JP4663987B2 - 精子減少・無力・奇形症の治療のためのl−カルニチン、アセチルl−カルニチンおよびプロピオニルl−カルニチンの併用 - Google Patents
精子減少・無力・奇形症の治療のためのl−カルニチン、アセチルl−カルニチンおよびプロピオニルl−カルニチンの併用 Download PDFInfo
- Publication number
- JP4663987B2 JP4663987B2 JP2003581766A JP2003581766A JP4663987B2 JP 4663987 B2 JP4663987 B2 JP 4663987B2 JP 2003581766 A JP2003581766 A JP 2003581766A JP 2003581766 A JP2003581766 A JP 2003581766A JP 4663987 B2 JP4663987 B2 JP 4663987B2
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- Prior art keywords
- carnitine
- salt
- acid
- acetyl
- propionyl
- 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.)
- Expired - Lifetime
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- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 title claims abstract description 50
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 title claims abstract description 36
- 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 title claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 206010067162 Asthenospermia Diseases 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 16
- 206010003549 asthenia Diseases 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 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
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 229940009098 aspartate Drugs 0.000 claims description 4
- 239000002552 dosage form Substances 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
- -1 mucate Chemical compound 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
- XOAAWQZATWQOTB-UHFFFAOYSA-M 2-aminoethanesulfonate Chemical compound NCCS([O-])(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-M 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
- 208000007799 Asthenozoospermia Diseases 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 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
- YZURQOBSFRVSEB-UHFFFAOYSA-L magnesium;2-aminoethanesulfonate Chemical compound [Mg+2].NCCS([O-])(=O)=O.NCCS([O-])(=O)=O YZURQOBSFRVSEB-UHFFFAOYSA-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
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 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
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims 1
- 229960005336 magnesium citrate Drugs 0.000 claims 1
- 235000002538 magnesium citrate Nutrition 0.000 claims 1
- 239000004337 magnesium citrate Substances 0.000 claims 1
- 230000036244 malformation Effects 0.000 claims 1
- 206010003883 azoospermia Diseases 0.000 abstract description 4
- 206010050208 Teratospermia Diseases 0.000 abstract description 2
- 208000002312 Teratozoospermia Diseases 0.000 abstract description 2
- 208000008634 oligospermia Diseases 0.000 abstract 1
- 230000036616 oligospermia Effects 0.000 abstract 1
- 231100000528 oligospermia Toxicity 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 230000019100 sperm motility Effects 0.000 description 10
- 229960004203 carnitine Drugs 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 230000004899 motility Effects 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000000414 obstructive effect Effects 0.000 description 4
- 230000002381 testicular Effects 0.000 description 4
- 201000004822 varicocele Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 201000010063 epididymitis Diseases 0.000 description 3
- 208000021267 infertility disease Diseases 0.000 description 3
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- 230000035800 maturation Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 210000000582 semen Anatomy 0.000 description 3
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- 210000001550 testis Anatomy 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
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- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000002710 gonadal effect Effects 0.000 description 2
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- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 206010053164 Alcohol withdrawal syndrome Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010057362 Underdose Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
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- 230000003078 antioxidant effect Effects 0.000 description 1
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- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 238000002648 combination therapy Methods 0.000 description 1
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- 230000003247 decreasing effect Effects 0.000 description 1
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- 229960005309 estradiol Drugs 0.000 description 1
