CN119816308A

CN119816308A - Chemical exfoliation method

Info

Publication number: CN119816308A
Application number: CN202380063865.XA
Authority: CN
Inventors: J·P·钱伯斯; P·M·辛格; R·G·M·奥尔德里克林克; F·R·埃姆斯利; I·G·塔克; D·文卡塔查兰
Original assignee: Villefield Concept Co ltd
Current assignee: Villefield Concept Co ltd
Priority date: 2022-09-05
Filing date: 2023-08-31
Publication date: 2025-04-11
Also published as: EP4583875A1; WO2024052765A1; AU2023336907A1

Abstract

A cytotoxic agent and its use in animal dehorning or inhibiting horn growth of young animals. The cytotoxic agent can be a sclerosant, a p53 activator, an antiprotozoal agent, a cell apoptosis inducer or a local anesthetic.

Description

Chemical chamfering method

RELATED APPLICATIONS

The present application claims priority from australian provisional patent application number 2022902547 filed at month 9 and 5 of 2022, the entire contents of which are incorporated herein by reference.

Technical Field

The present invention relates broadly to cytotoxic agents and their use in the removal of corners of animals or in inhibiting the growth of corners in young animals. In particular, the cytotoxic agent is a sclerosant, a p53 activator, an antiprotozoal agent, an apoptosis inducer and/or a local anesthetic.

Background

Horn bud removal is a common feeding practice for most groups of cows around the world.

Chamfering is a procedure that uses a thermal cautery (soldering iron) device to cauterize and destroy tissue surrounding the horn to remove or destroy the horn of the calf. Soldering iron devices for chamfering are potentially dangerous due to the use of high temperatures. Successful chamfer requires experience and skill, while incorrect techniques can lead to injury to animals and operators.

Even if properly performed, soldering iron chamfering procedures can be painful and stressful to the animal if not properly anesthetized and analgesic is performed. In new zealand, it is illegal to remove the calf's horn unless the calf is "under the influence of a properly placed and effective local anesthetic" (animal welfare (caretaking and procedure) regulations in 2018). Desirable deltoid regimens include administration of sedatives to relieve stress during procedures, injection of local anesthetics to anesthetize the horn and surrounding tissues, and administration of non-steroidal anti-inflammatory drugs (NSAIDs) to relieve post-operative pain. However, the combination of these procedures still does not guarantee a comfortable experience for the animal. In most countries there are obstacles to the cost and availability of the proper medication for animal breeders. The above-mentioned recommended methods of treatment also require experience and skill in administering appropriate drug regimens. In particular, proper administration of anesthetic to the diagonal nerve requires training for the proper procedure.

Other less common methods of chamfering include direct removal of the buds with a spade or chisel, and chemical chamfering with caustic soda. It was observed that removal of the horn by cutting caused more pain and stress than the use of soldering iron and left a large open wound.

The literature reports on the tested chamfering test method. A paper in 1976 (Koger LM. Dehorning by injection of calcium chloride. Vet MED SMALL ANIM CLIN 1976;71 (6): 824-825) describes a method of injecting high concentrations of calcium chloride into the horn buds to cause tissue necrosis. This approach also causes significant inflammation, which is expected to cause considerable pain. The authors suggested the use of analgesics and sedatives.

The use of caustic soda has been tested. Caustic soda often inadvertently diffuses from the application site to other areas of the animal and other animals, causing the treated animal to become blind and to be adversely affected by rainfall.

Attempts have been made to destroy the tissue of the horn using liquid nitrogen as the cryogenic liquid, but it was found to be almost completely ineffective.

The injection of clove oil (eugenol) under the horn buds has been tested for causing necrosis of the horn bud tissue, but has been found to be relatively ineffective, in many cases retarding the growth of the horn rather than preventing it, and the original researchers did not recommend this procedure (Sutherland et al Vet Sci.2019Dec;6 (4): 102).

Thus, there is a need for an improved composition or method for preventing angular growth in young animals.

Object of the Invention

It is an aim of one or more embodiments of the present invention to address one or more of the above problems. Alternatively, it is an object of one or more embodiments of the present invention to provide a composition or method for chemical chamfering that overcomes or minimizes the above-mentioned drawbacks of known chamfering methods. Alternatively, it is an object of the present invention to provide the public with a useful choice.

Disclosure of Invention

The present invention relates broadly to cytotoxic agents and their use in animal exfoliating.

According to a first aspect of the present invention there is provided a method of chemically dehorning a young animal by administering at least one cytotoxic agent to the animal's keratinocytes, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anesthetic.

According to a second aspect of the present invention there is provided the use of at least one cytotoxic agent for chemically delocalising a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosing agent, a p53 activator, an antiprotozoal agent, an apoptosis inducing agent or a local anaesthetic.

According to a third aspect of the present invention there is provided at least one cytotoxic agent for use or when used for chemically delocalising a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anaesthetic.

According to a fourth aspect of the present invention there is provided the use of at least one cytotoxic agent in the manufacture of a medicament for chemically delocalising a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anaesthetic.

According to a fifth aspect of the present invention there is provided a corner-removal composition comprising at least one cytotoxic agent formulated for administration to and chemical removal of corners from young animals, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anesthetic.

According to a sixth aspect of the present invention there is provided a method of inhibiting the growth of the horn of a young animal by administering at least one cytotoxic agent to the animal's horn cells, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anesthetic.

According to a seventh aspect of the present invention there is provided the use of at least one cytotoxic agent for inhibiting the growth of the horn of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

According to an eighth aspect of the present invention there is provided at least one cytotoxic agent for use or when used for inhibiting angular growth in a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis-inducing agent or local anaesthetic.

According to a ninth aspect of the present invention there is provided the use of at least one cytotoxic agent in the manufacture of a medicament for inhibiting the growth of the horn of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anaesthetic.

According to a tenth aspect of the present invention there is provided a composition comprising at least one cytotoxic agent formulated for administration to a young animal and for inhibiting the growth of the corners of the young animal, wherein the at least one cytotoxic agent comprises at least one sclerosing agent, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anaesthetic.

According to an eleventh aspect of the present invention there is provided a syringe containing at least one cytotoxic agent for use in or when used in the removal of a horn from a young animal or in inhibiting the growth of a horn from a young animal, wherein the syringe is capable of administering the at least one cytotoxic agent to the horn bud cells of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis-inducing agent or local anesthetic.

According to a twelfth aspect of the present invention there is provided a kit for or when used in a method of chamfering or inhibiting the growth of the horn of a young animal, wherein the kit comprises a syringe capable of administering at least one cytotoxic agent to the horn cells of the young animal, and at least one cytotoxic agent which kills the horn cells in an amount, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

According to a thirteenth aspect of the present invention there is provided a composition formulated as a solution, suspension, dispersion, emulsion, low viscosity gel or other slow release liquid formulation, the composition comprising at least one cytotoxic agent and one or more excipients and being capable of providing a slow release of the at least one cytotoxic agent, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer and local anesthetic.

According to a fourteenth aspect of the present invention there is provided a composition formulated as a solution, suspension, dispersion, emulsion, low viscosity gel or other slow release liquid formulation, the composition comprising at least one cytotoxic agent in an amount capable of exfoliating or inhibiting angular growth in a young animal, and one or more excipients, and capable of providing a slow release of the at least one cytotoxic agent, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

According to a fifteenth aspect of the present invention there is provided a composition formulated as a low viscosity injectable gel comprising, all in about% w/v,

10% W/v of at least one cytotoxic agent, preferably melalin or a melalin salt providing 10% w/v of melalin, such as 11.8% w/v of melalin dihydrochloride, or melalin dihydrochloride dihydrate;

40-85%w/v SAIB;

0-2%w/v Tween 80;

0-50% w/v glyceryl triacetate;

0-50% w/v DEGEE (Transcutol ^TM), and

Ethanol is made up to 100% by volume, wherein:

the concentration of ethanol is 0-30% w/v, or

In the absence of other solvents and Tween, and at SAIB levels of 85% w/v, the ethanol concentration is about 15% w/v assuming a weight of 1.1g per mL of the composition formulation.

According to a sixteenth aspect of the present invention there is provided a composition formulated as a low viscosity injectable gel comprising, all in about% w/v,

20% W/v of at least one cytotoxic agent, preferably melarson or a melarson salt providing 20% w/v melarson, such as 23.6% w/v melarson dihydrochloride, or 25.4% w/v melarson dihydrochloride dihydrate;

40-85%w/v SAIB;

0-2%w/v Tween 80;

0-50% w/v glyceryl triacetate;

0-50% w/v DEGEE (Transcutol ^TM), and

Ethanol is made up to 100% by volume, wherein:

the concentration of ethanol is 0-30% w/v, or

In the absence of other solvents and Tween, and at a level of 85% w/v at 20% w/v of miparin base and SAIB, assuming a weight of 1.1g per mL of the composition formulation, the ethanol concentration is 5% w/v, which may be too low, in which case the maximum concentration of SAIB must be reduced.

According to a seventeenth aspect of the present invention there is provided a composition formulated as a low viscosity injectable gel comprising, all in about% w/v,

10% W/v of at least one cytotoxic agent, preferably melalin or a melalin salt providing 10% w/v of melalin, such as 11.8% w/v of melalin dihydrochloride;

70%w/v SAIB;

1%w/v Tween 80;

5% w/v glyceryl triacetate;

0% w/v DEGEE (Transcutol ^TM), and

Ethanol is made up to 100% by volume, i.e., about 22% w/v ethanol assuming a weight of 1.1g per mL of final formulation and assuming use of the miparin dihydrochloride.

According to an eighteenth aspect of the present invention there is provided a composition formulated as a low viscosity injectable gel comprising, all in about% w/v,

20% W/v of at least one cytotoxic agent, preferably melalin, more preferably 23.6% w/v of melalin dihydrochloride;

70%w/v SAIB;

1%w/v Tween 80;

5% w/v glyceryl triacetate;

0% w/v DEGEE (Transcutol ^TM), and

Ethanol is made up to 100% by volume, i.e., about 10.4% w/v ethanol, assuming a weight of 1.1g per mL of final formulation.

