MXPA98004683A - The use of tetrahydrofolates in a natural stereoisomeric form for the production of an adequate pharmaceutical preparation to influence the homocysteine level, particularly to help in the homociste remedy - Google Patents
The use of tetrahydrofolates in a natural stereoisomeric form for the production of an adequate pharmaceutical preparation to influence the homocysteine level, particularly to help in the homociste remedyInfo
- Publication number
- MXPA98004683A MXPA98004683A MXPA/A/1998/004683A MX9804683A MXPA98004683A MX PA98004683 A MXPA98004683 A MX PA98004683A MX 9804683 A MX9804683 A MX 9804683A MX PA98004683 A MXPA98004683 A MX PA98004683A
- Authority
- MX
- Mexico
- Prior art keywords
- tetrahydrofolic acid
- tetrahydrofolic
- methyl
- homocysteine
- acid
- Prior art date
Links
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N Tetrahydrofolic acid Chemical class N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 title claims abstract description 33
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 title claims abstract description 31
- 239000005460 tetrahydrofolate Substances 0.000 title claims abstract description 23
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 10
- ZNOVTXRBGFNYRX-STQMWFEESA-N 5-methyltetrahydrofolic acid Chemical compound C([C@@H]1N(C=2C(=O)N=C(N)NC=2NC1)C)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-STQMWFEESA-N 0.000 claims abstract description 30
- 239000011780 sodium chloride Substances 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- VVIAGPKUTFNRDU-STQMWFEESA-N (6S)-5-formyltetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1C=O)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-STQMWFEESA-N 0.000 claims abstract description 11
- 102000005954 Methylenetetrahydrofolate Reductase (NADPH2) Human genes 0.000 claims abstract description 9
- 108010030837 Methylenetetrahydrofolate Reductase (NADPH2) Proteins 0.000 claims abstract description 9
- 230000002265 prevention Effects 0.000 claims abstract description 8
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- 239000002671 adjuvant Substances 0.000 claims abstract description 6
- 230000000240 adjuvant Effects 0.000 claims abstract description 6
- AUFGTPPARQZWDO-YPMHNXCESA-N 10-formyltetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)N(C=O)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 AUFGTPPARQZWDO-YPMHNXCESA-N 0.000 claims abstract description 5
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- 239000000126 substance Substances 0.000 claims abstract description 5
- YCWUVLPMLLBDCU-STQMWFEESA-N 5-formimidoyltetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1C=N)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 YCWUVLPMLLBDCU-STQMWFEESA-N 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims description 7
- QYNUQALWYRSVHF-OLZOCXBDSA-N (6R)-5,10-methylenetetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1C1)N)N1C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QYNUQALWYRSVHF-OLZOCXBDSA-N 0.000 claims description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
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- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- WZRJTRPJURQBRM-UHFFFAOYSA-N 4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1.COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 WZRJTRPJURQBRM-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
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- RWSXRVCMGQZWBV-WDSKDSINSA-N Glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
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- ILRYLPWNYFXEMH-WHFBIAKZSA-N L-cystathionine dizwitterion Chemical compound [O-]C(=O)[C@@H]([NH3+])CCSC[C@H]([NH3+])C([O-])=O ILRYLPWNYFXEMH-WHFBIAKZSA-N 0.000 description 1
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- KIWQWJKWBHZMDT-VKHMYHEASA-N L-homocysteine thiolactone Chemical compound N[C@H]1CCSC1=O KIWQWJKWBHZMDT-VKHMYHEASA-N 0.000 description 1
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Abstract
This invention relates to the use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the level of homocysteine, particularly to assist in the remethylation of homocysteine. The clinical areas of application include all abnormalities of the homocysteine level, particularly the prevention and treatment of cardiovascular diseases and the prevention of neural tube deficiencies. The present invention also relates to pharmaceutical preparations comprising at least one compound selected from the group consisting of 5-formyl- (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5,10-methylene- ( 6R) -tetrahydrofolic, 5-10-methenyl- (6R) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid or (6S) -tetrahydrofolic acid or salts thereof. pharmaceutically compatible themselves, together with pharmaceutically compatible adjuvants and active substances, for influencing the homocysteine level particularly when there is a deficiency of methylene tetrahydrofolate reductase, such as when there is, for example, methylene tetrahydrofolate reductase thermolabile
Description
THE USE OF TETRAHYDROFOLATES IN THE NATURAL STEREOISOMERIC FORM FOR THE PRODUCTION OF A
ADEQUATE PHARMACEUTICAL PREPARATION TO INFLUENCE THE
HOMOCYSTEINE LEVEL, PARTICULARLY TO HELP IN HOMOCYSTEINE REMEDY
FIELD OF THE INVENTION
This invention relates to the use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the level of homocysteine, particularly to assist in the remethylation of homocysteine. The clinical areas of application include all abnormalities of the homocysteine level, particularly the prevention and treatment of cardiovascular diseases and the prevention of neural tube deficiencies. In the present text, the term "tetrahydrofolate in the natural stereoisomeric form" refers to 5-formyl- (65> -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5,10-methylene- (6R) acid ) -tetrahydrofolic or the acije (6S) -tetrahydrofolic or pharmaceutically compatible salts thereof.
