CA1305724C - Calcium lactate-glycerol adduct, a process for its preparation and itsuse - Google Patents
Calcium lactate-glycerol adduct, a process for its preparation and itsuseInfo
- Publication number
- CA1305724C CA1305724C CA000562536A CA562536A CA1305724C CA 1305724 C CA1305724 C CA 1305724C CA 000562536 A CA000562536 A CA 000562536A CA 562536 A CA562536 A CA 562536A CA 1305724 C CA1305724 C CA 1305724C
- Authority
- CA
- Canada
- Prior art keywords
- glycerol
- calcium lactate
- adduct
- calcium
- preparation
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
- C07C59/08—Lactic 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%
' :
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
(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.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3710177.3 | 1987-03-27 | ||
| DE19873710177 DE3710177A1 (en) | 1987-03-27 | 1987-03-27 | CALCIUM LACTATE-GLYCERINE ADDUCT, METHOD FOR THE PRODUCTION AND USE THEREOF |
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 |
|---|---|---|---|
| CA000562536A Expired - Lifetime CA1305724C (en) | 1987-03-27 | 1988-03-25 | Calcium lactate-glycerol adduct, a process for its preparation and itsuse |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5081150A (en) |
| EP (1) | EP0288747B1 (en) |
| JP (1) | JP2560073B2 (en) |
| AT (1) | ATE63898T1 (en) |
| AU (1) | AU602201B2 (en) |
| CA (1) | CA1305724C (en) |
| DE (2) | DE3710177A1 (en) |
| DK (1) | DK165988A (en) |
| ES (1) | ES2022501B3 (en) |
| GR (1) | GR3002215T3 (en) |
| IE (1) | IE60853B1 (en) |
| PT (1) | PT87071B (en) |
| ZA (1) | ZA882146B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US5359831A (en) | 1989-08-01 | 1994-11-01 | United States Surgical Corporation | Molded suture retainer |
| US5246104A (en) * | 1989-08-01 | 1993-09-21 | United States Surgical Corporation | Molded suture retainer |
| AU2002234178A1 (en) * | 2000-10-26 | 2002-05-06 | Banner Pharmacaps Inc. | Supplement and method for nutritional supplementation of calcium, including a prophylactic motility agent |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA485664A (en) * | 1952-08-12 | Hart Lock Ritchie | Manufacture of addition compounds of lactic acid salts with acetic acid | |
| DE331695C (en) * | 1920-04-14 | 1921-01-10 | Chem Fab | Process for the production of a double salt of glycerol phosphoric acid 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 |
| JPS53104720A (en) * | 1977-02-21 | 1978-09-12 | Yamanouchi Pharmaceut Co Ltd | Calcium lactate hydrate and its preparation |
-
1987
- 1987-03-27 DE DE19873710177 patent/DE3710177A1/en not_active Withdrawn
-
1988
- 1988-03-24 DE DE8888104745T patent/DE3862994D1/en not_active Expired - Lifetime
- 1988-03-24 EP EP88104745A patent/EP0288747B1/en not_active Expired - Lifetime
- 1988-03-24 AT AT88104745T patent/ATE63898T1/en not_active IP Right Cessation
- 1988-03-24 ES ES88104745T patent/ES2022501B3/en not_active Expired - Lifetime
- 1988-03-24 AU AU13554/88A patent/AU602201B2/en not_active Ceased
- 1988-03-24 PT PT87071A patent/PT87071B/en not_active IP Right Cessation
- 1988-03-25 JP JP63069924A patent/JP2560073B2/en not_active Expired - Lifetime
- 1988-03-25 ZA ZA882146A patent/ZA882146B/en unknown
- 1988-03-25 DK DK165988A patent/DK165988A/en not_active Application Discontinuation
- 1988-03-25 CA CA000562536A patent/CA1305724C/en not_active Expired - Lifetime
- 1988-03-25 IE IE91088A patent/IE60853B1/en not_active IP Right Cessation
-
1990
- 1990-04-12 US US07/512,078 patent/US5081150A/en not_active Expired - Lifetime
-
1991
- 1991-06-28 GR GR91400799T patent/GR3002215T3/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE880910L (en) | 1988-09-27 |
| ES2022501B3 (en) | 1991-12-01 |
| JP2560073B2 (en) | 1996-12-04 |
| IE60853B1 (en) | 1994-08-24 |
| EP0288747B1 (en) | 1991-05-29 |
| AU602201B2 (en) | 1990-10-04 |
| DK165988A (en) | 1988-09-28 |
| ZA882146B (en) | 1988-09-12 |
| DE3862994D1 (en) | 1991-07-04 |
| EP0288747A1 (en) | 1988-11-02 |
| PT87071B (en) | 1992-07-31 |
| DK165988D0 (en) | 1988-03-25 |
| ATE63898T1 (en) | 1991-06-15 |
| AU1355488A (en) | 1988-09-29 |
| US5081150A (en) | 1992-01-14 |
| PT87071A (en) | 1988-04-01 |
| GR3002215T3 (en) | 1992-12-30 |
| DE3710177A1 (en) | 1988-10-13 |
| JPS63264549A (en) | 1988-11-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |