CN102964612B - Polyvinyl alcohol-borax microsphere and preparation method thereof - Google Patents
Polyvinyl alcohol-borax microsphere and preparation method thereof Download PDFInfo
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- CN102964612B CN102964612B CN201210313249.9A CN201210313249A CN102964612B CN 102964612 B CN102964612 B CN 102964612B CN 201210313249 A CN201210313249 A CN 201210313249A CN 102964612 B CN102964612 B CN 102964612B
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Abstract
The invention relates to a polyvinyl alcohol-borax microsphere and a preparation method thereof. In particular, the technical method adopts borax as the crosslinking agent to prepare a polyvinyl alcohol microsphere by means of water-in-oil reversed phase suspension polymerization. The method consists of: taking liquid paraffin-sorbitan monooleate system as the dispersion phase, adopting a polyvinyl alcohol water solution as the polymerization phase, and using borax as the crosslinking agent, subjecting them and polyvinyl alcohol to an esterification crosslinking reaction in an acidic condition, employing sodium phosphate as the pH adjusting agent and the curing agent, and leaving a microsphere to cure, thus obtaining the polyvinyl alcohol-borax microsphere. In the invention, borax is adopted as the crosslinking agent, which is non-toxic and non-simulating to human bodies, thus avoiding using dialdehyde, diacyl chloride and other crosslinking agents having toxicity to human bodies and stimulation to the skin, as well as potential safety hazards. The prepared polyvinyl alcohol microsphere has good thermal stability, no bacterium, no toxicity, no pyrogen, and good biocompatibility.
Description
Technical field
The present invention relates to a kind of polyvinyl alcohol-borax microballoon and preparation method thereof, specifically prepare the processing method of polyvinyl alcohol microparticles taking borax as linking agent, by water in oil inverse suspension polymerization method, utilize the esterification and crosslinking of borax and polyvinyl alcohol, make polyvinyl alcohol in water, solidify to form microballoon.It is simple that the present invention has reaction conditions, and linking agent utilization ratio is high, the better heat stability of microballoon, aseptic nontoxic pyrogen-free, the advantages such as biocompatibility.
Background technology
Polyvinyl alcohol (PVA) is a kind of water-soluble high-molecular material, experimentation on animals shows, it is completely harmless, nontoxicity, nonirritant, and have good biocompatibility, slow degradation in vivo, be widely used in preparing stanch fibre, artificial skin, can also be used for contraceptive film, plasma substitute, medicament for the eyes film etc., also can be used as slow releasing carrier of medication material and prepare targeted microspheres.
Polyvinyl alcohol microparticles carries out soft tissue filling for soft tissue filler, can reach and stimulate body to produce collagen, is wrapped up the object of the filling effect of its generation of long sustaining by fibrillar connective tissue.
Zhao great Qing, Tan Jinquans etc. are once at " preparation of polyvinyl alcohol microparticles " (" Chinese Journal of New Drugs ", the 14th the 2nd phase of volume in 2005,181-184 page) in employing glutaraldehyde is disclosed as linking agent, utilize aldolization to prepare the processing method of polyvinyl alcohol microparticles, but glutaraldehyde is a kind of sterilant of broad-spectrum high efficacy, human body is had to strong impulse effect, therefore, the polyvinyl alcohol microparticles of preparing as linking agent using glutaraldehyde, when as soft tissue filler, can have certain risk.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of polyvinyl alcohol-borax microballoon.Adopt the medical sodium tetraborate decahydrate (borax) of the nontoxic non-stimulated safety of human body as linking agent, utilize the hydroxyl generation esterification in itself and polyvinyl alcohol and reach crosslinked effect, take the method for inverse suspension polymerization to make crosslinked polyvinyl alcohol solidify balling-up, there is reaction conditions simple, linking agent utilization ratio is high, the better heat stability of microballoon, aseptic nontoxic pyrogen-free, the advantages such as biocompatibility have been prepared polyvinyl alcohol-borax microballoon simple and effective.
A kind of polyvinyl alcohol-borax microballoon provided by the invention is taking polyvinyl alcohol and borax as raw material, be that 1:0.04 ~ 0.4 is prepared from according to the mass ratio of polyvinyl alcohol and borax, concrete preparation process is first polyvinyl alcohol water solution to be dissolved in the whiteruss of sorbitan mono-oleic acid ester (Span-80) to be dispersed into liquid pearl, use again salt acid for adjusting pH value to acidity, add borax, heating makes borax and polyvinyl alcohol generation esterification, solidify with sodium phosphate again, obtain polyvinyl alcohol-borax microballoon.
