CN106975098A - A kind of complex polysaccharide hemostatic composition and preparation method and application - Google Patents
A kind of complex polysaccharide hemostatic composition and preparation method and application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L3/00—Compositions of starch, amylose or amylopectin or of their derivatives or degradation products
- C08L3/04—Starch derivatives, e.g. crosslinked derivatives
- C08L3/08—Ethers
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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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2303/00—Characterised by the use of starch, amylose or amylopectin or of their derivatives or degradation products
- C08J2303/04—Starch derivatives
- C08J2303/08—Ethers
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Abstract
The invention discloses a kind of complex polysaccharide hemostatic composition and preparation method and application, including the following component of weight/mass percentage composition：Absorbability composite starch 20% 99%；Forming agent 0.1% 60%；Plasticizer 0.001% 20%.The molecular structure that the complex polysaccharide hemostatic composition that the present invention is provided has can be with the water in quick adsorption blood, make blood platelet, red blood cell and coagulated protein (fibrin ferment and fibrinogen) concentration, the dehydration can accelerate normal blood coagulation speed, and anastalsis is played more quickly.The composition of the present invention can form gel and adhesive base and provide mechanical barrier for follow-up hemostasis, and its Superhydrophilic and strong adhesion characteristics can reduce the probability of bleeding again；Further, since present composition degradation speed is very fast, the safety in utilization of patient is improved.
Description
Technical field
The present invention relates to medical hemostatic technical field of compositions, more particularly to a kind of complex polysaccharide hemostatic composition and its
Preparation method and application.
Background technology
Hemostasis is an important step in the operation of each section office of hospital, reduces bleeding, shortens operating time, to operation into
Work(and the safety important role of patient.At present, in certain operative site, as long as processing method is proper, mechanical hemostasis is still
It is so a kind of simple and effective hemostatic fashion.But, can be straight when some intraoperative hemorrhages can not be stopped blooding by suitable mechanical means
Connect and just played important function for the absorbable hemostasia material of bleeding part.Therefore it provides it is a kind of safely, effectively, use
Convenient and easy to process hemostatic material is particularly important.
Existing frequently-used surgery Absorbable hemostatic material mainly includes following several：Gelatin class or collagen class or shell are poly-
Carbohydrate styptic sponge, oxycellulose class hemostatic gauze or haemostatic membrane, synthetic protein class colloid styptic, starch-polysaccharides class or shell
Glycan class styptic powder.
Gelatin class styptic sponge and the collagen class styptic sponge (biology as disclosed in Publication No. CN101455857A
Compatibility modified starch sponges) can be by absorbing the moisture concentrate blood in blood, can also be by activating intrinsic coagulation
Mechanism and promote to coagulate, and because it has good anthemorrhagic performance, biocompatibility and degradability, application has been obtained in clinic.But
It is the collagen extract that gelatin and collagen derive from animal tissue, is foreign protei；And human body absorbs slow to it, is facing
Easily occur that allergic reaction, wound healing be slow on bed and the complication such as wound easy infection, therefore Clinical practice is greatly limited.And shell
Glycan is the primary derivative of chitin deacetylation, is rare alkaline polysaccharide in nature.HemCon companies of the U.S. release
Can rapidly be stopped as the tourniquet bandage (HemCon Bandage) of matrix using lyophilized chitosan and bleeding profusely, but due to chitosan
Anastalsis it is limited, it is not highly desirable for extensive bleeding surface of a wound haemostatic effect, be only used for the hemostasis of exterior trauma bleeding, no
With can be used for internal organ etc. in vivo bleeding hemostasis.
The hemostatic mechanism of oxycellulose is：There is iron ion (Fe in the carboxyl and hemoglobin of acidity on cellulose3+)
With reference to rear, form the damaged capillary of stickiness blob of viscose closing and play anastalsis, stick and assemble work while having to blood platelet
With so as to activate internal clotting mechanism, acceleration blood coagulation, the hemostatic mechanism of oxidized regenerated cellulose is identical with this.But it is normal
Tissue is relatively slow to such product infiltration rate due to a lack of the metabolism enzyme of oxycellulose, according to consumption and uses
The time that position absorbs in vivo is general at 3-6 weeks.Nagamatsu etc. has found in the research that neuropathy is formed：Oxidized fibre
The peracidity environment that element is produced can cause its bottom neuron denaturation by a kind of diffusivity chemical mechanism.Pusateri etc. is to oxygen
Cellulose material is improved, and develops the oxidized cellulose hemostat that a kind of calcium is modified, its haemostatic effect and bad anti-
The former should be superior to, but still needs to avoid directly largely using in peripheral nerve.
In terms of synthetic protein class colloid styptic, clinical practice in recent years it is relatively broad be fibrin sealant (such as
The absorbability or biocompatible hemostatic material of converted starch in Publication No. CN101361986A patent application), be
The sprayer unit of fibrinogen bind thrombin.Wasted time and energy when the sprayer unit product is because using, limited source, cost it is high
And be restricted；And the fibrin in people, ox or the pig body is allosome or foreign protei, be easily caused allergic reaction and
The generation of zoonotic infection disease；In addition, adhesiveness is weaker when protide colloid styptic is used on the tissue surface of a wound is moistened, it is impossible to
Effective control is carried out to active hemorrhage.
Starch-polysaccharides class disclosed in United States Patent (USP) US6060461 and Publication No. CN101584876A patent application or
Chitosan class styptic powder, its water absorption rate is relatively low, and the gel viscosity formed after water suction is poor, therefore the sludged blood that is formed after being acted on blood
With the poor adhesion of tissue, it is impossible to produce effective viscosity to damaged tissue, blood vessel and block, haemostatic effect is undesirable.
Publication number CN101121041A application for a patent for invention discloses a kind of converted starch Absorbable hemostatic material, is ether
Change converted starch or etherified and crosslinking composite modified starch or etherified and esterification composite modified starch, the denaturation is formed sediment
Powder is made through cohesion, pill, screening.Publication number CN101361986A application for a patent for invention, which discloses a kind of converted starch, to inhale
Receive hemostatic material, for etherificate converted starch, or it is etherified and crosslinking composite modified starch, the converted starch through cohesion, pill,
Screening is made.Publication No. CN105688265A application for a patent for invention discloses a kind of Absorbable hemostatic material and its preparation side
Method, the hemostatic material is at least two in etherificate converted starch, esterification converted starch or etherified, esterification, three kinds of modes of crosslinking
The converted starch of Combined Processing, the converted starch raw material is made through being gelatinized, being crosslinked, going solvent processing, washing, dry and sieve.
