Source: http://www.google.com/patents/US6417236?dq=patent:5881444
Timestamp: 2017-07-26 16:11:03
Document Index: 435903459

Matched Legal Cases: ['Application No. 60', 'art 1', 'art 1', 'art 2', 'art 2', 'art 3', 'art 3', 'art 4', 'art 4', 'art 4', 'art 5', 'art 5', 'art 4', 'art 1']

Patent US6417236 - Active topical skin protectants using hybrid organic polysilsesquioxane ... - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsA topical skin protectant formulation containing a barrier cream and an active hybrid organic-inorganic polysilsesquioxane material for protecting warfighters and civilians against all types of harmful chemicals, specifically chemical warfare agents (CWA's). The topical skin protectant offers a barrier...http://www.google.com/patents/US6417236?utm_source=gb-gplus-sharePatent US6417236 - Active topical skin protectants using hybrid organic polysilsesquioxane materialsAdvanced Patent SearchTry the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.Publication numberUS6417236 B1Publication typeGrantApplication numberUS 09/872,097Publication dateJul 9, 2002Filing dateJun 1, 2001Priority dateJun 2, 2000Fee statusLapsedPublication number09872097, 872097, US 6417236 B1, US 6417236B1, US-B1-6417236, US6417236 B1, US6417236B1InventorsStephen T. Hobson, Ernest H. Braue, Kenneth SheaOriginal AssigneeThe United States Of America As Represented By The Secretary Of The Army, The Regents Of The University Of CaliforniaExport CitationBiBTeX, EndNote, RefManPatent Citations (6), Non-Patent Citations (2), Referenced by (32), Classifications (91), Legal Events (6) External Links: USPTO, USPTO Assignment, EspacenetActive topical skin protectants using hybrid organic polysilsesquioxane materials
US 6417236 B1Abstract
A topical skin protectant formulation containing a barrier cream and an active hybrid organic-inorganic polysilsesquioxane material for protecting warfighters and civilians against all types of harmful chemicals, specifically chemical warfare agents (CWA's). The topical skin protectant offers a barrier property and an active moiety that serves to neutralize chemical warfare agents into less toxic agents.
What is claimed is: 1. A topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising: a barrier base cream; and one or more hybrid organic-inorganic polysilsesquioxane as an active moiety.
3. The topical skin protectant formulation of claim 1, wherein said hybrid organic-inorganic polysilsesquioxanes is selected from the group consisting of:
a) bridged polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene/40% 3-Triethoxysilyl-propane-1-thiol; b) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene/60% 3-Triethoxysilyl-propane-1-thiol; c) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene/80% 3-Triethoxysilyl-propane-1-thiol; d) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene/40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; e) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene/60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; f) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene/80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; g) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in tetrahydrofuran; and h) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in ethanol. 4. The topical skin protectant formulation of claim 1, wherein said hybrid organic-inorganic polysilsesquioxanes comprises monomers and wherein said monomers are 1,4-Bis-triethoxysilyl-benzene, 3-Triethoxysilyl-propane-1-thiol or 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane.
a) a barrier base cream, said barrier base cream comprising poly(tetrafluoroethylene) resins dispersed in perfluorinated polyether oils; and b) one or more active moieties comprising one or more hybrid organic-inorganic polysilsesquioxanes. 6. The topical skin protectant formulation of claim 5, further comprising one or more additives.
a) a barrier base cream, said barrier base cream comprising poly(tetrafluoroethylene) resins dispersed in perfluorinated polyether oils; b) one or more active moieties comprising hybrid organic-inorganic polysilsesquioxanes selected from the group consisting of hybrid organic-inorganic polysilsesquioxane prepared from a) 60% 1,4-Bis-triethoxysilyl-benzene, 40% 3-Triethoxysilyl-propane-1-thiol, b) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene, 60% 3-Triethoxysilyl-propane-1-thiol, c) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene, 80% 3-Triethoxysilyl-propane-1-thiol, d) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene, 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane, e) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene, 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane, f) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene, 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane, g) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in THF, h) and Hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in EtOH; and i) one or more additives. 9. The topical skin protectant formulation of claim 8, wherein said additives comprise one or more of water, surfactants, stabilizers, camouflage paints, and sunscreens.
