US20050080018A1 - Use of alkanoyl l-carnitine for the treatment of erectile dysfunction - Google Patents
Use of alkanoyl l-carnitine for the treatment of erectile dysfunction Download PDFInfo
- Publication number
- US20050080018A1 US20050080018A1 US10/497,498 US49749804A US2005080018A1 US 20050080018 A1 US20050080018 A1 US 20050080018A1 US 49749804 A US49749804 A US 49749804A US 2005080018 A1 US2005080018 A1 US 2005080018A1
- Authority
- US
- United States
- Prior art keywords
- treatment
- erectile dysfunction
- acid
- carnitine
- alkanoyl
- 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
- -1 alkanoyl l-carnitine Chemical compound 0.000 title claims abstract description 34
- 208000010228 Erectile Dysfunction Diseases 0.000 title claims abstract description 27
- 201000001881 impotence Diseases 0.000 title claims abstract description 27
- 229960001518 levocarnitine Drugs 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract description 35
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 claims description 24
- 229940079593 drug Drugs 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 20
- 229960003310 sildenafil Drugs 0.000 claims description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 claims description 8
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 claims description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- 229930008281 A03AD01 - Papaverine Natural products 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- 229960001789 papaverine Drugs 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- WGAOZGUUHIBABN-UHFFFAOYSA-N 1-aminopentan-1-ol Chemical compound CCCCC(N)O WGAOZGUUHIBABN-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 claims description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 2
- QWJSAWXRUVVRLH-LREBCSMRSA-M 2-hydroxyethyl(trimethyl)azanium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical compound C[N+](C)(C)CCO.OC(=O)[C@H](O)[C@@H](O)C([O-])=O QWJSAWXRUVVRLH-LREBCSMRSA-M 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 229940009098 aspartate Drugs 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229960005336 magnesium citrate Drugs 0.000 claims description 2
- 235000002538 magnesium citrate Nutrition 0.000 claims description 2
- 239000004337 magnesium citrate Substances 0.000 claims description 2
- 229940091250 magnesium supplement Drugs 0.000 claims description 2
- 229940095060 magnesium tartrate Drugs 0.000 claims description 2
- MUZDLCBWNVUYIR-ZVGUSBNCSA-L magnesium;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Mg+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O MUZDLCBWNVUYIR-ZVGUSBNCSA-L 0.000 claims description 2
- QUIOHQITLKCGNW-TYYBGVCCSA-L magnesium;(e)-but-2-enedioate Chemical compound [Mg+2].[O-]C(=O)\C=C\C([O-])=O QUIOHQITLKCGNW-TYYBGVCCSA-L 0.000 claims description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 2
- 229940066528 trichloroacetate Drugs 0.000 claims description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 2
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 7
- 210000005226 corpus cavernosum Anatomy 0.000 description 6
- 150000003180 prostaglandins Chemical class 0.000 description 6
- 210000003899 penis Anatomy 0.000 description 5
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000004907 flux Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 3
- 229960004046 apomorphine Drugs 0.000 description 3
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229960000711 alprostadil Drugs 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000009552 doppler ultrasonography Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- WIZMKNQXIAYADR-UHFFFAOYSA-N 3-hydroxy-6-methyl-4-oxo-3-[(trimethylazaniumyl)methyl]heptanoate Chemical compound C(CC(C)C)(=O)C(O)(C[N+](C)(C)C)CC([O-])=O WIZMKNQXIAYADR-UHFFFAOYSA-N 0.000 description 1
- UCTWMZQNUQWSLP-UHFFFAOYSA-N Adrenaline Natural products CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 206010052004 Organic erectile dysfunction Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940102884 adrenalin Drugs 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000001856 erectile effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000001129 nonadrenergic effect Effects 0.000 description 1
- 230000002536 noncholinergic effect Effects 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003442 weekly 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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 the use of an alkanoyl L-carnitine for the treatment of the erectile dysfunction.
