CN1208373C - Method for preparing hydrophilic core/hydrophilic or hydrophobic shell functional macromolecule microballoon and corresponding microballoon product and application - Google Patents
Method for preparing hydrophilic core/hydrophilic or hydrophobic shell functional macromolecule microballoon and corresponding microballoon product and application Download PDFInfo
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- CN1208373C CN1208373C CN 03158217 CN03158217A CN1208373C CN 1208373 C CN1208373 C CN 1208373C CN 03158217 CN03158217 CN 03158217 CN 03158217 A CN03158217 A CN 03158217A CN 1208373 C CN1208373 C CN 1208373C
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Abstract
The present invention relates to a preparation method of a functionalized macromolecular microsphere with a hydrophilic core/a hydrophilic or hydrophobic shell, corresponding microsphere products and the application thereof, which relates to the technical filed of the preparation of functionalized macromolecular materials, medicine coating materials and release control materials. The present invention solves the technical problem of using functionalized macromolecular materials to coat medicine and control the release of medicine. Firstly, a macromolecular crosslinking microsphere with a hydrophilic core/a hydrophobic shell is synthesized by the grafting and crosslinking reaction of a macromonomer of PBMA (poly butyl methacrylate), Am (acrylamide) and a crosslinking agent; then, the macromolecular crosslinking microsphere with a hydrophilic core/a hydrophobic shell is dried at constant temperature and is hydrolyzed in acidic solution so as to obtain a macromolecular crosslinking microsphere with a hydrophilic core/a hydrophilic shell. The macromolecular crosslinking microsphere with a hydrophilic core/a hydrophobic shell can be used as an impact resistant and toughening modifying agent. The macromolecular crosslinking microsphere with a hydrophilic core/a hydrophilic shell has pH value sensibility and achieves the effect of medicine coating and release control. The preparation method is an initiative technological line for synthesizing functionalized macromolecular microspheres.
Description
Technical field
Preparation method and the corresponding microspheres product and the application of a kind of hydrophilic nuclear/parent or hydrophobic shell functionalized macromolecular microballoon, the present invention is the functional polymer microballoon that preparation has the pH irritability, can be used for medicine coating, sustained release, reach macromolecular material in the medical field application aims.The present invention relates to prepare functionalized macromolecular material, medicine coating, control release technic field.
Background technology
Along with the high development of modern medicine, macromolecular material is widely used in medical field, and it is one of the most popular purposes as the carrier of medicine sustained release.Traditional administering mode, medicine all are to enter human body by oral or injection, and in the short period of time after advancing medicine, the concentration of medicament is considerably beyond the required concentration of treatment in the blood, and too high concentration may make that the people poisons, allergy etc.Simultaneously they rate of metabolism is fast in vivo, the transformation period is short, easily drain, so along with the putting off of time, the very fast reduction of the concentration of medicament and affecting the treatment.On the other hand, appointed part also lacks selectivity to medicine in the body to entering, and this also is to make into that dose increases, one of reason that curative effect is lower.Under this background, controlled drug delivery system is subject to people's attention day by day in research and application medically.Controlled drug delivery system, be utilize natural or the synthetic macromolecular compound as pharmaceutical carrier or medium, make certain formulation, place the environment of release then, biologically active substance in the carrier is discharged in the environment by diffusion or other approach, thereby reaches the purpose of treatment disease.High molecular controlled drug delivery system is compared with some traditional administering mode, has long-acting, efficient, low toxicity, slowly-releasing, an advantage such as selectivity is good, side effect is little.Thereby the character of pharmaceutical carrier macromolecular material also just becomes the focus of research.In general, the macromolecular material that is used for the medicine sustained release can be divided into biodegradation type and non-biodegradation type.The macromolecular material that typical non-biodegradation type system adopts is silicon rubber, ethene and acetate ethylene copolymer, polyurethane elastomer etc.Concerning controlled drug delivery system, the biodegradation type polymer is better than non-biodegradation type polymer.The former is behind its performance medical functions, and the energy degradation in vivo becomes small molecules to be absorbed or excretes.At present, aliphatic polyester series is widely used biodegradation type macromolecular material.
Summary of the invention
(1) technical problem that will solve: the invention provides preparation method and the corresponding microspheres product and the application of a kind of hydrophilic nuclear/parent or hydrophobic shell functionalized macromolecular microballoon.
(2) technical scheme: technical scheme of the present invention is a preparation functionalized macromolecular microballoon.
