CA2610821C - Organic salts of .beta.-alanine - Google Patents
Organic salts of .beta.-alanine Download PDFInfo
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- CA2610821C CA2610821C CA2610821A CA2610821A CA2610821C CA 2610821 C CA2610821 C CA 2610821C CA 2610821 A CA2610821 A CA 2610821A CA 2610821 A CA2610821 A CA 2610821A CA 2610821 C CA2610821 C CA 2610821C
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- alanine
- beta
- organic acid
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- 150000003839 salts Chemical class 0.000 title claims abstract description 22
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 150000007524 organic acids Chemical class 0.000 claims abstract description 17
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 25
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 21
- -1 .beta.-alanine organic acid salt Chemical class 0.000 claims description 15
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- 229940049920 malate Drugs 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 5
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000007910 chewable tablet Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000007766 cera flava Substances 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 1
- 235000021355 Stearic acid Nutrition 0.000 claims 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims 1
- 239000008117 stearic acid Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 2
- 235000016709 nutrition Nutrition 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000008247 solid mixture Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 13
- 235000011090 malic acid Nutrition 0.000 description 10
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 9
- 239000001630 malic acid Substances 0.000 description 9
- 229940099690 malic acid Drugs 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 235000011087 fumaric acid Nutrition 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 5
- 108010087806 Carnosine Proteins 0.000 description 5
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 5
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 5
- 229940044199 carnosine Drugs 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 229960002598 fumaric acid Drugs 0.000 description 5
- 235000005985 organic acids Nutrition 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000001530 fumaric acid Substances 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000002407 ATP formation Effects 0.000 description 3
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 3
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229940050411 fumarate Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- CEGRHPCDLKAHJD-UHFFFAOYSA-N 1,1,1-propanetricarboxylic acid Chemical compound CCC(C(O)=O)(C(O)=O)C(O)=O CEGRHPCDLKAHJD-UHFFFAOYSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 206010049565 Muscle fatigue Diseases 0.000 description 1
- 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 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000001087 myotubule Anatomy 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
- 230000000050 nutritive effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/06—Anabolic agents
-
- 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
- C07C229/06—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 having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/08—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 having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/13—Dicarboxylic acids
- C07C57/15—Fumaric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
- C07C59/265—Citric acid
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to stable salts of .beta.-alanine and an organic acid endowed with enhanced nutritional and/or therapeutical efficacy in respect to their individual effects and to solid compositions containing such salts, particularly suited to oral administration. A method of preparation is also provided.
Description
Organic salts of Q-Alanine Field of the Invention The present invention relates to a structure and method for producing stable salts of fl-alanine and organic acids. More specifically, formed salts of the present invention are particularly well suited for oral administration thereby the formed salts may provide enhanced nutritional andlor therapeutical efficacy in relation to the individual components alone.
Background of the Invention It is commonly known that increased muscle mass, strength and extended muscular performance occur in the most effective manner when exercise routines are done to complete exhaustion. However, during extended periods of exercise, metabolites from the breakdown of adenosine triphosphate (ATP), mainly hydrogen ions (H+), begin to accumulate leading to a decline in the pH
levels of blood and muscle, which can be problematic or undesirable. The increase in acidity of the muscle, as a result of the accumulation of H+ ions, is directly linked to muscle fatigue, which ultimately causes a decrease in the duration of intensive bouts of exercise (Cooke R, Pate E. The effects of ADP
and phosphate on the contraction of muscle fibers. Biophys J. 1985 Nov;48(5):789-98). This fatigue is a result of inhibition of enzymes, by decreased pH, which are vital for energy production and the force-producing capacity of muscles (Febbraio MA, Dancey J. Skeletal muscle energy metabolism during prolonged, fatiguing exercise. J Appl Physiol. 1999 Dec;87(6):2341-7).
Carnosine is one of the most effective buffers, or pH stabilizers, in human skeletal muscle, and as such is very efficient at mopping up excess H+ ions.
