US2953493A - Therapeutic compositions containing 1-hexyl 3, 7-dimethylxanthine and nicotinates - Google Patents
Therapeutic compositions containing 1-hexyl 3, 7-dimethylxanthine and nicotinates Download PDFInfo
- Publication number
- US2953493A US2953493A US650080A US65008057A US2953493A US 2953493 A US2953493 A US 2953493A US 650080 A US650080 A US 650080A US 65008057 A US65008057 A US 65008057A US 2953493 A US2953493 A US 2953493A
- Authority
- US
- United States
- Prior art keywords
- hexyl
- dimethylxanthine
- nicotinic acid
- nicotinates
- therapeutic compositions
- 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
- 235000001968 nicotinic acid Nutrition 0.000 title claims description 18
- 239000000203 mixture Substances 0.000 title claims description 11
- 230000001225 therapeutic effect Effects 0.000 title claims description 11
- MRWQRJMESRRJJB-UHFFFAOYSA-N pentifylline Chemical compound O=C1N(CCCCCC)C(=O)N(C)C2=C1N(C)C=N2 MRWQRJMESRRJJB-UHFFFAOYSA-N 0.000 title description 4
- 150000002814 niacins Chemical class 0.000 title 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 32
- 229960003512 nicotinic acid Drugs 0.000 claims description 17
- 239000011664 nicotinic acid Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 7
- -1 NICOTINIC ACID COMPOUND Chemical class 0.000 claims description 3
- KFLRWGSAMLBHBV-UHFFFAOYSA-M sodium;pyridine-3-carboxylate Chemical compound [Na+].[O-]C(=O)C1=CC=CN=C1 KFLRWGSAMLBHBV-UHFFFAOYSA-M 0.000 description 11
- 208000009999 tuberous sclerosis Diseases 0.000 description 10
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 8
- 229960004559 theobromine Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 230000000916 dilatatory effect Effects 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- NWPRCRWQMGIBOT-UHFFFAOYSA-N 7-(2-hydroxyethyl)-1,3-dimethylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CCO)C=N2 NWPRCRWQMGIBOT-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010020852 Hypertonia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003555 analeptic effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- KSCFJBIXMNOVSH-UHFFFAOYSA-N dyphylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)CO)C=N2 KSCFJBIXMNOVSH-UHFFFAOYSA-N 0.000 description 1
- 229960005387 etofylline Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 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
- 230000000304 vasodilatating effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
Definitions
- This invention relates to novel therapeutic compositions. More particularly, it relates to a composition comprising 1-hexyl 3,7-dimethylxanthine and nicotinic acid or its salts having particular value in the treatment of the symptoms of cerebral sclerosis.
- derivatives of xanthine such as theophylline, theobromine and caffeine
- their therapeutic pure form and in the form of their salts or double salts (for instance, cafieine citrate, theophylline sodium salicylate).
- Their therapeutic indications are maintainly attributable to their dilating elfect on peripheral blood vessels and their diuretic properties.
- caffeine there is a certain observable, analeptic effect.
- Derivatives of these same substances have also been suggested for the same use due to their superior water solubility.
- Such derivatives include compounds such as dihydroxypropyltheophylline, oxyethyl theophylline, and like compounds.
- fl-pyridine carbonic acid (nicotinic acid)
- thesyn'ergistic "effect 'of the combination of the substances can be proven on the coronary vessels of a cat. 'I hecoronary spasm produced experimentallyby the inieetion of hormones deiiv'edfrom inseam-silencer the pituitaryj gland (method according to Antopol-ahd Roessl-er) "can indeed be prevented; or, in some cases weakened by the prophylactic administration of the 1- hexyl compound and sodium nicotinate. (For reasons of pH control the sodium salt of nicotinic acid rather than nicotinic acid is used in this test.) Yet, the same elfect cannot be produced by using one of the two components alone even by using greater doses.
- l-hexyl 3,7-dimethylxanthine and sodium nicotinate are tableted in a ratio, by weight, of about 4:1.
- a typical tablet contains 50 mgs. of sodium nicotinate and 200 mgs. of l-hexyl 3,7-dimethylxanthine.
- the normal dose is one tablet at a time.
- one tablet is taken 3 or 4 times daily. After, about two weeks, one tablet is taken twice daily.
- one tablet may be taken daily for maintenance purposes, and where remission of the symptoms of cerebral sclerosis is apparently complete, the medication may be discontinued.
