Title:  Delivery system for antimethanogenic agents

United States Patent:  6,251,879

Assignee:  Commonwealth Scientific and Industrial Research Organisation (Campbell, AU)

Filed:  June 14, 1999

Foreign Application Priority Data:  Nov 04, 1994[AU] (PM9225)

A delivery system is provided to reduce methane production in animals or to improve the weight gain of an animal. Embodiments include a delivery system comprising a volatile and/or water soluble antimethanogenic agent with cyclodextrin or a cyclodextrin-like compound.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

It has been surprisingly found by the present inventors that cyclodextrin completed with a volatile and/or water soluble antimethanogenic agent delays release of the agent to provide prolonged or sustained release of the agent.

The term "volatile" used herein refers to the tendency of the agent to evaporate and generally refers to fluid substances.

The volatile and/or water soluble antimethanogenic agent may be any antimethanogenic agent which is volatile and/or water soluble. The term refers to any compound not normally in a solid state which is capable of inhibiting methanogenesis in animals with the proviso that the compound is physiologically acceptable to animals. Such agents include bromochloromethane and analogues thereof such as bromochloroethane or bromochloropropane and other compounds such as halothane, 2-bromoethane sulphonate and 2-bromo-2-chloroethane sulphonate.

The cyclodextrin may be selected from .alpha.-cyclodextrin, .beta.-cyclodextrin or .gamma.-cyclodextrin or derivatives thereof which may be naturally and/or synthetically produced. The cyclodextrin-like compound may be any compound capable of slowing or controlling the release of said agent and includes mannose based ring compounds.

The term "such that sustained release of the agent is provided" means that the antimethanogenic agent and cyclodextrin or cyclodextrin-like compound are capable of dissociation whereupon the agent is released at a reduced rate compared to the agent administered on its own.

Accordingly in one aspect the invention provides an antimethanogenic composition for use in animals comprising a volatile and/or water soluble antimethanogenic agent together with a cyclodextrin or a cyclodextrin-like compound such that sustained release of the agent is provided.

The term "animals" used above refers to any animal in which it is desirable to deliver an antimethanogenic compound. Preferably the animals are mammals. The mammals will generally be domestic animals such as ruminants (cattle, sheep, goats, deer, elk, alpacas, llamas), and other animals including horses, pigs, dogs, cats, humans.

The antimethanogenic agent is at least partly enclosed in, confined by, or encapsulated by the cyclodextrin or cyclodextrin-like compound. Once the composition is administered the agent dissociates from the cyclodextrin or cyclodextrin-like compound. Preferably the cyclodextrin forms an inclusion complex with the agent.

Preferably the composition is a pharmaceutical or veterinary composition in order to comply with the various regulatory standards for such compositions in different countries.

The dose of the antimethanogenic agent is in the range from about 1 to 150 mg per kg. More preferably the dose range is from 1 to 120 mg per kg, still more preferably 1 to 50 mg, even more preferably from 1 to 20 mg, even more preferably from 1 to 10 mg per kg of body weight.

Preferably the composition is in a particulate form. More preferably the particles are 50-100 mesh BSM.

Alternatively preferably the composition may be in the form of a capsule such as a gelatin capsule or the capsules described in Australian Patents 520409, 558009 and 555998.

In another aspect the invention provides an animal feed comprising the composition of the invention described above together with a nutrient source. The animal feed may be for a vegetarian animal such as cows, sheep, etc. or for carnivores or omnivores such as pigs and dogs.

In one particularly preferred aspect the composition of the present invention is incorporated into lucerne pasture, hay, cereals, legumes, by-products from food industries and/or polenta in the case of domestic animals such as cattle. In the case of dogs and cats the composition may be incorporated into dried pet or moist pet food. The animal feed or pet food may comprise other active ingredients in addition to the composition of the present invention. Such active ingredients include hormones, particularly growth hormones such as hormonal growth promotant, antibacterial compounds such as ionophores including Rumensin and the like.

In another aspect the invention provides a method of producing an anti-methanogenic composition comprising a volatile and/or water soluble antimethanogenic agent together with a cyclodextrin or cyclodextrin-like compound, said method comprising mixing said anti-methanogenic agent with a cyclodextrin or cyclodextrin-like compound such that sustained release of the agent will be provided upon administration, and optionally bringing the composition into a suitable dosage form.

The antimethanogenic agent is at least partly enclosed in, confined by, or encapsulated by the cyclodextrin or cyclodextrin-like compound.

The composition of the present invention may be prepared by the technique described in Budai and Szejtli (1981).

The terms "antimethanogenic agent", "cyclodextrin" and "cyclodextrin-like compound" have the same meaning as given above.

Those skilled in the art will be familiar with the conditions necessary to produce the antimethanogenic composition.

In another aspect the present invention provides a method of administering an antimethanogen to animal over an extended period comprising administering a composition comprising a volatile and/or water soluble antimethanogenic agent together with a cyclodextrin or cyclodextrin-like compound such that sustained release of the agent is provided, in a manner such that said composition is retained by said animal over said period.

The term "over an extended period" refers to a period of time which is longer than the time taken for the volatile and/or water soluble antimethanogenic agent to evaporate when it is not present in the composition.

The term "in a manner such that said composition is retained by said animal over said period" means that the composition is applied in a suitable manner to allow sustained release. In a ruminant for example administration may be provided in the form of a controlled release device or may be provided in the feed. In monogastric animals the composition will be administered in the feed or alone.

Where the animal in the method is a ruminant the method leads to increased weight gains. The method is also of benefit in both ruminants and non-ruminants in that it reduces greenhouse gas emissions In addition the method is also beneficial in humans and household pets where the antimethanogenic effects lead to reduced flatulence.

In a particularly preferred embodiment the invention relates to a method of reducing methane production in an animal over an extended period comprising administering a methane reducing effective amount of an antimethanogenic composition said composition comprising volatile and/or water soluble antimethanogenic compound together with a cyclodextrin or cyclodextrin-like compound such that sustained release of said agent is provided.

The antimethanogenic compound is at least partly enclosed by, confined by or encapsulated by the cyclodextrin or cyclodextrin-like compound.

In a related aspect the present invention provides a method of prolonging methane reduction in an animal where an antimethanogenic compound is administered to said animal, said method comprising administering a volatile and/or water soluble antimethanogenic compound complexed with a cyclodextrin or cyclodextrin-like compound such that sustained release is provided to said animal.

In another related aspect the present invention provides a method-of improving weight gain in a ruminant comprising administering to said ruminant an effective amount of the composition of the invention for a time and under conditions sufficient to allow weight gain to occur.

The inventors have found that treatment of ruminants which are being fed on heliotrope with the antimethanogenic composition of the present invention leads to increased rumen metabolism of heliotrine. Presumably this leads to reduced toxicity in the animals. Thus the present invention also extends to a method of increasing pyrrolizidine alkaloid metabolism in a ruminant feeding on material containing pyrrolizidine alkaloids comprising administering to said ruminant an effective amount of a volatile and/or water soluble antimethanogen which is complexed with a cyclodextrin or cyclodextrin-like compound in accordance with the invention.

Preferably the antimethanogenic agent is at least partly enclosed in, confined by, or encapsulated by the cyclodextrin or cyclodextrin-like compound.

The dose of the antimethanogen may be in the range from about 1 to 150 mg per kg of body weight although those skilled in the art will be able to establish an effective administration dose for the particular application.

The composition may be administered by means of an intra ruminal control release device, in the form of granulated powder, in animal feed, or any other appropriate means.

In their work on the present invention, the inventors have surprisingly found that administration of an antimethanogen to sheep results in decreased wool fibre diameter.

Accordingly in another aspect the present invention provides a method of reducing wool fibre diameter in a wool producing animal comprising administering an effective amount of an antimethanogenic agent for a time and under conditions sufficient to allow wool growth.

The term "reducing wool fibre diameter" means to reduce the diameter of the wool fibre compared to the diameter of the fibre produced in an animal when not treated by the method.

The term "wool" used above refers to any natural fibre grown by an animal and includes wool, hair and other fibres whether or not they are keratin based.

The term "wool producing animal" includes any animal which produces wool or hair which is desirable to harvest. This includes sheep, goats (Cashmere and Angora), rabbits, alpacas and llamas and the like. Preferably the animal is a ruminant. More preferably the animal is a sheep or a goat.

The term "for a time and under conditions sufficient to allow wool growth" means that the treatment must be carried out for a sufficient length of time, in the wool growing season (where applicable) and under adequate nutritional and other conditions to allow the animal to produce wool. Preferably the treatment is carried out over an extended period of time so that the wool grown is of a reduced diameter along its length.

The antimethanogenic agent may be any antimethanogenic agent. Preferably the antimethanogenic agent is administered as part of the composition of the present invention, however the method is not so limited.

The dose of the antimethanogenic agent may be in the range from about 1 to 150 mg per kg, preferably 1 to 50 mg per kg, more preferably 1 to 20, still more preferably 1 to 10 mg per kg of animal.

Claim 1 of 17 Claims

What is claimed is:

1. A method of reducing wool fibre diameter in a wool producing animal comprising administering an effective amount of an antimethanogenic agent for a time and under conditions sufficient to allow wool growth.

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