Aqueous pharmaceutical composition comprising SGLT-2 inhibitor

Abstract

The present invention relates to novel aqueous pharmaceutical compositions comprising at least one SGLT-2 inhibitor and one or more solubilizers as well as corresponding processes for preparing such aqueous pharmaceutical compositions and medical uses thereof.

Description

[0001] Reference Addition

[0002] All documents mentioned in this specification are incorporated herein by reference. Technical Field

[0003] The present invention relates to the medical field, in particular to the veterinary field. In particular, the present invention relates to novel aqueous pharmaceutical compositions comprising at least one SGLT-2 inhibitor and one or more solubilizers. Background Art

[0004] Treatment of diabetes and other metabolic disorders includes inhibition of the renal sodium-dependent glucose co-transporter SGLT-2. SGLT-2 in the kidney regulates glucose levels by mediating glucose reabsorption back into the plasma after blood filtration. Thus SGLT-2 inhibition induces glucosuria and can reduce blood glucose levels.

[0005] A wide variety of SGLT-2 inhibitors are known. Pharmaceutical formulations of SGLT-2 inhibitors are necessary to administer such compounds to patients in an appropriate manner.

[0006] EP 1 609 785 discloses C-glycoside derivatives and salts thereof, wherein the B ring is bonded to the A ring via -X- and the A ring is directly bonded to a glucose residue, and which can be used as Na+-glucose cotransporter inhibitors, in particular therapeutic and / or preventive agents for diabetes, such as insulin-dependent diabetes mellitus (type 1 diabetes) and insulin-independent diabetes mellitus (type 2 diabetes) and diabetes-related diseases, such as insulin resistance and obesity.

[0007] WO 2006 / 064033 discloses glucopyranosyl-substituted benzene derivatives useful for treating metabolic disorders, including tautomers, stereoisomers, mixtures thereof and salts thereof.

[0008] SGLT-2 inhibitors are described, for example, in WO 2007 / 028814, which is directed to crystalline forms of 1-chloro-4-([β]-D-glucopyranose-1-yl)-2-(4-ethynyl-benzyl)-benzene, methods for its preparation, and its use for preparing medicaments. It discloses a solution of 1-chloro-4-([β]-D-glucopyranose-1-yl)-2-(4-ethynyl-benzyl)-benzene in a solvent or a solvent mixture and further specifies a suitable organic solvent, such as ethanol or an ethanol / water mixture, by way of example.

[0009] WO 2007 / 080170 describes 1'-(1-methylethyl)-4'-[(2-fluoro-4-methoxyphenyl)methyl]-5'-methyl-1H-pyrazole-3'-O-[β]-D-glucopyranoside in crystalline form, a process for its preparation and its use for the preparation of medicaments. It discloses a solution of 1'-(1-methylethyl)-4'-[(2-fluoro-4-methoxyphenyl)methyl]-5'-methyl-1H-pyrazole-3'-O-[β]-D-glucopyranoside in a solvent or a solvent mixture and further specifies exemplarily suitable organic solvents such as ethanol or ethanol / water mixtures.

[0010] In addition, WO 2007 / 093610 describes benzonitrile derivatives substituted with glucopyranosyl, pharmaceutical compositions containing such compounds, their medical uses and methods for their preparation. It is mentioned that such benzonitrile derivatives substituted with glucopyranosyl can be formulated with one or more inert carriers and / or diluents such as water / ethanol, water / glycerol, propylene glycol and the like. It further discloses 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranosyl-1-yl)-benzene (velagliflozin) among many other compounds.

[0011] SGLT-2 inhibitors are further described in WO 2007 / 128749, which is about pyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their medical uses and methods for their preparation. It is mentioned that such pyranosyl-substituted benzonitrile derivatives can be formulated with one or more inert carriers and / or diluents (such as water / ethanol, water / glycerol, propylene glycol and the like). Among many other compounds, it also further discloses 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-pyranosyl-1-yl)-benzene (vilagliflozin).

[0012] US 2011 / 077213 discloses methods for treating and / or preventing kidney stones using an SGLT-2 inhibitor alone or in combination with a carbohydrate supply and / or in combination with a diuretic.

[0013] WO 2013 / 079501 ​​is directed to a crystalline dapagliflozin hydrate and a method for preparing the same, which discloses a solution of dapagliflozin in a solvent or a solvent mixture and further exemplarily specifies suitable solvents such as water and C1-C4 alcohols or mixtures thereof.

[0014] WO 2014 / 016381 (US 2014 / 031540) describes a crystalline complex of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranose-1-yl)-benzene with a natural amino acid, a method for preparing the same, and its use for preparing a medicament. It discloses a solution of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranose-1-yl)-benzene in a solvent or a solvent mixture and further specifies, by way of example, suitable organic solvents such as C1-C4 alkanols, ethanol, and mixtures thereof, in particular mixtures with water.

[0015] In addition, WO 2014 / 195966 describes an amorphous form of canagliflozin and a method for preparing the same, as well as a corresponding pharmaceutical composition and its medical use. It discloses a solution of canagliflozin in one or more organic solvents and further exemplarily specifies a suitable organic solvent, such as ethanol.

[0016] WO 2015 / 110402 relates to SGLT-2 inhibitors for use in the treatment and / or prevention of metabolic disorders in canines.

[0017] WO 2015 / 173584 discloses a method for avoiding the increase in glucagon secretion associated with the administration of a sodium glucose cotransporter 2 (SGLT-2) inhibitor by co-administering a dipeptidyl peptidase IV (DPP IV) inhibitor. In addition, a method for normalizing the glucagon secretion associated with the administration of a sodium glucose cotransporter 2 (SGLT-2) inhibitor by co-administering a dipeptidyl peptidase IV (DPP IV) inhibitor is disclosed. The WO publication relates to a method for treating diabetes, particularly type 2 diabetes, as well as hyperglycemia, hyperinsulinemia, obesity, hypertriglyceridemia, syndrome X, diabetic complications, atherosclerosis and related diseases, comprising administering an SGLT-2 inhibitor and a dipeptidyl peptidase IV (DPP IV) inhibitor.

[0018] WO 2017 / 032799 relates to liquid pharmaceutical compositions comprising at least one SGLT-2 inhibitor and one or more polar organic solvents, wherein the one or more polar organic solvents preferably always comprise propane-1,2-diol (propylene glycol).

[0019] US2017 / 145000 discloses canagliflozin monohydrate and its crystalline form.

[0020] US2020 / 237794 discloses one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for treating and / or preventing metabolic disorders in equines, such as laminitis, vascular dysfunction, hypertension, hepatic lipidosis, atherosclerosis, hyperadrenocorticism, pituitary pars intermedia dysfunction and / or equine metabolic syndrome.

[0021] WO 2020 / 219645 discloses a method for reducing weight loss and / or increasing body weight in a cat in need thereof and / or a method for treating a cat with diabetes and higher IGF-1 concentrations, the methods comprising administering to a cat in need thereof a total daily dose of about 2 to 50 mg of vilagagliflozin or a pharmaceutically acceptable form thereof.

[0022] WO 2021 / 105152 discloses the use of at least one SGLT-2 inhibitor in non-human mammals (preferably ruminants), preferably for the dry milk of non-human mammals (preferably ruminants); and corresponding methods, such as improving and / or promoting the dry milk of non-human mammals (preferably ruminants), which comprises administering at least one SGLT-2 inhibitor to such non-human mammals (preferably ruminants).

[0023] WO 2021 / 165177 discloses the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for preventing and / or treating one or more heart diseases in felines.

[0024] US2022 / 016078 discloses a method for treating or preventing kidney stones in a patient: administering to a patient in need thereof a therapeutically effective amount of a compound that induces glucosuria or a pharmaceutical composition thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof.

[0025] WO 2023 / 006718 discloses the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammal patients other than cats, in particular dogs / canine patients.

[0026] WO 2023 / 006745 discloses the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for preventing and / or treating hypertension in non-human mammals, preferably carnivorous animals, especially cats or dogs.

[0027] WO 2023 / 006747 discloses the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for preventing and / or treating one or more renal diseases in non-human mammals, such as carnivores, in particular cats or dogs.

[0028] Xu G et al. (Journal of Medical Chemistry 2014, 57: 1236-1251) are about the design, synthesis and biological evaluation of deuterated C-aryl glycosides as potent and long-acting renal SGLT-2 inhibitors for the treatment of type 2 diabetes.

[0029] Other challenges known in the prior art are the limited solubility of SGLT-2 inhibitors in water due to their positive log10P values, which often affects bioavailability in patients or makes it difficult to find a suitable solvent to get the substance dissolved in a liquid formulation before administering it to a patient. Summary of the invention

[0030] The present invention relates to an aqueous pharmaceutical composition comprising at least one SGLT-2 inhibitor and one or more solubilizers.

[0031] In the course of the present invention, the term "aqueous" with respect to the term "pharmaceutical composition" refers to an aqueous pharmaceutical composition, wherein such water is preferably present in the form of an aqueous buffer, such as a citric acid buffer. However, any suitable aqueous buffer (system) may be used according to the knowledge and skill of a person skilled in the art. Such aqueous pharmaceutical compositions have a water content / aqueous buffer content of 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), and most preferably 50 to 80 g / 100 mL (50 to 80% w / v).

[0032] The present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the at least one SGLT-2 inhibitor is selected from the group consisting of:

[0033] (1) Benzene derivatives substituted with pyranose

[0034]

[0035] Where R 1 represents cyano, Cl or methyl (most preferably cyano);

[0036] R 2represents H, methyl, methoxy or hydroxy (most preferably H) and

[0037] R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-but-1-yl, cyclobutyl,

[0038] Cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl,

[0039] 1-Hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl,

[0040] 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-prop-1-yl, 3-hydroxy-3-methyl-but-1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano;

[0041] Where R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and most preferably R 3 is cyclopropyl,

[0042] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl group acylation;

[0043] (2) Vilagliflozin, represented by formula (2):

[0044]

[0045] (3) Dapagliflozin, represented by formula (3):

[0046]

[0047] (4) Canagliflozin, represented by formula (4):

[0048]

[0049] (5) Empagliflozin, represented by formula (5):

[0050]

[0051] (6) Luseogliflozin, represented by formula (6):

[0052]

[0053] (7) Tofogliflozin, represented by formula (7):

[0054]

[0055] (8) Ipragliflozin, represented by formula (8):

[0056]

[0057] (9) Ertugliflozin, represented by formula (9):

[0058]

[0059] (10) Agliflozin, represented by formula (10):

[0060]

[0061] (11) Remogliflozin, represented by formula (11):

[0062]

[0063] (11A) Remogliflozin etabonate, represented by formula (11A):

[0064]

[0065] (12) Thiophene derivatives of formula (12)

[0066]

[0067] wherein R represents a methoxy group or a trifluoromethoxy group;

[0068] (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by formula (13);

[0069]

[0070] (14) Spiroketal derivatives of formula (14):

[0071]

[0072] wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl or tert-butyl;

[0073] (15) Pyrazole-O-glucoside derivatives of formula (15)

[0074]

[0075] in

[0076] R 1 Represents C 1-3 Alkoxy,

[0077] L 1 , L 2 independently of each other represent H or F,

[0078] R 6 Indicates H, (C 1-3 alkyl)carbonyl, (C 1-6 alkyl)oxycarbonyl, phenoxycarbonyl,

[0079] benzyloxycarbonyl or benzylcarbonyl;

[0080] (16) Sotagliflozin, represented by formula (16):

[0081]

[0082] (17) Sergliflozin, represented by formula (17):

[0083]

[0084] (18) A compound represented by formula (18):

[0085]

[0086] in

[0087] R 3represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-butan-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propan-1-yl, 3-hydroxy-3-methyl-butan-1-yl -yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, and wherein R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and R 3 Most preferably, it is cyclopropyl,

[0088] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 (19) bexagliflozin, represented by formula (19):

[0089]

[0090] (20) Janagliflozin, represented by formula (20):

[0091]

[0092] (21) Rongliflozin, represented by formula (21):

[0093]

[0094] (22) Wanpagliflozin;

[0095] (23) Enagagliflozin, represented by formula (23):

[0096]

[0097] (24) TFC-039, represented by formula (24):

[0098]

[0099] The present invention also relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition comprises only one SGLT-2 inhibitor, preferably only vilagagliflozin as the single SGLT-2 inhibitor.