According to a nineteenth aspect of the present invention there is provided a composition formulated as an injectable oily solution or suspension comprising, all in about% w/v,

10-15% W/v of at least one cytotoxic agent, preferably melarson or a salt thereof providing 10-15% w/v melarson, such as 11.8-17.7% w/v melarson dihydrochloride, and

At least one oily excipient.

It is to be understood that features which are referred to in the context of a particular aspect of the invention can be, or are reconstructed from, features of any and all other aspects of the invention. For example, where the context allows, one or more features of a "method" (method, use, procedure, etc.) may be reconstituted as features of a "product" (cytotoxic agent, composition, drug, formulation, syringe, kit of parts, etc.), and vice versa.

By "cytotoxic agent" is meant an agent that is toxic to keratinocytes (especially the dermis), which may be destroyed and/or inactivated by the cytotoxic agent. Unless otherwise indicated, "cytotoxic agent" refers to at least one type of agent, and in some embodiments may be two, three, four, or more different types of agents used together. For example, another suitable cytotoxic agent may be eugenol (clove oil). For example, eugenol may be used in combination with melarson.

In some embodiments, the cytotoxic agent may be in the free acid or free base form, or a salt. The term "cytotoxic agent" includes, where the context permits, the free acid or free base form of the cytotoxic agent, as well as any salt or salts of the cytotoxic agent. For example, the micropaline is a base/free base, so the use of "micropaline" throughout the specification and claims includes micropaline as the free base as well as any salt of micropaline, such as micropaline dihydrochloride or micropaline dihydrochloride dihydrate. One or more salts of melarson may sometimes be specifically mentioned for purposes of more clarity.

Although not always explicitly stated, it is to be understood that cytotoxic agents are typically administered to animals in the form of compositions, formulations or medicaments.

It is understood that the removal of corners or inhibition of corner growth can be achieved by administration of a cytotoxic agent directly to or in the vicinity of the animal's keratinocytes (keratinocyte tissue). Preferably, dehazeng or corner inhibition is performed when the corner buds drift freely in the skin. Preferably, the chamfering or corner inhibition is performed before the corner buds are attached to the skull. The cytotoxic agent is preferably administered under or around the horn bud, more preferably under the horn bud. Successful corner removal or corner inhibition requires inactivation or destruction of corner-producing cells (dermis) of the corner buds (i.e., "corner bud cells").

Preferably, the cytotoxic agent is administered in an amount (i.e., an "effective amount") sufficient to prevent or significantly reduce horn growth such that the horn/stump/bud produced is not dangerous to other animals. Preferably, corner growth is completely prevented.

The inventors have found that young animals may be dehorned by applying at least one hardener(s) to the shoots.

Any suitable hardener or hardeners may be used. Techniques for identifying and evaluating new potential sclerosants are known in the art, including in vitro assays. Sclerosants are commonly used in sclerotherapy. In sclerotherapy procedures, a sclerosant is generally a substance that, when introduced into a lumen of a blood vessel, causes damage to the wall of the blood vessel, thereby causing occlusion of the blood vessel due to fibrosis resulting therefrom. Sclerotherapy is commonly used to treat varicose veins.

Preferred hardening agents include miparin (quinacrine), chloroquine, polidocanol and quinine. Preferred sclerosants are agents that also provide a local anesthetic effect, such as melarson, chloroquine and polidocanol.

Acridine hardeners, such as quinacrine (mpalin), are particularly preferred active agents.

The inventors found that animals can be dehorned by applying one or more p53 activators to the horn bud.

Any suitable p53 activator or activators may be used. The skilled person knows suitable p53 activators useful in the present invention, in particular for potential use in cancer therapy. The proteins p53, also known as tumor protein p53 and tumor suppressor p53, act as tumor suppressors in cells. Agents that result in activation of the p53 protein are referred to as p53 activators.

Preferred p53 activators are small molecules, including mipaline and chloroquine.

Acridine p53 activators, such as quinacrine (quinacrine), are particularly preferred active agents.

Particularly preferred p53 activators provide local anesthetic effects such as melarson and chloroquine.

The inventors have found that animals can be dehorned by administering one or more anti-protozoan agents to the horn buds.

Any suitable one or more antiprotozoal agents may be used. A number of antiprotozoal agents are known in the art. For example, suitable antiprotozoal agents may include antimalarial agents. Techniques for identifying and evaluating new potential antiprotozoal agents are known in the art.

Preferred antiprotozoal agents include miparin, chloroquine, and quinine.

Acridine antiprotozoal agents, such as quinacrine (quinacrine), are particularly preferred agents.

Particularly preferred antiprotozoal agents are agents that also provide a local anesthetic effect, such as miparin and chloroquine.

The inventors have found that animals can be delusted by administering one or more apoptosis inducers to the horn bud.

Any suitable apoptosis-inducing agent or agents may be used. Suitable apoptosis inducers useful in the present invention are known to the skilled artisan. Preferred apoptosis inducers include miparin and cinchocaine.

Acridine apoptosis inducers, such as quinacrine (mpalin), are particularly preferred agents. Particularly preferred apoptosis inducers provide local anesthetic effects such as melarson and cinchocaine.

The inventors have found that animals can be delustered by administering one or more anesthetics to the diagonal buds.

Any suitable anesthetic or anesthetics may be used. Suitable anesthetics include amide anesthetics, ester anesthetics, or nonionic surfactant anesthetics. Suitable anesthetics include lidocaine, chloroprocaine, mepivacaine, bupivacaine, atecrine, etidocaine, levobupivacaine, tetracaine, prilocaine, benzocaine, ropivacaine, cocaine, hydroxyprocaine, hexacaine (hexocaine), dibucaine, perralcaine, and procaine, and pharmaceutically acceptable acids, bases, and salts (including acid salts) thereof. In some embodiments, the anesthetic is present in the form of an acidic salt or an acidic solution. (local anesthetic solutions typically have an acidic pH to maximize their water solubility suitable anesthetics include melarson (quinacrine), polidocanol, cinchocaine, chloroquine and quinine.

For example, chloroquine diphosphate can be applied.

Preferably, the cytotoxic agent is miparin, polidocanol, cinchocaine, chloroquine or quinine. In addition to these cytotoxicity, these agents also provide local anesthetic effects.

The animal may be any type of animal that can develop a true positive angle from a horn bud. Such animals include, but are not limited to, bovine animals (cows or bulls), goats, sheep, bison, african buffalo, gazelle, musk, and antelope. The young animal is preferably a calf or a goat.

Any suitable amount of one or more cytotoxic agents may be used provided that it is cytotoxic to the keratinocytes. The amount applied depends on the effectiveness of the cytotoxic agent and the size or volume of the horn region being treated. The amount of cytotoxic agent applied to the keratinocytes is preferably in the range of about 5-1000mg, including all values between 5-1000. More preferably, the amount of cytotoxic agent administered to the keratinocytes is in the range of about 20-400mg, including all values between 20-400, including 20, 21, 22, etc.

For melarson, in some embodiments, at least about 100mg (total amount of single or multiple injections) is administered. For melarson, it is preferred to administer about 100-300mg, preferably about 100-150mg, more preferably about 100mg, including all values (100, 101, 102, etc.) between 100-300 and 100-150. For example, salts of miparin, such as miparin dihydrochloride or miparin dihydrochloride dihydrate, may be administered.

Typically, the cytotoxic agent will be administered to the animal in a composition, formulation or medicament suitable for injection. The preferred composition, formulation or medicament is a liquid composition. Preferred liquid compositions, formulations or medicaments include solutions, suspensions, dispersions, emulsions, low viscosity gels and other sustained release formulations.

The preferred composition (formulation or medicament) for administration is a liquid composition suitable for injection. Injectable compositions may be prepared by dissolving or mixing the cytotoxic agent in a suitable veterinarily acceptable vehicle, carrier, solvent or excipient, etc., which may include other ingredients such as solubilizers, acids, bases, buffer salts, antioxidants and/or preservatives. These compositions may be sterilized, such as by heating, filtration, or irradiation, or may be prepared aseptically. Injectable compositions can be prepared by methods and techniques known to those skilled in the art.

The composition (formulation or medicament) may include one or more of the following types of veterinarily acceptable ingredients, vehicles, aqueous or oily diluents, carriers, excipients, bases, buffers, pH adjusters, suspensions, flocculants, thickeners, viscosity building agents, gelling agents, solvents, co-solvents, solvent systems, emulsifiers, stabilizers, dispersants, solubilisers, fragrances, preservatives, surfactants, detergents, complexing agents, acids, bases, antioxidants, wetting agents, chelating agents, reducing agents, fillers, protecting agents, osmotic pressure modifiers, and colorants.

Examples of the osmotic pressure regulator used in the liquid injection include electrolytes, dextrose, glycerol, sodium chloride, glycerol, and mannitol.

Preservatives used in liquid injection solutions include antioxidants, antimicrobials and chelating agents including ascorbic acid, acetylcysteine, sulfites (bisulfites, metabisulfites), monothioglycerol, phenol, m-cresol, benzyl alcohol, parabens (methyl, propyl, butyl), benzalkonium chloride, chlorobutanol, thimerosal, phenylmercuric salts, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA) and alpha-tocopherol.

Examples of the solubilizing agent used in the liquid injection include surfactants, solvents and cosolvents, and include water, tween, polysorbate, nonionic surfactants, polyoxyethylene sorbitan monooleate (Tween 80), EDTA, sorbitan monooleate, polyoxyethylene sorbitan monolaurate (Tween 20), lecithin, polyoxyethylene copolymers (pluronics)), propylene glycol, glycerin, ethanol, polyethylene glycols (300 and 400), sorbitol, dimethylacetamide and cremophor EL.

Examples of complexing agents and dispersants used in liquid injection solutions include cyclodextrins and modified cyclodextrins, such as hydroxypropyl-b-cyclodextrin and sulfobutyl ether-b-cyclodextrin.

Examples of buffers used in liquid injections include phosphate, citrate, acetate, lactate and tartrate buffers.