Method prepared by a kind of polyvinyl alcohol-borax microballoon provided by the invention comprises the steps:
1) aqueous solution of polyvinyl alcohol is equaled to 0.1 ~ 2(using this solution as water with sour adjust pH), then join in the whiteruss solution (oil phase) that contains Span-80, fully stir and make water form liquid pearl;
2) at 40-60 DEG C, add borax, carrying out crosslinking reaction is 4 ~ 6h;
3) add sodium radio-phosphate,P-32 solution, be warming up to 90 DEG C simultaneously microballoon is solidified, the time is 1 ~ 2h, and filtration can obtain polyvinyl alcohol-borax microballoon;
4) water washing of 70-80 DEG C 4-5 time for thus obtained microsphere, with the unreacted boric acid of wash-out; Microballoon is placed in to the apparatus,Soxhlet's 8 ~ 12h that refluxes, ethanol is extracting solution, when identical with dehydrated alcohol refractive index, is wash-out terminal, removes Span-80 and whiteruss impurity in microballoon again.
The polymerization degree 200 to the 2000(preferred degree of polymerization of described polyvinyl alcohol are 800 to 1000), alcoholysis degree is greater than 97%.
The mass percent of the aqueous solution of described polyvinyl alcohol is 1% to 20%(preferably 5% to 10%).
Described sodium tetraborate decahydrate (borax) is selected medical grade, and the mass ratio of borax and polyvinyl alcohol is preferred: 0.16 ~ 0.24:1.
In the whiteruss solution of described Span-80, the mass percent of Span-80 is 1% ~ 5%.In the whiteruss solution of Span-80, the volume ratio of water and oil phase is preferred 1:2 ~ 3 of 1:1 ~ 5().
Described acid is that mass concentration is the hydrochloric acid of 0.1 ~ 10mol/L; The massfraction of described sodium phosphate aqueous solution is 1 ~ 20% the aqueous solution (preferably 10 ~ 15%).
The present invention adopts the method for inverse suspension polymerization to prepare polyvinyl alcohol microparticles, taking whiteruss-sorbitan mono-oleic acid ester system as disperse phase, polyvinyl alcohol water solution is polymerization phase, using borax as linking agent, under acidic conditions, react (seeing that Fig. 1 and Fig. 2 polyvinyl alcohol-borax chain are cross-linked schematic diagram structure) with polyvinyl alcohol generation esterification and crosslinking, taking sodium phosphate as acid-base modifier and solidifying agent, allow microballoon solidify, thereby prepare polyvinyl alcohol-borax microballoon.The present invention adopts borax as linking agent, this linking agent is nontoxic to human body, non-stimulated,, the linking agent with potential safety hazard that skin had to hormesis poisonous to human body of twain-aldehyde compound, diacid chloride class etc. are avoided adopting, prepare better heat stability, aseptic nontoxic pyrogen-free, and there is the polyvinyl alcohol microparticles of good biocompatibility.Detect through jigger coupling-plasma emission spectrum (ICP), the boron content remaining in microballoon is all no more than 10mg/g.It is simple that the present invention has reaction conditions, and linking agent utilization ratio is high, the better heat stability of microballoon, aseptic nontoxic pyrogen-free, the advantages such as biocompatibility.
Brief description of the drawings
Fig. 1 is crosslinking structure schematic diagram in polyvinyl alcohol-borax chain.
Fig. 2 is the crosslinked schematic diagram of polyvinyl alcohol-borax chain.
Fig. 3 is the electron scanning micrograph of polyvinyl alcohol-borax microballoon.
Embodiment
Following examples are used for illustrating the present invention, but do not limit the present invention.
Embodiment 1:
The reagent that the present invention uses is medical grade or pharmaceutical grade.
