ITRM20010030A1 - CARNITINE SALTS USEFUL AS DIET / NUTRITIONAL SUPPLEMENTS OR AS DRUGS, COMPOSITIONS CONTAINING THEM AND PROCEDURES FOR THEIR PR - Google Patents
CARNITINE SALTS USEFUL AS DIET / NUTRITIONAL SUPPLEMENTS OR AS DRUGS, COMPOSITIONS CONTAINING THEM AND PROCEDURES FOR THEIR PR Download PDFInfo
- Publication number
- ITRM20010030A1 ITRM20010030A1 IT2001RM000030A ITRM20010030A ITRM20010030A1 IT RM20010030 A1 ITRM20010030 A1 IT RM20010030A1 IT 2001RM000030 A IT2001RM000030 A IT 2001RM000030A IT RM20010030 A ITRM20010030 A IT RM20010030A IT RM20010030 A1 ITRM20010030 A1 IT RM20010030A1
- Authority
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- Italy
- Prior art keywords
- carnitine
- galactarate
- magnesium
- calcium
- cooy
- Prior art date
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- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical class C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 title claims description 39
- 239000000203 mixture Substances 0.000 title claims description 18
- 238000000034 method Methods 0.000 title description 10
- 235000015872 dietary supplement Nutrition 0.000 title description 7
- 239000003814 drug Substances 0.000 title description 5
- 229940079593 drug Drugs 0.000 title description 4
- 235000005911 diet Nutrition 0.000 title description 2
- 230000037213 diet Effects 0.000 title 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 claims description 61
- 239000011777 magnesium Substances 0.000 claims description 36
- 239000011575 calcium Substances 0.000 claims description 27
- 229910052749 magnesium Inorganic materials 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 23
- 229910052791 calcium Inorganic materials 0.000 claims description 17
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 15
- 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 claims description 14
- 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 13
- IGQBPDJNUXPEMT-SNVBAGLBSA-N isovaleryl-L-carnitine Chemical compound CC(C)CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C IGQBPDJNUXPEMT-SNVBAGLBSA-N 0.000 claims description 10
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 229960004203 carnitine Drugs 0.000 claims description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
- UGZVNIRNPPEDHM-UEXKISHTSA-L calcium;(2s,3r,4s,5r)-2,3,4,5-tetrahydroxyhexanedioate Chemical compound [Ca+2].[O-]C(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C([O-])=O UGZVNIRNPPEDHM-UEXKISHTSA-L 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000000144 pharmacologic effect Effects 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 3
- 235000016709 nutrition Nutrition 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000007910 chewable tablet Substances 0.000 claims description 2
- 239000002270 dispersing agent Substances 0.000 claims description 2
- 239000008298 dragée Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 239000003086 colorant Substances 0.000 claims 1
- 238000004040 coloring Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 229940091250 magnesium supplement Drugs 0.000 description 14
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 11
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 9
- 239000000347 magnesium hydroxide Substances 0.000 description 9
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 4
- 239000000920 calcium hydroxide Substances 0.000 description 4
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 159000000003 magnesium salts Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- -1 alkanoyl L-carnitine Chemical compound 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- VSSQQROXKQQXDN-UNKACTGFSA-L magnesium;(e)-but-2-enedioate;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound [Mg+2].[O-]C(=O)\C=C\C([O-])=O.C[N+](C)(C)C[C@H](O)CC([O-])=O VSSQQROXKQQXDN-UNKACTGFSA-L 0.000 description 3
- ZQJMKXKBQGAVCW-QYCVXMPOSA-L magnesium;2,3-dihydroxybutanedioate;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound [Mg+2].[O-]C(=O)C(O)C(O)C([O-])=O.C[N+](C)(C)C[C@H](O)CC([O-])=O ZQJMKXKBQGAVCW-QYCVXMPOSA-L 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 239000001358 L(+)-tartaric acid Substances 0.000 description 2
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 2
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 235000011837 pasties Nutrition 0.000 description 2
- VIOYPGDQEDDCJB-UUCJDPIKSA-H trimagnesium;2-hydroxypropane-1,2,3-tricarboxylate;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound [Mg+2].[Mg+2].[Mg+2].C[N+](C)(C)C[C@H](O)CC([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O VIOYPGDQEDDCJB-UUCJDPIKSA-H 0.000 description 2
- RZALONVQKUWRRY-XOJLQXRJSA-N (2r,3r)-2,3-dihydroxybutanedioate;hydron;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O RZALONVQKUWRRY-XOJLQXRJSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- BHUHZIVZTZACBR-UEXKISHTSA-L magnesium;(2s,3r,4s,5r)-2,3,4,5-tetrahydroxyhexanedioate Chemical compound [Mg+2].[O-]C(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C([O-])=O BHUHZIVZTZACBR-UEXKISHTSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000003236 psychic effect Effects 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000002700 urine Anatomy 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
- A61K31/185—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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A23L33/16—Inorganic salts, minerals or trace elements
- A23L33/165—Complexes or chelates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Descrizione dell'invenzione avente per titolo: Description of the invention entitled:
"Sali di carnitine utili come integratori dietetici/nutrizionali o come farmaci, composizioni che li contengono e procedimenti per la loro preparazione "Carnitine salts useful as dietary / nutritional supplements or as drugs, compositions containing them and processes for their preparation
La presente invenzione riguarda sali alcalino-terrosi di carnitine utili come integratori dietetici/nutrizionali o come farmaci, procedimenti per la loro preparazione e le composizioni contenenti tali sali. The present invention relates to alkaline earth salts of carnitines useful as dietary / nutritional supplements or as drugs, processes for their preparation and compositions containing such salts.
