Combined systemic and topical treatment of disordered tissues
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A01N-043/04
A61K-031/70
A61K-031/522
A61K-031/14
A61K-031/7072
A61K-009/00
A61K-045/06
A61K-031/52
A61K-031/662
A61K-031/675
A61K-031/7125
A61K-031/7052
A61K-031/7076
A61K-031/706
A61K-031/7064
출원번호
US-0823830
(2015-08-11)
등록번호
US-9545408
(2017-01-17)
발명자
/ 주소
Johnson, B. Ron
출원인 / 주소
QUADEX PHARMACEUTICALS, INC.
대리인 / 주소
Workman Nydegger
인용정보
피인용 횟수 :
0인용 특허 :
116
초록▼
Kits and methods for treating disordered or infected tissue caused by a virus in a mammal involve co-administering a systemic anti-virus drug and topically administered anti-infective composition. The systemic anti-virus drug is internally administered and disrupts or inhibits virus replication syst
Kits and methods for treating disordered or infected tissue caused by a virus in a mammal involve co-administering a systemic anti-virus drug and topically administered anti-infective composition. The systemic anti-virus drug is internally administered and disrupts or inhibits virus replication systemically within the mammal. Examples include nucleoside analogs, nucleoside analog precursors, and nucleotide analogs. The topically administered anti-infective composition includes at least one anti-infective agent, such as an organohalide (e.g., benzalkonium chloride), and is formulated to penetrate below the skin surface and allow the anti-infective agent to kill viruses at the infected tissue site. The topical anti-infective composition renders the systemic anti-virus drug more efficacious and reduces the time and/or number of dosages otherwise required for the systemic anti-virus drug to treat the disordered tissue. In some cases, the topical anti-infective composition is more beneficial than the systemic anti-virus drug in killing viruses and can reduce or eliminate post-herpetic neuralgia.
대표청구항▼
1. A kit for use in treating a skin infection of a mammal infected by a virus that causes disordered tissue, including a skin infection in prodromal stage and/or with blisters or lesions, the kit comprising: a systemic treatment composition formulated for systemic administration, including at least
1. A kit for use in treating a skin infection of a mammal infected by a virus that causes disordered tissue, including a skin infection in prodromal stage and/or with blisters or lesions, the kit comprising: a systemic treatment composition formulated for systemic administration, including at least one of oral administration, subcutaneous administration, intramuscular administration, intravenous administration, intradermal administration, intrathecal administration, or epidural administration, the systemic treatment composition comprising an effective amount of a systemic anti-virus drug that, when systemically administered to a mammal in need thereof, provides systemic anti-viral activity and disrupts or inhibits virus replication systemically within the mammal, wherein the systemic anti-virus drug is selected from the group consisting of:aciclovir (2-amino-1,9-dihydro-9-((2-hydroxyethoxy)methyl)-6H-purin-6-one);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of aciclovir;aciclovir phosphate derivatives selected from the group consisting of: aciclovir monophosphate (ACV-MP);aciclovir diphosphate (ACV-DP);aciclovir monophosphate glycerol (ACV-MP-G);aciclovir diphosphate glycerol (ACV-DP-G);aciclovir monophosphate morpholidate (ACV-MP-morpholine);aciclovir monophosphate isopropylidene glycerol (ACV-MP-isoP-G); andaciclovir diphosphate isopropylidene glycerol (ACV-DP-isoP-G);aciclovir amino acid ester derivatives selected from the group consisting of: aciclovir amino acid esters;aciclovir glycine ester;aciclovir alanine ester; andaciclovir valine ester;aciclovir derivatives selected from the group consisting of:3R-(3α,4β,5α)]-2-amino-1,9-dihydro-9-tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]-6H-purin-6-one;[3R-(3α,4β,5α)]-5-methyl-1-[tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]2,4(1H,3H)pyrimidinedione;[3R-(3α,4β,5α)]-4-amino-1-[tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]-2(1H)-pyrimidinone; and[3R-(3α,4β,5α)]-1-[tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]-2,4(1H,3H)pyrimidinedione;valaciclovir ((S)-2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl-2-amino-3-methylbutanoate);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of valaciclovir;valaciclovir derivatives selected from the group consisting of:2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl N-[(benzyloxy)carbonyl]L-valinate;2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate;2-(2-Amino-1,6-dihydro-6-oxo-9H(purin-9-yl)methoxy)ethyl L-valinate hydrochloride monohydrate;2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl N-[(benzyloxy)carbonyl]L-valinate; and2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate hydrochloride monohydrate;penciclovir (2-amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-6,9-dihydro-3H-purin-6-one);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of penciclovir;penciclovir derivatives selected from the group consisting of:2-Amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]-6H-purine;2-Amino-6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-purine;9-[4-Hydroxy-3-(hydroxymethyl)but-1-yl]guanine;9-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine;7-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine;9-(4-Hydroxy-3-hydroxymethylbut-1-yl)guanine, sodium salt;9-(4-Hydroxy-3-hydroxymethylbut-1-yl)guanine, potassium salt;2-Amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine hydrochloride;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-methoxypurine;2-Amino-6-ethoxy-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine;2-Amino-6-benzyloxy-9-(4-hydroxy-3-hydroxymethylbut-1-yl) purine;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-thiopurine;2-Amino-6-azido-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-purine;2,6-Diamino-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]purine;2,6-Diamino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine;9-(4-Acetoxy-3-acetoxymethylbut-1-yl)guanine;9-(4-Propionyloxy-3-propionyloxymethylbut-1-yl)guanine;N2-Propionyl-9-(4-propionyloxy-3-propionyloxymethyl-but-1-yl)guanine;9-(4-Hexanoyloxy-3-hexanoyloxymethylbut-1-yl)guanine;9-(4-Formyloxy-3-formyloxymethylbut-1-yl)guanine;9-[4-(N-Imidazolylcarbonyloxy)-3-(N-imidazolylcarbonyloxymethyl)-but-1-yl]guanine;N2-Monomethoxytrityl-9-(4-monomethoxytrityloxy-3-hydroxymethylbut-1-yl)guanine;N2-Monomethoxytrityl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-guanine;9-(4-Pivalyloxy-3-pivalyloxymethylbut-1-yl)guanine;9-(4-Acetoxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Benzoyloxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Hexanoyloxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Hexadecanoyloxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Hydroxy-3-hydroxymethylbut-1-yl)guanine 4′-phosphate, diammonium salt;N2-Acetyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine;N2-Hexanoyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-isopropoxypurine; and2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-phenoxypurine;famciclovir (2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of famciclovir;famciclovir derivatives selected from the group consisting of:2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(4-acetoxy-3-acetoxymethylbut-1-yl)purine;2-amino-9-(4-acetoxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(3-hydroxymethyl-4-methoxycarbonyloxybut-1-yl)purine;2-amino-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]purine;2-amino-9-(4-propionyloxy-3-propionyloxymethylbut-1-yl)purine;2-amino-9-(4-butyryloxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(4-benzoyloxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine 4′-phosphate; and2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine 4′:4″phosphate;ganciclovir (2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-3H-purin-6-one);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of ganciclovir;cidofovir (({[(S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of cidofovir;adefovir ({[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}phosphonic acid);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of adefovir;tenofovir (({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl) phosphonic acid);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of tenofovir; andcombinations thereof; anda topical treatment composition separate from the systemic treatment composition and formulated for topical administration to an infection site in order to kill viruses at the infection site without entering the bloodstream of the mammal, the topical treatment composition comprising benzalkonium chloride in an amount so as to kill viruses at the infection site and a tissue penetrating liquid carrier comprising water and an organic solvent that promotes penetration of the topical treatment composition into the infection site of the mammal and below the skin surface so as to allow the topical treatment composition to kill viruses at the infection site independent of the systemic anti-viral activity of the systemic anti-virus drug. 2. The kit of claim 1, the systemic treatment composition further comprising at least one additional systemic anti-virus drug selected from the group consisting of idoxuridine, 4-oxo-dihydroquinones, fomivirsen, pyrazoloquinoline, benzothiophene, acridones, thiourea inhibitors, phenylenediamine-sulfonamides, ribosylbenzimazoles, roscovitine, cyclooxygenase inhibitors, and forscarnet. 3. The kit of claim 1, further comprising an applicator for use in topically administering the topical treatment composition to the skin infection. 4. The kit of claim 1, wherein the systemic anti-virus drug comprises acyclovir. 5. The kit of claim 1, wherein the systemic anti-virus drug comprises valaciclovir. 6. The kit of claim 1, the topical treatment composition further comprising at least one of an organohalide, decosanol, iodine, nucleoside analogue, or nucleotide analogue. 7. The kit of claim 1, wherein the water and organic solvent are a tissue penetrating component. 8. The kit of claim 7, wherein the organic solvent comprises a lower alkyl solvent. 9. The kit of claim 8, wherein the lower alkyl solvent comprises at least one of isopropyl alcohol, ethyl alcohol, or acetone. 10. The kit of claim 7, wherein the topical treatment composition is free of oils or other compounds that inhibit penetration. 11. The kit of claim 1, wherein the kit comprises a plurality of dosages of the systemic anti-virus drug for periodic administration over a prescribed period of time. 12. The kit of claim 11, wherein the number of dosages of the systemic anti-virus drug is reduced by at least about 10% compared to a prescription comprising the systemic anti-virus drug in the absence of topical administration of the topical treatment composition. 