25 When carnosine is ingested as food, it must be broken down to its constituent amino acids (.8-aianine and histidine) in order cross cell membranes, after which it is then reassembled. Due to lack of absorption, in addition to the financial cost of the raw material, carnosine, administration of the constituent amino acids has been explored. For example, administration of exogenous 8-alanine has been 30 shown to increase the levels of carnosine in skeletal muscle cells (Bate-Smith EC. The buffering of muscle in rigour: protein, phosphate, and carnosine. J
Physiol. 1938;92:336-43).
Additionally, other methods for increasing the duration of exercise have been explored. One such method is the administering of compounds that are 35 essential for ATP synthesis and are depleted during exhaustive exercise, such as malic acid. Malic acid is a naturally occurring compound found in a large number of fruits and vegetables, as well as all living cells; which plays a key role in the transportation of NADH from the cytosol to the mitochondria for energy production (ATP production). Malic acid is part of the initiation of the Krebs cycle 40 and is one of the only metabolites that actually decrease in concentration during exercise. Thus, administration of exogenous malic acid will result in increased ATP production as a result of attenuation of malic acid depletion.
Supplementation with other deprotonated organic acids can be used for attenuation of metabolic acidosis. For example, citrate lacks all of its acidic 45 protons, yielding three carboxylate functionalities that can readily take up free
Background of the Invention It is commonly known that increased muscle mass, strength and extended muscular performance occur in the most effective manner when exercise routines are done to complete exhaustion. However, during extended periods of exercise, metabolites from the breakdown of adenosine triphosphate (ATP), mainly hydrogen ions (H+), begin to accumulate leading to a decline in the pH
levels of blood and muscle, which can be problematic or undesirable. The increase in acidity of the muscle, as a result of the accumulation of H+ ions, is directly linked to muscle fatigue, which ultimately causes a decrease in the duration of intensive bouts of exercise (Cooke R, Pate E. The effects of ADP
and phosphate on the contraction of muscle fibers. Biophys J. 1985 Nov;48(5):789-98). This fatigue is a result of inhibition of enzymes, by decreased pH, which are vital for energy production and the force-producing capacity of muscles (Febbraio MA, Dancey J. Skeletal muscle energy metabolism during prolonged, fatiguing exercise. J Appl Physiol. 1999 Dec;87(6):2341-7).
Carnosine is one of the most effective buffers, or pH stabilizers, in human skeletal muscle, and as such is very efficient at mopping up excess H+ ions.
25 When carnosine is ingested as food, it must be broken down to its constituent amino acids (.8-aianine and histidine) in order cross cell membranes, after which it is then reassembled. Due to lack of absorption, in addition to the financial cost of the raw material, carnosine, administration of the constituent amino acids has been explored. For example, administration of exogenous 8-alanine has been 30 shown to increase the levels of carnosine in skeletal muscle cells (Bate-Smith EC. The buffering of muscle in rigour: protein, phosphate, and carnosine. J
Physiol. 1938;92:336-43).
Additionally, other methods for increasing the duration of exercise have been explored. One such method is the administering of compounds that are 35 essential for ATP synthesis and are depleted during exhaustive exercise, such as malic acid. Malic acid is a naturally occurring compound found in a large number of fruits and vegetables, as well as all living cells; which plays a key role in the transportation of NADH from the cytosol to the mitochondria for energy production (ATP production). Malic acid is part of the initiation of the Krebs cycle 40 and is one of the only metabolites that actually decrease in concentration during exercise. Thus, administration of exogenous malic acid will result in increased ATP production as a result of attenuation of malic acid depletion.
Supplementation with other deprotonated organic acids can be used for attenuation of metabolic acidosis. For example, citrate lacks all of its acidic 45 protons, yielding three carboxylate functionalities that can readily take up free
2 protons. Since all of acidic protons are removed, the citrate has three sites which are capable of taking up free protons in serum and working muscle. Therefore, administration of deprotonated organic acids can inhibit the decrease in pH, which is a result of ATP hydrolysis, thereby leading to less fatigue resulting from 50 the inhibition of enzymes that are vital for energy production and the force-producing capacity of muscles.
Summary of the Invention In the present invention, compounds and methods for their production are disclosed. Specifically, the compounds are salts comprising an organic acid and 55 Q-alanine, and having a structure of Formula.1:
Formula 1 NH3 0 ~ AO
~OH
wherein:
A" represents a deprotonated organic acid selected from the group 60 consisting of: malate, citrate and fumarate; and where A- is malate or fumarate, n = 2, and where A- is citrate; n = 3.