Più particolarmente, la presente invenzione riguarda sali di magnesio o calcio, stabili e non-igroscopici, di carnitine con l'acido mucico (noto anche come acido galattarico, denominazione che verrà usata nel prosieguo della presente descrizione). Pertanto tali sali Con il termine di "non-igroscopico" ci si intende riferire alla capacità posseduta da certi sali di carnitine di resistere, quando si presentano sotto forma di polveri o granuli, a una umidità relativa di almeno il 60%, a 25°C, per 24 ore, senza dar luogo a fenomeni di impaccamento o agglomerazione o addirittura a deliquescenza, con perdita delle loro proprietà di scorrimento. More particularly, the present invention relates to stable and non-hygroscopic magnesium or calcium salts of carnitine with mucic acid (also known as galactaric acid, a name which will be used in the rest of the present description). Therefore these salts The term "non-hygroscopic" refers to the ability of certain carnitine salts to resist, when they are in the form of powders or granules, to a relative humidity of at least 60%, at 25 ° C, for 24 hours, without giving rise to phenomena of packing or agglomeration or even to deliquescence, with loss of their sliding properties.
Con il termine di "igroscopico" ci si intende riferire alla caratteristica mostrata dalla maggior parte dei sali di carnitine (particolarmente dai loro sali "interni"), di subire, quando sotto forma di polveri o granuli, profonde modificazioni della loro proprietà di scorrimento, dovute al loro impaccamento, agglomerazione o addirittura a deliquescenza, a seguito di esposizione ad un ambiente di umidità relativa inferiore al 50-60%, a 25°C, per 24 ore. The term "hygroscopic" refers to the characteristic shown by most carnitine salts (particularly by their "internal" salts), to undergo, when in the form of powders or granules, profound changes in their sliding properties, due to their packing, agglomeration or even deliquescence, following exposure to an environment of relative humidity below 50-60%, at 25 ° C, for 24 hours.
Sono da tempo noti i problemi di stoccaggio e lavorazione provocati dalla notevole igroscopicità della L-carnitina e delle alcanoil L-carnitine sali interni, che rende difficile la produzione e conservazione di forme solide di somministrazione orale. The storage and processing problems caused by the considerable hygroscopicity of L-carnitine and alkanoyl L-carnitine internal salts have been known for some time, making it difficult to produce and store solid forms of oral administration.
Tuttavia tali forme di somministrazione uali com re se accettabili, in base al presupposto che siffatti sali mantengono le stesse attività terapeutiche/nutrizionali dei sali interni e non presentano indesiderati effetti tossici o collaterali. However, such forms of administration as acceptable if acceptable, based on the assumption that such salts maintain the same therapeutic / nutritional activities of the internal salts and do not have unwanted toxic or side effects.
Sebbene esista ormai un'ampia letteratura, particolarmente brevettuale, sulla produzione di sali stabili e non igroscopici della L-carnitina, in realtà solo il fumarato acido di L-carnitina (US 4.602.039, ) e l'L-(+)-tartrato di L-carnitina (US 5.703.376, Lonza) sono stati finora sviluppati su scala industriale e commercializzati. Although there is now a large literature, particularly patent, on the production of stable and non-hygroscopic salts of L-carnitine, in reality only L-carnitine acid fumarate (US 4.602.039,) and L - (+) - L-carnitine tartrate (US 5,703,376, Lonza) have so far been developed on an industrial scale and commercialized.
È interessante notare che sia l'acido fumarico che l'acido L-(+) -tartarico, che formano sali non-igroscopici con la L-carnitina, non sono adatti a fornire sali stabili e non-igroscopici con le alcanoil L-carnitine. Per contro, come descritto nel brevetto US 5.952.379 , l'acido galattarico è atto a formare sali stabili e non igroscopici sia con la L-carnitina, sia con le alcanoil (C2-C5)-L-carnitine, ed è a tutt'oggi l'unico acido noto dotato di tale proprietà. Interestingly, both fumaric acid and L - (+) -tartaric acid, which form non-hygroscopic salts with L-carnitine, are not suitable for providing stable, non-hygroscopic salts with alkanoyl L-carnitines. . On the other hand, as described in US Patent 5,952,379, galactaric acid is able to form stable and non-hygroscopic salts both with L-carnitine and with alkanoyl (C2-C5) -L-carnitine, and is completely today the only known acid with this property.
