Topical compositions useful as skin penetration barriers

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Titel: Topical compositions useful as skin penetration barriers
Patent Number: 6,086,905
Publikationsdatum: July 11, 2000
Appl. No: 08/102,176
Application Filed: August 04, 1993
Abstract: Methods for preventing the penetration of toxic chemicals through the stratum corneum of the skin of a mammal are disclosed which employ, as a penetration prevention agent, at least one compound selected from the group consisting of compounds represented by the formula: ##STR1## wherein W.sub.1 is a divalent oxygen, sulfur or nitrogen radical, W.sub.2 and W.sub.3 are independently a divalent oxygen or sulfur radical, R' is an alkyl radical comprising from 1 to 4 carbon atoms, y is 0 or 1, R.sub.1 and R.sub.2 are alkyl radicals comprising from 1 to 10 carbon atoms and R and R.sub.3 are individually a hydrocarbyl radical containing from 1 to 20 carbon atoms or a heteroatom-substituted derivative thereof wherein at least one but not two adjacent carbon atoms may be replaced by a divalent oxygen or sulfur radical or by NR", wherein R" is hydrogen or R', n is an integer from 2 to 5 and compounds represented by the above formula in which the ring and/or R includes one to three carbon carbon double bonds.
Inventors: Peck, James V. (Richmond, VA); Minaskanian, Gevork (Richmond, VA); Hadgraft, Jonathan (Penarth, S. Glenn, GBX)
Claim: What is claimed is
Claim: 1. A method for decreasing the percutaneous absorption of toxic chemicals through the skin of a mammal in need of said decreasing which comprises applying to the stratum corneum of the skin of said mammal an effective amount to decrease the percutaneous absorption of toxic chemicals of a compound having the formula: ##STR4## wherein W.sub.1, W.sub.2 and W.sub.3 are each divalent oxygen, n is 2 and R is a straight chain alkyl radical containing 6 to 20 carbon atoms;
Claim: wherein when the skin of said mammal is exposed to said toxic chemicals, the penetration of said toxic chemicals through the skin is decreased.
Claim: 2. The method of claim 1, wherein said compound is N-dodecanoyl-2-oxazolidione.
Claim: 3. A method for increasing the stability of lipid bilayers in mammalian skin in order to decrease passage of bioactive agents through the skin of a mammal in need of said decreasing, said method comprising the step of applying to the stratum corneum of the skin of said mammal an amount effective to decrease passage of bioactive agents through said lipid bilayers of a lipid-bilayer-stability-increasing compound having the formula: ##STR5## wherein W.sub.1, W.sub.2 and W.sub.3 are each divalent oxygen, n is 2 and R is a straight chain alkyl radical containing 6 to 20 carbon atoms;
Claim: wherein when the skin of said mammal is exposed to bioactive agents, the passage of said bioactive agents through the skin is decreased.
Claim: 4. The method of claim 3, wherein said stability-increasing compound is N-dodecanoyl-2-oxazolidinone.
Current U.S. Class: 424/406; 424/59; 424/709; 574/376
Current International Class: A01N 2532
Patent References Cited: 3100180 August 1963 Smith et al.
4960771 October 1990 Rajadhyaksha
5091379 February 1992 Aungst
Other References: Brain, K.R. et al., Abstract of "Electrostatic Factors in the Activity of Penetration Enhancers," presented at the Third International Prediction of Percutaneous Penetration Conference held in La Grande Motte, Apr. 1993.
Bronaugh, R.L. et al., "Vehicle Effects on Percutaneous Absorption: in vivo and in vitro Comparisons with Human Skin," British Journal of Dermatology 115: 1-11 (1986).
Franz, T.J., "The Finite Dose Technique as a Valid in vitro Model for the Study of Percutaneous Absorption in Man," Curr. Probl. Dermatol. 7: 58-68 (1978).
Hadgraft, J. et al., "Investigations on the Percutaneous Absorption of the Antidepressant Rolipram in vitro and in vivo," Pharmaceutical Research 7(12) : 1307-1312 (1990).
Williams, D. G., "Mechanisms of Action of Penetration Enhancers," Ph.D. Thesis, University of Wales, 1991.
Primary Examiner: Levy, Neil
Attorney, Agent or Firm: Sterne, Kessler, Goldstein & Fox
Dokumentencode: edspgr.06086905
Datenbank: USPTO Patent Grants
Beschreibung
Abstract:Methods for preventing the penetration of toxic chemicals through the stratum corneum of the skin of a mammal are disclosed which employ, as a penetration prevention agent, at least one compound selected from the group consisting of compounds represented by the formula: ##STR1## wherein W.sub.1 is a divalent oxygen, sulfur or nitrogen radical, W.sub.2 and W.sub.3 are independently a divalent oxygen or sulfur radical, R' is an alkyl radical comprising from 1 to 4 carbon atoms, y is 0 or 1, R.sub.1 and R.sub.2 are alkyl radicals comprising from 1 to 10 carbon atoms and R and R.sub.3 are individually a hydrocarbyl radical containing from 1 to 20 carbon atoms or a heteroatom-substituted derivative thereof wherein at least one but not two adjacent carbon atoms may be replaced by a divalent oxygen or sulfur radical or by NR", wherein R" is hydrogen or R', n is an integer from 2 to 5 and compounds represented by the above formula in which the ring and/or R includes one to three carbon carbon double bonds.