WO1998020872B1 - Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infections - Google Patents
Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infectionsInfo
- Publication number
- WO1998020872B1 WO1998020872B1 PCT/DK1997/000524 DK9700524W WO9820872B1 WO 1998020872 B1 WO1998020872 B1 WO 1998020872B1 DK 9700524 W DK9700524 W DK 9700524W WO 9820872 B1 WO9820872 B1 WO 9820872B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hpid
- pharmaceutical formulation
- titer
- millimolar
- formulation according
- Prior art date
Links
- 235000014113 dietary fatty acids Nutrition 0.000 title claims abstract 16
- 239000000194 fatty acid Substances 0.000 title claims abstract 16
- 239000003795 chemical substances by application Substances 0.000 title claims abstract 15
- 150000004665 fatty acids Chemical class 0.000 title claims abstract 12
- 201000009910 diseases by infectious agent Diseases 0.000 title claims abstract 4
- 150000002191 fatty alcohols Chemical class 0.000 title claims 6
- 210000004877 mucosa Anatomy 0.000 title claims 3
- BVDRUCCQKHGCRX-UHFFFAOYSA-N 2,3-dihydroxypropyl formate Chemical class OCC(O)COC=O BVDRUCCQKHGCRX-UHFFFAOYSA-N 0.000 title abstract 2
- 230000001225 therapeutic Effects 0.000 title 1
- 239000012049 topical pharmaceutical composition Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 67
- 239000000203 mixture Substances 0.000 claims abstract 65
- 238000009472 formulation Methods 0.000 claims abstract 56
- 241000700605 Viruses Species 0.000 claims abstract 23
- 239000002904 solvent Substances 0.000 claims abstract 16
- -1 e.g. lauric acid Chemical class 0.000 claims abstract 15
- 239000000017 hydrogel Substances 0.000 claims abstract 13
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims abstract 12
- 150000002632 lipids Chemical class 0.000 claims abstract 10
- POULHZVOKOAJMA-UHFFFAOYSA-N Lauric acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims abstract 8
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 claims abstract 7
- 230000003641 microbiacidal Effects 0.000 claims abstract 7
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 claims abstract 6
- 239000012528 membrane Substances 0.000 claims abstract 5
- 239000005639 Lauric acid Substances 0.000 claims abstract 4
- 210000003491 Skin Anatomy 0.000 claims abstract 4
- 241000894006 Bacteria Species 0.000 claims abstract 3
- 241000233866 Fungi Species 0.000 claims abstract 3
- 210000004392 Genitalia Anatomy 0.000 claims abstract 3
- 241000124008 Mammalia Species 0.000 claims abstract 3
- 150000001875 compounds Chemical group 0.000 claims 35
- 238000004113 cell culture Methods 0.000 claims 30
- 230000000875 corresponding Effects 0.000 claims 30
- 239000003349 gelling agent Substances 0.000 claims 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 11
- 241000606153 Chlamydia trachomatis Species 0.000 claims 10
- 230000001580 bacterial Effects 0.000 claims 10
- 241000700588 Human alphaherpesvirus 1 Species 0.000 claims 9
- 150000001298 alcohols Chemical class 0.000 claims 9
- 125000004432 carbon atoms Chemical group C* 0.000 claims 9
- 239000002736 nonionic surfactant Substances 0.000 claims 9
- 230000002335 preservative Effects 0.000 claims 9
- 239000003755 preservative agent Substances 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 9
- 239000011780 sodium chloride Substances 0.000 claims 9
- 125000004430 oxygen atoms Chemical group O* 0.000 claims 7
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims 6
- SECPZKHBENQXJG-FPLPWBNLSA-N Palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 claims 6
- 239000002253 acid Substances 0.000 claims 6
- 125000004433 nitrogen atoms Chemical group N* 0.000 claims 5
- 229920001515 polyalkylene glycol Polymers 0.000 claims 5
- 239000004480 active ingredient Substances 0.000 claims 4
- 230000000694 effects Effects 0.000 claims 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 4
- 229920001888 polyacrylic acid Polymers 0.000 claims 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 4
- VUKAUDKDFVSVFT-UHFFFAOYSA-N 2-[6-[4,5-bis(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)-6-methoxyoxan-3-yl]oxy-4,5-dimethoxy-2-(methoxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)-5-methoxyoxane-3,4-diol Chemical compound COC1C(OC)C(OC2C(C(O)C(OC)C(CO)O2)O)C(COC)OC1OC1C(COCC(C)O)OC(OC)C(OCC(C)O)C1OCC(C)O VUKAUDKDFVSVFT-UHFFFAOYSA-N 0.000 claims 3
- BBMFSGOFUHEVNP-UHFFFAOYSA-N 4-hydroxy-2-methylbenzoic acid Chemical compound CC1=CC(O)=CC=C1C(O)=O BBMFSGOFUHEVNP-UHFFFAOYSA-N 0.000 claims 3
- ALEVUYMOJKJJSA-UHFFFAOYSA-N 4-hydroxy-2-propylbenzoic acid Chemical compound CCCC1=CC(O)=CC=C1C(O)=O ALEVUYMOJKJJSA-UHFFFAOYSA-N 0.000 claims 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims 3
- 235000021319 Palmitoleic acid Nutrition 0.000 claims 3
- 229950008882 Polysorbate Drugs 0.000 claims 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims 3
- 229920003081 Povidone K 30 Polymers 0.000 claims 3
- 150000007513 acids Chemical class 0.000 claims 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 3
- 239000003443 antiviral agent Substances 0.000 claims 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 3
- 239000001913 cellulose Substances 0.000 claims 3
- 229920002678 cellulose Polymers 0.000 claims 3
- 150000004676 glycans Polymers 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 3
- 229920000642 polymer Polymers 0.000 claims 3
- 229920000193 polymethacrylate Polymers 0.000 claims 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims 3
- 229920001282 polysaccharide Polymers 0.000 claims 3
