CN101856603A - Nanometer/microencapsulation and release of hyaluronic acid - Google Patents
Nanometer/microencapsulation and release of hyaluronic acid Download PDFInfo
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- CN101856603A CN101856603A CN200910143973A CN200910143973A CN101856603A CN 101856603 A CN101856603 A CN 101856603A CN 200910143973 A CN200910143973 A CN 200910143973A CN 200910143973 A CN200910143973 A CN 200910143973A CN 101856603 A CN101856603 A CN 101856603A
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Abstract
The present invention describes a capsulation and control method through warpping or encapsulating hyaluronic acid in the later period of processing or preparing period of porous and non-porous template, and a subsequent releasing method. According to the capsulation method, deposition or absorbing of organic matters such as polymer; or deposition or absorbing of inorganic matters such as particles or nanometer particles; or deposition or absorbing of composite are used for forming organic matter or inorganic matter, namely mixed nanometer synthetic housing, nanometer and microcapsule. Through the method, various applications comprise (but are not limited to) injection in living mechanism. The controllable transmission, control and subsequent releasing are realized through self-degration or outer function for using the hyaluronic acid which is capsulated in the nanometer synthetic housing or fixed in the template.
Description
Detailed description of the invention
To 1000 nanometers, 1 micron to 1000 microns, 1 millimeter to 10 millimeters various templates encapsulate hyaluronic acid to the use size from 10 nanometers.Template can be synthetic by nanometer synthetic material, silicon for example, calcium carbonate, polystyrene etc.
Template is prepared, porose template and encapsulation
Can select commercial the purchase or homemade porose or non-porous nano synthetic template.The synthetic of porose template can form raw material by mixed sediment under accurate the stirring.In this case, porose template encapsulation has two kinds of approach:
1, packed hyaluronic acid to be attracted in the pattern hole, covered by the synthetic shell of nanometer subsequently.
2, when template forms, add hyaluronic acid and finish encapsulation.For example form and contain hyaluronic calcium carbonate particle with calcium chloride and sodium carbonate coprecipitation.Mixing velocity, composition and want packed hyaluronic concentration produce the hyaluronic acid that template concentrates or template is fixing that mixed subsequently organic and inorganic (polymer particles or nano particle) encapsulating shell covers.Hyaluronic concentration also can add relative amount to the template parent of precipitation formation by its initial concentration control.
Template can be removed (for example calcium carbonate can be in slightly acidic solution the dissolved or coordination by calcium), stays the hyaluronic acid free-floating in nanocapsule and micro-capsule, perhaps is kept perfectly.Under the kind situation of back, can discharge from the template or organic and inorganic (polymer particles and nano particle) the covering template of biodegradable or biologically inert.Under all scenario, packed hyaluronic acid can be from nanocapsule and micro-capsule as requested release order or release embodiments discharge.
Hyaluronic acid can only be incorporated in the shell.For example: by positive electric polymer such as collagen, poly arginine, hyaluronic acid oneself or other material make up layer by layer.The degraded of hyaluronic acid shell and discharge subsequently and can be induced by the shell degradation process is such as by the collagen of degraded by collagenase in the synthetic shell of collagen/hyaluronic acid.
This class template, mixing organic and inorganic covering template and nanocapsule and micro-capsule can make its functionalization with magnetic nanometer, makes described transmission medium have the magnetic respond, perhaps realizes perspective display or mobilizing function with other nano particle.Metal nanoparticle (gold, silver particles) is put into mixed shell can make these capsules have the optical excitation releasability.
The encapsulation of atresia template
For carrying out the encapsulation of atresia template, at first around template, form the synthetic or synthetic shell of mixing nanometer of nanometer.Then, two kinds of situations are arranged:
1, packed hyaluronic acid directly to be inhaled into template, covered by the synthetic shell of nanometer subsequently.Remove then or dissolve template and form hollow shell.
2, the at first synthetic or synthetic shell covering of mixing nanometer of template by nanometer, next step encapsulates again then.In this method, template at first is removed or dissolves.Under common or enhanced permeability, packed hyaluronic acid to penetrate in the synthetic shell of nanometer.Reduce permeability then or fierce the reduction realized inclusion and encapsulation.The permeability control method comprises the polymerization attribute, heat treatment, acidity, ionic forces, and outfield.
Nanometer is synthesized cover layer
By absorption, Interfacial Adsorption, the interface coordination, spatial induction polymerization and precipitation, or relevant chemical combination precipitate nanometer and synthesize or mix the synthetic shell (polymer particles or nano particle) of nanometer on template.The synthetic cover layer of nanometer is synthesized or mixed to nanometer is precipitated by adsorbing, and absorption can rely on salt, and pH value isoconcentration comes fixed.Template can be from bio-inert material, and for example silicon, or biocompatible material is for example selected in the calcium carbonate.Structural support when the biodegradable template can be used as transmission.When being necessary to realize technical advantage, cover layer and polymerization cover layer also can be used by spraying.
Another imagination is also feasible, decomposes by the center exactly to remove template.Because solvent can permeate the synthetic shell of nanometer, so just can stay the synthetic shell of complete nanometer in the removal center.The synthetic shell of nanometer has protection and discharges the control function.Discharge as control, the time interval will be determined in the thickness of nanoshell or outside stimulus/field, divide the encapsulation hyaluronic acid of setting to leave nanocapsule or micro-capsule at midseptum.
Synthetic and/or the polymerization cover layer of nanometer also can be by being called as ' clever ' biodegradable polymer and the nanometer synthetic is formed.Cover and tectal thickness and combination condition are controlled release, release can be regulated in certain period of time, such as hour, day, week, the moon etc.Instant-free can realize by the outfield.The nanometer synthesized polymer cover layer of micromolecular encapsulation and nanometer encapsulation can be with water-fast/water-soluble polymer, colloidal sol and gel covering, and chemical crosslinking, or the oil base covering strengthens.
The improvement of nanocapsule and micro-capsule
The synthetic shell of the nanometer of nanometer and little synthetic capsular can be improved to avoid absorption with appropriate formulation.On the other hand, nanometer and little synthetic softgel shell also can modifiedly induce the locality to take in.
Progressive explanation
The synthetic covering of nanometer can the extensive use condensate, polymer composition, and the organic nano synthetic mixes organic-inorganic nano synthetic etc.Can make the synthetic covering of polymer/nanometer with polymer and compound, include but not limited to polylysine, poly arginine, polyglutamic acid, gel, collagen, hyaluronic acid oneself, polysaccharide, shitosan, glucan and their growth.' clever ' biodegradable polymerization covering is used to be applied to those does not need outside releasing operation and activation.Outfield and outer mixing organic-inorganic nano synthesis of nano capsule and the micro-capsule that needing to be applied to specific release order that activate.Mix the organic and inorganic synthetic and comprise polymer, organic principle, inorganic particulate and nano particle, noble metal for example, metal oxide, magnetic particle etc.During some was used, the encapsulation hyaluronic acid was freely in nanocapsule and micro-capsule.During also some was used, the encapsulation hyaluronic acid was that template is fixed in nanocapsule and the micro-capsule.Be to be exposed under the temperate condition in nanocapsule and the micro-capsule when encapsulation process, its structure is can not be changed with affected.Step described above is widely used in, but is not limited to, tissue, and skin is at Living Organism etc.Packaging environment is a water, buffer solution, or all kinds of solvents.
Claims (11)
1. the method that hyaluronic acid is encapsulated in the following manner
A, absorption enter in the hole of foraminous die plate;
B, when the formation of foraminous die plate, add hyaluronic acid;
C, absorption enter in the atresia template;
D, hyaluronic acid penetrate in the synthetic shell of existing nanometer and inclusion;
E or directly hyaluronic acid encapsulation is entered the synthetic shell of nanometer.
2. according to the method described in the claim 1, be removed or complete staying at the final front template that uses.
3. according to the method described in the claim 1, decompose the removal template from the center.
4. according to the process of claim 1 wherein applied magnetic, metal or fluorescent particles, nano particle and dyestuff increase locking, move, and activate location or video picture function.
5. according to the method described in the claim 1, template is used as the structural support when transmitting.
6. according to claim 1 method, wherein the synthetic shell of nanometer provides the control release function.
7. according to the process of claim 1 wherein that shell can modifiedly be used for inducing the locality to take in.
8. according to the process of claim 1 wherein that shell can modifiedly be used for inducing bonding or specific cell and the tissue of being adhered to.
9. according to the process of claim 1 wherein that shell can modifiedly be used for preventing that the nanometer synthetic capsular is adhered to cell and tissue.
10. precipitate the synthetic or synthetic covering of mixing nanometer of nanometer according to the process of claim 1 wherein by absorption or spraying.
11. according to the method for claim 10, wherein said with insoluble in water/molten aqueous polymer, grease, the collosol and gel covering, or the oil base covering strengthens cover layer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16791709P | 2009-04-09 | 2009-04-09 | |
| US61167917 | 2009-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101856603A true CN101856603A (en) | 2010-10-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910143973A Pending CN101856603A (en) | 2009-04-09 | 2009-06-04 | Nanometer/microencapsulation and release of hyaluronic acid |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103764272A (en) * | 2011-08-30 | 2014-04-30 | 哈佛学院院长等 | Systems and methods for shell encapsulation |
| US9238206B2 (en) | 2011-05-23 | 2016-01-19 | President And Fellows Of Harvard College | Control of emulsions, including multiple emulsions |
| US10195571B2 (en) | 2011-07-06 | 2019-02-05 | President And Fellows Of Harvard College | Multiple emulsions and techniques for the formation of multiple emulsions |
| US10874997B2 (en) | 2009-09-02 | 2020-12-29 | President And Fellows Of Harvard College | Multiple emulsions created using jetting and other techniques |
-
2009
- 2009-06-04 CN CN200910143973A patent/CN101856603A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10874997B2 (en) | 2009-09-02 | 2020-12-29 | President And Fellows Of Harvard College | Multiple emulsions created using jetting and other techniques |
| US9238206B2 (en) | 2011-05-23 | 2016-01-19 | President And Fellows Of Harvard College | Control of emulsions, including multiple emulsions |
| US9573099B2 (en) | 2011-05-23 | 2017-02-21 | President And Fellows Of Harvard College | Control of emulsions, including multiple emulsions |
| US10195571B2 (en) | 2011-07-06 | 2019-02-05 | President And Fellows Of Harvard College | Multiple emulsions and techniques for the formation of multiple emulsions |
| CN103764272A (en) * | 2011-08-30 | 2014-04-30 | 哈佛学院院长等 | Systems and methods for shell encapsulation |
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Application publication date: 20101013 |