Sono altresì noti l'im orta t ru l Im orta t ru l are also known
bilità a irritabilità neuromuscolare, convulsioni e gravi alterazioni psichiche (delirio, allucinazioni). Per una discussione dettagliata delle attività fisiologiche e farmacologiche e degli usi terapeutici del magnesio e del calcio si fa riferimento a Goodman and Gilman's "The pharmacological basis of therapeutics", Eight Edition, 1990, pag. 704-706 e 1496-1501, rispettivamente. bility to neuromuscular irritability, convulsions and severe psychic alterations (delirium, hallucinations). For a detailed discussion of the physiological and pharmacological activities and therapeutic uses of magnesium and calcium, reference is made to Goodman and Gilman's "The pharmacological basis of therapeutics", Eight Edition, 1990, p. 704-706 and 1496-1501, respectively.
Sono stati pertanto descritti sali magnesiaci di carnitine con acidi organici polibasici quali l'acido fumarico, l'acido L-(+) -tartarico e Γ acido citrico: la L-carnitina magnesio fumarato e le alcanoil (C2-C5) L-carnitine magnesio fumarato nel brevetto US 6.051.608 Therefore magnesium salts of carnitines with polybasic organic acids such as fumaric acid, L - (+) -tartaric acid and Γ citric acid have been described: L-carnitine magnesium fumarate and alkanoyl (C2-C5) L-carnitine magnesium fumarate in US 6,051,608
; la L-carnitina magnesio tartrato e le alcanoil (C2-C5) L-carnitine magnesio tartrato nella domanda di brevetto PCT WO 98/45250 ; la L-carnitina magnesio citrato nel brevetto US 5,071,874 (Lonza) e le alcanoil (C2-C5) L-carnitine magnesio citrato nella domanda PCT WO 98/44918 . ; L-carnitine magnesium tartrate and alkanoyl (C2-C5) L-carnitine magnesium tartrate in PCT WO 98/45250; L-carnitine magnesium citrate in US patent 5,071,874 (Lonza) and alkanoyl (C2-C5) L-carnitine magnesium citrate in PCT application WO 98/44918.
Il richiedente non è invece a conoscenza di sali di calcio noti di carnitine. On the other hand, the applicant is not aware of known calcium salts of carnitines.
il sudore e nell'urina, è evidente l’utilità di sali magnesiaci della carnitina quali integratori dietetici per sportivi. sweat and urine, the usefulness of magnesian carnitine salts as dietary supplements for athletes is evident.
In considerazione delle note proprietà terapeutiche della L-carnitina, dell'acetil L-carnitina e della propionìl L-carnitina (come, ad esempio, l'azione protettiva della L-carnitina sul sistema cardiovascolare), sali magnesiaci di carnitine trovano utile impiego anche come farmaci. In consideration of the known therapeutic properties of L-carnitine, acetyl L-carnitine and propionyl L-carnitine (such as, for example, the protective action of L-carnitine on the cardiovascular system), magnesium salts of carnitines are also useful such as drugs.
E pertanto sentita la necessità di disporre di sali alcalinoterrosi di carnitine con acidi farmacologicamente accettabili che siano stabili e non igroscopici e ciò alio scopo di favorire la preparazione di forme solide di somministrazione orale utilizzando apparecchiature di tipo tradizionale ed evitando di ricorrere ad ambienti deumidificati. The need is therefore felt to have available alkaline earth salts of carnitines with pharmacologically acceptable acids that are stable and non-hygroscopic and this in order to favor the preparation of solid forms of oral administration using traditional equipment and avoiding the use of dehumidified environments.
I sali magnesiaci noti precedentemente menzionati non soddisfano tali requisiti a causa della loro notevole igroscopicità. The previously mentioned known magnesium salts do not satisfy these requirements due to their considerable hygroscopicity.
È stato ora trovato che i nuovi sali alcalino-terrosi di carnitine con l'acido galattarico di formula (I): It has now been found that the new alkaline earth salts of carnitine with the galactaric acid of formula (I):
n è 1 o 1/2; n is 1 or 1/2;
m è 1 o 2; e m is 1 or 2; And
(a) se m = 1 (a) if m = 1
COOY è COO· se n = 1; oppure COOY is COO · if n = 1; or
COOY è COOH se n = 1/2; oppure (b) se m = 2 COOY is COOH if n = 1/2; or (b) if m = 2
i COOY sono entrambi COO se n = 1; oppure un COOY = COOH, l’altro è COO se n = 1/2, sono stabili e non igroscopici. the COOYs are both COOs if n = 1; or one COOY = COOH, the other is COO if n = 1/2, they are stable and non-hygroscopic.
