CN106693040A - Preparation method of drug-loadable polyvinyl alcohol eluted microspheres - Google Patents
Preparation method of drug-loadable polyvinyl alcohol eluted microspheres Download PDFInfo
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- CN106693040A CN106693040A CN201611137420.XA CN201611137420A CN106693040A CN 106693040 A CN106693040 A CN 106693040A CN 201611137420 A CN201611137420 A CN 201611137420A CN 106693040 A CN106693040 A CN 106693040A
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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
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
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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
- A61L24/0015—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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/12—Ionomer cements, e.g. glass-ionomer cements
-
- 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
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
Abstract
The invention discloses a preparation method of drug-loadable polyvinyl alcohol eluted microspheres, and relates to the field of biological medicinal materials. Preparation comprises the following steps: (1) preparing a certain concentration of a polyvinyl alcohol aqueous solution, and then adding 2-acrylamide-2-methylpropanesulfonic acid and N,N-methylene bisacrylamide, and stirring evenly by magnetic force; and (2) with persulfate and sulfite as an oxidation-reduction initiation system and glutaraldehyde as a curing agent, preparing the modified polyvinyl alcohol microspheres with the particle size of 100-700 [mu]m by an inverse micro-suspension crosslinking method, namely the drug-loadable polyvinyl alcohol eluted microspheres. Because the microspheres contain a large number of sulfonic acid groups, the microspheres can be effectively loaded with positively charged drugs such as doxorubicin hydrochloride as vascular embolization agents.
Description
Technical field
The present invention relates to it is a kind of can the permanent pharmaceutical carrier of embolism preparation method, be related to biomedicine field, especially relate to
And a kind of medicine-carried polyvinyl alcohol elutes the preparation method of microballoon.
Background technology
Primary carcinoma of liver is a kind of common malignant tumour, and its morbidity and mortality is higher, the morbidity of global liver cancer
Rate is in the trend for rising year by year.China is global onset of liver cancer rate highest and dies of illness several most countries, the incidence of disease of liver cancer into
For the death rate is only second to stomach cancer, the third-largest malignant tumour of lung cancer.The disease seriously threatens healthy, the common treatment of people
Anti-tumor regimen is to use surgical excision, but for the tumor patient of middle and advanced stage, interventional therapy (ranscatheter
Arterial chemoembolization, TACE) it is more satisfactory therapeutic scheme.PCI is referred to through transcatheter arterial
Chemoembolization, i.e., be input into target tissue through conduit by medicine-containing microsphere, blocks the feeding artery and slow Slow release of tumour, so that
The local concentration of chemotherapeutics is improved, the toxic and side effect of whole body is reduced.A series of clinical analysis display TACE can be controlled effectively
Tumour growth processed, extends patient survival.For the mid and late liver cancer patient for being unable to surgery excision, TACE is first-selected No operation
Treatment method.
Polyvinyl alcohol (PVA) is a kind of high molecular weight water soluble polymer, carries functional group single (only hydroxyl) and again may be used
With a large amount of artificial synthesized, it is widely used in multiple fields in production and living, is a kind of very safe larger molecular organicses.It
It is nontoxic to human body, have no side effect, and with good biocompatibility, had a wide range of applications in medical field, such as PVA water
Gel application is in wound dressing, joint prosthesis and ophthalmology；PVA film is applied at aspects such as artificial kidney film, medicinal films；For cancer
Treatment, by PVA prepare vascular occlusive agent have been supplied on clinical medicine.At present, embolism microball is prepared as raw material using PVA
There are reports, but PVA is still defective for preparing drug bearing microsphere:One is that traditional PVA microballoons can only play mechanical bolt
The effect of plug, it is impossible to carrying medicament；Although two be in recent years someone PVA microballoons are carried out surface be modified, it is intended to grafting upload medicine
Group, but grafting rate is low so that and the carrying drug ratio of microballoon is low, and medicine is easily prominent to be released.Hydrogen bond is more in other pure PVA molecules, segment it
Interphase interaction is strong, the microballoon of the formation swelling difference due to high crystalline, and elasticity is not enough, used as the material softness of vascular occlusive agent
Property is inadequate.
