CN108853564A - Hemostasis cross-link dextran particle and preparation method thereof - Google Patents
Hemostasis cross-link dextran particle and preparation method thereof Download PDFInfo
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- CN108853564A CN108853564A CN201710317242.7A CN201710317242A CN108853564A CN 108853564 A CN108853564 A CN 108853564A CN 201710317242 A CN201710317242 A CN 201710317242A CN 108853564 A CN108853564 A CN 108853564A
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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
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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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- 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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- 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
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/02—Dextran; Derivatives thereof
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Abstract
The invention discloses a kind of hemostasis cross-link dextran particles and preparation method thereof, are prepared using epoxychloropropane as crosslinking agent using reverse phase suspension method, product obtained is low through detection residual crosslinker amount, and good biocompatibility is suitable for use as hemostatic material.The present invention is during preparing cross-link dextran particle without introducing other organic solvent washings, avoiding the residual of organic solvent in product and then influencing product quality.Cross-link dextran particle obtained by the present invention has irregular edge contour, it is not easy to shift after use, be capable of fixing hemostasis site, the present invention obtained by cross-link dextran particle have biodegradability, non-immunogenicity, no cytotoxicity, can be used as styptic powder in clinical use.
Description
Technical field
The present invention relates to the systems of a kind of cross-link dextran particle used as styptic powder and the cross-link dextran particle
Preparation Method.
Background technique
In various surgical operations, reduces bleeding, shortens operating time, there is important influence to patient's prognosis.It is ideal
Hemostatic material should have following characteristics：Hemostasis is rapid, nontoxicity, no antigen, do not increase Infection probability, does not influence tissue is cured
It closes, is cheap.
Medical absorbable hemostatic material causes the great attention of various countries' medical field and industrial circle in recent years.Absorbable hemostatic
Material refers to applied to wound bleeding position, reaches hemostasis purpose by acceleration Blood Coagulation Process, within a certain period of time can quilt
The medical material of absorption of human body.Currently used Absorbable hemostatic material have Fibrin Glue, gelfoam, oxycellulose,
Microfibrillar collagen, chitosan and Sorbsan etc..
About hemostatic material, Chinese patent literature CN100402096 (application number 02818207.3) discloses a kind of drying
Hemostatic composition and preparation method thereof, this rapid rehydration of composition energy is to generate the gelatin water-setting for being preferably used as hemostatic sealants
Glue.The preparation method of the composition is as follows：A kind of water combined comprising uncrosslinked gelatin at least one re-hydration aid is provided
Solution；The solution of the gelatin and re-hydration aid is dried to form solid；The solid is ground to form powder；Cross-linked gelatin is with shape
At hydrogel；At least 50% (w/w) re-hydration aid is removed from hydrogel；And the cross-linked gelatin is dried to be formed
A kind of water capacity is lower than the powder of 20% (w/w)；Wherein the re-hydration aid is selected from glycerol, glucan, polyethylene
Base pyrrolidones and polyethylene glycol.
Chinese patent literature CN102178977A (application number 201110094127.0) discloses a kind of gentle with hemostasis
The preparation and preparation method thereof for releasing granulocyte colony stimulating factor double action, is gathered by the Portugal containing granulocyte colony stimulating factor
Sugared particle, degradable slow controlled-release material and hemostatic material skeleton composition, wherein：Glucan containing granulocyte colony stimulating factor
The weight per unit area that particle and degradable slow controlled-release material account for hemostatic material skeleton respectively is respectively 0.004~400mg/cm2
And 0.001mg~4mg/cm2.Preparation method is by the degradable slow controlled-release material to liquid or to be dissolved in organic solvent
It is suspended in degradable slow controlled-release material and suspension is made into the glucan particles containing granulocyte colony stimulating factor, finally with spray
It applies, suspension is coated on Biodegradable fiber or porous material by brushing or dipping method.The degradable slow controlled release material
Material be polylactic acid (PLA), poly- acetic acid (PGA), poly lactide-glycolide acid (PLGA), polycaprolactone (PCL), poly- (ester),
Poly (lactic acid-glycolic acid) and its derivative or other biodegradable slow release materials and combinations thereof.
