CN106279644B - A kind of Biodegradable high molecular absorbable hemostatic sponge and preparation method thereof - Google Patents
A kind of Biodegradable high molecular absorbable hemostatic sponge and preparation method thereof Download PDFInfo
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- CN106279644B CN106279644B CN201610653383.1A CN201610653383A CN106279644B CN 106279644 B CN106279644 B CN 106279644B CN 201610653383 A CN201610653383 A CN 201610653383A CN 106279644 B CN106279644 B CN 106279644B
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- high molecular
- block copolymer
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- caprolactone
- biodegradable high
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- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 229920001400 block copolymer Polymers 0.000 claims abstract description 41
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 28
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000007151 ring opening polymerisation reaction Methods 0.000 claims abstract description 23
- 239000007789 gas Substances 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 229910052786 argon Inorganic materials 0.000 claims abstract description 13
- 229920001610 polycaprolactone Polymers 0.000 claims abstract description 12
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 10
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 9
- 230000001681 protective effect Effects 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 239000004626 polylactic acid Substances 0.000 claims abstract description 6
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims description 24
- 238000010438 heat treatment Methods 0.000 claims description 14
- 230000008018 melting Effects 0.000 claims description 14
- 238000002844 melting Methods 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000004108 freeze drying Methods 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 230000023597 hemostasis Effects 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 claims description 4
- -1 Polyethylene Polymers 0.000 claims description 3
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- 239000002685 polymerization catalyst Substances 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 241000628997 Flos Species 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 23
- 239000012948 isocyanate Substances 0.000 abstract description 4
- 150000002513 isocyanates Chemical class 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 4
- 239000004970 Chain extender Substances 0.000 abstract description 3
- 239000003431 cross linking reagent Substances 0.000 abstract description 3
- 238000006116 polymerization reaction Methods 0.000 abstract description 3
- 230000033228 biological regulation Effects 0.000 abstract description 2
- 238000012662 bulk polymerization Methods 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 238000005187 foaming Methods 0.000 abstract description 2
- 238000001556 precipitation Methods 0.000 abstract description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 18
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 229920001577 copolymer Polymers 0.000 description 7
- 238000005227 gel permeation chromatography Methods 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 229920002635 polyurethane Polymers 0.000 description 5
- 239000004814 polyurethane Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 206010039509 Scab Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000000025 haemostatic effect Effects 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 238000012661 block copolymerization Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 210000000613 ear canal Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- JBFHTYHTHYHCDJ-UHFFFAOYSA-N gamma-caprolactone Chemical compound CCC1CCC(=O)O1 JBFHTYHTHYHCDJ-UHFFFAOYSA-N 0.000 description 1
- 238000002682 general surgery Methods 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 210000003695 paranasal sinus Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 210000001154 skull base Anatomy 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
-
- 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
- A61L24/0036—Porous materials, e.g. foams or sponges
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
- C08G63/82—Preparation processes characterised by the catalyst used
- C08G63/85—Germanium, tin, lead, arsenic, antimony, bismuth, titanium, zirconium, hafnium, vanadium, niobium, tantalum, or compounds thereof
-
- 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
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
-
- 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
- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Materials Engineering (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Polyesters Or Polycarbonates (AREA)
Abstract
The present invention provides a kind of Biodegradable high molecular absorbable hemostatic sponge, and the styptic sponge is polylactic acid, poly-epsilon-caprolactone and polyethyleneglycol block copolymer, and the general formula of the block copolymer is A-B-C-B-A or B-A-C-A-B；Wherein A is PLA, B PCL, C PEG.The present invention has the following technical effect that 1) hemostatic material is made of block copolymer, and composition is uniform, and performance is more stable, and there is no blends during foaming prepares mandruka the phenomenon that split-phase precipitation occurs because of the difference of compatibility.Since hemostatic material is the block copolymer prepared by ring-opening polymerisation twice, performance is easy regulation.2) isocyanates is not used in preparation process as chain extender or crosslinking agent, and the block type Biodegradable high molecular absorbable hemostatic sponge material that elasticity is good is directly prepared by polymerization reaction twice.3) preparation process carries out bulk polymerization using nitrogen or argon gas as protective gas under non-vacuum condition, and reaction condition is mild, easy to accomplish.