Detailed Description of the Invention In the following description, for the purposes of explanations, numerous 65 specific details are set forth in order to provide a thorough understanding of the present invention. It will be apparent, however, to one of ordinary skill in the art that the present invention may be practiced without these specific details.
Summary of the Invention In the present invention, compounds and methods for their production are disclosed. Specifically, the compounds are salts comprising an organic acid and 55 Q-alanine, and having a structure of Formula.1:
Formula 1 NH3 0 ~ AO
~OH
wherein:
A" represents a deprotonated organic acid selected from the group 60 consisting of: malate, citrate and fumarate; and where A- is malate or fumarate, n = 2, and where A- is citrate; n = 3.
Detailed Description of the Invention In the following description, for the purposes of explanations, numerous 65 specific details are set forth in order to provide a thorough understanding of the present invention. It will be apparent, however, to one of ordinary skill in the art that the present invention may be practiced without these specific details.
3 The present invention is directed towards the structures and synthesis of salts of a-alanine and organic acids.
70 The present invention provides for the production of stable salts, which may afford a combination of,B-alanine and an organic acid, free of physiologically unsafe additives to an individual upon administration to said individual.
Furthermore, the present invention is particularly well suited for use in tablets, capsules, powders, granules, powdered beverage mixes and other forms known 75 in the art of dietary supplements.
,8-alanine combined with an organic acid forms a non-hygroscopic crystalline powder, which is stable in storage and can be processed without special precautions. Due to the non-hygroscopic nature of the /3-alanine salt it would be understood by one of skill in the art, that the salt is easy to process and 80 is particularly suitable for processing with rapidly running machines, since it does not tend to stick together or become lumpy.
As used herein, '/3-alanine' refers to the chemical beta-alanine, also known as 3-aminopropionic acid. Additionally, as used herein, ',8-aianine' also includes derivatives of fl-alanine such as esters, amides, and salts, as well as other 85 derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
As used herein, 'malic acid' refers to the chemical 1-Hydroxy-1,2-ethanedicarboxylic acid, (CAS Registry No. 6915-15-17), also known as, hydroxybutanedioic acid, hydroxysuccinic acid, malate, or 2-90 hydroxybutanedioate. Additionally, as used herein, 'malic acid' also includes
70 The present invention provides for the production of stable salts, which may afford a combination of,B-alanine and an organic acid, free of physiologically unsafe additives to an individual upon administration to said individual.
Furthermore, the present invention is particularly well suited for use in tablets, capsules, powders, granules, powdered beverage mixes and other forms known 75 in the art of dietary supplements.
,8-alanine combined with an organic acid forms a non-hygroscopic crystalline powder, which is stable in storage and can be processed without special precautions. Due to the non-hygroscopic nature of the /3-alanine salt it would be understood by one of skill in the art, that the salt is easy to process and 80 is particularly suitable for processing with rapidly running machines, since it does not tend to stick together or become lumpy.
As used herein, '/3-alanine' refers to the chemical beta-alanine, also known as 3-aminopropionic acid. Additionally, as used herein, ',8-aianine' also includes derivatives of fl-alanine such as esters, amides, and salts, as well as other 85 derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
As used herein, 'malic acid' refers to the chemical 1-Hydroxy-1,2-ethanedicarboxylic acid, (CAS Registry No. 6915-15-17), also known as, hydroxybutanedioic acid, hydroxysuccinic acid, malate, or 2-90 hydroxybutanedioate. Additionally, as used herein, 'malic acid' also includes
4 derivatives of malate such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
As used herein, 'citric acid' refers to the chemical 2-hydroxy-1,2,3-95 propane-tricarboxylic acid, (CAS Registry No. 77-92-9), also known as, ,6-hydroxytricarboxylic acid . Additionally, as used herein, 'citric acid' also includes derivatives of citrate such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
100 As used herein, 'fumaric acid' refers to the chemical (E)-2-butenedioic acid, (CAS Registry No. 110-17-8), also known as, trans-1,2-ethylenedicarboxylic acid, allomaleic acid, and boletic acid. Additionally, as used herein, 'fumaric acid' also includes derivatives of fumarate such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon 105 metabolism to an active form.
