CA1102240A - Method for the manufacture and the application of pharmaceutical products for the veterinary science - Google Patents
Method for the manufacture and the application of pharmaceutical products for the veterinary scienceInfo
- Publication number
- CA1102240A CA1102240A CA276,697A CA276697A CA1102240A CA 1102240 A CA1102240 A CA 1102240A CA 276697 A CA276697 A CA 276697A CA 1102240 A CA1102240 A CA 1102240A
- Authority
- CA
- Canada
- Prior art keywords
- admixture
- aroma
- dosage unit
- unit form
- pharmaceutical compound
- 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
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
Abstract
Abstract of patent application The present invention relates to a method for the manufacture and the application of pharmaceutical products for the vete-rinary science and has for its purpose to facilitate the up-take of the products by animals to be treated.
The method according to the invention is characterized in that the products have added thereto or chemically combined therein natural or artificial odorous and flavouring substances speci-fic to the category and/or to the species and/or to the breed or other substances unspecific to the category and/or the spe-cies and/or to the breed.
The method according to the invention is characterized in that the products have added thereto or chemically combined therein natural or artificial odorous and flavouring substances speci-fic to the category and/or to the species and/or to the breed or other substances unspecific to the category and/or the spe-cies and/or to the breed.
Description
A METIIOD FOR THE MANUFACTURE AND THE APPLICATION OF
PHARMACEUTICAL PRODUCTS FOR ~IE VETERINARY SCIENCE
The present invention relates to a method for the manufac-ture and the application of pharmaceutical products for the veterinary science and has for its purpose to facilitate the uptake of the products by animals to be treated.
The method according to the invention is characterized in that the products have added thereto or chemically combined therein odorous and flavouring substances specific to the category and/or to the species.
The said odorous and flavouring substances have the purpose of masking the product and of stimulating the appetence. These specific aromae are ready available on the open market and are used so far exclusively in aromatisation o feeds. The novelty lies in the fact, that there is now an decisive improvement in administering pharmaceutical preparations for veterinary use by the oral route, i.a. the mucuous membranes, in using there specific aromae. This method may not be compounded with the preparation of pet food etc., because there is only use made of unspecific aromae.
For the better understanding of the invention an embodiment is now disclosed ln the following description.
.
A pharmaceutical compound intended for the oral intake by young pigs has added thereto in the manner described the flavour of sow milk. This compound is accepted by the animals even when not weaned from the milk nutrition and not yet ad~pted to solid feed.
page-~
SUPPLEMENTAR~ DISCLOSURE 276 697 REFERENCES
Canadian Paten~s521 875 2 / 14 / 56 Landau 552 482 2/04/58 Anderson et al 604 518 9/06/60 Tribble 665 556 6/25/63 Tribble 905 930 7/25/72 Brouwer et al 918 997 1/16/73 Coppage et al 929 855 7/10/73 Dietrich et al 982 474 1/26/76 Miler et al 999 603 11/09/76 Sundt Other Patents126 9615/1882 United States 275 524 4/1883 id.
327 231 9/1885 id.
PHARMACEUTICAL PRODUCTS FOR ~IE VETERINARY SCIENCE
The present invention relates to a method for the manufac-ture and the application of pharmaceutical products for the veterinary science and has for its purpose to facilitate the uptake of the products by animals to be treated.
The method according to the invention is characterized in that the products have added thereto or chemically combined therein odorous and flavouring substances specific to the category and/or to the species.
The said odorous and flavouring substances have the purpose of masking the product and of stimulating the appetence. These specific aromae are ready available on the open market and are used so far exclusively in aromatisation o feeds. The novelty lies in the fact, that there is now an decisive improvement in administering pharmaceutical preparations for veterinary use by the oral route, i.a. the mucuous membranes, in using there specific aromae. This method may not be compounded with the preparation of pet food etc., because there is only use made of unspecific aromae.
For the better understanding of the invention an embodiment is now disclosed ln the following description.
.
A pharmaceutical compound intended for the oral intake by young pigs has added thereto in the manner described the flavour of sow milk. This compound is accepted by the animals even when not weaned from the milk nutrition and not yet ad~pted to solid feed.
page-~
SUPPLEMENTAR~ DISCLOSURE 276 697 REFERENCES
Canadian Paten~s521 875 2 / 14 / 56 Landau 552 482 2/04/58 Anderson et al 604 518 9/06/60 Tribble 665 556 6/25/63 Tribble 905 930 7/25/72 Brouwer et al 918 997 1/16/73 Coppage et al 929 855 7/10/73 Dietrich et al 982 474 1/26/76 Miler et al 999 603 11/09/76 Sundt Other Patents126 9615/1882 United States 275 524 4/1883 id.
327 231 9/1885 id.
2 450 318 3/1948 id.
909 461 10/1959 id.
909 461 10/1959 id.
3 005 753 10/1961 id.
3 367 834 2/1968 id.
7 110 5/1884 United Kingdom 415 266 6/1966 Switzerland 264 911 9/1968 Austria 519 303 2/1972 Switzerland 2 712 662 9/1977 Germany 7 704 758 ~ 977 Netherlands 2 716 629 ~ 977 Germany 772 514 8/1978 South Africa 773 161 8/1979 Austria Other References Veterinary Drug Ecyclopedia, 10th Edition, New York Pharmacopoea Helvetica, Bern 1971, Editio sexta Webster's New World Dictionary/ 2nd Edition, New York and Cleveland 1970 Barnes, E.M., J. Appl. Bacteriol. 27 (1964) 461 ~.
Coultas, M.K. et al., J. Bacteriol. 92 (1966) 516~.
Hartmann, P.A. et al., Int. J. Syst. Bac-teriol.~'l6 (1966) 19 ; ibid., Adv. Appl. Microbiol. 8 (1966) 253ff.
Whittenbury, R., J. Gen. Mlcrobiol. 38 (1965) 279ff.
.
Drugs or pharmaceutical compounds in the present speclfi-cation and claims are understood to mean dosage unit forms, i.e. pharmaceutical preparations "suitable for administration in convenient quantity to a patient, to provide a predeter-, " ' ' '' ' ' ' ' ~, . . .
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. ; , " , . - ' ' . ' ' "" ' ' ' "' ', ' " .. " ' , . ' ' " . . , .. ', . ', ~ . .
~ ~ zz ~ ~ page--2--3 mined dose of the active ingredients. Solid dosage unit forms include tablets, capsules, powders, coated particles, soft pills and the like. Liquid dosage unit forms include solutions, tinctures, elixirs, emulsions, suspensions and the like" ~Ehrenford, United States 2 909 461). All of these dosage unit forms are intended for oral intake and use.
Any drug or pharmaceutical compound which can be prescribed for therapeutical and/or prophylactical use being intended for oral intake by domestic animals, and which is approved by and registered with the Food and Drug Administration, may be combined with concentrated specific odorous and flavouring substances (aromae) by the step of admixture as set forth.
