BUOYANT FORMULATIONS OF BETAINE

• US 20100221330A1
• Filed: 02/11/2010
• Published: 09/02/2010
• Est. Priority Date: 04/17/2003
• Status: Abandoned Application

• Current Assignee: Jallal Messadek
• Original Assignee: Jallal Messadek
• Inventors: Messadek, Jallal
• Application Number:
  US12/704,294
• Publication Number:
  US 20100221330A1
• Time in Patent Office: Days
• US Class Current: 424/463
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation comprising at least one pharmaceutically acceptable means ensuring an at least partial floating of the formulation releasing at least one betaine in the gastro-intestinal tractus.

Claims

1. An oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation having a density greater than 1 and comprising at least one pharmaceutically acceptable means for ensuring buoyancy of the formulation releasing at least one betaine in the gastro-intestinal tractus.

2. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy means is a water insoluble means.

3. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy means is a gastric insoluble means.

4. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy is a means insoluble at least in the pH range comprised between 3 and 7.5.

5. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy is a means insoluble at least in the pH range comprised between 2 and 7.5.

6. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy is a means insoluble at least in the pH range comprised between 1 and 7.5.

7. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy means is a means suitable to pass the human transit without degradation.

8. The formulation of claim 7, in which the pharmaceutically acceptable buoyancy means comprises fibers adapted for passing the human transit without degradation.

9. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy means comprises a support swelling in the presence of water.

10. The formulation of claim 1, in which the pharmaceutically acceptable buoyancy means comprises spherical support swelling in the presence of water.

11. The formulation of claim 1, which comprises solid micro-spheres containing betaine, said micro-spheres being coated with at least one layer of a hydrophilic polymer or copolymer swelling in contact with human gastric medium, but insoluble in human gastric medium.

12. The formulation of claim 11, in which for each micro-sphere, a controlled release layer that is non swelling in gastric medium is located between the betaine micro-sphere and the hydrophilic polymer or copolymer swelling in contact with human gastric medium.

13. The formulation of claim 1, which comprises solid micro-spheres containing glycine betaine, said micro-spheres being coated with at least one layer of a hydrophilic polymer or copolymer swelling in contact with human gastric medium, but insoluble in human gastric medium.

14. The formulation of claim 1, which comprises solid micro-spheres containing betaine, said micro-spheres being coated with at least one layer of a hydrophilic polymer or copolymer swelling in contact with human gastric medium with a swelling rate of at least 2, but insoluble in human gastric medium.

15. The formulation of claim 1, which comprises solid micro-spheres containing betaine, said micro-spheres being coated with at least one layer of a hydrophilic polymer or copolymer swelling in contact with human gastric medium with a swelling rate of at least 4, but insoluble in human gastric medium.

16. The formulation of claim 1, which comprises solid micro-spheres containing betaine, said micro-spheres being coated with at least one layer of a hydrophilic polymer or copolymer swelling in contact with human gastric medium with a swelling rate comprised between 5 and 20.

17. The formulation of claim 1, which comprises solid micro-spheres containing betaine, said micro-spheres being coated with at least one layer of a hydrophilic polymer or copolymer swelling in contact with human gastric medium, but insoluble in human gastric medium, and in which each micro-sphere is provided with at least one water impermeable barrier layer for protecting at least the hydrophilic swelling polymer layer, said barrier layer being selected among the group consisting of layers soluble in human gastric medium, layers degradable in human gastric medium and combinations thereof.

18. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 3 hours after the oral administration.

19. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 6 hours after the oral administration.

20. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 9 hours after oral administration.

21. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 12 hours after oral administration.

22. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 85% by weight of the betaine in the gastro-intestinal tractus for at least 3 hours after the administration.

23. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 75% by weight of the betaine in the gastro-intestinal tractus for at least 3 hours after the oral administration.

24. The formulation of claim 1, which comprises an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus, so as to ensure the floating of at least 75% by weight of the betaine in the gastro-intestinal tractus for at least 6 hours after the oral administration.