a) a topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising a barrier cream and one or more active moieties, said active moieties comprising hybrid organic-inorganic polysilsesquioxanes; b) a second formulation for applying a thin solid active moiety powder on top or below said topical skin protectant formulation comprising one or more hybrid organic-inorganic polysilsesquioxanes. 11. The topical skin protectant system of claim 10 wherein said one or more active moieties in the topical skin protectant formulation and in the solid active moiety powder is an hybrid organic-inorganic polysilsesquioxanes selected from the group consisting of:
a) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; b) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 3-Triethoxysilyl-propane-1-thiol; c) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 3-Triethoxysilyl-propane-1-thiol; d) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; e) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; f) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; g) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in tetrahydrofuran; and h) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in ethanol. 12. A method of protecting a user against chemical warfare agents comprising: applying a topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising:
a) a barrier cream; and b) one or more active moieties, said one or more active moieties comprising hybrid organic-inorganic polysilsesquioxanes. 13. A method of protecting a user against chemical warfare agents comprising:
a) applying a first thin layer of solid active moiety powder comprising one or more hybrid organic-inorganic polysilsesquioxanes; and b) applying a second layer of a topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising a barrier cream and one or more active moieties comprising one or more hybrid organic-inorganic polysilsesquioxanes. 14. The method of claim 13, wherein said one or more active moieties in the topical skin protectant formulation and in the solid active moiety powder is an organic hybrid organic-inorganic polysilsesquioxane selected from the group consisting of
a) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; and b) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 3-Triethoxysilyl-propane-1-thiol; c) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 3-Triethoxysilyl-propane-1-thiol; d) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; e) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; f) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; g) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in tetrahydrofuran; and h) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in ethanol. 15. A method of protecting a user against chemical warfare agents comprising:
a) applying a first layer of a topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising a barrier cream and one or more active moieties, said one or more active moieties comprising one or more hybrid organic-inorganic polysilsesquioxanes; and b) applying a thin layer of solid active moiety powder over the first layer, said solid active moiety powder comprising one or more hybrid organic-inorganic polysilsesquioxanes. 16. The method of claim 15, wherein said one or more active moieties in the topical skin protectant formulation and in the solid active moiety powder is an hybrid organic-inorganic polysilsesquioxanes selected from the group consisting of
a) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; b) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 3-Triethoxysilyl-propane-1-thiol; c) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 3-Triethoxysilyl-propane-1-thiol; d) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; e) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; f) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; g) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in tetrahydrofuran; and h) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in ethanol. 17. A method of making a topical skin protectant formulation comprising:
mixing a) one or more active moieties comprising hybrid organic-inorganic polysilsesquioxanes with b) a barrier cream comprising poly(tetrafluoroethylene) resins dispersed in perfluorinated polyether oils. 18. The method of claim 17, wherein said hybrid organic-inorganic polysilsesquioxanes are selected from the group consisting of
a) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; b) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 3-Triethoxysilyl-propane-1-thiol; c) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 3-Triethoxysilyl-propane-1-thiol; d) hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; e) hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; f) hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; g) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in tetrahydrofuran; and h) hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in ethanol. 19. A topical skin protectant formulation comprising: about 4% of hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol, and
