CN100347225C - Process for preparing biologically degradable reverse temperature sensitive material - Google Patents
Process for preparing biologically degradable reverse temperature sensitive material Download PDFInfo
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- CN100347225C CN100347225C CNB2005100114107A CN200510011410A CN100347225C CN 100347225 C CN100347225 C CN 100347225C CN B2005100114107 A CNB2005100114107 A CN B2005100114107A CN 200510011410 A CN200510011410 A CN 200510011410A CN 100347225 C CN100347225 C CN 100347225C
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- biodegradable
- temperature sensitive
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- sensitive material
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- 239000000463 material Substances 0.000 title claims abstract description 25
- 238000004519 manufacturing process Methods 0.000 title 1
- 239000000499 gel Substances 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 238000004132 cross linking Methods 0.000 claims abstract description 9
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical class [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims abstract description 7
- 229920001661 Chitosan Polymers 0.000 claims abstract description 6
- 108010010803 Gelatin Proteins 0.000 claims abstract description 6
- 239000008273 gelatin Substances 0.000 claims abstract description 6
- 229920000159 gelatin Polymers 0.000 claims abstract description 6
- 235000019322 gelatine Nutrition 0.000 claims abstract description 6
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229920001285 xanthan gum Polymers 0.000 claims abstract description 6
- 229920001221 xylan Polymers 0.000 claims abstract description 6
- 150000004823 xylans Chemical class 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 239000012535 impurity Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 6
- 239000005457 ice water Substances 0.000 claims description 6
- 229920001451 polypropylene glycol Polymers 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000230 xanthan gum Substances 0.000 claims description 5
- 229940082509 xanthan gum Drugs 0.000 claims description 5
- 235000010493 xanthan gum Nutrition 0.000 claims description 5
- 229930091371 Fructose Natural products 0.000 claims description 4
- 239000005715 Fructose Substances 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 235000019830 sodium polyphosphate Nutrition 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical group OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 claims description 2
- XYZZKVRWGOWVGO-UHFFFAOYSA-N Glycerol-phosphate Chemical group OP(O)(O)=O.OCC(O)CO XYZZKVRWGOWVGO-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 9
- 230000002209 hydrophobic effect Effects 0.000 abstract description 3
- 230000003993 interaction Effects 0.000 abstract description 3
- 229910019142 PO4 Inorganic materials 0.000 abstract description 2
- 238000009792 diffusion process Methods 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 3
- 150000004291 polyenes Chemical class 0.000 abstract 3
- 229920001282 polysaccharide Polymers 0.000 abstract 2
- 239000005017 polysaccharide Substances 0.000 abstract 2
- 150000004804 polysaccharides Chemical class 0.000 abstract 2
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 abstract 1
- 230000005540 biological transmission Effects 0.000 abstract 1
- 239000003431 cross linking reagent Substances 0.000 abstract 1
- 238000009396 hybridization Methods 0.000 abstract 1
- 230000000149 penetrating effect Effects 0.000 abstract 1
- 235000021317 phosphate Nutrition 0.000 abstract 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 230000035945 sensitivity Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 239000000017 hydrogel Substances 0.000 description 5
- 238000009533 lab test Methods 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 230000036760 body temperature Effects 0.000 description 4
- 229960002901 sodium glycerophosphate Drugs 0.000 description 4
- REULQIKBNNDNDX-UHFFFAOYSA-M sodium;2,3-dihydroxypropyl hydrogen phosphate Chemical compound [Na+].OCC(O)COP(O)([O-])=O REULQIKBNNDNDX-UHFFFAOYSA-M 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 108010064696 N,O-diacetylmuramidase Proteins 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- -1 poly-hydroxy phosphate Chemical compound 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 229940093916 potassium phosphate Drugs 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- OPPYZCPAQWRKNF-VWFNIEHNSA-K trisodium (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O OPPYZCPAQWRKNF-VWFNIEHNSA-K 0.000 description 2
- 206010005908 Body temperature conditions Diseases 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 229920000471 Poly(ethylene oxide)-block-polylactide Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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Abstract
The present invention relates to a preparation method for a biodegradable reverse temperature-sensitive material, which relates to the preparation of a material used for the fields of medicine transmission systems, cell embedding, biological tissue engineering and medical appliances. Polysaccharide biodegradable materials, such as gelatin, xanthan and chitosan or xylan are used as framework materials, and polyene alcohol used as a network penetrating auxiliary agent is led in to form a double crosslinking or hybridization gel network structure. The preparation method comprises the following steps: polysaccharide and a water solution of the polyene alcohol are crosslinked through a crosslinking agent, and then, an obtained solution is dissolved with polyhydroxy phosphates in an ice bath; after the previous reaction, the pH value of the obtained solution is regulated to 6.8 to 7.4 by a saturated disodium hydrogen phosphate solution to obtain an injectable biodegradable sol-jel conversion system. The biodegradable reverse temperature-sensitive material can rapidly form jel at 37 DEG C, and has temperature sensitivity. The addition of the polyene alcohol strengthens a hydrophobic interaction and enhances the intensity of the gel, and at the same time, the diffusion velocity of medical molecules in a gel network can be reduced.