Description
Technical field
The present invention relates to a kind of Biodegradable high molecular absorbable hemostatic sponges and preparation method thereof, belong to absorbable biological
Medical macromolecular materials field.
Background technique
Ear nose larynx nasal cavity, ear canal, nasal sinus, basis cranii, Gynecological cervical, uterine cavity, the surgical operation of the lumens such as Gastroenterology dept.'s alimentary canal
It is very extensive in the world, the surgical operations of these lumens because of many reasons such as its range is small, rich blood vessel, position are deep not
It can only pass through the hemostasis with packs of styptic sponge by sewing hemostasis.Therefore, the hemostatic material for these positions causes people
Extensive concern.
The development for making a general survey of hemostatic material experienced the following four stage: first is that non-degradable material, is with Vaseline Oil Gauze
It represents, production is simple, by oppressing hemostasis with packs.The haemostatic effect of this kind of hemostatic material is bad, and material is non-degradable, easily
It with scab adhesion, is easy to cause scab to fall off during taking-up, causes bleeding again.Second is that non-degradable Hydrogels material
Material, using PVA as representative, this kind of hydrogel performance of sucking blood is good, but due to non-degradable, equally exists and causes to go out again during taking-up
The problem of blood.Third is that degradable natural high molecular material, such as with poly- polysaccharide such as starch, alginic acid, chitosan etc. and protein
Based on collagen etc..The good biocompatibility of this kind of material can be absorbed by the body in vivo, be not necessarily to secondary taking-up, therefore avoid
Material take out during cause wound again bleeding the problem of.However, making this due to a large amount of hydrogen bond action in natural polymer
The rigidity of class hemostatic material is stronger, and the usual brittleness of sponge of preparation is larger, lacks flexibility, the patient used has foreign body sensation, art
Comfort level is bad afterwards.And the protides such as the collagen in animal body source hemostatic material there is also vivo immunization activate, microorganism and
The potential risks such as virus infection.Using poly-epsilon-caprolactone/lactide urethanes as the biodegradable polyurethane of representative heat
Thermoplastic elastic be forth generation hemostatic material, have elasticity is good, haemostatic effect is good, it is degradable outflow, not lumen adherency, nothing
Many advantages, such as need to clearing up.Be in recent years scientists from all over the world all in the novel lumen hemostatic material competitively developed.
Chinese patent (publication number CN 104031287) reports a kind of novel degradable nasal cavity styptic sponge.Using
Diisocyanate carries out chain extension, the polyurethane of synthesising biological degradation to Biodegradable high molecular segment, then passes through freeze-drying
Method prepares degradable polyurethane styptic sponge.Chinese patent (publication number CN 102939113) is with the PEG with isocyanates
Crosslinked bio degraded macromolecular prepares polyurethane, and prepares styptic sponge by the methods of coating and dipping.In the two patents
It has used isocyanates as chain extender or crosslinking agent, has prepared the biodegradable styptic sponge with polyurethane structural.And gather
The safety for the amine compound that urethane degradation generates, academia always exist extensive dispute, it is believed that have potential carcinogenic
It is dangerous.
Summary of the invention
Place, the present invention provide a kind of Biodegradable high molecular absorbable hemostatic sponge for overcome the deficiencies in the prior art
And preparation method thereof.
First goal of the invention of the invention is to provide a kind of Biodegradable high molecular absorbable hemostatic sponge, the life
Object degraded macromolecular absorbable hemostatic sponge is polylactic acid, poly-epsilon-caprolactone and polyethyleneglycol block copolymer, the block
The general formula of copolymer is A-B-C-B-A or B-A-C-A-B；Wherein A is PLA, B PCL, C PEG.The weight of block copolymer is equal
Molecular weight is 2000-80000.
