CA1120402A - Preparation and method for treatment of hypocalcemia, hypophosphatemia and downer cow syndrome in animals - Google Patents

Preparation and method for treatment of hypocalcemia, hypophosphatemia and downer cow syndrome in animals

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Publication number
CA1120402A
CA1120402A CA000306934A CA306934A CA1120402A CA 1120402 A CA1120402 A CA 1120402A CA 000306934 A CA000306934 A CA 000306934A CA 306934 A CA306934 A CA 306934A CA 1120402 A CA1120402 A CA 1120402A
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Canada
Prior art keywords
calcium
levulinate
lactate
chloride
ion
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
Application number
CA000306934A
Other languages
French (fr)
Inventor
Allen R. Carnes
Douglas D. Mann
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Individual
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Individual
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/14Alkali metal chlorides; Alkaline earth metal chlorides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

ABSTRACT OF THE DISCLOSURE

The invention relates to pharmaceutical prepara-tions comprising calcium lactate, calcium chloride and calcium levulinate. The solutions contain 7 to 28 grams of calcium ion with 10% to 30% of the calcium provided from calcium chloride, 20% to 60% from calcium lactate, and 20% to 60% from calcium levulinate and serves as an effective treatment for hypocalcemia, hypophosphatemia and downer cow syndrome.

Description

PREPAR~TION AND METHOD FOR TREATMENT OF HYPOCALCE-MIA, HYPOPHOSPHATEMIA AND DO~ER COW ~NDROME IN ANIMA~

The present invention relates to therapeutic calci-um electrolytic solutions ~or intravenous administration in ruminant animals suffering with the clinical signs or pathology of hypocalcemia, hypophosphatemia and downer cow syndrome. These conditions describe what is commonly known as ~milk fever~
In ruminant animals, the occurance of hypocalcemia has several profound effects. Physically, paresis is ex-hibited in varying degrees ranging from ataxia to para-plegia. Clinical pathology of the serum of these animals reveals significant decreases in serum calcium, serum phosphorus and declining insulin levels. Simultaneous-ly, the serum magnesium and serum glucose levels climb to abnormal highs.
Traditional treatment has consisted of the adminis-stration of calcium salts intravenously, subcutaneouslyor intramuscularly. Examples of these treatments are cal-cium salts such as calcium chloride, calcium gluconate, calcium borogluconate, calcium hypophosPhite, calcium lac-tate, calcium glycerophosphate, calcium levulinate used either alone or in combination or with salts of magnesium, potassium, phosphites and glucose~ Examples of prepa~a-tions previously tried are glven in U. S. Patents Nos.

1 2,140,291 and 3,553,148.
Calcium chloride, while providing a rapid response in the patient animals, has potential for toxicity and acute neart block if administered too raPidly or in too con-centrated a solution. Perivascular administration resultsin tissue necrosis.
Calcium borogluconate has the disadvantage of con-taining boron which is noted for its toxic effect on hepatic tissue making this salt, although widely used, 10 less than good therapy.
Calcium hypophosphite is proclaimed as a s~urce of ~both calcium and phosphorus. ~owever, studies have shown that the hypophosphite, in addition to being a strong re-ducing agent, i5 excreted in the urine, biologically un-15 changed and unutilized.
Certain combinations of calcium salts in suspensionhave been tried, i.e. calcium lactate and calcium gly-cerophosphate. This combination contains insufficient calcium ~o ~e efective by recommended intermuscula~ ad- :
20 ministration.
The addition of magnesium salts to these solutions is contraindicated since hypocalcemic ruminants already have an elevated serum magnesium level.
The addition of glucose to calcium solutions is 25 unacceptable. In order for the body to use glucose r it must utilize phosphorus from the serum thus aggravating the pre-existing hypophosphatemia. When serum phospho-rus levels drop low enough, a serious shift in the oxy-hemoglobin occurs which can result in tissue anoxia with 30 brain, hepatic and eryth~ocyte damage.
It is an object of this invention to provide a new ccmbination of calcium salts containinq calcium chloride, calcium lactate and calcium levulinate. This is a clear, stable, aqueous solution.
An important advantage of the present invention is to provide therapeutic solutions which produce a ra-pid rate of therapeutic response in the patient. A fur-3L~

