) preparation of collagenous fibres solution: 10 parts of abortive calfskins after above-mentioned scrub are sent into freeze drier, and drying is extremely Water content using onal machine is ground into the particle that granularity is 2-3mm after being 10-15%, adds above-mentioned made 40 parts of Extraction solvents In, 15min is stood after fully dispersed, is transferred in ball mill after standing, is milled to fineness less than 50 μm, quality is then added The 3 parts of PVP K30s and 1 part of hydrogenated castor oil polyoxyethylene ether mixed aqueous solution of score 5% utilize work frequency after being sufficiently mixed Rate 40Hz, power 600W Surface Treatment with Plasma machine 15s is handled to gained mixture, after treatment is transferred to 0~5 DEG C of environment Middle standing 5h is then added 0.5 part of polyacrylic acid and 1 part of polyethylene glycol oxide, and is heated to reflux state insulated and stirred 30min, 270 meshes are finally crossed, gained filtrate is collagenous fibres solution；
(4) preparation of modified collagen fiber solution: 5 parts are added into above-mentioned made 30 parts of collagenous fibres solution and is gathered in oneself Ester, 2 parts of Macrogol 4000s and 0.5 part of methionine are sufficiently mixed, so in 35~40 DEG C of sealing and standing 2h after being uniformly dispersed The microwave treatment 3min under microwave frequency 2450MHz, power 700W afterwards, is sufficiently mixed again, and utilizes working frequency 40Hz, function The Surface Treatment with Plasma machine of rate 600W handles 15s, and gained mixture is cooling with the speed of 10~15 DEG C/min under ice-water bath Cooling, insulated and stirred 15min is after temperature is down to 0~5 DEG C to get modified collagen fiber solution；
(5) 2 parts of polyglycolic acids, 2 parts the preparation of hemostasis gel: are added into above-mentioned made 25 parts of modified collagen fiber solutions (haemostatic medicament is selected from, and there are the chemicals of hemostasia effect or Chinese medicine to mention for Polycarbophil, 0.5 part of cystine and 1 part of haemostatic medicament Take object), it is distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays sterilization, in 0~5 DEG C of item after being finally packaged Cryo-conservation under part.
The modification of polyacrylic acid: 10 parts of polyacrylic acid and 1 part of tyrosine are added in double weight part ethyl alcohol, are uniformly dispersed After be heated to reflux state insulated and stirred 10min, add 3 parts of resveratrols and 0.5 part of disodium ethylene diamine tetraacetate, continue at Insulated and stirred 30min under reflux state, gained mixture are transferred in 0-5 DEG C of environment immediately after naturally cooling to 35-40 DEG C and stand 8h is then fed into spray dryer, and obtained solid is ground after drying is made powder.
Embodiment 2
(1) abortive calfskin pre-processes: purifying abortive calfskin as raw material can trace to the source, is wrapped up after being fully deployed with preservative film It is good, it is placed in -5~0 DEG C of environment and freezes 5h, then with 5-10 DEG C of temperature, the sodium bicarbonate and calgon of mass fraction 5% (the dosage mass ratio of sodium bicarbonate and calgon is 3:1) mixed aqueous solution impregnates 15min, then under deionized water shower With sponge brush brushing surface 2 times；
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of molar ratio 1.2:1 by Cyclopropyl Bromide and 2-Pyrrolidone It is sufficiently mixed, prior to being ultrasonically treated 30min under supersonic frequency 40kHz, power 50W, then at microwave frequency 2450MHz, power Microwave treatment 4min under 700W, is then heated to reflux state insulated and stirred 60min, and solution to be mixed naturally cools to 50-55 5-10 DEG C of deionized water of the weight such as addition after DEG C, is sufficiently stirred rear stratification, water intaking is mutually to get Extraction solvent；