Second goal of the invention of the invention is to provide the preparation method of Biodegradable high molecular absorbable hemostatic sponge, packet
Include following steps:
1) by PEG heating melting, lactide or ε-caprolactone is added, by carrying out the under catalyst in protective gas
ε-caprolactone or lactide is added in ring-opening polymerization, carries out second of open loop by catalyst in protective atmosphere
Polymerization reaction obtains block copolymer；
If front be added lactide, behind be added ε-caprolactone, then obtain block copolymer: poly- (ε-caprolactone)-poly- third
Lactide-polyethylene glycol-polylactide-is poly- (ε-caprolactone)；
If front be added ε-caprolactone, behind lactide is added, then obtain block copolymer: polylactide-it is poly- (ε-in
Ester)-polyethylene glycol (ε-caprolactone)-polylactide；
2) block copolymer made from step 1) is dissolved in solvent, is stopped by freeze-drying or solvent volatilization pore, preparation
The sea of blood is continuous.
The weight average molecular weight Mw of the polyethylene glycol is 600-20000.
The lactide is at least one of L- lactide, D- lactide, DL- lactide.
The protective gas is at least one of nitrogen, argon gas.
The ring-opening polymerization catalyst is stannous octoate.
The polyethylene glycol, lactide, ε-caprolactone mass ratio are 1:(0.5-10): (0.5-10).
The mass concentration of the stannous octoate is 0.1wt%-50ppm.
The first time ring-opening polymerization temperature is 100-170 DEG C, and the reaction time is 1-72 hours.
Second of ring-opening polymerization temperature is 100-150 DEG C, and the reaction time is 12-72 hours.
The solvent is at least one of chloroform, methylene chloride, tetrahydrofuran, dioxane.
Third goal of the invention of the invention is to provide the Biodegradable high molecular absorbable hemostatic sponge and is preparing
Ear nose larynx Head and neck tumour, gynaecology, orthopaedics, neurosurgery, Gastroenterology dept., the application in department of general surgery's hemostatic material.
1) Biodegradable high molecular absorbable hemostatic sponge of the invention and preparation method thereof, has the following technical effect that
Hemostatic material is made of block copolymer, and composition is uniform, and performance is more stable, prepares porous sea in foaming
There is no blends during continuous there is the phenomenon that split-phase precipitation because of the difference of compatibility.Due to hemostatic material
It is the block copolymer prepared by ring-opening polymerisation twice, performance is easy regulation.
2) isocyanates is not used in preparation process as chain extender or crosslinking agent, is directly prepared by polymerization reaction twice
The block type Biodegradable high molecular absorbable hemostatic sponge material that elasticity is good.
3) preparation process carries out bulk polymerization using nitrogen or argon gas as protective gas under non-vacuum condition, reacts item
Part is mild, easy to accomplish.
Detailed description of the invention
Fig. 1 is gel permeation chromatography (GPC) map of block copolymer prepared by embodiment 3.
Fig. 2 is the nucleus magnetic hydrogen spectrum (1H NMR) of block copolymer prepared by embodiment 3.
Fig. 3-1 is the scanning electron microscope (SEM) in Biodegradable high molecular absorbable hemostatic sponge section prepared by embodiment 3
Figure.
Fig. 3-2 is the scanning electron microscope (SEM) of Biodegradable high molecular absorbable hemostatic sponge surface prepared by embodiment 3
Figure.
Specific embodiment
Embodiment 1
By 5 grams of PEG(Mw=1000) heating melting, 10 grams of L- lactide are added, by 0.05wt% octanoic acid in argon gas protection
20 grams of ε-caprolactones are added after 100 DEG C are reacted 72 hours in stannous catalyzed ring opening polymerization, react 48 hours, obtain embedding in 120 DEG C
Section copolymer.
Block copolymer after reaction is dissolved in dioxane, styptic sponge is prepared by freeze-drying.
Embodiment 2
By 5 grams of PEG(Mw=600) heating melting, 50 grams of DL- lactide are added, it is sub- by 0.1wt% octanoic acid in argon gas protection
50 grams of ε-caprolactones are added after 130 DEG C are reacted 36 hours in tin catalyzed ring opening polymerization, react 12 hours in 150 DEG C, obtain block
Copolymer.