Description
Technical field
The present invention relates to a kind of biodegradable, have material of reverse temperature sensitive and preparation method thereof, this material will have a good application prospect at drug delivery system, cell embedding, bioengineered tissue, medical instruments field.
Background technology
Succeeding in developing for the medical technology that develops rapidly of type material has very important significance.Particularly bioabsorbable polymer material has a very wide range of applications in medicine-feeding technology field, field of tissue engineering technology.The material that tradition is used as silicon rubber, does not have biocompatibility and biological degradability, thereby can have some toxicity and pungency; Simultaneously as the carrier of giving drug material, particularly be applied to such as in the heeling-in drug delivery system time, inevasiblely to use operation to implant, this is the shortcoming of the maximum that exists of this class system.At present, the substitutes of synthesis type temperature sensitive type Biodegradable materials as a new generation are adopted in great majority research, and as the PLA-PEO-PLA multipolymer etc.: the solution of this analog copolymer is solution state in the time of 45 ℃, solidifies for 37 ℃ at body temperature, form gel, belong to the forward temperature-sensitive material.High and superpolymer concentration height may influence its potential applicability in clinical practice but this class material is because of its injection temperature.Existing some problems aspect stability, gel-strength, biocompatibility or the biodegradability for the solid temperature-sensitive material down for liquid, body temperature under some room temperatures of external report at present, document " Yong Qiu; KinamPark; Environment-sensitive hydrogels for drug delivery, Advanced Drug DeliveryReviews 53 (2001) 321-339 " for example.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of biologically degradable reverse temperature sensitive material, a kind of gelling properties is stable, gel-strength is bigger thereby develop, the biodegradable material with reverse temperature sensitive that can use in fields such as drug delivery system, cell embedding, biological tissue's reparation, medicine equipments.
Technical scheme of the present invention is as follows: a kind of preparation method of biologically degradable reverse temperature sensitive material is characterized in that this method carries out as follows:
1) the saccharan powder dissolution that removal of impurities is obtained is made the solution of mass/volume concentration 0.5%～4% in weak acid or water, filtering and impurity removing is standby;
2) add network in described solution and run through the auxiliary agent polyalkenylalcohols, be heated to fully in 70～80 ℃ and dissolve, the mass ratio of polyalkenylalcohols and saccharan is 10: 1～1: 10, and the final quality/volumetric concentration of the hierarchy of control is 1.0～8.0%, is cooled to room temperature, froth breaking;
3) drip linking agent while stirring, the ultimate density of linking agent in system is 0.1～1000 μ M; Described linking agent adopts Epicholorohydrin, glutaraldehyde or sodium polyphosphate;
4) after crosslinking reaction finishes, change ice-water bath over to, add the saturated aqueous solution of the salt that contains the poly-hydroxy phosphate group, making the phosphatic final quality/volumetric concentration of poly-hydroxy is 0.5～15%, stirs at least 30 minutes;
5) slowly drip the saturated Sodium phosphate dibasic aqueous solution, regulate pH to 6.8～7.4, obtain injectable biodegradable sol gel transformsystem.
