Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Reexamination Certificate
2002-02-07
2004-03-30
Carr, Deborah D. (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
C514S560000, C554S035000, C554S051000, C554S223000, C554S224000, C554S229000, C562S553000, C562S556000
Reexamination Certificate
active
06713511
ABSTRACT:
FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to acylates for treatment of a disease or condition related to a neurotransmitter defect or deficiency, or to another central or peripheral. nervous system defect or deficiency.
As detailed, for example, in U.S. Pat. No. 4,826,877 (Stewart et al.) and U.S. Pat. No. 4,868,212 (Horrobin), the essential fatty acids consist of the n-3 series derived from and including &agr;-linolenic acid and the n-6 series derived from and including linoleic acid; since neither &agr;-linolenic acid nor linoleic acid are manufactured in the body, they must be provided by food. The n-3 series thus includes &agr;-linolenic, &Dgr;-6,9,12,15-octadecatetraenoic, &Dgr;-8,11,14,17-eicosatetraenoic, &Dgr;-5,8,11,14,17-eicosapentaenoic, &Dgr;-7,10,13,16,19-docosapentaenoic and &Dgr;-4,7,10,13,16,19-docosahexaenoic acids, and the n-6 series thus includes linoleic, &Dgr;-6,9,12-octadecatrienoic (&ggr;-linolenic), &Dgr;-8,11,14,-eicosatrienoic (dihomo-&ggr;-linolenic), &Dgr;-5,8,11,14-eicosatetraenoic (arachidonic), &Dgr;-7,10,13,16-docosatetraenoic (adrenic) and &Dgr;-4,7,10,13,16-docosapentaenoic acids. The term “essential fatty acids” in the present specification and claims means all twelve of the above-mentioned fatty acids.
In U.S. Pat. No. 4,826,877, there is described use of the essential fatty acids for the prevention or treatment of diabetic neuropathy and other long term complications of diabetes mellitus. In U.S. Pat. No. 4,868,212, such acids are used in treatment of atopic disorders, while in U.S. Pat. No. 5,591,446 (Melnik et al.), &ggr;-linolenic and/or dihomo-&ggr;-linolenic acids are used for atopy prophylaxis. In U.S. Pat. No. 4,497,827 (Nelson), arachidonic acid analogues are utilized as anti-inflammatory, antiallergenic and antibrochoconstriction agents. In U.S. Pat. No. 3,995,059 (Fukumaru), N-(&agr;-alkyl) benzylamides of C
13
-C
25
aliphatic carboxylic acids are used for lowering elevated levels of cholesterol in the blood.
In U.S. Pat. Nos. 5,599,840, 5,468,776, 5,416,114, 5,288,755, 5,120,763 and 4,851,431, to Yehuda, S., there are described compositions which comprise a combination of &agr;-linolenic acid and linoleic acid, within a range of strictly defined proportions, stated to be useful in enhancing memory, producing analgesia, regulating sleep, inhibiting senility symptoms, and in treating Alzheimer's disease and related dementia, and epilepsy. In International Patent Application No. PCT/IL97/00366, published May 28, 1998 as WO 98/21949, the same inventor described the application of essentially the same combination of acids, for the treatment of multiple sclerosis. By contrast, use of mixtures of &agr;-linolenic acid and linoleic acid in proportions outside of the specified range, or (as is implicit from the U.S. patents and explicit in WO 98/21949), each acid or &ggr;-linolenic acid taken separately, or substituting &ggr;-linolenic acid for &agr;-linolenic acid in a pharmacologically active mixture with linoleic acid, did not afford any significant pharmacological activity.
The contents of the U.S. Patents referred to in the present application, and of WO 98/21949, are incorporated herein by reference.
To the best of the present inventor's knowledge, it has been neither disclosed nor suggested in the prior art, to utilize acylates derived from essential fatty acids, for treatment of a disease or condition related to a neurotransmitter defect or deficiency, or to another central or peripheral nervous system defect or deficiency. From another aspect, it does not appear to have been previously disclosed or suggested in the prior art, that essential fatty acids, by forming covalent bonds with naturally occurring &agr;-aminocarboxylic acids, neurotransmitters other than such acids, or central or peripheral nervous system pharmacologically active compounds, would thereby have the ability to transport such substances, in the form of the resultant acylates, across the blood-brain barrier.
Although a vast number of drugs are known to medicine, many do not realize their full potential because of the problem of applying them at an internal body site (such as appropriate receptors), where they would be most efficacious. Another aspect of this problem is the necessity to administer a relatively large amount of an expensive drug, in order that a very small fraction will reach the appropriate body site and exert a pharmacological effect. The usual procedures for drug administration are consequently uneconomical and also frequently produce undesired side-effects.
It is an important object of the present invention to advance the science of pharmacology in order to avoid so far as possible the problems set forth in the preceding paragraph. Other objects of the invention will appear from the description which follows.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides an acylate which is the reaction product of: (a) a substance which is selected from the group consisting of naturally occurring &agr;-aminocarboxylic acids, neurotransmitters other than such acids, and central nervous system pharmacologically active compounds, and containing a functional group including an acylatable hydrogen atom, or a reactive derivative thereof; and (b) an essential fatty acid or a reactive derivative thereof.
In another aspect, the invention provides use of at least one acylate as defined in the preceding paragraph, in the manufacture of a medicament for treatment of a disease or condition related to a neurotransmitter defect or deficiency, or to another central or peripheral nervous system defect or deficiency.
In still another aspect, the invention provides a method for treatment of a disease or condition related to a neurotransmitter defect or deficiency, or to another central or peripheral nervous system defect or deficiency, wherein there is administered to a human or non-human mammal an effective amount of at least one acylate as defined in the last paragraph but one.
In yet a further aspect, the present invention also provides a pharmaceutical formulation which comprises at least one acylate of the invention, together with at least one carrier, diluent or adjuvant.
For the avoidance of doubt, it is to be noted that the preparation of the acylates of the present invention involves the formation of a covalent bond or bonds between a substance defined under (a), above, and one or more molecular proportions of component (b) as defined above. The acylates may be N-acylates, O-acylates or S-acylates, or a mixture of more than one of these types of acylate.
Included in the compounds of the present invention are functional derivatives of the present acylates, and in particular of such acylates which contain residual amino, carboxyl and/or hydroxyl groups. The nature and range of such functional groups will be well known to persons of the art. Presently preferred functional derivatives of acylates containing one or more carboxylic groups are esters thereof with alcohols containing 1-4 carbon atoms. The functional derivatives appear to have similar biological activity to the non-functionalized acylates.
While the scope of the present invention is deemed not to be restricted by any theory, it is nevertheless presently believed that enzymes associated with relevant receptors will split the covalent bond between moieties (a) and (b), whereby component (a) exhibits its pharmacological activity at the site in question while the essential fatty acid—component (b)—is absorbed in the neuronal membrane.
DETAILED DESCRIPTION OF THE INVENTION
The acylates of the present invention, which by way of non-limiting exemplification may result from acylation with formation of a —CO—O—, —CO—S— or —CO—NR
1
R
2
moiety (where each of R
1
and R
2
is independently selected from a hydrogen atom or an optionally substituted hydrocarbyl group and NR
1
R
2
may also constitute a heterocyclic ring), may be prepared by any of the appropriate methods known to the organic chemist, and thus the manner of their preparation does not constitute, per
Carr Deborah D.
Nixon & Vanderhye P.C.
LandOfFree
Fatty acid derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Fatty acid derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Fatty acid derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3191031