EP2120941A1 - Utilisation d'acide folique, de vitamine b6 et de vitamine b12 - Google Patents

Utilisation d'acide folique, de vitamine b6 et de vitamine b12

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Publication number
EP2120941A1
EP2120941A1 EP08708160A EP08708160A EP2120941A1 EP 2120941 A1 EP2120941 A1 EP 2120941A1 EP 08708160 A EP08708160 A EP 08708160A EP 08708160 A EP08708160 A EP 08708160A EP 2120941 A1 EP2120941 A1 EP 2120941A1
Authority
EP
European Patent Office
Prior art keywords
vitamin
osteoporosis
folic acid
acid
use according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08708160A
Other languages
German (de)
English (en)
Inventor
Martin GÖRNE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Phrontier Sarl
Original Assignee
Phrontier Sarl
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Phrontier Sarl filed Critical Phrontier Sarl
Publication of EP2120941A1 publication Critical patent/EP2120941A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • 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
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis

Definitions

  • the present invention relates to the use of folic acid, vitamin B6 and vitamin B12 for the preventive and acute treatment of osteoporosis. Described are in particular pharmaceutical agents and dietary supplements with a corresponding combination of active ingredients and agents in the form of commercial packs with corresponding combination preparations or mono-preparations for combined use.
  • Osteoporosis is a disease characterized by excessive degradation of the bone (quantitative deterioration) and bone structure (deterioration of quality) resulting in increased fracture susceptibility affecting the whole skeleton, but especially stressed bones such as the spine, femoral neck and wrist. It is therefore also referred to as bone loss.
  • Known risk factors include genetic factors, estrogen deficiency, plasmocytoma, hyperthyroidism, nutritional deficiencies, lack of exercise and consumption of stimulants.
  • osteoporosis can be triggered by a variety of factors, as well as "primary osteoporosis" occur without apparent underlying disease, and in these cases, also affect younger patients.
  • WO 2006/092294 relates to agents which contain folic acid, vitamin B6 and vitamin B12, and their use for regulating homocysteine levels.
  • the weight ratio of folic acid to vitamin B6 and vitamin B12 to vitamin B6 is given in a range of about 1: 33-75 and the weight ratio of folic acid to vitamin B12 is in a range of about 1: 0.67-1.50.
  • These agents have a homocysteine-lowering effect and are therefore useful in the treatment of vascular diseases such as arteriosclerosis, venous thrombosis and arterial occlusions, fetal damage such as neural tube defects, and neurodegenerative diseases such as certain forms of Alzheimer's disease. see dementia, useful.
  • vascular diseases such as arteriosclerosis, venous thrombosis and arterial occlusions
  • fetal damage such as neural tube defects
  • neurodegenerative diseases such as certain forms of Alzheimer's disease. see dementia, useful.
  • the present invention therefore relates to the use of folic acid, physiologically acceptable derivatives or salts thereof (also referred to for simplicity as “folic acids” or “folic acid component”), vitamin B6, physiologically acceptable derivatives or salts thereof (for the sake of simplicity also as “B6 Vitamins or vitamin B6 component) and vitamin B12, physiologically acceptable derivatives or salts thereof (for the sake of simplicity also referred to as "B12 vitamins” or “vitamin B12 component”) for the treatment of osteoporosis, wherein the Ratios of folic acid to vitamin B6 and vitamin B12 to vitamin B6 in a range from about 1:33 to about 1:75, and the ratio of folic acid to vitamin B12 in a range from about 1: 0.67 to about 1: 1 , 50 lies.
  • the present invention also relates to corresponding compositions based on the combination according to the invention of folic acid, vitamin B6 and vitamin B12 or physiologically acceptable derivatives and / or salts thereof for the treatment of osteoporosis.
  • the ratio of folic acid to vitamin B6 to vitamin B12 is about 1 to 50 to 1.
  • the stated proportions relate to weight amounts of the active ingredients folic acid, vitamin B6 and vitamin B12, so that for salts and derivatives, if necessary, a corresponding conversion has to be made.
  • the ratios can be molar amounts, so that assuming that 1 mole of the derivative or salt concerned contains 1 mole of folic acid, vitamin B6 or vitamin B12, the molar ratios for folic acid, vitamin B6, vitamin B12 and their derivatives and / or salts can be uniformly expressed.
  • Frolic acid refers according to the invention N-pteroylglutamic acid of the formula
  • the folic acid derivatives mainly include folic acid metabolites as well as amides and esters of folic acid as well as the metabolites.
  • Amides and esters which are hydrolyzable under physiological conditions such as amides with C 1 -C 10 -alkylamines or esters with C 1 -C 10 -hydroxy alcohols, are advantageous.
  • a particular form of the amides are N-pteroylpolyglutamic acids.
  • the folic acid metabolites mainly include H 4 -foluenes of the formula Ib O COOH
  • the optical isomers covered by this formula are correspondingly included above, the L-glutamic acid derivatives being preferred here as well.
  • tetrahydrofolic acid 5-methyltetrahydrofolic acid, 5,10-methylenetetrahydrofolic acid, 5-formyltetrahydrofolic acid, 10-formyltetrahydrofolic acid, 5-formiminotetrahydrofolic acid and 5,10-methenyltetrahydrofolic acid.
  • Physiologically acceptable salts of folic acid or folic acid derivatives include acid and base addition salts as well as corresponding mixed forms.