1 ther impor-tant advantage is to provide such solutions which provide a high level of ccntinuing effectiveness after administratlon. Further important advantages of the invention are the provision of therapeutic electrolytic solutions having very low toxicity and lowered irrita-bility. The solutions also have the advantage of stabi-lity and ease of induction. ~nother advantage is the pre-sence in the solution of calcium lacta~.e which provides a vehicle for potential buffer formation thus avoiding un-desirable pH variations.
Calcium chloride, when used as 10~ to 30% of the cal-cium ion source in such combination of ingredients,provides a more rapid recovery without the previously noted toxicity effects.
~he calcium lactate supplying 20~ to 60% of the cal-cium ion source also provides the lactate fraction which may be converted to bicarbonate. This may provide a buffering capability ~o the solutions which restores the ruminant's base deficit ~hat exists in hypocalcemia and hypophosphatemia.
l'he calcium levulinate is an excellent source for 20 to 60~ of the calcium ions. Because it is non irritating it dilutes the irritating effect of the lactate and chloride salts.
The foregoing and related objects of the invention can be achieved by preparing an aqueous solution containing from 7 to 28 grams of dissolved calcium ion per 500 cc's of solution in the form of a water soluble mixture of calcium chloride, calcium lactate and -calcium levulinate. Such solu-tions have been found effective in formulations wherein 10%
to 30~ of the dissolved cal~ium ion is provided by calcium -chloride, 20% to 60-~ thereof by calcium lactate and 20~ to 60~ thereof by calcium levulinate.
Solutions of the present invention are preferably pre-pared by adding the salts in the foregoing proportions towater and heating the resultant mixture until all of the salts have been dissolved. The solution is then cooled and 3~

l filtered to remove impurities. The resulting solution is colorless and stable even at low temperatures and after long periods of storage.
The preferred formulation of this invention is a mix-ture in which calcium chloride furnishes 20~ o~ the calci-um ions by weight, calcium levulinate furnishes 40~ by weight and calcium lactate furnishes 40~ by weight. This specific combination after exte~sive testing has been determined to provideroptimum results in the treatment of dairy cows suffering ~rom the above no~ed milk fever symptoms.
In accordance with the present invention it has been determined that superior results are achieved in the treat-ment of ruminant animals suffering from milk fever symp-~oms by intravenous administration of the preparations of the present invention if they are free of sugars such as glucose or dextrose, free of boron compounds and free of magnesium compounds. These ingredients, which are usually present in commercially available preparations, have been found to be unnecessary or to cause undesirable complica-tions, or both.
It will be appreciated by those s~illed in the artthat the preparation of this invention can be modiied by the addition thereto in minor amounts of calcium acetate, calcium chlorate, calcium gluconate or calcium propionate without departing from the spirit of the invention~
While the foregoing discussion has contemplated the use of water as a preferred vehicle, or pharmaceu~ically acceptable base, for carrying the mixture o calcium salts of the present invention it will be apparent to those s~illed in t~e ar~ that other bases might be employed. Other modifi-cations falling within the purview of the invention will also be apparent to those skilled in the art.

- s -1 The following examples illustrate the principles and practice of the present invention.

