CN101962464A - Method for preparing calcium alginate microspheres with temperature response performance - Google Patents
Method for preparing calcium alginate microspheres with temperature response performance Download PDFInfo
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- CN101962464A CN101962464A CN 201010292330 CN201010292330A CN101962464A CN 101962464 A CN101962464 A CN 101962464A CN 201010292330 CN201010292330 CN 201010292330 CN 201010292330 A CN201010292330 A CN 201010292330A CN 101962464 A CN101962464 A CN 101962464A
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- calcium alginate
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- hexanolactam
- ethene hexanolactam
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- 235000010410 calcium alginate Nutrition 0.000 title claims abstract description 19
- 239000000648 calcium alginate Substances 0.000 title claims abstract description 19
- 229960002681 calcium alginate Drugs 0.000 title claims abstract description 19
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 title claims abstract description 19
- 230000004044 response Effects 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title abstract description 9
- 239000004005 microsphere Substances 0.000 title abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 17
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 14
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- 239000000661 sodium alginate Substances 0.000 claims abstract description 12
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 12
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000004945 emulsification Methods 0.000 claims abstract description 7
- 239000000839 emulsion Substances 0.000 claims abstract description 5
- 239000003999 initiator Substances 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 239000012153 distilled water Substances 0.000 claims abstract description 4
- 238000009775 high-speed stirring Methods 0.000 claims abstract description 3
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 12
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical group CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 12
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 8
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 6
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 3
- 238000006392 deoxygenation reaction Methods 0.000 claims description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
- UZIQYDXSZVYYCF-UHFFFAOYSA-N azepan-2-one;ethene Chemical compound C=C.O=C1CCCCCN1 UZIQYDXSZVYYCF-UHFFFAOYSA-N 0.000 claims description 2
- 229910001424 calcium ion Inorganic materials 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- JWYVGKFDLWWQJX-UHFFFAOYSA-N 1-ethenylazepan-2-one Chemical compound C=CN1CCCCCC1=O JWYVGKFDLWWQJX-UHFFFAOYSA-N 0.000 abstract 1
- 239000004971 Cross linker Substances 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- 238000001723 curing Methods 0.000 abstract 1
- 238000004108 freeze drying Methods 0.000 abstract 1
- 230000001376 precipitating effect Effects 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
- 239000011521 glass Substances 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000004848 nephelometry Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-SYJWYVCOSA-N (2s,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-SYJWYVCOSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229920005601 base polymer Polymers 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000012674 dispersion polymerization Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000011806 microball Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- -1 polyethylene hexanolactam Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a method for preparing calcium alginate microspheres with temperature response performance, which comprises the following steps of: fully dissolving selected amount of N-vinylcaprolactam and the like and sodium alginate in water, preparing into aqueous solution, adding an initiator, uniformly mixing for deoxidation, and performing stirring reaction at constant temperature for 3 to 6 hours; cooling the reaction liquid obtained in the last step to room temperature, slowly adding into an oil phase in which an emulsifier 1 is dissolved for emulsification, adding into aqueous solution with an emulsifier 2 for emulsification, dripping a cross-linker with high-speed stirring, stirring, and curing; and precipitating the emulsion obtained in the last step by using absolute ethyl alcohol, performing centrifugal separation, washing with absolute ethyl alcohol and distilled water respectively, and performing freeze drying to obtain the finished product. The calcium alginate microspheres have certain temperature response performance, and the response temperature is near the physiological temperature; and the calcium alginate microspheres have good biocompatibility and biodegradability, and have wide application prospect in the field of biomedicines, particularly in the aspect of control release of medicines.
Description
Technical field
The invention belongs to the material technology field, relate to a kind of preparation method, specifically relate to a kind of preparation method with calcium alginate compounded microballoon of temperature response performance with microballoon of temperature response performance.
Background technology
Study new and effective drug release material and control delivery, be the human main path that improves drug release pattern, reduction toxic side effect, strengthens absorption and result of treatment of exploring always, attracted very big interest from chemistry, materialogy and pharmaceutical field researchist.