The content of the invention
For drawbacks described above, 2- acrylamide-2-methyl propane sulfonics (AMPS) are added to polyvinyl alcohol first herein molten
In liquid, under initiator effect, polyvinyl alcohol is modified, makes the upper substantial amounts of sulfonic acid group of its grafting, meanwhile, with N, N- is sub-
Bisacrylamide (MBA) makees crosslinking agent, under the conditions of anti-phase micro suspension, prepares the polyethylene containing sulfonic acid group micro-
Ball.Because the sulfonic group in 2- acrylamide-2-methyl propane sulfonic molecules is dense ionization group, hydrophily is extremely strong, by the group
It is incorporated on polyvinyl alcohol molecule, load factor of the polyvinyl alcohol sugar microballoon to drug adriamycin can be greatly improved；On the other hand
After polyvinyl alcohol is modified, the destruction of segmented structure regularity reduces crystallinity, can improve the swelling of polyvinyl alcohol microparticles
Property and compliance, are more beneficial for microballoon targeting embolism in the blood vessel.And the polyvinyl alcohol microparticles containing sulfonic acid group have nothing
The advantages of cytotoxicity, good biocompatibility, extensive raw material sources.
The present invention is provided and prepares a kind of medicine-carried polyvinyl alcohol wash-out microballoon as the technical scheme of pharmaceutical carrier, is wrapped successively
Include following steps：
1) polyvinyl alcohol liquid is prepared, polyvinyl alcohol, 2- acrylamide-2-methyl propane sulfonics is dissolved by a certain percentage
In distilled water, after being completely dissolved, N is added, N- methylene-bisacrylamide solution, magnetic agitation under normal temperature is well mixed；So
The potassium peroxydisulfate of metering is added afterwards, stirs several minutes.
2) preparation of modified polyvinylalcohol microballoon, above-mentioned polyvinyl alcohol liquid is added dropwise in oil phase, after completing emulsification,
The sodium hydrogensulfite of metering is added, using anti-phase micro suspension cross-linking method, the stirring reaction after 8 hours under the conditions of 40 DEG C, plus
Enter a small amount of hydrochloric acid and glutaraldehyde, react 2 hours, solidify balling-up, finally cleaned with a large amount of ethanol for several times, distilled water immersion wash number
Secondary, vacuum drying obtains the modified polyvinylalcohol microballoon that particle diameter contains sulfonic acid group in 100~700um, you can carry medicine polyethylene
Alcohol elutes microballoon.
Specifically, the step 1) in, polyvinyl alcohol specification is 1788 types, and the mass fraction of polyvinyl alcohol liquid is
The consumption of 5%~15%, 2- acrylamide-2-methyl propane sulfonic accounts for 1~2 times of polyvinyl alcohol quality, N, N- di-2-ethylhexylphosphine oxide third
Acrylamide accounts for the 1%~10% of polyvinyl alcohol quality, and its method is that, first by N, N- methylene-bisacrylamides are dissolved in its quality 6
Solution is formed in DMA again, then this solution is added in poly-vinyl alcohol solution.
Specifically, the step 1) in, initiator is the oxidation-reduction trigger system of potassium peroxydisulfate and sodium hydrogensulfite,
The consumption of potassium peroxydisulfate accounts for the 1% of polyvinyl alcohol quality, and the consumption of sodium hydrogensulfite is 1/5th of potassium peroxydisulfate quality.
Specifically, the step 2) in, oil phase is normal heptane, normal octane, paraffin oil or soybean oil, the body of oil phase and water phase
Product is than being 4:1~8:1.
Specifically, the step 2) in, emulsifying agent is Span 80 and polysorbate60 by weight 4:1 compound, its total use
Amount accounts for the 1%~5% of oil phase quality.
Specifically, the step 2) in, above-mentioned polyvinyl alcohol liquid is gradually dropped in oil phase, lead to nitrogen protection,
After completing emulsification, add the aqueous solution of sodium bisulfite of metering, be then warming up to 40 DEG C, and control mixing speed for 300~
500rad/min, after reaction 8h, adds glutaraldehyde, under the hydrochloric acid catalysis of concentration 36%, solidifies balling-up, and hydrochloric acid consumption accounts for poly- second
The 10% of enol quality, glutaraldehyde consumption accounts for the 5%~20% of polyvinyl alcohol quality.