La non igroscopicità dei sali di formula (I) è sorprendente in quanto ci si sarebbe potuto aspettare che, pur essendo i galattarati di L-carnitina e alcanoil (C2-C5) L-carnitine non igroscopici, i corrispondenti sali alcalino-terrosi, in particolare i sali magnesiaci, lo fossero. Infatti, pur essendo il fumarato acido e l'L(+)-tartrato di L-carnitina non igroscopici, i corrispondenti sali magnesiaci, L-carnitina magnesio fumarato ed L-carnitina magnesio tartrato, sono igroscopici. The non-hygroscopicity of the salts of formula (I) is surprising since it could have been expected that, although the galactarates of L-carnitine and alkanoyl (C2-C5) L-carnitine are non-hygroscopic, the corresponding alkaline-earth salts, in particularly the magnesian salts, they were. In fact, although the acid fumarate and L-carnitine L (+) - tartrate are non-hygroscopic, the corresponding magnesium salts, L-carnitine magnesium fumarate and L-carnitine magnesium tartrate, are hygroscopic.
Con uno dei simboli "1:1:1", "1:1: 1/2", "1:2:1” e "l:2:l/2" posto dopo il nome di un particolare galattarato si indica brevemente il rapporto molare fra acido galattarico, carnitina e magnesio (o calcio) presente in quel galattarato. With one of the symbols "1: 1: 1", "1: 1: 1/2", "1: 2: 1" and "l: 2: l / 2" placed after the name of a particular galactarate it is indicated briefly the molar ratio of galactaric acid, carnitine and magnesium (or calcium) present in that galactarate.
Galattarati particolarmente preferiti sono i seguenti: galattarato di L-carnitina e magnesio 1:1:1; Particularly preferred galactarates are the following: L-carnitine galactarate and magnesium 1: 1: 1;
galattarato di L-carnitina e magnesio 1: 1:1/2; galattarato di acetil L-carnitina e magnesio 1:1:1; galattarato di acetil L-carnitìna e magnesio l:l:l/2; galattarato di propionil L-carnitina e magnesio 1:1:1; galattarato di propionil L-carnitina e magnesio l:l:l/2; galattarato di isovaleril L-carnitina e magnesio 1:1:1; galattarato di isovaleril L-carnitina e magnesio 1:1: 1/2; galattarato di L-carnitina e calcio 1:1:1; galactarate of L-carnitine and magnesium 1: 1: 1/2; galactarate of acetyl L-carnitine and magnesium 1: 1: 1; galactarate of acetyl L-carnitine and magnesium 1: 1: 1/2; galactarate of propionyl L-carnitine and magnesium 1: 1: 1; galactarate of propionyl L-carnitine and magnesium l: l: l / 2; galactarate of isovaleryl L-carnitine and magnesium 1: 1: 1; galactarate of isovaleryl L-carnitine and magnesium 1: 1: 1/2; L-carnitine galactarate and calcium 1: 1: 1;
galattarato di L-carnitina e calcio 1:1: 1/2; galactarate of L-carnitine and calcium 1: 1: 1/2;
galattarato di acetil L-carnitina e calcio 1:1:1; galattarato di acetil L-carnitina e calcio 1:1: 1/2; acetyl L-carnitine and calcium galactarate 1: 1: 1; acetyl L-carnitine and calcium galactarate 1: 1: 1/2;
galattarato di acetil L-carnitina e magnesio 1:2:1; acetyl L-carnitine and magnesium galactarate 1: 2: 1;
galattarato di propionil L-carnitina e magnesio 1:2:1; galactarate of propionyl L-carnitine and magnesium 1: 2: 1;
galattarato di isovaleril L-carnitina e magnesio 1:2:1; galactarate of isovaleryl L-carnitine and magnesium 1: 2: 1;
galattarato di acetil L-carnitina e calcio 1:2:1; acetyl L-carnitine and calcium galactarate 1: 2: 1;
galattarato di propionil L-carnitina e calcio 1:2:1; e galactarate of propionyl L-carnitine and calcium 1: 2: 1; And
galattarato di isovaleril L-carnitina e calcio 1:2:1. isovaleryl L-carnitine galactarate and calcium 1: 2: 1.
I galattarati di formula (I) possono venir preparati secondo una delle procedure alternative che vengono di seguito illustrate. Il comune esperto potrà facilmente scegliere la procedura più opportuna in base alle apparecchiature disponibili. The galactarate of formula (I) can be prepared according to one of the alternative procedures which are illustrated below. The common expert can easily choose the most appropriate procedure based on the equipment available.