- the erectile dysfunction is a syndrome characterised by a persistent inability to obtain or maintain a penis erection, for a time sufficient for a sexual intercourse.
- the current knowledge indicates that the relaxation of the smooth musculature of the corpus cavernosum which is necessary for the erection is due to a non adrenergic, non cholinergic mechanism, mediated by nitric oxide (ON), in which prostaglandin (PG) is involved (Medicina Pratica, 2000; 12-16).
- ON nitric oxide
- PG prostaglandin
- the maximum relaxation level may not be sufficient to permit an haematic flux sufficient for a normal erection.
- VIP Vasoactive Intestinal Peptides
- cGMP guanosin mono phosphate cyclic
- alkanoyl L-carnitines wherein the alkanoyl group, linear or branched, has 2-6 carbon atoms, or a pharmaceutically acceptable salt thereof are useful agents for treating the erectile dysfunction.
- 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, magnesium citrate, acid phosphate, fumarate and acid fumarate, magnesium fumarate, lactate, maleate, acid maleate, mucate, acid oxalate, pamoate, acid pamoate, acid sulphate, glucose phosphate, tartrate, acid tartrate, magnesium tartrate, 2-amino ethansulphonate, magnesium 2-amino etansulphonate, Choline tartrate and trichloroacetate.
- alkanoyl L-carnitines are acetyl, propionyl, butyryl, isobutyryl, valeryl and isovalery L-carnitine.
- a further object of the present invention is the use of an alkanoyl L-carnitine for preparing a medicine for the treatment of erectile dysfunction in patients suffering from diabetes mellitus.
- propionyl L-carnitine is preferred.
- “useful drugs” it is intended any drug useful for treating E.D.
- a further object of the present invention are pharmaceutical compositions comprising as active ingredient an alkanoyl L-carnitine in combination with one or more of said useful drugs, and at least an excipient and/or diluent pharmaceutically acceptable.
- Non-limiting examples of said useful drugs are sildenafil, apomorphine, prostaglandin E1, pentolamine or papaverine.
- a further object of the present invention is the use of an alkanoyl L-carnitine, or a pharmaceutical acceptable salt thereof, in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction.
- a further object of the present invention is the use of an alkanoyl L-carnitine in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction in patients affected by diabetes mellitus.
- a further object of the present invention is the use of an alkanoyl L-carnitine in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction, wherein said patients do not respond to the treatment with said useful drugs.
- a further object of the present invention is the use of an alkanoyl L-carnitine in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction in patients suffering from diabetes mellitus, wherein said patients do not respond to the treatment with said useful drugs.
- propionyl L-carnitine is preferred.
- alkanoyl L-carnitines and the useful drugs above mentioned can be prepared for a simultaneous, sequential or separated administration.
- the daily dose will depend, according to the judgement of the primary care physician, on the patient's weight, age and general condition, it is generally advisable to administer 0.5 to 4 g/die of alkanoyl L-carnitine or a stoichiometrically equivalent amount of one of its pharmacologically acceptable salts. 1-2 g/die are preferred.
- the of administration regimen of the two active ingredients will depend on the primary care physician's judgement, the patient's weight, age and general conditions, it is generally advisable to administer the alkanoyl L-carnitine daily and said combined useful drug twice weekly.
Abstract
The use of an alkanoyl L-carnitine for preparing a medicament for treating the erectile dysfunction is described.
Description
- The present invention relates to the use of an alkanoyl L-carnitine for the treatment of the erectile dysfunction.
- The erectile dysfunction (E.D.) is a syndrome characterised by a persistent inability to obtain or maintain a penis erection, for a time sufficient for a sexual intercourse.
- The current knowledge indicates that the relaxation of the smooth musculature of the corpus cavernosum which is necessary for the erection is due to a non adrenergic, non cholinergic mechanism, mediated by nitric oxide (ON), in which prostaglandin (PG) is involved (Medicina Pratica, 2000; 12-16).