Though these three hemostatic materials improve in terms of water absorption rate, it can also be absorbed by organisms, have no toxic side effect, be due to
The characteristic of starch in itself, the sponge individually prepared with it as raw material or membranaceous lyophilized hemostasia products are crisp frangible, no
Beneficial to formed product and use.
Therefore, find and possess Superhydrophilic, water absorption rate height, strongly adherent, can be nonantigenic with quick-acting haemostatic powder, plant origin
Property, in non-stimulated, the internal degradation speed of neutrality it is fast, pack simple Clinical practice it is convenient, easily the function such as sterilizing, can also be according to wound
Mouth-shaped is cut randomly, form flexible, and its preparation technology is simple, efficient, hemostatic material that is being adapted to large-scale production, for ability
The research and development in domain have profound meaning.
The content of the invention
The purpose of the present invention is that, for technological deficiency present in prior art, there is provided one kind hemostasis is fast, viscous for first aspect
The strong complex polysaccharide hemostatic composition of attached property, its raw material includes the following component of weight/mass percentage composition：
Absorbability composite starch 20%-99%, forming agent 0.1%-60%, plasticizer 0.001%-20%；
It is preferred that absorbability composite starch 50%-80%, forming agent 0.1%-40%, plasticizer 0.1%-15%；
More preferably absorbability composite starch 50%-75%, forming agent 10%-40%, plasticizer 2%-10%；
Most preferably absorbability composite starch 70%, forming agent 25%, plasticizer 5%.
The absorbability composite starch is obtained respectively through micro- cross-linking reaction with crosslinking agent by a variety of converted starch raw materials
After micro- crosslinking modified starch of respective numbers species, then obtained a variety of micro- crosslinking modified starch are mixed to get.
The converted starch raw material is one or more in etherification starch, esterification starch, oxidized starch；The etherification starch
It is preferred that one or more of in CMS, HES, hydroxypropul starch and cationic starch；More preferably CMS
And/or HES；The esterification starch preferred starch phosphate, starch xanthate, starch acetate, octenyl succinic
It is one or more of in acid-starch sodium；More preferably starch phosphate；The preferred hydrogen peroxide oxidation starch of oxidized starch, periodic acid
It is one or more of in oxidized starch, hypochlorite oxidation starch, potassium permanganate oxidation starch and potassium ferrate oxidized starch.
The crosslinking agent is glutaraldehyde, Geniposide, carbodiimides, acetic anhydride, sodium tetraborate, epoxychloropropane, three inclined
One kind in sodium phosphate, POCl3；It is preferred that a kind of or several in epoxychloropropane, Geniposide, POCl3, sodium trimetaphosphate
Plant, more preferably epoxychloropropane or Geniposide, most preferably epoxychloropropane.
It is described it is micro- crosslinking be specially：The converted starch raw material of 1 parts by weight is added and stirred in the distilled water of 10-100 parts by weight
Mix, converted starch liquid is made；The pH value of converted starch liquid is adjusted to 8-11, temperature adds 0.01-20 weight to 30 DEG C -80 DEG C
The crosslinking agent stirring of part makes converted starch raw material occur micro- cross-linking reaction with crosslinking agent for 0.5-48 hours；Then successively it is scrubbed,
It is dehydrated, dries, obtains micro- crosslinking modified starch.
The forming agent is carboxymethyl chitosan, hydroxyethyl cellulose, carboxymethyl cellulose, Sodium Hyaluronate, agar, sulphur
It is one or more of in aching and limp ossein.
The plasticizer is one or more in ethylene glycol, propane diols, lactic acid, sodium lactate, D-sorbite, polyethylene glycol.
Second aspect, the present invention provides a kind of method for preparing above-mentioned complex polysaccharide hemostatic composition, first by absorbability
Composite starch is dissolved in water, adds forming agent mixing, adds plasticizer, be mixed to get feed liquid；Feed liquid is poured into lyophilized mould
In, first pre-freeze vacuum freeze drying again obtains spongiform complex polysaccharide hemostatic composition after sterilizing.
Comprise the following steps：
(1) preparation of micro- crosslinking modified starch：Several converted starch raw material is weighed, is separately added into distilled water, is made
Converted starch liquid；The mass ratio of converted starch raw material and distilled water is 1：(10-100)；Adjust each respectively with sodium hydroxide solution
The pH value of converted starch liquid to 8-11, temperature to 30 DEG C -80 DEG C, be separately added into crosslinking agent stirring, make each converted starch raw material with
Micro- crosslinking occurs for crosslinking agent, and micro- crosslinking time is 0.5-48 hours, and the addition quality of crosslinking agent is each converted starch material quality
0.01%-20%；Then respectively obtained several through water washing, absolute ethyl alcohol dehydration, 30 DEG C -60 DEG C dry 2-48h successively
Micro- crosslinking modified starch；
(2) preparation of absorbability composite starch liquid：Several micro- crosslinking modified starch difference that step (1) is obtained is molten
In distilled water, micro- crosslinking modified starch solution is obtained；Several micro- crosslinking modified starch solution is mixed again, obtains inhaling
The property received composite starch liquid；Or be dissolved in after several micro- crosslinking modified starch that step (1) is obtained is mixed in distilled water, obtaining can
Absorbability composite starch liquid；The mass ratio of micro- crosslinking modified starch and distilled water is 1：(5-100)；
(3) shaping agent solution is prepared：Forming agent is weighed, the distilled water of 2-100 times of forming agent quality is added, is mixed to get into
Type agent solution；
(4) mix：The shaping agent solution that step (3) is obtained is added to the absorbability composite starch that step (2) is obtained
Stirred in liquid；Feed liquid is obtained after adding plasticizer, stirring；
(5) freeze：The feed liquid that step (4) is obtained is poured into lyophilized mould, first -60 DEG C--20 in freeze drier
Pre-freeze 0.5h-24h at DEG C；Then vacuum freeze drying is continued in freeze drier, vacuum is less than 20P, and temperature is -50
DEG C--20 DEG C, the time is 4h-72h；Sterilizing, obtains spongiform complex polysaccharide hemostatic composition.
