Matrices formed of polymer and hydrophobic compounds for use in drug delivery
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/10
A61K-009/16
A61K-047/30
A61K-047/24
출원번호
US-0384902
(2003-03-06)
발명자
/ 주소
Bernstein, Howard
Chickering, Donald
Khattak, Sarwat
Straub, Julie
출원인 / 주소
Acusphere, Inc.
대리인 / 주소
Holland & Knight LLP
인용정보
피인용 횟수 :
9인용 특허 :
18
초록▼
A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time a
A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.
대표청구항▼
A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time a
A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug. as shown in SEQ ID NO:1.7. A pharmaceutical composition comprising an Hsp70 complex, said Hsp70 complex comprising a first portion and a second portion covalently joined, said first portion comprising Hsp70 protein, or a fragment thereof capable of intracellular and intranuclear transport; and said second portion comprising a nuclear protein or nuclear peptide. 8. The pharmaceutical composition of claim 7 wherein said nuclear protein or nuclear peptide comprises the p50 subunit of the transcription factor NF-&kgr;B.9. The pharmaceutical composition of claim 7 wherein said Hsp70 complex is a fusion protein.10. The method of claim 4, wherein said Hsp70 or fragment of Hsp70 is the fragment of Hsp70 consisting of the amino acid sequence shown in SEQ ID NO:2.11. The method of claim 5, wherein said Hsp70 or fragment of Hsp70 is the fragment of Hsp70 consisting of the amino acid sequence shown in SEQ ID NO:3.12. The pharmaceutical composition of claim 9 further comprising at least one additional active compound selected from the group consisting of: an immunosuppressant, an anti-cancer agent, an anti-viral agent, an anti-inflammatory agent, an anti-fungal agent, an antibiotic, or an anti-vascular hyperproliferation compound.13. The pharmaceutical composition of claim 9 wherein said Hsp70 or fragment of Hsp70 comprises an amino acid sequence as shown in SEQ ID NO:2.14. The pharmaceutical composition of claim 9 wherein said Hsp70 or fragment of Hsp70 comprises an amino acid sequence as shown in SEQ ID NO:3.15. The pharmaceutical composition of claim 13 or14 wherein Hsp70 or fragment of Hsp70 is C-terminal to said nuclear protein or nuclear peptide.16. The pharmaceutical composition of claim 7 wherein said nuclear protein or nuclear peptide comprises residues 37-409 of the p50 subunit of the transcription factor NF-&kgr;B as shown in SEQ ID NO:1.17. A method of delivering a compound into a cell or cells, said method comprising: associating said compound with Hsp70, or a fragment of Hsp70 capable of intracellular and intranuclear transport, to form an Hsp70 complex; and providing said Hsp70 complex to said cell or cells or to the environment surrounding said cell or cells so that said Hsp70 complex is imported into said cell or cells; wherein said compound comprises residues 37-409 of the p50 subunit of the transcription factor NF-&kgr;B as shown in SEQ ID NO:1. 18. The method of claim 1, wherein said nuclear protein or nuclear peptide is covalently joined to a fragment of Hsp70 capable of intracellular and intranuclear transport.19. The method of claim 1, wherein said Hsp70 or fragment of Hsp70 is of human origin.20. The method of claim 1, wherein said nuclear protein or nuclear peptide is capable of modulating gene expression in said nuclear compartment.21. The method of claim 20, wherein said modulation of gene expression provides immunosuppressive or immunostimulatory control.22. The method of claim 20, wherein said nuclear protein or nuclear peptide is a transcription factor.23. The method of claim 22, wherein said transcription factor is a regulator of inflammatory responses.24. A pharmaceutical composition comprising an Hsp70 complex, said Hsp70 complex comprising a first portion and a second portion covalently joined, said first portion comprising Hsp70 of human origin, or a fragment of Hsp70 of human origin capable of intracellular and intranuclear transport, and said second portion comprising a nuclear protein or nuclear peptide. 25. The pharmaceutical composition of claim 7, wherein said nuclear protein or nuclear peptide is capable of modulating gene expression in said nuclear compartment.26. The pharmaceutical composition of claim 25, wherein said modulation of gene expression provides immunosuppressive or immunostimulatory control.27. The pharmaceutical composition of claim 25, wherein said nuclear protein or nuclear peptide is a transcription factor.28. The pharmaceutical composition of claim 27, where
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