阅读说明：本技术 二氨基胍衍生物及其饲用组合物在制备兽医用药物中的应用 (Application of diaminoguanidine derivative and feeding composition thereof in preparation of veterinary medicine ) 是由 彭险峰 于 2019-07-22 设计创作，主要内容包括：二氨基胍衍生物及其饲用组合物在制备兽医用药物中的应用。一种结构如式(Ⅰ)所示的二氨基胍衍生物或其立体异构体,几何异构体,互变异构体,溶剂合物,药学上可接受的盐或其前药,在制备动物用药物中的应用,所述药物是用于防护、处理、治疗或减轻由细菌感染引起的疾病的药物：其中R为NO<Sub>2</Sub>、式(Ⅱ)或式(Ⅲ)所示基团；R<Sub>1</Sub>为直链或支链的C<Sub>1</Sub>-C<Sub>20</Sub>烷基；A为O,N或S；R<Sub>2</Sub>为直链或支链的C<Sub>3</Sub>-C<Sub>14</Sub>烷基,C<Sub>5</Sub>-C<Sub>6</Sub>环烷基,C<Sub>5</Sub>-C<Sub>6</Sub>芳基或CH<Sub>2</Sub>(C<Sub>5</Sub>-C<Sub>6</Sub>芳基)。该二氨基胍衍生物是一种对动物无毒安全的化合物,应用在养殖动物的生殖系统、皮肤等感染性疾病的治疗具有显著的疗效。<Image he="96" wi="700" file="DDA0002506520790000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(Application of diaminoguanidine derivatives and feeding compositions thereof in preparation of veterinary drugs. Use of a diaminoguanidine derivative having the structure of formula (i) or a stereoisomer, geometric isomer, tautomer, solvate, pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for use in the prevention, treatment or alleviation of a disease caused by a bacterial infection in an animal: wherein R is NO 2 A group of formula (II) or (III); r 1 Is straight-chain or branched C 1 ‑C 20 An alkyl group; a isO, N or S; r 2 Is straight-chain or branched C 3 ‑C 14 Alkyl radical, C 5 ‑C 6 Cycloalkyl radical, C 5 ‑C 6 Aryl or CH 2 (C 5 ‑C 6 Aryl). The diaminoguanidine derivative is a compound which is nontoxic and safe to animals, and has obvious curative effect when being applied to the treatment of infectious diseases of reproductive systems, skins and the like of cultured animals.)

1. Use of a diaminoguanidine derivative having the structure of formula (i) or a stereoisomer, geometric isomer, tautomer, solvate, pharmaceutically acceptable salt or prodrug thereof for the manufacture of a medicament for use in the prevention, treatment or alleviation of a disease caused by a bacterial infection:

wherein R is NO₂A group of formula (II) or (III);

R₁is straight-chain or branched C₁-C₂₀An alkyl group; a is O, N or S; r₂Is straight-chain or branched C₃-C₁₄Alkyl radical, C₅-C₆Cycloalkyl radical, C₅-C₆Aryl or CH₂(C₅-C₆Aryl).

2. The use according to claim 1, wherein R is of formula (II)₁Is a straight chain C₁-C₂₀An alkyl group.

3. The use of claim 2, wherein R is₁Is a straight chain C₁-C₁₂An alkyl group.

4. The use of claim 3, wherein R is₁Is methyl.

5. The use according to claim 1, wherein R is of formula (III) and A is O.

6. The use according to claim 1, wherein R is of formula (III) and A is N.

7. The use according to claim 1, wherein R is of formula (III)₂Is a straight chain C₃-C₁₄An alkyl group.

8. The use according to claim 1, wherein R is of formula (III)₂C being a branch₃-C₁₄An alkyl group.

9. The use of claim 8, wherein R is₂C being a branch₃Alkyl or branched C₄And A is O.

10. The use according to any one of claims 1 to 9, wherein the medicament is a medicament for the prevention, treatment or alleviation of a disease caused by a staphylococcus aureus infection.