13. The kit of claim 11, wherein the number of dosages of the systemic anti-virus drug is reduced by at least about 20% compared to a prescription comprising the systemic anti-virus drug in the absence of topical administration of the topical treatment composition. 14. The kit of claim 11, wherein the number of dosages of the systemic anti-virus drug is reduced by at least about 30% compared to a prescription comprising the systemic anti-virus drug in the absence of topical administration of the topical treatment composition. 15. The kit of claim 1, wherein the kit comprises 5 dosages or less of the topical treatment composition. 16. The kit of claim 1, wherein the kit comprises 3 dosages or less of the topical treatment composition. 17. The kit of claim 1, wherein the kit comprises a single dosage of the topical treatment composition. 18. The kit of claim 1, wherein the topical treatment composition further comprises at least one topical anesthetic. 19. The kit of claim 18, wherein the at least one topical anesthetic is included in an amount so as to enhance efficacy of the topical treatment composition in treating the skin infection and accelerate healing. 20. The kit of claim 18, wherein the at least one topical anesthetic is selected from the group consisting of benzocaine, butamben, dibucaine, lidocaine, oxybuprocaine, pramoxine, proparacaine, proxymetacaine, novocaine, tetracaine, and combinations thereof. 21. A kit for use in treating a skin infection of a mammal infected by a virus that causes disordered tissue, including a skin infection in prodromal stage and/or with blisters or lesions, the kit comprising: a systemic treatment composition formulated for systemic administration, including at least one of oral administration, subcutaneous administration, intramuscular administration, intravenous administration, intradermal administration, intrathecal administration, or epidural administration, the systemic treatment composition comprising an effective amount of a systemic anti-virus drug that, when systemically administered to a mammal in need thereof, provides systemic anti-viral activity and disrupts or inhibits virus replication systemically within the mammal, wherein the systemic anti-virus drug comprises valaciclovir or a pharmaceutically acceptable salt, phosphate ester, or acyl derivative of valaciclovir; anda topical treatment composition separate from the systemic treatment composition and formulated for topical administration to an infection site in order to kill viruses at the infection site without entering the bloodstream of the mammal, the topical treatment composition comprising a quaternary ammonium halide compound and a tissue penetrating liquid carrier comprising an organic solvent that promotes penetration of the anti-infective composition into the infection site of the mammal and below the skin surface so as to allow the topical treatment composition to kill viruses at the infection site independent of the systemic anti-viral activity of the systemic anti-virus drug. 22. The kit of claim 21, wherein the quaternary ammonium halide compound comprises benzalkonium chloride. 23. The kit of claim 21, wherein the benzalkonium chloride has the following formula: wherein n=8, 10, 12, 14, 16, or 18. 24. The kit of claim 23, wherein the benzalkonium chloride includes a mixture of benzalkonium chloride compounds in which n=12, 14, and 16. 25. A kit for use in treating a skin infection of a mammal infected by a virus that causes disordered tissue, including a skin infection in prodromal stage and/or with blisters or lesions, the kit comprising: a systemic treatment composition formulated for systemic administration, including at least one of oral administration, subcutaneous administration, intramuscular administration, intravenous administration, intradermal administration, intrathecal administration, or epidural administration, the systemic treatment composition comprising an effective amount of a systemic anti-virus drug that, when systemically administered to a mammal in need thereof, provides systemic anti-viral activity and disrupts or inhibits virus replication systemically within the mammal, wherein the systemic anti-virus drug comprises aciclovir or a pharmaceutically acceptable salt, phosphate ester, or acyl derivative of aciclovir; anda topical treatment composition separate from the systemic treatment composition and formulated for topical administration to an infection site in order to kill viruses at the infection site without entering the bloodstream of the mammal, the topical treatment composition comprising a quaternary ammonium halide compound and a tissue penetrating liquid carrier comprising an organic solvent that promotes penetration of the anti-infective composition into the infection site of the mammal and below the skin surface so as to allow the topical treatment composition to kill viruses at the infection site independent of the systemic anti-viral activity of the systemic anti-virus drug. 26. The kit of claim 1, wherein the systemic anti-virus drug is selected from the group consisting of: aciclovir (2-amino-1,9-dihydro-9-((2-hydroxyethoxy)methyl)-6H-purin-6-one);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of