Organic compounds -- part of the class 532-570 series – Organic compounds – Fatty compounds having an acid moiety which contains the...
Reexamination Certificate
1999-02-23
2002-04-09
Carr, Deborah (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Fatty compounds having an acid moiety which contains the...
C435S135000
Reexamination Certificate
active
06369252
ABSTRACT:
FIELD OF THE INVENTION
The present invention is directed to structured lipids comprising triacylglycerols containing at least two different fatty acids esterified to the same glycerol moiety. In particular, the invention is directed to structured lipids, methods of forming structured lipids enzymatically, and methods of use of such lipids.
BACKGROUND OF THE INVENTION
Long-chain triacylglycerols (LCTs) from soybean and safflower oils have been the standard lipids used in making fat emulsions for total parenteral nutrition and enteral administration. However, long-chain fatty acids are metabolized slowly in the body. Medium-chain triacylglycerols (MCTs) have therefore been proposed as being more desirable than LCTs because they are readily metabolized to quickly release energy. Unfortunately, pure MCT emulsions are problematic, particularly when administered intravenously.
In some cases, particular triacylglycerols have been correlated with certain physiological conditions. For example, there are indications that high levels of certain polyunsaturated fatty acids found in fish oils in Eskimo diets are responsible for their remarkably low incidence of arterial disease. Therefore, there is an interest in providing compositions which have clinical applications such as reducing the risk of arterial disease, yet which have increased absorption rates over pure LCTs.
In one approach, MCTs and LCTs are chemically interesterified, so that a single glycerol moiety contains a mixture of fatty acid chains thereon. This structure is termed a structured lipid (also called a synthetic triacyiglycerol herein).
Structured lipids are disclosed in U.S. Pat. No. 4,906,664 to Bistrian, et al., which describes a nutritional supplement for the treatment of cancer cachexia including specific structured lipids having long and medium chain fatty acids. U.S. Pat. No. 5,661,180 to DeMichele discloses a method for modulating metabolic response to trauma and disease comprising administering a structured lipid containing a gamma-linolenic or dihomogamma-linolenic fatty acid, a medium chain fatty acid, and an n-3 fatty acid. Additionally, U.S. Pat. No. 5,312,836 to Bistrian describes specific triglycerides which have at least one short chain fatty acid and at least one medium chain fatty acid, wherein at least one of the short or medium chain fatty acids is at the sn-2 position. These disclosures however provide a limited number of structured lipids for specific purposes. Moreover, they do not disclose mixtures containing a relatively high concentration or proportion of the desired structured lipid.
In efforts to provide structured lipids, a number of different approaches have been taken. In one approach, structured lipids are chemically synthesized. Chemical synthesis usually involves reaction of glycerol esters from one source with alkyl esters or glycerol esters from another to form a product with a random distribution of acyl groups. The reaction is catalyzed by alkali metals or alkali metal alkylates such as sodium methoxide. This process usually requires a temperature of 80-90° C. and anhydrous conditions. Chemical synthesis has a number of drawbacks including the high temperature conditions, randomness of the reaction, a low percentage yield of the desired structured lipid and production of undesirable by-products.
Examples of chemically synthesized structured lipids include caprenin which is a common name for caprocaprylobehenin, a structured lipid containing 8:0, 10:0, and 22:0 fatty acids esterified to glycerol. See, e.g., Akoh,
Lipid Technology
, 61-66 (May 1997). Another product is salatrim which contains 2:0, 3:0, 4:0, and 18:0 fatty acids esterified to glycerol. See, e.g., Akoh,
Lipid Technology
, 61-66 (May 1997). The fatty acids of these structured lipids are each saturated.
An alternative to the chemical synthesis of structured lipids is the use of lipases. Lipases can catalyze the transesterification of triacylglycerols with fatty acids (acidolysis), the transesterification of glycerol esters (ester-ester transfer) or direct esterification of free fatty acids with glycerol. Enzymatic approaches to forming structured lipids have been previously described, e.g., Akoh, INFORM, 6(9):1056-1061 (September 1995) and Akoh and Sista,
J. Food Lipids
, 2:231-238 (1995). However, despite these disclosures, there remains a need for a greater variety of structured lipids and mixtures comprising structured lipids.
It is therefore an object of the invention to provide novel structured lipids. It is also an object to provide novel mixtures comprising structured lipids in relatively high yields. It is further an object to provide enzymatic methods of forming these structured lipids and mixtures comprising structured lipids.
It is additionally an object of the invention to provide methods of modulating total cholesterol levels, low-density lipoprotein cholesterol levels, triacylglycerol levels, and/or the ratio of T-helper cells to T-cytotoxic cells in an individual comprising administrating a structured lipid mixture. It is further an object to provide a method of modulating weight in an individual comprising administrating a structured lipid mixture.
SUMMARY OF THE INVENTION
In accordance with the foregoing objectives, structured lipids and mixtures comprising structured lipids are disclosed as well as enzymatic methods of forming them.
The invention includes a synthetic triacylglycerol having fat acids R
1
, R
2
and R
3
esterified to the glycerol moiety. In one embodiment, at least one of R
1
, R
2
and R
3
is a short chain fatty acid and R
2
, in the sn-2 position, is an unsaturated fatty acid. In another embodiment, at least one of R
1
, R
2
and R
3
is a short chain fatty acid and at least one of R
1
, R
2
and R
3
is an n-9 fatty acid. In an alternative embodiment, two of R
1
, R
2
and R
3
is a short chain fatty acid and one of R
1
, R
2
and R
3
is an unsaturated fatty acid. In yet another embodiment, one of R
1
, R
2
and R
3
is a short chain fatty acid and each of the remaining R
1
, R
2
and R
3
is a long chain fatty acid. Additional synthetic triacylglycerols provided by the methods described herein are also provided.
The enzymatic methods of the invention generally include combining acylglycerols, preferably triacylglycerols, or glycerophospholipids with one or more lipases under conditions which allow formation of mixtures comprising structured lipids by transesterification. In some cases, fatty acids and/or esters are combined with one or more acylglycerols or glycerophospholipids in the presence of an appropriate lipase(s).
In a specific embodiment, triolein, caproic acid, butyric acid and a lipase are combined. In another specific embodiment, a gamma-linolenic rich oil, a short or medium chain fatty acid, an unsaturated fatty acid other than the gamma-linolenic fatty acid and a lipase are combined. In an alternative specific embodiment, an n-3 fatty acid rich oil, tricaprylin and a lipase are combined. In yet another specific embodiment, tricaprin or trilinolein, capric acid ethyl ester and a lipase are combined. In yet a further specific embodiment, tristearin, a medium chain fatty acid and a lipase are combined. In an additional specific embodiment, trilinolein, tricaprin or caproic acid and a lipase are combined. In another specific embodiment, tricaprylin, an n-3 unsaturated fatty acid and a lipase are combined.
The lipase(s) used in the specific embodiments can be specific, non-specific, or a combination thereof. In a preferred embodiment, the lipase is specific for the sn-1 and sn-3 positions of the triacylglycerol.
All of the mixtures and structured lipids formed from the methods herein are within the scope of this invention. Generally, the mixtures resulting from the enzymatic reactions have higher percentages of the desired structured lipid than when using chemical synthesis. Moreover, the enzymatic reactions result in less side products than chemical synthesis using the same starting materials.
Also provided herein are methods of modulating total cholesterol levels, low-
Carr Deborah
Flehr Hohbach Test Albritton & Herbert LLP
The University of Georgia Research Foundation Inc.
Trecartin Esq. Richard F.
LandOfFree
Structured lipids does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Structured lipids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Structured lipids will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2884097