US20050026846A1 - Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism - Google Patents
Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism Download PDFInfo
- Publication number
- US20050026846A1 US20050026846A1 US10/928,156 US92815604A US2005026846A1 US 20050026846 A1 US20050026846 A1 US 20050026846A1 US 92815604 A US92815604 A US 92815604A US 2005026846 A1 US2005026846 A1 US 2005026846A1
- Authority
- US
- United States
- Prior art keywords
- carnitine
- alkanoyl
- acid
- statin
- composition
- 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.)
- Abandoned
Links
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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a pharmaceutical composition for the prevention and treatment of cardiovascular diseases caused by abnormal lipid metabolism.
- Cardiovascular diseases related to abnormal lipid metabolism are very frequent in industrialised countries. In Italy, for instance, they account for more than 40% of the overall mortality (Capocaccia R., Farchi G., Prati S. et al.: La mortalitá in Italia nell'anno 1989. Rapporto ISTISAN 1992/22).
- Our knowledge of the relationships between cholesterol and coronarv heart disease stem from epidemiological studies conducted over the past few years. The conclusions reached in these studies indicate that the development of severe coronary atherosclerosis and coronarv heart disease are closely correlated with serum cholesterol levels (McGill H. C. Jr. et al.: The International Atherosclerosis Project. Lab. Invest. 18: 463-653, 1968; Keys A.: Seven countries: Death and Coronary Heart Disease. Harvard University Press, Cambridge, 1980).
- Hypolipaemic drugs fall into two categories: those which above all reduce cholesterol and those which mainly reduce triglycerides.
- the former group of drugs includes the statins, probucol and resins, while the latter group includes the fibrates, nicotinic acid and fatty acids belonging to the omega-3 series.
- statins are inhibitors of hydroxy-methyl-glutaryl-coenzyrne A (HMG-CoA) reductase. By inhibiting this enzyme, they reduce the hepatic synthesis of cholesterol (Lancet 1994; 334: 1383-1389). To compensate for the reduction of intracellular cholesterol the liver cell produces several receptors for LDL and VLDL lipoproteins, which are thus removed from the bloodstream.
- HMG-CoA hydroxy-methyl-glutaryl-coenzyrne A
- statins also give rise to reduced intestinal absorption of cholesterol of dietary orion and to a reduced output of apoprotein B present in low-density lipoproteins (LDL).
- LDL low-density lipoproteins
- statins are drugs which are better tolerated than the other anticholesterolaemic agents, but are not without drawbacks, the side effects most commonly induced by these drugs being gastrointestinal disorders, skin rashes and headache.
- statins lead to a reduction in the number of deaths due to coronary heart disease, an increase has been observed, in treated patients, of deaths caused by other events such as tumours or trauma
- pharmacological treatment with statins should be given only to patients at high risk for coronary disease in the short term (JAMA. 1996; 275: 55-60).
- U.S. Pat. No. 4,268,524 describes a therapeutic method for increasing high-density lipoprotein (HDL) levels so as to selectively reduce the HDL: (LDL+VLDL) ratio in the plasma of patients at risk for cardiovascular disease, in which this ratio is abnormally high; the method comprises administering 5-50 mg/kg/day of alkanoyl carnitine or one of its pharmacologically acceptable salts.
- HDL high-density lipoprotein
- an alkanoyl L-carnitine in which the linear or branched alkanoyl has 2-6 carbon atoms, or of one of its pharmacologically acceptable salts, and a statin enables an enhanced effect on the anticholesterolaemic and antitriglyceridaemic action to be achieved as compared to the separate, independent administration of the two active ingredients. This enables the same therapeutic results to be achieved using lower doses of statins, thus making for a marked reduction in their toxic and side effects.
- statin dose can be reduced to 5-20 mg/day, whereas the alkanoyl L-carnitine dose can be reduced to 2-30 mg/kg/day.
