MXPA06007247A - Non-animal product containing veterinary formulations - Google Patents

Abstract

This invention provides for a chewable veterinary formulation, which does not contain animal products, which comprises:-effective amount of a pharmaceutically active agent which comprises either:a) at least one nodulisporamide acid or nodulisporic acid derivative;or b) a combination comprising i) at least one avermectin or milbemycin derivative;and i) at least one compound selected from the group consisting of praziquantel and pyrantel;-at least one binder;-at least one disintegrant;-at least one non-animal product containing flavor or flavor derived from a non-animal source;-at least one binder;-at least one humectant;-at least one granulating solvent;and -optionally, a t least o ne antioxidant, a t least o ne buffering a gent, at least one preservative, or at least one colorant.

Description

NON-ANIMAL PRODUCT CONTAINING VETERINARY FORMULATIONS BACKGROUND OF THE INVENTION Field of the Invention This invention provides improved oral veterinary formulations, which do not contain animal products or flavors derived from animal sources, which are pleasing to the animal due to its good organoleptic properties, as well as to a method to improve the pleasant taste of oral veterinary formulations, without resorting to the use of animal products or derived flavors - of animal products. This invention further provides improved chewable veterinary formulations or tablets, which do not contain animal products or flavors derived from animal sources and possess good consistency and acceptability by the animal. Description of the Related Art Therapeutic agents are administered to animals by a variety of routes. These routes include, for example, oral ingestion, topical application or parenteral administration. The particular route selected by the professional depends on factors such as the physiochemical properties of the pharmaceutical or therapeutic agent, the condition of the host and the economy. For example, a method for formulating a therapeutic agent for oral, topical, dermal or subdermal administration is to formulate the therapeutic agent as a paste or as an injectable formulation and reference is made to US Application Serial No. 09 / 504,741, filed on February 16, 2000, now pending, titled IMPROVED PASTE FORMULATIONS or Ser. No. 09 / 346,905, filed July 2, 1999, now US Patent No. 6,239,112; Ser. No. 09 / 112,690, filed July 9, 1999, now US Patent No. 5,958,888; and not . of Ser. 09 / 152,775, filed on September 14, 1998, now US Patent No. 6,174,540, entitled LONG ACTING INJECTABLE FOR ULATIONS CONTAINING HIDROGENATED CASTOR OIL. The descriptions of these patent applications as well as the references cited therein and the references cited therein are expressly incorporated by reference. Other methods include placing the therapeutic agent in a solid or liquid matrix for oral delivery. These methods include chewable drug delivery formulations. The problem associated with oral formulations is that the therapeutic agent frequently provides an unpleasant taste, aroma or mouthfeel to the formulation, which causes, especially in the situation with animals, that the oral formulation be rejected by the patient. See, for example, US Patent No. 5,380,535 to Geyer et al., Which provides lipid-based chewable formulations for the oral delivery of therapeutic agents, such as aspirin, ibuprofen or erythromycin, which are unpleasant to humans; US Patent No. 5,894,029 to Brown et al., which provides pet food in dehydrated buns comprising farinaceous materials, proteinaceous materials, such as meats or vegetable protein sources, and optionally medicaments or vitamins; or US Pat. No. 5,637,313 to Chau et al., which describes chewable dosage forms comprising a water-soluble matrix comprising a hydrolyzed, hydrogenated starch volume agent and a water-insoluble volume agent. Traditionally, in veterinary formulations, the pleasant taste has been achieved by the inclusion of animal by-products or flavors derived from animal sources in the formulation. For example, it is usual to include attractable agents, such as chicken powder, liver powder, beef, ham, fish or leather-derived products in dog chews to make the dog chewable. See, for example, U.S. Patent No. 6,086,940; U.S. Patent No. 6,093,441; U.S. Patent No. 6,159,516; U.S. Patent No. 6,110,521; U.S. Patent No. 5,827,565; US Patent No. 6,093,427, all of Axelrod et al. However, the use of animal products or by-products or flavors derived from animal sources has recently fallen to an unfavorable point due to the possibility of chemical or biological contamination, which leads to toxicity, or diseases such as bovine spongiform encephalopathy. Accordingly, there is a need for oral veterinary formulations that do not contain animal products, by-products or flavors derived from animal sources while still exhibiting good organoleptic properties. While non-animal derived products such as valerian plants are known as perfumable attractants in food products or pet toys (US Patent No. 5,785,382 to Childers-Zadah) or chews for animals that contain fruit flavors as the attractant ( see, US Patents Nos. 6,274,182; 6,200,616 and 6,126,978 to Axelrod et al.), these patents do not disclose the use of valerian plants or fruit flavors in oral formulations in which pharmaceutical agents need to be masked. DESCRIPTION OF THE INVENTION The present invention provides improved oral veterinary formulations comprising at least one nodulisporic acid or nodulisporic acid derivative, which does not contain animal products or flavors derived from animal sources, which exhibit organoleptic properties so that the animal finds them attractive. . This invention further provides improved chewable veterinary formulations or those that do not contain animal products or flavors derived from animal sources and possess good consistency and acceptability by the animal, as well as an improved process for providing chewable veterinary formulations. In this description and in the appended claims, terms such as "comprising" and "is understood" and the like have the meanings ascribed to these in the US Patent Case Law. The terms "understood" and "comprising" are open and allow the inclusion of additional ingredients or steps. Clearly, a chewable veterinary formulation, containing no animal products comprising at least one nodulisporic acid or a derivative thereof, advantageously t-butyl nodulisporamide, is a basic or novel feature of the present invention, as well as methods to prevent or treat parasites in an animal, eg, dog, cat, by application of the formulation, for example, monthly and methods for preparing the formulations, for example, by administering the ingredients, are also novel and basic features of the invention. What the invention performs as described herein is surprising, unexpected and not obvious. These and other embodiments are disclosed or are obvious, and are comprised of, the following detailed description. DETAILED DESCRIPTION The present invention provides a chewable veterinary formulation, which does not contain animal products, comprising: an effective amount of a pharmaceutically active agent comprising either: a) at least one nodulisporamide acid or nodulisporic acid derivative; or b) a combination comprising i) at least one derivative of avermectin or milbe icin; ii) at least one compound selected from the group consisting of praziquantel and pyrantel; -at least one filler; -at least one disintegrant; -at least one non-animal product that contains flavor or flavor derived from a non-animal source; -at least one binder; -at least one humectant; - at least one granulation solvent, for example, water or an aqueous solution of sorbitol; and - optionally, at least one antioxidant, at least one pH regulating agent, • at least one preservative, or at least one colorant; and optionally, a coating; or preferably, a chewable veterinary formulation, containing no animal products, comprising: an effective amount of a pharmaceutically active agent comprising either: a) at least one nodulisporamide acid or nodulisporic acid derivative; or b) a combination comprising ~ i) at least one avermectin or milbemycin derivative; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel; - a filler selected from the group consisting of soy protein, corn cob or glutinous corn flour; -disintegrating; - a non-animal product that contains a flavor or flavor derived from a non-animal source that is a flavor of American walnut smoke; -a binder; -humidifier; -granulation solvent; -optionally, an antioxidant, a pH regulating agent, preservative or a dye; and - is optionally coated with at least one coating. In addition, the present invention provides a method for increasing the palatability of an oral veterinary formulation comprising at least one nodulisporic acid or nodulisporic acid derivative, which does not contain animal products or flavors derived from animal sources which comprises adding a smoke flavor of American walnut, which optionally also comprises caramel, the oral veterinary formulation. More preferred are the chewable veterinary formulations, which do not contain animal products, which comprise: an effective amount of a pharmaceutically active agent comprising either a) at least one nodulisporamide acid or nodulisporic acid derivative; or b) a combination comprising: i) at least one avermectin or itiilbemycin derivative; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel; -about 20 to about 60% of a filler selected from the group consisting of soy protein, corn cob or corn glutinous flour; -about 1 to about 20% of a disintegrant; -approximately 0.1 to about 20% of a flavor containing non-animal product; or a flavor derived from a non-animal source; -about 0.5 to 10% of a binder; -about 5 to about 20% of a humectant; and -approximately 5 to about 20% granulation solvent, based on the total weight of the formulation. Especially preferred are chewable veterinary formulations, which do not contain animal products comprising: an effective amount of a pharmaceutically active agent comprising either: a) at least one nodulisporamide acid or nodulisporic acid derivative; or b) a combination comprising: i) at least one avermectin or milbemycin derivative; and ii) at least one compound selected from the group consisting of praziquantel and pirantel: -about 20 to about 60% of a filler selected from the group consisting of soy protein, corn cob or corn glutinous flour; -about 1 to about 20% of a disintegrant; -about 0.1 to about 20% of the flavor that the non-animal product contains or flavor derived from a non-animal source that taste of American walnut barbecue; -about 0.5 to 10% of a binder; -about 5 to about 20% of a humectant; and -approximately 5 to about 20% granulation solvent, and, optionally -about 0.05% to about 1.0% of an antioxidant, -approximately 0.05 to about 1.0% of a preservative, and -about 0.001 to about 10% of a colorant , based on the total weight of the formulation. Formulations wherein the nodulisporic acid derivative is t-butyl nodulisporamide (or "nodulisporamide") are especially preferred. Another preferred embodiment is a tablet, which does not contain animal products, comprising: an effective amount of a pharmaceutically active agent comprising either: a) at least one nodulisporamide acid or nodulisporic acid derivative; or b) a combination comprises: i) at least one avermectin or ilbemicin derivative; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel; -at least one filler; -at least one flavor that contains non-animal product or flavor derived from a non-animal source; -at least one lubricant; -at least one flow aid; and - optionally, at least one antioxidant, at least one pH modifier, at least one binder, at least one disintegrant, at least one surfactant, at least one preservative and at least one dye, and optionally coated with at least one coating. Also provided by the present invention are chewable veterinary formulations comprising at least two pharmaceutically active agents wherein at least one of the agents is nodulisporic acid or nodulisporic acid derivatives. Additional pharmaceutically active agents in this embodiment may include nodulisporic acid or an additional nodulisporic acid derivative or an additional pharmaceutically active compound. The classes of additional pharmaceutical agents that can be included in the inventive formulations include insecticides, acaricides, parasiticides, growth enhancers, nonsteroidal anti-inflammatory prodrugs (NSAIDS), oil-soluble proton pump inhibitors and anti-bacterial compounds. Specific classes of compounds that fall into these classes include, for example, avermectins (such as ivermectin, abamectin, emamectin, eprinomectin, doramectin, moxidectin and selamectin), milbemycins, estrogens, progestins, androgens, substituted pyridylmethyl derivatives, phenylpyrazoles, COX-2 inhibitors, 2- (2-benzimidazolyl) -pyrimidine derivatives, macrolide antibiotics of 2-acyl-4-oxo-pyrazino-isoquinoline derivatives, such as praziquantel or 1, 4, 5, 6-tetrahydro-2 - [2-substituted] vinyl pyrimidines and 2- [(2-substituted) vinyl] -2-imidazolines such as pyrantel (see U.S. Patent No. 3,502,661, incorporated herein by reference). Nodulisporic acid and nodulisporic acid derivatives are known in the art as potent endo- and ectoantiparasitic agents. These compounds are based on three structures, A, B or C, which have the following structures: nodulisporic acid (compound A) 29, 30-dihydro-20, 30-oxa-nodulisporic acid (compound B) and 31-hydroxy-20, 30-oxa-29, 30, 31, 32-tetrahydro-nodulisporic acid (Compound C) These compounds were obtained from the fermentation culture of Nodulisporium sp. MF-5954 (ATCC 74245) and the isolation and purification of the three nodulisporic acids are disclosed in U.S. Patent No. 5,399,582. Derivatives of these compounds are described in WO 96/29073 and U.S. Patent Nos. 5,945,317; 5,962,499; 5,834,260; 6,399,796; 6,221,894; 6,136,838; 5,595,991; 5,299,582; and 5,614,546. Nodulisporic acid derivatives possess potent activity against parasites, particularly helminths, ectoparasites, insects and acaricides, which infect humans, animals and plants. These compounds have utility in human and animal health, agriculture and pest control in domestic and commercial areas. The disease or group of diseases generally described as helminthiasis is due to the infection of an animal host with parasitic worms known as helminths. Helminthiasis is a prevalent and serious economic problem in domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats, fish, buffalo, camels, llamas, reindeer, laboratory animals, animals that have fur, animals zoo and exotic species and poultry. Among the helminths, the group of worms described as nematodes cause widespread and sometimes serious infection in several species of animals. The most common genera of nematodes that infect the animals referred to above are Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Druschia, Capillaria, Habronema, Druschia, Heterakis. , Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Certain of these, such as Nematodirus, Cooperia and Oesophagostomum mainly attack the intestinal tract while others, such as Haemonchus and Ostertagia, are more prevalent in the stomach while still others such as Dictyocaulus are found in the lungs. Still other parasites can be located in other tissues and organs of the body such as the heart and blood vessels, subcutaneous and lymphatic tissue and the like. Parasitic infections known as helminthiasis lead to anemia, poor nutrition, weakness, weight loss, severe damage to the walls of the intestinal tract and other tissues and organs and, if left untreated, can result in the death of the infected host. The compounds of this invention have activity against these parasites, and in addition they are also active against Dirofilaria in dogs and cats, Nematospiroides, Syphacia, Aspiculuris in rodents, ectoparasites of arthropods of animals and birds such as ticks, mites such as lice, scabies, fleas, blowfly and other spicy insects in domesticated animals and poultry, such as Ctenophalides, Ixodes, Psoroptes and Hematobia, in Lucilia sp. sheep, spicy insects and such migratory diphtheria larvae as Hypoderma sp. in cattle, Gasterophilus in horses and Cuterebra sp. in rodents and annoying flies including flies that feed on blood and fly trash. Nodulisporic acid derivatives are also useful against parasites that infect mammals, such as cats, dogs and humans. The most common genera of parasites from the gastrointestinal tract of man are Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris and Enterobius. Other medically important genera of parasites that are found in the blood or other tissues and organs outside the gastrointestinal tract are filiaric worms such as Wuchereria, Brugia, Onchocerca and Loa, Dracunculus and extra intestinal stages of the intestinal worms Strongyloides and Trichinella. The compounds are also valuable against man parasitic arthropods, spicy insects and other dipterous species that cause discomfort to man. The nodulisporic acid derivatives are also active against domestic pests such as cockroach, Blatella sp., Clothing moth, Tineloa sp., Carpet beetle, Attagenus sp., The housefly Musca domestica as well as fleas, house dust mites, termites and ants. The nodulisporic acid derivatives are also useful against insect pests of stored grains such as Triboliüm sp., Tenebrio sp. and of agricultural plants such as aphids, (Acyrtiosiphon sp.); against migratory orthoptera such as locusts and immature stages of insects that live in the tissue of plants. The compounds are useful as a nematocide for the control of earth nematodes and plant parasites such as Meloidogyne sp., Which may be of importance in agriculture. The compounds are also highly useful in treating surfaces of acres infested with red ants and nests. The compounds are dispersed above the infested area at low levels in bait formulations that are carried back to the nest. In addition to a toxic effect of direct but slow onset in the red ants, the compounds have a long-term effect on the nest by sterilizing the queen so that the nest is effectively destroyed. Nodulisporic acid and its derivatives are also effective against arthropod pests, for example fleas, ticks, lice and other spicy insects in domesticated animals and poultry, such as Ctenocephalides, Ixodes, Psoroptes, Lucilia and Hematobia. It is possible to combine nodulisporic acid or nodulisporic acid derivatives with other insecticides, parasiticides and acaricides in order to achieve a broader spectrum of activity or, in some cases, synergy. For example, U.S. Patent No. 5,945,317 discloses the co-administration of nodulisporic acid derivatives with avermectin, ivermectin, e amectin, eprinomectin, abamectin or milbemycins, or other anthelmintic agents, such as morantel, pyrantel or febantel, praziquantel or benzimidizoles, such as thiabendazole or carbendazole. Other agents described therein include IGR compounds, such as lufenuron, methoprene or 1-N-aripirazoles, such as a fipronil. See also, US Patents Nos. 5,962,499 and 6,221,894. While it is known in the art that it is sometimes possible to combine several parasiticides in order to broaden the antiparasitic spectrum, it is not possible to predict, a priori, which combinations will work for a particular animal or disease state. For this reason, the results of various combinations are not always successful and there is a need in the art for more effective formulations that can be easily administered to the animal. This invention includes all nodulisporic acid derivatives known in the art, including all stereoisomers, such as those described in the prior publication described above, which are expressly incorporated by reference. Especially preferred are formulations comprising the nodulisporic acid derivatives of the formula: wherein Ri is (1) hydrogen, (2) optionally substituted alkyl, (3) optionally substituted alkenyl, (4) optionally substituted alkynyl, (5) optionally substituted cycloalkyl, (6) optionally substituted cycloalkenyl, wherein the substituents on the alkyl , 'alkenyl, alkynyl, cycloalkyl and cycloalkenyl are 1 to 3 groups independently selected from (i) alkyl, (ii) X-alkyl, where X is O. or S (0) m. (iii) cycloalkyl, (iv) hydroxy, (v) halogen, (vi) cyano, (vii) carboxy, (viii) NY - '? 2, where Y1 and Y2 are independently H or alkyl, (ix) alkanoylamino and (x) aroylamino wherein the aroyl is optionally substituted with 1 to 3 groups independently selected from Rf (7) aryl or arylalkyl, wherein the aryl is optionally substituted with 1 to 3 groups independently selected from Rr, (8) perfluoroalkyl (9) a 5- or 6-membered heterocycle containing from 1 to 4 independently selected heteroatoms, from atoms of oxygen, sulfur and nitrogen optionally substituted by 1 to 3 groups independently selected from hydroxy, oxo, alkyl and halogen, and which may be saturated or partially unsaturated, R2, R3 and R4 are independently ORa, OC02Rb, OC (0) NRcRd; or Ri and R2 represent = 0, = N0Ra or = N-NRcRd; R5 and R6 are H; or R5 and R6 together represent -O-; R7 is (1) CHO, or (2) the fragment R8 is (1) H, (2) ORa, 0 (3) NRcRd R3 is (1) H, 0 (2) 0Ra Rio is (1) CN, (2) C (0) ORb, (3) C ( 0) N (0Rb) Rc, (4) C (0) NRcRd, (5) NHC (0) ORb, (6) NHC (0) NRCRd, (7) CH2ORa, (8) CH2OC02Rb, (9) CH2OC ( 0) NRcRd, (10) C (0) NRcNRcRd, or (11) C (0) NRcS02R represents a single or double bond; (1) hydrogen, 2) optionally substituted alkyl, (3) optionally substituted alkenyl, (4) optionally substituted alkynyl, (5) optionally substituted alkanoyl, (6) optionally substituted alkenoyl, (7) optionally substituted alkynyl, (8) aroyl optionally substituted, (9) optionally substituted aryl, (10) optionally substituted cycloalkanoyl, (11) optionally substituted cycloalkenoyl, (12) optionally substituted alkylsulfonyl, (13) optionally substituted cycloalkyl, (14) optionally substituted cycloalkenyl, wherein the substituents on the alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, alkynyl, aroyl, aryl, cycloalkanoyl, cycloalkenoyl, alkylsulfonyl, cycloalkyl and cycloalkenyl are from 1 to 10 groups independently selected from hydroxy, alkoxy, cycloalkyl, arylalkoxy NRgRh, C02Rb, CONRcRd and halogen, ( 15) perfluoroalkyl, (16) arylsulfonyl optionally substituted with 1 to 3 groups independently selected from alkyl, perfluoroalkyl, nitro, halogen and cyano, (17) a 5- or 6-membered heterocycle containing 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by 1 to 4 groups independently selected from alkyl, alkenyl, perfluoroalkyl , amino, C (0) NRcRd, cyano, C02Rb and halogen, and which may be saturated or partially unsaturated; (1) H, (2) optionally substituted aryl, (3) optionally substituted alkyl, (4) optionally substituted alkenyl, (5) optionally substituted alkynyl, (6) optionally substituted cycloalkyl, (7) optionally substituted cycloalkenyl, or (8) optionally substituted heterocycle containing from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen; wherein the substituents on the aryl, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle or alkynyl are from 1 to 10 groups independently selected from (i) hydroxy, (ii) alkyl, (iii) oxo, (iv) S02NRgRh, (v) arylalkoxy, (vi) hydroxyalkyl, (vii) alkoxy, (viii) hydroxyalkoxy, (ix) aminoalkoxy, (x) cyano, (xi) mercapto, (xii) alkyl S (0) m, (xiii) cycloalkyl optionally substituted with 1 to 4 groups independently selected from R% (xiv) cycloalkenyl, (xv) halogen, (xvi) alkanoyloxy, (xvii) C (0) NRgRh, (xviii) CO ^ 1, (xix) formyl, (xx) -NRgRh, (xxi) 5- to 9-membered heterocycle, which may be saturated or partially unsaturated , which contains from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 to 5 groups independently selected from Re, (xxii) optionally substituted aryl, wherein the aryl substituents are 1,2-methylenedioxy ola 5 groups independently selected from Re, (xxiii) optionally substituted arylalkoxy, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from Re, and (xxiv) perfluoroalkyl; Rc and Rd are independently selected from Rb; or Rc and Rd together with the