5g polyvinyl alcohol (PVA) is dissolved in to the PVA aqueous solution 100ml that makes massfraction 5% in boiling water, equals 1 with 2mol/L hydrochloric acid adjust pH, using this solution as water.2g sorbitol anhydride oleate (Span-80) is dissolved in 200ml whiteruss, using this solution as oil phase.Above-mentioned two kinds of solution are joined in 500ml there-necked flask, and adjusting rotary speed to 600 rev/min, so that water liquid pearl reaches appropriate particle size.1.0g sodium tetraborate decahydrate (borax) is dissolved in the hydrochloric acid that 10ml concentration is 1mol/L and is added dropwise in reaction system.Be warming up to 60 DEG C of reaction 4h, with the now particle diameter of PVA spherical gel particles in system of microscopic examination, then to add massfraction be 15% medicinal sodium radio-phosphate,P-32 solution 10ml, is warming up to 90 DEG C to solidify PVA spherical gel particles, curing reaction 1h.Question response liquid cooling is but filtered with G6 sintered glass funnel afterwards, isolates microballoon.The microballoon obtaining after reaction, with 80 DEG C of hot distilled water washings 5 times, each 300ml, with the unreacted boric acid of wash-out; Again microballoon is placed in to the apparatus,Soxhlet's 10h that refluxes, dehydrated alcohol is extracting solution, determine impurity (Span-80 in microballoon by the refractive index of measuring extracting solution, pharmaceutical grade whiteruss) residual quantity, when the refractive index of extracting solution reaches 1.10(25 DEG C), when identical with dehydrated alcohol refractive index, show the impurity (Span-80 in microballoon, pharmaceutical grade whiteruss) by complete wash-out, be both wash-out terminal.Fig. 3 is shown in by polyvinyl alcohol-borax microballoon of gained.
Embodiment 2:
10g polyvinyl alcohol (PVA) is dissolved in to the PVA aqueous solution 100ml that makes massfraction 10% in boiling water, equals 1 with 2mol/L hydrochloric acid adjust pH, using this solution as water.8g sorbitol anhydride oleate (Span-80) is dissolved in 200ml whiteruss, using this solution as oil phase.Above-mentioned two kinds of solution are joined in 500ml there-necked flask, and adjusting rotary speed to 700 rev/min, so that water liquid pearl reaches appropriate particle size.4.0g sodium tetraborate decahydrate (borax) is dissolved in the hydrochloric acid that 30ml concentration is 1mol/L and is added dropwise in reaction system.Be warming up to 60 DEG C of reaction 4h, with the now particle diameter of PVA spherical gel particles in system of microscopic examination, then to add massfraction be 20% medicinal sodium radio-phosphate,P-32 solution 10ml, is warming up to 90 DEG C to solidify PVA spherical gel particles, curing reaction 1h.Question response liquid cooling is but filtered with G6 sintered glass funnel afterwards, isolates microballoon.Carry out follow-up cleaning microballoon operation with reference to embodiment 1.
Embodiment 3:
8g polyvinyl alcohol (PVA) is dissolved in to the PVA aqueous solution 100ml that makes massfraction 8% in boiling water, equals 1 with 2mol/L hydrochloric acid adjust pH, using this solution as water.5g sorbitol anhydride oleate (Span-80) is dissolved in 200ml whiteruss, using this solution as oil phase.Above-mentioned two kinds of solution are joined in 500ml there-necked flask, and adjusting rotary speed to 650 rev/min, so that water liquid pearl reaches appropriate particle size.1.0g sodium tetraborate decahydrate (borax) is dissolved in the hydrochloric acid that 10ml concentration is 1mol/L and is added dropwise in reaction system.Be warming up to 60 DEG C of reaction 4h, with the now particle diameter of PVA spherical gel particles in system of microscopic examination, then to add massfraction be 20% medicinal sodium radio-phosphate,P-32 solution 10ml, is warming up to 90 DEG C to solidify PVA spherical gel particles, curing reaction 1h.Question response liquid cooling is but filtered with G6 sintered glass funnel afterwards, isolates microballoon.Carry out follow-up cleaning microballoon operation with reference to embodiment 1.
Embodiment 4:
5g polyvinyl alcohol (PVA) is dissolved in to the PVA aqueous solution 100ml that makes massfraction 5% in boiling water, equals 1 with 2mol/L hydrochloric acid adjust pH, using this solution as water.8g sorbitol anhydride oleate (Span-80) is dissolved in 400ml whiteruss, using this solution as oil phase.Above-mentioned two kinds of solution are joined in 1000ml there-necked flask, and adjusting rotary speed to 600 rev/min, so that water liquid pearl reaches appropriate particle size.1.0g sodium tetraborate decahydrate (borax) is dissolved in the hydrochloric acid that 10ml concentration is 1mol/L and is added dropwise in reaction system.Be warming up to 60 DEG C of reaction 4h, with the now particle diameter of PVA spherical gel particles in system of microscopic examination, then to add massfraction be 15% medicinal sodium radio-phosphate,P-32 solution 10ml, is warming up to 90 DEG C to solidify PVA spherical gel particles, curing reaction 1h.Question response liquid cooling is but filtered with G6 sintered glass funnel afterwards, isolates microballoon.