The third aspect, the present invention provides a kind of hemostatic material, including above-mentioned complex polysaccharide hemostatic composition, described compound many
Sugared hemostatic composition is used as hemostatic function component.
Compared with prior art, the beneficial effects of the invention are as follows：
The molecular structure that the complex polysaccharide hemostatic composition that the present invention is provided has can be made with the water in quick adsorption blood
Blood platelet, red blood cell and coagulated protein (fibrin ferment and fibrinogen) concentration, the dehydration can accelerate normal blood coagulation speed
Degree, plays anastalsis more quickly.It is that follow-up hemostasis is carried that the composition of the present invention, which can form gel and adhesive base,
For mechanical barrier, and its Superhydrophilic and strong adhesion characteristics can reduce the probability of bleeding again；Further, since the present composition
Degradation speed is very fast, improves the safety in utilization of patient.
The complex polysaccharide hemostatic composition of the present invention has the characteristics that：1. bleeding stopping period is short：For wound of bleeding profusely,
1-2min pressures can stop blooding；2. water imbibition and adhesiveness are strong；3. it is i.e. degradable in 48-72 hours in body；4. biocompatibility
Good, tissue reaction is light.Therefore, complex polysaccharide hemostatic composition of the invention is expected to turn into more satisfactory surgical hemostasis material.
Brief description of the drawings
Fig. 1 show the electron microscope photo scanning of the complex polysaccharide hemostatic composition of the preparation of the embodiment of the present invention 1.
Embodiment
The complex polysaccharide hemostatic composition that the present invention is provided is in shaping by two or more multiple converted starch
In the presence of agent and plasticizer, a kind of hemostatic material being composited through vacuum freeze drying.Multiple converted starch is existing
Handled on the basis of converted starch：Existing converted starch is subjected to micro- crosslinking Treatment, effect of the converted starch in crosslinking agent
It is crosslinked lower progress low crosslinking degree, its viscosity, swellbility is made moderate progress；Then two or more micro- crosslinking is become
Property starch mixing, can further improve its water absorbent rate, rate of water absorption and its adhesiveness；Mixed again with forming agent, plasticizer
By pre-freeze and vacuum freeze drying, soft texture is obtained, wound is easily attached, facilitates the hemostasia products of clinical manipulation.
The converted starch that the present invention is used, is to obtain starch using two or more complex denaturation processing method
Starch derivatives, complex denaturation processing mainly passes through the combination such as oxidation reaction, esterification, etherification reaction, cross-linking reaction
Realize.Converted starch in the present invention is multiple denaturation, improves water imbibition and adhesiveness, solves the performance of single starch
It is not enough；Again several multiple converted starch be combined and obtain absorbability composite starch, further increase converted starch
Water absorption rate, finally with forming agent, plasticizer mixed preparing, lyophilized obtain soft texture, easily attach wound, facilitate clinical manipulation
Hemostasia products.
The invention provides a kind of complex polysaccharide hemostatic composition of good biocompatibility, including weight/mass percentage composition are as follows
Component：
Absorbability composite starch 20%-99%, forming agent 0.1%-60%, plasticizer 0.001%-20%；
It is preferred that absorbability composite starch 50%-80%, forming agent 0.1%-40%, plasticizer 0.1%-15%；
More preferably absorbability composite starch 50%-75%, forming agent 10%-40%, plasticizer 2%-10%；
Most preferably absorbability composite starch 70%, forming agent 25%, plasticizer 5%.
Wherein, absorbability composite starch is to be obtained with converted starch raw material through processing.Converted starch raw material forms sediment for etherificate
It is one or more of in powder, esterification starch, oxidized starch.Etherification starch be CMS, HES, hydroxypropul starch and
It is one or more of in cationic starch；It is preferred that CMS and/or HES.Esterification starch is starch phosphate, formed sediment
It is one or more of in powder xanthate, starch acetate, starch Sodium Octenyl Succinate；Preferred starch phosphate.Oxidized starch
For hydrogen peroxide oxidation starch, periodate oxidation starch, hypochlorite oxidation starch, potassium permanganate oxidation starch and potassium ferrate
It is one or more of in oxidized starch.
Forming agent can solve the problem of pure starch hemostatic sponge is frangible, can be carboxymethyl chitosan, hydroxy ethyl fiber
It is one or more of in element, carboxymethyl cellulose, Sodium Hyaluronate, agar, chondroitin sulfate.
Plasticizer is one or more in ethylene glycol, propane diols, lactic acid, sodium lactate, D-sorbite, polyethylene glycol.Plasticising
Agent molecule can enter between polysaccharide molecule, weaken the active force between polysaccharide molecule in the presence of Van der Waals force, increase
The distance between polysaccharide molecule and activity space, increase composition plasticity and toughness, so as to get product it is more soft, solve
Current polysaccharide sponge hard and crisp shortcoming.Add after plasticizer, the tensile strength of composition can reach not less than 1KPa.
The shape of complex polysaccharide hemostatic composition including but not limited to sheet, bulk, column, cotton-shaped, stratiform or membranaceous, with
The need for meeting under different operations.
Present invention also offers a kind of method for preparing above-mentioned complex polysaccharide hemostatic composition, comprise the following steps：
(1) preparation of micro- crosslinking modified starch：Two or more converted starch raw material is weighed, distillation is separately added into
In water, it is stirred continuously, converted starch liquid is made；The mass ratio of converted starch raw material and distilled water is 1：(10-100).Use hydrogen-oxygen
Change the pH value of each converted starch liquid of sodium solution regulation to 8-11, the temperature of converted starch liquid is adjusted to 30 DEG C -80 DEG C, to each denaturation
Crosslinking agent is separately added into starch fluid, micro- cross-linking reaction occurs for strong stirring, and the reaction time is 0.5-48 hours, crosslinking agent
Quality for each converted starch material quality 0.01wt%-20wt% (preferably
0.1wt%-8wt%)；Then obtained successively through water washing, absolute ethyl alcohol dehydration, 30 DEG C -60 DEG C dry 2-48h
Several micro- crosslinking modified starch；
Converted starch raw material can be etherification starch, specially CMS, HES, hydroxypropul starch and sun
Ionic starch；Can be esterification starch, specially starch phosphate, starch xanthate, starch acetate, ocentyl succinic
Sodium starch；Can be oxidized starch, specially hydrogen peroxide oxidation starch, periodate oxidation starch, hypochlorite oxidation starch,
Potassium permanganate oxidation starch and potassium ferrate oxidized starch.Two or more converted starch raw material weighed in step (1)
Can be that etherification starch, esterification starch and a class or a few classes in the class of oxidized starch three, i.e. converted starch raw material can be selected from ether
Change in starch two or more, two kinds or two kinds in two or more or oxidized starch in esterification starch with
On, converted starch raw material can also be used as selected from two or more material in wantonly two class or three classes；In other words, become
Property starch material can be in etherification starch, esterification starch and oxidized starch it is any two or more, can all be three classes
In a class or inhomogeneity.