- 239000005017 polysaccharide Substances 0.000 claims 3
- 150000004804 polysaccharides Polymers 0.000 claims 3
- 229920000136 polysorbate Polymers 0.000 claims 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims 3
- 102000004169 proteins and genes Human genes 0.000 claims 3
- 108090000623 proteins and genes Proteins 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 150000002148 esters Chemical class 0.000 claims 2
- 150000002170 ethers Chemical class 0.000 claims 2
- 239000000499 gel Substances 0.000 claims 2
- 230000001717 pathogenic Effects 0.000 claims 1
- 208000009889 Herpes Simplex Diseases 0.000 abstract 1
- 241000700584 Simplexvirus Species 0.000 abstract 1
Abstract
The present invention relates to a method for counteracting infections caused by bacteria, fungi or virus such as Herpes Simplex Virus in skin or mucosal membranes, in particular genital membranes, of a mammal. The method comprises topically administering to the skin or mucosal membrane an effective amount of a formulation comprising a) at least one microbicidal lipid, b) at least one solubilizing agent which keeps the lipid dissolved in the formulation, and optionally c) a gel-forming agent. The formulation used in the method may suitably be in the form of a hydrogel. The microbicidal lipid is preferably a C6-18 fatty acid, such as e.g. lauric acid, or a derivative thereof, e.g. a monoglyceride such as capric acid 1-monoglyceride. The solubilizing agent may suitably be a glycofurol such as the commercially available glycofurol 75. The invention also relates to novel pharmaceutical formulations for use in the method.
Claims
1. A method for preventing infection of the genital mucosa of a mammal, including a human, by virus, pathogenic bacteria or fungi, comprising topically administering, to the genital mucosa of the mammal, an effective prophylactic amount of a formulation comprising a hydrogel which contains a) at least one microbicidal lipid as an active ingredient, b) at least one water gelling agent, and c) at least one solubilizing agent which keeps the lipid dissolved in the hydrogel, the formulation being one which
when incubated for 5 minutes with HSV-1 in a titer of 100 million CCIDBO per ml in Cell
Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the virus titer, or which,
when incubated for 1 minute with HIV- 1 in a titer of 10 million CCIDβo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a hundred fold reduction of the virus titer, or which,
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the bacterial titer.
2. A method according to claim 1, wherein the lipid is selected from the group consisting of Cβ iβ fatty acids or salts thereof, Cβ- is fatty acid monoglycerides, Cβ iβ fatty acid esters of monohydric alcohols, Cβ- is fatty alcohols, and Cβ- is fatty alcohol monoglyceride ethers, the Cβ- is chain containing at least one double or triple bond when the number of carbon atoms thereof exceeds 15.
3. A method according to claim 2, wherein the hpid is selected from the group consisting of Cβ-π fatty acids or salts thereof, Cβ-u fatty acid monoglycerides, Cβ-u fatty acid esters of monohydric alcohols, CΘ-H fatty alcohols, and Cβ-w fatty alcohol monoglyceride ethers.
4. A method according to claim 3, wherein the fatty moieties are saturated.
5. A method according to any of the preceding claims, wherein the formulation is one which
when incubated for 5 minutes with HSV-1 in a titer of 100 million CCID∞ per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar lipid will cause at least a ten thousand fold reduction of the virus titer, or which, 66
when incubated for 1 minute with HIV- 1 in a titer of 10 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar lipid will cause at least a thousand fold reduction of the virus titer, or which,
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a ten thousand fold reduction of the bacterial titer.
6. A method according to claim 5, wherein the formulation is one which
when incubated for 5 minutes with HSV-1 in a titer of 100 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a hundred thousand fold reduction of the virus titer, or which,
when incubated for 1 minute with HIV-1 in a titer of 10 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a ten thousand fold reduction of the virus titer, or which,
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a hundred thousand fold reduction of the bacterial titer.
7. A method according to any of the preceding claims, wherein the hpid is selected from capric acid 1-monoglyceride, lauric acid and palmitoleic acid.
8. A method according to claim 7, wherein the hpid is capric acid 1-monoglyceride.
9. A method according to any of the preceding claims, wherein the solubihzing agent is selected from lower polyhydric alcohols, polyalkylene glycols, and polyhydroxy ether derivatives.
10. A method according to claim 9, wherein the solubihzing agent is a compound or compounds selected from the group consisting of compounds of the general formula I:
wherein n is an integer in the range from 1 to 4, m is an integer in the range from 1 to 15, and 67
wherein Ri designates a 5- or 6-membered ahphatic ring wherein from one to three carbon atoms may be replaced by nitrogen and/or oxygen atoms, said 5- or 6-membered ring optionally carrying from one to three substituents selected from the group consisting of halogen, amino, carboxy, and hydroxy;
and compounds of the general formula II:
R-(0-CH2-CH(CH3))k-OH (II)
wherein k is an integer in the range from 1 to 15, and
wherein Ri is as defined above.