The present invention also provides a kind of application process of medicine-carried polyvinyl alcohol wash-out microballoon in pharmaceutical carrier is prepared, and it is special
It is that method according to claim 1 first prepares medicine-carried polyvinyl alcohol wash-out microballoon to levy, and selects the microballoon of any of which one
Kind 0.5g, by vacuum drying, is immersed in the ADMh aqueous solution of saturated concentration, 3 is stirred at a temperature of 8 DEG C small
When, drug bearing microsphere is filtered out, with deionized water rinsing microsphere surface left drug, sealing preserve after vacuum drying microballoon can be
Medicine is discharged in the phosphoric acid buffer liquid medium of pH 7.4.
The wash-out microballoon of medicine-carried not only blocks the nutrition supplying to tumor tissues in targeting is oriented to the artery of tumor tissues
Give, antineoplastic can also be discharged, with the rising of cancer therapy drug concentration in tumor tissues, suppression is played to diseased region
Effect.
By such scheme, the present invention at least has advantages below：
1. a kind of new preparation method is used, and first the sulfonic acid group in polyvinyl alcohol molecule grafting, re-forms microballoon so that
Contain substantial amounts of sulfonic acid group in microballoon, so as to improve the carrying drug ratio of microballoon；
2. the internal structure of microballoon is improved, the swellability and flexibility of microballoon is improve, microballoon is more beneficial in blood vessel
In targeting embolism；
3., because the microballoon contains sulfonic acid group, by charge adsorption drug molecule, microsphere surface physics is eliminated significantly
The prominent purpose released, serve slow releasing pharmaceutical adsorbed and cause；
4. the wash-out microballoon prepared is nontoxic, cell compatibility preferably, meet the safety standards that human body is used；In human body
It is interior can permanent embolism；
5. the wash-out microballoon for being synthesized by homogeneous nucleation method, method is simple, mild condition, and no coupling product is produced
Raw, reaction is complete, products pure.
Described above is only the general introduction of technical solution of the present invention, in order to better understand technological means of the invention,
And can be practiced according to the content of specification, the following is presently preferred embodiments of the present invention and coordinate accompanying drawing describe in detail as after.
Brief description of the drawings
Fig. 1 is the synthetic route that medicine-carried polyvinyl alcohol elutes microballoon.
Fig. 2 is the infrared spectrum of rear polyvinyl alcohol before modified, wherein a：Unmodified polyethylene alcohol；b：Modified polyvinyl alcohol
Microballoon.
Fig. 3 is the super depth-of-field microscope photo of medicine-carried polyvinyl alcohol wash-out microballoon in the present invention.
Fig. 4 is accumulative release rate of the medicine-carried polyvinyl alcohol wash-out microballoon in the phosphate buffer of pH 7.4 in the present invention
Curve.
Specific embodiment
With reference to the accompanying drawings and examples, specific embodiment of the invention is described in further detail.Hereinafter implement
Example is not limited to the scope of the present invention for illustrating the present invention.
1) medicine-carried polyvinyl alcohol elutes the preparation of microballoon：
Embodiment 1.
1.1g polyvinyl alcohol and 2.2g, 2- acrylamide-2-methyl propane sulfonic are added in 8.9g distilled water, normal temperature
Under, magnetic agitation is subsequently adding 0.314g to being completely dissolved, and 14%MBA solution after being well mixed, adds metering 0.275g,
4% potassium persulfate solution, stirs several minutes.50ml normal heptanes are measured, is put into 250ml there-necked flasks, add 0.68g (to account for
2%) emulsifying agent of oil phase quality, wherein Span 80 are 0.544g, and polysorbate60 is that (Span 80 is 0.134g with polysorbate60 mass ratio
4:1), mechanical agitation under normal temperature, rotating speed is 350rad/min, leads to nitrogen protection.After completing emulsification, dropwise added with micro syringe
Enter 0.22g, 1% solution of sodium bisulfite then heats to 40 DEG C, after reaction 8h, add 0.3ml hydrochloric acid and 0.5g, 25% penta
Dialdehyde solution, after 2h, is demulsified with a large amount of ethanol, cleans microballoon, and microballoon for several times, is finally put into 35 DEG C of vacuum drying by cyclic washing
Dried 24 hours in case, obtain modified polyvinylalcohol microballoon of the particle diameter in 100~700um.