a) about 58% perfluoropolyether; and b) about 38% polytetrafluoroethylene. 20. A topical skin protectant formulation comprising:
a) about 4% of hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 3-Triethoxysilyl-propane-1-thiol, and b) about 58% perfluoropolyether; and c) about 38%polytetrafluoroethylene. 21. A topical skin protectant formulation comprising:
a) about 4% of hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 3-Triethoxysilyl-propane-1-thiol, and b) about 58% perfluoropolyether; and c) about 38% polytetrafluoroethylene. 22. A topical skin protectant formulation comprising:
a) about 5% of hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl).-propane; b) about 7% perfluoropolyether; and c) about 38% polytetrafluoroethylene. 23. A topical skin protectant formulation comprising:
a) about 4% of hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl).-propane; b) about 58% perfluoropolyether; and c) about 38% polytetrafluoroethylene. 24. A topical skin protectant formulation comprising:
a) about 4% of hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl).-propane; b) about 58% perfluoropolyether; and c) about 38% polytetrafluoroethylene. 25. A topical skin protectant formulation comprising:
a) about 3% of hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol b) about 57% perfluoropolyether; and c) about 40% polytetrafluoroethylene. 26. A topical skin protectant formulation comprising:
a) about 4% of hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol, and b) about 96% perfluoropolyether. 27. A topical skin protectant formulation comprising:
a) about 5% of hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in EtOH; b) about 51% perfluoropolyether; and c) about 44% polytetrafluoroethylene. 28. A topical skin protectant formulation comprising:
a) about 1% of Hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl).-propane b) about 50% perfluoropolyether; and c) about 49% polytetrafluoroethylene. 29. A topical skin protectant formulation comprising:
a) about 1% of hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl).-propnae; b) about 50% perfluoropolyether; and c) about 49%polytetrafluoroethylene. 30. A topical skin protectant formulation comprising:
a) about 1% of hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; b) about 50% perfluoropolyether; and c) about 49% polytetrafluoroethylene. 31. A topical skin protectant formulation comprising:
a) about 2.5% of Silica Gel; b) about 50% perfluoropolyether; and c) about 47% polytetrafluoroethylene. 32. A topical skin protectant formulation comprising:
a) about 5% of hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene polymerized in tetrahydrofuran; b) about 51% perfluoropolyether; and c) about 44% polytetrafluoroethylene. 33. A topical skin protectant formulation comprising:
a) about 5% of hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene polymerized in ethanol; b) about 51% perfluoropolyether; and c) about 44% polytetrafluoroethylene. 34. A topical skin protectant formulation comprising:
a) about 5% of 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; b) about 51% perfluoropolyether; and c) about 44% polytetrafluoroethylene. 35. A topical skin protectant formulation comprising:
a) about 5% of 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; b) about 51% perfluoropolyether; and c) about 44% polytetrafluoroethylene. 36. A topical skin protectant formulation comprising:
a) about 5% of 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; b) about 51% perfluoropolyether; and c) about 44% polytetrafluoroethylene. 37. A topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising:
a) a barrier base cream, said barrier base cream comprising of about 30-50% poly(tetrafluoroethylene) resins dispersed in 40-60% perfluorinated polyether oils; b) one or more active moieties comprising one or more hybrid organic-inorganic polysilsesquioxanes selected from the group consisting of i. hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 3-Triethoxysilyl-propane-1-thiol; ii. hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 3-Triethoxysilyl-propane-1-thiol; iii. hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 3-Triethoxysilyl-propane-1-thiol; iv. hybrid organic-inorganic polysilsesquioxane prepared from 60% 1,4-Bis-triethoxysilyl-benzene and 40% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; v. hybrid organic-inorganic polysilsesquioxane prepared from 40% 1,4-Bis-triethoxysilyl-benzene and 60% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; vi. hybrid organic-inorganic polysilsesquioxane prepared from 20% 1,4-Bis-triethoxysilyl-benzene and 80% 1-Triethoxysilyl-3-(3-triethoxysilyl-propyldisulfanyl)-propane; vii. hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in tetrahydrofuran; viii. hybrid organic-inorganic polysilsesquioxane prepared from 1,4-Bis-triethoxysilyl-benzene in ethanol; and ix. one or more additives consisting of water, surfactants, stabilizers, camouflage paints, and sunscreens. 38. A topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising one or more active moieties, wherein said active moiety is one or more hybrid organic-inorganic polysilsesquioxanes.
