GB2061920A - Aluminum co-precipitate of sucrose sulfate dihydroxyaluminium allantoinate - Google Patents
Aluminum co-precipitate of sucrose sulfate dihydroxyaluminium allantoinate Download PDFInfo
- Publication number
- GB2061920A GB2061920A GB8029031A GB8029031A GB2061920A GB 2061920 A GB2061920 A GB 2061920A GB 8029031 A GB8029031 A GB 8029031A GB 8029031 A GB8029031 A GB 8029031A GB 2061920 A GB2061920 A GB 2061920A
- Authority
- GB
- United Kingdom
- Prior art keywords
- aluminum
- sucrose sulfate
- allantoinate
- active
- precipitate
- 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.)
- Granted
Links
Classifications
-
- 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, vitamin B12
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate of the general formula <IMAGE> (R = SO3H, m = 1-3 and n = 7-12) is useful for treatment of peptic ulcers.
Description
SPECIFICATION
Aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate and process for preparing the
same -This invention relates to a novel aluminum co-precipitate of sucrose sulfate dihydroxyaluminum
allantoinate, a process for preparing the same and a pharmaceutical composition containing the same as an
active agent useful for prophylaxis and treatment of peptic ulcer.
Hitherto, an aluminum compound of sucrose sulfate has been used as an agent for treatment of peptic
ulcer as having a mucous membrane protection effect, an anti-pepsin activity and an antacid activity. Also,
dihydroxyaluminum allantoinate has been used as an agent for treatment of peptic ulcer as having a
granulation formation activity, a necrotic tissue removing activity and an antacid activity.
Japanese Patent Publication No. 20525/77/ and Swiss Patent 577,526 disclose a compound in which an
aluminum compound of a disaccharide polysulfate is chemically bonded to dihydroxyaluminum allantoinate
having the above anti-peptic ulcer activities superior to the activities exhibited by a mere formulation of
these compound, prepared by reacting an alkali salt of a disaccharide polysulfate with chiorohydroxyalumi- num allantoinate and then with aluminumhydroxy chloride or aluminumdihydroxy chloride, followed by pH
adjustment with an alkaline solution.However, the above conventional process does not produce a specific
product and generally results in a mixture of various products wherein R's in the formula hereinafter
described are hydrogen, -S03A12(OH)5 and/or
As a result of further studies, the present inventors found that an aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate represented by the formula (I)
wherein R represents a -SO3H group, m is an integer of 1 to 3 and n is an integer of 7 to 12, which exhibits a therapeutically valuable anti-ulcer activity can be produced easily on an industrial scale and in high yield without contamination of by-products by the process of this invention.
The aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate of the formula (I) can be prepared by the following two alternative procedures.
In one process, the compound of the formula (I) can be prepared by treating an ammonium salt of sucrose sUlfate with a cation exchange resin to convert the ammonium salt of sucrose sulfate into free sucrose sulfate, reacting the free sucrose sulfate first with active aluminum hydroxide and then with active dihydroxyaluminum allantoinate, and further reacting the resulting water-soluble aluminum composite of sucrose sulfate dihydroxyaluminum allantoinate with active aluminum hydroxide. The process can be illustrated by the following reaction scheme.
C12Hl403 (0S03N114) 8
(tri)
C1 2111403 (oS03H) 8
(III) (III) + A1(OH)3
C12Ii14O3(oSo3I)8 zeal [A1(OH)3]2 to 3
The ammonium salt of sucrose sulfate of the formula (II) can be prepared by reacting sucrose with chlorosulfonic acid in formamide as a solvent to produce a formamide salt of sucrose sulfate and adding methanol to the resulting formamide to cleave the formamide moiety.
In carrying out the process of this invention, the ammonium salt of sucrose sulfate obtained as described above is first treated with a cation exchange resin, for example, by passing an aqueous solution of the ammonium salt of sucrose sulfate through a column packed with a cation exchange resin (H form) or by mixing the aqueous solution with the cation exchange resin, followed by separating the solution from the resin.
Examples of cation exchange resins which can be used are strongly acidic cation exchange resins, for example, those sold under the Registered Trade Marks Amberlite IR-120, iR-121 (Rohm 5 Haas Co.), Dowex
MSC-1 (Dow Chemical Company), Duolite ES-20 (Diamond Shamrock Co.), but the resin is not limited to the above specific examples.
The sucrose sulfate of the formula (II) obtained from the above resin treatment is then reacted in an aqueous solvent with 2 to 3 mols of active aluminum hydroxide and then with 1 to 3 mols of active dihydroxyaluminum allantoinate per mol of sucrose sulfate to obtain an aluminum composite of sucrose sulfate dihydroxyaluminum allantoinate of the formula (Vl (hereinafter referred to as "intermediate").