(3) preparation of collagenous fibres solution: 15 parts of abortive calfskins after above-mentioned scrub are sent into freeze drier, and drying is extremely Water content using onal machine is ground into the particle that granularity is 2-3mm after being 10-15%, adds above-mentioned made 50 parts of Extraction solvents In, 15min is stood after fully dispersed, is transferred in ball mill after standing, is milled to fineness less than 50 μm, quality is then added The 2 parts of PVP K30s and 2 parts of hydrogenated castor oil polyoxyethylene ether mixed aqueous solutions of score 5% utilize work frequency after being sufficiently mixed Rate 40Hz, power 600W Surface Treatment with Plasma machine 15s is handled to gained mixture, after treatment is transferred to 0~5 DEG C of environment 0.5 part of polyacrylic acid and 0.5 part of polyethylene glycol oxide is then added in middle standing 5h, and be heated to reflux state insulated and stirred 15~ 30min finally crosses 270 meshes, and gained filtrate is collagenous fibres solution；
(4) preparation of modified collagen fiber solution: 4 parts are added into above-mentioned made 25 parts of collagenous fibres solution and is gathered in oneself Ester, 1 part of Macrogol 4000 and 0.5 part of methionine are sufficiently mixed, so in 35~40 DEG C of sealing and standing 2h after being uniformly dispersed The microwave treatment 3min under microwave frequency 2450MHz, power 700W afterwards, is sufficiently mixed again, and utilizes working frequency 40Hz, function The Surface Treatment with Plasma machine of rate 600W handles 15s, and gained mixture is cooling with the speed of 10~15 DEG C/min under ice-water bath Cooling, insulated and stirred 15min is after temperature is down to 0~5 DEG C to get modified collagen fiber solution；
(5) 3 parts of polyglycolic acids, 2 parts the preparation of hemostasis gel: are added into above-mentioned made 30 parts of modified collagen fiber solutions (haemostatic medicament is selected from, and there are the chemicals of hemostasia effect or Chinese medicine to mention for Polycarbophil, 0.5 part of cystine and 1 part of haemostatic medicament Take object), it is distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays sterilization, in 0~5 DEG C of item after being finally packaged Cryo-conservation under part.
The modification of polyacrylic acid: 15 parts of polyacrylic acid and 2 parts of tyrosine are added in double weight part ethyl alcohol, are uniformly dispersed After be heated to reflux state insulated and stirred 10min, add 5 parts of resveratrols and 0.5 part of disodium ethylene diamine tetraacetate, continue at Insulated and stirred 30min under reflux state, gained mixture are transferred in 0-5 DEG C of environment immediately after naturally cooling to 35-40 DEG C and stand 8h is then fed into spray dryer, and obtained solid is ground after drying is made powder.
Performance measurement is carried out to hemostasis gel prepared by Examples 1 and 2, as a result as follows:
Appearance: gel, surface is smooth, the impurity being visible by naked eyes；
Moisture content :≤80% (wt)；
Gel strength: 100~500g/cm2；
Content of beary metal :≤10 μ g/g (m/m)；
Liposome :≤1% (m/m)；
Ash content :≤2% (m/m)；
PH value: >=4.0；
Biological degradability: it all degrades in internal January；
Antibacterial/bacteriostasis property: equal to the bacteriostasis rate of Escherichia coli, gold goal bacterium, Candida albicans and Pseudomonas aeruginosa >=50%；
Hemolysis rate :≤5%；
Cytotoxicity: cell-cytotoxic reaction is not more than 1 grade；
Sterility test: sterile；
Sensitization test (STT): without delayed type hypersensitivity, DTH；
Intradermal reaction test: primary stimulus index PII < 0.4；
Exogenous DNA content: Residual exogenous DNA amount answers≤10ng/ml (m/v)
Heat source: without heat source；
Acute systemic toxicity: without Acute systemic toxicity；
Genetoxic: hereditary-less toxicity；
Gel time :≤30s；
Bleeding stopping period :≤1min.
The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention.The technology of the industry Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its Equivalent thereof.

