WO1997006795A1 - Compositions pharmaceutiques a base de gamma-butyrobetaine pour le traitement des troubles de la circulation sanguine - Google Patents
Compositions pharmaceutiques a base de gamma-butyrobetaine pour le traitement des troubles de la circulation sanguine Download PDFInfo
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- WO1997006795A1 WO1997006795A1 PCT/LV1996/000003 LV9600003W WO9706795A1 WO 1997006795 A1 WO1997006795 A1 WO 1997006795A1 LV 9600003 W LV9600003 W LV 9600003W WO 9706795 A1 WO9706795 A1 WO 9706795A1
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- pharmaceutical composition
- composition according
- active principle
- pharmaceutically acceptable
- blood
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Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- 230000017531 blood circulation Effects 0.000 title claims abstract description 14
- JHPNVNIEXXLNTR-UHFFFAOYSA-N 4-(trimethylammonio)butanoate Chemical compound C[N+](C)(C)CCCC([O-])=O JHPNVNIEXXLNTR-UHFFFAOYSA-N 0.000 title claims description 43
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- -1 aromatizers Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000008298 dragée Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 239000007894 caplet Substances 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 239000000644 isotonic solution Substances 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000011505 plaster Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 4
- 229920001223 polyethylene glycol Polymers 0.000 claims 3
- 235000015112 vegetable and seed oil Nutrition 0.000 claims 3
- 239000008158 vegetable oil Substances 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 239000003995 emulsifying agent Substances 0.000 claims 2
- 239000003925 fat Substances 0.000 claims 2
- 235000019197 fats Nutrition 0.000 claims 2
- 235000011187 glycerol Nutrition 0.000 claims 2
- 239000003381 stabilizer Substances 0.000 claims 2
- 229910002012 Aerosil® Inorganic materials 0.000 claims 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 1
- 229920002472 Starch Polymers 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- 239000003086 colorant Substances 0.000 claims 1
- 235000013681 dietary sucrose Nutrition 0.000 claims 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 1
- 235000019441 ethanol Nutrition 0.000 claims 1
- 239000000796 flavoring agent Substances 0.000 claims 1
- 235000013355 food flavoring agent Nutrition 0.000 claims 1
- 235000001727 glucose Nutrition 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 1
- 239000008108 microcrystalline cellulose Substances 0.000 claims 1
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 239000002861 polymer material Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 235000019698 starch Nutrition 0.000 claims 1
- 239000008107 starch Substances 0.000 claims 1
- 229960004793 sucrose Drugs 0.000 claims 1
- 239000000454 talc Substances 0.000 claims 1
- 229910052623 talc Inorganic materials 0.000 claims 1
- 235000012222 talc Nutrition 0.000 claims 1
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 abstract description 10
- 210000004204 blood vessel Anatomy 0.000 abstract description 8
- 230000007423 decrease Effects 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 abstract description 5
- 208000005392 Spasm Diseases 0.000 abstract description 5
- 230000023555 blood coagulation Effects 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- 241000282326 Felis catus Species 0.000 abstract description 4
- 208000007101 Muscle Cramp Diseases 0.000 abstract description 4
- 230000036772 blood pressure Effects 0.000 abstract description 4
- 102000008299 Nitric Oxide Synthase Human genes 0.000 abstract description 3
- 108010021487 Nitric Oxide Synthase Proteins 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- 240000007711 Peperomia pellucida Species 0.000 abstract description 2
- 230000004807 localization Effects 0.000 abstract description 2
- 230000000903 blocking effect Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- 230000010410 reperfusion Effects 0.000 abstract 1
- 230000033764 rhythmic process Effects 0.000 abstract 1
- 238000007920 subcutaneous administration Methods 0.000 abstract 1
- PVBQYTCFVWZSJK-UHFFFAOYSA-N meldonium Chemical compound C[N+](C)(C)NCCC([O-])=O PVBQYTCFVWZSJK-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 5
- 229960004373 acetylcholine Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229960002937 meldonium Drugs 0.000 description 3
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229960004203 carnitine Drugs 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000000476 Fatty Acid Transport Proteins Human genes 0.000 description 1
- 108010055870 Fatty Acid Transport Proteins Proteins 0.000 description 1
- MRAUNPAHJZDYCK-BYPYZUCNSA-N L-nitroarginine Chemical compound OC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O MRAUNPAHJZDYCK-BYPYZUCNSA-N 0.000 description 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical class C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000003504 ach effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 230000005792 cardiovascular activity Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- OJYGBLRPYBAHRT-IPQSZEQASA-N chloralose Chemical compound O1[C@H](C(Cl)(Cl)Cl)O[C@@H]2[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]21 OJYGBLRPYBAHRT-IPQSZEQASA-N 0.000 description 1
- 229950009941 chloralose Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000001435 haemodynamic effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000010344 pupil dilation Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
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
- A61K31/185—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
Definitions
- the present invention relates to pharmaceutical compositions, namely to the pharmaceutical compositions which are providing for treatment of blood flow disturbances of various genesis and localisation.
- the therapeutic composition contains the known chemical substance, the novel action of which gives unexpected pharmacological effects, namely, there is disclosed pharmaceutical composition which contains ⁇ -butyrobetaine as an active principle in a combination with pharmaceutically acceptable fillers and/or solvents.
- ⁇ -Butyrobetaine (actinine), from which the mammalian organism synthesises carnitine, was primarily characte ⁇ sed as a toxic substance which accelerates respiration, causes salivation and lacrimation, pupil dilation, vasoconstriction and heart stop in diastole (W.Linneweh, Z.Physiol.Chem., 42,181,1929).
- ⁇ -butyrobetaine is extremely low toxic (LD S0 7000 mg/kg, s.c).
- Literature lacks the data on cardiovascular effects of ⁇ - butyrobetaine, though it was reported (Hosein E.A., McLennan H. Pharmacological action of ⁇ - butyrobetaine. Nature, 1956, 183, 328-329) j that butyrobetaine is a substance similar to acetyl choline with a
- ⁇ -betaine aza-analog - 3-(2,2,2- trimethylhydrazinium)propionate (Mildronate, Quaterine). Its mechanism of action is based on limitation of carnitine biosynthesis rate and related long- chain fatty acid transport decrease through mitochondria membranes [Simkhovich B.Z., Shutenko Z.V., Meirena D.V. et al. 3-(2,2,2- trimethylhydrazinium)propionate (THP) - a novel ⁇ -butyrobetaine inhibitor with cardioprotective properties. Biochem. Pharmacol. 1988, 37, 195-202].
- the cardiovascular activity and the toxicity of pharmaceutical compositions containing ⁇ -butyrobetaine was determined. Acute toxicity was evaluated on male and female mice (19-26 g), 10 animals in a group. The substances were administered in the form of 10% solution in water or in isotonic solution orally or intravenously (with 0.004 ml/sec rate, if i.v.). It was established that at oral administration LD 50 of ⁇ - butyrobetaine is >4500 mg/kg, but at intravenous injection LD 5 o is 1860(1430-2418) mg/kg, which testifies that ⁇ -butyrobetaine is practically non-toxic substance.
- Substance Dose i.v., Blood Pulse rate Blood flow mg/kg pressure changes rate changes, % changes, %
- the chest was opened in the experimental animals, they were artificially respirated, and blood pressure in the carotid artery as well as general aorta blood flow were measured on physiograph DMP-4B of "Narco
- ⁇ -butyrobetaine effect on the blood flow was connnected with earlier erroneously attributed cholinergic component which, mainly relates to ⁇ -butyrobetaine ester (The Merck Index, Eleventh Edition, 1871) impurities in the samples of insufficiently purified ⁇ - butyrobetaine, then one would anticipate a significant decrease in the blood pressure and heart rate (see acetyl choline effect, Table I).
- the observed cardiovascular effect indicates a positive inotropic effect of the proposed therapeutic composition with simultaneous peripheral resistance decrease by a completely another mechanism, which can be used in the treatment of low heart potency and of blood circulation disturbances of various genesis.