- The relaxation of the smooth musculature of the corpus cavernosum and the penis erection depend on a fine equilibrium between the effects of vasoconstrictor and vasodilator factors.
- To bring the penis to erection, it is necessary that the relaxation of the smooth musculature of the corpus cavernosum exceeds a determined minimum level [Cardiovasc. Drugs Ther. 1991; 5 Supp (1): 77-83].
- It has been shown that the basic defect in patients suffering from (E.D.) may be, independently from the aetiology, an imbalance between the contraction and the capacity of the relaxation of the corpus cavernosum smooth musculature.
- If the base tone of the corpus cavernosum smooth musculature is too high, the maximum relaxation level may not be sufficient to permit an haematic flux sufficient for a normal erection.
- If a minimum level of relaxation of the smooth musculature is not reached or maintained, the resistance to the venous runoff due to the intracavernous haematic pressure and the consequent compression of the veins will be insufficient for a normal erection.
- In patients suffering from diabetes mellitus, the onset of an autonomic neuropathy is the main cause of the loss of the cholinergic activation during the erectile process, with consequent reduction of the ON and prostaglandin release, furthermore, a reduced function of the noradrenergic nervous ending could arise leading to a decrease of the vasodilator neurotransmitter levels such as the Vasoactive Intestinal Peptides (VIP).
- In fact, it is recognised the role of the autonomic activation linked to a sexual excitation which leads to the release of nitric oxide (ON) and prostaglandin (PGI2) exerted by the endothelium of the tissue cavernous of the penis as response to a cholinergic activation (Fed. Proc. 1982; 41, 2858-62).
- ON and PG activate a second messenger the cGMP (guanosin mono phosphate cyclic) which mediates a relaxant effect of the smooth muscle in the trabecules of the cavernous tissue, thus permitting the haematic flux to fill the sinuses and lead to the penis tumefaction.
- The exact contrary occurs under the effect of the adrenalin activity through the (α1) adrenergic nervous endings
- In particular in the study of the E.D. in diabetes mellitus it has been demonstrated that an endothelial impairment is responsible for the decreased “relaxation” of the trabecular smooth musculature of the corpus cavernosum which, in normal conditions, is mediated by the ON and that is the base of the organic impotence.
- It has been demonstrated that about 90% of patients suffering from Type II diabetes mellitus show an E.D. [Diabetologia 2001, Oct. 44, (10), 1296-1301].
- Previous uses of alkanoyl L-carnitines are already known.
- In U.S. Pat. No. 5,811,457 the use of propionyl L-carnitine for treating chronic obliterant arteriopathy is described.
- In U.S. Pat. No. 6,063,820 the use of alkanoyl L-carnitines for preparing a therapeutical nutritional composition for individuals suffering from diabetes mellitus is described.
- In WO99/06039 the use of L-carnitine or an alkanoyl L-carnitine in combination with long chain aliphatic alcohols useful for the prevention and treatment of pathologies due to an altered lipid metabolism and an higher platelet aggregation is described.
- Further patents and publications describe the use of alkanoyl L-carnitines for therapeutical scopes, but none of these publications describe or suggest the use of an alkanoyl L-carnitine, alone or in combination with other compounds, for treating the erectile dysfunction.
- Compounds useful for treating erectile dysfunction are already known. For example, in Int. Urol. Nephrol 2001; 32 (3), 403-7 the use of sildenafil for treating erectile dysfunction is described.
- In Diabetologia 2001, Oct. 44, (10), 1296-1301 the use of sildenafil for treating erectile dysfunction in patients suffering from Type II diabetes mellitus is described.
- In Salute Europa of Jun. 11, 2001 have been presented the first data (published in British Journal of Urology) relating to an Italian and European clinical trial using sub-lingual apomorphine, for treating erectile dysfunction.
- Further publications describe the use of compounds useful for treating erectile dysfunction, but none of them describe or suggest the use of these compounds in combination with an alkanoyl L-carnitine, for treating said pathology.