There is only question in this specification and claims of drugs or pharmaceutical compounds which are suited to be absorbed and assimilated through the mucuous membranes;
or which improve synthesis of substances by, and/or in-tended for absorption and assimilation through, the mucuous membranes. Thus, the dosage unit forms disclosed supra are ' intended for the oral route of administration, as taught by the Pharmacopoea Helvetica.
In the present specification and claims, an odorous and flavouring substance (aroma) is considered to be specific to the specie~ of the domestic animal treated, if the sub-stance in question is closely physiologically and biologi-cally related to the species of that domestic animal, and, therefore, expresses a special attraction and affinity to it, founded by relationship and not by palatability, only.
As an example, the concentrated flavour of synthesized sow milk, consisting of an adequate mixture of Butyl Bu~yryl Lactate and other esters, Gamma Nonalactone and other Lac-tones, Diathecyl and other aldehydes and Iso-Butyric Acids and other organic acids - readily available on the market -is closely physiologically and biologically related and, therefore, specific to piglets; it expresses the aromatic ,: . : :.:
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ingredients of sow milk. Or, as another example, an ade-quate mixture of Ethyl Lactate and other esters and Vanil-lin and other aldehydes - readily available on the open market - is closely physiologically and biologically re-lated to cattle, because it expresses the aromatic ingre-dients of cow milk.
On the other hand, odorous and flavouring substances (aromae) not being physiologically and biologically related to the species of a domestic animal treated, are considered in this specification as being non-specific. So it is, when the aroma of synthesized sow milk is administered in a suitable dosage unit form to calves, or the flavour of synthesized cow milk is administered to piglets, or, more extremely, the flavour of meat is administered to dogs etc.
According to the present specification and claims it does not suffice for an axoma to smell and/or taste pleasant, that this aroma i5 considered as being specific to the species of domestic animal treated. There has to be, more-over, a close physiological and biological relationship between the aroma used and the species of the doemstic animal treated.
In the present specification and claims, the "domestic animal" means one out of the categories of domesticated suidae scrofae, ruminantia, avidae, equidae, rodentia, canidae and feles. I.e. one out of the common species of breeding and fattening pigs; large ruminants as calves, beef cattle, cows; small ruminants as sheep and goats; breeding and fattening poultry; horses and ponies; rabbits and rodents; cats and dogs of all races.
The subject matter may be clearly distinguished from animal feed in any form. "Feed" means food, fodder, given to do-mestic animals (Webster's New World Dictionary). A "supple-ment" ist something to be added, especially to make up for a lack or deficiency (op. cit.). In the feed industry "supple~
ments" or "feed supplements'i are commonly added to eed in ~, .
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the form of socalled "supplemented feed" to make up ~or a lack, especially of vitamines and minerals (Veterinary Drug Encyclopedia). When medicines are used as supplements in therapeutic dosage, the "medicated feed" is created (op.
cit.).
But a dosage unit form, as understood by this application and claims, may be manufactured completely with inert carrier substances; when meal of cereals or feed grain by-products are incorporated into the dosage unit form, as disclosed fur~her, these components have strictly therapeutic effect, in excluding or reducing well known medication stress~ The dosage unit forms are not administered in order to have the domestic animal fed, but to cure it. The subject matter is not intended to be used as a feed supplement neither, but administered to the domestic animal directly.
A disadvantage of the supplemented or medicated feed in comparison with the subject matter lays in the well known danger of disintegration of the mixtures during manipu-lations. In supplemented feed this danger is not 50 impor-tant, because dosage per unit is installed more or less accidentially. In medicated feed, however, this fact is vexy important; it exists the latent danger that dosage is inappropriate and not steadily under con~rol. Atmospheric influences ~re not excluded and the medicinal active in-gredients may be deteriorated or inactivated.
Moreover, an animal being in bad health - domestic animals for breeding and fattening very frequently suffer of di-gestive troubles - lacks of appetite. How could one force such an animal to gobble up daily large quantities of feed, in order to provide it with an appropriate dosage of medicine?
These are the reasons, why medicated feed has never gained the importance in Veterinary Science one could have ex-pected: The dosaye of the mediclne may be inappropriate and not steadlly under control because of khe danger of de-,` ,,~,"~J
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~ ~ z ~ ~ page 5 composition o~ the mi~ture during manipulations; the medi-cine is not protected against exogenous influences; a suffering domestic animal is lacking of appetite and, there-fore, not in a good humor to take up the large quantities of feed necessary to an appropriate medication.
That is why the subject matter teaches the aromatization of highly concentrated dosage unit forms as medicines and the direct administration per os of these high concen-trations of medicinal active ingredients to the suf~ering domestic animal. Avoiding by this the roundabout and unse-cure way of feed.
The aromatization is necessary to facilitate the uptake of the pharmaceutical compounds by the domestic animal by the mean of a familiar smell and taste; a carrier substance may be necessary to give the dosage unit an appropriate form;
and a covering may be necessary to protect the dosage unit form from exogenous influences. There can be no doubt, that the subject ma~ter teaches an improvement in oral medi-cation of domestic animals, especially with respect to the species specific aromatization of dosage unit forms.
The carrier substance may be composed-of an inert substance in physiological respect, alone, as disclosed supra, e.g.
of the polymeric carbohydrate cellulose, or of dextrose, starch and meal of cereals or feed graîn by-products. The latter two feed components having the advantage of exclu-ding medication-stress when used as carrier substance for the oral administering of drugs or pharmaceutical compounds to domestic animals.
The concentrated specific odorous and flavouring substances (aromae) do consist of formulae which are synthesized and marketed by the leading flavour manufac~urers and are offered and used exclusively ~or aromatisation of feed products for dom stic animals. There has been no use, so far, of these concentrated specific odorous and flavouring substances ,~..
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(aromae) in aromatisation of drugs or pharmaceutical com-pounds for oral intake by domestic animals.
The concentrated specific odorous and flavouring substances (aromae) may be physically combined by the step of admixture either with the said compounds or with the carrier substance or with the covering, or in a combination thereof. Further-more, the concentrated specific odorous and flavouring substances (aromae) may be chemically bound to the carrier substance as to the covering as well.
If a covering is used, in order to mask the compound and/or for protecting the preparation against nuisable inter-ferences, this covering may consist of a colloidal emulsion mainly of sugar sirup, starch and gum arabic in adeguate proportions. In this emulsion, pressed pellets or pills consisting of the pharmaceutical compound, or of both carrier substance, drugs and/or concentrated specific odo-rous and flavouring substances (aromae), are processed into dragees, in a way as a person skilled in the art is used to and as it is disclosed by David (Switzerland 415 266) and as set forth.
If the concentrated specific odorous and flavouring sub-stances (aromae) are combined with the colloidal emulsion, these substances may also be dissolved in the emulsion.
