Patent Application: US-32776002-A

Abstract:
a composition including a dose of flavonoids extracted from pine bark extract is described that decreases the rate of senescence of a mammal after onset of senescence . the same compound also increases mammal lifespan and increases neuromuscular performance after onset of senescence . methods of treatment and use of this composition are also described . the composition has the advantage of being a useful general aging remedy to avoid many common age related decreases in performance .

Description:
the invention will now be further described with reference to more detailed examples . with reference to the attached drawings , the methodology and process is described below : a first experiment was conducted on same aged white mice of the swiss outbreed and balb - c strains . “ weaners ” were young animals aged 110 days , obtained shortly after weaning and independent from their mothers . “ geriatric ” mice , about 470 days old , were obtained after having served as breeding stock for their productive lives . both sexes were investigated separately . preferably , the pine bark extract used in the present composition includes primarily flavonoid compounds and associated compounds . most preferably the pine bark extract composition as described above is an extract which exhibits antioxidant behavior in vivo . preferably , the pine bark extract used in the above composition is sourced from the bark of pinus radiata ( the monterey pine or radiata pine ). most preferably , the pine bark extract ( from pinus radiata bark ), is extracted using a water - based process . one example process is that of nz329658 / u . s . pat . no . 5 , 968 , 517 , incorporated herein by reference . it is a complex mixture of mainly flavonoids with some non - flavonoid compounds . phenolic compounds of pinus radiata bark include catechin , epicatechin , quercetin , dihydroquercetin , taxifolin , phenolic acids , and rprocyanidin dimers , trimers , oligomers and polymers formed from catechin and epicatechin . the extract is non - toxic to mice and humans , and it has a broad spectrum of action against a wide variety of free radical events . optionally , the composition , substantially as described above , further includes other anti - oxidant active components . these include vitamin c , vitamin e , ginko biloba , and other known therapeutically active compounds . in a further option the composition , substantially as described above , is also formulated using components selected from the group including ; fillers ; excipients ; modifiers ; humectants ; stabilizers ; emulsifiers ; and other known formulation components . the mice were divided up into groups and fed varying doses of pine bark extract manufactured in accordance with the method described in nz329658 / u . s . pat . no . 5 , 968 , 517 ( incorporated herein by reference ) as shown in table 1 below : the experimental mice were fed ad libitum on archer &# 39 ; s mouse food pellets dosed with measured doses of pine bark extract manufactured as above . preferably , the present composition is administered in a form selected from the group including : a tablet ; a capsule ; a suppository ; an injection ; a suspension ; a drink ; a tonic ; a syrup ; a powder ; an ingredient in solid foods ; an ingredient in liquid foods ; and combinations thereof , all of which are considered equivalent . most preferably , the composition is administered orally as a powder mixed with food . the antioxidant composition of the food was as follows ( table 2 below ): [ 0056 ] table 3 typical gel permeation chromatography fractionation of pine bark extract manufactured as above quoted as percentages of the total phenolic compounds present in the extract . olig - carbohy - mono - omeric poly - drates , esters & amp ; eric to trimeric proantho - meric otganic acids proanthocyanidins cyanidins proanthocyanadins 15 % 22 % 25 % 38 % the doses were arranged in a logarithmic series based on doses of 0 , 1 , 5 , 21 and 100 mg of pine bark extract / kg of body mass . because mice did not eat all the proffered food and wasted a portion of their ration , the dose was adjusted to compensate for this wastage so that they received the correct dose in the food they did consume . the preferred dose rate for the composition is between 0 . 5 and 100 mg / kg of body mass per day for the purpose of extension of life . it is understood by the applicant that dose rates may vary between these levels depending on the metabolism level of the mammal and other biochemical factors , such as seasonal dietary requirements . more preferably , the dose is 5 mg / kg of body mass per day . it will also be appreciated by those skilled in the art that a dosage greater than that of 100 mg / kg is also possible . pine bark extract is non - toxic and has a naturally occurring source that is a flavonoid - rich substance . higher doses would not produce any toxic reactions to the subject and may in fact be advantageous for some subjects that require additional oxidative treatment for reasons described above . a statistical analysis of the results showed that dietary supplementation was found to have profound effects on demographic performance of the mice . in both sexes , both strains and in all