Embodiment 2.
1.1g polyvinyl alcohol and 2.2g, 2- acrylamide-2-methyl propane sulfonic are added in 8.06g distilled water, normal temperature
Under, magnetic agitation is to being completely dissolved.Other building-up processes and embodiment 1 are identical.
Embodiment 3.
1.1g polyvinyl alcohol and 2.2g, 2- acrylamide-2-methyl propane sulfonic are added in 9.90g distilled water, normal temperature
Under, magnetic agitation is to being completely dissolved.Other building-up processes and embodiment 1 are identical.
Embodiment 4
1.1g polyvinyl alcohol and 2.2g, 2- acrylamide-2-methyl propane sulfonic are added in 11.12g distilled water, normal temperature
Under, magnetic agitation is to being completely dissolved.Other building-up processes and embodiment 1 are identical.
The polyvinyl alcohol concentration of the various concentrations of table 1 is to preparing the influence of microballoon
Embodiment 5
1.1g polyvinyl alcohol and 2.2g, 2- acrylamide-2-methyl propane sulfonic are added in 8.9g distilled water, normal temperature
Under, magnetic agitation is subsequently adding 0.314g to being completely dissolved, and 14%MBA solution after being well mixed, adds metering 0.275g,
4% potassium persulfate solution, stirs several minutes.50ml paraffin oils are measured, is put into 250ml there-necked flasks, add 0.80g Spans
80 (accounting for oil phase quality 2%), mechanical agitation under normal temperature, rotating speed is 400rad/min, leads to nitrogen protection.After completing emulsification, with micro-
Amount syringe is added dropwise over 0.22g, and 1% solution of sodium bisulfite then heats to 40 DEG C, after reaction 8h, adds 0.3ml hydrochloric acid
And 0.5g, 25% glutaraldehyde solution, after 2h, microballoon being cleaned with a large amount of n-hexanes, isopropanol, cyclic washing for several times, finally will be micro-
Ball is dried 24 hours in being put into 35 DEG C of vacuum drying chambers, obtains modified polyvinylalcohol microballoon of the particle diameter in 100~700um.
Embodiment 6
The modified polyvinylalcohol microballoon 25mg of above-described embodiment 1 is weighed, 10ml is put into, in the Doxorubicin solution of 2mg/ml.Room
Under temperature, slow concussion, by using ultraviolet specrophotometer, in different time sections, Detection wavelength Doxorubicin solution at 483nm
Concentration, calculate microballoon carrying drug ratio, according to the following formula calculate microballoon carrying drug ratio (LR)：
LR (%)=WD/WS×100
W in formulaD--- the quality of medicine, mg in microballoon
WS--- the quality of input microballoon, mg
By calculating, modified polyvinyl alcohol microparticles carrying drug ratio reaches 23.5%.
Embodiment 7
Surface-functionalized medicine-carried elutes the synthetic route chart of microballoon.Such as Fig. 1.
Embodiment 8
A small amount of unmodified polyethylene alcohol and modified polyvinyl alcohol microparticles are taken respectively, use total reflection Fourier's infrared light
Spectrometer, in 4000~500cm-1Wave-number range in carry out INFRARED ABSORPTION scanning, obtain infrared spectrum.Fig. 2 is to gather afterwards before modified
The infrared spectrum of vinyl alcohol, wherein a：Unmodified polyethylene alcohol；b：Modified polyvinyl alcohol microparticles.
Embodiment 9
Particle diameter is chosen in the modified polyvinyl alcohol microparticles of 400~500um, microballoon is observed under super depth-of-field microscope respectively
Pattern.Fig. 3 is the super depth-of-field microscope photo of medicine-carried polyvinyl alcohol wash-out microballoon in the present invention.
