The United States of America as represented by the Secretary of the Army
인용정보
피인용 횟수 :
7인용 특허 :
34
초록
A controlled release microcapsulate pharmaceutical formulation for burst-free, sustained, programmable release of hydrophobic bioactive agent over a duration from 24 hours to 100 days comprising: and a blend of end-capped uncapped biocompatible, biodegradable poly(lactide/glycolide).
대표청구항▼
1. A method of preparing a controlled release microcapsule pharmaceutical composition of burst-free sustained, programmable release of a hydrophobic bioactive agent over a duration of 24 hours to 100 days, comprising the steps of:a) mixing a hydrophobic bioagent with a blend of end-capped and uncapp
1. A method of preparing a controlled release microcapsule pharmaceutical composition of burst-free sustained, programmable release of a hydrophobic bioactive agent over a duration of 24 hours to 100 days, comprising the steps of:a) mixing a hydrophobic bioagent with a blend of end-capped and uncapped biocompatible, biodegradable poly(lactide/glycolide) copolymer, wherein said end-capped polymer has terminal residues functionalized as esters and said uncapped polymer has terminal residues existing as carboxylic acids; and b) performing a solvent evaporation process to form said microcapsules. 2. The method of claim 1, wherein said copolymer has a molecular weight from 10 to 100 kDa.3. The method of claim 1, wherein said agent is selected from the group consisting of chemotherapeutics, antibiotics, antivirals, antiinflammatories, cytokines, immunotoxins, anti-tumor antibodies, anti-angiogenic agents, anti-edema agents, radiosensitizers, and combinations thereof.4. The method of claim 1, wherein said agent is selected from the group consisting of paclitaxel, doxorubicin, 5-fluorouracil, camptothecin, cisplatin, metronicdazole, and combinations thereof.5. The method of claim 1, further comprising manipulating a ratio of said uncapped polymer and said capped polymer to maximize core loading efficiencies of said hydrophobic bioagent.6. The method of claim 1, further comprising adjusting a percentage of said capped and a percentage of said uncapped copolymers to stabilize a structure of said microcapsules.7. The method of claim 1, further comprising increasing an amount of said uncapped polymer relative to said capped polymer to decrease a resulting size of said microcapsules while incorporating said hydrophobic bioagent into said microspheres.8. The method of claim 1, further comprising manipulating a parameter of acceleration of release of hydrophobic bioagent by adjusting an amount of uncapped polymer, wherein by increasing said uncapped polymer, said acceleration of release increases.9. The method of claim 1, further comprising manipulating a parameter of acceleration of release of hydrophobic bioagent by adjusting an amount of low molecular weight polymer wherein the greater the amount of low molecular weight polymer, the greater the acceleration of release of said hydrophobic bioagent.10. The method of claim 1, further comprising manipulating a parameter of acceleration of release of hydrophobic bioagent by adjusting external stir rates in the mixing step, wherein by increasing external stir rates, said release rates are increased.11. The method of claim 10, further comprising manipulating a parameter of acceleration of release of hydrophobic bioagent by sonification of the polymer and hydrophobic bioagent mixture before performing the external phase stirring.12. The method of claim 1, further comprising adding sucrose to the polymer and hydrophobic bioagent mixture to increase release rates of the hydrophobic bioagent.13. The method of claim 1, further comprising cooling the hydrophobic bioagent and said polymer for a first 15 minutes of said mixing to a temperature of 15° C. to form smaller microspheres.
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