REP: 27699 BACKGROUND OF THE INVENTION
As drugs, tetrahydrofolates have been predominantly used so far as the calcium salt of 5-formyl-5,6,7,8-tetrahydrofolic acid (leucovorin) or of 5-methyl-5,6,7,8-tetrahydrofolic acid for the treatment of megaloblastic folic acid deficiency anemia, as an antidote to increase the compatibility of folic acid antagonists, particularly aminopterin and methotrexate in cancer therapy ("antifolate rescue"), to increase the therapeutic effect of fluorinated pyrimidines and for the treatment of immunological diseases such as psoriasis and rheumatoid arthritis, to increase the compatibility of some parasitic agents, for example trimethoprim-sulfamethoxazole, and to decrease the toxicity of didesaza-tetrahydrofolates in chemotherapy. Homocysteine is an amino acid that contains thiol which is formed on the demethylation of methionine. In body fluids, homocysteine exists in the oxidized form as a disulfide
(homocysteine), as mixed disulfides and as a cyclized oxidation product (homocysteine thiolactone). Hyperhomocysteinemia is a clinical disorder which can have several congenital or acquired causes. These disorders result in an increased concentration of homocysteine in the blood and urine. The most common form of hyperhomocysteinemia results from a deficiency of cystathione β-synthase, an enzyme involved in the form of Be-dependent transulphurization, in which homocysteine is converted to cysteine via cystathionine. Another form is due to a deficiency of 5,10-methylene tetrahydrofolate reductase, which provides the substrate, 5-methyl- (6S) -tetrahydrofolic acid, for the Bi2-dependent conversion of homocysteine to methionine. Hyperhomocysteinemia can also occur as a consequence of functional disorders of the kidneys. In all these cases, the term "hyperhomocysteinemia" refers to a temporary or permanent increase in the level of homocysteine in the blood, which is sometimes accompanied by an increased urinary secretion of homocysteir.a. Hyperhomocysteinemia results from a series of diseases, manifested in vascular, ocular, neurological and severe skeletal disorders. Several clinical studies have shown a clear connection between an increased level of homocysteine in the serum and the development of cardiovascular diseases. Homocysteinemia is considered to be an independent risk factor in cardiovascular diseases. General information can be found in K.L Resch (ed.), Risikofa tor Homocystein Daten-Fakten-Strategien [Homocysteine Risk Factor - Data-Facts-Strategies], Gesellschaft für Medizinische Information ISBN 3-980 45 36-0-X. Reference is made to L.J. Fortin et al, Clinical Biochemistry, Vol. 28 (2), 1995, pages 155-162 regarding the relationship between hyperhomocysteinemia and arteriosclerosis. Hyperhomocysteinemia and neural tube deficiency have been described by J.L. Mills et al, Supplement Publication to the Ceres Forum on June 14, 1995, 1996, pages 756S-760S. The use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the level of homocysteine has neither been proposed nor described so far.