- Known compounds useful for treating the E.D. are not free of disadvantage.
- For example, in Eur. Urol. 2001 Aug; 40 (2): 176-80 it is reported that not all patients respond to the treatment with sildenafil.
- In Diabetologia 2001 Oct; 44 (10): 1296-301 it is reported that not all diabetic patients respond to the treatment with sildenafil.
- In Salute Europa of Jun. 11, 2001, it is reported that not all patients affected by E.D. treated with apomorphine respond to this treatment.
- In Hosp. Med. 1998 Oct; 59 (10): 777 and in Br. J. Urol. 1996 Oct; 78(4): 628-31 it is reported that the administration of prostaglandin E1 and of papaverine, respectively, is carried out intracavernously, and it is well known how troublesome is this way of administration.
- The need to have new drugs, useful for the treatment of the erectile dysfunction, which do not present the disadvantages of the known drugs, is therefore very much felt.
- It has now been found that the alkanoyl L-carnitines wherein the alkanoyl group, linear or branched, has 2-6 carbon atoms, or a pharmaceutically acceptable salt thereof are useful agents for treating the erectile dysfunction.
- 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, magnesium citrate, acid phosphate, fumarate and acid fumarate, magnesium fumarate, lactate, maleate, acid maleate, mucate, acid oxalate, pamoate, acid pamoate, acid sulphate, glucose phosphate, tartrate, acid tartrate, magnesium tartrate, 2-amino ethansulphonate, magnesium 2-amino etansulphonate, Choline tartrate and trichloroacetate.
- Non-limiting examples of alkanoyl L-carnitines are acetyl, propionyl, butyryl, isobutyryl, valeryl and isovalery L-carnitine.
- Preliminary experimental data related to the use of an alkanoyl L-carnitine, propionyl L-carnitine, have shown that this compound is useful for treating the erectile dysfunction, in diabetics or in non-diabetics patients, not previously treated with sildenafil.
- It is therefore an object of the present invention the use of an alkanoyl L-carnitine, or a pharmaceutical acceptable salt thereof, for preparing a medicine for the treatment of erectile dysfunction.
- A further object of the present invention is the use of an alkanoyl L-carnitine for preparing a medicine for the treatment of erectile dysfunction in patients suffering from diabetes mellitus.
- In both cases propionyl L-carnitine is preferred.
- In the medical field it is known that specific drugs for treat E.D. which show not to be active (when used alone) on a particular group of patients in need of such drugs, they become active if combined between them (Br. J. Urol 1996 May; 77(5): 736-9).
- The following experimental data show that the compounds according to the present invention are suitable to be used in combination with further drugs useful for treating E.D.
- According to the present invention by “useful drugs” it is intended any drug useful for treating E.D.
- It is therefore an object of the present invention the combination of an alkanoyl L-carnitine with one or more drugs useful for treating erectile dysfunction.
- A further object of the present invention are pharmaceutical compositions comprising as active ingredient an alkanoyl L-carnitine in combination with one or more of said useful drugs, and at least an excipient and/or diluent pharmaceutically acceptable.
- Non-limiting examples of said useful drugs are sildenafil, apomorphine, prostaglandin E1, pentolamine or papaverine.
- A further object of the present invention is the use of an alkanoyl L-carnitine, or a pharmaceutical acceptable salt thereof, in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction.
- A further object of the present invention is the use of an alkanoyl L-carnitine in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction in patients affected by diabetes mellitus.
- A further object of the present invention is the use of an alkanoyl L-carnitine in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction, wherein said patients do not respond to the treatment with said useful drugs.
- A further object of the present invention is the use of an alkanoyl L-carnitine in combination with one or more of said useful drugs, for preparing a medicine for the treatment of erectile dysfunction in patients suffering from diabetes mellitus, wherein said patients do not respond to the treatment with said useful drugs.
- Also in these further aspects of the present invention propionyl L-carnitine is preferred.