Lalgine is the natural polysaccharide polymkeric substance that extracts from marine alga, be a kind of by (1 → 4) α-L-guluronic acid and (1 → 4) beta-D-mannuronic acid dependence 1, the copolymerized macromolecule that the 4-glycosidic link connects to form, nontoxic, have excellent biological compatibility and a degradability, cheap, have a good application prospect at biomedical sector, especially receive certain concern as drug delivery system (DDS).The researchist successively adopts W/O emulsification-ionic cross-linking, micro-fluidic technologies, dropping method etc. to prepare the calcium alginate microsphere drug delivery system both at home and abroad.In order to strengthen the function of Lalgine pharmaceutical carrier, the researchist is also compound with the natural polymer (as soybean protein isolate, chitosan) of Lalgine and other biologically active.
Lalgine DDS exists significantly not enough: most of Lalgine DDS just have certain slow releasing function to medicine, lack the sustained release ability of response physiological event (especially temperature variation) but at present.
Temperature sensitivity superpolymer with low critical transformation temperature (LCST) is the superpolymer that a class has special thermal characteristics.When envrionment temperature was lower than LCST, its solvability in solution can slowly reduce along with temperature raises.In case but in temperature was elevated near the LCST very among a small circle, its solvability can reduce suddenly, heat sink falling occur, and this variation is a reversible.In this class superpolymer the most representative be poly-(N-N-isopropylacrylamide) (PNIPAm) and polyethylene hexanolactam (PVCL).Because the LCST of these two kinds of polymkeric substance is in the physiological temp scope (30～40 ℃), make their serial superpolymer in biological and medical material, extremely application prospects be arranged.Compare with PNIPAm, PVCL has better biocompatibility and lower toxicity, but less with application about its research.
Summary of the invention
The object of the present invention is to provide a kind of preparation method with calcium alginate compounded microballoon of temperature response performance, the product that adopts this method to obtain not only has excellent biological compatibility, biodegradability, and has good temperature-responsive.
Its technical solution is:
A kind of preparation method with calcium alginate compounded microballoon of temperature response performance comprises the steps:
(1) with N-ethene hexanolactam or contain the mixture of N-ethene hexanolactam, fully soluble in water with sodium alginate, be made into massfraction and be 2% the aqueous solution, wherein N-ethene hexanolactam or the massfraction that contains the mixture of N-ethene hexanolactam are 25～75% (being preferably 40～60%), the massfraction of sodium alginate is 25～75% (being preferably 40～60%), add initiator, and carry out thorough mixing, dissolving, deoxygenation is then at 45～75 ℃ of (being preferably 50～60 ℃) constant temperature stirring reactions 3～6 hours (being preferably 4～5 hours);
(2) step (1) is obtained reaction solution be cooled to room temperature, slowly add and be dissolved with in the oil phase of emulsifying agent 1, the volume ratio of oil phase and reaction solution is 2: 3, emulsification 15 minutes; The aqueous solution that adds emulsifying agent 2 then, emulsification 10 minutes; Adding 25mL dropping linking agent by every 100mL emulsion at last under high-speed stirring is the calcium ions aqueous solution, stirs, solidifies 15 minutes;
(3) emulsion that step (2) is obtained is used dehydrated alcohol, distilled water wash respectively again with dehydrated alcohol precipitation, centrifugation, and lyophilize gets product.
In the above-mentioned steps (1), the mixture of the described N-of containing ethene hexanolactam is mixture or N-ethene hexanolactam and acrylic acid mixture of N-ethene hexanolactam and methacrylic acid, the mixture of N-ethene hexanolactam and methacrylic acid wherein, the quality proportioning of N-ethene hexanolactam and methacrylic acid is 90～99: 10～1, is preferably 94～97: 6～3; N-ethene hexanolactam and acrylic acid mixture, N-ethene hexanolactam and acrylic acid quality proportioning are 90～99: 10～1, are preferably 94～97: 6～3.
In the above-mentioned steps (1), described initiator is a Diisopropyl azodicarboxylate, and consumption is 1%～5% of N-ethene hexanolactam or the mixture mole number that contains N-ethene hexanolactam, is preferably 2%; In the above-mentioned steps (2), described oil phase is a normal hexane, described emulsifying agent 1 is Span-85, consumption is that 0.01～0.06g/mL (is preferably 0.03～0.05g/mL) oil phase, described emulsifying agent 2 is Tween-85, the total mass number of using is identical with the total mass number of emulsifying agent 1 use, during use emulsifying agent 2 is diluted to massfraction and is 50% the aqueous solution, and described linking agent is that massfraction is 8% CaCl
2The aqueous solution.
In the above-mentioned steps (1), described stirring velocity is 200r/min, and described temperature of reaction is 60 ℃, and the described reaction times is 5 hours; In the above-mentioned steps (2), described stirring velocity is 1000～1400r/min, is preferably 1200～1350r/min.
The present invention has following useful technique effect:
(1) one of raw material of utilization preparation microballoon-sodium alginate is as diffuse-aggregate stablizer, obtain temperature sensitive property sodium alginate/polyethylene hexanolactam base polymer mixing solutions, safety simple to operate by original position dispersion polymerization one step of monomers such as N-ethene hexanolactam in sodium alginate aqueous solution.
(2) the calcium alginate compounded microballoon that is obtained has certain temperature-responsive and response temperature on the one hand near physiological temp, have excellent biological compatibility and biodegradability on the other hand, in the bio-medical field, especially controlled delivery of pharmaceutical agents release aspect has wide application prospects.
Description of drawings
The invention will be further described below in conjunction with accompanying drawing and embodiment:
Fig. 1 is that the embodiment of the invention 1 is obtained finished product is that calcium alginate compounded microballoon adheres on the slide glass, after handling through metal spraying, slide glass is placed under the scanning electron microscope (the Japanese JEOL JSM-6390LV of company type) photo of shooting.
Fig. 2 is that the embodiment of the invention 2 is obtained finished products is that calcium alginate compounded microballoon adheres on the slide glass, after handling through metal spraying, slide glass is placed under the scanning electron microscope (the Japanese JEOL JSM-6390LV of company type) photo of shooting.
Embodiment
Embodiment 1
In the 250mL there-necked flask, add 0.4g sodium alginate, 0.8g N-ethene hexanolactam, 58.8g water, 0.02g being Diisopropyl azodicarboxylate, Diisopropyl azodicarboxylate is about 2.14% of N-ethene hexanolactam mole number, stir, carry out thorough mixing, dissolving, deoxygenation is as charging into nitrogen half an hour, heat temperature raising to 60 ℃ reacted 5 hours then, and reaction process can be accompanied by that continuity stirs or intermittent the stirring.Reaction mixture is cooled to room temperature, slowly is added to 40mL and is dissolved with in the normal hexane of 2g Span-85, behind the stirring 15min, drip 2g Tween-85 (with the water dilution of 2mL), continue emulsification 10min.Drip the 25mL massfraction at last and be 8% calcium chloride water, stir and solidify 15min.With dehydrated alcohol precipitation, centrifugation, use dehydrated alcohol, distilled water wash then respectively, lyophilize obtains finished product as shown in Figure 1.
Embodiment 2
Roughly with the method for embodiment 1, the consumption of different is sodium alginate, N-ethene hexanolactam, Diisopropyl azodicarboxylate is respectively 0.6g, 0.6g, 0.015g, and above-mentioned Diisopropyl azodicarboxylate is about 2.12% of N-ethene hexanolactam mole number.The gained finished product as shown in Figure 2.
Embodiment 3
Roughly with the method for embodiment 1, different is to add 0.8g sodium alginate, 0.4gN-ethene hexanolactam, 0.01g Diisopropyl azodicarboxylate, and above-mentioned Diisopropyl azodicarboxylate is about 2.13% of N-ethene hexanolactam mole number.
Embodiment 4
Roughly with the method for embodiment 1, different is to add 0.6g sodium alginate, 0.57g N-ethene hexanolactam, 0.03g methacrylic acid, 0.015g Diisopropyl azodicarboxylate, and above-mentioned Diisopropyl azodicarboxylate is about 2.08% of N-ethene hexanolactam and methacrylic acid mixture mole number.
Embodiment 5
Roughly with the method for embodiment 1, different is to add 0.6g sodium alginate, 0.57g N-ethene hexanolactam, 0.03g vinylformic acid, 0.015g Diisopropyl azodicarboxylate, and above-mentioned Diisopropyl azodicarboxylate is 2.03% of N-ethene hexanolactam and a vinylformic acid mole number.
The calcium alginate compounded microballoon of aforesaid way preparation has temperature-responsive preferably, the volume phase transition temperature is near physiological temp, and the calcium alginate compounded microballoon phase transition temperature that the above-mentioned corresponding embodiment that utilizes 721 type spectrophotometers to record by nephelometry obtains is listed in table 1.