DESCRIPTION OF THE INVENTION
It has been found that the use of pharmaceutical preparations containing the natural stereoisomeric form of tetrahydrofolates influences the level of homocysteine, and in particular aids in the remethylation of homocysteine. The natural stereoisomeric form of tetrahydrofolate refers to 5-formyl- (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5,10-methylene- (6R) -tetrahydrofolic acid, 5,10-methenyl acid - (6R) -tetrahydrofolic, 10-formyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid or (6S) -tetrahydrofolic acid or pharmaceutically compatible salts thereof. Reduced folates are used, which as a rule can be generally transformed mutually in the folate metabolism. 5-Methyl- (6S) -tetrahydrofolic acid and pharmaceutically compatible salts thereof are preferably used, however, since 5-methyl- (6S) -tetrahydrofolic acid is directly involved, as a methyl donor, in the transfer of the methyl group from homocysteine to methionine. This applies in particular when there is a deficiency of existing methylene tetrahydrofolate reductase, wherein this deficiency involves disorders such as, for example, restricted functionality or lack of activity. The existence of thermolabile methylene tetrahydrofolate reductase should be mentioned here as the most frequent example of a methylene tetrahydrofolate reductase deficiency. Under these circumstances, tetrahydrofolates can only be converted to a limited extent and therefore can only be used in conjunction in the methylation reaction to a limited extent. The pharmaceutically compatible salts should be compatible both pharmacologically and pharmaceutically. Pharmacologically and pharmaceutically compatible salts such as these can be alkali metal or alkaline earth metal salts, preferably sodium, potassium, magnesium or calcium salts. The term "pharmaceutical preparations" refers to organic or inorganic substances enteric (eg, oral, sublingual or rectal), parenteral or topical (eg, transdermal) which do not react with the active ingredient, can be used as carriers , for example, water, oil, benzyl alcohol, polyethylene glycol, glycerol triacetate or other glycerides of fatty acids, gelatin, lecithin, cyclodextrin, carbohydrates such as lactobiose or starch, magnesium stearate, talc or cellulose. Tablets, dragees, capsules, powders, drops or syrup concentrates are preferred for oral application, suppositories are preferred for rectal application and solutions based on water or oil or lyophilisates are preferably used for parenteral application. Suspensions, emulsions or implants can also be used, and patches or creams can be used for topical application. Pharmaceutical preparations for parenteral application comprise aqueous and non-aqueous, sterile injection solutions of the pharmaceutically active compounds, which are preferably isotonic with the blood of the recipient or recipient. These preparations may comprise stabilizers, additives for the controlled release of the pharmaceutically active compounds, antioxidants, buffers, bacteriostatic agents and adjuvants to obtain an isotonic solution. Aqueous and non-aqueous sterile suspensions may contain suspension additives and thickeners. The pharmaceutical preparation can exist as a single-dose or multi-dose container or container, such as sealed ampoules, and can be stored as a freeze-dried product (lyophilized) and prepared for use if necessary with a sterile liquid, for example water or salt solution. Sterile powders, granules or tablets can be used in the same way. All pharmaceutical preparations can additionally contain active compounds that act separately or synergistically. The vitamins could be mentioned here, especially those from the group of vitamin B, such as B6 and / or Bi2, which have a synergistic effect in this application. In this regard, vitamin B can be used in a dose between 1 mg and 20 mg, preferably between 1 mg and 6 mg per day, for a normal dosage application, and can be used in a dose between 6 mg and 20 mg per day for a high dosing application. Vitamin Bi2 can be used in a dose between 0.001 mg and 0.5 mg, preferably between 0.001 mg and 0.15 mg per day, for a normal dosage application, and can be used in a dose between 0.15 and 0.5 mg per day for an application of high dosage.
The pharmaceutical preparation contains between 0.001 mg and 100 mg of the active ingredient per dose. In prophylaxis, preparations containing preferably between 5 μg and 1000 μg of the active ingredient per dose are used. In therapy, preparations which preferably contain between 0.1 mg and 200 mg of the active ingredient per dose are used. The dosage depends on the form of the therapy, on the form of application of the pharmaceutical preparation, and on the age, weight, nutrition and condition of the patient. The treatment can be started with a low dosage below the optimal amount and this can be increased until the optimum effect is achieved. The dosages used in the prophylaxis may preferably vary between 5 μg and 1000 μg per day, particularly between 50 μg and 500 μg per day. Optimal dosages in therapy vary between 0.1 mg and 100 mg per day, particularly between 0.5 mg and 5 mg per day. The application can be carried out as a single or simple administration or as a repeated dosage.
Examples to illustrate the invention
Example 1 A tablet containing 1 mg of 5-formyl- (6S) -tetrahydrofolic acid
A mixture of 13.3 g of the calcium salt pentahydrate of 5-formyl- (6S) -tetrahydrofolic acid (corresponding to 10 g of 5-formyl- (6S) -tetrahydrofolic acid), 4 kg of lactose, 1.2 kg of starch , 0.2 kg of talc and 0.1 kg of magnesium stearate are compressed to form tablets, so that each tablet contains 1 mg of 5-formyl- (6S) -tetrahydrofolic acid. The tablet can be coated as a film tablet or it can be ground and used in the capsule form.
Example 2
A suppository containing 60 mg of 5-methyl- (6S) -tetrahydrofolic acid
A mixture of 632 g of the calcium salt pentahydrate of 5-methyl- (6S) -tetrahydrofolic acid (corresponding to 500 g of 5-methyl- (6S) -tetrahydrofolic acid), 50 g of hydroxypropylcellulose and 2 kg of Semisynthetic glycerides melt to form suppositories, so that each suppository contains 500 mg of 5-methyl- (6S) -tetrahydrofolic acid.
Example 3
An injectable solution containing 0.5 mg of 5-methyl- (6S) -tetrahydrofolic acid
0. 5 g of 5-methyl- (6S) -tetrahydrofolic acid, 10 g of glutathione, 30 g of citric acid, 160 g of mannitol, 1 g of methyl-p-hydroxybenzoic acid, 17.7 g of sodium hydroxide (or the amount required to obtain a pH of the solution from 7.3 to 7.8) are dissolved in 3 liters of water for injection and introduced into ampoules, so that each ampoule contains 0.5 mg of 5-methyl- (6S) -tetrahydrofolic acid.
Example 4
An injectable lyophilisate containing 1 mg of (6S) -tetrahydrofolic acid
A solution of 1 g of the sodium salt of (6S) -tetrahydrofolic acid in 1000 ml of double-distilled water is introduced via sterile filtration into ampoules and lyophilized, so that each ampoule contains 1 mg of the (6S) -tetrahydrofolic acid . Tetrahydrofolic acid is very sensitive to oxygen, and to severely oxygen-free conditions and therefore has to be used. The use of an antioxidant such as ascorbic acid may be necessary.
Axis 5
An injectable lyophilisate containing 20 mg of 5,10-methylene- (6R) -tetrahydrofolic acid
A solution of 10 g of the inclusion compound of β-hydroxypropyl-cyclodextrin of the sodium salt of 5,10-methylene- (6R) -tetrahydrofolic acid in 2000 ml of twice distilled water is introduced via sterile filtration into ampoules, so that each ampoule contains 20 mg of 5, 10-methylene- (6R) -tetrahydrofolic acid. The same precautionary measures apply to 5, 10-methylene tetrahydrofolic acid as for tetrahydrofolic acid (Example 4).
Example 6 A tablet containing 0.4 mg of 5-formyl- (6S) -tetrahydrofolic acid A mixture of 5.32 g of the pentahydrate of the calcium salt of 5-formyl- (6S) -tetrahydrofolic acid (corresponding to 4 g of the acid -formyl- (6S) -tetrahydrofolic), 4 kg of lactose, 1.2 kg of starch, 0.2 kg of talc and 0.1 kg of magnesium stearate are compressed to form tablets, so that each tablet contains 4 mg of 5-formyl acid - (6S) -tetrahydrofolic. The tablet can be coated as a film tablet or it can be ground and used in the capsule form.
Example 7
An injectable lyophilisate containing 10 μg of 6-methyl- (6S) -tetrahydrofolic acid
A solution of 10 mg of the sodium salt of 5-methyl- (6S) -tetrahydrofolic acid in 1000 ml of twice distilled water is introduced via sterile filtration under an inert gas, into ampoules and lyophilized, so that each Ampoule contains 10 μg of 5-methyl- (6S) -tetrahydrofolic acid. Tetrahydrofolic acid is very sensitive to oxygen and to severely oxygen-free conditions therefore it has to be used. The use of an antioxidant such as ascorbic acid may be necessary.
Example 8
One tablet containing 15 mg of 5-methyl- (6S) -tetrahydrofolic acid
A mixture of 19.18 g of the calcium salt pentahydrate of 5-methyl- (6S) -tetrahydrofolic acid (corresponding to 15 g of 5-methyl- (6S) -tetrahydrofolic acid), 120 g of lactose, 21.5 g of corn starch, 7.08 g of acetylcellulose, 2.28 g diethyl phthalate, 0.64 g of silicone HK-15 and 2 g of magnesium stearate are pressed to form tablets, so that each tablet contains 15 mg of 5-methyl- ( 6S) -tetrahydrofolic. The tablet can be coated as a film tablet or can be ground and used in capsule form.