- afore-mentioned compounds are either their co-administration, i.e. the substantially simultaneous administration of one of the aforesaid alkanoyl L-carnitines, or one of their pharmacologically acceptable salts, and of a statin, or, indifferently, the administration of a composition comprising a combination or mixture of the aforesaid active ingredients, optionally in addition to suitable excipients.
- the scope of the present invention encompasses therefore both the co-administration of one of the aforesaid alkanoyl L-camitines, or one of their pharmacologically acceptable salts, together with a statin, and orally or parenterally administrable pharmaceutical compositions comprising a mixture of the two active ingredients.
- statin is selected from the group comprising lovastatin, simvastatin, provastatin and fluvastatin
- alkanoyl L-carnitine is selected from the group comprising acetyl, propionyl, butyryl, valeryl and isovaleryl L-carnitine or one of their pharmacologically acceptable salts.
- statin is simvastatin and the alkanoyl L-carnitine propionyl L-carnitine or one of its pharmacologically acceptable salts.
- pharmacologically acceptable salt of an alkanoyl L-carnitine is any salt of the latter with an acid that does not give rise to unwanted toxic or side effects.
- Non-limiting examples of pharmacologically acceptable salts of alkanoyl L-carnitines are chloride, bromide, orotate, acid aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, lactate, maleate and acid maleate, acid oxalate, acid sulphate, glucose phosphate, tartrate and acid tartrate.
- compositions in unit dosage form, are a composition comprising statin 5-10 mg and alkanoyl L-carnitine 100-1000 ma.
- propionyl L-carnitine 2 g/day os for 60 days, which was discontinued on day 61 for a 30-day wash-out period.
- Simvastatin was then administered at a dose of 10 mg/day os in the evening for 30 days, followed by a further 30-day washout period and then by another 30-day period during which propionyl L-carnitine 1.5 g/day os and simvastatin 5 mg/day os were administered simultaneously.
- the mean triglvceride value was 205.37 ⁇ 13.98 mg %.
- the mean triglyceride value was 146.62 ⁇ 27.93 mg % and presented a statistically significant reduction as compared to baseline conditions (p ⁇ 0,0001).
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The co-ordinated use of an alkanoyl L-carnitine (e.g. propionyl L-carnitine) and a statine (e.g. simvastatin) is disclosed for treating pathologies brought about by an altered lipid metabolism, wherein by coordinated use both the substantially contemporaneous co-administration of the two active ingredients and the administration of a combination composition comprising a mixture of the two active ingredients, is meant.
Description
- The present invention relates to a pharmaceutical composition for the prevention and treatment of cardiovascular diseases caused by abnormal lipid metabolism.
- Cardiovascular diseases related to abnormal lipid metabolism are very frequent in industrialised countries. In Italy, for instance, they account for more than 40% of the overall mortality (Capocaccia R., Farchi G., Prati S. et al.: La mortalitá in Italia nell'anno 1989. Rapporto ISTISAN 1992/22). Our knowledge of the relationships between cholesterol and coronarv heart disease stem from epidemiological studies conducted over the past few years. The conclusions reached in these studies indicate that the development of severe coronary atherosclerosis and coronarv heart disease are closely correlated with serum cholesterol levels (McGill H. C. Jr. et al.: The International Atherosclerosis Project. Lab. Invest. 18: 463-653, 1968; Keys A.: Seven Countries: Death and Coronary Heart Disease. Harvard University Press, Cambridge, 1980).
- Correction of eating habits through suitable diet is invariably the first measure adopted in cases of hyperlipidaemia. Satisfactory results are not always achieved, however, owing to widespread intolerance of strict dietarv discipline, to the severity of the hypercholesterolaemia, or to genetic-type resistance.
- To achieve the desired results in these patients, i.e. normalisation of blood levels of triglycerides and cholesterol, pharmacological treatment has to be resorted to. Hypolipaemic drugs fall into two categories: those which above all reduce cholesterol and those which mainly reduce triglycerides.
- The former group of drugs includes the statins, probucol and resins, while the latter group includes the fibrates, nicotinic acid and fatty acids belonging to the omega-3 series.