Suspensions (including aqueous or oily suspensions) may provide for a more sustained release of the cytotoxic agent from the injection site than comparable solutions. Examples of excipients used in suspensions include flocculants/suspensions, viscosity building agents, wetting agents, solvent systems, preservatives, antioxidants, chelating agents, buffers and tonicity adjusting agents. Examples of excipients or oily suspensions used in oily suspensions include oils, preferably vegetable oils, such as castor oil, cottonseed oil, soybean oil, ethyl oleate, olive oil, peanut oil, sesame oil, sunflower oil, soybean oil and safflower oil.

Examples of flocculants/suspensions include electrolytes, surfactants and hydrocolloids, including potassium chloride/sodium, potassium citrate/sodium and potassium acetate/sodium.

Examples of viscosity building agents include sodium carboxymethyl cellulose, gum arabic, gelatin, methyl cellulose, and polyvinylpyrrolidone.

Examples of wetting agents include glycerol, alcohols, propylene glycol, lecithin, polysorbate 20, polysorbate 80, pramipexole F-68, sorbitan trioleate.

Examples of solvents include water, ethanol, glycerol, propylene glycol, n-lactamide, and polyethylene glycol (PEG).

In some embodiments, the composition (formulation or drug) is in the form of a low viscosity injectable gel that rapidly gels at the injection site to retain the cytotoxic agent for an appropriate period of time. In this way, a relatively large amount of cytotoxic agent can be delivered to the keratinocytes (the keratinous tissue).

The composition may be gelled in situ in any suitable manner. In some embodiments, the composition comprises one or more gelling agents. In some embodiments, the composition comprises one or more solvents or solvent systems. In some embodiments, the composition comprises one or more surfactants. In some embodiments, the composition comprises Sucrose Acetate Isobutyrate (SAIB) and at least one type of solvent. In some embodiments, the composition comprises Sucrose Acetate Isobutyrate (SAIB), at least one type of solvent, and at least one type of surfactant. Upon injection of a composition comprising an SAIB formulation and a solvent (and optionally a surfactant), the solvent can diffuse out, leaving behind a viscous and thick matrix. The matrix may retain the cytotoxic agent in the keratinocytes for an effective period of time rather than the cytotoxic agent being dispersed almost immediately.

SAIB can have a molecular weight of 846.9 (CAS No. 27216-37-1 or 126-13-6).

In some embodiments, the composition comprises about 30% to 90% w/v SAIB, preferably about 40% to 85% w/v SAIB, more preferably about 70% to 80% w/v SAIB, even more preferably about 70% w/v SAIB. These ranges include all values and subranges between 30-90, 40-85, and 70-80, including 30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、86、87、88、89 and 90.

Any suitable solvent or solvents may be used provided that they produce a low viscosity injectable gel. Preferred solvents include ethanol, diethylene glycol monoethyl ether (DEGEE) sold under the trade mark Transcutol ^TM, N-methyl pyrrolidone (NMP), glyceryl triacetate, benzyl benzoate, miglyol, propylene carbonate, benzyl alcohol, ethyl lactate, tetraethylene glycol (glycofurol), 2-pyrrolidone, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decyl methyl sulfoxide, oleic acid, and 1-dodecyl azepan-2-one. The amount of the one or more solvents may be about 0-50% w/v, preferably about 10-30% w/v. These ranges include all values and subranges from 0 to 50 and from 10 to 30, inclusive 0、1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50.

Any suitable surfactant or surfactants may be used provided that they produce a low viscosity injectable gel. Preferred surfactants include nonionic surfactants, polysorbates, tween, polyoxyethylene (20) sorbitan monooleate (Tween 80) or polyoxyethylene (20) sorbitan monolaurate (Tween 20). The amount of surfactant may be up to about 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75 or 3.0% w/v, or, for example, about 0-3% w/v, 0-2% w/v, 0-1% w/v, 1-3% w/v or 1-2% w/v. These ranges include all values and subranges between 0-3, 0-2, 0-1, 1-3, and 1-2.

The concentration of the cytotoxic agent in the composition administered to the animal is preferably in the range of about 0.01% weight/volume (w/v) to about 100% w/v, depending on the efficacy of the cytotoxic agent, including all values and subranges between 0.01 and 100, including about 0.01、0.05、0.1、0.15、0.2、0.25、0.3、0.35、0.4、0.45、0.5、0.55、0.6、0.65、0.7、0.75、0.8、0.85、0.9、0.95、1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、86、87、88、89、90、91、92、93、94、95、96、97、98、99 and 100.

The volume of the composition applied to the horn bud is preferably in the range of about 0.05 to about 10mL, including all values between 0.05 and 10. Particularly preferred ranges are from 0.1 to 2.0mL, including all values between 0.1 and 2.0. For example, an amount of the composition of about 0.1mL, 0.2mL, 0.3mL, 0.4mL, 0.5mL, 0.6mL, 0.7mL, 0.8mL, 0.9mL, 1.0mL, 1.1mL, 1.2mL, 1.3mL, 1.4mL, or 1.5mL may be administered to the horn bud. Preferably up to about 0.5mL, 0.6mL, 0.7mL, 0.8mL, 0.9mL, 1mL, 1.25mL or 1.5mL of the composition is injected.

The cytotoxic agent may be administered to the young animal in any suitable manner. Preferably, the cytotoxic agent is administered by injection. In some embodiments, a single injection is administered. In some embodiments, more than one injection is administered, such as 2, 3, or 4 injections over a suitable time period.

The animals are preferably injected (administered) using a syringe. Preferably, a syringe suitable for one-handed use is used in order to stabilize the animal's head and position the horn bud using the other hand.

In some embodiments, the injector is adapted to provide multiple doses, such as an auto-inoculation injector, a self-filling injection injector, or a multiple dose auto-injector. One example of a suitable syringe is the McLintock syringe, commonly used in tuberculin tests, but may be configured to administer the required dose volume.

Preferred embodiments of the invention are defined in the following numbered paragraphs:

1. A method of chemically dehorning or inhibiting horn growth in a young animal by administering at least one cytotoxic agent to the animal's horn cells, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent, or local anesthetic.

2. Use of at least one cytotoxic agent for chemically delocalizing or inhibiting the growth of the horn of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

3. At least one cytotoxic agent for use in or when used in chemically delocalizing or inhibiting the growth of the horn of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anesthetic.

4. Use of at least one cytotoxic agent in the manufacture of a medicament for chemically delocalizing or inhibiting the growth of the horn of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosing agent, p53 activator, antiprotozoal agent, apoptosis inducing agent or local anesthetic.

5. A composition comprising at least one cytotoxic agent formulated for administration to a young animal to chemically exfoliate or inhibit the growth of the corners of the young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent, or local anesthetic.

6. A syringe containing at least one cytotoxic agent for use in or when used in the removal of a corner of a young animal or in inhibiting the growth of a corner of a young animal, wherein the syringe is capable of administering the at least one cytotoxic agent to the keratinocytes of a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent, or local anesthetic.

7. A kit for use in or when used in a method of exfoliating or inhibiting the growth of the horn of a young animal, wherein the kit comprises a syringe capable of administering at least one cytotoxic agent to the horn cells of the young animal, and at least one cytotoxic agent that kills the horn cells in an amount, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducing agent, or local anesthetic.

8. The method of paragraph 1, the use of paragraph 2, the use of paragraph 3, or the use of at least one cytotoxic agent for chemically dehorning or inhibiting the growth of the horn of a young animal when used, the use of paragraph 4, the composition of paragraph 5, the syringe of paragraph 6, or the kit of parts of paragraph 7, wherein the at least one cytotoxic agent is in the form of a free acid, a free base, or a salt.

9. The method according to paragraph 1 or 8, the use according to paragraph 2 or 8, the at least one cytotoxic agent according to paragraph 3 or 8 for chemically chamfering or inhibiting the angular growth of a young animal, the use according to paragraph 4 or 8, the composition according to paragraph 5 or 8, the syringe according to paragraph 6 or 8, or the kit of parts according to paragraph 7 or 8, wherein the at least one cytotoxic agent comprises at least one sclerosant.

10. The method of paragraph 9, the use of paragraph 9, the at least one cytotoxic agent for chemically dehorning or inhibiting the growth of the horn of a young animal according to paragraph 9 or when used, the use of paragraph 9, the composition of paragraph 9, the syringe of paragraph 9 or the kit of parts of paragraph 9, wherein:

the at least one hardener comprises miparin (quinacrine), chloroquine, polidocanol, or quinine;

The at least one hardener comprises an acridine, preferably melarson, or

The at least one hardener includes miparin.

11. The method according to paragraph 1 or 8, the use according to paragraph 2 or 8, the at least one cytotoxic agent according to paragraph 3 or 8 for chemically chamfering or inhibiting the angular growth of a young animal, the use according to paragraph 4 or 8, the composition according to paragraph 5 or 8, the syringe according to paragraph 6 or 8 or the kit according to paragraph 7 or 8, wherein the at least one cytotoxic agent comprises at least one p53 activator.

12. The method of paragraph 11, the use of paragraph 11, the at least one cytotoxic agent according to paragraph 11 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, the use of paragraph 11, the composition of paragraph 11, the syringe of paragraph 11, or the kit of parts of paragraph 11, wherein:

The at least one p53 activator comprises miparin or chloroquine;

the at least one p53 activator comprises an acridine, preferably melanine, or

The at least one p53 activator comprises miparin.

13. The method according to paragraph 1 or 8, the use according to paragraph 2 or 8, the at least one cytotoxic agent according to paragraph 3 or 8 for chemically chamfering or inhibiting the growth of the horn of a young animal, the use according to paragraph 4 or 8, the composition according to paragraph 5 or 8, the syringe according to paragraph 6 or 8, or the kit of parts according to paragraph 7 or 8, wherein the at least one cytotoxic agent comprises at least one antiprotozoal agent.

14. The method of paragraph 13, the use of paragraph 13, the at least one cytotoxic agent according to paragraph 13 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, for use according to paragraph 13, the composition according to paragraph 13, the syringe according to paragraph 13, or the kit of parts according to paragraph 13, wherein:

the at least one antiprotozoal agent comprises at least one antimalarial agent;

The at least one antiprotozoal agent comprises miparin, chloroquine, or quinine;

The at least one antiprotozoal agent comprises an acridine, preferably melanine, or

The at least one antiprotozoal agent comprises miparin.

