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CA2137469A1 - Veterinary rehydration product - Google Patents

Veterinary rehydration product

Info

Publication number
CA2137469A1
CA2137469A1 CA002137469A CA2137469A CA2137469A1 CA 2137469 A1 CA2137469 A1 CA 2137469A1 CA 002137469 A CA002137469 A CA 002137469A CA 2137469 A CA2137469 A CA 2137469A CA 2137469 A1 CA2137469 A1 CA 2137469A1
Authority
CA
Canada
Prior art keywords
litre
millimoles
sodium
composition according
composition
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.)
Abandoned
Application number
CA002137469A
Other languages
French (fr)
Inventor
Drew Holmes
Alan Patterson
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.)
Norbrook Laboratories Ltd
Original Assignee
Individual
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
Application filed by Individual filed Critical Individual
Publication of CA2137469A1 publication Critical patent/CA2137469A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/42Phosphorus; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

A composition for the treatment of livestock suffering from disorders such as fluid depletion, acidosis, and imbalances or loss of essential electrolytes, same to be made up in water at point of use as an oral rehydration formulation, comprises an inti-mate mixture of an energy source, electrolytes, and bicarbonate precursors, which precursors are provided as physiologically ac-ceptable carboxylic acid anions with corresponding physiologically acceptable cations including sodium, the yield of bicarbonate being in excess of 30 millimole/litre (mmol/l) of final formulation, and the concentration of sodium being in excess of 80 mmol/l of final formulation.

Description

~ I W o 93/25214 213 7 4 6 9 P ~ /GB93/01220 VETERINARY REHYDRATION PRODUCT
~ his invention relates to veterinary produc~s for the ~reatmen~ of livestock suffering from disorders w~ich may arise from nutri~ional, bacterial, viral or protozoal causes and lead to fluid depletion, acidosis, and imbalances or loss of essential elect_olytes. These problems t~pica31y arise in immature an~m~l S such as calves and lambs.
The intestinal losses of water and elec~rolytes, including bicarbonate, are major fac~ors in the pathogenesis _o or diarrhoea in calves. Calf scour continues to represent a major ~inancial loss to the farmer and also a great deal o~
concern tO the veterinary pro~ession. Thus ~his invencion is primarily intended to be applied in rehabilitating ca1ves suff~r~ng from scour and descrlption of the invention here~n 1~ will ke related there~o. However it will be appreciated tha~ other ~nim~l S may also suffer f_om abnormal conditi~ns leading ~o similar dehydra~lon, acidosis and electro~y~e loss. Thus it could be used for promoting recovery of compecition horses severely stressed from fluid loss after a vigorous evenc.
The causes of dehydration have been well researched and although many interacring factors have to be considered it is observed that severe dehydration includes reduced fluid a~sorption as well as increased excretion and is accompanied __ by loss o~ sodium and other electro~ytes from the extracellular fluids. Acidosis, where blood pH drops from about 7.34 - 7.40 to a lower range of pernaps 6.8S - 7.15, is mainly attributable to increases in loss of bicarbonate ion, increases in lactic acid which dissociates to the ~actate and hydrogen ions, and additional factors such as increases in other organic acid levels produced by infecting bacteria. ~
Losses of sodium and bicarbonate ions are considered to be the most serious aspects of diarrhoea but losses or __ Dotassium and calcium are also observed. - .
There are already many veterinary products curren~ly availa~le which have varying degrees of ef~icacy with respect to replacement or electrolytes, correcrion of acidosis and provision or an energy sourcP. ~he Applicant's ~0 own L~fe Ald P (trade mark) is one such rehydration product, SUt~llUTESHEET

