GB1593909A – Process for the preparation of tris (hydroxymethyl)-amino methane-lactate-dihydroxyaluminate
– Google Patents
GB1593909A – Process for the preparation of tris (hydroxymethyl)-amino methane-lactate-dihydroxyaluminate
– Google Patents
Process for the preparation of tris (hydroxymethyl)-amino methane-lactate-dihydroxyaluminate
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Publication number
GB1593909A
GB1593909A
GB21860/78A
GB2186078A
GB1593909A
GB 1593909 A
GB1593909 A
GB 1593909A
GB 21860/78 A
GB21860/78 A
GB 21860/78A
GB 2186078 A
GB2186078 A
GB 2186078A
GB 1593909 A
GB1593909 A
GB 1593909A
Authority
GB
United Kingdom
Prior art keywords
hydroxymethyl
tris
aminomethane
lactic acid
added
Prior art date
1977-06-07
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
Application number
GB21860/78A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Scharper SpA Per L’industria Farmaceutica
SCHARPER SpA
Original Assignee
Scharper SpA Per L’industria Farmaceutica
SCHARPER SpA
Priority date (The priority date 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 date listed.)
1977-06-07
Filing date
1978-05-24
Publication date
1981-07-22
1978-05-24
Application filed by Scharper SpA Per L’industria Farmaceutica, SCHARPER SpA
filed
Critical
Scharper SpA Per L’industria Farmaceutica
1981-07-22
Publication of GB1593909A
publication
Critical
patent/GB1593909A/en
Status
Expired
legal-status
Critical
Current
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Classifications
C—CHEMISTRY; METALLURGY
C07—ORGANIC CHEMISTRY
C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
C07F5/06—Aluminium compounds
C07F5/069—Aluminium compounds without C-aluminium linkages
Description
PATENT SPECIFICATION ( 11) 1 593 909
O’ ( 21) Application No 21860/78 ( 22) Filed 24 May 1978 ( 19) ( 31) Convention Application No 24428 ( 32) Filed 7 Jun 1977 in ( 33) Italy (IT) ( 44) Complete Specification Published 22 Jul1981 j ( 51) INT CL 3 C 07 C 59/08 91/10 ( 52) Index at Acceptance C 2 C 20 Y 292 29 Y 30 Y 321 32 Y 360 361 362 366 367 36 Y 431 434 620 623 628 643 802 AB CZ LD ( 72) Inventor: MASSIMO FAZZINI ( 54) PROCESS FOR THE PREPARATION OF TRIS (HYDROXYMETHYL)AMINO METHANE-LACTATE-DIHYDROXYALUMINATE ( 71) We, SCHARPER S p A PER L’INDUSTRIA FARMACEUTICA, an Italian Joint-Stock Company, of Via Montenapoleone, 27, 20121 Milan, Italy, do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed to be particularly described in and by the following statement:-
The present invention relates relates to a method for producing tris(hydroxymethyl) 5 aminomethane-lactate dihydroxyaluminate, which has an empirical formula of C 7 H 18 NO 8 A 1, a molecular weight of 271 21, and the following structural formula:
10 OH CH 2 OH CH 3-CH-O-Al H 2 N-C-CH 2 OH (I) COOH OH CH 2 OH 15 The compound obtained according to the process of the present invention has a very high 20 activity as an antacid, particularly due to its high neutralizing capacity on a weight by weight basis.
The process of the present invention comprises the reaction of lactic acid, tris(hydroxymethyl)amino methane and aluminium isopropylate in equimolar quantities In a practical embodiment, the process begins with the solubilization in water of lactic acid and with the 25 subsequent addition of tris-hydroxymethyl aminomethane (THAM) and of aluminium isopropylate, said additions being capable of being effected in any sequence.
The present invention will be better understood by the following operative examples of the invention given purely by way of illustration and not of limitation.
30 Example 1
In a 1-liter round-bottom flask, equipped with stirrer, reflux condenser and thermometer, there is dissolved 51 g of lactic acid ( 88 %) ( 0 5 mol) in 300 ml of water.
To this solution there is added portion wise 102 g of aluminium isopropylate ( 0 5 mol).
There results a fair exothermic reaction which raises the interior temperature of the flask 35 to about 50 C.
The suspension is then heated, with stirring to 60 C for two hours It is then cooled to C.
There is thus obtained an opalescent solution to which there is added 60 5 g of THAM ( 0 5 mol) The mixture is stirred at room temperature for one hour 40 The insoluble residue is then removed by filtration and the filtrate is concentrated under reduced pressure to a dry residue, keeping the bath temperature below 50 C.
The solid residue is then dried under reduced pressure to constant weight, at a temperature of 40 C.