It is compound only that Chinese patent literature CN103721247B (application number 201410009613.1) discloses a kind of collagen-based
Blood meal agent and preparation method thereof is modified type i collagen using dencichine, with the chitosan of polylysine modification, will change
Property after type i collagen be configured to the solution that concentration is 1%~2%, medical gelatin is configured to 1%~3% solution, and will modification
Chitosan be configured to 1%~3% solution, then by above-mentioned three kinds of solution be in mass ratio 0.5~1: 2~8: 8~2 be blended,
In 4~10 DEG C of 8~10h of stirring of temperature, composite sponge is made in freeze-drying.It at room temperature, will be compound in ultrasonic cleaner
Sponge is successively impregnated in modifying agent and coagulation factor, sufficiently washes, freeze-dried, and collagen-based is prepared in pulverizer crushing
Compound hemostatic pulvis.
Above-mentioned hemostatic material complicated composition, corresponding product safety risk are larger.The biological safety of many materials is all deposited
In certain drawbacks, portioned product even non-degradable.
Chinese patent literature CN 102989031B (application number 201210439078.4) discloses a kind of high-expansion polysaccharide
Medical material and its application, it is soluble polysaccharide and supermolecule powdery or graininess solid content that crosslinking action is formed, institute
The soluble polysaccharide stated is cellulose derivative, starch and its derivative, glucan and its derivative, chitin and its derivative
Object, chitosan and its derivative, chondroitin sulfate and its derivative, hyaluronic acid and its derivative, alginic acid and its derivative,
One or both of konjac glucomannan, Bletilla glucomannan, pachymaran.
Glucan therein is a kind of glucose polymer being keyed with α -1,6-.Glucan is non-toxic and has good
Bioadhesive, biocompatibility, biological degradability and gel characteristic, in terms of medicine controlled releasing and embolotherapy have uniqueness
Advantage.The dextran generally used in hospital is exactly glucan (also referred to as dextran).Glucan is as good microballoon
Raw material is prepared, safety and validity are that any hemostatic material cannot compare, and dextran microparticles are in biomedicine field
It is with a wide range of applications.
Although Chinese patent literature CN 102989031B refers to that glucan and its derivative and crosslinking action are formed super
Molecule powdery or graininess solid content can be used for stopping blooding, but the preparation method of the cross-link dextran of the undisclosed hemostasis of full text.
It is poly- that Chinese patent literature CN 101182380 (application number 200610107398.4) discloses a kind of reverse phase crosslinking Portugal
The synthetic method of sugar, weighs glucan 100g, and sodium hydroxide 10g, which is dissolved in the distilled water of 75ml, is configured to glucan lye,
Polyvinyl acetate 25-60g is weighed, is dissolved in the epoxychloropropane of 500-900ml under agitation, poly-vinegar acid is configured to
Glucan lye is poured into polyvinyl acetate and ring under conditions of stirring speed is 500rpm by ethylene rouge epoxychloropropane solution
In oxygen chloropropane solution, cross-linking reaction is carried out, temperature is 50 DEG C, is reacted 5 hours；Reaction product successively uses 3 times of amount ethyl alcohol and steaming
Distilled water is washed 3 times, then is dried 2 hours through 50 DEG C, and product can be obtained.Cross-link dextran made from this method is a kind of compound friendship
Join glucan, polyvinyl acetate used in preparation process is that one kind is difficult biodegradable macromolecule organic material, and poly-vinegar
The biological safety of sour ethylene rouge and polyvinyl acetate crosslinking or dispersion product there is no report, therefore according to method preparation
Cross-link dextran is not suitable for hemostasis and uses.
Summary of the invention
First technical problem to be solved by this invention is to provide one kind and sucks blood that effect is good, biological safety is high, can drop
The hemostasis of solution cross-link dextran particle；Second technical problem to be solved is to provide a kind of cross-link dextran of hemostasis
The preparation method of particle.