Block copolymer after reaction is dissolved in dioxane, styptic sponge is prepared by freeze-drying.
Embodiment 3
By 5 grams of PEG(Mw=12000) heating melting, 2.5 grams of DL- lactide are added, it is pungent by 0.01wt% in argon gas protection
2.5 grams of ε-caprolactones are added after 170 DEG C are reacted 1 hour in sour stannous catalyzed ring opening polymerization, react 72 hours, obtain in 100 DEG C
Block copolymer.
Block copolymer after reaction is dissolved in chloroform, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 4
By 5 grams of PEG(Mw=6000) heating melting, 10 grams of L- lactide are added, it is sub- by 50ppm octanoic acid in argon gas protection
20 grams of ε-caprolactones are added after 120 DEG C are reacted 48 hours in tin catalyzed ring opening polymerization, react 48 hours in 120 DEG C, obtain block
Copolymer.
Block copolymer after reaction is dissolved in tetrahydrofuran, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 5
By 5 grams of PEG(Mw=5000) heating melting, 10 grams of D- lactide are added, by 0.08wt% octanoic acid in argon gas protection
10 grams of ε-caprolactones are added after 150 DEG C are reacted 12 hours in stannous catalyzed ring opening polymerization, react 48 hours, obtain embedding in 130 DEG C
Section copolymer.
Block copolymer after reaction is dissolved in chloroform, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 6
By 5 grams of PEG(Mw=8000) heating melting, 2.5 grams of D- lactide are added, by 0.01wt% octanoic acid in argon gas protection
2.5 grams of ε-caprolactones are added after 170 DEG C are reacted 1 hour in stannous catalyzed ring opening polymerization, react 50 hours, obtain embedding in 130 DEG C
Section copolymer.
Block copolymer after reaction is dissolved in methylene chloride, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 7
By 5 grams of PEG(Mw=600) heating melting, 10 grams of ε-caprolactone are added, it is sub- by 0.05wt% octanoic acid in nitrogen protection
20 grams of L- lactides are added after 100 DEG C are reacted 72 hours in tin catalyzed ring opening polymerization, react 48 hours in 130 DEG C, obtain block
Copolymer.
Block copolymer after reaction is dissolved in dioxane, styptic sponge is prepared by freeze-drying.
Embodiment 8
By 5 grams of PEG(Mw=2000) heating melting, 50 grams of ε-caprolactone are added, it is sub- by 50ppm octanoic acid in argon gas protection
50 grams of DL- lactides are added after 130 DEG C are reacted 36 hours in tin catalyzed ring opening polymerization, react 12 hours, obtain embedding in 150 DEG C
Section copolymer.
Block copolymer after reaction is dissolved in dioxane, styptic sponge is prepared by freeze-drying.
Embodiment 9
By 5 grams of PEG(Mw=12000) heating melting, 2.5 grams of ε-caprolactone are added, it is pungent by 0.01wt% in argon gas protection
2.5 grams of DL- lactides are added after 170 DEG C are reacted 1 hour in sour stannous catalyzed ring opening polymerization, react 24 hours, obtain in 150 DEG C
To block copolymer.
Block copolymer after reaction is dissolved in chloroform, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 10
By 5 grams of PEG(Mw=8000) heating melting, 10 grams of ε-caprolactone are added, by 0.05wt% octanoic acid in nitrogen protection
20 grams of L- lactides are added after 120 DEG C are reacted 48 hours in stannous catalyzed ring opening polymerization, react 30 hours, obtain embedding in 140 DEG C
Section copolymer.
Block copolymer after reaction is dissolved in tetrahydrofuran, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 11
By 5 grams of PEG(Mw=5000) heating melting, 10 grams of ε-caprolactone are added, by 0.08wt% octanoic acid in argon gas protection
10 grams of D- lactides are added after 150 DEG C are reacted 12 hours in stannous catalyzed ring opening polymerization, react 48 hours, obtain embedding in 130 DEG C
Section copolymer.