- The statins (lovastatin, simvastatin, provastatin, fluvastatin, and the like) are inhibitors of hydroxy-methyl-glutaryl-coenzyrne A (HMG-CoA) reductase. By inhibiting this enzyme, they reduce the hepatic synthesis of cholesterol (Lancet 1994; 334: 1383-1389). To compensate for the reduction of intracellular cholesterol the liver cell produces several receptors for LDL and VLDL lipoproteins, which are thus removed from the bloodstream.
- The statins also give rise to reduced intestinal absorption of cholesterol of dietary orion and to a reduced output of apoprotein B present in low-density lipoproteins (LDL).
- The statins are drugs which are better tolerated than the other anticholesterolaemic agents, but are not without drawbacks, the side effects most commonly induced by these drugs being gastrointestinal disorders, skin rashes and headache.
- A number of patients have also reported sleep disorders (EJ Schaffer, N Engl J Med, 319; 1222, 1988; Lancet, 339: 547, 29 February 1992), while, in 1-2% of patients taking high doses of statins, an at least 3-fold increase in plasma aminotransferase activity has been noted compared to baseline values, which may even require discontinuation of the treatment.
- In addition, it has been reported that though the statins lead to a reduction in the number of deaths due to coronary heart disease, an increase has been observed, in treated patients, of deaths caused by other events such as tumours or trauma (Davey-Smith G., Song F., Sheldon T. A.: Cholesterol lowering and mortality: the importance of considering initial level at risk. BMJ, 1993; 306: 1367-1373; Ravnshov U.: Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. BMJ 1992; 305: 15-19). The results of experiments in animals and human subjects have suggested that, to reduce cholesterol levels, pharmacological treatment with statins should be given only to patients at high risk for coronary disease in the short term (JAMA. 1996; 275: 55-60).
- Equally well known is the antitriglyceridaemic and anticholesterolaemic effect of a number of alkanoyl carnitines, particularly acetyl L-carnitine. U.S. Pat. No. 4,268,524 describes a therapeutic method for increasing high-density lipoprotein (HDL) levels so as to selectively reduce the HDL: (LDL+VLDL) ratio in the plasma of patients at risk for cardiovascular disease, in which this ratio is abnormally high; the method comprises administering 5-50 mg/kg/day of alkanoyl carnitine or one of its pharmacologically acceptable salts.
- It has now been found, unexectedly, that the coordinated use—this term being defined precisely here below—of an alkanoyl L-carnitine in which the linear or branched alkanoyl has 2-6 carbon atoms, or of one of its pharmacologically acceptable salts, and a statin enables an enhanced effect on the anticholesterolaemic and antitriglyceridaemic action to be achieved as compared to the separate, independent administration of the two active ingredients. This enables the same therapeutic results to be achieved using lower doses of statins, thus making for a marked reduction in their toxic and side effects.
- The well-known lack of toxic and side effects of the alkanoyl L-carnitines and the use of lower doses of statins as compared to the routine doses (10-40 mg/day) makes the coordinated use as per the invention particularly useful and safe both for the treatment of hypercholesterolaemic and/or hypertriglyceridaemic patients at high risk for cardiovascular disease in the short, medium or long term and for the prevention of such diseases.
- As a result of the above-mentioned synergistic effect, it has been found, in fact, that the statin dose can be reduced to 5-20 mg/day, whereas the alkanoyl L-carnitine dose can be reduced to 2-30 mg/kg/day.
- According to the present invention, what is meant by “co-ordinated use” of the afore-mentioned compounds is either their co-administration, i.e. the substantially simultaneous administration of one of the aforesaid alkanoyl L-carnitines, or one of their pharmacologically acceptable salts, and of a statin, or, indifferently, the administration of a composition comprising a combination or mixture of the aforesaid active ingredients, optionally in addition to suitable excipients.
- The scope of the present invention encompasses therefore both the co-administration of one of the aforesaid alkanoyl L-camitines, or one of their pharmacologically acceptable salts, together with a statin, and orally or parenterally administrable pharmaceutical compositions comprising a mixture of the two active ingredients.
