Drug – bio-affecting and body treating compositions – Topical sun or radiation screening – or tanning preparations
Patent
1996-05-28
1998-09-15
Rotman, Alan
Drug, bio-affecting and body treating compositions
Topical sun or radiation screening, or tanning preparations
424 73, 514846, 514847, 514848, A61K 742, A61K 715, A61K 3104
Patent
active
058075429
DESCRIPTION:
BRIEF SUMMARY
CROSS REFERENCE
This application is a 371 of PCT/EP94/03264 filed Oct. 3, 1994.
The present invention relates to the use of certain compounds to inhibit nitrosation reactions (especially the formation of N-nitrosamines), to compositions comprising such compounds and to various methods of inhibiting nitrosation reactions.
N-Nitrosamines (hereinafter referred to simply as "nitrosamines") result from reaction of a nitrosating agent, such as nitrite, with a nitrosatable amino compound, for example an amine such as morpholine or dimethylamine. Most nitrosatable amines are secondary or tertiary amines, especially secondary amines. However, primary amines may be nitrosatable under certain circumstances. The properties and reactions of nitrosamines are reviewed in Kirk-Othmer "Encyclopedia of Chemical Technology" (John Wiley & Sons), Third Edition, Volume 15, pages 988 to 996.
As noted in the Kirk-Othmer reference, nitrosamines have been shown to be carcinogenic in many animal species. Accordingly, it is desirable to reduce the levels of nitrosamines in compositions with which humans and animals may come into contact, especially foodstuffs and consumer products such as toiletries, pharmaceuticals and cosmetics, but also in household and industrial products.
DE-A-3939475 (Eisenbrand) describes the use of certain amines to inhibit nitrosamine formation in cosmetics and lubricants.
WO-A-9200122 (University of Missouri) describes polymers useful for scavenging nitrosating agents, which polymers may be used in compositions to prevent nitrosating agents from reacting with any amines present to form nitrosamines.
GB-A-2274648, EP-A-0498346 and EP-A-0553800 (Albright & Wilson) describe the use of various inhibitors of nitrosamine formation, including carbonates, bicarbonates and certain phosphonates.
Wilcox et al ("Pyrroles as Effective Agents for Blocking Amine Nitrosation", Chem. Res. Toxicol. (1991), 4, 373-381) discuss ways in which nitrosamine formation may be inhibited/blocked, and state that blocking agents can be divided into three categories, viz a) those that chemically reduce the nitrosating agent (such as ascorbic acid, .alpha.-tocopherol, hydroquinone, catechols and thiols) b) those that promote deamination (such as urea and hydrazide) and c) those that covalently bind the nitrosating agent (such as certain phenols, anilines or alkenes). The authors describe various pyrroles which appear to act by the third of these mechanisms, i.e. by covalent binding of the nitrosating agent.
Schmeltz and Wenger ("2-Bromo-2-Nitropropane-1,3-Diol as a Nitrosating Agent for Diethanolamine: A Model Study", Fd Cosmet Toxicol (1979), 17, 105-109) describe a study which is alleged to show that the antimicrobial agent 2-bromo-2-nitropropane-1,3-diol (BNPD, also known as "Bronopol") caused nitrosation of diethanolamine and triethanolamine. The authors propose a mechanism by which BNPD releases nitrite ions, which are believed to be the nitrosating species, and further note that breakdown of BNPD may generate formaldehyde.
Casado et al ("Nitrite Ion as a Nitrosating Reagent. Nitrosation of Morpholine and Diethylamine in the Presence of Formaldehyde" J. Chem. Soc. Perkin Trans II (1984) pp 1963-1966) describe the kinetics of the nitrosation of morpholine and of diethylamine in the presence of formaldehyde at pH values from 6.5 to 8.2 and from 6.9 to 8.7 respectively. The authors propose a mechanism whereby the amines react with formaldehyde to form an iminium ion which then reacts with a nitrite ion to form a corresponding nitrosamine.
According to the present invention, there is provided the use of an iminium ion scavenger to inhibit nitrosation reactions.
The term "iminium ion scavenger" as used herein denotes an agent which reacts with iminium ions more readily then does a nitrosating agent such as the nitrite ion. Suitably, the iminimum ion scavenger is chosen such that at a concentration of 1M, preferably 500 mM, preferably 100 mM, suitably 10 mM, it reduces the rate of formation of nitrosamines by at least about 25%, preferabl
REFERENCES:
patent: 4189465 (1980-02-01), Rosenthal
patent: 4200542 (1980-04-01), Sedlak
patent: 4251563 (1981-02-01), Gruetzmacher et al.
patent: 4331468 (1982-05-01), Williams
patent: 4342789 (1982-08-01), Ueno et al.
patent: 4368330 (1983-01-01), Andrews
patent: 4443483 (1984-04-01), Sato et al.
patent: 4576825 (1986-03-01), Tracy et al.
Jul. 20. 1991). Feb. 9, 1990).
Fellion et al., IARC Science Publication No. 31, 1980, pp. 435-443.
Kabacoff et al., IARC Science Publication No. 57, 1984, pp. 347-352.
Kabacoff et al., JACS Symposium Series, No. 174, 1981 part 174, pp. 149-156.
Dunnett et al., Int'l. J. of Cosmetic Science, vol. 6, pp. 241-247, 1984.
Havery et al., ACS Symp. Series 553 Chap. 2, pp. 20-33, 1994.
Casado et al., J. Chem. Soc. Perkin Trans. II, pp. 1963-1966, 1984.
Wilcox et al., Chem. Res. Toxicol., vol. 4, pp. 373-381, 1991.
Schmeltz et al., Fd. Cosmet. Toxicol., vol. 17, pp. 105-109, 1979.
Chem. Abst., vol. 115, 182618f, 1991 (DE 3,939,475).
Kirk-Othmer, Enc. of Chem. Tech., 3rd Ed., vol. 15, pp. 988-996.
Ikeda et al., J. Soc. Cosmet. Chem., vol. 41, pp. 283-333, Sep./Oct. 1990.
Ong et al., J. Soc. Cosmet. Chem., vol. 31, pp. 153-159, May/Jun. 1980.
Bharucha et al., J. Argic. Food Chem., vol. 35, pp. 915-917, 1987.
Bao et al., Chem. Res. Toxicol., vol. 4, pp. 382-389, 1991.
Keefer et al., Science, vol. 181, pp. 1245-1247, Sep. 1973.
Rosenberg et al., CFTA Cosmetic Journal, pp. 30-37, 1981.
Challis Brian Christopher
Guthrie Walter Graham
Roper David Vincent
Trew David Frank
Knoll Aktiengesellschaft
Rotman Alan
LandOfFree
Chemical compositions for inhibiting nitrosation reaction in toi does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Chemical compositions for inhibiting nitrosation reaction in toi, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Chemical compositions for inhibiting nitrosation reaction in toi will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-84647