11. A method according to claim 10, wherein n is 2 or 3, and R is H or R∑CH∑,
wherein R2 designates a 5- or 6-membered ahphatic ring wherein from one to three carbon atoms may be replaced by nitrogen and/or oxygen atoms.
12. A method according to claim 11 wherein n is 2, and
wherein R3 designates a 5- or 6-membered ahphatic ring wherein one or two carbon atoms may be replaced by oxygen atoms.
13. A method according to claim 12, wherein
14. A method according to any of claims 10- 13, wherein m is an integer in the range from 1 to 8. 68
15. A method according to claim 14, wherein the solubihzing agent is a compound or compounds selected from the group consisting of compounds of the general formula I
wherein m is an integer in the range from 1 to 4, and
and compounds of the general formula (II)
H-(0-CH2-CH(CH3))k-OH (II)
wherein k is an integer in the range from 1 to 4.
16. A method according to claim 15, wherein m is 1 or 2, and k is 1 or 2.
17. A method according to claim 15 or 16, wherein the solubilizing agent is selected from the group consisting of glycofurol 75, ethylene glycol and propylene glycol, and mixtures thereof.
18. A method according to claim 17, wherein the solubilizing agent is glycofurol 75.
19. A method according to any of the preceding claims, wherein the hpid is present in the formulation in a concentration of from about 1 to about 40 millimolar.
20. A method according to claim 19, wherein the hpid is present in the formulation in a concentration of about 5-30 millimolar.
21. A method according to claim 20, wherein the hpid is present in the formulation in a concentration of about 10-25 millimolar.
22. A method according to claim 21, wherein the hpid is present in the formulation in a concentration of about 20 millimolar. 69
23. A method according to any of the preceding claims, wherein the solubilizing agent is present in such a concentration in the range of about 5-70% by weight, based on the formulation, that the formulation, at room temperature, is substantially clear to the naked eye.
24. A method according to claim 23, wherein the solubilizing agent is present in a concentration of about 10-50% by weight, based on the formulation.
25. A method according to any of the preceding claims, wherein the hydrogel is a hydrogel established by means of a water gelling agent selected from the group consisting of polysaccharides, acryhc polymers, proteins and high molecular weight polyhydroxy compounds.
26. A method according to claim 25, wherein the water gelling agent used in the establishment of the hydrogel is selected from the group consisting of cellulose derivatives, polyacryhc acids, polymethacrylates, polyvinylpyrrohdones, polyvinyl alcohols and high molecular weight polyalkylene glycols.
27. A method according to claim 26, wherein the water gelling agent used in the establishment of the hydrogel is selected from the group consisting of carboxymethylcellulose and salts thereof, carbopol 934, povidone K30, and hydroxypropylmethylcellulose.
28. A method according to any of the preceding claims, wherein the formulation additionally contains a pharmaceutically acceptable non-ionic surfactant in such a concentration between about 0.01 and 2% by weight, calculated on the formulation, that it does not to any substantial extent impair the activity of the hpid.
29. A method according to claim 28, wherein the non-ionic surfactant is a polysorbate.
30. A method according to claim 29, wherein the non-ionic surfactant is Tween 20.
31. A method according to any of the preceding claims, wherein the formulation contains a preservative which does not to any substantial extent impair the activity of the hpid.
32. A method according to claim 31, wherein the preservative is a mixture of methyl-p-hydroxy- benzoic acid and propyl-p-hydroxy-benzoic acid, in the proportion of about 4: 1 by weight.
33. A method according to claim 32, wherein the preservative mixture is present in the formulation in a concentration of about 0.05-0.2% by weight. 70
34. A method according to any of the preceding claims, wherein the formulation contains one or more antiviral agents in addition to the microbicidal hpid.
35. A pharmaceutical formulation comprising a hydrogel which contains a) at least one microbicidal hpid as an active ingredient, b) at least one water gelling agent, and c) at least one solubihzing agent which keeps the hpid dissolved in the hydrogel, the formulation being one which
when incubated for 5 minutes with HSV-1 in a titer of 100 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the virus titer, or which
when incubated for 1 minute with HIV-1 in a titer of 10 million CCID50 per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a hundred fold reduction of the virus titer, or which
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the bacterial titer.
36. A pharmaceutical formulation according to claim 35, wherein the formulation is one which
when incubated for 5 minutes with HSV-1 in a titer of 100 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a ten thousand fold reduction of the virus titer, or which
when incubated for 1 minute with HIV-1 in a titer of 10 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a thousand fold reduction of the virus titer, or which
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a ten thousand fold reduction of the bacterial titer.
37. A pharmaceutical formulation according to claim 36, wherein the formulation is one which when incubated for 5 minutes with HSV- 1 in a titer of 100 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a hundred thousand fold reduction of the virus titer, or which
when incubated for 1 minute with HIV-1 in a titer of 10 miihon CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a ten thousand fold reduction of the virus titer, or which
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a hundred thousand fold reduction of the bacterial titer.
38. A pharmaceutical formulation according to any of claims 35-37, wherein the hpid is selected from the group consisting of Cβ-iβ fatty acids or salts thereof, Cβ iβ fatty acid monoglycerides, Cβ- lβfatty acid esters of monohydric alcohols, Cβ-iβfatty alcohols, and Ce-iβfatty alcohol monoglyceride ethers, the Cβ iβ chain containing at least one double or triple bond when the number of carbon atoms thereof exceeds 15.
39. A pharmaceutical formulation according to claim 38, wherein the hpid is selected from the group consisting of Cβ-u fatty acids or salts thereof, Cβ-u fatty acid monoglycerides, Cβ-u fatty acid esters of monohydric alcohols, Cβ-u fatty alcohols, and Cβ-u fatty alcohol monoglyceride ethers.
