CN109985273A - A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing and is preparing the application in anti-coagulants sustained release dressing - Google Patents
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing and is preparing the application in anti-coagulants sustained release dressing 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
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Abstract
The invention discloses the preparation methods that a kind of polymer microsphere carries the sustained release dressing of medicine anti-coagulants, specifically include the preparation of medicine-carrying polymer gel micro-ball, the four big steps that couple and foam are blended with PVA Carrier dressing solution for the preparation of PVA Carrier dressing solution, medicine-carrying polymer gel micro-ball.Meanwhile the present invention discloses and the preparation method that above-mentioned polymer microsphere carries the sustained release dressing of medicine anti-coagulants is applied in the anti-coagulants sustained release dressing for preparing polymer microsphere load medicine.The anti-coagulants sustained release dressing that the polymer microsphere that preparation method disclosed by the invention is prepared carries medicine solves negative pressure drainage trauma care material in the prior art.Since Coagulation test occurs in aperture for blood, clot residual will cause material aperture and blocked drainage tube, so that the technical issues of negative pressure drainage trauma care material application life substantially reduces.The anti-coagulants sustained release dressing that the polymer microsphere that preparation method is prepared carries medicine is disclosed through the invention.
Description
Technical field
Medicine anti-coagulants is carried the present invention relates to the preparation of anti-coagulants sustained release dressing more particularly to a kind of polymer microsphere to delay
It releases the preparation method of dressing and is preparing the application in anti-coagulants sustained release dressing.
Background technique
Clinically, during negative pressure drainage, it is often necessary to using shield traumatic material such as foam dressing, be using foam dressing
The surface of a wound or wound chamber provide enclosed environment.
However, negative pressure drainage trauma care material disclosed in the prior art, mostly using by polyurethane or polyvinyl alcohol material
Composition, wherein through there is Pan Shi drainage tube to be drained.Since Coagulation test occurs in aperture for blood, clot residual be will cause
Material aperture and blocked drainage tube, so that negative pressure drainage trauma care material application life substantially reduces.
In the prior art, in order to solve the problems, such as above-mentioned blood coagulation, choked technique, often through in drainage tube pipeline coating drug
Covering, injection anti-coagulants cleaning solution, above-mentioned processing mode not can guarantee anticoagulant comprehensive, the solution solution material of drainage system
The long-term effect of inner hole and drainage tube.
Summary of the invention
Technical problem to be solved by the present invention lies in provide a kind of polymer microsphere to carry the sustained release dressing of medicine anti-coagulants
Preparation method and preparing anti-coagulants sustained release dressing in application.
The present invention is to solve above-mentioned technical problem by the following technical programs:
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing, comprising the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
The acetum of PVA acidic aqueous solution and chitosan is added in reactor, stirring, is added in whipping process anticoagulant
Agent after dissolution is sufficiently stirred, obtains water phase A；
Oily phase B is prepared in Triton reagent and atoleine after mixing；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, after stirring, by penta
Dialdehyde solution is added in reaction system, is warming up to reflux, after back flow reaction 2h, after isopropanol is added, stands, is centrifugated, from
Heart separation terminates, and removes upper liquid, with ether solvent washing mashing centrifugation object, is filtered, obtains filter cake, filter cake is to carry medicine height
Molecular gel microballoon；
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed, added water and stirred, after mixing evenly, it is molten that addition defoaming agent obtains starch
Liquid, it is spare；
PVA is mixed with water, under the conditions of 95 DEG C, PVA dissolution, dissolution are finished in heat preservation 2h, insulating process, are cooled to 72
DEG C, starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, and is down to temperature of reaction system
At 54 DEG C, PVA Carrier dressing solution is obtained, PVA Carrier dressing solution is placed under constant temperature, is kept the temperature standby
With；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
The medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load being prepared in step (1)
In medicine high-molecular gel microballoon, formalin is added, is cooled to 51 DEG C to reaction system, sulfuric acid is added, after stirring, is added
Into negative pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) is placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62
DEG C, end of reaction removes mold, obtains dressing, applies after washing dressing to get the anti-coagulants sustained release for carrying medicine to polymer microsphere
Material.
