Glycine betaine and its use
First Claim
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1. A pharmaceutical antithrombotic combination comprising:
- (a) a therapeutically effective amount of a therapeutically antithrombotic active agent causing at least one haemorrhagic side effect, said active agent being selected from the group consisting of anti aggregants selected from the group consisting of abciximab, acetylsalicylate basic aluminium, acetylsalicylate carbonate sodium, acetylsalicylate lysine, acetylsalicylic acid, aloxiprine, anagreli chlorydrate, bencyclane furamate, carbasalate calcium, clopidogrel sulfate, epoprostenol sodium, epifibati, hydroxychloroquine sulfate, iloprost, nicergoline, nifepidine, pyricarbate, sulfinpyrazone, ticlopidine chlorhydrate, tirofiban chlorhydrate, verapamil chlorhydrate, compounds structurally similar to one of said preceding anti aggregant compounds, and mixtures thereof, anticoagulants selected from the group consisting of acenocoumarol, anisindione, biscoumacetate ethyl, bromindione, coumetarol, sirudine, oxazidione, phenindione, phenprocoumone, tioclomarol, warfarine sodium, compounds structurally similar to one of the preceding anti coagulant compounds, and mixtures thereof, fibrinolytics selected from the group consisting of altepase, anistreplase, atorvastatine calcium, bromelaines, ciprofibrate, defibrotide, fluvastatine sodium, glicazide, lovastatine, lysplasminogene, phenformine, pravastatine sodium, reteplase, simvastatine, streptokinase, urokinase, compounds structurally similar to one of the preceding fibrinolytic compounds, and mixtures thereof, thrombin inhibitors, anti vitamin K, and mixtures thereof; and
(b) a therapeutically effective amount of a compound selected from the group consisting of compounds of the formula (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof, said combination operable for preventing or reducing the incidence or severity of said haemorrhagic side effect or for potentialising the therapeutic antithrombotic effect of said antithrombotic active agent.
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Abstract
The present invention provides pharmaceutical uses of betaines, and especially glycine betaine, such as for the treatment of thromboses not induced by hyperhomocystenemia or homocystinuria, of blood disorders, such as blood coagulation and thrombi formation.
30 Citations
41 Claims
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1. A pharmaceutical antithrombotic combination comprising:
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(a) a therapeutically effective amount of a therapeutically antithrombotic active agent causing at least one haemorrhagic side effect, said active agent being selected from the group consisting of anti aggregants selected from the group consisting of abciximab, acetylsalicylate basic aluminium, acetylsalicylate carbonate sodium, acetylsalicylate lysine, acetylsalicylic acid, aloxiprine, anagreli chlorydrate, bencyclane furamate, carbasalate calcium, clopidogrel sulfate, epoprostenol sodium, epifibati, hydroxychloroquine sulfate, iloprost, nicergoline, nifepidine, pyricarbate, sulfinpyrazone, ticlopidine chlorhydrate, tirofiban chlorhydrate, verapamil chlorhydrate, compounds structurally similar to one of said preceding anti aggregant compounds, and mixtures thereof, anticoagulants selected from the group consisting of acenocoumarol, anisindione, biscoumacetate ethyl, bromindione, coumetarol, sirudine, oxazidione, phenindione, phenprocoumone, tioclomarol, warfarine sodium, compounds structurally similar to one of the preceding anti coagulant compounds, and mixtures thereof, fibrinolytics selected from the group consisting of altepase, anistreplase, atorvastatine calcium, bromelaines, ciprofibrate, defibrotide, fluvastatine sodium, glicazide, lovastatine, lysplasminogene, phenformine, pravastatine sodium, reteplase, simvastatine, streptokinase, urokinase, compounds structurally similar to one of the preceding fibrinolytic compounds, and mixtures thereof, thrombin inhibitors, anti vitamin K, and mixtures thereof; and
(b) a therapeutically effective amount of a compound selected from the group consisting of compounds of the formula (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof,said combination operable for preventing or reducing the incidence or severity of said haemorrhagic side effect or for potentialising the therapeutic antithrombotic effect of said antithrombotic active agent. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A method of preventing side effects associated with an active agent selected from the group consisting of anti aggregants selected from the group consisting of abciximab, acetylsalicylate basic aluminium, acetylsalicylate carbonate sodium, acetylsalicylate lysine, acetylsalicylic acid, aloxiprine, anagreli chlorydrate, bencyclane furamate, carbasalate calcium, clopidogrel sulfate, epoprostenol sodium, epifibati, hydroxychloroquine sulfate, iloprost, nicergoline, nifepidine, pyricarbate, sulfinpyrazone, ticlopidine chlorhydrate, tirofiban chlorhydrate, verapamil chlorhydrate, compounds structurally similar to one of the preceding anti aggregant compounds, and mixtures thereof, anticoagulants selected from the group consisting of acenocoumarol, anisindione, biscoumacetate ethyl, bromindione, coumetarol, dalteparine sodium, sirudine, xtran sulfate, enoxaparine sodium, fluindione, heparinate magnesium, heparin calcium, heparine sodium, lepirudine nadroparine calcium, oxazidione, pentosane polyester sulfuric, phenindione, phenprocoumone, reviparine sodium, tinzaparine sodium, tioclomarol, warfarine sodium, glycoaminoglycans, heparins, unfractioned heparin, standard heparin, low molecular heparins, heparinoids, heparin-like molecules, compounds structurally similar to one of the preceding anti coagulant compounds, and mixtures thereof, fibrinolytics selected from the group consisting of altepase, anistreplase, atorvastatine calcium, bromelaines, ciprofibrate, defibrotide, fluvastatine sodium, glicazide, lovastatine, lys-plasminogene, phenformine, pravastatine sodium, reteplase, simvastatine, streptokinase, urokinase, compounds structurally similar to one of the preceding fibrinolytic compounds, and mixtures thereof, thrombin inhibitors such as argatroban, novastan, and mixtures thereof, anti vitamin K, and mixtures thereof, said method comprising the step of:
administering an antidote composition comprising an active antidote agent compound selected from the group consisting of glycine betaine, compounds of the formula (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts of said compound, esters of said compound, precursors of said compound, and mixtures thereof.