- Preferably the statin is selected from the group comprising lovastatin, simvastatin, provastatin and fluvastatin, while the alkanoyl L-carnitine is selected from the group comprising acetyl, propionyl, butyryl, valeryl and isovaleryl L-carnitine or one of their pharmacologically acceptable salts.
- Even more preferably, the statin is simvastatin and the alkanoyl L-carnitine propionyl L-carnitine or one of its pharmacologically acceptable salts.
- What is meant by pharmacologically acceptable salt of an alkanoyl L-carnitine is any salt of the latter with an acid that does not give rise to unwanted toxic or side effects.
- These acids are well known to pharmacologists and to experts in pharmacy.
- Non-limiting examples of pharmacologically acceptable salts of alkanoyl L-carnitines are chloride, bromide, orotate, acid aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, lactate, maleate and acid maleate, acid oxalate, acid sulphate, glucose phosphate, tartrate and acid tartrate.
- One preferred composition, in unit dosage form, is a composition comprising statin 5-10 mg and alkanoyl L-carnitine 100-1000 ma.
- The enhanced effect of alkanoyl L-carnitine and statin has been confirmed, for example, by the results of a clinical study which are given here below.
- Eight hypertriglyceridaemic patients (3 males and 5 females) were recruited for the study, with a mean age of 65 years (range: 52-70), presenting mean triglyceridaemia values of 213.0±21.18 mg % and mean cholesterolaemia values of 158.1±25.90 mg %, who were put on a dietary regimen consisting in 40 Kcal/kg, 1.2 g/kg proteins and 1.4 g/kg lipids daily.
- After baseline determinations of cholesterolaemia, triglyceridaemia, bilirubinaemia, alkaline phosphatase, protidaemia, GOT and GPT, all subjects took propionyl L-carnitine 2 g/day os for 60 days, which was discontinued on day 61 for a 30-day wash-out period. Simvastatin was then administered at a dose of 10 mg/day os in the evening for 30 days, followed by a further 30-day washout period and then by another 30-day period during which propionyl L-carnitine 1.5 g/day os and simvastatin 5 mg/day os were administered simultaneously.
- Blood-chemistry tests were performed before and after each course of drug treatment and at the end of each wash-out period. The data obtained were subjected to statistical analysis using Student's t-test for paired data (Table 1).
TABLE 1 Experimental protocol/baseline study Treatment with Treatment with Treatment propionyl L-carni- propionyl L- with sim- tine 1.5 g/day carnitine 2 g/ vastatin 10 os + simvastatin day os Wash-out mg/day os Wash-out 5 mg/day os 60 days 30 days 30 days 30 days 30 days Blood- Blood- Blood- Blood- Blood- chemistry chemistry chemistry chemistry chemistry tests tests tests tests tests -
TABLE 2 Statistical analysis of results Propionyl Propionyl L-carnitine + Time L-carnitine Simvastatin simvastatin Cholesterolaemia 0 — — — 30 days p < 0.4795 p < 0.0585 p < 0.0389 60 days p < 0.0198 — — Triglyceridaemia 0 — — — 30 days p < 0.3671 p < 0.0247 p < 0.0015 60 days p < 0.0272 — — - Owing to the low dose of simvastatin and the substantial non-toxicity of propionyl L-carnitine, no side effects attributable to the drugs used were detected during the study period. All patients completed the study according to the procedures described. As regards triglyceridaemia during the period of treatment with propionyl L-carnitine, only a slight, statistically non-significant reduction (p<0.3671) was recorded after 30 days as compared to baseline values and this reduction proved statistically significant (p<0.0272) only after 60 days' treatment with propionyl L-carnitine. During the wash-out period the mean triglyceridaemia value recorded was 202.5±9.71 mg %, whereas the mean baseline value was 213.0±21.1 1 mg % (Table 2).
- After treatment with simvastatin a statistically significant reduction in triglycerides was recorded as compared to basal values (p<0.024), with a mean post-treatment triglyceride value of 193.8±22.63 mg % (Table 2).
