US3562273A - Tris (hydroxymethyl) aminomethane theophylline acetate - Google Patents
Tris (hydroxymethyl) aminomethane theophylline acetate Download PDFInfo
- Publication number
- US3562273A US3562273A US616780A US3562273DA US3562273A US 3562273 A US3562273 A US 3562273A US 616780 A US616780 A US 616780A US 3562273D A US3562273D A US 3562273DA US 3562273 A US3562273 A US 3562273A
- Authority
- US
- United States
- Prior art keywords
- tris
- hydroxymethyl
- aminomethane
- theophylline
- alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 title abstract description 23
- VYEYJCBEXFTGBN-UHFFFAOYSA-N acetic acid;1,3-dimethyl-7h-purine-2,6-dione Chemical compound CC(O)=O.O=C1N(C)C(=O)N(C)C2=C1NC=N2 VYEYJCBEXFTGBN-UHFFFAOYSA-N 0.000 title description 6
- 208000010444 Acidosis Diseases 0.000 abstract description 15
- 230000007950 acidosis Effects 0.000 abstract description 14
- 208000026545 acidosis disease Diseases 0.000 abstract description 14
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 8
- HCYFGRCYSCXKNQ-UHFFFAOYSA-N 2-(1,3-dimethyl-2,6-dioxo-7-purinyl)acetic acid Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)=O)C=N2 HCYFGRCYSCXKNQ-UHFFFAOYSA-N 0.000 abstract description 4
- 229950003769 acefylline Drugs 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 abstract description 4
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 abstract description 3
- 235000019136 lipoic acid Nutrition 0.000 abstract description 3
- 229960002663 thioctic acid Drugs 0.000 abstract description 3
- RVSTWRHIGKXTLG-UHFFFAOYSA-N Pangamic acid Natural products CC(C)N(C(C)C)C(N(C(C)C)C(C)C)C(=O)OCC(O)C(O)C(O)C(O)C(O)=O RVSTWRHIGKXTLG-UHFFFAOYSA-N 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 229960005010 orotic acid Drugs 0.000 abstract description 2
- ZQTHOIGMSJMBLM-BUJSFMDZSA-N pangamic acid Chemical compound CN(C)CC(=O)OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O ZQTHOIGMSJMBLM-BUJSFMDZSA-N 0.000 abstract description 2
- 229940055705 pangamic acid Drugs 0.000 abstract description 2
- 108700024047 pangamic acid Proteins 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 235000019441 ethanol Nutrition 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000009471 action Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 229940068511 thioctate Drugs 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229960000278 theophylline Drugs 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000003826 Respiratory Acidosis Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- QHQZEEGNGSZBOL-UHFFFAOYSA-N 2-(aminomethyl)-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(CO)(CO)CO QHQZEEGNGSZBOL-UHFFFAOYSA-N 0.000 description 1
- WTFUTSCZYYCBAY-SXBRIOAWSA-N 6-[(E)-C-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-N-hydroxycarbonimidoyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C/C(=N/O)/C1=CC2=C(NC(O2)=O)C=C1 WTFUTSCZYYCBAY-SXBRIOAWSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000005156 Dehydration Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010023388 Ketonuria Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 231100000645 Reed–Muench method Toxicity 0.000 description 1
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960000182 blood factors Drugs 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 238000010573 double replacement reaction Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- -1 hydrogen ions Chemical class 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940106978 pangamate Drugs 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 229940043200 pentothal Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000001034 respiratory center Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MKVDFFROCUECAJ-CKDSBIORSA-M sodium;(2r,3s,4r,5r)-6-[2-(dimethylamino)acetyl]oxy-2,3,4,5-tetrahydroxyhexanoate Chemical compound [Na+].CN(C)CC(=O)OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O MKVDFFROCUECAJ-CKDSBIORSA-M 0.000 description 1
- QVGLHVDBDYLFON-UHFFFAOYSA-M sodium;1,3-dimethylpurin-7-ide-2,6-dione Chemical compound [Na+].O=C1N(C)C(=O)N(C)C2=C1[N-]C=N2 QVGLHVDBDYLFON-UHFFFAOYSA-M 0.000 description 1
- UUDFBRWLHZIIQX-UHFFFAOYSA-M sodium;5-(dithiolan-3-yl)pentanoate Chemical compound [Na+].[O-]C(=O)CCCCC1CCSS1 UUDFBRWLHZIIQX-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/02—Five-membered rings
- C07D339/04—Five-membered rings having the hetero atoms in positions 1 and 2, e.g. lipoic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
Definitions
- the present invention concerns new compounds of antiacidotic action such as the derivatives of tris (hydroxymethyl) amiuomethane, of important therapeutic applications.