Block copolymer after reaction is dissolved in chloroform, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 12
By 5 grams of PEG(Mw=20000) heating melting, be added 2.5 grams of ε-caprolactone, it is pungent by 0.01wt% in nitrogen protection
2.5 grams of D- lactides are added after 170 DEG C are reacted 1 hour in sour stannous catalyzed ring opening polymerization, react 50 hours, obtain in 130 DEG C
Block copolymer.
Block copolymer after reaction is dissolved in methylene chloride, styptic sponge is prepared by solvent in vacuo evaporation.
Embodiment 13
The detection method reference literature Polymer of GPC and nucleus magnetic hydrogen spectrum, 2003,44 (4): 989-994
The block copolymer of embodiment 3 is detected by gel permeation chromatography, nucleus magnetic hydrogen spectrum.
Fig. 1, Fig. 2 are the block copolymer testing results of embodiment 3.The result of GPC can be seen that block copolymerization from Fig. 1
The number-average molecular weight of object is 20314.In Fig. 2 nucleus magnetic hydrogen spectrum it can be seen that on polyethylene glycol, poly- (6-caprolactone) and polylactide
The vibration peak of proton.
With the styptic sponge of scanning electron microscopic observation embodiment 3.Fig. 3-1 is that Biodegradable high molecular prepared by embodiment 3 can
Absorb scanning electron microscope (SEM) figure in styptic sponge section.Fig. 3-2 is that Biodegradable high molecular prepared by embodiment 3 is absorbable only
Scanning electron microscope (SEM) figure of blood sponge surface.It can be seen that resulting materials are porous structure from Fig. 3-1 and Fig. 3-2.
The testing result of styptic sponge obtained by other embodiments and the styptic sponge of scanning electron microscopic observation result and embodiment 3
Result it is similar.
Claims (10)
1. a kind of preparation method of Biodegradable high molecular absorbable hemostatic sponge, the Biodegradable high molecular is absorbable only
Sea of blood silk floss is polylactic acid, poly-epsilon-caprolactone and polyethyleneglycol block copolymer, and the general formula of the block copolymer is A-B-C-
B-A or B-A-C-A-B；Wherein A is PLA, B PCL, C PEG；The weight average molecular weight of block copolymer is 2000-80000,
It is characterized in that, the method includes the following steps:
1) by PEG heating melting, lactide or ε-caprolactone is added, by carrying out for the first time under catalyst in protective gas
ε-caprolactone or lactide is added in ring-opening polymerization, carries out second of ring-opening polymerisation by catalyst in protective atmosphere
Reaction, obtains block copolymer；
If front be added lactide, behind be added ε-caprolactone, then obtain block copolymer: poly- (ε-caprolactone)-polylactide-
Polyethylene glycol-polylactide-is poly- (ε-caprolactone)；
If front be added ε-caprolactone, behind lactide is added, then obtain block copolymer: polylactide-is poly- (ε-caprolactone)-
Polyethylene glycol (ε-caprolactone)-polylactide；
2) block copolymer made from step 1) is dissolved in solvent, passes through freeze-drying or solvent volatilization pore, preparation hemostasis sea
It is continuous.
2. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
The weight average molecular weight Mw for the polyethylene glycol stated is 600-20000.
3. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
The lactide stated is at least one of L- lactide, D- lactide, DL- lactide.
4. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
The protective gas stated is at least one of nitrogen, argon gas.
5. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
The ring-opening polymerization catalyst stated is stannous octoate.
6. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
Polyethylene glycol, lactide, the ε-caprolactone mass ratio stated are 1:(0.5-10): (0.5-10).
7. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 5, which is characterized in that institute
The mass concentration for the stannous octoate stated is 0.1wt%-50ppm.
8. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
The first time ring-opening polymerization temperature stated is 100-170 DEG C, and the reaction time is 1-72 hours.
9. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that institute
Second of the ring-opening polymerization temperature stated is 100-150 DEG C, and the reaction time is 12-72 hours.
10. the preparation method of Biodegradable high molecular absorbable hemostatic sponge according to claim 1, which is characterized in that
The solvent is at least one of chloroform, methylene chloride, tetrahydrofuran, dioxane.
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