aciclovir;aciclovir phosphate derivatives selected from the group consisting of: aciclovir monophosphate (ACV-MP);aciclovir diphosphate (ACV-DP);aciclovir monophosphate glycerol (ACV-MP-G);aciclovir diphosphate glycerol (ACV-DP-G);aciclovir monophosphate morpholidate (ACV-MP-morpholine);aciclovir monophosphate isopropylidene glycerol (ACV-MP-isoP-G); andaciclovir diphosphate isopropylidene glycerol (ACV-DP-isoP-G);aciclovir amino acid ester derivatives selected from the group consisting of: aciclovir amino acid esters;aciclovir glycine ester;aciclovir alanine ester; andaciclovir valine ester;aciclovir derivatives selected from the group consisting of:3R-(3α,4β,5α)]-2-amino-1,9-dihydro-9-tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]-6H-purin-6-one;[3R-(3α,4β,5α)]-5-methyl-1-[tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]2,4(1H,3H)pyrimidinedione;[3R-(3α,4β,5α)]-4-amino-1-[tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]-2(1H)-pyrimidinone;[3R-(3α,4β,5α)]-1-[tetrahydro-4-hydroxy-5-(hydroxymethyl)-3-furanyl]-2,4(1H,3H)pyrimidinedione; andcombinations thereof. 27. The kit of claim 1, wherein the systemic anti-virus drug is selected from the group consisting of: valaciclovir ((S)-2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl-2-amino-3-methylbutanoate);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of valaciclovir;valaciclovir derivatives selected from the group consisting of:2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl N-[(benzyloxy)carbonyl] L-valinate;2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate;2-(2-Amino-1,6-dihydro-6-oxo-9H(purin-9-yl)methoxy)ethyl L-valinate hydrochloride monohydrate;2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl N-[(benzyloxy)carbonyl] L-valinate; and2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl L-valinate hydrochloride monohydrate; and combinations thereof. 28. The kit of claim 1, wherein the systemic anti-virus drug is selected from the group consisting of: penciclovir (2-amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-6,9-dihydro-3H-purin-6-one);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of penciclovir;penciclovir derivatives selected from the group consisting of:2-Amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]-6H-purine;2-Amino-6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-purine;9-[4-Hydroxy-3-(hydroxymethyl)but-1-yl]guanine;9-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine;7-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine;9-(4-Hydroxy-3-hydroxymethylbut-1-yl)guanine, sodium salt;9-(4-Hydroxy-3-hydroxymethylbut-1-yl)guanine, potassium salt;2-Amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine hydrochloride;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-methoxypurine;2-Amino-6-ethoxy-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine;2-Amino-6-benzyloxy-9-(4-hydroxy-3-hydroxymethylbut-1-yl) purine;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-thiopurine;2-Amino-6-azido-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-purine;2,6-Diamino-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]purine;2,6-Diamino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine;9-(4-Acetoxy-3-acetoxymethylbut-1-yl)guanine;9-(4-Propionyloxy-3-propionyloxymethylbut-1-yl)guanine;N2-Propionyl-9-(4-propionyloxy-3-propionyloxymethyl-but-1-yl)guanine;9-(4-Hexanoyloxy-3-hexanoyloxymethylbut-1-yl)guanine;9-(4-Formyloxy-3-formyloxymethylbut-1-yl)guanine;9-[4-(N-Imidazolylcarbonyloxy)-3-(N-imidazolylcarbonyloxymethyl)-but-1-yl]guanine;N2-Monomethoxytrityl-9-(4-monomethoxytrityloxy-3-hydroxymethylbut-1-yl)guanine;N2-Monomethoxytrityl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-guanine;9-(4-Pivalyloxy-3-pivalyloxymethylbut-1-yl)guanine;9-(4-Acetoxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Benzoyloxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Hexanoyloxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Hexadecanoyloxy-3-hydroxymethylbut-1-yl)guanine;9-(4-Hydroxy-3-hydroxymethylbut-1-yl)guanine 4′-phosphate, diammonium salt;N2-Acetyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine;N2-Hexanoyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-isopropoxypurine;2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)-6-phenoxypurine; andcombinations thereof. 29. The kit of claim 1, wherein the systemic anti-virus drug is selected from the group consisting of: famciclovir (2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate);pharmaceutically acceptable salts, phosphate esters, and acyl derivatives of famciclovir;famciclovir derivatives selected from the group consisting of:2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(4-acetoxy-3-acetoxymethylbut-1-yl)purine;2-amino-9-(4-acetoxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(3-hydroxymethyl-4-methoxycarbonyloxybut-1-yl)purine;2-amino-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]purine;2-amino-9-(4-propionyloxy-3-propionyloxymethylbut-1-yl)purine;2-amino-9-(4-butyryloxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(4-benzoyloxy-3-hydroxymethylbut-1-yl)purine;2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine 4′-phosphate;2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine 4′:4″phosphate; andcombinations thereof.
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