The technical solution for realizing an object of the present disclosure is a kind of hemostasis cross-link dextran particle, which is glucan
With the cross-linking products of epoxychloropropane, it is made in accordance with the following steps：1. at room temperature that glucan dry powder is evenly dispersed in acetone；
2. sodium hydroxide solution is added dropwise into the material of step 1., finely dispersed floccule is stirred to get when being added dropwise, and hydrogen-oxygen is added dropwise
Gradient increased temperature is carried out to material during changing sodium solution, 30~40 DEG C is warming up to and temperature is kept to stir 15~30min；3. to
2. epoxychloropropane is added dropwise in finely dispersed floccule for step, the ratio between dextran and the amount of substance of epoxychloropropane are 5:
3~5, epoxychloropropane, which finishes, to be continued to be stirred to react 4~15h；4. hydrochloric acid is added dropwise into the step 3. material of end of reaction, adjust
The pH value of reacting rear material is 4.5~5.5；Material in bottle is poured out and filtered, the sephadex obtained above filter paper
Particle is to be processed；5. the sephadex particle 4. obtained with acetone washing step；6. after step 5. acetone washing
Cross-link dextran particle forced air drying；7. the cross-link dextran that the particle after 6. drying to step is sieved to obtain hemostasis is micro-
Grain.
Above-mentioned particle has irregular edge contour, and the partial size of particle is 135 μm~350 μm.
The technical solution for realizing the second purpose of the invention is a kind of preparation method of the cross-link dextran particle of hemostasis, packet
Include following steps：
1. at room temperature that glucan dry powder is evenly dispersed in acetone.
2. sodium hydroxide solution is added dropwise into the material of step 1., finely dispersed floccule is stirred to get when being added dropwise,
Be added dropwise sodium hydroxide solution during to material carry out gradient increased temperature, be warming up to 30~40 DEG C and keep temperature stirring 15~
30min。
3. epoxychloropropane, the substance of dextran and epoxychloropropane are added dropwise into step 2. finely dispersed floccule
The ratio between amount be 5:3~5, epoxychloropropane, which finishes, to be continued to be stirred to react 4~15h.
4. hydrochloric acid is added dropwise into the step 3. material of end of reaction, the pH value for adjusting reacting rear material is 4.5~5.5；It will
Material is poured out and is filtered in bottle, and the sephadex particle obtained above filter paper is to be processed.
5. the sephadex particle 4. obtained with acetone washing step.
6. by the cross-link dextran particle forced air drying after step 5. acetone washing.
7. the particle after 6. drying to step is sieved to obtain the cross-link dextran particle of hemostasis.
Above-mentioned steps 2. gradient increased temperature when, every 10min rises 4~6 DEG C.
Above-mentioned steps 6. forced air drying when, control temperature be lower than 40 DEG C.
Above-mentioned steps 7. to step 6. dry after particle sieve when, particle to be sieved first passes through 60 mesh mesh screens
Point, by the particle of the sieve, the sieve through 170 mesh is sieved again, takes the particle above the sieve poly- as the crosslinking Portugal of hemostasis
Sugared particle.
The present invention has the effect of positive：(1) present invention prepares cross-link dextran particle using reverse phase suspension method, prepares
Method is simple and easy to operate, it can be achieved that solid-state prepares particle, and product obtained is low through detection residual crosslinker amount, biocompatibility
It is good, it is suitable for use as hemostatic material.
(2) present invention is avoided without introducing other organic solvent washings during preparing cross-link dextran particle
The residual of organic solvent influences product quality in turn in product, and reduces production cost, thereby reduces the price of styptic powder.
(3) the smooth spherical shape in cross-link dextran particle not instead of surface obtained by the present invention, has irregular side
Edge profile is not easy to shift after use, is capable of fixing in hemostasis site, the partial size of particle is 135 μm~350 μm, and particle can load
It is pushed in injection tube, when use in blutpunkte, cross-link dextran particle is sucked blood rapidly swelling, and anastalsis is played.