Saccharan of the present invention is preferably gelatin, xanthan gum, chitosan or xylan.Described polyalkenylalcohols is preferably polyvinyl alcohol or POLYPROPYLENE GLYCOL.Described poly-hydroxy phosphate group adopts Phosphoric acid glycerol esters group, glucose phosphate group or fructose phosphate group.
The present invention compared with prior art has the following advantages and the high-lighting effect: preparation technology of the present invention is simple, it is a kind of hydrogel that forms based on the saccharan material, but the water-content of this class hydrogel of common methods preparation is higher, thereby causes the intensity of gel lower.The present invention imports network and runs through auxiliary agent (polyalkenylalcohols) in aquogel system, can form double cross connection or hybrid gel network structure.This network structure is maintained by covalent linkage, electrostatic interaction, hydrophobic interaction usually.The adding that network runs through auxiliary agent can improve the intensity of gel, increases hydrophobic interaction, can slow down the velocity of diffusion of drug molecule in gel network simultaneously.The present invention can be used as a kind of responsive to temperature type drug-delivery preparation, is solution state under the normal temperature state, during as drug-delivery preparation, can be made into lyophilized injectable powder.In the application, can form gel behind the subcutaneous injection several minutes, solution solidifies under the body temperature state soon, need not implant and take out by operation.Compare with the poly-hydroxy phosphate system with simple saccharan, drug molecule is had the better controlled releasability, have good clinical application potentiality.
Description of drawings
Fig. 1 is for utilizing Brookfield rotor viscometer, and the fixed shear rate is 1rpm, and the viscosity of the following four kinds of embodiment of mensuration body temperature condition is curve over time.
Fig. 2 is the shear modulus G of four kinds of embodiment.
Fig. 3 is the release profiles of N,O-Diacetylmuramidase in four kinds of embodiment.
Embodiment
The present invention with saccharan such as gelatin, xanthan gum, chitosan or xylan Biodegradable material are main framework material, earlier with it in the water-soluble or weak acid, make mass/volume concentration and be 0.5%～4% solution, running through IPN auxiliary agent (polyalkenylalcohols) with network again is total to molten, the mass ratio of polyalkenylalcohols and saccharan is 10: 1～1: 10, final quality/the volumetric concentration of the hierarchy of control is 1.0～8.0%, react 30min at least, be generally 30～60min, warp and Epicholorohydrin, glutaraldehyde or sodium polyphosphate linking agent are crosslinked, crosslinking time is generally 1～10min, molten altogether with poly-hydroxy phosphoric acid salt ice bath again, regulate pH to 6.8～7.4, promptly make injectable biodegradable sol gel transformsystem.Its characteristics are that at normal temperature (room temperature) be liquid down, can form gel at short notice in (about 37 ℃, pH=6.8～7.4) under the Human Physiology environment.
The present invention is described further below by several specific embodiments descriptions.
Embodiment 1:
The gelatin powder that removal of impurities is obtained is dissolved in the water, and makes the solution of mass/volume concentration 4%, and filtering and impurity removing is standby; Add network and run through the auxiliary agent POLYPROPYLENE GLYCOL in solution, the mass ratio of gelatin and POLYPROPYLENE GLYCOL is 1: 1, is heated to fully in 70～80 ℃ and dissolves, and the final quality/volumetric concentration of the hierarchy of control is 8.0%, is cooled to room temperature, froth breaking; Dripping Epicholorohydrin concentration to ultimate density while stirring is 100 μ M; Crosslinking reaction changes ice-water bath over to after finishing, and adds the saturated aqueous solution that contains glucose phosphate sodium, and making glucose phosphate sodium final quality/volumetric concentration is 10%, 30～60 minutes; Slowly drip the saturated Sodium phosphate dibasic aqueous solution, regulate pH to 7.4,3 groups of parallel laboratory tests are done in packing.
