WO2014001588A1 - Antiparasitic composition for controlling and treating parasites of different animal species, characterised in that it combines moxidectin with vitamins a, d3 and e - Google Patents
Antiparasitic composition for controlling and treating parasites of different animal species, characterised in that it combines moxidectin with vitamins a, d3 and e Download PDFInfo
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- WO2014001588A1 WO2014001588A1 PCT/ES2013/000153 ES2013000153W WO2014001588A1 WO 2014001588 A1 WO2014001588 A1 WO 2014001588A1 ES 2013000153 W ES2013000153 W ES 2013000153W WO 2014001588 A1 WO2014001588 A1 WO 2014001588A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
Definitions
- Antiparasitic composition for the control and treatment of parasites of different animal species, characterized by combining Moxidectin with vitamins: A, D3 and E.
- SECTOR OF THE TECHNIQUE It is a sterile antiparasitic composition of molecules used in veterinary medicine, which combines a milbemycin, from the macrocyclic lactone family, whose name is: Moxidectin, with vitamins: A, D3 and E.
- Moxidectin Moxidectin
- This combination is characterized by the endectocidal action of Moxidectin, for the treatment and control of different parasite species, external and internal, as well as the adjuvant action of vitamins: A, D3 and E to alleviate the harmful effects of the passage of these parasites by the organism.
- This solution has application in the following animal species: horses, cattle, sheep, goats, dogs, pigs, cats and the like.
- STATE OF THE TECHNIQUE STATE OF THE TECHNIQUE:
- Antiparasitic control is today a necessary and habitual practice among animal owners, which is carried out periodically, from an early age and to the last stages of the animal's life.
- the endectocides are endoparasiticidal agents with a wide spectrum of action, both against the immature phases and against the larval phases of a large number of parasite species, in addition to presenting a wide margin of safety.
- the endectocides are effective against many parasites at much lower concentrations than most classical parasiticides.
- the endectocid is of the order of a thousand times more potent than the classic insecticide. This allows less amount of active substance to be used to obtain an equal or superior effect.
- the main routes of administration of endectocides are: injectable, oral and "pour-on".
- the endectocid designation derives from the fact that, in addition to controlling ectoparasites, they are highly effective against a myriad of endoparasites that commonly affect different animal species.
- the endectocides act on the GABA receptors of the nervous system cells: blocking the transmission of the nerve impulse, which leads to paralysis and death of the parasite.
- Avermectins are one of the families of macrocyclic lactones, isolated from the Actinomycete Streptomyces Avermitilis, which includes a series of naturally occurring or semi-synthetic compounds, which share similar structural and physical-chemical characteristics, in addition to presenting a common mechanism of action associated with a potent anthelmintic and endectocidal activity. To this group, among others, belong: Ivermectin and Doramectin.
- Milbemycins are part of the second family of macrocyclic lactones. These have a chemical structure of 16 carbons, which is closely related to the structure of the Avermectins.
- Milbemycins are compounds isolated from another species of Actinomycetes. The Milbemycin of greater scope as endectocida until the present year (2012) is Moxidectin.
- Moxidectin has a mechanism of action similar to that of Avermectins; but, nevertheless, it is singled out for having greater potency, antiparasitic activity and goodness than any known Avermectin, both for the animal, for the owner and for the environment.
- Moxidectin is a Milbemycin obtained by chemical modification of Nemadectin, a natural product of the fermentation of Streptomyces cyanogriseus noncyanogenus, characterized by being a compound of low molecular weight, more water soluble (4.3 mg / 1) than Ivermectin and Abamectin.
- Avermecins, Milbemycins and antiparasitic derivatives of both macrocyclic lactones have been described in numerous publications; see, for example, European patent applications publication no .: 0214731, 0284176, 0317148, 0308 145, 0340832, 0335541, 0350187, 0170 006, 0254583, 0334484, 0410615; British patent application numbers: 1573955, 1390336; International patent applications: WO 94/15944 and WO 95/22552, "Ivermectin and Abamectin", WC Campbell, Springer Verlag, New York (1989), and "Doramectin-a potent novel endectocide", AC Goudie et al., Vet . Parasite!. 49 (1993) 5.
- Ivermectin Ivomec ⁇
- Doramectin Dectomax T " M
- Moxidectin Cydectin T ⁇ 4
- Moxidectin The anthelmintic efficacy of Moxidectin varies according to: species, concentration, route of administration, degree of infestation and nature of the parasites, mechanism of action of the drug, pharmacokinetic properties as well as the characteristics derived from its relationship with the host animal.
- efficacy of Moxidectin against the following parasites of the following species has been demonstrated:
- Moxidectin in sheep persists preventing reinfestation for 5 weeks for parasites: Ostertagia circumcincta and Haemonchus contortus; 4 weeks for Oesophagostomum columbianum.
- this drug is effective against benzimidazole-resistant parasites, such as: Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus colubriformi and Cooperia curticei.
- Trichostrongylus axei Trichostrongylus axei.
- Nematodirus helvetianus adults.
- Oesophagostomum radiatum (adults).
- Trichostrongylus colubriformis Trichostrongylus colubriformis.
- Haematopinus euryste nus Haematopinus euryste nus.
- Moxidectin in cattle in addition, presents a persistent action protecting for a certain period of time against the re-infestation caused by the following parasites during the indicated period:
- Moxidectin is effective against Hypoderma larvae at the time of treatment, but its persistent activity against this parasite has not been evaluated. If the medicine is administered before the end of the fly season, a complementary treatment with an effective product against Hypoderma may be necessary.
- Triodontophorus serratas adults.
- Oxy ris equi adults and larval stages.
- Habronema muscae adults.
- Gasterophilus intestinalis (L2, L3).
- Trichostrongylus axei Trichostrongylus axei.
- Moxidectin in horses moreover, has a persistent activity for 2 weeks against the small estróngilos. It suppresses the excretion of eggs of small estróngilos during 90 days. It is equally effective against stages L4 in development of small strontiles of the mucosa. At 8 weeks after treatment, the early L3 larvae (hypobiotics) of small strobes are removed. CANINOS.
- Moxidectin is effective in preventing cardiopulmonary dirofilariosis (D. immitis); for the prevention of skin lesions and dermatitis caused by D. repens; for the treatment of infections caused by larvae or adults of: Ancylostomum c ninum and Uncinaria stenocephala present at the time of prevention of dirofilariosis.
- Toxocara cati L4 larvae, immature adults and adults
- the sample was determined, segmenting it into five different groups of pigs, eight per group. Stool samples were taken from all the individuals in the experiment and previous coprological examinations were performed to determine the degree and nature of the infestation existing before treatment.
- Moxidectin or other macrocyclic lactones such as: Doramectin, Ivermectin, Milbemycin oxime, Selamectin or Emodepside. At higher doses than recommended, they may have more or less severe tolerance problems. Therefore, the dosage should be done as accurately as possible.
- MDR-1 MDR-1 gene that affects the blood-brain barrier, which causes certain medications not to enter the brain of mammals. This gene encodes the P-glycoprotein that acts as a drug extractor pump, which helps limit their absorption and distribution, especially at the brain level, increasing their excretion.
- Vitamin A has a preponderant role in the proper development of every animal. In the field of parasites, it accelerates the healing of damage caused by endoparasites in the intestine walls, a fact that causes the syndrome of malabsorption and the development of normochromic and normocytic anemias; Add to these pictures the effects of external parasitosis, such as pruritus or anemia.
- This vitamin also fulfills immuno-stimulant functions, causing increased lymphocytes and killer cells, and improving the functionality of neutrophils and macrophages. There are also positive effects of this vitamin on the state of the skin and against the processes of secondary rickets.
- Vitamin A has a daily need per kilo of live weight of between 50 and 200 IU: an optimal intake of vitamin A, therefore, would be: 1,000 IU per kilo of live weight and day.
- Vitamin E synergizes the effects of vitamin A, since the immune system cells and phagocytes stimulated by vitamin A are sensitive to oxidative deterioration caused by free radicals; hence the key role of vitamin E in the prevention of peroxidation of lipids and cell membranes; Therefore, the central role of vitamin E is to help improve the immune system. From this point of view, vitamin E is considered as protective of the effects caused by vitamin A.
- Vitamin D 3 Vitamin D 3
- Vitamin D is responsible for regulating the passage of calcium to the bones. Therefore, if vitamin D is missing, this mechanism is not produced and the bones begin to weaken and curl, producing irreversible malformations. Vitamin D represents an important role in the maintenance of organs and systems through multiple functions, such as: the regulation of calcium and phosphorus levels in blood, promoting their intestinal absorption from food and reabsorption. of calcium at the renal level. It also inhibits secretions of parathyroid hormone (PTH) from the parathyroid gland and affects the immune system by its immunosuppressive role, promotion of phagocytosis and antitumor activity. Vitamin D 3 plays a secondary role, since for a climate of high solar intensity a correct production is expected by animal metabolism. It follows that the provision per kilogram of live weight is 7.3 IU.
- PTH parathyroid hormone
- the present invention relates to an antiparasitic composition for use in veterinary medicine and application in different species of homeothermal, farm and domestic animals, characterized by combining the action of a milbemycin, of the macrocyclic lactone family, whose name is : Moxidectin, against ecto and endoparasites, with the palliative and healing benefits of vitamins: A, D3 and E.
- ecto and endoparasites are common practice among animal owners. Its frequency ranges from one to several times a year; being performed, either by a single antiparasitic molecule or with any combination of them.
- edectocidal treatment effectively eliminates most of the undesirable parasites, the ravages caused by their presence in the organism cause, in addition to lesions in tissues and organs, important consequences for the health of the animal in general and for the level of production in particular, since the levels of production that these animals presented before the parasitic infestation will take a long time to recover; being, therefore, an important limiting factor in animal production.
- Moxidectin is intended for the treatment and control of endo and ectoparasites of numerous animal species.
- the vitamin A + Ü3 + E complex for its part, has a triple purpose: on the one hand it contributes to the recovery of the lesions caused by the parasites during their stay in the animal organism; on the other, it contributes to the physiological and / or productive recovery prior to parasitic infestation; and finally, it compensates the deficits that the animal will present against any of these three vitamins before treatment.
- Moxidectin has a greater spectrum of action than Avermectins (*). In cases where Ivermectin fails against resistant gastrointestinal netnatodos, Moxidectin offers some control.
- Moxidectin has a greater potency of action: with less concentration, an effect equal to or greater than the most common Avermectins is achieved: Ivermectin and Doramectin.