Preferably, the anti-coagulants be heparin sodium, sodium citrate, in EDTAP dipotassium ethylene diamine tetraacetate any one or two
The mixture of kind substance.
Preferably, the Triton reagent is any one in TritonX-100, TritonX-114, TritonX-45
Reagent.
Preferably, in the step (1) PVA acidic aqueous solution the preparation method is as follows:
1.67g PVA and 100ml water is mixed, is warming up to 90 DEG C, keeps the temperature 2h, PVA after completely dissolution, then by 3.5mL matter
The concentrated hydrochloric acid for measuring score 33%, is added in above-mentioned PVA solution, is configured to the PVA acidic aqueous solution that mass concentration is 1.67%；
The mass fraction of chitosan is 3% in the acetum of the chitosan；
The acetum additive amount of the chitosan is 10mL, and the additional amount of the isopropanol is 10mL, and isopropanol is added
Afterwards, time of repose 10min；
The mass fraction of the glutaraldehyde solution is 50%, and the glutaraldehyde solution is added in a manner of being added dropwise, described penta
The dripping quantity of dialdehyde solution is 0.55mL.
Preferably, the oily phase B's the preparation method is as follows:
By the atoleine of the Triton reagent of 4.5mL and 60mL after mixing to get oily phase B.
Preferably, the ether solvent is petroleum ether.
Preferably, in the step (2), cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62
It closes, mixture gross mass is 3.62g；
After the cornstarch and potato starch mixing, water 10mL is added to be stirred, after mixing evenly, 1.0g is added and disappears
Infusion obtains starch solution, spare；
The mode that the PVA is mixed with water are as follows: mixed with the PVA of 10g with 60mL water.
Preferably, the additive amount of formalin is 7mL in the step (3), and the additive amount of sulfuric acid is 4.5mL, is added
After sulfuric acid, after stirring 15min, it is added into negative pressure drainage auxiliary material mold.
The preparation method for carrying the sustained release dressing of medicine anti-coagulants present invention simultaneously discloses above-mentioned polymer microsphere is preparing anti-coagulants
The application being sustained in dressing.
The present invention has the advantage that compared with prior art
The present invention discloses a kind of preparation method of polymer microsphere load medicine anti-coagulants sustained release dressing, disclosed by the invention
Technical solution solves negative pressure drainage trauma care material in the prior art.Since Coagulation test occurs in aperture for blood, clot is residual
It stays and will cause material aperture and blocked drainage tube, so that the technical issues of negative pressure drainage trauma care material application life substantially reduces.
The anti-coagulants sustained release dressing that the polymer microsphere that preparation method is prepared carries medicine is disclosed through the invention.
Detailed description of the invention
Fig. 1 is the medicine-carrying polymer gel micro-ball particle diameter distribution schematic diagram that the embodiment of the present invention 1 is prepared；It is micro- in Fig. 1
Ball number is 285, and average grain diameter evaluation is 1.75 microns, deviation 2.18；
Fig. 2 is the anti-coagulants sustained release dressing drug release rate that the polymer microsphere that the embodiment of the present invention 1 is prepared carries medicine
Datagram.
Specific embodiment
It elaborates below to the embodiment of the present invention, the present embodiment carries out under the premise of the technical scheme of the present invention
Implement, the detailed implementation method and specific operation process are given, but protection scope of the present invention is not limited to following implementation
Example.