A mixture consisting of 42.2 grams calcium lactate, 42.2 grams calcium levulinate and 8.32 grams calcium chloride was dissolved in 1000 ccls of QS water by heating and stirring. When all of the salts were completely dissolved, the solu~ion was cooled and filtered. The solution was ad-ministered to 83 dairy cows having mil]c fever symptoms.
The solution was administered in~ravenously in doses of 1000 cc's. Sixty-four of the cows got up without relapse after a single treatmen~ and recovered Eully. ~en of the cows recovered after two or more treatments~ Nine of the cows failed to recover after treatment.
A group of 147 dair~ cows suffering from milk fever symptoms was treated under similar controlled conditions with the largest selling commercially available formula-tion for treatment of milk fever, which was a solution de-termined to contain calcium borogluconate, dextrose, magne-sium and phosphorus compounds. Of these cows 111 recovered after one or more treatments of the solution by intravenous in~ection (76~. Thirty-six cows either died or had to be disposed of (24%). Thus the death rate of patients treated with the preparation of the present invention was considera-bly less than hal`f that experienced ~ith the leading commer-cially available preparation.

Tb 500 cc's dis~lled water were added enoug~ calcium ~ s to provide 7 grams of dissolved calcium ions. This consisted of suffi-30 cient calcium chloride to provide 2.1 grams of calcium ions, calciumlactate to provide 1.4 grams of calcium ions and calcium levulinate to pr~vide 3.5 grams of calcium ions. The weight percentages of the cal cium ions were thus provided in the ratio of 30~ frcm ca~ciu~ chloride, 20~ frcm calcium lac~ate and 50~ from calcium l~linate. The m~re 35 was formed into a solution by heatin~ the m~Yture~and was ~ subsequently filtered to remove impurities. The re~ting solution was colorless and could be autoclaved. The solution was intravenously admmistered to a z 1 dairy cow which had been diagnosed as suffering from hypo~
calcemla. The patient rapidly recovered af~er administration of the solution.
S EX~IPL13 3 To 500 cc's distilled water were added enough cal-cium compounds to provide 7 grams of dissolved calcium ions.
This consisted of sufficient calcium chloride to provide
2,1 grams of calcium ions, calcium lactate to pravide 3.5 grams o~ calcium ions and calcium levulinate to provide 1.4 grams of calcium ions. The weight percentages of the cal-cium ions were thus provided in the ratio o~ 30~ from cal-cium chloride, 50~ from calcium lactate and 20~ from cal-cium levulinate. The mixture was formed into a solut.ion by heating the mixture and was subsequently filtered to remove impurities. The resulting solution was colorle.ss and stable and could be au~oclaved. The solution was suitable for intra-venous administration to cattle suffering from hypocalcemia.
EX~tLE 4 To S00 cc's distilled water were added enough calcium compounds to provide 7 grams of dissolved calcium ions. This consisted of sufficient calcium chloride to provide 0.7 grams of calcium ions, calcium lactate to provide 3~15 grams of calcium ions and calcium levulinate to provide 3.15 grams of calcium ions. The weight percentages of the calcium ions were thus provided in the ratio of 10% from calcium chloride, 45% from calcium lactate and 45~ from calcium levulinate.
The mixture was formed into a solution by heating the mixture and was subsequently filtered to remove impurities. The re-sulting solution was colorless and stable and could be auto-claved. The solution was administered to a dairy cow which had bsen diagnosed as suffering from hypocalcemia. The pa-tient rapidly recovered a~ter administration of the solution, To 500 cc's distilled water were added enoush calcium compounds to provide 7 grams of dissolved calcium ions. This consisted of sufficient calcium chloride to provide 0.7 grams ` -l of calcium ions, calcium lactate to provide 2.1 grams of cal-cium ions and calcium levulinate to provide 4.2 grams of cal-cium ions. The weigh~ percentages of the calcium ions were thus provided in ~he ra~io of lO~ from calcium chloride, 30%
from calcium lacta-te and 60% from calcium levullnate. The mixture was formed into a solution by heating the mixture and was subsequently iltered to remove impuri.ties. The re-sulting soLution was colorless and stable and could be auto-claved. The solution was administered to a dairy cow which had been diagnosed as su~fering from hypocalcemia. The pa-tient rapidly recovered after administration of the solution.
EX~MPLE 6 To S00 cc's distilled water were added enough calcium compounds to provide 7 grams of dissolved calcium ions. This consisted of sufficient calcium chloride to provide 0.7 grams of calcium ions, calcium lac~ate to provide 4.2 grarns of calcium ions and calcium levulinate to provide 2.1 grams of calcium ions. The weight percentages of the calcium ions were thus provided in the ratio of 10% from calcium chloride, 60% from calcium lactate and 30% from calcium levu-linate. The mixture was formed into a solution by heating the mixture and was subsequen~ly filtered to remove impuri~
ties. The resulting solution was colorless and stable and could be autoclaved. The solu~ion was administered to a dairy cow which had been diagnosed as suffering from hypocalcemia.
The patienk rapidly recovered after administration of the so-lution.