(4) the cross-link dextran particle obtained by the present invention has biodegradability, non-immunogenicity, acellular poison
Property, it can be used as styptic powder in clinical use.
Detailed description of the invention
Fig. 1 is the microphoto (64 times of amplification) of cross-link dextran particle made from embodiment 1；
Fig. 2 is the particle size distribution figure of cross-link dextran particle made from embodiment 1；
Fig. 3 is the gas chromatogram of cross-link dextran detection of particulates acetone residue amount made from embodiment 1；
Fig. 4 is the gas chromatogram of cross-link dextran detection of particulates residual crosslinker amount made from embodiment 1；
Fig. 5 is the microphoto (64 times of amplification) of cross-link dextran particle made from embodiment 2；
Fig. 6 is the particle size distribution figure of cross-link dextran particle made from embodiment 2；
Fig. 7 is the gas chromatogram of cross-link dextran detection of particulates acetone residue amount made from embodiment 2；
Fig. 8 is the gas chromatogram of cross-link dextran detection of particulates residual crosslinker amount made from embodiment 2；
Fig. 9 is the microphoto (64 times of amplification) of cross-link dextran particle made from embodiment 3；
Figure 10 is the particle size distribution figure of cross-link dextran particle made from embodiment 3.
Figure 11 is the gas chromatogram of cross-link dextran detection of particulates acetone residue amount made from embodiment 3；
Figure 12 is the gas chromatogram of cross-link dextran detection of particulates residual crosslinker amount made from embodiment 3.
Specific embodiment
(embodiment 1)
The preparation method of the cross-link dextran particle of the present embodiment includes the following steps：
1. 300mL acetone is added into the three-neck flask of 500mL, (15~30 DEG C) addition 20g dextrans are (again at room temperature
Claim glucan, is synthesized by sucrose through leuconostoc mesenteroide -1226 (Leuconostoc mesenteroides) fermentation, molecule
Measuring 4, ten thousand) dry powder, stirring make dry powder be uniformly dispersed in acetone.
2. the sodium hydrate aqueous solution of 0.2mol/L is added dropwise in dropping funel into the three-neck flask of step 1.
120mL sodium hydroxide solution, 30min are dripped off；It stirs when being added dropwise so that the floccule in three-neck flask is uniformly dispersed.
Gradient increased temperature is carried out to three-neck flask during sodium hydroxide solution is added dropwise, every 10min rises 4~6 DEG C of (this realities
Apply is 5 DEG C in example), it is warming up to 40 DEG C and the temperature is kept to stir 20min.
3. epoxychloropropane, dextran and epoxy chloropropionate is added dropwise into the step 2. finely dispersed three-neck flask of floccule
The ratio between amount of substance of alkane is 5:3.Epoxychloropropane, which is finished, to be continued to be stirred to react 14h at 40 DEG C.
4. the hydrochloric acid of 2mol/L is added dropwise into the step 3. three-neck flask of end of reaction, until the pH value of liquid is in bottle
4.5~5.5 (being 5.0 in the present embodiment)；Material in bottle is poured out and filtered, the sephadex obtained above filter paper is micro-
Grain is to be processed.
5. sephadex particle 2~3 times 4. obtained with acetone washing step, washing the acetone used every time
Volume is 4 times of sephadex particle volume, and each wash time is 30min.
6. by the cross-link dextran particle after step 5. acetone washing in 40 DEG C of temperature or less forced air drying 1h, obtained friendship
The particle size distribution figure of connection dextran microparticles is shown in Fig. 2, and particle average grain diameter obtained is 212.471 μm.Use Britain Malvern public affairs
The 2000 type particle size analyzer of Mastersizer of department carries out granularity Detection, the granularity of following embodiment to particle obtained above
Detection also uses the particle size analyzer.