Embodiment 1
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing, comprising the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
By PVA acidic aqueous solution 10mL (PVA acidic aqueous solution configuration method are as follows: mix 1.67g PVA and 100ml water
It closes, is warming up to 90 DEG C, keep the temperature 2h, PVA after completely dissolution, then by the concentrated hydrochloric acid of 3.5mL mass fraction 33%, is added to above-mentioned
In PVA solution, be configured to the PVA acidic aqueous solution that mass concentration is 1.67%) and 10mL mass fraction be 3% chitosan
Acetum is added in reactor, stirring, and the heparin sodium (adding manner of heparin sodium are as follows: with active unit is added in whipping process
The injection 2mL of 25000U/mL is added), after dissolution is sufficiently stirred, obtain water phase A；
By the atoleine of the TritonX-100 of 4.5mL and 60mL after mixing to get oily phase B；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, will after stirring
0.55mL, mass fraction are that 50% glutaraldehyde solution is added drop-wise in reaction system, are warming up to reflux (reflux temperature is 65 DEG C), return
After stream reaction 2h, after 10mL isopropanol is added, 10min, centrifuge separation are stood, centrifuge separation terminates, and upper liquid is removed, with ethers
Solvent washing mashing centrifugation object, is filtered, obtains filter cake, filter cake is medicine-carrying polymer gel micro-ball.
Under above-mentioned condition (acidity), chitosan is reacted with the glutaraldehyde solution of addition according to such as following formula I mode:
Be prepared the dimer of chitosan according to reactive mode disclosed in above-mentioned Formulas I, the dimer of above-mentioned chitosan it
Between form network molecular structure.
PVA is reacted with the glutaraldehyde solution of addition according to II mode of following formula:
By reactive mode disclosed in formula II, the glutaraldehyde for foring PVA and addition forms acetal product, acetal product with
Formulas I reactive mode be prepared chitosan dimer the reaction was continued formed network molecular structure.
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62, mixture gross mass is
3.62g adds 10mL water to stir, and after mixing evenly, 1g defoaming agent is added and obtains starch solution, spare；
The PVA of 10g is mixed with 60mL water, under the conditions of 95 DEG C, PVA dissolution, has dissolved in heat preservation 2h, insulating process
Finish, be cooled to 72 DEG C, starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, wait react
When system temperature is down to 54 DEG C, PVA Carrier dressing solution is obtained, PVA Carrier dressing solution is placed in constant temperature item
Under part, keep the temperature spare；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
The medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load being prepared in step (1)
In medicine high-molecular gel microballoon, 7mL formalin is added, is cooled to 51 DEG C to reaction system, addition sulfuric acid 4.5mL be (sulfuric acid
Mass fraction is 98%), after stirring 15min, to be added into negative pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) is placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62
DEG C, end of reaction removes mold, obtains dressing, and after washing dressing, the anti-coagulants for obtaining 10.75g polymer microsphere load medicine is slow
Dressing is released, the diameter that polymer microsphere carries the anti-coagulants sustained release dressing of medicine is 8cm, with a thickness of 1.0cm.
Embodiment 2
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing, comprising the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
By PVA acidic aqueous solution 10mL (PVA acidic aqueous solution configuration method is same as Example 1) and 10mL mass point
Number is added in reactor for the acetum of 3% chitosan, stirring, and sodium citrate (control citric acid is added in whipping process
The final concentration of 4.8mol/L of sodium), after dissolution is sufficiently stirred, obtain water phase A；
By the atoleine of the TritonX-114 of 4.5mL and 60mL after mixing to get oily phase B；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, will after stirring
0.55mL, mass fraction are that 50% glutaraldehyde solution is added drop-wise in reaction system, are warming up to reflux (reflux temperature is 65 DEG C), return
After stream reaction 2h, after 10mL isopropanol is added, 10min, centrifuge separation are stood, centrifuge separation terminates, and upper liquid is removed, with ethers
Solvent washing mashing centrifugation object, is filtered, obtains filter cake, filter cake is medicine-carrying polymer gel micro-ball.