- At the end of the wash-out period following simvastatin treatment, the mean triglvceride value was 205.37±13.98 mg %. At the end of the treatment with propionvi L-carnitine and simvastatin administered simultaneously, the mean triglyceride value was 146.62±27.93 mg % and presented a statistically significant reduction as compared to baseline conditions (p<0,0001). On comparing statistically the triglyceridaemia values recorded after treatment with propionyl L-carnitine and simvastatin, respectively, administered alone, with those recorded after treatment with the combination, the following significance values were found: p<0.167 (propionyl L-carnitine vs simvastatin); p<0.00031 (propionyl L-carnitine vs propionyl L-carnitine+simvastatin); p<0.0004 (simvastatin vs propionyl L-carnitine+simvastatin) (Table 2).
- As regards cholesterolaemia values, which were within normal limits in baseline conditions (mean 158.12±25.90 mg %), statistically significant reductions were recorded in the comparison among values recorded at the end of the first washout period (158.37±25.90 mg %), after treatment with simvastatin (156.75±22.82) and in the comparison between baseline values (158.19±25.90 mg/o) and those obtained after the period of treatment with the combination of propionyl L-carnitine and simvastatin (135.51±15.2 mg %) (p<0.0038) (Table 2).
- The results of this clinical study provide significant evidence in support of the enhanced effect of alkanoyl L-carnitine and statin, which constitutes the basis of the present invention. The data obtained, in fact, demonstrate without doubt that the pharmacological combination of propionyl L-carnitine and simvastatin presents a superior cholesterolaemia-lowering and triglyceridaemia-lowering effect as compared to the administration of propionyl L-carnitine and simvastatin separately and independently. This allows a drastic reduction in the daily dose of simvastatin (from 10 mg/day to 5 mg/day), which thus falls below the threshold at which the above-mentioned unwanted toxic and side effects usually manifest themselves.
Claims (11)
1. An orally or parenterally administrable pharmaceutical composition which comprises an alkanoyl L-carnitine wherein the linear or branched alkanoyl group has 2-6 carbon atoms, or one of its pharmacologically acceptable salts, and a statin.
2. The composition of claim 1 , wherein the alkanoyl L-carnitine is selected from the group comprising acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl L-carnitine.
3. The composition of claim 1 , wherein the statin is selected from the group comprising lovastatin, simvastatin, provastatin and fluvastatin.
4. The composition of claim 1 , wherein the pharmacologically acceptable salt of the alkanoyl L-carnitine is selected from the group comprising chloride, bromide, orotate, acid aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, lactate, maleate and acid maleate, acid oxalate, acid sulphate, glucose phosphate, tartrate and acid tartrate.
5. The composition of claim 1 , wherein the statin is simvastatin and the alkanoyl L-carnitine is propionyl L-carnitine or one of its pharmacologically acceptable salts.
6. The composition of claim 1 with a cholesterolaemia-lowering and triglyceridaemia-lowering action for the treatment of diseases caused by abnormal lipid metabolism.
7. The composition of claim 6 for the treatment of cardiovascular, thrombotic, atherosclerotic diseases and of peripheral vascular diseases.
8. The composition of claim 1 , in unit dosage form, comprising of 5-10 mg of statin and 100-1000 mg of alkanoyl L-carnitine.
9. Co-ordinated use of an alkanoyl L-carnitine wherein the linear or branched alkanoyl group has 2-6 carbon atoms, or of one of its pharmacologically acceptable salts, and a statin, for the prevention and treatment of diseases caused by abnormal lipid metabolism.
10. Use of an alkanoyl L-carnitine wherein the linear or branched alkanoyl group has 2-6 carbon atoms, or of one of its pharmacologically acceptable salts, and a statin, to produce a medicament for the prevention and treatment of diseases caused by abnormal lipid metabolism.
11. The use of claim 9 , in which the statin is selected from the group comprising lovastatin, simvastatin, provastatin and fluvastatin and the alkanoyl L-carnitine is selected from among the group comprising acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl L-carnitine or one of their pharmacologically acceptable salts.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/928,156 US20050026846A1 (en) | 1997-01-07 | 2004-08-30 | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITRM97A000390 | 1997-07-01 | ||
IT97RM000390A IT1293067B1 (en) | 1997-07-01 | 1997-07-01 | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF PATHOLOGIES CAUSED BY ALTERED LIPID METABOLISM |
US09/446,806 US6180680B1 (en) | 1997-07-01 | 1998-06-18 | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism |
US62834500A | 2000-07-28 | 2000-07-28 | |
US10/928,156 US20050026846A1 (en) | 1997-01-07 | 2004-08-30 | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US62834500A Continuation | 1997-01-07 | 2000-07-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050026846A1 true US20050026846A1 (en) | 2005-02-03 |
Family
ID=11405149
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/446,806 Expired - Fee Related US6180680B1 (en) | 1997-01-07 | 1998-06-18 | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism |
US10/928,156 Abandoned US20050026846A1 (en) | 1997-01-07 | 2004-08-30 | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/446,806 Expired - Fee Related US6180680B1 (en) | 1997-01-07 | 1998-06-18 | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism |
Country Status (10)
Country | Link |
---|---|
US (2) | US6180680B1 (en) |
EP (2) | EP1623708A3 (en) |
JP (1) | JP2002507223A (en) |
KR (1) | KR100539066B1 (en) |
AU (1) | AU726822B2 (en) |
CA (1) | CA2295748A1 (en) |
IL (1) | IL133492A (en) |
IT (1) | IT1293067B1 (en) |
NZ (1) | NZ501844A (en) |
WO (1) | WO1999001126A1 (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100725263B1 (en) * | 1999-06-08 | 2007-06-07 | 시그마타우 인두스트리에 파르마슈티케 리우니테 에스.피.에이. | Antilipemic combinations comprising HMG-CoA reductase inhibitors and carnitines |
US6245800B1 (en) * | 1999-06-08 | 2001-06-12 | Sigma-Tau | Method of preventing or treating statin-induced toxic effects using L-carnitine or an alkanoyl L-carnitine |
ES2237073T3 (en) * | 1999-06-30 | 2005-07-16 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | COMBINATION WITH HYPOLIPEMIAN ACTIVITY SUBSTANTIALLY EXEMPT FROM TOXIC OR SECONDARY EFFECTS INDUCED BY HYPOLIMIATING PHARMACOS. |
US20050232911A1 (en) * | 2004-04-19 | 2005-10-20 | Schreiber Brian D | Prevention and treatment of metabolic abnormalities associated with excess intramyocellular lipid |
ITRM20040307A1 (en) | 2004-06-23 | 2004-09-23 | Sigma Tau Ind Farmaceuti | PACKAGE OF AT LEAST TWO DIFFERENT PRODUCTS TO SELL AND USE TOGETHER. |
US20100029759A1 (en) * | 2007-02-27 | 2010-02-04 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Composition useful for the treatment of type 2 diabetes |
CN101663030B (en) | 2007-03-21 | 2013-08-21 | 希格马托制药工业公司 | Composition useful for the prevention of type 2 diabetes and its complications in pre-diabetic patients with insulin resistance |
HUE042168T2 (en) * | 2008-02-29 | 2019-06-28 | Biolab Sanus Farmaceutica Ltda | Pharmaceutical composition comprising racetam and carnitine and process for its preparation |
US11591288B2 (en) | 2017-08-23 | 2023-02-28 | Gavish-Galilee Bio Applications Ltd. | Compositions and methods for treating atherosclerotic cardiovascular disease |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2903579A1 (en) * | 1978-02-03 | 1979-08-09 | Sigma Tau Ind Farmaceuti | USE OF ACETYL CARNITINE AND OTHER ACYLDER DERIVATIVES OF CARNITINE FOR THE TREATMENT OF HYPERLIPOPROTEINEMIC AND HYPERLIMPIDAEMIA AND MEDICINAL PRODUCTS |