39. The topical skin protectant formulation of claim 38, further comprising a base cream.
40. The topical skin protectant formulation of claim 2, wherein the amount of active moiety is about 1-20%; the amount of perfluorinated polyether oil is about 40 to 60%, and the amount of poly(tetrafluoroethylene) is about 30 to 50%.
41. The topical skin protectant formulation of claim 1, wherein said chemical warfare agents are one or more of the group consisting of blistering agents, G class nerve agents, and VX.
42. The topical skin protectant formulation of claim 41, wherein said blistering agent is sulfur mustard.
43. The topical skin protectant formulation of claim 41, wherein said G class nerve agent is soman.
An organic molecule, S-330, that reacts with CWA's was incorporated into a product and fielded as the M-5 ointment kit at the end of World War II (Formula 1). However, the unacceptable barrier properties and the undesirable cosmetic properties (specifically foul odor and sticky texture) caused a recall of this product.
Two non-active topical skin protectant (TSP) formulations were developed at the United States Army Medical Research Institute of Chemical Defense (USAMRICD) and were transferred to advanced development following a Milestone Zero (MS0) Review in October 1990. The timeline of the approval of the TSP continued with MSI in 1993, a Investigational New Drug (IND) filed with the FDA in 1994, MSII in 1995, and culminated with New Drug Application (NDA) approval in February, 2000. Upon approval by the FDA, the TSP was designated Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA). SERPACWA is a 50:50 (wt/wt) mixture of perfluoropolyether oil (Fomblin® Y25 from Ausimont) and poly(tetrafluoroethylene)(polymist® F5a powder from Ausimont). The formulation described in McCreery U.S. Pat. No. 5,607,979 is directed to a topical skin protectant cream that acts as a barrier to CWA's.
It is still a further object of the invention to provide an active topical skin protectant that is practical for field operations. Specifically, the active TSP should have a stable shelf life, should not be easily washed off with water, and should not react with insecticides or camouflage paint.
A topical skin protectant formulation for neutralizing chemical warfare agents into less toxic products comprising: a barrier base cream and one or more active moieties. The base cream comprises poly(tetrafluoroethylene) resins dispersed in perfluorinated polyether oils. The active moieties that have been found to be effective with the base cream are listed in Table 1. The active barrier cream is applied to the skin prior to exposure of persons at risk of exposure to harmful chemicals to provide an active barrier to protect the skin. The active barrier cream chemically or physically reacts with harmful chemicals such as CWA's to neutralize these harmful chemicals while the barrier properties of the cream prevent penetration of harmful chemicals through the cream to the skin.
FIG. 2 is a picture of bridged polysilsesquioxanes/Y25 after exposure to DFP (t=20 hr). Examination of 31P NMR revealed no signals from hydrolyzed or native DFP.
The types of materials that decontaminate harmful agents use two main modes of action: elimination or hydrolysis.
However, selection of the active materials is restricted by operating criteria. Thus, the active moiety must not irritate the skin, react with insecticides or camouflage paints, or be unstable. This restriction eliminates many of the most active species. Furthermore, the active moiety must be incorporated into a highly fluorinated environment that is not amenable to many reaction pathways.
Table 1 is a list of active moieties that are acceptable for use in the present invention.
LIST OF ACTIVE HYBRID ORGANIC-INORGANIC
POLYSILSESQUIOXANES FOR ACTIVE TOPICAL SKIN
PROTECTANTS AND EXAMPLE FORMULATONS
Wt % PTFE
60% PhB/40% MPTES
40% PhB/60% MPTES
20% PhB/80% MPTES
60% PhB/40% TESDS
40% PhB/60% TESDS
20% PhB80% TESDS
100% PhB
40% PhB 60%/TESDS
20% PhB/80% TESDS
100% PhB/THF
100% PhB/ethanol (3540)
60% PhB/40% MPTES (3541)
60% PhB/40% MPTES (3542)
60% PhB/40% MPTES (3543)
Abbreviations: PTFE: poly(tetrafluoroethylene)available as F5A powder from Ausimont, Morristown, NJ PFPE: perfluoropolyether available as FOMBLIM ™ Y25 oil from Ausimont, Morristown, NJ PhB 1,4-triethoxysilylbenzene MPTES mercaptopropyltriethoxysilane (3-triethoxysilyl-propane-1-thiol) TESDS 3,3′-triethoxysilylpropyl disulfide (1-triethoxysilyl-3-(3-triethoxysilylpropyldisulfanyl)-propane) THF tetrahydrofuran EtOH ethanol *Silica gel SiO2 Aldrich 70-230 mesh, 60 A, 500 m2/g, #28862-4 Two monomers listed above are organic-bridged bis-triethoxysilyl compounds (MPTES, PhB) prepared in the laboratory of Ken Shea at the University of California on Mar. 30, 2001 (Provisional Patent Application No. 60/280,711). Monomers used in the synthesis of bridged polysilsesquioxanes.
Chemical structures for the bridged polysilsesquioxanes are below: Structures of bridged polysilsesquioxanes incorporated into active TSPs
All active moieties listed above are useful for both liquid and vapor challenges. The amount of each varies with each formulation. The object is to optimize the quantity of active moiety in the base cream without losing the barrier properties of the base cream. The amount of active moiety can vary from about 1-20%. The amount of perfluorinated polyether oil can vary from about 40 to 60%. The amount of poly(tetrafluoroethylene) can vary from about 30 to 50%. One criterion for selection of the active materials is increased efficacy against HD and/or GD vapor. Many formulations have significantly (P=0.05) increased protection compared to SERPACWA (ICD 3004) in the penetration cell model against HD and GD respectively. The best candidate compound listed in Table 1 for HD is ICD3553 and for GD is ICD3362.
The bridged polysilsesquioxane must also be incorporated into the TSP matrix without degradation of the barrier properties. These materials were incorporated into the cream as solids. Typically, they are dispersed into the perfluorinated oil followed by sequential addition of the appropriate amount of F5A polytetrafluoroethylene.
SERPACWA (ICD3004) consists of fine particles of poly(tetrafluoroethylene) resin dispersed in perfluorinated polyether oil. The excellent barrier properties of this high molecular weight polymer formulation are related to the low solubility of most materials in it. Only highly fluorinated solvents like Freon® have been observed to show appreciable solubility. This aprotic non-polar polymer mixture provides a unique. medium for active moieties of the invention. Reaction mechanisms that do not involve charged transition states should be favored in this chemical environment.
Suitable perfluorinated polyether oils are Fomblin® HC- and Y-oils (Ausmont) and Krytox.® oils (Dupont). The Fomblin® oils are mixtures of linear polymers based on perfluoropropylene oxide having the following chain structure: CF3—[(OCF(CF3)CF2)n—(OCF2CF2)m]OCF3. The Krytox® oils are mixtures of linear polymers also based on perfluoropropylene oxide and have the chemical structure F—[(CF(CF3)CF2O)]mCF2CF3. Fomblin® Z oils having the formula: CF3. [(OCF2CF2)n—(OCF2)m]—OCF3, may also be useful in the practice of the invention. The indices n and m indicate the average number of repeating polymeric subunits in the oil molecules. The oils may have a viscosity of about 20 cSt to about 500 cSt or more. The creams were generally prepared according to U.S. Pat. No. 5,607,979, incorporated herein in its entirety.
Temperature and mixing sheer should be monitored to maintain the base cream at the desired consistency and quality. The active TSPs are typically prepared at ambient temperature using mechanical mixing. Depending on the oxygen sensitivity of the active material, some of the bridged polysilsesquioxanes may be added to the perfluorinated oil under an inert (i. e. nitrogen) atmosphere. Mixing times of 10-20 minutes are usually sufficient for dispersal of bridged polysilsesquioxanes into the SERPACWA matrix. A typical procedure for the preparation of an active aTSP with a bridge polysilsesquioxane is presented below:
In a polypropylene container is added the appropriate amount of bridged polysilsesquioxane (1-3% by weight) and Y25 (50-55% by weight) perfluorinated oil. The suspension is mixed either with a mechanical stirrer at ambient temperature for 5 to 15 minutes or with a magnetic stirrer for 12 to 24 hours. To the suspension is added F5A poly(tetrafluoroethylene) in three portions with vigorous mechanical stirring for 5 to 10 minutes between each addition. After the final addition, the container is tightly capped and sealed with Parafilm®.