11. The use of any one of claims 1 to 9, wherein the medicament is a medicament for the treatment of postpartum endometritis in a sow, postpartum mastitis in a sow and/or skin infection in a mouse.

12. The use according to claim 1, wherein the pharmaceutically acceptable salt of a diaminoguanidine derivative is D L-lactate, methanesulfonate, 2-isethionate, citrate, tartrate, benzoate, succinate, fumarate, maleate, acetate, sulfate, phosphate or oxalate.

13. A pharmaceutical composition comprising at least one diaminoguanidine derivative of the formula (i) or a stereoisomer, a geometric isomer, a tautomer, a solvate, a pharmaceutically acceptable salt or a prodrug thereof according to any one of claims 1 to 9 and optionally a feedable adjuvant.

14. The pharmaceutical composition of claim 13, comprising one or more therapeutic agents.

15. Use of a pharmaceutical composition according to any one of claims 13 to 14 for the manufacture of a medicament for use in an animal for the prevention, treatment or alleviation of a disease caused by a bacterial infection.

16. The use according to claim 15, wherein the medicament is a medicament for inhibiting bacterial growth.

17. The use of claim 15, wherein the disease is an epidermal infection, a reproductive infection or a glandular infection.

The technical field is as follows:

the invention belongs to the field of medicines, and particularly relates to application of diaminoguanidine derivatives and pharmaceutical compositions thereof in preparation of medicines for animals, in particular to preparation of medicines for preventing, treating or relieving diseases caused by bacterial infection.

Background art:

in animal breeding industry, livestock and poultry often suffer from inflammatory diseases caused by bacterial infection, such as urogenital system diseases, gastrointestinal tract diseases, respiratory system diseases, skin infection and the like, which can seriously affect the production performance and health of the livestock and poultry, and a common and effective method is antibacterial drugs or hormone therapy. With the use of a large amount of antibacterial drugs, drug-resistant strains are continuously increased, and drug residues in animal products inevitably occur due to the application of the antibacterial drugs or hormones and the like, so that serious harm is brought to human health.

The invention content is as follows:

based on this, the invention provides a pharmaceutical composition comprising at least one diaminoguanidine derivative or its stereoisomer, geometric isomer, tautomer, solvate, pharmaceutically acceptable salt or its prodrug and optionally a feedable adjuvant; also provides the application of the medicinal composition and the diaminoguanidine derivative or the stereoisomer, the geometric isomer, the tautomer, the solvate, the pharmaceutically acceptable salt or the prodrug thereof in preparing medicaments for animals, and aims to provide safe and effective anti-infective medicaments for animals for the breeding industry at the present stage.

In order to achieve at least one purpose of the application, the following technical scheme is adopted:

in one aspect, the invention provides a diaminoguanidine derivative represented by the structural formula (I) or a stereoisomer, a geometric isomer, a tautomer, a solvate, a pharmaceutically acceptable salt or a prodrug thereof.

In some embodiments, R is NO₂A group of formula (II) or (III);

R₁is straight-chain or branched C₁-C₂₀An alkyl group; a is O, N or S; r₂Is straight-chain or branched C₃-C₁₄Alkyl radical, C₅-C₆Cycloalkyl radical, C₅-C₆Aryl or CH₂(C₅-C₆Aryl).

In some technical schemes, R is a formula (II), R₁Is a straight chain C₁-C₂₀An alkyl group.

In some technical schemes, R is a formula (II), R₁Is a straight chain C₁-C₁₂An alkyl group.

In some technical schemes, R is a formula (II), R₁Preferably methyl.

In some embodiments, R is formula (III), wherein A is preferably O.

In some embodiments, R is formula (III), wherein A is preferably N.

In some embodiments, R is of formula (III), wherein R is₂Is a straight chain C₃-C₁₄An alkyl group.

In some embodiments, R is of formula (III), wherein R is₂C being a branch₃-C₁₄An alkyl group.

In some embodiments, R is of formula (III), wherein R is₂Preferably branched C₃Alkyl or branched C₄An alkyl group.