Further, in the dry microspheres obtained by gas chromatographic detection solvent acetone and crosslinking agent epoxychloropropane it is residual
It stays, Fig. 3 is the gas chromatogram of cross-link dextran detection of particulates acetone residue amount made from the present embodiment, and acetone residue amount is 46
μg/g；Fig. 4 is the gas chromatogram of cross-link dextran detection of particulates epoxychloropropane residual quantity made from the present embodiment, epoxy chlorine
Propane is not detected.
7. the particle 6. step is dried after carries out two step screenings, two steps screening apparatus structure used see application No. is
2017200921496, patent name is a kind of Chinese patent literature of shaking screen for being used to prepare microballoon, the sieve on concussion sieve
According to screening situation selection.The mesh mesh number of two sieves in the present embodiment is respectively 60 mesh and 170 mesh, particle to be sieved
The screening of 60 mesh screens is first passed through, the sieve through 170 mesh sieves again by the particle of the sieve, and the particle above the sieve is taken to obtain
Target product, that is, hemostasis cross-link dextran particle.
The microphoto for sieving resulting cross-link dextran particle is shown in Fig. 1.Obtained crosslinking Portugal as we can see from the figure
The smooth spherical shape in glycan particle not instead of surface, has irregular edge contour, and the particle of this shape mutually touches indirectly
Area is big, so that frictional force is big, is not easy to shift.
(embodiment 2)
Remaining is same as Example 1 for the preparation method of the cross-link dextran particle of the present embodiment, the difference is that：
Step is 2. 45 DEG C of temperature of charge in gradient increased temperature to bottle.
3. epoxychloropropane is added in step after, the ratio between amount of substance of dextran and epoxychloropropane is 5:4.Epoxy chlorine
Propane, which is finished, to be continued to be stirred to react 8h at 45 DEG C.
The microphoto of cross-link dextran particle made from the present embodiment (by screening) is shown in Fig. 5.
Particle size distribution figure before cross-link dextran particle made from the present embodiment is not sieved is shown in Fig. 6, and particle obtained is average
Partial size is 134.922 μm.
6. the residual of solvent acetone and crosslinking agent epoxychloropropane in the dry microspheres obtained with gas chromatographic detection step,
Fig. 7 is the gas chromatogram of cross-link dextran detection of particulates acetone residue amount made from the present embodiment, and acetone residue amount is 46ug/
g；Fig. 8 is the gas chromatogram of cross-link dextran detection of particulates epoxychloropropane residual quantity made from the present embodiment, epoxy chloropropionate
Alkane is not detected.
(embodiment 3)
Remaining is same as Example 1 for the preparation method of the cross-link dextran particle of the present embodiment, the difference is that：
Step is 2. 35 DEG C of temperature of charge in gradient increased temperature to bottle.
3. epoxychloropropane is added in step after, the ratio between amount of substance of dextran and epoxychloropropane is 5:5.Epoxy chlorine
Propane, which is finished, to be continued to be stirred to react 15h at 35 DEG C.
The microphoto of cross-link dextran particle made from the present embodiment (by screening) is shown in Fig. 9.
Particle size distribution figure before cross-link dextran particle made from the present embodiment is not sieved is shown in Figure 10, and particle obtained is average
Partial size is 348.129 μm.
6. the residual of solvent acetone and crosslinking agent epoxychloropropane in the dry microspheres obtained with gas chromatographic detection step,
Figure 11 is the gas chromatogram of cross-link dextran detection of particulates acetone residue amount made from the present embodiment, and acetone residue amount is
52ug/g；Figure 12 is the gas chromatogram of cross-link dextran detection of particulates epoxychloropropane residual quantity made from the present embodiment, ring
Oxygen chloropropane is not detected.
(test example)
The water absorbing properties of cross-link dextran particle, the degree of cross linking and hemostatic function made from above-described embodiment 1 to 3 are examined
It surveys, detection method and result are as follows.