- Moxidectin offers a residual effect superior to that of any Avermectin (*) ⁇
- Moxidectin has a high affinity for fatty tissue, from where it is slowly released into the blood. This is the key to keeping your action longer than any Avermectin (*). Its excretion period is therefore longer, with a relatively low amount of waste excreted by feces. This property allows to eliminate the parasites that hatch from their eggs, since the eggs are not eliminated by the action of the endectocide. In addition, this persistence also has its effects on the environment, maintaining its antiparasiticidal effects for when these eggs hatch in the feces, and thus attenuate, or eliminate, the restart of the parasitic cycle. Moxidectin, therefore, represents an important advance in the sanitation of pastures and in the reduction of parasitic reinfestations.
- Moxidectin provides an average daily weight gain (GMD) of 8% greater than that of other macrocyclic lactones.
- Moxidectin has a greater capacity to delay the onset of drug resistance.
- Moxidectin has minimal impact on insects that feed on animal feces (coprophages), and that directly influence the quality and quantity in pasture production.
- Moxidectin has no harmful effects in some cases, null in others and beneficial in some: it repels water and is strongly fixed to the particles of the earth where it degrades rapidly ( half-life of approximately 60 days in the soil in the presence of oxygen). It has little chance of contaminating the waters. By joining the soil and fecal matter, it is resistant to infiltration and leaching. It is also sensitive to light, so if traces have been left on the ground or on the surface of the water, they will be rapidly degraded by sunlight (half-life of approximately 7 hours).
- Moxidectin has a lower toxicity for mammals, plants and environmental bacteria than that of any Avermectin (*). As for birds, levels in the environment after normal use do not cause intoxication, even when they consume hairs from the flanks of cattle treated with Moxidectin 'pour on'.
- Moxidectin being a non-volatile compound, represents little risk as an air pollutant.
- Moxidectin has no effects on manure beetles, or they are of minimal importance compared to Avermectins or synthetic pyrethroids, which are usually lethal to them.
- Fecal matter collected from fattening animals can be used as fertilizer, but it is possible that this material contains ecologically unacceptable levels of chemical waste, such as endectocides.
- Moxidectin the calculations show that the residues resulting from a single treatment with Moxidectin during a fattening cycle, is much lower than the lowest toxic level that would support the earthworm and the dung beetle larvae.
- the work of beetles and worms on manure is therefore very beneficial for the environment, but it also helps to eliminate the stress of animals, since manure can contain eggs from parasites that attract large numbers of insects, some of them very annoying for cattle.
- Moxidectin exhibits less resistance against parasites than classical endectocides.
- Moxidectin has a lower concentration of residues in tissues and organs after administration, in addition to being authorized, due to its lower toxicity, higher concentrations ( Figure 1. Data: 34 a Meeting of the Codex Alimentarius Commission of 201 1). Figure 1.
- Residues of Residues of Residues of Residues of Moxidectina Ivermectina: Doramectina:
- the present invention provides an antiparasitic composition that combines an endectocide, of the milbemycin family, with a vitamin complex, namely: Moxidectin + the AD3E vitamin complex. Moxidectin activity is described more particularly in US4916154 (moxidectin).
- Moxidectin like other ecto and endoparasiticidal agents, can be administered: orally in the form of food concentrates, by food additives, tablets, wafers, bowling, gels, pastes or the like, and can also be administered in parallel as: an injectable or "puor- on ".
- Vitamin D3 1.0 to 2.5 kg.
- Antioxidant X or 0.5 to 1.25 kg. • Antioxidant X a ?? 0.5 to 1, 25 kg.
- Antioxidant X or preferably is Butylated Hydroxyanisole (HAB), without restriction of any other similar and / or equivalent antioxidant.
- HAB Butylated Hydroxyanisole
- Antioxidants X a preferably is butylated Hydroxytoluene (HTB), without restriction of any other similar and / or equivalent preservative.
- HTB butylated Hydroxytoluene
- the Preferred Preservative is benzyl Alcohol, without restriction of any other similar and / or equivalent preservative.
- the Solvent of preference is coconut oil, without restriction of any other similar and / or equivalent solvent.
- Preservatives such as: ascorbic acid, 2-hydroxybiphenyl, and the like.
- Thickeners such as: ethyl cellulose, xanthan gum, carrageenan, hydroxypropylcellulose, hydroxypropyl methylcellulose, and the like.
- Surfactants for use with the antiparasitic composition of the invention include nonionic surfactants, such as: polyoxyethylene sorbitan esters, polysorbate 80, glycol polyethylene hydroxystarate 660, castor oil polyoxyl 35, and the like. Or any other conventional inert excipient, commonly used in pharmaceutical compositions for animal health.
- Oils suitable for use with the anti-parasitic composition of the invention include: propylene glycol dicaprilat / dicaprate, caprylic / capric triglyceride, and the like.
- the effective amounts of the invention may vary according to multiple circumstances: the general health of the animal, the degree of infection or infestation, the nature and / or species of parasites, the age of the animal, its immune status, the infested organs, the animal species, productive level, physiological status or others.
- the modalities of preparation are, by virtue of their kind of destination and circumstances, multiple.
- a / Receipt of raw materials verify that the products come from authorized suppliers, in optimal physical-chemical conditions, and whose containers do not present any blow or breakage. Check that the weight of each product matches that reflected in the indications of each supplier. To reflect in a document all the activity carried out, whether there are incidents or if everything is correct.
- the present invention is not limited to its application on the details and steps described herein; the same provisions and other modalities can be put into practice and carried out in a wide variety of ways, making it clear that the purpose of the example set forth is merely to demonstrate a way of manufacturing the invention, without limiting, in this way, Any other susceptible.
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Description
TÍTULO: TITLE:
"Composición antiparasitaria para el control y tratamiento de parásitos de diferentes especies animales, caracterizada por combinar Moxidectina con las vitaminas: A, D3 y E". "Antiparasitic composition for the control and treatment of parasites of different animal species, characterized by combining Moxidectin with vitamins: A, D3 and E".
SECTOR DE LA TÉCNICA: Se trata de una composición antiparasitaria estéril de moléculas de uso en medicina veterinaria, que combina una milbemicina, de la familia de las lactonas macrocíclicas, cuyo nombre es: Moxidectina, con las vitaminas: A, D3 y E. Esta combinación está caracterizada por la acción endectocida de la Moxidectina, para el tratamiento y control de diferentes especies de parásitos, externos e internos, así como por la acción coadyuvante de las vitaminas: A, D3 y E para paliar los efectos nocivos del paso de esos parásitos por el organismo. Esta solución tiene aplicación en las siguientes especies animales: equinos, bovinos, ovinos, caprinos, caninos, porcinos, felinos y similares. ESTADO DE LA TÉCNICA: SECTOR OF THE TECHNIQUE: It is a sterile antiparasitic composition of molecules used in veterinary medicine, which combines a milbemycin, from the macrocyclic lactone family, whose name is: Moxidectin, with vitamins: A, D3 and E. This combination is characterized by the endectocidal action of Moxidectin, for the treatment and control of different parasite species, external and internal, as well as the adjuvant action of vitamins: A, D3 and E to alleviate the harmful effects of the passage of these parasites by the organism. This solution has application in the following animal species: horses, cattle, sheep, goats, dogs, pigs, cats and the like. STATE OF THE TECHNIQUE:
La infección e infestación de animales homeotermos, de granja y domésticos, por parásitos de distinta naturaleza supone, además de un grave problema tanto para la sanidad animal como para la salud pública, un grave menoscabo para el desarrollo del animal afectado, así como una clara merma para su potencial productivo; estos hechos conllevan un perjuicio productivo y económico importante para los propietarios. Infection and infestation of homeothermal, farm and domestic animals, by parasites of different nature, in addition to a serious problem for both animal health and public health, is a serious impairment to the development of the affected animal, as well as a clear decrease for its productive potential; These facts entail a significant productive and economic damage for the owners.
El control antiparasitario es hoy una práctica necesaria y habitual entre los propietarios de animales, que se lleva a cabo de forma periódica, desde temprana edad y hasta los últimos estadios de la vida del animal. Antiparasitic control is today a necessary and habitual practice among animal owners, which is carried out periodically, from an early age and to the last stages of the animal's life.
Los endectocidas son agentes endoparasiticidas con un amplio espectro de acción, tanto contra las fases inmaduras como frente a las fases larvales de gran número de especies de parásitos, además de presentar un amplio margen de seguridad. Los endectocidas son eficaces contra muchos parásitos a concentraciones mucho menores que la mayoría de los parasiticidas clásicos. Así, por ejemplo, mientras que la dosis letal de un organofosforado, carbamato o piretroide contra una larva de mosca puede ser de 1 ppm. (una parte por millón= 1 mg kg), la dosis letal de un endectocida puede ser de 1 ppb. (una parte por billón= ^g kg); es decir, mil veces menor: o lo que es lo mismo, el endectocida es del orden de mil veces más potente que el insecticida clásico. Esto permite utilizar menos cantidad de sustancia activa para obtener un efecto igual o superior. Las principales vías de administración de los endectocidas son: inyectables, orales y "pour-on". La denominación endectocida deriva del hecho que, además de controlar ectoparásitos, son altamente eficaces contra una miríada de endoparásitos que afectan comúnmente a diferentes especies animales. Los endectocidas actúan sobre los receptores GABA de las células del sistema nervioso: bloqueando la transmisión del impulso nervioso, lo que conduce a la parálisis y muerte del parásito. The endectocides are endoparasiticidal agents with a wide spectrum of action, both against the immature phases and against the larval phases of a large number of parasite species, in addition to presenting a wide margin of safety. The endectocides are effective against many parasites at much lower concentrations than most classical parasiticides. Thus, for example, while the lethal dose of an organophosphate, carbamate or pyrethroid against a fly larva can be 1 ppm. (one part per million = 1 mg kg), the lethal dose of an endectocide can be 1 ppb. (one part per billion = ^ g kg); that is to say, a thousand times smaller: or what is the same, the endectocid is of the order of a thousand times more potent than the classic insecticide. This allows less amount of active substance to be used to obtain an equal or superior effect. The main routes of administration of endectocides are: injectable, oral and "pour-on". The endectocid designation derives from the fact that, in addition to controlling ectoparasites, they are highly effective against a myriad of endoparasites that commonly affect different animal species. The endectocides act on the GABA receptors of the nervous system cells: blocking the transmission of the nerve impulse, which leads to paralysis and death of the parasite.