40. A pharmaceutical formulation according to claim 39, wherein the fatty moieties are saturated.
41. A pharmaceutical formulation according to claim 38, wherein the hpid is selected from capric acid 1-monoglyceride, lauric acid and palmitoleic acid.
42. A pharmaceutical formulation according to claim 41, wherein the hpid is capric acid 1- monoglyceride.
43. A pharmaceutical formulation according to any of claims 35-42, , wherein the solubilizing agent is a compound or compounds selected from the group consisting of compounds of the general formula Ilia
Rι-CH2-(0-CH2-CH2)q-OH (IHa) 72
wherein q is an integer in the range from 1 to 15, and Ri is as defined in claim 14.
44. A pharmaceutical formulation according to claim 43, wherein the solubihzing agent is a compound or compounds selected from the group consisting of compounds of the general formula Illb
R2-CH2-(0-CH2-CH2)q-OH (IHb)
wherein q is an integer in the range from 1 to 15, and R2 is as defined in claim 15.
45. A pharmaceutical formulation according to claim 44, wherein the solubihzing agent is a compound or compounds selected from the group consisting of compounds of the general formula IIIc
R3-CH2-(0-CH2-CH2)q-OH (IHc)
wherein q is an integer in the range from 1 to 15, and R3 is as defined in claim 16.
46. A pharmaceutical formulation according to claim 45, wherein the solubihzing agent is a compound or compounds selected from the group consisting of compounds of the general formula Hid
47. A pharmaceutical formulation according to any of claims 43-46, wherein q is an integer in the range from 1 to 8.
48. A pharmaceutical formulation according to claim 47, wherein q is an integer in the range from 1 to 4.
49. A pharmaceutical formulation according to claim 48, wherein the solubihzing agent is Glycofurol 75. 73
50. A pharmaceutical formulation according to any of claims 35-49, wherein the hpid is present in the formulation in a concentration of from about 1 to about 40 millimolar.
51. A pharmaceutical formulation according to claim 50, wherein the hpid is present in the formulation in a concentration of about 5-30 millimolar.
52. A pharmaceutical formulation according to claim 51, wherein the hpid is present in the formulation in a concentration of about 10-25 millimolar.
53. A pharmaceutical formulation according to claim 52, wherein the hpid is present in the formulation in a concentration of about 20 millimolar.
54. A pharmaceutical formulation according to any of claims 35-53, wherein the water gelling agent is selected from the group consisting of polysaccharides, acryhc polymers, proteins and high molecular weight polyhydroxy compounds.
55. A pharmaceutical formulation according to claim 54, wherein the water gelling agent is selected from the group consisting of cellulose derivatives, polyacrylic acids, polymethacrylates, polyvinylpyrrohdones, polyvinyl alcohols and high molecular weight polyalkylene glycols.
56. A pharmaceutical formulation according to claim 55, wherein the water gelling agent is selected from the group consisting of carboxymethylcellulose and salts thereof, hydroxypropylmethylcellulose, carbopol 934, povidone K30.
57. A pharmaceutical formulation according to any of claims 35-56, wherein the solubilizing agent is present in a concentration in the range of about 5-70% by weight, based on the formulation, so that the formulation, at room temperature, is substantially clear to the naked eye.
58. A pharmaceutical formulation according to claim 57, wherein the solubilizing agent is present in a concentration of about 10-50% by weight, based on the formulation.
59. A pharmaceutical formulation according to any of claims 35-58, wherein the formulation additionally contains a pharmaceutically acceptable non-ionic surfactant in a concentration between about 0.01 and 2% by weight.
60. A pharmaceutical formulation according to claim 59, wherein the non-ionic surfactant is a polysorbate. 74
61. A pharmaceutical formulation according to claim 60, wherein the non-ionic surfactant is Tween 20.
62. A pharmaceutical formulation according to any of claims 35-61, wherein the formulation additionally contains a preservative.
63. A pharmaceutical formulation according to claim 62, wherein the preservative is a mixture of methyl-p-hydroxy-benzoic acid and propyl-p-hydroxy-benzoic acid, substantially in the proportion of 4: 1 by weight.
64. A pharmaceutical formulation according to claim 63, wherein the preservative mixture is present in the formulation in a concentration of about 0.05-0.2% by weight.
65. A pharmaceutical formulation according to any of claims 35-64, wherein the formulation additionally contains one or more antiviral agents.
66. A pharmaceutical formulation comprising a) at least one microbicidal hpid as an active ingredient selected from the group consisting of Cβ-u fatty acids or salts thereof, Cβ-u fatty acid monoglycerides, Cβ-u fatty acid esters of monohydric alcohols, Cβ-u fatty alcohols, Cβ-u fatty alcohol monoglyceride ethers, unsaturated Ciβfatty acids or salts thereof, unsaturated Ciβfatty acid monoglycerides, unsaturated Ciβfatty acid esters of monohydric alcohols, unsaturated Ciβ fatty alcohols, and unsaturated Ciβ fatty alcohol monoglyceride ethers and b) a solubilizing agent which keeps the hpid dissolved in the formulation, the formulation being one which
when incubated for 5 minutes with HSV-1 in a titer of 100 miihon CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the virus titer, or which,
when incubated for 1 minute with HIV-1 in a titer of 10 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a hundred fold reduction of the virus titer, or which,
when incubated for 10 minutes with C. trachomatis in a titer of 10 miihon IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar lipid will cause at least a thousand fold reduction of the bacterial titer. 75
67. A pharmaceutical formulation according to claim 66, wherein the formulation further comprises a gel-forming agent.
68. A pharmaceutical formulation according to claim 67, wherein the formulation is in the form of a gel or a gel-like composition.
69. A pharmaceutical formulation according to claim 68, wherein the gel is a hydrogel.
70. A pharmaceutical formulation according to claim 66, wherein the fatty moieties are saturated.
71. A pharmaceutical formulation according to any of the preceding claims, wherein the formulation is one which
when incubated for 5 minutes with HSV-1 in a titer of 100 miihon CCIDeo per ml in Cell
Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a ten thousand fold reduction of the virus titer, or which,
when incubated for 1 minute with HTV-1 in a titer of 10 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a thousand fold reduction of the virus titer, or which,
when incubated for 10 minutes with C. trachomatis in a titer of 10 million IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a ten thousand fold reduction of the bacterial titer.
72. A pharmaceutical formulation according to claim 71, wherein the formulation is one which
when incubated for 5 minutes with HSV-1 in a titer of 100 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a hundred thousand fold reduction of the virus titer, or which,
when incubated for 1 minute with HIV- 1 in a titer of 10 miihon CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a ten thousand fold reduction of the virus titer, or which, 76
when incubated for 10 minutes with C. trachomatis in a titer of 10 miihon IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a hundred thousand fold reduction of the bacterial titer.
73. A pharmaceutical formulation according to any of claims 66-72, wherein the hpid is selected from lauric acid and palmitoleic acid.
74. A pharmaceutical formulation according to any of claims 66-72, wherein the hpid is capric acid 1-monoglyceride.
75. A pharmaceutical formulation according to any of claims 66-74, wherein the solubilizing agent is selected from lower polyhydric alcohols, polyalkylene glycols, and polyhydroxy ether derivatives.
76. A pharmaceutical formulation according to claim 75, wherein the solubilizing agent is a compound or compounds selected from the group consisting of compounds of the general formula I:
wherein n is an integer in the range from 1 to 4, m is an integer in the range from 1 to 15, and
wherein Ri designates a 5- or 6-membered ahphatic ring wherein from one to three carbon atoms may be replaced by nitrogen and/or oxygen atoms, said 5- or 6-membered ring optionally carrying from one to three substituents selected from the group consisting of halogen, amino, carboxy, and hydroxy;
and compounds of the general formula II:
R-(0-CH2-CH(CH3))k-OH (ID
wherein k is an integer in the range from 1 to 15, and
wherein Ri is as defined above. 77
77. A pharmaceutical formulation according to claim 76, wherein n is 2 or 3, and R is H or
wherein R2 designates a 5- or 6-membered ahphatic ring wherein from one to three carbon atoms may be replaced by nitrogen and/or oxygen atoms.
78. A pharmaceutical formulation according to claim 77 wherein n is 2, and
wherein R3 designates a 5- or 6-membered ahphatic ring wherein one or two carbon atoms may be replaced by oxygen atoms.
79. A pharmaceutical formulation according to claim 78, wherein
80. A pharmaceutical formulation according to any of claims 76-79, wherein m is an integer in the range from 1 to 8.
81. A pharmaceutical formulation according to claim 80, wherein the solubihzing agent is a compound or compounds selected from the group consisting of compounds of the general formula I
wherein m is an integer in the range from 1 to 4, and
and compounds of the general formula (II)
I l-(0-CI l2-CH(CH3))k-OH (II) 78
wherein k is an integer in the range from 1 to 4.
82. A pharmaceutical formulation according to claim 81, wherein m is 1 or 2, and k is 1 or 2.
83. A pharmaceutical formulation according to claim 81 or 82, wherein the solubihzing agent is selected from the group consisting of glycofurol 75, ethylene glycol and propylene glycol, and mixtures thereof.
84. A pharmaceutical formulation according to claim 83, wherein the solubilizing agent is glycofurol 75.
85. A pharmaceutical formulation according to any of claims 66-84, wherein the hpid is present in the formulation in a concentration of from about 1 to about 40 millimolar.
86. A pharmaceutical formulation according to claim 85, wherein the hpid is present in the formulation in a concentration of about 5-30 millimolar.
87. A pharmaceutical formulation according to claim 86, wherein the hpid is present in the formulation in a concentration of about 10-25 millimolar.
88. A pharmaceutical formulation according to claim 87, wherein the hpid is present in the formulation in a concentration of about 20 millimolar.
89. A pharmaceutical formulation according to any of claims 66-88, wherein the solubihzing agent is present in a concentration in the range of about 5-70% by weight, based on the formulation, so that the formulation, at room temperature, is substantially clear to the naked eye.
90. A pharmaceutical formulation according to claim 89, wherein the solubihzing agent is present in a concentration of about 10-50% by weight, based on the formulation.
91. A pharmaceutical composition according to any of claims 69-90, wherein the hydrogel is established by means of a water gelling agent selected from the group consisting of polysaccharides, acryhc polymers, proteins and high molecular weight polyhydroxy compounds.
92. A pharmaceutical formulation according to claim 91, wherein the water gelling agent used in the estabhshment of the hydrogel is selected from the group consisting of cellulose 79
derivatives, polyacryhc acids, polymethacrylates, polyvinylpyrrohdones, polyvinyl alcohols and high molecular weight polyalkylene glycols.