In some embodiments, the pharmaceutically acceptable salt of the diaminoguanidine derivative is D L-lactate, mesylate, 2-isethionate, citrate, tartrate, benzoate, succinate, fumarate, maleate, acetate, sulfate, phosphate, or oxalate.

In another aspect, the present invention provides a pharmaceutical composition, which comprises at least one diaminoguanidine derivative represented by formula (i) or a stereoisomer, a geometric isomer, a tautomer, a solvate, a pharmaceutically acceptable salt or a prodrug thereof, and optionally pharmaceutically acceptable auxiliary materials.

In some embodiments, the pharmaceutical composition further comprises one or more therapeutic agents.

In another aspect, the invention provides application of diaminoguanidine derivatives with a structure shown as a formula (I) or stereoisomers, geometric isomers, tautomers, solvates, pharmaceutically acceptable salts or prodrugs thereof and pharmaceutical compositions thereof in preparing medicaments for animals.

In some embodiments, the medicament is for protecting against a disease caused by a bacterial infection.

In some embodiments, the medicament is for treating a disease caused by a bacterial infection.

In some embodiments, the medicament is for alleviating a symptom of a disease caused by a bacterial infection.

In another aspect, the present invention provides a method for preventing, treating or alleviating a disease caused by bacterial infection, which is based on inhibiting bacterial growth by a medicament prepared from diaminoguanidine derivatives represented by the following formula (i) or stereoisomers, geometric isomers, tautomers, solvates, pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions thereof.

The invention has the beneficial effects that:

the diaminoguanidine derivative provided by the invention is a compound which is nontoxic and safe to animals, and has obvious curative effect when being applied to treatment of infectious diseases of reproductive systems, skins and the like of cultured animals.

Any embodiment of any aspect of the invention may be combined with other embodiments as long as there is no conflict between them. Furthermore, in any embodiment of any aspect of the present invention, any technical feature may be applied to that technical feature in other embodiments as long as there is no contradiction therebetween.

Detailed Description

The foregoing merely outlines certain aspects of the application, but is not limited to these aspects. The foregoing and other aspects are more fully described below.

Further details of the invention are described.

Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. Furthermore, certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment or in any suitable subcombination.

Compound (I)

The compound related by the invention is a diaminoguanidine derivative with a structure shown as a formula (I) or a stereoisomer, a geometric isomer, a tautomer, a solvate, a pharmaceutically acceptable salt or a prodrug thereof.

Wherein R is a substituent at the 4-position on the phenyl ring of formula (I) selected from NO₂Formula (II) or formula (III). R₁Is straight-chain or branched C₁-C₂₀An alkyl group; a is O, N or S; r₂Is straight-chain or branched C₃-C₁₄Alkyl radical, C₅-C₆Cycloalkyl, substituted or unsubstituted C₅-C₆Aryl or CH₂(C₅-C₆Aryl).

In general, "substituted" means that one or more substitutable hydrogen atoms in a given structure are substituted with a particular substituent, a substituted group may have one substituent at each substitutable position of the group, and when more than one position in a given formula can be substituted with one or more substituents of a particular group, then the substituents may be substituted at each position, either identically or differently.

The prodrug is a compound which is converted into a compound shown as a formula (I) in vivo. Such conversion is effected by hydrolysis of the prodrug in the blood or by enzymatic conversion to the parent structure in the blood or tissue.

In the present invention, "C_a-C_bAlkyl "denotes a straight or branched chain saturated alkyl group containing from a to b carbon atoms, e.g. methyl, ethyl, propyl, isopropyl, … …, e.g." C₁-C₅Alkyl "represents a straight or branched chain saturated alkyl group containing 1 to 5 carbon atoms; "C₅-C₆Cycloalkyl "denotes cyclic alkyl containing only two elements of carbon and hydrogen, containing 5 or 6 carbon atoms, such as cyclopentyl or cyclohexyl, etc.; "C₅-C₆Aryl "means a cyclic group having aromatic character containing 5 or 6 carbon atoms, such as benzene ring, etc.

In some embodiments, the diaminoguanidine derivative wherein R is of formula (II), R₁Is a straight chain C₁-C₂₀An alkyl group.

Further, said R₁Is a straight chain C₁-C₁₂An alkyl group.

In one embodiment, R in the diaminoguanidine derivative is represented by formula (II)₁Is methyl.

In some embodiments, the diaminoguanidine derivative wherein R is of formula (II), R₁C being a branch₁-C₂₀An alkyl group.

Further, said R₁C being a branch₃-C₄An alkyl group.

In one embodiment, R in the diaminoguanidine derivative is represented by formula (II)₁Is isopropyl.

In some embodiments, the diaminoguanidine derivative wherein R is formula (iii).

Optionally, a is O, N or S.

In some embodiments, when R is formula (iii) in the diaminoguanidine derivative, a is O.

In other embodiments, when R is formula (iii) in the diaminoguanidine derivative, a is N.

In some embodiments, the diaminoguanidine derivative wherein R is of formula (III), R₂Is straight-chain or branched C₃-C₁₄An alkyl group.

Optionally, R is₂Is a straight chain C₃-C₁₄An alkyl group.

Further, said R₂Is a straight chain C₃-C₁₂An alkyl group.

In some embodiments, R is₂Is n-propyl.

In other embodiments, R is₂Is n-butyl.

Optionally, R is₂C being a branch₃-C₁₄An alkyl group.

Further, said R₂C being a branch₃-C₅An alkyl group.

In some embodiments, R is₂Is isopropyl.

In some embodiments, the diaminoguanidine derivative wherein R is of formula (III), R₂Is C₅-C₆A cycloalkyl group.

In some embodiments, R is₂Is cyclopentyl.

In some embodiments, the diaminoguanidine derivative wherein R is of formula (III), R₂Is substituted or unsubstituted C₅-C₆And (4) an aryl group.

Further, said R₂Is unsubstituted C₅-C₆And (4) an aryl group.

In one embodiment, R is₂Is phenyl.

Still further, said R₂Is substituted C₅-C₆Aryl, said aryl being optionally substituted with 1, 2, 3, 4 or 5R³Substituted, R³is-OH, -NH₂、-NO₂、-CN、-SH、-X、-C₁-C₅Alkoxy, -C₁-C₅Alkyl or C substituted by X₁-C₅Alkyl, wherein X is selected from F, Cl, Br or I.

Specifically, said C₅-C₆Aryl is preferably phenyl.

In some embodiments, the diaminoguanidine derivative wherein R is of formula (III), R₂Is substituted or unsubstituted CH₂(C₅-C₆Aryl).

Further, said R₂Is unsubstituted CH₂(C₅-C₆Aryl).

In one embodiment, R is₂Is benzyl.

Further, said R₂Is substituted CH₂(C₅-C₆Aryl) optionally substituted with 1, 2, 3, 4 or 5R³Substituted, R³is-OH, -N H₂、-NO₂、-CN、-SH、-X、-C₁-C₅Alkoxy, -C₁-C₅Alkyl or C substituted by X₁-C₅Alkyl, wherein X is selected from F, Cl, Br or I.

Specifically, the R is₂Is a substituted benzyl group, the phenyl ring of said benzyl group being optionally substituted with 1, 2, 3, 4 or 5R³Substituted, R³is-OH, -NH₂、-N O₂、-CN、-SH、-X、-C₁-C₅Alkoxy, -C₁-C₅Alkyl or C substituted by X₁-C₅Alkyl, wherein X is selected from F, Cl, Br or I.

In some specific embodiments, diaminoguanidine derivatives encompassed by the present invention include compound 1, compound 2, compound 3, and compound 4, having the following sequential structures:

in some embodiments, the diaminoguanidine derivative is a pharmaceutically acceptable salt, preferably a complex salt in combination with an acid.

Optionally, the acid is an organic acid or an inorganic acid.

Specifically, the inorganic acid includes, but is not limited to, sulfuric acid, methanesulfonic acid, hydrochloric acid, or phosphoric acid, and the organic acid includes, but is not limited to, D L-lactic acid, 2-isethionic acid, citric acid, tartaric acid, benzoic acid, succinic acid, fumaric acid, maleic acid, acetic acid, or oxalic acid.

Preparation and purification of compounds

The diaminoguanidine derivative is a series of compounds obtained by Schiff base reaction of diaminoguanidine and 4-substituted benzaldehyde, the method is detailed in CN103880712A, and the structure of the 4-substituted benzaldehyde is shown in formula (IV).

Wherein R is a substituent at the 4-position on the phenyl ring of formula (I) selected from NO₂Formula (II) or formula (III). R₁Is straight-chain or branched C₁-C₂₀An alkyl group; a is O, N or S; r₂Is straight-chain or branched C₃-C₁₄Alkyl radical, C₅-C₆Cycloalkyl, substituted or unsubstituted C₅-C₆Aryl or CH₂(C₅-C₆Aryl).

When R is a substituent with a chiral structure, the benzaldehyde compound shown in the formula (IV) will present certain chiral characteristics, and the product generated by the reaction with diaminoguanidine may also have chiral characteristics, and will present different stereoisomer compounds or tautomers.

When the diaminoguanidine derivative generated by the reaction of the diaminoguanidine and the benzaldehyde compound shown in the formula (IV) has a rigid structure, different geometric isomer products can be generated during the reaction of the reaction substrate.

The stereoisomers, geometric isomers and tautomers described above are also included in the practice of the present invention.

"stereoisomers" as referred to herein refers to compounds having the same chemical structure but differing in the arrangement of atoms or groups in space, including enantiomers, diastereomers, conformers, geometric isomers, atropisomers, and the like. "enantiomer" refers to two isomers of a compound that are not overlapping but are in mirror image relationship to each other. "diastereomer" refers to a stereoisomer having two or more chiral neutrals whose molecules are not mirror images of each other, and having different physical properties such as melting point, boiling point, spectral properties, and reactivity. Mixtures of diastereomers may be separated by high resolution analytical procedures such as electrophoresis or chromatography; "tautomers" refer to structural isomers that have different energies that can interconvert through a low energy barrier.

In some embodiments, the present invention provides processes for the preparation of diaminoguanidine derivatives that also involve isolation, purification, or recrystallization of the reaction product. The reaction product can be used for obtaining crude products from the reaction system by a solvent removal method. In order to obtain a solid substance with higher chemical purity and lower impurity content, the crude product is dissolved, crystallized or precipitated or recrystallized and separated in an alcohol solvent, an alcohol-water mixed solvent or other organic solvents which can be used for product recrystallization under the conditions of proper temperature, illumination, mechanical vibration and the like to obtain the diaminoguanidine derivative with a certain crystal form state. The diaminoguanidine derivative having a certain crystal form state is a diaminoguanidine derivative crystal or a solvate of a diaminoguanidine derivative. The solvate of the diaminoguanidine derivative can be selected from a hydrate of the diaminoguanidine derivative or an ethanolate of the diaminoguanidine derivative.

The term "solvate" as used herein refers to a eutectic association formed by binding a stoichiometric or non-stoichiometric amount of solvent molecules by non-covalent intermolecular forces due to external and internal conditions during the contact between the compound of the present invention and the solvent molecules. Solvents that form solvates include, but are not limited to, water, acetone, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, isopropanol, and the like. "hydrate" refers to an association or crystal of solvent molecules with water, i.e., a compound that binds a stoichiometric or non-stoichiometric amount of water by non-covalent intermolecular forces.

The diaminoguanidine derivative provided by the invention can be prepared by salting out and then treating solid substances with higher chemical purity and lower impurity content. The salting-out method is a process of salt-forming precipitation of the amino acid derivative and corresponding organic base, inorganic base, organic acid or inorganic acid by utilizing the principles of an acid-base neutralization method, an acid-base coordination method or an acid-base chelation method to obtain pharmaceutically acceptable salt; the inorganic acid includes, but is not limited to, hydrochloride, hydrobromide, phosphate, sulfate, nitrate, or combinations thereof.

