Organic compounds -- part of the class 532-570 series – Organic compounds – Fatty compounds having an acid moiety which contains the...
Reexamination Certificate
2000-04-14
2001-08-14
Carr, Deborah D. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Fatty compounds having an acid moiety which contains the...
Reexamination Certificate
active
06274748
ABSTRACT:
FIELD OF THE INVENTION
The invention relates generally to a process of reacting acids and alcohols. More particularly the invention relates to the reaction of a water-insoluble fatty acid with a water-soluble (hydroxyalkyl)amino alkane acid or (hydroxyalkyl)amine.
BACKGROUND OF THE INVENTION
Current methods for preparing fatty acid esters include the reaction of fatty acid with an alcohol under acid catalytic conditions. The reaction requires the removal of water to drive the equilibrium of the reaction in the desired direction. Additionally, some polyhydroxy compounds which are crystalline or have high melting points, such as tris(hydroxymethyl)methylamino ethanesulfonic acid (TES) and bis(hydroxyethyl)amino ethanesulfonic acid (BES) do not mix readily with fatty acids. TES and BES will dissolve in aqueous acid, but the resulting solution is not miscible with liquid fatty acid, and the reaction does not readily proceed. Therefore, this reaction is of limited use in forming fatty derivatives of such water soluble compounds.
Alternatively, esters of fatty acids can be prepared by reacting a fatty acid halide with a polyhydroxy compound in acetonitrile. For example, the tri-oleoyl ester of TES may be prepared by reacting oleoyl chloride and TES in acetonitrile. However, oleoyl chloride is not readily available in the quantities or purity necessary for commercial production of such esters. While it is possible to generate the oleoyl chloride in situ from relatively pure oleic acid and sulfuryl chloride, or other agents suitable for generating an acid chloride from a fatty acid, the process has not been demonstrated on a commercial scale.
SUMMARY OF THE INVENTION
The present invention relates generally to the reaction of a fatty acid and a (hydroxyalkyl)amino alkane acid or a (hydroxyalkyl) amine to form a compound having multiple ester groups and, under appropriate conditions, an amide group. In part, the present invention relates to a process for manufacturing compounds which is more economical than methods previously known in the art. This process is advantageous over the known processes because it does not require the use of a water-insoluble fatty acid chloride which is not readily available in commercial quantities. Additionally, the process of the present invention does not require the use of a solvent, such as acetonitrile, capable of solubilizing both lipids and water-soluble substances.
In a preferred embodiment, the present invention provides a process which employs a water-insoluble fatty acid and a (hydroxyalkyl)amino alkane acid or a (hydroxyalkyl) amine, to produce compounds, containing fatty acid ester moieties and/or fatty acid amide moieties, which have cytoprotective properties. For example, the compounds have antioxidant, emollient, skin penetration enhancing and/or anti-inflammatory properties and, therefore, are useful as pharmaceuticals and cosmetics.
Accordingly, it is an object of the present invention to provide a process which overcomes problems associated with other methods which use oleoyl chloride or other fatty acid chlorides which are not readily available in the bulk and purity to produce the desired compounds in commercially viable quantities.
It is another object of the present invention to provide a process which eliminates the problems associated with the use of acetonitrile or similar solvents, thereby providing a process which is subject to less stringent regulatory controls with respect to solvent residues and solvent disposal.
Yet another object of the present invention is to provide a process which is more economical than current methods for the production of fatty acid derivatives of BES and TES, and other water-soluble (hydroxyalkyl)amino alkane acids or (hydroxyalkyl)amines.
It is a further object of the present invention to provide a process which allows for more control, milder conditions, and less manipulation than current methods while producing a useful product.
Still another object of the present invention is to provide a process which is more versatile, allowing for the production of several different products based upon the particular reactants and reaction conditions.
A further object of the present invention is to produce compounds containing fatty acid ester and amide moieties by reacting a fatty acid with a (hydroxyalkyl)amino alkane acid or a (hydroxyalkyl) amine in the presence of an aqueous base.
Yet another object of the present invention is to provide a process for the production of TES-trioleate and TES-trioleate monoleoylamide by reacting TES with oleic acid.
Another object of the present invention to provide a process for the production of BES-dioleate and BES-monooleate by reacting BES with oleic acid.
It is an object of the present invention to provide a means of bringing the reactants of the process together in a homogeneous mixture so that they may more readily and effectively combine to produce the desired product.
These and other objects, features, and advantages of the present invention will become apparent after a review of the following detailed description.
DETAILED DESCRIPTION
Generally, the process of the present invention comprises mixing one or more fatty acids with a (hydroxyalkyl)amino alkane acid or a (hydroxyalkyl) amine to form compounds containing multiple fatty acid ester groups. More particularly, the process comprises mixing one or more water-insoluble fatty acids with a water-soluble (hydroxyalkyl)amino alkane acid or a (hydroxyalkyl) amine and an aqueous base to form a homogeneous mixture in which the water-insoluble fatty acid and the water-soluble (hydroxyalkyl)amino alkane acid or (hydroxyalkyl) amine may readily undergo chemical reaction to produce compounds containing multiple fatty acid ester groups, and, under certain circumstances, a fatty acid amide group.
Preferred fatty acids are those which are water-insoluble, especially unsaturated fatty acids. Due to the tendency of unsaturated fatty acids to oxidize at temperatures over 80° C., it is necessary to protect such compounds from atmospheric oxygen when temperatures above 80° C. are employed. This may be accomplished, for example, by the use of an inert gas to displace oxygen, such as argon or nitrogen, or other non-oxidizing gases such as carbon dioxide.
Fatty acids which are useful in the present invention include, but are not limited to, those having the following structural formula:
wherein n is an integer from 1 to 18, m is an integer from 0 to 4, and x is an integer from 0 to 12. Optionally, one or both of the hydrogen atoms of one or more of the —(CH
2
)— groups may be replaced by a bond. Thus, the fatty acids of the present invention may be fully saturated or may contain unsaturations in the form of one or more double or triple bonds between any of the carbon atoms. Further, any of the —(CH
2
)— groups can be exchanged for an —O—, —S—, or —N— atom, resulting in an ether, thioether, or amine containing fatty acid.
Those fatty acids useful in the present invention are either known in the art or can be prepared by conventional methods. The number and positions of the unsaturations may be varied by methods known in the art. Preferred unsaturated fatty acids include, but are not limited to, oleic acid, linoleic acid, linolenic acid, palmitoleic acid, and arachidonic acid, with oleic acid being especially preferred. Preferred saturated fatty acids include, but are not limited to, lauric acid, myristic acid, palmitic acid, stearic acid and eicosanoic acid. It is understood that fatty acids available commercially in large quantities may contain mixtures of these and other fatty acids. For example, oleic acid available in bulk is typically 75%-90% oleic acid with varying amounts of mono-unsaturated, di-unsaturated and tri-unsaturated fatty acids, as well as saturated fatty acids.
Any (hydroxyalkyl)amino alkane acid or (hydroxyalkyl)amine may be employed in the present invention. However, the invention is particularly useful for (hydroxyalkyl)amino alkane acids or (hydroxyalkyl)amines which are lipid-insoluble, crystalline, or solid
Carr Deborah D.
Kilpatrick & Stockton LLP
Zenith Cosmetic Technologies LLC
LandOfFree
Process for the manufacture of compounds containing a fatty... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the manufacture of compounds containing a fatty..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the manufacture of compounds containing a fatty... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2512745