Crosslinking agent is selected from：Formaldehyde, glutaraldehyde, Geniposide, carbodiimides, acetic anhydride, sodium tetraborate, aluminium chloride, N- hydroxyls
Methacrylamide, epoxychloropropane, sodium trimetaphosphate or POCl3.It is preferred that epoxychloropropane, POCl3 or three inclined phosphorus
Sour sodium.
Occur chemical low cross-linking with a small amount of crosslinking agent between converted starch raw molecule to react to form space net structure.
Crosslinking is the alcoholic extract hydroxyl group of starch and the polynary functional group of crosslinking agent forms diether bond or ester bond, this bonding action can make two or
More than two starch molecules " bridge formation " and form hyperspace network structure, strengthen the combination between starch granules.
It is divided into according to the crosslinking degree of starch molecule and crosslinking agent：Micro- crosslinking (low cross-linking), moderate are crosslinked and highly cross-linked.The degree of cross linking
When relatively low (micro- crosslinking) (amount of crosslinking agent accounts for the percentage ＜ 20% of converted starch material quality), due on the hydroxyl of starch chain
Hydrogen bond be substituted, small group is replaced by macoradical, the intermolecular adhesion of steric restriction, space increase, and crystal region is by broken
Bad, the penetration increase of water, water absorption rate increase, viscosity is in rising trend, and after micro- crosslinking, converted starch shows good water suction
Property and solution viscosity are larger.When moderate is crosslinked (percentage that the amount of crosslinking agent accounts for converted starch material quality is 20%-50%),
Bonding action between starch molecule becomes big, and molecular mass increase, intermolecular intensity enhancing, starch granules is difficult expansion, or can only
Demi-inflation, water absorption rate reduction, viscosity declines.(amount of crosslinking agent accounts for converted starch raw material during the degree of cross linking higher (highly cross-linked)
The percentage ＞ 50% of quality), cross-bond almost prevents particle from being expanded in water completely, and it shows as very low water absorption rate and very
Low viscosity number.
(2) preparation of absorbability composite starch：Several micro- crosslinking modified starch that step (1) is obtained is dissolved in respectively
In distilled water, micro- crosslinking modified starch solution is obtained, then several micro- crosslinking modified starch solution is well mixed, obtaining can
Absorbability composite starch liquid；The mixed proportion of every kind of micro- crosslinking modified starch solution is not limited；Micro- crosslinking modified starch is with steaming
The mass ratio of distilled water is 1：(5-100)；
(3) shaping agent solution is prepared：Forming agent is weighed, the distilled water that quality is 2-100 times of forming agent quality is added, is stirring
Lower dissolving is mixed, obtains being molded agent solution.
(4) mix：The shaping agent solution that step (3) is obtained is added to the absorbability composite starch that step (2) is obtained
In liquid, stir；Feed liquid is obtained after adding plasticizer, strong stirring.
(5) freeze：The feed liquid that step (4) is obtained is poured into lyophilized mould, first the pre-freeze 0.5h- at -60 DEG C--20 DEG C
24h, is then placed in vacuum in freeze drier and is less than 20Pa, -50 DEG C--20 DEG C vacuum freeze drying 4h-72h again；It is loaded on
In packaging, radiation sterilization or ethylene oxide sterilization processes obtain spongiform complex polysaccharide hemostatic composition, can be directly used as
Hemostasia products.
Below in conjunction with specific embodiment, present disclosure is further illustrated, and the present invention is further elaborated, but
These embodiments limit the invention absolutely not.
Embodiment 1
(1) 3g CMSs are weighed to be added in 100ml distilled water, are stirred continuously, CMS liquid is made, are fallen
Enter reactor, bath temperature is 60 DEG C, and regulation pH value adds epoxychloropropane 0.2g, strong stirring 3 hours between 8-11；
It is dehydrated again through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinked carboxymethyl fecula.
Weigh 3g HESs to be added in 100ml distilled water, be stirred continuously, hydroxyethyl starch is made, pour into
Reactor, bath temperature is 60 DEG C, and regulation pH value adds epoxychloropropane 0.2g, strong stirring 3 hours between 8-11；Again
It is dehydrated through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinking HES.
(2) the micro- crosslinked carboxymethyl feculas of 0.5g and the micro- crosslinking HESs of 0.5g are weighed, 90ml distilled water is added to
In, it is stirred continuously, starch fluid is made；
(3) hydroxyethyl cellulose 0.35g is weighed, is added in 30ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.07g propane diols, by force
Power is stirred 1 hour.
(5) feed liquid will be obtained in step (4) to pour into lyophilized mould, first the pre-freeze in freeze drier under the conditions of -20 DEG C
6h, be then placed in again -40 DEG C, vacuum be freeze-dried 24h under conditions of being less than 20Pa, obtain the hemostasis of spongiform complex polysaccharide
Composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its thickness is first determined, is measured with Texture instrument suffered during fracture
Power F, regulation rate of extension be 10mm/min, load 5kg, calculate tensile strength：Plane of disruption when P=F/S, S are sample fracture
Area, measure its tensile strength for 36.2KPa.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, the nature that is cut into small pieces is dispersed in alcohol, then takes alcohol
In disperse sample be placed on electron microscopic sample seat on, after alcohol volatilizees naturally, sample abutment surface absorption affinity is sticked on specimen holder,
Scanning sample structure, obtains stereoscan photograph, as shown in Figure 1.It can be seen that complex polysaccharide hemostatic composition
Irregular hole is presented in internal structure, and spongy multi-pore structure adds the absorption rate to liquid, can be with quick adsorption blood
Water in liquid, causes blood platelet, red blood cell and coagulated protein concentration, can accelerate normal blood coagulation, so as to accelerate hemostasis.