  • the acid addition salts include salts of folic acid or folic acid derivatives with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid, or organic acids, especially carboxylic acids, e.g. Acetic acid, tartaric acid, lactic acid, citric acid, malic acid, mandelic acid, ascorbic acid, maleic acid, fumaric acid, gluconic acid or sulfonic acids, e.g. Methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid, and the like.
  • inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid
  • organic acids especially carboxylic acids, e.g. Acetic acid, tartaric acid, lactic acid, citric acid, malic acid, mandelic acid, ascorbic acid, maleic acid, fumaric acid, gluconic acid or sulfonic acids, e.
  • the base addition salts include salts of folic acid or folic acid derivatives with inorganic bases, for example metal hydroxides or carbonates of alkali metals, alkaline earth metals or transition metals, or with organic bases, for example ammonia or basic amino acids, such as arginine and lysine, amines, for example Methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, 1-amino-2-propanol, 3-amino-1-propanol or hexamethylenetetramine, saturated cyclic amines having 4 to 6 ring carbon atoms, such as piperidine, piperazine, pyrrolidine and morpholine, and other organic bases, for example N-methylglucamine, creatine and tromethamine, and quaternary ammonium compounds, such as tetramethylammonium and the like.
  • Vitamin B6 denotes according to the invention 4,5-bis (hydroxymethyl) -2-methyl-3-pyridinol of the formula II
  • the vitamin B6 derivatives include, in particular, pyridoxals and pyridoxamines, as well as pyridoxine, pyridoxale and pyridoxamine esters. Also advantageous here are esters which are hydrolyzable under physiological conditions.
  • R3 is CH 2 OH, CHO or CH 2 NH 2 and R4 is OH or OPO 3 H 2 .
  • Physiologically acceptable salts of vitamin B6 or vitamin B6 derivatives include, in particular, acid addition salts, e.g. with the above-mentioned inorganic and organic acids.
  • the hydrochloride, especially pyridoxine HCl, to call are particularly preferred.
  • Vitamin B12 is also called cyanocobalamin or cobalamin.
  • the vitamin B12 derivatives include cobalamins in which the cyano group of cyanocobalamin is replaced by other cobalt coordination partners is. These include, in particular, hydroxocobalamin, aquocobalamin, nitrosocobalamin, methylcobalamin and adenosylcobalamin (coenzyme B12).
  • Physiologically acceptable salts of vitamin B12 or vitamin B12 derivatives include, in particular, acid addition salts, e.g. with the above-mentioned inorganic and organic acids.
  • acid addition salts e.g. with the above-mentioned inorganic and organic acids.
  • acetate of Hydroxocobalamins be mentioned.
  • Folic acids, B6 and B12 vitamins are well known and can either be obtained or made available in a manner known per se.
  • compositions according to the invention may include further active ingredients.
  • active substances may in particular be those whose action is similar to or supplements the folic acid, vitamin B6 or vitamin B12-mediated action and which in particular corresponds to the uses according to the invention.
  • the use according to the invention is directed in particular to the treatment of one or more of the following clinical pictures:
  • Type 2 Primary osteoporosis, preferably: 1. Idiopathic osteoporosis 2. Postmenopausal osteoporosis (Type 1) 3. Senile osteoporosis (Type 2)
  • Metabolic / endocrine conditional especially by: a. Hyperthyroidism and hyperparathyroidism b. Cushing's disease c. Diabetes mellitus d. Hypogonadism e. Acromegaly f. Homocysteinemia / homocystinuria
  • hereditary connective tissue diseases especially: a. Osteogenesis imperfecta b. Marfan syndrome c. Ehlers-Danlos Syndrome
  • One aim of the prophylactic treatment is to prevent the degradation of bone substance and / or bone structure and to avoid bone instability and / or fracture susceptibility resulting from the degradation.
  • One goal of the acute treatment is to slow down the degradation of bone structure and / or bone structure and to reduce bone instability and / or fracture susceptibility resulting from the degradation of the substance, as well as to improve healing and regeneration.
  • the T-value refers to the ratio of the measured value to the standard deviation of an osteolo- o healthy healthy reference population (typically 20-year-old of the same sex). According to the WHO guidelines, a T-value of -1, 0 or higher is still considered normal, a T-value between -1, 0 and -2.5 is considered to be "osteopenia" and a value of less than -2.5 as manifest osteoporosis.
  • the agents and applications of the invention are gaining importance in adults with increasing age.
  • the treatment brings special benefits.
  • the treatment according to the invention is indicated in particular when there is evidence or a risk of a degradation of bone substance or a change in the bone structure.
  • the individual to be treated preferably a mammal, in particular a human and also a useful or pet, an effective amount of the active ingredient combination of folic acid component, vitamin B6 component and vitamin B12 component of the invention, usually the pharmaceutical veterinary or food technology practice.
  • An amount is effective according to the invention in particular if it slows down the qualitative and quantitative deterioration of the bone material, for.
  • a slowdown in the further reduction of the T value preferably a qualitative and / or quantitative improvement of the bone material, for. B. causes an increase in the T value compared to the state before the start of treatment.