The phase transition temperature of the gel micro-ball that table 1 nephelometry records
| Product | Embodiment 1 | Embodiment 2 | Embodiment 3 |
| Phase transition temperature ℃ | 37.0 | 36.0 | 35.5 |
Claims (5)
1. the preparation method with calcium alginate compounded microballoon of temperature response performance is characterized in that comprising the steps:
(1) with massfraction is 25～75% N-ethene hexanolactam or the mixture that contains N-ethene hexanolactam, with massfraction be that 25～75% sodium alginate is fully soluble in water, be made into massfraction and be 2% the aqueous solution, add initiator, and carry out thorough mixing, dissolving, deoxygenation is then 45～75 ℃ of constant temperature stirring reactions 3～6 hours;
(2) reaction solution that step (1) is obtained is cooled to room temperature, slowly adds the oil phase that is dissolved with emulsifying agent 1, and the volume ratio of oil phase and reaction solution is 2: 3, emulsification 15 minutes; The aqueous solution that adds emulsifying agent 2 then, emulsification 10 minutes; Adding 25mL dropping linking agent by every 100mL emulsion at last under high-speed stirring is the calcium ions aqueous solution, stirs, solidifies 15 minutes;
(3) emulsion that step (2) is obtained is used dehydrated alcohol, distilled water wash respectively again with dehydrated alcohol precipitation, centrifugation, and lyophilize gets product.
2. the preparation method with calcium alginate compounded microballoon of temperature response performance according to claim 1, it is characterized in that: in the described step (1), the mixture of the described N-of containing ethene hexanolactam is mixture or N-ethene hexanolactam and acrylic acid mixture of N-ethene hexanolactam and methacrylic acid, the mixture of N-ethene hexanolactam and methacrylic acid wherein, the quality proportioning of N-ethene hexanolactam and methacrylic acid is 90～99: 10～1; N-ethene hexanolactam and acrylic acid mixture, N-ethene hexanolactam and acrylic acid quality proportioning are 90～99: 10～1.
3. the preparation method with calcium alginate compounded microballoon of temperature response performance according to claim 1 and 2, it is characterized in that: in the described step (1), described initiator is a Diisopropyl azodicarboxylate, and consumption is 1～5% of N-ethene hexanolactam or the mixture mole number that contains N-ethene hexanolactam; In the described step (2), described oil phase is a normal hexane, described emulsifying agent 1 is Span-85, consumption is 0.01～0.06g/mL oil phase, described emulsifying agent 2 is Tween-85, the total mass number of using is identical with the total mass number of emulsifying agent 1 use, during use emulsifying agent 2 is diluted to massfraction and is 50% the aqueous solution, and described linking agent is that massfraction is 8% CaCl
2The aqueous solution.
4. the preparation method with calcium alginate compounded microballoon of temperature response performance according to claim 1 and 2, it is characterized in that: in the described step (1), described stirring velocity is 200r/min, and described temperature of reaction is 60 ℃, and the described reaction times is 5 hours; In the described step (2), described stirring velocity is 1000～1400r/min.
5. the preparation method with calcium alginate compounded microballoon of temperature response performance according to claim 3, it is characterized in that: in the described step (1), described stirring velocity is 200r/min, and described temperature of reaction is 60 ℃, and the described reaction times is 5 hours; In the described step (2), described stirring velocity is 1000～1400r/min.
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|---|---|---|---|---|
| CN103191657A (en) * | 2013-04-02 | 2013-07-10 | 天津工业大学 | Hybridized gel film for filtration of organic solvent and preparation method thereof |
| CN103224633A (en) * | 2013-04-02 | 2013-07-31 | 天津工业大学 | Self-reinforced hybrid hydrogel used for artificial muscles and preparation method thereof |
| CN103224633B (en) * | 2013-04-02 | 2014-11-19 | 天津工业大学 | Self-reinforced hybrid hydrogel used for artificial muscles and preparation method thereof |
| CN103191657B (en) * | 2013-04-02 | 2015-04-22 | 天津工业大学 | Hybridized gel film for filtration of organic solvent and preparation method thereof |
| CN114377195A (en) * | 2021-12-30 | 2022-04-22 | 南京医科大学附属口腔医院 | Strontium alginate nano-microsphere and preparation method and application thereof |
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| CN101962464B (en) | 2012-05-30 |
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