Embodiment 2
Step (1) be the same as Example 1.
(2) the micro- crosslinked carboxymethyl feculas of 0.99g and the micro- crosslinking HESs of 0.01g are weighed, 90ml distillation is added to
In water, it is stirred continuously, starch fluid is made.
(3) hydroxyethyl cellulose 0.05g is weighed, is added in 5ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.15g propane diols, by force
Power is stirred 1 hour.
(5) feed liquid will be obtained in step (4) to pour into lyophilized mould, first the pre-freeze 4h in refrigerator-freezer under the conditions of -25 DEG C, then
Be placed in again -35 DEG C, vacuum be less than 20Pa under conditions of vacuum freeze drying 40h, obtain spongiform complex polysaccharide hemostasis group
Compound.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
15.4KPa, its internal structure such as embodiment 1.
Embodiment 3
Step (1) and (2) be the same as Example 1.
(3) hydroxyethyl cellulose 0.15g is weighed, is added in 15ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.1g propane diols, strength
Stirring 1 hour.
(5) be the same as Example 2, obtain spongiform complex polysaccharide hemostatic composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
23.8KPa, its internal structure such as embodiment 1.
Embodiment 4
Step (1) be the same as Example 1.
(2) the micro- crosslinked carboxymethyl feculas of 0.04g and the micro- crosslinking HESs of 0.2g are weighed, 100ml distillation is added to
In water, it is stirred continuously, starch fluid is made.
(3) carboxymethyl chitosan 0.72g is weighed, is added in 50ml distilled water, is stirred continuously, carboxymethyl chitosan is made
Solution.
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.24g propane diols, by force
Power is stirred 1 hour.
(5) be the same as Example 2, obtain spongiform complex polysaccharide hemostatic composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
10.7KPa, its internal structure such as embodiment 1.
Embodiment 5
Step (1) be the same as Example 1.
(2) the micro- crosslinked carboxymethyl feculas of 0.7g and the micro- cross-linked hydroxypropylated starchs of 0.3g are weighed, 100ml distilled water is added to
In, it is stirred continuously, starch fluid is made.
(3) carboxymethyl chitosan 0.4g is weighed, is added in 40ml distilled water, is stirred continuously, carboxymethyl chitosan is made
Solution.
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.1g polyethylene glycol
400, strong stirring 1 hour.
(5) be the same as Example 1, obtains spongiform complex polysaccharide hemostatic composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
28.5KPa, its internal structure such as embodiment 1.
Embodiment 6
Step (1) be the same as Example 1.
(2) the micro- cross-linked hydroxypropylated starchs of 0.8g and the micro- cross-linked hydroxypropyl base PASELLI EASYGELs of 0.1g are weighed, 90ml is added to
Distilled water in, be stirred continuously, starch fluid be made.
(3) carboxymethyl chitosan 0.3g is weighed, is added in 25ml distilled water, is stirred continuously, carboxymethyl chitosan is made
Solution.
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.1g sorbitol solutions,
Strong stirring 1 hour.
(5) feed liquid for obtaining step (4) is poured into lyophilized mould, first the pre-freeze 5h in refrigerator-freezer under the conditions of -20 DEG C, then
It is placed in again in freeze drier, 48h is freeze-dried under conditions of -40 DEG C, vacuum are less than 20 handkerchiefs, obtains spongiform compound
Polysaccharide hemostatic composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
30.6KPa, its internal structure such as embodiment 1.
Embodiment 7
Step (1) be the same as Example 1.
(2) the micro- cross-linked hydroxypropylated starchs of 0.95g and the micro- cross-linked hydroxypropyl base PASELLI EASYGELs of 0.05g are weighed, is added to
In 100ml distilled water, it is stirred continuously, starch fluid is made.
(3) carboxymethyl cellulose 0.15g is weighed, is added in 15ml distilled water, is stirred continuously, carboxymethyl cellulose is made
Solution.
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.2g propane diols, strength
Stirring 1 hour.
(5) be the same as Example 1, obtains spongiform complex polysaccharide hemostatic composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
25.1KPa, its internal structure such as embodiment 1.
Embodiment 8
Step (1) be the same as Example 1.
(2) the micro- friendship carboxymethyl connection starch of 0.9g and the micro- cross-linked hydroxypropyl base PASELLI EASYGELs of 0.1g are weighed, 100ml is added to
Distilled water in, be stirred continuously, starch fluid be made；
(3) hydroxyethyl cellulose 0.15g is weighed, is added in 15ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.2g polyethylene glycol
400, strong stirring 1 hour.
(5) be the same as Example 1, obtains spongiform complex polysaccharide hemostatic composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
27.9KPa, its internal structure such as embodiment 1.
Comparative example 1
(1) 3g CMSs are weighed to be added in 100ml distilled water, are stirred continuously, CMS liquid is made, are fallen
Enter reactor, bath temperature is 85 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 52 hours between 8-11；
Again through water washing, dehydration, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinked carboxymethyl fecula.
Weigh 3g HESs to be added in 100ml distilled water, be stirred continuously, hydroxyethyl starch is made, pour into
Reactor, bath temperature is 85 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 52 hours between 8-11；Again
It is dehydrated through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinking HES.
(2) the micro- crosslinked carboxymethyl feculas of 0.5g and the micro- crosslinking HESs of 0.5g are weighed, 90ml distilled water is added to
In, it is stirred continuously, starch fluid is made；
(3) hydroxyethyl cellulose 0.35g is weighed, is added in 50ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.07g propane diols, by force
Power is stirred 1 hour.