~o 500 cc's distilled water were added enough calcium compounds to provide 7 grams of dissolved calcium ions. This consisted of sufficient calcium chloride to provide 1.5 grams of calcium ions, calcium lactate to provide 2.75 grams of cal-cium ions and calcium levulinate to provide 2.75 grams of cal-cium ions. The weight percentages of the calcium ions were thus provided in the ratio of 21.4% from calcium chloride, 39.3% from calcium lactate and 39.3% from calcium levulinate.
The mixture was formed into a solution by heating the mixture --8-- .

1 and was subsequently filtered to remove impurities. The re-sulting solution was administered to a dairy cow which had been diagnosed as suffering from hyp~calcemia. The patient rapidly recovered after administration of the solution.

Claims (9)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as:
1. A pharmaceutical composition for treating animals suffering with hypocalcemia and hypophosphatemia, comprising a mixture of calcium chloride, calcium lactate and calcium levulinate in such amounts as to provide about 7 to about 28 grams of calcium ion per 1,000 cc's when in aqueous solution, and wherein the proportions of calcium chloride, calcium lactate and cal-cium levulinate are such that the calcium chloride provides about 10% to 30% of the calcium ion, the calcium lactate pro vides about 20% to 60% of the calcium ion, and the calcium le-vulinate provides about 20% to 60% of the calcium ion.
2. A pharmaceutical composition which is free of sugar, boron compounds and magnesium oompounds useful for the treatment of animals by intravenous administration com-prising a pharmaceutically acceptable base and mixture of calcium chloride, calcium lactate and calcium levulinate in amounts sufficient to provide about 7 grams of calcium ions per 500 cc's when in solution, and the proportion6 of calcium chloride, calcium lactate and calcium levulinate being such that 10 percent to 30 percent of the calcium ions are provided by the calcium chloride, 20 percent to 60 percent of the calcium ions are provided by the calcium lactate and 20 percent to 60 percent of the calcium ions are provided by the calcium levulinate
3. A pharmaceutical composition for treating milk fever and downer cow syndromes in cattle comprising a water soluble mixture of calcium chloride, calcium lactate and cal-cium levulinate in such amounts as to provide from 7 to 28 grams of dissolved calcium per 1000 cc's of aqueous solution, with the calcium chloride, calcium lactate and calcium levu-linate being in such proportions in said mixture that the calcium chloride provides from about 10% to about 30% of the calcium, the calcium lactate provides from about 20% to about 60% of the calcium and the calcium levulinate from about 20% to about 60% of the calcium.
4. A pharmaceutlcal composition for treating milk fe-ver and downer cow syndromes in cattle comprising a water soluble mixture of calcium chloride, calcium lactate and cal cium levulinate in such amounts as to provide from 7 to 28 grams of dissolved calcium per 500 cc's of aqueous solution, with the calcium chloride, calcium lactate and calcium levu-linate being in such proportions in said mixture that the calcium chloride provides from about 10% to about 30% of the calcium, the calcium lactate provides from about 20%
to about 60% of the calcium and the calcium levulinate pro-vides from about 20% to about 60% of the calcium.
. A pharmaceutical composition for treating ani-mals suffering with hypocalcemia and hypophosphatemia, com-prising a mixture of calcium chloride, calcium lactate and calcium levulinate in such amounts as to provide about 7 to about 28 grams of calcium ion per l,OOO cc's when in aqueous solution, with the proportions of calcium chloride, calcium lactate and cal-cium levulinate being such that calcium chloride provides about 20% of the calcium ion, the calcium lactate provides about 40% of the calcium ion and the calcium levulinate provides about 40% of the calcium ion.
6. An aqueous solution containing from about 7 to 28 grams of dissolved calcium per 1000 cc in the form of a wa-ter soluble mixture of calcium chloride, calcium lactate and calcium levulinate, wherein 10% to 30% of the dissolved cal-cium is provided by calcium chloride, 20% to 60% thereof by calcium lactate and 20% to 60% thereof by calcium levulinate.
7. A clear, stable, autoclaved therapeutic electrolytic solution comprising from about 7 to 28 grams of dissolved cal-cium ions per 1000 cc wherein 10% to 30% of the dissolved cal-cium is provided by calcium chloride, 20% to 60% by calcium lactate and 20% to 60% by calcium levulinate.
8. An aqueous solution comprising calcium chloride, calcium lac-tate and calcium levulinate, with said solution containing from about 7 to 28 grams of calcium ion per 500 cc, wherein calcium chloride pro-vides from 10% to 30% of the calcium ion, calcium lactate provides from 20% to 60% of the calcium ion and calcium levulinate provides from 20%
to 60% of the calcium ion.
9. An aqueous solution comprising calcium chloride, calcium lactate and calcium levulinate, with said solution containing from about 7 to 28 grams of calclum ion per 500 cc's, and wherein 20% of the calcium ion in said solution is provided by calcium chloride, 40% of the calcium ion is pro-vided by calcium lactate and 40% of the calcium ion is provided by calcium levulinate.
CA000306934A 1977-07-14 1978-07-06 Preparation and method for treatment of hypocalcemia, hypophosphatemia and downer cow syndrome in animals Expired CA1120402A (en)