The aqueous solvent used in the above reaction can be generally water, and the first reaction with active aluminum hydroxide is preferably conducted at room temperature (about 15 to 30"C) and the subsequent reaction is preferably carried out at a temperature of about 50 to about 60"C for a period of about 10 to about 30 minutes.
The active aluminum hydroxide used in the above reaction can be prepared, for example, by adding an aqueous solution of an alikali such as an aqueous sodium hydroxide solution or aqueous ammonia to an aqueous solution of chlorohydrol [ClAl2(OH)5j or aluminumdihydroxy chloride [CIAI(OH)2] in an equimolar proportion, and is preferably used in the form of a freshly prepared gelatinous aqueous suspension.
The active dihydroxyaluminum allantoinate can be prepared, for example, by adding an aqueous solution of aluminumdihydroxy chloride to an aqueous solution of an alkali metal allantoinate, for example, sodium allantoinate in an equimolar proportion and is preferably used in the form of a freshly prepared aqueous suspension.
The intermediate of the formula (V) obtained as described above can be isolated by concentrating the reaction mixture under reduced pressure at a temperature below 60"C until an oily substance is obtained or by adding an aqueous organic solvent such as ethanol, but the reaction mixture containing the intermediate can be used in the subsequent step without isolating the intermediate.
The intermediate of the formula (V) is then reacted with about 4 to about 10 mols of active aluminum hydroxide per mol of the intermediate in an aqueous solvent such as water to obtain the desired product of the formula (I). The reaction is preferably conducted under ice cooling. The active aluminum hydroxide used in this reaction can be the same as that described before. The reaction is preferably carried out in an aqueous solvent whereby the desired product of the formula (I) can be precipitated as crystals which are easily isolated from the reaction mixture.
The above process, of course, can be used effectively for the production of the compound of the formula (I) above on an industrial scale, but is less preferred as compared with the following alternative process since the use of cation exchange resins results in handling a large volume of liquid during the process and requires a prolonged period of time in concentration of the liquid. Further, the process requires a large amount of organic solvents such as methanol and also requires regeneration of the cation exchange resins.
An alternative procedure for preparing the compound of the formula (I) comprises reacting an alkali salt of sucrose sulfate first with active aluminum hydroxide and then with active dihydroxyaluminum aliantoinate in an aqueous hydrochloric acid solution and reacting the resulting water-soluble aluminum composite of sucrose sulfate dihydroxyaluminum allantoinate with active aluminum hydroxide.
The alkali salt of sucrose sulfate used as starting material is preferably one having no possibility of causing contamination with inorganic sulfate and examples of salts are calcium salt, barium salt, ammonium salt.
These salts can be prepared by a procedure well known in the art. For example, a calcium or barium salt of sucrose sulfate can be prepared by reacting sucrose with an hydros sulfonic acid in pyridine to produce sucrose sulfate, dissolving the resulting sulfate in water and neutralizing the solution with calcium hydroxide or barium hydroxide. An ammonium salt of sucrose sulfate can be prepared as described previously.
In carrying out the alternative process of this invention, an alkali salt of sucrose sulfate is dissolved in hydrochloric acid and then active aluminum hydroxide and active dihydroxyaluminum allantoinate are added to the solution to produce an aluminum composite of sucrose sulfate dihydroxyaluminum allantoinate as an intermediate.
Hydrochloric acid solutions having a hydrogen chloride concentration of 5 to 15% is preferred and is used in a proportion of an equimolar amount to a slightly molar excess relative to the alkali salt of sucrose sulfate.
The active aluminum hydroxide can be prepared as described previously and used in the form of a freshly prepared gel, preferably, in an amount of about 2 to about 3 mols per mol of the alkali salt of sucrose sulfate.
The active dihydroxy-aluminum allantoinate can be prepared as described above and is preferably used in the form of a freshly prepared aqueous suspension in an amount of about 1 to 3 mols per mols of the alkali salt of sucrose sulfate.
The reaction proceeds smoothly by warming the reaction mixture to about 60 to about 80"C and is completed within a short period of time, e.g., about 20 minutes to produce a clear reaction solution.
The aqueous solution of the intermediate thus obtained is then added to a suspension of active aluminum hydroxide gel to precipitate the desired product as crystals. After completion of the reaction, an equal volume of methanol to the volume of the reaction mixture is added to the reaction mixture under ice cooling whereby the crystals can be easily separated. The active aluminum hydroxide gel used in this reaction can be prepared in the same manner as described above and is preferably used in an amount of about 4 to about 10 mols per mol of the starting alkali salt of sucrose sulfate.