Embodiment 2:
The chitosan powder that removal of impurities is obtained is dissolved in the acetum, makes the solution of mass/volume concentration 0.9%, and filtering and impurity removing is standby; Add network and run through auxiliary pva in solution, the mass ratio of chitosan and polyvinyl alcohol is 10: 1, is heated to fully in 70～80 ℃ and dissolves, and the final quality/volumetric concentration of the hierarchy of control is 1.0%, is cooled to room temperature, froth breaking; Dripping glutaraldehyde concentration to ultimate density while stirring is 0.1 μ M; Crosslinking reaction changes ice-water bath over to after finishing, and adding saturated aqueous solution to the whole mass/volume concentration of the quality of Sodium Glycerophosphate that contains Sodium Glycerophosphate is 15%, 30～60 minutes; Slowly drip the saturated Sodium phosphate dibasic aqueous solution, regulate pH to 7.2,3 groups of parallel laboratory tests are done in packing.
Embodiment 3:
The xanthan gum powder dissolution that removal of impurities is obtained is made the solution of mass/volume concentration 0.2% in water, filtering and impurity removing is standby; Add network and run through the auxiliary agent POLYPROPYLENE GLYCOL in solution, the mass ratio of xanthan gum and POLYPROPYLENE GLYCOL is 1: 10, is heated to fully in 70～80 ℃ and dissolves, and the final quality/volumetric concentration of the hierarchy of control is 2.0%, is cooled to room temperature, froth breaking; Dripping sodium polyphosphate to ultimate density while stirring is 1000 μ M; After crosslinking reaction finishes, change ice-water bath over to, adding the saturated aqueous solution that contains the fructose potassiumphosphate to the mass/volume concentration of fructose potassiumphosphate is 0.5%, 30～60 minutes; Slowly drip the saturated Sodium phosphate dibasic aqueous solution, regulate pH to 7.4,3 groups of parallel laboratory tests are done in packing.
Embodiment 4:
The xylan powder dissolution that removal of impurities is obtained is made the solution of mass/volume concentration 0.5% in water, filtering and impurity removing is standby; Add network and run through auxiliary pva in solution, the mass ratio of xylan and polyvinyl alcohol is 1: 5, is heated to fully in 70～80 ℃ and dissolves, and the final quality/volumetric concentration of the hierarchy of control is 3.0%, is cooled to room temperature, froth breaking; Dripping glutaraldehyde to ultimate density while stirring is 100 μ M; After crosslinking reaction finishes, change ice-water bath over to, adding the saturated aqueous solution that contains Sodium Glycerophosphate to the quality final concentration of Sodium Glycerophosphate is mass/volume concentration 10%, 30～60 minutes; Slowly drip the saturated Sodium phosphate dibasic aqueous solution, regulate pH to 6.8,3 groups of parallel laboratory tests are done in packing.
Hydrogel character is estimated as follows:
A: measure above-mentioned everywhere the side under body temperature, certain shearing rate is that viscosity number changes in time under the 1rpm, describes the viscosity change curve, sees accompanying drawing 1.This material has the temperature sensitive characteristic, generally forms gel in 10 minutes, and temperature is high slightly, solidifies faster.
B: the intensity of gel can characterize with the shear modulus G of gel.Can measure with simple method.Diameter A0 and height L0 are the cylindrical batten of 1cm, apply certain pressure F again above it, read the height L1 that sample is compressed to after the 30s relaxation.Stress strain relationship can be characterized by equation:
F/A
0=-G (λ-λ
-2); λ=L
1/ L
0Be deformation ratio (λ=1.0～0.7)
According to this formula can calculated for gel shearing modulus.The shear modulus G of the hydrogel of different degree of crosslinking is seen accompanying drawing 2.
C: the release of macromolecular drug N,O-Diacetylmuramidase in this material:
Prescription:
N,O-Diacetylmuramidase 24mg
Embodiment 1～4 colloidal sol consumption 12mL
4 groups of parallel laboratory tests are done in packing.
Release conditions: the water-bath shaker, dissolution medium: PBS buffered soln (pH=7.4,0.2M); Temperature: 37 ℃: rotating speed: 80rpm.Period sampling measuring discharges activity of lysozyme in the liquid, and its release profiles is seen accompanying drawing 3.The saccharan that the present invention is more simple, poly-hydroxy phosphoric acid salt aquogel system have the ability of control drug release preferably.
The character of the coagulating property in the foregoing description, gel-strength and drug release is seen Figure of description.