- Substance Systolic pressure (mm Hg) max/min Decrease concentra of the tion ( uM) sxstolic pressure
- ⁇ -Butyrobetaine also affects blood coagulation time. This was determined in male ICE-JCL albino mice (24-28 g), 10 mice in a group, using Moravic's method (Thodorov Y. Khlinicheskye laboratomie issledovania v pediatrii, Medic. Phys.”, Sophia, 1966, p.p.479-480, in Russian). Time when fibrin strings develop was determined. The blood was sampled from jugular vein, mice were preliminarily anaesthetized with urethane (1000 mg/kg, i.p.). The solutions ofthe substances were infusively administered directly before detection ofthe blood coagulation time.
- Table 4 shows that ⁇ -butyrobetaine considerably prolongs blood coagulation I-II phase, i.e. the time when fibrin strings develop. This means that pharmaceutical compositions on the butyrobetaine basis can be applied in the therapy of such blood circulation failures which are connected with thrombus formation and thrombus embolia.
- Table 4 Influence of ⁇ -butyrobetaine (GBB) on blood coagulation time in mice (after Moravica)
- the pharmaceutical composition on the basis of ⁇ -butyrobetaine possesses a wide spectrum of vascular action which is connected with its effect on blood vessel and miocardium tonus as well on NO-synthase, being more potent than known preparation Mildronate which is a close ⁇ -butyrobetaine structural analogue.
- the pharmaceutical composition containing ⁇ - butyrobetaine is a promising agent for the treatment of blood flow disturbances of various genesis.
- the preparation can be administered both orally, parenterally, rectally or transcutaneously.
- the pharmaceutical composition contains ⁇ -butyrobetaine in the total amount of 0.5 to 40% by weight, and as a pharmaceutically acceptable solvent - distilled water, isotonic or glucose or buffer solution.
- the active principle is administered orally or sublingually in tablets, caplets, dragee, granules, powders or capsules they contain ⁇ - butyrobetaine in total amount of 0.01 to 0.5 g in a tablet, caplet, dragee, capsule or in one portion of powder or granule.
- the active principle are administered transcutaneously its content in an ointment or plaster makes up 0.5 to 40%) by weight.
- the active principle is administered rectally its content in a suppository or microenema accounts for 0.5 to 40% by weight.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
La présente invention concerne des compositions pharmaceutiques à base de η-butyrobétaïne pour administration orale, parentérale, sous-cutanée ou rectale, destinées au traitement des troubles de la circulation sanguine de diverses origines et localisations. En expérimentation, cette composition administrée in vivo à raison de 10mg/kg à des chats anesthésiés, fait remonter le débit sanguin total de 12 %, sans changement notable de la tension artérielle et du rythme cardiaque. Cette composition bloque les spasmes induits par l'adrénaline au niveau des vaisseaux sanguins d'une oreille isolée de lapin. Lorsqu'elle est administrée à une concentration de 2,0 mM, cette composition fait baisser de 18 % la pression de reperfusion. Le blocage de la NO-synthétase inverse l'effet de la composition sur les spasmes induits par l'adrénaline au niveau des vaisseaux sanguins. Administrée en perfusion à raison de 200mg/kg, la composition fait monter de façon significative le taux de coagulation sanguine pendant les phases I-II. Dans le cas d'expériences comparatives, la composition de l'invention fait preuve d'un effet plus puissant que celui obtenu avec un médicament connu [3-(2,2,2-triméthylhydrazinium) propionate]. La composition est remarquable pour sa faible toxicité et sa grande marge de sécurité.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LV950255A LV11727B (en) | 1995-08-21 | 1995-08-21 | Pharmaceutical composition |