25. The formulation of claim 1, which comprises a physiologically acceptable polymer or copolymer forming, when in contact with the gastric medium, a system having a density lower than the density of the gastric medium.

26. The formulation of claim 25, in which the physiologically acceptable polymer or copolymer is selected to form a system selected from the group consisting of gelatinous systems, gelified systems and combinations thereof, when in contact with the gastric medium.

27. The formulation of claim 25, in which the physiologically acceptable polymer or copolymer is a water insoluble hydrophilic polymer or copolymer, said polymer or copolymer being insoluble in human gastric medium.

28. The formulation of claim 1, which comprises a physiologically acceptable polymer or copolymer forming, when in contact with the gastric medium, a system having a density lower than 1.

29. The formulation of claim 1, which has a form selected in the group consisting of capsules, microcapsules, spheroids, liquids, gels, flakes and combinations thereof.

30. The formulation of claim 1, which has a form selected in the group consisting of capsules, microcapsules, spheroids, liquids, gels, flakes, paillettes and combinations thereof, said form being placed in an envelope soluble in contact to the gastric medium.

31. The formulation of claim 1, which comprises at least one therapeutically active agent other than betaine.

32. The formulation of claim 31, in which the weight ratio betaine/therapeutically active agent other than betaine is comprised between 0.1 and 100.

33. The formulation of claim 1, which further comprises at least one therapeutically active agent selected from the group consisting of clopidogrel, the salts thereof, the esters thereof, aspirin, the salts thereof, the esters thereof and combinations thereof.

34. The formulation of claim 33, which comprises an effective amount of less than 200 mg of said therapeutically active agent selected from the group consisting of clopidogrel, the salts thereof, the esters thereof, aspirin, the salts thereof, the esters thereof and combinations thereof.

35. The formulation of claim 1, which comprises betaine containing particles selected from the group consisting of microparticles, nanoparticles and mixtures thereof.

36. The formulation of claim 35, in which the betaine containing particles are selected from the group consisting of uncoated matrix particles, coated matrix particles and mixtures thereof.

37. An unit oral dosage form comprising:

a first oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation comprising at least one pharmaceutically acceptable means for ensuring an at least partial floating of the formulation releasing at least one betaine in the gastro-intestinal tractus, and

a second oral formulation for releasing at least one therapeutically active agent different from the betaine released from the first oral controlled formulation.

38. An unit oral dosage form comprising:

a first oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation comprising at least one pharmaceutically acceptable means for ensuring an at least partial floating of the formulation releasing at least one betaine in the gastro-intestinal tractus, and

a second oral formulation for releasing at least one therapeutically active agent, said second formulation having a different release profile than the controlled release profile of the first oral control release formulation.

39. Use of at least one means ensuring buoyancy of at least one betaine in the gastro-intestinal tractus for the preparation of an oral controlled release formulation of betaine having a density of greater than 1.

40. The use of claim 39, for the preparation of an oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation comprising at least one pharmaceutically acceptable means ensuring buoyancy of the formulation releasing at least one betaine, in the gastro-intestinal tractus, for at least 3 hours after oral administration.

41. The use of claim 39, in which an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus is used, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 3 hours after the oral administration.

42. The use of claim 39, in which an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus is used, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 6 hours after the oral administration.

43. The use of claim 39, in which an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus is used, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 9 hours after oral administration.

44. The use of claim 39, in which an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus is used, so as to ensure the floating of at least 50% by weight of the betaine in the gastro-intestinal tractus for at least 12 hours after oral administration.

45. The use of claim 39, in which an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus is used, so as to ensure the floating of at least 85% by weight of the betaine in the gastro-intestinal tractus for at least 3 hours after the administration.

46. The use of claim 39, in which an efficient amount of at least one means ensuring buoyancy of at least one betaine in the gastro intestinal tractus is used, so as to ensure the floating of at least 75% by weight of the betaine in the gastro-intestinal tractus for at least 3 hours after the oral administration.