(1) water imbibition detects
The cross-link dextran particle 0.5g for taking 0.5g dry powder-shaped, is fitted into the test tube of known weight, slowly adds into test tube
Water, until cross-link dextran particle fully absorbs moisture to stopping when just having excessive moisture precipitation plus water, inclination test tube slowly will
The moisture not absorbed is poured out, then weighs the weight of test tube and its content respectively, subtracts the weight of former test tube itself, is obtained each
The data of tester are as follows：
The every g water suction 12.4g of the cross-link dextran particle of embodiment 1, the every g water suction of the cross-link dextran particle of embodiment 2
10.3g, the every g of the cross-link dextran particle of embodiment 3 absorb water 8.2g, show that crosslinking agent dosage is bigger, and water imbibition is poorer
Trend, probably due to crosslinking agent dosage is bigger, the degree of cross linking is higher for this, therefore water absorbing properties decline.
(2) detection of the degree of cross linking
Using the detection method of the applicant's exploitation, the degree of cross linking is crosslinking agent modified part in microballoon for degree of cross linking detection
Quality account for the percentage of entire microspheres quality, wherein modified part quality includes the glucan quality, monosubstituted of crosslinking modification
The glucan quality and crosslinking agent segment three parts quality sum of modification；Detection method is as follows：
The tested cross-link dextran microballoon that 0.20000g is weighed with electronic balance precision, transfers them to 50mL volumetric flask
In, the sodium periodate solution 50.00mL of 50mM is measured with pipette and is transferred in above-mentioned 50mL volumetric flask, is shaken up, volumetric flask
Periphery is wrapped with tinfoil and is protected from light, and carries out redox reaction at 4 DEG C, every shake well volumetric flask one for 24 hours in reaction process
It is secondary.
The equation of redox reaction is as follows：
Every drawing the solution in 0.1mL volumetric flask for 24 hours into 100mL volumetric flask in reaction process, it is diluted with water to quarter
Degree, shakes up, and the light absorption value of solution is measured at 223nm.
Reaction reaches stable to light absorption value, at this time from 20.00mL supernatant is drawn in volumetric flask into conical flask, to taper
2mL ethylene glycol is added in bottle, shakes up, after standing 20min under room temperature, dark condition, 2~3 drop phenolphthalein are added into conical flask
Reagent shakes up, and is then titrated with the sodium hydroxide solution of 0.01M, and the volume V of consumption is recorded1。
Add 2mL ethylene glycol solution to do blank with same volume 20mL distilled water, operate, titrated in the same way,
Record the volume V of blank consumption0。
Substitute into degree of cross linking calculation formula：In.
In above formula, V1The volume of sodium hydroxide titration liquid, units/ml are consumed for sample liquid.
V0The volume of sodium hydroxide titration liquid, units/ml are consumed for blank control liquid.
C is sodium hydroxide titration liquid concentration, unit mol/L.
162g/mol is glucose residue molecule molal weight in dextran chain.
M is the quality of dextran microspheres, unit g.
According to the method described above, the 1 particle degree of cross linking 62.66% of embodiment；The 2 particle degree of cross linking 64.28% of embodiment；Embodiment
The 3 particle degrees of cross linking 65.15%.The conjecture of verification test example 1：Since crosslinking agent dosage is bigger, the degree of cross linking is higher, therefore absorbs water
Performance decline.
(3) zoopery of hemostatic function
This experiment is hemostasis experiment of the cross-link dextran particle styptic powder on mouse.
36 stochastic averaginas of mouse are divided into 3 groups：Control group, positive controls, cross-link dextran particle group.
By mouse anesthesia, exposure simultaneously cuts femoral artery, and control group mice allows it to stop blooding naturally, and positive controls mouse is going out
Blood point pushes commercial plant polysaccharide styptic powder 0.5g with injection tube, and the blutpunkte of cross-link dextran particle group mouse is pushed away with injection tube
Cross-link dextran particle 0.5g prepared by embodiment 1 is squeezed, the femoral hemostasis time is recorded, it is as a result as follows：
| Group | The femoral hemostasis time (min) |
| Control group | 12.10±4.23 |
| Positive controls | 8.41±3.64 |
| Cross-link dextran particle group | 2.80±1.58 |
Above-mentioned experiment confirms that cross-link dextran styptic powder of the invention can be substantially reduced surface of a wound bleeding stopping period, has good
Haemostatic effect.