Under above-mentioned condition (acidity), the glutaraldehyde solution of chitosan and addition carries out according to the same manner as in Example 1
Reaction:
PVA is reacted according to the same manner as in Example 1 with the glutaraldehyde solution of addition:
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62, mixture gross mass is
3.62g adds 10mL water to stir, and after mixing evenly, 1g defoaming agent is added and obtains starch solution, spare；
The PVA of 10g is mixed with 60mL water, under the conditions of 95 DEG C, PVA dissolution, has dissolved in heat preservation 2h, insulating process
Finish, be cooled to 72 DEG C, starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, wait react
When system temperature is down to 54 DEG C, PVA Carrier dressing solution is obtained, PVA Carrier dressing solution is placed in constant temperature item
Under part, keep the temperature spare；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
The medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load being prepared in step (1)
In medicine high-molecular gel microballoon, 7mL formalin is added, is cooled to 51 DEG C to reaction system, concentrated sulfuric acid 4.5mL (sulfuric acid is added
Mass fraction be 98%), after stir 15min, addition into negative pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) is placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62
DEG C, end of reaction removes mold, obtains dressing, and after washing dressing, the anti-coagulants for obtaining 10.75g polymer microsphere load medicine is slow
Dressing is released, the diameter that polymer microsphere carries the anti-coagulants sustained release dressing of medicine is 8cm, with a thickness of 1.0cm.
Embodiment 3
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing, comprising the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
By PVA acidic aqueous solution 10mL (PVA acidic aqueous solution configuration method is same as Example 1) and 10mL mass point
Number is added in reactor for the acetum of 3% chitosan, stirring, and EDTAP dipotassium ethylene diamine tetraacetate (control is added in whipping process
The final concentration of 2.5mol/L of EDTAP dipotassium ethylene diamine tetraacetate processed), after dissolution is sufficiently stirred, obtain water phase A；
By the atoleine of the TritonX-45 of 4.5mL and 60mL after mixing to get oily phase B；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, will after stirring
0.55mL, mass fraction are that 50% glutaraldehyde solution is added drop-wise in reaction system, are warming up to reflux (reflux temperature is 65 DEG C), return
After stream reaction 2h, after 10mL isopropanol is added, 10min, centrifuge separation are stood, centrifuge separation terminates, and upper liquid is removed, with ethers
Solvent washing mashing centrifugation object, is filtered, obtains filter cake, filter cake is medicine-carrying polymer gel micro-ball.
Under above-mentioned condition (acidity), the glutaraldehyde solution of chitosan and addition carries out according to the same manner as in Example 1
Reaction:
PVA is reacted according to the same manner as in Example 1 with the glutaraldehyde solution of addition:
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62, mixture gross mass is
3.62g adds 10mL water to stir, and after mixing evenly, 1g defoaming agent is added and obtains starch solution, spare；
The PVA of 10g is mixed with 60mL water, under the conditions of 95 DEG C, PVA dissolution, has dissolved in heat preservation 2h, insulating process
Finish, be cooled to 72 DEG C, starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, wait react
When system temperature is down to 54 DEG C, PVA Carrier dressing solution is obtained, PVA Carrier dressing solution is placed in constant temperature item
Under part, keep the temperature spare；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
The medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load being prepared in step (1)
In medicine high-molecular gel microballoon, 7mL formalin is added, is cooled to 51 DEG C to reaction system, concentrated sulfuric acid 4.5mL (sulfuric acid is added
Mass fraction be 98%), after stir 15min, addition into negative pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) is placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62
DEG C, end of reaction removes mold, obtains dressing, and after washing dressing, the anti-coagulants for obtaining 10.75g polymer microsphere load medicine is slow
Dressing is released, the diameter that polymer microsphere carries the anti-coagulants sustained release dressing of medicine is 8cm, with a thickness of 1.0cm.