(5) feed liquid will be obtained in step (4) to pour into lyophilized mould, first the pre-freeze in freeze drier under the conditions of -20 DEG C
12h, be then placed in again -40 DEG C, vacuum be less than 20Pa under conditions of be freeze-dried 80h, obtain spongiform complex polysaccharide and stop
Blood composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
3.4KPa。
Comparative example 2
(1) 3g CMSs are weighed to be added in 100ml distilled water, are stirred continuously, CMS liquid is made, are fallen
Enter reactor, bath temperature is 15 DEG C, and regulation pH value adds epoxychloropropane 0.3g between 8-11, and strong stirring 0.3 is small
When；Again through water washing, dehydration, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinked carboxymethyl fecula.
Weigh 3g HESs to be added in 100ml distilled water, be stirred continuously, hydroxyethyl starch is made, pour into
Reactor, bath temperature is 15 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 0.3 hour between 8-11；
It is dehydrated again through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinking HES.
(2) the micro- crosslinked carboxymethyl feculas of 0.5g and the micro- crosslinking HESs of 0.5g are weighed, 90ml distilled water is added to
In, it is stirred continuously, starch fluid is made；
(3) hydroxyethyl cellulose 0.35g is weighed, is added in 30ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.1g propane diols, strength
Stirring 1 hour.
(5) feed liquid will be obtained in step (4) to pour into lyophilized mould, first the pre-freeze in freeze drier under the conditions of -20 DEG C
12h, be then placed in again -65 DEG C, vacuum be freeze-dried 8h under conditions of being less than 20Pa, obtain the hemostasis of spongiform complex polysaccharide
Composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
4.8KPa。
Comparative example 3
(1) 3g CMSs are weighed to be added in 100ml distilled water, are stirred continuously, CMS liquid is made, are fallen
Enter reactor, bath temperature is 60 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 3 hours between 8-11；
It is dehydrated again through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinked carboxymethyl fecula.
Weigh 3g hydroxypropul starch to be added in 100ml distilled water, be stirred continuously, hydroxypropul starch liquid is made, pours into
Reactor, bath temperature is 60 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 3 hours between 8-11；Again
It is dehydrated through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- cross-linked hydroxypropylated starch.
(2) the micro- crosslinked carboxymethyl feculas of 0.5g and the micro- cross-linked hydroxypropylated starchs of 0.05g are weighed, 50ml distilled water is added to
In, it is stirred continuously, starch fluid is made.
(3) hydroxyethyl cellulose 2.5g is weighed, is added in 100ml distilled water, is stirred continuously, hydroxyethyl cellulose is made
Solution；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, adds 0.8g propane diols, strength
Stirring 1 hour.
(5) feed liquid will be obtained in step (4) to pour into lyophilized mould, first the pre-freeze in freeze drier under the conditions of -20 DEG C
6h, be then placed in again -40 DEG C, vacuum be freeze-dried 24h under conditions of being less than 20Pa, obtain the hemostasis of spongiform complex polysaccharide
Composition.
The above-mentioned bar composition of 10mm × 50mm specifications is taken, its tensile strength is measured as described in Example 1 is
5.2KPa。
Comparative example 4
(1) 3g CMSs are weighed to be added in 100ml distilled water, are stirred continuously, CMS liquid is made, are fallen
Enter reactor, bath temperature is 60 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 3 hours between 8-11；
It is dehydrated again through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- crosslinked carboxymethyl fecula.
Weigh 3g hydroxypropul starch to be added in 100ml distilled water, be stirred continuously, hydroxypropul starch liquid is made, pours into
Reactor, bath temperature is 60 DEG C, and regulation pH value adds epoxychloropropane 0.3g, strong stirring 3 hours between 8-11；Again
It is dehydrated through water washing, absolute ethyl alcohol, 50 DEG C of forced air dryings 4 hours obtain micro- cross-linked hydroxypropylated starch.
(2) the micro- crosslinked carboxymethyl feculas of 0.05g and the micro- cross-linked hydroxypropylated starchs of 1g are weighed, 90ml distilled water is added to
In, it is stirred continuously, starch fluid is made.
(3) hydroxyethyl cellulose 0.1g is weighed, is added in 5ml distilled water, is stirred continuously, hydroxyethyl cellulose is made molten
Liquid；
(4) liquid for obtaining above-mentioned steps (2) and (3) is mixed under agitation, without plasticizer, strong stirring
1 hour.
(5) feed liquid will be obtained in step (4) to pour into lyophilized mould, first the pre-freeze in freeze drier under the conditions of -20 DEG C
6h, be then placed in again -40 DEG C, vacuum be less than 20Pa under conditions of be freeze-dried 24h, obtain the complex polysaccharide hemostasis group of powdery
Compound.
The complex polysaccharide hemostatic composition that this comparative example is obtained is powdered, it is impossible to obtain tensile strength.
Experimental example 1
To embodiment 1-8 complex polysaccharide hemostatic composition, comparative example 1-4 and contrast product, absorbent time, water suction are carried out
Rate and sticky work index detection experiment, result of the test are as shown in table 1.Wherein, contrast product is respectively：Medafor companies of the U.S.
The Arista of productionTMStyptic powder, belongs to plant amylum class hemostasia products；The Surgicel oxidation regenerations of Johnson Co.'s production
Cellulose, belongs to oxidized regenerated cellulose class；The chitosan styptic sponge of HEMCON companies of U.S. production, belongs to chitosan class and stops
Blood products；The collagen protein sponge of Beijing Ke Laode productions, belongs to collagen class hemostasia products.
Absorbent time：1cm × 1cm composition samples (thickness 0.5cm) are taken, (water temperature is lain against on the water surface of glassware
20 DEG C ± 2 DEG C of degree), and avoid sample and vessel contacts；Sink to the time used in liquid level completely with stopwatch measurement sample simultaneously.
Water absorption rate：Weigh 0.025g composition samples (W0), the distilled water for adding 2ml or so (adds total matter after distilled water
Amount is designated as W1), after sample is swelled 5min or so extremely water suction saturations, remaining moisture is collected, W is designated as2, then water absorption rate=(W1-
W2)/W0× 100%.
Sticky work index：1g compositions are weighed, adds water to and the sticky glue of solidifying aqueous mixtures is formed after water suction saturation, use Texture instrument
Its sticky work index is determined, test probe is：P36R (cylindrical probe).Test condition is：Under normal temperature, speed before experiment：
0.5mm/s；Test speed：1mm/s；Speed after test：10mm/s；Stress 100g；Reply apart from 5.0mm；Time of contact：10s；
Trigger type：Automatically -5g.