The compound of the formula (I) thus obtained is a white powder which is practically insoluble in water and most organic solvents, and contains 9 to 13% sulfur, 13 to 18% aluminum, and 8 to 16% allantoin. It turns into a brown color substance at a temperature of about 21 0 C.
The pharmacological activity and the acute toxicity of the aluminum co-precipitate of sucrose sulfate dihydroxy-aluminum allantoinate of the formula (I) were studied according to the following methods and the results obtained are shown below.
I. Anti-ulcerActivity (1) Pyloric Ligation Ulcer Wister male rats weighing 200 to 220 g (8 rats per group for the first run and 10 rats per group for the second run) which fasted for 24 hours before the test were subjected to pyloric ligation under ether anesthesia and immediately thereafter the compound of the formula (i) was administered orally to the rats.
The rats were then allowed to stand for 14 hours without feeding foods or drinking water and thereafter stomach was extracted and the area of ulcer generated in the preventriculus portion was observed by anatomic microscope to determine ulcerous index and the activity of the compound in terms of % inhibition.
The results obtained are shown in Table 1 below.
TABLE 1
Ulcerous
Dose Index
Run No. Test Compound* (mg/kg) (mm2) %Inhibition Control - 4.2
1 Compound of
Formula (1) 100 0.5 86.8
Control - 3.8
Compound of
2 Formula (1) 100 0.4 89.5
Compound of
Formula (1) 300 1.0 97.4
*The test compound having the formula (I) had a value of m of about 2 and n of about 10 (hereinafter the same).
(2) Aspirinulcer Male Donryu rats weighing 200 to 220 g (10 rats per group) which fasted for 24 hours before test were subjected to pylorus ligature under ether anesthesia and immediately thereafter the compound of the formula (I) was administered orally. After abdominal incised section was closed, 100 mg/kg of aspirin (acetylsalicylic acid) was administered orally as a suspension in a 1% aqueous CMC solution. After 7 hours, stomach was extracted, treated with 1% formalin solution and the length of ulcer generated in glandular stomach was observed to determine ulcerous index and the compound was evaluated in terms of % inhibition. The results obtained are shown in Table 2 below.
TABLE 2
Ulcerous
Test Compound Dose Index % inhibition
(mg/kg) (mm)
Control 7.4
Compound of 30 2.4 67.6
Formula (I) 100 1.3 82.4
II. Acute toxicity
The compound of the formula (I) was administered orally to ddy male mice weighing 20 to 25 g (5 groups each 10 mice) and 50% lethal dose (LD50) was determined. The LD50 of the compound oftheformula (I) was found to be more than 20 g/kg.
As is apparent from the results shown in Tables 1 and 2 above, the compound of the formula (I) according to the present invention exhibits low toxicity and is useful for prophylaxis and treatment of peptic ulcer.
The compound of the formula (I) can be administered alone or in the form of tablets, granules, powders and other pharmaceutical compositions formulated with excipients, auxiliary agents and the like which are generally used in preparing pharmaceutical compositions. These pharmaceutical compositions can be prepared by a conventional procedure which is well known in the art.
The dose level of the compound of the formula (I) is generally in the range of 0.5 to 8 g, preferably 1 to 4 g, per day in adult human by oral administration, but the dose level can be varied depending upon the species of animals to be treated, severity of conditions, age of patients and other factors.
The present invention is further illustrated in greater detail by the following Examples, but they are not to be construed as limiting the present invention. Unless otherwise indicated, all percents, ratios, parts and the like are by weight.
Example 1
10 g of ammonium sucrose sulfate was dissolved in 10 ml of water and the solution was passed through a column packed with 50 ml of Amberlite IR-120 (H-form). The column was washed water, and the effluent and washing were combined. To the resulting solution was then added 26 ml of an aqueous suspension containing 1.2 g of freshly prepared active aluminum hydroxide, followed by stirring whereby the pH of the mixture increased to 1.5 to give a substantially clear solution. Then, 26 ml of an aqueous suspension containing 3.2 g of freshly prepared dihydroxyaluminum allantoinate was added to the solution and the mixture was warmed to 60"C whereby the pH of the mixture increased to 3.2 to give a substantially clear solution.The resulting solution was concentrated under reduced pressure at a temperature of 60"C to an oil, and ethanol was added to the residual oil. The solidified substance was filtered to obtain 13.2 g of an aluminum composite of sucrose sulfate dihydroxyaluminum allantoinate. Yield, 94.3%. Sulfur contant, 14.8%. Aluminum content, 5.9%. Allantoin content, 19.8%.