The DTN is divided into two pathways: one for vesicants and the other for nerve agents. Within these pathways, there are three blocks each with a decision point. The first block consists of a series of three mechanical (in vitro) modules used to determine the initial efficacy of candidate formulations and to eliminate non-effective candidates before animal testing, the second block consists of in vivo modules and the third block consists of an advanced animal module to determine the influence of time, water and interactions with other products.
The M8 paper test is used to evaluate the barrier resistance of liquid CWA challenges, including HD, pinacolyl methylphosphonofluoridate (soman, GD), and O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX). In this test a 0.15 mm layer of active TSP is placed over a well-defined area of M8 chemical detection paper and challenged with an 8 μl droplet of CWA. When agent penetrates the active TSP barrier and reaches the M8 paper, a colored spot develops on the paper. The test assemblies are observed for 6 hr and the breakthrough time is reported for each sample. Nine replicates are run for each test, and a standard reference compound is included each day for quality control.
The penetration cell test is used to evaluate the barrier properties against both liquid and vapor CWA challenges (Braue, E. H. Jr. Journal of applied Toxicology, 1999, 19(S), S47-S53). In this test, the lower half of a Reifenrath diffusion cell (Reifenrath Consulting and Research, Richmond, Calif.) is used. A 0.15 mm thick layer of active TSP is supported by nitrocellulose paper on top of the cell. The active TSP layer is challenged with a 10 μl liquid droplet of HD or an 8 μl droplet of GD, or a saturated vapor cup of HD or GD. Breakthrough of CWA into the lower chamber of the diffusion cell is monitored using a miniature continuous air monitoring system (MINICAMS, CMS Research, Birmingham, Ala.). This system has been automated to allow continuous monitoring of five cells in a 40-min cycle. The test runs for 20 hr and the accumulated amounts of agent that break through the active TSP barrier are calculated. From these data, we obtained two values: the cumulative amount of CWA that penetrates through the active TSP, and the time at which a “breakthrough” occurs. We defined “breakthrough” values at the minimum amount of HD (1000 ng) and GD (1000 ng) that results in a physiological response. Minimal amount of HD for vesication =1000 ng. See F. R. Sidell, J. S. Urbanetti, W. J. Smith, and C. G. Hurst in Textbook of Military Medicine, Medical Aspects of Chemical and Biological Warfare, edited by F. R. Sidell, E. T.Takafuji, and D. R. Franz (Office of the Surgeon General at TMM Publications, Washington, D. C. 1997) p 201. LD50 for soman (GD) =350 mg/70 kg man. See F. R. Sidell in Textbook of Military Medicine, Medical Aspects of Chemical and Biological Warfare, edited by F. R. Sidell, E. T.Takafuji, and D. R. Franz (Office of the Surgeon General at TMM Publications, Washington, D. C. 1997) p 141. These two values allow us to rank the active TSP formulations and to select the appropriate component for advanced development.
The rabbit acetyl cholinesterase (AChE) inhibition test is performed by applying a 0.10 mm thick layer of active TSP on the clipped dorsa of rabbit followed by a fixed dose of GD (1 LD50), TGD (1 LD50), or VX (20 LD50). The effectiveness of the active TSP is determined by lethality and by measuring the erythrocyte acetyl cholinesterase activity 0.5, 1, 2, and 24 hr following exposure.