The colloidal emulsion with the admixed or dissolved con-centrated specific odorous and flavouring substances (aromae) is then used to cover the preparation, which pre-viously has been pressed and transformed into pellets or pills. By subsequent drying and crystallization of the odorous and flavouring colloidal emulsion on the surface of the peLlets or pilLs, a speci~ic odourous and flavou-ring aromatized outside layer crust is formed, which at the same time serves for conservation and protection of the preparation against interferences caused e.g. by the atmospheric air.
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page For the better understanding of my invention, eleven embo-diments are now disclosed in the following descxiption.
The first four, when no carrier substance is used and the concentrated specific odorous and flavouring substances (aromae) are directly compounded with ~he drugs; the second four, when a carrier substance is used and compounded with the drugs and the concentrated specific odorous and fla-vouring substances (aromae); the nineth, when the first eight examples are covered with a covering; the tenth, when the covering is compounded wi~h the concentrated specific odorous and flavouring substances (aromae); and the eleventh, when the concentrated specific odorous and flavouring substances (aromae) are used in the covering, only.
The sufficient proportion of the concentrated specific odo7 rous and flavouring substances (aromae) presently in mar-ket is of 0,05~ to 4,0% of the weight of the dry crystal~
line colloidal emulsion; calculated in weight of the fi-nished preparation, this sufficient proportion amounts to 10 - 25 ppm, i.e. 10 - 25mg per one kilogram. When used in a pharmaceutical compound alone or with a carrier sub-stance, the proportion of the concentrated speci~ic odorous and flavouring substances (aromae) may make up to 1 g or more per kilogram.
Dry Hog Feed Nectar (Flavor Corporation of America~ and Pig Krave (Feed Flavors Inc.), resp. Dry Cream-nectar (Flavor Corporation of America) and Calf-ade (Feed Fla-vors Inc.), as well as Dry Horse Feed Nectar (Flavor Corporation of America) and Fresh-Arome (Feed Flavors Inc.) mentioned in the following examples, are to my knowledge specific aromae mainly consis-ting of synthe-sized organlc acids, esters and aldehydes, as disclosed supra. For equidae, malonic acid and its derivatives are used. The exact proportion of the different ingredients beLng a manufa~tuFing secret, and is not subject to this .
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patent application. The aromae in qu~stion are readily available on the open market and are used, so far, in feed production, only, and not in pharmaceutical com-pounds for veterinary purposes.
Stabilized extract of rumen is used in the examples one to three as it is produced by the method diclosed by Bio-fac A/S (Switzerland 519 303). This invention claims the manufacturing method and the admixture of the product to feed, only. I claim the admixture of this stablized ex-tract of rumen to dosage unit forms being aromatized specifically, as set forth.
The Bezimidazole referred to in examples five to seven is produced by Merck & Co. Inc., Rahway N.J. (et al.) and thePiperazine used in the same examples is produced by Jefferson Chemicals Co. Inc., Houston, Texas (et al.);
both are readily available on -the open market.
LBC (Lactic-acid Bacteria Concentrate) referred to in the examples four and eight is a po~der containing lyophi-lized lactic-acid producing bacteria of the strain Strep-tococcus faecium Cernelle 68 (SF68) in a sustaining carrier.
lg LBC contains minimum 35~109 viable cells~ It may be used in order to normalize the intestinal flora and to prevent and cure intestinal disorder in pigs, cattle, equids, poultry etc. SF68 belongs to the normal intestinal flora and makes a valuable contribution to the digestive process.
The bacteria are lyophilized, and the metabolic activity of the micro-organisms in the LBC powder is blocked. As soon as they reach the intestinal tract their reproduc-tive activity is resumed. There are a large numer of strains o~ lactic-acid bacteria. They differ in their ability to digest different types of sugar and in their stability against external influences. Their stability in the lyophilized state and their ability to remain ac-tive also di~fer fxom one strain to another. As to the minimum delay in action and effectiveness, rate of re-~' , page `~ I D
production, inhibition of yrowth, restistance against anti-biotics and stability the strain SF68 clearly outclasses competitive biological preparations. The strain contained in LBC (SF68) was isolated byscientists of AB Cernelle, Vegeholm, Engelholm, Sweden.
Example one Stabilized extract of rumen is physically combined by admixture with feed enzymes in a proportion of 38 : 10.
To this combination 1%o of colour and 1%o of Dry Hog Nectar (Flavor Corporation of America) or Pig-Krave (Feed Flavors Inc.) are added by mixture. The compound is then pressed and transformed into pellets or pills. The prepara-tion is now ready for final analysis and control according to Good Manufacturing Practice (GMP) and for subsequent administe-ring per os to piglets and hogs for the prevention of and curing from indigestions.
Example two In ~he preparation according to example one the specific pig aroma is replaced by Dry Creamnectar (Flavor Corpo-ra~ion o America) or Calf-Ade (Feed Flavors Inc~)O This preparation is ready for administering per os to calves for the prevention of and curing from indigestions.
Example three In the preparation according to example one the specific pig aroma is replaced by Dry Horse Feed Nectar (Flavor Corporation of America) or Fresh-Aroma (Feed Flavors Inc.).
This preparation is ready for administering peros to equids for the prevention of and curing from indigestions.
Example four In the preparation according to examples one to -three the stabilized extract of rumen is replaced by LBC in a pro-:
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~ z ~ page portion of lg LBC/g of dosage unit form.
Example five 75 g of 2-(4 Thiazolyle)-benzimidazol~ are physically com-bined with 90 g of Piperazine base, 137 g Wheat bran, 28 g Vaseline oil and 670 g Barley meal. To this compound 1%o of Dry Horse Feed Nectar (Flavor Corporation of America) or Fresh-Aroma (Feed Flavors Inc.) is added by mixture, as well as l~o of colour. When e.g. dextrose or starch or sub-stances with similar properties are used as a carrier sub-stance or combined with a carrier substance, the concen-trated specific odorous and flavouring substances (aromae) may also be chemically bound to the carrier substance or with part thereof, e.g. by ~he step of hydration. This com-pound is then pressed and transformed into pellets or pills. The preparation is now ready for final analysis and control according to GMP and for subsequent administering per os to equids suffering from animal parasites.
Exampl~ SlX
In the preparation according to example five, the specific horse aroma is replaced by Dry Hog Feed Nectar (Flavor Corporation of America) or Pig Krave (Feed Flavors Inc.).
This preparation is ready for administering peros to pig-lets and hogs suffering from animal parasites.
Exam~le seven In the preparation according to example five, the specific horse aroma is xeplaced by Dry Creamnectar (Flavor Corpo-ration of America) or Calf-Ade (Feed Flavors Inc.). This preparation is ready for administering per os to calves suffering from animal parasites.
Example eight In the preparation accordiny to examples five to seven the _. .
~ paye Benzimidazole and Piperazine are replaced by LBC in a proportion of lg LBC/g of dosage unit form.
