A kind of hydrogel and preparation method thereofTechnical 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.