- compositions hereof are well within the dose recommended for known xanthine derivatives of the type mentioned above for their field of therapeutic use.
- compositions of this invention may be used with great flexibility of doses without having a toxic elfeot. 'Ihis absence of deleterious side effects in effective doses may be attributable to the very low toxic ef-, fect of the l-hexyl compound.
- theophyllene is 2.5 times as toxic as the l-hexyl 3,7-dimethylxanthine.
- the therapeutic compositions of this invention are prepared in tablets containing 200 mgs. of the l-hexyl compound and between 20 and 200 mgs. of sodium nicotinate.
- sodium nicotina-te has been used. It is generally understood, however, that nicotinic acid and therapeutic inorganic salts of nicotinic acid are therapeutically substantially equivalent, although the sodium nicotinate is usually preferred.
- the inorganic salts of nicotinic acid usually provide a more favorable pH than nicotinic acid per se.
- nicotinic acid can be substituted, somewhat less advantageously, for the sodium nicotinate and like therapeuticinorganic salts of nicotinic acid.
- Parts are expressed herein as parts by weight.
- A'therap'eutic composition compi ising 1-hexy1 3,7-
- a composition effective in the remission of cerebral 1 sclerosis comprising nicotinic acid and at :least an equal quantity of l-hexyl 3,7-dimethy1xanthine.
- a mherapeut-ieal composition consisting essentially 4 of l-hexyl 3,7-dimethylxanthine and 10100% as much by weight of an inorganic salt of nicotinic acid.
- a therapeutical composition comprising l-hexyl 3,7- dimethylxanthine and sodium nicotinate in a ratio of 5 about 4:1.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent? Ernst Schroeder and Mario Reiser, 'Wiesbaden, Germany, assignors to Chemische Werke Albert Wiesbaden, Biebrich, Germany, a corporation of Germany No Drawing. Filed Apr. 2, 1957, Ser. No. 650,080
4 Claims. 01. 167-55) This invention relates to novel therapeutic compositions. More particularly, it relates to a composition comprising 1-hexyl 3,7-dimethylxanthine and nicotinic acid or its salts having particular value in the treatment of the symptoms of cerebral sclerosis.
There are known therapeutic utilities for derivatives of xanthine, such as theophylline, theobromine and caffeine, in their therapeutic pure form, and in the form of their salts or double salts (for instance, cafieine citrate, theophylline sodium salicylate). Their therapeutic indications are maintainly attributable to their dilating elfect on peripheral blood vessels and their diuretic properties. In the case of caffeine, there is a certain observable, analeptic effect. Derivatives of these same substances have also been suggested for the same use due to their superior water solubility. Such derivatives include compounds such as dihydroxypropyltheophylline, oxyethyl theophylline, and like compounds.
The compounds mentioned in the foregoing paragraph have been suggested for use in the treatment of cerebral sclerosis. However, it is generally recognized and experience proves that they do not have any direct effect on functional failures or dysfunctioning associated with the illness. At most, these known xanthine derivatives have an indirect effect in that they mitigate hypertonia, which accompanies cerebral sclerosis, to a moderate extent.
Also, fl-pyridine carbonic acid (nicotinic acid), is
known to have a blood vessel dilating eflfect. Yet, it is known that this dilating effect is only temporary or transitory. For instance, scientific publications indicate that the elfect extends over a few minutes only. Nevertheless, it has been suggested that nicotinic acid be applied therapeutically for the treatment of cerebral sclerosis. Likewise, clinical experience has taught that nicotinic acid has a very mild, or no effect, in the treatment of cerebral sclerosis. According to Drill (Pharmacology in Medicine, 1954, p. 61/9) has no therapeutic effect whatsoever in the treatment of cerebral sclerosis.
Recently a xa-nthine derivative, akin to those mentioned above, has become available. This product, 1- hexyl 3,7-dimethylxanthine, is disclosed in German Patent No. 860,217. This new product, sometimes referred to herein as l-hexyl compound, has very pronounced peripheral blood vessel dilating eflz'ects which 1 is many times that of the known xanthine derivatives, discussed above, such as theophylline, and the like. Even though the l-hexyl compound has striking vasodilating effects, it has not provensatisfactory as a medicament for obtaining a remission of cerebral sclerosis.