13.2 g of the resulting composite was dissolved in 55 ml of water, and 130 ml of an aqueous suspension containing 4.2 g of freshly prepared active aluminum hydroxide was added to the solution while cooling with ice whereby the pH of the mixture increased to 5 to precipitate crystals. The crystals were separated by filtration, washed with methanol and dried to obtain 11.1 g of an aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate having a melting point of 210 C (with decomposition) as a white crystalline powder. Yield, 63.6%. Sulfur content, 12.1%. Aluminum content, 16.5%. Allantoin content, 11.2%.
Example 2
An aqueous solution of sucrose sulfate was prepared in the same manner as described in Example 1 but using 10 g of ammonium sucrose sulfate. To the resulting solution was added 39 ml of an aqueous suspension containing 1.8 g of freshly prepared active aluminum hydroxide whereby the pH of the mixture increased to 2.8 to give a substantially clear solution. Then, 30 ml of an aqueous suspension containing 5 g of freshly prepared active dihydroxyaluminum allantoinate was added to the solution, and the mixture was warmed to 60"C whereby the pH of the mixture increased to 3.4 to give a substantially clear solution.The resulting solution was cooled with ice and 60 ml of an aqueous suspension containing 4 g of freshly prepared active aluminum hydroxide was added to the solution while cooling with ice whereby the pH of the mixture increased to 5 to precipitate crystals. The crystals were separated by filtration, wash with methanol and dried to obtain 12.8 g of an aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate having a melting point of 205"C (with decomposition) as a white crystalline powder. Yield, 69%. Sulfur content, 12.5%. Aluminum content, 14.8%. Allantoin content, 13.5%.
Example 3
100 g of ammonium sucrose sulfate was dissolved in 230 ml of 10% hydrochloric acid at 18" to 20"C, and the resulting solution was added to 320 ml of an aqueous suspension containing 20 g of freshly prepared active aluminum hydroxide gel with stirring (pH 3.0). The resulting solution thus obtained was then added to 240 mi of an aqueous suspension containing 37.8 g of freshly prepared active dihydroxyaluminum ailantoinate with stirring and the mixture was warmed to 65 to 70"C to obtain a clear reaction solution. Then, the resulting reaction solution was added to 630 ml of an aqueous suspension containing 47.6 g of freshly prepared active aluminum hydroxide gel with stirring whereby the pH of the mixture increased to 4.0 and crystals precipitated. After allowing the mixture to stand for 30 minutes, the mixture was cooled to about 1 5"C and 1.5 liter of methanol was added to the mixture, followed by stirring for 30 minutes. The mixture was filtered, the filtrate was washed successively with aqueous methanol and methanol and dried to obtain 152.4 g of an aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate having a melting point of 210"C (with decomposition) as a white crystalline powder. Yield, 77.6%. Sulfur content, 10.6%. Aluminum content, 15.9%.Allantoin content, 10.7%
Claims (5)
1. An aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate of the general formula
wherein R represents a -SO3H group, is an integer of 1 to 3 and n is an integer of 7 to 12.
2. A process for preparing an aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate of the formula (I)
wherein R represents a -S03H group, m is an integer of 1 to 3 and n is an integer of 7 to 12, which comprises treating an ammonium salt of sucrose sulfate with a cation exchange resin to convert said ammonium salt into free sucrose sulfate, reacting the resulting free sucrose sulfate first with active aluminum hydroxide and then with active dihydroxyaluminum allantoinate in an aqueous solvent, and reacting the resulting water-soluble aluminum composite of sucrose sulfate dihydroxyaluminum aliantoinate with active aluminum hydroxide.
3. A process for preparing an aluminum co-precipitate of sucrose sulfate dihydroxyaluminum allantoinate of the formula (I)
wherein R represents a -SO3H group, m is an integer of 1 to 3 and n is an integer of 7 to 12, which comprises reacting an alkali salt of sucrose sulfate first with active aluminum hydroxide and then with active dihydroxy-aluminum allantoinate in an aqueous hydrochloric acid solution, and reacting the resulting water-soluble aluminum composite of sucrose sulfate dihydroxyaluminum allantoinate with active aluminum hydroxide.
4. A pharmaceutical composition for prophylaxis and treatment of peptic ulcer containing as active ingredient an aluminum co-precipitate of sucrose sulfate dihydroxy-aluminum allantoinate of the formula (I)
wherein R represents a -SO3H group, m is an integer of 1 to 3 and n is an integer of 7 to 12.
