CA1282701C - Rumen-stable pellets - Google Patents
Rumen-stable pelletsInfo
- Publication number
- CA1282701C CA1282701C CA000523200A CA523200A CA1282701C CA 1282701 C CA1282701 C CA 1282701C CA 000523200 A CA000523200 A CA 000523200A CA 523200 A CA523200 A CA 523200A CA 1282701 C CA1282701 C CA 1282701C
- Authority
- CA
- Canada
- Prior art keywords
- coating
- rumen
- pellets
- ruminant
- inorganic particulate
- 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.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K40/00—Shaping or working-up of animal feeding-stuffs
- A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
- A23K40/35—Making capsules specially adapted for ruminants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/501—Inorganic compounds
Abstract
Rumen-Stable Pellets Abstract Disclosed are rumen-stable compositions for coating medicaments and nutrients for ruminant animals. The coatings comprise a film-forming polymeric substance containing basic nitrogen groups, and an inorganic particulate material dispersed throughout the polymeric substance.
Description
121~2~
Descri~tion Rumen Stable Pellet~
Technical Field This invention relates in general to pellets adapted to be srally administered to ruminants and which are beneficial to ruminants after passing the rumen and reaching the abomasum and/or inte6tines.
~ore particularly, this invention relate6 to pellets having, in term6 of structure, a core material such as a nutrient or medicament, and a coating over the core material which protects the core in the environment of the rumen, but which loses continuity under the more acidic conditions of the abomasum and~or intestines ~o render ~he core material available for utilization by the animal.
Backqround of the Inven~ion In ruminants, inge6ted feed first passes into the rumen. where it is pre-digested or degraded by fermentation. Durinq thiæ period of fermentation the ingested feed may be regurgitated to the mouth where it is salivated and ma6ticated. After a period of fermentation requlated by natural processes and variables depending on the animal and the feed6tuff, absorption of digested nutrients 6tarts and continue~
in the subsequent 6ections of the digestive tract by the ruminant animal. This process iB de~cribed in detail by D. C. Church, "Digestive Phy6iology and Nutrition of Ruminants", Vol. 1, Oregon State University Pre6s.
The rumen serves as an important location for metabolic breakdown of inge6ted foodstuffs through the action of microorganisms which are pre6ent therein.
In preparing nutrients and medicaments intended for administration to ruminants, it is important to protect the active ingredients against the environ-mental condition~ of the rumen, i.e., microbial degradation and the effect6 oE a pH of about 5.5, BO
the active substance will be saved until it reache6 the particular location where absorption take6 place.
It i6 well known that the rate of meat, wool and/or milk production can be increa6ed if 60urce6 of growth limiting e6sential amino acids, and/or medicament6, are protected from alteration by microorganism6 re6iding in the rumen and become available for direct absorption by the animal later in the ga6trointe~tinal tract.
Materials which protect the core against degrada-tion by the rumen content6 6hould be re6i6tant to attack by the rumen fluid which contain6 enzyme6 or microorgani6m6 but mu6t make the active ingredient available rapidly in the more acidic fluid of the aboma6um at a pH within the normal phy6iological range of about 2 to about 3.5. To more ea6ily coat or encapsulate active ingredients in protective materials, the protective material6 should be 601uble in certain organic 601vent6 for coating purpose6.
Because protein6 are subject to breakdown in the rumen, it has been sugge6ted that protein-containing nutrients fed to ruminants be treated 60 as to permit pa66age without microbial breakdown through the rumen to the aboma6um. Sugge6ted procedure6 have included coating the protein material, for example, with fats and vegetable oil6; heat treating of the protein material; reacting the protein material with variou6 compounds 6uch a6 formaldehyde, acetylenic ester6, polymerized un6aturated carboxylic acid or anhydride6 and phosphonitrilic halides, etc.
It i6 well-known that medicaments are more effective when they are protected from the environment ., ~
, '~ ' of the rumen. See, for example, ~.S. Patents 3~041,243 and 3,697,640.
The need and the value of post-ruminal delivery of nutrients and pharmaceuticals by means of supplementing rumen-stable preparations in fe~d is discussed in a paper entitled, "Controlled-Release Additives for Ruminant~: Cellulose-Based Coating Composition for Rumen-Stable Nutrient~", by Wu, et al., in a book, Controlled Release of Pesticides and Pharmaceuticals, edited by D. H. Lewis, Plenum Press, New York, New York, 1981, p. 319.
The following patents by Dannelly, ~t al, teach the art of formulating rumen-stable coatings for a variety of nutrient~ and medicaments: U.S. Pa~ent~ 4,117,801:
15 4,177,255: 4,181,708; 4,181,709: 4,181,710 and 4,196,187.
U.S. Patent 4,181,708 specifically teaches the ternary composition of a rumen-s~able coating which comprises a polymeric material cuch as a copolymer of 2-methyl-5-vinylpyridine and styrene [copoly~2M5VP~ST)~
which is resistant to mildly acidic environment of the rumen, and a hydrophobic fiubstance of from about 5 to 50% of the polymer weight, and a flake material o~ from about 10 to 200~ of the polymer weight di6per~ed 25 throughout the continuous matrix. U.S. patent 4,181,709 specifically teaches the quaternary composition of a rumen-stable coating w~ich comprises a polymeric material such as copoly(2M5VP/ST), a hydrophobic material of from about 2 to about 40% of the polymer weight, and a reactive fatty acid of from about 5 to about 40~ of the polymer weight. U.S. patent 4,1~1,710 specifically ~eache6 a binary compo ition of rumen-ztable coating compri~ed of a polymeric matrix and a hydrophobic material being present in an amount be~ween 5-50% of the polymer weight.
~27~
U.S. Pat. ~o. 4,177,255 specifically ~eaches a composition for a rumen ~table coating which comprises a polymeric ma~rix which i~ resis~an~ to acid and a subs~ance di6per~ed therein whlch i6 leachable from the ma~rix in the en~ironment of the abomasum but not the rumen.
Other patents of interest are as follows:
U.S. Pat. No. 3,619,200 relates to chemically modifying pellets and/or using a 6urface coating therefor. Various polymers are disclosed in thi~
patent including copolymers of vinylpyridine and styrene. Canadian Pat. No. 911,649 discloses treat-ment of proeteinaceous materials with substances which are capable of reacting with proteins to form a poly-meric proteinaceou~ complex on the surface of thematerial or by treating the proteinaceous material with a polymer or copolymer of a basic vinyl or acrylic monomer. This patent also di6closes the use of copolymers and terpolymers derived from essentially a basic sub~tituted acrylate or methacrylate monomer and at least one ethylenically unsaturated compound as rumen stable coatings. U.S. Pat. No. 3,880,990 and British Pat. No. 1,346,739 relate to an orally admin-istratable ruminant composition wherein a medicinal 6ubstance is encapsulated or embedded in a normally 601id, physiologically acceptable ba6ic polymer. The compositions are produced by disper~ing a medicinal sub~tance in a fir6t solvent and adding thereto a second solvent which i5 miscible with the first solvent but in which the polymer and medicinal substance are substantially insoluble. U.S. Pat. No.
Descri~tion Rumen Stable Pellet~
Technical Field This invention relates in general to pellets adapted to be srally administered to ruminants and which are beneficial to ruminants after passing the rumen and reaching the abomasum and/or inte6tines.
~ore particularly, this invention relate6 to pellets having, in term6 of structure, a core material such as a nutrient or medicament, and a coating over the core material which protects the core in the environment of the rumen, but which loses continuity under the more acidic conditions of the abomasum and~or intestines ~o render ~he core material available for utilization by the animal.
Backqround of the Inven~ion In ruminants, inge6ted feed first passes into the rumen. where it is pre-digested or degraded by fermentation. Durinq thiæ period of fermentation the ingested feed may be regurgitated to the mouth where it is salivated and ma6ticated. After a period of fermentation requlated by natural processes and variables depending on the animal and the feed6tuff, absorption of digested nutrients 6tarts and continue~
in the subsequent 6ections of the digestive tract by the ruminant animal. This process iB de~cribed in detail by D. C. Church, "Digestive Phy6iology and Nutrition of Ruminants", Vol. 1, Oregon State University Pre6s.
The rumen serves as an important location for metabolic breakdown of inge6ted foodstuffs through the action of microorganisms which are pre6ent therein.
In preparing nutrients and medicaments intended for administration to ruminants, it is important to protect the active ingredients against the environ-mental condition~ of the rumen, i.e., microbial degradation and the effect6 oE a pH of about 5.5, BO
the active substance will be saved until it reache6 the particular location where absorption take6 place.
It i6 well known that the rate of meat, wool and/or milk production can be increa6ed if 60urce6 of growth limiting e6sential amino acids, and/or medicament6, are protected from alteration by microorganism6 re6iding in the rumen and become available for direct absorption by the animal later in the ga6trointe~tinal tract.
Materials which protect the core against degrada-tion by the rumen content6 6hould be re6i6tant to attack by the rumen fluid which contain6 enzyme6 or microorgani6m6 but mu6t make the active ingredient available rapidly in the more acidic fluid of the aboma6um at a pH within the normal phy6iological range of about 2 to about 3.5. To more ea6ily coat or encapsulate active ingredients in protective materials, the protective material6 should be 601uble in certain organic 601vent6 for coating purpose6.
Because protein6 are subject to breakdown in the rumen, it has been sugge6ted that protein-containing nutrients fed to ruminants be treated 60 as to permit pa66age without microbial breakdown through the rumen to the aboma6um. Sugge6ted procedure6 have included coating the protein material, for example, with fats and vegetable oil6; heat treating of the protein material; reacting the protein material with variou6 compounds 6uch a6 formaldehyde, acetylenic ester6, polymerized un6aturated carboxylic acid or anhydride6 and phosphonitrilic halides, etc.
It i6 well-known that medicaments are more effective when they are protected from the environment ., ~
, '~ ' of the rumen. See, for example, ~.S. Patents 3~041,243 and 3,697,640.
The need and the value of post-ruminal delivery of nutrients and pharmaceuticals by means of supplementing rumen-stable preparations in fe~d is discussed in a paper entitled, "Controlled-Release Additives for Ruminant~: Cellulose-Based Coating Composition for Rumen-Stable Nutrient~", by Wu, et al., in a book, Controlled Release of Pesticides and Pharmaceuticals, edited by D. H. Lewis, Plenum Press, New York, New York, 1981, p. 319.
The following patents by Dannelly, ~t al, teach the art of formulating rumen-stable coatings for a variety of nutrient~ and medicaments: U.S. Pa~ent~ 4,117,801:
15 4,177,255: 4,181,708; 4,181,709: 4,181,710 and 4,196,187.
U.S. Patent 4,181,708 specifically teaches the ternary composition of a rumen-s~able coating which comprises a polymeric material cuch as a copolymer of 2-methyl-5-vinylpyridine and styrene [copoly~2M5VP~ST)~
which is resistant to mildly acidic environment of the rumen, and a hydrophobic fiubstance of from about 5 to 50% of the polymer weight, and a flake material o~ from about 10 to 200~ of the polymer weight di6per~ed 25 throughout the continuous matrix. U.S. patent 4,181,709 specifically teaches the quaternary composition of a rumen-stable coating w~ich comprises a polymeric material such as copoly(2M5VP/ST), a hydrophobic material of from about 2 to about 40% of the polymer weight, and a reactive fatty acid of from about 5 to about 40~ of the polymer weight. U.S. patent 4,1~1,710 specifically ~eache6 a binary compo ition of rumen-ztable coating compri~ed of a polymeric matrix and a hydrophobic material being present in an amount be~ween 5-50% of the polymer weight.
~27~
U.S. Pat. ~o. 4,177,255 specifically ~eaches a composition for a rumen ~table coating which comprises a polymeric ma~rix which i~ resis~an~ to acid and a subs~ance di6per~ed therein whlch i6 leachable from the ma~rix in the en~ironment of the abomasum but not the rumen.
Other patents of interest are as follows:
U.S. Pat. No. 3,619,200 relates to chemically modifying pellets and/or using a 6urface coating therefor. Various polymers are disclosed in thi~
patent including copolymers of vinylpyridine and styrene. Canadian Pat. No. 911,649 discloses treat-ment of proeteinaceous materials with substances which are capable of reacting with proteins to form a poly-meric proteinaceou~ complex on the surface of thematerial or by treating the proteinaceous material with a polymer or copolymer of a basic vinyl or acrylic monomer. This patent also di6closes the use of copolymers and terpolymers derived from essentially a basic sub~tituted acrylate or methacrylate monomer and at least one ethylenically unsaturated compound as rumen stable coatings. U.S. Pat. No. 3,880,990 and British Pat. No. 1,346,739 relate to an orally admin-istratable ruminant composition wherein a medicinal 6ubstance is encapsulated or embedded in a normally 601id, physiologically acceptable ba6ic polymer. The compositions are produced by disper~ing a medicinal sub~tance in a fir6t solvent and adding thereto a second solvent which i5 miscible with the first solvent but in which the polymer and medicinal substance are substantially insoluble. U.S. Pat. No.
3,041,293 relates to coating~ for oral medicaments.
These coatings are water-insoluble but acid-soluble film-forming polymers. An example mentioned in thi6 paten~ is 2-methyl-5-vinylpyridine copolymerized with 7~
vinyl acetate acrylonitrile, methyl acrylate or styrene.
U.S. Pat. No. 3,697,6~0 relates to ma~erials 6uch as medicaments and nutrients for ruminan~s which are coated with nitrogen-containing cellulosic material6 such a~, for example, cellulo~e propionate morpholino butyrate. U.S. Patr No, 3,988,480 relate~ to a pro-teinaceous feedstuff for ruminant~ which has been treated with acetic acid to render it rumen stable.
U.S. Pat. No. 3,38~,28~ relates to coatiny phar-maceutical pellets with a plurality of charges of fatty acid as a melt or in 601ution. The fatty acid may then be dusted with a fine enert powder such as talc.
U.S. Pat. No. 3,275,518 relates to a tablet coating composition comprising a film-forming resin or plastic and a hard water-soluble or water-di~persible sub~tance. Stearic acid is mentioned as an optional water-insoluble wax which may be included as an addi-tive. Additional ma~erial~ such a~ dyes, pigments, water-insoluble waxes, plasticizing agent~, etc., may also be added to the coating.
U.S. Pat. No. 3,62~,997 relates to a method of sealiny polymeric material walls of minute capsule6 by treating the capsules with a waxy material.
U.S. Pat. No . 3, 073,748 relates to tablets coated with a ~olution of an amphoteric film-forming poly-mer. The polymer is described as one selec~ed from the group consi6ting of copolymers of (a) vinyl-pyridine~ with (b) a lower aliphatic, a,B-unsaturated monocarboxylic acid of 3 to 4 carbon atom~ and copoly-mers of (a), (b~ and a neutral comonomer 6elected from the group con6i~ting of methyl acrylate, acryloni-trile, vinyl acetate, methyl methacrylate and styrene.
~Lq~t7~3~
British Pat. No. 1,217,365 and Canadian counter-parc No. 851,128 relate to a particulate feed additive composition for ruminants wherein each particle com-prises one or more amino acid~ totally encased in a 5 continuous film of protective material which i~
transportable through th~ rumen without subs~antial degradation ~herein but which releases the active substance posterior to the omasum. Suggested as protective materials are fatty acid triglyceride such as hydro~enated vegetable and animal fat~, waxes such as rice-brand wax, and resin wax blends which are emulsified and/or dissolved in the intestinal tract.
Also of interest is U.S. Pat. No. 4,060,59~ which relates to coated tablets prepared by applyiny to a core of active material a coating composition made up of a film forming aqueous synthetic re6in di6per~ion and a water or alkaline soluble material.
This invention describes binary coating composi-tion~ compri6ed of a polymer and at leas~ one inor-ganic substance which are ~ui~able for rumen-~table preparation of nutrients and medicaments such as methionine, glucose, and lysine.
In accc,rdance with this invention, coating composition~ which comprise a physiologically acceptable, pH-6ensitive, film-forming polymeric ~ub6tance and an inorganic 6ubstance or mixture of inorganic substances di6persed throughout the poly-meric material are provided. These coating composi-tions are resi~tant to environmental condition6 of the rumen but release the core material under the environ-mental conditions of the abomasum and/or intestine and are particularly suitable for rumen-stable prepara-tions of cores con~aining nutrients or medicaments.
3~.
Description o the Inventio~
The polymeric ~ubstances which are useful in the coatings of this inven~ion include those which, in combination with ~he inorganic sub6tance descri~ed hereinafter, are physiologically acceptable and resistant ~o a p~ of greater than about 5 but capable of releasing the core of the pel~ets at a p~ o~ less than about 3.5, at the normal body temperature of euminants (37C.). The polymeric substances include polymers, copolymers and mixtures of polymers, and~or copolymers having basic amino group~ in which the nitrogen content of the polymeric substance is between about 2 and about 14% and typical weight average molecular weights of 9O,O~O or more. The polymeric substances are of 6ufficient molecular weight to have film-forming properties when the polymer is deposited from a solution and after removal of a solvent, dis-persing medium or on cooling from a melt. Polymeric substances having the characteri6tics defined herein include certain modi.fied natural polymers, homo- and interpolymers obtained by addition polymerization methods, homo- and copolymers obtained by condensation polymeriz.ation methods and mixtures thereof. The polymeric material is comprised of at least one polymer, copolymer, or blend of polymers (herein sometimes collectively referred to ~s polymer or polymeric substance) selected from the group con-si~ting of cellulose derivatives such as cellulose propionate morpholinobutyrate; polymer containing addition-type monomeric moieties such as acryloni-trile, vinylated derivatives of pyridine, styrene, methylstyrene, and vinyl toluene esters and amides of methacrylic acid or acrylic acid such as a dialkyl-amino ethyl acrylate or methacrylate in which the alkyl group contains from 1 to 6 carbon atoms;
7~iL
polymerizable ethylenically unsaturated aliphatic hydrocarbon monomers such as ethylene, propylene or butadiene; vinyl esters such as vinyl acetate, vinyl propiona~e or vinyl stearate; ~inyl esters such as methyl, ethyl, propyl or stearyl, vinyl ~ubstituted heterocyclic ring or condensed ring compounds contain-ing basic nitrogen configurations such as vinyl carbazole, vinyl quinoline, N-vinylpyrrole and 5-vinyl pyrozoline; polymer of the condensation-type wherein a diacid such as phthalic, terephthalic, or succinic i6 combined with a polyfunctional alcohol to form poly-esters wherein either the acid or glycol moiety may contain basic nitrogen not reactive in the polymeriza-tion process but reactive to variable pH environments and wherein the same or similar diacids may be reacted with polyfunctional amines to form polyamide-type polymers containing basic nitrogen not reacted in t~e polymerization process; and other basic nitrogen containing polymers such as preformed polymers which ha~e been formed by reacting an existing polymer with a nitrogen containing organic or inorganic moiety such as polybutadiene to ~hich ammonia has been reacted with the remaining double bond. Especially preferred are poly(vinylpyridine), polymeric derivatives of vinylpyridine, and the copolymers of the variou~
isomer~ and derivatives of vinylpyridine copo}ymerize3 with one or more of the above-mentioned addition-type monomers. Many of these polymers are commercially available. They can be prepared by conventional techniques well known in the art.
Also, especially preferred are cellulose pro-pionate morpholinobutyrate, and polymers, copolymers, and blends of polymers selected from the group con-sisting of vinylpyridine, styrene, acrylonitrile, methacrylate, and methylmethacrylate. Most especially preferred are the copolymers of vinyl pyridine and s~yrene, e.g., 2-vinylpyridine/styrene copolymer (~out 65~5).