Now it has been found that the combination of 1- hexyl-3,7-dimethylxanthine and nicotinic acid (or sodium nicotinate) has a stronger peripheral dilating effect than either of the two substances alone. This can be proven by administering a combination, and the two substances separately, to healthy pesrons and measuring the skin temperature. Actually the temperature rises more strongly with the peroral intake of both compo- 2,953,493 Patented Sept. 20, 1960 nents than the intake of the individual components. As is known, the rise in temperatureof theskin is an indication, or measure, of the dilation of the'skin vessels.
' Also, thesyn'ergistic "effect 'of the combination of the substances can be proven on the coronary vessels of a cat. 'I hecoronary spasm produced experimentallyby the inieetion of hormones deiiv'edfrom inseam-silencer the pituitaryj gland (method according to Antopol-ahd Roessl-er) "can indeed be prevented; or, in some cases weakened by the prophylactic administration of the 1- hexyl compound and sodium nicotinate. (For reasons of pH control the sodium salt of nicotinic acid rather than nicotinic acid is used in this test.) Yet, the same elfect cannot be produced by using one of the two components alone even by using greater doses.
Even more strikingly, however, the combination of l-hexyl 3,7-dimethylxanthine and sodium nicotinate can be used in therapeutically elfective doses to obtain remission of the symptoms of cerebral sclerosis without having any deleterious side effects.
In accordance with a practical application of the invention, l-hexyl 3,7-dimethylxanthine and sodium nicotinate are tableted in a ratio, by weight, of about 4:1. A typical tablet contains 50 mgs. of sodium nicotinate and 200 mgs. of l-hexyl 3,7-dimethylxanthine. In the treatment of cerebral sclerosis, the normal dose is one tablet at a time. Generally speaking, in initiating the treatment, one tablet is taken 3 or 4 times daily. After, about two weeks, one tablet is taken twice daily. Eventually one tablet may be taken daily for maintenance purposes, and where remission of the symptoms of cerebral sclerosis is apparently complete, the medication may be discontinued.
It will be seen from the foregoing that an elfective dose of the compositions hereof is well within the dose recommended for known xanthine derivatives of the type mentioned above for their field of therapeutic use. Yet, the compositions of this invention may be used with great flexibility of doses without having a toxic elfeot. 'Ihis absence of deleterious side effects in effective doses may be attributable to the very low toxic ef-, fect of the l-hexyl compound. For example, theophyllene is 2.5 times as toxic as the l-hexyl 3,7-dimethylxanthine.
It will be understood that it is not necessary to use the l hexyl 3,7-dimethylxanthine and the sodium nicotinate in the ratio of 4: 1. Experience indicates that the 1-hexyl 3,7-dirnethylxanthine should be used in a dose of the order of 200 mgs. The sodium nicotinate is usually used in a lesser quantity than the l-llexy-l compound but may be used satisfactorily in any quantity between the ratio of 1:10 and 1:1. Thus, in practical embodiments of the invention, the therapeutic compositions of this invention are prepared in tablets containing 200 mgs. of the l-hexyl compound and between 20 and 200 mgs. of sodium nicotinate.
In the practical embodiments of this invention sodium nicotina-te has been used. It is generally understood, however, that nicotinic acid and therapeutic inorganic salts of nicotinic acid are therapeutically substantially equivalent, although the sodium nicotinate is usually preferred. For example, the inorganic salts of nicotinic acid usually provide a more favorable pH than nicotinic acid per se. Yet, nicotinic acid can be substituted, somewhat less advantageously, for the sodium nicotinate and like therapeuticinorganic salts of nicotinic acid.
Parts are expressed herein as parts by weight.
The foregoing description constitutes illustrative embodiments of the invention but clearly they are not a limitation thereupon. The invention contemplates various adaptations, alterations and modifications which will been to those skilled in them-t and which are within the scope and spirit of the invention defined by the QJP" pended claims.
We claim:
1'. A'therap'eutic composition compi ising 1-hexy1 3,7-
2. A composition effective in the remission of cerebral 1 sclerosis comprising nicotinic acid and at :least an equal quantity of l-hexyl 3,7-dimethy1xanthine.
3. A mherapeut-ieal composition consisting essentially 4 of l-hexyl 3,7-dimethylxanthine and 10100% as much by weight of an inorganic salt of nicotinic acid.
4. A therapeutical composition comprising l-hexyl 3,7- dimethylxanthine and sodium nicotinate in a ratio of 5 about 4:1.
References Cited in the file of this patent Ph-i'la pp. 893-896, 1407, 1408.