93. A pharmaceutical formulation according to claim 92, wherein the water gelling agent used in the estabhshment of the hydrogel is selected from the group consisting of carboxymethylcellulose and salts thereof, carbopol 934, povidone K30, and hydroxypropylmethylcellulose.
94. A pharmaceutical formulation according to any of claims 66-93, wherein the formulation additionally contains a pharmaceutically acceptable non-ionic surfactant in a concentration between about 0.01 and 2% by weight, calculated on the formulation, so that it does not to any substantial extent impair the activity of the hpid.
95. A pharmaceutical formulation according to claim 94, wherein the non-ionic surfactant is a polysorbate.
96. A pharmaceutical formulation according to claim 95, wherein the non-ionic surfactant is Tween 20.
97. A pharmaceutical formulation according to any of claims 66-96, wherein the formulation contains a preservative which does not substantially impair the activity of the hpid.
98. A pharmaceutical formulation according to claim 97, wherein the preservative is a mixture of methyl-p-hydroxy-benzoic acid and propyl-p-hydroxy-benzoic acid, substantially in the proportion of 4: 1 by weight.
99. A pharmaceutical formulation according to claim 98, wherein the preservative mixture is present in the formulation in a concentration of about 0.05-0.2% by weight.
100. A pharmaceutical formulation according to any of claims 66-99, wherein the formulation additionally contains one or more antiviral agents.
101. A method for preventing or treating infections caused by bacteria, fungi or virus in skin or mucosal membranes, in particular oral or anal mucosal membranes and/or skin adjacent thereto, comprising topically administering an effective amount of a formulation which contains a) at least one microbicidal lipid as an active ingredient, and b) at least one solubilizing agent which keeps the hpid dissolved in the formulation, the solubilizing agent is a 80
compound or compounds selected from the group consisting of compounds of the general formula I:
R-(0-(CH2)n)m-OH (I)
wherein n is an integer in the range from 1 to 4, m is an integer in the range from 1 to 15, and
wherein Ri designates a 5- or 6-membered ahphatic ring wherein from one to three carbon atoms may be replaced by nitrogen and/or oxygen atoms, said 5- or 6-membered ring optionally carrying from one to three substituents selected from the group consisting of halogen, amino, carboxy, and hydroxy;
and compounds of the general formula II:
R-(O-CH2-CH(CH3))k-OH (II)
wherein k is an integer in the range from 2 to 15, and
wherein Ri is as defined above, and the formulation being one which
when incubated for 5 minutes with HSV-1 in a titer of 100 miihon CCIDeo per ml in Cell
Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the virus titer, or which,
when incubated for 1 minute with HIV-1 in a titer of 10 million CCIDeo per ml in Cell Culture Maintenance Medium in a concentration corresponding to 20 millimolar hpid will cause at least a hundred fold reduction of the virus titer, or which,
when incubated for 10 minutes with C. trachomatis in a titer of 10 miihon IFU per ml in Cell Culture Maintenance Medium in a concentration corresponding to 5 millimolar hpid will cause at least a thousand fold reduction of the bacterial titer.
102. A method according to claim 101 , wherein the formulation is a formulation defined in any of claims 2- 100.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/297,921 US6596763B1 (en) | 1996-11-14 | 1997-11-14 | Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infections |
| AU49411/97A AU729546B2 (en) | 1996-11-14 | 1997-11-14 | Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infections |
| EP97912073A EP0941087B1 (en) | 1996-11-14 | 1997-11-14 | Topical formulations containing as a therapeutic active agent a monoglyceride for treating of mucosa infections |
| CA002271843A CA2271843A1 (en) | 1996-11-14 | 1997-11-14 | Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infections |
| AT97912073T ATE442844T1 (en) | 1996-11-14 | 1997-11-14 | TOPICAL COMPOSITIONS CONTAINING A MONOGLYCERIDE AS A THERAPEUTICALLY ACTIVE INGREDIENT FOR THE TREATMENT OF MUCOUS COMBINATIONS |
| JP52206398A JP2001504461A (en) | 1996-11-14 | 1997-11-14 | Topical preparation for treating mucosal infections containing fatty acids or fatty alcohols or their monoglyceride derivatives as therapeutic active ingredients |
| APAP/P/1999/001551A AP1209A (en) | 1996-11-14 | 1997-11-14 | Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglceride derivatives thereof for treating of mucosa infections. |
| DE69739583T DE69739583D1 (en) | 1996-11-14 | 1997-11-14 | TOPICAL COMPOSITIONS CONTAIN AS A THERAPEUTICALLY ACTIVE AGENT A MONOGLYCERIDE FOR THE TREATMENT OF SLEW-TONE INFECTIONS |
| IS5051A IS5051A (en) | 1996-11-14 | 1999-05-12 | Fertilizers for mucosal infections |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IS4386 | 1996-11-14 | ||
| IS4386 | 1996-11-14 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/408,235 Continuation-In-Part US20050043402A1 (en) | 1996-11-14 | 2003-04-08 | Methods and formulations for counteracting infection of mucosa or skin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1998020872A1 WO1998020872A1 (en) | 1998-05-22 |
| WO1998020872B1 true WO1998020872B1 (en) | 1998-06-25 |
Family
ID=36699955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DK1997/000524 WO1998020872A1 (en) | 1996-11-14 | 1997-11-14 | Topical formulations containing as a therapeutic active agent fatty acids or fatty alcohols or monoglyceride derivatives thereof for treating of mucosa infections |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6596763B1 (en) |
| EP (1) | EP0941087B1 (en) |
| JP (1) | JP2001504461A (en) |
| AP (1) | AP1209A (en) |
| AT (1) | ATE442844T1 (en) |
| AU (1) | AU729546B2 (en) |
| CA (1) | CA2271843A1 (en) |
| DE (1) | DE69739583D1 (en) |
| IS (1) | IS5051A (en) |
| WO (1) | WO1998020872A1 (en) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19648545B4 (en) † | 1996-11-25 | 2009-05-07 | Ceramtec Ag | Monolithic multilayer actuator with external electrodes |
| DE69816620T2 (en) * | 1997-06-20 | 2004-02-19 | Prometics Bodycare Ltd. | SKIN PROTECTION PRODUCTS |
| US6096332A (en) * | 1998-06-30 | 2000-08-01 | Mcneil-Ppc, Inc. | Adding pharmaceutically active compounds to substrates |
| IL137559A (en) * | 2000-07-27 | 2006-12-31 | Amnon Sintov | Transdermal drug delivery system |
| AU2002221412B2 (en) * | 2000-12-05 | 2006-04-13 | Alexander Macgregor | Hydrostatic delivery system for controlled delivery of agent |
| DE10156794B4 (en) * | 2001-11-19 | 2006-05-18 | Medigene Ag | Medicines for the treatment of warts |
| DE122009000073I1 (en) | 2001-11-19 | 2010-03-25 | Medigene Ag Lochhamer Strase 1 | DRUGS FOR THE TREATMENT OF VIRAL SKIN AND TUMOR DISEASES |
| US20050032896A1 (en) * | 2002-06-21 | 2005-02-10 | Liisa Neumann | Use of synthetic retinoic acid in form of 13-cis vitamin A for treatment of autism |
| US20050095281A1 (en) * | 2003-03-14 | 2005-05-05 | Optime Therapeutics, Inc. | Liposomal formulations and methods of use |
| ES2237298B1 (en) | 2003-07-16 | 2006-11-01 | Italfarmaco, S.A. | SEMISOLID MUCOADHESIVE FORMULATIONS. |
| GB0317999D0 (en) * | 2003-07-31 | 2003-09-03 | Univ Liege | Improvements in or relating to drug delivery systems |
| BRPI0414198B1 (en) * | 2003-09-09 | 2014-09-30 | 3M Innovative Properties Co | ANTIMICROBIAN COMPOSITION, ANTIMICROBIAN KIT AND METHODS OF USING THE KIT AND COMPOSITION AND METHOD OF HANDLING GROUND MEAT |
| US20050058673A1 (en) | 2003-09-09 | 2005-03-17 | 3M Innovative Properties Company | Antimicrobial compositions and methods |
| US20050079235A1 (en) * | 2003-10-09 | 2005-04-14 | Eggert Stockfleth | Use of a polyphenol for the treatment of actinic keratosis |
| RU2366447C2 (en) | 2003-10-09 | 2009-09-10 | Медигене Аг | Therapeutic agent for treatment of precancerous skin lesions |
| US20050215634A1 (en) * | 2003-11-11 | 2005-09-29 | Schlievert Patrick M | Regulation of cell membrane-mediated effects |
| US8796332B2 (en) * | 2004-08-03 | 2014-08-05 | Regents Of The University Of Minnesota | Compositions and methods for controlling infections |
| AU2005275594A1 (en) * | 2004-08-23 | 2006-03-02 | Synergy Pharmaceuticals Pte Ltd | Gastric therapies and compositions therefor |
| US8535709B2 (en) * | 2004-12-13 | 2013-09-17 | Southeastern Medical Technologies, Llc | Agents for controlling biological fluids and methods of use thereof |
| EP1833298B1 (en) * | 2004-12-17 | 2013-05-08 | Halldor Thormar | Stable concentrated anti-bacterial emulsions of monocaprin in water |
| CA2598985A1 (en) * | 2005-03-10 | 2006-09-21 | 3M Innovative Properties Company | Antimicrobial pet wipes and methods |
| US20060229364A1 (en) * | 2005-03-10 | 2006-10-12 | 3M Innovative Properties Company | Antiviral compositions and methods of use |
| EP3025704B1 (en) | 2005-03-10 | 2019-01-16 | 3M Innovative Properties Company | Methods of reducing microbial contamination |
| MX2007010908A (en) | 2005-03-10 | 2007-12-05 | 3M Innovative Properties Co | Antimicrobial compositions comprising esters of hydroxycarboxylic acids. |
| WO2006099325A2 (en) | 2005-03-10 | 2006-09-21 | 3M Innovative Properties Company | Methods of treating ear infections |
| US20080075793A1 (en) * | 2006-09-21 | 2008-03-27 | Dunshee Wayne K | Antiviral compositions and methods of use |
| ES2561330T3 (en) * | 2007-10-17 | 2016-02-25 | Rudolf Wild Gmbh & Co. Kg | Composition comprising melissa extracts |
