Controlled release protective matrices for zootechnical and veterinary use

Abstract: This invention concerns compositions for zootechnical and veterinary use, characterized in that biologically active substances are incorporated in protective matrices, which have the following properties: 1) controlled release (ruminal by-pass) effect; 2) chemical-physical protection of active principles against degradation induced by technological processes of production, storage and pellettization of fodders for all animal species. The matrices object of the invention are characterized by a plastic rheological behaviour due to the presence of lipogelling agents. The obtained products show the following advantages: - increased active principle stability in feeds for to all animal species; - protection of the active principles from attack of Rumen microorganisms in fodders for ruminants.

Description: The present invention relates to compositions for zootechnical and veterinary use with ruminal by-pass effect and/or suitable to preserve biologically active principles, from the chemical-physical degradation occuring in feed, to protective matrices employed in said compositions and to a process for the preparation thereof as defined by present claims 1 to 7. In every field of the industrial zootechnical stock farming, completion of alimentary diet with some biologically active principles is needed, said principles being suitable to cover possible metabolic deficiencies or to increase productive efficiencies, as well as treatment for preventive or therapeutic purpose with different kind of drugs (antibiotics, chemotherapeutic drugs etc.). Substances used for alimentary completion and for therapeutic purpose may undergo a loss of titre, more or less notable, depending on the nature thereof, due to technological processes of production, storage and pellettization of feed. This results in a lack of agreement between the expected dose and the actually administered dose of active principles. In polygastric animals an amount of active principles orally administered is in its turn consumed by Rumen microorganisms and this involves the consequent problems: 1) remarkable degradation of active principles such as vitamins, amino acids and proteins with a consequent drastic decrease in systemic supply; 2) antibacterial action of the administered drugs against ruminal microorganisms making ineffective the oral therapy in ruminants. In short, an optimal zootechnical or veterinary composition should: for all animal species: grant titre stability of the active principles contained therein, even if subjected to a drastic treatment such as pelletization; for ruminants: enable a rumen by-pass effect, in order to provide suitable systemic supply of the administered active principles and enable antibiotic treatments by the oral route. The problems cited above are not satisfactorily overcome by the actually available zootechnical compositions. The use of alkaline earth soaps as fatty carriers in ruminants is known. Indeed, calcium by-passes rumen (by-pass effect) and releases in abomasum the fatty acid which can be used in metabolism. EP-A 0037478 discloses compositions for administering active principles containing a sodium, potassium or calcium soap combined with long-chain fatty acids and/or hydrogenated fats. Ruminal protection systems have been developed with long chain fatty acids, but said systems besides not granting a complete by-pass effect, markedly degrade some of the utilized active principles e.g.: A Markus et al. : "Encapsulation of vitamin A", J. Microencapsulation 6(3), 389-94). It has now been found that protective matrices as defined by the claims can improve stability of the active principles therein, due to the chemical-physical properties thereof, with the following advantages: a) Low heat transmissivity with consequential decrease of incidence of the thermochemical degradation of the active principles held in the matrix. b) Decreased permeability to light and therefore decreased photolysis. c) Remarkably decreased oxidative processes of the active principles which are protected from direct air-oxygen contact due to the protective film thereover. d) High resistance to hydrolytic reactions of active principles given by the hydrophobic nature of the matrix. e) Disappearance of interactions between various active principles and between these and the substrate. f) Increased resistance to pellettization. Ruminal by-pass effect is obtained due to the following matrix characteristics: 1) presence in the interior of the matrix of a tridimensional network substance which, incorporating the active principle, avoids ruminal microorganisms attack. 2) high melting point of the preparation. In reticulum and abomasum these materials do not undergo peculiar transformations. Once in the abomasum, the matrices undergo a first degradation due to the high acidity present, which splits molecules from the gelling agent causing a decreased consistency and an increased porosity of the material. The so transformed material reaches duodenum where it is emulsified by bile acids and therefore completely releases the active principles contained therein, which are absorbed in the following segments of intestine. The use of active principles, protected by the materials object of the present application, in ruminant feed field, shows the following advantages: a) increased systemic supply of biologically active principles introduced by diet; b) disappearance of negative phenomena against rumen microorganisms, due to oral administration of antibiotic or chemoterapeutic drugs. The compositions according to the present invention are obtained by a process consisting of the following steps: step 1: melting lipidic material and mixing the mass; step 2: adding solutions of lipogelling agents and/or lyophobic or lyophilic colloids; step 3: controlling chemical-physical parameters and adding the active principles; step 4: drying under odinary or reduced pressure the so obtained material. Lipogelling agent to total mass ratio may range widely, generally from 1 to 90% by weight. Nevertheless, a weight ratio from 2 to 80%, more preferably from 5 to 50%, is preferred to obtain better rheological characteristics. Under these conditions a matrix is obtained, which is notably desired for the foreseen uses. The active principles, which can be included in the matrices of the invention, are those commonly used in zootechnics or veterinary, for instance B group vitamins, liposoluble vitamins (A, D, E), choline, amino acids, proteins, antibiotics (for instance tetracycline, erithromycine, β-lactams etc.), chemotherapeutic drugs. The amount of active principles in the compositions will be obviously defined by the kind of the active principle itself or by the intended purpose and it will be easily determined by those skilled in the art. The compositions object of the invention can obviously contain other excipients or additives, such as flavours, antioxidants, fillers etc., which will be used according to the conventional modalities. The following examples are given for illustrative purposes. EXAMPLE 1 Formulation for zootechnical use of vitamin A and E. Vitamin A I.U. 50.000.000 Vitamin E g. 50 Saturated triglycerides g. 800 Glycerylmonolaurate g. 80 B.H.T. g. 2 Ethyl cellulose g. 5 Dibutylphthalate g. 5 Silica g. 5 Flavours g. 2 EXAMPLE 2 Formulation for zootechnical use of vitamins A, D3, E. Vitamin A I.U. 100.000.000 Vitamin D3 I.U. 8.000.000 Vitamin E g. 30 Saturated triglycerides g. 650 Glycerylmonolaurate g. 100 B.H.T. g. 2 Maize starch g. 90 Bentonite g. 100 Flavours g. 2 EXAMPLE 3 Formulation for zootechnical use of vitamins of group B. Vitamin B1 g. 30 Vitamin B2 g. 30 Vitamin B6 g. 15 Vitamin B12 g. 0.1 Saturated triglycerides g. 740 Glyceryl dioleate g. 40 Glyceryl monoleate g. 40 Bentonite g. 100 Cellulose acetophthalate g. 2 Ethoxyquine g. 2 Flavours g. 2 EXAMPLE 4 Formulation for zootechnical use of choline. Choline chloride g. 300 Silica g. 200 Gliceryl oleate g. 200 Polyoxyethylene alcohol g. 5 Saturated triglycerides g. 295 EXAMPLE 5 Formulation for zootechnical use of oxitetracycline. Oxytetracycline base g. 100 Saturated triglycerides g. 880 Ethyl cellulose g. 5 Cellulose acetophthalate g. 5 Methyl cellulose g. 0.5 EXAMPLE 6 Formulation for zootechnical use of a sulphamidic. Sulfamethazine g. 100 Sulfamerazine g. 100 Saturated triglycerides g. 740 Glyceryl monolaurate g. 50 Tween g. 2 Polyacrylates g. 5