Secondo un primo procedimento, si miscelano intimamente, nei rapporti desiderati, l'acido galattarico, la carnitina prescelta e l'idrossido di Mg o di Ca, finemente polverizzati, e si aggiunge acqua in una percentuale compresa tra il 15% e il 25% (per i sali di Ca tra il 20% e il 35%). La miscela viene scaldata rapidamente sotto agitazione a 70-100°C circa e quando ha raggiunto la consistenza di una massa pastosa e semiliquida, viene agitata ancora vigorosamente per alcuni minuti e quindi scaricata in una o più vasche di raccolta. According to a first process, the galactaric acid, the chosen carnitine and the finely pulverized Mg or Ca hydroxide are intimately mixed in the desired ratios, and water is added in a percentage between 15% and 25%. (for Ca salts between 20% and 35%). The mixture is heated rapidly under stirring to about 70-100 ° C and when it has reached the consistency of a pasty and semi-liquid mass, it is stirred vigorously for a few minutes and then discharged into one or more collection tanks.
Alternativamente, la massa pastosa semiliquida di cui sopra, viene scaricata in un mulino a palle riscaldato, in cui viene fatta circolare aria calda e asciutta; il prodotto solido che si forma viene così portato al contenuto di acqua desiderato e la macinazione continuata fino alla granulometria prescelta. Alternatively, the above semiliquid pasty mass is discharged into a heated ball mill, in which hot and dry air is circulated; the solid product that is formed is thus brought to the desired water content and the grinding continues until the selected particle size.
Secondo un diverso procedimento, si miscelano intimamente, nei rapporti desiderati, l'acido galattarico, la carnitina prescelta e l'idrossido di Mg o di Ca, finemente polverizzati, e si aggiunge acqua in una percentuale compresa tra il 25% e il 40%. La miscela viene scaldata rapidamente a 70- 100° C circa e agitata vigorosamente per alcuni minuti. Si aggiunge quindi acetone nella misura di circa 10 volte in mL il peso in grammi del sale che si intende preparare. Si formano due fasi di cui la più viscosa e pesante comprende il sale in preparazione che, sotto l'azione estraente dell'acetone, va man mano impoverendosi di acqua, aumentando la sua viscosità e indurendosi, fino a che, dopo 5-15 minuti circa, si trasforma completamente in un solido cristallino. According to a different procedure, the galactaric acid, the chosen carnitine and the Mg or Ca hydroxide, finely pulverized, are intimately mixed in the desired ratios, and water is added in a percentage between 25% and 40%. . The mixture is heated rapidly to about 70-100 ° C and vigorously stirred for a few minutes. Acetone is then added to the extent of approximately 10 times the weight in grams of the salt to be prepared in mL. Two phases are formed of which the most viscous and heavier includes the salt being prepared which, under the extracting action of acetone, gradually becomes depleted of water, increasing its viscosity and hardening, until, after 5-15 minutes approximately, it completely transforms into a crystalline solid.
assorbono piccole quantità d'acqua con la quale formano degli idrati stabili. they absorb small quantities of water with which they form stable hydrates.
Esempio 1 Example 1
Galattarato di L-carnitina e Mg 1:1:1 Galactarate of L-carnitine and Mg 1: 1: 1
A g 21 di acido galattarico (0,1 moli), g 16,1 di L-carnitina sale interno (0.1 moli) e g 5,83 di idrossido di magnesio (0,1 moli) finemente polverizzati e miscelati intimamente, vennero aggiunti 14 mL di acqua e la risultante miscela portata rapidamente, sotto agitazione, tra i 70 e gli 80°C, con un bagno riscaldante esterno a 100-110°C. Appena la miscela raggiunse una sufficiente fluidità, venne agitata energicamente ancora per circa 2 minuti e quindi scaricata rapidamente in vasche di raccolta. Il processo di solidificazione venne favorito muovendo il prodotto così ottenuto, facendovi passare sopra una corrente di aria calda e asciutta e riscaldando le vasche di raccolta. To 21 g of galactaric acid (0.1 moles), 16.1 g of L-carnitine internal salt (0.1 moles) and 5.83 g of magnesium hydroxide (0.1 moles) finely pulverized and intimately mixed, 14 were added mL of water and the resulting mixture brought rapidly, under stirring, between 70 and 80 ° C, with an external heating bath at 100-110 ° C. As soon as the mixture reached a sufficient fluidity, it was vigorously stirred again for about 2 minutes and then rapidly discharged into collection tanks. The solidification process was favored by moving the product thus obtained, making a stream of hot and dry air pass over it and heating the collection tanks.
Resa quantitativa Quantitative yield
14 mL di acqua e la risultante miscela portata rapidamente, sotto agitazione, tra i 70 e gli 80°C, con un bagno riscaldante esterno a 100-1 10°C. Appena la miscela raggiunse una sufficiente fluidità, venne agitata energicamente ancora per circa 2 minuti e quindi si aggiunsero 450 mL dì acetone. Si formarono due fasi; quella più pesante e viscosa fu mantenuta dispersa per mezzo di una vigorosa agitazione. In 10 minuti circa l'intera massa si trasformò attraverso un progressivo aumento di viscosità e consistenza, in un solido cristallino, che venne filtrato ed essiccato sotto vuoto. 14 mL of water and the resulting mixture brought rapidly, under stirring, between 70 and 80 ° C, with an external heating bath at 100-1 10 ° C. As soon as the mixture reached a sufficient fluidity, it was stirred vigorously again for about 2 minutes and then 450 mL of acetone was added. Two phases were formed; the heavier and more viscous one was kept dispersed by vigorous agitation. In about 10 minutes the entire mass was transformed through a progressive increase in viscosity and consistency, into a crystalline solid, which was filtered and dried under vacuum.