15. The method according to paragraph 1 or 8, the use according to paragraph 2 or 8, the at least one cytotoxic agent according to paragraph 3 or 8 for chemically chamfering or inhibiting the angular growth of a young animal, the use according to paragraph 4 or 8, the composition according to paragraph 5 or 8, the syringe according to paragraph 6 or 8 or the kit according to paragraph 7 or 8, wherein the at least one cytotoxic agent comprises at least one apoptosis-inducing agent.

16. The method of paragraph 15, the use of paragraph 15, the at least one cytotoxic agent for use according to paragraph 15 for chemically dehorning or inhibiting the growth of the horn of a young animal when used, the use of paragraph 15, the composition of paragraph 15, the syringe of paragraph 15 or the kit of parts of paragraph 15, wherein:

the at least one apoptosis-inducing agent comprises miparin or cinchocaine;

the at least one apoptosis-inducing agent comprises acridine, preferably melarson, or

The at least one apoptosis-inducing agent comprises miparin.

17. The method according to paragraph 1 or 8, the use according to paragraph 2 or 8, the at least one cytotoxic agent according to paragraph 3 or 8 for chemically chamfering or inhibiting the angular growth of a young animal, the use according to paragraph 4 or 8, the composition according to paragraph 5 or 8, the syringe according to paragraph 6 or 8 or the kit according to paragraph 7 or 8, wherein the at least one cytotoxic agent comprises at least one anesthetic.

18. The method of paragraph 17, the use of paragraph 17, the at least one cytotoxic agent for use in or when used in chemically dehorning a young animal or inhibiting the growth of a young animal, the use of paragraph 17, the composition of paragraph 17, the syringe of paragraph 17, or the kit of parts of paragraph 17, wherein:

the at least one anesthetic comprises an amide anesthetic, an ester anesthetic, or a nonionic surfactant anesthetic;

The at least one anesthetic comprises lidocaine, chloroprocaine, mepivacaine, bupivacaine, atecaine, etidocaine, levobupivacaine, tetracaine, prilocaine, benzocaine, ropivacaine, cocaine, hydroxyprocaine, hexacaine, dibucaine, perralcaine, or procaine, or a pharmaceutically acceptable acid, base, or salt thereof;

the at least one anesthetic comprises miparin, polidocanol, cinchocaine, chloroquine, or quinine;

the at least one anesthetic comprises acridine, preferably melarson, or

The at least one anesthetic agent comprises melarson.

19. The method of paragraph 1 or 8, the use of paragraph 2 or 8, the at least one cytotoxic agent for chemically chamfering or inhibiting the growth of the horn of a young animal according to paragraph 3 or 8, or when used, the use of paragraph 4 or 8, the composition of paragraph 5 or 8, the syringe of paragraph 6 or 8, or the kit of parts of paragraph 7 or 8, wherein the at least one cytotoxic agent comprises mipaline, polidocanol, cinchocaine, chloroquine, or quinine.

20. The method of paragraph 19, the use of paragraph 19, the at least one cytotoxic agent for use in or when used in chemically dehorning a young animal or inhibiting the growth of a young animal, the use of paragraph 19, the composition of paragraph 19, the syringe of paragraph 19, or the kit of parts of paragraph 19, wherein:

The administration or administrable amount of the at least one cytotoxic agent comprises about 100-400mg of miparin as free base;

The administration or administrable amount of at least one cytotoxic agent comprises about 100-400mg of miparin as a salt;

The administration or administrable amount of at least one cytotoxic agent comprises about 100-400mg of miparin dihydrochloride;

the amount of at least one cytotoxic agent administered or administered includes an amount equivalent to about 0.5mL of polidocanol (95% -100%);

The administration or administrable amount of at least one cytotoxic agent comprises about 150-250mg chloroquine as the free base;

the administration or administrable amount of at least one cytotoxic agent comprises about 150-250mg chloroquine as a salt, or

The amount of at least one cytotoxic agent administered or administered comprises about 150-250mg chloroquine diphosphate.

21. The method of any one of paragraphs 1 and 8-20, the use of any one of paragraphs 2 and 8-20, the at least one cytotoxic agent for use in or when used in chemically exfoliating or inhibiting the angular growth of a young animal of any one of paragraphs 3 and 8-20, the use of any one of paragraphs 4 and 8-20, the composition of any one of paragraphs 5 and 8-20, the syringe of any one of paragraphs 6 and 8-20, or the kit of any one of paragraphs 7 and 8-20, wherein the at least one cytotoxic agent is administered or is administered to the young animal by one or more injections, preferably a single injection.

22. The method of any one of paragraphs 1 and 8-21, the use of any one of paragraphs 2 and 8-21, the at least one cytotoxic agent for use in or when used in chemically exfoliating or inhibiting the angular growth of a young animal, the use of any one of paragraphs 4 and 8-21, the composition of any one of paragraphs 5 and 8-21, the syringe of any one of paragraphs 6 and 8-21, or the kit of any one of paragraphs 7 and 8-21, wherein the at least one cytotoxic agent is administered or is administered to the young animal in the form of a liquid composition capable of providing a sustained release of the at least one cytotoxic agent.

23. The method of paragraph 22, the use of paragraph 22, the at least one cytotoxic agent according to paragraph 22 for chemically exfoliating or inhibiting the growth of the horn of a young animal, or when used, for chemically exfoliating or inhibiting the growth of the horn of a young animal, the use of paragraph 22, the composition according to paragraph 22, the syringe according to paragraph 22, or the kit of parts according to paragraph 22, wherein the liquid composition is in the form of a solution, suspension, dispersion, emulsion, or low viscosity gel.

24. The method of paragraph 23, the use of paragraph 23, the at least one cytotoxic agent for chemically exfoliating or inhibiting the growth of the horn of a young animal, according to paragraph 23, the use of paragraph 23, the composition of paragraph 23, the syringe of paragraph 23, or the kit of parts according to paragraph 23, wherein the liquid composition is in the form of a low viscosity injectable gel that is formulated to rapidly gel at the injection site and prolong the release of the at least one cytotoxic agent from the gel.

25. The method of paragraph 24, the use of paragraph 24, the at least one cytotoxic agent for chemically exfoliating or inhibiting the growth of the horn of a young animal according to paragraph 24, or when used, the use of paragraph 24, the composition of paragraph 24, the syringe of paragraph 24, or the kit of parts of paragraph 24, wherein the low viscosity injectable gel comprises one or more gelling agents, one or more solvents or solvent systems, and optionally one or more surfactants.

26. The method of paragraph 25, the use of paragraph 25, the at least one cytotoxic agent for use in or when used in chemically dehorning a young animal or inhibiting the growth of a young animal, the use of paragraph 25, the composition of paragraph 25, the syringe of paragraph 25, or the kit of parts of paragraph 25, wherein the low viscosity injectable gel comprises:

sucrose Acetate Isobutyrate (SAIB) and at least one solvent as the one or more gelling agents, or

SAIB as the one or more gelling agents, at least one solvent, and at least one surfactant.

27. The method of paragraph 26, the use of paragraph 26, the at least one cytotoxic agent for use in or when used in chemically dehorning a young animal or inhibiting the growth of a young animal according to paragraph 26, the use of paragraph 26, the composition of paragraph 26, the syringe of paragraph 26 or the kit of parts of paragraph 26, wherein the low viscosity injectable gel comprises:

about 30% -90% w/v SAIB;

About 40% -85% w/v SAIB;

about 70% -80% w/v SAIB, or

About 70% w/v SAIB.

28. The method of paragraph 26 or 27, the use of paragraph 26 or 27, the at least one cytotoxic agent for chemically chamfering or inhibiting the angular growth of a young animal according to paragraph 26 or 27, the use of paragraph 26 or 27, the composition of paragraph 26 or 27, the syringe of paragraph 26 or 27, or the kit of parts of paragraph 26 or 27, wherein the low viscosity injectable gel comprises:

About 0-50% w/v of the at least one solvent, or

About 15-30% w/v of the at least one solvent.

29. The method of paragraph 28, the use of paragraph 28, the at least one cytotoxic agent for chemically dehorning or inhibiting the growth of the horn of a young animal, according to paragraph 28, the use of paragraph 28, the composition of paragraph 28, the syringe of paragraph 28, or the kit of parts of paragraph 28, wherein the at least one solvent comprises one or more of ethanol, diethylene glycol monoethyl ether (DEGEE), N-methylpyrrolidone (NMP), glyceryl triacetate, benzyl benzoate, miglyol, propylene carbonate, benzyl alcohol, ethyl lactate, tetraethylene glycol, 2-pyrrolidone, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decyl methyl sulfoxide, oleic acid, and 1-dodecyl azepan-2-one.

30. The method of paragraph 26, 27, 28 or 29, the use of paragraph 26, 27, 28 or 29, the at least one cytotoxic agent of paragraph 26, 27, 28 or 29 for chemically chamfering or inhibiting the angular growth of a young animal, or when used, the use of paragraph 26, 27, 28 or 29, the composition of paragraph 26, 27, 28 or 29, the syringe of paragraph 26, 27, 28 or 29 or the kit of parts 26, 27, 28 or 29, wherein the low viscosity injectable gel comprises:

about 0-3% w/v of the at least one surfactant;

About 0-2% w/v of the at least one surfactant;

about 0-1% w/v of the at least one surfactant;

about 1-3% w/v of the at least one surfactant, or

About 1-2% w/v of the at least one surfactant.

31. The method of paragraph 30, the use of paragraph 30, the at least one cytotoxic agent according to paragraph 30 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, for chemically dehorning or inhibiting the growth of the horn of a young animal, the use of paragraph 30, the composition according to paragraph 30, the syringe according to paragraph 30, or the kit of parts according to paragraph 30, wherein the at least one surfactant comprises one or more of a nonionic surfactant, polysorbate, tween, polyoxyethylene (20) sorbitan monooleate (Tween 80) or polyoxyethylene (20) sorbitan monolaurate (Tween 20).

