초록 ▼

Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In variou

Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In various embodiments, the invention also discloses compositions and devices that may further include a targeting agent, such as a polypeptide that is reactive with an FGF receptor (e.g., bFGF), or another ligand that binds to cell surface receptors on neuronal cells, or a support cell. The invention also discloses methods of promoting neuronal survival and regeneration via transfection of an axon as it grows through a device or composition of the present invention, or via transfection of a repair cell.

대표청구항 ▼

Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In variou

Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In various embodiments, the invention also discloses compositions and devices that may further include a targeting agent, such as a polypeptide that is reactive with an FGF receptor (e.g., bFGF), or another ligand that binds to cell surface receptors on neuronal cells, or a support cell. The invention also discloses methods of promoting neuronal survival and regeneration via transfection of an axon as it grows through a device or composition of the present invention, or via transfection of a repair cell. 9 A, Sep. 2000, Anonymous.* "Photostable Cosmetic Light Screening Composition", Author: Anon. Organization, UK Publication Source, Research Disclosure (1999), 418(Feb.), P175 (No. 41803). Identifier-CODEN RSDSBB ISSN 0374-4363 Publisher Kenneth Mason Publications Ltd. Patent Information. "Polyester And Copolyester Sheeting, Film And Structured Products Stabilized Against Degradation By Sunlight Or Other UV Light Sources", Author: Anon. Organization, Research Disclosure (1994), (Nov.), P601 (No. 36708). Fox , Charles, Fox Associates, Fair Lawn, New Jersey, "Gels and Sticks Review and Update", Cosmetics & Toiletries, vol. 99, Nov. 1984 (pp. 19, 20, 22, 24, 25, 28-30, 32, 34, 36, 38, 40, 42, 44, 47, 48, 50, 52, 54). Fox, Charles, Charles Fox Associates Inc., Fair Lawn New Jersey, "Antiperspirants & Deodorants Review and Update" Cosmetics & Toiletries, vol. 100, Dec. 1985 (pp. 27-33, 35-36, 40-41). "Deodorant & Antiperspirant Formulary", Cosmetics & Toiletries, vol. 100, Dec. 1985 (pp. 65-75). Goldemberg, et al., "Silicones In Clear Formulations", D&CI, Feb. 1986, (pp. 34, 38, 40, 44). STN, File Supplier, Karlsruhe, DE, File Chemical Abstracts, vol. 130, AN=158258 see the abstract XP002126186 & Research Disclosure, No. 418003, Feb. 10, 1999, p. 175 UK the whole document. Database WPI, Section Ch, Week 200114, Derwent Publications Ltd., London, GB; Class A96, AN 2001-135326 XP002166356 Anonymous: "Cosmetic emulsions containing amino acids to prevent photochemical reactions are stabilized by addition of oils such as fatty acid esters or silicones" abstract & Research Disclosure, vol. 437, No. 019, Sep. 10, 2000 Emsworth, GB. Zouboulis, Christos C., (Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Berlin, Germany) "Retinoids: Is there a New Approach?", IFSCC Magazine--vol. 3, No. 3/2000, pp. 9-19. Zatz, Joel L., "Skin Delivery of Retinoids--Reducing The Skin Irritancy of Topical Retinoids", .COPYRGT. 1998, 1999 Joel L. Zatz (pp. 1-8) (http://www-rci.rutgers.edu/＿zatz/SkinPermeation?Retinoids.html. Weber, Fritz et al.--"Vitamin A and Retinoids", (pp. 1-3) http://www.chem.qmw.ac.uk/iubmb/newsletter/1996/news2.html; 1996. Maddin, S. MD, et al.--"Isotretinoin improves the appearance of photodamaged skin: Results of a 36-week, multicenter, double-blind, placebo-controlled trail" Journal Of The American Academy Of Dermatology, Jan. 2000, Part 1 。 vol. 42 。 No. 1 (pp. 1-13) http://www.eblue.org/scripts/om.dll/serve . . . . SIGMA .COPYRGT. ProductInformation (all trans-RETINOIC ACID Sigma Prod. No. R2625 Oct. 8, 1996--ARO pp. 1-3. Quigley, et al., "Reduced skin irritation with tretinoin containing polyolprepolymer-2, a new topical tretinoin delivery system: A sumary of preclinical and clinical investigations", Bertek Pharmaceuticals http://www.bertek.com/article_reprints/resources/skin_irritation.html Apr. 1998. Kang, Sewon, M.D., et al., "Photoaging therapy with topical tretinoin: an evidence-based analysis", Journal Of The American Academy Of Dermatology, Aug. 1998, Part ○ vol. 39 ○ No. 2 (pp. 1-9) http://www.eblue.org/scripts/om.dll/serve . . . Kligman, Albert M., MD, PhD., "Topical treatments for photoaged skin--separating the reality from the hype", Postraduate Medicin: Skin Disorders Symposium: Topical treatments for photoaged skin, vol. 102 / No. 2 / Aug. 1997 / Postgraduate Medicine p. 1-8 http://www.postgradmed.com/issues/1997/08_97/Kligman.htm. Kligman, Albert M., MD, PhD., "The growing importance of topical retinoids in clinical dermatology: a retrospective and prospective analysis" Journal Of The American Academy Of Dermatology, Aug. 1998, Part 3 。 Volume 39 。 