- Nahas introduced the organic amines, among whichby its efficacy and non-toxicitythe tris (hydroxymethyl) aminomethane or THAM, which not only acts as a plasmatic buffer but also as an intracellular buffer.
- the mixture is constantly and vigorously agitated until a limpid liquid is obtained which is dropped, still scalding, into steel trays and, finally, is subjected to vacuum desiccation to preserve from moisture.
- the desiccated product must be manipulated rapidly and in a very dry medium as it is very hygroscopic. In this way are obtained some 145 g. of tris (hydroxymethyl) aminomethane theophylline acetate.
- EXAMPLE 4 15.8 g. of tris (hydroxymethyl) aminomethane hydrochloride are dissolved in the smallest possible quantity of water and 22.8 g. of sodium thioctate are previously added, dissolved in the smallest possible quantity of water.
- EXAMPLE 5 4 The product thus obtained is a microcrystalline powder, soluble in water and in alcohol and insoluble in ether.
- the LD 50 of tris (hydroxymethyl) aminomethane theophylline acetate in albino mice by oral route is 4.05:0.174 g./kg. and 2.45 i0.145 g./kg. by intravenous route.
- the LD 50 is 1600:168 mg./kg. by oral route, 345.2: 27.1 mg./kg. by intravenous route and 365:255 mg./ kg. by intraperitoneal route.
- the tris (hydroxymethyl) aminomethane theophylline. acetate can be considered, by its characteristics, as a complete antiacidotic product since it acts not only on the blood factors that regulate the pH but also on the cellular pulmonary and renal factors.
- the new compound acts as a proton acceptor neutralizing the intracellular hydrogen ions.
- respiratory acidosis the depressant action of tris (hydroxymethyl) aminomethane on the respiratory centers is counter acted by the stimulant action exerted by the theophylline on them.
- renal acidosis there is a synergism between the diuretic action of osmotic and tubular type of the tris (hydroxymethyl) aminomethane with that of glomerular type of the theophylline.
- the tris (hydroxymethyl) aminomethane theophylline-acetate is indicated in all types of toxic, respiratory or metabolic acidosis of tissular, pulmonary, plasmatic, or renal origin. Also in intoxications of medicamental origin produced by barbiturates, salicylic derivatives and the like, in which it facilitates the quick elimination of the toxic substances by renal route.
- the new compound can be administered, unlike the tris (hydroxymethyl) aminomethane, by oral route without producing digestive troubles, and by intravenous route without provoking irritations.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES0323195A ES323195A1 (es) | 1966-02-17 | 1966-02-17 | Procedimiento de obtenciën de compuestos de acciën antiacidëtica |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3562273A true US3562273A (en) | 1971-02-09 |
Family
ID=8442738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US616780A Expired - Lifetime US3562273A (en) | 1966-02-17 | 1967-02-17 | Tris (hydroxymethyl) aminomethane theophylline acetate |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US3562273A (enrdf_load_stackoverflow) |
| BE (1) | BE694127A (enrdf_load_stackoverflow) |
| CH (1) | CH469659A (enrdf_load_stackoverflow) |
| DE (1) | DE1695358A1 (enrdf_load_stackoverflow) |
| ES (1) | ES323195A1 (enrdf_load_stackoverflow) |
| FR (1) | FR1511911A (enrdf_load_stackoverflow) |
| GB (1) | GB1113600A (enrdf_load_stackoverflow) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4071517A (en) * | 1974-09-10 | 1978-01-31 | Claude Dufour | Soluble salts containing sulphur |
| US4572811A (en) * | 1978-06-29 | 1986-02-25 | Yoshino Kogyosho Co., Ltd. | Method for producing polyester containers |
| WO2003011852A1 (de) * | 2001-07-31 | 2003-02-13 | Viatris Gmbh & Co. Kg | Neue modifikationen des trometamolsalzes der r-thioctsäure sowie verfahren zu ihrer herstellung |
| US20070196442A1 (en) * | 2006-02-10 | 2007-08-23 | Heuer Marvin A | Method for improving the oral administration of alpha-lipoic acid |