Embodiment 4
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing, comprising the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
By PVA acidic aqueous solution 10mL (PVA acidic aqueous solution configuration method is same as Example 1) and 10mL mass point
Number is added in reactor for the acetum of 3% chitosan, stirring, and EDTAP dipotassium ethylene diamine tetraacetate and Chinese holly is added in whipping process
The mixture (molar ratio of EDTAP dipotassium ethylene diamine tetraacetate and sodium citrate is 1:2 in mixture) of rafter acid sodium, is sufficiently stirred dissolution
Afterwards, water phase A is obtained；
By the atoleine of the TritonX-45 of 4.5mL and 60mL after mixing to get oily phase B；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, will after stirring
0.55mL, mass fraction are that 50% glutaraldehyde solution is added drop-wise in reaction system, are warming up to reflux (reflux temperature is 65 DEG C), return
After stream reaction 2h, after 10mL isopropanol is added, 10min, centrifuge separation are stood, centrifuge separation terminates, and upper liquid is removed, with ethers
Solvent washing mashing centrifugation object, is filtered, obtains filter cake, filter cake is medicine-carrying polymer gel micro-ball.
Under above-mentioned condition (acidity), the glutaraldehyde solution of chitosan and addition carries out according to the same manner as in Example 1
Reaction:
PVA is reacted according to the same manner as in Example 1 with the glutaraldehyde solution of addition:
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62, mixture gross mass is
3.62g adds 10mL water to stir, and after mixing evenly, 1g defoaming agent is added and obtains starch solution, spare；
The PVA of 10g is mixed with 60mL water, under the conditions of 95 DEG C, PVA dissolution, has dissolved in heat preservation 2h, insulating process
Finish, be cooled to 72 DEG C, starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, wait react
When system temperature is down to 54 DEG C, PVA Carrier dressing solution is obtained, PVA Carrier dressing solution is placed in constant temperature item
Under part, keep the temperature spare；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
The medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load being prepared in step (1)
In medicine high-molecular gel microballoon, 7mL formalin is added, is cooled to 51 DEG C to reaction system, concentrated sulfuric acid 4.5mL (sulfuric acid is added
Mass fraction be 98%), after stir 15min, addition into negative pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) is placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62
DEG C, end of reaction removes mold, obtains dressing, and after washing dressing, the anti-coagulants for obtaining 10.75g polymer microsphere load medicine is slow
Dressing is released, the diameter that polymer microsphere carries the anti-coagulants sustained release dressing of medicine is 8cm, with a thickness of 1.0cm.
Embodiment 5
A kind of polymer microsphere carries the preparation method of medicine anti-coagulants sustained release dressing, comprising the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
By PVA acidic aqueous solution 10mL (PVA acidic aqueous solution configuration method is same as Example 1) and 10mL mass point
Number is added in reactor for the acetum of 3% chitosan, stirring, and the mixed of heparin sodium and sodium citrate is added in whipping process
Object (molal weight of EDTAP dipotassium ethylene diamine tetraacetate and sodium citrate ratio is 1:2:1 in mixture) is closed, after dissolution is sufficiently stirred, is obtained
To water phase A；
By the atoleine of the TritonX-45 of 4.5mL and 60mL after mixing to get oily phase B；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, will after stirring
0.55mL, mass fraction are that 50% glutaraldehyde solution is added drop-wise in reaction system, are warming up to reflux (reflux temperature is 65 DEG C), return
After stream reaction 2h, after 10mL isopropanol is added, 10min, centrifuge separation are stood, centrifuge separation terminates, and upper liquid is removed, with ethers
Solvent washing mashing centrifugation object, is filtered, obtains filter cake, filter cake is medicine-carrying polymer gel micro-ball.