Example 9
Tablets containing 15 mg of 5-methyl- (6S) -tetrahydrofolic acid
In a manner analogous to that described in example 8, tablets containing 15 mg of 5-methyl- (6S) -tetrahydrofolic acid are produced using corn starch, lactose, magnesium stearate, polyethylene glycol 6000, polymethacrylate, polysorbitol 80, dimethyl polysiloxane, sodium hydroxide and talc.
Example 10
A combination preparation comprising the acid
-methyl- (6S) -tetrahydrofolic, vitamin B6 and vitamin
B? 2 A film-coated tablet containing the following constituents is formulated for preparations for oral application: 0.4 mg 5-methyl- (6S) -tetrahydrofolic acid 3 mg vitamin B6 0.002 mg vitamin Bi2 pharmaceutically compatible adjuvants This combination preparation it can also be formulated as a solution, for example for parenteral application.
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which refers to the manufacture of the objects to which it refers. Having described the invention as above, the content of the following is claimed as property
Claims (9)
1. The use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the level of homocysteine.
2. The use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for the prevention and treatment of cardiovascular diseases.
3. The use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for the prevention of neural tube deficiencies.
4. The use of tetrahydrofolates in the natural stereoisomeric form according to claims 1 to 3, characterized in that 5-formyl- (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5, 10- methylene- (6R) -tetrahydrofolic, 5,10-methenyl- (6R) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid or (6S) acid ) -tetrahydrofolic, or pharmaceutically compatible salts thereof, are used as a tetrahydrofolate.
5. The use of tetrahydrofolates in the natural stereoisomeric form according to claims 1 to 3, characterized in that the 5-methyl- (6S) -tetrahydrofolic acid or a pharmaceutically compatible salt of 5-methyl- (6S) -tetrahydrofolic acid is used as a tetrahydrofolate.
6. The use of tetrahydrofolates in the natural stereoisomeric form according to claims 1 to 3, characterized in that the 5-methyl- (6S) -tetrahydrofolic acid or a pharmaceutically compatible salt of 5-methyl- (6S) -tetrahydrofolic acid is used as a tetrahydrofolate, and the application is made when a deficiency of methylene tetrahydrofolate reductase exists.
7. The use of tetrahydrofolates in the natural stereoisomeric form according to claims 1 to 3, characterized in that the 5-methyl- (6S) -tetrahydrofolic acid or a pharmaceutically compatible salt of 5-methyl- (6S) -tetrahydrofolic acid is used as a tetrahydrofolate and the application is carried out when thermolabile methylene tetrahydrofolate reductase exists.
8. Pharmaceutical preparations for influencing the level of homocysteine, characterized in that they contain, as an active ingredient, at least one compound selected from the group consisting of 5-formyl- (6S) -tetrahydrofolic acid, 5-methyl acid - (6S) -tetrahydrofolic, 5,10-methylene- (6R) -tetrahydrofolic acid, 5,10-methenyl- (6R) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5-methanediol -formimino- (6S) -tetrahydrofolic or (6S) -tetrahydrofolic acid or pharmaceutically compatible salts thereof, together with adjuvant and pharmaceutically compatible active substances.
9. Pharmaceutical preparations for influencing the level of homocysteine when thermolabile methylene tetrahydrofolate reductase is present, characterized in that they contain, as an active ingredient, 5-methyl- (6S) -tetrahydrofolic acid or a pharmaceutically compatible salt of 5- methyl- (6S) -tetrahydrofolic, together with pharmaceutically compatible adjuvants and active substances. SUMMARY OF THE INVENTION This invention relates to the use of tetrahydrofolates in the natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the level of homocysteine, particularly to assist in the remethylation of homocysteine. The clinical areas of application include all abnormalities of the homocysteine level, particularly the prevention and treatment of cardiovascular diseases and the prevention of neural tube deficiencies. The present invention also relates to pharmaceutical preparations comprising at least one compound selected from the group consisting of 5-formyl- (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid,, 10-methylene- (6R) -tetrahydrofolic acid, 5,10-methenyl- (6R) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid or (6S) -tetrahydrofolic acid or pharmaceutically compatible salts thereof, together with adjuvant and pharmaceutically compatible active substances, to influence the level of homocysteine particularly when there is a deficiency of methylene tetrahydrofolate reductase, such as when there is, for example, thermolabile methylene tetrahydrofolate reductase.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1456/97 | 1997-06-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA98004683A true MXPA98004683A (en) | 1999-09-20 |
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