| US20090264651A1 (en) * | 2008-04-17 | 2009-10-22 | Thomas Daly | Biological Buffers with Wide Buffering Ranges |
| US20100099868A1 (en) * | 2008-04-17 | 2010-04-22 | Thomas Daly | Biological Buffers with Wide Buffering Ranges |
| US20100190993A1 (en) * | 2008-04-17 | 2010-07-29 | Thomas Daly | Biological Buffers with Wide Buffering Ranges |
| US20110137076A1 (en) * | 2008-04-17 | 2011-06-09 | Thomas Daly | Biological Buffers with Wide Buffering Ranges |
| US8519141B2 (en) | 2008-04-17 | 2013-08-27 | Thomas Daly | Biological buffers with wide buffering ranges |
| US8541601B2 (en) | 2009-06-24 | 2013-09-24 | Celltrion Chemical Research Institute | Piperazine dithioctate and pharmaceutical composition comprising the same |
| CN103360393A (zh) * | 2013-07-29 | 2013-10-23 | 上海万巷制药有限公司 | 茶碱乙酸的制备方法 |
| US8822728B2 (en) | 2008-04-17 | 2014-09-02 | Thomas Daly | Biological buffers with wide buffering ranges |
| US9090638B2 (en) | 2008-04-17 | 2015-07-28 | Thomas Daly | Biological buffers with wide buffering ranges |
| US9447310B2 (en) | 2008-04-17 | 2016-09-20 | Thomas P. Daly | Biological buffers with wide buffering ranges |
| US9475754B2 (en) | 2011-10-06 | 2016-10-25 | Thomas P. Daly | Biological buffers with wide buffering ranges |
| US10927279B2 (en) | 2008-04-17 | 2021-02-23 | Thomas Daly | Biological buffers with wide buffering ranges |
| CN113200959A (zh) * | 2020-12-16 | 2021-08-03 | 南京海融制药有限公司 | 一种硫辛酸氨丁三醇盐晶型及其制备方法 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2038733T3 (es) * | 1987-12-04 | 1993-08-01 | Asta Medica Ag | Procedimiento para preparar una solucion inyectable de la sal de acido tioctico con trometanol y/o aminoacidos basicos. |
| US5136096A (en) * | 1989-08-31 | 1992-08-04 | University Of South Florida | Multifunctional synthons as used in the preparation of cascade polymers or unimolecular micelles |
| DE4433764A1 (de) | 1994-09-22 | 1996-03-28 | Asta Medica Ag | Darreichungsformen enthaltend alpha-Liponsäure, feste Salze von R-Thioctsäure mit verbesserter Freisetzung und Bioverfügbarkeit |
-
1966
- 1966-02-17 ES ES0323195A patent/ES323195A1/es not_active Expired
-
1967
- 1967-02-15 GB GB7186/67A patent/GB1113600A/en not_active Expired
- 1967-02-16 DE DE19671695358 patent/DE1695358A1/de active Pending
- 1967-02-16 BE BE694127D patent/BE694127A/xx unknown
- 1967-02-17 US US616780A patent/US3562273A/en not_active Expired - Lifetime
- 1967-02-17 FR FR95468A patent/FR1511911A/fr not_active Expired
- 1967-02-17 CH CH240367A patent/CH469659A/fr unknown
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| US4071517A (en) * | 1974-09-10 | 1978-01-31 | Claude Dufour | Soluble salts containing sulphur |
| US4572811A (en) * | 1978-06-29 | 1986-02-25 | Yoshino Kogyosho Co., Ltd. | Method for producing polyester containers |
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| CN1309718C (zh) * | 2001-07-31 | 2007-04-11 | 维亚特里斯两合公司 | R－硫辛酸的氨基丁三醇盐的新的变性体及其制备方法 |
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| KR100913684B1 (ko) * | 2001-07-31 | 2009-08-24 | 에보니크 데구사 게엠베하 | Ｒ-티옥트산의 트로메타몰 염의 신규한 결정체, 이의 제조방법 및 이를 포함하는 약제 |
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| US8541601B2 (en) | 2009-06-24 | 2013-09-24 | Celltrion Chemical Research Institute | Piperazine dithioctate and pharmaceutical composition comprising the same |
| US9475754B2 (en) | 2011-10-06 | 2016-10-25 | Thomas P. Daly | Biological buffers with wide buffering ranges |
| CN103360393A (zh) * | 2013-07-29 | 2013-10-23 | 上海万巷制药有限公司 | 茶碱乙酸的制备方法 |
| CN103360393B (zh) * | 2013-07-29 | 2016-01-06 | 上海万巷制药有限公司 | 茶碱乙酸的制备方法 |
| CN113200959A (zh) * | 2020-12-16 | 2021-08-03 | 南京海融制药有限公司 | 一种硫辛酸氨丁三醇盐晶型及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1113600A (en) | 1968-05-15 |
| BE694127A (enrdf_load_stackoverflow) | 1967-07-31 |
| CH469659A (fr) | 1969-03-15 |
| ES323195A1 (es) | 1966-12-01 |
| DE1695358A1 (de) | 1972-04-13 |
| FR1511911A (fr) | 1968-02-02 |
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