Patent Abstract:
a method is provided for the prevention and treatment of selective progressive degeneration within the central nervous system caused by hydroxyl - free or ferryl - free radicals formed by fenton - type catalyzed reactions between diffusible hydrogen peroxide and localized bivalent iron . the invention embodies unique pharmacologic composition for antioxidant protection by oral supplementation with hypoxanthine conjointly with either sodium l - ascorbate or l - ascorbic acid . the hypoxanthine is provided for its sodium - dependent intestinal absorption and transport for the systemic production of higher antioxidant and iron - chelating uric acid levels . ascorbate is provided as potent antioxidant to raise body ascorbic acid levels concurrently and to protect against possible deleterious effect from nucleobase or other molecular injury induced by oxidized uric acid as urate anion free radical caused in the antioxidant action of the uric acid . it is contemplated that such oral supplementation conjointly with hypoxanthine and l - ascorbate will support better health and will mitigate the progressive oxidative neuronal damage in alzheimer &# 39 ; s disease , amnestic mild cognitive impairment , down syndrome , amyotrophic lateral sclerosis , and parkinson &# 39 ; s disease .

Detailed Description:
the chemicals hypoxanthine and l - ascorbic acid or the sodium salt of l - ascorbic acid in the pharmacologic composition in this invention are available from various commercial listed sources such as those listed in the directory : chem sources in u . s . a ., 1999 edition , clemson , s . c . 29633 - 1824 , u . s . a . sodium ascorbate usp as well as l - ascorbic acid usp in granular or powder form and hypoxanthine ( 6 - oxypurine ) are available from spectrum chemicals and laboratory products , inc , gardena , calif . 90248 - 9985 , for example . all chemicals used in the following first 4 examples for this invention were of analytical quality . a colorimeter was used to detect peroxidations of o - dianisidine , 9 mg / dl , as chromogenic hydrogen donor when oxidized , with its absorbance measured at 460 nm in saline solutions ( 140 mm nacl , buffered by 3 mm phosphate salts at ph 7 . 4 ). ferrous sulfate or human hemoglobin was added to control and to test solutions containing uric acid or ascorbic acid shortly before the addition of hydrogen peroxide , with oxidized molecules of dianisidine measured promptly . the saline solutions were mimetic of cerebrospinal fluid except devoid of possible confounding other molecules . uric acid inhibition of substrate oxidations induced by reaction of ferrous sulfate ( 9 . 8 micromolar ) with 20 micromolar hydrogen peroxide time after h 2 o 2 absorbance increase % inhibition control 5 min . 0 . 049 ± 0 . 004 10 min . 0 . 049 ± 0 . 004 urate , 6 . 0 mg / dl 5 min . 0 . 012 ± 0 . 003 75 . 3 ± 4 . 8 ** 10 min . 0 . 014 ± 0 . 003 70 . 9 ± 4 . 5 ** urate , 0 . 5 mg / dl 5 min . 0 . 030 ± 0 . 003 36 . 8 ± 5 . 3 ** 10 min . 0 . 034 ± 0 . 017 26 . 5 ± 5 . 5 * values are means ± s . e . m ., n is 5 . significance from control : p = *& lt ; 0 . 01 ; **& lt ; 0 . 001 . uric acid inhibition of substrate oxidation by human hemoglobin level of 12 mg / dl in reaction with 20 micromolar hydrogen peroxide ascorbic acid inhibition at 1 . 6 mg / dl of substrate oxidation induced by reaction of ferrous sulfate ( 9 . 8 micromolar ) with 20 micromolar hydrogen peroxide ascorbic acid inhibition at 1 . 6 mg / dl of substrate oxidation induced by human hemoglobin level of 12 mg // dl in reaction with 20 micromolar hydrogen peroxide time after h 2 o 2 absorbance increase % inhibition control 5 min . 0 . 050 ± 0 . 028 10 min . 0 . 094 ± 0 . 006 ascorbate , 1 . 6 mg / dl 5 min . 0 . 000 ± 0 . 000 100 . 0 ± 0 . 0 * 10 min . 0 . 001 ± 0 . 008 99 . 8 ± 1 . 2 * values are means ± s . e . m ., n = 4 . p = *& lt ; 0 . 0001 . comments : the inhibition remained virtually complete in example 4 at 10 minutes of continued exposure to the hydrogen peroxide , in spite of greater absorbance increase or oxidation in the control solutions from continuing reaction of the peroxide with the iron that resided in the hemoglobin . the demonstrated hemoglobin - hydrogen peroxide reactions with absorbance increases confirm the fenton - chemistry oxidation finding of gutteridge ( gutteridge j m c ., 1986 ). he used higher concentrations of hemoglobin and hydrogen peroxide ( e . g . 0 . 67 or 0 . 8 mm of hydrogen peroxide ) in phosphate - saline buffer with 2 hour incubations at 37 ° c . a preferred embodiment of this invention employs a method which in millimole units contains 2 . 5 - times more sodium ascorbate than hypoxanthine in capsule or tablet form . their respective molecular weights are 198 . 1 and 136 . 1 . thus a preferred compositional mole ratio is supplied readily by blending the following amounts of sodium ascorbate usp and hypoxanthine as used in example 5 . about 0 . 9 gram of hypoxanthine given orally was required to raise serum or plasma uric acid level by about 2 . 4 mg / dl in persons of near 70 kg in weight ( 0 . 1 mmole / kg : clifford a j et al ., 1976 ). a more tolerable and non - acidity effect in the digestive tract is accomplished by use of sodium ascorbate in place of ascorbic acid ( hendler s s et al ., 2001 ). alternatively , when l - ascorbic acid ( of molecular weight of 176 . 1 ) is employed in the same compositional mole ratio of 2 . 5 to 1 , a slightly lesser weight amount of ascorbic acid is used in a preferred embodiment . hypoxanthine powder = 129 . 3 mg ( 0 . 95 mmole ) approximate net weight = 600 mg per capsule for example , mix 4 . 70 g of sodium ascorbate granules and 1 . 29 g of hypoxanthine by blending for about a minute . then , fill no . 00 - sized gelatin capsules to an average net weight of approximately 600 mg per blend per capsule , to make 9 plus filled capsules . two or three capsules per serving may be taken by month with liquid usually once or twice daily to raise plasma urate and ascorbate levels conjointly . while the invention has been described with reference to a specific embodiment , it will be appreciated that numerous variations , modifications , and embodiments are possible , and accordingly , all such variations , modifications , and embodiments are to be regarded as being within the spirit and scope of the invention . ames b h et al . uric acid provides an antioxidant defense in humans against oxidant - and radical - caused aging and cancer : a hypothesis . proc . natl . acad . sci . usa 1981 ; 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