Claims (6)
1. a kind of hemostasis cross-link dextran particle, it is characterised in that the particle is the crosslinking production of glucan and epoxychloropropane
Object is made in accordance with the following steps：1. at room temperature that glucan dry powder is evenly dispersed in acetone；2. being dripped into the material of step 1.
Adding sodium hydroxide solution stirs to get finely dispersed floccule when being added dropwise, and is added dropwise during sodium hydroxide solution to object
Material carries out gradient increased temperature, is warming up to 30~40 DEG C and temperature is kept to stir 15~30min；3. 2. finely dispersed cotton-shaped to step
Epoxychloropropane is added dropwise in object, the ratio between dextran and the amount of substance of epoxychloropropane are 5:3~5, epoxychloropropane finishes
Continue to be stirred to react 4~15h；4. hydrochloric acid is added dropwise into the step 3. material of end of reaction, the pH value for adjusting reacting rear material is
4.5~5.5；Material in bottle is poured out and filtered, the sephadex particle obtained above filter paper is to be processed；5. using acetone
4. sephadex particle that washing step obtains；6. the cross-link dextran particle air blast after step 5. acetone washing is done
It is dry；7. the particle after 6. drying to step is sieved to obtain the cross-link dextran particle of hemostasis.
2. hemostasis cross-link dextran particle according to claim 1, it is characterised in that：Particle has irregular edge
Profile, the partial size of particle are 135 μm~350 μm.
3. a kind of preparation method of the cross-link dextran particle of hemostasis, it is characterised in that include the following steps：
1. at room temperature that glucan dry powder is evenly dispersed in acetone；
2. sodium hydroxide solution is added dropwise into the material of step 1., finely dispersed floccule is stirred to get when being added dropwise, is added dropwise
Gradient increased temperature is carried out to material during sodium hydroxide solution, be warming up to 30~40 DEG C and temperature is kept to stir 15~30min；
3. epoxychloropropane is added dropwise into step 2. finely dispersed floccule, the amount of the substance of dextran and epoxychloropropane
The ratio between be 5:3~5, epoxychloropropane, which finishes, to be continued to be stirred to react 4~15h；
4. hydrochloric acid is added dropwise into the step 3. material of end of reaction, the pH value for adjusting reacting rear material is 4.5~5.5；It will be in bottle
Material is poured out and is filtered, and the sephadex particle obtained above filter paper is to be processed；
5. the sephadex particle 4. obtained with acetone washing step；
6. by the cross-link dextran particle forced air drying after step 5. acetone washing；
7. the particle after 6. drying to step is sieved to obtain the cross-link dextran particle of hemostasis.
4. the preparation method of the cross-link dextran particle of hemostasis according to claim 3, it is characterised in that：Step is 2. terraced
When degree heating, every 10min rises 4~6 DEG C.
5. the preparation method of the cross-link dextran particle of hemostasis according to claim 3, it is characterised in that：6. step is roused
When air-drying dry, control temperature is lower than 40 DEG C.
6. the preparation method of the cross-link dextran particle of hemostasis according to claim 3, it is characterised in that：Step is 7. right
Step 6. dry after particle when being sieved, particle to be sieved first passes through the screening of 60 mesh screens, passes through the particle of the sieve
Sieve screening through 170 mesh again, takes the particle above the sieve as the cross-link dextran particle of hemostasis.
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| CN113209359A (en) * | 2021-04-26 | 2021-08-06 | 青岛大学 | Alkylated chitosan hemostatic microcapsule and preparation method thereof |
| CN114748413A (en) * | 2022-03-14 | 2022-07-15 | 云南贝泰妮生物科技集团股份有限公司 | Hydrogel composition for inhibiting scar formation and preparation method and application thereof |
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