Los endectocidas más utilizados en medicina veterinaria son las lactonas macrocíclicas, que se dividen en dos familias: Avermectinas (Ivermectina, Doramectina,...) y Milbemicinas (Moxidectina,...). The most commonly used endectocides in veterinary medicine are macrocyclic lactones, which are divided into two families: Avermectins (Ivermectin, Doramectin, ...) and Milbemycins (Moxidectin, ...).
Las Avermectinas son una de las familias de las lactonas macrocíclicas, aisladas desde el Actinomicete Streptomyces Avermitilis, que incluye una serie de compuestos de origen natural o semisintéticos, los cuales comparten características estructurales y físico-químicas similares, además de presentar un mecanismo de acción común asociado a una potente actividad antihelmíntica y endectocida. A este grupo, entre otros, pertenecen: Ivermectina y Doramectina. Avermectins are one of the families of macrocyclic lactones, isolated from the Actinomycete Streptomyces Avermitilis, which includes a series of naturally occurring or semi-synthetic compounds, which share similar structural and physical-chemical characteristics, in addition to presenting a common mechanism of action associated with a potent anthelmintic and endectocidal activity. To this group, among others, belong: Ivermectin and Doramectin.
Las Milbemicinas forman parte de la segunda familia de las lactonas macrocíclicas. Estas presentan una estructura química de 16 carbonos, la cual está estrechamente relacionada con la estructura de las Avermectinas. La principal diferencia estructural que existe entre ambas, Milbemicinas y Avermectinas, reside en la sustitución del anillo macrólido de la Avermectinas por un grupo disacárido en posición 13 en las Milbemicinas; además, las Milbemicinas son compuestos aislados de otra especie de Actinomicetes. La Milbemicina de mayor alcance como endectocida hasta el presente año (2012) es la Moxidectina. Este compuesto, la Moxidectina, presenta un mecanismo de acción similar al de las Avermectinas; pero, sin embargo, se singulariza por tener mayor potencia, actividad antiparasitaria y bondades que cualquier Avermectina conocida, tanto para el animal, como para el propietario y para el medio ambiente. Milbemycins are part of the second family of macrocyclic lactones. These have a chemical structure of 16 carbons, which is closely related to the structure of the Avermectins. The main structural difference that exists between both, Milbemycins and Avermectins, lies in the substitution of the macrolide ring of Avermectins with a disaccharide group in position 13 in the Milbemycins; In addition, Milbemycins are compounds isolated from another species of Actinomycetes. The Milbemycin of greater scope as endectocida until the present year (2012) is Moxidectin. This compound, Moxidectin, has a mechanism of action similar to that of Avermectins; but, nevertheless, it is singled out for having greater potency, antiparasitic activity and goodness than any known Avermectin, both for the animal, for the owner and for the environment.
MOXIDECTINA (Ficha técnica). MOXIDECTINE (Technical sheet).
La Moxidectina es una Milbemicina obtenida por modificación química de la Nemadectina, producto natural de la fermentación del Streptomyces cyanogriseus noncyanogenus, caracterizada por ser un compuesto de bajo peso molecular, más hidrosoluble (4,3 mg/1) que la Ivermectina y la Abamectina. Estas pequeñas diferencias físico-químicas pueden producir diferencias notables en: la flexibilidad de la formulación, la conducta farmacocinética, los mecanismos de captación de la droga por el parásito, así como en el desarrollo más tardío de resistencia y toxicidad. Moxidectin is a Milbemycin obtained by chemical modification of Nemadectin, a natural product of the fermentation of Streptomyces cyanogriseus noncyanogenus, characterized by being a compound of low molecular weight, more water soluble (4.3 mg / 1) than Ivermectin and Abamectin. These small physical-chemical differences can produce notable differences in: the flexibility of the formulation, the pharmacokinetic behavior, the mechanisms of drug uptake by the parasite, as well as in the later development of resistance and toxicity.
Aunque es una lactona macrocíclica, con una estructura química muy semejante a la Ivermectina, presenta algunas diferencias en lo relativo a su conducta metabólica y a sus características farmacocinéticas. Se metaboliza principalmente a nivel microsomal, dando origen a metabolitos hidroximetilados en C29/C30. La principal vía de eliminación es a través de las heces. Although it is a macrocyclic lactone, with a chemical structure very similar to Ivermectin, it presents some differences regarding its metabolic behavior and its pharmacokinetic characteristics. It is mainly metabolized at the microsomal level, giving rise to hydroxymethylated metabolites in C29 / C30. The main route of elimination is through feces.
Existen formulaciones de Moxidectina administradas por vía: oral, subcutánea, intramuscular y tópica "pour-on". Las Avermecíinas, las Milbemicinas y los derivados antiparasitarios de ambas lactonas macrocíclicas se han descrito en numerosas publicaciones; véanse, por ejemplo, las solicitudes de patente europea n° de publicación: 0214731, 0284176, 0317148, 0308 145, 0340832, 0335541, 0350187, 0170 006, 0254583, 0334484, 0410615; números de solicitud de patente británica: 1573955, 1390336; solicitudes de patente internacional: WO 94/15944 y WO 95/22552, "Ivermectin and Abamectin", WC Campbell, Springer Verlag, Nueva York (1989), y "Doramectin-a potent novel endectocide", AC Goudie y col., Vet. Parásito!. 49 (1993) 5. There are Moxidectin formulations administered by the oral, subcutaneous, intramuscular and topical "pour-on". Avermecins, Milbemycins and antiparasitic derivatives of both macrocyclic lactones have been described in numerous publications; see, for example, European patent applications publication no .: 0214731, 0284176, 0317148, 0308 145, 0340832, 0335541, 0350187, 0170 006, 0254583, 0334484, 0410615; British patent application numbers: 1573955, 1390336; International patent applications: WO 94/15944 and WO 95/22552, "Ivermectin and Abamectin", WC Campbell, Springer Verlag, New York (1989), and "Doramectin-a potent novel endectocide", AC Goudie et al., Vet . Parasite!. 49 (1993) 5.
Varias de estas sustancias han sido desarrolladas para la comercialización, por ejemplo: Ivermectina (Ivomec Τϊνΐ ), Doramectina (Dectomax T"M ), Moxidectina (Cydectin T\4 ). Several of these substances have been developed for commercialization, for example: Ivermectin (Ivomec Τϊνΐ), Doramectin (Dectomax T " M), Moxidectin (Cydectin T \ 4).
La eficacia antihelmíntica de la Moxidectina varía según: especie, concentración, vía de administración, grado de infestación y naturaleza de los parásitos, mecanismo de acción del fármaco, propiedades farmacocinéticas así como de las características derivadas de su relación con el animal huésped. Se ha demostrado, sin embargo, la eficacia de la Moxidectina frente a los siguientes parásitos de las siguientes especies: The anthelmintic efficacy of Moxidectin varies according to: species, concentration, route of administration, degree of infestation and nature of the parasites, mechanism of action of the drug, pharmacokinetic properties as well as the characteristics derived from its relationship with the host animal. However, the efficacy of Moxidectin against the following parasites of the following species has been demonstrated:
OVINO. OVINE.
-Nematodos gastrointestinales adultos e inmaduros: - Adult and immature gastrointestinal nematodes:
.Nematodirus spathiger (adultos). Spathiger nematodirus (adults).
.Nematodirus filicolis (adultos). Nematodirus filicolis (adults).
.Sírong loides papillosus (estadios larvarios). .Sirong loides papillosus (larval stages).
.Cooperia curticei (macmasteri) (adultos). .Cooperia curticei (macmasteri) (adults).
.Cooperia oncophora. .Cooperia oncophora.
.Cooperi punctata (adultos). .Cooperi punctata (adults).
.Oesophagostomum columbianum (L3). .Oesophagostomum columbianum (L3).
.Oesophagostomum venulosym (adultos). .Oesophagostomum venulosym (adults).
.Gaigeria pachyscelis (L3). .Gaigeria pachyscelis (L3).
.Chaberíia ovina (adultos). Sheep shark (adults).
.Trichuris ovis (adultos). .Trichuris ovis (adults).
-Nematodos adultos del tracto respiratorio: - Adult respiratory tract nematodes:
.Dictyocaul s filaría (adultos). .Dictyocaul s filaría (adults).
-Larvas de dípteros: -Diptera lanes:
.Oestr s ovis: Ll, L2, L3. .Oestr s ovis: Ll, L2, L3.
-Acaros de la sarna: -Scabies mites:
.Psoropies ovis. Ovis propopies.
La Moxidectina en ovino, además, persiste previniendo la reinfestación durante 5 semanas para los parásitos: Ostertagia circumcincta y Haemonchus contortus; 4 semanas para Oesophagostomum columbianum. Además, ensayos clínicos han mostrado que este fármaco es efectivo frente a parásitos resistentes a benzimidazoles, como son: Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus colubriformi y Cooperia curticei. In addition, Moxidectin in sheep persists preventing reinfestation for 5 weeks for parasites: Ostertagia circumcincta and Haemonchus contortus; 4 weeks for Oesophagostomum columbianum. In addition, clinical trials have shown that this drug is effective against benzimidazole-resistant parasites, such as: Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus colubriformi and Cooperia curticei.
BOVINO. BOVINE.
-Nematodos gastrointestinales adultos e inmaduros: - Adult and immature gastrointestinal nematodes:
.Haemonchus placei. .Haemonchus placei.
. Ostertagia ostertagi (incluyendo larvas inhibidas). . Ostertagia ostertagi (including inhibited larvae).
. Trichostrongylus axei. . Trichostrongylus axei.
.Nematodirus helvetianus (adultos). Nematodirus helvetianus (adults).
. Cooperia oncophora. . Cooperia oncophora.
. Cooperia punctata (adultos). . Cooperia punctata (adults).
. Cooperia sumabada. . Cooperia sumabada.
. Cooperia oncophora. . Cooperia oncophora.
. Cooperia pectinata. . Cooperia pectinata
.Haemonchus contortus. Haemonchus contortus.
. Oesophagostomum radiatum (adultos). . Oesophagostomum radiatum (adults).
.Bunostomum phlebotomum (adultos). .Bunostomum phlebotomum (adults).
. Trichostrongylus colubriformis. . Trichostrongylus colubriformis.
.Nematodirus spathiger. Spathiger nematodirus.
. Chabertia ovina (adultos). . Sheep Chabertia (adults).
. Trichuris spp. (adultos). . Trichuris spp. (Adults).
-Nematodos adultos e inmaduros del tracto respiratorio: -Adult and immature respiratory tract nematodes:
.Dictyocaulus viviparus. .Dictyocaulus viviparus.