- 230000013439 flagellum movement Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 229940094892 gonadotropins Drugs 0.000 description 1
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- 229940052665 nadh Drugs 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 201000002663 oligoasthenoteratozoospermia Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
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- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
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- 235000019165 vitamin E Nutrition 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Reproductive Health (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polymers & Plastics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Food Science & Technology (AREA)
- Endocrinology (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Claims (10)
- 分子内塩または医薬上許容される塩の形態の、L−カルニチン、アセチルL−カルニチンおよびプロピオニルL−カルニチンを含む、精子減少・無力・奇形症の治療用医薬組成物。
- 精子減少症の治療用の請求項1の医薬組成物。
- 精子無力症の治療用の請求項1の医薬組成物。
- 精子奇形症の治療用の請求項1の医薬組成物。
- 医薬上許容される塩が、塩化物、臭化物、オロチン酸塩、アスパラギン酸塩、酸アスパラギン酸塩、クエン酸塩、酸クエン酸塩、クエン酸マグネシウム塩、リン酸塩、酸リン酸塩、フマル酸塩、酸フマル酸塩、フマル酸マグネシウム塩、グリセロリン酸塩、乳酸塩、マレイン酸塩および酸マレイン酸塩、ムケート、シュウ酸塩、酸シュウ酸塩、パモ酸塩、酸パモ酸塩、硫酸塩、酸硫酸塩、グルコースリン酸塩、酒石酸塩、酸酒石酸塩、酒石酸マグネシウム塩、2−アミノエタンスルホン酸塩、2−アミノエタンスルホン酸マグネシウム塩、メタンスルホン酸塩、コリン酒石酸塩、トリクロロ酢酸塩およびトリフルオロ酢酸塩からなる群から選択される請求項1の医薬組成物。
- 分子内塩または医薬上許容される塩の形態の、L−カルニチン、アセチルL−カルニチンおよびプロピオニルL−カルニチンが、混合物として存在しているか、または別々に包装されている、請求項1から5のいずれかの医薬組成物。
- 分子内塩または医薬上許容される塩の形態の、L−カルニチンおよびアセチルL−カルニチンおよびプロピオニルL−カルニチンのモル比が2.48:0.098:0.092〜0.186:0.98:0.92の範囲である請求項6の医薬組成物。
- 分子内塩または医薬上許容される塩の形態の、L−カルニチンおよびアセチルL−カルニチンおよびプロピオニルL−カルニチンのモル比が2.48:0.49:0.46〜0.62:0.49:0.46の範囲である請求項6の医薬組成物。
- 単位用量形態において、L−カルニチン分子内塩を4.0 g〜0.30 gの範囲の量、アセチルL−カルニチン分子内塩を0.20〜2.0 gの範囲の量、そしてプロピオニルL−カルニチン分子内塩を0.20 g〜2.0 gの範囲の量、あるいは等モル量のそれらの医薬上許容される塩を含む、請求項7の医薬組成物。
- 単位用量形態が2 gのL−カルニチン分子内塩、1 gのアセチルL−カルニチン分子内塩および0.5 gのプロピオニルL−カルニチン分子内塩または等モル量のそれらの医薬上許容される塩を含む、請求項9の医薬組成物。
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IT2002RM000194A ITRM20020194A1 (it) | 2002-04-09 | 2002-04-09 | Composizione utile per aumentare la concentrazione e la motilita' degli spermatozoi e migliorarne la morfologia nell'uomo. |
PCT/IT2003/000214 WO2003084526A1 (en) | 2002-04-09 | 2003-04-08 | Combined use of l-carnitine, acetyl l-carnitine and propionyl l-carnitine for the treatment of oligoasthenoteratospermia |
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US7776913B2 (en) | 2002-12-13 | 2010-08-17 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Carnitines for treating or preventing disorders caused by andropause |
EP2429299B1 (en) * | 2009-05-01 | 2016-06-01 | Celloxess Llc | Treating male infertility secondary to sperm oxidative stress |
US20110015154A1 (en) * | 2009-07-20 | 2011-01-20 | Kellermann Gottfried H | Supporting acetylcholine function |
US20110098265A1 (en) * | 2009-10-28 | 2011-04-28 | Neuroscience, Inc. | Methods for reducing cravings and impulses associated with addictive and compulsive behaviors |
CN108041588A (zh) * | 2017-12-08 | 2018-05-18 | 冯纪敏 | 一种含有海藻糖的组合物及其应用 |
CN109999042B (zh) * | 2019-05-16 | 2021-05-18 | 北京华睿鼎信科技有限公司 | 包含脱氢表雄酮或其硫酸酯、左卡尼汀、乙酰左卡尼汀或它们的可药用盐的组合物及其应用 |
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ITRM20010029A1 (it) * | 2001-01-23 | 2002-07-23 | Aldo Fassi | Sali metallici di carnitine utili come integratori dietetici/nutrizionali o come farmaci, composizioni che li contengono e procedimenti per |
ITRM20020055A1 (it) | 2002-02-04 | 2003-08-04 | Aldo Fassi | Sali metallici di carnitine, integratori dietetici/nutritivi che li contengono e kit dietetici per contrastare disturbi sessuali in soggetti |
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ITRM20020194A1 (it) | 2003-10-09 |
HK1078460A1 (en) | 2006-03-17 |
WO2003084526A1 (en) | 2003-10-16 |
US8415392B2 (en) | 2013-04-09 |
EP1492521B1 (en) | 2010-08-11 |
EP1492521A1 (en) | 2005-01-05 |
ATE476974T1 (de) | 2010-08-15 |
BR0309055A (pt) | 2005-02-22 |
DE60333742D1 (de) | 2010-09-23 |
CA2478674A1 (en) | 2003-10-16 |
US20090012169A1 (en) | 2009-01-08 |
CN1330301C (zh) | 2007-08-08 |
ES2350338T3 (es) | 2011-01-21 |
AU2003224443B2 (en) | 2008-09-11 |
CN1638754A (zh) | 2005-07-13 |
ITRM20020194A0 (it) | 2002-04-09 |
JP2006505499A (ja) | 2006-02-16 |
PL372924A1 (en) | 2005-08-08 |
US20050107470A1 (en) | 2005-05-19 |
CY1111273T1 (el) | 2015-08-05 |
AU2003224443A1 (en) | 2003-10-20 |
MXPA04009763A (es) | 2004-12-13 |
SI1492521T1 (sl) | 2010-12-31 |
CA2478674C (en) | 2010-10-19 |
DK1492521T3 (da) | 2010-11-22 |
KR20040098005A (ko) | 2004-11-18 |
PL214859B1 (pl) | 2013-09-30 |
PT1492521E (pt) | 2010-11-11 |
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