As used herein, the term 'organic acid' refers to organic compounds which contain carboxylic acids (-C(O)OH). Typical examples of organic acids include, but are not limited to; malic acid, fumaric acid, citric acid, orotic acid, lactic acid, pyruvic acid, and tartaric acid.
110 As used herein, the term 'pharmaceutically acceptable excipients' refers to substances added to produce quality tablets, chewable tablets, capsules, granulates or powders, but which do not provide nutritive value. A non-exhaustive list of examples of excipients includes monoglycerides, magnesium stearate, modified food starch, gelatin, microcrystalline cellulose, glycerin, stearic 115 acid, silica, yellow beeswax, lecithin, hydroxypropyicel lu lose, croscarmellose sodium, and crosprovidone.
According to the present invention, the compounds disclosed herein comprise molecules of Q-alanine combined with an organic acid to form a salt having a structure according to Formula 1. The aforementioned compound being 120 prepared according to the reaction as set forth for the purposes of the description in Scheme 1:
Scheme 1 1) Heat ~ AO
NH2 0 2) Cool (RT to 4 C) NH3 0 '-~A+ HA ~
OH Lower Alcohol OH n With reference to Scheme 1, in the first step of the reaction the fl-alanine 125 (1) is dissolved in an excess of hot lower alcohol. The lower alcohol is considered to be hot, as would be known by one of ordinary skill in the art.
Preferably the lower alcohol is considered to be hot when heated to a temperature about 5 C below the boiling point of the corresponding lower alcohol.
130 In various embodiments of the present invention, the lower alcohol is selected from the group consisting of methanol, ethanol, propanol, and isopropanol. These lower alcohols may be used singly or in admixture containing two or more alcohols.
Concurrently, in the second step of the reaction the organic acid (2) is 135 dissolved into an excess of hot lower alcohol. The lower alcohol is considered to be hot, as would be known by one of ordinary skill in the art. Preferably the lower alcohol is considered to be hot when heated to a temperature about 5 C below the boiling point of the corresponding lower alcohol.
Both solutions above are then mixed together and heated to about the 140 boiling point of the corresponding lower alcohol. If there are solids still present after heating, the solution is filtered while hot to remove any unreacted starting materials. The solution is then allowed to cool to room temperature, covered and refrigerated or cooled until crystallization occurs, preferably for between about 24 to about 48 hours. The resultant crystals are filtered under vacuum and washed 145 with ice cold lower alcohol, yielding a crystalline powder, the a-alanine organic acid salt (3).
In larger scale preparations of the present invention, diethyl ether can be added until the cloud point, as would be known to one of skill in the art, is reached after the mixture is cooled to room temperature, after which the solution 150 is refrigerated or cooled to allow crystallization to complete. This will facilitate greater precipitation of the product thus yielding more of the a-alanine organic acid salt (3), which would be desired in industrial settings.
,Q-alanine organic acid salts are used advantageously alone or with additional active ingredients, such as, trace elements, vitamins, mineral 155 substances, or other amino acids as well as, optionally, excipients usually used for the preparation of the respective forms of administration. The forms of administration include, particularly, all varieties of tablets, both those that are swallowed without being chewed, and tablets to be chewed or dissolved in the mouth of an individual, as well as those that are dissolved in a liquid before being 160 ingested by an individual. The tablet forms include uncoated tablets, one-layer or multilayer or encased forms or effervescent tablets. Further preferred forms of administration are capsules of hard and soft gelatin, the latter being particularly suitable to include a liquid core. Additionally, 8-alanine organic acid salts can be used advantageously for the preparation of solutions and suspensions and as a 165 powder, either effervescent or granulated.
The examples given below explain the execution of the invention with respect to the production of /3-alanine organic acid salts. Provided below is a basic method for producing fl-alanine organic acid salts. However, those of skill in the art will appreciate certain changes may be made in the process of "scaling-170 up" the reaction to manufacture larger batches of B-alanine organic acid salts which may be required for commercial uses and supply requirements. Other methods of synthesis may also be apparent to those of skill in the art.