Sarros (larvas migratorias). Sarros (migratory larvae).
.Hypoderma bovis. Hypoderma bovis
.Hypoderma lineatum. Hypoderma lineatum
-Piojos: - Lice:
.Linognathus vituli. .Linognathus vituli.
.Haematopinus euryste nus. Haematopinus euryste nus.
Solenopotes capillatus. Solenopotes capillatus.
.Bovicola bovis (ayuda en el control). Bovicola bovis (help in control).
-Ácaros de la sarna: -Scabies mites:
.Sarcoptes scabiei. Sarcoptes scabiei.
.Psoroptes ovis. .Poroptes ovis.
. Chorioptes bovis (ayuda en el control). . Chorioptes bovis (help in control).
La Moxidectina en bovino, además, presenta una acción persistente protegiendo durante cierto periodo de tiempo frente a la re-infestación causada por los siguientes parásitos durante el periodo indicado: Moxidectin in cattle, in addition, presents a persistent action protecting for a certain period of time against the re-infestation caused by the following parasites during the indicated period:
-Especies y periodo de protección: -Species and protection period:
.Dictyocaulus viviparus, 120 días. .Ostertagia ostertagi, 120 días. .Dictyocaulus viviparus, 120 days. Ostertagia ostertagi, 120 days.
.Haemonchus placei, 90 días. .Haemonchus placei, 90 days.
.Oesophagostomum radiatum, 150 días. .Oesophagostomum radiatum, 150 days.
.Trichostrongylus axei,90 días. .Trichostrongylus axei, 90 days.
.Linognathus vituli, 133 días. .Linognathus vituli, 133 days.
La Moxidectina es eficaz frente a larvas de Hypoderma en el momento del tratamiento, pero su actividad persistente frente a este parásito no ha sido evaluada. Si se administra el medicamento antes de que acabe la temporada de moscas, puede ser necesario un tratamiento complementario con un producto eficaz frente a Hypoderma. Moxidectin is effective against Hypoderma larvae at the time of treatment, but its persistent activity against this parasite has not been evaluated. If the medicine is administered before the end of the fly season, a complementary treatment with an effective product against Hypoderma may be necessary.
EQUINO. EQUINE.
-Grandes estróngilos: -Big strungles:
.Strongylus vulgaris (adultos y estadios arteriales). .Strongylus vulgaris (adults and arterial stages).
.Strongylus edentatus (adultos y estadios viscerales). .Strongylus edentatus (adults and visceral stages).
.Triodontophorus brevicauda (adultos). .Triodontophorus brevicauda (adults).
. Triodontophorus serratas (adultos). . Triodontophorus serratas (adults).
.Triodontophorus tenuicollis (adultos). .Triodontophorus tenuicollis (adults).
-Pequeños estróngilos (adultos y estadios larvarios intraluminales): -Small strontils (adults and intraluminal larval stages):
. Cyathostomum spp. . Cyathostomum spp.
. Cylicocyclus spp. . Cylicocyclus spp.
. Cylicostephanus spp. . Cylicostephanus spp.
.Cylicodontophorus spp. .Cylicodontophorus spp.
. Gyalocephalus spp. . Gyalocephalus spp.
-Ascáridos: -Ascarids:
.Parascaris equorum (adultos y estadios larvarios). -Otras especies: Parascaris equorum (adults and larval stages). -Other species:
. Oxy ris equi (adultos y estadios larvarios). . Oxy ris equi (adults and larval stages).
.Habronema muscae (adultos). Habronema muscae (adults).
.Gasterophilus intestinalis (L2, L3). Gasterophilus intestinalis (L2, L3).
.Gasterophilus nasalis (L2, L3). .Gasterophilus nasalis (L2, L3).
.Strongyloides westeri (adultos). .Strongyloides Westeri (adults).
. Trichostrongylus axei. . Trichostrongylus axei.
La Moxidectina en equino, además, tiene una actividad persistente durante 2 semanas frente a los pequeños estróngilos. Suprime la excreción de huevos de pequeños estróngilos durante 90 días. Es igualmente eficaz frente a estadios L4 en desarrollo de pequeños estróngilos de la mucosa. A las 8 semanas después del tratamiento, se eliminan las larvas L3 tempranas (hipobióticas) de pequeños estróngilos. CANINOS. Moxidectin in horses, moreover, has a persistent activity for 2 weeks against the small estróngilos. It suppresses the excretion of eggs of small estróngilos during 90 days. It is equally effective against stages L4 in development of small strontiles of the mucosa. At 8 weeks after treatment, the early L3 larvae (hypobiotics) of small strobes are removed. CANINOS.
La Moxidectina es efectiva en la prevención de dirofilariosis cardiopulmonar (D. immitis); para la prevención de las lesiones cutáneas y dermatitis causadas por D. repens; para el tratamiento de infecciones producidas por larvas o adultos de: Ancylostomum c ninum y Uncinaria stenocephala presentes en el momento de la prevención de dirofilariosis. Moxidectin is effective in preventing cardiopulmonary dirofilariosis (D. immitis); for the prevention of skin lesions and dermatitis caused by D. repens; for the treatment of infections caused by larvae or adults of: Ancylostomum c ninum and Uncinaria stenocephala present at the time of prevention of dirofilariosis.
FELINOS. FELINOS
La Moxidectina es efectiva para el tratamiento de: Moxidectin is effective for the treatment of:
. Ctenocephalides felis. . Ctenocephalides felis.
.Otodecíes cynotis. -Nematodos gastrointestinales: .You hate cynotis. - Gastrointestinal nematodes:
. Toxocara cati (larvas L4, adultos inmaduros y adultos . Toxocara cati (L4 larvae, immature adults and adults
.Ancylostoma tubaeforme (larvas L4, adultos inmaduros y adultos^. .Ancylostoma tubaeforme (L4 larvae, immature adults and adults ^.
- Filariosis: - Filariosis:
.Dirofüaria immitis. (larvas L3 y L4). .Dirofüaria immitis. (larvae L3 and L4).
Puede también usarse como coadyuvante del tratamiento de la dermatitis alérgica por picadura de pulgas. It can also be used as an adjunct to the treatment of allergic dermatitis from flea bites.
HURONES. HURONES.
La Moxidectina es efectiva para el tratamiento de: Moxidectin is effective for the treatment of:
-Pulgas: -Fleas:
.Ctenocephalides felis . Ctenocephalides felis.
La Moxidectina es efectiva para la prevención de: Moxidectin is effective for the prevention of:
-Filariosis: -Filariosis:
.Dirofüaria immitis (larvas L3 y L4). .Dirofüaria immitis (larvae L3 and L4).
VENADOS. Venados
La Moxidectina es efectiva en el tratamiento de: Moxidectin is effective in the treatment of:
.D. viviparus (adultos e inmaduros). .D. viviparus (adults and immature).
.Ostertagia (adultos y larvas). .Ostertagia (adults and larvae).
PORCINO. Basamos la efectividad de la Moxidectina en el tratamiento antiparasitario de la especie porcina sobre los estudios de Stewart y col. (27 julio de 2000/ Stewart TB, Wiles SE, Miller JE, Rulli RD/ Veterinary Parasitology 87 (1): 39-44, 1999.), en los cuales se realizaron varias pruebas experimentales para comprobar los efectos de la utilización de la Moxidectina en el tratamiento y control de parásitos en cerdos. PORCINE. We base the effectiveness of Moxidectin on the antiparasitic treatment of the swine species on the studies by Stewart et al. (July 27, 2000 / Stewart TB, Wiles SE, Miller JE, Rulli RD / Veterinary Parasitology 87 (1): 39-44, 1999.), in which several experimental tests were performed to verify the effects of the use of Moxidectin in the treatment and control of parasites in pigs.
En primer lugar, se determinó la muestra, segmentándola en cinco grupos de cerdos distintos, ocho por grupo. Se tomaron muestras de heces de todos los individuos del experimento y se realizaron exámenes coprológicos previos, para determinar el grado y naturaleza de la infestación existente antes del tratamiento. First, the sample was determined, segmenting it into five different groups of pigs, eight per group. Stool samples were taken from all the individuals in the experiment and previous coprological examinations were performed to determine the degree and nature of the infestation existing before treatment.
A todos los grupos se les indujo deliberadamente una infestación de los parásitos a controlar. 14 días después, se obtuvieron los siguientes hechos y datos en un nuevo análisis coprológico: All groups were deliberately induced an infestation of the parasites to be controlled. 14 days later, the following facts and data were obtained in a new coprological analysis:
.Efectividad de 98,3% con 1,25 mg/kg contra Ascaris suum. .Effectiveness of 98.3% with 1.25 mg / kg against Ascaris suum.
.Efectividad de 100% con 0,75 mg/kg contra Metastrongylus spp. .Effectiveness of 100% with 0.75 mg / kg against Metastrongylus spp.
.Efectividad del 100% a 1,5 mg/kg contra Oesophagostomum quadrispinulatum. .Effectiveness of 100% at 1.5 mg / kg against Oesophagostomum quadrispinulatum.
.Efectividad del 93,5% a 0,75 mg/kg contra Trichuris suis. Effectiveness of 93.5% at 0.75 mg / kg against Trichuris suis.
.Efectividad del 81 ,3 % al 100% contra O. dentatum. .Effectiveness of 81.3% to 100% against O. dentatum.
Posteriormente, los días 14 y 15, se realizaron necropsias post- ratamiento, para determinar el nivel de residuos de Moxidectina en distintos órganos y tejidos, sin encontrar ningún hallazgo significativo. INTOLERANCIAS DESCRITAS CON EL TRATAMIENTO DE MOXIDECTINA. Subsequently, on days 14 and 15, post-treatment necropsies were performed to determine the level of Moxidectin residues in different organs and tissues, without finding any significant findings. INTOLERANCES DESCRIBED WITH THE TREATMENT OF MOXIDECTINE.
Hay razas de perros que no toleran bien ni la Moxidectina ni otras lactonas macrocíclicas como: Doramectina, Ivermectina, Milbemicina oxima, Selamectina o la Emodepsida. A dosis mayores de las recomendadas, pueden presentar problemas de tolerancia más o menos graves. Por ello, la dosificación debe hacerse lo más exactamente posible. Se trata, sobre todo, de los Collies y de razas próximas a estas, que tienen una mutación en e] gen MDR-1 que afecta a la barrera hematoencefálica, que provoca que ciertos medicamentos no entren en el cerebro de los mamíferos. Dicho gen codifica la glicoproteína-P que actúa como bomba extractara de drogas, la cual ayuda a limitar la absorción y distribución de estas, especialmente a nivel del cerebro, aumentando la excreción de las mismas. Además de los Collies, otras razas también han mostrado problemas similares: Bobtail, Border Collie, Collie Barbudo, McNab, Galgo Silken, Galgo Whippet, Pastor Australiano, Pastor Blanco Suizo, Pastor Inglés, Pastor Shetland, Waller, si bien la mutación defectuosa descrita, no se ha confirmado aún en todas estas razas There are breeds of dogs that do not tolerate either Moxidectin or other macrocyclic lactones such as: Doramectin, Ivermectin, Milbemycin oxime, Selamectin or Emodepside. At higher doses than recommended, they may have more or less severe tolerance problems. Therefore, the dosage should be done as accurately as possible. These are, above all, Collies and races close to them, which have a mutation in the MDR-1 gene that affects the blood-brain barrier, which causes certain medications not to enter the brain of mammals. This gene encodes the P-glycoprotein that acts as a drug extractor pump, which helps limit their absorption and distribution, especially at the brain level, increasing their excretion. In addition to the Collies, other races have also shown similar problems: Bobtail, Border Collie, Bearded Collie, McNab, Silken Greyhound, Whippet Greyhound, Australian Shepherd, Swiss White Shepherd, English Shepherd, Shetland Shepherd, Waller, although the defective mutation described , has not yet been confirmed in all these races
COMPLEJO VITAMÍNICO ADaE ADAE VITAMIN COMPLEX
Vitamina A. Vitamin A.
La vitamina A tiene un ro] preponderante en el correcto desarrollo de todo animal. En el ámbito de los parásitos, acelera la curación del daño provocado por endoparásitos en las paredes del intestino, hecho que provoca el síndrome de mala absorción y el desarrollo de anemias normocrómica y normocítica; súmese a estos cuadros los efectos de las parasitosis extemas, como prurito o anemia. Esta vitamina cumple, además, funciones inmuno-estimulantes, provocando aumento de linfocitos y células killer, y mejorando la funcionalidad de neutrófílos y macrófagos. También hay efectos positivos de esta vitamina en el estado de la piel y frente a los procesos de raquitismo secundario. Vitamin A has a preponderant role in the proper development of every animal. In the field of parasites, it accelerates the healing of damage caused by endoparasites in the intestine walls, a fact that causes the syndrome of malabsorption and the development of normochromic and normocytic anemias; Add to these pictures the effects of external parasitosis, such as pruritus or anemia. This vitamin also fulfills immuno-stimulant functions, causing increased lymphocytes and killer cells, and improving the functionality of neutrophils and macrophages. There are also positive effects of this vitamin on the state of the skin and against the processes of secondary rickets.
Se ha demostrado la eficacia de esta vitamina en terneros neonatos; los cuales, por insuficiencia o deficiencia en el calostro materno, no han desarrollado adecuadamente su sistema inmune y su sistema epitelial. The efficacy of this vitamin has been demonstrated in newborn calves; which, due to insufficiency or deficiency in the maternal colostrum, have not adequately developed their immune system and epithelial system.
Otro hecho destacable es que la forma farmacéutica de la vitamina A es mejor aprovechada (biodisponibilidad) que el caroteno natural (pro vitamina A) contenido en las plantas; a lo que hay que añadir la ventaja que ofrece la estabilidad de la misma en la formulación farmacéutica. Another remarkable fact is that the pharmaceutical form of vitamin A is better used (bioavailability) than the natural carotene (pro vitamin A) contained in plants; To which we must add the advantage offered by its stability in the pharmaceutical formulation.
La vitamina A presenta una necesidad diaria por kilo de peso vivo de entre 50 y 200 UI: un aporte óptimo de vitamina A, por tanto, sería: 1.000 UI por kilo de peso vivo y día. Vitamin A has a daily need per kilo of live weight of between 50 and 200 IU: an optimal intake of vitamin A, therefore, would be: 1,000 IU per kilo of live weight and day.
Vitamina E. Vitamin E.
La vitamina E sinergiza los efectos de la vitamina A, por cuanto las células del sistema inmune y los fagocitos estimulados por la vitamina A son sensibles al deterioro oxidativo causado por los radicales libres; de ahí el papel clave de la vitamina E en la prevención de la peroxidación de lípidos y membranas celulares; por ello, el papel central de la vitamina E es coadyuvar en la mejora del sistema inmune. Desde esta óptica se considera a la vitamina E como protectora de los efectos provocados por la vitamina A. Vitamin E synergizes the effects of vitamin A, since the immune system cells and phagocytes stimulated by vitamin A are sensitive to oxidative deterioration caused by free radicals; hence the key role of vitamin E in the prevention of peroxidation of lipids and cell membranes; Therefore, the central role of vitamin E is to help improve the immune system. From this point of view, vitamin E is considered as protective of the effects caused by vitamin A.
Vitamina D3. Vitamin D 3 .
La vitamina D es la encargada de regular el paso de calcio a los huesos. Por ello si la vitamina D falta, no se produce este mecanismo y los huesos empiezan a debilitarse y a curvarse produciéndose malformaciones irreversibles. La Vitamina D representa un papel importante en el mantenimiento de órganos y sistemas a través de múltiples funciones, tales como: la regulación de los niveles de calcio y fósforo en sangre, promoviendo la absorción intestinal de los mismos a partir de los alimentos y la reabsorción de calcio a nivel renal. También inhibe las secreciones de la hormona paratiroidea (PTH) desde la glándula paratiroides y afecta al sistema inmune por su rol inmunosupresor, promoción de fagocitosis y actividad antitumoral. La vitamina D3 cumple un rol secundario, puesto que para un clima de alta intensidad solar se espera una correcta producción por el metabolismo animal. De ahí deriva que la provisión por kilo de peso vivo sea 7,3 UI. Vitamin D is responsible for regulating the passage of calcium to the bones. Therefore, if vitamin D is missing, this mechanism is not produced and the bones begin to weaken and curl, producing irreversible malformations. Vitamin D represents an important role in the maintenance of organs and systems through multiple functions, such as: the regulation of calcium and phosphorus levels in blood, promoting their intestinal absorption from food and reabsorption. of calcium at the renal level. It also inhibits secretions of parathyroid hormone (PTH) from the parathyroid gland and affects the immune system by its immunosuppressive role, promotion of phagocytosis and antitumor activity. Vitamin D 3 plays a secondary role, since for a climate of high solar intensity a correct production is expected by animal metabolism. It follows that the provision per kilogram of live weight is 7.3 IU.
-La combinación de las vitaminas: A, D3 y E con la Moxidectina, provoca un shock antiparasitario/vitamínico que potencia, de una forma singular y más efectiva el tratamiento antiparasitario, ya que al efecto normalmente esperado por la acción endectocida de la Moxidectina, se le unen las bondades de una provisión de vitaminas que hacen frente a los estragos causados, en tejidos y órganos, por el paso de estos parásitos por el organismo, suponiendo, en su conjunto, una gran ventaja con respecto a los tratamientos antiparasitarios clásicos. -The combination of vitamins: A, D3 and E with Moxidectin, causes an antiparasitic / vitamin shock that enhances, in a unique and more effective way the antiparasitic treatment, since to the effect normally expected by the endectocidal action of Moxidectin, the benefits of a supply of vitamins that cope with the damage caused, in tissues and organs, by the passage of these parasites through the body, are joined assuming, as a whole, a great advantage over classic antiparasitic treatments.
EXPLICACIÓN: La presente invención se refiere a una composición antiparasitaria de uso en medicina veterinaria y aplicación en diferentes especies de animales homeotermos, de granja y domésticos, caracterizada por combinar la acción de una milbemicina, de la familia de las lactonas macrocícliclas, cuyo nombre es: Moxidectina, frente a ecto y endoparásitos, con las bondades paliativas y curativas de las vitaminas: A, D3 y E. EXPLANATION: The present invention relates to an antiparasitic composition for use in veterinary medicine and application in different species of homeothermal, farm and domestic animals, characterized by combining the action of a milbemycin, of the macrocyclic lactone family, whose name is : Moxidectin, against ecto and endoparasites, with the palliative and healing benefits of vitamins: A, D3 and E.
La infección e infestación de animales homeotermos, de granja o de compañía, por endo y ectoparásitos genera, además de importantes pérdidas en términos económicos, un riesgo potencial para la sanidad animal en general y para la salud pública en particular, toda vez que algunos de estos parásitos presentan ciclos vitales con etapas dentro de un animal de producción y otras dentro de un ser humano. Infection and infestation of homeothermal, farm or companion animals, by endo and ectoparasites generates, in addition to significant losses in economic terms, a potential risk for animal health in general and for public health in particular, since some of These parasites have life cycles with stages within a production animal and others within a human being.
El tratamiento y control de ecto y endoparásitos es una práctica habitual entre los propietarios de animales. Su frecuencia oscila de una a varias veces al año; realizándose, bien mediante una sola molécula antiparasitaria bien con alguna combinación de ellas. Sin embargo, aunque el tratamiento edectocida elimina de forma eficaz la mayor parte de los parásitos indeseables, los estragos causados por la presencia de estos en el organismo causa, además de lesiones en tejidos y órganos, importantes consecuencias para la salud del animal en general y para el nivel de producción en particular, ya que los niveles de producción que presentaban estos animales antes de la infestación parasitaria, tardarán mucho tiempo en recuperarse; siendo, por tanto, un importante factor limitante en la producción de animal. The treatment and control of ecto and endoparasites is a common practice among animal owners. Its frequency ranges from one to several times a year; being performed, either by a single antiparasitic molecule or with any combination of them. However, although edectocidal treatment effectively eliminates most of the undesirable parasites, the ravages caused by their presence in the organism cause, in addition to lesions in tissues and organs, important consequences for the health of the animal in general and for the level of production in particular, since the levels of production that these animals presented before the parasitic infestation will take a long time to recover; being, therefore, an important limiting factor in animal production.
La Moxidectina tiene como finalidad el tratamiento y control de endo y ectoparásitos de numerosas especies anímales. El complejo de vitaminas A+Ü3+E presenta, por su parte, una triple finalidad: por un lado contribuye a la recuperación de las lesiones que han provocado los parásitos durante su estancia en el organismo animal; por otro, contribuye a la recuperación fisiológica y/o productiva previa a la infestación parasitaria; y por último, compensa los déficits que presentara el animal frente a cualquiera de estas tres vitaminas antes del tratamiento. Moxidectin is intended for the treatment and control of endo and ectoparasites of numerous animal species. The vitamin A + Ü3 + E complex, for its part, has a triple purpose: on the one hand it contributes to the recovery of the lesions caused by the parasites during their stay in the animal organism; on the other, it contributes to the physiological and / or productive recovery prior to parasitic infestation; and finally, it compensates the deficits that the animal will present against any of these three vitamins before treatment.
Existen patentes que combinan Avermectinas con el complejo vitamínico AD3E, como son: la "Doramectina+AD3E" y la "Ivermectina+AD3E"; véase, por ejemplo, la patente brasileña: P05010 1-9A. La composición an ti parasitaria reivindicada en esta invención, que combina Moxidectina con las vitaminas: A, D3 y E, presenta, sin embargo, numerosas ventajas frente a la combinaciones ya expuestas: Avermectinas + el complejo vitamínico: There are patents that combine Avermectins with the AD3E vitamin complex, such as: "Doramectin + AD3E" and "Ivermectin + AD3E"; see, for example, the Brazilian patent: P05010 1-9A. The parasitic composition claimed in this invention, which combines Moxidectin with vitamins: A, D3 and E, has, however, numerous advantages. against the combinations already exposed: Avermectins + the vitamin complex:
Las ventajas de esta nueva combinación se asientan tanto en la naturaleza y propiedades de la Moxidectina, idénticas en unos casos y superiores en otros al de cualquier Avermectina conocida (Ivermectina, Doramectina), como en la incorporación del complejo vitamínico: A+D3+E. The advantages of this new combination are based both on the nature and properties of Moxidectin, identical in some cases and superior in others to that of any known Avermectin (Ivermectin, Doramectin), as well as the incorporation of the vitamin complex: A + D3 + E .
Diferencias de la Moxidectina frente a cualquier Avermectina conocida(*): Differences of Moxidectin versus any known Avermectin (*):
1. La Moxidectina tiene mayor espectro de acción que las Avermectinas (*). En los casos en donde falla la Ivermectina contra los netnatodos gastrointestinales resistentes, la Moxidectina ofrece cierto control. 1. Moxidectin has a greater spectrum of action than Avermectins (*). In cases where Ivermectin fails against resistant gastrointestinal netnatodos, Moxidectin offers some control.
2. La Moxidectina tiene mayor potencia de acción: con menos concentración, se logra un efecto igual o superior a las Avermectinas más comunes: Ivermectina y Doramectina. 2. Moxidectin has a greater potency of action: with less concentration, an effect equal to or greater than the most common Avermectins is achieved: Ivermectin and Doramectin.
3. La Moxidectina ofrece un efecto residual superior al de cualquier Avermectina (*)· 3. Moxidectin offers a residual effect superior to that of any Avermectin (*) ·
4. La Moxidectina tiene elevada afinidad por el tejido graso, desde donde se va liberando lentamente hacia la sangre. Esta es la clave de que su acción se mantenga más tiempo que cualquier Avermectina (*). Su periodo de excreción es, por tanto, más prolongado, con una cantidad de residuos excretados por las heces relativamente baja. Esta propiedad permite ir eliminando los parásitos que eclosionan de sus huevos, toda vez que los huevos no son eliminados por la acción del endectocida. Además, esa persistencia tiene también sus efectos sobre el medio ambiente, manteniendo sus efectos antiparasiticidas para cuando estos huevos eclosionen en las heces, y así atenuar, o eliminar, el reinicio del ciclo parasitario. La Moxidectina, por tanto, supone un avance importante en el saneamiento de pastos y en la disminución de reinfestaciones parasitarias. 4. Moxidectin has a high affinity for fatty tissue, from where it is slowly released into the blood. This is the key to keeping your action longer than any Avermectin (*). Its excretion period is therefore longer, with a relatively low amount of waste excreted by feces. This property allows to eliminate the parasites that hatch from their eggs, since the eggs are not eliminated by the action of the endectocide. In addition, this persistence also has its effects on the environment, maintaining its antiparasiticidal effects for when these eggs hatch in the feces, and thus attenuate, or eliminate, the restart of the parasitic cycle. Moxidectin, therefore, represents an important advance in the sanitation of pastures and in the reduction of parasitic reinfestations.
5. La Moxidectina proporciona una ganancia media diaria de peso (GMD) superior en un 8% a la del resto de lactonas macrocíclicas. 5. Moxidectin provides an average daily weight gain (GMD) of 8% greater than that of other macrocyclic lactones.
6. La Moxidectina tiene mayor capacidad para retrasar la aparición de resistencias farmacológicas. 6. Moxidectin has a greater capacity to delay the onset of drug resistance.
7. La Moxidectina tiene mínimo impacto sobre los insectos que se alimentan de las heces de los animales (coprófagos), y que influyen directamente sobre la calidad y cantidad en la producción de los pastos. 7. Moxidectin has minimal impact on insects that feed on animal feces (coprophages), and that directly influence the quality and quantity in pasture production.
8. Donde las Avermectinas presentan un riesgo para el medio ambiente, la Moxidectina presente efectos nocivos nimios en unos casos, nulos en otros y beneficiosos en algunos: repele el agua y se fija fuertemente a las partículas de la tierra donde se degrada con rapidez (vida media de aproximadamente 60 días en el suelo en presencia de oxígeno). Tiene pocas posibilidades de contaminar las aguas. Al unirse al suelo y a la materia fecal, es resistente a la infiltración y la lixiviación. También es sensible a la luz, por lo que si han quedado trazas en la tierra o en la superficie del agua, serán degradadas rápidamente por la luz del sol (vida media de aproximadamente 7 horas). 8. Where Avermectins present a risk to the environment, Moxidectin has no harmful effects in some cases, null in others and beneficial in some: it repels water and is strongly fixed to the particles of the earth where it degrades rapidly ( half-life of approximately 60 days in the soil in the presence of oxygen). It has little chance of contaminating the waters. By joining the soil and fecal matter, it is resistant to infiltration and leaching. It is also sensitive to light, so if traces have been left on the ground or on the surface of the water, they will be rapidly degraded by sunlight (half-life of approximately 7 hours).
9. La Moxidectina presenta una toxicidad más baja para los mamíferos, las plantas y las bacterias ambientales que la de cualquier Avermectina (*). En cuanto a las aves, los niveles en el ambiente después de su uso normal no causan intoxicación, ni siquiera cuando estas consumen pelos de los flancos de los bovinos tratados con Moxidectina 'pour on'. 9. Moxidectin has a lower toxicity for mammals, plants and environmental bacteria than that of any Avermectin (*). As for birds, levels in the environment after normal use do not cause intoxication, even when they consume hairs from the flanks of cattle treated with Moxidectin 'pour on'.
10. La Moxidectina, al ser un compuesto no-volátil, representa poco riesgo como contaminante atmosférico. 10. Moxidectin, being a non-volatile compound, represents little risk as an air pollutant.
1 1. Existen muchas especies en el mundo de escarabajos peloteros que viven en los excrementos o en sus alrededores. Estos insectos tienen una función esencial para la agricultura y para el medio ambiente como limpiador del suelo, al eliminar los excesos de material fecal de los pastos. Son de gran ayuda para la fertilidad y la palatabilidad del pasto y reducen las oportunidades de reproducción de insectos que causan estrés a los animales. Sin la presencia del escarabajo, el estiércol persiste casi el doble de tiempo en el pasto. Los escarabajos peloteros rompen las fibras de la bola de estiércol y reducen su estructura compacta favoreciendo la ventilación. Excavan un túnel en el suelo e introducen el estiércol a unos 15 cm de profundidad, favoreciendo el crecimiento de bacterias. Estas bacterias transforman el amonio en nitrato: fertilizante natural de la hierba y las plantas. Además preparan el estiércol para que sea atacado por las lombrices de tierra; por tanto, los escarabajos peloteros intervienen activamente en la destrucción del estiércol y en la aparición de nitrato. A nivel de uso recomendado, la Moxidectina no tiene efectos sobre los escarabajos del estiércol, o son de importancia mínima comparados con las Avermectinas o los piretroides sintéticos, que suelen ser letales para ellos. 1 1. There are many species in the world of dung beetles that live in or droppings. These insects have an essential function for agriculture and for the environment as a soil cleaner, by eliminating excess fecal material from pastures. They are of great help for the fertility and palatability of grass and reduce the opportunities for reproduction of insects that cause stress to animals. Without the presence of the beetle, manure persists almost twice as long in the grass. The dung beetles break the fibers of the dung ball and reduce its compact structure favoring ventilation. They dig a tunnel in the ground and introduce the manure to about 15 cm deep, favoring the growth of bacteria. These bacteria transform ammonium into nitrate: a natural fertilizer for herbs and plants. They also prepare manure to be attacked by earthworms; therefore, dung beetles are actively involved in the destruction of manure and the appearance of nitrate. At the recommended level of use, Moxidectin has no effects on manure beetles, or they are of minimal importance compared to Avermectins or synthetic pyrethroids, which are usually lethal to them.
12. El nivel de Moxidectina que se excreta en las heces es muy bajo, y se reduce todavía más en el momento en el que las lombrices entran en contacto con la materia fecal. En un estudio realizado en Australia, se demostró que este principio activo no tiene efectos adversos sobre la lombriz de tierra, que también contribuye de forma efectiva a la eliminación del estiércol. 12. The level of Moxidectin that is excreted in the feces is very low, and it is reduced even more at the time when the worms come into contact with the stool. In a study conducted in Australia, it was shown that this active substance has no adverse effects on the earthworm, which also contributes effectively to the elimination of manure.
13. La materia fecal recogida de los animales de engorde se puede usar como fertilizante, pero cabe la posibilidad de que esta materia contenga niveles ecológicamente inaceptables de residuos químicos, como los de endectocidas. En el caso de la Moxidectina, los cálculos demuestran que los residuos resultantes de un solo tratamiento con Moxidectina durante un ciclo de engorde, es muy inferior al nivel tóxico más bajo que soportaría la lombriz de tierra y las larvas de escarabajos del estiércol. La labor de escarabajos y lombrices sobre el estiércol es, por tanto, muy beneficiosa para el medio ambiente, pero también contribuye a eliminar el estrés de los animales, toda vez que el estiércol puede contener huevos de parásitos que atraen a gran cantidad de insectos, algunos de ellos muy molestos para el ganado. 13. Fecal matter collected from fattening animals can be used as fertilizer, but it is possible that this material contains ecologically unacceptable levels of chemical waste, such as endectocides. In the case of Moxidectin, the calculations show that the residues resulting from a single treatment with Moxidectin during a fattening cycle, is much lower than the lowest toxic level that would support the earthworm and the dung beetle larvae. The work of beetles and worms on manure is therefore very beneficial for the environment, but it also helps to eliminate the stress of animals, since manure can contain eggs from parasites that attract large numbers of insects, some of them very annoying for cattle.
14. La Moxidectina presenta menor resistencia frente a los parásitos que los endectocidas clásicos. 14. Moxidectin exhibits less resistance against parasites than classical endectocides.
15. La Moxidectina presenta menor concentración de residuos en tejidos y órganos tras su administración, además de tener autorizada, por su menor toxicidad, concentraciones superiores (Figura 1. Datos: 34a Reunión de la Comisión del Codex Alimentarius de 201 1). Figura 1. 15. Moxidectin has a lower concentration of residues in tissues and organs after administration, in addition to being authorized, due to its lower toxicity, higher concentrations (Figure 1. Data: 34 a Meeting of the Codex Alimentarius Commission of 201 1). Figure 1.
Residuos de Residuos de Residuos de Moxidectina: Ivermectina: Doramectina: Residues of Residues of Residues of Moxidectina: Ivermectina: Doramectina:
Vacuno/Vaca Grasa 500 ;>¾ VacunoAfaca Grasa 40 μ k Vacuno/Vaca Grasa 150 μί>Λ¾ Vacuno Vaca Hígado 100 g/kg VacunoA^aca Hígado 100 μ í'k Vacuno/Vaca Hígado 100 ¾/ϊ¾ Vacuno Vaca Músculo 20 ^, Cerdo Grasa 20 μg l g Vacuno/Vaca Músculo 10 μ /kg Vacuno/Vaca Riñon 50 g/k Cerdo Hígado 15 kg VacunoAíaca Riñón 30 μg k Oveja Grasa 500 Oveja Grasa 20 μg kg Cerdo Grasa 150 μg kg Oveja Hígado 100 μξ ίξ Oveja Hígado 15 g/kg Cerdo Hígado 100 μ kg Oveja Músculo 50 μg kg Cerdo Músculo 5 μ¾ kg Oveja Riñon 50 μ kg Cerdo Riñon 30 μg kg Ciervo Grasa 500 μ;>/]¾ Beef / Fatty Cow 500;> ¾ BeefFatty Fat 40 μ k Beef / Fatty Cow 150 μί> Λ¾ Beef Beef Liver 100 g / kg Beef A ^ here Liver Liver 100 μ í'k Beef / Liver Cow 100 ¾ / ϊ¾ Beef Cow Muscle 20 ^ pork fat 20 g lg Beef / cow Muscle 10 μ / kg Beef / cow Kidney 50 g / k pig liver 15kg VacunoA í aca Kidney 30 .mu.g k Sheep Fat 500 Sheep Fat 20 .mu.g kg Pork Fat 150 mg kg Sheep liver 100 μξ ίξ Sheep Liver 15 g / kg Pig Liver 100 μ kg Sheep Muscle 50 μg kg Pig Muscle 5 μ¾ kg Sheep Kidney 50 μ kg Pig Kidney 30 μg kg Fat Deer 500 μ;> /] ¾
Ciervo Hígado 100 μξ/ g Liver deer 100 μξ / g
Ciervo Músculo 20 μg/kg Deer Muscle 20 μg / kg
Ciervo Riftón 50 μg kg Riftón deer 50 μg kg
EXPOSICIÓN DETALLADA PE REALIZACIÓN. La presente invención proporciona una composición antiparasitaria que combina un endectocida, de la familia de las milbemicinas, con un complejo vitamínico, concretamente: Moxidectina + el complejo vitamínico AD3E. La actividad de la Moxidectina se describe más particularmente en la Patente US4916154 (moxidectina). DETAILED EXHIBITION PE REALIZATION. The present invention provides an antiparasitic composition that combines an endectocide, of the milbemycin family, with a vitamin complex, namely: Moxidectin + the AD3E vitamin complex. Moxidectin activity is described more particularly in US4916154 (moxidectin).
La Moxidectina, como otros agentes ecto y endoparasiticidas, puede administrarse: oralmente en forma de concentrados de alimentos, mediante aditivos alimentarios, tabletas, obleas, bolos, geles, pastas o similares, y también pueden administrarse paralelamente como: un inyectable o "puor-on". Moxidectin, like other ecto and endoparasiticidal agents, can be administered: orally in the form of food concentrates, by food additives, tablets, wafers, bowling, gels, pastes or the like, and can also be administered in parallel as: an injectable or "puor- on ".
La presente invención se ilustra adicionalmente mediante el siguiente ejemplo, el cual no pretende ser limitativo, en ningún caso, de su alcance. Ejemplo: The present invention is further illustrated by the following example, which is not intended to limit, in any case, its scope. Example:
-Preparación de 1000 litros de combinación de Moxidectina con el complejo vitamínico AD3E en solución estéril inyectable. -Preparation of 1000 liters of combination of Moxidectin with the AD3E vitamin complex in sterile injectable solution.
Componentes básicos: Basic Components:
• Moxidectina 5,0 a 12,0 kg. • Moxidectin 5.0 to 12.0 kg.
· Vitamina A Palmitato 100,0 a 160,0 kg. Vitamin A Palmitate 100.0 to 160.0 kg.
• Vitamina D3 1 ,0 a 2,5 kg. • Vitamin D3 1.0 to 2.5 kg.
• Vitamina E 40,0 a 90,0 kg. • Vitamin E 40.0 to 90.0 kg.
• Antioxidante Xo 0,5 a 1,25 kg. • Antioxidante Xa .....0,5 a 1 ,25 kg. • Antioxidant X or 0.5 to 1.25 kg. • Antioxidant X a ..... 0.5 to 1, 25 kg.
■ Conservantes.... ...80,0 a 120,0 litros. ■ Preservatives .... ... 80.0 to 120.0 liters.
• Solvente oleoso. 1000,0 litros. • Oily solvent. 1000.0 liters
Las necesidades cuantitativas para una formulación inyectable de 100 mi. son: Quantitative needs for an injectable formulation of 100 ml. They are:
• Moxidectina 1 , 180 g. • Moxidectin 1, 180 g.
• Vitamina A Palmitato (24.850.000 UI) 14,910 g. • Vitamin A Palmitate (24,850,000 IU) 14,910 g.
• Vitamina Ü3 (9.400.000 UI) 0,235 g. • Vitamin Ü3 (9,400,000 IU) 0.235 g.
• Vitamina E (6.680 UI) 6,68 g. • Vitamin E (6,680 IU) 6.68 g.
• Antioxidante Xo 0,08 g. • Antioxidant X or 0.08 g.
• Antioxidante Xa 0,08 g. • Antioxidant X at 0.08 g.
• Conservante Y 10,0 mi. • Preservative and 10.0 mi.
• Solvente oleoso 100,0 mi. • 100.0 ml oily solvent.
El Antioxidante Xo de preferencia es el Hidroxianisol butilado (HAB), sin restricción de cualquier otro antioxidante similar y/o equivalente. Antioxidant X or preferably is Butylated Hydroxyanisole (HAB), without restriction of any other similar and / or equivalent antioxidant.
El Antioxidantes Xa de preferencia es el Hidroxitolueno butilado (HTB), sin restricción de cualquier otro conservante similar y/o equivalente. Antioxidants X a preferably is butylated Hydroxytoluene (HTB), without restriction of any other similar and / or equivalent preservative.
El Conservante de preferencia es el Alcohol bencílico, sin restricción de cualquier otro conservante similar y/o equivalente. The Preferred Preservative is benzyl Alcohol, without restriction of any other similar and / or equivalent preservative.
El Solvente de preferencia es el aceite de coco, sin restricción de cualquier otro solvente similar y/o equivalente. The Solvent of preference is coconut oil, without restriction of any other similar and / or equivalent solvent.
Componentes opcionales: Optional components:
Los conservantes, tales como: el ácido ascórbico, 2-hidroxibifenilo, y similares. Preservatives, such as: ascorbic acid, 2-hydroxybiphenyl, and the like.
Los espesantes, tales como: celulosa de etilo, goma xantana, carrageninan, hidroxipropilcelulosa, hidroxipropilmetilcelulosa, y similares. Los tensoactivos para su uso con la composición antiparasitaria de la invención, incluyen tensoactivos no- iónicos, tales como: los ésteres de sorbitan de polioxietileno, el polisorbato 80, hidroxiestarato de polietileno glico 660, aceite de ricino polioxil 35, y similares. O cualquier otro excipiente inerte convencional, usado comúnmente en composiciones farmacéuticas para la salud animal. Thickeners, such as: ethyl cellulose, xanthan gum, carrageenan, hydroxypropylcellulose, hydroxypropyl methylcellulose, and the like. Surfactants for use with the antiparasitic composition of the invention include nonionic surfactants, such as: polyoxyethylene sorbitan esters, polysorbate 80, glycol polyethylene hydroxystarate 660, castor oil polyoxyl 35, and the like. Or any other conventional inert excipient, commonly used in pharmaceutical compositions for animal health.
Los aceites adecuados para su uso con la composición antjparasitaria de la invención incluyen: dicaprilato/dicaprato de propilenglicol, triglicérido caprilico/cáprico, y similares. Oils suitable for use with the anti-parasitic composition of the invention include: propylene glycol dicaprilat / dicaprate, caprylic / capric triglyceride, and the like.
Las cantidades efectivas de la invención pueden variar de conformidad con múltiples circunstancias: la salud general del animal, el grado de infección o infestación, la naturaleza y/o especie de parásitos, la edad del animal, su estado inmunológico, los órganos infestados, la especie animal, el nivel productivo, el estado fisiológico u otros. Las modalidades de preparación son, en virtud de su especie de destino y circunstancias, múltiples. The effective amounts of the invention may vary according to multiple circumstances: the general health of the animal, the degree of infection or infestation, the nature and / or species of parasites, the age of the animal, its immune status, the infested organs, the animal species, productive level, physiological status or others. The modalities of preparation are, by virtue of their kind of destination and circumstances, multiple.