Under above-mentioned condition (acidity), the glutaraldehyde solution of chitosan and addition carries out according to the same manner as in Example 1
Reaction:
PVA is reacted according to the same manner as in Example 1 with the glutaraldehyde solution of addition:
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62, mixture gross mass is
3.62g adds 10mL water to stir, and after mixing evenly, 1g defoaming agent is added and obtains starch solution, spare；
The PVA of 10g is mixed with 60mL water, under the conditions of 95 DEG C, PVA dissolution, has dissolved in heat preservation 2h, insulating process
Finish, be cooled to 72 DEG C, starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, wait react
When system temperature is down to 54 DEG C, PVA Carrier dressing solution is obtained, PVA Carrier dressing solution is placed in constant temperature item
Under part, keep the temperature spare；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
The medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load being prepared in step (1)
In medicine high-molecular gel microballoon, 7mL formalin is added, is cooled to 51 DEG C to reaction system, concentrated sulfuric acid 4.5mL (sulfuric acid is added
Mass fraction be 98%), after stir 15min, addition into negative pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) is placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62
DEG C, end of reaction removes mold, obtains dressing, and after washing dressing, the anti-coagulants for obtaining 10.75g polymer microsphere load medicine is slow
Dressing is released, the diameter that polymer microsphere carries the anti-coagulants sustained release dressing of medicine is 8cm, with a thickness of 1.0cm.
Embodiment 6
Performance detection:
Medicine-carrying polymer gel micro-ball is prepared to the embodiment of the present invention 1 and carries out particle diameter distribution detection；
The anti-coagulants sustained release dressing for carrying medicine to the polymer microsphere that the embodiment of the present invention 1 is prepared carries out medicament slow release inspection
It surveys:
Gel micro-ball carries out particle diameter distribution result such as Fig. 1, medicament slow release test result such as Fig. 2；
Particle diameter distribution detection method is as follows:
Using hot type petrographic microscope, observation when heat is not added in natural optical path carries scale to microsphere diameter using microscope
It measures, microspherulite diameter calculates 285, sample.
As shown in Figure 1: the microballoon good dispersion degree of this method preparation, 1.7 microns of average grain diameter.Drug bearing microsphere size distribution is equal
It is even, be conducive to the uniform release of drug.
Wherein, microspherulite diameter is calculated according to following formula:
In above-mentioned formula: diIt indicates: single microspherulite diameter；N is indicated: microballoon number；D is indicated: microsphere average grain diameter；DP table
Show: dispersion degree (dispersibility that dispersion degree is used to measure microballoon).
Medicament slow release detection method is as follows:
The anti-coagulants sustained release dressing that the polymer microsphere that above-described embodiment 1 is prepared carries medicine is disclosed according to the prior art
Mode load to negative pressure drainage device (dressing is according on drainage tube), adjust negative pressure drainage device on valve, preceding 2h
According to sterile water 1000mL/h hasten carry out drainage procedure, and collect drainage-fluid, rear 6h according to sterile water 1000mL/h speed
Degree carries out drainage procedure, and collection liquid measures drug concentration (high performance liquid chromatography), and calculates drainage medicament elution speed.