No. 2 (pp. 1-7). http://www.eblue.org/scripts/om.dll/serve . . . . Hamilton, Joan O'C, "Lilly gets a Vitamin $hot from Ligan--The Retinoid Renaissance", SIGNALS Article: The Retinoid Renaissance, published Dec. 3, 1997 (pp. 1-9) http://www.signalsmag.com/signalsmag.nsf/0/665D05084647BA28825656A0 06B0F9D. Moss, G.P. (World Wide Web versions prepared by)--Department of Chemistry, Queen Mary and Westfield College, United Kingdom, "Nomenclature of Retinoids--Recomendations 1981)", International Union Of Pure And Applied Chemistry And International Union Of Biochemistry And Molecular Biology, IUPAC-IUB Joint Commission On Biochemical Nomenclature (JCBN) pp. 1-10 http://www.chem.qmw.ac.uk/iupac/misc/ret.html; 1981. "Retinoids", Molecular Medicine--News from Research Laboratories--pp. 1-2 http://www.aston.it/biomedicine/biom0054.htm Dec. 1997. 014875, WO; WO96/017053, WO; WO96/018418, WO; WO96/033282, WO; WO96/034969, WO; WO96/036365, WO; WO97/001358, WO; WO97/029201, WO; WO98/035028, WO; WO98/039465, WO; WO98/039466, WO; WO98/039467, WO a vasoactive peptide, an antisense agent, an oligonucleotide, DNase, a cyclosporin, ribavirin or a mixture of any of the foregoing medicaments. 9. The formulation as defined in claim 7 wherein said medicament is selected from the group consisting of an insulin, an insulin analog, an amylin, glucagon, LH-RH, deltirex, leuprolide, gosorelin, nafarelin, octreotide, somatostatin, a calcitonin, parathyroid hormone, TRH, growth hormone-releasing hormone, G-CSF, G-SF, a cytokine, rhDNAse, a heparin, an oligoneucleotide, ribavirin, glucagon, acetohexamide, chiorpropamide, tolazemide, tolbutamide, glipizide, glyburide, metformin, phentolamine, tumor neurosis factor (TNF), nerve growth factor (NGF), macrophage-colony stimulating factor (M-CSF), heparinase, bone morphogenic protein (BMP), hANP, glucagon-like peptide (GLP-1), renin, bradykinin, a bacitracin, a polymyxin, a colistin, tyrocidine, a gramicidin, a monoclonal antibody, a vaccine or a mixture of any of the foregoing medicaments. 10. The formulation as defined in claim 6 wherein said polymer is present in an amount of about 0.000001 to about 10 percent by weight of the total weight of the formulation. 11. The formulation as defined in claim 1 wherein said fluid carrier is selected from the group of propellants consisting of 1,1,1,2-tetrafluoethane, 1,1,1,2,3,3,3-heptafluoropropane or a mixture thereof. 12. The formulation as defined in claim 1 wherein said fluid carrier is a compressed gas selected from the group consisting of air, carbon dioxide, nitrogen and a mixture of any of the foregoing compressed gases. 13. The formulation as defined in claim 1 wherein said fluid carrier is a hydrocarbon selected from the group consisting of n-butane, propane, isopentene and a mixture of any of the foregoing hydrocarbons. 14. The formulation as defined in claim 1 wherein said fluid carrier is a chlorofluorocarbon selected from the group consisting of propellant 11, propellant 12, propellant 114 and a mixture of any of the foregoing propellants. 15. The formulation as defined in claim 1 wherein said stabilizer is present in an amount ranging from about 300 parts by weight to about 2000 parts by weight to the total weight of the formulation. 16. A method of preparing a stable medicinal aerosol formulation according to claim 1, which comprises, a. combining said selected medicament with said polymer to form said polymeric construct, wherein said medicament is associated with said polymer in an amount sufficient to provide a plurality of therapeutically effective doses; b. combining said stabilizer with said construct to form a stabilizer combined construct; c. combining said construct with a fluid carrier, where said carrier is present in an amount sufficient to transport and deliver a plurality of said therapeutically effective doses, to form a mixture; and d. dispersing said mixture. 17. A method of treating in a human being or another animal a condition capable of treatment by oral or nasal inhalation, which comprises; administering a formulation according to claim 1 to said human being or animal by oral or nasal inhalation. 18. A formulation according to claim 1 in an aerosol canister equipped with a metered dose valve. 19. A metered dose inhaler containing a modulated release medicinal formulation, the formulation consisting essentially of, a. a particulate medicament in a therapeutically effective amount; b. a polysaccharide polymer with which said particulate medicament is associated to form a particulate polymeric construct; c. a fluid carrier for containing and transporting said particulate polymeric construct; and d. a suitable stabilizer selected from the group consisting of a first stabilizer, a second stabilizer and a mixture of the foregoing stabilizers present in an amount sufficient to stabilize the formulation to prevent settling, creaming or flocculation thereof for a time sufficient to allow reproducible dosing of said associated medicament after agita