CN101856341A - Nanometer/micropackaging and releasing of botulinum toxin - Google Patents
Nanometer/micropackaging and releasing of botulinum toxin Download PDFInfo
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- CN101856341A CN101856341A CN200910143630A CN200910143630A CN101856341A CN 101856341 A CN101856341 A CN 101856341A CN 200910143630 A CN200910143630 A CN 200910143630A CN 200910143630 A CN200910143630 A CN 200910143630A CN 101856341 A CN101856341 A CN 101856341A
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- nanometer
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Abstract
The present invention describes a packaging and control method through packaging or packing botulinum toxin in later period of processing or preparing period of porous and non-porous template (colloidal particles), and a subsequent releasing method. According to the packaging method, deposit or adsorption of organic matter such as polymer; or deposit or adsorption of inorganic matter, such as particles or nanometer particles; or deposit or adsorption of compound is applied for forming the organic matter or organic-inorganic compound, namely combined nanometer synthetic housing, nanometer and micro-capsules. Through the methods, various applications includes (but are not limited to) injection in alive organic matter. The controllable transportation, control and subsequent releasing are realized through self-degration or external action for using the botulinum toxin which is packaged 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 Botulinum toxin to the use size from 10 nanometers.Template can be synthetic by nanometer synthetic material, silicon for example, carbonate, 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 Botulinum toxin to be attracted in the pattern hole, covered by the synthetic shell of nanometer subsequently.
2, when template forms, add Botulinum toxin and finish encapsulation.For example form and contain botulinal calcium carbonate particle with calcium chloride and sodium carbonate coprecipitation.Mixing velocity, composition and the template of wanting packed botulinal concentration to produce the covering of mixed subsequently organic and inorganic (polymer particles or nanoparticle) encapsulating shell concentrate or the fixed Botulinum toxin of template.Botulinal 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 Botulinum toxin free-floating in nanocapsule and microcapsule, perhaps is kept perfectly.Under the kind situation of back, can discharge from the template or organic and inorganic (polymer particles and nanoparticle) the covering template of biodegradable or biologically inert.Under all scenario, packed Botulinum toxin can be from nanocapsule and microcapsule as requested release order or release embodiments discharge.
Botulinum toxin can be incorporated in the capsule in two ways.First kind of mode, Botulinum toxin can be by combination of positive electricity biocompatible/biodegradable polymer or absorption, collagen for example, and polyethylene and/or other are used for making the raw material of synthetic Botulinum toxin shell.Botulinum toxin can be induced release by the shell degradation process, for example by the degraded by collagenase collagen in collagen/Botulinum toxin shell.Another method is that botulinal micropartical and nanoparticle are encapsulated in the blister cavities.
The Botulinum toxin of any packing forms is capsule for example, filling template, mix organic and inorganic covering template and nanocapsule and microcapsule and can make its functionalization with magnetic nanometer, make described transmission medium have the magnetic respond, perhaps realize perspective display or mobilizing function with other nanoparticle.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 Botulinum toxin 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 Botulinum toxin to penetrate in the synthetic shell of nanometer.Reduce permeability then or fierce the reduction realized enclose 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 nanoparticle) 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 the 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.As sustained release, interval will be determined in the thickness of nanoshell or outside stimulus/field, divide the encapsulation Botulinum toxin of setting to leave nanocapsule or microcapsule 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 come sustained 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 microcapsule
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 polymer, polymer composition, and the organic nano synthetic mixes organic-inorganic nano synthetic etc.Can make the synthetic covering of polymer/nanometer with polymer and chemical compound, include but not limited to polylysine, poly arginine, polyglutamic acid, gel, collagen, polysaccharide, chitosan, glucosan and their derivatives.' clever ' biodegradable polymerization covering is used to be applied to those does not need outside releasing operation and activated.Outfield and outer mixing organic-inorganic nano synthesis of nano capsule and the microcapsule 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 nanoparticle, noble metal for example, metal-oxide, magnetic particle etc.During some was used, the encapsulation Botulinum toxin was freely in nanocapsule and microcapsule.During also some was used, the encapsulation Botulinum toxin was that template is fixed in nanocapsule and the microcapsule.Be to be exposed under the temperate condition in nanocapsule and the microcapsule 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, or all kinds of solvents.
Claims (11)
1. the method that encapsulates in the following manner of Botulinum toxin
A, absorption enter in the hole of foraminous die plate;
B, when the formation of foraminous die plate, add Botulinum toxin;
C, absorption enter in the atresia template;
D, Botulinum toxin penetrate in the synthetic shell of existing nanometer and enclose;
E or directly Botulinum toxin 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, nanoparticle 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 sustained 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, oils and fats, the collosol and gel covering, or the oil base covering strengthens cover layer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16791309P | 2009-04-09 | 2009-04-09 | |
| US61167913 | 2009-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101856341A true CN101856341A (en) | 2010-10-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910143630A Pending CN101856341A (en) | 2009-04-09 | 2009-05-27 | Nanometer/micropackaging and releasing of botulinum toxin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101856341A (en) |
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2009
- 2009-05-27 CN CN200910143630A patent/CN101856341A/en active Pending
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Application publication date: 20101013 |