As shown in Figure 2: the anti-coagulants sustained release dressing that the polymer microsphere that the present invention is prepared carries medicine is shown preferably
Medicament slow release characteristic.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (9)
1. the preparation method that a kind of polymer microsphere carries the sustained release dressing of medicine anti-coagulants, which comprises the following steps:
(1) preparation of medicine-carrying polymer gel micro-ball:
The acetum of PVA acidic aqueous solution and chitosan is added in reactor, stirring, anti-coagulants is added in whipping process,
After dissolution is sufficiently stirred, water phase A is obtained；
Oily phase B is prepared in Triton reagent and atoleine after mixing；
Water phase A is added dropwise in oily phase B, stir mixing during dropwise addition is added dropwise, and continues to stir, after stirring, by glutaraldehyde
Solution is added in reaction system, is warming up to reflux, after back flow reaction 2h, after isopropanol is added, stands, centrifuge separation, centrifugation divides
From end, upper liquid is removed, mashing centrifugation object is washed with ether solvent, is filtered, obtains filter cake, filter cake is medicine-carrying polymer
Gel micro-ball；
(2) preparation of PVA Carrier dressing solution:
Cornstarch and potato starch are mixed, added water and stirred, after mixing evenly, defoaming agent is added and obtains starch solution, it is standby
With；
PVA is mixed with water, under the conditions of 95 DEG C, PVA dissolution, dissolution are finished in heat preservation 2h, insulating process, 72 DEG C are cooled to,
Starch solution is added, stir mixing, during stir mixing, temperature of reaction system is reduced, and is down to 54 to temperature of reaction system
DEG C when, obtain PVA Carrier dressing solution, PVA Carrier dressing solution be placed under constant temperature, keep the temperature it is spare；
(3) medicine-carrying polymer gel micro-ball is blended with PVA Carrier dressing solution and couples:
It is high that the medicine-carrying polymer gel micro-ball solution being prepared in step (2) is added to the load medicine being prepared in step (1)
In molecular gel microballoon, formalin is added, is cooled to 51 DEG C to reaction system, sulfuric acid is added, after stirring, is added to negative
In pressure drainage auxiliary material mold；
(4) it foams:
Mold in step (3) being placed into baking oven, reaction 10h, in reaction process, controlling the temperature in baking oven is 62 DEG C,
End of reaction removes mold, obtains dressing, is sustained dressing after washing dressing to get the anti-coagulants for carrying medicine to polymer microsphere.
2. the preparation method that polymer microsphere according to claim 1 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
State the mixture that anti-coagulants is heparin sodium, sodium citrate, any one or two kinds of substances in EDTAP dipotassium ethylene diamine tetraacetate.
3. the preparation method that polymer microsphere according to claim 2 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
Stating Triton reagent is any one reagent in TritonX-100, TritonX-114, TritonX-45.
4. the preparation method that polymer microsphere according to claim 3 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
State PVA acidic aqueous solution in step (1) the preparation method is as follows:
1.67g PVA and 100ml water is mixed, is warming up to 90 DEG C, keeps the temperature 2h, PVA after completely dissolution, then by 3.5mL mass divides
The concentrated hydrochloric acid of number 33% is added in above-mentioned PVA solution, is configured to the PVA acidic aqueous solution that mass concentration is 1.67%；
The mass fraction of chitosan is 3% in the acetum of the chitosan；
The acetum additive amount of the chitosan is 10mL, and the additional amount of the isopropanol is 10mL, quiet after isopropanol is added
Setting the time is 10min；
The mass fraction of the glutaraldehyde solution is 50%, and the glutaraldehyde solution is added in a manner of being added dropwise, the glutaraldehyde
The dripping quantity of solution is 0.55mL.
5. the preparation method that polymer microsphere according to claim 4 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
State oily phase B's the preparation method is as follows:
By the atoleine of the Triton reagent of 4.5mL and 60mL after mixing to get oily phase B.
6. the preparation method that polymer microsphere according to claim 4 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
Stating ether solvent is petroleum ether.
7. the preparation method that polymer microsphere according to claim 4 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
It states in step (2), cornstarch and potato starch are mixed according to the ratio that mass ratio is 2:1.62, and mixture gross mass is
3.62g；
After the cornstarch and potato starch mixing, water 10mL is added to be stirred, after mixing evenly, 1.0g defoaming agent is added
Starch solution is obtained, it is spare；
The mode that the PVA is mixed with water are as follows: mixed with the PVA of 10g with 60mL water.
8. the preparation method that polymer microsphere according to claim 4 carries the sustained release dressing of medicine anti-coagulants, which is characterized in that institute
The additive amount for stating formalin in step (3) is 7mL, and the additive amount of sulfuric acid is 4.5mL, after sulfuric acid is added, by stirring
After 15min, it is added into negative pressure drainage auxiliary material mold.
9. the preparation side that a kind of polymer microsphere using as described in claim 1-8 any one carries the sustained release dressing of medicine anti-coagulants
Method is preparing the application in anti-coagulants sustained release dressing.
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