  • the treatment is usually carried out by administering a suitable dose once or several times, if appropriate together or alternately with other active substances or active substance-containing preparations, so that an individual to be treated with the weight of an average adult of about 75 kg usually has a minimum daily dose about 0.8 mg, preferably about 0.9 mg and advantageously about 1 mg folic acid, about 40 mg, preferably about 45 mg and advantageously about 50 mg vitamin B6, and about 0.8 mg, preferably about 0 , 9 mg and advantageously about 1 mg of vitamin B12 is administered.
  • the maximum daily dose is typically about 1.2 mg, preferably about 1.1 mg and advantageously about 1 mg folic acid, about 60 mg, preferably about 55 mg, and advantageously about 50 mg vitamin B6, and about 1.2 mg, preferably about 1, 1 mg and advantageously about 1 mg of vitamin B12.
  • the daily dose should be adjusted accordingly. This adjustment is usually carried out by the skilled person, if necessary taking account of analytical control investigations. Furthermore, deviations in the Daily dose by the prescribing physician also due to the state of health of the individual to be treated.
  • Treatment usually takes a reasonable amount of weeks or months. Useful are increases in bone density, decrease in fracture frequency, and diminution of quantifiable subjective complaints (eg, pain, immobilization) within a treatment period of about 1 to 12 months. If necessary, treatment will continue even after normalization of the individual's condition.
  • the invention also relates to the preparation of agents for treating an individual, preferably a mammal, in particular a human and also a useful or pet.
  • the means include, in particular, pharmaceutical agents, nutritional supplements and foods, e.g. functional or dietary foods.
  • the foods according to the invention additionally have an active ingredient-related function, which relates in particular to the active ingredient combination according to the invention. They are therefore referred to as functional or dietary foods or foods.
  • Nutritional supplements serve to supplement the daily diet with the combination of active substances according to the invention, whereby the nutrition-related function of the dietary supplement alone takes a back seat.
  • the present invention relates to formulations comprising i) at least one active ingredient from the folic acid group (folic acid, physiologically acceptable derivatives and / or salts thereof), ii) at least one active ingredient from the vitamin B6 group (vitamin B6, physiologically acceptable Derivatives and / or salts thereof), and iii) at least one active ingredient from the vitamin B12 group (vitamin B12, physiologically acceptable derivatives and / or salts thereof), and optionally at least one further active ingredient and a formulation base, in the quantitative ratios indicated according to the invention.
  • the active ingredient combination according to the invention as active ingredient component i) comprises folic acid, a physiologically acceptable derivative and / or salt thereof. Mixtures of these forms are possible, but only in certain cases to be considered. According to a particular embodiment, the active ingredient component i) consists of at least 90% by weight of folic acid.
  • the active ingredient combination according to the invention as active ingredient component ii) vitamin B6, a physiologically acceptable derivative and / or salt thereof. Gemi- see these forms are also possible, but only in certain cases into consideration.
  • the active ingredient component ii) consists of at least 90% by weight of pyridoxine HCl.
  • active ingredient combination according to the invention as active ingredient component iii) vitamin B12, a physiologically acceptable derivative and / or salt thereof. Mixtures of these forms are also possible, but only considered in certain cases.
  • the active ingredient component iii) consists of at least 90% by weight of cobalamin.
  • the proportion of the active ingredient combination in the formulation is greater than a proportion which may be present in natural sources, in particular foods. In this sense, the agents according to the invention are enriched with regard to the active ingredient combination.
  • the proportion of the active ingredient combination of i), ii) and iii) in the formulation is preferably at least about 0.01 wt .-%, advantageously at least about 0.05 wt .-% and in particular at least about 0.1 wt .-%.
  • the proportion is usually about 1 to 60 wt .-%, preferably about 5 to 35 wt .-% and in particular about 10 to 30 wt .-%, in the case of a dietary supplement and especially if appropriate, correspondingly lower for foods if the formulation is supplied in larger quantities.
  • the formulations contain the stated daily dose.
  • the formulation base of pharmaceutical formulations according to the invention contains physiologically acceptable excipients.
  • physiologically acceptable excipients which are known to be useful in the field of pharmacy, food technology and related fields, in particular those listed in relevant pharmacopoeias (eg DAB, Ph. Eur., BP, NF), and also other excipients whose properties do not preclude physiological application .
  • Excipients in the sense of the invention may also have a nutritional value and therefore be commonly used as a nutritional component. Also nutrients, especially essential nutrients, can belong to it.
  • Suitable adjuvants may be: wetting agent; emulsifying and suspending agents; conserving agents; antioxidants; Antiirritatives; chelating agents; coating aids; Emulsion stabilizers; film formers; gelling agents; Odor masking agents;
  • Food components usually contain one or more amino acids, carbohydrates or fats and are suitable for human and / or animal nutrition. They include individual components, often plant or animal products, in particular sugar, if appropriate in the form of syrups, fruit preparations, such as fruit juices, nectars, fruit pulps, purees or dried fruits, for example apple juice, grapefruit juice, orange juice, applesauce, tomato sauce, tomato juice, tomato puree; Cereal products, such as wheat flour, rye flour, oatmeal, maize flour, barley flour, spelled flour, corn syrup, and starches of said cereals; Dairy products such as milk protein, whey, yoghurt, lecithin and lactose.