N to which they are attached form a ring of 3 to 10 members containing 0 to 2 additional heteroatoms selected from 0, -S (0) m and N, optionally substituted with 1 to 3 independently selected groups of Rg , hydroxy, thioxo and oxo; Re is (1) halogen, (2) alkyl, (3) perfluoroalkyl, (5) cyano, (6) nitro, (7) R10 (CH2) v-, (8) RiC02 (CH2) v-, (9) Ri0C0 (CH2) v-, (10) optionally substituted aryl wherein the substituents are from 1 to 3 of halogen, alkyl, alkoxy or hydroxy, (11) S02NRgRh, or (12) amino; Rf is (1) alkyl, (2) X-C? -C alkyl, where X is O or S (0) ra, (3) alkenyl, (4) alkynyl, (5) perfluoroalkyl, (6) NY ^ 2, wherein Y1 and Y2 are independently H or alkyl, (7) hydroxy, (8) halogen, and (9) alkanoylamino, Rg and Rh are independently (1) hydrogen, (2) alkyl optionally substituted with hydroxy, amino or C02R1 (3) aryl optionally substituted with halogen, 1,2-methylenedioxy, alkoxy, alkyl or perfluoroalkyl, (4) arylalkyl, wherein the aryl is optionally substituted with perfluoroalkyl or 1,2-methylenedioxy; (.5) alkoxycarbonyl, (6) alkanoyl, (7) alkanoylalkyl, (9) aryl alkoxycarbonyl, (10) aminocarbonyl, (11) monoalkylaminocarbonyl (12) dialkylaminocarbonyl; or Rg and Rh together with the N to which they are attached form a 3 to 7 member ring containing 0 to 2 additional heteroatoms selected from O, S (0) m N, optionally substituted with 1 to 3 groups independently selected from Re and oxo; R1 is (1) hydrogen, (2) perfluoroalkyl, (3) alkyl, (4) aryl or optionally substituted arylalkyl, wherein the aryl substituents are from 1 to 3 groups independently selected from halogen, alkyl, alkoxy and hydroxy; m is 0 to 2; and v is 0 to 3; or a pharmaceutically acceptable salt thereof. In a preferred embodiment, the present invention provides compounds of Formula I wherein Rx is (1) hydrogen, (2) optionally substituted alkyl, (3) optionally substituted alkenyl, (4) optionally substituted alkynyl, (5) optionally substituted cycloalkyl , (6) optionally substituted cycloalkenyl wherein the substituents on the alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl are 1 to 3 groups independently selected from (i) alkyl, (ii) X-C6-C6 alkyl, where X is O or S (0) m, (iii) cycloalkyl, (iv) hydroxy, (v) halogen, (vi) cyano, (vii) carboxy, and (viii) NY1Y2, where Y1 and Y2 are independently H or alkyl, (7) ) aryl or arylalkyl wherein the aryl is optionally substituted with 1 to 3 groups independently selected from Rf, (8) perfluoroalkyl, (9) a 5- or 6-membered heterocycle containing from 1 to 4 heteroatoms independently selected from oxygen atoms, sulfur and nitrogen optionally substituted by 1 to 3 groups independently selected from hydroxy, oxo, alkyl and halogen, and which may be saturated or partially unsaturated, R8 is (1) H, (2) OH, or (3) NH2; R9 is (1) H or (2) OH; Rio is (1) C (0) ORb, (2) C (0) N (ORb) Rc, (3) C (0) NRcRd, (4) NHC (0) ORb, (5) NHC (0) NRcRd , (6) CH20Ra, (7) CH20C02Rb, (8) CH2OC (0) NRcRd, (9) C (0) NRcNRcRd, or (10) C (0) NRcS02Rb; Ra is (1) hydrogen, (2) alkyl optionally, (3) optionally substituted alkenyl, '(4) optionally substituted alkynyl, (5) optionally substituted alkanoyl, (6) optionally substituted alkenoyl, (7) optionally substituted alkynyl, ( 8) optionally substituted aroyl, (9) optionally substituted aryl, (10) optionally substituted cycloalkanoyl, (11) optionally substituted cycloalkenoyl, (12) optionally substituted alkylsulfonyl, (13) optionally substituted cycloalkyl, (14) optionally substituted cycloalkenyl where substituents in the alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, alkynoyl, aroyl, aryl, cycloalkanoyl, cycloalkenoyl, alkylsulfonyl, cycloalkyl and cycloalkenyl are from 1 to 10 groups independently selected from hydroxy, alkoxy, cycloalkyl, aryl alkoxy, NRgRh, C02Rb and halogen , (15) perfluoroalkyl, (16) arylsulfonyl optionally substituted with 1 to 3 independently selected groups of alkyl, perfluoroalkyl, halogen and cyano, (17) a 5- or 6-membered heterocycle containing from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by 1 to 4 groups independently selected from alkyl, alkenyl, perfluoroalkyl, amino, C (0) NRcRd, cyano and halogen, and which may be saturated or partially unsaturated; (1) H, (2) optionally substituted aryl, (3) optionally substituted alkyl, (4) optionally substituted alkenyl, (5) optionally substituted alkynyl, (6) optionally substituted cycloalkyl, (7) optionally substituted cycloalkenyl, or (8) optionally substituted 5 to 10 membered heterocycle containing from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen; wherein the substituents on the aryl, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle or alkynyl are from 1 to 10 groups independently selected from (i) hydroxy, (ii) C 1 -C 3 alkyl, (iii) oxo, (iv) S02NRgRh, (v) aryl alkoxy, (vi) hydroxy alkyl, (vii) alkoxy, (viii) hydroxyalkoxy, (ix) aminoalkoxy, (x) cyano, (xi) perfluoroalkyl, (xii) alkyl-S (0) m, (xiii) cycloalkyl optionally substituted with 1 to 4 groups independently selected from Re, 5 (xiv) cycloalkenyl, (xv) halogen, (xvi) alkanoyloxy, (xvii) C (0) NRgRh, (xviii) CO ^ 1, 10 ( xix) optionally substituted arylalkoxy, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from Re, (xx) -NRgRh, 15 (xxi) 5- to 6-membered heterocycle, which may be saturated or partially unsaturated, containing 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 to 5 groups independently selected from Re, and (xxii) optionally substituted aryl, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from Re; 25 Re is (1) halogen, (2) alkyl, (3) perfluoroalkyl, (4) -S (0) mR \ (5) cyano, (6) amino, (7) RIO (CE2) vr (8) RiC02 (CH2) v-, (9) -R'-OCO (CE2) v-, (10) optionally substituted aryl wherein the substituents are from 1 to 3 of halogen, alkyl, alkoxy or hydroxy, or (11) S02NRgRh; R1 is (1) methyl, (2) X-C alquilo-C2 alkyl, where X is or S (0) m, (3) halogen, (4) acetylamino, (5) trifluoromethyl, (6) NY1Y2, where Y1 and Y2 are independently H or methyl, and (7) hydroxy; R9 and Rh are independently (1) hydrogen, (2) alkyl optionally substituted by hydroxy, amino or C02 to (3) aryl optionally substituted with halogen, 1,2-methylenedioxy, alkoxy, alkyl or perfluoroalkyl, (4) arylalkyl, wherein the aryl is optionally substituted with perflu-alkylalkyl or 1,2-methylenedioxy; (5) alkoxycarbonyl, (6) alkanoyl, (7) alkanoyl alkyl, (9) arylalkoxycarbonyl, (10) aminocarbonyl, (11) monoalkylaminocarbonyl, (12) dialkylaminocarbonyl; or Rg and Rh together with the N to which they are attached form a 5 to 6 member ring containing from 0 to 2 additional heteroatoms selected from O, S (0) m and N, optionally substituted with 1 to 3 groups independently selected from and oxo; R1 is (1) hydrogen, (2) perfluoroalkyl, (3) alkyl, (4) arylalkyl optionally substituted, wherein the aryl substituents are from 1 to 3 groups independently selected from halogen, alkyl, alkoxy and hydroxy; all variables are as defined under Formula I. In another preferred embodiment, the present invention provides compounds of Formula I wherein R 1 is (1) hydrogen, (2) optionally substituted alkyl, (3) optionally substituted alkenyl, ( 4) optionally substituted alkynyl, wherein the substituents on the alkyl, alkenyl and alkynyl are 1 to 3 groups independently selected from (i) methyl, (ii) X-methyl, where X is 0 or S (0) m and (iii) halogen , (5) aryl or arylalkyl wherein the aryl is optionally substituted with 1 to 3 groups independently selected from Rf. (6) trifluoromethyl R8 is (1) H, (2) OH, or (3) NH2 R9 is (1) H, or (2) OH; Rio is (1) C (0) 0Rb, (2) C (0) N (ORb) Rc, (3) C (0) NRcRd, (4) NHC (0) ORb, (5) NHC (0) NRcRd , (6) CH2ORa, [7) CH2OC02Rb, (8) CH2OC (0) NRcR ° (9) C (0) NRcNRcR, or (10) C (0) NRcS02Rb; (1) hydrogen, (2) optionally substituted alkyl, optionally substituted (3) alkenyl, (4) optionally substituted alkynyl, (5) optionally substituted alkanoyl, (6) optionally substituted aroyl, (7) optionally substituted cycloalkanoyl, (8) optionally substituted cycloalkenoyl, (9) optionally substituted alkylsulfonyl wherein the substituents on the alkyl, alkenyl, alkynyl, alkanoyl, aroyl, cycloalkanoyl, cycloalkenoyl and alkylsulfonyl are from 1 to 5 groups independently selected from hydroxy, alkoxy, aryl alkoxy, NRgRh, C02Rb, CONRcRd and halogen, (10) trifluoromethyl, (11) arylsulfonyl optionally substituted with 1 a 3 groups independently selected from methyl, trifluoromethyl and halogen, (12) a 5- or 6-membered heterocycle containing from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by 1 to 4 groups independently selected from methyl, trifluoromethyl, C (0) NRcRd, C02Rb and halogen, and which may be saturated or partially unsaturated; (1) H, (2) optionally substituted aryl, (3) optionally substituted alkyl, (4) optionally substituted alkenyl, (5) optionally substituted alkynyl, (6) optionally substituted cycloalkyl, (7) optionally substituted cycloalkenyl, or (8) optionally substituted 5 to 6 membered heterocycle containing from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen; wherein the substituents on the aryl, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle or alkynyl are from 1 to 10 groups independently selected from (i) hydroxy, (ii) alkyl, (iii) oxo, (iv) S02NRgRh, (v) arylalkoxy, (vi) hydroxyalkyl, (vii) alkoxy, (viii) hydroxy alkoxy, (ix) amino alkoxy, (x) cyano, (xi) - alkyl S (0) m, 5 (xii) cycloalkyl optionally substituted with 1 to 4 groups independently selected from Re, (xiii) cycloalkenyl, (xiv) halogen, 10 (xv) alkanoyloxy, (xvi) C (0) NRgRh, (xvii) C02R1, (xvii) -NRgRh, (xix) heterocycle of 5 to 6 members, which may be saturated or partially unsaturated, containing 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 to 5 groups independently selected from Re, 20 (xx) optionally substituted aryl, wherein the aryl substituents are 1, 2-methylenedioxy or 1 to 5 independently selected groups Reeds, (xxi) aryl optionally substituted alkoxy, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from Re, and (xxii) perfluoroalkyl; Re is (1) halogen, (2) alkyl, (3) perfluoroalkyl, (4) -S (0) mRl, (5) cyano, (6) RaO (CH2) v-, (8) R? OCO (CH2 ) v-, (9) optionally substituted aryl wherein the substituents are from 1 to 3 of halogen, alkyl, alkoxy or hydroxy, (10) S02NRgRh, or (11) amino; Rf is (1) methyl, (2) X-alkyl of L-C4, where X is O or S (0) m, (3) trifluoromethyl, (4) NYXY2, where Y1 and Y2 are independently H or alkyl, ( 5) hydroxy, (6) halogen, and (7) acetylamino, Rg and Rh are independently (1) hydrogen, (2) alkyl optionally substituted by hydroxy, amino or C02Ri (3) aryl optionally substituted with halogen, 1-2 methylenedioxy, alkoxy, alkyl or perfluoroalkyl, (4) arylalkyl, wherein the aryl is optionally substituted with perfluoroalkyl or 1,2-methylenedioxy; (5) alkoxycarbonyl, (6) alkanoyl, (7) alkanoylalkyl, (9) arylalkoxycarbonyl, (10) aminocarbonyl, (11) monoalkylaminocarbonyl (12) dialkylaminocarbonyl; or R9 and Rh together with the N to which they are attached form a 5 to 6 member ring containing from 0 to 2 additional heteroatoms selected from O, S (0) m N, optionally substituted with 1 to 3 groups independently selected from and oxo; Ra is (1) hydrogen, (2) perfluoroalkyl, (3) alkyl, (4) aryl or optionally substituted arylalkyl, wherein the aryl substituents are from 1 to 3 groups independently selected from halogen, alkyl, alkoxy and hydroxy; and all other variables are as defined under Formula I. More especially preferred are chewable veterinary formulations, wherein the composition comprises nodulisporic acid derivatives which are nodulisers, which are compounds of the formula Rx is (1) hydrogen, (2) optionally substituted Ci-Cio alkyl, (3) C2-C? Or optionally substituted alkenyl, (4) C2-C? Or optionally substituted, (5) cycloalkyl of C3-C8 optionally substituted, (6) optionally substituted C5-C8 cycloalkenyl wherein the substituents on the alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl are from 1 to 3 groups independently selected from C1-C5 alkyl, C1-C10 alkoxy, Clycyl alkylthio C1-C10 alkylsulfonyl, C3-C8 cycloalkyl, hydroxy, halogen, cyano, carboxy, amino, C1-C10 