The feed acceptable salt is a salt of the diaminoguanidine derivative of the present invention with an organic base, an inorganic base, an organic acid or an inorganic acid which is non-toxic to animals. By "feed acceptable" is meant that the substance or composition must be chemically or toxicologically compatible in connection with the constituent feed or the edible farmed animals.

In some embodiments, the diaminoguanidine derivative of the present invention forms an acid-base complex salt and or an acid-base chelate salt during the post-treatment salting-out precipitation with an organic acid including, but not limited to, acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, malic acid, 2-hydroxypropionic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, glucuronic acid, galactaric acid, citric acid, tartaric acid, aspartic acid, glutamic acid, benzoic acid, p-toluic acid, cinnamic acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid or combinations thereof.

The invention relates to a pharmaceutical composition

A feed composition comprising at least one diaminoguanidine derivative represented by formula (I) and its racemate, stereoisomer, geometric isomer, tautomer, solvate or pharmaceutically acceptable salt and pharmaceutically acceptable adjuvants, wherein the amount of diaminoguanidine derivative in the composition is effective for controlling the condition of diseased livestock.

The composition refers to a compound set comprising one or more compounds as active ingredients.

The term "comprising" as used herein is open-ended, meaning that the meaning of the term is included, but not exclusive of other aspects.

The medicinal auxiliary materials are medicinal carriers, auxiliary agents, diluents, excipients, menstruum, dispersing agents, suspending agents, surfactants, isotonic agents, thickening agents, emulsifying agents, preservatives, solid adhesives or lubricating agents or the combination of the medicinal carriers, the auxiliary agents, the diluents, the excipients, the menstruum, the dispersing agents, the suspending agents, the surfactants, the isotonic agents, the thickening agents, the emulsifying agents, the preservatives and the solid adhesives or lubricating. The carrier of the invention is a pharmaceutically acceptable substance which can carry active ingredients, improve the dispersibility of the active ingredients and has good chemical stability and adsorbability. The auxiliary materials comprise but are not limited to ion exchangers, aluminum stearate, lecithin, serum protein, buffer substances such as phosphate, glycine, sorbic acid, potassium sorbate, glyceride mixtures of saturated vegetable fatty acids, water, salt, electrolyte, protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, lanolin, sugar, starch, cellulose and derivatives thereof, gum powder, malt, gelatin and talcum powder; adjuvants such as cacao butter, suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, soybean oil; glycols such as propylene glycol, polyethylene glycol; esters such as ethyl oleic acid, ethyl laurate, agar; buffering agents such as magnesium hydroxide, aluminum hydroxide; lubricants such as alginic acid, ethanol, phosphoric acid buffer solution, sodium laurate, etc., coloring agent coating material, sweetening agent, flavoring agent, perfume, preservative, antioxidant.

The auxiliary agent is a wetting agent for inducing the inherent viscosity of the substance, a binding agent for binding the substance, a disintegrating agent for breaking the sheet-shaped substance into a plurality of fine particles, a retention aid for reducing the friction force between the particles or an anti-sticking agent for preventing the adhesion of the material, and comprises but is not limited to magnesium stearate, talcum powder, vegetable oil, magnesium lauryl sulfate, starch slurry, water, inorganic salt, dextrin, powdered sugar and the like.

The term "vehicle" as used herein refers to a solvent necessary to dissolve or disperse a solid, and includes, but is not limited to, water, ethanol, glycerol, and the like.

In some embodiments, the pharmaceutical composition further comprises one or more therapeutic agents.

The therapeutic agent includes but is not limited to anthelmintic health care agents, veterinary antibiotics or herbal feed additives.

Specifically, the pharmaceutical feed additive includes, but is not limited to, veterinary drug premix substances having effects of preventing animal diseases, promoting animal growth, and incorporating carriers or diluents for long-term use as additives in feeds.

More specifically, the pharmaceutical feed additive is a feeding antibiotic, and the feeding antibiotic includes, but is not limited to, polymyxin, salinomycin, avilamycin, bacitracin, virginiamycin, nosiheptide, flavomycin, enramycin, griseofulvin, olaquindox, oxytetracycline, or aureomycin.

The invention relates to application of diaminoguanidine derivatives and medicinal compositions thereof.

The invention provides application of the diaminoguanidine derivative and a medicinal composition containing the diaminoguanidine derivative in preparation of medicaments for animals.

In some embodiments, the medicament is a substance for protection against diseases caused by bacterial infections.

In some embodiments, the medicament is a substance for protection against diseases caused by bacterial infections.

In some embodiments, the medicament is a substance for treating a disease caused by a bacterial infection.

In some embodiments, the medicament is a substance for alleviating symptoms of a disease caused by a bacterial infection.

Optionally, the bacteria are gram-positive bacteria, including but not limited to streptococcus pneumoniae, staphylococcus aureus, staphylococcus epidermidis, streptococcus hemolyticus, enterococcus, and streptococcus viridis.

Further, the bacterium is preferably staphylococcus aureus.

In some embodiments, the disease caused by a bacterial infection is a skin infection caused by staphylococcus aureus.

In some embodiments, the disease caused by a bacterial infection is a gastrointestinal infection.

In some embodiments, the disease caused by a bacterial infection is a respiratory infection.

In some embodiments, the disease caused by bacterial infection is a urogenital disease, including mastitis, endometritis, urethritis, and the like.

In some embodiments, the diaminoguanidine derivative or pharmaceutical composition thereof is present in a specific dosage form in the preparation of an animal medicament.

Optionally, the specific dosage form includes, but is not limited to, oral dosage form, injection dosage form, suppository, external dosage form or perfusate.

Specifically, the specific dosage form contains diaminoguanidine derivatives with effective treatment dosage except pharmaceutical excipients.

More specifically, the specific dosage form has specific independent available specifications according to the clinical medication rule.

Methods of treatment of animals.

The invention also provides a method of treating a disease caused by a bacterial infection in an animal.

Alternatively, the methods include, but are not limited to, oral or injectable administration of pharmaceutical formulations of diaminoguanidine derivatives or pharmaceutical compositions thereof to animals.

Further, the pharmaceutical preparation includes, but is not limited to, tablets, capsules, injections, aqueous solutions, pills, patches and the like.

Still further, the formulation contains different dosages of diaminoguanidine derivatives as required for effective dosages at different animal growth stages.

An "effective dose" of a diaminoguanidine derivative or a pharmaceutical composition of the invention refers to an amount effective to treat or reduce the severity of one or more of the conditions mentioned herein.

In some embodiments, the animal is a pet, livestock, or poultry at various stages of growth.

Optionally, the pet includes, but is not limited to, a dog or a cat; the livestock include, but are not limited to, pigs, cattle, sheep, donkeys or horses at various stages of growth; the poultry includes but is not limited to chicken, duck, goose and quail.

In some embodiments, the method of treatment comprising the diaminoguanidine derivative or pharmaceutical composition thereof further comprises administering to the animal subject an additional therapeutic agent, wherein the additional therapeutic agent includes, but is not limited to, chemotherapy, anti-inflammatory agents, herbal preparations, physical therapy, and the like. Wherein an additional therapeutic agent is appropriate for the disease to be treated, which additional therapeutic agent may be administered in combination with the diaminoguanidine derivative or pharmaceutical composition thereof of the present invention. The diaminoguanidine derivatives or pharmaceutical compositions thereof of the present invention are in a single dosage form, or separate compounds or compositions are part of a multiple dosage form. The additional therapeutic agent may be administered simultaneously or non-simultaneously with the diaminoguanidine derivative of the present invention.

In order to make the objects, technical solutions and advantages of the present invention more apparent, the compounds, compositions and applications of the present invention are further described in detail by examples below. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.