Patent Application: US-14106198-A

Abstract:
a method of replenishing plasmalogens in mammals comprising treatment with a plasmalogen - replenishing - effective amount of one or more stantially pure monoethers of glycerols and their carboxylic acid ester derivatives of formula i : wherein r is a c 12 - c 22 linear or branched alkyl or alkenyl group ; and r 1 and r 2 are , each independently , hydrogen or an acyl moiety — r 3 } wherein r 3 is a linear or branched c 1 - c 30 alkyl or alkenyl ; and pharmaceutically - acceptable salts thereof , is disclosed . nutritional supplements , dietary supplements and food additives comprising one or more substantially pure compounds of formula i is also disclosed .

Description:
it has been found that nutritional and dietary compositions containing compounds of formula i are effective to replenish plasmalogens in mammals , including human beings . the subject compounds are metabolic precursors of plasmalogens which are believed to protect against the damaging effects of free radicals . while expressly disavowing any limitation to a given mode of action , it is thought that the nutritional action of the present invention is accomplished by increasing the availability of metabolic precursors or suitable substrates for the biosynthesis of free radical - scavenging molecules , most notably plasmalogens . by providing cells with either suitable substrates for plasmalogen synthesis by normal routes , or by inducing alternative pathways for plasmalogen synthesis , it is believed that the cells are thereby enabled to circumvent real or potential deterioration . this protective effect is believed to result from an increase in the free radical - scavenging ability of the cells . consequently , the present invention provides a method of providing a nutritional supplement or food additive to prevent free radical - mediated cell degeneration in a host mammal which comprises administering to the mammal an nutritionally - effective amount of one or more compounds of formula i or pharmaceutically - acceptable salts thereof . the active ingredients used in the above - described method are c 12 to c 22 alkyl mon - ethers of glycerol and their mono - and di - ester derivatives . the compounds are known and several methods for their preparation are described in the chemical literature . as noted above , all positional and optical isomers of the compounds of formula i , including racemic mixtures , pure or enriched enantiomeric forms , and mixtures thereof , are within the scope of the invention . from among the compounds of formula i , the preferred compounds for use in the present invention are the compounds wherein r is a c 16 to c 18 linear or branched alkyl group . chimyl and batyl alcohol are most preferred . the preferred pharmaceutically - acceptable salts of the compounds of formula i are mono or di - substituted basic salts such as sodium , potassium , and calcium salts . when hydroxy is evident in the formula i compound , the formula i compound may exist in the form of a basic pharmaceutically - acceptable salt . as used herein , the term “ pharmaceutically - acceptable salts ” means any salt conventionally used in the formulation and administration of foodstuffs , nutritional supplements and other dietary preparations . this term encompasses mono - and di - substituted basic salts of sodium , potassium , calcium , and the like of . the foregoing list is exemplary , not exclusive . a large number of salts acceptable for dietary administration are known to those of skill in the art . the salts of the invention are made by conventional methods well - known to those in the art . dietary compositions of the present invention comprise one or more nutritionally - effective compounds , i . e . one or more formula i compounds , pharmaceutically - acceptable salts thereof , or combinations thereof , together with an acceptable carrier . the formula i compounds may also be used as additives to other foodstuffs . the carrier must be pharmaceutically - acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof . the formulations include those suitable for oral , topical , or parenteral ( including subcutaneous , intramuscular and intravenous ) administration . the formulations may be manufactured in unit dosage form and may be prepared by any of the methods well - known in the art of the formulation of foods . all methods include the step of bringing the active compound into association with a carrier and one or more optional accessory ingredients . in general , the formulations are prepared by uniformly and intimately bringing the active compound into association with a liquid or solid carrier and then , if necessary , shaping the product into desired unit dosage form . the in vivo dosage in humans and other mammals depends largely upon the age and general health of the patient being treated . determining the optimum dosage for any given mammal is essentially an empirical and ongoing process . replenishment of plasmalogens in infants and children may optimally require more ( or less ) aggressive nutritional considerations than in older patients . in mammalian subjects , the compounds of formula i are preferably administered orally in combination with a suitable inert liquid or solid orally - acceptable carrier . such carriers are well known in the art . formulations of the present invention suitable for oral administration include discrete units such as capsules , cachets , tablets , boluses or lozenges ; each containing a predetermined amount of the nutritionally - effective compound ; as a powder or a granular form ; or in liquid form . tablets are made by compression or molding , optionally with one or more accessory ingredients . compressed tablets are prepared by compressing the active compound in a free - flowing form , e . g ., a powder or granules , optionally mixed with accessory ingredients , e . g ., binders , lubricants , inert diluents , surface active or dispersing agents , using conventional tabletting machinery . molded tablets may be made by molding a mixture of the powdered active compound with an suitable carrier , again using conventional and well - known