CN102532564B - Hydrogel and preparation method thereof - Google Patents
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- CN102532564B CN102532564B CN 201210012353 CN201210012353A CN102532564B CN 102532564 B CN102532564 B CN 102532564B CN 201210012353 CN201210012353 CN 201210012353 CN 201210012353 A CN201210012353 A CN 201210012353A CN 102532564 B CN102532564 B CN 102532564B
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 238000002347 injection Methods 0.000 claims abstract description 21
- 239000007924 injection Substances 0.000 claims abstract description 21
- 239000000243 solution Substances 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 238000004132 cross linking Methods 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 15
- 235000010443 alginic acid Nutrition 0.000 claims description 13
- 229920000615 alginic acid Polymers 0.000 claims description 13
- 238000013016 damping Methods 0.000 claims description 13
- 239000012530 fluid Substances 0.000 claims description 13
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 12
- 229940072056 alginate Drugs 0.000 claims description 12
- 159000000009 barium salts Chemical class 0.000 claims description 3
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- 150000003751 zinc Chemical class 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 239000000872 buffer Substances 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 abstract description 11
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 8
- 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 abstract description 3
- 235000010413 sodium alginate Nutrition 0.000 abstract description 3
- 239000000661 sodium alginate Substances 0.000 abstract description 3
- 229940005550 sodium alginate Drugs 0.000 abstract description 3
- 210000004292 cytoskeleton Anatomy 0.000 abstract description 2
- 108010010803 Gelatin Proteins 0.000 abstract 2
- 239000003431 cross linking reagent Substances 0.000 abstract 2
- 239000008273 gelatin Substances 0.000 abstract 2
- 229920000159 gelatin Polymers 0.000 abstract 2
- 235000019322 gelatine Nutrition 0.000 abstract 2
- 235000011852 gelatine desserts Nutrition 0.000 abstract 2
- 238000004026 adhesive bonding Methods 0.000 abstract 1
- 239000007853 buffer solution Substances 0.000 abstract 1
- 239000000945 filler Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 description 9
- 230000001954 sterilising effect Effects 0.000 description 8
- 230000009286 beneficial effect Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 210000004153 islets of langerhan Anatomy 0.000 description 4
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000011243 crosslinked material Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000037303 wrinkles Effects 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](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]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical group [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000199919 Phaeophyceae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229940025708 injectable product Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/04—Alginic acid; Derivatives thereof
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/04—Alginic acid; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention relates to a hydrogel and a preparation method thereof as well as biomedical application of the hydrogel used for a subcutaneous filling agent or a medicament carrier or a cytoskeleton. The preparation method comprises the following steps: firstly, dissolving sodium alginate in a buffer solution so as to prepare a gelatin solution, putting the gluing solution into an injector, putting a crosslinking agent into the other injector, and connecting the two injectors together; then pushing the two injectors back and forth so that the gelatin solution is evenly mixed with the crosslinking agent, injecting, and carrying out a crosslinking reaction after injection, so as to obtain the hydrogel. In the method, crosslinking and injection are integrated without disinfection after reaction, thereby avoiding the influence of a disinfection process on performances of a product.
Description
Technical field
The present invention relates to a kind of hydrogel and preparation method thereof, belong to the bio-medical field.
Background technology
The hydrogel that with the natural biologic material is matrix is widely used in subcutaneous packing material with its excellent biological compatibility, pharmaceutical carrier and tissue engineering technique.For making material present peculiar shape, or have certain mechanical strength, or delay degradation speed to increase the service life, need improve starting material usually, such as crosslinked be exactly a kind of method commonly used.If yet linking agent control is improper, though can guarantee the injection of material such as very few crosslinked concentration, owing to react slower, the sol solution of injection can not remain on fixing scope; And too high crosslinker concentration can cause reacting too fast, and crosslinked material later will become one and lose syringeability.For material is injected, need usually crosslinked material chopping, or be prepared into micron or nanoparticle, and mix with appropriate carriers, just can become injectable product.And the process for preparing particulate needs reaction usually, cleans, and screening mixes, and reaches series of steps such as sterilization, and is comparatively loaded down with trivial details.If inject sol solution and linking agent respectively, can't mix in the body, can influence result of use.If can both can be injected appointed part in complete reaction before losing syringeability with a kind of method, above-mentioned preparation process will be simplified greatly, product impurity reduces, and cost reduces.