Le caratteristiche del prodotto furono le stesse di quelle descritte per il composto dellEsempio 1. The characteristics of the product were the same as those described for the compound of Example 1.
Esempio 3 Example 3
Galattarato di L-camitina e Ca 1:1:1 Il composto del titolo venne preparato come descritto nell'Esempio 1, sostituendo le 0,1 moli di idrossido di magnesio con 0,1 moli di idrossido di calcio, usando nella miscela di reazione iniziale una percentuale di acqua di circa il 30%. Galactarate of L-Camitin and Ca 1: 1: 1 The title compound was prepared as described in Example 1, replacing the 0.1 moles of magnesium hydroxide with 0.1 moles of calcium hydroxide, using in the reaction mixture initial a percentage of water of about 30%.
Esempio 4 Example 4
Galattarato di L-carnitina e Mg 1:1: 1/2 Galactarate of L-carnitine and Mg 1: 1: 1/2
Il composto del titolo venne preparato come descritto nell'Esempio 1, usando 2,92 g di idrossido di magnesio (0,05 moli) al posto della quantità doppia. The title compound was prepared as described in Example 1, using 2.92 g of magnesium hydroxide (0.05 mol) in place of the double amount.
Resa quantitativa Quantitative yield
Esempio 5 Example 5
Galattarato di L-carnitina e Ca 1.1.1/2 L-carnitine galactarate and Ca 1.1.1 / 2
Il composto del titolo venne preparato come descritto nell'Esempio 4, sostituendo le 0,05 moli di idrossido di magnesio con 0,05 moli di idrossido di calcio e usando nella miscela di reazione iniziale una percentuale di acqua di circa il 30%. The title compound was prepared as described in Example 4, replacing 0.05 moles of magnesium hydroxide with 0.05 moles of calcium hydroxide and using about 30% water in the initial reaction mixture.
Resa quantitativa Quantitative yield
Esempi 6 e 7 Examples 6 and 7
Galattarato di acetil L-carnitina e Mg 1:1:1 Acetyl L-carnitine galactarate and Mg 1: 1: 1
Partendo da g 21 di acido galattarico (0,1 moli), g 20,3 di acetil L-carnitina sale interno (0,1 moli) e g 5,83 di idrossido di magnesio (0,1 moli) finemente polverizzati e miscelati intimamente e 13 mL di acqua si operò esattamente come descritto nell'Esempio 1 (Esempio 6) e, rispettivamente, nell'Esempio 2 (Esempio 7). Starting from 21 g of galactaric acid (0.1 moles), 20.3 g of acetyl L-carnitine internal salt (0.1 moles) and 5.83 g of magnesium hydroxide (0.1 moles) finely pulverized and intimately mixed and 13 mL of water was operated exactly as described in Example 1 (Example 6) and, respectively, in Example 2 (Example 7).
Resa quantitativa Quantitative yield
Esempi 8 e 9 Examples 8 and 9
Galattarato di propionil L-carnitina e Mg 1:1:1 Galactarate of propionyl L-carnitine and Mg 1: 1: 1
Partendo da g 21 di acido galattarico (0,1 moli), g 21,7 di propionil L-carnitina sale interno (0,1 moli) e g 5,83 di idrossido di magnesio (0, 1 moli) finemente polverizzati e miscelati intimamente e 14 mL di acqua si operò esattamente come descritto nell'Esempio Esempio 10 Starting from 21 g of galactaric acid (0.1 moles), 21.7 g of propionyl L-carnitine internal salt (0.1 moles) and 5.83 g of magnesium hydroxide (0.1 moles) finely pulverized and intimately mixed and 14 mL of water was operated exactly as described in Example Example 10
Galattarata di L-carnitina e Mg 1:2; 1 Galactarate of L-carnitine and Mg 1: 2; 1
Venne ripetuta la procedura dell'Esempio 1, raddoppiando la quantità di L-carnitina sale interno (32,2 g; 0,2 moli). The procedure of Example 1 was repeated, doubling the quantity of L-carnitine internal salt (32.2 g; 0.2 mol).
Resa quantitativa Quantitative yield
Esempio 11 Example 11
Galattarato di L-carnitina e Mg 1:2:1 Galactarate of L-carnitine and Mg 1: 2: 1
A g 21 di acido galattarico (0,1 moli), g 32,2 di L-carnitina sale interno (0,2 moli) e g 5,83 di idrossido di magnesio (0,1 moli) finemente polverizzati e miscelati intimamente, vennero aggiunti 14 mL di acqua e la risultante miscela portata rapidamente, sotto agitazione, tra i 70 e gli 80°C, con un bagno riscaldante esterno a 100-110°C. Appena la miscela raggiunse una sufficiente fluidità, venne agitata energicamente ancora per circa 2 minuti e quindi si Esempio 12 21 g of galactaric acid (0.1 moles), 32.2 g of L-carnitine internal salt (0.2 moles) and 5.83 g of magnesium hydroxide (0.1 moles) finely pulverized and intimately mixed, were added 14 mL of water and the resulting mixture rapidly brought, under stirring, between 70 and 80 ° C, with an external heating bath at 100-110 ° C. As soon as the mixture reached a sufficient fluidity, it was stirred vigorously again for about 2 minutes and then Example 12 was applied
Galattarato di L-carnitina e Ca 1:2:1 L-carnitine galactarate and Ca 1: 2: 1
Il composto del titolo venne preparato come descritto nell'Esempio 10, sostituendo le 0,1 moli di idrossido di magnesio con 0,1 moli di idrossido di calcio, usando nella miscela di reazione iniziale una percentuale di acqua di circa il 30%. The title compound was prepared as described in Example 10, substituting 0.1 moles of magnesium hydroxide with 0.1 moles of calcium hydroxide, using about 30% water in the initial reaction mixture.
Resa quantitativa Quantitative yield
Esempio 13 Example 13
Galattarato di L-carnitina e Me 1:2: 1/2 Galactarate of L-carnitine and Me 1: 2: 1/2
Il composto del titolo venne preparato come descritto nell'Esempio 10, usando 2,92 g di idrossido di magnesio (0,05 moli) al posto della quantità doppia. The title compound was prepared as described in Example 10, using 2.92 g of magnesium hydroxide (0.05 mol) in place of the double amount.
Resa quantitativa Quantitative yield
magnesio (0,1 moli) finemente polverizzati e miscelati intimamente e 18 mL (18 mL) di acqua si operò esattamente come descritto nell'Esempio 1 (Esempio 14) e nell'Esempio 2 (Esempio 15). magnesium (0.1 moles) finely pulverized and intimately mixed and 18 mL (18 mL) of water was operated exactly as described in Example 1 (Example 14) and Example 2 (Example 15).
Resa quantitativa Quantitative yield
IR (KBr), cm-<1 >3500-3000 (OH); 1740 (COCH3); 1598 (COO ); 1385 (COO); 1240, 1100, 1065 (C-O) IR (KBr), cm- <1> 3500-3000 (OH); 1740 (COCH3); 1598 (COO); 1385 (COO); 1240, 1100, 1065 (C-O)
Analisi per C24H42MgN2O16 Calc. C 45,12; H 6,63; Mg 3,80; N 4,38 Analysis for C24H42MgN2O16 Calc. C 45.12; H 6.63; Mg 3.80; N 4.38
Trov. C 44,94; H 6,80; Mg 3,72; N 4,32 Esempi 16 e 17 Found C 44.94; H 6.80; Mg 3.72; N 4.32 Examples 16 and 17
Galattarato di acetil L-carnitina e Ca 1:2:1 Il composto del titolo venne preparato come descritto negli Esempi 14 e 15 usando 0,1 moli di idrossido di calcio ed una percentuale d'acqua nella miscela iniziale di reazione di circa il 30%. IR (KBr), cm <1 >3500-3000 (OH); 1740 (COCH3); 1598 (COO ); 1385 (COO ); 1240, 1100, 1065 (C-O) Acetyl L-carnitine galactarate and Ca 1: 2: 1 The title compound was prepared as described in Examples 14 and 15 using 0.1 moles of calcium hydroxide and a percentage of water in the initial reaction mixture of about 30. %. IR (KBr), cm <1> 3500-3000 (OH); 1740 (COCH3); 1598 (COO); 1385 (COO); 1240, 1100, 1065 (C-O)
Analisi per C24H42MgN2O16 Calc. C 44,03; H 6,47; Ca 6,12; N 4,28 Analysis for C24H42MgN2O16 Calc. C 44.03; H 6.47; Ca 6.12; N 4.28
Trov. C 44,04; H 6,50; Ca 6,30; N 4,22 Utilizzando alternativamente le procedure indicate negli galattarato di propionil L-carnitina e Mg 1:2:1; galattarato di propionil L-carnitina e Ca 1:2:1; galattarato di isovaleril L-carnitina e Mg 1:2:1; e galattarato di isovaleril L-carnitina e Ca 1:2:1. Found C 44.04; H 6.50; Ca 6.30; N 4.22 Using alternatively the procedures indicated in the galactarate of propionyl L-carnitine and Mg 1: 2: 1; propionyl L-carnitine galactarate and Ca 1: 2: 1; galactarate of isovaleryl L-carnitine and Mg 1: 2: 1; and isovaleryl L-carnitine galactarate and Ca 1: 2: 1.
