WO2016159898A1 - Slow release composition comprising potassium citrate and magnesium citrate - Google Patents
Slow release composition comprising potassium citrate and magnesium citrate Download PDFInfo
- Publication number
- WO2016159898A1 WO2016159898A1 PCT/TR2015/000137 TR2015000137W WO2016159898A1 WO 2016159898 A1 WO2016159898 A1 WO 2016159898A1 TR 2015000137 W TR2015000137 W TR 2015000137W WO 2016159898 A1 WO2016159898 A1 WO 2016159898A1
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- WO
- WIPO (PCT)
- Prior art keywords
- citrate
- slow release
- magnesium
- potassium
- potassium citrate
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/04—Drugs for disorders of the urinary system for urolithiasis
Definitions
- Potassium citrate is a potassium salt of citric acid (Molecular formula C 6 H 5 K 3 O 7 ). Molecular weight of anhidr and monohydraie compound is 306,39 g/mol and 324,41 g/mol. 1080mg of potassium citrate monohydrate equals 10 mEq potassium.
- Potassium citrate alkalinizes the urine and reduces the formation of the two most common types of kidney stones: calcium oxalate and uric acid stones.
- the citrate moiety which is largely oxidized, is absorbed while the K ion remains, leaving an alkali load.
- the alkali load increases urinary citrate and urinary pH. As a result, it decreases urinary saturation of calcium oxalate and inhibits both calcium oxalate and its crystallization.
- compositions comprising potassium citrate is indicated for the management of renal tubular acidosis (RTA) with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones.
- RTA renal tubular acidosis
- Mission Pharmacal sells an extended-release potassium citrate tablet, Urocit-K, in three strengths: 5 mEq, 10 mEq, and 15 mEq tablets.
- Urocit-K is a wax matrix tablet containing potassium citrate, carnauba wax as extended-release agent, and magnesium stearate as lubricant.
- WO 2014051443 discloses a new method for preparing extended-release potassium citrate tablet containing carnauba wax, wherein the potassium citrate and carnauba wax are mixed and heated to a temperature below the temperature at which carnauba wax liquefies.
- US20080131504 (Mission Pharmacal) relates to a novel short term slow release drug delivery system for solid oral dosage forms of water-soluble, alkaline salts of alkali metals and alkaline earth metals comprising polyvinylpyrrolidone and a cross-linked polyacrylic acid and preferably a wax component.
- Magnesium may help to prevent calcium oxalate stone development. Magnesium inhibits the growth of these stones in the test tube and decreases stone formation in rats.
- Magnesium citrate is a magnesium salt of citric acid (Molecular formula Mg 3 (C 6 H 5 O 7 ) 2 ). Molecular weight is 451 ,11 g/mol.
- US 4985593 relates to dual mineral salts comprising magnesium, potassium and citrate in a single compound.
- Dual mineral salt is synthesized by reacting stoichiometric quantities of citric acid, a magnesium compound and a potassium compound: Mg 2 + +4K + +2H 3 C 6 H 5 O 7 ⁇ MgK 4 (C 6 H 6 O 7 ) 2
- This dual salt comprise about 27 weight percent potassium, 4 weight percent magnesium, 68 weight percent citrate, and have a magnesium/potassium/citrate molar composition of 1 :4:2.
- This compound represents a densified source of potassium, magnesium and citrate, and is directly compressible.
- a tableting composition is formed by blending it with a lubricant, such as magnesium stearate.
- Potassium-magnesium citrate effectively prevents recurrent calcium oxalate stones, and this treatment given for up to 3 years reduces risk of recurrence by 85%. New calculi had formed in 63.6% of subjects receiving placebo and in 12.9% of subjects receiving potassium-magnesium citrate. (Ettinger B, et al Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis, J Urol. 1997 Dec;158(6):2069-73).
- the present invention relates to the slow release pharmaceutical composition
- the slow release pharmaceutical composition comprising potassium citrate and magnesium citrate for the treatment and prophylaxis of calcium renal stones in persons susceptible to such stone formations.
- Potassium citrate monohydrate uses in the composition.
- each slow release tablet comprising potassium citrate and magnesium citrate characterized in that,
- the amount of potassium citrate monohydrate is between 540mg (5mEq) and 2160mg (20mEq) in unit dosage form, and
- the amount of magnesium citrate is between 100mg and 400mg in unit dosage form.
- This invention relates to a new composition of potassium citrate and magnesium citrate in a slow release composition.