32. The method of paragraph 26, the use of paragraph 26, the at least one cytotoxic agent according to paragraph 26 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, for chemically dehorning or inhibiting the growth of the horn of a young animal, the use of paragraph 26, the composition of paragraph 26, the syringe of paragraph 26, or the kit of parts of paragraph 26, wherein the low viscosity injectable gel comprises all in about% w/v,

10% W/v of the at least one cytotoxic agent, preferably melalin or a melalin salt providing 10% w/v of melalin, such as 11.8% w/v of melalin dihydrochloride;

40-85%w/v SAIB;

0-2%w/v Tween 80;

0-50% w/v glyceryl triacetate;

0-50% w/v DEGEE, and

Ethanol is made up to 100% by volume, wherein:

the concentration of ethanol is 0-30% w/v, or

In the absence of other solvents and Tween, and at a 10% miparin and SAIB level of 80% w/v, assuming a weight of 1.1g per mL of formulation, the ethanol concentration was 20% w/v.

33. The method of paragraph 26, the use of paragraph 26, the at least one cytotoxic agent according to paragraph 26 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, for chemically dehorning or inhibiting the growth of the horn of a young animal, the use of paragraph 26, the composition of paragraph 26, the syringe of paragraph 26, or the kit of parts of paragraph 26, wherein the low viscosity injectable gel comprises all in about% w/v,

20% W/v of the at least one cytotoxic agent, preferably melalin or a melalin salt providing 20% w/v of melalin, such as 23.6% w/v of melalin dihydrochloride;

40-85%w/v SAIB;

0-2%w/v Tween 80;

0-50% w/v glyceryl triacetate;

0-50% w/v DEGEE, and

Ethanol is made up to 100% by volume, wherein:

the concentration of ethanol is 0-30% w/v, or

In the absence of other solvents and Tween, and at a level of 85% w/v for 23.6% miparin dihydrochloride and SAIB, assuming a weight of 1.1g per mL, the ethanol concentration is 1.4% w/v, which may be too low, in which case the maximum concentration of SAIB must be reduced.

34. The method of paragraph 26, the use of paragraph 26, the at least one cytotoxic agent according to paragraph 26 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, for chemically dehorning or inhibiting the growth of the horn of a young animal, the use of paragraph 26, the composition of paragraph 26, the syringe of paragraph 26, or the kit of parts of paragraph 26, wherein the low viscosity injectable gel comprises all in about% w/v,

70%w/v SAIB;

1%w/v Tween 80;

5% w/v glyceryl triacetate;

0% w/v DEGEE, and

Ethanol is made up to 100% by volume, i.e., 22.2% w/v ethanol assuming a weight of 1.1g per mL.

35. The method of paragraph 26, the use of paragraph 26, the at least one cytotoxic agent according to paragraph 26 for chemically dehorning or inhibiting the growth of the horn of a young animal, or when used, for chemically dehorning or inhibiting the growth of the horn of a young animal, the use of paragraph 26, the composition of paragraph 26, the syringe of paragraph 26, or the kit of parts of paragraph 26, wherein the low viscosity injectable gel comprises all in about% w/v,

70%w/v SAIB;

1%w/v Tween 80;

5% w/v glyceryl triacetate;

0% w/v DEGEE, and

Ethanol is made up to 100% by volume, i.e. 10.4% w/v ethanol assuming a weight of 1.1g per mL.

36. A composition formulated as a solution, suspension, dispersion, emulsion, low viscosity gel, or other sustained release liquid formulation comprising at least one cytotoxic agent and one or more excipients and capable of providing sustained release of the at least one cytotoxic agent, wherein the at least one cytotoxic agent is one or more of a sclerosant, a p53 activator, an antiprotozoal agent, an apoptosis inducer, and a local anesthetic.

37. A composition according to paragraph 36, which is formulated as an injectable oily solution or suspension and comprises at least one oily excipient.

38. A composition according to paragraph 37, comprising, all in about% w/v,

Aqueous or oily suspensions, preferably oily suspensions.

39. The composition of paragraph 36 formulated as a low viscosity injectable gel.

40. A composition according to paragraph 39, which is formulated to rapidly gel at the injection site of an animal and to prolong the release of the at least one cytotoxic agent from the gel.

41. A composition according to paragraph 39 or 40, comprising, all in about% w/v,

10-15% W/v of at least one cytotoxic agent, preferably melarson or a salt thereof providing 10-15% w/v melarson, such as 11.8-17.7% w/v melarson dihydrochloride.

42. The composition of paragraphs 39, 40 or 41, wherein the low viscosity injectable gel comprises one or more gelling agents, one or more solvents or solvent systems, and optionally one or more surfactants.

43. The composition of paragraph 42, wherein the low viscosity injectable gel comprises:

44. The composition of paragraph 43, wherein the low viscosity injectable gel comprises:

about 30% -90% w/v SAIB;

About 40% -85% w/v SAIB;

about 70% -80% w/v SAIB, or

About 70% w/v SAIB.

45. The composition of paragraph 43 or 44, wherein the low viscosity injectable gel comprises:

About 0-50% w/v of the at least one solvent, or

About 15-30% w/v of the at least one solvent.

46. A composition according to paragraph 45, wherein the at least one solvent comprises one or more of ethanol, diethylene glycol monoethyl ether (DEGEE), N-methylpyrrolidone (NMP), glyceryl triacetate, benzyl benzoate, miglyol, propylene carbonate, benzyl alcohol, ethyl lactate, tetraethylene glycol, 2-pyrrolidone, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decyl methyl sulfoxide, oleic acid, and 1-dodecyl azepan-2-one.

47. The composition of paragraphs 42, 43, 44, 45 or 46, wherein the low viscosity injectable gel comprises:

about 0-3% w/v of the at least one surfactant;

About 0-2% w/v of the at least one surfactant;

about 0-1% w/v of the at least one surfactant;

about 1-3% w/v of the at least one surfactant, or

About 1-2% w/v of the at least one surfactant.

48. The composition of paragraph 47 wherein the at least one surfactant comprises one or more of a nonionic surfactant, a polysorbate, tween, polyoxyethylene (20) sorbitan monooleate (Tween 80), or polyoxyethylene (20) sorbitan monolaurate (Tween 20).

49. The composition of paragraphs 41, 42, 43, 44, 45, 46, 47 or 48 wherein the low viscosity injectable gel comprises all in about% w/v,

40-85%w/v SAIB;

0-2%w/v Tween 80;

0-50% w/v glyceryl triacetate;

0-50% w/v DEGEE, and

Ethanol is made up to 100% by volume, wherein:

the concentration of ethanol is 0-30% w/v, or

In the absence of other solvents and Tween, and at SAIB levels of 80% w/v, assuming a weight of 1.1g per mL of formulation, the ethanol concentration is 18.2% w/v.

50. The composition of paragraphs 41, 42, 43, 44, 45, 46, 47 or 48 wherein the low viscosity injectable gel comprises all in about% w/v,

40-85%w/v SAIB;

0-2%w/v Tween 80;

0-50% w/v glyceryl triacetate;

0-50% w/v DEGEE, and

Ethanol is made up to 100% by volume, wherein:

the concentration of ethanol is 0-30% w/v, or

In the absence of other solvents and Tween, and at SAIB levels of 85% w/v, assuming a weight of 1.1g per mL, the ethanol concentration is 1.4% w/v, which may be too low, in which case the maximum SAIB concentration must be reduced.

51. The composition of paragraphs 41, 42, 43, 44, 45, 46, 47 or 48 wherein the low viscosity injectable gel comprises all in about% w/v,

70%w/v SAIB;

1%w/v Tween 80;

5% w/v glyceryl triacetate;

0% w/v DEGEE, and

52. The composition of paragraphs 41, 42, 43, 44, 45, 46, 47 or 48 wherein the low viscosity injectable gel comprises all in about% w/v,

70%w/v SAIB;

1%w/v Tween 80;

5% w/v glyceryl triacetate;

0% w/v DEGEE, and

53. The composition of any one of paragraphs 36-52, wherein the at least one cytotoxic agent is melalin dihydrochloride.

54. The method of paragraph 1, the use of paragraph 2, the at least one cytotoxic agent according to paragraph 3 for chemically dehorning or inhibiting the growth of the horn of a young animal when used, the use of paragraph 4, the syringe of paragraph 6 or the kit of parts of paragraph 7, wherein the at least one cytotoxic agent is formulated as a composition according to any one of paragraphs 36-53.

A composition, medicament or formulation as described herein (including examples and claims, including any tables set forth herein).

Drawings

Other aspects of the invention will become apparent from the ensuing description (embodiments) and with reference to the accompanying drawings, which description is given by way of example only, in which:

FIG. 1-relates to example 3. The calves were chemically dehorned with eugenol. Painless swelling of eugenol injection site.

FIG. 2-relates to example 3. Representative images of different chemical dehorning treatments were used on calves 1) eugenol, 2) melarson, 3) eugenol + melarson aqueous solution (20:80), and 4) eugenol + melarson aqueous solution (80:20).

Examples

Example 1 chemical corner removal Using Mipalin

A study was conducted to test the chamfering effect of the application of melalin dihydrochloride to the horn buds as compared to the traditional iron chamfering method. The miparin dihydrochloride is administered as a composition comprising miparin dihydrochloride suspended in water. The composition is prepared by dispersing the powder of the miparin dihydrochloride in water for injection. Immediately prior to administration, the composition was shaken to re-suspend the miparin dihydrochloride salt.

Animals under study (calves) were divided into groups. Groups 1-4 were administered with a single dose of 0.5mL of the melarsoprol dihydrochloride composition, and each group was administered with a composition having a different concentration of melarsoprol dihydrochloride, ranging from 50mg/mL to 400mg/mL.

Groups 5-8 were administered with divided doses of 0.5mL of the combination of miparin dihydrochloride, each group was administered with a combination of miparin dihydrochloride at a different concentration ranging from 50mg/mL to 400mg/mL. Each divided dose included administration of 5 0.1mL doses around the horn bud.

The administration of the miparin dihydrochloride is performed by injecting the miparin dihydrochloride composition using a McLintock preset syringe configured to administer up to 0.5 mL. Single dose administration of groups 1-4 was performed by injecting the composition directly into the horn buds. The divided dose administrations of groups 5-8 were performed by injecting smaller multiple doses into the area immediately surrounding the horn buds. Animals in control group 9 were first treated with 2% lidocaine injection as a corner nerve blocker and then corner removed using a conventional soldering iron.

Each animal in the study had a chamfering procedure, i.e. the use of melalin dihydrochloride or iron chamfering, was applied only to the right-angle buds. The left-hand buds of each animal were not treated as a control.

The animals in the study were calves of cows, gradually entering the study and receiving treatment at 7 days of age.

The study protocol and results are shown in table 1. Success rate is based on the proportion of corner buds that are treated with subsequent no corner growth or the presence of a corner residue. The stub angle is the angle of deformation that is not attached to the skull. For higher concentrations of miparin dihydrochloride, the miparin chamfering procedure was found to be most successful. In particular, administration of 0.5mL of 200mg/mL and 400mg/L of melalin dihydrochloride has a high success rate in both single injections and divided doses using multiple injections. Untreated horn buds developed into horns on each animal.

Animals receiving the miparin corner-removal treatment were observed to exhibit very little pain response. Animals receiving injections exhibited discomfort during the injection and no subsequent pain activity after the end of the injection.

TABLE 1 Minpalin corner removal study

The success rate was higher for the 200 and 400mg/mL high concentration groups compared to the 50 and 100mg/mL lower concentration groups. There is no obvious advantage in dividing the dose into multiple injections.

The application procedure for chamfering by applying mipaline to each animal was less than 1 minute, whereas chamfering the animals with a soldering iron required 5-10 minutes. Animals treated with miparin showed little discomfort during administration, nor did they show pain response/behavior.

EXAMPLE 2 chemical corner removal Using chloroquine diphosphate and polidocanol

A study was conducted on calves to test the chamfering efficacy of chloroquine diphosphate and polidocanol applied to diagonal buds.

The chloroquine diphosphate is applied as a composition comprising chloroquine diphosphate suspended in water. The composition is prepared by dispersing chloroquine diphosphate powder into water for injection. Immediately prior to administration, the composition is shaken to resuspend the chloroquine diphosphate.

Polidocanol is administered as undiluted polidocanol at 100% concentration at the time of administration or as a diluted solution in the 90%, 50% and 10% concentration groups diluted with water.

Animals under study were divided into groups. Group 1 and group 2 were administered with physiological saline solution (0.9% sodium chloride), group 1 was administered as a single dose, and group 2 was administered as divided doses. Each divided dose included 5 0.1mL doses administered around the horn bud.

Groups 3 and 4 were administered 100mg/mL or 300mg/mL chloroquine diphosphate, groups 5-8 were administered polidocanol at different concentrations ranging from 100% -10% w/v.

The saline control group did not change the normal angular growth. Chloroquine diphosphate showed some success at a concentration of 300mg/mL, with half animals having no horn growth at all, while other animals formed only residual horns. Polidocanol was successful at 100% and 10% concentrations, while at other concentrations the success rate was lower. Higher concentrations of the composition were observed to have high viscosity, and the lack of success was likely due to insufficient application into the horn bud-e.g., when applied at a concentration of 90%.

TABLE 2 corner removal study of chloroquine and polidocanol

EXAMPLE 3 chemical corner removal Using Mipalin and eugenol

Methodology of

16 Calves (4-6 days old) obtained from commercial dairy farms were used in this study. Calves were randomly assigned to receive one of four formulations (Table 3). The animals were gently bound and the hair around the horn bud area was cut. Formulations (0.3-0.5 mL) were then subcutaneously injected under or around the right-angle buds using McLintock syringes and needles (22 g 11/64",0.71 x 4.3 mm), delivering 0.1mL per injection. The left-hand buds served as controls. Details of the processing are shown in table 3 below. The animals were observed for pain-related behavior during and after injection. The difference in the growth rate of the left and right buds was determined by periodically measuring the heights of the buds. At the same time, a photograph of the horn bud is taken. After 4 months, calves were euthanized by intravenous injection of sodium pentobarbital (100 mg/kg body weight) for general pathology and histopathology of the horn buds.

TABLE 3 details of the treatment

Eugenol-SIGMA ALDRICH (Lot#STBG9481); mipaline or quinicoline dihydrochloride-SIGMA ALDRICH (Lot# BCBR 3327)

Results

During injection of the formulation, calves show minimal resistance. The time of each injection is less than one second, and the total time of injection after calf restraint is less than one minute. No pain-related behavioral signs, such as shaking or grabbing the head, were observed in any animals after injection of the formulation. Periangular bud swelling was observed following injection of eugenol and eugenol + melalin aqueous solutions (80:20). Swelling is painless to the touch and detumescence after a few days. In addition, scars and pits were observed at the injection site of animals receiving eugenol and eugenol + melalin (80:20). No such adverse reactions were observed in the other two groups. The growth rate of the horn buds is shown in Table 4.

TABLE 4 growth Rate of the buds following injection of formulation into Right-angle buds

Summary

TABLE 5 subjective evaluation of efficacy

Findings of example 3

The chamfering technique of this embodiment appears to be simple, quick, effective, and does not require post-operative pain relief.

The main findings are:

1) The use of McLintock syringes and needles to inject the formulation is quick, simple and causes minimal pain.

2) All formulations appeared to prevent growth when injected under the horn buds.

3) Injection around the horn buds reduced growth but did not completely prevent growth in most animals.

4) Eugenol and its combination (eugenol + melalin aqueous solution (80:20)) produced slight swelling and scarring at the injection site. Such effects were not seen after injection of aqueous solutions of miparin or eugenol + aqueous solutions of miparin (20:80).

5) The absence of pain-related behavioral signs after injection may mean that if these formulations are used, no post-operative pain relief is required.

General conclusion

The inventors have found that miparin, polidocanol and chloroquine act as effective chemical exfoliants, thereby overcoming or reducing many of the disadvantages of previously known exfoliating procedures.

Animals appear to be well tolerated by injection of these chemical keratoses.

These chemical exfoliants are safer and easier to apply than conventional exfoliating techniques.

A single injection of these chemical exfoliants can exfoliate animals.

These chemical exfoliants target the keratinocytes/horn tissue and therefore cause much less collateral damage to surrounding tissue than some conventional exfoliating techniques.

These chemical keratolytic agents provide local anesthetic action, thereby eliminating the need for post-operative pain relief.

Unlike eugenol, these chemical exfoliants do not produce swelling at the injection site.

Unlike eugenol, these chemical exfoliants do not create open wounds or scars at the injection site, thereby reducing the chance of infection.

EXAMPLE 4 Low viscosity injectable gel formulation SAIB+cytotoxic Agents

It is believed that compositions that provide prolonged release of the cytotoxic agent from the injection site may provide the same or better chamfer results. It is believed that lower amounts of cytotoxic agent may be used in the injectable extended release composition than in the cytotoxic agent tested. It is contemplated that the composition to be administered may be in the form of a low viscosity injectable gel (solution or suspension) that rapidly gels at the injection site to retain the cytotoxic agent for an appropriate (therapeutically effective) time. In this way, a relatively large amount of cytotoxic agent can be delivered to the keratinocytes (the keratinous tissue). It is believed that this can be achieved with a composition comprising a cytotoxic agent, sucrose Acetate Isobutyrate (SAIB) and a solvent. Upon injection of the composition comprising the SAIB formulation and the solvent, the solvent diffuses out leaving a viscous and thick matrix. The matrix may retain the cytotoxic agent in the keratinocytes for a period of time rather than immediately dispersing the cytotoxic agent.

Preferred cytotoxic agent + SAIB formulations are described below.

Component ranges

Although the solvents glyceryl triacetate, transcutol ^TM (diethylene glycol monoethyl ether) and ethanol are exemplified below, other solvents may be used instead of or in addition to these solvents. The inventors' research principle is that they require 40-85% SAIB and up to 30% ethanol to adjust the release rate of the cytotoxic agent.

TABLE 6 component ranges for cytotoxic agent + SAIB formulations

Composition of the components	g	%w/v
			Cytotoxic agent:)	0.1	10
SAIB	0.4-0.85	40-85
			Tween 80	0.0-0.02	0-2
Glyceryl triacetate	0-0.5	0-50
			Transcutol^TM	0-0.5	0-50
Ethanol make-up to	1.0mL	100

* Melalin dihydrochloride is taken as an example.

* The mass of ethanol varies from 0 to 0.3g, i.e., 0-30% w/v, and 0.15g (15% w/v) ethanol, assuming a weight of 1.1g per mL of formulation, at an SAIB level of 0.85g (85%) in the absence of other solvents and Tween.

TABLE 7 cytotoxicity agent+SAIB formulation ingredient ranges

* Melalin dihydrochloride is taken as an example.

* The mass of ethanol may vary from 0 to 0.45g, i.e. 0 to 30% w/v, at an SAIB level of 1.275g (85%) without other solvents and Tween, ethanol is 0.075g (5%), which may be too low, in which case the maximum concentration of SAIB must be reduced.

TABLE 8 preferred cytotoxic agent+SAIB formulations

Composition of the components	g	%w/v
			Cytotoxic agent:)	0.1	10
SAIB	0.7	70
			Tween 80	0.01	1
Glyceryl triacetate	0.05	5
			Transcutol^TM	0	0
Ethanol make-up to	1.0mL	100 (I.e., about 24% w/v)

* Take as an example the mipaline as dihydrochloride, thus 0.118g of mipaline dihydrochloride.

* The mass of ethanol required was 0.22g or 22% w/v (assuming a weight per mL of 1.1 g).

TABLE 8 preferred cytotoxic agent+SAIB formulations

Composition of the components	g	%w/v
			Cytotoxic agent:)	0.3	20
SAIB	0.975	65
			Tween 80	0.015	1
Glyceryl triacetate	0.075	5
			Transcutol^TM	0	0
Ethanol make-up to	1.5mL	100, I.e., about 19% w/v)

* Take as an example the mipaline as dihydrochloride, thus 0.355g mipaline dihydrochloride.