La presente invenzione riguarda inoltre composizioni che comprendono quale principio attivo almeno uno dei predetti galattarati alcalino-terrosi di carnitine, e un eccipiente farmacologicamente accettabile. The present invention also relates to compositions which comprise as active principle at least one of the aforementioned alkaline-earth galactarate of carnitines, and a pharmacologically acceptable excipient.
Le composizioni possono presentarsi sotto forma di preparati farmaceutici o preparati da banco, integratori alimentari, prodotti dietetici, prodotti veterinari o mangimi. The compositions may come in the form of pharmaceutical preparations or over-the-counter preparations, food supplements, dietary products, veterinary products or feeds.
Le composizioni possono inoltre comprendere sia altri principi attivi di natura nutrizionale e/o farmacologica, sia sostanze riempitive, agenti leganti, lubrificanti, agenti distaccanti, agenti regolatori di flusso, agenti disperdenti, coloranti ed aromatizzanti, come risulta evidente ad ogni esperto in tecnologia farmaceutica. The compositions can also comprise both other active ingredients of a nutritional and / or pharmacological nature, as well as fillers, binding agents, lubricants, release agents, flow regulating agents, dispersing agents, dyes and flavoring agents, as is evident to any expert in pharmaceutical technology. .
Le forme solide di somministrazione orale comprendono pastiglie, compresse, compresse masticabili, confetti, capsule, polveri 400, preferibilmente da 250 a 300, mg di calcio. Solid forms of oral administration include lozenges, tablets, chewable tablets, dragees, capsules, powders 400, preferably 250 to 300, mg of calcium.
Claims (9)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001RM000030A ITRM20010030A1 (en) | 2001-01-23 | 2001-01-23 | CARNITINE SALTS USEFUL AS DIET / NUTRITIONAL SUPPLEMENTS OR AS DRUGS, COMPOSITIONS CONTAINING THEM AND PROCEDURES FOR THEIR PR |
| PCT/IT2001/000172 WO2002059075A1 (en) | 2001-01-23 | 2001-04-03 | Salts of carnitines useful as dietary/nutritional supplements or drugs, processes for preparing same and compositions containing such salts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001RM000030A ITRM20010030A1 (en) | 2001-01-23 | 2001-01-23 | CARNITINE SALTS USEFUL AS DIET / NUTRITIONAL SUPPLEMENTS OR AS DRUGS, COMPOSITIONS CONTAINING THEM AND PROCEDURES FOR THEIR PR |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ITRM20010030A0 ITRM20010030A0 (en) | 2001-01-23 |
| ITRM20010030A1 true ITRM20010030A1 (en) | 2002-07-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT2001RM000030A ITRM20010030A1 (en) | 2001-01-23 | 2001-01-23 | CARNITINE SALTS USEFUL AS DIET / NUTRITIONAL SUPPLEMENTS OR AS DRUGS, COMPOSITIONS CONTAINING THEM AND PROCEDURES FOR THEIR PR |
Country Status (2)
| Country | Link |
|---|---|
| IT (1) | ITRM20010030A1 (en) |
| WO (1) | WO2002059075A1 (en) |
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| CN101209975B (en) * | 2006-12-29 | 2010-12-01 | 沈阳科硕营养科技有限公司 | Levulorotation carnitine calcium fumarate and its preparing method and use |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3463261D1 (en) * | 1983-12-28 | 1987-05-27 | Sigma Tau Ind Farmaceuti | Salts of l-carnitine and alkanoyl l-carnitines and process for preparing same |
| US5073376A (en) * | 1989-12-22 | 1991-12-17 | Lonza Ltd. | Preparations containing l-carnitine |
| IT1261808B (en) * | 1993-07-06 | 1996-06-03 | USE OF L-CARNITINE OR L-CARNITINE AND VALPROATE ACID IN THE TREATMENT OF CONVULSIVE DISSODS | |
| EE03604B1 (en) * | 1996-05-31 | 2002-02-15 | Fassi Aldo | Stable non-hygroscopic salts of L (-) - carnitine and alkanoyl L (-) - carnitine, process for their preparation and solid oral compositions containing these salts |
| IT1312018B1 (en) * | 1999-03-19 | 2002-04-04 | Fassi Aldo | IMPROVED PROCEDURE FOR THE PRODUCTION OF NON HYGROSCOPICIDAL SALTS OF L (-) - CARNITINE. |
-
2001
- 2001-01-23 IT IT2001RM000030A patent/ITRM20010030A1/en unknown
- 2001-04-03 WO PCT/IT2001/000172 patent/WO2002059075A1/en active Application Filing
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| WO2002059075A1 (en) | 2002-08-01 |
| ITRM20010030A0 (en) | 2001-01-23 |
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