WO1999053921A1 - Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph - Google Patents
Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph Download PDFInfo
- Publication number
- WO1999053921A1 WO1999053921A1 PCT/IT1999/000088 IT9900088W WO9953921A1 WO 1999053921 A1 WO1999053921 A1 WO 1999053921A1 IT 9900088 W IT9900088 W IT 9900088W WO 9953921 A1 WO9953921 A1 WO 9953921A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carnitine
- nadh
- composition
- alkanoyl
- acid
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- Composition comprising L-carnitine or an alkanoyl L-carnitine and NADH and/or NADPH
- the present invention relates to a composition which exerts an action both on the metabolism and energy performance of skeletal muscle and on the regulation of muscle movement and co-ordination at central level through potentiation of effects at both peripheral muscle and central nervous system level.
- the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in.
- the composition of the invention is particularly suitable both for facilitating adaptation of skeletal muscle in individuals engaging in intense, prolonged physical activity and to combat the sensation of muscle fatigue and exhaustion experienced by asthenic subjects even in the total absence of any form of more or less intense physical activity.
- asthenia is the diffuse set of aspecific symptoms typical of the stressful life conditions currently prevailing particularly in the major conurbations and built-up areas and involving a vast population, largely regardless of factors relating to age and social status, characterised by a lack or loss of muscular strength, with easy fatigability and inadequate reaction to stimuli.
- composition of the invention When used as a strictly therapeutic agent, one particular application of the composition of the invention is in the treatment of chronic fatigue syndrome and Parkinson's disease and of a syndrome similar to idiopathic parkinsonism, induced by the administration of illicit drugs.
- Chronic fatigue syndrome (CFS), officially described for the first time in 1988 in Annals of Internal Medicine, is a disease characterised by a degree of tiredness not explained by any known cause, often much more intense than that encountered in very serious diseases, such as tumours and AIDS, and debilitating to the extent of causing a more than 50% reduction in working activity and normal social relations, lasting more than 6 months.
- neuropsychological disorders such as memory loss, excessive irritability, mental confusion, difficulty with thinking and concentrating;
- sleep disorders characterised by insomnia or hypersomnia or drowsiness
- Parkinson's disease is generally regarded as an idiopathic condition
- the symptoms of parkinsonism can result from the abuse of drugs such as phenothiazine, butyrophenones and reserpine.
- drugs such as phenothiazine, butyrophenones and reserpine.
- parkinsonism has been studied in drug abusers injecting themselves with compounds similar to meperidine, the abusive synthesis of which had produced MPTP and MPPP.
- l-methyl-4-phenyl-l,2,3,6-tetrahydro ⁇ yridine MPTP or NMPTP
- MPPP l-methyl-4-phenyl-propoxy-piperidine
- L-dopa levo-dopa
- dopamine the metabolic precursor of dopamine
- carbidopa an inhibitor of dopa decarboxylase which prevents the systemic metabolism of levo-dopa before the latter reaches the brain.
- composition of the invention which, as will be described in detail here below, consists in a new combination comprising as its basic ingredients L-carnitine or a lower C2-C6 alkanoyl-L-carnitine or their pharmacologically acceptable salts and nicotinamide adenine dinucleotide (NADH) or a NADH precursor and/or nicotinamide adenine dinucleotide phosphate, reduced form (NADPH).
- NADH nicotinamide adenine dinucleotide
- NADPH nicotinamide adenine dinucleotide
- L-carnitine is unique in performing a vital physiological role as a vector of long-chain fatty acids across the internal mitochondrial membrane into the mitochondrial matrix, which is the site of their oxidation, and since a primary deficiency of L-carnitine was first recognised (Engel and Angelini, Science, 1973, 179: 899-902) as the cause of a severe, sometimes fatal, though rare, form of myopathy (lipid storage myopathy), there have been enormous advances in our knowledge of the pathological consequences of primary and secondary L-carnitine deficiencies and, conversely, of the therapeutic and nutritional value of an exogenous supply of L-carnitine.