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9. A method of preventing or reducing the incidence or severity of a side effect of a therapeutically active agent having at least one possible haemorrhagic side effect in a patient comprising the step of:
administering to said patient an effective amount of a compound selected from the group consisting of compounds having the formula (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts of said compound, esters of said compound, precursors of said compound, and mixtures thereof, said administration preventing or reducing the incidence or severity of said side effect or potentialising the therapeutic effect of said therapeutically active agent.- View Dependent Claims (10)
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11. A method of potentializing the therapeutic effect of a therapeutically active agent having at least one possible haemorrhagic side effect in a patient comprising the step of:
administering to said patient an effective amount of a compound selected from the group consisting of glycine betaine, compounds having the formula (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts of said compound, esters of said compound, precursors of said compound, and mixtures thereof.
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12. A method of treating or preventing thrombosis troubles for a patient and preventing or reducing a haemorrhagic side effect comprising the steps of:
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administering to said patient a therapeutically effective amount of an anti thrombotic active agent with at least one possible haemorrhagic side effect; and
administering a therapeutic effective amount of glycine betaine to said patient and thereby preventing or reducing said haemorrhagic side effect. - View Dependent Claims (13)
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14. A controlled release pharmaceutical system suitable for delivering after administration in a time-controlled manner to the bloodstream of a mammal a compound selected from the group consisting of glycine betaine, or an effective amount of a compound of formula (CH3)3N+(CH2)nCOO−
- with n equal to 1 or a pharmaceutically acceptable salt thereof, esters thereof, precursors thereof, and mixtures thereof.
- View Dependent Claims (15, 16, 17, 18)
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19. A controlled release pharmaceutical system for treating, reducing the incidence or severity of, or preventing a condition selected from the group consisting of blood flow disturbances, thrombosis, thromboembolic disorders, and combinations thereof, said system releasing in a time controlled manner for at least 120 minutes, after administration, a therapeutically effective amount of an active selected from the group consisting of glycine betaine, a compound of formula (CH3)3N+(CH2)nCOO−
- with n equal to 1, pharmaceutically acceptable salts of said compound, esters of said compound, precursors of said compound, and mixtures thereof.
- View Dependent Claims (20, 21, 22, 23, 24, 25, 26)
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27. A controlled release pharmaceutical system for releasing an effective therapeutic amount of a compound selected from the group consisting of betaines, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof, wherein said system controls for at least 120 minutes the release of a glycine betaine or an effective amount of a compound of formula (CH3)3N+(CH2)nCOO−
- with n equal to 1, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof.
- View Dependent Claims (28, 29, 30)
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31. A method for treating, reducing the incidence or severity of, or preventing a condition selected from the group consisting of blood flow disturbances, thrombosis, thromboembolic disorders, and combinations thereof, said method comprising the step of administering in a time controlled manner to the bloodstream of a mammal, a therapeutically effective amount of an active selected from the group consisting of glycine betaine, a compound of the formula (CH3)3N+(CH2)nCOO−
- with n equal to 1, pharmaceutically acceptable salts of said compound, esters of said compound, precursors of said compound, and mixtures thereof.
- View Dependent Claims (32)
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33. A pharmaceutical combination for oral, parenteral or rectal administration comprising:
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a therapeutically effective amount of a therapeutically active agent causing at least one haemorrhagic side effect, said active agent being selected from the group consisting of dalteparine sodium, sirudine, xtran sulfate, enoxaparine sodium, fluindione, heparinate magnesium, heparin calcium, heparine sodium, lepirudine nadroparine calcium, pentosane polyester sulfuric, reviparine sodium, tinzaparine sodium, glycoaminoglycans, heparins, unfractioned heparin, standard heparin, low molecular heparins, heparinoids, heparin-like molecules, compounds structurally similar to one of the preceding anti coagulant compounds, and mixtures thereof; and
a therapeutically effective amount of a compound selected from the group consisting of glycine betaine, (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof,said combination preventing or reducing the incidence or severity of said haemorrhagic side effect or potentialising the therapeutic effect of said active agent. - View Dependent Claims (34, 35, 36, 37)
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38. A method of treating a patient comprising the steps of:
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administering to said patient an effective amount of a therapeutic active agent with at least one possible haemorrhagic side effect, and administering to said patient an effective amount of a compound selected from the group consisting of compounds of the formula (CH3)3N+(CH2)nCOO−
with n being an integer from 1 to 5, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof, wherein administration of said compound prevents or reduces the incidence or severity of said at least one side effect of said therapeutically active agent or potentializes the therapeutic effect of said therapeutically active agent. - View Dependent Claims (39)
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40. A method for treating or preventing at least one trouble selected from the group consisting of blood flow disturbance, thrombosis, thromboembolic disorders and combinations thereof comprising the step of administering to the bloodstream of a mammal in a controlled manner a therapeutically effective amount of a compound selected from the group consisting of glycine betaine, compounds of the formula (CH3)3N+(CH2)nCOO−
- with n being an integer from 1 to 5, pharmaceutically acceptable salts thereof, esters thereof, precursors thereof, and mixtures thereof.
- View Dependent Claims (41)
Specification