- each slow release tablet comprises potassium citrate monohydrate between 540mg (5mEq) and 2160mg (20mEq) and also magnesium citrate between 100mg and 400mg in unit dosage form.
- each slow release tablet comprises about 540mg of potassium citrate monohydrate and about 100mg of magnesium citrate. In another embodiment, each slow release tablet comprises about 1080mg of potassium citrate monohydrate and about 200mg of magnesium citrate
- each slow release tablet comprises about 2160mg of potassium citrate monohydrate and about 400mg of magnesium citrate.
- each slow release tablet comprises about 540mg of potassium citrate monohydrate and about 200mg of magnesium citrate.
- each slow release tablet comprises about 1080mg of potassium citrate monohydrate and about 400mg of magnesium citrate.
- each slow release tablet comprises about 540mg of potassium citrate monohydrate and about 187.5mg of magnesium citrate.
- each slow release tablet comprises about 1080mg of potassium citrate monohydrate and about 375mg of magnesium citrate.
- swelling and erodible polymeric substances are used for slow release. These polymeric substances release active pharmaceutical ingredients.when they contact with gastric and intestinal fluids.
- Polyvinylpyrrolidone also known as "PVP” or “povidone” and is a polymer of 1-vinylpyrrolidone
- PVP polyvinylpyrrolidone
- cross-linked polyacrylic acid waxes and polymeric substances having swelling and erodible characteristics
- the amount of the polymeric substances in the formulation is from 0.5% (w/w) to 10% (w/w) of cross-linked polyacrylic acid and from 1.0% (w/w) to 25% (w/w) of PVP.
- PVP All grades of PVP are useful in the present invention.
- Preferred grades of PVP include Povidone K25, Povidone K30, Povidone K60, and Povidone K90.
- Carbopol® (also known as Carbomer®) is a class of synthetic high molecular weight polymers of acrylic acid cross-linked with, for example, allyl ether of sucrose, allyl ether of pentaerythritol, and allyl ether of propylene.
- Preferred grades of Carbopol® include Carbopol® 974P, Carbopol® 1934, and any other Carbopol® approved for use in humans by official regulatory agencies.
- wax generally refers to a substance, which is a plastic solid at room temperature and a liquid of low viscosity above its melting point.
- waxes, fat or lipid have often been used interchangeably.
- carnauba wax is preferred.
- excipienis of pharmaceutical practice can be used as binder, disintegrant, glidant and lubricant.
- Magnesium stearate or other metal stearates, stearic acid and other fatty acids, colloidal silica, hydrogenated castor oil, substituted triglycerides and giycerides, various grades of polyethylene glycols (PEG) and derivatives thereof having a different molecular weight may be used as lubricant.
- These tablets may be coated by conventional means with known coating compositions.
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
The present invention relates to slow release tablet comprising potassium citrate and magnesium citrate for the treatment and prophylaxis of renal stones.
Description
SLOW RELEASE COMPOSITION COMPRISING POTASSIUM CITRATE AND MAGNESIUM CITRATE
DESCRIPTION
Potassium citrate is a potassium salt of citric acid (Molecular formula C6H5K3O7). Molecular weight of anhidr and monohydraie compound is 306,39 g/mol and 324,41 g/mol. 1080mg of potassium citrate monohydrate equals 10 mEq potassium.
Potassium citrate alkalinizes the urine and reduces the formation of the two most common types of kidney stones: calcium oxalate and uric acid stones.
The citrate moiety, which is largely oxidized, is absorbed while the K ion remains, leaving an alkali load. The alkali load increases urinary citrate and urinary pH. As a result, it decreases urinary saturation of calcium oxalate and inhibits both calcium oxalate and its crystallization.
Pharmaceuticals comprising potassium citrate is indicated for the management of renal tubular acidosis (RTA) with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones.
Mission Pharmacal sells an extended-release potassium citrate tablet, Urocit-K, in three strengths: 5 mEq, 10 mEq, and 15 mEq tablets. Urocit-K is a wax matrix tablet containing potassium citrate, carnauba wax as extended-release agent, and magnesium stearate as lubricant.
WO 2014051443 discloses a new method for preparing extended-release potassium citrate tablet containing carnauba wax, wherein the potassium citrate and carnauba wax are mixed and heated to a temperature below the temperature at which carnauba wax liquefies.
US20080131504 (Mission Pharmacal) relates to a novel short term slow release drug delivery system for solid oral dosage forms of water-soluble, alkaline salts of alkali metals and alkaline earth metals comprising polyvinylpyrrolidone and a cross-linked polyacrylic acid and preferably a wax component.
Magnesium may help to prevent calcium oxalate stone development. Magnesium inhibits the growth of these stones in the test tube and decreases stone formation in rats.
Magnesium citrate is a magnesium salt of citric acid (Molecular formula Mg3(C6H5O7)2). Molecular weight is 451 ,11 g/mol.
US 4985593 relates to dual mineral salts comprising magnesium, potassium and citrate in a single compound. Dual mineral salt is synthesized by reacting stoichiometric quantities of citric acid, a magnesium compound and a potassium compound:
Mg2+ +4K+ +2H3 C6 H5 O7→MgK4 (C6 H6 O7)2
This dual salt comprise about 27 weight percent potassium, 4 weight percent magnesium, 68 weight percent citrate, and have a magnesium/potassium/citrate molar composition of 1 :4:2.
This compound represents a densified source of potassium, magnesium and citrate, and is directly compressible. A tableting composition is formed by blending it with a lubricant, such as magnesium stearate.
Potassium-magnesium citrate effectively prevents recurrent calcium oxalate stones, and this treatment given for up to 3 years reduces risk of recurrence by 85%. New calculi had formed in 63.6% of subjects receiving placebo and in 12.9% of subjects receiving potassium-magnesium citrate. (Ettinger B, et al Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis, J Urol. 1997 Dec;158(6):2069-73).
SUMMARY OF THE INVENTION
The present invention relates to the slow release pharmaceutical composition comprising potassium citrate and magnesium citrate for the treatment and prophylaxis of calcium renal stones in persons susceptible to such stone formations. Potassium citrate monohydrate uses in the composition.
According to present invention, each slow release tablet comprising potassium citrate and magnesium citrate characterized in that,
a) the amount of potassium citrate monohydrate is between 540mg (5mEq) and 2160mg (20mEq) in unit dosage form, and
b) the amount of magnesium citrate is between 100mg and 400mg in unit dosage form.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to a new composition of potassium citrate and magnesium citrate in a slow release composition.
According to the invention, each slow release tablet comprises potassium citrate monohydrate between 540mg (5mEq) and 2160mg (20mEq) and also magnesium citrate between 100mg and 400mg in unit dosage form.
In one embodiment, each slow release tablet comprises about 540mg of potassium citrate monohydrate and about 100mg of magnesium citrate.
In another embodiment, each slow release tablet comprises about 1080mg of potassium citrate monohydrate and about 200mg of magnesium citrate
In another embodiment, each slow release tablet comprises about 2160mg of potassium citrate monohydrate and about 400mg of magnesium citrate.
in another embodiment, each slow release tablet comprises about 540mg of potassium citrate monohydrate and about 200mg of magnesium citrate.
In another embodiment, each slow release tablet comprises about 1080mg of potassium citrate monohydrate and about 400mg of magnesium citrate.
In another embodiment, each slow release tablet comprises about 540mg of potassium citrate monohydrate and about 187.5mg of magnesium citrate.
In another embodiment, each slow release tablet comprises about 1080mg of potassium citrate monohydrate and about 375mg of magnesium citrate.
In the present invention, swelling and erodible polymeric substances are used for slow release. These polymeric substances release active pharmaceutical ingredients.when they contact with gastric and intestinal fluids.
Polyvinylpyrrolidone (also known as "PVP" or "povidone" and is a polymer of 1-vinylpyrrolidone), cross-linked polyacrylic acid, waxes and polymeric substances having swelling and erodible characteristics is used as the said polymeric substances. The amount of the polymeric substances in the formulation is from 0.5% (w/w) to 10% (w/w) of cross-linked polyacrylic acid and from 1.0% (w/w) to 25% (w/w) of PVP.
All grades of PVP are useful in the present invention. Preferred grades of PVP include Povidone K25, Povidone K30, Povidone K60, and Povidone K90.
Carbopol® (also known as Carbomer®) is a class of synthetic high molecular weight polymers of acrylic acid cross-linked with, for example, allyl ether of sucrose, allyl ether of pentaerythritol, and allyl ether of propylene. Preferred grades of Carbopol® include Carbopol® 974P, Carbopol® 1934, and any other Carbopol® approved for use in humans by official regulatory agencies.
The term wax generally refers to a substance, which is a plastic solid at room temperature and a liquid of low viscosity above its melting point. In the pharmaceutical literature, the term waxes, fat or lipid have often been used interchangeably. In the present invention, carnauba wax is preferred.
Other excipienis of pharmaceutical practice can be used as binder, disintegrant, glidant and lubricant.
Magnesium stearate or other metal stearates, stearic acid and other fatty acids, colloidal silica, hydrogenated castor oil, substituted triglycerides and giycerides, various grades of polyethylene glycols (PEG) and derivatives thereof having a different molecular weight may be used as lubricant.
Other pharmaceutical inactive ingredients may also be used in the preparation of the present invention. Such ingredients are known to those of ordinary skill in the art.
These tablets may be coated by conventional means with known coating compositions.
Claims
1. A slow release tablet comprising potassium citrate and magnesium citrate characterized in that,
a) the amount of potassium citrate monohydrate is between 540mg (5mEq) and 2160mg (20mEq) in unit dosage form, and
b) the amount of magnesium citrate is between 100mg and 400mg in unit dosage form.
2. A slow release tablet according to claim 1 , wherein the amount of potassium citrate monohydrate is 2160mg (20mEq) and the amount of magnesium citrate is 400mg in unit dosage form.
3. A slow release tablet according to claim 1 , wherein the amount of potassium citrate monohydrate is 108Gmg (10mEq) and the amount of magnesium citrate is 200mg in unit dosage form.
4. A slow release tablet according to claim 1 , wherein the amount of potassium citrate monohydrate is 540mg (5mEq) and the amount of magnesium citrate is 100mg in unit dosage form.
5. A slow release tablet according to preceeding claims, wherein it comprises at least one polymer for slow release.
6. A slow release tablet according to claim 5, wherein slow release polymer is PVP or carbopol or carnauba wax.
7. A slow release tablet according to any of preceeding claims, wherein it uses for the treatment and preventing the formation of the kidney stones.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2015/000137 WO2016159898A1 (en) | 2015-04-01 | 2015-04-01 | Slow release composition comprising potassium citrate and magnesium citrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2015/000137 WO2016159898A1 (en) | 2015-04-01 | 2015-04-01 | Slow release composition comprising potassium citrate and magnesium citrate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2016159898A1 true WO2016159898A1 (en) | 2016-10-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2015/000137 WO2016159898A1 (en) | 2015-04-01 | 2015-04-01 | Slow release composition comprising potassium citrate and magnesium citrate |
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| WO (1) | WO2016159898A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022223650A1 (en) * | 2021-04-21 | 2022-10-27 | Prosalix Ag | Inhibition of crystallization and/or biofilm formation on an indwelling urinary catheter |
| WO2023272696A1 (en) * | 2021-07-01 | 2023-01-05 | 思瑰瑞保健食品有限公司 | Sustained-and-controlled-release potassium ion tablet and preparation method therefor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985593A (en) | 1988-01-05 | 1991-01-15 | Mission Pharmacal Company, Inc. | Magnesium potassium citrate |
| US20070003613A1 (en) * | 2005-04-05 | 2007-01-04 | Christy Martha M | Preparations to support maintenance of acid-alkaline balance in the human body and methods directed to using same |
| US20080131504A1 (en) | 2006-12-01 | 2008-06-05 | Mission Pharmacal Co. | Short Term Slow Release Drug Delivery System |
| WO2014051443A1 (en) | 2012-09-27 | 2014-04-03 | Mendoza Wendell G | Method for producing extended-release potassium citrate wax matrix tablet |
-
2015
- 2015-04-01 WO PCT/TR2015/000137 patent/WO2016159898A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985593A (en) | 1988-01-05 | 1991-01-15 | Mission Pharmacal Company, Inc. | Magnesium potassium citrate |
| US20070003613A1 (en) * | 2005-04-05 | 2007-01-04 | Christy Martha M | Preparations to support maintenance of acid-alkaline balance in the human body and methods directed to using same |
| US20080131504A1 (en) | 2006-12-01 | 2008-06-05 | Mission Pharmacal Co. | Short Term Slow Release Drug Delivery System |
| WO2014051443A1 (en) | 2012-09-27 | 2014-04-03 | Mendoza Wendell G | Method for producing extended-release potassium citrate wax matrix tablet |
Non-Patent Citations (1)
| Title |
|---|
| ETTINGER B ET AL.: "Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis", J UROL., vol. 158, no. 6, December 1997 (1997-12-01), pages 2069 - 73 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022223650A1 (en) * | 2021-04-21 | 2022-10-27 | Prosalix Ag | Inhibition of crystallization and/or biofilm formation on an indwelling urinary catheter |
| WO2023272696A1 (en) * | 2021-07-01 | 2023-01-05 | 思瑰瑞保健食品有限公司 | Sustained-and-controlled-release potassium ion tablet and preparation method therefor |
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