monoalkylamino, C1-C10 dialkylamino, C1-C10 alkanoyl, amino and benzoyl amino wherein the benzoyl is optionally substituted with 1 to 3 groups independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 4 alkylthio / C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 3 perfluoroalkyl, amino, hydroxy, halogen , C1-C5 monoalkylamino, C1-C5 dialkylamino and C1-C5 alkanoylamino, (7) wherein the C0-C5 phenyl is optionally substituted with 1 to 3 groups independently selected from C1-C4 alkyl, alkoxy C1-C4, C 1 -C 4 alkylthio, C 2 -C 4 alkenyl, C 2 -C alkynyl, perfluoroalkyl C 1 -C 3 uole / amino, hydroxy, carboxy, halogen, C 1 -C 5 monoalkylamino, C 1 -C 5 dialkylamino and C 1 -C 5 alkanoylamino, (8) C 1 -C 5 perfluoroalkyl, (9) a ring of 5 or 6 members selected from morpholino, pyridyl and piperazino, optionally substituted by 1 to 3 groups independently selected from hydroxy, oxo, C1-C10 alkyl and halogen, R2, R3 and R4 are independently ORa, OC02Rb, OC (0) NRcRd; or R1 and R2 jointly represent = 0, = NORa or = N-NRcRd; Ra is i) hydrogen, optionally substituted C 1 -C 0 alkyl, optionally substituted C 3 -C 10 alkenyl, optionally substituted C 3 -C 10 alkynyl, optionally substituted QL-CIO alkanoyl, optionally substituted C 1 -C 10 alkenoyl, optionally substituted C 1 -C 10 alkyloyl, optionally substituted benzoyl, optionally substituted phenyl, (optionally substituted C 1 -C 7 cycloalkanoyl, optionally substituted C 4 -C 7 cycloalkenoyl, optionally substituted C 1 -C 8 alkylsulfonyl, (13) C3-C8 cycloalkyl optionally substituted (14) optionally substituted C5-C8 cycloalkenyl wherein the substituents on the alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, alkynyl, benzoyl, phenyl, cycloalkanoyl, cycloalkenoyl, alkylsulfonyl, cycloalkyl and cycloalkenyl are from 1 to 5 independently selected hydroxy groups , C? -C6 alkoxy, C3-C7 cycloalkyl, C1-C3 aryl-alkoxy, Rh-NRg, C02Rb, CONRc Rd and halogen, (15) perfluoroalkyl, (16) phenylsulfonyl optionally substituted with 1 to 3 independently selected groups of alkyl of C1-C5, C1-C5 perfluoroalkyl, nitro, halogen or cyano, (17) a 5- or 6-membered ring selected from piperidino, morpholino, pyridyl and piperazino optionally substituted by 1 to 4 groups independently selected from C1-C5 alkyl , C1-C5 alkenyl, C1-C5 perfluoroalkyl, amino, C (0) RcRd, cyano, C02Rb or halogen; (1) H, (2) optionally substituted phenyl, (3) optionally substituted C 1 -C 10 alkyl, (4) optionally substituted C 3 -C 0 alkenyl, or optionally substituted C 3 -C 10 alkynyl, wherein the substituents on phenyl, alkyl, alkenyl or alkynyl are from 1 to 5 groups independently selected from hydroxy, C? -C6 alkoxy, C3-C7 cycloalkyl, halogen, C1-C5 alkanoyloxy, C (0) NRcRd, C02Rb , formyl, -NRgRh, optionally substituted phenyl and optionally substituted C1-C3 alkoxy phenyl, wherein the phenyl substituents are from 1 to 3 groups independently selected from Re; Rc and Rb are independently Rb; or Rc and Rd together with the N to which they are attached form a piperidino, morpholino or piperazino optionally substituted with 1 to 3 groups independently selected from Rg and oxo; Re is (1) halogen, (2) C1-C7 alkyl, (3) C1-C3 perfluoroalkyl, (4) -S (0) mR \ (5) cyano, (6) nitro, (7) RjO ( CH2) v-, (8) RjC02 (CH2) v-, (9) RJOCO (CH2) v-, (10) optionally substituted phenyl wherein the substituents are from 1 to 3 halogens, C6-C6 alkyl, alkoxy Ci-Cs or hydroxy; v is 0 to 3; Rs and Rh are independently (1) hydrogen, (2) C?-C6 alkyl, (3) aryl, (4) aryl-C de-C6 alkyl, (5) C1-C5 alkoxycarbonyl, (6) alkylcarbonyl of C1-C5, or (7) Ci-Cs alkanoyl-C?-C5 alkyl; or R'3 and Rh together with the N to which they are attached form a piperidino, morpholino or piperazino optionally substituted with 1 to 3 groups independently selected from Rg and oxo; R1 and Rj are independently (1) hydrogen, (2) C1-C3 perfluoroalkyl, (3) optionally substituted C? -Cd alkyl, wherein the substituents are aryl or substituted phenyl; (4) phenyl or substituted phenyl wherein the substituents are from 1 to 3 groups independently selected from halogen, C? -C6 alkyl, C? -C6 alkoxy or hydroxy; m is 0 to 2; or a pharmaceutically acceptable salt thereof. More especially preferred are the compounds of the formula where Rx is selected from the group consisting of: H, CH3, CH2CH3, C (CH3) 3, CH2CH2CH3, CH2CH2OH, CH (C02CH3) CH2OH, CH2CO2CH3, CH2CH (OCH2CH3) 2 / CH2CH2OCH2CH2OH, CH (CH3) (CH2) 3C (CH3) 2? H, (CH2) 3OH, (CH2) 4? H, (CH2) SOH, CH (CH2OH) CH2CH3, NHC (CH3) 3 / CH2CN, (CH2) 6OH , CH2CH (OH) CH3, CH (CH2? H) CH2CH2CH3, CH2CH2SCH3, CH2CH2SCH2CH3, CH2CONH, CH (CH3) (CH2OH) 2, CH2CH2NHCH2CH2OH, CH (CH2OH) (CH2) 3CH3, CH (CH2OCH3) CH3, (CH2) 2SH, (CH2) 4NH2, CH2CH2S02CH3, CH2CH2S (0) CH3, CH (CH (CH3) 2) CH2OH, (CH2) 3NH2, (CH2) 3N (CH2CH3) 2, (CH2) ) 3N (CH3) 2, OCH2CH3, CH2CH (OH) CH2OH, OCH3, CH2CH2OHC3, CH2CH2NHC (0) CH3, CH2CH2NHC (0) CH3, C (CH3) 2CH20H, C-C3-H5, c-Ce-Hu, (CH2) 3OCH2CH3, CH2CHsCH2, C (CH2CH3) (CH20H) 2, CH2C = CH, CH2C02CH2CH3, CH2CH2F, (CH2) 3OCH2) ?? CH3, CH2CH2N (CH3) 2 / CH2CH2OCH2CH2 H2, CH2CF3, NHCH2C02CH2CH3, CH (CH3) C02CH3, C (CH3) 2CH2C (O) CH3, CH (C02CH2CH3) 2, CH2CH3, CH (CH2CH2CH3) C02CH3, CH2CH2CH20CH3, C (CH3) 2C = CH, (CH2) 4CH3, CH (CH2CH2CH3) 2, (CH2) 5CH3CH2CH2CO2H, CH (CH (CH3) 2) C02CH3, OCH2CO2H, CH (CH (CH3) 2) CH2OH, CH (CH (CH3) 2) CH20H, CH ( CH3) CH20H, CH (CH3) CH20H, CH (CH3) 2, C (CH3) 3, (CH2) CH (CH3) 2, CH (CH3) CH2CH3, CH2CH (CH3) 0H, (CH2) 3CH3, (CH2) ) 20CH2CH3, 1-adamantyl, (CH2) 8CH3, CH (CH3) CH (CH3) 2, (CH2) 3NHCH3, (CH2) 2 (CH2CH3) 2, , An especially preferred nodulisporamide derivative is one in which Rx is t-butyl. "Alkyl" as well as other groups having the prefix "alq", such as alkoxy, alkanoyl, alkenyl, alkynyl and the like, mean carbon chains which may be linear or branched or combinations thereof. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec- and tert-butyl, pentyl, hexyl, heptyl and the like. "Alkenyl" and other similar terms include carbon chains containing at least one unsaturated C-C bond. The term "cycloalkyl" means carbocycles that do not contain heteroatoms, and include saturated monocyclic carbocycles., bi- and tricyclics, as well as benzofused carbocycles. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, decahydronaphthalene, adamantine, indanyl, indenyl, fluorenyl, 1, 2, 3, 4-tetrahydronaphthalene and the like. Similarly "cycloalkenyl" means carbocycles that do not contain heteroatoms and at least one non-aromatic C-C double bond, and include partially saturated mono-, bi- and tricyclic carbocycles, as well as benzofused cycloalkenes. Examples of cycloalkenyl include cyclohexenyl, indenyl and the like. The term "halogen" is proposed to include the halogen, fluorine, chlorine, bromine and iodine atoms. The term "heterocycle", unless otherwise specified, means mono- or bicyclic compounds which are saturated or partially unsaturated, as well as saturated heterocycles fused to benzo- or heteroaromatic ring or partially unsaturated heterocycles, and which contain from 1 to 4. heteroatoms independently selected from oxygen, sulfur and nitrogen. Examples of saturated heterocycles include morpholine, thiomorpholine, piperidine, piperazine, tetrahydropyran, tetrahydrofuran, dioxane, tetrahydrothiophene, oxazolidine, pyrrolidine.; examples of partially unsaturated heterocycles include, dihydropyran, dihydrofuran, dihydrooxazole, dihydropyrazole, dihydropyridine, dihydropyridazine and the like. Examples of fused benzo- or heteroaromatic ring heterocycles include 2,3-dihydrobenzofuranyl, benzopyranyl, tetrahydroquinoline, tetrahydroisoquinoline, benzomorpholinyl, 1,4-benzodioxanyl, 2,3-dihydrofuro (2,3-b) pyridyl and the like. The term "aryl" is intended to include mono- and bicyclic aromatic and heteroaromatic rings containing from 0 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur. The term "aryl" is also proposed to include benzofused cycloalkyl, benzofused cycloalkenyl and benzofused heterocyclic groups. Examples of "aryl" groups include phenyl, pyrrolyl, isoxazolyl, pyrazinyl, pyridinyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, triazinyl, thienyl, pyrimidinyl, pyridazinyl, pyrazinyl, naphthyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furo (2,3-B) pyridyl, 2,3-dihydrofuro (2,3-b) pyridyl, benzoxazinyl, benzothiophenyl, quinolinyl, indolyl, 2,3-dihydrobenzofuranyl, benzopyranyl, 1-benzodioxanyl, indanyl, indenyl, fluorenyl, 1, 2, 3, 4-tetrahydronaphthalene and the like. Aroyl means arylcarbonyl in which aryl is as defined above. Examples of NRcRd or NRgRh which form a 3 to 10 member ring containing 0 to 2 additional heteroatoms selected from O, S (0) m and are aziridine, azetidine, pyrrolidine, piperidine, thiomorpholine, morpholine, piperazine, octahydroindole, tetrahydroisoquinoline and the Similar. The term "optionally substituted" is intended to include both substituted and unsubstituted; thus, for example, optionally substituted aryl could represent a pentafluorophenyl or a phenyl ring. Certain of the terms defined in the above can be presented more than once in the previous formula and in such occurrence each term will be defined independently of the other; so, for example, 0Ra in C4 can represent OH. The compounds of the formula (I) are commercially available or can be prepared according to one or another of the processes or any other process which falls within the competence of a person skilled in the art who is an expert in chemical synthesis. For the chemical preparation of the products of the invention, a person skilled in the art is considered to have at his disposal, inter alia, the complete contents of "Chemical Abstracts" and the documents that are cited therein. Semi-synthetic processes are described, for example, in U.S. Patent No. 6,399,786 or WO 96/29073, both of which are incorporated by reference. The terms "nodulisporic acid or nodulisporic acid derivative" also include pharmaceutically or veterinarily acceptable base acid salts, where applicable, of these compounds. The term "acids" contemplates all pharmaceutically or veterinarily acceptable inorganic or organic acids. Inorganic acids include mineral acids such as hydrohalic acids, such as hydrobromic and hydrochloric acid, sulfuric acids, phosphoric acids and nitric acids. Organic acids include all pharmaceutically or veterinarily acceptable aliphatic, alicyclic and aromatic carboxylic acids, dicarboxylic acids, tricarboxylic acids and fatty acids. Preferred acids are saturated or unsaturated straight or branched C 1 -C 20 aliphatic carboxylic acids. , which are optionally substituted by halogen or by hydroxyl groups, or aromatic carboxylic acids of C6-C? 2. Examples of such acids are carbonic acid, formic acid, fumaric acid, acetic acid, propionic acid, isopropionic acid, valeric acid, a-hydroxyl acid, such as glycolic acid and lactic acid, chloroacetic acid, benzoic acid, methane sulphonic acid and salicylic acid. Examples of dicarboxylic acids include oxalic acid, malic acid, succinic acid, tartaric acid and maleic acid. An example of a tricarboxylic acid is citric acid. The fatty acids include the pharmaceutically or veterinarily acceptable saturated or unsaturated aliphatic or aromatic carboxylic acids having from 4 to 24 carbon atoms. Examples include butyric acid, isobutyric acid, sec-butyric acid, lauric acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid and phenylsteric acid. Other acids include gluconic acid, glycoheptonic acid and lactobionic acid. The term "base" contemplates all pharmaceutically or veterinarily acceptable inorganic or organic bases. Such bases include, for example, the alkali metal and alkaline earth metal salts, such as the lithium, sodium, potassium, magnesium or calcium salts. Organic bases include the common hydrocarbyl amine and heterocyclic salts, which include, for example, the morpholine and piperidine salts. The ester and amide derivatives of these compounds, where applicable, are also contemplated. The specific compounds belonging to these classes of therapeutic agents are well known to the practitioner of this technique.