Example nine The preparations described in the first eight examples are covered with a colloidal emulsion, consisting mainly of sugar sirup, starch and gum arabic. After coating being completed, the preparations are dried by processing it in sugar powder and a stream of warmed air, until a cry-stalline crust is showing up on the surface of the pel-lets or pills. The preparations are now ready for final analysis and control according to G~P and for subsequent administering per os to the respective domestic animals.
Example ten The preparations of the examples one to four are coated with a colloidal emulsion, consisting of 62% sugar sirup, 25% starch, 8,5% CaC03, 3% gum arabic, 0,8% MgC03, 0,35%
colour and 0,35% of the respective specific aromae. After coating being completed, the preparation is dried by processing it in sugar powder and a stream of warmed air, until a crystalline crust is showing up on the surface of the pellets or pills. The preparation is now ready for final analysis and control according to GMP and for sub-sequent administering per os to the respective domestic animals.
The preparations of the examples five to eight are coa~ed with a colloidal emulsion consisting of 82,5% sugar sirup, 12% CaC03, 3,5% gum ararbic, 1% MgC03, 0,5% colour and 0,5~ o the respective specific aromae. After coating being completed, the preparation is dried by processing it in sugar powder and a stream of warmed air, until a crystal-line crust is showing up on the surface of the pellets or pills. The preparation is now ready for 1nal analysis and control according to GMP and for subsequent administe-;
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rin~ per os to the respective domestic animals.
Example eleven The preparations according to examples one to eight are pro-duced by admixture and physical combination withou-t the addition of colour and concentrated specific odorous and flavouring substances (aromae) and then processed as des-cribed in example ten by coating with the disclosed colloidal emulsions, to which the respective colours and concentrated specific odorous and flavouring substances (aromae) have been added in the right proportions. After drying, the preparations are ready for final analysis and control,according to GMP and for subsequent administering per os to the respective domestic animals.
Age and environment are decisive of domestic animal's alimentary physiologica] capacity of absorption and meta-bol1sm. The age is determining the composition of the con-centra'ted specific odorous and flavouring substances (aromae) and the environment may determine the combination and nature of the other active substances, i.e. drugs for admlnistering per os.
The environment is insofar concerned in domestic animal's alimentary physiological capacity of absorption and meta-bolism, as it may influence this capacity and the meta-bolism in any stage of age and may depend on the lieu, con-ditions and systems of bxeeding and ~attening. It may occur by so called stress or continuous chronic disease in breeds or cattLes. This influence shows up e.g. when suckling pi'gs are weaned from the milk nutrition or at the moment whe,n young hogs are installed ~or fattening (stress) or when the whole breed or cattle are su~ering from indigestionsover several generations. In such cases, the usual com-bination~ and nature of the active substances, i.e. druys,have to be varied adequately, also.
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3 367 834 2/1968 id.
7 110 5/1884 United Kingdom 415 266 6/1966 Switzerland 264 911 9/1968 Austria 519 303 2/1972 Switzerland 2 712 662 9/1977 Germany 7 704 758 ~ 977 Netherlands 2 716 629 ~ 977 Germany 772 514 8/1978 South Africa 773 161 8/1979 Austria Other References Veterinary Drug Ecyclopedia, 10th Edition, New York Pharmacopoea Helvetica, Bern 1971, Editio sexta Webster's New World Dictionary/ 2nd Edition, New York and Cleveland 1970 Barnes, E.M., J. Appl. Bacteriol. 27 (1964) 461 ~.
Coultas, M.K. et al., J. Bacteriol. 92 (1966) 516~.
Hartmann, P.A. et al., Int. J. Syst. Bac-teriol.~'l6 (1966) 19 ; ibid., Adv. Appl. Microbiol. 8 (1966) 253ff.
Whittenbury, R., J. Gen. Mlcrobiol. 38 (1965) 279ff.
.
Drugs or pharmaceutical compounds in the present speclfi-cation and claims are understood to mean dosage unit forms, i.e. pharmaceutical preparations "suitable for administration in convenient quantity to a patient, to provide a predeter-, " ' ' '' ' ' ' ' ~, . . .
: . ' ' . ` . . .
. ; , " , . - ' ' . ' ' "" ' ' ' "' ', ' " .. " ' , . ' ' " . . , .. ', . ', ~ . .
~ ~ zz ~ ~ page--2--3 mined dose of the active ingredients. Solid dosage unit forms include tablets, capsules, powders, coated particles, soft pills and the like. Liquid dosage unit forms include solutions, tinctures, elixirs, emulsions, suspensions and the like" ~Ehrenford, United States 2 909 461). All of these dosage unit forms are intended for oral intake and use.
Any drug or pharmaceutical compound which can be prescribed for therapeutical and/or prophylactical use being intended for oral intake by domestic animals, and which is approved by and registered with the Food and Drug Administration, may be combined with concentrated specific odorous and flavouring substances (aromae) by the step of admixture as set forth.
There is only question in this specification and claims of drugs or pharmaceutical compounds which are suited to be absorbed and assimilated through the mucuous membranes;
or which improve synthesis of substances by, and/or in-tended for absorption and assimilation through, the mucuous membranes. Thus, the dosage unit forms disclosed supra are ' intended for the oral route of administration, as taught by the Pharmacopoea Helvetica.
In the present specification and claims, an odorous and flavouring substance (aroma) is considered to be specific to the specie~ of the domestic animal treated, if the sub-stance in question is closely physiologically and biologi-cally related to the species of that domestic animal, and, therefore, expresses a special attraction and affinity to it, founded by relationship and not by palatability, only.
As an example, the concentrated flavour of synthesized sow milk, consisting of an adequate mixture of Butyl Bu~yryl Lactate and other esters, Gamma Nonalactone and other Lac-tones, Diathecyl and other aldehydes and Iso-Butyric Acids and other organic acids - readily available on the market -is closely physiologically and biologically related and, therefore, specific to piglets; it expresses the aromatic ,: . : :.:
.: ' . ' ' . .. : . . . . .. .
~ 4~ page ~ ~
ingredients of sow milk. Or, as another example, an ade-quate mixture of Ethyl Lactate and other esters and Vanil-lin and other aldehydes - readily available on the open market - is closely physiologically and biologically re-lated to cattle, because it expresses the aromatic ingre-dients of cow milk.
On the other hand, odorous and flavouring substances (aromae) not being physiologically and biologically related to the species of a domestic animal treated, are considered in this specification as being non-specific. So it is, when the aroma of synthesized sow milk is administered in a suitable dosage unit form to calves, or the flavour of synthesized cow milk is administered to piglets, or, more extremely, the flavour of meat is administered to dogs etc.
According to the present specification and claims it does not suffice for an axoma to smell and/or taste pleasant, that this aroma i5 considered as being specific to the species of domestic animal treated. There has to be, more-over, a close physiological and biological relationship between the aroma used and the species of the doemstic animal treated.