Examples Example 1 1) Heat NH2 0 HO O OH 2) Cool (RT to 4 C) NH3 O O 0 ~
+ ~ 0 (,-OH -~ EtOH
178.18 g (2 mol) of fl-alanine (1) is dissolved into 400mL of hot ethanol, 180 solution 1. Concurrently, 134.09 g (1 mol) of malic acid (2) is dissolved in 200mL
of hot ethanol, solution 2. Solution 2 is added to solution I with stirring and the resultant solution is heated to the boiling point. If there are solids still present the solution is filtered at this temperature to remove unreacted starting materials.
The solution is then allowed to cool to room temperature and then covered and 185 refrigerated to allow crystallization to complete; about 24 hours. The resultant crystals are filtered under vacuum and washed with ice cold ethanol, yielding a crystalline powder, the,8-alanine malate (3).
Example 2 1) Heat NH2 0 + 0/ OH 2) Cool (RT to 4 C) NH3 O = 0I/ O
~OH HO~ ~~ O
0 Propanol OH 2 O
178.18 g (2 mol) of ,r33-alanine (1) is dissolved into 400mL of hot propanol, solution 1. Concurrently, 116.07 g (1 mol) of fumaric acid (2) is dissolved in 200mL of hot propanol, solution 2. Solution 2 is added to solution I with stirring and the resultant solution is heated to the boiling point. If there are solids still 195 present the solution is filtered at this temperature to remove unreacted starting materials. The solution is then allowed to cool to room temperature and refrigerated to allow crystallization to complete; about 24 hours. The resultant crystals are filtered under vacuum and washed with ice cold ethanol, yielding a crystalline powder, the fl-alanine fumarate (3).
Example 3 1) Heat NH2 0 HO OH 2) Cool (RT to 4 C) NH3 [ OH]3[!HO]
- OH + sHO
OO
267.27 g (3 mol) of a-alanine (1) is dissolved into 600mL of hot isopropanol, solution 1. Concurrently, 192.12 g (1 moI) of citric acid (2) is 205 dissolved in 300mL of hot isopropanol, solution 2. Solution 2 is added to solution I with stirring and the resultant solution is heated to the boiling point. If there are solids still present the solution is filtered at this temperature to remove unreacted starting materials. The solution is then allowed to cool to room temperature and refrigerated to allow crystallization to complete; about 24 hours. The resultant 210 crystals are filtered under vacuum and washed with ice cold ethanol, yielding a crystalline powder, the,8-alanine citrate (3).
Extensions and Alternatives 215 In the foregoing specification, the invention has been described with a specific embodiment thereof; however, it will be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention.
As used herein, 'citric acid' refers to the chemical 2-hydroxy-1,2,3-95 propane-tricarboxylic acid, (CAS Registry No. 77-92-9), also known as, ,6-hydroxytricarboxylic acid . Additionally, as used herein, 'citric acid' also includes derivatives of citrate such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
100 As used herein, 'fumaric acid' refers to the chemical (E)-2-butenedioic acid, (CAS Registry No. 110-17-8), also known as, trans-1,2-ethylenedicarboxylic acid, allomaleic acid, and boletic acid. Additionally, as used herein, 'fumaric acid' also includes derivatives of fumarate such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon 105 metabolism to an active form.
As used herein, the term 'organic acid' refers to organic compounds which contain carboxylic acids (-C(O)OH). Typical examples of organic acids include, but are not limited to; malic acid, fumaric acid, citric acid, orotic acid, lactic acid, pyruvic acid, and tartaric acid.
110 As used herein, the term 'pharmaceutically acceptable excipients' refers to substances added to produce quality tablets, chewable tablets, capsules, granulates or powders, but which do not provide nutritive value. A non-exhaustive list of examples of excipients includes monoglycerides, magnesium stearate, modified food starch, gelatin, microcrystalline cellulose, glycerin, stearic 115 acid, silica, yellow beeswax, lecithin, hydroxypropyicel lu lose, croscarmellose sodium, and crosprovidone.