- Carnitine is present in all biological tissues in relatively high concentrations as free carnitine and in lower concentrations in the form of acyl ca nitines which are metabolic products of the reversible reaction: acyl CoA + carnitine - ⁇ - ⁇ acyl carnitine + CoASH catalysed by three groups of enzymes, i.e.
- the transferases which mainly distinguish themselves by virtue of their specificity for reagent substrates: the carnitine acetyl transferase (CAT) group whose substrate are the short-chain acyl groups (such as acetyl and propionyl); the carnitine octanoyl transferase (COT) group whose substrate comprises the medium-chain acyl groups; and the carnitine palmitoyl transferase (CPT) group whose substrate comprises the long- chain acyl groups.
- CAT carnitine acetyl transferase
- COT carnitine octanoyl transferase
- CPT carnitine palmitoyl transferase
- L-carnitine has been proposed in the cardiovascular field for the treatment of cardiac arrhythmias and congestive heart failure (US 4,656,191), myocardial ischaemia and myocardial anoxia (US 4,649,159); in the field of disorders of lipid metabolism, for the treatment of hyperlipidaemias and hyperlipoproteinaemias (US 4,315,944) and for normalising an abnormal HDL:LDL-VLDL ratio (US 4,255,449); in the field of total parenteral nutrition (US 4,254,147 and US 4,320,145); in nephrology, to counter myasthenia and onset of muscle cramps caused by carnitine losses in dialysis fluid in chronic uraemic patients undergoing regular haemodialytic treatment (US 4,272,549); to counter the toxic effects induced by anticancer agents such as adriamycin (US 4,400,371 and US 4,713,370) and by halogenated an
- L-carnitine has also been proposed in combination with other active ingredients, such as the L-carnitine coenzyme 10 combination with a broad spectrum of metabolic/anti-atherosclerotic action (US 4,599,232).
- acetyl L-carnitine is known for the treatment of central nervous system diseases, particularly Alzheimer's disease (US 4,346,107) and for the treatment of diabetic neuropathy (US 4,751,242), whereas propionyl L-carnitine has been proposed for the treatment of peripheral vasculopathy (US 4,343,816) and congestive heart failure (US 4,194,006).
- Equally complex is the activity exerted by the coenzyme nicotinamide adenine dinucleotide (NADH) whose role at the energy level is well known.
- NADH coenzyme nicotinamide adenine dinucleotide
- the various complexes located in the internal mitochondrial membrane constitute a chain of oxidative systems going under the name of the cytochrome and Coenzyme Q10 chain, allowing the electrons to be transported from a lower- to a higher-potential system with the use of oxygen and formation of ATP. It is, in fact, from the respiratory chain that the oxidative phosphorylation derives which leads from NADH to the production of ATP.
- NADH along with the cytochrome and Coenzyme Q10 complexes, are the elements necessary for the transformation of energy to ATP and the NADH to be found at the start of this chain is the main conditioning element in this process.
- NADH quinodihydroxy-pteridine reductase
- L-dopa can act as a precursor of dopamine and thus transform itself metabolically into this latter substance, the same does not happen in the case of tyrosine, which can also be regarded as a precursor capable of leading to the formation of L-dopa, without the presence of tyrosine hydroxylase.
- a reduction in this enzyme has, in fact, been found at the level of the substantia nigra of parkinsonian subjects.
- H4-biopterin does not cross the blood-brain barrier and the direct administration of H4-biopterin is therefore of no avail, it appeared to be useful, in contrast, to resort to stimulation of the formation of H4-biopterin by administering the coenzyme necessary for the activity of quinodihydroxy-pteridine reductase
- DHPR for the formation of H4-biopterin, a function which is known to be performed by NADH. Administration of NADH therefore activates
- DHPR leading to the formation of the H4-biopterin necessary, in turn, for activating tyrosine hydroxylase so as to achieve the neosynthesis of dopa.
- composition of the invention comprises the following components in combination:
- the NADH precursor is nicotinamide.
- the weight-to-weight ratio of (a) to (b) generally ranges from 1:0.01 to 1:1, and should preferably range from 1:0.05 to 1:0.5; for example, the weight-to-weight ratio may be 1:0.1.