The inorganic substance~ are 6elected from, for example, alkaline earth fatty acid salts, clays, silicates, silicon oxides, metallic flake material, and alkaline earth carbonates. Alkaline earth fatty acid salts include, for example, calcium stearate, magnesium stearate, and the like. Inorganic clays include, for example, talc, bentonite, kaolin and zeolite. Inorganic silicate6 include, for example, masnesium silicate. Alkaline ear~h carbonates include, for example, calcium carbonate and magne6ium carbonate. Metallic flake materials include, for example, aluminum flake. Silicon oxides include, for example, silicon dioxide. The amount of inorganic 6ubstances in the coating i6 from about 20% to about 84% of the coating weight.
The inorganic substances may be treated by comminutation to reduce the particle size and to increase the dispersibility in the coating so as to further improve the effectiveness of the coating. The comminutation can be carried out by any mean6 for crushing or reducing the particle 6ize of the inor-ganic substance. Such mean6 can be by ball milling, grinding, and the like. The particle size of at lea6t 15~ of the particle~ should be less than 5 microns, and 85~ of the particles les~ than 10 microns. The specified size6 are measurements at the large~t dimension, e.g., largest diameter if a sphere or platele~.
One preferred method for comminutation is to ball mill the inorganic substance. A preferred ball mill useful in the practice of this invention compri~e6 a cylindrical container mounted horizontally and partially filled with ceramic balls. Surface modification of the flake material in acetone i6 accomplished by rotating the ball mill and it~
contents about the horizontal axis of the mill a~ a rate sufficient to lift the balls to one side and then cause them to roll, slide, and tumble (cascade) to the lower side.
A laboratory procedure practiced in this invention is described as follows:
1. Weigh approximately 570 g of ceramic balls and add these balls into a ball mill. The total volume of the balls i6 approximately 15-25% of the volume of the cylindrical container.
2. Add 137 g of a mixture of flake material and 320 mL acetone to the ball mill and seal the container to minimize evaporation of acetone during the operation.
3. Rotate the ball mill on a roller at a speed of ~90 rpm for about 16 hr.
These coatings are water-insoluble but acid-soluble film-forming polymers. An example mentioned in thi6 paten~ is 2-methyl-5-vinylpyridine copolymerized with 7~
vinyl acetate acrylonitrile, methyl acrylate or styrene.
U.S. Pat. No. 3,697,6~0 relates to ma~erials 6uch as medicaments and nutrients for ruminan~s which are coated with nitrogen-containing cellulosic material6 such a~, for example, cellulo~e propionate morpholino butyrate. U.S. Patr No, 3,988,480 relate~ to a pro-teinaceous feedstuff for ruminant~ which has been treated with acetic acid to render it rumen stable.
U.S. Pat. No. 3,38~,28~ relates to coatiny phar-maceutical pellets with a plurality of charges of fatty acid as a melt or in 601ution. The fatty acid may then be dusted with a fine enert powder such as talc.
U.S. Pat. No. 3,275,518 relates to a tablet coating composition comprising a film-forming resin or plastic and a hard water-soluble or water-di~persible sub~tance. Stearic acid is mentioned as an optional water-insoluble wax which may be included as an addi-tive. Additional ma~erial~ such a~ dyes, pigments, water-insoluble waxes, plasticizing agent~, etc., may also be added to the coating.
U.S. Pat. No. 3,62~,997 relates to a method of sealiny polymeric material walls of minute capsule6 by treating the capsules with a waxy material.
U.S. Pat. No . 3, 073,748 relates to tablets coated with a ~olution of an amphoteric film-forming poly-mer. The polymer is described as one selec~ed from the group consi6ting of copolymers of (a) vinyl-pyridine~ with (b) a lower aliphatic, a,B-unsaturated monocarboxylic acid of 3 to 4 carbon atom~ and copoly-mers of (a), (b~ and a neutral comonomer 6elected from the group con6i~ting of methyl acrylate, acryloni-trile, vinyl acetate, methyl methacrylate and styrene.
~Lq~t7~3~
British Pat. No. 1,217,365 and Canadian counter-parc No. 851,128 relate to a particulate feed additive composition for ruminants wherein each particle com-prises one or more amino acid~ totally encased in a 5 continuous film of protective material which i~
transportable through th~ rumen without subs~antial degradation ~herein but which releases the active substance posterior to the omasum. Suggested as protective materials are fatty acid triglyceride such as hydro~enated vegetable and animal fat~, waxes such as rice-brand wax, and resin wax blends which are emulsified and/or dissolved in the intestinal tract.
Also of interest is U.S. Pat. No. 4,060,59~ which relates to coated tablets prepared by applyiny to a core of active material a coating composition made up of a film forming aqueous synthetic re6in di6per~ion and a water or alkaline soluble material.
This invention describes binary coating composi-tion~ compri6ed of a polymer and at leas~ one inor-ganic substance which are ~ui~able for rumen-~table preparation of nutrients and medicaments such as methionine, glucose, and lysine.
In accc,rdance with this invention, coating composition~ which comprise a physiologically acceptable, pH-6ensitive, film-forming polymeric ~ub6tance and an inorganic 6ubstance or mixture of inorganic substances di6persed throughout the poly-meric material are provided. These coating composi-tions are resi~tant to environmental condition6 of the rumen but release the core material under the environ-mental conditions of the abomasum and/or intestine and are particularly suitable for rumen-stable prepara-tions of cores con~aining nutrients or medicaments.
3~.
Description o the Inventio~
The polymeric ~ubstances which are useful in the coatings of this inven~ion include those which, in combination with ~he inorganic sub6tance descri~ed hereinafter, are physiologically acceptable and resistant ~o a p~ of greater than about 5 but capable of releasing the core of the pel~ets at a p~ o~ less than about 3.5, at the normal body temperature of euminants (37C.). The polymeric substances include polymers, copolymers and mixtures of polymers, and~or copolymers having basic amino group~ in which the nitrogen content of the polymeric substance is between about 2 and about 14% and typical weight average molecular weights of 9O,O~O or more. The polymeric substances are of 6ufficient molecular weight to have film-forming properties when the polymer is deposited from a solution and after removal of a solvent, dis-persing medium or on cooling from a melt. Polymeric substances having the characteri6tics defined herein include certain modi.fied natural polymers, homo- and interpolymers obtained by addition polymerization methods, homo- and copolymers obtained by condensation polymeriz.ation methods and mixtures thereof. The polymeric material is comprised of at least one polymer, copolymer, or blend of polymers (herein sometimes collectively referred to ~s polymer or polymeric substance) selected from the group con-si~ting of cellulose derivatives such as cellulose propionate morpholinobutyrate; polymer containing addition-type monomeric moieties such as acryloni-trile, vinylated derivatives of pyridine, styrene, methylstyrene, and vinyl toluene esters and amides of methacrylic acid or acrylic acid such as a dialkyl-amino ethyl acrylate or methacrylate in which the alkyl group contains from 1 to 6 carbon atoms;
7~iL
polymerizable ethylenically unsaturated aliphatic hydrocarbon monomers such as ethylene, propylene or butadiene; vinyl esters such as vinyl acetate, vinyl propiona~e or vinyl stearate; ~inyl esters such as methyl, ethyl, propyl or stearyl, vinyl ~ubstituted heterocyclic ring or condensed ring compounds contain-ing basic nitrogen configurations such as vinyl carbazole, vinyl quinoline, N-vinylpyrrole and 5-vinyl pyrozoline; polymer of the condensation-type wherein a diacid such as phthalic, terephthalic, or succinic i6 combined with a polyfunctional alcohol to form poly-esters wherein either the acid or glycol moiety may contain basic nitrogen not reactive in the polymeriza-tion process but reactive to variable pH environments and wherein the same or similar diacids may be reacted with polyfunctional amines to form polyamide-type polymers containing basic nitrogen not reacted in t~e polymerization process; and other basic nitrogen containing polymers such as preformed polymers which ha~e been formed by reacting an existing polymer with a nitrogen containing organic or inorganic moiety such as polybutadiene to ~hich ammonia has been reacted with the remaining double bond. Especially preferred are poly(vinylpyridine), polymeric derivatives of vinylpyridine, and the copolymers of the variou~
isomer~ and derivatives of vinylpyridine copo}ymerize3 with one or more of the above-mentioned addition-type monomers. Many of these polymers are commercially available. They can be prepared by conventional techniques well known in the art.
Also, especially preferred are cellulose pro-pionate morpholinobutyrate, and polymers, copolymers, and blends of polymers selected from the group con-sisting of vinylpyridine, styrene, acrylonitrile, methacrylate, and methylmethacrylate. Most especially preferred are the copolymers of vinyl pyridine and s~yrene, e.g., 2-vinylpyridine/styrene copolymer (~out 65~5).
The inorganic substance~ are 6elected from, for example, alkaline earth fatty acid salts, clays, silicates, silicon oxides, metallic flake material, and alkaline earth carbonates. Alkaline earth fatty acid salts include, for example, calcium stearate, magnesium stearate, and the like. Inorganic clays include, for example, talc, bentonite, kaolin and zeolite. Inorganic silicate6 include, for example, masnesium silicate. Alkaline ear~h carbonates include, for example, calcium carbonate and magne6ium carbonate. Metallic flake materials include, for example, aluminum flake. Silicon oxides include, for example, silicon dioxide. The amount of inorganic 6ubstances in the coating i6 from about 20% to about 84% of the coating weight.
The inorganic substances may be treated by comminutation to reduce the particle size and to increase the dispersibility in the coating so as to further improve the effectiveness of the coating. The comminutation can be carried out by any mean6 for crushing or reducing the particle 6ize of the inor-ganic substance. Such mean6 can be by ball milling, grinding, and the like. The particle size of at lea6t 15~ of the particle~ should be less than 5 microns, and 85~ of the particles les~ than 10 microns. The specified size6 are measurements at the large~t dimension, e.g., largest diameter if a sphere or platele~.
One preferred method for comminutation is to ball mill the inorganic substance. A preferred ball mill useful in the practice of this invention compri~e6 a cylindrical container mounted horizontally and partially filled with ceramic balls. Surface modification of the flake material in acetone i6 accomplished by rotating the ball mill and it~
contents about the horizontal axis of the mill a~ a rate sufficient to lift the balls to one side and then cause them to roll, slide, and tumble (cascade) to the lower side.
A laboratory procedure practiced in this invention is described as follows:
1. Weigh approximately 570 g of ceramic balls and add these balls into a ball mill. The total volume of the balls i6 approximately 15-25% of the volume of the cylindrical container.
2. Add 137 g of a mixture of flake material and 320 mL acetone to the ball mill and seal the container to minimize evaporation of acetone during the operation.
3. Rotate the ball mill on a roller at a speed of ~90 rpm for about 16 hr.
4. Decant the contents and wash the container and balls with acetone. The dispersion i6 ready to be used for the preparation of a coating dope, or the dispersion is dried by evaporating acetone at 50C. The dry product is then redispersed into 2 polymer solution to make a coating dope Pellet cores are formed from a material which i6 beneficial to the ho~t ruminant upon passing through the rumen and entering the abomasum and/or intestine.
Such material can be drugs or antibiotics, sugars, proteins, starches, amino acids, and the like.
One method for preparing the cores i~ to make a dough of the core material and extrude the dough into cylindrical pellets. The pellets are then rounded by rolling or other suitable means and dried to remove the water or diluent used in forming the do~gh.
The pellets are then coated. One convenient means for coating the pellets is by con~aeting them with the coating material in a suitable solvent or mixture of solvents. The polymeric material may conveniently be dissolved in the solvent~ which Ehould be physiologically acceptable in ~he event there are residues upon evaporation of the solvent. The inorganic substance is then blended in the olution.
The coating material may be applied by any conYenient means such as dipping, spraying, etc. The coating material forms a continuou~ film around the core~ by the evaporation of the coating solvent. The coating is continued until the desired coating weight is obtained. Suitable coating apparatus is disclosed in U.S. Patent No. 4,117,801.
This invention can be ~urther illustrated by the following examples of preferred embodiments thereof, although it will be unders~ood that these examples are included merely for purposes of illustration. When the inorganic particulate material in the examples is de6cribed as ball~milled. it is meant that at least 15% of the particles are less than 5 microns and at least 85~ are less than lO micron6.
E~AMPLE 1 A mix~ure of about 450 g lysine~HCl (9O ~t %~
and 50 g ~icrocry~talline cellulose (lO wt %) is thoroughly blended and then mixed with about llO g water. The moisture con~ent of the dough is adjusted to about 18% water. The wet dough is then extruded and pelletized by using an extruder equipped with a 2-in. diameter die and a rotating chopper blade at the o~
die face. The die openings are 1.6 mm in diameter and the chopper blade is controlled to produce 6hort cylindrical rods with a length to diame~er ratio of about 1 to 1.5. The wet, raw pellets are rounded or polished to an average aspect ratio of about 1.3. The rounded pellets are then dried to a water content of 1~ or le6s.
A portion of the dried pellets is coated to a coating weight of about 14 wt % with a coating composition containing S0 wt% 2-vinylpyridine~s~yrene (80/203 copolymer and 40 wt % ball milled talc. The ball milled talc is prepared by ball milling talc with 50~ of the particles having a number average particle diameter of 10 ~ for 24 hr in a ball mill to obtain talc having a reduced average particle size in the specified range (15% less than 5 ~ and ~5% le~s than 10 ~). A Coulter counter is used to determine the particle size di6tribution.
A sample of the coated pellets is extracted in synthetic buffered rumen test fluid for 24 hr at ~9C. The supernatan~ i6 analyzed for lysine-HCl by using an X-ray emission spectroscopic method.
The in vitro rumen-protection value is determined as percent protection of total amino acid in the pellets after 24 hr. The ~ollowing equation is u~ed for ~he calculation of percent protection:
% protection =
(1 - concentration of amino acid in the extract) 30total amino acid in the pellet sample x 100.
The rumen protection of the sample of coated pellets i6 greater than 90%.
Other portions of ~he drie~ pellets are coated to a coa~ing weight of about 12 and 10% with the 6ame coating composition used in the 14% coating. T~e ru~en pro~ection of these coated pellets is about 85%
and 70%, respectively.
The rumen stable pellet samples are then placed in synthetic abomasal ~est fluid for one hour at 39C. The extracts are analyzed by the X-ray emission spectroscopic method. The release values are O calculated from the following equation:
% aboma~al release =
(l - concentration of amino acid in the extract) total amino acid in the pellet sample The percent of release of the rumen stable pellets in the abomasal fluid is about (93~.
This example shows that a two-component coating composed of copoly~er and 40% by weiqht ball milled talc provides ~ood rumen protection and excellent a~masum release.
EXAMPLE 2 ~Control~
A mixture of about 450 g lysine-HCl (90 wt %) and 50 g microcrystalline cellulose (lO wt %) i5 -thoroughly blended and then mixed with water, extruded, rounded or polished, and dried according to Example l.
The dried pellets are coated to a coating weight of about l~ wt % with a coating composition containinq 60 wt % 2-vinylpyridine/styrene (80/20) copolymer and about 40 wt ~ talc with 50% of the particles having an average particle size of about lO ~ or more.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at ambient temperakure. The rumen protection of the coated pellets is only about ~q~ 7~
15%. These rumen s~able pellet~ are then placed in abomasal test fluid for one hour at ambient temperature. The percent of release of the rumen stable pellet6 in the abomasum test fluid i6 92~.
This example 6hows that the two-component coa~ing con~aining only 40% talc which had not been ball milled at a coating wei~ht of only 1~% provide~
pellets having very poor rumen stability and delivered only abou~ 12% of ~he original highly water-soluble amino acid in abomasal fluid.
_XAMPI.E ~
A mixture of about 450 g lysine-HCl (9O wt %) and 50 g microcrystalline cellulose (lO wt %) iB
15 thoroughly blended and then mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
The dried pellet~ are coated to a coating weight of about 14% with a coating compo6ition containing about 31.5~; 2-vinylpyridine/styrene (65~5) copolymer and about 68.5 wt % ball milled talc.
A sample of the coated pellets is placed in rumen te6t fluid for 24 hr at ambient temperature. The rumen protection of the coated pellets is about 85%, and abomasum release is greater than 90~.
This example show6 that two-component coatin~6 using about 70 wt % ball milled talc have excellent rumen 6tability.
EXAMPLE 4 ~Control) A mixture of about 450 g lysine-HCl (9O wt %) and 50 g microcry~talline cellulose (lO wt %) is thoroughly blended and ~hen mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
The dried pellets are coated to a coating weight of about 14~ with a coa~ing composition containing about 31~S~ 2-vinylpyridine~styrene ~65~3~) copolymer and abou~ 68.5 wt ~ talc used in Example 2.
A sample of the coated pellets i8 plaGed in rumen test fluid for 24 hr at ambient temperature. The rumen protectisrl of the coated pelle~s is only about 20~.
This example shows that a two-component coating with talc which has not been ball milled provides poor rumen protection compared with that ob~ained with ball milled talc.
EXAMPL~ 5 A mixture of about 450 g glucose (90 wt ~) and 50 g microcrystalline cellulose (10 wt %~ i6 thoroughly blended and then mixed with water, extruded, pelletized, rounded or poli6hed, and dried according to Example 1.
The dried pellets are coated to a coating weight of about 14% with a coating compoition containing 31.5% 2-methyl-5-vinylpyridine/styrene ~80/20~
copolymer and 68.5~ ball milled talc of Examp~le 1.
A ~ample of the coated pellets i~ placed in rumen test fluid ~Eor 29 hr at ambient temperature. The rumen protection of the coated pellets is about 90-95%
and abomasum relea~e is greater than 90%.
This example shows that 2-methyl-5-vinyl-pyridine~styrene copolymer can ~e used in place of the 2-vinylpyridine/~tyrene copolymer.
Similar results are obtained using other inorganic clays such as bentonite, kaolin, or mica in place of talc.
This example also ~hows that cores of highly water--soluble substances other than amino acid~ ~an be ~8~
coated with the two-co~ponent coating to provide rumen stable pellets.
EXAMPl,E 6 A mixture of abou~ ~S0 g methionine (90 w~ ~ and 50 g binders composed of compres~ible sugar ~6% by wt), sodium carboxymethyl cellulose (4% by wt) is blended and then mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
I'he dried pellets are coa~ed to a coating weight from about 4.5% to about 14% with a coating composition containing about 31.5% 2-methyl-5-vinyl-pyridine/~yrene (80/20) copolymer and about 68.5 wt S
talc or ball milled talc of Example 1.
The rumen protection and abomasal release of the coaled pellets are compared in the following table.
% Protection ~ Relea~e % Coat nq Talc, tTalc]~ Talc, tTalc]*
14 89 98 86 ~6 *[Talc]: Ball milled talc.
. .
A mixture of about 400 g ly6ine-HCl (80 wt %) and 100 g methionine (20 wt %) is thoroughly blended and ~hen mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
The dried pellets are coated to a coating weight of about 14~ with a coating composition containing 20%
2-vinylpyridine/styxene (70~30) copolymer and 80 wt %
talc with and without ball mill treatment.
~x~
A sample of the coated pellets from each prepara--tion is placed in ru~en test fluid for 2~ hours at 39OC. The lysine protection of the coated pellets containing talc without ball mill treatment in the coating is about 10~, but the ly6ine protection is about 75% for the coated pellets containing ball milled talc in the coating.
A mixture of about 450 g methionine (solubility less than 5 g per 80 g water at 20C) (90 w~ ~) and 50 g microcrystalline cellulose (10 wt %) is thoroughly blended and then mixed with about llO g water. The moi~ture content of the dough is adjusted to about 13.8% water. The wet dough i6 then extruded and pelletized by u~ing an extruder equipped with a 2-in diameter die and a rotating chopper blade at the die face. The die openi~gs are 1.6 mm in diameter and the chopper blade i6 controlled to produce short cylindri-cal rods with a length to diameter ratio of about 1 to 1.5. The wet, raw pellets are rounded or polishea to remove the sharp corners and edges. The rounded pellets are then dried to a water content of 1% or le~s.
A portion of the dried pellet6 are coated to a coating weight of about 1~ wt % with a coating composition containiny 31.5 wt % 2-vinylpyridine~
styrene (80/20) copolymer and 68.5 wt % ball milled talc.
The rumen protection of the sample of coated pellets is about 90% and abomasum release i~ greater than 90%.
Other portions of the dried pellets are coated to a coating weight of about 12 and 10~ with the same coating composition used in ~he 1~% coating. The Z~7~
rumen protection of these coated pelle~s is about 85%
and 70~, respectively.
The rumen stable pellets are then placed in synthetic abomasal test fluid for l hr at 30C. The percent of release of the rumen stable pellets in the abomasum was about 93%.
The dried pellets prepared according to Example 8 are coated to a coating weight of about 15 wt ~ with a coating composition containing 80 wt % 2-vinylpyridine/-styrene (80/20) copolymer and about 20 wt % ball milled talc.
A sample of the coated pellets i6 placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 90~. These rumen ~table pellets are then placed in abomasal test fluid for l hr at 39C. The percent of release of the rumen stable pellets in the abomasum test fluid is 78% with 22~ of the pellets remaining undissolved.
This example shows that the two-component coating containing only 20% talc at a coating weight of 14%
provides pellets having good rumen stability and good abomasum release.
The dried pellet6 according to Example B, are coated to a coa~ing weight of about ~ ~ith a coating composition containing 31.5% Z-vinylpyridine/styrene 30 (80~20) copolymer and 68.5 wt ~ calcium stearate.
Fifteen percent of the particles of calcium carbonate is less than 5 micron and 85% is less than lO microns.
A sample of ~he coated pellet~ is placed in rumen test fluid for 24 hr at 39~C. The rumen protection of the coated pellets is about 90-95% and aboma~um release is qreater than about 90~.
This example ~hows that using calcium stearate in place of talc provides a coating which at only 8%
coating weight provides excellent rumen stability even when 50~ le6s coa~ing maeerial is used.
In Examples 11-14 which follow, 15% of the inorganic particles is less than 5 microns and 85~ is less than 10 microns.
The dried pelletfi, according to Example 8r are coated to a coating weight of about 14% with a coating composition containing 31.5% 2-methyl-5-vinylpyridine/-15 styrene (80/20) copolymer and 68.5 wt % of particulate calcium carbonate.
A sample of the coated pellets i6 placed in rumen tet fluid for 2g hr at 39C. The rumen protection of the coated pellets is about 85~ and abomasum release iB
greater than 90%.
This example shows that calcium carbonate can be used in place of talc and provides similar result6.
The dried pellets, according to ~xample 8, are coated to a coating weight of about 14~ with a coating compo6ition containing 31.5~ 2-methyl-~-vinylpyridine~-fityrene (80/20) copolymer and 68.5% of particulate bentonite.
A sample of the coated pellet6 is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 90~ and abomasum release is greater than 90~.
Similar results are obtained using other inorganic clays such as kaolin in place of bentonite.
7~.
EXP~MPLF. 1 3 The dried pellets, according to Example 1, are coated to a ccating weight of about 14~ with a coating composition containing 31.5% 2-me~hyl-5-vinylpyridine/-styrene ~Bo/2~) copolymer ana 68.5% of particulatesilicon dioxide.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets i5 about 90-95~ and abomasum release is greater than 90%.
The dried pellets, according to Example 8, are coated to a coating weight of about 14~ with a coating 15 composition containing 31.5~ 2-methyl-5-vinylpyridine~-styrene (80/20) copolymer and 68.5% of particulate magnesium silicate.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 90-95% and abomasum release is greater than 90~.
EXAMPLE 15 (Control) The dried pellets, according to Example 8, are coated to a coating weight of about 12% with a coating composition containing 31.5% 2-vinylpyridine/styrene (80/20) copolymer and 68.5~ calcium chloride.
A ~ample of the coated pellets i6 placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is only aboue Z0~.
E~AMPLE 16 (Control) The dried pelle~s, according to Example 8, are coated to a coating weigh~ of about 12~ with a coating composition containing 31.5~ 2-vinylpyridine~styrene (80/20) copolymer and 68.5~ calcium sulfate.
A sample of the coa~ed pellets is placed in rumen test fluid for 24 hr a~ ambient temperature. The undissolved pellets are removed from the test fluid, dried, and weighed. The rumen protection of the coated pellets i~ only about 20~.
EX~MPL~ 17 The dried pellets, according to Example 8, are coated to a coating weigh~ of about 12~ with a coa~ing composition containing 31.5~ 2-vinylpyridine/styrene (80~20) copolymer and 68.5% magnesium stearate.
A sample of ~he coated pellets is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 70%.
EXAMPLE lB (Control) The dried lysine-HCl-containing pellets, according to Example 1, are coated to a coating weight of about lZ% with a coating composi~ion containiDq 20 31.5% 2-vinyLpyridine/styrene (80/20) copolymer and 68.5 wt % calcium stearate (particle size greater than that of the ~present invention).
A sample of the coated pellets is placed in rumen test fluid for 2g hr at 39C. The rumen protection of the coated pellets is only about 20%.
.
A mixture of about 450 g phenylalanine (solubility of les6 than 2 g per 100 cc water at 20~C) (90 wt ~) and S0 g microcrystalline cellulose (10 wt %) is thoroughly blended and then mixed with about 110 g water. The moisture content of the dough is adjusted to about 18% water. The wet dough is then extruded, pelle~ized, rounded or polished, and dried according to Example 1.
The dried pellet~ are coated to a coating weight of about 12~ with a coa~ing composition containing ~1.5~
2-methyl-5-vinylpyridine~styrene (80~20) copolymer and 68.5% particulate bentonite.
A sample of the coated pellet6 is placed in rumen test fluid for 24 hr at 3soc. The rumen protection of the coated pellets is about 90-95~ and aboma6um relea~e i~ greater than 90~.
Similar results are obtained using other inorganic clays such as kaolin in place of bentonite.
EXAMPLE ~0 A mixture of about ~50 g leucine (solubility less than 3 g per 100 cc water at 20C) (90 wt ~) and 50 g microcrystalline cellulose (10 wt ~) is thoroughly blended and then mixed with about 110 g water~ The moisture content of the dough is adjusted to about 18%
water. The wet dough is then extruded, pelletized, rounded or polished, and dried according eO Example 1~
1'he dried pellets are coated to a coating weigh~ of about 12% with a coating composition containing 31.5%
2-methyl-5-vinylpyridine/styrene (80~20) copolymer and 6~.5% particulate silicon dioxide.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at ~C. The rumen protection of the coated pellets is about 90-95% and abomasum release i6 yreater than 90~.
EX~MPLE Z1 A mixture of about 450 g tryptophan (solubility less than 2 g per 100 cc water at 20C) (90 wt ~) and 50 g microcry~talline cellulose (10 wt ~ is thoroughly blended and then mixed with about 110 g water. T~e moisture content of the dough is adju6ted to about 18%
water. The wet dough is then extruded, pelletized, rounded ox poli~hed, and dried according to ~xample 1.
7~
The dried pellets are coated to a coating weight of about lZ~ with a coating composi~ion containing 31.~%
2-methyl-5-vinylpyridine/styrene (80/20) copolymer and 68.5~ particulate silicon dioxide.
A sample of the coa~ed pellets i6 placed in rumen test fluid f~r 24 hr at 39C. The rumen protection of the coated pellets is abou~ 90-95~ and aboma~um release is greater than 90~.
The dried pellets, according to Example 1, are coated to a coating weight of 14~ ba6ed on total pellet weiyht with a coating composition containing 31.5t Z-vinylpyridine~styrene (80/20) copolymer and 68.5%
particulate aluminum flake. A sample of the coated pellets is placed in a rumen test fluid for 2q hour~ at 39C. The rumen protection is about 82~, and release in abomasum test fluid is about 92~.
ExamPle 23 The dried pellets, according to Example 8 are coated to a coating weight of 12~ ba~ed on total pellet weight with a coating composition containing 30%
2-vinylpyridine/styrene (80/20) copolymer and 70%
particulate aluminum flake. A sample of the coated pellets is placed in a rumen test fluid for 24 hours at 39C. The ru~en protection is 93%, and relea6e in abomasum test fluid is about 90%.
In Examples 17 and 19-23, 15% of the particles of inorganic material is less than 5 micron~ and 85% i6 less than 10 microns.
~ henever the term "inherent viscosity" (I.V.) i6 used in this application, it will be understood to refer to viscosity determinations made at 25C using 0.50 gram of polymer per 100 ml of a solvent composed of 60 wt % p~enol and gO w~ % tetrachloroethane.
- ~4 -Unless otherwise specified, all parts, percentages, ratios, etc., are on a weight ba~is.
The invention has been described in detail with particular reference to preferred embodiment~ tbereo~, but it will be understood that variations and modifica-tions can be effected within the spirit and scope of tbe invention.
Such material can be drugs or antibiotics, sugars, proteins, starches, amino acids, and the like.
One method for preparing the cores i~ to make a dough of the core material and extrude the dough into cylindrical pellets. The pellets are then rounded by rolling or other suitable means and dried to remove the water or diluent used in forming the do~gh.
The pellets are then coated. One convenient means for coating the pellets is by con~aeting them with the coating material in a suitable solvent or mixture of solvents. The polymeric material may conveniently be dissolved in the solvent~ which Ehould be physiologically acceptable in ~he event there are residues upon evaporation of the solvent. The inorganic substance is then blended in the olution.
The coating material may be applied by any conYenient means such as dipping, spraying, etc. The coating material forms a continuou~ film around the core~ by the evaporation of the coating solvent. The coating is continued until the desired coating weight is obtained. Suitable coating apparatus is disclosed in U.S. Patent No. 4,117,801.
This invention can be ~urther illustrated by the following examples of preferred embodiments thereof, although it will be unders~ood that these examples are included merely for purposes of illustration. When the inorganic particulate material in the examples is de6cribed as ball~milled. it is meant that at least 15% of the particles are less than 5 microns and at least 85~ are less than lO micron6.
E~AMPLE 1 A mix~ure of about 450 g lysine~HCl (9O ~t %~
and 50 g ~icrocry~talline cellulose (lO wt %) is thoroughly blended and then mixed with about llO g water. The moisture con~ent of the dough is adjusted to about 18% water. The wet dough is then extruded and pelletized by using an extruder equipped with a 2-in. diameter die and a rotating chopper blade at the o~
die face. The die openings are 1.6 mm in diameter and the chopper blade is controlled to produce 6hort cylindrical rods with a length to diame~er ratio of about 1 to 1.5. The wet, raw pellets are rounded or polished to an average aspect ratio of about 1.3. The rounded pellets are then dried to a water content of 1~ or le6s.
A portion of the dried pellets is coated to a coating weight of about 14 wt % with a coating composition containing S0 wt% 2-vinylpyridine~s~yrene (80/203 copolymer and 40 wt % ball milled talc. The ball milled talc is prepared by ball milling talc with 50~ of the particles having a number average particle diameter of 10 ~ for 24 hr in a ball mill to obtain talc having a reduced average particle size in the specified range (15% less than 5 ~ and ~5% le~s than 10 ~). A Coulter counter is used to determine the particle size di6tribution.
A sample of the coated pellets is extracted in synthetic buffered rumen test fluid for 24 hr at ~9C. The supernatan~ i6 analyzed for lysine-HCl by using an X-ray emission spectroscopic method.
The in vitro rumen-protection value is determined as percent protection of total amino acid in the pellets after 24 hr. The ~ollowing equation is u~ed for ~he calculation of percent protection:
% protection =
(1 - concentration of amino acid in the extract) 30total amino acid in the pellet sample x 100.
The rumen protection of the sample of coated pellets i6 greater than 90%.
Other portions of ~he drie~ pellets are coated to a coa~ing weight of about 12 and 10% with the 6ame coating composition used in the 14% coating. T~e ru~en pro~ection of these coated pellets is about 85%
and 70%, respectively.
The rumen stable pellet samples are then placed in synthetic abomasal ~est fluid for one hour at 39C. The extracts are analyzed by the X-ray emission spectroscopic method. The release values are O calculated from the following equation:
% aboma~al release =
(l - concentration of amino acid in the extract) total amino acid in the pellet sample The percent of release of the rumen stable pellets in the abomasal fluid is about (93~.
This example shows that a two-component coating composed of copoly~er and 40% by weiqht ball milled talc provides ~ood rumen protection and excellent a~masum release.
EXAMPLE 2 ~Control~
A mixture of about 450 g lysine-HCl (90 wt %) and 50 g microcrystalline cellulose (lO wt %) i5 -thoroughly blended and then mixed with water, extruded, rounded or polished, and dried according to Example l.
The dried pellets are coated to a coating weight of about l~ wt % with a coating composition containinq 60 wt % 2-vinylpyridine/styrene (80/20) copolymer and about 40 wt ~ talc with 50% of the particles having an average particle size of about lO ~ or more.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at ambient temperakure. The rumen protection of the coated pellets is only about ~q~ 7~
15%. These rumen s~able pellet~ are then placed in abomasal test fluid for one hour at ambient temperature. The percent of release of the rumen stable pellet6 in the abomasum test fluid i6 92~.
This example 6hows that the two-component coa~ing con~aining only 40% talc which had not been ball milled at a coating wei~ht of only 1~% provide~
pellets having very poor rumen stability and delivered only abou~ 12% of ~he original highly water-soluble amino acid in abomasal fluid.
_XAMPI.E ~
A mixture of about 450 g lysine-HCl (9O wt %) and 50 g microcrystalline cellulose (lO wt %) iB
15 thoroughly blended and then mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
The dried pellet~ are coated to a coating weight of about 14% with a coating compo6ition containing about 31.5~; 2-vinylpyridine/styrene (65~5) copolymer and about 68.5 wt % ball milled talc.
A sample of the coated pellets is placed in rumen te6t fluid for 24 hr at ambient temperature. The rumen protection of the coated pellets is about 85%, and abomasum release is greater than 90~.
This example show6 that two-component coatin~6 using about 70 wt % ball milled talc have excellent rumen 6tability.
EXAMPLE 4 ~Control) A mixture of about 450 g lysine-HCl (9O wt %) and 50 g microcry~talline cellulose (lO wt %) is thoroughly blended and ~hen mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
The dried pellets are coated to a coating weight of about 14~ with a coa~ing composition containing about 31~S~ 2-vinylpyridine~styrene ~65~3~) copolymer and abou~ 68.5 wt ~ talc used in Example 2.
A sample of the coated pellets i8 plaGed in rumen test fluid for 24 hr at ambient temperature. The rumen protectisrl of the coated pelle~s is only about 20~.
This example shows that a two-component coating with talc which has not been ball milled provides poor rumen protection compared with that ob~ained with ball milled talc.
EXAMPL~ 5 A mixture of about 450 g glucose (90 wt ~) and 50 g microcrystalline cellulose (10 wt %~ i6 thoroughly blended and then mixed with water, extruded, pelletized, rounded or poli6hed, and dried according to Example 1.
The dried pellets are coated to a coating weight of about 14% with a coating compoition containing 31.5% 2-methyl-5-vinylpyridine/styrene ~80/20~
copolymer and 68.5~ ball milled talc of Examp~le 1.
A ~ample of the coated pellets i~ placed in rumen test fluid ~Eor 29 hr at ambient temperature. The rumen protection of the coated pellets is about 90-95%
and abomasum relea~e is greater than 90%.
This example shows that 2-methyl-5-vinyl-pyridine~styrene copolymer can ~e used in place of the 2-vinylpyridine/~tyrene copolymer.
Similar results are obtained using other inorganic clays such as bentonite, kaolin, or mica in place of talc.
This example also ~hows that cores of highly water--soluble substances other than amino acid~ ~an be ~8~
coated with the two-co~ponent coating to provide rumen stable pellets.
EXAMPl,E 6 A mixture of abou~ ~S0 g methionine (90 w~ ~ and 50 g binders composed of compres~ible sugar ~6% by wt), sodium carboxymethyl cellulose (4% by wt) is blended and then mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
I'he dried pellets are coa~ed to a coating weight from about 4.5% to about 14% with a coating composition containing about 31.5% 2-methyl-5-vinyl-pyridine/~yrene (80/20) copolymer and about 68.5 wt S
talc or ball milled talc of Example 1.
The rumen protection and abomasal release of the coaled pellets are compared in the following table.
% Protection ~ Relea~e % Coat nq Talc, tTalc]~ Talc, tTalc]*
14 89 98 86 ~6 *[Talc]: Ball milled talc.
. .
A mixture of about 400 g ly6ine-HCl (80 wt %) and 100 g methionine (20 wt %) is thoroughly blended and ~hen mixed with water, extruded, pelletized, rounded or polished, and dried according to Example 1.
The dried pellets are coated to a coating weight of about 14~ with a coating composition containing 20%
2-vinylpyridine/styxene (70~30) copolymer and 80 wt %
talc with and without ball mill treatment.
~x~
A sample of the coated pellets from each prepara--tion is placed in ru~en test fluid for 2~ hours at 39OC. The lysine protection of the coated pellets containing talc without ball mill treatment in the coating is about 10~, but the ly6ine protection is about 75% for the coated pellets containing ball milled talc in the coating.
A mixture of about 450 g methionine (solubility less than 5 g per 80 g water at 20C) (90 w~ ~) and 50 g microcrystalline cellulose (10 wt %) is thoroughly blended and then mixed with about llO g water. The moi~ture content of the dough is adjusted to about 13.8% water. The wet dough i6 then extruded and pelletized by u~ing an extruder equipped with a 2-in diameter die and a rotating chopper blade at the die face. The die openi~gs are 1.6 mm in diameter and the chopper blade i6 controlled to produce short cylindri-cal rods with a length to diameter ratio of about 1 to 1.5. The wet, raw pellets are rounded or polishea to remove the sharp corners and edges. The rounded pellets are then dried to a water content of 1% or le~s.
A portion of the dried pellet6 are coated to a coating weight of about 1~ wt % with a coating composition containiny 31.5 wt % 2-vinylpyridine~
styrene (80/20) copolymer and 68.5 wt % ball milled talc.
The rumen protection of the sample of coated pellets is about 90% and abomasum release i~ greater than 90%.
Other portions of the dried pellets are coated to a coating weight of about 12 and 10~ with the same coating composition used in ~he 1~% coating. The Z~7~
rumen protection of these coated pelle~s is about 85%
and 70~, respectively.
The rumen stable pellets are then placed in synthetic abomasal test fluid for l hr at 30C. The percent of release of the rumen stable pellets in the abomasum was about 93%.
The dried pellets prepared according to Example 8 are coated to a coating weight of about 15 wt ~ with a coating composition containing 80 wt % 2-vinylpyridine/-styrene (80/20) copolymer and about 20 wt % ball milled talc.
A sample of the coated pellets i6 placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 90~. These rumen ~table pellets are then placed in abomasal test fluid for l hr at 39C. The percent of release of the rumen stable pellets in the abomasum test fluid is 78% with 22~ of the pellets remaining undissolved.
This example shows that the two-component coating containing only 20% talc at a coating weight of 14%
provides pellets having good rumen stability and good abomasum release.
The dried pellet6 according to Example B, are coated to a coa~ing weight of about ~ ~ith a coating composition containing 31.5% Z-vinylpyridine/styrene 30 (80~20) copolymer and 68.5 wt ~ calcium stearate.
Fifteen percent of the particles of calcium carbonate is less than 5 micron and 85% is less than lO microns.
A sample of ~he coated pellet~ is placed in rumen test fluid for 24 hr at 39~C. The rumen protection of the coated pellets is about 90-95% and aboma~um release is qreater than about 90~.
This example ~hows that using calcium stearate in place of talc provides a coating which at only 8%
coating weight provides excellent rumen stability even when 50~ le6s coa~ing maeerial is used.
In Examples 11-14 which follow, 15% of the inorganic particles is less than 5 microns and 85~ is less than 10 microns.
The dried pelletfi, according to Example 8r are coated to a coating weight of about 14% with a coating composition containing 31.5% 2-methyl-5-vinylpyridine/-15 styrene (80/20) copolymer and 68.5 wt % of particulate calcium carbonate.
A sample of the coated pellets i6 placed in rumen tet fluid for 2g hr at 39C. The rumen protection of the coated pellets is about 85~ and abomasum release iB
greater than 90%.
This example shows that calcium carbonate can be used in place of talc and provides similar result6.
The dried pellets, according to ~xample 8, are coated to a coating weight of about 14~ with a coating compo6ition containing 31.5~ 2-methyl-~-vinylpyridine~-fityrene (80/20) copolymer and 68.5% of particulate bentonite.
A sample of the coated pellet6 is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 90~ and abomasum release is greater than 90~.
Similar results are obtained using other inorganic clays such as kaolin in place of bentonite.
7~.
EXP~MPLF. 1 3 The dried pellets, according to Example 1, are coated to a ccating weight of about 14~ with a coating composition containing 31.5% 2-me~hyl-5-vinylpyridine/-styrene ~Bo/2~) copolymer ana 68.5% of particulatesilicon dioxide.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets i5 about 90-95~ and abomasum release is greater than 90%.
The dried pellets, according to Example 8, are coated to a coating weight of about 14~ with a coating 15 composition containing 31.5~ 2-methyl-5-vinylpyridine~-styrene (80/20) copolymer and 68.5% of particulate magnesium silicate.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 90-95% and abomasum release is greater than 90~.
EXAMPLE 15 (Control) The dried pellets, according to Example 8, are coated to a coating weight of about 12% with a coating composition containing 31.5% 2-vinylpyridine/styrene (80/20) copolymer and 68.5~ calcium chloride.
A ~ample of the coated pellets i6 placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is only aboue Z0~.
E~AMPLE 16 (Control) The dried pelle~s, according to Example 8, are coated to a coating weigh~ of about 12~ with a coating composition containing 31.5~ 2-vinylpyridine~styrene (80/20) copolymer and 68.5~ calcium sulfate.
A sample of the coa~ed pellets is placed in rumen test fluid for 24 hr a~ ambient temperature. The undissolved pellets are removed from the test fluid, dried, and weighed. The rumen protection of the coated pellets i~ only about 20~.
EX~MPL~ 17 The dried pellets, according to Example 8, are coated to a coating weigh~ of about 12~ with a coa~ing composition containing 31.5~ 2-vinylpyridine/styrene (80~20) copolymer and 68.5% magnesium stearate.
A sample of ~he coated pellets is placed in rumen test fluid for 24 hr at 39C. The rumen protection of the coated pellets is about 70%.
EXAMPLE lB (Control) The dried lysine-HCl-containing pellets, according to Example 1, are coated to a coating weight of about lZ% with a coating composi~ion containiDq 20 31.5% 2-vinyLpyridine/styrene (80/20) copolymer and 68.5 wt % calcium stearate (particle size greater than that of the ~present invention).
A sample of the coated pellets is placed in rumen test fluid for 2g hr at 39C. The rumen protection of the coated pellets is only about 20%.
.
A mixture of about 450 g phenylalanine (solubility of les6 than 2 g per 100 cc water at 20~C) (90 wt ~) and S0 g microcrystalline cellulose (10 wt %) is thoroughly blended and then mixed with about 110 g water. The moisture content of the dough is adjusted to about 18% water. The wet dough is then extruded, pelle~ized, rounded or polished, and dried according to Example 1.
The dried pellet~ are coated to a coating weight of about 12~ with a coa~ing composition containing ~1.5~
2-methyl-5-vinylpyridine~styrene (80~20) copolymer and 68.5% particulate bentonite.
A sample of the coated pellet6 is placed in rumen test fluid for 24 hr at 3soc. The rumen protection of the coated pellets is about 90-95~ and aboma6um relea~e i~ greater than 90~.
Similar results are obtained using other inorganic clays such as kaolin in place of bentonite.
EXAMPLE ~0 A mixture of about ~50 g leucine (solubility less than 3 g per 100 cc water at 20C) (90 wt ~) and 50 g microcrystalline cellulose (10 wt ~) is thoroughly blended and then mixed with about 110 g water~ The moisture content of the dough is adjusted to about 18%
water. The wet dough is then extruded, pelletized, rounded or polished, and dried according eO Example 1~
1'he dried pellets are coated to a coating weigh~ of about 12% with a coating composition containing 31.5%
2-methyl-5-vinylpyridine/styrene (80~20) copolymer and 6~.5% particulate silicon dioxide.
A sample of the coated pellets is placed in rumen test fluid for 24 hr at ~C. The rumen protection of the coated pellets is about 90-95% and abomasum release i6 yreater than 90~.
EX~MPLE Z1 A mixture of about 450 g tryptophan (solubility less than 2 g per 100 cc water at 20C) (90 wt ~) and 50 g microcry~talline cellulose (10 wt ~ is thoroughly blended and then mixed with about 110 g water. T~e moisture content of the dough is adju6ted to about 18%
water. The wet dough is then extruded, pelletized, rounded ox poli~hed, and dried according to ~xample 1.
7~
The dried pellets are coated to a coating weight of about lZ~ with a coating composi~ion containing 31.~%
2-methyl-5-vinylpyridine/styrene (80/20) copolymer and 68.5~ particulate silicon dioxide.
A sample of the coa~ed pellets i6 placed in rumen test fluid f~r 24 hr at 39C. The rumen protection of the coated pellets is abou~ 90-95~ and aboma~um release is greater than 90~.
The dried pellets, according to Example 1, are coated to a coating weight of 14~ ba6ed on total pellet weiyht with a coating composition containing 31.5t Z-vinylpyridine~styrene (80/20) copolymer and 68.5%
particulate aluminum flake. A sample of the coated pellets is placed in a rumen test fluid for 2q hour~ at 39C. The rumen protection is about 82~, and release in abomasum test fluid is about 92~.
ExamPle 23 The dried pellets, according to Example 8 are coated to a coating weight of 12~ ba~ed on total pellet weight with a coating composition containing 30%
2-vinylpyridine/styrene (80/20) copolymer and 70%
particulate aluminum flake. A sample of the coated pellets is placed in a rumen test fluid for 24 hours at 39C. The ru~en protection is 93%, and relea6e in abomasum test fluid is about 90%.
In Examples 17 and 19-23, 15% of the particles of inorganic material is less than 5 micron~ and 85% i6 less than 10 microns.
~ henever the term "inherent viscosity" (I.V.) i6 used in this application, it will be understood to refer to viscosity determinations made at 25C using 0.50 gram of polymer per 100 ml of a solvent composed of 60 wt % p~enol and gO w~ % tetrachloroethane.
- ~4 -Unless otherwise specified, all parts, percentages, ratios, etc., are on a weight ba~is.
The invention has been described in detail with particular reference to preferred embodiment~ tbereo~, but it will be understood that variations and modifica-tions can be effected within the spirit and scope of tbe invention.
Claims (17)
1. A composition adapted for use as a coating material for pellets orally administerable to ruminants which protects the core of said pellets in the rumen and releases it postruminally characterized as consisting essentially of (a) a physiologically acceptable film-forming polymeric substance comprising a polymer, copolymer or mixture thereof having basic amino groups, the nitrogen content of which constitutes between 2 and 14% by weight of the polymeric substance. and (b) an inorganic particulate material dispersed throughout said polymeric substance, at least 15% of the inorganic particulate material having a size of less than 5 microns and at least 85% of the inorganic particulate material having a size of less than 10 microns.
2. A composition according to Claim 1 character-ized in that said polymeric substance is a copolymer comprising repeat units from vinylpyridene.
3. A composition according to Claim 2 character-ized in that said vinylpyridene is 2-vinylpyridene.
4. A composition according to Claim 1 character-ized in that said polymeric substance is a copolymer comprising repeat units from 2-vinylpyridene and styrene.
5. A composition according to Claim 4 character-ized in that the ratio of repeat units of 2-vinylpyridene to styrene is 65:35.
6. A composition according to Claim 1 character-ized in that said inorganic particulate mate-rial is selected from alkaline earth fatty acid salts, inorganic clays, inorganic sili-cates, silicon oxides, and alkaline earth carbonates.
7. A composition according to Claim 1 character-ized in that said inorganic particulate material is selected from calcium stearate, magnesium stearate, talc, bentonite, kaolin, zeolite, magnesium silicate, calcium carbonate, magnesium carbonate, and silicon dioxide.
8. A composition according to Claim 1 character-ized in that said inorganic substance accounts for 20-84% of the total weight of the coating.
9. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and a coating comprising the composition of Claim 1.
10. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and a coating comprising the composition of Claim 2.
11. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and a coating comprising the composition of Claim 4.
12. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and a coating comprising the composition of Claim 6.
13. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and a coating comprising the composition of Claim 7.
14. A composition adapted for use as a coating material for pellets orally administerable to ruminants which protects the core of said pellets in the rumen and releases it postruminally characterized as consisting essentially of (a) a physiologically acceptable film-forming polymeric substance comprising a polymer, copolymer or mixture thereof having basic amino groups, the nitrogen content of which constitutes between 2 and 14% by weight of the polymeric substance, and (b) an inorganic particulate material dispersed throughout said polymeric substance, at least 15% of the inorganic particulate material having a size of less than 5 microns and at least 85% of the inorganic particulate material having a size of less than 10 microns, said inorganic particulate material being selected from the group consisting of alkaline earth fatty acid salts, in-organic silicates, silicon oxides and alkaline earth carbonates.
15. A composition adapted for use as a coating material for pellets orally administerable to ruminants which protects the core of said pellets in the rumen and releases it post-ruminally characterized as comprising (a) a physiologically acceptable film-forming polymeric substance comprising a polymer, copolymer or mixture thereof having basic amino groups, the nitrogen content of which constitutes between 2 and 14% by weight of the polymeric substance, and (b) an inorganic particulate material dis-persed throughout said polymeric sub-stance, at least 15% of the inorganic particulate material having a size of less than 5 microns and at least 85% of the inorganic particulate material having a size of less than 10 microns, said inorganic particulate material being selected from the group consisting of calcium stearate, magnesium stearate, bentonite, kaolin, zeolite, magnesium silicate, calcium carbonate, magnesium carbonate and silicon dioxide.
16. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and characterized by having coating comprising the composition of Claim 14.
17. A pellet adapted for oral administration to a ruminant comprising a core material beneficial to a ruminant postruminally and characterized by having coating comprising the composition of Claim 15.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/802,105 US4780315A (en) | 1985-11-25 | 1985-11-25 | Rumen-stable pellets |
| US802,105 | 1985-11-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1282701C true CA1282701C (en) | 1991-04-09 |
Family
ID=25182850
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000523200A Expired - Lifetime CA1282701C (en) | 1985-11-25 | 1986-11-18 | Rumen-stable pellets |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US4780315A (en) |
| EP (1) | EP0246310B1 (en) |
| JP (1) | JPS63501684A (en) |
| CA (1) | CA1282701C (en) |
| DE (1) | DE3668409D1 (en) |
| ES (1) | ES2007027A6 (en) |
| WO (1) | WO1987003173A1 (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4837004A (en) * | 1985-10-18 | 1989-06-06 | Eastman Kodak Company | Rumen-stable pellets |
| FR2603458B1 (en) * | 1986-09-04 | 1990-11-02 | Rhone Poulenc Sante | NOVEL COMPOSITIONS FOR COATING FOOD ADDITIVES FOR RUMINANTS AND FOOD ADDITIVES THUS COATED |
| JP2547995B2 (en) * | 1987-01-26 | 1996-10-30 | 昭和電工株式会社 | Granules for ruminants and method for producing the same |
| US6306427B1 (en) * | 1989-12-28 | 2001-10-23 | Rhone-Poulenc Nutrition Animale | Pellets containing active ingredients protected against degradation in the rumen of ruminants |
| FR2663207B1 (en) * | 1990-06-15 | 1993-04-30 | Rhone Poulenc Nutrition Animal | PROCESS FOR COATING A ACTIVE SENSITIVE PH POLYMER OF ACTIVE INGREDIENTS. |
| JPH0479844A (en) * | 1990-07-20 | 1992-03-13 | Ajinomoto Co Inc | Feed additive for ruminant |
| US5352448A (en) * | 1992-07-20 | 1994-10-04 | Purdue Research Foundatioin | Oral administration of antigens |
| JP2000512671A (en) | 1996-06-14 | 2000-09-26 | エミスフェアー テクノロジーズ インク | Microencapsulated fragrance and preparation method |
| EP0918456A1 (en) * | 1996-07-23 | 1999-06-02 | Fmc Corporation | Disintegrant composition for dispersible solids |
| ATE299696T1 (en) | 2000-05-12 | 2005-08-15 | Pharmacia & Upjohn Co Llc | VACCINE COMPOSITION AND METHOD FOR PRODUCING THE SAME AND METHOD FOR VACCINATION OF VERTEBRATE ANIMALS |
| US6776904B2 (en) * | 2000-12-22 | 2004-08-17 | Ethicon, Inc. | Device and method of use for aldehyde removal |
| US20040202695A1 (en) * | 2003-04-11 | 2004-10-14 | Agri-Nutrients Technology Group, Inc. | Nutritional supplement for post rumen metabolism |
| FR2879075B1 (en) * | 2004-12-15 | 2007-01-19 | Adisseo France Sas Soc Par Act | PROCESS FOR PREPARING EXTRUSION-ACTIVE HYDROPHILIC ACTIVE INGREDIENT PELLETS |
| FR2879074B1 (en) * | 2004-12-15 | 2007-08-03 | Adisseo France Sas Soc Par Act | PELLETS OF ACTIVE HYDROPHILIC PRINCIPLE |
| US20140141124A1 (en) * | 2012-11-16 | 2014-05-22 | Elwha LLC. | Urea food pellets and associated methods |
| US20140141118A1 (en) * | 2012-11-16 | 2014-05-22 | Elwha LLC. | Urea food pellets and associated methods |
| TWI658842B (en) * | 2014-03-31 | 2019-05-11 | 日商東麗股份有限公司 | Coating agent for solid preparation, coating and coated solid preparation formed by the same |
| CN115413735B (en) * | 2022-09-06 | 2023-11-21 | 湖北欣和生物科技有限公司 | Rumen protected docosahexaenoic acid enteric-coated particles and preparation method thereof |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3041243A (en) * | 1959-07-25 | 1962-06-26 | Tanabe Seiyaku Co | Sealing coat for tablets and the like |
| US3619200A (en) * | 1966-06-21 | 1971-11-09 | Commw Scient Ind Res Org | Method and food composition for feeding ruminants |
| US3562806A (en) * | 1968-09-10 | 1971-02-09 | Eastman Kodak Co | Rumen stable medicament and/or nutrient compositions |
| US3829564A (en) * | 1970-07-17 | 1974-08-13 | Commw Scient Ind Res Org | Coated products for veterinary use |
| EG10802A (en) * | 1971-02-19 | 1976-10-31 | Bayer Ag | A process for embeding veterinary substances and their protection against the influence of the gastric juice of the rumen |
| US4117801A (en) * | 1976-06-10 | 1978-10-03 | Eastman Kodak Company | Apparatus for spray coating discrete particles |
| US4181708A (en) * | 1977-09-02 | 1980-01-01 | Eastman Kodak Company | Rumen-stable pellets |
| US4196187A (en) * | 1977-09-02 | 1980-04-01 | Eastman Kodak Company | Rumen-stable pellets |
| US4181710A (en) * | 1977-09-02 | 1980-01-01 | Eastman Kodak Company | Rumen-stable pellets |
| US4181709A (en) * | 1977-09-02 | 1980-01-01 | Eastman Kodak Company | Rumen-stable pellets |
| US4177255A (en) * | 1977-09-02 | 1979-12-04 | Eastman Kodak Company | Rumen-stable pellets |
| JPS57122931A (en) * | 1981-01-22 | 1982-07-31 | Chiyoda Chem Eng & Constr Co Ltd | Fine powder and preparation thereof |
| FR2514261B1 (en) * | 1981-10-08 | 1986-08-22 | Aec Chim Organ Biolog | NOVEL COMPOSITION FOR COATING FOODS AND DRUGS AND GRANULES THUS COATED |
| DE3366815D1 (en) * | 1982-07-12 | 1986-11-20 | Eastman Kodak Co | ROOM STABLE PELLETS |
| US4595584A (en) * | 1983-05-26 | 1986-06-17 | Eastman Kodak Company | Rumen-stable pellets |
| CA1240267A (en) * | 1983-05-26 | 1988-08-09 | Eastman Kodak Company | Rumen-stable pellets |
| BR8506634A (en) * | 1984-12-20 | 1986-09-09 | Rhone Poulenc Sante | COMPOSITES FOR COATING FOOD ADDITIVES INTENDED FOR RUMINANTS AND GRANULATES IN THE FORM OF MICROCAPSULES SO COATED |
| ZA86252B (en) * | 1985-01-30 | 1986-09-24 | Warner Lambert Co | Coated dosage forms |
-
1985
- 1985-11-25 US US06/802,105 patent/US4780315A/en not_active Expired - Fee Related
-
1986
- 1986-11-17 DE DE8686907181T patent/DE3668409D1/en not_active Expired - Fee Related
- 1986-11-17 JP JP61506299A patent/JPS63501684A/en active Pending
- 1986-11-17 EP EP86907181A patent/EP0246310B1/en not_active Expired - Lifetime
- 1986-11-17 WO PCT/US1986/002461 patent/WO1987003173A1/en active IP Right Grant
- 1986-11-18 CA CA000523200A patent/CA1282701C/en not_active Expired - Lifetime
- 1986-11-24 ES ES8603157A patent/ES2007027A6/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63501684A (en) | 1988-07-14 |
| EP0246310A1 (en) | 1987-11-25 |
| ES2007027A6 (en) | 1989-06-01 |
| US4780315A (en) | 1988-10-25 |
| EP0246310B1 (en) | 1990-01-24 |
| DE3668409D1 (en) | 1990-03-01 |
| WO1987003173A1 (en) | 1987-06-04 |
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| MKLA | Lapsed |