There is obtained 133 g of the product of formula (I) 45 1 593 909 Example 2
In a 3-liter round bottom flask, equipped with stirrer, reflux condenser and thermometer, there is dissolved 102 g of lactic acid ( 88 %) ( 1 mol) in 600 ml of water.
To the flask there is then added 121 g of THAM ( 1 mol) After a solution is obtained, there is added 204 g of aluminium isopropylate ( 1 mol) dissolved in 1 liter of isopropyl 5 alcohol.
The mixture is then stirred for 2 hours at room temperature.
The insoluble residue is filtered and the filtrate is concentrated under reduced pressure until a dry residue is obtained.
Said residue is then removed from the flask and dried under reduced pressure in the 10 presence of silica gel to constant weight.
There is obtained 268 g of the product of formula (I).
Example 3
In a 10-liter round bottom flask, equipped with stirrer, reflux condenser and 15 thermometer, there is dissolved 510 g of lactic acid ( 88 %) ( 5 mol) in 3 liters of water.
To the solution there is added 605 g of THAM ( 5 mol) and the resulting mixture is stirred for 30 minutes at room temperature.
There is then added in small portions 1020 g ( 5 mol) of aluminum isopropylate.
There is as a result a slight exothermic reaction (to about 35 C) 20 The mixture is then heated for a period of 2 hours at 65 C until an opalescent solution is obtained.
The product is isolated by removing the water by means of a spray-drying apparatus.
There is obtained 1340 g of the product of formula (I).
ANALYTICAL COMPARATIVE TABLE Example %H 20
No Karl Fischer method 4.65 2.66 2.05 Complexometric PH Antacid Elemental Analysis Titer ( 5 % Sol)Activity C H ml HC 1 0 1 N Calc Found Calc Found 99.6 7 88 151 31 00 30 64 6 68 6 96 98.2 8 02 149 31 00 31 21 6 68 6 59 99.1 7 91 152 31 00 30 75 6 68 6 44 N Calc Found 5.16 4 99 5.16 5 07 5.16 4 98 I,O v} \ O .0 1 593 909 For a better understanding of the invention there follows a description which illustrates how the antacid activity was determined.
To a glass vessel having a capacity of 400 ml and maintained at a constant temperature of 37 C in a bath, there is added 200 ml of 0 015 N HCI.
When the liquid in the vessel has reached the bath temperature of 37 C, there is added 5 thereto a quantity of the test sample equivalent to 2 3 g of product, stirring with a glass rod to facilitate the solubilization of the powder At 30 minutes after the addition of the powder, the p H of the solution is measured, verifying that said p H is between 5 0 and 6 5.
There is then added, by means of a 50-ml burette, 0 1 N H Cl at the rate of 1 ml per minute, with slight agitation The determination is considered finished when the p H of the solution 10 has reached 3 0.
While there have been given only few examples of the performance of the process of the present invention, it is obvious to one skilled in the art that various modifications thereof can be effected.
Claims (1)
WHAT WE CLAIM IS: 15
1 A process for the production of tris (hydroxymethyl)-aminomethanelactatedihydroxyaluminate, which has the formula:
OH CH 2 OH 20 / I CH 3-CH-O-AI H 2 N-C-CH 2 OH COOH OH CH 2 OH 25 which comprises reacting in equimolar quantities lactic acid, tris(hydroxymethyl)aminomethane and aluminium isopropylate.
2 A process as claimed in Claim 1 in which to the lactic acid there is first added the aluminium isopropylate and then the tris(hydroxymethyl)aminomethane 30 3 A process as claimed in Claim 1 which comprises the addition of the trishydroxymethyl aminomethane reactant to an aqueous solution of lactic acid and the subsequent addition thereto of a solution of aluminium isopropylate in isopropyl alcohol.
4 A process as claimed in Claim 1 or 3 in which the aluminium isopropylate is added in small portions 35 A process for the production of tris (hydroxymethyl)-aminomethane-lactatedihydroxyaluminate, substantially as hereinbefore described in any one of Examples 1 to 3.
6 Tris(hydroxymethyl)-aminomethane-lactate-dihydroxyaluminate, when prepared by a process as claimed in any one of the preceding claims.
40 For the Applicants, D YOUNG & CO, Chartered Patent Agents, 9 & 10 Staple Inn, London WC 1 V 7RD 45 Printed for Her Majesty’s Stationery Office, by Croydon Printing Company Limited Croydon Surrey 1981.
Published by The Patent Office 25 Southampton Buildings London, WC 2 A l AY, from which copies may be obtained.