-
1997
- 1997-07-01 IT IT97RM000390A patent/IT1293067B1/en active IP Right Grant
-
1998
- 1998-06-18 KR KR10-1999-7012633A patent/KR100539066B1/en not_active IP Right Cessation
- 1998-06-18 US US09/446,806 patent/US6180680B1/en not_active Expired - Fee Related
- 1998-06-18 WO PCT/IT1998/000163 patent/WO1999001126A1/en active IP Right Grant
- 1998-06-18 JP JP50684499A patent/JP2002507223A/en not_active Ceased
- 1998-06-18 EP EP05105620A patent/EP1623708A3/en not_active Withdrawn
- 1998-06-18 IL IL13349298A patent/IL133492A/en not_active IP Right Cessation
- 1998-06-18 AU AU79310/98A patent/AU726822B2/en not_active Ceased
- 1998-06-18 EP EP98929631A patent/EP0983066A1/en not_active Ceased
- 1998-06-18 NZ NZ501844A patent/NZ501844A/en not_active IP Right Cessation
- 1998-06-18 CA CA002295748A patent/CA2295748A1/en not_active Abandoned
-
2004
- 2004-08-30 US US10/928,156 patent/US20050026846A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
KR20010014439A (en) | 2001-02-26 |
US6180680B1 (en) | 2001-01-30 |
KR100539066B1 (en) | 2005-12-26 |
WO1999001126A1 (en) | 1999-01-14 |
JP2002507223A (en) | 2002-03-05 |
ITRM970390A0 (en) | 1997-07-01 |
IT1293067B1 (en) | 1999-02-11 |
NZ501844A (en) | 2001-10-26 |
ITRM970390A1 (en) | 1999-01-01 |
IL133492A0 (en) | 2001-04-30 |
EP1623708A3 (en) | 2006-02-15 |
AU7931098A (en) | 1999-01-25 |
EP0983066A1 (en) | 2000-03-08 |
AU726822B2 (en) | 2000-11-23 |
CA2295748A1 (en) | 1999-01-14 |
EP1623708A2 (en) | 2006-02-08 |
IL133492A (en) | 2004-07-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8853229B2 (en) | Composition containing statins and omega-3 fatty acids | |
US9125903B2 (en) | Composition useful for the treatment of lipid metabolism disorders | |
AU726822B2 (en) | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism | |
US9642860B2 (en) | Combinations of corroles and statins | |
US6245800B1 (en) | Method of preventing or treating statin-induced toxic effects using L-carnitine or an alkanoyl L-carnitine | |
JPH04257518A (en) | Medicine composition for prevention or treatment of iii type high lipoproteinemia | |
US6066664A (en) | Method for decreasing the appetite in bulimic, overweight individuals | |
US7956091B2 (en) | Use of carnitines for the prevention and/or treatment of disorders caused by the andropause | |
KR100725263B1 (en) | Antilipemic combinations comprising HMG-CoA reductase inhibitors and carnitines | |
US8003652B2 (en) | Use of acetyl L-carnitine in combination with propionyl L-carnitine and Sildenafil for the treatment of erectile dysfunction | |
US7776913B2 (en) | Carnitines for treating or preventing disorders caused by andropause | |
WO2020028124A1 (en) | NEW USE OF CARBAMATE β PHENYLETHANOLAMINE ANALOGUES FOR ENHANCING INTRACELLULAR CLEARANCE OF LDL CHOLESTEROL AND FOR COMBINING THERAPY WITH STATINS TO ENHANCE THE EFFICACY AND REDUCE ADVERSE EFFECTS | |
MXPA99011665A (en) | Pharmaceutical compositions comprising alkanoyl l-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism | |
EP1064943B1 (en) | Combination having antilipemic activity substantially free from toxic or side effects due to antilipemic drugs | |
EP2124925B1 (en) | Composition useful for the treatment of type 2 diabetes | |
US7504435B2 (en) | Method for stimulating weight loss and/or for lowering triglycerides in patients |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |