Injectable anthelmintic compositions and methods for using same

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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C514S943000, C424S422000

Reexamination Certificate

active

06653288

ABSTRACT:

BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to injectable compositions containing a liquid solvent free of solid polymers, anthelmintic agent(s)and hormonal growth promoter(s), the anthelmintic agent(s) and the hormonal growth promoter(s) are dissolved in the solvent. The present invention additionally relates to methods of promoting animal growth and treating and/or preventing parasitic infection/infestation with these compositions, as well as methods of preparing such compositions.
DESCRIPTION OF THE BACKGROUND
To a great extent, the pituitary gland and its secretions of growth or somatotrophic hormone regulate animal growth. Anabolic implants increase (via the pituitary gland) growth hormone and insulin at the cellular level, resulting in increased synthesis of muscle tissue, and frequently, reduced deposition of body fat. The result is usually increased growth rate and improved feed efficiency.
Certain growth promoting hormones have been approved for use at very low concentrations to increase the rate of weight gain and/or improve feed efficiency in beef cattle. The livestock producer generally administers hormonal growth-promoting drugs at specific stages of production. Residual levels of these hormones in food have been demonstrated to be safe, as they are well below any level that would have a known effect in humans.
Estradiol, progesterone, and testosterone are naturally-occurring (endogenous) steroid hormones produced in significant quantities throughout the lifetime and are required for the proper physiological functioning and maturation of every mammal. All endogenous steroid hormone products marketed in the U.S. and in many other countries for beef growth-promotion are formulated as implantable pellets and are designed to deliver the hormones at a slow, constant rate when injected subcutaneously under the skin of the animal's ear. Numerous scientific studies have demonstrated that when these drugs are used in accordance with their approved conditions of use, concentrations of the hormones in edible tissues remain within the normal physiological range that has been established for untreated animals of the same age and sex. Consumers are not at risk from eating food from animals treated with these compounds because the amount of added hormone is negligible compared to the amount normally found in the edible tissues of untreated animals and that are naturally produced by the consumer's own body.
Unlike naturally occurring steroid hormones, there is no natural production of the synthetic compounds, trenbolone acetate, zeranol, and melengestrol acetate (MGA). Zeranol and its metabolites &bgr;-zearalanol and zearalanone, and zearalenone, and its metabolites &bgr;-zearalenol and &agr;-zearalenol, are members of the class of compounds known as resorcyclic acid lactones.
To obtain a prolonged effect of the action of growth-promoting hormones, which is an essential condition to allow these substances to play the role of anabolic agents, several modes of administration were envisaged such as: Intramuscular injections of oily suspensions of these substances as esters: acetate, propionate, benzoate: Intramuscular injections of aqueous suspensions of micro-crystals of active products: Subcutaneous administration of implant in which the active is placed.
Some implants are “matrix” type, and consist of an active compound dispersed in a matrix of carrier material. The carrier material may be porous or non-porous, solid or semisolid, and permeable or impermeable to the active compound. Matrix devices may be biodegradable, i.e. they may slowly erode after administration. Alternatively, matrix devices may be non-degradable, and rely on diffusion of the active compound through the walls or pores of the matrix. Other devices are “reservoir” type, and consist of a central reservoir of active compound surrounded by a rate controlling membrane (rcm). The rcm may be either porous or non-porous, but is not usually biodegradable. However, reservoir devices often suffer from an inadequate rate of delivery: the rcm surface area required maintaining an effective concentration of active compound is frequently so large that it is impractical to administer the device. Additionally, reservoir devices are sensitive to rupture: if the rcm is breached, an excessive (possibly lethal) dose of active compound may be released instantaneously. Some sustained release devices are hybrids, having a matrix core surrounded by a rcm. Other sustained release devices may be mechanical in nature, and include small compound-filled electrical or osmotic pumps. While these devices may be capable of zero order release, they are typically too expensive to compete economically with matrix and reservoir devices.
Implantation is the most commonly used method to administer growth-promoting hormones, even if several are active after oral administration.
Implants are widely used in veterinary medicine and often consist of compressed pellets or silicone-containing rubber. The active substances are dispersed in the solid rubber or located inside a hollow rubber body. The release rate of the active substances from the implant, and hence the period for which the implant is effective, are generally determined by the accuracy of the calibration (amount of active ingredient in the implant) of the implant, the environment of the implant and the polymer formulation from which the implant is made. Growth promoting implants commercially available are applied to the ears of cattle. Implanting elsewhere may be ineffective and result in condemnation of the carcass.
Animals, particularly calves, should be implanted two or more times during the growth period. Maximum benefit is obtained by having an approved, viable growth implant in cattle for most (or all) of their life from birth to harvest.
During implantation of implants in animals, conditions are typically unsanitary, causing infection, which can result in loss of implants. Use of an antibiotic or germicide layer or coating on the surface of the implant to reduce infections and to improve implant retention has often been adopted. The antibiotic coating facilitates parenteral administration of the implants under non-sterile conditions; requirements for cleaning the implant needle, the site of implantation on the animal, and the implantation device are minimized. However, this leads to introduce an antibiotic active agent into the composition, what has the effect of increasing the risks of resistance to the antibiotic and of complicating the manufacture of the implant.
The implanting technique must be done properly to obtain the greatest response and avoid undesirable side effects. One has to be especially careful to follow recommendations on correct implant usage, implant replacement, and implanting technique. For example, the animal has to be properly restrained in a squeeze chute or headgate to allow access to the ear, the implant has to be deposited between the skin and cartilage on the back side of the ear and below the midline of the ear, the implant must not be placed closer to the head than the edge of the cartilage ring, farthest from the head, which essentially means it must be placed in the middle one-third of the ear. Proper procedures for using implants, which are non-sterile injectable devices, require to cleanse the skin at the implant insertion site, to avoid placing an implant at the site of an old implant or other injury or in an area that will be used for an ear tag, to avoid crushing implants, to avoid injuring major blood vessels of the ear, to disinfect the implant needle between applications. The tissue irritation caused by an undiluted disinfectant can cause the expulsion of an implant or the formation of scar tissue that could interfere with the effective release of growth promotant from the implant and care should be taken when selecting an implant needle cleaning solution. Some breeders coat the cleaned implanting needle with an approved, non-irritating antibiotic between animals as an additional safeguard to help

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