Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2002-02-14
2003-07-01
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S017000
Reexamination Certificate
active
06586628
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to novel 1-(3-methoxybenzyl)-3-substituted thiourea compounds and lipid and oil compositions supplemented with such compounds having enhanced oxidative stability.
BACKGROUND OF THE INVENTION
Natural lipids and oils are used in pharmaceutical preparations, food products, cosmetics, and various industrial products such as lubricants, coatings, inks, paints, plastics and the like. Such lipids are subject to oxidative degradation which can affect color, odor, viscosity, and lubricity characteristics thereof, adversely affecting the quality of the commercial products containing such lipids. In the food, cosmetics and pharmaceutical industries, maintaining high quality color and odor of oils and other lipids is important to avoiding oxidation-induced rancidity which is affected by factors such as the oxygen concentration, light and heat, as well as the degree of unsaturation of the lipid or oil, and the amount of natural or synthetic antioxidants present therein. Biodegradable lipids, oils and derivatives thereof used as cutting lubricants are recognized to be adversely affected by heat-induced oxidation.
Meadowfoam (
Limnanthes alba
) seed oil has been demonstrated to be highly stable to oxidation. It is more oxidatively stable than other vegetable oils. Although the identity of the compound(s) responsible for exceptional oxidative stability of meadowfoam seed oil is heretofore unknown, mixing meadowfoam seed oil with other oils imparts enhanced oxidative stability to the resulting mixtures. (Isbell, T. A., Abbott, T. A. and Carlson, K. D., 1999, “Oxidative Stability Index of Vegetable Oils in Binary Mixtures with Meadowfoam Oil,” Ind. Crops Prod. 9(2): 115-123). Several minor constituents in meadowfoam seed oil which either diminish oxidative stability or impart small increases in oxidative stability of meadowfoam seed oil are known, however. (Abbott, T. P. and Isbell, T. A., 1998, Abstracts of the 89th American Oil Chemist's Society Annual Meeting & Expo, Chicago, Ill., May 10-13, p 66). Refined meadowfoam seed oil (and other refined seed oils and vegetable oils) exhibit reduced oxidative stability as a result of the refining process. After processing, meadowfoam seed oil has been shown to contain glucolimnanthin, a glucosinolate, and its degradation products 3-methoxyphenyl actetonitrile, 3-methoxybenzyl isothiocyanate and 3-methoxybenzaldehyde. (Vaughn, S. F., Boydston, R. A. and Mallory-Smith, C. A., 1996, “Isolation and Identification of (3-Methoxyphenyl) Acetonitrile as a Phytotoxin from Meadowfoam (
Limnanthes alba
) Seedmeal,” J. Chem. Ecol. 22, 1939-1949). Glucosinolates have been shown to have little or no antioxidant effects. (Plumb, G. W., Lambert, N., Chambers, S. J., Wanigatunga, S., Heaney, R. K., Plumb, J. A., Aruoma, O. I., Halliwell, B. and Miller, N. J., 1996, “Are Whole Extracts and Purified Glucosinolates from Cruciferous Vegetables Antioxidants?” Free Rad. Res. 25, 75-86). When added to refined meadowfoam seed oil at levels from about 0.1% to 1.0%, the other compounds exhibit only small to moderate antioxidative effects, at best.
Thiourea has been shown to possess antioxidative activity in oils (Kajimoto and Murakami Nippon Eiyo, Shokuryo Gakkaishi 51(4):207-212, 1998; Chemical Abstract 129:188538); but thiourea is not very soluble in oils. The oxidative stability of ester-based synthetic lubricants (i.e., not vegetable oils) stabilized with amine antioxidants has been shown to be enhanced with specific thioureas (Chao T. S. and Kjonaas, M., “Some Synergistic Antioxidants for Synthetic Lubricants,” Amer. Chem. Soc. Preprints, Div. Pet. Chem. 27(2):362-379, 1982). Camenzind and Rolf, Eur. Pat. Appl. EP 91-810474, Chemical Abstract 117:30273, show that certain acylated thioureas are able to increase the oxidative stability to lubricants and hydraulic fluids. Vegetable oils may be stabilized by other alkyl- and aryl-substituted thioureas that are not plant derived, as well (Martin, G. D., “Stabilization of Fatty Acid Compounds,” 1939, U.S. Pat. No. 2,154,341).
Mono- and di-substituted thiourea compounds also have been described in U.S. Pat. Nos. 2,662,096, 3,852,348 and 3,991,008. Migirab et al., “Isothiocyanates, thioureas and Thiocarbamates Extracted from
Pentadiplandra brazzeanna,”
Phytochem. 16(11): 1719-1721, (1977), disclose methoxy-substituted aromatic thioureas, such as N,N′-bis[(4-methoxyphenyl)methyl]-thiourea (CAS #22313-70-8) and N,N′-di(4-methoxybenzyl)thiourea, which were isolated in extracts from
Pentadiplandra brazzeana.
Properties beneficial for commercial applications of lipid antioxidants include antioxidant activity in oils, thermal stability, low toxicity and lipid solubility. If the antioxidant will be employed in a sunscreen formulation for the skin and or hair, UVA and UVB absorbence activities of the antioxidant are also a benefit. Further, a thorough scientific characterization of the antioxidant compounds should include an elemental analysis, as well as NMR and IR spectral data.
There is a need for antioxidant compounds and compositions, especially natural antioxidants or derivatives thereof, that are soluble in lipids and oils, that are capable of imparting oxidative stability thereto when added at low concentrations, that exhibit thermal stability, that are not toxic and/or that absorb UVA and UVB wavelengths of sunlight.
Antioxidant compounds within the present invention are capable of imparting oxidative stability to lipids and/or oils when added at low concentrations, and are soluble in lipids and oils, exhibit thermal stability, are not toxic and/or absorb UVA and/or UVB wavelengths of sunlight. 1,3-di(3-methoxybenzyl)thiourea, for example, appears to have many of the qualities that are beneficial for an effective lipid antioxidant.
SUMMARY OF THE INVENTION
We have now unexpectedly discovered that excellent oxidative stability may be imparted to lipids and oils by compounds of the formula I:
wherein R is a C
1
-C
20
linear or branched alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, octyl, decyl, nonyl, dodecyl, and the like, C
5
-C
7
cycloalkyl, such as cyclopentyl, cyclohexyl or cycloheptyl and the like, hydroxy- or -alkoxy-substituted C
5
-C
7
cycloalkyl, C
1
-C
20
linear or branched alkenyl, such as propenyl, butenyl or octadecenyl and the like, C
5
-C
7
cycloalkenyl, C
6
-C
7
aryl, such as phenyl or benzyl and the like, hydroxy- or alkoxy-substituted C
6
-C
7
aryl, such as hydroxyphenyl, methoxyphenyl, ethoxyphenyl, hydroxybenzyl, methoxybenzyl or ethoxybenzyl and the like, benzoyl or hydroxy- or alkoxy-substituted benzoyl. Among compounds of the formula I, a presently preferred compound is 1,3-di(3-methoxybenzyl) thiourea, that is a compound of such formula I where R is a 3-methoxybenzyl moiety. An amount of a compound of formula I sufficient to impart oxidative stability to a lipid or oil (or compositions containing such lipids or oils) is from about 0.01 wt. % to about 5.0 wt. % based on the total weight of the lipid or oil.
The present invention also provides oxidatively stable lipid compositions comprising from about 95 wt. % to about 99.99 wt. % of a base lipid or oil and between about 0.01 wt. % and about 5.0 wt. %, more preferably between about 0.05 wt. % and 2.0 wt. %, and most preferably between about 0.1 wt. % and 1.0 wt. % of a compound of formula I. Lipids or oils of the present invention containing between about 3 wt. % and about 5 wt. % or more of a substituted thiourea compound of formula I, based on the total weight of the base lipid or oil composition, may be used as “concentrates” and conveniently added to processed seed oils or other lipids in need of enhanced oxidative stability to provide a lipid or oil composition of the present invention.
The present invention further provides a method for imparting oxidative stability to a base lipid or oil composition in need of enhanced oxidative stability, comprising the step of supplementing a base lipid or oil with an amount
Abbott Thomas P.
Wohlman Alan
Hastreiter Roberta L.
Lord, Bissell & Brook
Price Elvis O.
Richter Johann
The United States of America as represented by the Secretary of
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