GB2153670A - A stable pharmaceutical composition for treating ketosis containing propylene glycol - Google Patents

A stable pharmaceutical composition for treating ketosis containing propylene glycol Download PDF

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Publication number
GB2153670A
GB2153670A GB08500143A GB8500143A GB2153670A GB 2153670 A GB2153670 A GB 2153670A GB 08500143 A GB08500143 A GB 08500143A GB 8500143 A GB8500143 A GB 8500143A GB 2153670 A GB2153670 A GB 2153670A
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GB
United Kingdom
Prior art keywords
propylene glycol
weight
per cent
pharmaceutical composition
magnesium
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
Application number
GB08500143A
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GB8500143D0 (en
GB2153670B (en
Inventor
Karoly Magyar
Ferenc Simon
Denes Bezzegh
Jozsef Kelemen
Gabor Zalai
Attila Mislei
Peter Sarkozi
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.)
Egyt Gyogyszervegyeszeti Gyar
Original Assignee
Egyt Gyogyszervegyeszeti Gyar
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Application filed by Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar
Publication of GB8500143D0 publication Critical patent/GB8500143D0/en
Publication of GB2153670A publication Critical patent/GB2153670A/en
Application granted granted Critical
Publication of GB2153670B publication Critical patent/GB2153670B/en
Expired legal-status Critical Current

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    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Obesity (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Fodder In General (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Saccharide Compounds (AREA)

Abstract

The pharmaceutical composition for treating ketosis comprises 50 to 80 per cent by weight of calcium propionate, 1 to 15 percent by weight of dextrose, 2 to 20 percent by weight of propylene glycol and 0.1 to 3 per cent by weight of additives, wherein the propylene glycol is bound to a solid carrier consisting of magnesium oxide, magnesium carbonate, magnesium peroxide and/or silica and the amount of the carrier ranges from 33 to 300 per cent by weight, calculated on the propylene glycol. The composition may also contain B vitamins, mineral salts e.g. Cu, Zn, Mn and Co salts, nicotinamide, tripelenamine HCl, and/or amino acids.

Description

SPECIFICATION A stable pharmaceutical composition for treating ketosis and a process for the preparation thereof The invention relates to a stable pharmaceutical composition and a process for the preparation thereof. The pharamceutical composition of the invention is suitable forthe treatment of ketosis in cows.
In cattle keeping the disease of ketosis in cows is more and more frequent as milk production becomes higher. The ketosis can be characterized by a degeneration of liver and the appearance of a fatty liver. The cause of this illness is that for about 2 months before calving the cows are fed with a fodder having too high protein and low carbohydrate content resulting in troubles in the metabolism at the time of calving. Due to the developed lactation ketosis, milk production is decreased. Especially the Holstein-Friesian species and their interbred offsprings are inclined to these troubles of metabolism.
In the moderate cases of ketosis daze or paralysis develops, while in the serious cases of ketosis the fat reserves of the cow deliberate, lipid appears in the blood and deposits in the liver, leading to an irreversible degeneration of liver and usually to the death of the animal.
Extremely high economical damages are produced by ketosis in cattle keeping since just the cows giving very much milk perish. In addition to the direct material losses it is a genetic damage, too, since the cows giving high quantities of milk are not able to transmit this property.
To avoid ketosis, the animals are fed with substances enhancing the glucose formation, e.g. propylene glycol, or directly with sugar. A well working pharmaceutical composition consists of calcium propionate, dextrose, propylene glycol and various additives. The formation of ketosis can be effectively inhibited if the cows are regularly treated with this composition.
In accordance with the known process, this pharmaceutical composition is prepared by admixing the solid components - i.e. every component except propylene glycol - and adding the propylene glycol to the solid mixture obtained directly before use, preferably by spraying. The composition prepared must be used within a short time since, owing to the hygroscopic nature of propylene glycol, the composition easily deliquesce on standing. Thus, it is not feasible to manufacture the known pharmaceutical composition as a powder mixture in forms suitable for use and to employ it like other pharmaceutical compositions at any time before the day of expiry. Therefore, propylene glycol must be introduced into the composition on the site of use. In most cases this is not feasible since the cattle keeping farms are not prepared for producing pharmaceutical compositions.Consequently, this effective prophylaxis of ketosis is barely employed presently.
Now it has been found that a stable pharmaceutical composition for treating ketosis can be obtained by binding the liquid propylene glycol to a solid carrier consisting of magnesium oxide, magnesium carbonate, magnesium peroxide andor silica.
The stable pharmaceutical composition of the invention comprises 50 to 80 per cent by weight of calcium propionate, 1 to 15 per cent by weight of dextrose, 2 to 20 per cent by weight of propylene glycol and 0.1 to 3 per cent by weight of additives, wherein the propylene glycol is used in such a form that it is bound to a solid carrier consisting of magnesium oxide, magnesium carbonate, magnesium peroxide, and/or silica, the amount of the carrier ranging from 33 to 300 per cent by weight, calculated on the propylene glycol.
The propylene glycol bound to the above solid carrier can be treated like a solid powder. Thus, each component of the pharmaceutical composition of the invention can be homogenized simultaneously. Of course, it is also feasible to transfer the components in optional order of succession to the blender being in operation.
The carrier comprising propylene glycol is prepared by admixing 25 to 75 per cent by weight of propylene glycol to 75 to 25 per cent by weight of magnesium oxide and/or magnesium peroxide and or magnesium carbonate a n d!or silica, preferably by spraying. In general, 80 per cent of the solid carrier are smaller than 10 Fm in particle size. The average particle size of the solid carrier is preferably 1 to 5 Wm. The thus-obtained solid mixture of high propylene glycol content can be treated like solid propylene glycol during mixing and does not deliquesce even when it is stored on air of 75 per cent relative humidity for a longer time such as 30 days.
A preferred carrier is the magnesium carbonate or a mixture of magnesium carbonate and silica or magnesium oxide and silica.
The additive of the pharmaceutical composition of the invention consists, in the first place of various vitamins, such as B,, B2, B6 and B12, and mineral salts, such as copper, zinc, manganese and cobalt salts, but can comprise also other biologically active substances, for example nicotininamide ortripelenamine hydrochloride [N,N-dimethyl-N'-benzyl-N'-(pydd-2-yl)-ethylenediamine hydrochloride].
The pharmaceutical composition of the invention is administered in the form of a suspension or it is admixed to the fodder. If a suspension is used, the pharmaceutical composition of the invention is suspended in a liquid, preferably in water. The pregnant cows are treated from about 2 to 3 weeks before calving until about 2 weeks after it.
It is preferred to fill such a quantity of the composition prepared by admixing the components thereof into suitable packing means such as plastic bags or containers that unit dosage forms are obtained. In this case one unit dosage form is used for each treatment.
The pharmaceutical composition of the invention is stable for at least one year when it is stored in the manner usual with pharmaceutical compositions. Thus, special precautions are not required. Economical production is possible in blenders of high capacity, and the continuous administration of the composition eliminates the ketosis of cows.
The invention is further elucidated by means of the following Examples.
Bonding propylene glycol to solid carrier 40 parts by weight of magnesium carbonate (average particle size: 1 to 2 Item; 80 per cent of the particles have a size of 0.5 to 5 'ism) are transferred into an eddy current blender of Lödige type equipped with spraying nozzles. Mixing is started and 50 parts by weight of propylene glycol are sprayed at a steady rate.
After completing the spraying, mixing is continued for a further hour, then 10 parts by weight of finely divided silica are added and the mixture is homogenized for further 10 minutes. The mixture obtained contains 50 per cent by weight of propylene glycol, 40 per cent by weight of magnesium carbonate and 10 per cent by weight of silica.
The following powder mixtures are prepared in a similar way: 60 per cent by weight of propylene glycol + 40 per cent by weight of magnesium oxide; 70 per cent by weight of propylene glyciol + 30 per cent by weight of magnesium carbonate; 52 per cent by weight of propylene glycol + 48 per cent by weight of magnesium peroxide; 75 per cent by weight of proplene glycol + 25 per cent by weight of silica; 50 per cent by weight of propylene glycol + 50 per cent by weight of magnesium carbonate; 25 per cent by weight of propylene glycol + 60 per cent by weight of magnesium carbonate + 15 per cent by weight of silica.
Example 1 Into a blender of Lödige type the following components are introduced in the given order: DL-methionine 7 kg calcium propionate 150 kg powder mixture comprising 50 per cent by weight of propylene glycol and 50 per cent by weight of magnesium carbonate 50 kg tripelenamine hydrochloride 0.5 kg vitamin B1 0.08 kg vitamin B2 0.13 kg vitamin B6 0.13 kg vitamin B12 6x10-5 kg nicotinamide 0.8 kg cupric sulfate pentahydrate 0.2 kg zinc sulfate pentahydrate 0.5 kg manganous sulfate 0.25 kg cobaltous sulfate heptahydrate '~ 0.01 kg dextrose to 225 kg The components are homogenized, then filled into polyethylene bags. Each bag contains 225 g of the above composition. This quantity is suitable for one treatment of one cow. The composition obtained is administered to the animals twice a day.
Example 2 Example 1 is repeated with the difference that a powder mixture comprising 60 per cent by weight of propylene glycol and 40 per cent by weight of magnesium oxide is used.
Example 3 Example 1 is repeated with the difference that a powder mixture comprising 52 per cent by weight of propylene glycol and 48 per cent by weight of magnesium peroxide is employed.
Example 4 Example 1 is repeated with the difference that a powder mixture comprising 25 per cent by weight of propylene glycol, 60 per cent by weight of magnesium carbonate and 15 per cent by weight of silica is employed.

Claims (9)

1. A stable pharmaceutical composition for treating ketosis comprising 50 to 80 per cent by weight of calcium propionate, 1 to 15 per cent by weight of dextrose, 2 to 20 per cent by weight of propylene glycol and 0.1 to 3 per cent by weight of additives, in which the propylene glycol is bound to a solid carrier consisting of magnesium oxide, magnesium carbonate, magnesium peroxide and/or silica, the amount of the carrier ranging from 33 to 300 per cent by weight, calculated on the propylene glycol.
2. A stable pharmaceutical composition as claimed in claim 1, in which the propylene glycol is bound to magnesium carbonate.
3. A stable pharmaceutical composition as claimed in claim 1, in which the propylene glycol is bound to a mixture of magnesium carbonate and silica or magnesium oxide and silica.
4. A process for preparing a stable pharmaceutical composition for treating ketosis by admixing 50 to 80 per cent by weight of calcium propionate, 1 to 15 per cent by weight of dextrose, 2 to 20 per cent by weight of propylene glycol and 0.1 to 3 per cent by weight of additives, in which the propylene glycol is bound to a solid carrier consisting of magnesium oxide, magnesium carbonate, magnesium peroxide and/or silica, and the amount of the carrier ranges from 33 to 300 per cent by weight calculated on the propylene glycol.
5. A process as claimed in claim 4, in which the propylene glycol is bound to magnesium carbonate.
6. A process as claimed in claim 4, in which the propylene glycol is bound to a mixture of magnesium carbonate and silica or magnesium oxide and silica.
7. A pharmaceutical composition for treating ketosis which composition comprises propylene glycol and one or more active agents useful for treating ketosis, wherein the propylene glycol is bound to a solid carrier in the form of magnesium oxide, magnesium carbonate, magnesium peroxide and/or silica.
8. A pharmeceutical composition substantially as hereinbefore described in any one of Examples 1 to 4.
9. A process as claimed in claim 4 substantially as hereinbefore described in any one of Examples 1 to 4.
GB08500143A 1984-01-06 1985-01-04 A stable pharmaceutical composition for treating ketosis containing propylene glycol Expired GB2153670B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
HU8440A HU191245B (en) 1984-01-06 1984-01-06 Process for the production of stbale pharmaceutical preparation against ketosis

Publications (3)

Publication Number Publication Date
GB8500143D0 GB8500143D0 (en) 1985-02-13
GB2153670A true GB2153670A (en) 1985-08-29
GB2153670B GB2153670B (en) 1988-03-23

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Family Applications (1)

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GB08500143A Expired GB2153670B (en) 1984-01-06 1985-01-04 A stable pharmaceutical composition for treating ketosis containing propylene glycol

Country Status (6)

Country Link
JP (1) JPS60214747A (en)
BE (1) BE901433A (en)
DE (1) DE3500187A1 (en)
FR (1) FR2565105B1 (en)
GB (1) GB2153670B (en)
HU (1) HU191245B (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2202742A (en) * 1987-03-26 1988-10-05 Univ London Preventing adp-ribosylation of g-proteins
WO1996008167A1 (en) * 1994-09-13 1996-03-21 Don J. Pestell Limited Composition for the treatment or prevention of an energy imbalance in ruminants
US5560920A (en) * 1995-04-07 1996-10-01 The United States Of America, As Represented By The Secretary Of Agriculture Calcium formulations for prevention of parturient hypocalcemia
US5601836A (en) * 1993-06-28 1997-02-11 Great Lakes Biochemical Company, Inc. Nutritional supplement for calving ruminant animals
US6126986A (en) * 1999-02-23 2000-10-03 Westway Trading Corporation Process for formulating a liquid animal feed ingredient containing sugar and neutralized carboxylic acid
US6183794B1 (en) 1997-03-21 2001-02-06 Basf Aktiengesellschaft Propionic acid, ammonia, propanediol and water solutions and the use thereof
CN104922064A (en) * 2015-05-28 2015-09-23 广东大华农动物保健品股份有限公司 Nano-scale nutrient microemulsion for preventing ketosis of dairy cows and preparation method thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU643703B2 (en) * 1989-09-15 1993-11-25 Cima Labs, Inc. Magnesium carbonate and oil tableting aid

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DE156999C (en) * 1902-04-02
US3196073A (en) * 1961-03-16 1965-07-20 Dow Chemical Co Method of tranquilizing with 1, 2-dihydroxy propane
FR1546819A (en) * 1967-01-14 1968-11-22 Union Agricole Ag Fuer Landw S Process for supplemental feeding of high-yield dairy cows, in particular before and after calving, and supplemental feed for the implementation of the process
US3621163A (en) * 1970-01-19 1971-11-16 Acb Corp Inertia switch
DE2014844C2 (en) * 1970-03-26 1984-09-06 Boliden Ab, Stockholm Process for the manufacture of a granulated magnesium oxide product
DE2518189A1 (en) * 1975-04-24 1976-11-04 Astra Ewos Ab Trace element concentrate for animal feeds - heavy mineral substance coated with binder which contains trace elements
SE421042B (en) * 1976-06-29 1981-11-23 Kockums Chem WANT TO REDUCE THE QUANTITY OF BIOLOGICAL ACTIVE SUBSTANCE REQUIRED FOR SOME BIOLOGICAL EFFECT
JPS5344636A (en) * 1976-10-05 1978-04-21 Mitsubishi Chem Ind Ltd Remedy and prevention for milk fever
GB1596505A (en) * 1976-11-23 1981-08-26 Unilever Ltd Food manufacture
DE3010250A1 (en) * 1980-03-17 1981-09-24 Wolf Freiherr von 8183 Rottach-Egern Tucher Animal e.g. pig feed pre:concentrate - to reduce odour of animal excrement contg. a poly:hydric alcohol, a saturated fatty acid and a carrier
AT372854B (en) * 1981-02-03 1983-11-25 Moser Siegfried Dr METHOD FOR PREVENTING THE DEVELOPMENT OF ENGRAVING HEALTH INTERFERENCE IN RETURNS AND FOR PREVENTING DEER BITE
US4486412A (en) * 1983-03-15 1984-12-04 Pharmacaps, Inc. Encapsulated antacid dispersions
HU191244B (en) * 1984-01-06 1987-01-28 Egyt Gyogyszervegyeszeti Gyar Dust mixture of high propylene-glycol content and process for producing same
HU190866B (en) * 1984-01-06 1986-11-28 Egis Gyogyszergyar,Hu Process for producing concentratum increasing the weight output and containing agent of 1-25 mass pct. and/or animal food containing agent of 0,001-0,075 mass pct.

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2202742A (en) * 1987-03-26 1988-10-05 Univ London Preventing adp-ribosylation of g-proteins
GB2202742B (en) * 1987-03-26 1990-11-28 Univ London Preventing adp-ribosylation of g-proteins
US5601836A (en) * 1993-06-28 1997-02-11 Great Lakes Biochemical Company, Inc. Nutritional supplement for calving ruminant animals
WO1996008167A1 (en) * 1994-09-13 1996-03-21 Don J. Pestell Limited Composition for the treatment or prevention of an energy imbalance in ruminants
US5660852A (en) * 1994-09-13 1997-08-26 Don J. Pestell Limited Composition for the treatment or prevention of an energy imbalance in ruminants
AU697784B2 (en) * 1994-09-13 1998-10-15 Don J. Pestell Limited Composition for the treatment or prevention of an energy imbalance in ruminants
US5560920A (en) * 1995-04-07 1996-10-01 The United States Of America, As Represented By The Secretary Of Agriculture Calcium formulations for prevention of parturient hypocalcemia
US6183794B1 (en) 1997-03-21 2001-02-06 Basf Aktiengesellschaft Propionic acid, ammonia, propanediol and water solutions and the use thereof
US6126986A (en) * 1999-02-23 2000-10-03 Westway Trading Corporation Process for formulating a liquid animal feed ingredient containing sugar and neutralized carboxylic acid
CN104922064A (en) * 2015-05-28 2015-09-23 广东大华农动物保健品股份有限公司 Nano-scale nutrient microemulsion for preventing ketosis of dairy cows and preparation method thereof

Also Published As

Publication number Publication date
GB8500143D0 (en) 1985-02-13
HUT37336A (en) 1985-12-28
FR2565105B1 (en) 1988-07-01
GB2153670B (en) 1988-03-23
JPH0324450B2 (en) 1991-04-03
JPS60214747A (en) 1985-10-28
FR2565105A1 (en) 1985-12-06
HU191245B (en) 1987-01-28
DE3500187A1 (en) 1985-07-18
BE901433A (en) 1985-07-03

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PCNP Patent ceased through non-payment of renewal fee

Effective date: 19970104