Claims: Protective matrices for active principles for zootechnical and veterinary use, consisting of substances of lipidic origin selected from fatty acids or esters thereof, mono, di and triglicerides, corresponding alcohols and mixtures thereof, which are lipogelled by addition of suitable lipogelling substances selected from ethyl cellulose, methyl cellulose, cellulose acetophthalate, polyacrylates, polyvinyl alcohol, polyoxyethylene alcohol or metal hydroxides selected from zinc, aluminium, iron, cobalt and manganese hydroxides and/or optionally transformed in pastes by addition of colloidal substances selected from starch, caoline, bentonite or silica. Matrices according to claim 1, wherein the ration of lipogelling and/or colloidal substances to lipidic substances is from 1% to 90% by weight. Matrices according to claim 2, wherein the ratio of lipogelling and/or colloidal substances to lipidic substances is from 2 to 80% by weight. Matrices according to claim 3, wherein the ratio of lipogelling and/or colloidal substances to lipidic substances is from 5 to 50% by weight. Compositions for zootechnical and veterinary use containing active principles included in the matrices of claims 1 to 4. Compositions according to claim 5, wherein active principles are selected from the group of vitamins. proteins, amino acids, antibiotics, chemoterapeutics and other biologically active substances suited for animal therapy and feeding. A process for preparing compositions of claims 5-6 consisting of the following steps: 1) melting the lipidic material and mixing the mass; 2) adding lipogelling substances and/or colloids; 3) controlling chemical/physical parameters and adding active principles; 4) drying under normal or reduced pressure the so obtained material.

Inventors: FEZZI LUIGI, GRASSIGLI GIACOMO, FEZZI, LUIGI, GRASSIGLI, GIACOMO
Applicants: IND ITALIANA INTEGRATORI TREI, INDUSTRIA ITALIANA INTEGRATORI TREI S.P.A.
Application year: 1990
Main classification: A61K9
IPC codes: A61K9, A23K1