Embodiment 10
Particle diameter is chosen in the modified drug bearing microsphere and unmodified drug bearing microsphere of 400~500um, 25mg is respectively weighed, is put into
In PBS (pH 7.4) cushioning liquid, then it is placed in thermostatic control oscillator vibration, temperature control is in 37 ± 0.5 DEG C, fixed point amount
5mL supernatants are taken, and supplements the fresh medium of same volume in time, contained by medicine in UV spectrophotometer measuring buffer solution
Amount, repeats 3 times and averages, and calculates accumulative release rate of the different time sections in PBS (pH 7.4) medium, and draw phase
Answer curve.
Fig. 4 is accumulative release rate curve of the drug bearing microsphere in PBS (pH 7.4) medium in the present invention.
The above is only the preferred embodiment of the present invention, is not intended to limit the invention, it is noted that for this skill
For the those of ordinary skill in art field, on the premise of the technology of the present invention principle is not departed from, can also make it is some improvement and
Modification, these are improved and modification also should be regarded as protection scope of the present invention.
Claims (7)
1. a kind of medicine-carried polyvinyl alcohol elutes the preparation method of microballoon, it is characterized in that preparation is carried out in two steps：
1) polyvinyl alcohol liquid is prepared, polyvinyl alcohol, 2- acrylamide-2-methyl propane sulfonics is dissolved in steaming by a certain percentage
In distilled water, after being completely dissolved, N is added, N- methylene-bisacrylamide solution, magnetic agitation under normal temperature is well mixed；Then again
The potassium peroxydisulfate of metering is added, several minutes are stirred.
2) preparation of modified polyvinylalcohol microballoon, above-mentioned polyvinyl alcohol liquid is added dropwise in oil phase, after completing emulsification, is added
The sodium hydrogensulfite of metering, using anti-phase micro suspension cross-linking method, stirring reaction is added few after 8 hours under the conditions of 40 DEG C
Amount hydrochloric acid and glutaraldehyde, react 2 hours, solidify balling-up, finally cleaned with a large amount of ethanol for several times, distilled water immersion wash for several times,
Vacuum drying, obtains the modified polyvinylalcohol microballoon that particle diameter contains sulfonic acid group in 100~700um, you can carry medicine polyvinyl alcohol
Wash-out microballoon.
2. a kind of medicine-carried polyvinyl alcohol according to claim 1 elutes the preparation method of microballoon, it is characterised in that：It is described
Step 1) in, polyvinyl alcohol specification is 1788 types, the mass fraction of polyvinyl alcohol liquid for 5%~15%, 2- acrylamides-
The consumption of 2- methyl propane sulfonic acids accounts for 1~2 times of polyvinyl alcohol quality, and N, N- methylene-bisacrylamide account for polyvinyl alcohol quality
1%~10%, its method is that, first by N, N- methylene-bisacrylamides are dissolved in the DMA of 6 times of its quality
Solution is formed, then this solution is added in poly-vinyl alcohol solution.
3. a kind of medicine-carried polyvinyl alcohol according to claim 1 elutes the preparation method of microballoon, it is characterised in that：It is described
Step 2) in, initiator is the oxidation-reduction trigger system of potassium peroxydisulfate and sodium hydrogensulfite, and the consumption of potassium peroxydisulfate accounts for poly- second
The 1% of enol quality, the consumption of sodium hydrogensulfite is 1/5th of potassium peroxydisulfate quality.
4. a kind of medicine-carried polyvinyl alcohol according to claim 1 elutes the preparation method of microballoon, it is characterised in that：It is described
Step 2) oil phase is normal heptane, normal octane, paraffin oil or soybean oil, the volume ratio of oil phase and water phase is 4:1~8:1.
5. a kind of medicine-carried polyvinyl alcohol according to claim 1 elutes the preparation method of microballoon, it is characterised in that：It is described
Step 2) in, emulsifying agent is Span 80 and polysorbate60 by weight 4:1 compound, its total consumption account for oil phase quality 1%~
5%.
6. a kind of medicine-carried polyvinyl alcohol according to claim 1 elutes the preparation method of microballoon, it is characterised in that：It is described
Step 2) in, above-mentioned polyvinyl alcohol liquid is gradually dropped in oil phase, lead to nitrogen protection, after completing emulsification, add metering
Aqueous solution of sodium bisulfite, be then warming up to 40 DEG C, and control mixing speed for 300~500rad/min, after reaction 8h, plus
Enter glutaraldehyde, under the hydrochloric acid catalysis of concentration 36%, solidify balling-up, hydrochloric acid consumption accounts for the 10% of polyvinyl alcohol quality, glutaraldehyde
Consumption accounts for the 5%~20% of polyvinyl alcohol quality.