GB21860/78A
1977-06-07
1978-05-24
Process for the preparation of tris (hydroxymethyl)-amino methane-lactate-dihydroxyaluminate
Expired
GB1593909A
(en)
Applications Claiming Priority (1)
Application Number
Priority Date
Filing Date
Title
IT24428/77A
IT1081804B
(en)
1977-06-07
1977-06-07
TRIS (HYDROXYMETHYL) -AMINOMETHANE-LACTATE-DIHYDROXYALUMINATE PREPARATION PROCEDURE
Publications (1)
Publication Number
Publication Date
GB1593909A
true
GB1593909A
(en)
1981-07-22
Family
ID=11213486
Family Applications (1)
Application Number
Title
Priority Date
Filing Date
GB21860/78A
Expired
GB1593909A
(en)
1977-06-07
1978-05-24
Process for the preparation of tris (hydroxymethyl)-amino methane-lactate-dihydroxyaluminate
Country Status (12)
Country
Link
US
(1)
US4176129A
(en)
JP
(1)
JPS543009A
(en)
BE
(1)
BE867875A
(en)
CA
(1)
CA1080244A
(en)
CH
(1)
CH633511A5
(en)
DE
(1)
DE2825010A1
(en)
ES
(1)
ES470496A1
(en)
FR
(1)
FR2393807A1
(en)
GB
(1)
GB1593909A
(en)
GR
(1)
GR63617B
(en)
IT
(1)
IT1081804B
(en)
NL
(1)
NL7806140A
(en)
Cited By (1)
* Cited by examiner, † Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
GB2117756A
(en)
*
1982-04-05
1983-10-19
Corvi Camillo Spa
Organometal complexes of n-cyclohexyl-piperazino acetamides or propionamides, and the preparation and use thereof
Family Cites Families (7)
* Cited by examiner, † Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
US2844551A
(en)
*
1952-04-09
1958-07-22
Hoechst Ag
Aluminum compounds and the process of preparing them
US2910494A
(en)
*
1958-01-24
1959-10-27
J W Ayers & Co
Polyaluminum oxide carboxylates
GB888666A
(en)
*
1959-04-13
1962-01-31
Hardman & Holden Ltd
Improvements relating to organic aluminium compounds
US3267091A
(en)
*
1962-01-03
1966-08-16
Ruth C Denison
Complexes containing aluminum, boron and hydroxy organic compounds and process therefor
GB1086502A
(en)
*
1964-07-17
1967-10-11
Rech S Scient Et D Expl De Mar
New organometallic or organoboron complexes of tris-(hydroxymethyl) amino-methane and process for preparing the same
DE2518584A1
(en)
*
1975-04-25
1976-11-04
Scharper Spa
Tri-hydroxymethyl-amino methane-gluconate dihydroxy-aluminate prepn. – by reacting gluconic acid with aluminium isopropylate and gluconate with tri-hydroxymethyl aminomethane
US4042680A
(en)
*
1976-08-02
1977-08-16
Indiana University Foundation
Anticariogenic maloaluminate complexes
1977
1977-06-07
IT
IT24428/77A
patent/IT1081804B/en
active
1978
1978-05-24
GB
GB21860/78A
patent/GB1593909A/en
not_active
Expired
1978-05-25
CH
CH570678A
patent/CH633511A5/en
not_active
IP Right Cessation
1978-05-26
US
US05/910,085
patent/US4176129A/en
not_active
Expired – Lifetime
1978-05-30
JP
JP6483178A
patent/JPS543009A/en
active
Pending
1978-06-01
CA
CA304,574A
patent/CA1080244A/en
not_active
Expired
1978-06-05
ES
ES470496A
patent/ES470496A1/en
not_active
Expired
1978-06-05
GR
GR56438A
patent/GR63617B/en
unknown
1978-06-06
BE
BE188368A
patent/BE867875A/en
not_active
IP Right Cessation
1978-06-06
NL
NL7806140A
patent/NL7806140A/en
not_active
Application Discontinuation
1978-06-07
FR
FR787817089A
patent/FR2393807A1/en
active
Granted
1978-06-07
DE
DE19782825010
patent/DE2825010A1/en
not_active
Withdrawn
Cited By (1)
* Cited by examiner, † Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
GB2117756A
(en)
*
1982-04-05
1983-10-19
Corvi Camillo Spa
Organometal complexes of n-cyclohexyl-piperazino acetamides or propionamides, and the preparation and use thereof
Also Published As
Publication number
Publication date
DE2825010A1
(en)
1978-12-21
FR2393807B1
(en)
1983-02-25
CH633511A5
(en)
1982-12-15
IT1081804B
(en)
1985-05-21
BE867875A
(en)
1978-10-02
CA1080244A
(en)
1980-06-24
GR63617B
(en)
1979-11-26
US4176129A
(en)
1979-11-27
ES470496A1
(en)
1979-01-01
NL7806140A
(en)
1978-12-11
FR2393807A1
(en)
1979-01-05
JPS543009A
(en)
1979-01-11
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Legal Events
Date
Code
Title
Description
1981-12-16
PS
Patent sealed [section 19, patents act 1949]
1991-01-23
PCNP
Patent ceased through non-payment of renewal fee