Lalgine (Alginate) is the natural polymer that is present in the phaeophyta, it is the natural polysaccharide that from brown alga or bacterium, extracts, be similar to the glycosaminoglycan GAGs in the extracellular matrix, no subacute/reaction of chronic toxicity or carinogenicity, can be used as edible foodstuff additive, also can be used as timbering material and be used for medical usage, possess excellent biological compatibility.Lalgine is easy to be combined with some divalent cations, forms gel.But just there are the problems referred to above in conventional cross-linking method, and namely the alginate that mix with linking agent namely can lose syringeability as not making particulate.Be effectively to use the key of this material so control crosslinked concentration and method.Moreover, other similar gelatinous material such as collagens, chitosan, natural polymer gels such as hyaluronic acid all can be taked similar method and technology, make injectable biomaterial for medical purpose.
Summary of the invention
For avoiding preparing the required reaction of particulate, clean, screening, mix, and a series of complicated processes such as sterilization, and the problem of injecting the product degree of crosslinking inequality that mixing inequality that reagent brings causes respectively, the invention provides integrated hydrogel of a kind of crosslinked injection and preparation method thereof, to simplify preparation process, reduce cost.
The technical scheme that the present invention solves the problems of the technologies described above is as follows:
The preparation method of the integrated hydrogel of a kind of crosslinked injection may further comprise the steps: at first sodiun alginate is dissolved in the damping fluid, is mixed with sol solution, be loaded in the syringe, linking agent is loaded in another syringe, and described two syringes are linked at together; Then described two syringes are promoted back and forth, make described sol solution and described linking agent mix, crosslinking reaction is finished in injection after the injection then, obtains described hydrogel;
Wherein, the volume ratio of described sodiun alginate and damping fluid is 1:100～5:100; The mass ratio of described sol solution and linking agent is 10000:1～15000:1.
The invention has the beneficial effects as follows:
1. simplification preparation process reduces cost;
2. avoid using the obstruction of the injection process that particulate may cause; Need not assistant carrier, thus avoid owing to the problem of using carrier to bring, as inflammation, the absorption of carrier, degraded is removed etc.
3. crosslinked injection is integrated, the sterilization after need not to react, the influence of avoiding sterilizing process to cause to product performance; (need not other reagent and be used for the cleaning of purifying, so influence such as inflammation that the resistates that nothing retains may cause; )
4. as subcutaneous weighting agent, effect can be finished namely with crosslinking reaction and show;
Subcutaneous weighting agent is a kind ofly can be injected at subcutaneous natural or synthetic material, fills and leads up depression or wrinkle part, to reach wrinkle-removal cosmetic, increases the effect of confidence even job opportunity.
5. betide in the general injection thing because of crosslinked, but not in the single particulate, be conducive to fill and lead up continuing of depression or wrinkle effect.
On the basis of technique scheme, the present invention can also do following improvement.
Further, described damping fluid is sodium phosphate buffer.
Adopt the beneficial effect of previous step technical scheme to be, add damping fluid in the present invention, with keep with body in identical perviousness, and be unlikely to the local edema or the dehydration that are caused by its difference.
Further, described linking agent is calcium chloride, the divalence barium salt, or divalent zinc salt etc.
Adopt the beneficial effect of previous step technical scheme to be, use the reaction of described linking agent and alginates, can make material present certain volume and shape, or have certain mechanical strength, or delay degradation speed to increase the service life.
Further, the time that promotes described two syringes back and forth is 3～8 seconds.
Adopt the beneficial effect of previous step technical scheme to be, the composition in two syringes is fully mixed.
Further, described is 3～5 minutes from being expelled to the time of finishing crosslinking reaction.
Adopt the beneficial effect of previous step technical scheme to be, make material can be injected into the position of appointment like this, be unlikely to again to flow to other positions slowly because reacting.
The another technical scheme that the present invention solves the problems of the technologies described above is as follows:
A kind of integrated hydrogel of crosslinked injection according to above-mentioned method preparation.
The another technical scheme that the present invention solves the problems of the technologies described above is as follows:
A kind of hydrogel is used for subcutaneous weighting agent or pharmaceutical carrier or cytoskeletal biomedical applications.
Embodiment
Below principle of the present invention and feature are described, institute only gives an actual example and to be used for explaining the present invention, is not for restriction scope of the present invention.
