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CA1305724C - Calcium lactate-glycerol adduct, a process for its preparation and itsuse - Google Patents

Calcium lactate-glycerol adduct, a process for its preparation and itsuse

Info

Publication number
CA1305724C
CA1305724C CA 562536 CA562536A CA1305724C CA 1305724 C CA1305724 C CA 1305724C CA 562536 CA562536 CA 562536 CA 562536 A CA562536 A CA 562536A CA 1305724 C CA1305724 C CA 1305724C
Authority
CA
Grant status
Grant
Patent type
Prior art keywords
calcium
glycerol
lactate
adduct
anhydrous
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
Application number
CA 562536
Other languages
French (fr)
Inventor
Bernhard Reul
Walter Petri
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.)
Sanofi-Aventis Deutschland GmbH
Original Assignee
Hoechst AG
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.)
Filing date
Publication date
Grant date

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/01Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
    • C07C59/08Lactic acid

Abstract

Abstract of the disclosure: HOE 87/F 090 Calcium lactate-glycerol adduct, a molecular compound of 1 mole of calcium lactate and 2 moles of glycerol, and a process for its preparation are described. The adduct can be used as a calcium donor or auxiliary in pharmacy, cosmetics and the production of foodstuffs.

Description

7;~

HOECHST AKTIENGESELLSCHAFT HOE 87/F 090 Dr.D/mu Description:

Calcium lacta~e-glycerol adduct, a process for its preparation and its use The invention relates to calc;um lactate-gLycerol adduct, which is a solid, pulverulent, crystalLine reaction pro-duct between calcium lactate and glycerol, and a process for the preparation of this novel substance~ The inven-tion furthermore relates to the use of the adduct in pharmacy, cosoetics and foodstuffs.

Calcium lactate-glycerol adduct is a molecular compound between 1 mole of calcium lactate and 2 moles of glycerol~
of the formula I

(CH3-CHOH-C00)2 Ca x 2 H2COH-HCOH-H2COH

The process for its preparation comprises reacting cal~
ciu~ lactaSe ~ith anhydrous glycerol in a molar ratio of 1 to at least 2, ~hile ~arming in an anhydrous C1- ~
C3-alcohol, cooLing the resulting clear solution and separating off the calcium lactate-glyceroL adduct.

The calcium lactate is advantageously used either in the form of hydraees, for example the 5-hydrate, or in anhydrous form. In the re~ction, at least 2 ~oles, pre-ferably 4 moles, of glycerol are added to 1 mole of cal-cium lactate. The anhydrous glycerol is preferably mixed with anhydrous methanol, mixtures of 1 - 5 parts, in part;cular 2 partst of methanol with 1 - 7, in particular 3 parts* of ~lycerol preferably being used. The reaction mixture is h~ated to the boiling point under reflux;
a cLear solut;on is formed, from which the adduct precipitates in the form of granular crystals on coolin~. For co~plete crystallization, the solubility * by weight D3~

~3~

of the adduct in the glycerol/methanol reaction mixture can be reduced by adding acetone tequal pares by weigI1t of acetone~
based on the gLycerol employed). The substance is ~ashed ~ith a methanol/acetone mixture for complete removal of the glycerol. The adduct is separated off, for example, by f;ltration~

The product is wh;te, solid, crystall;ne, finely pow-dered~ free-flowing, pourable and physiologicaLly tolera-ted.

It was surprising that, in spite of the high glycerol content (45~7~ weight/weight)~ the ~ovel substance is considerably less hygroscopic than anhydrous glycerolO

Another advantage is that the novel substance has a con-siderably h;gher short-term solubility than calcium lac-tate, as the following comparison shows:

Solubility in ~ater at room temperature under constant condit;ons Solubility after Calcium lactate Calcium lactate-(minutes) x 5 H20, MW=308 glycerol adduct __MW=402 5 ~inutes 7.7%tw/w)-1% of Ca 17.0%(w/w)=1.70% of Ca 15 minutes --17.0~(w/w)=1.70% of Ca 1440 minutes 7.7%(w/w)=1% of Ca 9.8%(~/w)=0.9B% of Ca (w/w = weight X) The low absorption of water vapor and the high solubility o~ calcium lactate-ylycerol adduct, combined ~ith the other propert;es mentioned, makes the novel substance suitable as an aux;liary ;n all cases where calcium is rer~uired w;th a good solubility and good processability, such as, for example, in pharmacy, cosmetics or produc-~ion of foodstuffs 13~5i7~

The novel substance has a neutral taste, so that it can also be used ~or oral caLcium ~herapyu All oral formula tion forms are suitable for this. They are prepared by known processes, i.eY the pulverulent, crystalline cal-S ciuw lactate-glycerol adduct is mixed ~ith the customary auxiliaries for the particular formulation form, and the mixture is granulated, if appropriate, and then pro-cessed, for example to tablets, solu~le or water-suspendible powders, granules, hard gelatin capsules and soft geLatin capsules.

The adduct can also be incorporated into foodstuffs and restGrative agents as a calcium donor. The adduct per se or the adduct in granule form is suitable for this~ The no~el sub~tance furthermore has a good dermal tolerabil-ity, so that it can also be used for dermal calciumtherapy. The anhydrous dermal formulation forms, such as, for example, ointments and powders, are preferably suitable for this. For this use form, the pulverulent, crystall;ne calcium lactate-glycerol adduct is m;cronized 2D and then incorporated into ointment and powder bases by known processes.

As well as having these possible uses in the field of foodstuffs and restorative agents and calcium therapy, calcium lactate-glyceroL adduct can also be used as a tableting aux;liary, for example for promoting compacting, instead of lac~ose or as a filler, on the bas;s of its phys;cal properties and technological peculiaritiesO

~ecause of its ~ood physiological tolerability and as a result of its favorable dissolving properties, the novel substance finds a particular use in solid drug delivery systems (DDS), for exampLe in moldings, extrudates, pellets or microcapsules, in that calcium lactate-gly-cerol adduct controls the release of the active sub-stances incorporated.

~3~

The corresponding known processes are used to produce the drug delivery systems.

From the pharmaceutical technology point of view and from the point of view o~ calcium therapy, the novel calcium S compound~ calc;um lactate-glycerol adduct, as a specific aux;l;ary for pharmacy and cosmet;cs, is a d;st;nct advance over the prior art because of its particular physical properties coupled with a good physiolog;cal tolerabil;ty.

Preparation Exa~ples Exa~pLe 1 30.8 9 of çalcium lactate x 5 H~0 are heated ;n a solu-t;on of 92.0 9 of anhydrous glycerol and 76.2 ml of methanol (anhydrous) under reflux for 10 minutes. The clear solution is cooled rapidly (5 minutes) to roo~
temperature and 115 m~ of~acetone are added. After the m;xture has been stirred for 24 hours, the crystals formed are filtered off with suction and dr;ed at room temperature in vacuo for 24 hours.

Y;eld: 37.6 9 = 93% of theory Exa~ple 2 30.8 9 of calcium lactate x 5 HzO are heated in 2 SOlU-t;on of 92.0 g of anhydrous glycerol and 76.2 ml of methanol (anhydrous) at 50C for 20 minutes, with st;rring. The clear solution ;s cooled slowly (2 hours) ~o room te~perature, ~;th st;rring, seeded and st;rred at room temperature for a further 24 hours. The crystal sludge formed is pressed off ~2.5 bar) and the filter cake is ~ashed w;th 50 ml of an acetone/me~hanol m;xture *

~3 : 1) and then dried ;n v~cuo at room temperature for 24 hours.
* parts by weight ~3~

Yield: 3Da6 9 = 76% of theory Ana~ysis of the reastion product:

Analytical result Theoretical value Calcium9.70X 9-95%
Lactate43070% 44.28X
Glycerol43.70% 45.70%

' :

Claims (4)

1. Calcium lactate-glycerol adduct of the formula I

(CH3-CHOH-COO)2 Ca x 2 H2COH-HCOH-H2COH I
2. A process for the preparation of the calcium lactate-glycerol adduct as claimed in claim 1, which comprises reacting calcium lactate with anhydrous glycerol in a molar ratio of 1 to at least 2, while warming in an anhydrous C1- to C3-alcohol, cooling the resulting clear solution and separating off the calcium lactate-glycerol adduct.
3. The use of the calcium lactate-glycerol adduct as claimed in claim 1 as a calcium donor in pharmacy, cosmetics and foodstuffs.
4. The use of the calcium lactate-glycerol adduct as claimed in claim 1 as an auxiliary in pharmacy and cosmetics.
CA 562536 1987-03-27 1988-03-25 Calcium lactate-glycerol adduct, a process for its preparation and itsuse Expired - Lifetime CA1305724C (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE19873710177 DE3710177A1 (en) 1987-03-27 1987-03-27 Calcium lactate-glycerol adduct, methods for its production and its use
DEP3710177.3 1987-03-27

Publications (1)

Publication Number Publication Date
CA1305724C true CA1305724C (en) 1992-07-28

Family

ID=6324158

Family Applications (1)

Application Number Title Priority Date Filing Date
CA 562536 Expired - Lifetime CA1305724C (en) 1987-03-27 1988-03-25 Calcium lactate-glycerol adduct, a process for its preparation and itsuse

Country Status (7)

Country Link
US (1) US5081150A (en)
EP (1) EP0288747B1 (en)
JP (1) JP2560073B2 (en)
CA (1) CA1305724C (en)
DE (1) DE3710177A1 (en)
DK (1) DK165988D0 (en)
ES (1) ES2022501B3 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5359831A (en) 1989-08-01 1994-11-01 United States Surgical Corporation Molded suture retainer
US5222978A (en) 1987-08-26 1993-06-29 United States Surgical Corporation Packaged synthetic absorbable surgical elements
US5366081A (en) 1987-08-26 1994-11-22 United States Surgical Corporation Packaged synthetic absorbable surgical elements
US5246104A (en) * 1989-08-01 1993-09-21 United States Surgical Corporation Molded suture retainer
WO2002034069A3 (en) * 2000-10-26 2003-03-13 Banner Pharmacaps Inc Supplement and method for nutritional supplementation of calcium, including a prophylactic motility agent

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA485664A (en) * 1952-08-12 Howards And Sons Limited Manufacture of addition compounds of lactic acid salts with acetic acid
DE331695C (en) * 1920-04-14 1921-01-10 Merck E A process for the preparation of a double salt of glycerophosphoric and lactic acid
US2420255A (en) * 1944-06-22 1947-05-06 Howards & Sons Ltd Manufacture of addition compounds of lactic acid salts with acetic acid
US4013773A (en) * 1971-12-09 1977-03-22 Yamanouchi Pharmaceutical Co., Ltd. Solid composition
JPS5629846B2 (en) * 1977-02-21 1981-07-10

Also Published As

Publication number Publication date Type
DK165988D0 (en) 1988-03-25 grant
JPS63264549A (en) 1988-11-01 application
DE3710177A1 (en) 1988-10-13 application
JP2560073B2 (en) 1996-12-04 grant
US5081150A (en) 1992-01-14 grant
ES2022501B3 (en) 1991-12-01 grant
EP0288747A1 (en) 1988-11-02 application
EP0288747B1 (en) 1991-05-29 grant
DK165988A (en) 1988-09-28 application

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