The avermectin and milbemycin series of compounds are potent anthelmintic and antiparasitic agents against a wide range of internal and external parasites. The compounds belonging to this series are either natural products or are semi-synthetic derivatives thereof. The structure of these two series of compounds are closely related and both share a complex 16-membered macrocyclic lactone ring; however, milbemycin does not contain the aglycone substituent at position 13 of the lactone ring. The avermectin natural products are disclosed in U.S. Patent No. 4,310,519 the Albers-Schonberg et al, and compounds 22, 23-dihydro avermectin are disclosed in Chabala et al, U.S. Patent No. 4,199,569. For a general discussion of avermectins that includes a discussion of their uses in humans and animals, see "Ivermectin and Abamectin", W.C. Campbell, ed., Springer-Verlag, New York (1989). The milbemycins are described naturally occurring in Auki et al, U.S. Patent No. 3,950,360 as well as in the various references cited in "The Merck Index" 12th Edition, S. Budavari, Ed, Merck &Co. Inc. Whitehouse Station, New Jersey (1996). Semi-synthetic derivatives of these classes of compounds are well known in the art and are described, for example, in US Patent No. ,077,308, U.S. Patent No. 4,859,657, U.S. Patent No. 4,963,582, U.S. Patent No. 4,855,317, U.S. Patent No. 4,871,719, U.S. Patent No. 4,874,749, U.S. Patent No. 4,427,663, U.S. Patent No. 4,310,519, U.S. Patent No. 4,199,569, U.S. Patent No. 5,055,596, U.S. Patent No. 4,973,711, U.S. Patent No. 4,978,677 and U.S. Patent No. 4,920,148. The avermectins and milbemycins share the same common 16-membered macrocyclic lactone ring; however, milbemycins do not possess the disaccharide substituent at position 13 of the lactone ring. While many avermectin compounds are known in the art, a structure representative of the class of compounds is as follows: where the dashed line indicates a single or double link at positions 22, 23; Ri is hydrogen or hydroxy, with the proviso that R1 is present only when the dashed line indicates a single bond; R 2 is alkyl of 1 to 6 carbon atoms or alkenyl of 3 to 6 carbon atoms or cycloalkyl of 3 to 8 carbon atoms; R3 is hydroxy, methoxy or = NOR5 where R5 is hydrogen or lower alkyl; and R4 is hydrogen, hydroxy or where Re is hydroxy, amino, mono- or di-lower alkylamino or lower alkanoylamino. The preferred compounds are avermectin Bla / Blb (abamectin), 22, 23-dihydro (ivermectin) Bla / Blb and avermectin and the 4"-acetylamino-5-ketoximino derivative of avermectin Bla / Blb. Both abamectin and ivermectin are approved as broad spectrum antiparasitic agents. The structures of abamectin and ivermectin are as follows: wherein for abamectin the ion line represents a double bond and Ri is not present and for ivermectin the double bond represents a single bond and Ri is hydrogen; and R2 is isopropyl or sec-butyl. The 4"-acetyl amino-5-ketoximino derivatives of avermectin Bla / Blb have the following structural formula: where R2 is isopropyl or sec-butyl. The avermectin products are generally prepared as a mixture of at least 80% of the compound wherein R2 is sec-butyl and not more than 20% of the compound where R2 is isopropyl. Other preferred avermectins, include ememectin, eprinomectin and doramectin. Dora ectin is disclosed in U.S. Patent No. 5,089,490 and EP 214 738. This compound has the following structure: In the present formulations, ivermectin and eprinomectin are especially preferred. A representative structure for a milbemicin is that for milbemicin cti: An especially preferred milbemycin is moxidectin, whose structure is as follows: The compound is disclosed in U.S. Patent No. 5,089,490.

The avermectin derivatives of monosaccharide are also especially preferred where an oxime substitution is present at the 5-position of the lactone ring. Such compounds are described, for example, in EP 667,054. Selamectin is an especially preferred compound of this class of derivatives. Other pharmaceutical or therapeutic agents are those known in the art to treat parasitic infection "caused by nematodes and trematodes." In order to treat cestode (and trematode) infections in warm-blooded animals, it is known to administer 2-acyl derivatives. -4-oxo-pyrazino-isoquinoline to the animal (see, for example, U.S. Patent No. 4,001,441, incorporated herein by reference.) A compound of this class that is frequently used to treat cestode and nematode infections is praziquantel, which has the following structure: It is often beneficial to administer a formulation containing a combination of two or more anthelmintics, which have different activity, in order to obtain a composition with a broad spectrum of activity. For example, avermectin is ineffective against cestodes, such as tapeworms, and thus is ineffective against an infestation, caused by round worms and tapeworms. In addition, the combination allows the user to administer a formulation in place of two or more different formulations to the animal. Formulations that administer a combination of two or more anthelmintics are known in the art. These formulations may be in the form of solutions, suspensions, pastes, soaps or formulations of 'determined emptying (see, for example, the Patent North American 6,165,987 by Harvey, the North American Patent No.- 6,340,672 of Mihalik or the co-pending application USSN / 177,822 entitled Anthelmintic Oral Homogeneous Veterinary Pastes, filed on June 21, 2002, incorporated herein by reference). For example, U.S. Patent No. 4,468,390 to Gypsy and U.S. Patent No. 5,824,653 to Beuvry et al. Describe anthelmintic compositions for treating nematode and cestode infections in animals, such as horses, comprising an avermectin or a milbemycin and a compound of isoquinoline, such as praziquantel, to the animal. In these formulations, the avermectin or milbemycin compound and the isoquinoline compound. Similarly, U.S. Patent No. 6,207,179 to Mihalik discloses formulations of anthelmintic pastes wherein the avermectin or milbemycin dissolves in a non-aqueous liquid and the pyrantel or morantel compounds which are of the same class as praziquantel, but which is said to be which are much less effective like praziquantel, are suspended in the liquid. These prior patents do not describe a formulation wherein both praziquantel and avermectin or milbemycin are in a chewable formulation. For example, US Patent No. 6,165,987 describes anthelminthic formulations containing praziquantel and at least one avermectin or milbemycin dissolved in an ester or ester-like compounds, such as glycerol formal, benzyl alcohol and N-methyl-2-pyrrolidone, which they may be liquids, pastes or soaps. No mention is made of a chewable formulation or one that contains non-animal products and a pleasant taste to the animal. Other pharmaceutical agents, such as vitamins, mineral supplements, which are known in the veterinary art can also be included in the inventive formulations. An important feature of the present invention is the taste that does not contain animal products or is not derived from an animal source. The flavors derived from calamento, the valerian plant or fruit are not contemplated by the present invention. The flavors include those known in pet foods that are artificial and include, for example: The sources for these flavors are well known to a professional in this technique. For example, Kermine Petfood Nutrisurance is a vegetarian flavor for pet food that is sold by Kemine Industries, Inc., Des Moines, IW. A discussion of commercial smoke flavorings is provided by Guillen et al., J. Agr. and Food Chemistry vol. 4. The flavors of the GRILLIN grill line and mixtures marketed by the Red Arrow Products Company, LLC, Manitowoc, Wl human and pet food are preferred. These include GRILLIN 'TYPE CB-200, GRILLIN' TYPES SD, GRILLIN 'TYPE W S-50, GRILLIN' TYPE CN, GRILLIN 'TYPE CB, GRILLIN' TYPE GS and GRILLIN 'TYPE NBF. Especially preferred are the American walnut smoke flavorings produced by combining torula yeast and a solution of American walnut or aqueous smoke sold by Red Arrow Products Co. as CHARTOR HICKORY or a flavoring of American walnut smoke produced by combining maltodextine with a solution of aqueous American walnut smoke, sold by Red Arrow Products Co. as CHARDEX HICKORY. Other flavors contemplated by the invention include those that impart a natural dry smoke flavor. These include CHARZYME (a smoke flavor produced by combining barley malt flour with an aqueous smoke flavor), CHARMAIZE (a smoke flavor produced by combining yellow flower and a watery smoke flavor) and CHARSALT (a mixture of dendritic salt). , taste of aqueous smoke, and dehydrated silicon dioxide). All these flavors can be obtained through Red Arrow Products Co. The determination of the taste quantities for a particular product is easily determined by a professional of this technique. Typical ranges are up to about 10%. Flavors that provide an appetizing flavor are also preferred. These flavors are well known to a professional of this technique. Disintegrants include for example sodium starch glycolate, crospovidone, croscarmellose sodium, starch, microcrystalline cellulose, alginic acid, veegum, crospovidone, bentonite and pregelatinized starch. The binders can be for example polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, ethylcellulose, sodium alginate, tragacanth and acacia.