  • fruit preparations such as fruit juices, nectars, fruit pulps, purees or dried fruits, for example apple juice, grapefruit juice, orange juice, applesauce, tomato sauce, tomato juice, tomato puree
  • Cereal products such as wheat flour, rye flour, oatmeal, maize flour, barley flour, spelled flour, corn syrup,
  • the essential nutrients include, in particular, vitamins, provitamins, trace elements, amino acids and fatty acids.
  • Essential amino acids include isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and VaNn. These also include semi-essential amino acids, which have to be supplied, for example, during growth phases or deficiencies, such as arginine, histidine, cysteine and tyrosine.
  • Trace elements are: essential trace elements whose need for humans has been proven and whose deficiency leads to the manifestation of clinical symptoms: iron, copper, zinc, chromium, selenium, calcium, magnesium, potassium, lithium, cobalt, molybdenum, iodine, Silicon, fluorine, manganese. Similarly, elements whose function is not sufficiently secured for humans: tin, nickel, vanadium, arsenic, manganese. As for humans essential fatty acids may be mentioned: linoleic acid and linolenic acid. A comprehensive list of vitamins can be found in "Reference Values for the supply of nutrients ", 1st edition, Umschau Braus Verlag, Frankfurt am Main, 2000, published by the German Nutrition Society.
  • the sum of active ingredient component and formulation base is generally 100% by weight.
  • suitable formulations for nutritional supplements are capsules, tablets, pills, powder pouches, liquid ampoules and vials with dropping inserts, and the remainder of the dosage forms mentioned below.
  • suitable pharmaceutical formulations are solid dosage forms such as powders, powders, granules, tablets, in particular film-coated tablets, lozenges, sachets, cachets, dragees, capsules such as hard and soft gelatin capsules, suppositories or vaginal dosage forms, semisolid dosage forms such as ointments, creams, Hydrogels, pastes or patches, as well as liquid dosage forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, injection and infusion preparations, eye and ear drops. Implanted delivery devices may also be used to deliver drugs of the invention. Furthermore, liposomes or microspheres may also be used.
  • Food-grade formulations usually have the usual form and are preferably in the form of infant food, breakfast preparations, especially in the form of cereals or bars, sports drinks, complete meals, especially in the context of total balanced diets, dietary preparations such as diet drinks, diet meals and Slide bars, offered.
  • the formulations are preferably oral, but may also be administered, in particular in the pharmaceutical field, by rectal, transdermal, subcutaneous, intravenous, intramuscular or intranasal routes.
  • the active ingredients will usually be mixed or diluted with a suitable excipient, in this case also referred to as an excipient.
  • Excipients may be solid, semi-solid or liquid materials which serve as a vehicle, carrier or medium for the active ingredient. If necessary, the admixing of further auxiliaries takes place in a manner known per se. Shaping steps, optionally in conjunction with blending operations, may be performed, eg granulation, compression and the like.
  • the active ingredient components can be formulated together. However, they can also initially be processed separately and then combined in a compartmentalised, for example multi-layer drug form. As a result, possible drug incompatibilities and different active ingredient properties, such as bioavailability, stability, solubility and the like, can be taken into account.
  • a 22-year-old male patient with osteogenesis imperfecta with condition following multiple bone fractures (more than 20 individual fractures) was treated according to the invention for 12 months.
  • the therapy consisted of the daily oral administration of a capsule with the following active ingredient mixture: 1 mg folic acid, 1 mg vitamin B12, 50 mg vitamin B6.
  • a 78-year-old male patient with senile osteoporosis and multiple fractures was initially exposed for 6 months to one capsule of a drug mixture daily 10 mg of vitamin B6, 0.8 mg of folic acid and 1 mg of vitamin B12, taking measurements as in Example 1 (Table 2). During this therapy a spontaneous rib fracture occurred.
  • the patient was treated for a further 12 months according to the invention with one capsule daily with an active ingredient mixture of 50 mg vitamin B6, 1 mg folic acid and 1 mg vitamin B12, measurements being carried out as in Example 1 (Table 3, times relative to the beginning of the invention Therapy). During this second therapy phase there was no further fracture.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne l'utilisation d'acide folique, de vitamine B6 et de vitamine B12 pour le traitement préventif et sévère de l'ostéoporose. L'invention concerne en particulier des agents pharmaceutiques et des compléments alimentaires avec une combinaison appropriée d'agents actifs, ainsi qu'un agent sous forme d'emballages commerciaux avec des préparations appropriées de la combinaison ou des monopréparations pour utilisation combinée.
EP08708160A 2007-01-25 2008-01-24 Utilisation d'acide folique, de vitamine b6 et de vitamine b12 Withdrawn EP2120941A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007003795A DE102007003795A1 (de) 2007-01-25 2007-01-25 Verwendung von Folsäure, Vitamin B6 und Vitamin B12
PCT/EP2008/050821 WO2008090201A1 (fr) 2007-01-25 2008-01-24 Utilisation d'acide folique, de vitamine b6 et de vitamine b12

