CALCIUM COMPOSITION The present invention relates to a composition for oral administration of a calcium compound to animals, both to monogastric animals such as dogs and to poly- gastric animals such as cattle, preferably cows, and a device for administering a composition according to an embodiment of the present invention. More specifically, the present invention concerns a composition for oral administration of calcium propionate in solid state to animals with a view to preventing the occurrence in poly- gastric animals of parturient pares, paresis puerperalis, calving paralysis or, as it is also referred to, milk fever, and preventing the occurrence in monogastric ani- mals of dystocia, so-called secondary uterine inertia, and eclampsia, so-called calcium deficiency in the blood plasma.

The composition according to the present invention can be used for oral administration to different kinds of animals, but in order to simplify the specification, it will be described based on oral administration to cows.

Calving paralysis can appear in connection with calving and is caused by calcium deficiency in blood plasma when the milk production has been initiated in connection with calving. The calcium deficiency makes the animal feel faint, and if calcium is not supplied, the calcium deficiency will affect the muscles, thus causing paralysis.

When calving paralysis has occurred, this state can be cured by means of an intravenous injection of a calcium compound. This makes it necessary to send for a veterinary, which involves heavy expenses for the owner of the animal.

The risk of calving paralysis can be reduced if, for prophylactic purposes, calcium is administered to a cow

before calving. This can be effected orally, which the owner of the animal can take care of on his own without sending for a veterinary.

There are today a number of various preparations for oral administration of calcium. One is a calcium chloride bolus, i. e. a moulded large tablet of calcium chloride which is administered orally by the aid of an administer- ing means, by means of which the bolus is thrown into the rumen of a cow. Calcium chloride, however, suffers from the drawback of being corrosive and therefore noxious to the mucous membranes in the rumen. However, the calcium chloride is a compound with high calcium availability, which has resulted in it being used despite the risk of the mucous membranes in the rumen being injured.

Apart from the calcium chloride bolus, there are also various gels and powders, the powder often being intended to be dissolved before administration or being intended to be added directly to the feedstuff. These gels and powders contain different calcium compounds.

US-A-5,560,920 discloses a gel comprising calcium propionate, propylene glycol and an acid, wherein the acid may consist of citric acid or phosphoric acid. US-A- 5,560,920 intends to solve the problem that in gels of calcium propionate and propylene glycol unmanageable hard gel masses often form which are difficult to eject from tubes and the like. This problem has been solved by add- ing an acid to the composition, which prevents the form- ing of these hard gel masses.

US-A-4,346,077 discloses a method for reducing the occurrence of calving paralysis by administration of a nutritional supplement of readily resorbable calcium after calving. This calcium is present in the form of a finely powdered calcium carbonate. Preferably, it is administered as a supplement to fodder or water.

The problems with gels and powders are that they are difficult to forcibly administer orally to cattle in a predetermined quantity.

As a rule, gels are administered by being poured into the mouth of the cow, but in such forced administra- tion there is a risk that part of the gel does not get into the gullet but rather into the trachea, which makes the cow feel uncomfortable and which may cause death by suffocation. The cow may be wilful and part of the gel gets outside the mouth and flows down onto the floor and part of it lands on the person administering the gel. In other words, this may be a rather smeary operation.

If the calcium compound furthermore comprises cal- cium chloride, it causes a corrosive feeling in the throat of the cow, and also a bitterness in the oral cavity, which increases the cow's reluctance of swallow- ing the preparation.

Powder is usually administered either mixed in the feedstuff or dissolved in water. In this type of admini- stration, there is a risk that the powder may give the water or the feedstuff an unnatural taste in the form of bitterness, which makes the cow refrain from drinking or eating. It may therefore be difficult to get the cow to take a sufficient amount of the composition at issue.

Regarding devices for administration of a bolus of calcium chloride, there are today different types of administering means. A common feature of these admi- nistering means is that they comprise a casing and a plunger, the casing having recesses for the plunger and the bolus. What is different is the way in which the bolus is held in place up to administration, as well as the administration mechanism.

One type of administering means has lugs arranged in the bottom of the recess, in which the bolus is mount- ed before administration. These lugs engage the bolus and hold it by partly deforming it until the plunger ejects it from the casing and into the stomach of the cow.

In another type of administering means, the casing is slit transversely of the radial plane in the part where the bolus is mounted before administration, and

the recess at this end has a smaller cross-sectional area than the bolus, whereby the bolus is clamped between the slots before administration, the plunger ejecting it from the casing and down into the stomach of the cow.

AU-B-72087/91 discloses one more type of administer- ing means. In the opening of this administering means, a spring-actuated locking flap is arranged, which prevents the bolus from falling out of the administering means before being pushed into the throat of a cow.

One object of the present invention is to provide a composition which does not have the drawbacks of the above compositions.

A further object of the present invention is to pro- vide an administering means for a composition according to an embodiment of the present invention.

Further objects, features and advantages of the pre- sent invention will appear from the following specifica- tion.

These objects are achieved by a composition accord- ing to appended claim 1 and a device according to append- ed claim 10. Particularly preferred embodiments are de- fined in the dependent claims.

In brief, the present invention concerns a composi- tion for oral administration of at least one calcium com- pound to animals, preferably as a preventive measure to reduce the occurrence of calving paralysis. According to the invention, the calcium compound comprises calcium propionate, and the composition is present in solid state and has the form of a standard dose, i. e. it contains the entire amount of calcium that is desired to be adminis- tered on a certain occasion.

Moreover, the present invention concerns a device for administering a composition according to an embodi- ment of the present invention.

The advantage of the present invention is that the solid composition in the form of a standard dose can be forcibly administered, i. e. one may be sure that the

entire dose has been administered to the cow. The compo- sition also has the advantage that there is no risk that the composition partly gets into the trachea instead of the gullet. Besides, the calcium propionate as a calcium source does not give any side-effects similar to those of calcium chloride.

Preferred embodiments of the present invention will now be described with reference to the accompanying draw- ings. These embodiments and drawings are not to be consi- dered restrictive to the scope of the present invention.

Fig. 1 is a side view of a composition according to Examples 1 and 3.

Fig. 2 is a sectional view along line II-II in Fig. 1.

Fig. 3 shows a composition according to Example 2.

Fig. 4 shows a composition according to Example 4.

Figs 5 and 6 show a preferred embodiment of the device for administering a composition according to Example 4.

The inventive composition can comprise, in addition to calcium propionate, other additives, such as cellu- lose, calcium carbonate, gypsum, magnesium stearate, cal- cium stearate and other known tablet additives.

When these additives are included in the composition according to the present invention, the amounts used are preferably as follows: 0.5-6% by weight cellulose, 1-17% by weight calcium carbonate, 0.5-17% by weight gypsum, 0.5-6% by weight magnesium stearate and 0.5-6% by weight calcium stearate, based on the total weight of the compo- sition.

Some of these additives, such as calcium carbonate or cellulose, preferably microcrystalline cellulose, may act as"explosives". When the composition contains these explosives, the following effect is achieved after admi- nistration: the composition is"burst"into small pieces, and the contact surface between the composition and the

rumen fluid increases, the calcium compounds added being resorbed and reaching the blood more quickly.

The solid form of the composition may consist of a bolus, which can be solid or divided into disks. In the latter case, the disks can be joined by means of a phar- maceutically acceptable binder, which is rapidly dissolv- ed in the neutral environment in the rumen of a cow.

Examples of such binders comprise gum arabic, carbohy- drates, glucoses, starch, casein, agar-agar, gluten, methyl cellulose, sodium alginate and potassium alginate, but use is preferably made of gum arabic. The disks can alternatively be arranged in a capsule which is dissolved in the rumen.

The bolus, either in solid form or divided into disks, can further be arranged in a sleeve surrounding the bolus until the composition is administered, the sleeve made of e. g. cardboard being held in an adminis- tering means, while the bolus is pushed into the gullet of the cow.

If the bolus is divided into disks when the compo- sition according to the present invention reaches the rumen, a larger contact surface is obtained between the rumen fluid and the composition, the dissolution rate of the composition increasing and the calcium compounds being more rapidly absorbed in the blood.

Below follow Examples of the preparation of the inventive composition.

Example 1 140 g calcium propionate were pressed radially in a steel die with a press power of 25 tonnes/cm2. A slightly elliptic bolus was obtained, having a length of 120 mm, a height of 40 mm and a width of 36 mm.

The obtained bolus had satisfactory strength and gave no corrosive effect when contacting mucous mem- branes.

Example 2 519 g calcium propionate were dry mixed with 115 g gypsum, in the form of calcium sulphate semi/hemihydrate (CaS04 x 1/2H20). Then 273 g demineralised water were added. After homogenisation of the composition, 146 g of the paste of the above-mentioned quantity were transfer- red to a Teflon die. The composition was compacted by vibration, whereupon it was pressed axially by means of a hydraulic press with a press power of 3 kN. The bolus formed was pressed out of the Teflon die, and was then allowed to mature at room temperature for 5-6 days so as to achieve a suitable physical storage life of the bolus.

The obtained bolus had good strength and gave no corrosive effect when contacting mucous membranes.

Example 3 114 g calcium propionate, 26 g gypsum in the form of CaSO4 x 2H2O, and 4 g microcrystalline cellulose were dry mixed. The composition was placed in an extrusion die, which had been sprayed with Teflon/silicone to achieve improved release from the die after compacting. The com- position was compacted radially to a bolus with a slight- ly elliptic cross-section, about 60% of the original volume remaining after being subjected to a pressure of 40 x 103 kg/m2 Example 4 57.5 g calcium propionate and 2.4 g microcrystalline cellulose were mixed in dry state. Aliqouts of 5 g of the composition were pressed to tablets by applying a pres- sure of 10 kN. 12 tablets were transferred to a cardboard sleeve.

Experimental Examples The different compositions according to the above Examples were examined in respect of dissolution and/or decomposition in vitro. The in vitro environment con- sisted of water at a temperature of 37°C, which should recreate the environment in the rumen of a cow where the pH was 6.5. In the cases where the composition contained

gypsum in some form, a complete dissolution of the gypsum was not always achieved, but a decomposition occurred, in which the remaining decomposed gypsum formed a calcium depot. The Table below shows the different dissolution times for the various compositions according to the pre- sent invention. Composition according to Decomposition Example (min) 1 36 2 40 3 90 4 5 As appears from the Table, the composition according to Example 4 had the best decomposition time, and this composition can be resorbed by a cow much more rapidly than the compositions according to the other Examples.

Preferred embodiments of the device according to the present invention for administering a composition accord- ing to Example 4 will be described below with reference to the accompanying Figs 5 and 6.

The device comprises a casing 1 and a plunger 2. The casing 1 has at its one end an opening 3 for receiving the plunger 2 and at its other end an opening 4 for receiving and discharging the composition 5 which is arranged in a sleeve 7. In the opening 4 of the other end there is also a means 6 adapted to hold the sleeve 7 when administering the composition, such that only the bolus is pushed forwards by the plunger 2 and administered orally to the stomach of the cow. The means 6 comprises in this embodiment a detachably arranged socket 6 having a flange 8, which peripherally covers the opening 4. This socket 6 can, for instance, be threaded onto the casing 1. Apart from the socket 6 having the function of holding the sleeve 7 in the interior of the casing 1 when admi- nistering the bolus to the cow, the socket 6 gives the

advantage of protecting the mucous membranes in the throat of the cow from being injured when inserting the device in the administration of the composition.

When the composition is to be placed in the device, the socket 6 is unscrewed, the sleeve 7 containing the composition 5 is inserted into the opening 4 of the cas- ing 1 and then the socket 6 is again screwed on. The com- position is then ready for oral administration to the cow.

The device according to the present invention can, of course, be used for administration of other mineral supplements which exist in the corresponding physical state.