Non-limiting examples of humectants include propylene glycol, glycerin, polyethylene glycol 400 and polyethylene glycol 3350. Absorbents can also be added to the inventive formulations. Such compounds are well known in the art for the practitioner as well as their use in pastes. These compounds effectively prevent, or alleviate, phase separation of the product during storage. Preferred absorbers include magnesium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, starch, cellulose and its derivatives, or mixtures of sorbents, with magnesium carbonate which is especially preferred. The inclusion of these compounds is optional with amounts of 0% about 30%, 0 to about 15% or about 1% to about 15% or about "1% to about 10%, based on the total weight of the formulation which is especially Additionally, the inventive formulations may contain other inert ingredients such as antioxidants, preservatives, stabilizers or surfactants.These compounds are well known in the art of formulation.The antioxidant such as alpha tocoferal, ascorbic acid, ascorbyl palmitate, fumaric acid , malic acid, sodium ascorbate, sodium metabisulfate, n-propyl gallate, BHA (butylated hydroxy anisole), BHT (butylated hydroxy toluene), monothioglycerol and the like, can be added to the present formulation. to the formulation in amounts of about 0.01 to about 2.0%, based on the total weight of the formulation n, with about 0.1 to about 1.0% being especially preferred. Preservatives, such as parabens (methylparaben and / or propylparaben), are suitably used in the formulation in amounts ranging from about 0.01 to about 2.0%, with about 0.05 to about 1.0% being especially preferred. Other preservatives include benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butylparaben, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, methylparaben, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium propionate, sorbic acid, thimerosal, propylparaben, gamma-picolinium myristyl chloride, methylparaben, propylparaben and quaternary ammonium compounds and the like. Granulating solvents are well known to those skilled in the art. Examples of such solvents are water, aqueous sorbitol solution, etc. Other compounds that can act as solvents include polyethylene glycol 3350, caprylate / glycerol caprate and polyglycolized glycerides (GELUCIRE). Moisturizers are known in the art and include compounds such as propylene glycol, glycerin, polyethylene glycol 400 and polyethylene glycol 3350. Moisturizers may be present in amounts, for example, from about 0.01% to 20% based on the total weight of the formulation. The surfactants in amounts of approximately 0. 001 to about 1%, based on the total weight can also be added to help solubilize the active drug, to prevent crystallization and to prevent phase separation. Some examples of surfactants are: glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters, sorbitan esters, polyvinyl alcohol, Pluronics, polysorbate 80, sodium laurel sulfate, poloxomers (LUTROL F87), propylene glycol laurate (LAUROGLYCOL), caprylate / glycerol caprate (CAPMUL MCM), polyglycolized glycerides (GELUCIRE), etc. Again these compounds, as well as their amounts are well known in the art. The . dyes can be added to the inventive formulations. The colorants contemplated by the present invention are those commonly known in the art. Specific dyes include, for example, dyes, an aluminum lacquer, caramel (which may also function as a flavor), dye based on iron oxide or a mixture of any of the foregoing. Especially preferred are organic dyes and titanium dioxide. Preferred ranges include from about 0.5% to about 25%. The chewable formulations provided in the present invention may also include lubricants, such as polyethylene glycols (PEG's or CARBOWAX), corn oil, mineral oil, hydrogenated vegetable oils (STEROTEX OR LUBRI ), peanut oil, magnesium stearate, soybean oil and / or resin oil. The inclusion and identity of a lubricant is easily determined by a professional of this technique to be in present amounts, for example, from about 0.01 to about 20%, based on the total weight in the composition. Compounds that stabilize the pH of the formulation (pH modifiers) are also contemplated. Again, such compounds are well known to a person skilled in the art as well as to the extent of using these compounds. The pH regulating systems include, for example, systems selected from the group consisting of acetic acid / acetate, malic acid / malate, citric acid / citrate, tartaric acid / tartrate, lactic acid / lactate, phosphoric acid / phosphate, glycine / glycytate, tris, glutamate / glutamate and sodium carbonate. Preferred ranges for pH include from about 4 to about 6.5. Other compounds contemplated by the inventive formulations include complexing agents, such as cyclodextrins, PVP, PEG, ethyl lactate and niacinamide, and quantities of such compounds that are included in the inventive formulation are well known to a person skilled in the art. therapeutic agents that are in the form of emulsions, liposomes or micelles are contemplated The inventive formulation can be administered to warm-blooded animals, such as cattle, sheep, pigs, cats, dogs, horses, llamas, deer, rabbits, skunks , raccoons, camels and the like or birds.The formulations contemplated by the invention can also be used with humans.The amount of pharmaceutical active agent depends on the individual therapeutic agent, the animal being treated, the state of disease and the severity of the condition. The determination of these factors is well within the skill level of the professional. Generally, such a preparation normally contains about 0.0005 to about 50% therapeutic agent per total weight of the composition. For nodulisporic acid and nodulisporic acid derivatives, a formulation containing about 0.0005 to about 5% of the active compound is preferred. Preferred formulations are those containing about 0.01 to 10% therapeutic agent and especially preferred formulations are those containing from about 2.5 to about 5% therapeutic agent. Other preferred amounts include from about 0.1 to about 0.01 about 50% or about 10% or about 0.5 to about 3%. For avermectins and milbemycins, the formulations are generally prepared to administer from about 0.1 to about 2 mg / kg, preferably from about 0.4 to about 0.85 mg / kg and much more preferably from about 0.6 to about 0.7 mg / kg of the ingredient active. In a preferred dose volume of about 1 ml to treat 50 kg body weight of the animal the formulation contains from about 5 to about 50 mg of the active agent per ml of solution or about 0.5 to about 10%, preferably about 2.5 to approximately 5% p / v. However, depending on the activity of the compound and the animal being treated, doses as low as about 0.3% of the active ingredient are usable. For nodulisporic acid and its derivatives, a formulation containing about 0.0005 to about 5% of the active compound is preferred. For a chewable veterinary formulation comprising an avermectin or a milbemycin and an antiparasitic agent for nematodes or trematodes, such as praziquantel or pyrantel, preferred amounts of praziquantel include, for example, from about 0.5 mg / kg to about 7.5 mg / kg of body weight of the animal, with a range of about 0.5 mg / kg to about 2 mg / kg or 2.5 mg / kg of body weight which is especially preferred. A more especially preferred amount is about 1.0 mg / kg body weight of the animal. Preferred ranges for the anthelmintic macrolide compounds include, for example, about 0.01 to about 200 mg / kg body weight of the animal, with ranges from about 0.1 to about 50 mg / kg and from about 1 to about 30 mg / kg which they are especially preferred. This invention further provides tablets that do not contain animal products comprising, in addition to the flavor containing non-animal product or flavor derived from a non-animal source, at least one nodulisporic acid or nodulisporic acid derivative, flavor, filler, lubricant and auxiliary flow. Optionally, the inventive tablets may also contain at least one of the following ingredients: colorants, binders, antioxidants, disintegrants or preservatives. In addition, in an alternative embodiment, this invention provides tablets that are coated. The inventive tablets are prepared according to methods conventional in the art, such as wet and dry granulation processes. Many of the ingredients for the tablets include those provided for the chewable formulations. With respect to fillers (or diluents), the inventive tablets contemplate all the fillers that are known in the tablet art. Non-limiting examples of fillers include anhydrous lactose, hydrated lactose, dehydrated lactose by dew, crystalline maltose and maltodextrins. Flow auxiliaries or slip agents are also well known in the art and include, for example, silicon dioxide (CARBOSIL), or silica gel (SYLOID), talc, starch, calcium, stearate, magnesium stearate and magnesium aluminum silicate (NEUSILIN). The amounts of flow aids are readily determined by a professional in this art and include using about 0.01 to about 25%, based on the weight of the total composition. Non-limiting examples of lubricants for the tablets include magnesium and calcium stearate and stearic acid. Again, the various lubricants are well known to a professional of this technique as well as the amounts of these compounds. The ranges include from about 0.01 to about 20%. The chewable formulations and tablets provided by this invention can be coated using techniques conventional in the art. Coatings for chewable veterinary formulations include gelatin, glyceryl behenate, cocoa butter and beeswax. Other coatings would be known to a professional in this art. Coatings for tablets include sugar coatings, such as sealant coatings, undercoats and syrup coatings, as well as film coatings, such as tray castings and tray spray coatings. As is well known to a professional in this art, the coatings contain additional components such as solvents, plasticizers, colorants, opacifiers, enderers and film formers. The inventive oral formulations can be used to treat a number of disease states by administering to the host in need thereof an effective amount of the oral formulation containing the pharmaceutical agent. The determination of a protocol for the treatment of a specific indication will be well within the skill level of a professional in the pharmaceutical or veterinary techniques. The hosts include all animals, for example, cats, dogs, cattle, sheep, horses and pigs. As mentioned in the above, the oral formulation provided by this invention could also be used to treat disease states in human hosts. EXAMPLES A better understanding of the present invention and its many advantages will be obtained from the following examples, given by way of illustration. Example 1: Studies of Pleasant Flavor This test determined which of the four flavors containing non-animal product, alternative for a pharmaceutical agent such as a COX-2 inhibitor, nodulisporic acid or a nodulisporic acid derivative will be more readily accepted by dogs in a situation of daily domestic use. The four non-animal, alternative flavors were selected from a field of sixteen flavors in the qualitative test with employed dogs. The control was a tablet that contained the liver of a real pig. The formulations, which were in the form of tablets, were prepared as follows: Control: Formulation containing 6% of real pig liver: Inventive: Formulation containing 2% of CHARDEX and 2% of Caramel The granulation of extract contained the following ingredients: Total 100.00 The results of the experiments are summarized below: TABLE I: Pleasant Taste Study The four synthetic test flavors were accepted by the dogs although not as easily as the flavor formulations with real pig liver. • Specifically, 94% of the dogs accepted the pork liver tablets completely, with 80% accepting this shot on the first attempt (refusion ratio was 6%). • For artificial flavors, 74% to 85% of the dogs accepted the tables completely, with an interval of 25% to 60% of them accepting the flat tablets on the first try (ie, remelting ratios outside 15% to 26%). • Pork liver registry of "Accepted - 94%)" "Plant accepted, 1- attempt - 80%", "Plan accepted - 94%" and "1- Attempt accepted -83%) are records significantly higher than for all the tablets at 95% + the level of confidence • CHARTOR was accepted by 85% of the dogs compared to 74-79% for the CHARDEX options The CHARTOR was also more easily accepted, with 60% accepting the flat tablet in the first attempt compared to 26 to 38% to the CHARDEX. • The "Accepted" record significantly higher than CHARDEX 2% and 4% options at 90% + confidence level. • There were no statistically significant differences between CHARTOR and CHARDEX + Carmel. • There were no statistically significant differences in the registry between CHARDEX 2%, 4% and the options of + Caramelo. While dog owners considered synthetic flavor formulations to be more difficult to administer, the "easy" registration with flavor formulations with CHARTOR was very acceptable. TABLE II: Ease of Administration Example 2: Study to Determine the Acceptability of Chewable Formulations Not of Beef in Dogs: Table III: Descriptions of Animals and Sequences M = Male, F = female All dogs were Beagles and were originally purchased from Harlan Sprague Dawley, Madison, Wl, Merial Limited, Athens, GA, or Sinclair Research Center, Colombia, MO. Formulation 1: All chews were offered once on day O, 2 or 4. Table IV: Acceptability Records All chews were offered once on Day 0, 2 or 4. Acceptability Registry System: 1 = Easily digested 2 = Digested with persuasion or food 3 - Rejected * An acceptability record of 2 was recorded as such because the dog played with the chew before eating it. No chew had to be given with the food. Example 2 The following chewable formulations containing non-animal product were prepared with conventional techniques: Example 2A Chewable Nodulisporamide * Amount of Nodulisporamide in CoA base: 100% (% Assay) 97.5 x 6 g = 6.15 g ** Quantity adjusted from the Soy Protein Fines