| LVP-95-255 | 1995-08-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997006795A1 true WO1997006795A1 (fr) | 1997-02-27 |
Family
ID=19736012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/LV1996/000003 WO1997006795A1 (fr) | 1995-08-21 | 1996-08-20 | Compositions pharmaceutiques a base de gamma-butyrobetaine pour le traitement des troubles de la circulation sanguine |
Country Status (2)
| Country | Link |
|---|---|
| LV (1) | LV11727B (fr) |
| WO (1) | WO1997006795A1 (fr) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000051596A1 (fr) * | 1999-03-02 | 2000-09-08 | Jallal Messadek | La glycine betaïne pour son usage antithrombotique |
| WO2002062322A3 (fr) * | 2001-02-05 | 2002-11-28 | Jallal Messadek | Glycine-betaine et utilisation correspondante |
| WO2003022262A1 (fr) * | 2001-09-07 | 2003-03-20 | Ivars Kalvinsh | Composition pharmaceutique contenant de la gamma-butyrobetaine |
| WO2004049095A2 (fr) * | 2002-11-25 | 2004-06-10 | Jallal Messadek | Compositions de betaine |
| WO2005012233A1 (fr) * | 2003-08-04 | 2005-02-10 | 'joint Stock Company Grindeks' | Sels de meldonium, leur procede de preparation et compositions pharmaceutiques les contenant |
| JP2007500705A (ja) * | 2003-07-28 | 2007-01-18 | スミスクライン ビーチャム コーポレーション | 化合物 |
| WO2006050585A3 (fr) * | 2004-11-10 | 2007-03-22 | Jallal Messadek | Modulation de synthases d'oxyde nitrique par des betaines |
| US7608640B2 (en) | 1999-03-02 | 2009-10-27 | Jallal Messadek | Glycine betaine and its use |
| US7780990B2 (en) | 2005-02-15 | 2010-08-24 | Jallal Messadek | Combination therapeutic compositions and method of use |
| US7786077B2 (en) | 2005-04-27 | 2010-08-31 | Jallal Messadek | Insulins combinations |
| US8343947B2 (en) | 2003-07-15 | 2013-01-01 | Jallal Messadek | Therapeutic treatment |
| US20140088125A1 (en) * | 2011-04-27 | 2014-03-27 | Jsc Grindeks | Use of 3-carboxy-n-ethyl-n,n-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4382092A (en) * | 1981-01-06 | 1983-05-03 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pharmaceutical composition comprising gamma-butyrobetaine for the treatment of syndromes induced by L-carnitine deficiency |
| US4451485A (en) * | 1981-09-17 | 1984-05-29 | Institu Organicheskogo Sinteza Akademii Nauk Latviiskoi Ssr | Treatment of cardio-vascular diseases with 3-(2,2,2-trimethylhydrazinium) propionate dihydrate |
| US4474812A (en) * | 1982-10-29 | 1984-10-02 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pharmaceutical composition for improving the biochemical and behavioral parameters of senility |
| JPH01213259A (ja) * | 1988-02-23 | 1989-08-28 | Kyowa Hakko Kogyo Co Ltd | カルニチンおよびカルニチンアミドの精製法 |
| US5030458A (en) * | 1989-11-27 | 1991-07-09 | Shug Austin L | Method for preventing diet-induced carnitine deficiency in domesticated dogs and cats |
-
1995
- 1995-08-21 LV LV950255A patent/LV11727B/lv unknown
-
1996
- 1996-08-20 WO PCT/LV1996/000003 patent/WO1997006795A1/fr active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4382092A (en) * | 1981-01-06 | 1983-05-03 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pharmaceutical composition comprising gamma-butyrobetaine for the treatment of syndromes induced by L-carnitine deficiency |
| US4451485A (en) * | 1981-09-17 | 1984-05-29 | Institu Organicheskogo Sinteza Akademii Nauk Latviiskoi Ssr | Treatment of cardio-vascular diseases with 3-(2,2,2-trimethylhydrazinium) propionate dihydrate |
| US4474812A (en) * | 1982-10-29 | 1984-10-02 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pharmaceutical composition for improving the biochemical and behavioral parameters of senility |
| JPH01213259A (ja) * | 1988-02-23 | 1989-08-28 | Kyowa Hakko Kogyo Co Ltd | カルニチンおよびカルニチンアミドの精製法 |