The preparation method of a kind of hydrophilic nuclear/parent or hydrophobic shell functionalized macromolecular microballoon, the at first synthetic hydrophilic nuclear of polymethyl tert-butyl acrylate (PBMA) graft crosslinking acrylamide (Am)/hydrophobic shell microballoon dispersion liquid, after separating drying, hydrolysis in acidic solution again, after the acidolysis, the hydrophobic side group of microsphere surface changes the hydrophilic carboxyl into, obtains hydrophilic nuclear/hydrophilic shell polymer crosslinked microsphere, and the former is used for rubber-plastics material shock resistance, plasticized modifier by hydrophilic nuclear/hydrophobic shell crosslinked microsphere; The hydrophilic nuclear of the latter/hydrophilic shell polymer crosslinked microsphere has the pH irritability, promptly along with acidity increase microspherulite diameter reduces, thereby reaches the purpose of sustained release.
The preparation of hydrophilic nuclear/hydrophobic shell crosslinked microsphere: with monomer A m, the PBMA macromonomer, linking agent N, N-methylene-bisacrylamide (Bis-A) is put in the sample bottle by 100: 5～20: 1～10mol proportioning, the mixed solvent dissolving that adds the ethanol/water of 10～20: 1 volume ratio, the initiator 2 that adds 1～8mol again, 2 '-azo, two (N, N '-dimethylene isopropylimdazole) (VA), after treating to dissolve fully reaction solution is moved in the reaction tubes, with nitrogen replacement 10 minutes, except that tube sealing behind the deoxidation, in 60～80 ℃ isothermal vibration water-bath, reacted 10～24 hours, obtain PBMA graft crosslinking PAm microballoon dispersion liquid, the degree of crosslinking of thus obtained microsphere is 1～10, carrying out centrifugation with the speed more than the 15000r/min on the whizzer, heavily disperse with dehydrated alcohol then, again centrifugation, repetitive operation 3 times is to remove unreacted monomer.
The preparation of hydrophilic nuclear/hydrophilic shell crosslinked microsphere: with the hydrophilic nuclear of gained/hydrophobic shell crosslinked microsphere drying at room temperature 3 days in vacuum drying oven, join in 5～20 equivalent concentration hydrochloric acid solns of 10 times of amounts, under 50～70 ℃ of temperature, reacted 3～10 hours, then reaction solution was dialysed in deionized water 3 days with the Mierocrystalline cellulose dialysis membrane, get hydrophilic nuclear/hydrophilic shell crosslinked microsphere.
When improving the pH value, in the grafted chain-COOH is neutralized gradually, formation-COO-, the grafted chain that the repulsive interaction between negative charge causes unfold the swelling capacity that has improved particle greatly, particle diameter increases fast; When the pH value hour, grafted chain is rolled up the swelling that has hindered particle, particle diameter is less.The particle degree of crosslinking also is to influence its swollen important factor, can see that its particle diameter was less relatively when degree of crosslinking was big.When pH drops to 3 from 10, the particle diameter of microballoon can be reduced to about 500nm from 1000nm, and volume reduces about 8 times.Can control the variation of size by control degree of crosslinking, pH value.
(3) beneficial effect
The polymer microsphere of hydrophilic nuclear/hydrophilic shell has certain pH response characteristic, it is centrifugation and dispersed with stirring repeatedly, and the hydrophilic chain tensible of its surface grafting is in water, both having played the protection polymeric microspheres stabilize disperses to prevent to condense, can fully occupy the space in the water again, have very high specific surface area; The pH value can be controlled the variation of size, thereby such microballoon can be done sorbent material, the sustained release of medicine.
Hydrophilic nuclear/hydrophobic shell polymer microsphere can be used for shock resistance in the rubber-plastics material, plasticized modifier.
Present method is a kind of efficient, simple, feasible operational path, and preparation method of this hydrophilic nuclear/parent or hydrophobic shell functional high-polymer microballoon and products thereof belongs to initiative work with using.
Embodiment
Example example 1
A, synthesizing of hydrophilic nuclear/hydrophobic shell polymer crosslinked microsphere: Am, the PBMA macromonomer, crosslinking agent B is-A puts into sample bottle, the mixed solvent dissolving of the ethanol/water of adding 10～20: 1, add initiator VA again, after treating to dissolve fully reaction solution is moved in the reaction tubes, with nitrogen replacement 10 minutes, remove tube sealing behind the deoxidation, reaction is 24 hours in 60 ℃ isothermal vibration water-bath, obtain PBMA graft crosslinking PAm microballoon dispersion liquid, carrying out centrifugation with the speed more than the 15000r/m on the whizzer, heavily disperse with dehydrated alcohol then, again centrifugation, so operation is 3 times, to remove unreacted monomer.Room temperature vacuum-drying is weighed.
