Compositions and methods for enhancing drug delivery across and into ocular tissues
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/522
A61K-038/03
A61K-038/13
A61K-038/16
출원번호
US-0800358
(2007-05-04)
등록번호
US-8278264
(2012-10-02)
발명자
/ 주소
Rothbard, Jonathan B.
Wender, Paul A.
McGrane, P. Leo
Sista, Lalitha V. S.
Kirschberg, Thorsten A.
출원인 / 주소
Kai Pharmaceuticals, Inc.
대리인 / 주소
Morrison & Foerster LLP
인용정보
피인용 횟수 :
3인용 특허 :
29
초록▼
This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier.
This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length (for example, SEQ ID NO:86).
대표청구항▼
1. A method for enhancing delivery of a compound into and across an animal ocular tissue, the method comprising: administering to the ocular tissue a conjugate comprising the compound and a delivery-enhancing transporter,wherein the delivery-enhancing transporter comprises fewer than 50 subunits and
1. A method for enhancing delivery of a compound into and across an animal ocular tissue, the method comprising: administering to the ocular tissue a conjugate comprising the compound and a delivery-enhancing transporter,wherein the delivery-enhancing transporter comprises fewer than 50 subunits and comprises at least 5 guanidino or amidino moieties, thereby increasing delivery of the conjugate into the ocular tissue compared to delivery of the compound in the absence of the delivery-enhancing transporter. 2. The method of claim 1, wherein delivery of the conjugate into the ocular tissue is increased at least two-fold compared to delivery of the compound in the absence of the delivery-enhancing transporter. 3. The method of claim 1, wherein delivery of the conjugate into the ocular tissue is increased at least ten-fold compared to delivery of the compound in the absence of the delivery-enhancing transporter. 4. The method of claim 1, wherein the ocular tissue is one or more layers of epithelial or endothelial tissue. 5. The method of claim 1, wherein the ocular tissue is the retina. 6. The method of claim 1, wherein the ocular tissue is the optic nerve. 7. The method of claim 1, wherein the subunits are amino acids. 8. The method of claim 1, wherein the conjugate comprises at least two delivery-enhancing transporters. 9. The method of claim 1, wherein the conjugate is administered as an eye drop. 10. The method of claim 1, wherein the conjugate is administered as an injection. 11. The method of claim 1, wherein the delivery-enhancing transporter comprises a non-peptide backbone. 12. The method of claim 1, wherein the delivery-enhancing transporter is not attached to an amino acid sequence to which the delivery enhancing transporter molecule is attached in a naturally occurring protein. 13. The method of claim 1, wherein the delivery-enhancing transporter comprises from 5 to 25 guanidino or amidino moieties. 14. The method of claim 13, wherein the delivery-enhancing transporter comprises between 7 and 15 guanidino moieties. 15. The method of claim 13, wherein the delivery-enhancing transporter comprises at least 6 contiguous guanidino and/or amidino moieties. 16. The method of claim 1, wherein the delivery-enhancing transporter consists essentially of 5 to 50 amino acids, at least 50 percent of which amino acids are arginines or analogs thereof. 17. The method of claim 16, wherein the delivery-enhancing transporter comprises 5 to 25 arginine residues or analogs thereof. 18. The method of claim 17, wherein at least one arginine is a D-arginine. 19. The method of claim 18, wherein all of the arginines are D-arginines. 20. The method of claim 16, wherein at least 70 percent of the amino acids that comprise the delivery-enhancing transporter are arginines or arginine analogs. 21. The method of claim 16, wherein the delivery-enhancing transporter is seven contiguous D-arginines. 22. The method of claim 1, wherein the compound is a therapeutic for a disease selected from the group consisting of bacterial infections, viral infections, fungal infections, glaucoma, anterior uveitis, intermediate uveitis, posterior uveitis, optic neuritis, Leber's neuroretinitis, retinitis, pseudotumor/myositis, orbital myositis, hemangioma/lymphangioma, toxocariasis, Behcet's panuveitis, inflammatory chorioretinopathies, vasculitis, dry eye syndrome (Sjögren's syndrome), corneal edema, accommodative esotropia, cycloplegia, mydriasis, reverse mydriasis, and macular degeneracy. 23. The method of claim 1, wherein the compound is selected from the group consisting of anti-bacterial compounds, anti-viral compounds, anti-fungal compounds, anti-protozoan compounds, anti-histamines, compounds that dilate the pupil, anesthetic compounds, steroidal antiinflammatory agents, antiinflammatory analgesics, chemotherapeutic agents, hormones, anticataract agents, neovascularization inhibitors, immunosuppressants, protease inhibitors, aldose reductase inhibitors, corticoid steroids, cholinergic agents, anticholinesterase agents, muscarinic antagonists, sympathomimetic agents, alpha-adrenergic antagonists, beta-adrenergic antagonists, and anti-angiogenic factors. 24. The method of claim 23, wherein the compound is selected from the group consisting of acyclovir and cyclosporins. 25. The method of claim 1, wherein the compound is transported across the blood-brain barrier. 26. The method of claim 1, wherein the ocular tissue is one or more layers of epithelial and one or more layers of endothelial tissue. 27. The method of claim 1, wherein the ocular tissue is one or more layers of epithelial tissue. 28. The method of claim 1, wherein the ocular tissue is one or more layers of endothelial tissue.
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이 특허에 인용된 특허 (29)
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Rothbard, Jonathan B.; Wender, Paul A.; McGrane, P. Leo; Sista, Lalitha V. S.; Kirschberg, Thorsten A., Compositions and methods for enhancing drug delivery across and into epithelial tissues.
Rothbard, Jonathan B.; Wender, Paul A.; McGrane, P. Leo; Sista, Lalitha V. S.; Kirschberg, Thorsten A., Compositions and methods for enhancing drug delivery across and into epithelial tissues.
Rothbard, Jonathan B.; Wender, Paul A.; McGrane, P. Leo; Sista, Lalitha V. S.; Kirschberg, Thorsten A., Compositions and methods for enhancing drug delivery across and into epithelial tissues.
Rothbard,Jonathan B.; Wender,Paul A.; McGrane,P. Leo; Sista,Lalitha V. S.; Kirschberg,Thorsten A., Compositions and methods for enhancing drug delivery across and into ocular tissues.
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Rothbard, Jonathan B.; Wender, Paul A.; McGrane, P. Leo; Sista, Lalitha V. S.; Kirschberg, Thorsten A., Compositions and methods for enhancing drug delivery across and into epithelial tissues.
Rothbard, Jonathan B.; Wender, Paul A.; McGrane, Leo P.; Sista, Lalitha V. S.; Kirschberg, Thorsten A., Compositions and methods for enhancing drug delivery across and into ocular tissues.
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