5. A process as claimed in Claim 2 or 3, for preparing an aluminum co-precipitate, substantially as hereinbefore described in any of Examples 1 to 3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11732179A JPS5677295A (en) | 1979-09-14 | 1979-09-14 | Co-precipitation substance of aluminum of sucrose sulfate and dihydroxy aluminum allantoinate |
| JP54180A JPS5699496A (en) | 1980-01-09 | 1980-01-09 | Preparation of coprecipitation product of sucrose sulfate dihydroxyaluminum allantoinate with aluminum |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2061920A true GB2061920A (en) | 1981-05-20 |
| GB2061920B GB2061920B (en) | 1983-02-23 |
Family
ID=26333543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8029031A Expired GB2061920B (en) | 1979-09-14 | 1980-09-09 | Aluminum co-precipitate of sucrose sulphate dihydroxyaluminum allantoinate |
Country Status (4)
| Country | Link |
|---|---|
| CA (1) | CA1156224A (en) |
| DE (1) | DE3034506A1 (en) |
| FR (1) | FR2464963A1 (en) |
| GB (1) | GB2061920B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT515027B1 (en) | 2013-09-26 | 2015-08-15 | Universität Innsbruck | intumescent |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3838150A (en) * | 1971-07-06 | 1974-09-24 | Maruko Pharmaceutical Co | Disaccharide polysulfate ester hydroxyaluminum allantoinate-aluminum complex and process for preparing same |
-
1980
- 1980-09-09 GB GB8029031A patent/GB2061920B/en not_active Expired
- 1980-09-10 CA CA000360389A patent/CA1156224A/en not_active Expired
- 1980-09-12 DE DE19803034506 patent/DE3034506A1/en not_active Withdrawn
- 1980-09-12 FR FR8019778A patent/FR2464963A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA1156224A (en) | 1983-11-01 |
| GB2061920B (en) | 1983-02-23 |
| DE3034506A1 (en) | 1981-04-09 |
| FR2464963A1 (en) | 1981-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5212326A (en) | Sodium hydrogen divalproate oligomer | |
| US3058882A (en) | N'-substituted-3-carboxy-6-halo-sulfanilamide and derivatives thereof | |
| EP0243968B1 (en) | Diacetylrhein potassium salt and its therapeutical use in the treatment of arthritis | |
| IE49547B1 (en) | Pyrimidine derivatives | |
| US4137326A (en) | Use of magnesium monospartate hydrochloride complex | |
| IE64112B1 (en) | New strontium salt process for the preparation thereof and pharmaceutical compositions containing it | |
| GB2061920A (en) | Aluminum co-precipitate of sucrose sulfate dihydroxyaluminium allantoinate | |
| US4873223A (en) | Zinc salt of fructose-1,6-diphosphate | |
| GB2098989A (en) | Lysine salts | |
| US4849417A (en) | Acetylsalicylic acid derivative and pharmaceutical composition thereof | |
| US4198431A (en) | Alkyl N-(3-trifluoromethylphenyl)-anthranilate | |
| US4013699A (en) | Aluminium and/or magnesium salts of amino-acids | |
| US3268508A (en) | Process for the preparation of kanamycin-nu, nu'-dimethanesulfonic acid | |
| US4076745A (en) | Process for calcium salts α-ketocarboxylic acids | |
| US4229446A (en) | Aluminum acetylsalicylate glutaminate | |
| US3719665A (en) | Chondroitin sulphuric acid salts | |
| EP0400558B1 (en) | Phenylacetic acid derivative | |
| JPS6281365A (en) | Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivative | |
| GB2054556A (en) | Preparation of hydroxy derivatives of 2-isopropylamino-pyrimidine | |
| EP0001266B1 (en) | Substituted 2-aminomethylphenyl sulfamates, process for preparing, and pharmaceutical compositions containing the same | |
| US4722923A (en) | Double sulfate salt of desoxyfructosyl serotonin and creatinine and compositions containing it | |
| Jackson | Certain N-Alkyl, N-Carboxyalkyl and N-Hydroxyalkyl Derivatives of 4, 4'-Diamino-diphenyl Sulfone | |
| US2668852A (en) | Neutral calcium 4-aminosalicylate hemihydrate and preparation of the same | |
| US5011974A (en) | Process for the preparation of derivative of 2-diethylamino-1-methylethyl-1-hydroxy-(bicyclohexyl)-2-carboxylate | |
| US3318893A (en) | Hydroxy aluminum nicotinate salicylate and method of preparing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |