Method of controlling release of medicament and bolus therefor

Claim 1

A prolonged release oral dosage drug composition for administration to ruminant animals comprising: a solid, compressed dosage form of a size and shape to be orally administered to said ruminant animals and containing a medically effective amount of a drug distributed throughout an essentially water-insoluble disintegration resistant, slowly digestible matrix, said dosage form comprising originally undenatured native milk solids which have been (1) insolubilized in the presence of the drug added thereto by chemical reaction with an effective quantity of an aqueous solution of a substantially water soluble, volatile, aliphatic aldehyde insolubilizing agent having from 1 to 5 carbon atoms, (2) treated to entrap the drug in an essentially dry cross-linked lattice-like matrix of the aldehyde reacted milk protein solids and containing no more than a residual, non-toxic amount of said agent and an insignificant quantity of moisture, and (3) compressed into a self-sustaining body having a density at least greater than 1 to cause the dosage form to sink in the rumino-reticular fluids and become entrapped in the rumino-reticular sacs for slow digestion thereof by proteolytic enzymes upon administration of said dosage form to a ruminant animal, said drug being of a type which does not significantly react in a deleterious manner with said aldehydic agent during use thereof to insolubilize the native milk solids and making up about 0.5% to 80% by weight of the compressed dosage form, there being about 20% to 99.5% of dried reacted milk solids in said compressed dosage form, the ratio of aldehydic insolubilizing agent to milk protein solids and the degree of compression of said reacted milk solids and drug into said dosage form being correlated to provide a densified body which resists total disintegration when tumbled in water at a temperature of about 37° C. for a time period exceeding about 24 hours.

Claim 37

A method of orally treating feverish ruminant animals with a prolonged release thereapeutic drug composition comprising: administering to an afflicted ruminant animal a solid, compressed dosage form containing a medically effective amount of an anti-bacterial drug distributed throughout an essentially water insoluble, disintegration resistant slowly digestible matrix, said dosage form consisting essentially of originally undenatured native milk solids which have been (1) insolubilized in the presence of the drug added thereto by chemical reaction with an effective quantity of an aqueous solution of a substantially water soluble, volatile, aliphatic aldehyde insolubilizing agent having from 1 to 5 carbon atoms, (2) treated to entrap the drug in an essentially dry cross-linked lattice-like matrix of the aldehyde reacted milk protein solids and containing no more than a residual, non-toxic amount of said agent and an insignificant quantity of moisture, and (3) compressed into a self-sustaining body having a density at least greater than 1 to cause the dosage form to sink in the ruminoreticular fluids and become entrapped in the ruminoreticular sacs for slow digestion thereof by proteolytic enzymes upon administration of said dosage form to said feverish ruminant animal, the ratio of aldehydic insolubilizing agent to milk protein solids and the degree of compression of said granules into said dosage form being correlated to provide a densified body which resists total disintegration when tumbled in water at a temperature of about 37° C. for a time period exceeding 24 hours, said anti-bacterial drug being of a type which does not significantly react in a deleterious manner with said aldehydic agent during use thereof to insolubilize the native milk solids and making up about 0.5% to 80% by weight of the compressed dosage form, there being about 20% to 99.5% of reacted milk solids in said compressed dosage form with the ultimate drug release rate in the feverish ruminant animal being slower with higher body temperatures.

Claim 38

A method of orally treating feverish ruminant animals with a prolonged release thereapeutic drug composition comprising: administering to an afflicted ruminant animal a solid, compressed dosage form containing a medically effective amount of an anti-bacterial drug distributed throughout an essentially water insoluble, disintegration resistant slowly digestible matrix, said dosage form consisting essentially of originally undenatured native milk solids which have been (1) insolubilized in the presence of the drug added thereto by chemical reaction with an effective quantity of an aqueous solution of a substantially water soluble, volatile, aliphatic aldehyde insolubilizing agent having from 1 to 5 carbon atoms, (2) treated to entrap the drug in an essentially dry cross-linked lattice-like matrix of the aldehyde reacted milk protein solids and containing no more than a residual, non-toxic amount of said agent and an insignificant quantity of moisture, and (3) compressed into a self-sustaining body having a density at least greater than 1 to cause the dosage form to sink in the ruminoreticular fluids and become entrapped in the ruminoreticular sacs for slow digestion thereof by proteolytic enzymes upon administration of said dosage form to said feverish ruminant animal, the ratio of aldehydic insolubilizing agent to milk protein solids and the degree of compression of said granules into said dosage form being correlated to provide a densified body which resists total disintegration when tumbled in water at a temperature of about 37° C. for a time period exceeding 24 hours, said anti-bacterial drug being of a type which does not significantly react in a deleterious manner with said aldehydic agent during use thereof to insolubilize the native milk solids and making up about 0.5% to 80% by weight of the compressed dosage form, there being about 20% to 99.5% of reacted milk solids in said compressed dosage form with the ultimate drug release rate in the feverish ruminant animal being slower with higher body temperatures.