- the alkanoyl L-carnitine should preferably be selected from the group comprising acetyl L-carnitine, propionyl L-carnitine, butyryl L- 10
- L- carnitine acetyl L-carnitine, propionyl L-carnitine and isovaleryl L- carnitine is these compounds in the form of inner salts.
- pharmacologically acceptable salt of L-carnitine or of an alkanoyl L-carnitine is any salt of these with an acid that does not give rise to unwanted toxic or side effects. These acids are well known to pharmacologists and to experts in pharmacy.
- Non-limiting examples of such salts are: chloride; bromide; iodide; aspartate, acid aspartate; citrate, acid citrate; tartrate; phosphate, acid phosphate; fumarate, acid fumarate; glycerophosphate; glucose phosphate; lactate; maleate, acid maleate; orotate; oxalate, acid oxalate; sulphate, acid sulphate; trichloroacetate; trifLuoroacetate and methane sulphonate.
- composition of the invention may further comprise vitamins, coenzymes, mineral substances and antioxidants.
- compositions of the invention comprise, for instance, 100-500 mg of (a) L-carnitine or alkanoyl L-carnitine or an equivalent amount of one of their pharmacologically acceptable salts and a quantity by weight of (b) NADH or NADPH such that the weight-to-weight ratio (a):( b) ranges from 1:0.01 to 1:1, and preferably from 1:0.02 and 1:0.2.
- Muscle enzyme activity was assessed after seven or after thirty days' training following isolation and homogenising of the gastrocnemius muscle of each rat (Oscai L.B., J. Biol. Med., 245, 6968, 1971). The enzymes assessed were citrate synthetase, isocitrate dehydrogenase and succinate dehydro- genase. 12
- Another group of animals served as a control group receiving no treatment. At the end of the third day of treatment all animals were sacrificed, their hearts were extracted and sections of papillary muscle measuring 1 mm in diameter and 4.5 mm in thickness were isolated. The tissues thus isolated were perfused in a thermostatic bath with a 100% saturated O 2 solution. The experimental hypoxia was then produced by introducing 100% N 2 in the bath in place of O 2 . The ATP content of the papillary muscle was analysed using the method described by Strehler B.L. (Strehler B.L., Methods in Enzymology III. New York. Acad. Press, 871, 1957). The analysis was carried out on tissue samples maintained under normal perfusion for a period of 90 min and after a period of hypoxia also lasting 90 min.
- hypoxia Treatment Before hypoxia After hypoxia
- MPTP as a neurotoxin mainly active at the level of the neuroskeletal system may be a significant experimental model for the study of parkinsonism and its biochemical and clinical pathogenesis.
- mice of the C57 BE/6 strain with a body weight of 20 g were used; one group of these mice were kept as controls, while the other groups were injected with two injections of 40 mg/kg MPTP subcutaneously with a 24 hr interval.
- the dopa assay was also carried out three weeks after MPTP treatment. Treatment both with NADH and with carnitine was given immediately prior to the start of the motility test; motility was assessed using a plexiglas camera traversed at different heights by two infrared rays according to the procedure described by Archer (Archer T., Fredrikson A., Psychopharmacology, 88, 141, 1986).
- compositions according to the invention are reported here below:
Abstract
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020007011499A KR20010042765A (en) | 1998-04-17 | 1999-04-14 | Composition comprising L-carnitine or an alkanoyl L-carnitine and NADH and/or NADPH |
EEP200000601A EE200000601A (en) | 1998-04-17 | 1999-04-14 | A composition comprising L-carnitine or alkanoyl L-carnitine and NADH and / or NADPH |
IL13901499A IL139014A0 (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph |
JP2000544325A JP2002512191A (en) | 1998-04-17 | 1999-04-14 | A composition comprising L-carnitine or alkanoyl L-carnitine and NADH and / or HADPH. |
AU34428/99A AU750645B2 (en) | 1998-04-17 | 1999-04-14 | Composition comprising L-carnitine or an alkanoyl L-carnitine and NADH and/or NADPH |
BR9909712-5A BR9909712A (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl-l-carnitine and nadh and / or madph |
SK1544-2000A SK15442000A3 (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph |
HU0101914A HUP0101914A3 (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph |
EP99916039A EP1071424A1 (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph |
CA002328331A CA2328331A1 (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph |
NO20005128A NO20005128L (en) | 1998-04-17 | 2000-10-12 | Composition comprising L-carnitine or an alkanoyl-L-carnitine and NADH and / or NADPH |
IS5663A IS5663A (en) | 1998-04-17 | 2000-10-13 | A composition comprising L-carnitine or alkanoyl L-carnitine and NADH and / or NADHP |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT98RM000238A IT1299161B1 (en) | 1998-04-17 | 1998-04-17 | COMPOSITION INCLUDING L-CARNITINE OR AN ALCANOYL L-CARNITINE AND NADH AND / OR NADPH |
ITRM98A000238 | 1998-04-17 |
Publications (1)
Publication Number | Publication Date |
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WO1999053921A1 true WO1999053921A1 (en) | 1999-10-28 |
Family
ID=11405812
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IT1999/000088 WO1999053921A1 (en) | 1998-04-17 | 1999-04-14 | Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP1071424A1 (en) |
JP (1) | JP2002512191A (en) |
KR (1) | KR20010042765A (en) |
CN (1) | CN1299283A (en) |
AU (1) | AU750645B2 (en) |
BR (1) | BR9909712A (en) |
CA (1) | CA2328331A1 (en) |
EE (1) | EE200000601A (en) |
HU (1) | HUP0101914A3 (en) |
IL (1) | IL139014A0 (en) |
IS (1) | IS5663A (en) |
IT (1) | IT1299161B1 (en) |
NO (1) | NO20005128L (en) |
PL (1) | PL343482A1 (en) |
SK (1) | SK15442000A3 (en) |
TR (1) | TR200002894T2 (en) |
WO (1) | WO1999053921A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10326822A1 (en) * | 2003-06-11 | 2005-01-05 | Herzpharma Vita-Check Diagnosegeräte GmbH | Dietary supplement, e.g. for increasing general performance, concentration and endurance, comprises NADH, L-carnitine, coenzyme Q10, L-carnosine, succinic acid, ascorbic acid and bioflavonoids |
WO2011022786A1 (en) * | 2009-08-31 | 2011-03-03 | Pharmaqest Pty Ltd | Methods for diagnosis and treatment of chronic fatigue syndrome |
US8252309B2 (en) | 2000-04-04 | 2012-08-28 | Sigma-Tau Industrie Farmaceutiche Riunite Spa | Dietary supplement energy-providing to skeletal muscles |
US20200121709A1 (en) * | 2017-12-22 | 2020-04-23 | Bontac Bio-Engineering (Shenzhen) Co., Ltd | Nadh compound composition, and preparation and use thereof |
EP3864969A4 (en) * | 2018-10-10 | 2022-06-15 | Leung, So Ngor Sally | Health product composition for supplementing deficiency, preparation method therefor and application thereof |
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MX2009012042A (en) * | 2007-05-11 | 2009-12-01 | Sigma Tau Ind Farmaceuti | Gel useful for the delivery of cosmetic active ingredients. |
CN104306390A (en) * | 2014-10-23 | 2015-01-28 | 苏州人本药业有限公司 | Application of reduced coenzyme II |
CN104840479A (en) * | 2015-02-17 | 2015-08-19 | 苏州人本药业有限公司 | Application of NADPH in preparation of drugs used for treating heart diseases |