W093/2~21~ 1 3 7 4 6 9 ~ PCT/GB93/01220 wnil~t another is ~ectade Plus (traae mark~, of SmithKline Beecham ~nim~l Health.
Whereas rehyaration products may ~e ~nmi ni ~terea intrG~enously, orally, or suDcutaneously, ~he oral route is much preferred unless dehydration has alre'ady progressed to a serious leveL ~perhaps 6 to lO~ or above) when a combination of parenteral and oral ,.~m~ni stration is emplcyed. ^-An object of this invention is to provide an improved ~C veterinary product providing for effective rehydrationwhils~ countering metabolic acidosis more effectively than was previously possible.
Accordingly this invention provides a composition to be made ~ip in wa~er at point of use as an oral rehydration :_ formulation, ~hich composltion comprises an in~imate mlxcure of an energy source, electrolytes, and hicarDonate precursors, which precursors are provided as physiologically acceDtable carboxyllc acid anions with corresponding physiologically acceptable cations including sodium, ~he in vivo yield of bicar~onate being in excess of 3Q millimole per l_tre Immol/l), and the concentration of sodium being in excess of 80 mmol/l of final formulation. The composition preferaDly also contains potassium chloride and may conta~n Dotassium dlhydrogen orthophosphate to obtain an ionically ,_ balanced produc~.
PreferaDly the composition cont~i n~ d_ffering bicarbonate precursors to increase the probability of absorption and achieves a yield of about 50 to lO0 mmol/l ~ic~rhon~te.- The most preferred group of precursors includes alkali metal, especially sodium, salts of a tricar~oxylic acid and two other carboxylic acids.
Propionate (propanoate), acetate and citrate are the preferred bicar~onate precursors being converted to this anion in: vivo to yield the desired concentration.
3r~ ~etabolism of these precursors âlsO contributes to the energy yield of the present product.
The composition of this invention also contains a significantly greater level of energy source than prior art ~om~ositions prefera~ly in excess of 160 mmoi~l, and this is ~refera~ly as glucose to facilitate sodium u~take. A sliqht SU~IIUTESHEET

213746~ ~ ~ t~
O ,WO93/25214 PCT/GBg3/01220 hypertonici~y has been shown to ~e t~lerable (osmality 391.7 mmol/l in comparison with normal calf plasma at abou~
300 mmol/l) and this may arise i ~inal glucose concentration is in excess of abou~ 3~ but much greater _ _oncer.tr~tions are to be avoided.
The composition is preferably provided in particulate form e.g. as a substantially dry Dowder or granules but may alternatively be provided as a liouid con~entrate for dilution when required for ~mi ni ~tration.
;0 In the form of an intlma~e mix~ure of dry ttypically not more than abou~ l.8~ w/w water content) ~omponents of this invention (which may include a dessicant), the formulation is s~orage s~able for ex~ended periods.
This new product may be produced f_r distribution as a :_ substantially dry powder composition, or as a liquld concentrate for make up to a dosage formulation a~ poin- o~
use~ Whereas prior ~ormula~ions (including Li~e Aid p TM) have typically been distributed as two part powder composltions for subsequent mixing and maKe up with wa~er for use, one uniaue aspect of this lnvention lies in the composition being packaged as a single mix in a dosage quantity in a cont~i n~ such as a sachet, or capsule or example. This "one dosage per ~nim~l per sachet~ packaging greatly simpiifies ~m; ni stration. Thus the product may be ,-5 ideally packaged in sachets connec~ed by edge portions having perfora~ions for ease or separa~ion. The ~ - -practitioner or farmer ~ay there~y simply and reliably remove one dosage in a sachet and make up the formulation as directed fo~ ~;n;~tration to the sick ~n;m~l Other suitable packaging will be apparent to those in this .. ... . . ..
industry and no particular limitation is to be inferred.
Thus the product may be distributed as a plurality of sachets connected end to end as in a continuoùs strip pack which may be reeled for storage' or connectea eage to ëaqe as sheets of a convenient size. or the discre~e sache~s mav simply be loose filled in a suitable dispenser cont~;ning from l0 to 50 sachets.
The invention will now be further described by way o~
t~e following examples.

SU~IIUTE5HEET
. W O 93/25214 . PC~r/GB93/01220 ~ ~

_x~mnle 1 A water soiuble powder o~ the com~osi~ion shown i- the ~able below is contained in a single 165.9 g sachet wnich _orms an orange solution on mixing with wacer ~or oral ,,rlmini~tration. Apart ~rom the active ingredients listed in tne ta~le a drying agent e.g., silicon dioxide is included ar up ~0 3~ by weight and about 0.1~ by weight of a _olouring agent (Sunset Yellow) is incluaed to facilitate ~roduct identification after make up. These last ~0 -ngreaients may be varied (i.e., P~rh~nged for ~unctionai equivalents) wichou~ a~fec~ing the e~icacy o~ the ~omposition.
Table la __ Composition ~- ~w/w Active ~'~Ton~n tS
Sodium Citrate 5.895 2~
Sodium Acetate 3.279 Sodium Propionate 1.157 Sodium Chloride 2.821 Potassium Chloride 1.796 Dextrose 81.977 Auxiliary Additi~es Silicon Dioxide 3.015 3~ Sunset Yellow (dye) 0.06 .
The propionate, acetate and citrate ions togethe~ yield ~3 mmol/l bicarbonate. ~t is to be noted that the drying agent is insoluble and will remain in the mixing ~essel so ~hat on reconstitution with 2 litres or water the available concentrations are as indicated below.