Applications Claiming Priority (2)

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US81549277A 1977-07-14 1977-07-14
US815,492 1991-12-31

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CA1120402A true CA1120402A (en) 1982-03-23

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AT (1) AT362955B (en)
AU (1) AU527439B2 (en)
BE (1) BE868956A (en)
CA (1) CA1120402A (en)
DE (1) DE2830636A1 (en)
DK (1) DK311178A (en)
FR (1) FR2413091A1 (en)
GR (1) GR64839B (en)
IL (1) IL55117A (en)
LU (1) LU79973A1 (en)
NL (1) NL7807610A (en)
NZ (1) NZ187856A (en)
ZA (1) ZA784001B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005117852A1 (en) * 2004-06-01 2005-12-15 Cameco Corporation Composition for treatment of a hydrofluoric acid burn

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005117852A1 (en) * 2004-06-01 2005-12-15 Cameco Corporation Composition for treatment of a hydrofluoric acid burn

Also Published As

Publication number Publication date
FR2413091B1 (en) 1981-05-08
ZA784001B (en) 1979-07-25
IL55117A (en) 1981-11-30
LU79973A1 (en) 1978-12-12
AU3797078A (en) 1980-01-17
FR2413091A1 (en) 1979-07-27
GR64839B (en) 1980-06-04
BE868956A (en) 1979-01-15
NZ187856A (en) 1981-05-01
IL55117A0 (en) 1978-09-29
NL7807610A (en) 1979-01-16
AU527439B2 (en) 1983-03-03
DE2830636A1 (en) 1979-01-25
ATA501478A (en) 1980-11-15
DK311178A (en) 1979-01-15
AT362955B (en) 1981-06-25

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