Both the phenyl-bridged polysilsesquioxane (PhB) and the phenyl-bridged/bistriethyoxysilylpropyldisulfide (PhB/BTESPDS) are effective active moieties reducing the amount of HD vapor by ˜98% relative to the TSP alone. Although the exact mechanism for HD neutralization is not clear, the HD may react by either hydrolysis or dehydrohalogenation (Scheme 1). The hydrolysis of HD to thiodiglycol 1 perhaps is due to adventitious water trapped on the polysilsesquioxane surface or in the internal pore structure. Since these materials have high surface areas (up to 850 m2/g), this reaction may be facilitated by the physical or chemical adsorption of the HD into the polysilsesquioxane. This adsorption should be energetically favorable due to the hydrophobic nature of the hybrid organic-inorganic polysilsesquioxanes. On the other hand, since these materials are not completely condensed (˜80% condensation as determined by 29Si SS-NMR) it is possible that the residual silanols (RSiOH) will act as an acid catalyst for the dehydrohalogenation reaction giving vinylsulfide 2. This hypothesis is supported by the high activity of silica gel (SiO2, ICD 3533).
Against GD vapor, the most effective bridged polysilsesquioxanes were the phenyl-bridged polysilsesquioxane (PhB) that reduced the amount of GD by 88% compared to TSP alone. The most likely mechanism for the neutralization of GD is hydrolysis (Scheme 2). All active TSPs that have shown efficacy against GD contain water, and the products from the GD simulant, diisopropylfluorophosphate, (DFP), have FT-IR and 31P NMR spectra that are consistent with hydrolysis. Adventitious adsorbed water on the surface of the bridged polysilsesquioxanes or in the internal surface structure may act as a reagent for this hydrolysis. Furthermore, a physical or chemical adsorption of the GD into the relatively hydrophobic polysilsesquioxane matrix may also play a role (vide infra).
The increase in protection for the bridged polysilsesquioxane was impressive against GD vapor as seen by the increase in the time for 1000 ng of GD vapor to penetrate the active TSP as compared to SERPACWA (ICD 3004) (Chart 1). Chart 1. Time for 1000 ng GD to penetrate aTSPs with bridged polysilsesquioxane.
This protection is also evident in a comparison of the cumulative amount of GD vapor that penetrates the active TSP over 20 hours in comparison to SERPACWA (ICD3004) (Chart 2). Chart 2. Cumulative amount of GD vapor through aTSP over 20 hr.
Formulations ICD 3530, 3548, and 3450 show the greatest protection against GD vapor reducing the amount of GD by 80, 83, and 88% respectively and all have significantly (P=0.05) increased protection compared to SERPACWA (ICD 3004) in the penetration cell model against GD. The importance of the organic bridging group is also obvious by comparing the 22% reduction of the amount of GD penetration for silica gel (SiO2, ICD 3533) and the ˜90% reduction for the hybrid organic-inorganic polysilsesquioxanes ˜90% (ICD 3450, PhB). Apparently, the organic bridge is a necessary to for the increased protection and for the neutralization of the organophosphate.
The increase in protection for the bridged polysilsesquioxanes was also remarkable against HD vapor as demonstrated in the increase in the time needed for 1000 ng of HD vapor to penetrate the active TSP as compared to SERPACWA (ICD 3004) (Chart 3). Chart 3. Time for 1000 ng HD to penetrate active TSPs containing bridged polysilsesquioxane
A comparison of the cumulative amount of HD vapor that penetrates the active TSP over 20 hours also shows the increase in protection (Chart 4). Chart 4. Cumulative amount of HD vapor through aTSP over 20 hr.
As clearly seen in Chart 4, the majority of formulations have shown outstanding protection against HD vapor in the penetration cell model. In fact, as few as 52 ng of HD vapor penetrated through the active TSP over 20 hours. All but one formulation show the same protection or significantly better (P=0.05) protection against HD vapor compared to ICD 3004 in the penetration cell model.