- The alkanoyl L-carnitines and the useful drugs above mentioned can be prepared for a simultaneous, sequential or separated administration.
- Though the daily dose will depend, according to the judgement of the primary care physician, on the patient's weight, age and general condition, it is generally advisable to administer 0.5 to 4 g/die of alkanoyl L-carnitine or a stoichiometrically equivalent amount of one of its pharmacologically acceptable salts. 1-2 g/die are preferred.
- Larger doses can be administered in view of the alkanoyl L-carnitines substantial lack of toxicity.
- Also the of administration regimen of the two active ingredients will depend on the primary care physician's judgement, the patient's weight, age and general conditions, it is generally advisable to administer the alkanoyl L-carnitine daily and said combined useful drug twice weekly.
- The following examples illustrate the invention.
- In this trial, 24 diabetics patients suffering from E.D. which were not responder to the treatment with sildenafil alone were enrolled.
- 2 g/day (1 g tablet twice a day) of propionyl L-carnitine were orally administered daily to the patients, and 50 mg sildenafil orally, twice a week.
- After 3 and 6 months from the beginning of the treatment controls were made using the dynamic colour Doppler ultrasonography, these controls showed an improvement of the arterial flux which was coincident with a satisfactory clinical response evaluated with IIEF (Urology 1997 Jun;49(6):822-30) in 60% of treated patients.
- In this trial, 30 diabetics patients suffering from E.D. which were not responder to the treatment with sildenafil alone were enrolled.
- 2 g/day (1 g tablet twice a day) of propionyl L-carnitine, were orally administered daily to the patients, and 50 mg sildenafil orally, twice a week.
- After 3 and 6 months from the beginning of the treatment controls were made using the dynamic colour Doppler ultrasonography, these controls showed an improvement of the arterial flux which was coincident with a satisfactory clinical response evaluated with IIEF in 60% of treated patients.
Claims (12)
1. Use of an propionyl L-carnitine or a pharmaceutically acceptable salt thereof, for preparing a medicament for the treatment of erectile dysfunction.
2. Use according to claim 1 , for the treatment of erectile dysfunction in patients affected by diabetes mellitus.
3. Use according to claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of chloride, bromide, orotate, acid aspartate, acid citrate, magnesium citrate, acid phosphate, fumarate and acid fumarate, magnesium fumarate, lactate, maleate, acid maleate, mucate, acid oxalate, pamoate, acid pamoate, acid sulphate, glucose phosphate, tartrate, acid tartrate, magnesium tartrate, 2-amino ethansulphonate, magnesium 2-amino etansulphonate, choline tartrate and trichloroacetate.
4. Combination of an alkanoyl L-carnitine wherein the alkanoyl group, linear or branched, has 2-6 carbon atoms, or a pharmaceutically acceptable salt thereof, with one or more useful drugs for the treatment of erectile dysfunction.
5. Combination according to claim 4 , wherein said useful drugs are selected from the group consisting of sildenafil, apomorfine prostaglandine E1, pentolamine and papaverine.
6. Pharmaceutical compositions comprising as active ingredient the combination of claim 4 and at least an excipient and/or diluent pharmaceutically acceptable.
7. Use of the combination of claim 4 , for preparing a medicament for the treatment of erectile dysfunction.
8. Use of the combination of claim 4 , for preparing a medicament for the treatment of erectile dysfunction in patients affected by diabetes mellitus.
9. Use of the combination of claim 4 , for preparing a medicament for the treatment of erectile dysfunction in patients that do not respond to the treatment with said useful drugs.
10. Use of the combination of claim 4 , for preparing a medicament for the treatment of erectile dysfunction in diabetic patients that do not respond to the treatment with said useful drugs.
11. Use according to claim 7 in which said useful drugs are selected from the group consisting of sildenafil, apomorfine prostaglandine E1, pentolamine and papaverine.