Claims (5)
1. polyvinyl alcohol-borax microballoon, is characterized in that: it is taking polyvinyl alcohol and borax as raw material, is that 1:0.04 ~ 0.4 is prepared from according to the mass ratio of polyvinyl alcohol and borax, and concrete preparation process is:
1) aqueous solution of polyvinyl alcohol is equaled to 0.1 ~ 2 with sour adjust pH, then join in the whiteruss solution that contains Span-80, fully stir and make water form liquid pearl;
2) at 40-60 DEG C, add borax, carrying out crosslinking reaction is 4 ~ 6h;
3) add sodium phosphate aqueous solution, be warming up to 90 DEG C simultaneously microballoon is solidified, the time is 1 ~ 2h, and filtration can obtain polyvinyl alcohol-borax microballoon;
4) water washing of 70-80 DEG C 4-5 time for thus obtained microsphere, with the unreacted boric acid of wash-out; Microballoon is placed in to the apparatus,Soxhlet's 8 ~ 12h that refluxes, ethanol is extracting solution, when identical with dehydrated alcohol refractive index, is wash-out terminal, removes Span-80 and whiteruss impurity in microballoon again.
2. a preparation method for polyvinyl alcohol-borax microballoon claimed in claim 1, is characterized in that: it comprises the steps:
1) aqueous solution of polyvinyl alcohol is equaled to 0.1 ~ 2 with sour adjust pH, then join in the whiteruss solution that contains Span-80, fully stir and make water form liquid pearl;
2) at 40-60 DEG C, add borax, carrying out crosslinking reaction is 4 ~ 6h;
3) add sodium phosphate aqueous solution, be warming up to 90 DEG C simultaneously microballoon is solidified, the time is 1 ~ 2h, and filtration can obtain polyvinyl alcohol-borax microballoon;
4) water washing of 70-80 DEG C 4-5 time for thus obtained microsphere, with the unreacted boric acid of wash-out; Microballoon is placed in to the apparatus,Soxhlet's 8 ~ 12h that refluxes, ethanol is extracting solution, when identical with dehydrated alcohol refractive index, is wash-out terminal, removes Span-80 and whiteruss impurity in microballoon again;
The polymerization degree 200 to 2000 of described polyvinyl alcohol, alcoholysis degree is greater than 97%;
The mass percent of the aqueous solution of described polyvinyl alcohol is 1% to 20%;
In the whiteruss solution of described Span-80, the mass percent of Span-80 is 1% ~ 5%.
3. method according to claim 2, is characterized in that: in the whiteruss solution of described Span-80, the volume ratio of water and oil phase is 1:1 ~ 5.
4. method according to claim 2, is characterized in that: described acid is that mass concentration is the hydrochloric acid of 0.1 ~ 10mol/L.
5. method according to claim 2, is characterized in that: the massfraction of described sodium phosphate aqueous solution is 1 ~ 20%.
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| CN104387600A (en) * | 2014-12-01 | 2015-03-04 | 杨子中 | Preparation method of composite crosslinking sodium hyaluronate gel microspheres for facial injection |
| EP3393641B1 (en) * | 2015-12-22 | 2020-04-29 | DDP Specialty Electronic Materials US 8, LLC | Method of suspension polymerization of droplets distributed in an aqueous medium |
| CN105462915B (en) * | 2016-01-28 | 2018-10-16 | 爱美客技术发展股份有限公司 | Polyvinyl alcohol microcarrier and the preparation method and application thereof |
| CN109270056B (en) * | 2018-10-12 | 2021-05-14 | 中国肉类食品综合研究中心 | Method for detecting high-flux antibiotic residues and microbial chromogenic kit |
| CN113773020B (en) * | 2021-09-22 | 2022-10-11 | 中国核动力研究设计院 | Curing agent, preparation method and combustible technical waste treatment method |
| CN113855848B (en) * | 2021-10-18 | 2022-11-01 | 四川大学 | Monodisperse boric acid cross-linked polyvinyl alcohol embolization microspheres and preparation method thereof |
| CN115501378B (en) * | 2022-09-23 | 2023-08-22 | 江南大学 | A kind of modified polyvinyl alcohol embolic microspheres and preparation method thereof |
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Address after: Beikong science and technology building, No. 10 Beijing 102200 Changping District science and Technology Park floating Stephen White Road 4 416B room Patentee after: Limited by Share Ltd technology development Address before: Beikong science and technology building, No. 10 Beijing 102200 Changping District science and Technology Park floating Stephen White Road 4 416B room Patentee before: Beijing Aimeike Biotechnology Co., Ltd. |