In the present specification and claims, the "domestic animal" means one out of the categories of domesticated suidae scrofae, ruminantia, avidae, equidae, rodentia, canidae and feles. I.e. one out of the common species of breeding and fattening pigs; large ruminants as calves, beef cattle, cows; small ruminants as sheep and goats; breeding and fattening poultry; horses and ponies; rabbits and rodents; cats and dogs of all races.
The subject matter may be clearly distinguished from animal feed in any form. "Feed" means food, fodder, given to do-mestic animals (Webster's New World Dictionary). A "supple-ment" ist something to be added, especially to make up for a lack or deficiency (op. cit.). In the feed industry "supple~
ments" or "feed supplements'i are commonly added to eed in ~, .
: ............. . . .
. :, .
. . .
. .
..
- : , . 1 ' , , . ..
~ . ' page~ S
the form of socalled "supplemented feed" to make up ~or a lack, especially of vitamines and minerals (Veterinary Drug Encyclopedia). When medicines are used as supplements in therapeutic dosage, the "medicated feed" is created (op.
cit.).
But a dosage unit form, as understood by this application and claims, may be manufactured completely with inert carrier substances; when meal of cereals or feed grain by-products are incorporated into the dosage unit form, as disclosed fur~her, these components have strictly therapeutic effect, in excluding or reducing well known medication stress~ The dosage unit forms are not administered in order to have the domestic animal fed, but to cure it. The subject matter is not intended to be used as a feed supplement neither, but administered to the domestic animal directly.
A disadvantage of the supplemented or medicated feed in comparison with the subject matter lays in the well known danger of disintegration of the mixtures during manipu-lations. In supplemented feed this danger is not 50 impor-tant, because dosage per unit is installed more or less accidentially. In medicated feed, however, this fact is vexy important; it exists the latent danger that dosage is inappropriate and not steadily under con~rol. Atmospheric influences ~re not excluded and the medicinal active in-gredients may be deteriorated or inactivated.
Moreover, an animal being in bad health - domestic animals for breeding and fattening very frequently suffer of di-gestive troubles - lacks of appetite. How could one force such an animal to gobble up daily large quantities of feed, in order to provide it with an appropriate dosage of medicine?
These are the reasons, why medicated feed has never gained the importance in Veterinary Science one could have ex-pected: The dosaye of the mediclne may be inappropriate and not steadlly under control because of khe danger of de-,` ,,~,"~J
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.
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, ` . `, , .
~ ~ z ~ ~ page 5 composition o~ the mi~ture during manipulations; the medi-cine is not protected against exogenous influences; a suffering domestic animal is lacking of appetite and, there-fore, not in a good humor to take up the large quantities of feed necessary to an appropriate medication.
That is why the subject matter teaches the aromatization of highly concentrated dosage unit forms as medicines and the direct administration per os of these high concen-trations of medicinal active ingredients to the suf~ering domestic animal. Avoiding by this the roundabout and unse-cure way of feed.
The aromatization is necessary to facilitate the uptake of the pharmaceutical compounds by the domestic animal by the mean of a familiar smell and taste; a carrier substance may be necessary to give the dosage unit an appropriate form;
and a covering may be necessary to protect the dosage unit form from exogenous influences. There can be no doubt, that the subject ma~ter teaches an improvement in oral medi-cation of domestic animals, especially with respect to the species specific aromatization of dosage unit forms.
The carrier substance may be composed-of an inert substance in physiological respect, alone, as disclosed supra, e.g.
of the polymeric carbohydrate cellulose, or of dextrose, starch and meal of cereals or feed graîn by-products. The latter two feed components having the advantage of exclu-ding medication-stress when used as carrier substance for the oral administering of drugs or pharmaceutical compounds to domestic animals.
The concentrated specific odorous and flavouring substances (aromae) do consist of formulae which are synthesized and marketed by the leading flavour manufac~urers and are offered and used exclusively ~or aromatisation of feed products for dom stic animals. There has been no use, so far, of these concentrated specific odorous and flavouring substances ,~..
- . . :.: . : , . .. . ...
, . . : :
, .' ' ' :' ',', ,: '' ' -~ ~?~ paye"~
(aromae) in aromatisation of drugs or pharmaceutical com-pounds for oral intake by domestic animals.
The concentrated specific odorous and flavouring substances (aromae) may be physically combined by the step of admixture either with the said compounds or with the carrier substance or with the covering, or in a combination thereof. Further-more, the concentrated specific odorous and flavouring substances (aromae) may be chemically bound to the carrier substance as to the covering as well.
If a covering is used, in order to mask the compound and/or for protecting the preparation against nuisable inter-ferences, this covering may consist of a colloidal emulsion mainly of sugar sirup, starch and gum arabic in adeguate proportions. In this emulsion, pressed pellets or pills consisting of the pharmaceutical compound, or of both carrier substance, drugs and/or concentrated specific odo-rous and flavouring substances (aromae), are processed into dragees, in a way as a person skilled in the art is used to and as it is disclosed by David (Switzerland 415 266) and as set forth.
If the concentrated specific odorous and flavouring sub-stances (aromae) are combined with the colloidal emulsion, these substances may also be dissolved in the emulsion.
The colloidal emulsion with the admixed or dissolved con-centrated specific odorous and flavouring substances (aromae) is then used to cover the preparation, which pre-viously has been pressed and transformed into pellets or pills. By subsequent drying and crystallization of the odorous and flavouring colloidal emulsion on the surface of the peLlets or pilLs, a speci~ic odourous and flavou-ring aromatized outside layer crust is formed, which at the same time serves for conservation and protection of the preparation against interferences caused e.g. by the atmospheric air.
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~ .
page For the better understanding of my invention, eleven embo-diments are now disclosed in the following descxiption.
The first four, when no carrier substance is used and the concentrated specific odorous and flavouring substances (aromae) are directly compounded with ~he drugs; the second four, when a carrier substance is used and compounded with the drugs and the concentrated specific odorous and fla-vouring substances (aromae); the nineth, when the first eight examples are covered with a covering; the tenth, when the covering is compounded wi~h the concentrated specific odorous and flavouring substances (aromae); and the eleventh, when the concentrated specific odorous and flavouring substances (aromae) are used in the covering, only.
The sufficient proportion of the concentrated specific odo7 rous and flavouring substances (aromae) presently in mar-ket is of 0,05~ to 4,0% of the weight of the dry crystal~
line colloidal emulsion; calculated in weight of the fi-nished preparation, this sufficient proportion amounts to 10 - 25 ppm, i.e. 10 - 25mg per one kilogram. When used in a pharmaceutical compound alone or with a carrier sub-stance, the proportion of the concentrated speci~ic odorous and flavouring substances (aromae) may make up to 1 g or more per kilogram.
Dry Hog Feed Nectar (Flavor Corporation of America~ and Pig Krave (Feed Flavors Inc.), resp. Dry Cream-nectar (Flavor Corporation of America) and Calf-ade (Feed Fla-vors Inc.), as well as Dry Horse Feed Nectar (Flavor Corporation of America) and Fresh-Arome (Feed Flavors Inc.) mentioned in the following examples, are to my knowledge specific aromae mainly consis-ting of synthe-sized organlc acids, esters and aldehydes, as disclosed supra. For equidae, malonic acid and its derivatives are used. The exact proportion of the different ingredients beLng a manufa~tuFing secret, and is not subject to this .
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, page `8~c~
patent application. The aromae in qu~stion are readily available on the open market and are used, so far, in feed production, only, and not in pharmaceutical com-pounds for veterinary purposes.
Stabilized extract of rumen is used in the examples one to three as it is produced by the method diclosed by Bio-fac A/S (Switzerland 519 303). This invention claims the manufacturing method and the admixture of the product to feed, only. I claim the admixture of this stablized ex-tract of rumen to dosage unit forms being aromatized specifically, as set forth.
The Bezimidazole referred to in examples five to seven is produced by Merck & Co. Inc., Rahway N.J. (et al.) and thePiperazine used in the same examples is produced by Jefferson Chemicals Co. Inc., Houston, Texas (et al.);
both are readily available on -the open market.
LBC (Lactic-acid Bacteria Concentrate) referred to in the examples four and eight is a po~der containing lyophi-lized lactic-acid producing bacteria of the strain Strep-tococcus faecium Cernelle 68 (SF68) in a sustaining carrier.
lg LBC contains minimum 35~109 viable cells~ It may be used in order to normalize the intestinal flora and to prevent and cure intestinal disorder in pigs, cattle, equids, poultry etc. SF68 belongs to the normal intestinal flora and makes a valuable contribution to the digestive process.
The bacteria are lyophilized, and the metabolic activity of the micro-organisms in the LBC powder is blocked. As soon as they reach the intestinal tract their reproduc-tive activity is resumed. There are a large numer of strains o~ lactic-acid bacteria. They differ in their ability to digest different types of sugar and in their stability against external influences. Their stability in the lyophilized state and their ability to remain ac-tive also di~fer fxom one strain to another. As to the minimum delay in action and effectiveness, rate of re-~' , page `~ I D
production, inhibition of yrowth, restistance against anti-biotics and stability the strain SF68 clearly outclasses competitive biological preparations. The strain contained in LBC (SF68) was isolated byscientists of AB Cernelle, Vegeholm, Engelholm, Sweden.
Example one Stabilized extract of rumen is physically combined by admixture with feed enzymes in a proportion of 38 : 10.
To this combination 1%o of colour and 1%o of Dry Hog Nectar (Flavor Corporation of America) or Pig-Krave (Feed Flavors Inc.) are added by mixture. The compound is then pressed and transformed into pellets or pills. The prepara-tion is now ready for final analysis and control according to Good Manufacturing Practice (GMP) and for subsequent administe-ring per os to piglets and hogs for the prevention of and curing from indigestions.
Example two In ~he preparation according to example one the specific pig aroma is replaced by Dry Creamnectar (Flavor Corpo-ra~ion o America) or Calf-Ade (Feed Flavors Inc~)O This preparation is ready for administering per os to calves for the prevention of and curing from indigestions.
Example three In the preparation according to example one the specific pig aroma is replaced by Dry Horse Feed Nectar (Flavor Corporation of America) or Fresh-Aroma (Feed Flavors Inc.).
This preparation is ready for administering peros to equids for the prevention of and curing from indigestions.
Example four In the preparation according to examples one to -three the stabilized extract of rumen is replaced by LBC in a pro-:
.
, :
, , .:, . , ' , .
'.
~ z ~ page portion of lg LBC/g of dosage unit form.
Example five 75 g of 2-(4 Thiazolyle)-benzimidazol~ are physically com-bined with 90 g of Piperazine base, 137 g Wheat bran, 28 g Vaseline oil and 670 g Barley meal. To this compound 1%o of Dry Horse Feed Nectar (Flavor Corporation of America) or Fresh-Aroma (Feed Flavors Inc.) is added by mixture, as well as l~o of colour. When e.g. dextrose or starch or sub-stances with similar properties are used as a carrier sub-stance or combined with a carrier substance, the concen-trated specific odorous and flavouring substances (aromae) may also be chemically bound to the carrier substance or with part thereof, e.g. by ~he step of hydration. This com-pound is then pressed and transformed into pellets or pills. The preparation is now ready for final analysis and control according to GMP and for subsequent administering per os to equids suffering from animal parasites.
Exampl~ SlX
In the preparation according to example five, the specific horse aroma is replaced by Dry Hog Feed Nectar (Flavor Corporation of America) or Pig Krave (Feed Flavors Inc.).
This preparation is ready for administering peros to pig-lets and hogs suffering from animal parasites.
Exam~le seven In the preparation according to example five, the specific horse aroma is xeplaced by Dry Creamnectar (Flavor Corpo-ration of America) or Calf-Ade (Feed Flavors Inc.). This preparation is ready for administering per os to calves suffering from animal parasites.
Example eight In the preparation accordiny to examples five to seven the _. .
~ paye Benzimidazole and Piperazine are replaced by LBC in a proportion of lg LBC/g of dosage unit form.
Example nine The preparations described in the first eight examples are covered with a colloidal emulsion, consisting mainly of sugar sirup, starch and gum arabic. After coating being completed, the preparations are dried by processing it in sugar powder and a stream of warmed air, until a cry-stalline crust is showing up on the surface of the pel-lets or pills. The preparations are now ready for final analysis and control according to G~P and for subsequent administering per os to the respective domestic animals.
Example ten The preparations of the examples one to four are coated with a colloidal emulsion, consisting of 62% sugar sirup, 25% starch, 8,5% CaC03, 3% gum arabic, 0,8% MgC03, 0,35%
colour and 0,35% of the respective specific aromae. After coating being completed, the preparation is dried by processing it in sugar powder and a stream of warmed air, until a crystalline crust is showing up on the surface of the pellets or pills. The preparation is now ready for final analysis and control according to GMP and for sub-sequent administering per os to the respective domestic animals.
The preparations of the examples five to eight are coa~ed with a colloidal emulsion consisting of 82,5% sugar sirup, 12% CaC03, 3,5% gum ararbic, 1% MgC03, 0,5% colour and 0,5~ o the respective specific aromae. After coating being completed, the preparation is dried by processing it in sugar powder and a stream of warmed air, until a crystal-line crust is showing up on the surface of the pellets or pills. The preparation is now ready for 1nal analysis and control according to GMP and for subsequent administe-;
:`
.
.. .: . . ,, ' ~ ,'. ' ' ; ' , .. .
' . , ' :
~2Z4~ page ~
rin~ per os to the respective domestic animals.
Example eleven The preparations according to examples one to eight are pro-duced by admixture and physical combination withou-t the addition of colour and concentrated specific odorous and flavouring substances (aromae) and then processed as des-cribed in example ten by coating with the disclosed colloidal emulsions, to which the respective colours and concentrated specific odorous and flavouring substances (aromae) have been added in the right proportions. After drying, the preparations are ready for final analysis and control,according to GMP and for subsequent administering per os to the respective domestic animals.
Age and environment are decisive of domestic animal's alimentary physiologica] capacity of absorption and meta-bol1sm. The age is determining the composition of the con-centra'ted specific odorous and flavouring substances (aromae) and the environment may determine the combination and nature of the other active substances, i.e. drugs for admlnistering per os.
The environment is insofar concerned in domestic animal's alimentary physiological capacity of absorption and meta-bolism, as it may influence this capacity and the meta-bolism in any stage of age and may depend on the lieu, con-ditions and systems of bxeeding and ~attening. It may occur by so called stress or continuous chronic disease in breeds or cattLes. This influence shows up e.g. when suckling pi'gs are weaned from the milk nutrition or at the moment whe,n young hogs are installed ~or fattening (stress) or when the whole breed or cattle are su~ering from indigestionsover several generations. In such cases, the usual com-bination~ and nature of the active substances, i.e. druys,have to be varied adequately, also.
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Claims (2)
1 A method for the manufacture of pharmaceutical compounds in a dosage unit form, for oral treatment of piglets, comprising the step of admixture of synthesized sow milk aroma with either the pharmaceuti-cal compound itself or with a carrier substance and the pharmaceuti-cal compound or with a crystalline coating around the compound.
Claims Supported By Supplementary Disclosure:
2 A method for the preparation of a pharmaceutical compound in a do-sage unit form, for oral veterinary use, comprising the step of admixture of synthesized concentrated odorous and flavouring substan-ces (aromae) specific to the domestic animal treated, with either the pharmaceutical compound itself or with a carrier substance and the pharmaceutical compound or with a crystalline coating around the pharmaceutical compound in an amount of a range of 10 to 25 ppm of the preparation or of a range of 0,05 percent to 4,0 percent by weight of the crystalline coating, the aroma being selected from Butyl Butyryl Lactate (sow milk aroma) Gamma Nona Lactone (sow milk aroma) Diacethyl (sow milk aroma) Iso-Butyric Acid (sow milk aroma) Ethyl Lactate (cow milk aroma) Malonic Acid (equidae aroma) and the pharmaceutically active substance being selected from a preparation of useful micro-organisms in full and in part (including their metabolites and analogues) Stabilized Extract of Rumen a preparation of lactic-acid bacteria concentrate.
3 A method of preparing a pharmaceutical compound as claimed in claim 2 for piglets, comprising the step of admixture of synthesized sow milk aroma as specific flavour with the dosage unit form.
4 A method of preparing a pharmaceutical compound as claimed in claim 2 for hogs, comprising the step of admixture of synthesized sow milk aroma as specific flavour with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 for cattle, comprising the step of admixture of a synthesized cow milk aroma as specific flavour with the dosage unit form.
6 A method of preparing a pharmaceutical compound as claimed in claim 2 for equidae, comprising the step of admixture of synthesized malonic acid as specific flavour with the dosage unit form.
7 A method of preparing a pharmaceutical compound for domestic animals as claimed in claim 2, comprising the step of admixture of a preparation of useful micro-organisms as active substance with the synthetically and specifically aromatized dosage unit form.
8 A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for piglets, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
9 A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for hogs, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for cattle, comprising the step of admixture of synthesized cow milk flavour as specific aroma with the dosage unit form.
11 A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for equidae, comprising the step of admixture of synthesized malonic acid as specific aroma with the dosage unit form.
12 A method of preparing a pharmaceutical compound for domestic animals as claimed in claim 2, comprising the step of admixture of stabili-zed extract of rumen as active substance with the synthetically and specifically aromatized dosage unit form.
13 A method of preparing a pharmaceutical compound for domestic animals a claimed in claim 2 or 12 for piglets, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
14 A method of preparing a pharmaceutical compound as claimed in claim 2 or 12 for hogs, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 or 12 for cattle, comprising the step of admixture of synthesized cow milk flavour as specific aroma with the dosage unit form.
16 A method of preparing a pharmaceutical compound as claimed in claim 2 or 12 for equidae, comprising the step of admixture of synthesized malonic acid as specific aroma with the dosage unit form.
17 A method of preparing a pharmaceutical compound for domestic animals as claimed in claim 2, comprising the step of admixture of a prepara-tion of lactic-acid bacteria concentrate with the synthetically and specifically aromatized dosage unit form.
18 A method of preparing a pharmaceutical compound as claimed in claim 2 or 17 for piglets, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
19 A method of preparing a pharmaceutical compound as claimed in claim 2 or 17 for hogs, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 or 17 for cattle, comprising the step of admixture of synthesized cow milk flavour als specific aroma with the dosage unit form.
21 A method of preparing a pharmaceutical compound as claimed in claim
Claims Supported By Supplementary Disclosure:
2 A method for the preparation of a pharmaceutical compound in a do-sage unit form, for oral veterinary use, comprising the step of admixture of synthesized concentrated odorous and flavouring substan-ces (aromae) specific to the domestic animal treated, with either the pharmaceutical compound itself or with a carrier substance and the pharmaceutical compound or with a crystalline coating around the pharmaceutical compound in an amount of a range of 10 to 25 ppm of the preparation or of a range of 0,05 percent to 4,0 percent by weight of the crystalline coating, the aroma being selected from Butyl Butyryl Lactate (sow milk aroma) Gamma Nona Lactone (sow milk aroma) Diacethyl (sow milk aroma) Iso-Butyric Acid (sow milk aroma) Ethyl Lactate (cow milk aroma) Malonic Acid (equidae aroma) and the pharmaceutically active substance being selected from a preparation of useful micro-organisms in full and in part (including their metabolites and analogues) Stabilized Extract of Rumen a preparation of lactic-acid bacteria concentrate.
3 A method of preparing a pharmaceutical compound as claimed in claim 2 for piglets, comprising the step of admixture of synthesized sow milk aroma as specific flavour with the dosage unit form.
4 A method of preparing a pharmaceutical compound as claimed in claim 2 for hogs, comprising the step of admixture of synthesized sow milk aroma as specific flavour with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 for cattle, comprising the step of admixture of a synthesized cow milk aroma as specific flavour with the dosage unit form.
6 A method of preparing a pharmaceutical compound as claimed in claim 2 for equidae, comprising the step of admixture of synthesized malonic acid as specific flavour with the dosage unit form.
7 A method of preparing a pharmaceutical compound for domestic animals as claimed in claim 2, comprising the step of admixture of a preparation of useful micro-organisms as active substance with the synthetically and specifically aromatized dosage unit form.
8 A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for piglets, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
9 A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for hogs, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for cattle, comprising the step of admixture of synthesized cow milk flavour as specific aroma with the dosage unit form.
11 A method of preparing a pharmaceutical compound as claimed in claim 2 or 7 for equidae, comprising the step of admixture of synthesized malonic acid as specific aroma with the dosage unit form.