molding equipment . formulations suitable for parenteral administration comprises a pre - measured concentrated solution or solid formulation containing a compound of formula i , which upon dilution with an appropriate solvent yields a solution suitable for parenteral administration . another useful formulation for parenteral administration comprises a pre - measured concentrated solution or solid formulation containing a compound of formula i , which upon dilution with an appropriate solvent yields a solution suitable for parenteral administration . in addition to the aforementioned ingredients , the formulations of this invention may further include one or more optional accessory ingredient ( s ) utilized in the art of dietary formulations , e . g ., diluents , buffers , flavoring agents , colorants , binders , surface active agents , thickeners , lubricants , suspending agents , preservatives ( including anti - oxidants ) and the like . a suitable effective dose for most conditions ranges from about 1 mg / kg body weight to about 10 g / kg body weight per day , and is preferably in the range of from about 100 to about 500 mg / kg body weight per day ( calculated as the non - salt form ). the total daily dose may be given as a single dose , multiple doses , e . g ., two to six times per day , or by intravenous infusion for a selected duration . dosages above or below the above - cited ranges are within the scope of the invention and such dosages may be administered to individual subject if the circumstances so dictate . for example , in a 75 kg mammal , a typical daily dosage might fall with the range of from about 100 mg to about 100 g per day . if discrete multiple doses are indicated , treatment might typically comprise 4 equal fractional doses given at 8 hour intervals to supply the total daily dosage . in general , heavy physical exercise and disease conditions may require the intake of considerable quantiites of vitamins , minerals and nutritional supplements apart from those available in the normal diet . nutritional supplements are important primarily for individuals who have inadequate diets or a reduced ability to absorb or utilize the nutrients , especially the elderly . typically , older individuals are less able to utilize nutrients from foods and are ill more often than younger individuals . the added benefits of taking nutritional and dietary supplements to maintain health and protect against disease and illness is currently recognized . antioxidants , such as vitamin e and vitamin c , for instance , are taken by many individuals to help neutralize free radicals and other reactive oxygen species . free radicals are unstable molecules that damage cell structures . examples of endogenously produced free radicals are superoxide anion , hydrogen peroxide and alkoxy radicals . these ever - present molecules , which are a natural consequence of aerobic metabolism , can also be created by illness , smoking , heat , radiation , alcohol and certain pollutants . the damaging effects of free radicals are combated by antioxidants . administration of an amount of one or more compounds of formula i , either neat , or ( preferably ) in combination with a carrier , replenishes plasmalogens . such a nutritional composition is taken as needed or on a daily basis to maximize their effectiveness . the subject invention thus provides a method of replenishing plasmalogens which comprises administering pharmaceutically - acceptable amounts of one or more compounds of formula i or pharmaceutically - acceptable salts thereof . with respect to the foregoing discussion involving the administration of compounds of formula i as nutritional supplements , one or more compounds of formula i can also be administered as part of a nutritional system . the term “ nutritional system ” as used herein means a formulation comprised of a mixture of vitamins , minerals and other nutritional supplements . a nutritional system comprising one or more compounds of formula i is particularly efficacious for the geriatric population . the present invention encompasses nutritional systems comprising one or more compounds of formula i in combination with vitamins , such as vitamin a , vitamin c , vitamin d , vitamin e and the like , and minerals , such as calcium salts , magnesium salts , iron complexes and the like , and other nutritional supplements , such as essential amino acids , sugars , carbohydrates and the like . the subject invention thus provides a method of replenishing plasmalogens , to combat the damaging effect of free radicals and to normalize the amount of these necessary components of cell membranes , which comprises administering nutritionally - effective amounts of one or more compounds of formula i or pharmaceutically - acceptable salts thereof as part of a nutritional system . foodstuffs are often “ fortified ” with vitamins , minerals and nutritional supplements to enhance the nutritional value of the foodstuff . nutritionals , such as compounds of formula i , can also be added in substantially pure form to foodstuffs . the food additive is comprised of an amount of one or more compounds of formula i in an effective amount to replenish plasmalogens through the diet . the examples are included herein solely to illustrate , and not to limit , the scope and utility of the present invention . this is an illustrative example of tablets containing the following ingredients which may be prepared in the conventional manner : an illustrative example of capsules containing the following ingredients which may be prepared in a conventional manner : an illustrative example of elixirs containing the following ingredients which may be prepared in a conventional manner : an illustrative example of liquids containing the following ingredients which may be prepared in a conventional manner : an illustrative example of a nutritional system specifically formulated for administration to elderly humans containing the following ingredients combined into a tablet which may be prepared in a conventional manner : amon , u . ; von stebut , e . ; ramachers , u . ; and wolff , h . h . 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