according to the amount of Nodulisporamide: (19.98 + 6.0) - 6.15 g = 19.83 Example 2B Chewable Nodulisporamide Lot size 100 g * Amount of Nodulisporamide in the CoA base: 100% (% of Test) 97.5 x 6 g = 6.15 g ** Adjusted amount of Soy protein fines according to the amount of Nodulisporamide: (22.98 + 6.0) - 6.15 g = 22.83 g Example 2C Chewable Nodulisporamide Lot size 100 g * Amount of Nodulisporamide in the base of CoA: 100% (% of Essay) 97.5 x 6 g = 6.15 g ** Amount adjusted of the Soy Protein Fines according to the amount of Nodulisporamide: (19.98 g - 6.154 g = 19.826 g Example 2D Chewable Nodulisporamide Lot size 100 g * Amount of Nodulisporamide in the CoA base: 100% (% of Test) 97.5 x 6 g = 6.15 g ** Adjusted amount of Corn Starch according to the amount of Nodulisporamide: (20.9E g + 6.154 = 20.826 g Example 2E Chewable Nodulisporamide Lot size 100 g * Amount of Nodulisporamide in the base of CoA: 100% (% of Test) 97-5 x 6 g = 6.15 g ** Amount adjusted of the Soy Protein Fines according to the amount of Nodulisporamide: 34.98 g - (6.154 g - 6.0 g) = 38.826 g E xample 2A Chewable Nodulisporamide Lot size 100 g * Amount of Nodulisporamide in the base of CoA: 100% (% of Test) 97.5 x 6 g = 6.154 g ** Amount adjusted of the Soy Protein Fines according to the amount of Nodulisporamide: 19.98 g - (6.15 g) - + 6.0 g) = 19,826 g Example 2G Chewable Nodulisporamide Lot size 100 g * Amount of Nodulisporamide in the base of CoA: 100% / 97.4 x 8 gx 2 = 12,320 g ** Amount adjusted of the Soy Protein Fines according to the amount of Nodulisporamide: 39.64 g Example 2H Chewable of Nodulisporamide Lot size 100 g * Adjusted weight of Nodulisporamide: 100% / 97.4% x 6 = 6.160 g ** Adjusted weight of Soy Protein Fines: 17.48 g (6.160 g - 6 g) = 17.32 g Example 21 Chewable Nodulisporamide Lot size 100 g * Adjusted weight of Nodulisporamide: 100% / 97.4% x 6 = 6.160 g ** Adjusted weight of Soy Protein Fines: 33.3 g - (6.160 g - 6 g) = 33.64 g Example 2J Chewable of Nodulisporamide Lot size 100 g * Adjusted weight of Nodulisporamide: 100% / 97.4% x 6 = 6.160 g ** Adjusted weight of Soy Protein Fines: 26. i g - (6.160 g - 6 g) = 26.64 g Example 2K Chewable Nodulisporamide Lot size 100 g * Adjusted weight of Nodulisporamide: 100% / 97.4% x 6 = 6.160 g ** Adjusted weight of Soy Protein Fino: 32.48 g - (6.160 g - 6 6) = 32.32 g Example 3 The following four chewable formulations containing products no animals were prepared according to conventional techniques: Example 4 Chewable Eprinomectin-Praziquantel Formulation 4 * Amount of Eprinomectin in the base of CoA: 100% / (% of Test) 97.4% x 0.0114 x 2 g. = 0.023 g ** Amount of Praziquantel in the CoA base: 100% / (Test%) 99% x 4.25 x 2 g = 8856 g *** Adjust the amount of Soy Protein Fino according to the amount of Eprinomectin & Praziquantel: 75.351 g This Formula was prepared as follows: 1. Mix components 1 and 2. 2. Dissolve components 3, 4 and 5 in step 1 in the sequence with agitation. Be necessary, use heating to dissolve. 3. Mix items 6 to 9 in a planetary mixer for 10 minutes. 4. Granulate stage 3 with the solution from step 2. 5. Dissolve the citric acid in 50% water and add step 3. 6. Dissolve the potassium sorbate in the rest of the water and add step 3. 7 Mix as required. 8. Add corn oil and mix. 9. Make the material extruded. 10. Dry the extruded materials at 50 ° C for 2 hours. Example 5 A chewable non-animal containing formulation comprising the following components: Eprinomectin-Praziquantel chewable Formulation 5 * Amount of Eprinomectin in the base of CoA: 100% / (% of Test) 97.4% x 0.0114 x 2 g = 0.023 g ** Amount of Praziquantel in the base of CoA: 100% / (% of Test) 99% x 4.25 x 2 g = 8856 g *** Adjust the amount of Corn Starch according to the amount of Eprinomectin & Prazicuantel: 43,351 g. The above formula was prepared as follows: 1. Mix items 1 and 2. 2. Dissolve articles 3, 4 and 5 with agitation in stage 1 in sequence. Heat if necessary. 3. Mix items 6 to 10 in a planetary mixer for 10 minutes. 4. Granulate stage 3 with the solution from step 2. 5. Mix for 10 minutes or as required. 6. Dissolve the citric acid in 8 g of water. Continue the granulation of step 5. 7. Dissolve the potassium sorbate in 8 g of water. Add to stage 5 & continue the granulation. 8. Add Corn Oil. Mix for 5 minutes. 9. Make the material extruded. 10. Dry the extruded materials at 50 ° C for 2 hours. Example 6 The following chewable avermectin / pyrantel formulation is prepared according to conventional techniques. Ivermectin / Pirantel Pamoate 68 μ / 163 mg Lot Size 500 g / 200 Chews * Percentage that contains 5% average. a Weight adjustment of Ivermectin: 100% / 90.07% x 0.0143 g x 1000 mg = 16 mg b Weight adjustment of Pirantel Pamoate: 100% / 98.9% x 32.6 g = 32.96 c Adjusted Amount of Soy Protein Fino: 150,884 g Example 7 The following chewable formulations containing non-animal product are prepared according to conventional techniques. Chewable Tablets Not Eprinomectrin Beef Example 8 The following formulation is chewable tablets containing non-animal product are prepared according to conventional techniques. Example 8A: Chewable Non-Beef Tablets Containing Moxidectin Example 8B: Chewable Non-Beef Tablets Containing Moxidectin and Pirantel Pamoate Example 8C: Chewable Non-Beef Tablets Containing Moxidectin and Praziquantel Example 8D: Non-Beef Chewable Tablets Containing Milbemicin Oxima Example 8E: Non-Beef Tablets Containing Milbemicin Oxima and Pyrantel Pamoate Example 8F: Chewable Non-Beef Tablets Containing Milbemicin Oxima and Praziquantel The above description of the invention is proposed to be illustrative and not limiting. Various changes and modifications in the described modality can occur to those skilled in the art. These can be done without departing from the scope or spirit of the invention.

Claims (23)

1. CLAIMS 1. A chewable veterinary formulation, which does not contain animal products, characterized in that it comprises: an effective amount of a pharmaceutically active agent comprising either: a) at least one nodulisporamide acid or nodulisporic acid derivative; or b) a combination comprising: i) at least one avermectin or milbemycin derivative; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel, - at least one filler; - at least one disintegrant; - at least one flavor containing non-animal product or flavor derived from a non-animal source; - at least one binder; - at least one humectant; - at least one granulation solvent; optionally, at least one antioxidant, at least one pH modifier, at least one surfactant, at least one preservative, at least one lubricant or at least one colorant; and - optionally, a coating.
2. 2. The chewable veterinary formulation according to claim 1, characterized in that the pharmaceutically active agent comprises either: a) at least one nodulisporic acid derivative of the formula wherein Ri is (1) hydrogen, (2) optionally substituted alkyl, (3) optionally substituted alkenyl, (4) optionally substituted alkynyl, (5) optionally substituted cycloalkyl, (6) optionally substituted cycloalkenyl, wherein the substituents on the alkyl , alkenyl, alkynyl, cycloalkyl and cycloalkenyl are 1 to 3 groups independently selected from (i) alkyl, (ii) X-alkyl, where X is O or S (0) m. (iii) cycloalkyl, (iv) hydroxy, (v) halogen, (vi) cyano, (vii) carboxy, (viii) NY '? 2, where Y1 and Y2 are independently H or alkyl, (ix) alkanoylamino and (x) ) aroyl wherein the aroyl is optionally substituted with 1 to 3 groups independently selected from Rf (7) aryl or arylalkyl, wherein the aryl is optionally substituted with 1 to 3 groups independently selected from Rf, (8) perfluoroalkyl (9) a 5- or 6-membered heterocycle containing from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen atoms optionally substituted by 1 to 3 groups independently selected from hydroxy, oxo, alkyl and halogen, and which may be saturated or partially unsaturated , R2, R3 and R4 are independently ORa, 0C02Rb, OC (0) NRcRd; or Ri and R2 represent = 0, = N0Ra or = N-NRcRd; R5 and R6 are H; or R5 and R5 together represent -0-, R7 is (1) CHO, or (2) ORa, or (3) NRcRa (2) ORa Rio is (1) CN, (2) C (0) ORb, (4) C (0) NRcRd (5) NHC (0) 0Rß, (6) NHC (0) NRCRd, (7) CH20Ra (8) CH20C02Rb, (9) CH20C (0) NRcRü (10) C (0) NRcNRcRd, or (11) C (0) NRcS02Rb; represents a single or double bond; Ra is (1) hydrogen, 2) optionally substituted alkyl, (3) optionally substituted alkenyl, (4) optionally substituted alkynyl, (5) optionally substituted alkanoyl, (6) optionally substituted alkenoyl, (7) optionally substituted alkynyl, (8) optionally substituted aroyl, (9) optionally substituted aryl, (10) optionally substituted cycloalkanoyl, (11) optionally substituted cycloalkenoyl, (12) optionally substituted alkylsulfonyl, (13) optionally substituted cycloalkyl, (14) optionally substituted cycloalkenyl, where the substituents in the alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, alkynoyl, aroyl, aryl, cycloalkanoyl, cycloalkenoyl, alkylsulfonyl, cycloalkyl and cycloalkenyl are 1 to 10 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, aryl, alkoxy, NRgRh, C02Rb, C0NRcRd and halogen, (15) perfluoroalkyl, (16) aryisulfonyl optionally substituted with 1 to
3. 3 groups independently selected from alkyl, perfluoroalkyl, nitro, halogen and cyano, (17) a 5- or 6-membered heterocycle containing from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by 1 to 4 independently selected alkyl groups , alkenyl, perfluoroalkyl, amino, C (0) NRcRd, cyano, C? 2 by halogen, and which can be saturated or partially unsaturated; (1) H, (2) optionally substituted aryl, (3) optionally substituted alkyl, (4) optionally substituted alkenyl, (5) optionally substituted alkynyl, (6) optionally substituted cycloalkyl, (7) optionally substituted cycloalkenyl, or (8) optionally substituted heterocycle containing from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen; wherein the substituents on the aryl, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle or alkynyl are from 1 to 10 groups independently selected from (i) hydroxy, (ii) alkyl, (iii) oxo, (iv) S02NRgRh, (v) arylalkoxy, (vi) hydroxyalkyl, (vii) alkoxy, (viii) hydroxyalkoxy, (ix) aminoalkoxy, (x) cyano, (xi) mercapto, (xii) alkyl S (0) m, (xiii) cycloalkyl optionally substituted with 1 to 4 groups independently selected from Re, (xiv) cycloalkenyl, (xv) halogen, (xv) alkanoyloxy, (xvii) C (0) NR9Rh, (xviii) CO2R1, (xix) formyl, (xx) -NRgRh, (xxi) heterocycle from 5 to 9 members, which may be saturated or partially unsaturated, containing 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 to 5 groups independently selected from Re, (xxii) optionally substituted aryl, wherein the substituents of aryl are 1, 2-methylenedioxy or 5 groups independently selected from Re, (xxiii) arylalkoxy optionally substituted, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from Re, and (xxiv) perfluoroalkyl; Rc and Rd are independently selected from Rb; or Rc and Rd together with the N to which they are attached form a 3 to 10 member ring containing 0 to 2 additional heteroatoms selected from O, S (0) m and N, optionally substituted with 1 to 3 groups independently selected from Rg, hydroxy, thioxo and oxo; Re is (1) halogen, (2) alkyl, (3) perfluoroalkyl, (4) -SÍO R1, (5) cyano, (6) nitro, (7) R ^ ÍCHz -, (8) RiC02 (CH2) v -, (10) optionally substituted aryl wherein the substituents are from 1 to 3 of halogen, alkyl, alkoxy or hydroxy, (11) S02NRgRh, or (12) amino; Rf is (1) alkyl, (2) X-C alquilo-C4 alkyl / where X is 0 or S (0) m, (3) alkenyl, (4) alkynyl, (5) perfluoroalkyl, (6) NY1Y2, where Y1 and Y2 are independently H or alkyl, (7) hydroxy, (8) halogen, and (9) alkanoylamino, Rg and Rh are independently (1) hydrogen, (2) alkyl optionally substituted by hydroxy, amino or CO2R1 (3) ) aryl optionally substituted with halogen, 1,2-methylenedioxy, alkoxy, alkyl or perfluoroalkyl, (4) arylalkyl, wherein the aryl is optionally substituted with perfluoroalkyl or 1,2-methylenedioxy; (5) alkoxycarbonyl, (6) alkanoyl, (7) alkanoylalkyl, (9) arylalkoxycarbonyl, (10) aminocarbonyl, (11) monoalkylaminocarbonyl (12) dialkylaminocarbonyl; or Rg and Rh together with the N to which they are attached form a 3 to 7 member ring containing 0 to 2 additional heteroatoms selected from 0, S (0) m and N, optionally substituted with 1 to 3 groups independently selected from Re and oxo; R1 is (1) hydrogen, (2) perfluoroalkyl, (3) alkyl, (4) aryl or optionally substituted arylalkyl, wherein the aryl substituents are from 1 to 3 groups independently selected from halogen, alkyl, alkoxy and hydroxy; m is 0 to 2; and v is 0 to 3; or a pharmaceutically acceptable salt thereof; or b) a combination comprising i) at least one avermectin derivative or milbemicin wherein the avermectin derivative or milbemycin is selected from the group consisting of ivermectin, abamectin, doramectin, emamectin, eprinomectin, moxidectin, selemectin and ilbecin oxime; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel; - the filler is selected from the group consisting of soy protein, corn cob and corn glutinous flour; - the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, starch, microcrystalline cellulose, mannitol, alginic acid, veegum, microcrystalline dextrose, crospovidone, bentonite and pregelatinized starch; the binder is selected from the group consisting of polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, ethylcellulose, sodium alginate, tragacanth and acacia; the humectant is selected from the group consisting of propylene glycol, glycerin, polyethylene glycol 400 and polyethylene glycol 3350; and - the granulation solvent is water, a solution of aqueous sorbitol, glycerol or propylene glycol. 3. The chewable veterinary formulation according to claim 2, characterized in that it also comprises an antioxidant and the antioxidant is alpha tocoferal, ascorbic acid, ascorbyl palmitate, sodium ascorbate, sodium metabisulfate, n-propyl gallate, hydroxy anisole butylated, butylated hydroxy toluene, monothioglycerol or a mixture of any of the foregoing.