12 A method of preparing a pharmaceutical compound for domestic animals as claimed in claim 2, comprising the step of admixture of stabili-zed extract of rumen as active substance with the synthetically and specifically aromatized dosage unit form.
13 A method of preparing a pharmaceutical compound for domestic animals a claimed in claim 2 or 12 for piglets, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
14 A method of preparing a pharmaceutical compound as claimed in claim 2 or 12 for hogs, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 or 12 for cattle, comprising the step of admixture of synthesized cow milk flavour as specific aroma with the dosage unit form.
16 A method of preparing a pharmaceutical compound as claimed in claim 2 or 12 for equidae, comprising the step of admixture of synthesized malonic acid as specific aroma with the dosage unit form.
17 A method of preparing a pharmaceutical compound for domestic animals as claimed in claim 2, comprising the step of admixture of a prepara-tion of lactic-acid bacteria concentrate with the synthetically and specifically aromatized dosage unit form.
18 A method of preparing a pharmaceutical compound as claimed in claim 2 or 17 for piglets, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
19 A method of preparing a pharmaceutical compound as claimed in claim 2 or 17 for hogs, comprising the step of admixture of synthesized sow milk flavour as specific aroma with the dosage unit form.
A method of preparing a pharmaceutical compound as claimed in claim 2 or 17 for cattle, comprising the step of admixture of synthesized cow milk flavour als specific aroma with the dosage unit form.
21 A method of preparing a pharmaceutical compound as claimed in claim
2 or 17 for equidae, comprising the step of admixture of synthesized malonic acid as specific aroma with the dosage unit form.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH586276A CH630808A5 (en) | 1976-05-08 | 1976-05-08 | Process for aromatising pharmaceutical preparations for veterinary medicine |
| CH005862/76 | 1977-01-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1102240A true CA1102240A (en) | 1981-06-02 |
Family
ID=4300540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA276,697A Expired CA1102240A (en) | 1976-05-08 | 1977-04-21 | Method for the manufacture and the application of pharmaceutical products for the veterinary science |
Country Status (11)
| Country | Link |
|---|---|
| AT (1) | AT355859B (en) |
| AU (1) | AU2609277A (en) |
| CA (1) | CA1102240A (en) |
| CH (1) | CH630808A5 (en) |
| DE (1) | DE2716269A1 (en) |
| DK (1) | DK192277A (en) |
| FR (1) | FR2350105A1 (en) |
| GB (1) | GB1577765A (en) |
| IE (1) | IE45054B1 (en) |
| NL (1) | NL7704768A (en) |
| ZA (1) | ZA772514B (en) |
Cited By (1)
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|---|---|---|---|---|
| US10653633B2 (en) | 2013-12-04 | 2020-05-19 | Boehringer Ingelheim Vetmedica Gmbh | Pharmaceutical compositions of pimobendan |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1579862A1 (en) | 2004-03-25 | 2005-09-28 | Boehringer Ingelheim Vetmedica Gmbh | Use of PDE III inhibitors for the reduction of heart size in mammals suffering from heart failure |
| US8980894B2 (en) | 2004-03-25 | 2015-03-17 | Boehringer Ingelheim Vetmedica Gmbh | Use of PDE III inhibitors for the treatment of asymptomatic (occult) heart failure |
| EP1920785A1 (en) | 2006-11-07 | 2008-05-14 | Boehringer Ingelheim Vetmedica Gmbh | Liquid preparation comprising a complex of pimobendan and cyclodextrin |
| FR2934156B1 (en) * | 2008-07-23 | 2010-09-24 | Virbac | ORAL ADMINISTRATION MEDICAMENT IN SOLID FORM |
| ES2666868T3 (en) | 2011-09-15 | 2018-05-08 | Friulchem Spa | Compositions for oral administration to animals and method of obtaining |
| ES2924478T3 (en) | 2012-03-15 | 2022-10-07 | Boehringer Ingelheim Vetmedica Gmbh | Formulation of pharmaceutical tablets for the veterinary medical sector, method of production and use thereof |
| CA2883139C (en) | 2012-08-31 | 2021-08-10 | Friulchem Spa | Compositions for oral administration to animals, production methods thereof and uses of same |
| EP3021832B9 (en) | 2013-07-19 | 2023-03-15 | Boehringer Ingelheim Vetmedica GmbH | Preserved etherified cyclodextrin derivatives containing liquid aqueous pharmaceutical composition |
| US10537570B2 (en) | 2016-04-06 | 2020-01-21 | Boehringer Ingelheim Vetmedica Gmbh | Use of pimobendan for the reduction of heart size and/or the delay of onset of clinical symptoms in patients with asymptomatic heart failure due to mitral valve disease |
-
1976
- 1976-05-08 CH CH586276A patent/CH630808A5/en not_active IP Right Cessation
-
1977
- 1977-04-13 DE DE19772716269 patent/DE2716269A1/en not_active Withdrawn
- 1977-04-21 CA CA276,697A patent/CA1102240A/en not_active Expired
- 1977-04-27 ZA ZA00772514A patent/ZA772514B/en unknown
- 1977-05-02 NL NL7704768A patent/NL7704768A/en not_active Application Discontinuation
- 1977-05-03 DK DK192277A patent/DK192277A/en unknown
- 1977-05-03 GB GB18506/77A patent/GB1577765A/en not_active Expired
- 1977-05-04 AT AT316177A patent/AT355859B/en not_active IP Right Cessation
- 1977-05-06 FR FR7713960A patent/FR2350105A1/en active Granted
- 1977-05-06 IE IE933/77A patent/IE45054B1/en unknown
- 1977-06-14 AU AU26092/77A patent/AU2609277A/en not_active Expired
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10653633B2 (en) | 2013-12-04 | 2020-05-19 | Boehringer Ingelheim Vetmedica Gmbh | Pharmaceutical compositions of pimobendan |
| US10874620B2 (en) | 2013-12-04 | 2020-12-29 | Boehringer Ingelheim Vetmedica Gmbh | Pharmaceutical compositions of pimobendan |
| US11298325B2 (en) | 2013-12-04 | 2022-04-12 | Boehringer Ingelheim Vetmedica Gmbh | Pharmaceutical compositions of pimobendan |
Also Published As
| Publication number | Publication date |
|---|---|
| AT355859B (en) | 1980-03-25 |
| DE2716269A1 (en) | 1977-11-17 |
| CH630808A5 (en) | 1982-07-15 |
| AU2609277A (en) | 1978-12-21 |
| GB1577765A (en) | 1980-10-29 |
| FR2350105B3 (en) | 1980-03-07 |
| NL7704768A (en) | 1977-11-10 |
| IE45054L (en) | 1977-11-08 |
| DK192277A (en) | 1977-11-09 |
| FR2350105A1 (en) | 1977-12-02 |
| ZA772514B (en) | 1978-04-26 |
| IE45054B1 (en) | 1982-06-16 |
| ATA316177A (en) | 1979-08-15 |
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