SU~5 1 1 1 UTE 8HEET

~, ~ b 2 1 3 7 ~ 6 ~
, WO93/25214 . ~ . - PCT/GB93/01220 - ~ Table lb .

5 - C~rQn~nt . - - millimoles/litre Sodium . ~ 133`~
Potassium 20 ~.
LC
Chloride 60 Propionate 10 ~5 Acetate 33 Citrate 16.7 Dextrose 378 Exam~le 2 ~ .
A water soluble powder of the composition shown in the table below is contained in a single 83.74 g sachet which forms an orange solution on mixing with water for ora' 25 ~m;nl stration. Apart from the acti~e ingredients listed in the table a drying agent e.g. silicon dioxide is included at up to 3~ by weight and about 0.1 ~ by weight of a colouring agent (Sunset Yellow~ is included to facilitate product identification after make up. These last ingredien~s may be varied (i.e. P~rh~nged ~or functional equivalents) without affeccing the e~ficacy of the composition.
Table 2a C0m~p08ition% W~W r~
Act~ Ye c~ on tS
3~ Sodium Citrate 4.681 Sodium Acetate- ~ -~~ ` ~ ~ 3.917 ---Sodium Propionate 2.293 .. . . . . ~
Sodium Chioride . '.589 Potassium Chloride - ~ 3.559 40 Potassium Dihydrogen Ortho~hos~hace 1.624 Dex~rose . -. 75.237 SU~ UTE SI~EE 1 .

- ~ r 4 ~ PCT/GB93/01220 i ~

Auxil~ary additTves Silicon dioxide - - 3.000 Sunset Yellow (dye)~ ~ o . ïoo The propionate, acetate and citraTe ions together yield 50 mmol/l bicarbonate. It is to be noted_that the drying agen~ is insoluble and will remain in the mixing vessel so that on reconstitution with 2 litres o~ water the available iO concentrations are as indicated below.
Table 2b ComDonent millimoles/litre Sodium - go Potassium 25 ~5 Chloride 60 Phosphate 5 Propionate lO
Acetate 20 Citrate 6.67 GO Dextrose 175 ., .
The above for~ll~tions constitute a single dosage for the treatment of a calf suffering from scour and addresses the areas of electrolyte replacement, fluid replacement, 2~ correction of acido8is and provision of an energy source.

,, ., . ... ~ .,, . , .. ., ... ~. .. .. = .. . . . . .
The bulk material may be manufactured according to existing ph~rm~ceutical industry practice. Packaging thereof may also be carried out according to usual practice 30 Cor s;m; 1 ~r products. ~ -~ A cnmr~rison of the products of this invention with theprior art Tife Aid p TM and Lectade Plus TM iS represented in SUt~lll~JTESHEET

~ WO93/25214 ~13 7 4 6 ~ PCT/GB93/01220 Table 3 ~ife ~id prM ~m~le Example Lectade _ l 2 PlusTM
Con~tituent mmol~l mmol/l mmol/lmmol/l Glucose 112.5 378.0 175.0 158.2 l0 Glycine 4l.3 - - 20.0 Citrate - 16.7 6.7 9.5 Propionate 2.17 l0.0 l0.0 Acetate - 33.0 20.0 Phosphate l~.0 - 5.0 5.0 Sodium 75.7 133.0 90.0 49.5 Potassium '5.0 20.0 25.0 20.0 Chloride 73.6 60.0 60.0 39.3 ~5 Osmality 335.3 650.7 391.7301.~

The product of Exam~le 2 was evaluated against Lectade Plus TM as a positive control in a model of calf diarrhoea. The model used neonatal calves as the target species and a pathogenic specie-c o~ E. Coli as the test org~nicm ~which is widely accepred as being the cnmmnnect bacterial cause of diarrhoea in calves. As discussed ~y Bywater, R. J.
3~ ~merican Journal of Veterinary ~esearc~ 38, 1983 - 1987, ~s 1977), this model is nor. purely "coliform~; the E. Coli are -believed to facilitate the involvement of other pathogenic microor~n;c~c. It can therefore properly be regarded as a "mixed" infection. Moreover, the difficulties inevi~ably encountered in conducting clinical triais of neonatal diarrhoea and of sr~n~rdising important aspects of the trial under field conditions make the use of the disease model not only acceptable but preferable to field trials.
In addition, the reliable collection of quantitive scientific data under field conditions cannot be undertaken as readily as in a disease model.
Newborn calves of Ayrshire and Friesian breeds (7 Ayrshires and 2 Friesians in each treatment groupj were SUB~ ITE SHEET - -2137~69 ",,",.........
WO93/2S214 PCT/GB93/01220 ~

used. Their i ~ ~nological status was esta~lished by the ~inc sulphate turDidity test. Each cal~ was housed in an individual pen and maint~i nP~ ~ initially on a milk substitute product (2 l. per dayj. Clinical measurements 5 ~ and samples for laboratory analyses ~see ~elow ~or details~
were ta~en in healthy calves prior to in~ection.
E. Coli (strain B44) was used to establish the diarrhoea, ~ollowing ~ncl~h~tion at 34-37~ in Brain Heart Infusion Broth for 16 or 24 hours. Each cal~ received a lO ml aliquot of the culture cont~; ni ng lolO bacteria per ml orally twice daily for 2 days. Clinical e~m~n~tions were then carried out twice daily, with particular attention paid to ~aecal consistency, using the scoring system: l normal;
2 semi-solid; 3 diarrhoeic; 4 severely diarrhoeic. Calves with cumulative scores at a given level were deemed to have developed diarrhoea of su~icien~ severity to enter the ~reatment phases (phase II) o~ the study.
Of the ~nim~l ~ proceeding to Phase II, S0~ were assigned to Lectade Plus treatment and 50~ to LIFE-AID XTRA
therapy (~ormulations of this invention). Each calf received 2 litres of solution twice daily for 2 days, ~ollowed ~or 2 ~urther days by 2 litres of 50:50 mixture of oral re-hydration solution: milk replacer. ~n;m~l ~ then received 2 litres of milk replacer alone twice daily.
Efficacy was assessed: (a~ by clinical observations and measur~m~nts made twice daily and linked to a scoring system; (b) by ~iochemical analyses on plasma; (c) by measurement of haematological variables and; (d) by estimation ~f plasma volume using Evans Blue Dye. Variables (b~ and (c) were estimated at 24 hour intervals, from the time of cnmmPncing fluid therapy up to 96 hours and variables (d) were monitored twice, at 48 hour intervals from the time of CQmm~ncing ~luid therapy.
Prior to treatment, mean faecal scores of 2.89 (LIFE-AID XTRA group) and 2.67 (Lectade Plus group) were obtained, signifying a moderate degree of diarrhoea in both groups.
The reduction in faecal score was achieved more rapidly (16 hours) and the magnitude o~ the response was greater in the Calves receiving ~IFE-AID XTRA. Thus the percentage reductions, respecti~ely, at 88 and 96 hours were 46 and 46 SU~s~ ~ I I UTE SHEET

213~69 , g (LIFE-AID XTRA group3 and 17 and 29 (Lectade Plus group).
The overall impl~v~-,-el~t of ~nim~l s, as indicated in pre- and post treatment clinical scores was stm; 1 ~r in both treatment groups, although the response to LIFE-AID XTRA was again achie~ed more rapidly. Thus, the pre-treatment score of 1.9 was reduced to 0.3 (16 hours), 0.1 (24 hours~ and 0.2 (96 hours) after the comm~n~ement of LIFE-AID XTRA
treatment. Corresponding ~alues in the Lectade Plus group were 2.3 (pre-treatment3, 0.9 (16 hours), 0.6 (24 hours) and 1~ 0.2 (96 hours).
In this study a mild degree of acidosis was apparent in both treatment yroups at the start of the therapy. The total C02 concentration (which m.ay be regarded as a measure of plasma bicarbonate) was 27.0 mmol/l and 28.3 mmol/l at ~_ this time in TIFE-AID XTRA and Lectade Plus groups, respecti~ely. This ~ariable was increased only slightly in Lectade Plus treated ~nim~ls, by 8.6~ and 7.2~, at 24 and 48 hours, respec~i~ely. Corresponding in~reases in total C02 in the LIFE-AID XTRA treated Calves were 23.9~ and 29.0~, respectively, at 24 and 48 hours. These differences reflect the greater bicarbonate precursor concentration of LIFE-AID
XTRA (almost double that of Lectade Plus).
C~m~ed to the mean pre-infection ~alue, plasma volume -was reduced by 6~ in the LIFE-AID XTRA group and most of _ this deficit had been corrected at the 4~ hour measuring time. Mean plasm volume~ were 3.11 l (pre-infectionj, 2.81 l (time 0) and 3.05 l (48 hours).
A mild to moderate degree of haemoconcentration, indicated by 9.6~ (LIFE-AID XTRA group) and 5.7~ (Lectade Plus Group) increases in p.c.~., occurred in both treatment groups following the ectabl;~hm~nt of infection and prior to the A~m;ni ctration of fluids. With LIFE-AID XTRA the efficacy of re-hydration was indicated by a rapid decrease in p.c.v., an effect which was m~int~tn~ during and '_ ~ollowing fluid ~mint~tration. S;m;l~r, but somewhat smaller changes were obt~ i ne~ in the Lectade Plus group (Table 4).

SU~ ITE SHEET

2137~69 ~ t;' Table 4 Mean p.c.v. (n = 9) prior tO, during and following oral re-hydration.
~ife-Ald Xtra ~ Lectade Plus Time l l Change I ¦ Change (hours) ¦ (~) ¦ from controll (~ rom control Pre-infection 1 34.2 1 - I 36.8 0 1 37.5 1 +3.3 1 38.9 1 +2.1 24 1 32.3 1 -1.~ 1 36.1 1 -0.7 48 1 33.6 1 -0.6 1 36.8 1 0.0 72 1 32.3 1 -1.~ 1 35.9 1 -0.9 96 1 31.9 1 -2.3 1 35.~ 1 -1.3 In summary, the comparative trial in scouring calves yielded clinical signs of disease, including scours, and biochemical/haemotological evidence o~ mild/moderate dehydration and acidosis. In terms both o~ Clinical responses and biochemicalJhaematological changes, LIFE-AID
XTRA was shown to be at least as effective and, in several important respects, more Qffective than Lectade Plus.
Side-effects were not encountered in either group of Calves.
It is therefore concluded that LIFE-AID XTRA will be at least as effective as Lectade Plus in clinical use and hence more effective than the majority of other licensed oral re-hydration products.

,. ~, . . .

SUts~ I UTE SHEET

Claims (15)

  1. Claims l. A composition to be made up in water at point of use as an oral rehydration formulation, which composition comprises an intimate mixture of an energy source, electrolytes, and bicarbonate precursors, which precursors are provided as physiologically acceptable carboxylic acid anions with corresponding physiologically acceptable cations including sodium, the yield of bicarbonate being in excess of 30 millimole/litre (mmol/l) of final formulation, and the concentration of sodium being in excess of 80 mmol/l of final formulation.
  2. 2. A composition according to claim 1 further comprising potassium chloride and potassium dihydrogen orthophosphate.
  3. 3. A composition according to claim 1 or claim 2 wherein the composition contains a plurality of differing bicarbonate precursors to increase the probability of absorption.
  4. 4. A composition according to claim 3 wherein the composition contains bicarbonate precursors selected from alkali metal salts of a tricarboxylic acid and two other carboxylic acids.
  5. 5. A composition according to claim 4 wherein the carboxylic acid anions are citrate, acetate and propionate.
  6. 6. A composition according to any one of the preceding claims wherein the yield of bicarbonate is from about 50 to about 100 mmol/l of final formulation.
  7. 7. A composition to be made up in water according to any one of the preceding claims wherein the amount of energy source is in excess of 160 mmol/l of final formulation.
  8. 8. A composition according to claim 7 wherein the energy source is glucose in an amount of from 3 - 7 % by weight or the final formulation.
  9. 9. A composition according to any preceding claim which is in the form of a substantially dry powder.
  10. 10. A composition according to any preceding claim additionally comprising a dessicant.
  11. 11. A composition according to any one of claims 1 to 8 which is in the form of a liquid concentrate requiring dilution for administration.
  12. 12. A unitary dosage package of components to be made up in water at point of use as an oral rehydration formulation, which composition comprises an intimate mixture (approx %
    w/w) of sodium citrate (5.9), sodium acetate (3.3), sodium propionate (1.2), sodium chloride (2.8), potassium chloride (1.8), dextrose (82.0) with the balance consisting of a dessicant and a colouring additive.
  13. 13. A veterinary formulation in liquid form for oral administration comprising about 133 millimoles/litre sodium, about 20 millimoles/litre potassium, about 60 millimoles/litre chloride, about 10 millimoles/litre propionate, about 33 millimoles/litre acetate, about 16.7 millimoles/litre citrate, and about 378 millimoles/litre dextrose.
  14. 14. A unitary dosage package of components to be made up in water at point of use as an oral rehydration formulation, which composition comprises an intimate mixture (approx %
    w/w) of sodium citrate (4.7), sodium acetate (3.9), sodium propionate (2.3), sodium chloride (5.6), potassium chloride (3.6), potassium dihydrogen ortho-phosphate (1.6), dextrose (75.2) with the balance consisting of a dessicant and a colouring additive.
  15. 15. A veterinary formulation in liquid form for oral administration comprising about 90 millimoles/litre sodium, about 25 millimoles/litre potassium, about 60 milli-moles/litre chloride, about 5 millimoles/litre phosphate, about 10 millimoles/litre propionate, about 20 milli-moles/litre acetate, about 7 millimoles/litre citrate, and about 175 millimoles/litre dextrose.
CA002137469A 1992-06-16 1993-06-09 Veterinary rehydration product Abandoned CA2137469A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9212737.2 1992-06-16
GB929212737A GB9212737D0 (en) 1992-06-16 1992-06-16 Veterinary product

Publications (1)

Publication Number Publication Date
CA2137469A1 true CA2137469A1 (en) 1993-12-23

Family

ID=10717166

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002137469A Abandoned CA2137469A1 (en) 1992-06-16 1993-06-09 Veterinary rehydration product

Country Status (12)

Country Link
EP (1) EP0644767B3 (en)
JP (1) JPH07507788A (en)
AT (1) ATE157878T1 (en)
AU (1) AU669909B2 (en)
CA (1) CA2137469A1 (en)
DE (1) DE69313850T2 (en)
DK (1) DK0644767T3 (en)
ES (1) ES2108279T3 (en)
GB (1) GB9212737D0 (en)
GR (1) GR3025479T3 (en)
NZ (1) NZ253254A (en)
WO (1) WO1993025214A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016079640A1 (en) 2014-11-19 2016-05-26 Kalmarna Limited Oral rehydration composition and methods thereof

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2329336B (en) * 1996-05-14 1999-11-10 Norbrook Lab Ltd Oral rehydration product comprising glutamine
GB9609993D0 (en) * 1996-05-14 1996-07-17 Norbrook Lab Ltd Oral rehydration product
WO2021018938A1 (en) * 2019-07-29 2021-02-04 Nutreco Ip Assets B.V. Electrolyte composition and methods of use

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL175701C (en) * 1982-08-25 1984-12-17 Aesculaap Bv PREPARATION FOR THE PREPARATION OF AN ORAL ADMINISTRATIVE ANIMAL SOLUTION.
AU571011B2 (en) * 1983-10-07 1988-03-31 State Of Victoria, The Treatment of neonatal calf diarrhoea
NZ220230A (en) * 1986-05-09 1990-03-27 Beecham Group Plc Veterinary compositions containing dextrose and sodium, potassium, chloride, bicarbonate, magnesium, and citrate ions
US5096894A (en) * 1990-04-03 1992-03-17 Bristol-Myers Squibb Company Rice dextrin oral rehydration solution

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016079640A1 (en) 2014-11-19 2016-05-26 Kalmarna Limited Oral rehydration composition and methods thereof
US10463067B2 (en) 2014-11-19 2019-11-05 Kalmarna Limited Oral rehydration composition and methods thereof
EP3685682A1 (en) 2014-11-19 2020-07-29 Kalmarna Limited Oral rehydration composition

Also Published As

Publication number Publication date
EP0644767A1 (en) 1995-03-29
DE69313850T2 (en) 1998-01-22
EP0644767B1 (en) 1997-09-10
AU4343893A (en) 1994-01-04
DE69313850D1 (en) 1997-10-16
JPH07507788A (en) 1995-08-31
ATE157878T1 (en) 1997-09-15
EP0644767B3 (en) 2009-04-08
GB9212737D0 (en) 1992-07-29
WO1993025214A1 (en) 1993-12-23
NZ253254A (en) 1996-01-26
DK0644767T3 (en) 1997-10-13
AU669909B2 (en) 1996-06-27
ES2108279T3 (en) 1997-12-16
GR3025479T3 (en) 1998-02-27

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