IES80613B2 - Combined feed supplement and veterinary medicament composition - Google Patents

Abstract

The following are provided:- (a) a method for preparing a combined feed supplement and orally administrable veterinary medicament composition for the treatment of diarrhoea in domestic animals containing balanced proportions of electrolytes, sugar and vitamins of the B group, said composition being physically stable in sachets and multi-dose containers and being suitable for dissolution and suspension in water without appreciable formation of lumps, which method comprises dry blending the electrolytes, sugar and B vitamins with a commercially available hydroxyalkyl cellulose, together with at least one homogenising liquid excipient selected from the group comprising vegetable oils, fatty alcohols, lanolin derivatives, glycerol and propylene glycol; and (b) a combined feed supplement and orally administrable veterinary medicament composition for the treatment of diarrhoea or scour in domestic animals comprising 2% to 25% w/w of the composition hydroxyalkylcellulose, 40% to 90% w/w of the composition sugar and characterised in that it contains at least one homogenising liquid excipient selected from the group comprising vegetable oils, fatty alcohols, lanolin derivatives, glycerol and propylene glycol. The inclusion of the excipient enables a homogeneous mixture (with complete distribution of the low-quantity components) to be obtained which dissolves more satisfactorily in cold water.

Description

Combined feed supplement and veterinary medicament composition This invention relates to a combined feed supplement and orally administrable veterinary medicament composition for the treatment of diarrhoea in domestic animals, especially calves and piglets, and a method for preparing it.

Several such combinations are known which comprise balanced proportions of electrolytes, sugar and vitamins of the B group, with polysaccharide employed for its capacity to absorb water and form a gel which helps in the absorption and replacement of electrolytes lost to the gut, as well as in water retention. Such combinations are hereinafter called compositions of the type described.

Known compositions of the type described have several drawbacks, including inadequate solubility in cold water, and unsuitably low viscosity in the solutions thus produced. There are other problems including a problem with palatability, and a problem with the speed of onset of the therapeutic effect due to defective absorption of electrolytes and energy sources from the composition. A major defect is the tendency of the composition, which is commonly supplied as a dry powder, to form lumps on being added to water despite all efforts to produce a homogenous solution or suspension by agitation. A further defect of these compositions is the generation and containment of dust during both the manufacturing processes (blending and filling) and during the dissolution in water prior to administration. Another serious defect of these compositions is that they absorb moisture from the atmosphere and so must be packed in foil sachets to prevent moisture uptake.

To overcome some at least of the above disadvantages is among the objects of the invention; it seeks to provide a method for preparing a powdered composition of the type described, which shall be adapted on contact with water to form a smooth solution or suspension with little requirement for agitation to make it do so; and a composition thus prepared.

The invention accordingly provides a method for preparing a combined feed supplement and orally administrable veterinary medicament composition for the treatment of diarrhoea in domestic animals, especially calves and piglets, containing balanced proportions of electrolytes, sugar and vitamins of the B group, said composition being physically stable in sachets and multi-dose containers and being suitable for dissolution and suspension in water without appreciable formation of lumps, which method comprises dry blending the electrolytes, sugar and B-vitamins with a commercially available hydroxyalkyl cellulose, together with excipients which include at least one vegetable oil.

In a preferred embodiment, the vegetable oil(s) is/are added as the final step in the method.

The invention also provides a composition prepared by said method.

Preferably the alkyl component of the hydroxyalkyl cellulose is selected from methyl, ethyl and propyl. A particularly preferred alkyl component is ethyl.

A preferred quality specification for hydroxyethyl cellulose for use in the invention is that of the European Pharmacopoeia, which specification is hereby incorporated in the present disclosure by reference.

In a specially advantageous embodiment of the invention, the hydroxyethyl cellulose is a product available from Aqualon, a division of Hercules Incorporated and marketed under the trade mark NATROSOL. A product variety designated NATROSOL 250 HX Pharm is used for preference. The ratio of NATROSOL to salts and other solids ranges from 1:6.6 to 1:12.5.

In the commercial production of NATROSOL, high purity chemical cotton or wood pulp is treated with sodium hydroxide, which activates the three hydroxyl groups of each of the anhydroglucose units of the cellulose molecule. The activated groups are subsequently etherified with ethylene oxide to form hydroxyethyl ethers of cellulose. Moreover ethylene oxide, reacting with previously substituted hydroxyl groups, can cause polymerization to form a side chain. The reaction product is purified and ground to a fine powder.

The degree of molecular substitution (MS) of hydroxyethyl cellulose is defined as the average number of molecules of ethylene oxide that become attached to one anhydroglucose unit of the cellulose molecule. Complete and quick solubility in water is imparted to the product NATROSOL by selecting an appropriate MS and appropriate reaction conditions and controlling the uniformity of substitution. These procedures are employed by the manufacturers, of course, and do not form part of the invention.

Vegetable Oil(s) In a preferred embodiment of the invention, the vegetable oil(s), are added after the dry ingredients have been thoroughly blended, and the vegetable oil is gradually blended into the dry blended ingredients.

All common vegetable oils are suitable for this process. Preferred vegetable oils include coconut oil and especially preferred are the commercially available fractionated vegetable oils known as Miglyol 812 and Triol 91. These fractionated coconut oils meet the quality specification of the British and European Pharmacopoeiae.

Preferably, the vegetable oil is added as a fine spray to the dry blended ingredients. The quantity of vegetable oil added is sufficient to form a cohesive, dust-free readily water dispersable powder. The quantity of vegetable oil is not limited in this invention as the quantity required depends on the variable physical characteristics (particle size, surface area, etc.) of the powder components. Usually, a quantity of vegetable oil corresponding to approximately 5% of the composition is found to be suitable.

The addition of the vegetable oil is found to eliminate ( the creation of powder dust during the blending and filling of the composition as well as eliminating the creation of powder dust during the reconstitution of the composition with water. In addition the employment of the vegetable oil serves both to greatly increase the flowability of the composition and ensure greater product homogeneity during manufacture. During storage the presence of the vegetable oil serves to minimise the absorption of moisture from the atmosphere, and hence eliminates the lumping effect due to moisture uptake. As a result this composition is suitable for both packing either in sachets or in multi-dose containers which are open to the atmosphere during use. On reconstitution the presence of the vegetable oil serves to ensure that the powder composition is readily dispersable in cold water and as a result is rapidly dissolved.

The techniques used effectively separate the particles of hydroxyethyl cellulose so that no lumping is encountered when the dry mix is added to water. The product is a balanced combination of electrolytes and nutrients, which, when made up as disclosed above, provides a nearly isotonic solution of salts and nutrients for use as an aid in the treatment of diarrhoea in calves and piglets. It is primarily designed for use at the onset of diarrhoea. The product incorporates more energy sources, such as dextrose arid citrate, than most commercial products of this type. It is therefore considered particularly useful in the early stages of diarrhoea and in the convalescent stage where energy intake is important.

The major objective of oral electrolyte therapy is to correct dehydration and/or correct electrolyte imbalance, and to provide energy in neonatal diarrhoea. The product is approximately isotonic (Total mosm.L'1 = 321, from all sources; isotonic - 300 mOsm.L1) and provides circa 400 kcal.day'1 from 2.27 litres (4 pints) twice daily or approximately 20-25% of maintenance feeding.

The product, as stated, incorporates NATROSOL, a proprietary hydroxyethyl cellulose, which has the properties of non-ionic, highly purified cellulose.

This polyaccharide is not metabolised in the body and is effective by its capacity to absorb water forming a viscous gel. The powdered product is specially formulated to reduce powder dust problems during manufacture and dissolution and to facilitate homogeneous dispersion in water prior to administration. Once administered, the product rapidly exhibits its gelling property and promotes absorption and replacement of lost electrolytes. It also has excellent water retention properties.

The invention will be appreciated in greater detail from the following examples of specific and preferred embodiments thereof.