Claims (2)

1. a kind of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel preparation method, which is characterized in that including walking as follows It is rapid:
(1) abortive calfskin pre-processes: abortive calfskin is purified as raw material can trace to the source, and is wrapped after being fully deployed with preservative film, and It is placed in 5~8h of freezing in -5~0 DEG C of environment, then is mixed with the sodium bicarbonate of 5-10 DEG C of temperature, mass fraction 5% with calgon Then 10~15min of aqueous solution soaking is used sponge brush brushing surface 2~3 times under deionized water shower；
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of 1.2~1.5:1 of molar ratio by Cyclopropyl Bromide and 2- pyrrolidines Ketone is sufficiently mixed, prior under supersonic frequency 40kHz, power 50W be ultrasonically treated 15~30min, then at microwave frequency 2450MHz, 3~5min of microwave treatment under power 700W, is then heated to 30~60min of reflux state insulated and stirred, and solution to be mixed is natural 5-10 DEG C of deionized water of the weight such as addition after being cooled to 50-55 DEG C, is sufficiently stirred rear stratification, water intaking is mutually to get extraction Solvent；
(3) preparation of collagenous fibres solution: the abortive calfskin after above-mentioned scrub is sent into freeze drier, and drying to water content is It is ground into the particle that granularity is 2-3mm using onal machine after 10-15%, is added in above-mentioned made Extraction solvent, it is fully dispersed 10~15min is stood afterwards, is transferred in ball mill after standing, is milled to fineness less than 50 μm, mass fraction 5% is then added PVP K30 and hydrogenated castor oil polyoxyethylene ether mixed aqueous solution, after being sufficiently mixed utilize working frequency 40Hz, power The Surface Treatment with Plasma machine of 600W handles 10~15s to gained mixture, and after treatment is transferred in 0~5 DEG C of environment and stands 3 ~5h is then added polyacrylic acid and polyethylene glycol oxide, and is heated to reflux state 15~30min of insulated and stirred, finally crosses 270 Mesh, gained filtrate are collagenous fibres solution；
(4) polycaprolactone, polyethylene glycol the preparation of modified collagen fiber solution: are added into above-mentioned made collagenous fibres solution 4000 and methionine be sufficiently mixed, in 35~40 DEG C of 1~2h of sealing and standing after being uniformly dispersed then in microwave frequency 2~3min of microwave treatment under 2450MHz, power 700W, is sufficiently mixed again, and utilization working frequency 40Hz, power 600W Surface Treatment with Plasma machine handles 10~15s, and gained mixture is cooled under ice-water bath with the speed of 10~15 DEG C/min, 10~15min of insulated and stirred is after temperature is down to 0~5 DEG C to get modified collagen fiber solution；
(5) polyglycolic acid, Polycarbophil, Guang ammonia the preparation of hemostasis gel: are added into above-mentioned made modified collagen fiber solution Acid and haemostatic medicament are distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays sterilization, in 0 after being finally packaged Cryo-conservation under the conditions of~5 DEG C；
The dosage mass ratio of sodium bicarbonate and calgon is 2~3:1 in the step (1)；
Abortive calfskin in the step (3), Extraction solvent, PVP K30, hydrogenated castor oil polyoxyethylene ether, polyacrylic acid and poly- 10~15:40 of dosage mass ratio~50:2~3:1~2:0.5~1:0.5~1 of ethylene oxide；
Polyacrylic acid passes through chemical modification, method of modifying are as follows: add polyacrylic acid and tyrosine using preceding in the step (3) Enter in double weight part ethyl alcohol, reflux state insulated and stirred 10min is heated to after being uniformly dispersed, adds resveratrol and second two Amine tetraacethyl disodium, continues at insulated and stirred 30min under reflux state, gained mixture naturally cool to 35-40 DEG C after immediately It is transferred in 0-5 DEG C of environment and stands 8h, be then fed into spray dryer, obtained solid is ground after drying is made powder；
The polyacrylic acid, tyrosine, resveratrol and disodium ethylene diamine tetraacetate dosage mass ratio be 10~15:1~2:3 ~6:0.5~1；
Collagenous fibres solution in the step (4), polycaprolactone, Macrogol 4000 and methionine dosage mass ratio 25~ 30:3~6:1~2:0.5~1；
The dosage matter of modified collagen fiber solution, polyglycolic acid, Polycarbophil, cystine and haemostatic medicament in the step (5) Measure ratio 25~30:2~3:1~2:0.5~1:0.5~1.
2. polycaprolactone according to claim 1-abortive calfskin collagenous fibres compound hemostatic gel preparation method, feature Be: the haemostatic medicament is selected from chemicals or Chinese medical extract with hemostasia effect.
CN201610835998.6A 2016-09-20 2016-09-20 A kind of preparation method of polycaprolactone-abortive calfskin collagenous fibres compound hemostatic gel Active CN106267328B (en)

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CN105287997A (en) * 2015-11-13 2016-02-03 邢月军 Hemostatic gel for surgery

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CN1507358A (en) * 2001-01-25 2004-06-23 �ο���ҽҩ���޹�˾ Carrier with solid fibrinogen and solid thrombin
CN102939113A (en) * 2010-04-07 2013-02-20 巴克斯特国际公司 Hemostatic sponge
CN105287997A (en) * 2015-11-13 2016-02-03 邢月军 Hemostatic gel for surgery

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