* The mass of ethanol required was 0.23g or 15.3% w/v (assuming a weight of 1.1g per mL of formulation).

All estimates of% w/v ethanol assume a weight of 1.1g per mL of formulation. The actual values may vary, for example, as the SAIB content decreases, the weight per mL may be lower. The actual value will be determined experimentally using well known methods.

The various aspects of the present invention have been described by way of example only, and it should be appreciated that modifications and additions may be made thereto without departing from the scope thereof as defined in the accompanying claims.

All references, including any patents or patent applications cited in this specification are incorporated herein by reference. No admission is made that any reference constitutes prior art. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art in any country.

Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

The term "about" or "approximately" refers generally to plus or minus 10% of the referenced number, where the context permits, but this need not be the case.

Claims

1. A method for chemically dehorning or inhibiting horn growth in young animals by administering at least one cytotoxic agent to horn bud cells of the animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

2. Use of at least one cytotoxic agent for chemical dehorning of young animals or inhibiting horn growth of young animals, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

3. At least one cytotoxic agent for use in or when used for chemically dehorning a young animal or inhibiting horn growth in a young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

4. Use of at least one cytotoxic agent in the preparation of a medicament for chemical dehorning of young animals or inhibiting horn growth of young animals, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

5. A composition comprising at least one cytotoxic agent, the composition being formulated for administration to a juvenile animal and for chemically dehorning the juvenile animal or inhibiting horn growth in the juvenile animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

6. A syringe containing at least one cytotoxic agent, the cytotoxic agent is used or when used for dehorning a young animal or inhibiting horn growth of a young animal, wherein the syringe is capable of administering the at least one cytotoxic agent to the horn bud cells of the young animal, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

7. A kit of parts for use in or when used in a method for dehorning a young animal or inhibiting horn growth of a young animal, wherein the kit of parts comprises: a syringe capable of administering at least one cytotoxic agent to horn bud cells of a young animal; and at least one cytotoxic agent, wherein the at least one cytotoxic agent kills the horn bud cells in a certain amount, wherein the at least one cytotoxic agent comprises at least one sclerosant, p53 activator, antiprotozoal agent, apoptosis inducer or local anesthetic.

8. The method according to claim 1, the use according to claim 2, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 3, the use according to claim 4, the composition according to claim 5, the syringe according to claim 6 or the kit according to claim 7, wherein the at least one cytotoxic agent is in the form of a free acid, a free base or a salt.

9. The method according to claim 1 or 8, the use according to claim 2 or 8, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 3 or 8, the use according to claim 4 or 8, the composition according to claim 5 or 8, the syringe according to claim 6 or 8 or the kit according to claim 7 or 8, wherein the at least one cytotoxic agent comprises at least one sclerosing agent.

10. The method according to claim 9, the use according to claim 9, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 9, the use according to claim 9, the composition according to claim 9, the syringe according to claim 9 or the kit according to claim 9, wherein:

The at least one sclerosing agent comprises imipaline (quinacrine), chloroquine, polidocanol or quinine;

The at least one hardener comprises an acridine, preferably mepacrine; or

The at least one hardening agent comprises mepacrine.

11. The method according to claim 1 or 8, the use according to claim 2 or 8, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 3 or 8, the use according to claim 4 or 8, the composition according to claim 5 or 8, the syringe according to claim 6 or 8 or the kit according to claim 7 or 8, wherein the at least one cytotoxic agent comprises at least one p53 activator.

12. The method according to claim 11, the use according to claim 11, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 11, the use according to claim 11, the composition according to claim 11, the syringe according to claim 11 or the kit according to claim 11, wherein:

The at least one p53 activator comprises mepaline or chloroquine;

The at least one p53 activator comprises an acridine, preferably mepacrine; or

The at least one p53 activator comprises mepacrine.

13. The method according to claim 1 or 8, the use according to claim 2 or 8, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 3 or 8, the use according to claim 4 or 8, the composition according to claim 5 or 8, the syringe according to claim 6 or 8 or the kit according to claim 7 or 8, wherein the at least one cytotoxic agent comprises at least one antiprotozoal agent.

14. The method according to claim 13, the use according to claim 13, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 13, the use according to claim 13, the composition according to claim 13, the syringe according to claim 13 or the kit according to claim 13, wherein:

The at least one antiprotozoal agent comprises at least one antimalarial agent;

The at least one antiprotozoal agent comprises mepacrine, chloroquine, or quinine;

The at least one antiprotozoal agent comprises an acridine, preferably mepacrine; or

The at least one antiprotozoal agent comprises mepacrine.

15. The method according to claim 1 or 8, the use according to claim 2 or 8, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 3 or 8, the use according to claim 4 or 8, the composition according to claim 5 or 8, the syringe according to claim 6 or 8 or the kit according to claim 7 or 8, wherein the at least one cytotoxic agent comprises at least one apoptosis inducer.

16. The method according to claim 15, the use according to claim 15, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 15, the use according to claim 15, the composition according to claim 15, the syringe according to claim 15 or the kit according to claim 15, wherein:

The at least one apoptosis inducer comprises mepacrine or cinchocaine;

The at least one apoptosis inducing agent comprises an acridine, preferably mepacrine; or

The at least one apoptosis inducer comprises mepacrine.

17. The method according to claim 1 or 8, the use according to claim 2 or 8, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 3 or 8, the use according to claim 4 or 8, the composition according to claim 5 or 8, the syringe according to claim 6 or 8 or the kit according to claim 7 or 8, wherein the at least one cytotoxic agent comprises at least one anesthetic agent.

18. The method according to claim 17, the use according to claim 17, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 17, the use according to claim 17, the composition according to claim 17, the syringe according to claim 17 or the kit according to claim 17, wherein:

The at least one anesthetic agent comprises an amide anesthetic, an ester anesthetic, or a non-ionic surfactant anesthetic;

The at least one anesthetic agent comprises lidocaine, chloroprocaine, mepivacaine, bupivacaine, articaine, etidocaine, levobupivacaine, tetracaine, prilocaine, benzocaine, ropivacaine, cocaine, hydroxyprocaine, hexylcaine, dibucaine, perralcaine or procaine, or a pharmaceutically acceptable acid, base or salt thereof;

The at least one anesthetic agent comprises mepacrine, polidocanol, cinchocaine, chloroquine or quinine;

The at least one anesthetic comprises an acridine, preferably mepacrine; or

The at least one anesthetic agent comprises mepacrine.

19. The method according to claim 1 or 8, the use according to claim 2 or 8, the at least one cytotoxic agent for chemical dehorning of young animals or inhibiting horn growth of young animals according to claim 3 or 8, the use according to claim 4 or 8, the composition according to claim 5 or 8, the syringe according to claim 6 or 8 or the kit according to claim 7 or 8, wherein the at least one cytotoxic agent comprises mepacrine, polidocanol, cinchocaine, chloroquine or quinine.

20. The method according to claim 19, the use according to claim 19, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 19, the use according to claim 19, the composition according to claim 19, the syringe according to claim 19 or the kit according to claim 19, wherein:

The at least one cytotoxic agent is administered or administrable in an amount comprising about 100-400 mg of mepaline as a free base;

The at least one cytotoxic agent is administered or administrable in an amount comprising about 100-400 mg of mepacrine as a salt;

The amount of at least one cytotoxic agent administered or administrable comprises about 100-400 mg of mepaline as the dihydrochloride salt;

The at least one cytotoxic agent is administered or administrable in an amount comprising an amount equivalent to about 0.5 mL of polidocanol (95%-100%);

The at least one cytotoxic agent is administered or administrable in an amount comprising about 150-250 mg of chloroquine as a free base;

The at least one cytotoxic agent is administered or administrable in an amount comprising about 150-250 mg of chloroquine as a salt; or

The amount of at least one cytotoxic agent administered or administrable comprises about 150-250 mg of chloroquine diphosphate.

21. The method according to any one of claims 1 and 8-20, the use according to any one of claims 2 and 8-20, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to any one of claims 3 and 8-20, the use according to any one of claims 4 and 8-20, the composition according to any one of claims 5 and 8-20, the syringe according to any one of claims 6 and 8-20 or the kit according to any one of claims 7 and 8-20, wherein the at least one cytotoxic agent is administered or can be administered to the young animal by one or more injections, preferably a single injection.

22. The method according to any one of claims 1 and 8-21, the use according to any one of claims 2 and 8-21, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to any one of claims 3 and 8-21, the use according to any one of claims 4 and 8-21, the composition according to any one of claims 5 and 8-21, the syringe according to any one of claims 6 and 8-21 or the kit according to any one of claims 7 and 8-21, wherein the at least one cytotoxic agent is administered or is administerable to the young animal in the form of a liquid composition capable of providing a sustained release of the at least one cytotoxic agent.

23. The method according to claim 22, the use according to claim 22, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 22, the use according to claim 22, the composition according to claim 22, the syringe according to claim 22 or the kit according to claim 22, wherein the liquid composition is in the form of a solution, a suspension, a dispersion, an emulsion or a low viscosity gel.

24. The method of claim 23, the use of claim 23, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal, the use of claim 23, the composition of claim 23, the syringe of claim 23 or the kit of parts of claim 23, wherein the liquid composition is in the form of a low viscosity injectable gel formulated to gel rapidly at the injection site and to prolong the release of the at least one cytotoxic agent from the gel.

25. The method according to claim 24, the use according to claim 24, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 24, the use according to claim 24, the composition according to claim 24, the syringe according to claim 24 or the kit of parts according to claim 24, wherein the low viscosity injectable gel comprises one or more gelling agents, one or more solvents or solvent systems, and optionally one or more surfactants.

26. The method according to claim 25, the use according to claim 25, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 25, the use according to claim 25, the composition according to claim 25, the syringe according to claim 25 or the kit according to claim 25, wherein the low viscosity injectable gel comprises:

Sucrose acetate isobutyrate (SAIB) and at least one solvent as the one or more gelling agents; or

SAIB as the one or more gelling agents, at least one solvent and at least one surfactant.

27. The method according to claim 26, the use according to claim 26, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal, the use according to claim 26, the composition according to claim 26, the syringe according to claim 26 or the kit according to claim 26, wherein the low viscosity injectable gel comprises:

About 30%-90% w/v SAIB;

About 40%-85% w/v SAIB;

About 70%-80% w/v SAIB; or

About 70% w/v SAIB.

28. The method according to claim 26 or 27, the use according to claim 26 or 27, the at least one cytotoxic agent for or when used for chemical dehorning of young animals or inhibiting horn growth in young animals according to claim 26 or 27, the use according to claim 26 or 27, the composition according to claim 26 or 27, the syringe according to claim 26 or 27 or the kit according to claim 26 or 27, wherein the low viscosity injectable gel comprises:

about 0-50% w/v of the at least one solvent; or

About 15-30% w/v of the at least one solvent.

29. The method of claim 28, the use of claim 28, the at least one cytotoxic agent for or when used for chemically dehorning a young animal or inhibiting horn growth in a young animal, the use of claim 28, the composition of claim 28, the syringe of claim 28 or the kit of parts of claim 28, wherein the at least one solvent comprises one or more of ethanol, diethylene glycol monoethyl ether (DEGEE), N-methylpyrrolidone (NMP), triacetin, benzyl benzoate, miglyol, propylene carbonate, benzyl alcohol, ethyl lactate, tetraethylene glycol, 2-pyrrolidone, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decyl methyl sulfoxide, oleic acid and 1-dodecylazacycloheptan-2-one.

30. The method of claim 26, 27, 28 or 29, the use of claim 26, 27, 28 or 29, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal, the use of claim 26, 27, 28 or 29, the composition of claim 26, 27, 28 or 29, the syringe of claim 26, 27, 28 or 29 or the kit of parts of claim 26, 27, 28 or 29, wherein the low viscosity injectable gel comprises:

about 0-3% w/v of said at least one surfactant;

about 0-2% w/v of said at least one surfactant;

about 0-1% w/v of the at least one surfactant;

about 1-3% w/v of the at least one surfactant; or

About 1-2% w/v of the at least one surfactant.

31. The method according to claim 30, the use according to claim 30, the at least one cytotoxic agent for chemically dehorning a young animal or inhibiting horn growth in a young animal according to claim 30, the use according to claim 30, the composition according to claim 30, the syringe according to claim 30 or the kit according to claim 30, wherein the at least one surfactant comprises one or more of the following: a nonionic surfactant, a polysorbate, Tween, polyoxyethylene (20) sorbitan monooleate (Tween 80) or polyoxyethylene (20) sorbitan monolaurate (Tween 20).

32. The method of claim 26, the use of claim 26, the at least one cytotoxic agent for chemical dehorning of a young animal or inhibiting horn growth of a young animal, the use of claim 26, the composition of claim 26, the syringe of claim 26 or the kit of parts of claim 26, wherein the low viscosity injectable gel comprises: all in about % w/v,

10% w/v of the at least one cytotoxic agent, preferably mepacrine or a mepacrine salt providing 10% w/v mepacrine, such as 11.8% w/v mepacrine dihydrochloride;

40-85% w/v SAIB;

0-2% w/v Tween 80;

0-50% w/v triacetin;

0-50% w/v DEGEE; and

Ethanol is made up to 100% volume, where:

The concentration of ethanol is 0-30% w/v; or

In the absence of other solvents and Tween, and at a SAIB level of 80% w/v, assuming a weight of 1.1 g per mL of formulation, the ethanol concentration was 18.2% w/v.

33. The method of claim 26, the use of claim 26, the at least one cytotoxic agent for chemical dehorning of a young animal or inhibiting horn growth of a young animal, the use of claim 26, the composition of claim 26, the syringe of claim 26 or the kit of parts of claim 26, wherein the low viscosity injectable gel comprises: all in about % w/v,

20% w/v of the at least one cytotoxic agent, preferably mepacrine or a mepacrine salt providing 20% w/v mepacrine, such as mepacrine dihydrochloride at 23.6% w/v;

40-85% w/v SAIB;

0-2% w/v Tween 80;

0-50% w/v triacetin;

0-50% w/v DEGEE; and

Ethanol is made up to 100% volume, where:

The concentration of ethanol is 0-30% w/v; or

In the absence of other solvents and Tween, and at a SAIB level of 85% w/v, assuming a weight of 1.1 g per mL, the ethanol concentration is 1.4% w/v, which may be too low, in which case the maximum SAIB concentration must be reduced.

34. The method of claim 26, the use of claim 26, the at least one cytotoxic agent for chemical dehorning of a young animal or inhibiting horn growth of a young animal, the use of claim 26, the composition of claim 26, the syringe of claim 26 or the kit of parts of claim 26, wherein the low viscosity injectable gel comprises: all in about % w/v,

70% w/v SAIB;

1% w/v Tween 80;

5% w/v triacetin;

0% w/v DEGEE; and

The ethanol was made up to 100% volume, ie, 22.2% w/v ethanol, assuming a weight of 1.1 g per mL.

35. The method of claim 26, the use of claim 26, the at least one cytotoxic agent for chemical dehorning of a young animal or inhibiting horn growth of a young animal, the use of claim 26, the composition of claim 26, the syringe of claim 26 or the kit of parts of claim 26, wherein the low viscosity injectable gel comprises: all in about % w/v,

70% w/v SAIB;

1% w/v Tween 80;

5% w/v triacetin;

0% w/v DEGEE; and

The ethanol was made up to 100% volume, ie, assuming a weight of 1.1 g per mL, it was 10.4% w/v ethanol.

36. A composition formulated as a solution, suspension, dispersion, emulsion, low viscosity gel or other sustained release liquid preparation, comprising at least one cytotoxic agent and one or more excipients and capable of providing sustained release of the at least one cytotoxic agent, wherein the at least one cytotoxic agent comprises one or more of a sclerosant, a p53 activator, an antiprotozoal agent, an apoptosis inducer and a local anesthetic.

37. The composition according to claim 36, which is formulated as an injectable oily solution or suspension and comprises at least one oily excipient.

38. The composition of claim 37, comprising: all in about % w/v,

10-15% w/v of at least one cytotoxic agent, preferably mepacrine or a mepacrine salt providing 10-15% w/v mepacrine, such as 11.8-17.7% w/v mepacrine dihydrochloride; and

Aqueous or oily suspension, preferably oily suspension.

39. The composition of claim 36 formulated as a low viscosity injectable gel.

40. The composition of claim 39, formulated to rapidly gel at the injection site in an animal and to prolong the release of the at least one cytotoxic agent from the gel.

41. A composition according to claim 39 or 40 comprising: in total about % w/v, 10-15% w/v of at least one cytotoxic agent, preferably mepacrine or a mepacrine salt providing 10-15% w/v mepacrine, such as 11.8-17.7% w/v mepacrine dihydrochloride.

42. The composition of claim 39, 40 or 41, wherein the low viscosity injectable gel comprises one or more gelling agents, one or more solvents or solvent systems, and optionally one or more surfactants.

43. The composition of claim 42, wherein the low viscosity injectable gel comprises:

44. The composition of claim 43, wherein the low viscosity injectable gel comprises:

About 30%-90% w/v SAIB;

About 40%-85% w/v SAIB;

About 70%-80% w/v SAIB; or

About 70% w/v SAIB.

45. The composition of claim 43 or 44, wherein the low viscosity injectable gel comprises:

about 0-50% w/v of the at least one solvent; or

About 15-30% w/v of the at least one solvent.

46. The composition of claim 45, wherein the at least one solvent comprises one or more of ethanol, diethylene glycol monoethyl ether (DEGEE), N-methylpyrrolidone (NMP), triacetin, benzyl benzoate, miglyol, propylene carbonate, benzyl alcohol, ethyl lactate, tetraethylene glycol, 2-pyrrolidone, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decyl methyl sulfoxide, oleic acid, and 1-dodecylazacycloheptan-2-one.

47. The composition of claim 42, 43, 44, 45 or 46, wherein the low viscosity injectable gel comprises:

about 0-3% w/v of said at least one surfactant;

about 0-2% w/v of said at least one surfactant;

about 0-1% w/v of the at least one surfactant;

about 1-3% w/v of the at least one surfactant; or

About 1-2% w/v of the at least one surfactant.

48. The composition of claim 47, wherein the at least one surfactant comprises one or more of the following: a nonionic surfactant, a polysorbate, Tween, polyoxyethylene (20) sorbitan monooleate (Tween 80), or polyoxyethylene (20) sorbitan monolaurate (Tween 20).

49. The composition of claim 41, 42, 43, 44, 45, 46, 47 or 48, wherein the low viscosity injectable gel comprises: all in about % w/v,

40-85% w/v SAIB;

0-2% w/v Tween 80;

0-50% w/v triacetin;

0-50% w/v DEGEE; and

Ethanol is made up to 100% volume, where:

The concentration of ethanol is 0-30% w/v; or

50. The composition of claim 41, 42, 43, 44, 45, 46, 47 or 48, wherein the low viscosity injectable gel comprises: all in about % w/v,

40-85% w/v SAIB;

0-2% w/v Tween 80;

0-50% w/v triacetin;

0-50% w/v DEGEE; and

Ethanol is made up to 100% volume, where:

The concentration of ethanol is 0-30% w/v; or

51. The composition of claim 41, 42, 43, 44, 45, 46, 47 or 48, wherein the low viscosity injectable gel comprises: all in about % w/v,

70% w/v SAIB;

1% w/v Tween 80;

5% w/v triacetin;

0% w/v DEGEE; and

52. The composition of claim 41, 42, 43, 44, 45, 46, 47 or 48, wherein the low viscosity injectable gel comprises: all in about % w/v,

70% w/v SAIB;

1% w/v Tween 80;

5% w/v triacetin;

0% w/v DEGEE; and

53. The composition of any one of claims 36-52, wherein the at least one cytotoxic agent is mepaline dihydrochloride.

54. The method of claim 1, the use of claim 2, the at least one cytotoxic agent for or when used for chemical dehorning of a young animal or inhibiting horn growth in a young animal according to claim 3, the use of claim 4, the syringe of claim 6 or the kit of parts according to claim 7, wherein the at least one cytotoxic agent is formulated as a composition according to any one of claims 36-53.