Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice
Reexamination Certificate
2000-09-05
2001-08-28
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Cosmetic, antiperspirant, dentifrice
C424S458000, C424S450000, C514S943000, C514S844000, C514S887000, C514S863000, C514S861000, C514S864000, C514S859000, C514S858000
Reexamination Certificate
active
06280755
ABSTRACT:
The present invention relates to the new use of a non-methylene interrupted fatty acid in the prevention and/or the treatment of inflammation in superficial mammalian tissues.
BACKGROUND OF THE INVENTION
The use of fatty acids for preventing and/or treating inflammation in superficial tissues has been described in the literature.
For example, EP 5 472 705 (Prospa B. V.) discloses new pharmaceutical compositions for topical use containing esters of &ohgr;-3 polyunsaturated acids in a high concentration and intended for treating psoriasis, phlebitis and related pathologies.
EP 582 239 (Rhône-Poulenc Rorer) discloses topical pharmaceutical and cosmetic compositions containing linoleic acid or derivatives thereof as active ingredients, and a carrier for transporting the active ingredient into the skin. These compositions are used for the prophylaxis and treatment of impure skin, e.g. skin affected by pimples, pustules, urticaria or comedones, of acne and of acne-associated skin disorders.
Furthermore, EP 5 312 834 (Woobang Land Co.) discloses a pharmaceutical composition for treating acne comprising eicosapentaenoic acid and (&agr;-linolenic acid, in a weight ratio of 1:0.1 to 20:0.1 of eicosapentaenoic acid to &agr;-linolenic acid respectively. These fatty acids may be extracted from natural substances such as fish oil and/or perilla oil, for example.
The term non-methylene-interrupted fatty acid, the acronym for which is NMIFA, refers to a fatty acid with a series of double bonds in which at least one adjacent pair of double bonds is separated by at least two carbon atoms, i.e., by a group other than a single methylene group. NMIFAs have been the subject of only a few studies with the aim of developing an understanding of their incorporation into mammalian tissues and their potential role in the treatment of certain diseases.
For example, JP 61 058 536 (Nippon Oil) discloses a method for purifying pine nut oil containing at least 10% by weight of 5,9,12-cis-octadecatrienoic acid which exhibits a curative effect against arterial hypertension. WO 96 05 164 (Broadben Nominees Pty) discloses an anti-inflammatory preparation comprising a purified active fraction, for example 5,11,14,17-eicosatetraenoic acid, isolated from a lipid extract of
Perna canalicullus
or
Mytilus edulis.
WO 95 17 987 (The Regents of the University of California) shows that broad class of NMIFAs, including 5,11,14-eicosatrienoic acid, may be used in an effective amount for suppressing autoimmune diseases in general, for example rheumatoid arthritis, lupus erythmatosis, multiple sclerosis, myasthenia gravis, and about 30 other diseases currently known.
Incorporation of dietary 5,11,14-eicosatrienoate into various mouse phospolipid classes and tissues has been studied. Results show that feeding the mice 5,11,14-eicosatrienoate resulted in lower levels of 20:4n-6 in the hepatic phosphatidylinositol pool. Because leukotrienes and prostaglandins cannot be formed from 5,11,14-eicosatrienoate due to the lack of an internal &Dgr;8 double bond, and because 20:4n-6 was dramatically reduced in some phosphatidylinositol pools, it was expected that dietary intake of 5,11,14-eicosatrienate may alter eicosanoid metabolism, thus reducing potential inflammation in the hepatic system (Biochemica et Biophysica Acta, 1085, 371-376, 1991; J. Nutr. Biochem., 4, 409-420,1993).
So far, the following class of NMIFAs, especially 5,11,14-eicosatrienoic acid has not been reported as being capable of being incorporated into the lipid fraction of superficial mammalian tissues. Neither has an anti-inflammatory effect in superficial mammalian tissues been expected.
SUMMARY OF THE INVENTION
Accordingly, it has been found that the NMIFAs having the following formula, wherein the NMIFA is an acid, a salt or an ester, and R
1
is a C
1
-C
5
alkyl group and R
2
is a C
2
-C
6
alkyl group, may be advantageously used for the preparation of a composition intended to modulate the metabolism of lipids in superficial mammalian tissues.