12. Use according to claim 1 wherein the alkanoyl L-carnitine is propionyl L-carnitine.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/649,796 US20070117762A1 (en) | 2001-12-04 | 2007-01-05 | Use of an alkanoyl L-carnitine for the treatment of the erectile dysfunction |
US13/280,749 US8343979B2 (en) | 2001-12-04 | 2011-10-25 | Use of alkanoyl L-carnitine for the treatment of erectile dysfunction |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITRM2001A000708 | 2001-12-04 | ||
IT2001RM000708A ITRM20010708A1 (en) | 2001-12-04 | 2001-12-04 | USE OF AN ALCANOIL L-CARNITINE FOR THE TREATMENT OF ERECTILE DYSFUNCTION. |
PCT/IT2002/000758 WO2003047563A1 (en) | 2001-12-04 | 2002-12-04 | Use of alkanoyl l-carnitine for the treatment of erectile dysfunction |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IT2002/000758 A-371-Of-International WO2003047563A1 (en) | 2001-12-04 | 2002-12-04 | Use of alkanoyl l-carnitine for the treatment of erectile dysfunction |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/649,796 Division US20070117762A1 (en) | 2001-12-04 | 2007-01-05 | Use of an alkanoyl L-carnitine for the treatment of the erectile dysfunction |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050080018A1 true US20050080018A1 (en) | 2005-04-14 |
Family
ID=11455907
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/497,498 Abandoned US20050080018A1 (en) | 2001-12-04 | 2002-12-04 | Use of alkanoyl l-carnitine for the treatment of erectile dysfunction |
US11/649,796 Abandoned US20070117762A1 (en) | 2001-12-04 | 2007-01-05 | Use of an alkanoyl L-carnitine for the treatment of the erectile dysfunction |
US13/280,749 Expired - Fee Related US8343979B2 (en) | 2001-12-04 | 2011-10-25 | Use of alkanoyl L-carnitine for the treatment of erectile dysfunction |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/649,796 Abandoned US20070117762A1 (en) | 2001-12-04 | 2007-01-05 | Use of an alkanoyl L-carnitine for the treatment of the erectile dysfunction |
US13/280,749 Expired - Fee Related US8343979B2 (en) | 2001-12-04 | 2011-10-25 | Use of alkanoyl L-carnitine for the treatment of erectile dysfunction |
Country Status (16)
Country | Link |
---|---|
US (3) | US20050080018A1 (en) |
EP (1) | EP1450782B9 (en) |
JP (1) | JP4370169B2 (en) |
KR (1) | KR100907938B1 (en) |
AT (1) | ATE309800T1 (en) |
AU (1) | AU2002365847A1 (en) |
CA (1) | CA2465471C (en) |
DE (1) | DE60207442T2 (en) |
DK (1) | DK1450782T3 (en) |
ES (1) | ES2250749T3 (en) |
HU (1) | HU229214B1 (en) |
IT (1) | ITRM20010708A1 (en) |
MX (1) | MXPA04005269A (en) |
PL (1) | PL211211B1 (en) |
SI (1) | SI1450782T1 (en) |
WO (1) | WO2003047563A1 (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITRM20040561A1 (en) * | 2004-11-11 | 2005-02-11 | Sigma Tau Ind Farmaceuti | USE OF ACETYL L-CARNITINE IN COMBINATION WITH PROPIONYL L-CARNITINE AND SILDENAFIL FOR THE TREATMENT OF ERECTILE DYSFUNCTION. |
IT1397867B1 (en) * | 2010-02-03 | 2013-02-04 | Brotzu | LIPOSOMAS CONTAINING PROSTAGLANDINE E1 (PGE1), FORMULATIONS THAT CONTAIN THEM AND USE THEM |
US11813275B2 (en) | 2013-04-05 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
HUE041709T2 (en) | 2013-04-05 | 2019-05-28 | Boehringer Ingelheim Int | Therapeutic uses of empagliflozin |