[0100] The present invention also relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein at least one SGLT-2 inhibitor is vilagagliflozin, which is preferably the only SGLT-2 inhibitor contained in such aqueous pharmaceutical composition, and / or wherein the aqueous pharmaceutical composition is preferably for direct administration to an individual (more preferably an animal, even more preferably a mammal, especially a horse, cat, dog or cow), preferably without further mandatory processing and / or purification steps; wherein the aqueous pharmaceutical composition is preferably sterile.

[0101] The present invention also relates to an aqueous pharmaceutical composition as described and / or claimed herein for use in a method for the treatment and / or prevention of one or more medical indications selected from the following medical indications in a subject (preferably an animal, more preferably a mammal, especially a horse, cat, dog or cow) in need of such treatment and / or prevention:

[0102] (i) metabolic disorders of equines, wherein the metabolic disorders are preferably one or more disorders selected from the group consisting of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity, wherein the metabolic disorders are preferably insulin resistance, hyperinsulinemia, and / or clinical conditions associated with insulin resistance and / or hyperinsulinemia; wherein the clinical conditions are preferably one or more disorders selected from the group consisting of impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity;

[0103] (ii) metabolic disorders of equines, wherein the metabolic disorders are one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome, wherein the metabolic disorders are preferably clinical conditions / symptoms associated with insulin resistance and / or hyperinsulinemia, wherein the clinical conditions / symptoms are preferably one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome;

[0104] (iii) a metabolic disorder in a feline, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes, insulin resistance, acromegaly, diabetes with elevated IGF-1 concentrations, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function, and / or wherein remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained;

[0105] (iv) a metabolic disorder in a canine, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, obesity, hyperglycemia, hyperglycemia-induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, pancreatic inflammation, consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders, and / or Syndrome X (metabolic syndrome), preferably prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, wherein the development of hyperglycemia-induced cataract formation is preferably avoided or remission is achieved, and / or wherein the development of consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders is preferably avoided or the progression is slowed or remission is achieved;

[0106] (v) cardiac disease in a feline, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure, heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to cardiomyopathy of unspecified type (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), cardiomyopathy of unspecified type (UCM) and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), hypertrophic cardiomyopathy (HCM);

[0107] (vi) drying off of non-human mammals, preferably ruminants; improving and / or promoting drying off of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or swelling in the udder, preferably the breast and / or mammary gland of non-human mammals, preferably ruminants; reducing discomfort associated with udder swelling in non-human mammals, preferably ruminants, such as increasing daily lying time and / or reducing stress; reducing milk leakage after drying off of non-human mammals, preferably ruminants; reducing the incidence of intra-mammary infection (IMI), preferably mastitis and / or metritis, in non-human mammals, preferably ruminants;

[0108] (vii) cardiac disease in non-human mammals excluding cats, in particular dogs, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to (myxo)mitral valve disease [(M)MVD]; congestive heart failure due to (myxo)mitral valve disease [(M)MVD]; asymptomatic / preclinical / occult heart failure due to (myxo)mitral valve disease [(M)MVD]; (myxo)mitral valve disease [(M)MVD]; clinically evident (Myxomatous) Mitral Valve Disease [(M)MVD]; Asymptomatic / Preclinical / Latent (Myxomatous) Mitral Valve Disease [(M)MVD]; Heart Failure Attributed to Dilated Cardiomyopathy (DCM); Congestive Heart Failure Attributed to Dilated Cardiomyopathy (DCM); Asymptomatic / Preclinical / Latent Heart Failure Attributed to Dilated Cardiomyopathy (DCM); Dilated Cardiomyopathy (DCM); Clinically Apparent Dilated Cardiomyopathy (DCM); Asymptomatic / Preclinical / Latent Dilated Cardiomyopathy (DCM); Aortic Stenosis (Valvular, Supravalvular, and / or Subvalvular);

[0109] (viii) hypertension in a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the hypertension is preferably one or more selected from the group consisting of: situational hypertension, secondary hypertension and idiopathic hypertension, wherein secondary hypertension is preferably selected from the group consisting of: hypertension associated with chronic kidney disease (CKD), diabetes, obesity, heart disease, endocrine diseases (such as Cushing's disease, hyperthyroidism, acromegaly), and increased blood pressure (BP) induced by a pharmaceutical agent, preferably a glucocorticoid, a mineralocorticoid, an erythropoiesis stimulating agent, ephedrine and / or high-dose sodium chloride;

[0110] (ix) renal disease of a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the renal disease is preferably one or more selected from the group consisting of renal dysplasia, glomerular disease, polycystic kidney disease, amyloidosis, tubular nephritis / tubular interstitial nephritis (TIN), acute kidney disease, chronic kidney disease.

[0111] The present invention further relates to a process for preparing an aqueous pharmaceutical composition as described and claimed herein, comprising the following steps:

[0112] (i) mixing one or more organic solvents such as ethanol (if present) with water (if no organic solvent is present, only water is used as the starting material);

[0113] (ii) adding one or more solubilizing agents to the mixture prepared in step (i) (or water if no organic solvent is present);

[0114] (iii) dissolving at least one SGLT-2 inhibitor, preferably vilagagliflozin, in the mixture prepared in step (ii);

[0115] (iv) optionally, dissolving one or more preservatives in the mixture prepared in step (iii),

[0116] (v) optionally, further dissolving other excipients, such as pH adjusters, flavoring agents, sweeteners, antioxidants, viscosity enhancers and the like, in the mixture prepared by step (iii) or, optionally, (iv);

[0117] (vi) optionally, filtering the mixture prepared by step (iii), optionally, step (iv) or optionally, step (v);

[0118] Optionally, any of the selected individual method steps can thus be followed, either compulsorily or optionally, independently of one another, by an additional mixing step.

[0119] In the process of the present invention, such method steps (i) to (vi) do not need to be carried out in a given order, but can also be carried out in any other meaningful order, such as (i), (v), (ii), (iii), (iv), (vi). It is within the knowledge of the skilled person to change the order of the method steps so as to obtain the desired method result, that is, the aqueous pharmaceutical composition according to the present invention. For example, if one or more viscosity enhancers are added, it is preferred to heat the mixture until the one or more viscosity enhancers are completely dissolved. Subsequently, such resulting mixture needs to be cooled before adding at least one SGLT-2 inhibitor, preferably vilagagliflozin (e.g. in the form of its L-proline-water eutectic), so as to avoid unnecessary and undesirable degradation of the substance via such heating step.

[0120] The present invention further relates to a kit-of-parts comprising:

[0121] (a) an aqueous pharmaceutical composition as described and claimed herein; and

[0122] (b) a package insert comprising information that the aqueous pharmaceutical composition is used for the prevention and / or treatment of one or more medical indications in a subject in need of such prevention and / or treatment, the one or more medical indications being a medical indication selected from the group consisting of:

[0123] (i) metabolic disorders of equines, wherein the metabolic disorders are preferably one or more disorders selected from the group consisting of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity, wherein the metabolic disorders are preferably insulin resistance, hyperinsulinemia, and / or clinical conditions associated with insulin resistance and / or hyperinsulinemia; wherein the clinical conditions are preferably one or more disorders selected from the group consisting of impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity;

[0124] (ii) metabolic disorders of equines, wherein the metabolic disorders are one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome, wherein the metabolic disorders are preferably clinical conditions / symptoms associated with insulin resistance and / or hyperinsulinemia, wherein the clinical conditions / symptoms are preferably one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome;

[0125] (iii) a metabolic disorder in a feline, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes, insulin resistance, acromegaly, diabetes with elevated IGF-1 concentrations, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function, and / or wherein remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained;

[0126] (iv) a metabolic disorder in a canine, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, obesity, hyperglycemia, hyperglycemia-induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, pancreatic inflammation, consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders, and / or Syndrome X (metabolic syndrome), preferably prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, wherein the development of hyperglycemia-induced cataract formation is preferably avoided or remission is achieved, and / or wherein the development of consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders is preferably avoided or the progression is slowed or remission is achieved;

[0127] (v) cardiac disease in a feline, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure, heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to cardiomyopathy of unspecified type (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), cardiomyopathy of unspecified type (UCM) and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), hypertrophic cardiomyopathy (HCM);

[0128] (vi) drying off of non-human mammals, preferably ruminants; improving and / or promoting drying off of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or swelling in the udder, preferably the breast and / or mammary gland of non-human mammals, preferably ruminants; reducing discomfort associated with udder swelling in non-human mammals, preferably ruminants, such as increasing daily lying time and / or reducing stress; reducing milk leakage after drying off of non-human mammals, preferably ruminants; reducing the incidence of intra-mammary infection (IMI), preferably mastitis and / or metritis, in non-human mammals, preferably ruminants;

[0129] (vii) cardiac disease in non-human mammals excluding cats, in particular dogs, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to (myxo)mitral valve disease [(M)MVD]; congestive heart failure due to (myxo)mitral valve disease [(M)MVD]; asymptomatic / preclinical / occult heart failure due to (myxo)mitral valve disease [(M)MVD]; (myxo)mitral valve disease [(M)MVD]; clinically evident (Myxomatous) Mitral Valve Disease [(M)MVD]; Asymptomatic / Preclinical / Latent (Myxomatous) Mitral Valve Disease [(M)MVD]; Heart Failure Attributed to Dilated Cardiomyopathy (DCM); Congestive Heart Failure Attributed to Dilated Cardiomyopathy (DCM); Asymptomatic / Preclinical / Latent Heart Failure Attributed to Dilated Cardiomyopathy (DCM); Dilated Cardiomyopathy (DCM); Clinically Apparent Dilated Cardiomyopathy (DCM); Asymptomatic / Preclinical / Latent Dilated Cardiomyopathy (DCM); Aortic Stenosis (Valvular, Supravalvular, and / or Subvalvular);

[0130] (viii) hypertension in non-human mammals, preferably carnivores, more preferably cats or dogs, wherein the hypertension is preferably one or more selected from the group consisting of situational hypertension, secondary hypertension and idiopathic hypertension, wherein the secondary hypertension is preferably selected from the group consisting of hypertension associated with chronic kidney disease (CKD), diabetes, obesity, heart disease, endocrine diseases (such as Cushing's disease, hyperthyroidism, acromegaly), and increased blood pressure (BP) induced by pharmaceutical agents, preferably glucocorticoids, mineralocorticoids, erythropoiesis stimulating agents, ephedrine and / or high-dose sodium chloride;

[0131] (ix) renal disease of a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the renal disease is preferably one or more selected from the group consisting of renal dysplasia, glomerular disease, polycystic kidney disease, amyloidosis, tubular nephritis / tubular interstitial nephritis (TIN), acute kidney disease, chronic kidney disease.

[0132] The advantages of the aqueous pharmaceutical composition according to the present invention are as follows:

[0133] - It is suitable for administration preferably directly to an individual, preferably without further mandatory processing and / or purification steps. Preferably, it is therefore sterile and complies with GMP manufacturing conditions and GCP compliant clinical protocols;

[0134] - It is stable against undesirable contamination / growth of microorganisms;

[0135] - It is preferably a true solution, emulsion or suspension in a water-based system, more preferably a true solution, with a minimum amount of organic solvents (if present) to ensure biocompatibility and reduce costs. DETAILED DESCRIPTION

[0136] All references cited herein are hereby incorporated by reference.

[0137] Before describing the embodiments of the present invention in further detail, it should be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0138] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention belongs. Unless otherwise specified or otherwise known by those skilled in the art, all given ranges and values ​​may vary by 1 to 5%, and therefore, the term "about" is generally omitted in the specification and the scope of the patent application. Although any method and material similar or equivalent to those described herein can be used in the practice or testing of the present invention, preferred methods, devices and materials are now described. For the purpose of describing and disclosing the materials, excipients, carriers and methods reported in the publications that can be used in conjunction with the present invention, all publications mentioned herein are incorporated herein by reference. Nothing herein should be interpreted as admitting that the present invention is not entitled to such disclosures by virtue of prior inventions.

[0139] At least one SGLT-2 inhibitor according to the invention includes, but is not limited to, glucopyranosyl-substituted benzene derivatives, such as, for example, WO 01 / 27128, WO 03 / 099836, WO 2005 / 092877, WO 2006 / 034489, WO 2006 / 064033, WO 2006 / 117359, WO 2006 / 117360, WO 2007 / 025943, WO 2007 / 028814, WO 2007 / 031548, WO 2007 / 093610, WO 2007 / 128749, WO 2008 / 049923, WO 2008 / 055870, WO 2008 / 055940, WO 2009 / 022020 or WO Described in 2009 / 022008.

[0140] Furthermore, at least one SGLT-2 inhibitor according to the present invention may be selected from the group consisting of the following compounds or pharmaceutically acceptable (crystalline) forms thereof:

[0141] (1) Benzene derivatives substituted with pyranose

[0142]

[0143] Where R 1 represents cyano, Cl or methyl (most preferably cyano);

[0144] R 2 represents H, methyl, methoxy or hydroxy (most preferably H) and

[0145] R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-butan-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propan-1-yl, 3-hydroxy-3-methyl-butan-1-yl, -1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano;

[0146] Where R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and most preferably R 3 is cyclopropyl,

[0147] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl group acylation;

[0148] (2) Vilagliflozin, represented by formula (2):

[0149]

[0150] (3) Dapagliflozin, represented by formula (3):

[0151]

[0152] (4) Canagliflozin, represented by formula (4):

[0153]

[0154] (5) Empagliflozin, represented by formula (5):

[0155]

[0156] (6) Rupagliflozin, represented by formula (6):

[0157]

[0158] (7) Togliflozin, represented by formula (7):

[0159]

[0160] (8) Ipagliflozin, represented by formula (8):

[0161]

[0162] (9) Egliflozin, represented by formula (9):

[0163]

[0164] (10) Agliflozin, represented by formula (10):

[0165]

[0166] (11) Repagliflozin, represented by formula (11):

[0167]

[0168] (11A) Repagliflozin ectoate, represented by formula (11A):

[0169]

[0170] (12) Thiophene derivatives of formula (12)

[0171]

[0172] wherein R represents a methoxy group or a trifluoromethoxy group;

[0173] (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by formula (13);

[0174]

[0175] (14) Spiroketal derivatives of formula (14):

[0176]

[0177] wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl or tert-butyl; (15) pyrazole-O-glucoside derivative of formula (15)

[0178]

[0179] in

[0180] R 1 Represents C 1-3 Alkoxy,

[0181] L 1 , L 2 independently of each other represent H or F,

[0182] R 6 Indicates H, (C 1-3 alkyl)carbonyl, (C 1-6 alkyl)oxycarbonyl, phenoxycarbonyl, benzyloxycarbonyl or benzylcarbonyl;

[0183] (16) Sogliflozin, represented by formula (16):

[0184]

[0185] (17) Sergliflozin is represented by formula (17):

[0186]

[0187] (18) A compound represented by formula (18):

[0188]

[0189] in

[0190] R 3represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-butan-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propan-1-yl, 3-hydroxy-3-methyl-butan-1-yl -yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; and wherein R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and R 3 Most preferably, it is cyclopropyl,

[0191] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 (19) Bexagliflozin, represented by formula (19):

[0192]

[0193] (20) gagliflozin, represented by formula (20):

[0194]

[0195] (21) Jungliflozin, expressed by formula (21):

[0196]

[0197] (22) Vanpagliflozin

[0198] (23) Enagaliflozin is represented by formula (23):

[0199]

[0200] (24) TFC-039, represented by formula (24):

[0201]

[0202] The term "vilagliflozin" as used herein refers to the vilagliflozin of the above structure and its pharmaceutically acceptable form, including its hydrates and solvates and its crystalline form. The compound, its synthesis method and its cocrystal are described in, for example, WO 2007 / 128749, WO 2014 / 016381 and WO 2019 / 121509.

[0203] The term "dapagliflozin" as used herein refers to dapagliflozin of the above structure and its pharmaceutically acceptable form, including its hydrates and solvates and crystalline forms. The compound and its synthesis method are described in, for example, WO 03 / 099836. Preferred hydrates, solvates and crystalline forms are described in, for example, patent applications WO 2008 / 116179 and WO2008 / 002824.

[0204] As used herein, the term "canagliflozin" refers to the canagliflozin of the above structure and its pharmaceutically acceptable form, including its hydrates and solvates and crystalline forms. The compound and its synthesis method are described in, for example, WO2005 / 012326 and WO 2009 / 035969. Preferred hydrates, solvates and crystalline forms are described in, for example, patent application WO 2008 / 069327.

[0205] The term "empagliflozin" as used herein refers to the empagliflozin of the above structure and its pharmaceutically acceptable forms, including its hydrates and solvates and its crystalline forms. The compound and its synthesis method are described in, for example, WO2005 / 092877, WO 2006 / 120208 and WO 2011 / 039108. Preferred crystalline forms are described in, for example, patent applications WO 2006 / 117359 and WO 2011 / 039107.

[0206] The term "Apagliflozin" as used herein refers to Apagliflozin of the above structure and its pharmaceutically acceptable forms, including its hydrates and solvates and crystalline forms. The compound and its synthesis method are described in, for example, WO2004 / 007517.

[0207] As used herein, the term "ipagliflozin" refers to the ipagliflozin of the above structure and its pharmaceutically acceptable forms, including its hydrates and solvates and crystalline forms. The compound and its synthesis method are described in, for example, WO2004 / 080990, WO 2005 / 012326 and WO 2007 / 114475.

[0208] As used herein, the term "topagliflozin" refers to topagliflozin of the above structure and its pharmaceutically acceptable forms, including its hydrates and solvates and crystalline forms. The compound and its synthesis method are described in, for example, WO 2007 / 140191 and WO 2008 / 013280.

[0209] As used herein, the term "rupagliflozin" refers to the rupagliflozin of the above structure and pharmaceutically acceptable forms thereof, including hydrates and solvates thereof and crystalline forms thereof.

[0210] As used herein, the term "erpagliflozin" refers to erpagliflozin of the above structure and pharmaceutically acceptable forms thereof, including hydrates and solvates thereof and crystalline forms thereof. The compound is described, for example, in WO 2010 / 023594.

[0211] As used herein, the term "regagliflozin" refers to the above structured repagliflozin and its pharmaceutically acceptable forms, including prodrugs of repagliflozin, especially repagliflozin ectoate, including its hydrates and solvates and crystalline forms thereof. Its synthesis method is described in, for example, patent applications EP 1 213 296 and EP 1 354 888.

[0212] The term "sergliflozin" as used herein refers to the sergliflozin of the above structure and its pharmaceutically acceptable forms, including prodrugs of sergliflozin, especially sergliflozin etabonate, including its hydrates and solvates and crystalline forms thereof. Its preparation method is described in, for example, patent applications EP 1344 780 and EP 1 489 089.

[0213] The compound of formula (16) above, ie, solafloxacin, and its preparation are described, for example, in WO2008 / 042688 or WO2009 / 014970.

[0214] As used herein, the term "bexagliflozin" refers to bexagliflozin of the above structure and pharmaceutically acceptable forms thereof, including hydrates and solvates thereof and crystalline forms thereof. The compound and its synthesis method are described, for example, in WO 2009 / 026537.

[0215] As used herein, the term "TFC-039" refers to the above structure and its pharmaceutically acceptable forms, including its hydrates and solvates and crystalline forms. The compound and its synthesis method are described in, for example, WO 2012 / 160218.

[0216] Preferably, the SGLT-2 inhibitor is a benzene derivative substituted with a pyranose glucopyranose group. Optionally, one or more hydroxyl groups of the pyranose glucopyranose group in such one or more SGLT-2 inhibitors may be substituted with a (C1-18 alkyl)carbonyl group, ...1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl groups are acylated.

[0217] More preferred is the benzonitrile derivative substituted with glucopyranosyl group as disclosed above. Still more preferred is the benzonitrile derivative substituted with glucopyranosyl group as disclosed above.

[0218]

[0219] in

[0220] R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-butan-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propan-1-yl, 3-hydroxy-3-methyl-butan-1-yl -yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; and wherein R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and R 3 Most preferably, it is cyclopropyl,

[0221] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl groups are acylated.

[0222] Preferably, such SGLT-2 inhibitor is vilagaliflozin as shown in formula (2). Optionally, one or more hydroxyl groups of the β-D-glucopyranose group of vilagaliflozin may be selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl groups are acylated.

[0223] Therefore, in a preferred embodiment, as in each case defined above, at least one SGLT-2 inhibitor according to the present invention is a pyranoglucopyranosyl-substituted benzene derivative SGLT-2 inhibitor, preferably an SGLT-2 inhibitor of formula (1), more preferably an SGLT-2 inhibitor of formula (18) or even more preferably an SGLT-2 inhibitor of formula (2), i.e., vilagagliflozin.

[0224] In the course of the present invention, 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene (vilagliflozin) is also referred to as "substance", and is understood herein to also include co-crystalline 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene-L-proline and 1:1:1-co-crystalline 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene-L-proline-water (as disclosed in WO 2014 / 016381). In general, in the case of disclosed and claimed concentrations (% w / v) and amounts (g, mg), unless explicitly stated otherwise, the concentration or amount always refers to 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene itself, i.e. excluding L-proline and crystal water, even though in practice (and in the Examples section) a 1:1:1 co-crystalline 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene-L-proline-water was actually added / used.

[0225] In the course of the present invention, the term "for preferably direct administration to an individual" with respect to an "aqueous pharmaceutical composition" means that such an aqueous pharmaceutical composition can be administered directly to an individual, preferably without further mandatory treatment and / or purification steps, and explicitly excludes (mixtures of) organic solvents mentioned separately in the context of producing a crystalline complex of an SGLT-2 inhibitor. Preferably, therefore, such "aqueous pharmaceutical composition" "for direct administration to an individual" is sterile and / or complies with GMP manufacturing conditions and GCP compliance clinical protocols.

[0226] In one aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the aqueous pharmaceutical composition is preferably for direct administration to a subject (more preferably an animal, even more preferably a mammal, especially a horse, cat, dog or cow), preferably without further mandatory processing and / or purification steps; wherein the aqueous pharmaceutical composition is preferably sterile.

[0227] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the at least one SGLT-2 inhibitor is vilagagliflozin, which is preferably the only SGLT-2 inhibitor contained in such aqueous pharmaceutical composition.

[0228] In another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the aqueous pharmaceutical composition is a solution, emulsion or suspension, preferably a solution, emulsion or suspension with an NTU value equal to or less than 10.0, more preferably equal to or less than 7.0, even more preferably equal to or less than 3.0, and most preferably a solution, especially a solution with an NTU value equal to or less than 3.0.

[0229] In the course of the present invention, the term "NTU" refers to Nephelometric Turbidity Unit and refers to the opalescent value as defined and described in the 8th edition of the European Pharmacopoeia (Ph. Eur. 8, Chapter 2.2.1. "Clarity and degree of opalescence of liquids").

[0230] In another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, comprising one or more organic solvents which are independently of each other by negative log 10 The P value, preferably the negative decimal logarithmic distribution in the n-octanol / water system according to formula (II) is characterized by the number (P):

[0231] log 10 P 正辛醇 / 水 = concentration of unionized compounds in n-octanol / concentration of unionized compounds in water (II).

[0232] In another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition as a whole is characterized by a negative LogP parameter, preferably a negative LogP parameter equal to or higher than -2.0 (i.e. -2.0 ≤ LogP parameter < 0). For the avoidance of doubt, the LogP parameter is as defined in Equation 4 of Example 1 and is the same as the (negative) log 10 The P values ​​are inconsistent and should not be mistaken for that value.

[0233] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the one or more organic solvents are selected from the group consisting of: ethanol (log 10P: -0.16), propane-1,2,3-triol (glycerol; log 10 P: -1.84), pyrrolidone (log 10 P: -0.58), methyl pyrrolidone (log 10 P: -0.356), N,N-dimethylacetamide (log 10 P: -0.583) and / or N,N-dimethylformamide (log 10 P: -0.632).log 10 P values ​​were obtained from http: / / www.chemicalize.org / .

[0234] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition comprises at least two different organic solvents, preferably propane-1,2,3-triol (glycerol) and ethanol.

[0235] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such composition contains no more than 20 g / 100 mL (20% w / v) of organic solvent, preferably no more than 15 g / 100 mL (15% w / v) of organic solvent, more preferably no more than 10 g / 100 mL (10% w / v) of organic solvent.

[0236] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such composition does not contain propane-1,2-diol (propylene glycol).

[0237] In yet another aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition comprises ethanol as the only organic solvent contained in such aqueous pharmaceutical composition. Preferably, ethanol is present in such aqueous pharmaceutical composition at no more than 20 g / 100 mL (20% w / v), more preferably at no more than 15 g / 100 mL (15% w / v), even more preferably at no more than 10 g / 100 mL (10% w / v), and most preferably at 8 g / 100 mL (8% w / v).

[0238] In yet another aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such composition is substantially free of organic solvents, preferably free of any organic solvents. If no organic solvent is present, the solvent of the aqueous pharmaceutical composition is 100% water, preferably in the form of an aqueous buffer.

[0239] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition comprises water in the form of an aqueous buffer, such as a citrate buffer, a phosphate buffer, an ammonium sulfate buffer, an ammonium acetate buffer, a sodium acetate buffer and the like, preferably an aqueous buffer having a pH of 4.5, more preferably a citrate buffer having a pH of 4.5.

[0240] In yet another aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition contains 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), most preferably 50 to 80 g / 100 mL (50 to 80% w / v) of water, more preferably in the form of an aqueous buffer, such as a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5.

[0241] In yet another aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the (measured) pH of such aqueous pharmaceutical composition is from 2 to 7, preferably from 3 to 7, more preferably from 3.0 to 6.5, even more preferably from 4.0 to 6.5, even more preferably from 4.0 to 5.0, and most preferably 4.5. For the avoidance of doubt, the term "measured pH" refers to the pH actually measured for all aqueous pharmaceutical compositions according to the invention (i.e. which comprise both an organic solvent phase (if present) and an aqueous phase).

[0242] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition further comprises one or more preservatives, which are preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; most preferably benzoic acid and / or its salts, such as sodium benzoate.

[0243] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition further comprises one or more antioxidants, preferably selected from the group consisting of: ascorbic acid or a pharmaceutically acceptable salt thereof, in particular sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof, more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, in particular propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

[0244] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein the one or more solubilizers are selected from the group consisting of surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone, more preferably selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone), wherein the total amount of the one or more solubilizing agents is preferably 1 to 50 g / 100 mL (1-50% w / v), more preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v).

[0245] In yet another aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein two or more solubilizing agents are comprised in the aqueous pharmaceutical composition.

[0246] In yet another aspect, the invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein two solubilizing agents are contained in such aqueous pharmaceutical composition, wherein the amount of the first solubilizing agent and the amount of the second solubilizing agent are preferably independently selected from 1 to 50 g / 100 mL (1-50% w / v), more preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v), wherein the two solubilizing agents are more preferably independently selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone), wherein such two solubilizers are even more preferably Kollidon 12 (povidone) and PEG 200, PEG 300 or PEG 400, and most preferably Kollidon 12 (povidone) and PEG 300.

[0247] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition further comprises one or more viscosity increasing agents, preferably selected from the group consisting of: inorganic gelling agents, organic gelling agents, cellulose derivatives, more preferably selected from the group consisting of: hydroxyethylcellulose, hydroxypropylmethylcellulose, silicon dioxide.

[0248] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition further comprises one or more flavorings and / or sweeteners, preferably selected from the group consisting of: honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol.

[0249] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition does not comprise any non-polar organic solvent, which preferably and independently of each other consists of a log of equal to or greater than 0. 10 P value representation.

[0250] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, wherein such aqueous pharmaceutical composition is for oral and / or parenteral administration, preferably oral administration.

[0251] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, comprising, preferably consisting of:

[0252] (i) at least one SGLT-2 inhibitor, preferably vilagagliflozin, more preferably only one single SGLT-2 inhibitor, even more preferably only vilagagliflozin as the single SGLT-2 inhibitor;

[0253] (ii) optionally but preferably, one or more preservatives; preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; or combinations thereof; most preferably benzoic acid and / or its salts, such as sodium benzoate;

[0254] (iii) optionally one or more organic solvents, preferably selected from the group consisting of ethanol, propane-1,2,3-triol (glycerol), pyrrolidone, methylpyrrolidone, N,N-dimethylacetamide and / or N,N-dimethylformamide, more preferably ethanol;

[0255] (iv) optionally one or more flavorings and / or sweeteners, preferably selected from the group consisting of: honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol;

[0256] (v) water, preferably in the form of an aqueous buffer, more preferably a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5;

[0257] (vi) one or more solubilizers, preferably selected from the group consisting of surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone, more preferably selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone);

[0258] (vii) optionally one or more viscosity increasing agents, preferably selected from the group consisting of inorganic gelling agents, organic gelling agents, cellulose derivatives, more preferably selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide;

[0259] (viii) one or more antioxidants may be present, preferably selected from the group consisting of: ascorbic acid or a pharmaceutically acceptable salt thereof, in particular sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof, more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, in particular propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

[0260] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, comprising, preferably consisting of:

[0261] (i) 0.5-20.0 g / 100 mL (0.5-20.0% w / v), preferably 0.5-15.0 g / 100 mL (0.5-15.0% w / v), more preferably 1.0 -1.5 g / 100 mL (1.0-1.5% w / v) of at least one SGLT-2 inhibitor, preferably vilagagliflozin, more preferably only one single SGLT-2 inhibitor, even more preferably only vilagagliflozin as the single SGLT-2 inhibitor;

[0262] (ii) 0-3.0 g / 100 mL (0-3.0% w / v), preferably 0.05-3.0 g / 100 mL (0.05-3.0% w / v), more preferably 0.05-2.0 g / 100 mL (0.05-2.0% w / v) of one or more preservatives; even more preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; or combinations thereof; most preferably benzoic acid and / or its salts, such as sodium benzoate;

[0263] (iii) 0-20 g / 100 mL (0-20% w / v), preferably 0-15 g / 100 mL (0-15% w / v), more preferably 0-12 g / 100 mL (0-12% w / v), even more preferably 0-10 g / 100 mL (0-10% w / v) of one or more organic solvents, preferably selected from the group consisting of ethanol, propane-1,2,3-triol (glycerol), pyrrolidone, methylpyrrolidone, N,N-dimethylacetamide and / or N,N-dimethylformamide, more preferably ethanol;

[0264] (iv) 0-40 g / 100 mL (0-40% w / v), preferably 0-30 g / 100 mL (0-30% w / v), more preferably 0-2 g / 100 mL (0-2% w / v) of one or more flavorings and / or sweeteners, more preferably selected from the group consisting of: honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol;

[0265] (v) 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), most preferably 50 to 80 g / 100 mL (50 to 80% w / v) of water, preferably in the form of an aqueous buffer, more preferably a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5;

[0266] (vi) 1 to 50 g / 100 mL (1-50% w / v), preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v) of one or more solubilizers, preferably selected from the group consisting of surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone, more preferably selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone);

[0267] (vii) 0-40 g / 100 mL (0-40% w / v), preferably 10-30 g / 100 mL (10-30% w / v) of one or more viscosity increasing agents, preferably selected from the group consisting of inorganic gelling agents, organic gelling agents, cellulose derivatives, more preferably selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide;

[0268] (viii) 0-1.0 g / 100 mL (0-1.0% w / v), preferably 0-0.5 g / 100 mL (0-0.5% w / v), more preferably 0.1-0.3 g / 100 mL (0.1-0.3% w / v) of one or more antioxidants, preferably selected from the group consisting of ascorbic acid or a pharmaceutically acceptable salt thereof, especially sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof , more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, especially propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

[0269] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, comprising, preferably consisting of: vilagagliflozin; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; water.

[0270] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, comprising, preferably consisting of: vilagagliflozin; citric acid monohydrate; NaOH; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; water.

[0271] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, comprising, preferably consisting of: vilagagliflozin; citric acid monohydrate; NaOH; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; sorbitol and / or xylitol; honey flavoring and / or vanilla extract and / or meat flavoring; water.

[0272] In yet another aspect, the present invention relates to an aqueous pharmaceutical composition as described and / or claimed herein, selected from:

[0273]

[0274]

[0275] Examples

[0276] The following examples are used to further illustrate the present invention; however, they should not be considered as limiting the scope of the present invention disclosed herein.

[0277] Example 1

[0278] The test criteria applied were those for assessing the clarity of liquids (formulations) containing 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene (vilagliflozin) according to European Pharmacopoeia (Pharm. Eur.) 8, chapter 2.2.1. "Clarity and degree of opalescence of liquids", a liquid is considered clear if its opalescence is no more pronounced than that of reference suspension I (Table 1) having an opalescence value of 3 NTU.

[0279] Table 1: Measurement values ​​of reference suspensions I-IV according to Ph. Eur. 8, chapter 2.2.1

[0280]

[0281] Hereinafter, exemplary pharmaceutical compositions of solvents mixed with 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranose-1-yl)-benzene (vilagliflozin; substance) according to the present invention are given in detail. Turbidity was measured by using a HachLange 2100N IS device.

[0282] In order to quantify the characteristics of a solvent with respect to its suitability to form physically stable solutions with a substance, the LogP parameter is introduced (Equation 4). The LogP parameter describes the hydrophilicity / hydrophobicity of a solvent mixture containing organic and aqueous solvents and is calculated as follows:

[0283]

[0284] mo i [mol / g]: Molecular weight of the organic solvent in the organic phase of the solvent mixture

[0285] Mo i [-]: Organic solvent mo in the organic phase of the solvent mixture i The molecular fraction

[0286] LogP i [-]: log 10 P 正辛醇 / 水 = Concentration of unionized compounds in organic solvent n-octanol / Concentration of unionized compounds in water

[0287] LogPo[-]: Auxiliary parameter of the organic phase of a solvent mixture

[0288] a w [g]: mass of water or aqueous buffer in the solvent mixture

[0289] a sol [g]: mass of solvent mixture

[0290] X o [-]: Mass fraction of organic phase in solvent mixture

[0291] As described in WO 2017 / 032799, instability phenomena are expected when the LogP parameter is <-2.0.

[0292] Example Calculation

[0293] For ethanol, log 10 P value (=LogP i ) is given as -0.16 and the molecular weight is given as 46.07 g / mol. The solvent mixture of Composition 1 consists of 80.0 mg / mL ethanol and 644.3 mg / mL H2O (the sum of purified water and aqueous buffer), which corresponds to 11.0% (m / m) of the organic phase.

[0294] Since ethanol is the only organic solvent, the amount of ethanol in the organic phase is 100% (m / m) or 100 g / 100 g, which corresponds to 0.0217 mol / g (= mol 乙醇 ). Therefore, Mo 乙醇 =1 (Equation 1) and LogPo is calculated to be -0.16 (Equation 2). The mass fraction of the organic phase is 11.0% (m / m) or according to Equation 3X o =0.11. Following Equation 4, the LogP parameter of the solvent mixture of Composition 1 was calculated to be -1.45.

[0295] Example 2

[0296] In the following Table 2, exemplary pharmaceutical compositions (API: Active Pharmaceutical Ingredient) according to the present invention are given in detail.

[0297] Table 2: Exemplary pharmaceutical compositions according to the present invention

[0298]

[0299] The preparation procedure for an exemplary pharmaceutical composition according to the present invention for a single small-scale batch (1000 mL) in general illustrative form is as follows:

[0300] Preparation of buffer solution

[0301] Weigh the aqueous buffer solution into a container.

[0302] The solubilizer component was weighed and added to the buffer solution with stirring.

[0303] Preservatives, if present, were weighed and added to the solution with stirring.

[0304] The antioxidant was weighed and added to the solution with stirring.

[0305] The organic solvent is weighed and added to the solution (if present) with stirring.

[0306] Sweetener and / or viscosity enhancer are weighed and added to the solution with stirring.

[0307] At least one SGLT-2 inhibitor, preferably vilagagliflozin, is weighed and added portionwise to the solution.

[0308] Weigh the flavoring and add to the solution with stirring

[0309] Stir until fully dissolved.

[0310] The solution was filtered.

[0311] Example 3

[0312] Formulation samples (API: active pharmaceutical ingredient) were prepared by the compositions listed in Table 3 below.

[0313] Table 3: Exemplary pharmaceutical compositions according to the present invention

[0314]

[0315] The following procedure was used to prepare the samples:

[0316] 1. Weigh all the aqueous buffer into a container

[0317] 2. Weigh the entire amount of PEG into a beaker and slowly add to the stirring solution.

[0318] 3. Weigh the entire amount of ethanol (abs.) into a beaker and add to the stirring solution (if present). Stir until well mixed.

[0319] 4. Weigh the preservative and add to the solution (if present) with stirring.

[0320] 5. Weigh the entire amount of at least one SGLT-2 inhibitor, preferably vilagagliflozin, into a beaker and add portionwise to the stirring solution. Stir until fully dissolved.

[0321] 6. Weigh the entire amount of flavoring into a beaker and add to the stirring solution. Stir until fully dissolved.

[0322] 7. Weigh the total amount of sweetener and / or viscosity enhancer and add to the solution with stirring.

[0323] 8. Stir until fully dissolved.

[0324] 9. Filter the solution using an 8 μm filter

[0325] Example 4

[0326] Formulation samples were prepared with the compositions listed in Table 4 below.

[0327] Table 4: Exemplary pharmaceutical compositions according to the present invention

[0328]

[0329] The following procedure was used to prepare the samples:

[0330] Weigh all the water into the container

[0331] Weigh the entire amount of 1N NaOH and citric acid monohydrate into a beaker and add to the stirring water. Stir until fully dissolved.

[0332] The entire amount of solubilizer (Kollidon 12 or PEG 300) was weighed into a beaker and slowly added to the stirring solution.

[0333] Weigh the entire amount of absolute ethanol into a beaker and add to the stirring solution. Stir until well mixed.

[0334] Antioxidants (if required) and preservatives were weighed and added to the solution with stirring.

[0335] The total amount of sweetener and / or viscosity enhancer is weighed and added to the solution with stirring.

[0336] Weigh the entire amount of flavoring into a beaker and add to the stirring solution. Stir until fully dissolved.

[0337] The entire amount of vilagagliflozin was weighed into a beaker and added portionwise to the stirring solution.

[0338] Stir until fully dissolved.

[0339] Filter the solution using an 8 μm filter

[0340] The solutions were found to have the following characteristics (Table 5).

[0341] Table 5:

[0342]

[0343]

[0344] *) Density was measured using an Anton Paar DMA38 densitometer.

[0345] In addition, the efficacy of the antimicrobial preservation of compositions 1 to 4 was investigated. The test criteria applied were those for evaluating the antimicrobial activity of oral preparations according to European Pharmacopoeia 7 (tested at 14 and 28 days). European Pharmacopoeia 7, method 5.1.3 "Efficacy of Antimicrobial Preservation" and USP 34, method <51> The acceptance criteria for “Antimicrobial Effectiveness Testing” are listed in Table 6 below.

[0346] Table 6: Criteria for evaluating the antimicrobial activity of oral dosage forms according to Ph. Eur. 7 and USP 34

[0347]

[0348] 1) For Ph. Eur.: No increase = No increase in number

[0349] 2) For USP: No increase = not more than 0.5 log above the reference value 10 unit

[0350] The following microorganisms were tested: Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans, Aspergillus brasiliensis, Burkholderia cepacia.

[0351] In the tests conducted, it was found that for all microorganisms, all solutions met the USP 34 method as listed in Table 6 <51> Guidelines.

[0352] Example 5

[0353] After sample preparation, the solutions were filled in polyethylene bottles and closed with polypropylene caps for chemical stability studies.

[0354] For compositions 1, 2, 3 and 4, the API content remained constant at 15.0 ± 0.1 mg / mL and no additional degradation > 1.0% was measured by HPLC analysis after 6 months at 25°C / 60% rh and 40°C / 75% rh (Table 7).

[0355] Table 7

[0356]

[0357]

[0358] Example 6

[0359] Formulation samples were prepared by the compositions listed in Tables 8 and 9 below.

[0360] Table 8: Exemplary pharmaceutical compositions according to the present invention

[0361]

[0362] Table 9: Exemplary pharmaceutical compositions according to the present invention

[0363]

[0364] The following procedure was used to prepare the samples:

[0365] Weigh approximately 80% of the desired amount of water into the container.

[0366] Weigh the entire amount of 1N NaOH and citric acid monohydrate into a beaker and add to the stirring water. Stir until fully dissolved.

[0367] The entire amount of the respective solubilizer (Kollidon 12, PEG 300, sodium lauryl sulfate, Cremophor RH40, Polysorbate 80, Poloxamer 188 and / or PEG 400) was weighed into a beaker and slowly added to the stirring solution.

[0368] Antioxidants (if required) and preservatives were weighed and added to the solution with stirring.

[0369] The total amount of sweetener and / or viscosity enhancer is weighed and added to the solution with stirring.

[0370] Weigh the entire amount of flavoring into a beaker and add to the stirring solution. Stir until fully dissolved.

[0371] The entire amount of vilagagliflozin was weighed into a beaker and added portionwise to the stirring solution.

[0372] Stir until fully dissolved.

[0373] Fill to 1100 ml with water.

[0374] Stir until a homogeneous clear solution is achieved.

[0375] Temperature testing (storage alternating between 4°C and 23°C for 3 weeks) showed no visible changes for all samples (Table 10).

[0376] Table 10

[0377] Short-term storage test at 4°C and room temperature (23°C) for 3 weeks - Visual inspection

[0378] Appearance Composition 5 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 6 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 7 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 8 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 9 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 10 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 11 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change. Composition 12 No significant changes were observed visually after storage; no discernible precipitation, crystallization or color change.

[0379] References

[0380] (1) EP 1 609 785

[0381] (2) European Pharmacopoeia, 7th edition, method 5.1.3

[0382] (3) European Pharmacopoeia, 8th edition, Chapter 2.2.1

[0383] (4) United States Pharmacopeia (USP) 34, method <51>

[0384] (5) US2011 / 077213

[0385] (6) US2014 / 031540

[0386] (7) US2017 / 145000

[0387] (8) US2020 / 237794

[0388] (9) US2022 / 016078

[0389] (10) WO 2006 / 064033

[0390] (11) WO 2007 / 028814

[0391] (12) WO 2007 / 080170

[0392] (13) WO 2007 / 093610

[0393] (14) WO 2007 / 128749

[0394] (15) WO 2013 / 079501

[0395] (16) WO 2014 / 016381

[0396] (17) WO 2014 / 195966

[0397] (18) WO 2015 / 110402

[0398] (19) WO 2015 / 173584

[0399] (20) WO 2017 / 032799

[0400] (21) WO 2020 / 219645

[0401] (22) WO 2021 / 105152

[0402] (23) WO 2021 / 165177

[0403] (24) WO 2023 / 006718

[0404] (25) WO 2023 / 006745

[0405] (26) WO 2023 / 006747

[0406] (27) Xu G et al., Journal of Medical Chemistry 2014, 57: 1236-1251

[0407] The following technical solutions are also part of the present invention and are included in the spirit and scope of the present invention:

[0408] 1. An aqueous pharmaceutical composition comprising at least one SGLT-2 inhibitor and one or more solubilizers.

[0409] 2. The aqueous pharmaceutical composition according to technical solution 1, wherein at least one SGLT-2 inhibitor is selected from the group consisting of:

[0410] (1) Benzene derivatives substituted with pyranose

[0411]

[0412] Where R 1 represents cyano, Cl or methyl (most preferably cyano);

[0413] R 2 represents H, methyl, methoxy or hydroxy (most preferably H) and

[0414] R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-but-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl,

[0415] 1-Hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl,

[0416] 2-Hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-prop-1-yl, 3-hydroxy-3-methyl-but-1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-

[0417] ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano;

[0418] Where R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and most preferably R 3 is cyclopropyl,

[0419] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl group acylation;

[0420] (2) Vilagliflozin, represented by formula (2):

[0421]

[0422] (3) Dapagliflozin, represented by formula (3):

[0423]

[0424] (4) Canagliflozin, represented by formula (4):

[0425]

[0426] (5) Empagliflozin, represented by formula (5):

[0427]

[0428] (6) Rupagliflozin, represented by formula (6):

[0429]

[0430] (7) Togliflozin, represented by formula (7):

[0431]

[0432] (8) Ipagliflozin, represented by formula (8):

[0433]

[0434] (9) Egliflozin, represented by formula (9):

[0435]

[0436] (10) Agliflozin, represented by formula (10):

[0437]

[0438] (11) Repagliflozin, represented by formula (11):

[0439]

[0440] (11A) Repagliflozin ectoate, represented by formula (11A):

[0441]

[0442] (12) Thiophene derivatives of formula (12)

[0443]

[0444] wherein R represents a methoxy group or a trifluoromethoxy group;

[0445] (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by formula (13);

[0446]

[0447] (14) Spiroketal derivatives of formula (14):

[0448]

[0449] wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl or tert-butyl;

[0450] (15) Pyrazole-O-glucoside derivatives of formula (15)

[0451]

[0452] in

[0453] R 1 Represents C 1-3 Alkoxy,

[0454] L 1 , L2 independently of each other represent H or F,

[0455] R 6 Indicates H, (C 1-3 alkyl)carbonyl, (C 1-6 alkyl)oxycarbonyl, phenoxycarbonyl, benzyloxycarbonyl or benzylcarbonyl;

[0456] (16) Sogliflozin, represented by formula (16):

[0457]

[0458] (17) Sergliflozin is represented by formula (17):

[0459]

[0460] (18) A compound represented by formula (18):

[0461]

[0462] in

[0463] R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-butan-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propan-1-yl, 3-hydroxy-3-methyl-butan-1-yl -yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, and wherein R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and R 3 Most preferably, it is cyclopropyl,

[0464] or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3alkyl)-carbonyl group acylation;

[0465] (19) Bexagliflozin, represented by formula (19):

[0466]

[0467] (20) gagliflozin, represented by formula (20):

[0468]

[0469] (21) Jungliazine,

[0470]

[0471] (22) Vanpagliflozin.

[0472] 3. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 2, wherein at least one SGLT-2 inhibitor is vilagagliflozin, which is preferably the only SGLT-2 inhibitor contained in the aqueous pharmaceutical composition, and / or wherein the aqueous pharmaceutical composition is for administration to an individual, preferably an animal, more preferably a mammal, especially a horse, cat, dog or cow; wherein the aqueous pharmaceutical composition is preferably sterile.

[0473] 4. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 3, wherein the composition is substantially free of organic solvents, preferably free of any organic solvents.

[0474] 5. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 3, wherein the composition contains no more than 20 g / 100 mL (20% w / v) of organic solvent, preferably no more than 15 g / 100 mL (15% w / v) of organic solvent, more preferably no more than 10 g / 100 mL (10% w / v) of organic solvent, wherein the organic solvent preferably comprises ethanol, wherein ethanol is more preferably the only organic solvent contained in the aqueous pharmaceutical composition.

[0475] 6. The aqueous pharmaceutical composition according to technical solution 5, wherein the composition does not contain propane-1,2-diol (propylene glycol).

[0476] 7. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 6, wherein the one or more solubilizers are selected from the group consisting of: "surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone", preferably selected from the group consisting of: "sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone)", wherein the total amount of the one or more solubilizers is preferably 1 to 50 g / 100 mL (1-50% w / v), more preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v).

[0477] 8. The aqueous pharmaceutical composition according to any one of technical solutions 1 to 6, wherein two or more solubilizers are contained in the aqueous pharmaceutical composition.

[0478] 9. An aqueous pharmaceutical composition according to technical solution 8, wherein two solubilizers are contained in the aqueous pharmaceutical composition, wherein the amount of the first solubilizer and the amount of the second solubilizer are preferably independently selected from 1 to 50 g / 100 mL (1-50% w / v), more preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v), wherein the two solubilizers are more preferably independently selected from the group consisting of: “sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone)", wherein the two solubilizers are even more preferably Kollidon 12 (povidone) and PEG 200, PEG 300 or PEG 400, and most preferably Kollidon 12 (povidone) and PEG 300.

[0479] 10. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 9, wherein the aqueous pharmaceutical composition is a solution, emulsion or suspension, preferably a solution, emulsion or suspension having an NTU value equal to or less than 10.0, more preferably equal to or less than 7.0, even more preferably equal to or less than 3.0, and most preferably a solution, especially a solution having an NTU value equal to or less than 3.0.

[0480] 11. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 10, wherein the aqueous pharmaceutical composition contains 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), most preferably 50 to 80 g / 100 mL (50 to 80% w / v) of water, more preferably in the form of an aqueous buffer, such as a citric acid buffer.

[0481] 12. An aqueous pharmaceutical composition according to technical solution 11, wherein the measured pH value of the aqueous pharmaceutical composition is 2 to 7, preferably 3 to 7, more preferably 3.0 to 6.5, even more preferably 4.0 to 6.5, even more preferably 4.0 to 5.0, and most preferably 4.5.

[0482] 13. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 12, wherein the aqueous pharmaceutical composition further comprises one or more preservatives, preferably selected from the group consisting of: sorbic acid or its salts, more preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, more preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parahydroxybenzoic acid esters and their salts, more preferably methyl parahydroxybenzoate, parahydroxybenzoic acid ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, sodium butyl parahydroxybenzoate; most preferably benzoic acid and / or its salts, such as sodium benzoate; and / or additionally comprises one or more antioxidants, preferably selected from the group consisting of: ascorbic acid or its pharmaceutically acceptable salts, especially sodium ascorbate; citric acid (anhydrous and / or monohydrate) or its pharmaceutically acceptable salts, more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; metasulfuric acid Sodium bisulfate; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, especially propyl gallate, octyl gallate; vitamin E or its pharmaceutically acceptable salt; ascorbyl palmitate; edetic acid or its pharmaceutically acceptable salt; most preferably sodium metabisulfite; and / or additionally comprises one or more viscosity increasing agents, preferably selected from the group consisting of: "inorganic gelling agent, organic gelling agent, cellulose derivatives", more preferably selected from the group consisting of: "hydroxyethylcellulose, hydroxypropyl methylcellulose, silicon dioxide"; and / or additionally comprises one or more flavoring agents and / or sweeteners, preferably selected from the group consisting of: "honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol".

[0483] 14. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 13, comprising, preferably consisting of:

[0484] (i) at least one SGLT-2 inhibitor, preferably vilagagliflozin, more preferably only one single SGLT-2 inhibitor, even more preferably only vilagagliflozin as the single SGLT-2 inhibitor;

[0485] (ii) optionally but preferably, one or more preservatives; preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; or combinations thereof; most preferably benzoic acid and / or its salts, such as sodium benzoate;

[0486] (iii) optionally one or more organic solvents, preferably selected from the group consisting of: "ethanol, propane-1,2,3-triol (glycerol), pyrrolidone, methylpyrrolidone, N,N-dimethylacetamide and / or N,N-dimethylformamide", more preferably ethanol;

[0487] (iv) optionally one or more flavorings and / or sweeteners, preferably selected from the group consisting of: "honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol";

[0488] (v) water, preferably in the form of an aqueous buffer, more preferably a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5;

[0489] (vi) one or more solubilizers, preferably selected from the group consisting of: "surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone", more preferably selected from the group consisting of: "sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (Povidone)";

[0490] (vii) optionally one or more viscosity increasing agents, preferably selected from the group consisting of: "inorganic gelling agents, organic gelling agents, cellulose derivatives", more preferably selected from the group consisting of: "hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide";

[0491] (viii) one or more antioxidants may be present, preferably selected from the group consisting of: ascorbic acid or a pharmaceutically acceptable salt thereof, in particular sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof, more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, in particular propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

[0492] 15. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 14, comprising, preferably consisting of:

[0493] (i) 0.5-20.0 g / 100 mL (0.5-20.0% w / v), preferably 0.5-15.0 g / 100 mL (0.5-15.0% w / v), more preferably 1.0 -1.5 g / 100 mL (1.0-1.5% w / v) of at least one SGLT-2 inhibitor, preferably vilagagliflozin, more preferably only one single SGLT-2 inhibitor, even more preferably only vilagagliflozin as the single SGLT-2 inhibitor;

[0494] (ii) 0-3.0 g / 100 mL (0-3.0% w / v), preferably 0.05-3.0 g / 100 mL (0.05-3.0% w / v), more preferably 0.05-2.0 g / 100 mL (0.05-2.0% w / v) of one or more preservatives; more preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; or a combination thereof; most preferably benzoic acid and / or its salts, such as sodium benzoate;

[0495] (iii) 0-20 g / 100 mL (0-20% w / v), preferably 0-15 g / 100 mL (0-15% w / v), more preferably 0-12 g / 100 mL (0-12% w / v), even more preferably 0-10 g / 100 mL (0-10% w / v) of one or more organic solvents, preferably selected from the group consisting of: "ethanol, propane-1,2,3-triol (glycerol), pyrrolidone, methylpyrrolidone, N,N-dimethylacetamide and / or N,N-dimethylformamide", more preferably ethanol;

[0496] (iv) 0-40 g / 100 mL (0-40% w / v), preferably 0-30 g / 100 mL (0-30% w / v), more preferably 0-2 g / 100 mL (0-2% w / v) of one or more flavorings and / or sweeteners, more preferably selected from the group consisting of: "honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol";

[0497] (v) 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), most preferably 50 to 80 g / 100 mL (50 to 80% w / v) of water, preferably in the form of an aqueous buffer, more preferably a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5;

[0498] (vi) 1 to 50 g / 100 mL (1-50% w / v), preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v) of one or more solubilizers, preferably selected from the group consisting of: “surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone”, more preferably selected from the group consisting of: “sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (Povidone)";

[0499] (vii) 0-40 g / 100 mL (0-40% w / v), preferably 10-30 g / 100 mL (10-30% w / v) of one or more viscosity increasing agents, preferably selected from the group consisting of: "inorganic gelling agents, organic gelling agents, cellulose derivatives", more preferably selected from the group consisting of: "hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide";

[0500] (viii) 0-1.0 g / 100 mL (0-1.0% w / v), preferably 0-0.5 g / 100 mL (0-0.5% w / v), more preferably 0.1-0.3 g / 100 mL (0.1-0.3% w / v) of one or more antioxidants, preferably selected from the group consisting of ascorbic acid or a pharmaceutically acceptable salt thereof, especially sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof , more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, especially propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

[0501] 16. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 15, comprising: vilagagliflozin; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; water.

[0502] 17. The aqueous pharmaceutical composition according to any one of technical solutions 1 to 16, which is selected from the group consisting of the following compositions 1 to 12:

[0503]

[0504]

[0505] 18. The aqueous pharmaceutical composition according to any one of technical solutions 1 to 17, wherein the aqueous pharmaceutical composition is for oral and / or parenteral administration, preferably oral administration.

[0506] 19. An aqueous pharmaceutical composition according to any one of technical solutions 1 to 18, for use in a method for treating and / or preventing one or more medical indications in an individual, preferably an animal, more preferably a mammal, especially a horse, cat, dog or cattle, in need of such treatment and / or prevention, wherein the one or more medical indications are selected from the following medical indications:

[0507] (i) metabolic disorders of equines, wherein the metabolic disorders are preferably one or more disorders selected from the group consisting of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity, wherein the metabolic disorders are preferably insulin resistance, hyperinsulinemia, and / or clinical conditions associated with insulin resistance and / or hyperinsulinemia; wherein the clinical conditions are preferably one or more disorders selected from the group consisting of impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity;

[0508] (ii) metabolic disorders of equines, wherein the metabolic disorders are one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome, wherein the metabolic disorders are preferably clinical conditions / signs associated with insulin resistance and / or hyperinsulinemia, wherein the clinical conditions / signs are preferably one or more conditions selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome;

[0509] (iii) a metabolic disorder in a feline, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes, insulin resistance, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function, and / or wherein remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained;

[0510] (iv) a metabolic disorder in a canine, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, obesity, hyperglycemia, hyperglycemia-induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, pancreatic inflammation, consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders, and / or Syndrome X (metabolic syndrome), preferably prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, wherein the development of hyperglycemia-induced cataract formation is preferably avoided or remission is achieved, and / or wherein the development of consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders is preferably avoided or the progression is slowed or remission is achieved;

[0511] (v) cardiac disease in a feline, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure, heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to cardiomyopathy of unspecified type (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), cardiomyopathy of unspecified type (UCM) and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), hypertrophic cardiomyopathy (HCM);

[0512] (vi) drying off of non-human mammals, preferably ruminants; improving and / or promoting drying off of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or swelling in the udder, preferably the breast and / or mammary gland of non-human mammals, preferably ruminants; reducing discomfort associated with udder swelling in non-human mammals, preferably ruminants, such as increasing daily lying time and / or reducing pressure; reducing milk leakage after drying off of non-human mammals, preferably ruminants; reducing the incidence of intramammary infection (IMI), preferably mastitis and / or metritis in non-human mammals, preferably ruminants.

[0513] 20. A method for preparing an aqueous pharmaceutical composition as described in any one of technical solutions 1 to 18, comprising the following steps (in any meaningful order):

[0514] (i) mixing one or more organic solvents such as ethanol (if present) with water (if no organic solvent is present, only water is used as the starting material);

[0515] (ii) adding one or more solubilizing agents to the mixture (or water) prepared in step (i);

[0516] (iii) dissolving at least one SGLT-2 inhibitor, preferably vilagagliflozin, in the mixture prepared in step (ii);

[0517] (iv) optionally dissolving one or more preservatives in the mixture prepared in step (iii),

[0518] (v) optionally further dissolving other excipients, such as pH adjusters, flavoring agents, sweeteners, antioxidants, viscosity enhancers and the like, in the mixture prepared by step (iii) or optionally (iv);

[0519] (vi) optionally filtering the mixture prepared by step (iii), optionally step (iv) or optionally step (v);

[0520] Optionally, an additional mixing step can thus be carried out independently of one another after any of the mandatory or optionally selected individual method steps.

[0521] 21. A kit comprising:

[0522] (a) an aqueous pharmaceutical composition according to any one of technical solutions 1 to 18; and

[0523] (b) a package insert comprising information that the aqueous pharmaceutical composition is used for the prevention and / or treatment of one or more medical indications in a subject in need of such prevention and / or treatment, wherein the one or more medical indications are selected from the group consisting of:

[0524] (i) metabolic disorders of equines, wherein the metabolic disorders are preferably one or more disorders selected from the group consisting of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity, wherein the metabolic disorders are preferably insulin resistance, hyperinsulinemia, and / or clinical conditions associated with insulin resistance and / or hyperinsulinemia; wherein the clinical conditions are preferably one or more disorders selected from the group consisting of impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity;

[0525] (ii) metabolic disorders of equines, wherein the metabolic disorders are one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome, wherein the metabolic disorders are preferably clinical conditions / signs associated with insulin resistance and / or hyperinsulinemia, wherein the clinical conditions / signs are preferably one or more conditions selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome;

[0526] (iii) a metabolic disorder in a feline, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes, insulin resistance, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function, and / or wherein remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained;

[0527] (iv) a metabolic disorder in a canine, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, obesity, hyperglycemia, hyperglycemia-induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, pancreatic inflammation, consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders, and / or Syndrome X (metabolic syndrome), preferably prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, wherein the development of hyperglycemia-induced cataract formation is preferably avoided or remission is achieved, and / or wherein the development of consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders is preferably avoided or the progression is slowed or remission is achieved;

[0528] (v) cardiac disease in a feline, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure, heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to cardiomyopathy of unspecified type (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), cardiomyopathy of unspecified type (UCM) and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), hypertrophic cardiomyopathy (HCM);

[0529] (vi) drying off of non-human mammals, preferably ruminants; improving and / or promoting drying off of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or swelling in the udder, preferably the breast and / or mammary gland of non-human mammals, preferably ruminants; reducing discomfort associated with udder swelling in non-human mammals, preferably ruminants, such as increasing daily lying time and / or reducing pressure; reducing milk leakage after drying off of non-human mammals, preferably ruminants; reducing the incidence of intramammary infection (IMI), preferably mastitis and / or metritis in non-human mammals, preferably ruminants.

Claims

1. An aqueous pharmaceutical composition comprising at least one SGLT-2 inhibitor and one or more solubilizers.

2. The aqueous pharmaceutical composition of claim 1, wherein the at least one SGLT-2 inhibitor is selected from the group consisting of: (1) Benzene derivatives substituted with pyranose glucopyranosyl of formula (1): Where R 1 represents cyano, Cl or methyl (most preferably cyano); R 2 represents H, methyl, methoxy or hydroxy (most preferably H), and R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-but-1-yl, cyclobutyl, Cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-prop-1-yl, 3-hydroxy-3-methyl-but-1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; Where R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and most preferably R 3 is cyclopropyl, or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose group are selected from (C 1-18 alkyl)carbonyl, (C 1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl group acylation; (2) velagliflozin, represented by formula (2): (3) Dapagliflozin, represented by formula (3): (4) Canagliflozin, represented by formula (4): (5) Empagliflozin, represented by formula (5): (6) Luseogliflozin, represented by formula (6): (7) Tofogliflozin, represented by formula (7): (8) Ipragliflozin, represented by formula (8): (9) Ertugliflozin, represented by formula (9): (10) Agliflozin, represented by formula (10): (11) Remogliflozin, represented by formula (11): (11A) Remogliflozin etabonate, represented by formula (11A): (12) Thiophene derivatives of formula (12): wherein R represents a methoxy group or a trifluoromethoxy group; (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by formula (13); (14) Spiroketal derivatives of formula (14): wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl or tert-butyl; (15) Pyrazole-O-glucoside derivatives of formula (15): in R 1 Represents C 1-3 Alkoxy, L 1 , L 2 independently of each other represent H or F, R 6 Indicates H, (C 1-3 alkyl)carbonyl, (C 1-6 alkyl)oxycarbonyl, phenoxycarbonyl, benzyloxycarbonyl or benzylcarbonyl; (16) Sotagliflozin, represented by formula (16): (17) Sergliflozin, represented by formula (17): (18) A compound represented by formula (18): in R 3 represents cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, 3-methyl-butan-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxy-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propan-1-yl, 3-hydroxy-3-methyl-butan-1-yl -yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethoxy, trifluoromethoxy, 2-methoxy-ethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, and wherein R 3 is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; and R 3 Most preferably, it is cyclopropyl, or its derivatives, wherein one or more hydroxyl groups of the β-D-pyranoglucopyranose are selected from (C 1-18 alkyl)carbonyl, (C1-18 alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 alkyl)-carbonyl group acylation; (19) Bexagliflozin, represented by formula (19): (20) Janagliflozin, represented by formula (20): (21) Rongliflozin, represented by formula (21): (22) Wanpagliflozin; (23) Enagagliflozin, represented by formula (23): (24) TFC-039, represented by formula (24):

3. The aqueous pharmaceutical composition according to any one of claims 1 to 2, wherein the at least one SGLT-2 inhibitor is vilagagliflozin.

4. The aqueous pharmaceutical composition of claim 3, wherein vilagagliflozin is the only SGLT-2 inhibitor contained in the aqueous pharmaceutical composition.

5. The aqueous pharmaceutical composition according to any one of claims 1 to 4, wherein the aqueous pharmaceutical composition is preferably for direct administration to an individual, more preferably an animal, even more preferably a mammal, especially a horse, cat, dog or cow, preferably without further mandatory processing and / or purification steps.

6. The aqueous pharmaceutical composition of claim 5, wherein the aqueous pharmaceutical composition is sterile.

7. An aqueous pharmaceutical composition according to any one of claims 1 to 6, wherein the composition is substantially free of organic solvents, preferably free of any organic solvents.

8. The aqueous pharmaceutical composition of any one of claims 1 to 6, wherein the composition contains no more than 20 g / 100 mL (20% w / v) of an organic solvent, preferably no more than 15 g / 100 mL (15% w / v) of an organic solvent, and more preferably no more than 10 g / 100 mL (10% w / v) of an organic solvent.

9. The aqueous pharmaceutical composition of claim 8, wherein the organic solvent comprises ethanol.

10. The aqueous pharmaceutical composition of claim 9, wherein the organic solvent comprises, preferably consists of, propane-1,2,3-triol (glycerol) and ethanol.

11. The aqueous pharmaceutical composition of claim 9, wherein ethanol is the only organic solvent contained in the aqueous pharmaceutical composition.

12. An aqueous pharmaceutical composition as claimed in any one of claims 9 to 11, wherein the composition contains no more than 20 g / 100 mL (20% w / v) of ethanol, preferably no more than 15 g / 100 mL (15% w / v) of ethanol, more preferably no more than 10 g / 100 mL (10% w / v) of ethanol; and most preferably contains 8 g / 100 mL (8% w / v) of ethanol.

13. The aqueous pharmaceutical composition of claims 1 to 6, 8 to 10 and 12, wherein the composition does not contain propane-1,2-diol (propylene glycol).

14. The aqueous pharmaceutical composition according to any one of claims 1 to 13, wherein the one or more solubilizers are selected from the group consisting of surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone, preferably selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone), wherein the total amount of the one or more solubilizing agents is preferably 1 to 50 g / 100 mL (1-50% w / v), more preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v).

15. The aqueous pharmaceutical composition of any one of claims 1 to 14, wherein two or more solubilizing agents are included in the aqueous pharmaceutical composition.

16. The aqueous pharmaceutical composition of claim 15, wherein two solubilizers are contained in the aqueous pharmaceutical composition, wherein the amount of the first solubilizer and the amount of the second solubilizer are preferably independently selected from 1 to 50 g / 100 mL (1-50% w / v), more preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v).

17. The aqueous pharmaceutical composition of claim 16, wherein the two solubilizers are independently selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone).

18. The aqueous pharmaceutical composition of claim 17, wherein the two solubilizers are Kollidon 12 (povidone) and PEG 200, PEG 300 or PEG 400.

19. The aqueous pharmaceutical composition of claim 18, wherein the two solubilizers are Kollidon 12 (povidone) and PEG 300.

20. The aqueous pharmaceutical composition according to any one of claims 1 to 19, wherein the aqueous pharmaceutical composition is a solution, emulsion or suspension, preferably a solution, emulsion or suspension having an NTU value equal to or less than 10.0, more preferably equal to or less than 7.0, even more preferably equal to or less than 3.

0.

21. The aqueous pharmaceutical composition of claim 20, wherein the aqueous pharmaceutical composition is a solution having an NTU value equal to or less than 3.

0.

22. An aqueous pharmaceutical composition according to any one of claims 1 to 21, wherein the aqueous pharmaceutical composition contains 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), most preferably 50 to 80 g / 100 mL (50 to 80% w / v) of water, more preferably in the form of an aqueous buffer, such as a citric acid buffer.

23. The aqueous pharmaceutical composition of claim 22, wherein the pH of the aqueous pharmaceutical composition is 2 to 7, preferably 3 to 7, more preferably 3.0 to 6.5, even more preferably 4.0 to 6.5, even more preferably 4.0 to 5.0, and most preferably 4.

5.

24. The aqueous pharmaceutical composition of any one of claims 1 to 23, wherein the aqueous pharmaceutical composition further comprises one or more preservatives, which are preferably selected from the group consisting of: sorbic acid or a salt thereof, more preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or a salt thereof, more preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, more preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; most preferably benzoic acid and / or its salts, such as sodium benzoate.

25. The aqueous pharmaceutical composition of any one of claims 1 to 24, wherein the aqueous pharmaceutical composition additionally comprises one or more antioxidants, preferably selected from the group consisting of: ascorbic acid or a pharmaceutically acceptable salt thereof, in particular sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof, more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, in particular propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

26. The aqueous pharmaceutical composition according to any one of claims 1 to 25, wherein the aqueous pharmaceutical composition further comprises one or more viscosity increasing agents, preferably selected from the group consisting of inorganic gelling agents, organic gelling agents, cellulose derivatives, more preferably selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide.

27. The aqueous pharmaceutical composition of any one of claims 1 to 26, wherein the aqueous pharmaceutical composition additionally comprises one or more flavorings and / or sweeteners, preferably selected from the group consisting of honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol.

28. An aqueous pharmaceutical composition according to any one of claims 1 to 27, comprising, preferably consisting of: (i) at least one SGLT-2 inhibitor, preferably vilagagliflozin, more preferably only one single SGLT-2 inhibitor, even more preferably only vilagagliflozin as the single SGLT-2 inhibitor; (ii) optionally but preferably, one or more preservatives; preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; or combinations thereof; most preferably benzoic acid and / or its salts, such as sodium benzoate; (iii) optionally one or more organic solvents, preferably selected from the group consisting of ethanol, propane-1,2,3-triol (glycerol), pyrrolidone, methylpyrrolidone, N,N-dimethylacetamide and / or N,N-dimethylformamide, more preferably ethanol; (iv) optionally one or more flavorings and / or sweeteners, preferably selected from the group consisting of: honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol; (v) water, preferably in the form of an aqueous buffer, more preferably a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5; (vi) one or more solubilizers, preferably selected from the group consisting of surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone, more preferably selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone); (vii) optionally one or more viscosity increasing agents, preferably selected from the group consisting of inorganic gelling agents, organic gelling agents, cellulose derivatives, more preferably selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide; (viii) one or more antioxidants may be present, preferably selected from the group consisting of: ascorbic acid or a pharmaceutically acceptable salt thereof, in particular sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof, more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, in particular propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

29. An aqueous pharmaceutical composition according to any one of claims 1 to 28, comprising, preferably consisting of: (i) 0.5-20.0 g / 100 mL (0.5-20.0% w / v), preferably 0.5-15.0 g / 100 mL (0.5-15.0% w / v), more preferably 1.0-1.5 g / 100 mL (1.0-1.5% w / v) of at least one SGLT-2 inhibitor, preferably vilagagliflozin, more preferably only one single SGLT-2 inhibitor, even more preferably only vilagagliflozin as the single SGLT-2 inhibitor; (ii) 0-3.0 g / 100 mL (0-3.0% w / v), preferably 0.05-3.0 g / 100 mL (0.05-3.0% w / v), more preferably 0.05-2.0 g / 100 mL (0.05-2.0% w / v) of one or more preservatives; more preferably selected from the group consisting of: sorbic acid or its salts, preferably sodium sorbate, potassium sorbate, calcium sorbate; benzoic acid or its salts, preferably sodium benzoate; benzalkonium chloride; benzethonium chloride; benzyl alcohol, cetylpyridinium chloride; sodium metabisulfite; sodium acetate; parabens and their salts, preferably methylparaben, ethylparaben, propylparaben, butylparaben, sodium butylparaben; or a combination thereof; most preferably benzoic acid and / or its salts, such as sodium benzoate; (iii) 0-20 g / 100 mL (0-20% w / v), preferably 0-15 g / 100 mL (0-15% w / v), more preferably 0-12 g / 100 mL (0-12% w / v), even more preferably 0-10 g / 100 mL (0-10% w / v) of one or more organic solvents, preferably selected from the group consisting of ethanol, propane-1,2,3-triol (glycerol), pyrrolidone, methylpyrrolidone, N,N-dimethylacetamide and / or N,N-dimethylformamide, more preferably ethanol; (iv) 0-40 g / 100 mL (0-40% w / v), preferably 0-30 g / 100 mL (0-30% w / v), more preferably 0-2 g / 100 mL (0-2% w / v) of one or more flavorings and / or sweeteners, more preferably selected from the group consisting of: honey flavoring, lime / sage flavoring, jasmine flavoring, lavender flavoring, peppermint flavoring, raspberry flavoring, lemon flavoring, herbal flavoring, meat flavoring, vanilla extract / vanilla flavoring, saccharin, aspartame, sorbitol, xylitol; (v) 30 to 100 g / 100 mL (30 to 100% w / v), preferably 30 to 95 g / 100 mL (30 to 95% w / v), more preferably 30 to 90 g / 100 mL (30 to 90% w / v), more preferably 30 to 85 g / 100 mL (30 to 85% w / v), even more preferably 30 to 80 g / 100 mL (30 to 80% w / v), most preferably 50 to 80 g / 100 mL (50 to 80% w / v) of water, preferably in the form of an aqueous buffer, more preferably a citric acid buffer, even more preferably an aqueous buffer having a pH of 4.5, most preferably a citric acid buffer having a pH of 4.5; (vi) 1 to 50 g / 100 mL (1-50% w / v), preferably 1 to 45 g / 100 mL (1-45% w / v), even more preferably 1 to 40 g / 100 mL (1-40% w / v), even more preferably 1 to 35 g / 100 mL (1-35% w / v), even more preferably 1 to 30 g / 100 mL (1-30% w / v), even more preferably 1 to 25 g / 100 mL (1-25% w / v), most preferably 5 to 25 g / 100 mL (5-25% w / v) of one or more solubilizers, preferably selected from the group consisting of surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, propylene glycol derivatives, polyvinyl pyrrolidone, more preferably selected from the group consisting of sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone); (vii) 0-40 g / 100 mL (0-40% w / v), preferably 10-30 g / 100 mL (10-30% w / v) of one or more viscosity increasing agents, preferably selected from the group consisting of inorganic gelling agents, organic gelling agents, cellulose derivatives, more preferably selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl methyl cellulose, silicon dioxide; (viii) 0-1.0 g / 100 mL (0-1.0% w / v), preferably 0-0.5 g / 100 mL (0-0.5% w / v), more preferably 0.1-0.3 g / 100 mL (0.1-0.3% w / v) of one or more antioxidants, preferably selected from the group consisting of ascorbic acid or a pharmaceutically acceptable salt thereof, especially sodium ascorbate; citric acid (anhydrous and / or monohydrate) or a pharmaceutically acceptable salt thereof , more preferably sodium citrate; isoascorbic acid; fumaric acid; malic acid; monothioglycerol; phosphoric acid; sodium metabisulfite; potassium metabisulfite; propionic acid; sodium bisulfite; sodium sulfite; resveratrol; butylated hydroxyanisole; butylated hydroxytoluene; gallic acid ester derivatives, especially propyl gallate, octyl gallate; vitamin E or a pharmaceutically acceptable salt thereof; ascorbyl palmitate; edetic acid or a pharmaceutically acceptable salt thereof; most preferably sodium metabisulfite.

30. An aqueous pharmaceutical composition according to any one of claims 1 to 29, comprising, preferably consisting of: Vilaggliflozin; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; water.

31. An aqueous pharmaceutical composition according to any one of claims 1 to 29, comprising, preferably consisting of: Vilaggliflozin; citric acid monohydrate; NaOH; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; water.

32. An aqueous pharmaceutical composition according to any one of claims 1 to 29, comprising, preferably consisting of: Vilaggliflozin; citric acid monohydrate; NaOH; sodium dodecyl sulfate (SDS), Cremophor RH 40 (PEG-40 hydrogenated castor oil, polyethylene glycol glyceryl hydroxystearate 40), polysorbate 20, Lutrol F 68 (Poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate and / or Kollidon 12 (povidone); sodium benzoate; optionally sodium metabisulfite; optionally ethanol; sorbitol and / or xylitol; honey flavoring and / or vanilla extract and / or meat flavoring; water.

33. The aqueous pharmaceutical composition of any one of claims 1 to 32, selected from the group consisting of the following compositions 1 to 12:

34. The aqueous pharmaceutical composition according to any one of claims 1 to 33, wherein the aqueous pharmaceutical composition is for oral and / or parenteral administration, preferably oral administration.

35. An aqueous pharmaceutical composition according to any one of claims 1 to 34 for use in a method of treatment and / or prevention of one or more medical indications in a subject, preferably an animal, more preferably a mammal, in particular a horse, cat, dog or cow in need of such treatment and / or prevention, said one or more medical indications being selected from the following medical indications: (i) a metabolic disorder of an equine animal, wherein the metabolic disorder is preferably one or more disorders selected from the group consisting of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity, wherein the metabolic disorder is preferably insulin resistance, hyperinsulinemia, and / or a clinical condition associated with insulin resistance and / or hyperinsulinemia; wherein the clinical condition is preferably one or more disorders selected from the group consisting of impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity; (ii) metabolic disorders of equines, wherein the metabolic disorders are one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome, wherein the metabolic disorders are preferably clinical conditions / signs associated with insulin resistance and / or hyperinsulinemia, wherein the clinical conditions / signs are preferably one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome; (iii) a metabolic disorder in a feline, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes, insulin resistance, acromegaly, diabetes with elevated IGF-1 concentrations, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function, and / or wherein remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained; (iv) a metabolic disorder in a canine, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, obesity, hyperglycemia, hyperglycemia-induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, pancreatic inflammation, consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders, and / or Syndrome X (metabolic syndrome), preferably prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, wherein the development of hyperglycemia-induced cataract formation is preferably prevented or remission is achieved, and / or wherein the development of consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders is preferably prevented or the progression is slowed or remission is achieved; (v) cardiac disease in a feline, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure, heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to cardiomyopathy of unspecified type (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), cardiomyopathy of unspecified type (UCM) and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), hypertrophic cardiomyopathy (HCM); (vi) drying off of non-human mammals, preferably ruminants; improving and / or promoting said drying off of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or swelling in the udder, preferably the breast and / or mammary gland of non-human mammals, preferably ruminants; reducing discomfort associated with udder swelling in non-human mammals, preferably ruminants, such as increasing daily lying time and / or reducing stress; reducing milk leakage after drying off of non-human mammals, preferably ruminants; reducing the incidence of intramammary infection (IMI), preferably mastitis and / or metritis, in non-human mammals, preferably ruminants; (vii) a heart disease in a non-human mammal excluding cats, in particular a dog, wherein the heart disease is preferably one or more selected from the group consisting of: heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to (myxo)mitral valve disease [(M)MVD]; congestive heart failure due to (myxo)mitral valve disease [(M)MVD]; asymptomatic / preclinical / occult heart failure due to (myxo)mitral valve disease [(M)MVD]; (myxo)mitral valve disease [(M)MVD]; clinically evident Overt (myxo) mitral valve disease [(M)MVD]; Asymptomatic / preclinical / latent (myxo) mitral valve disease [(M)MVD]; Heart failure attributed to dilated cardiomyopathy (DCM); Congestive heart failure attributed to dilated cardiomyopathy (DCM); Asymptomatic / preclinical / latent heart failure attributed to dilated cardiomyopathy (DCM); Dilated cardiomyopathy (DCM); Clinically overt dilated cardiomyopathy (DCM); Asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); Aortic stenosis (valvular, supravalvular, and / or subvalvular); (viii) hypertension in a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the hypertension is preferably one or more selected from the group consisting of: situational hypertension, secondary hypertension and idiopathic hypertension, wherein the secondary hypertension is preferably selected from the group consisting of: hypertension associated with chronic kidney disease (CKD), diabetes, obesity, heart disease, endocrine diseases such as Cushing's disease, hyperthyroidism, acromegaly; and an increase in blood pressure (BP) induced by a pharmaceutical agent, preferably a glucocorticoid, a mineralocorticoid, an erythropoiesis stimulating agent, ephedrine and / or high-dose sodium chloride; (ix) renal disease of a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the renal disease is preferably one or more selected from the group consisting of renal dysplasia, glomerular disease, polycystic kidney disease, amyloidosis, tubular nephritis / tubule-interstitial nephritis (TIN), acute kidney disease, chronic kidney disease.

36. A process for preparing an aqueous pharmaceutical composition as claimed in any one of claims 1 to 34, comprising the following steps (in any meaningful order): (i) mixing the one or more organic solvents (if present), such as ethanol, with water (if no organic solvent is present, only water is used as the starting material); (ii) adding one or more solubilizing agents to the mixture prepared in step (i) (or water if no organic solvent is present); (iii) dissolving the at least one SGLT-2 inhibitor, preferably vilagagliflozin, in the mixture prepared in step (ii); (iv) optionally dissolving the one or more preservatives in the mixture prepared in step (iii), (v) optionally further dissolving other excipients, such as pH adjusters, flavoring agents, sweeteners, antioxidants, viscosity enhancers and the like, in the mixture prepared by step (iii) or optionally (iv); (vi) optionally filtering the mixture prepared by step (iii), optionally step (iv) or optionally step (v); Optionally, any of the mandatory or optionally selected individual method steps can thus be followed by an additional mixing step independently of one another.

37. A kit comprising: (a) an aqueous pharmaceutical composition according to any one of claims 1 to 34; and (b) a package insert comprising information that the aqueous pharmaceutical composition is to be used for the prevention and / or treatment of one or more medical indications in a subject in need of such prevention and / or treatment, wherein the one or more medical indications are selected from the following medical indications: (i) a metabolic disorder of an equine animal, wherein the metabolic disorder is preferably one or more disorders selected from the group consisting of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity, wherein the metabolic disorder is preferably insulin resistance, hyperinsulinemia, and / or a clinical condition associated with insulin resistance and / or hyperinsulinemia; wherein the clinical condition is preferably one or more disorders selected from the group consisting of impaired glucose tolerance, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, obesity and / or localized obesity; (ii) metabolic disorders of equines, wherein the metabolic disorders are one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome, wherein the metabolic disorders are preferably clinical conditions / signs associated with insulin resistance and / or hyperinsulinemia, wherein the clinical conditions / signs are preferably one or more disorders selected from the group consisting of laminitis, vascular dysfunction, hypertension, hepatic lipopathy, atherosclerosis, hyperadrenocorticism, pars intermedius dysfunction and / or equine metabolic syndrome; (iii) a metabolic disorder in a feline, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes, insulin resistance, acromegaly, diabetes with elevated IGF-1 concentrations, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function, and / or wherein remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained; (iv) a metabolic disorder in a canine, wherein the metabolic disorder is preferably one or more selected from the group consisting of ketoacidosis, prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, obesity, hyperglycemia, hyperglycemia-induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, subclinical inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipometabolism, pancreatic inflammation, consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders, and / or Syndrome X (metabolic syndrome), preferably prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, insulin resistance, wherein the development of hyperglycemia-induced cataract formation is preferably prevented or remission is achieved, and / or wherein the development of consequences of metabolic disorders such as hypertension, renal dysfunction and / or musculoskeletal disorders is preferably prevented or the progression is slowed or remission is achieved; (v) cardiac disease in a feline, wherein the cardiac disease is preferably one or more selected from the group consisting of: heart failure, heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to cardiomyopathy of unspecified type (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), cardiomyopathy of unspecified type (UCM) and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more cardiomyopathies, heart failure due to hypertrophic cardiomyopathy (HCM), hypertrophic cardiomyopathy (HCM); (vi) drying off of non-human mammals, preferably ruminants; improving and / or promoting said drying off of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or swelling in the udder, preferably the breast and / or mammary gland of non-human mammals, preferably ruminants; reducing discomfort associated with udder swelling in non-human mammals, preferably ruminants, such as increasing daily lying time and / or reducing stress; reducing milk leakage after drying off of non-human mammals, preferably ruminants; reducing the incidence of intramammary infection (IMI), preferably mastitis and / or metritis, in non-human mammals, preferably ruminants; (vii) a heart disease in a non-human mammal excluding cats, in particular a dog, wherein the heart disease is preferably one or more selected from the group consisting of: heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to (myxo)mitral valve disease [(M)MVD]; congestive heart failure due to (myxo)mitral valve disease [(M)MVD]; asymptomatic / preclinical / occult heart failure due to (myxo)mitral valve disease [(M)MVD]; (myxo)mitral valve disease [(M)MVD]; clinically evident Overt (myxo) mitral valve disease [(M)MVD]; Asymptomatic / preclinical / latent (myxo) mitral valve disease [(M)MVD]; Heart failure attributed to dilated cardiomyopathy (DCM); Congestive heart failure attributed to dilated cardiomyopathy (DCM); Asymptomatic / preclinical / latent heart failure attributed to dilated cardiomyopathy (DCM); Dilated cardiomyopathy (DCM); Clinically overt dilated cardiomyopathy (DCM); Asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); Aortic stenosis (valvular, supravalvular, and / or subvalvular); (viii) hypertension in a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the hypertension is preferably one or more selected from the group consisting of: situational hypertension, secondary hypertension and idiopathic hypertension, wherein the secondary hypertension is preferably selected from the group consisting of: hypertension associated with chronic kidney disease (CKD), diabetes, obesity, heart disease, endocrine diseases such as Cushing's disease, hyperthyroidism, acromegaly; and an increase in blood pressure (BP) induced by a pharmaceutical agent, preferably a glucocorticoid, a mineralocorticoid, an erythropoiesis stimulating agent, ephedrine and / or high-dose sodium chloride; (ix) renal disease of a non-human mammal, preferably a carnivore, more preferably a cat or dog, wherein the renal disease is preferably one or more selected from the group consisting of renal dysplasia, glomerular disease, polycystic kidney disease, amyloidosis, tubular nephritis / tubule-interstitial nephritis (TIN), acute kidney disease, chronic kidney disease.

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