4. 4. The chewable veterinary formulation according to claim 3, characterized in that it also comprises a dye and the dye is a dye, an aluminum lacquer, caramel, dye based on iron oxide or a mixture of any of the foregoing.
5. 5. The chewable veterinary formulation according to claim 4, characterized in that it also comprises a preservative and the preservative is a compound selected from the group consisting of benzalkanium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butylparaben, centrimide , chlorhexidine, chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, methylparaben, propylparaben, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium propionate, sorbic acid, thimerosal, propyl paraben, gamma-picolinium myristyl chloride, methyl paraben, propyl paraben, quaternary ammonium compounds and a mixture of any of the foregoing.
6. 6. The chewable veterinary formulation according to claim 2, characterized in that it also comprises a surfactant selected from the group consisting of glyceryl monooleate, polyoxyethylene, sorbitol esters of caprylate / glycerol caprate, polyvinyl alcohol, sodium lauryl sulfate, glycerides polyglycolized, propylene glycol laurate and poloxomers.
7. 7. The chewable veterinary formulation according to claim 2, characterized in that it further comprises a lubricant and the lubricant is selected from the group consisting of corn oil, polyethylene glycol, mineral oil, magnesium stearate, hydrogenated vegetable oil, peanut oil, soybean oil or castor oil.
8. 8. The chewable veterinary formulation according to claim 1, characterized in that it is coated and the coating is gelatin, glycerol behenate, cocoa butter or beeswax.
9. 9. The chewable veterinary formulation according to claim 1, characterized in that the pharmaceutically active agent comprises either: a) an effective amount of at least one nodulisporic acid derivative of the formula where Rx is selected from the group consisting of: H, CH3, CH2CH3, C (CH3) 3, CH2CH2CH3, CH2CH2OH, CH (C02CH3) CH2? H, CH2CO2CH3, CH2CH (OCH2CH3) 2, CH2CH2OCH2CH2OH, CH (CH 3) (CH 2) 3 C (CH 3) 20 H, (CH 2) 3 OH, (CH 2) 40 H, (CH 2) SOH, CH (CH2OH) CH2CH3, NHC (CH3) 3, CH2CN, (CH2) 6OH, CH2CH (OH) CH3, CH (CH2? H) CH2CH2CH3, CH2CH2SCH3, CH2CH2SCH2CH3, CH2CONH2, CH (CH3) (CH2OH) 2, CH2CH2NHCH2CH2OH, CH (CH2OH) (CH2) 3CH3, CH (CH2OCH3) CH3, (CH2) 2SH, (CH2) 4NH2, CH2CH2S02CH3, CH2CH2S (O) CH3, CH (CH (CH3) 2) CH2OH, (CH2) 3NH2, (CH2) 3N (CH2CH3) 2, (CH2) ) 3N (CH2) 2, OCH2CH3, CH2CH (OH) CH OH, 0CH3, CH2CH2 (O) CH3, CH2CH2NHC (O) CH3, CH2 (CH3) 2CH2OH, C-C3H5, C-C6-Hn, (CH2) 3OCH2CH3 , CH2CH = CH2, C (CH2CH3) (CH2OH) 2, CH2C = CH, CH2C02CH2CH3, CH2CH2F, (CH2) 30 (CH2) n CH3, CH2CH2N (CH3) 2, CH2CH20CH2CH2NH2, CH2CF3, NHCH2C02CH2CH3, CH (CH3) C02CH3, C (CH3) 2CH2C (0) CH3, CH (C02CH2CH3) 2, CH2CH3, CH (CH2CH2CH3) C02CH3, CH2CH2CH2OCH3, C (CH3) 2CH2C = CH, (CH2) 4CH3, CH (CH2CH2CH3) 2, (CH2) 2SCH3 / CH2CH2C02H, CH (CH (CH3) 2) CO2CH3, OCH2CO2H, CH (CH (CH3) 2) CH20H, CH (CH (CH3) 2) CH2OH, CH (CH3) CH2OH, CH (CH3) CH2OH, CH (CH3) 2, (CH2) CH (CH3) 2, CH (CH3) CH2CH3, CH2CH (CH3) OH, (CH2) 3CH3 / (CH2) 2OCH2CH3, 1-adamantyl, (CH2) 8CH3, CH (CH3) CH (CH3) 2, (CH2) 3NHCH3, (CH2) 2N (CH2CH3) 2, , b) a combination comprising i) at least one avermectin derivative or milbemicin wherein the avermectin or milbemycin derivative is selected from the group consisting of ivermectin, abamectin, doramectin, ememectin, eprinomectin, moxidectin, selemectin and milbemycin oxime; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel; - about 20 to about 60% of a filler selected from the group consisting of soy protein, corn cob or corn glutinous flour; about 1 to about 20% of a disintegrant; - about 0.1 to about 20% of a flavor that contains non-animal product or a flavor derived from a non-animal source; - approximately 0.5 to 10% of a binder; - about 5 to about 20% of a humectant; and - about 5 to about 20% granulation solvent, based on the total weight of the formulation.
10. 10. The chewable veterinary formulation according to claim 9, characterized in that it further comprises 0.05% to about 1.0% of an antioxidant, about 0.05 to about 1.0% of a preservative, about 0.01 to 20% of a lubricant and about 0.01 to about 10% of a dye.
11. 11. A chewable veterinary formulation, which does not contain animal products, characterized in that it comprises: an effective amount of a pharmaceutically active agent comprising either: a) t-butyl nodulisporamide; or b) a combination comprising i) at least one compound selected from the group consisting of ivermectin, eprinomectin, moxidectin or milbemycin oxime; and ii) at least one compound selected from the group consisting of pyrantel or praziquantel - a filler selected from the group consisting of soy protein, corn cob or corn glutinous flour; - disintegrant; - a flavor that contains non-animal product or a flavor derived from non-animal sources which is a flavor of American walnut smoke or a flavor of beef; - a binder; - humectant; - granulation solvent; and - optionally, an antioxidant, a pH modifier, preservative, a surfactant, a lubricant or a dye.
12. 12. The chewable veterinary formulation according to claim 11, characterized in that it comprises: - about 20 to about 60% of a filler selected from the group consisting of soy protein, corn cob or corn glutinous flour; - about 1 to about 20% of a disintegrant; - about 0.1 to about 20% of a flavor of American walnut smoke; - about 0.5 to about 10% of a binder; - about 5 to about 20% of a humectant; and about 5 to about 20% granulation solvent; and, optionally - about 0.05% to about 1.0% of an antioxidant; - about 0.05 to about 1.0% of a conservative; and - a pH modifier; - about 0.001% to about 1% of a surfactant; - about 0.01% to about 20% of a lubricant; - about 0.01 to about 10% of a colorant, based on the total weight of the formulation.
13. 13. The chewable veterinary formulation according to claim 1, characterized in that the pharmaceutically effective agent is nodulisporic acid or nodulisporic acid derivative and a second pharmaceutical agent that is different from nodulisporic acid or nodulisporic acid derivative.
14. 14. The chewable veterinary formulation according to claim 12, characterized in that the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, starches, microcrystalline cellulose, alginic acid, veegum, crospovidone, bentonite and pregelatinized starch. .
15. 15. The chewable veterinary formulation according to claim 12, characterized in that the binder is selected from the group consisting of polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, ethylcellulose, sodium alginate. , tragacanth and acacia; and the granulation solvent is water, a solution of aqueous sorbitol, glycerol or polypropylene glycerol.
16. 16. The chewable veterinary formulation according to claim 15, characterized in that it comprises an antioxidant and the antioxidant is selected group consisting of alpha tocopherol, ascorbic acid, ascorbyl palmitate, sodium ascorbate, sodium methobisulfate, n-propyl gallate, butylated hydroxy anisole, butylated hydroxy toluene or a mixture of any of the foregoing and monothioglycerol. The chewable veterinary formulation according to claim 15, characterized in that it comprises a preservative and the preservative is selected from the group consisting of the parabens, benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, cetrimide, chlorhexidine , chlorobutanol, chlorocresol, cresol, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium propionate, sorbic acid, and thimerosal, propyl paraben, gamma-picolinium chloride of myristyl, methyl paraben, propyl paraben, quaternary ammonium compounds and a mixture of any of the foregoing. 18. The chewable veterinary formulation according to claim 17, characterized in that it comprises a pH modifier and a lubricant and the pH modifier is selected from the group consisting of citric acid, fumaric acid and malic acid and the lubricant that is selected from the group consisting of polyethylene glycols, corn oil, mineral oil, hydrogenated vegetable oils, peanut oil and castor oil. The chewable veterinary formulation according to claim 8, characterized in that the pharmaceutically active combination is a combination comprising eprinomectin and either praziquantel or pyrantel. 20. A tablet, which does not contain animal products, characterized in that it comprises - an effective amount of a pharmaceutically active agent comprising either: a) at least one nodulisporic acid or nodulisporic acid derivative; b) a combination comprising i) at least one avermectin or milbemycin derivative; and ii) at least one compound selected from the group consisting of praziquantel and pyrantel; - at least one filler; - at least one flavor containing non-animal product or flavor derived from a non-animal source; - at least one lubricant; - at least one flow aid; and - optionally, at least one antioxidant, at least one pH modifier, at least one binder, at least one disintegrant, at least one surfactant, at least one preservative and at least one dye, and optionally coated with at least one coating. The tablet according to claim 20, characterized in that the filler is selected from the group consisting of anhydrous lactose, hydrated lactose, dehydrated lactose by dew, crystalline maltose and a maltodextrin; - the flow aid is selected from the group consisting of silicon dioxide, silica gel, talc, starch, calcium stearate, magnesium stearate and magnesium aluminum stearate; and the lubricant is selected from the group consisting of magnesium stearate, calcium stearate, stearic acid and wax. The tablet according to claim 21, characterized in that - the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, starch, icocrystalline cellulose, alginic acid, veegum, crospovidone, bentonite and pregelatinized starch; and the binder is selected from the group consisting of polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, sodium alginate, tragacanth and acacia. 23. The tablet according to claim 22, characterized in that it also comprises a colorant and the dye is a dye, an aluminum lacquer, caramel, dye based on iron oxide or a mixture of any of the above.