US20140303097A1 (en) | 2013-04-05 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
CN113181161A (en) | 2013-04-18 | 2021-07-30 | 勃林格殷格翰国际有限公司 | Pharmaceutical compositions, methods of treatment and uses thereof |
WO2016174155A1 (en) * | 2015-04-30 | 2016-11-03 | Boehringer Ingelheim International Gmbh | Methods and pharmaceutical compositions comprising a sglt2 inhibitor for treating or improving erectile dysfunction |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040087515A1 (en) * | 1999-04-12 | 2004-05-06 | Butler Terri L. | Compositions methods for improving cardio vascular function |
Family Cites Families (7)
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 |
DE69605531T2 (en) * | 1996-03-04 | 2000-05-31 | Sigma Tau Ind Farmaceuti | Carnitine derivative as a medicine for the treatment of arteriosclerosis obliterans |
IT1290801B1 (en) * | 1996-07-05 | 1998-12-11 | Mendes Srl | USE OF ACETYL L-CARNITINE, ISOVALERYL L-CARNITINE, PROPIONYL L-CARNITINE OR THEIR PHARMACOLOGICALLY ACCEPTABLE SALTS |
US6133281A (en) * | 1996-10-24 | 2000-10-17 | Harbor-Ucla Research And Education Institute | NMDA receptor blockers in the therapy of urogenital disease |
IT1293539B1 (en) * | 1997-07-16 | 1999-03-01 | Sigma Tau Ind Farmaceuti | NUTRITIONAL COMPOSITION FOR SUBJECTS IN A STATE OF DEBILITATION CAUSED BY STRESS |
US6241471B1 (en) * | 1999-08-26 | 2001-06-05 | General Electric Co. | Turbine bucket tip shroud reinforcement |
IT1306722B1 (en) * | 1999-10-08 | 2001-10-02 | Sigma Tau Healthscience Spa | COMPOSITION FOR THE PREVENTION AND / OR TREATMENT OF CIRCULATORY DYSFUNCTIONS, INCLUDING L-CARNITINE DERIVATIVES AND EXTRACTS OF |
-
2001
- 2001-12-04 IT IT2001RM000708A patent/ITRM20010708A1/en unknown
-
2002
- 2002-12-04 HU HU0402062A patent/HU229214B1/en not_active IP Right Cessation
- 2002-12-04 ES ES02804338T patent/ES2250749T3/en not_active Expired - Lifetime
- 2002-12-04 KR KR1020047007882A patent/KR100907938B1/en active IP Right Grant
- 2002-12-04 DK DK02804338T patent/DK1450782T3/en active
- 2002-12-04 AT AT02804338T patent/ATE309800T1/en active
- 2002-12-04 MX MXPA04005269A patent/MXPA04005269A/en active IP Right Grant
- 2002-12-04 DE DE60207442T patent/DE60207442T2/en not_active Expired - Lifetime
- 2002-12-04 CA CA2465471A patent/CA2465471C/en not_active Expired - Fee Related
- 2002-12-04 JP JP2003548819A patent/JP4370169B2/en not_active Expired - Fee Related
- 2002-12-04 US US10/497,498 patent/US20050080018A1/en not_active Abandoned
- 2002-12-04 SI SI200230234T patent/SI1450782T1/en unknown
- 2002-12-04 EP EP02804338A patent/EP1450782B9/en not_active Expired - Lifetime
- 2002-12-04 WO PCT/IT2002/000758 patent/WO2003047563A1/en active IP Right Grant
- 2002-12-04 PL PL371131A patent/PL211211B1/en unknown
- 2002-12-04 AU AU2002365847A patent/AU2002365847A1/en not_active Abandoned
-
2007
- 2007-01-05 US US11/649,796 patent/US20070117762A1/en not_active Abandoned
-
2011
- 2011-10-25 US US13/280,749 patent/US8343979B2/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040087515A1 (en) * | 1999-04-12 | 2004-05-06 | Butler Terri L. | Compositions methods for improving cardio vascular function |
Also Published As
Publication number | Publication date |