Embodiment 1
A kind of preparation method of hydrogel may further comprise the steps: at first sodiun alginate is dissolved in the damping fluid, is mixed with sol solution, be loaded in the syringe, the linking agent of divalence calcium salt is loaded in another syringe, and described two syringes are linked at together; Then described two syringes were promoted 3 seconds back and forth, make described sol solution and described linking agent mix, crosslinking reaction is finished in injection after the injection then, is 3 minutes from being expelled to the time of finishing crosslinking reaction, obtains described hydrogel.
The mass volume ratio of described sodiun alginate and damping fluid is 1:100.
Described hydrogel is used for subcutaneous weighting agent.
Embodiment 2
A kind of preparation method of hydrogel, may further comprise the steps: sodiun alginate is dissolved in the damping fluid, be mixed with sol solution, it is sterilization after 10 minutes under 110 ℃ the condition in temperature, be loaded in the syringe, be that sterilization was loaded in another syringe, and described two syringes are linked at together after 10 minutes under 110 ℃ the condition in temperature with the linking agent of barium salt; Then described two syringes were promoted 10 seconds back and forth, make described sol solution and described linking agent mix, crosslinking reaction is finished in injection after the injection then, is 5 minutes from being expelled to the time of finishing crosslinking reaction, obtains described hydrogel.
The mass volume ratio of described sodiun alginate and damping fluid is 5:100.
Embodiment 3
A kind of preparation method of hydrogel, may further comprise the steps: at first sodiun alginate is dissolved in the damping fluid, be mixed with sol solution, it is sterilization after 20 minutes under 130 ℃ the condition in temperature, be loaded in the syringe, be that sterilization was loaded in another syringe, and described two syringes are linked at together after 20 minutes under 130 ℃ the condition in temperature with the linking agent of divalence calcium salt; Then described two syringes were promoted 7 seconds back and forth, make described sol solution and described linking agent mix, crosslinking reaction is finished in injection after the injection then, is 4 minutes from being expelled to the time of finishing crosslinking reaction, obtains described hydrogel.
The mass volume ratio of described sodiun alginate and damping fluid is 1:100～5:100.
Embodiment 4
Described hydrogel is used for cytoskeleton:
Linking agent and islet cells are loaded on respectively in two syringes, both are mixed, and mixture is concentrated in the syringe.Take off empty syringe then, will have the syringe of mixture and the syringe that another is equipped with solution of sodium alginate to link, both are mixed.Inject subcutaneous or appointed part then, make that islet cells can be at local uelralante.
The hydrogel that embodiment 4 obtains mainly is that purposes is: the carrier and the support that are used for doing cell.Send into subcutaneous or appointed part with islet cells, islet cells can be located lasting uelralante, reaches injection repeatedly, also can reach the purpose for the treatment of diabetes.
Embodiment 5
Described hydrogel is used for medicinal slow release agent:
Solution of sodium alginate and anodyne composition are loaded on respectively in two syringes, both are mixed, and mixture is concentrated in the syringe.Take off empty syringe then, will have the syringe of mixture and the syringe that another is equipped with linking agent to link, both are mixed.Inject subcutaneous or appointed part then, the drug slow location is discharged.If this medicine is pain relieving class medicine, then can reach the effect of local analgesia.
Embodiment 5 provides useful as drug slow-released system of the present invention: namely send into subcutaneous or appointed part with medicine, medicine can be located and be continued to discharge, and reaches and need not take medicine repeatedly, also can reach the purpose for the treatment of disease.
The above only is preferred embodiment of the present invention, and is in order to limit the present invention, within the spirit and principles in the present invention not all, any modification of doing, is equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (6)
1. the preparation method of a hydrogel is characterized in that, may further comprise the steps: at first sodiun alginate is dissolved in the damping fluid, is mixed with sol solution, be loaded in the syringe, linking agent is loaded in another syringe, and described two syringes are linked at together; Then described two syringes are promoted back and forth, make described sol solution and described linking agent mix, crosslinking reaction is finished in injection after the injection then, obtains described hydrogel;
Wherein, the volume ratio of described sodiun alginate and damping fluid is 1:100～5:100; The mass ratio of described sol solution and linking agent is 10000:1～15000:1.
2. preparation method according to claim 1 is characterized in that, described damping fluid is phosphoric acid buffer.
3. preparation method according to claim 1 is characterized in that, described linking agent is a kind of in divalence calcium salt, barium salt or the divalent zinc salt.
4. preparation method according to claim 1 is characterized in that, the time that promotes described two syringes back and forth is 3～10 seconds.
5. preparation method according to claim 1 is characterized in that, described is 3～5 minutes from being expelled to the time of finishing crosslinking reaction.
6. hydrogel according to each described method preparation of claim 1 to 5.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210012353 CN102532564B (en) | 2012-01-16 | 2012-01-16 | Hydrogel and preparation method thereof |
| PCT/CN2012/073119 WO2013107092A1 (en) | 2012-01-16 | 2012-03-27 | Hydrogel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210012353 CN102532564B (en) | 2012-01-16 | 2012-01-16 | Hydrogel and preparation method thereof |
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| CN102532564A CN102532564A (en) | 2012-07-04 |
| CN102532564B true CN102532564B (en) | 2013-09-25 |
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| CN 201210012353 Expired - Fee Related CN102532564B (en) | 2012-01-16 | 2012-01-16 | Hydrogel and preparation method thereof |
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| WO (1) | WO2013107092A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10195282B2 (en) * | 2014-11-20 | 2019-02-05 | University Of Southern California | Use of alginate formulation for intraincisional drug delivery |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105169473B (en) * | 2015-10-19 | 2018-06-29 | 东南大学 | A kind of ultra-fine hole hydrogel scaffold and preparation method thereof |
| CN106435833B (en) * | 2016-09-22 | 2018-07-13 | 大连工业大学 | A kind of chemical crosslinking modified alginate fiber and preparation method thereof |
| CN107648664A (en) * | 2017-10-31 | 2018-02-02 | 无锡中科光远生物材料有限公司 | A kind of gel rubber material for backbone reparation of injectable and preparation method thereof |
| CN114409932A (en) * | 2022-03-11 | 2022-04-29 | 江苏集萃功能材料研究所有限公司 | Preparation method and application of intraoperative gastric filling hydrogel |
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| WO2009124388A1 (en) * | 2008-04-09 | 2009-10-15 | Mcmaster University | Hydrogel with covalently crosslinked core |
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| CN102070786A (en) * | 2009-11-19 | 2011-05-25 | 中国农业科学院农产品加工研究所 | Hyaluronic acid-sodium alginate composite hydrogel and preparation method thereof |
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| EP1714605B1 (en) * | 2005-04-21 | 2011-06-08 | Reckitt Benckiser (UK) Limited | Device and method |
| CN101423564B (en) * | 2008-12-08 | 2011-05-04 | 青岛明月海藻集团有限公司 | Method for preparing alginate for fast preparation of hydrogel |
| CN101768231B (en) * | 2010-01-06 | 2011-08-31 | 东华大学 | Method for preparing N-isopropyl acrylamide/multi-walled carbon nanotube composite microgel through in situ polymerization in microreactor |
| CN102020777B (en) * | 2010-11-29 | 2012-08-22 | 同济大学 | Method for preparing nano hydroxyl apatite calcium alginate injectable hydrogel and application thereof |
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| US6497902B1 (en) * | 1999-12-01 | 2002-12-24 | The Regents Of The University Of Michigan | Ionically crosslinked hydrogels with adjustable gelation time |
| CN1816359A (en) * | 2003-05-05 | 2006-08-09 | 宾-古里安尼格夫大学研究及发展部 | Injectable cross-linked polymeric preparations and uses thereof |
| CN101918049A (en) * | 2008-01-16 | 2010-12-15 | 赛尔麦德公司 | Monolithic in-situ cross-linked alginate implants |
| WO2009124388A1 (en) * | 2008-04-09 | 2009-10-15 | Mcmaster University | Hydrogel with covalently crosslinked core |
| CN101564558A (en) * | 2009-05-18 | 2009-10-28 | 中国人民解放军第二军医大学 | Alginate-barium sulfate microsphere, preparation method and application thereof |
| CN102070786A (en) * | 2009-11-19 | 2011-05-25 | 中国农业科学院农产品加工研究所 | Hyaluronic acid-sodium alginate composite hydrogel and preparation method thereof |
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| US10195282B2 (en) * | 2014-11-20 | 2019-02-05 | University Of Southern California | Use of alginate formulation for intraincisional drug delivery |
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| CN102532564A (en) | 2012-07-04 |
| WO2013107092A1 (en) | 2013-07-25 |
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