Example 1 To make a sample quantity of a combined feed supplement and orally administrable veterinary medicament composition, the following ingredients are dry blended together: Sodium chloride B.P 6.50 g Sodium citrate B.P 4.50 g Potassium chloride B.P. 2.50 g Potassium dihydrogen phosphate B.P. 1.30 g Hydroxyethyl cellulose 8.00 g Dextrose monohydrate B.P. 72.68 g Vitamin BI B.P. 75 mg Vitamin B2 B.P. 110 mg Vitamin B6 B.P. 40 mg Calcium pantothenate B.P. 150 mg Excipients to 100.00 g The excipients comprise vegetable oil(s) , aerosil (powdered silica) and colouring matter, the presence of the latter two being optional. The hydroxyethyl cellulose used is NATROSOL 250 HX Pharm. The vegetable oil(s) used are Miglyol 812 or Triol 91 and are added last. The composition, on being added to cold water, readily dispenses and dissolves without lump formation.

Example 2 A batch of combined feed supplement and veterinary anti-diarrhoeal medicament composition is made up under manufacturing conditions from the following ingredients using the amounts given, by the method described: 1. Sodium chloride B.P. 38.350 Kg 2. Sodium citrate B.P 26.550 Kg 3. Potassium chloride B.P. 14.750 Kg 4. Potassium dihydrogen phosphate B.P. 7.670 Kg 5. Thiamine hydrochloride B.P. 442.5 g 6. Riboflavin 5-sodium phosphate B.P. 649.0 g 7. Pyridoxine hydrochloride (Lutavit B6) 236.0 g 8. Calcium pantothenate B.P. powder 885.0 g 9. Hydroxyethyl cellulose Pharm. Eur. 47.920 Kg 10. Aerosil 200 B.P. 590.0 g 11. Dextrose monohydrate B.P. 421.826 Kg 12. Ariavit Quinoline Yellow E 104 119.8 g 13. Triol - 91 - approx. 30.000 Kg Batch weight 590.000 Kg 1. load a suitable blender with half the formula amount of Dextrose monohydrate (1.210Kg); 2. add, while mixing, ingredients numbered 1, 2, 3, 4, 9, 12, 5, 6, 7, 8 and 10 in that order, and blend for five minutes; 3. add the remainder of the Dextrose monohydrate and blend for a further five minutes; 4. weigh and add very slowly ingredient 13 (vegetable oil) and continue mixing until all the oil is mixed in and homogeneously distributed; . if the powder is dusty to the touch and does not come off cleanly from the surface of the blender, add a small amount of ingredient 13 (vegetable oil) and mix until homogeneous; record the additional quantity of oil used; 6. submit a sample from the batch to the lab for assay and dispersion test in water; and 7. fill the product into either foil/PVC sachets or multi-dose containers .

The invention is not limited by or to the details of the embodiment described, many of which can be widely varied without departing from the scope of the invention.

Claims (5)

1. A method for preparing a combined feed supplement and orally administrable veterinary medicament composition for the treatment of diarrhoea in domestic 5 animals containing balanced proportions of electrolytes, sugar and vitamins of the B group, said composition being physically stable in sachets and multi-dose containers and being suitable for dissolution and suspension in water without appreciable 10 formation of lumps, which method comprises dry blending the electrolytes, sugar and B vitamins with a commercially available hydroxyalkyl cellulose, together with excipients which include at least one vegetable oil. 15

2. A method as claimed in Claim 1 characterised in that the vegetable oil is added as the final step in the method.

3. A method as claimed in Claim 1 or Claim 2 characterised in that the alkyl component of the 20 hydroxyalkyl cellulose is selected from methyl, ethyl and propyl.

4. A method for preparing a combined feed supplement and orally administrable veterinary medicament composition substantially as hereinbefore described with reference to the examples.

5. A combined feed supplement and orally administrable veterinary medicament composition whenever prepared by a method as claimed in any of 5 Claims 1 to 4.