---|---|
SI1450782T1 (en) | 2006-02-28 |
HU229214B1 (en) | 2013-09-30 |
PL211211B1 (en) | 2012-04-30 |
ITRM20010708A1 (en) | 2003-06-04 |
US8343979B2 (en) | 2013-01-01 |
DK1450782T3 (en) | 2006-02-20 |
DE60207442T2 (en) | 2006-07-27 |
US20120041005A1 (en) | 2012-02-16 |
US20070117762A1 (en) | 2007-05-24 |
ATE309800T1 (en) | 2005-12-15 |
EP1450782B1 (en) | 2005-11-16 |
CA2465471A1 (en) | 2003-06-12 |
MXPA04005269A (en) | 2004-10-11 |
ITRM20010708A0 (en) | 2001-12-04 |
EP1450782A1 (en) | 2004-09-01 |
PL371131A1 (en) | 2005-06-13 |
KR20050044594A (en) | 2005-05-12 |
EP1450782B9 (en) | 2006-05-17 |
AU2002365847A1 (en) | 2003-06-17 |
JP2005511655A (en) | 2005-04-28 |
HUP0402062A3 (en) | 2012-09-28 |
WO2003047563A1 (en) | 2003-06-12 |
CA2465471C (en) | 2010-10-19 |
ES2250749T3 (en) | 2006-04-16 |
KR100907938B1 (en) | 2009-07-16 |
HUP0402062A2 (en) | 2005-02-28 |
JP4370169B2 (en) | 2009-11-25 |
DE60207442D1 (en) | 2005-12-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8343979B2 (en) | Use of alkanoyl L-carnitine for the treatment of erectile dysfunction | |
US4507323A (en) | Treatment of psychosexual dysfunctions | |
US20220151975A1 (en) | Low-Dose Doxepin For Treatment Of Sleep Disorders In Elderly Patients | |
JP2002505681A (en) | Compositions for modulating mood disorders in healthy individuals | |
US5426120A (en) | Pharmaceutical composition containing γ-hydroxybutyric acid or its lactone in the treatment of drug dependence and nutritional disorders | |
CA1323572C (en) | Doxazosin as an anti-atherosclerosis agent | |
TW589184B (en) | Pharmaceutical composition for preventing or reversing diabetic cardiomyopathy | |
EP1569635B1 (en) | Use of carnitines for the prevention and/or treatment of disorders caused by the andropause | |
TW201127387A (en) | Therapeutic or preventive agents for diabetes | |
KR0137927B1 (en) | Hydroxylated metabolites and derivatives of doxazosin as anti-atherosclerosis agents | |
US20040142879A1 (en) | Use of the acetyl l-carnitine in association with the biotin for the treatment of patients with type 2 insulin-resistant diabetes mellitus | |
US7776913B2 (en) | Carnitines for treating or preventing disorders caused by andropause | |
US7456291B2 (en) | Use of a vitamin combination for the treatment of primary headaches | |
US7485642B2 (en) | Method for treating septic shock | |
Nies et al. | Recent concepts in the clinical pharmacology of anithypertensive drugs | |
US8394854B2 (en) | Use of L-carnitine for the treatment of cardiovascular diseases | |
Mantero et al. | Effect of atenolol and metoprolol on the anticoagulant activity of acenocoumarin. | |
WO2023156275A1 (en) | Pharmaceutical composition and medicament comprising l-tryptophan, l-5-hydroxytryptophan and a peripheral degradation inhibitor | |
AU2001276672A1 (en) | Use of the combination of nicotinic acid or derivatives with riboflavin in the manufacture of a medicament for the treatment of primary headaches |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: SIGMA-TAU INDUSTRIE FARMACEUTICHE RIUNITE S.P.A., Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KOVERECH, ALEARDO;LENZI, ANDREA;REEL/FRAME:015951/0724 Effective date: 20040430 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |