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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0233794 (2016-08-10) |
등록번호 | US-10143655 (2018-12-04) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 0 인용 특허 : 892 |
Methods are provided for promoting the adsorption of an active agent to microparticles by modifying the structural properties of the active agent in order to facilitate favorable association to the microparticle.
1. A method for making a microparticle coated with an active agent, the method comprising: i. combining (a) a microparticle comprising crystalline fumaryl diketopiperazine, (b) an active agent, and (c) a solvent for said active agent thereby forming a suspension of said microparticles with said acti
1. A method for making a microparticle coated with an active agent, the method comprising: i. combining (a) a microparticle comprising crystalline fumaryl diketopiperazine, (b) an active agent, and (c) a solvent for said active agent thereby forming a suspension of said microparticles with said active agent;ii. adding an active agent modifier to said suspension wherein adding said active agent modifier causes adsorption of said active agent onto said microparticle. 2. The method of claim 1, wherein said active agent modifier is a salt, surfactant, ion, osmolyte, alcohol, chaotrope, kosmotrope, acid, base, or anti-solvent. 3. The method of claim 1 further comprising removing said solvent subsequent to said adsorption of the active agent. 4. The method of claim 2, wherein said anti-solvent is an aqueous solvent. 5. The method of claim 4 wherein said anti-solvent is an organic solvent. 6. The method of claim 2, wherein said anti-solvent is an organic solvent. 7. The method of claim 6 wherein said anti-solvent is water. 8. The method of claim 2, wherein said salt is sodium chloride. 9. The method of claim 2, wherein said osmolyte is hexylene-glycol, trehalose, glycine, polyethylene glycol, trimethylamine N-oxide, mannitol, or proline. 10. The method of claim 2, wherein said alcohol is methanol, ethanol, trifluoroethanol, or hexafluoroisopropanol. 11. The method of claim 2, wherein said chaotrope is NaSCN, (CH3)3N—HCl, Na2NO3, NaClO4, or CsCl. 12. The method of claim 2, wherein said kosmotrope is sodium citrate or sodium sulfate. 13. The method of claim 1, wherein at least 70% of said active agent becomes adsorbed to said microparticle. 14. The method of claim 1, wherein at least 80% of said active agent becomes adsorbed to said microparticle. 15. The method of claim 1, wherein at least 90% of said active agent becomes adsorbed to said microparticle. 16. The method of claim 1, wherein all of said active agent becomes adsorbed to said microparticle. 17. The method of claim 1, wherein said microparticle is coated with a monolayer of said active agent. 18. The method of claim 1, wherein adding said active agent modifier favorably modulates one or more energetic interactions with said microparticle. 19. The method of claim 18, wherein said one or more energetically favorable interactions between said active agent and said microparticle comprises a hydrophobic interaction. 20. The method of claim 18, wherein said one or more energetically favorable interactions between said active agent and said microparticle comprises a hydrogen bonding interaction. 21. The method of claim 18, wherein said one or more energetically favorable interactions between said active agent and said microparticle comprises an electrostatic interaction. 22. The method of claim 1, wherein adding said active agent modifier modifies the structure, flexibility, rigidity, solubility or stability of said active agent. 23. The method of claim 1, wherein said active agent is a peptide or a protein. 24. The method of claim 1, wherein said active agent is an insulin and an insulin analog.
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