trials the relationship of mean body mass with age followed a two - phase relationship . after birth , this relationship has a positive gradient until they reached a critical age that is understood by the applicant to mark the onset of senescence . after this critical age , the rate of decline correlated with dose of pine bark extract . the higher the dose of pine bark extract , the slower the rate of senescence ( see fig1 , 3 and 4 which show the rate of senescence corresponding to dose ). referring to fig5 and 7 , it can be seen that an increase life span results from taking pine bark extract . the mice fed with pine bark extract dosages showed an increased proportion of survivorship ( fig5 ), a higher mean survival rate ( fig6 ) and a greater average life span ( fig7 ). a further test was run towards the end of the study on the elderly mice . the analysis was done by repeated measure of the neuromuscular performance in very elderly female mice by measuring the time taken ( duration ) before a mouse placed on a wooden rod fell . the results of this analysis are shown in fig8 . the results show that the time taken before a mouse placed on a wooden rod fell was strongly non - linear and positively related to dose i . e . mice on average were able to balance for approximately 6 times longer with a dose of 21 mg / kg and approximately 9 times longer for a dose of 100 mg / kg . the results thus show that pine bark extract slows down neuromuscular senescent decline in a dose related manner . that is , it reduces the rate of neuromuscular performance decline and hence in at least this symptom , decreases the rate of senescent decline . thus , the present invention contemplates providing a composition including a dose of flavonoids extracted from pine bark that has at least one mode of action selected from the group including : decreasing the rate of senescence of a mammal after onset of senescence ; increasing the life span of a mammal ; maintaining neuromuscular performance of a mammal after onset of senescence ; increasing neuromuscular performance of a mammal after onset of senescence ; and combinations thereof . the above composition has been found by the applicant to be particularly advantageous in delaying the rate of senescence and its related symptoms in mammals . trials completed by the applicant on mice indicate a reduction in the rate of senescence after onset by as much as 37 % for mice fed with a regular dose of pine bark extract . this in itself has the implication of an improved quality of life for mammals after the onset of senescence . further results indicate an increase in life span by 8 to 17 %. further results also show that the proportion of mice surviving longer is 80 % higher for those taking a regular dose of pine bark extract . this combination of results and the close phylogenetic relationship between mice and humans 30 show that this composition can be used to effectively increase the lifespan of a human . while the present example has used pine bark extract as the main composition , it will be appreciated that other pinus radiata compounds with similar properties may also be used . while a particular embodiment of the increased lifespan formulation has been described herein , it will be appreciated by those skilled in the art that changes and modifications may be made thereto without departing from the invention in its broader aspects and as set forth in the following claims . 1 . harman d . 1956 . aging — a theory based on free radical and radiation chemistry . journal of gerontology , 11 : a614 . 2 . harman d . 1981 . the aging process . proc . natl . acad . sci . u . s . a . 3 . halliwell , b , gutteridge , j m c . 1984 . oxygen toxicity , oxygen radicals , transition metals , and disease , biochem . j . 219 : 1 - 14 . 4 . halliwell , b , gutteridge j m c . 1999 . free radicals in biology and medicine , ( 3 rd . ed .). oxford : oxford university press . 5 . ames , b n , shigenaga , m k , hagen , t m . 1993 . oxidants , and the degenerative diseases of aging . proc . natl . acad . sci , u . s . a . 90 : 7915 - 7922 . 6 . bland , j s 1995 . oxidants and antioxidants in clinical medicine : past , present , and future potential . j . nutr . env . med ., 5 : 255 - 280 . 7 . diplock , a . t . 1994 . antioxidants and disease prevention . mol . aspects med ., 15 : 293 376 . 8 . halliwell , b . 1996 . antioxidants in human health and disease . ann . rev . nutr . 16 : 33 - 50 . 9 . beckman k b , ames b n . 1998 . the free radial theory of aging matures . physiological revues , 78 : 547 - 581 . 10 . yan l - y , sohal r j . 2000 . prevention of flight activity prolongs the life span of the house fly , musca domestica , and attenuates the age - associated oxidative damage to specific mitochondrial proteins . free radical biology and medicine , 29 ( 11 ): 1143 1150 . 11 . cheesman , k h ., slatter , t f . 1993 . an introduction to free radical biochemistry . brit . med . bull ., 49 : 481 - 493 . 12 . gutteridge j m c , halliwell b . 2000 . free radicals and antioxidants in the year 2000 : a historic look to the future . in : reactive oxygen species : from radiation to molecular biology : a festschrift in honor of daniel l . gilbert . 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