47. The use of claim 39 for the preparation of a formulation comprising a betaine and having at least one characteristic selected from the group consisting of:

Increasing the residence time in the gastro-intestinal tractus of at least one betaine

Control and/or increase in function of the time of the release of at east one betaine towards the blood flow

Control and/or increase of the released amount of at least one betaine towards the blood flow

Control and/or increase of the bioavailability of at east one betaine, and

Combinations of said characteristics.

48. A method for treating a human suffering of at least one trouble selected from the group consisting of cardiovascular diseases, atherosclerosis, hypertension, diabetes, cardiac diseases, atrial fibrillation, blood coagulation troubles, Raynaud'"'"'s disease, Alzheimer disease, vascular dementia, Parkinson disease, memory troubles, intermittent claudication, blood circulation troubles, legs circulation troubles, peripheral arterial disease, peripheral arterial occlusive disease, haemodialysis troubles, renal diseases, liver diseases, metabolic syndrome, syndrome X, ocular troubles, pulmonary hypertension, angina pectoris, stroke, scleroderma, deep venous thrombosis, air travel troubles, polyps, nasal polyps, portal hypertension, sepsis, bleeding troubles, cancer, cancer therapy, chemotherapy, Idiopathic Thrombocytopenic Purpura, restinosis, stent restinosis, thrombocytopenia, psoriasis, inflammation, endothelial dysfunction, sexual dysfunctions, hemorrhoids, fatigue, pneumonia, asthma, trauma, surgery, inflammation, sub-fertility, lactation problems, gut disorders, arthritis and other joint problems, ageing, impaired immune function, burns, malaria, cystic fibrosis, tuberculosis, migraine, neurological problems, schizophrenia, depression, respiratory infections, HIV, muscle soreness, drug intoxication, homocysteine related troubles, homocystinuria, homocysteinemia, hyper-homocysteinemia, pain and combinations thereof, in which at least one oral formulation is timely administered to said patient, whereby said oral administration is an oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation comprising at least one pharmaceutically acceptable means ensuring buoyancy of the formulation releasing at least one betaine, in the gastro-intestinal tractus, for at least 3 hours after oral administration.

49. A method for treating a human at risk from suffering of at least one trouble selected from the group consisting of cardiovascular diseases, atherosclerosis, hypertension, diabetes, cardiac diseases, atrial fibrillation, blood coagulation troubles, Raynaud'"'"'s disease, Alzheimer disease, vascular dementia, Parkinson disease, memory troubles, intermittent claudication, blood circulation troubles, legs circulation troubles, peripheral arterial disease, peripheral arterial occlusive disease, haemodialysis troubles, renal diseases, liver diseases, metabolic syndrome, syndrome X, ocular troubles, pulmonary hypertension, angina pectoris, stroke, scleroderma, deep venous thrombosis, air travel troubles, polyps, nasal polyps, portal hypertension, sepsis, bleeding troubles, cancer, cancer therapy, chemotherapy, Idiopathic Thrombocytopenic Purpura, restinosis, stent restinosis, thrombocytopenia, psoriasis, inflammation, endothelial dysfunction, sexual dysfunctions, hemorrhoids, fatigue, pneumonia, asthma, trauma, surgery, inflammation, sub-fertility, lactation problems, gut disorders, arthritis and other joint problems, ageing, impaired immune function, burns, malaria, cystic fibrosis, tuberculosis, migraine, neurological problems, schizophrenia, depression, respiratory infections, HIV, muscle soreness, drug intoxication, homocysteine related troubles, homocystinuria, homocysteinemia, hyper-homocysteinemia, pain and combinations thereof, in which at least one oral formulation is timely administered to said patient, whereby said oral formulation is an oral control release formulation for releasing at least one betaine after oral administration to a human, said formulation comprising at least one pharmaceutically acceptable means ensuring buoyancy of the formulation releasing at least one betaine, in the gastro-intestinal tractus, for at least 3 hours after oral administration.