PT3755160T (en) | 2018-04-20 | 2022-01-06 | Pacotrade Ag | Device for crushing deep-frozen foodstuffs provided in block form |
CN109170907A (en) * | 2018-08-30 | 2019-01-11 | 泓博元生命科技(深圳)有限公司 | A kind of preparation method of composition containing NMN, application and sports drink |
CN109105702A (en) * | 2018-08-30 | 2019-01-01 | 泓博元生命科技(深圳)有限公司 | A kind of preparation method of composition containing NADH, application and energy extender |
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-
1998
- 1998-04-17 IT IT98RM000238A patent/IT1299161B1/en active IP Right Grant
-
1999
- 1999-04-14 EE EEP200000601A patent/EE200000601A/en unknown
- 1999-04-14 IL IL13901499A patent/IL139014A0/en unknown
- 1999-04-14 KR KR1020007011499A patent/KR20010042765A/en not_active Application Discontinuation
- 1999-04-14 BR BR9909712-5A patent/BR9909712A/en not_active IP Right Cessation
- 1999-04-14 EP EP99916039A patent/EP1071424A1/en not_active Withdrawn
- 1999-04-14 CA CA002328331A patent/CA2328331A1/en not_active Abandoned
- 1999-04-14 CN CN99805644A patent/CN1299283A/en active Pending
- 1999-04-14 SK SK1544-2000A patent/SK15442000A3/en unknown
- 1999-04-14 PL PL99343482A patent/PL343482A1/en not_active Application Discontinuation
- 1999-04-14 AU AU34428/99A patent/AU750645B2/en not_active Ceased
- 1999-04-14 WO PCT/IT1999/000088 patent/WO1999053921A1/en not_active Application Discontinuation
- 1999-04-14 TR TR2000/02894T patent/TR200002894T2/en unknown
- 1999-04-14 HU HU0101914A patent/HUP0101914A3/en unknown
- 1999-04-14 JP JP2000544325A patent/JP2002512191A/en active Pending
-
2000
- 2000-10-12 NO NO20005128A patent/NO20005128L/en not_active Application Discontinuation
- 2000-10-13 IS IS5663A patent/IS5663A/en unknown
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8252309B2 (en) | 2000-04-04 | 2012-08-28 | Sigma-Tau Industrie Farmaceutiche Riunite Spa | Dietary supplement energy-providing to skeletal muscles |
DE10326822A1 (en) * | 2003-06-11 | 2005-01-05 | Herzpharma Vita-Check Diagnosegeräte GmbH | Dietary supplement, e.g. for increasing general performance, concentration and endurance, comprises NADH, L-carnitine, coenzyme Q10, L-carnosine, succinic acid, ascorbic acid and bioflavonoids |
WO2011022786A1 (en) * | 2009-08-31 | 2011-03-03 | Pharmaqest Pty Ltd | Methods for diagnosis and treatment of chronic fatigue syndrome |
US20200121709A1 (en) * | 2017-12-22 | 2020-04-23 | Bontac Bio-Engineering (Shenzhen) Co., Ltd | Nadh compound composition, and preparation and use thereof |
ES2786774R1 (en) * | 2017-12-22 | 2020-10-16 | Bontac Bio Eng Shenzhen Co Ltd | Composition for coenzyme compound NADH, preparation and application thereof. |
US10894059B2 (en) * | 2017-12-22 | 2021-01-19 | Bontac Bio-Engineering (Shenzhen) Co., Ltd | NADH compound composition, and preparation and use thereof |
EP3864969A4 (en) * | 2018-10-10 | 2022-06-15 | Leung, So Ngor Sally | Health product composition for supplementing deficiency, preparation method therefor and application thereof |
Also Published As
Publication number | Publication date |
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KR20010042765A (en) | 2001-05-25 |
NO20005128L (en) | 2000-12-18 |
ITRM980238A0 (en) | 1998-04-17 |
HUP0101914A2 (en) | 2002-03-28 |
EE200000601A (en) | 2002-04-15 |
CN1299283A (en) | 2001-06-13 |
BR9909712A (en) | 2000-12-26 |
IL139014A0 (en) | 2001-11-25 |
PL343482A1 (en) | 2001-08-27 |
TR200002894T2 (en) | 2001-01-22 |
SK15442000A3 (en) | 2001-06-11 |
AU750645B2 (en) | 2002-07-25 |
IS5663A (en) | 2000-10-13 |
AU3442899A (en) | 1999-11-08 |
EP1071424A1 (en) | 2001-01-31 |
ITRM980238A1 (en) | 1999-10-17 |
IT1299161B1 (en) | 2000-02-29 |
CA2328331A1 (en) | 1999-10-28 |
JP2002512191A (en) | 2002-04-23 |
HUP0101914A3 (en) | 2002-12-28 |
NO20005128D0 (en) | 2000-10-12 |
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