Absorbent time, water absorption rate and the sticky work index experimental result of the sample of table 1
Experimental example 2
Purpose：Example 1-8 sample, by observation, evaluating combined polysaccharide composition to new zealand white rabbit liver
Haemostatic effect.
Method：Choose new zealand rabbit 66, body weight 2.5-3.0kg.It is randomly divided into blank control group, sample sets and listing production
Product reference substance group (AristaTMWith Surgicel oxidized regenerated celluloses), every group 6, male and female half and half.Rabbit is with 1% penta bar ratios
The appropriate left auricular vein injecting anesthetics of sodium 30mg/kg., immediately will combination in every animal's liver same area excision liver slice (0.4g)
Thing is placed on wound and pressed with medical surgical gloves or gauze on sponge, blocking blood flow, without sample is taken after hemostasis
Open or remove, but appropriate infiltration is made of physiological saline and is rinsed, blank control group is handled with hospital gauze pressing, is recorded
Bleeding stopping period, by taking embodiment 1, embodiment 3, embodiment 4, embodiment 8 as an example, is shown in Table 2.Other embodiments also have similar effect,
Do not repeat one by one.Result of the test refers to table 2.
The complex polysaccharide composition new zealand rabbit liver hemostasis trial result of table 2
| Group | Cut off liver weight (g) | Bleeding stopping period (s) |
| Blank control group | 0.34±0.03 | 497±185.4 |
| Embodiment 1 | 0.37±0.03 | 114±53.2 |
| Embodiment 3 | 0.37±0.02 | 150±65.3 |
| Embodiment 4 | 0.37±0.03 | 162±74.8 |
| Embodiment 8 | 0.37±0.03 | 145±45.8 |
| AristaTM | 0.37±0.06 | 183±55.2 |
| Surgicel oxidized regenerated celluloses | 0.35±0.05 | 216±45.4 |
| Comparative example 1 | 0.36±0.04 | 262±44.2 |
| Comparative example 2 | 0.36±0.06 | 258±58.5 |
| Comparative example 3 | 0.36±0.03 | 307±42.3 |
| Comparative example 4 | 0.36±0.03 | 226±64.7 |
The result of table 2 shows, sample sets and AristaTMWith Surgicel oxidized regenerated celluloses to new zealand rabbit liver bleeding
Hemostasis have significant hemostasis validity compared with blank control group.In process of the test, absorbed water immediately after embodiment sample group chance blood/
Blood simultaneously forms sticky colloid with blood, with very strong adhesiveness, promotes blood coagulation, to the envelope of surface of a wound blutpunkte damaged blood vessels
Close better.It can be seen that, complex polysaccharide composition of the invention can substantially shorten the new zealand rabbit liver surface of a wound bleeding time, have
Good haemostatic effect.
Experimental example 3
Purpose：Example 1-8 and comparative example 1-4 sample, by observation, evaluating combined polysaccharide composition in New Zealand
White Rabbit muscular grafting degraded situation.
Method：Some of new zealand white rabbit is chosen, rabbit vertebra both sides about 10cm × 15cm regions rabbit hair is cut off, during experiment
Su Mian Xin intramuscular anesthesia is used, by surgery routine operation requirement sterile surgical region；It is equidistant at the about 2.5cm of rabbit vertebra both sides
4 implantation points are selected from each, two blank control points are stayed, every interval 2cm cuts implantation point, by specimen material with knife blade
The intramuscular of rabbit both sides is implanted to, animal is put to death respectively at Post operation 24h, 48h, 72h, 7 days, 14 days, with the tincture of iodine to operation
Position dyeing observation sample degradation situation, and separately take histotomy to observe sample degradation and tissue reaction's situation.It is with embodiment 8
Example, the composition of other embodiments has similar effect, not repeated one by one.
After the product animal experiment that embodiment 8 is provided, 24h materials, there is unconspicuous blueness after tincture of iodine dyeing；48h draws materials
Afterwards, dye-free reacts after tincture of iodine dyeing.Draw materials and carry out histotomy observation, find 24h with the presence of a small amount of sample, and 48h,
72h and 7 day, 14 days test groups be showed no sample presence；After implantation 7 days, visible neutrophil cell is around blank control point
Main inflammatory reaction；It is light based on visible neutrophil cell, macrophage and lymphocytic infiltration around the sample spot of embodiment 8
Microinflammation.After implantation 14 days, visible collagenous fibres, fibroblast and a small amount of lymphocyte, thermophilic around blank control point
Light inflammation reaction based on neutrophil leucocyte, has loose blister cavities to be formed；Visible a small amount of neutrophil(e) granule around the sample spot of embodiment 8
Cell, macrophage and lymphocytic infiltration, have no that fiber blister cavities is formed.As a result show：The product that there is provided of the present invention 48 hours
I.e. degradable, after being implanted into 7 days, 14 days, tissue reaction is lighter, illustrates that this product has good biocompatibility.
The result of the test of comparative example 1, comparative example 2 and comparative example 4 is：24h draws materials, and has unconspicuous indigo plant after tincture of iodine dyeing
Color；48h draws materials, dye-free reaction after tincture of iodine dyeing；Carry out histotomy observation, 24h with the presence of a small amount of sample, and
48h, 72h and be showed no within 7 days sample presence.
The result of the test of comparative example 3 is：24h draws materials, and dye-free reacts after tincture of iodine dyeing, carries out histotomy observation,
24h, 48h are showed no sample presence for 72h and 7 day with the presence of a small amount of sample.
Described above is only the preferred embodiment of the present invention, it is noted that for the common skill of the art
For art personnel, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications
Also it should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of complex polysaccharide hemostatic composition, it is characterised in that its raw material includes the following component of weight/mass percentage composition：
Absorbability composite starch 20%-99%, forming agent 0.1%-60%, plasticizer 0.001%-20%；
It is preferred that absorbability composite starch 50%-80%, forming agent 0.1%-40%, plasticizer 0.1%-15%；
More preferably absorbability composite starch 50%-75%, forming agent 10%-40%, plasticizer 2%-10%；
Most preferably absorbability composite starch 70%, forming agent 25%, plasticizer 5%.