Publications (1)

Publication Number Publication Date
EP2120941A1 true EP2120941A1 (fr) 2009-11-25

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EP08708160A Withdrawn EP2120941A1 (fr) 2007-01-25 2008-01-24 Utilisation d'acide folique, de vitamine b6 et de vitamine b12

Country Status (3)

Country Link
EP (1) EP2120941A1 (fr)
DE (1) DE102007003795A1 (fr)
WO (1) WO2008090201A1 (fr)

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Publication number Priority date Publication date Assignee Title
EP2674159B1 (fr) * 2012-06-15 2016-04-27 Phrontier S.A.R.L. Composition pharmaceutique pour la régénération du foie
WO2014186723A1 (fr) * 2013-05-17 2014-11-20 Icahn School Of Medicine At Mount Sinai Procédés et compositions pour traiter l'ostéoporose, la ménopause et d'autres maladies liées à l'âge
CN110338423A (zh) * 2018-04-08 2019-10-18 北京奥萨医药研究中心有限公司 一种用于中老年人预防骨质疏松的保健食品

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Publication number Priority date Publication date Assignee Title
JPH06192105A (ja) * 1992-09-14 1994-07-12 Vesta Medicines Pty Ltd ホモシステインのレベルを下げるための医薬製剤
US20050032741A1 (en) * 2003-08-06 2005-02-10 Balaji Venkataraman Vitamin Compositions
DE102005009379A1 (de) * 2005-03-01 2006-09-07 Synavit Gmbh Mittel, enthaltend Folsäure, Vitamin B6 und Vitamin B12, und dessen Verwendung
US20060216361A1 (en) * 2005-03-10 2006-09-28 Edwards John B Compositions and methods for the treatment of osteoporosis and inflammatory joint disease

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Title
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WO2008090201A1 (fr) 2008-07-31

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