According to the present invention, the compounds disclosed herein comprise molecules of Q-alanine combined with an organic acid to form a salt having a structure according to Formula 1. The aforementioned compound being 120 prepared according to the reaction as set forth for the purposes of the description in Scheme 1:
Scheme 1 1) Heat ~ AO
NH2 0 2) Cool (RT to 4 C) NH3 0 '-~A+ HA ~
OH Lower Alcohol OH n With reference to Scheme 1, in the first step of the reaction the fl-alanine 125 (1) is dissolved in an excess of hot lower alcohol. The lower alcohol is considered to be hot, as would be known by one of ordinary skill in the art.
Preferably the lower alcohol is considered to be hot when heated to a temperature about 5 C below the boiling point of the corresponding lower alcohol.
130 In various embodiments of the present invention, the lower alcohol is selected from the group consisting of methanol, ethanol, propanol, and isopropanol. These lower alcohols may be used singly or in admixture containing two or more alcohols.
Concurrently, in the second step of the reaction the organic acid (2) is 135 dissolved into an excess of hot lower alcohol. The lower alcohol is considered to be hot, as would be known by one of ordinary skill in the art. Preferably the lower alcohol is considered to be hot when heated to a temperature about 5 C below the boiling point of the corresponding lower alcohol.
Both solutions above are then mixed together and heated to about the 140 boiling point of the corresponding lower alcohol. If there are solids still present after heating, the solution is filtered while hot to remove any unreacted starting materials. The solution is then allowed to cool to room temperature, covered and refrigerated or cooled until crystallization occurs, preferably for between about 24 to about 48 hours. The resultant crystals are filtered under vacuum and washed 145 with ice cold lower alcohol, yielding a crystalline powder, the a-alanine organic acid salt (3).
In larger scale preparations of the present invention, diethyl ether can be added until the cloud point, as would be known to one of skill in the art, is reached after the mixture is cooled to room temperature, after which the solution 150 is refrigerated or cooled to allow crystallization to complete. This will facilitate greater precipitation of the product thus yielding more of the a-alanine organic acid salt (3), which would be desired in industrial settings.
,Q-alanine organic acid salts are used advantageously alone or with additional active ingredients, such as, trace elements, vitamins, mineral 155 substances, or other amino acids as well as, optionally, excipients usually used for the preparation of the respective forms of administration. The forms of administration include, particularly, all varieties of tablets, both those that are swallowed without being chewed, and tablets to be chewed or dissolved in the mouth of an individual, as well as those that are dissolved in a liquid before being 160 ingested by an individual. The tablet forms include uncoated tablets, one-layer or multilayer or encased forms or effervescent tablets. Further preferred forms of administration are capsules of hard and soft gelatin, the latter being particularly suitable to include a liquid core. Additionally, 8-alanine organic acid salts can be used advantageously for the preparation of solutions and suspensions and as a 165 powder, either effervescent or granulated.
The examples given below explain the execution of the invention with respect to the production of /3-alanine organic acid salts. Provided below is a basic method for producing fl-alanine organic acid salts. However, those of skill in the art will appreciate certain changes may be made in the process of "scaling-170 up" the reaction to manufacture larger batches of B-alanine organic acid salts which may be required for commercial uses and supply requirements. Other methods of synthesis may also be apparent to those of skill in the art.
Examples Example 1 1) Heat NH2 0 HO O OH 2) Cool (RT to 4 C) NH3 O O 0 ~
+ ~ 0 (,-OH -~ EtOH
178.18 g (2 mol) of fl-alanine (1) is dissolved into 400mL of hot ethanol, 180 solution 1. Concurrently, 134.09 g (1 mol) of malic acid (2) is dissolved in 200mL
of hot ethanol, solution 2. Solution 2 is added to solution I with stirring and the resultant solution is heated to the boiling point. If there are solids still present the solution is filtered at this temperature to remove unreacted starting materials.
The solution is then allowed to cool to room temperature and then covered and 185 refrigerated to allow crystallization to complete; about 24 hours. The resultant crystals are filtered under vacuum and washed with ice cold ethanol, yielding a crystalline powder, the,8-alanine malate (3).