Se ilustra, a continuación, un ejemplo de una preparación inyectable, la cual ilustra, sin limitar el alcance o los principios subyacentes de la invención. De hecho, diversas modificaciones de la invención, además de la mostrada y descrita en el siguiente ejemplo, serán evidentes para aquellos expertos en la técnica, a partir del ejemplo y descripción siguiente. Tales modificaciones se pretende que caigan dentro del alcance de la presente invención y las reivindicaciones anexas. An example of an injectable preparation is illustrated below, which illustrates, without limiting the scope or underlying principles of the invention. In fact, various modifications of the invention, in addition to that shown and described in the following example, will be apparent to those skilled in the art, from the following example and description. Such modifications are intended to fall within the scope of the present invention and the appended claims.
Etapas: Stages:
a/ Recepción de materias primas: verificar que los productos provienen de proveedores autorizados, en óptimas condiciones físico-químicas, y cuyos envases no presenten ningún golpe o rotura. Comprobar que el peso de cada producto coincide con el reflejado en las indicaciones de cada proveedor. Reflejar en un documento toda la actividad realizada, tanto si existen incidencias como si todo es correcto. b/ Verificar el estado funcional y la asepsia de todos los equipos precisos para la fabricación de la invención según este ejemplo. Reflejar la acción documentalmente. c/ Se precisan tres reactores de acero inoxidable: uno de 100 litros, otro de 500 litros y un último de 1000 litros. En el reactor de 100 litros adicionar, en condiciones de asepsia, la mitad del conservante Y y agitar; sin parar de agitar, introducir poco a poco 1 1 ,8 kilos de Moxidectina hasta la completa solubilización de la mezcla. Reflejar la acción documentalmente. a / Receipt of raw materials: verify that the products come from authorized suppliers, in optimal physical-chemical conditions, and whose containers do not present any blow or breakage. Check that the weight of each product matches that reflected in the indications of each supplier. To reflect in a document all the activity carried out, whether there are incidents or if everything is correct. b / Verify the functional status and asepsis of all the equipment required for the manufacture of the invention according to this example. Reflect the action documentary. c / Three stainless steel reactors are required: one of 100 liters, another of 500 liters and one of 1000 liters. In the 100 liter reactor add, under aseptic conditions, half of the preservative Y and stir; Without stopping stirring, introduce 1, 8 kilos of Moxidectin little by little until the mixture is completely solubilized. Reflect the action documentary.
dJ En el reactor de 500 litros, añadir 300 litros del solvente oleoso y calentar a 40°C. Posteriormente añadir los antioxidantes Xo y Xa. Reflejar acción documentalmente. e/ Transferir el contenido del reactor de 500 litros al interior del reactor de 1000 litros y a continuación incorporar 100 litros del solvente oleoso. Agitar durante 18 minutos. Reflejar la acción documentalmente. f/ En el reactor de 1000 litros, incorporamos 149 kilos de vitamina A, que previamente hemos licuado al baño mana a 45°C durante 5 horas y 15 minutos. Recuperar todo el contenido del vaso mediante enjuagues con el solvente oleoso y agitación (el vaso sometido al baño mana). Reflejar la acción documentalmente. g/ Incorporar la mitad de la vitamina E en el reactor de 100 litros y agitar; a continuación, incorporar la vitamina D3 y agitar hasta solubilizar la mezcla. Reflejar la acción documentalmente. h/ Incorporar la otra mitad de la vitamina E y el resto del conservante en el reactor de 1000 litros, recuperando todo el contenido del vaso mediante enjuagues con pequeñas cantidades del solvente oleoso y agitación del vaso. Reflejar la acción documentalmente . iJ Transferir la solución del reactor de 100 litros, según pasos "a" y "g," al reactor de 1000 litros, manteniendo su contenido en agitación; sin detener dicha agitación, se incorpora el solvente oleoso hasta completar los 1000 litros, y se agita durante otros 35 minutos. Reflejar la acción documentalmente. j/ Enviar una muestra al departamento de control de calidad para verificar que el proceso se ha realizado correctamente. Reflejar la acción documentalmente. k/ Una vez que el departamento de control de calidad da su visto bueno, realizar una pre-filtración de la solución con un filtro de 0,45 mieras. Reflejar la acción documentalmente. dJ In the 500 liter reactor, add 300 liters of the oily solvent and heat to 40 ° C. Subsequently add the antioxidants X o and X a . Reflect action documentary. e / Transfer the contents of the 500-liter reactor into the 1000-liter reactor and then incorporate 100 liters of the oily solvent. Shake for 18 minutes. Reflect the action documentary. f / In the 1000 liter reactor, we incorporate 149 kilos of vitamin A, which we have previously liquefied to the mana bath at 45 ° C for 5 hours and 15 minutes. Recover all the contents of the glass by rinsing with the oily solvent and stirring (the glass subjected to the mana bath). Reflect the action documentary. g / Incorporate half of the vitamin E in the 100 liter reactor and stir; then add vitamin D3 and stir until the mixture is solubilized. Reflect the action documentary. h / Incorporate the other half of vitamin E and the rest of the preservative into the 1000 liter reactor, recovering the entire contents of the vessel by rinsing with small amounts of the oily solvent and stirring the vessel. Reflect the action documentary. iJ Transfer the solution from the 100 liter reactor, according to steps "a" and "g," to the 1000 liter reactor, keeping its content under stirring; without stopping said stirring, the oily solvent is incorporated until the 1000 liters is completed, and stirred for another 35 minutes. Reflect the action documentary. j / Send a sample to the quality control department to verify that the process was successful. Reflect the action documentary. k / Once the quality control department approves, pre-filtration of the solution with a 0.45 micron filter. Reflect the action documentary.
1/ En un área estéril y con un filtro esterilizado de 0,22 mieras, realizar el filtrado final de la solución para su inmediato envase: todo el proceso debe realizarse con total asepsia. Reflejar la acción documentalmente. mi Verificar el peso del envase. Reflejar la acción documentalmente. n/ Tomar muestras terminadas del inicio, medio y fin de todo el proceso de envasado para someterlas a ensayos de esterilidad en el departamento de calidad microbiológica. Reflejar la acción documentalmente. ñ/ Acondicionar los envases con su debida identificación, y esperar hasta el visto bueno del departamento de control de calidad microbiológico. Reflejar la acción documentalmente. o/ Tras el visto bueno del departamento de control de calidad microbiológico, remitir los envases a la zona destinada a su embalaje y, de ahí, al almacén. Reflejar la acción documentalmente. 1 / In a sterile area and with a sterile filter of 0.22 microns, perform the final filtration of the solution for immediate packaging: the whole process must be performed with total asepsis. Reflect the action documentary. mi Check the weight of the container. Reflect the action documentary. n / Take finished samples of the beginning, middle and end of the entire packaging process to undergo sterility tests in the microbiological quality department. Reflect the action documentary. ñ / Condition the containers with their proper identification, and wait until the approval of the microbiological quality control department. Reflect the action documentary. o / After the approval of the microbiological quality control department, forward the containers to the area destined for packaging and, hence, to the warehouse. Reflect the action documentary.
Muy importante: la presente invención no se limita a su aplicación sobre los detalles y etapas aquí descritas; las mismas disposiciones y otras modalidades pueden ponerse en práctica y llevarse a cabo con una amplia variedad de formas, dejando claro que la finalidad del ejemplo expuesto, no es más que poner en evidencia una forma de fabricar la invención, sin limitar, con ello, cualquier otra susceptible. Very important: the present invention is not limited to its application on the details and steps described herein; the same provisions and other modalities can be put into practice and carried out in a wide variety of ways, making it clear that the purpose of the example set forth is merely to demonstrate a way of manufacturing the invention, without limiting, in this way, Any other susceptible.
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR112014031760A BR112014031760A2 (en) | 2012-06-25 | 2013-06-24 | antiparasitic composition for control and treatment of different animal species characterized by the fact that it combines moxidectin and vitamins a, d3 and e |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ESP201200684 | 2012-06-25 | ||
| ES201200684A ES2436249B1 (en) | 2012-06-25 | 2012-06-25 | Antiparasitic composition for the control and treatment of parasites of different animal species, characterized by combining Moxidectin with vitamins: A, D3, and E |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2014001588A1 true WO2014001588A1 (en) | 2014-01-03 |
Family
ID=49753707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/ES2013/000153 Ceased WO2014001588A1 (en) | 2012-06-25 | 2013-06-24 | Antiparasitic composition for controlling and treating parasites of different animal species, characterised in that it combines moxidectin with vitamins a, d3 and e |
Country Status (3)
| Country | Link |
|---|---|
| BR (1) | BR112014031760A2 (en) |
| ES (1) | ES2436249B1 (en) |
| WO (1) | WO2014001588A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2016007786A (en) * | 2013-12-16 | 2017-03-03 | Massachusetts Inst Technology | Fortified micronutrient salt formulations. |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0501051A (en) * | 2005-03-28 | 2006-11-28 | Sespo Ind E Com Ltda | sterile solution applied in the treatment and control of endo and ectoparasites in cattle and others and process of obtaining the sterile solution |
| WO2010116267A1 (en) * | 2009-02-16 | 2010-10-14 | Pfizer Inc. | High dosage doramectin formulation |
-
2012
- 2012-06-25 ES ES201200684A patent/ES2436249B1/en not_active Expired - Fee Related
-
2013
- 2013-06-24 WO PCT/ES2013/000153 patent/WO2014001588A1/en not_active Ceased
- 2013-06-24 BR BR112014031760A patent/BR112014031760A2/en not_active IP Right Cessation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0501051A (en) * | 2005-03-28 | 2006-11-28 | Sespo Ind E Com Ltda | sterile solution applied in the treatment and control of endo and ectoparasites in cattle and others and process of obtaining the sterile solution |
| WO2010116267A1 (en) * | 2009-02-16 | 2010-10-14 | Pfizer Inc. | High dosage doramectin formulation |
Non-Patent Citations (2)
| Title |
|---|
| KANBUR M. ET AL.: "The curative and antioxidative efficiency of doramectin and doramectin + vitamin AD3E treatment on Psoroptes cuniculi infestation in rabbits.", RESEARCH IN VETERINARY SCIENCE., vol. 85, no. 2, 1 October 2008 (2008-10-01), pages 291 - 293 * |
| SINGH S K. ET AL.: "Psoroptes cuniculi induced oxidative imbalance in rabbits and its alleviation by using vitamins A, D3,E, and H as adjunctive remedial.", TROPICAL ANIMAL HEALTH AND PRODUCTION., vol. 44, no. 1, 4 June 2011 (2011-06-04), pages 43 - 48 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2436249A1 (en) | 2013-12-27 |
| ES2436249B1 (en) | 2014-06-23 |
| BR112014031760A2 (en) | 2017-06-27 |
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