In the proof of neutralization model, ICD 3450 (PhB polysilsesquioxanes) was tested in the head-space solid phase micro-extraction gas chromatography/mass spectrometry (HS-SPME/GC-MS) test against HD, GD, and VX liquid. In these tests, the active TSPs only showed significant efficacy against HD liquid (46±17%). The neutralization of diisopropylfluorophosphonate (DFP) was monitored via 31P NMR in the PFPE oil. After 20 hours, no perceptible signal from DFP was seen in the 31P NMR. An examination of the vial containing the bridged polysilsesquioxane indicated that physical removal of the DPF might have occurred (FIG. 2). Furthermore, examination of 31P NMR revealed no signals from hydrolyzed or native DFP.
Despite the excellent performance of the active TSPs containing bridged polysilsesquioxanes in the penetration cell models, the results from the weanling pig model were more varied (Chart 5) Chart 5. Results of active TSPs containing bridged polysilsesquioxanes.
The active TSPs containing bridged polysilsesquioxanes reduced the cumulative amount of HD vapor in the penetration cell by 88-96% (Chart 4). The recorded erythema from HD vapor in these active TSPs, however, is only slightly decreased or actually increased above control in the in vivo test. The only exception was seen when the thickness of the active TSP was increased from 0.1 mm to 0.2 mm. We have seen similar trends with other compounds and have four possible explanations. First, the skin is occluded by the aTSP, increasing agent penetration and thus the observed erythema. Second, the skin may be sensitized by the aTSP, and thus the small amount of HD vapor that penetrates the skin results in greater erythema. Third, the skin may be irritated by the reaction products. Fourth, agent may penetrate the aTSP during exposure and not be completely removed by the cleaning procedure.
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2002Jul 10, 2003University Of CaliforniaHybrid organic-inorganic adsorbents* Cited by examinerClassifications U.S. Classification514/759, 514/939, 514/723, 514/845, 514/937, 424/59, 514/944, 514/789, 514/772, 514/844International ClassificationA61Q19/00, A61K31/02, C02F1/24, A61K8/19, A62D101/02, A61K8/81, C02F1/56, A61K8/899, A61K8/04, B01D53/04, A61K8/46, A61K8/891, A61K8/24, A61K8/20, A61K8/49, A61K31/08, A62D3/00, A62D101/43, A61K8/27, A61K8/70, A61Q17/00, A61K8/55, A61K8/29, A61K8/66, A62D3/30, A62D3/33, C07F7/18Cooperative ClassificationY10S514/844, Y10S514/944, Y10S514/939, Y10S514/845, Y10S514/937, A61K8/55, C02F1/24, A62D2101/02, A61K8/4946, A62D3/33, A61K8/20, A61K8/70, A61K8/899, A61K8/466, B01D2253/10, A62D2101/43, C02F1/56, A61K31/02, A61K8/24, A62D3/30, C02F1/001, A61K8/66, A61K8/8123, B82Y5/00, A61K8/27, A61K8/19, C07F7/1836, A61Q17/00, A61K8/29, A61K31/08, A61K2800/413, B01D2253/20, A61K8/0241European ClassificationB82Y5/00, A61K8/02A, A61K8/46F, A61K8/49F1, A61K31/02, A61K8/70, A61K8/899, A61K8/66, A61Q17/00, A61K31/08, A62D3/30, A61K8/20, A61K8/55, A61K8/81E, A61K8/29, C02F1/56, A61K8/27, A62D3/33, A61K8/19, A61K8/24, C07F7/18C4BLegal EventsDateCodeEventDescriptionMay 13, 2002ASAssignmentOwner name: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE, CALIFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SHEA, KENNETH J.;REEL/FRAME:012895/0094Effective date: 20020501May 16, 2002ASAssignmentOwner name: ARMY, UNITED STATES, MARYLANDFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HOBSON, STEPHEN T.;BRAUE, ERNEST H.;REEL/FRAME:012917/0239Effective date: 20020307Nov 4, 2005FPAYFee paymentYear of fee payment: 4Feb 15, 2010REMIMaintenance fee reminder mailedJul 9, 2010LAPSLapse for failure to pay maintenance feesAug 31, 2010FPExpired due to failure to pay maintenance feeEffective date: 20100709RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData 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