Example 2 1) Heat NH2 0 + 0/ OH 2) Cool (RT to 4 C) NH3 O = 0I/ O
~OH HO~ ~~ O
0 Propanol OH 2 O
178.18 g (2 mol) of ,r33-alanine (1) is dissolved into 400mL of hot propanol, solution 1. Concurrently, 116.07 g (1 mol) of fumaric acid (2) is dissolved in 200mL of hot propanol, solution 2. Solution 2 is added to solution I with stirring and the resultant solution is heated to the boiling point. If there are solids still 195 present the solution is filtered at this temperature to remove unreacted starting materials. The solution is then allowed to cool to room temperature and refrigerated to allow crystallization to complete; about 24 hours. The resultant crystals are filtered under vacuum and washed with ice cold ethanol, yielding a crystalline powder, the fl-alanine fumarate (3).
Example 3 1) Heat NH2 0 HO OH 2) Cool (RT to 4 C) NH3 [ OH]3[!HO]
- OH + sHO
OO
267.27 g (3 mol) of a-alanine (1) is dissolved into 600mL of hot isopropanol, solution 1. Concurrently, 192.12 g (1 moI) of citric acid (2) is 205 dissolved in 300mL of hot isopropanol, solution 2. Solution 2 is added to solution I with stirring and the resultant solution is heated to the boiling point. If there are solids still present the solution is filtered at this temperature to remove unreacted starting materials. The solution is then allowed to cool to room temperature and refrigerated to allow crystallization to complete; about 24 hours. The resultant 210 crystals are filtered under vacuum and washed with ice cold ethanol, yielding a crystalline powder, the,8-alanine citrate (3).
Extensions and Alternatives 215 In the foregoing specification, the invention has been described with a specific embodiment thereof; however, it will be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention.
Claims (13)
1. A salt of .beta.-alanine and an organic acid, having the general formula:
wherein:
A- is malate, citrate, fumarate, orotate, pyruvate or tartarate; and where A- is orotate or pyruvate, n = 1, where A- is malate, fumarate or tartarate, n= 2, and where A- is citrate; n= 3.
wherein:
A- is malate, citrate, fumarate, orotate, pyruvate or tartarate; and where A- is orotate or pyruvate, n = 1, where A- is malate, fumarate or tartarate, n= 2, and where A- is citrate; n= 3.
2. A composition comprising the salt of .beta.-alanine and an organic acid of claim 1, wherein the composition further comprises pharmaceutically acceptable excipients.
3. The composition of claim 2 wherein the pharmaceutically acceptable excipients are monoglycerides, magnesium stearate, modified food starch, gelatin, microcrystalline cellulose, glycerin, stearic acid, silica, yellow beeswax, lecithin, hydroxypropylcellulose, croscarmellose sodium or crosprovidone.
4. The salt of .beta.-alanine and an organic acid of claim 1 wherein said salt is provided in a dosage form of tablets, chewable tablets, capsules, granulates or powders.
5. The composition of claim 2 wherein the composition is provided in a dosage form of tablets, chewable tablets, capsules, granulates or powders.
6. The salt of .beta.-alanine and an organic acid of claim 4 wherein said salt is suitable for administration to a mammal.
7. The composition of claims 2, 3 or 5 wherein the composition is suitable for administration to a mammal.
8. A .beta.-alanine organic acid salt having the molecular structure of:
wherein A- is malate and n = 2.
wherein A- is malate and n = 2.
9. A .beta.-alanine organic acid salt having the molecular structure of:
wherein A- is orotate and n = 1.
wherein A- is orotate and n = 1.
10. A .beta.-alanine organic acid salt having the molecular structure of:
wherein A- is pyruvate and n = 1.
wherein A- is pyruvate and n = 1.
11. A .beta.-alanine organic acid salt having the molecular structure of:
wherein A- is fumarate and n = 2.
wherein A- is fumarate and n = 2.
12. A .beta.-alanine organic acid salt having the molecular structure of:
wherein A- is tartarate and n = 2.
wherein A- is tartarate and n = 2.
13. A .beta.-alanine organic acid salt having the molecular structure of:
wherein A- is citrate and n= 3.
wherein A- is citrate and n= 3.
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