Particularly preferred NMIFAs are those in which R
1
is a C
3
alkyl group and R
2
is a C
2
-C
6
alkyl group, or in which R
2
is a C
4
alkyl group and R
1
is a C
1
-C
5
alkyl group. The most preferred is that in which R
1
is an n-propyl group and R
2
is an n-butyl group (5,11,14-eicosatrienoic acid, also called 20:3(5,11,14)).
The NMIFAs of the invention may also be used in this context for the preparation of a composition intended to treat or prevent inflammations is superficial mammalian tissues by modulating the metabolism of the lipids. The invention also relates to topical pharmaceutical and cosmetic compositions comprising the NMIFAs of the invention as active ingredient. In a last aspect, the invention provides a pharmaceutical, food or cosmetic composition comprising a combination of fish oil and the NMIFAs of the invention.
The NMIFAs of the invention offer similar advantages as fish oils known to one skilled in the art. However, they provide the advantage of being less oxidizable than fish oil, since they have only two methylene interrupted bonds as compared to docosahexaenoic acid contained in fish oil having 6 methylene interrupted bonds. In addition the NMIFAs of the invention are not a substrate for prostaglandin and leukotriene production, whereas prostaglandin and leukotriene can be formed from the fatty acids found in fish oil, such as 20:5n-3 and 22:6n-3. A further advantage over fish oil preparation is the lack of “fishy” odour.
DETAILED DESCRIPTION OF THE INVENTION
“Modulation of the metabolism of lipids” is understood as meaning more particularly catabolism of the lipid mediators associated with inflammation, differentiation, proliferation and/or barrier function of superficial tissues.
Furthermore, inflammation of superficial tissues must be understood as the physiological phenomenon involving the production of pro-inflammatory cytokines, such as cachectin &agr; (TNF&agr;), by the cells of superficial tissues, for example the keratinocytes and the epithelial cells of the cornea, and the cells of the immune system which are contained in these tissues (lymphocytes, Langerhans' cells and the like). The inflammation may result, for example, from an infection, an allergy, a wound and an exposure to radiation and/or irritating agents and/or sensitizing agents.
The fatty acid which is the subject of this invention is a polyunsaturated fatty acid which is linear and monocarboxylic, with all double bonds being cis-double bonds. Several types of nomenclature are used in this specification, and these are as follows.
a) Nomenclature for individual compounds indicating number of carbon atoms and number and position of double bonds, a typical example being “20:4(5,8,11,14)” for arachidonic acid: the number preceding the colon is the total number of carbon atoms, the number immediately following the colon is the number of double bonds, and the numbers in parentheses are the positions of the double bonds, starting from the end of the chain bearing the carboxylic acid group. In all compounds represented in this manner, except where otherwise indicated, all double bonds are cis.
b) Nomenclature for classes of compounds indicating the location of the double bond closest to the methyl end group, a typical example being “n-3” or “n-6”: the number following the dash denotes the position of the double bond closest to the methyl end of the molecule, counting from the methyl end. Thus, arachidonic acid is in the n-6 class, as is 5,11,14-eicosatrienoic acid (20:3(5,11,14,)), whereas 5,8,11,14,17-eicosapentaenoic acid (20:5(5,8,11,14,17)) is in the n-3 class. This nomenclature is equivalent to “&ohgr;” nomenclature in the literature, “&ohgr;” and “n” being interchangeable.
Some of the NMIFAs of the invention are naturally occurring substances. Others may be synthesized according to well known published methodology (see for example Evans et al., Chem. Phys. Lipids, 38, 327-342, 1995).
For example, 20:3(5,11,14) is a naturally occurring substance which generally occurs as one fatty acid in a mixture of fatt
Berger Alvin
Jomard Andre
Bennett Rachel M.
Burns Doane Swecker & Mathis L.L.P.
Page Thurman K.
Societe L'Oreal S.A.
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