| US5030458A (en) * | 1989-11-27 | 1991-07-09 | Shug Austin L | Method for preventing diet-induced carnitine deficiency in domesticated dogs and cats |
Non-Patent Citations (2)
| Title |
|---|
| DATABASE WPI Section Ch Week 8940, Derwent World Patents Index; Class B05, AN 89-289767, XP002017003 * |
| E.STRACK ET AL.: "L-Karnitin als Basis cholinomimetischer Substanzen", ACTA BIOL. MED. GERM., vol. 35, no. 5, 1976, pages 645 - 656, XP002017002 * |
Cited By (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000051596A1 (fr) * | 1999-03-02 | 2000-09-08 | Jallal Messadek | La glycine betaïne pour son usage antithrombotique |
| BE1012495A3 (fr) * | 1999-03-02 | 2000-11-07 | Messadek Jallal | La glycine-betaine pour son usage antithrombotique. |
| US6855734B2 (en) | 1999-03-02 | 2005-02-15 | Jallal Messadek | Glycine betaine and its use |
| US7608640B2 (en) | 1999-03-02 | 2009-10-27 | Jallal Messadek | Glycine betaine and its use |
| KR100767270B1 (ko) * | 1999-03-02 | 2007-10-17 | 잘랄 메사덱 | 글리신 베타인의 항혈전성 용도 |
| WO2002062322A3 (fr) * | 2001-02-05 | 2002-11-28 | Jallal Messadek | Glycine-betaine et utilisation correspondante |
| WO2003022262A1 (fr) * | 2001-09-07 | 2003-03-20 | Ivars Kalvinsh | Composition pharmaceutique contenant de la gamma-butyrobetaine |
| AU2002236340B2 (en) * | 2001-09-07 | 2008-06-12 | Anatolijs Birmans | Pharmaceutical composition comprising gamma-butyrobetaine |
| WO2004049095A2 (fr) * | 2002-11-25 | 2004-06-10 | Jallal Messadek | Compositions de betaine |
| WO2004049095A3 (fr) * | 2002-11-25 | 2004-12-23 | Jallal Messadek | Compositions de betaine |
| US8343947B2 (en) | 2003-07-15 | 2013-01-01 | Jallal Messadek | Therapeutic treatment |
| JP2007500705A (ja) * | 2003-07-28 | 2007-01-18 | スミスクライン ビーチャム コーポレーション | 化合物 |
| KR100745160B1 (ko) * | 2003-08-04 | 2007-08-01 | 조인트 스탁 컴퍼니 그린덱스 | 멜도늄 염, 그것의 제조방법 및 그것을 주성분으로 한약학적 조성물 |
| US7223797B2 (en) | 2003-08-04 | 2007-05-29 | Joint Stock Company “Grindeks” | Meldonium salts, method of their preparation and pharmaceutical composition on their basis |
| EA009083B1 (ru) * | 2003-08-04 | 2007-10-26 | Акционерное Общество "Гриндекс" | Соли мелдония, способ их получения и фармацевтические композиции на их основе |
| JP2007501222A (ja) * | 2003-08-04 | 2007-01-25 | “ジョイント ストック カンパニー グリンデクス” | メルドニウム（Ｍｅｌｄｏｎｉｕｍ）塩、メルドニウム塩の調製方法、およびメルドニウム塩を主成分とする薬学的組成物 |
| WO2005012233A1 (fr) * | 2003-08-04 | 2005-02-10 | 'joint Stock Company Grindeks' | Sels de meldonium, leur procede de preparation et compositions pharmaceutiques les contenant |
| WO2006050585A3 (fr) * | 2004-11-10 | 2007-03-22 | Jallal Messadek | Modulation de synthases d'oxyde nitrique par des betaines |
| US8318805B2 (en) | 2004-11-10 | 2012-11-27 | Jallal Messadek | Modulation of nitric oxide synthases by betaines |
| US7780990B2 (en) | 2005-02-15 | 2010-08-24 | Jallal Messadek | Combination therapeutic compositions and method of use |
| US7786077B2 (en) | 2005-04-27 | 2010-08-31 | Jallal Messadek | Insulins combinations |
| US20140088125A1 (en) * | 2011-04-27 | 2014-03-27 | Jsc Grindeks | Use of 3-carboxy-n-ethyl-n,n-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease |
| AU2012247467B2 (en) * | 2011-04-27 | 2016-07-28 | Grindeks, A Joint Stock Company | Use of 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease |
| US20180079728A1 (en) * | 2011-04-27 | 2018-03-22 | Jsc Grindeks | Use of 3-carboxy-n-ethyl-n,n-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease |
| US10351534B2 (en) | 2011-04-27 | 2019-07-16 | Jsc Grindeks | Use of 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease |
Also Published As
| Publication number | Publication date |
|---|---|
| LV11727A (lv) | 1997-04-20 |
| LV11727B (en) | 1997-08-20 |
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