Claims (4)
1. the preparation method of a biologically degradable reverse temperature sensitive material is characterized in that this method carries out as follows:
1) the saccharan powder dissolution that removal of impurities is obtained is made the solution of mass/volume concentration 0.5%～4% in weak acid or water, filtering and impurity removing is standby;
2) add network in described solution and run through the auxiliary agent polyalkenylalcohols, be heated to fully in 70～80 ℃ and dissolve, the mass ratio of polyalkenylalcohols and saccharan is 10: 1～1: 10, and the final quality/volumetric concentration of the hierarchy of control is 1.0～8.0%, is cooled to room temperature, froth breaking;
3) drip linking agent while stirring, the ultimate density of linking agent in system is 0.1～1000 μ M; Described linking agent adopts Epicholorohydrin, glutaraldehyde or sodium polyphosphate;
4) after crosslinking reaction finishes, change ice-water bath over to, add the saturated aqueous solution of the salt that contains the poly-hydroxy phosphate group, making the phosphatic final quality/volumetric concentration of poly-hydroxy is 0.5～15%, stirs at least 30 minutes;
5) slowly drip the saturated Sodium phosphate dibasic aqueous solution, regulate pH to 6.8～7.4, obtain injectable biodegradable sol gel transformsystem.
2. according to the described biodegradable reverse temperature sensitive preparation methods that has of claim 1, it is characterized in that: described saccharan is gelatin, xanthan gum, chitosan or xylan.
3. according to the described biodegradable reverse temperature sensitive preparation methods that has of claim 1, it is characterized in that: described polyalkenylalcohols is polyvinyl alcohol or POLYPROPYLENE GLYCOL.
4. according to the described biodegradable reverse temperature sensitive preparation methods that has of claim 1, it is characterized in that: described poly-hydroxy phosphate group is Phosphoric acid glycerol esters group, glucose phosphate group or fructose phosphate group.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101260191B (en) * | 2008-04-01 | 2011-04-20 | 武汉大学 | Temperature sensitive type chitosan/glutin hydrogel and its preparation method and use |
| US7943597B2 (en) | 2008-04-08 | 2011-05-17 | Cypress Pharmaceutical, Inc. | Phosphate-binding chitosan and uses thereof |
| CN103497466A (en) * | 2013-10-14 | 2014-01-08 | 成都市新津事丰医疗器械有限公司 | Semi-interpenetration hydrogel and method for preparing same |
| CN107607222B (en) * | 2017-08-10 | 2019-07-30 | 常州大学 | It is a kind of based on pectin/xanthan gum blend film flexibility temperature sensor and preparation method thereof |
| CN109232958A (en) * | 2018-07-05 | 2019-01-18 | 常州市阿曼特医药科技有限公司 | A kind of preparation method of porous aquagel |
| CN114149598B (en) * | 2021-12-14 | 2024-05-07 | 重庆医科大学 | Composite intelligent hydrogel with diabetes mellitus microenvironment responsiveness as well as preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06293632A (en) * | 1993-04-07 | 1994-10-21 | Nippon Kayaku Co Ltd | Temperature response type medicinal composition |
| US5904927A (en) * | 1997-03-14 | 1999-05-18 | Northeastern University | Drug delivery using pH-sensitive semi-interpenetrating network hydrogels |
| WO2004098756A2 (en) * | 2003-04-30 | 2004-11-18 | Drexel University | Thermogelling polymer blends for biomaterial applications |
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- 2005-03-11 CN CNB2005100114107A patent/CN100347225C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06293632A (en) * | 1993-04-07 | 1994-10-21 | Nippon Kayaku Co Ltd | Temperature response type medicinal composition |
| US5904927A (en) * | 1997-03-14 | 1999-05-18 | Northeastern University | Drug delivery using pH-sensitive semi-interpenetrating network hydrogels |
| WO2004098756A2 (en) * | 2003-04-30 | 2004-11-18 | Drexel University | Thermogelling polymer blends for biomaterial applications |
Non-Patent Citations (1)
| Title |
|---|
| Environment-sensitive hydrogels for drug delivery Yong Qiu,Kinam Park.Advanced Drug Delivery Reviews,Vol.53 . 2001 * |
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