Claims (1)
1. A THERAPEUTIC COMPOSITION COMPRISING-1-HEXYL 3,7DIMETHYLXANTHINE AND A NICOTINIC ACID COMPOUND SELECTED FROM THE GROUP CONSISTING OF NICOTINIC ACID AND ITS INORGANIC SALTS.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US650080A US2953493A (en) | 1957-04-02 | 1957-04-02 | Therapeutic compositions containing 1-hexyl 3, 7-dimethylxanthine and nicotinates |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US650080A US2953493A (en) | 1957-04-02 | 1957-04-02 | Therapeutic compositions containing 1-hexyl 3, 7-dimethylxanthine and nicotinates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2953493A true US2953493A (en) | 1960-09-20 |
Family
ID=24607359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US650080A Expired - Lifetime US2953493A (en) | 1957-04-02 | 1957-04-02 | Therapeutic compositions containing 1-hexyl 3, 7-dimethylxanthine and nicotinates |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2953493A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3079300A (en) * | 1960-09-21 | 1963-02-26 | Orsymonde | Phlorophenone derivatives for hepatic and nephritic colic |
| US3864469A (en) * | 1967-12-16 | 1975-02-04 | Hoechst Ag | Xanthines in pharmaceutical preparations and for stabilization of vitamins |
| US4515795A (en) * | 1968-11-25 | 1985-05-07 | Hoechst Aktiengesellschaft | Pharmaceutical compositions |
| US4576947A (en) * | 1967-12-16 | 1986-03-18 | Hoechst Aktiengesellschaft | Pharmaceutical compositions |
-
1957
- 1957-04-02 US US650080A patent/US2953493A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3079300A (en) * | 1960-09-21 | 1963-02-26 | Orsymonde | Phlorophenone derivatives for hepatic and nephritic colic |
| US3864469A (en) * | 1967-12-16 | 1975-02-04 | Hoechst Ag | Xanthines in pharmaceutical preparations and for stabilization of vitamins |
| US4576947A (en) * | 1967-12-16 | 1986-03-18 | Hoechst Aktiengesellschaft | Pharmaceutical compositions |
| US4515795A (en) * | 1968-11-25 | 1985-05-07 | Hoechst Aktiengesellschaft | Pharmaceutical compositions |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Leaf et al. | Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention | |
| MARTIN et al. | Inhibition by apomorphine of prolactin secretion in patients with elevated serum prolactin | |
| Astwood et al. | Treatment of hyperthyroidism with propylthiouracil | |
| US2953493A (en) | Therapeutic compositions containing 1-hexyl 3, 7-dimethylxanthine and nicotinates | |
| Leonard | Toxic effects of phenylbutazone | |
| JPH0320222A (en) | Remedy for ischemic disease in brain | |
| BARTELS et al. | l-Methyl-2-mercaptoimidazole: a new active antithyroid agent | |
| JPS6140288A (en) | Medicinal composition | |
| DE69132782T2 (en) | USE OF ANGIOTENSIN-II ANTAGONISTS IN THE TREATMENT OF LEFT VENTRICULAR HYPERTROPHY | |
| US3777020A (en) | Psoriasis treatment with mycophenolic acid | |
| WO2004006908A1 (en) | Remedies for pigmentation | |
| Okihiro et al. | Hypokalemic periodic paralysis: experimental precipitation with sodium liothyronine | |
| US3852453A (en) | Method of enhancing vincamine compositions | |
| US3689669A (en) | Antidepressant method and composition | |
| JPS626687B2 (en) | ||
| Fortier et al. | Limitations of the ACTH regulating effect of corticoids | |
| GB1210968A (en) | Improvements in or relating to the treatment of gastric ailments | |
| Pascale et al. | Inhibition of the uricosuric action of Benemid by salicylate | |
| US3733423A (en) | Hydrogenated ergot alkaloid compositions and methods of using same | |
| DE68912740T2 (en) | Acyclic derivatives with diuretic properties. | |
| Deschamps et al. | Pharmacokinetic and pharmacodynamic modeling of mizolastine in healthy volunteers with an indirect response model | |
| OLIVER-GONZÁLEZ et al. | TREATMENT OF FILARIASIS BANCROFTI WITH HETRAZAN®: Follow-up Observations Fifteen Months After Treatment | |
| Gubner et al. | Comparative effects of aminopterin, cortisone and ACTH in experimental formaldehyde arthritis and psoriatic arthritis | |
| US3863011A (en) | Process for treating neuroendocrinopathic diseases employing pimozide | |
| GB815969A (en) | Therapeutic compositions containing hexyl-3:7-dimethylxanthine |