B, the crosslinked PBMA-PAm microballoon that will prepare drying at room temperature 3 days in vacuum drying oven, the microballoon that takes by weighing joins in 10 times of amount 10 normal hydrochloric acid solns, 60 ℃ of reactions 4 hours down, then reaction solution is dialysed in deionized water 3 days with dialysis membrane.Get hydrophilic nuclear/hydrophilic shell polymer crosslinked microsphere.
Claims (2)
1. the preparation method of a functionalized macromolecular microballoon is characterized in that the at first synthetic hydrophilic nuclear of polymethyl tert-butyl acrylate graft crosslinking polyacrylamide/hydrophobic shell crosslinked microsphere dispersion liquid; Separation, drying; Hydrolysis in acidic solution again obtains hydrophilic nuclear/hydrophilic shell polymer crosslinked microsphere;
(1) hydrophilic nuclear/hydrophobic shell crosslinked microsphere is synthetic: with acrylamide, polymethyl tert-butyl acrylate large molecular monomer, linking agent N, the N-methylene-bisacrylamide, be put in the sample bottle by 100: 5～20: 1～10mol proportioning, the mixed solvent dissolving that adds the ethanol/water of 10～20: 1 volume ratio, the initiator 2 that adds 1～8mol again, 2 '-azo, two (N, N '-dimethylene isopropylimdazole), after treating to dissolve fully reaction solution is moved in the reaction tubes, with nitrogen replacement 10 minutes, remove tube sealing behind the deoxidation, in 60～80 ℃ isothermal vibration water-bath, reacted 10～24 hours, obtain polymethyl tert-butyl acrylate graft crosslinking polyacrylamide microsphere dispersion liquid, the degree of crosslinking of thus obtained microsphere is 1～10;
(2) separation, drying: gained polymethyl tert-butyl acrylate graft crosslinking polyacrylamide microsphere dispersion liquid is being carried out on the whizzer with the speed centrifugation more than the 15000r/min, heavily disperse with dehydrated alcohol then, centrifugation again, repetitive operation 3 times, to remove unreacted monomer, room temperature vacuum-drying;
(3) hydrolysis in acidic solution, obtain hydrophilic nuclear/hydrophilic shell polymer crosslinked microsphere: the hydrophilic nuclear that will prepare/hydrophobic shell crosslinked microsphere joins in 10 times of amount 5～20 centinormal 1 hydrochloric acid solns, under 50～70 ℃ of temperature, reacted 3～10 hours, then reaction solution was dialysed in deionized water 3 days with the Mierocrystalline cellulose dialysis membrane, get hydrophilic nuclear/hydrophilic shell crosslinked microsphere.
2, a kind of microspheres product for preparing according to the described method of claim 1 is characterized in that structure is the hydrophilic nuclear/hydrophilic shell polymer crosslinked microsphere of polymethyl tert-butyl acrylate graft crosslinking polyacrylamide, and the microsphere surface structure is the hydrophilic carboxyl.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 03158217 CN1208373C (en) | 2003-09-11 | 2003-09-11 | Method for preparing hydrophilic core/hydrophilic or hydrophobic shell functional macromolecule microballoon and corresponding microballoon product and application |
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| CN 03158217 CN1208373C (en) | 2003-09-11 | 2003-09-11 | Method for preparing hydrophilic core/hydrophilic or hydrophobic shell functional macromolecule microballoon and corresponding microballoon product and application |
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| CN1208373C true CN1208373C (en) | 2005-06-29 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101270190B (en) * | 2008-04-16 | 2010-12-08 | 武汉工程大学 | Method for increasing polyalcohol microspherulite diameter |
| CN102603962B (en) * | 2012-03-05 | 2014-02-05 | 厦门大学 | Preparation method of surface functionalized porous irregularly-shaped microspheres |
| CN102532406B (en) * | 2012-03-05 | 2014-02-05 | 厦门大学 | Morphological control method for functionalized microsphere |
| CN108435107B (en) * | 2018-03-14 | 2020-10-23 | 嘉兴杰赛生物科技有限公司 | Preparation and application of DNA affinity nano-microspheres |
| CN108997820B (en) * | 2018-07-25 | 2022-01-07 | 华南师范大学 | Dye microsphere, preparation method thereof, printing ink and electrowetting display device |
| CN112618169B (en) * | 2020-12-30 | 2021-11-12 | 广东茵茵股份有限公司 | Preparation method of antibacterial baby diaper |
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