2. complex polysaccharide hemostatic composition according to claim 1, it is characterised in that the absorbability composite starch be by
After a variety of converted starch raw materials obtain micro- crosslinking modified starch of respective numbers species through micro- cross-linking reaction respectively with crosslinking agent, then
Obtained a variety of micro- crosslinking modified starch are mixed to get.
3. complex polysaccharide hemostatic composition according to claim 2, it is characterised in that the converted starch raw material forms sediment for etherificate
It is one or more of in powder, esterification starch, oxidized starch；The preferred CMS of etherification starch, HES, hydroxypropyl
It is one or more of in starch and cationic starch；More preferably CMS and/or HES；The esterification starch is preferred
It is one or more of in starch phosphate, starch xanthate, starch acetate, starch Sodium Octenyl Succinate；More preferably starch
Phosphate；The preferred hydrogen peroxide oxidation starch of oxidized starch, periodate oxidation starch, hypochlorite oxidation starch, Gao Meng
It is one or more of in sour potassium oxidized starch and potassium ferrate oxidized starch.
4. the complex polysaccharide hemostatic composition according to Claims 2 or 3, it is characterised in that the crosslinking agent is glutaraldehyde, capital
Buddhist nun is flat, one kind in carbodiimides, acetic anhydride, sodium tetraborate, epoxychloropropane, sodium trimetaphosphate, POCl3；It is preferred that ring
One or more, more preferably epoxychloropropane or Geniposide, optimal in oxygen chloropropane, Geniposide, POCl3, sodium trimetaphosphate
Select epoxychloropropane.
5. according to any complex polysaccharide hemostatic compositions of claim 2-4, it is characterised in that micro- crosslinking is specially：
Stirred in the distilled water that the converted starch raw material of 1 parts by weight is added to 10-100 parts by weight, converted starch liquid is made；Regulation denaturation
The pH value of starch fluid is to 8-11, and temperature is to 30 DEG C -80 DEG C, and add the crosslinking agent stirring of 0.01-20 parts by weight makes for 0.5-48 hours
With crosslinking agent micro- cross-linking reaction occurs for converted starch raw material；Then successively it is scrubbed, dehydration, dry, obtain it is micro- crosslinking denaturation form sediment
Powder.
6. according to any complex polysaccharide hemostatic compositions of claim 1-5, it is characterised in that the forming agent is carboxymethyl
It is one or more of in chitosan, hydroxyethyl cellulose, carboxymethyl cellulose, Sodium Hyaluronate, agar, chondroitin sulfate.
7. according to any complex polysaccharide hemostatic compositions of claim 1-6, it is characterised in that the plasticizer is second two
It is one or more of in alcohol, propane diols, lactic acid, sodium lactate, D-sorbite, polyethylene glycol.
8. a kind of method for preparing any complex polysaccharide hemostatic compositions of claim 1-7, it is characterised in that can first inhale
The property received composite starch is dissolved in water, adds forming agent mixing, adds plasticizer, be mixed to get feed liquid；Feed liquid is poured into lyophilized
In mould, first pre-freeze vacuum freeze drying again obtains spongiform complex polysaccharide hemostatic composition after sterilizing.
9. the preparation method of complex polysaccharide hemostatic composition according to claim 8, it is characterised in that comprise the following steps：
(1) preparation of micro- crosslinking modified starch：Several converted starch raw material is weighed, is separately added into distilled water, denaturation is made
Starch fluid；The mass ratio of converted starch raw material and distilled water is 1：(10-100)；Adjust each denaturation respectively with sodium hydroxide solution
The pH value of starch fluid is to 8-11, and temperature is separately added into crosslinking agent stirring, makes each converted starch raw material and crosslinking to 30 DEG C -80 DEG C
Micro- crosslinking occurs for agent, and micro- crosslinking time is 0.5-48 hours, and the addition quality of crosslinking agent is each converted starch material quality
0.01%-20%；Then respectively obtained several micro- through water washing, absolute ethyl alcohol dehydration, 30 DEG C -60 DEG C dry 2-48h successively
Crosslinking modified starch；
(2) preparation of absorbability composite starch liquid：Several micro- crosslinking modified starch that step (1) is obtained is dissolved in steaming respectively
In distilled water, micro- crosslinking modified starch solution is obtained；Several micro- crosslinking modified starch solution is mixed again, absorbability is obtained
Composite starch liquid；Or be dissolved in after several micro- crosslinking modified starch that step (1) is obtained is mixed in distilled water, it is can absorb
Property composite starch liquid；The mass ratio of micro- crosslinking modified starch and distilled water is 1：(5-100)；
(3) shaping agent solution is prepared：Forming agent is weighed, the distilled water of 2-100 times of forming agent quality is added, is mixed to get forming agent
Solution；
(4) mix：The shaping agent solution that step (3) is obtained is added in the absorbability composite starch liquid that step (2) is obtained
Stirring；Feed liquid is obtained after adding plasticizer, stirring；
(5) freeze：The feed liquid that step (4) is obtained is poured into lyophilized mould, first in freeze drier at -60 DEG C--20 DEG C
Pre-freeze 0.5h-24h；Then vacuum freeze drying is continued in freeze drier, vacuum is less than 20P, temperature is -50 DEG C--
20 DEG C, the time is 4h-72h；Sterilizing, obtains spongiform complex polysaccharide hemostatic composition.
10. a kind of hemostatic material, including any complex polysaccharide hemostatic compositions of claim 1-7 or claim 8-9 appoint
The complex polysaccharide hemostatic composition that one methods described is prepared, the complex polysaccharide hemostatic composition is used as hemostatic function group
Point.
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| WO2020226587A1 (en) * | 2019-05-03 | 2020-11-12 | Vsy Biyoteknoloji Ve Ilac Sanayi Anonim Sirketi | A biocompatible, biodegradable and bioresorbable adhesion membrane including hyaluronic acid / chitosan / carboxymethyl cellulose and production method |
| CN112807480A (en) * | 2018-08-20 | 2021-05-18 | 稳得希林(杭州)生物科技有限公司 | Polysaccharide-based tissue adhesive medical adhesive and application thereof |
| CN114767930A (en) * | 2022-04-11 | 2022-07-22 | 山东大学齐鲁医院 | 3D nanofiber sponge, preparation method and application in spinal cord injury repair field |
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