7. application of a kind of medicine-carried polyvinyl alcohol wash-out microballoon in pharmaceutical carrier is prepared, it is characterized in that first will according to right
Ask the method described in 1 to prepare medicine-carried polyvinyl alcohol wash-out microballoon, select the microballoon kind 0.5g of any of which one, it is dry by vacuum
It is dry, it is immersed in the ADMh aqueous solution of saturated concentration, stirred 3 hours at a temperature of 8 DEG C, drug bearing microsphere is filtered out, use
Deionized water rinsing microsphere surface left drug, sealing preserve after vacuum drying microballoon.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108744020A (en) * | 2018-06-12 | 2018-11-06 | 杭州艾力康医药科技有限公司 | A kind of preparation method of ion-exchange type polyvinyl alcohol microparticles |
| CN110327300A (en) * | 2019-07-23 | 2019-10-15 | 赵修文 | A kind of polyvinyl alcohol microparticles of carrying medicament |
| CN113648283A (en) * | 2021-07-23 | 2021-11-16 | 丽水市中心医院 | Preparation method of drug-loaded microsphere for targeted inhibition of HIF-2 alpha, drug-loaded microsphere and application |
| CN113797383A (en) * | 2021-09-28 | 2021-12-17 | 迪格瑞医疗科技(苏州)有限公司 | High-elasticity high-drug-loading-rate embolism microsphere and preparation method thereof |
| CN114099765A (en) * | 2021-11-30 | 2022-03-01 | 上海汇禾医疗科技有限公司 | Photo-initiated cross-linked polyvinyl alcohol drug-loaded embolism microsphere and preparation method thereof |
| CN114272430A (en) * | 2022-01-24 | 2022-04-05 | 科睿驰（深圳）医疗科技发展有限公司 | Thermo-sensitive embolism microsphere and preparation method thereof |
| CN115590824A (en) * | 2022-11-11 | 2023-01-13 | 浙江大学（Cn） | Polyvinyl alcohol embolism microsphere with developer and preparation method and application thereof |
| CN115770224A (en) * | 2023-01-17 | 2023-03-10 | 中国人民解放军总医院第一医学中心 | Acrylic acid microsphere carrying paclitaxel medicine and preparation method thereof |
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| CN113648283A (en) * | 2021-07-23 | 2021-11-16 | 丽水市中心医院 | Preparation method of drug-loaded microsphere for targeted inhibition of HIF-2 alpha, drug-loaded microsphere and application |
| CN113648283B (en) * | 2021-07-23 | 2023-11-07 | 丽水市中心医院 | Preparation method of drug-loaded microsphere for targeted inhibition of HIF-2 alpha, drug-loaded microsphere and application |
| CN113797383A (en) * | 2021-09-28 | 2021-12-17 | 迪格瑞医疗科技(苏州)有限公司 | High-elasticity high-drug-loading-rate embolism microsphere and preparation method thereof |
| CN114099765A (en) * | 2021-11-30 | 2022-03-01 | 上海汇禾医疗科技有限公司 | Photo-initiated cross-linked polyvinyl alcohol drug-loaded embolism microsphere and preparation method thereof |
| CN114272430A (en) * | 2022-01-24 | 2022-04-05 | 科睿驰（深圳）医疗科技发展有限公司 | Thermo-sensitive embolism microsphere and preparation method thereof |
| CN115590824A (en) * | 2022-11-11 | 2023-01-13 | 浙江大学（Cn） | Polyvinyl alcohol embolism microsphere with developer and preparation method and application thereof |
| CN115770224A (en) * | 2023-01-17 | 2023-03-10 | 中国人民解放军总医院第一医学中心 | Acrylic acid microsphere carrying paclitaxel medicine and preparation method thereof |
| CN115770224B (en) * | 2023-01-17 | 2023-04-18 | 中国人民解放军总医院第一医学中心 | Acrylic acid microsphere carrying paclitaxel medicine and preparation method thereof |
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