| JP2009155257A (en) * | 2007-12-26 | 2009-07-16 | Taiyo Corp | Antibacterial agent and oral composition, food and drink containing the same |
| ES2344673B1 (en) | 2008-08-07 | 2011-05-03 | Italfarmaco, S.A. | USE OF ESTRIOL IN THE PREPARATION OF A PHARMACEUTICAL FORMULATION FOR THE TREATMENT OF VAGINAL ATROPHY IN WOMEN WITH RISK OF POTOLOGIATUMORAL. |
| ES2344675B1 (en) | 2008-12-19 | 2011-04-28 | Italfarmaco, S.A. | USE OF ESTRIOL IN THE PREPARATION OF A PHARMACEUTICAL FORMULATION FOR THE TREATMENT OF VAGINAL ATROPHY IN WOMEN WITH RISK OF VARIUM VARCOLOGY. |
| DE102009008094A1 (en) | 2009-02-09 | 2010-08-19 | Barnikol-Keuten, Doris, Dr. | In situ adhesive gel-forming preparations, in particular for topical application to moisturized skin / mucosa |
| PT3023009T (en) | 2009-08-06 | 2017-03-13 | Anitox Corp | Water and feed preservative |
| WO2011057133A1 (en) | 2009-11-09 | 2011-05-12 | Spotlight Technology Partners Llc | Fragmented hydrogels |
| CA2780294C (en) | 2009-11-09 | 2018-01-16 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
| CN103119144B (en) * | 2010-09-14 | 2014-08-27 | 日油株式会社 | Antibacterial cleaning composition |
| JP5749915B2 (en) * | 2010-11-02 | 2015-07-15 | 花王株式会社 | Autoinducer-2 inhibitor |
| WO2012078155A1 (en) * | 2010-12-09 | 2012-06-14 | The Research Foundation Of State University Of New York | Nitric oxide and its biomedical significance |
| WO2012142452A2 (en) | 2011-04-13 | 2012-10-18 | Biosafe Technologies, Inc. | Cleaning, insecticide, insect repellant, glue solvent and anti-irritation composition |
| MX2014004618A (en) | 2011-10-20 | 2014-05-27 | Anitox Corp | Antimicrobial formulations with pelargonic acid. |
| EP2785205B1 (en) | 2011-11-30 | 2020-12-30 | Anitox Corporation | Antimicrobial mixture of aldehydes, organic acids and organic acid esters |
| US20190209510A1 (en) * | 2016-06-20 | 2019-07-11 | Capretto Ehf. | Synergistic effects, augmenting antimicrobal effects of lipids |
| EP3481401A4 (en) * | 2016-07-11 | 2020-03-11 | Hennepin Life Sciences, LLC | Compositions for sexually transmitted diseases |
| JP6754030B2 (en) * | 2017-04-20 | 2020-09-09 | マイクロアルジェコーポレーション株式会社 | Method for Producing Monoacylglycerol, Antibacterial Agent, and Monoacylglycerol |
| CN114302707A (en) | 2019-06-14 | 2022-04-08 | 普洛拉治疗公司 | Topical acyclovir formulations and uses thereof |
| US11572342B2 (en) | 2020-09-18 | 2023-02-07 | Niche Biopharmaceuticals LLC | Antimicrobial and antiviral sulfur containing glycerol monoester derivatives |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4406884A (en) * | 1981-06-23 | 1983-09-27 | The Procter & Gamble Company | Topical antimicrobial composition |
| US4520132A (en) | 1982-09-27 | 1985-05-28 | Pennwalt Corporation | Use of undecylenic acid to treat herpes labialis |
| JPS5981329A (en) * | 1982-09-30 | 1984-05-11 | ユニオン、カーバイド、コーポレーシヨン | Curable epoxy resin-containing molding composition |
| US5208257A (en) | 1986-04-21 | 1993-05-04 | Kabara Jon J | Topical antimicrobial pharmaceutical compositions and methods |
| US5434182A (en) * | 1987-12-31 | 1995-07-18 | Isaacs; Charles E. | Antibacterial fatty acid compositions |
| US5342625A (en) | 1988-09-16 | 1994-08-30 | Sandoz Ltd. | Pharmaceutical compositions comprising cyclosporins |
| NZ250714A (en) * | 1990-10-30 | 1996-05-28 | Mcneil Ppc Inc | Liquid composition comprising esters of higher fatty acids for use as a vaginal douche and to prevent toxic shock toxin production |
| IL104283A (en) * | 1992-12-30 | 1996-12-05 | Agis Ind 1983 Ltd | Non-emulsion antiviral topical pharmaceutical composition comprising acyclovir an aqueous gel agent and an alkali oleate |
| IL110380A0 (en) | 1994-07-20 | 1994-10-21 | Agis Ind 1983 Ltd | Antiviral topical pharmaceutical compositions |
| MXPA99002575A (en) | 1996-09-17 | 2004-07-29 | Avanir Pharmaceuticals | Viral inhibition by long-chain alcohols, alkanes, fatty acids and amides. |
-
1997
- 1997-11-14 EP EP97912073A patent/EP0941087B1/en not_active Expired - Lifetime
- 1997-11-14 DE DE69739583T patent/DE69739583D1/en not_active Expired - Lifetime
- 1997-11-14 AU AU49411/97A patent/AU729546B2/en not_active Ceased
- 1997-11-14 US US09/297,921 patent/US6596763B1/en not_active Expired - Fee Related
- 1997-11-14 JP JP52206398A patent/JP2001504461A/en not_active Ceased
- 1997-11-14 WO PCT/DK1997/000524 patent/WO1998020872A1/en active Application Filing
- 1997-11-14 AP APAP/P/1999/001551A patent/AP1209A/en active
- 1997-11-14 CA CA002271843A patent/CA2271843A1/en not_active Abandoned
- 1997-11-14 AT AT97912073T patent/ATE442844T1/en not_active IP Right Cessation
-
1999
- 1999-05-12 IS IS5051A patent/IS5051A/en unknown
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