Systems for delivering liquid pharmaceutical compositions, particularly liquid pharmaceutical compositions containing one or more SGLT-2 inhibitors.

Abstract

Systems and methods for treating and / or preventing metabolic disorders and / or other medical conditions in patients (e.g., felines) are described, by administering a liquid pharmaceutical composition, preferably containing one or more SGLT-2 inhibitor compounds, to the patient via a delivery system including a syringe. The syringe is characterized by facilitating the simple, safe, and effective dosage of small volume measurements of the liquid pharmaceutical composition to the patient during administration.

Description

[Technical Field]

[0001] References All references cited herein are incorporated herein by reference in their entirety. This invention relates to the field of medicine, particularly veterinary medicine. In particular, the invention relates to a delivery system including a syringe, and a corresponding method for delivering a liquid pharmaceutical composition, in particular a liquid pharmaceutical composition comprising one or more SGLT-2 inhibitor compounds, to a patient. [Background technology]

[0002] One treatment for metabolic disorders in mammals is inhibition of the renal sodium-dependent glucose cotransporter SGLT-2. In the kidney, SGLT-2 regulates glucose levels by mediating the reabsorption of glucose into the plasma following blood filtration. SGLT-2 inhibition can therefore induce glucosuria and reduce blood glucose levels. For example, companion animals, including felines (e.g., cats) and canines (e.g., dogs), can suffer from a variety of metabolic disorders, including hyperglycemia, insulin resistance, diabetes (type 1 or 2 diabetes mellitus, or prediabetes, etc.), hepatic lipidosis, obesity, hyperinsulinemia, impaired glucose tolerance, ketosis (especially ketoacidosis), dyslipidemia, dyslipidemia, obesity, asymptomatic or systemic inflammation, particularly mild systemic inflammation including adipose tissue, syndrome X (metabolic syndrome), atherosclerosis, and / or pancreatic inflammation. Various correlations exist between these disorders. Among these disorders, diabetes mellitus, and especially prediabetes and type 2 diabetes mellitus, as well as hyperglycemia, insulin resistance, hepatic lipidosis, and obesity, are becoming increasingly important. Administration of pharmaceutical compositions comprising one or more SGLT-2 inhibitors for the treatment and / or prevention of metabolic disorders in felines and canines is described, for example, in WO2015 / 091313 and WO2015 / 110402.

[0003] Equidae (e.g., horses) suffer from a variety of metabolic disorders, including insulin resistance and hyperinsulinemia. These insulin-related disorders in equidae are rarely associated with, for example, diabetes mellitus and hyperglycemia, because these are conditions found in humans or various other mammals. However, in equidae, insulin also regulates metabolic functions essential for life; for example, it delivers glucose into tissues such as the liver, fat, and skeletal muscle; it induces vasoconstrictive and vasodilatory pathways; and it regulates protein and fat metabolism. Insulin-related disorders, therefore, have severe and serious effects on the health of equidae. These may correlate with or be associated with a number of further equine disorders, conditions, or syndromes, including impaired glucose tolerance, dyslipidemia, dyslipidemia, obesity and / or localized steatosis, asymptomatic or systemic inflammation, in particular mild systemic inflammation including adipose tissue, equine metabolic syndrome (EMS) and / or equine intermediate pituitary dysfunction (PPID) (also known as equine Cushing's syndrome, characterized by laminitis, vascular dysfunction, hypertension, hepatic lipidosis, hyperadrenocorticism and / or atherosclerosis). Administration of pharmaceutical compositions comprising one or more SGLT-2 inhibitors for the treatment and / or prevention of metabolic disorders in equines is described, for example, in WO2014 / 161836 and WO2015 / 150299.

[0004] Other uses of SGLT-2 inhibitors for the treatment and / or prevention of medical indications and / or conditions in animals include, for example, those disclosed in WO2020 / 219645, WO2021 / 105152, WO2021 / 165177, WO2023 / 006718, WO2023 / 006745 and WO2023 / 006747. A variety of SGLT-2 inhibitors are known and described in the art. Liquid pharmaceutical formulations of SGLT-2 inhibitors are particularly useful in ensuring that these compounds are administered appropriately to patients in a safe and effective manner. However, ensuring that the correct dose based on the patient's body weight is administered at any given time can be a challenge. This is especially true for smaller (e.g., companion) animals, including felines and canines, where the dose may be very small (e.g., less than 1 mL) based on the animal's body weight. [Overview of the project]

[0005] According to the embodiments described in this specification, a pharmaceutical delivery system includes a system for administering a liquid pharmaceutical composition to a patient, and the system includes a syringe. The syringe includes a barrel that includes a hollow elongated member including an open barrel front end and an open barrel rear end, the hollow elongated member includes a first portion that extends to a moving section disposed along the hollow elongated member from the open barrel front end, the first portion has a first cross-sectional dimension, and a second portion that extends from the moving section to the open barrel rear end, the second portion having a second cross-sectional dimension that is larger than the first cross-sectional dimension. The syringe further includes a plunger that includes an elongated member including a plunger front end and a plunger rear end. The plunger and the barrel are dimensioned such that a portion of the plunger including the plunger front end can be inserted into the hollow elongated member of the barrel at the open barrel rear end, and the plunger can be extended within the barrel until the plunger front end engages a surface portion inside the hollow elongated member at the barrel front end. The accommodation of the liquid pharmaceutical composition within the barrel of the syringe via the open barrel front end is limited to a volume defined within the first portion of the barrel, where the volume is adjustable by adjusting the movement of the plunger front end away from the barrel front end. Further, the surface wall section of the plunger includes an indication including a dosage scale indicating the volume of the liquid pharmaceutical composition accommodated within the first portion of the barrel based on the corresponding movement of the plunger front end away from the barrel front end.

[0006] According to additional embodiments described herein, one or more SGLT-2 inhibitor compounds are used in a method of treating a patient with a liquid pharmaceutical composition, comprising providing a syringe and a container containing the liquid pharmaceutical composition, withdrawing a desired dosage of the liquid pharmaceutical composition into a first portion of the barrel of the syringe by moving a forward end of the plunger a selected distance from the forward end of the barrel until a selected mark of a plurality of marks for a dosage scale is aligned with an outer surface of the barrel at a rearward end of the barrel, and administering the desired dosage of the liquid pharmaceutical composition from the syringe to the patient. Corresponding methods of treating a patient with a liquid pharmaceutical composition, and corresponding uses of one or more SGLT-2 inhibitor compounds for the preparation of a medicament for treating a patient with a liquid pharmaceutical composition are also intended to be included by the present invention. The above and further features and advantages of the present invention will become apparent upon consideration of the following detailed description of its specific embodiments.

Brief Description of the Drawings

[0007] [Figure 1] A figure showing an elevation view of components of a delivery system (10) for administering a liquid pharmaceutical composition according to an embodiment described herein. [Figure 2] A figure showing a partial cross-section (cap) of a container for the delivery system of FIG. 1. [Figure 3A] A figure showing a perspective view of an adapter for the container of the delivery system of FIG. 1. [Figure 3B] A figure showing an elevation side view in a cross-section of the adapter of FIG. 3A. [Figure 4] A figure showing a perspective view of a barrel of a syringe for the delivery system of FIG. 1. [Figure 5] A figure showing a perspective view of a plunger of a syringe for the delivery system of FIG. 1. [Figure 6] A figure showing a partial cross-sectional perspective view of a syringe including a plunger engaged with a barrel for the delivery system of FIG. 1. [Figure 7]Figure 1 shows an example of an embodiment of a dosage scale provided on a plunger for a syringe in a delivery system. [Modes for carrying out the invention]

[0008] Similar reference figures are used throughout this disclosure to identify similar elements. Before embodiments of the present invention are described in further detail, it should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" are considered to include plural references unless the context clearly indicates otherwise. Unless otherwise defined, all technical and chemical terms used herein have the same meaning as commonly understood by those skilled in the art. All given ranges and values ​​can vary by 1% to 5% unless otherwise indicated or known to those skilled in the art, and the term “about” is therefore omitted from the specification and claims. Any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of the present invention, but preferred methods, apparatus, and materials are described herein. All publications described herein are incorporated herein by reference for the purpose of describing and disclosing substances, excipients, carriers, and methodologies as reported in publications that may be used in connection with the present invention. Nothing herein should be construed as an acknowledgment that the present invention is not entitled to precede such disclosure by prior art.

[0009] A system comprising a liquid pharmaceutical composition and a syringe capable of effectively delivering small and precise doses of the liquid pharmaceutical composition to a patient is described herein. As described herein, the liquid pharmaceutical composition comprises, in particular, one or more SGLT-2 inhibitor compounds that, when administered to a patient, provide effective prevention and / or treatment of metabolic disorders and / or any other medical conditions of the patient / person. The liquid pharmaceutical composition may be supplied in a tamper-evident container as described herein, wherein the syringe and container cooperate in a manner that effectively facilitates the transfer of a precise volume of the liquid pharmaceutical composition from the container to the syringe during use. The system may also be supplied as a parts kit, wherein the container and syringe having the liquid pharmaceutical composition are supplied together for commercial sale / end use (e.g., combined in a single package structure). Alternatively, the liquid pharmaceutical composition may be supplied separately from the delivery device.

[0010] Pharmaceutical composition Liquid pharmaceutical compositions for use in the systems described herein preferably comprise one or more SGLT-2 inhibitor compounds suitable for the treatment and / or prevention of metabolic disorders and / or any other medical conditions in a patient. For example, a pharmaceutical composition comprises a single SGLT-2 inhibitor compound, or alternatively, two or more SGLT-2 inhibitor compounds. SGLT-2 inhibitors that can be used in liquid pharmaceutical compositions for the systems described herein include, but are not limited to, WO01 / 27128, WO03 / 099836, WO2005 / 092877, WO2006 / 034489, WO2006 / 064033, WO2006 / 117359, WO2006 / 117360, and WO2007. Examples include glucopyranosyl-substituted benzene derivatives as described in / 025943, WO2007 / 028814, WO2007 / 031548, WO2007 / 093610, WO2007 / 128749, WO2008 / 049923, WO2008 / 055870, WO2008 / 055940, WO2009 / 022020, or WO2009 / 022008.

[0011] Some non-limiting examples of SGLT-2 inhibitor compounds that can be provided in liquid pharmaceutical compositions as described herein include the following compounds or their pharmaceutically acceptable forms: (1) The following formula: [ka] (In the formula, R 1 This represents cyano, Cl, or methyl (most preferably cyano), R 2 This represents H, methyl, methoxy, or hydroxy (most preferably H), R 3This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy-3-methyl-propyl This represents ta-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, difluoromethyloxy, trifluoromethyloxy, 2-methyloxy-ethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; Here, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; most preferably, R 3 (It is cyclopropyl.) A glucopyranosyl-substituted benzene derivative or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups; (2) The following formula: [ka] Veragliflozin, represented by; (3) The following equation: [ka] Dapagliflozin, represented by; (4) The following formula: [ka] Canagliflozin, represented by; (5) The following equations: [ka] Empagliflozin, represented by; (6) The following equation: [ka] Luseogliflozin, represented by; (7) The following equation: [ka] Tofogliflozin, represented by; (8) The following equations: [ka] Ipragliflozin, represented by [the symbol]; (9) The following equation: [ka] Erzggliflozin, represented by; (10) The following equations: [ka] Atigliflozin, represented by; (11) The following equation: [ka] Remogliflozin, represented by [the symbol]; (11A) The following formula:

Chem.

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Chem.

[0012] When used herein, the term "bellagliflozin" refers to bellagliflozin having the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. The compound, methods for its synthesis, and cocrystals thereof are described, for example, in WO2007 / 128749, WO2014 / 016381, and WO2019 / 121509. When used herein, the term "dapagliflozin" refers to dapagliflozin of the above structure, as well as its pharmaceutically acceptable forms, including its hydrate and solvate and its crystalline form. The compound and methods for its synthesis are described, for example, in WO03 / 099836. Preferred hydrates, solvates and crystalline forms are described, for example, in patent applications WO2008 / 116179 and WO2008 / 002824. When used herein, the term "canagliflozin" refers to canagliflozin having the above structure, as well as its pharmaceutically acceptable forms, including its hydrate and solvate, and its crystalline form. The compound and methods for its synthesis are described, for example, in WO2005 / 012326 and WO2009 / 035969. Preferred hydrates, solvates, and crystalline forms are described, for example, in patent application WO2008 / 069327.

[0013] When used herein, the term “empagliflozin” refers to empagliflozin having the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. The compound and methods for its synthesis are described, for example, in WO2005 / 092877, WO2006 / 120208, and WO2011 / 039108. Preferred crystalline forms are described, for example, in patent applications WO2006 / 117359 and WO2011 / 039107. When used herein, the term "atigliflozin" refers to atigliflozin having the above-described structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable forms thereof. The compound and methods for its synthesis are described, for example, in WO2004 / 007517. When used herein, the term "ipragliflozin" refers to ipragliflozin having the above-described structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. The compound and methods for its synthesis are described, for example, in WO2004 / 080990, WO2005 / 012326 and WO2007 / 114475.

[0014] When used herein, the term "tofogliflozin" refers to tofogliflozin of the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. The compound and methods for its synthesis are described, for example, in WO2007 / 140191 and WO2008 / 013280. When used herein, the term "luseogliflozin" refers to luseogliflozin having the above-described structure, as well as its hydrate and solvate, and its crystalline form, and any other pharmaceutically acceptable form thereof. When used herein, the term "erzgliflozin" refers to erzgliflozin having the above-described structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable forms thereof. The compound is described, for example, in WO2010 / 023594.

[0015] When used herein, the term "lemogliflozin" refers to the pharmaceutically acceptable forms thereof, including the remogliflozin having the above structure, as well as its hydrate and solvate and its crystalline form, and prodrugs of remogliflozin, particularly remogliflozin etavonate. Methods for its synthesis are described, for example, in patent applications EP1213296 and EP1354888. When used herein, the term "cergliflozin" refers to cergliflozin having the above-described structure, as well as its hydrate and solvate and its crystalline form, including prodrugs of cergliflozin, particularly cergliflozin etavonate, and any pharmaceutically acceptable forms thereof. Methods for producing the same are described, for example, in patent applications EP1344780 and EP1489089. The compound of formula (16) above, namely sotagliflozin, and its preparation are described, for example, in WO2008 / 042688 or WO2009 / 014970.

[0016] When used herein, the term "bexagliflozin" refers to the bexagliflozin of the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable forms thereof. The compound and methods for its synthesis are described, for example, in WO2009 / 026537. When used herein, the term "TFC-039" refers to the above structure, as well as its pharmaceutically acceptable forms, including its hydrate and solvate, and its crystalline form. The compound and methods for its synthesis are described, for example, in WO2012 / 160218. The liquid pharmaceutical composition may be in any suitable form that facilitates convenient and effective administration using the delivery system described herein. For example, the composition may be in the form of a solution, syrup, or suspension. As described herein with respect to the delivery system, the liquid pharmaceutical composition can be administered in highly precise dosing based on the patient's body weight. Depending on the desired characteristics of the liquid pharmaceutical composition for a special form of treatment (e.g., viscosity, turbidity level, solubility / suspension level, number and type of pharmaceutically active ingredients, etc.), a number of other components may also be provided in the composition in addition to one or more SGLT-2 inhibitor compounds.

[0017] According to a preferred embodiment, the liquid pharmaceutical composition is in the form of a solution or suspension. In other words, the pharmaceutical composition comprises one or more SGLT-2 inhibitor compounds in a solution or suspension form. With respect to the composition in suspension form, it is preferable that the liquid pharmaceutical composition contains one or more SGLT-2 inhibitor compounds in the form of solid particles. In this context, the solid particles may have sizes in the range of 0.01 μm to 150 μm, or 0.1 μm to 15 μm, or 0.2 μm to 10.0 μm, or 0.5 μm to 5 μm, based on the largest particle size. SGLT-2 inhibitors may only be administered to patients as monotherapy for the treatment and / or prevention of metabolic disorders and / or other medical indications and / or conditions. Alternatively, the form of treatment may include one or more other active agents in addition to the SGLT-2 inhibitor compound.

[0018] For example, a liquid pharmaceutical composition may also contain one or more SGLT-2 inhibitors combined with any one or more other pharmaceutically active ingredients (APIs), so that both types are administered simultaneously. Alternatively, a liquid pharmaceutical composition containing one or more SGLT-2 inhibitor compounds may be administered separately from one or more other APIs. Some non-limiting examples of APIs that can be administered in combination with one or more SGLT-2 inhibitors (either in the same liquid pharmaceutical composition or separately) include: diuretics, e.g., furosemide, torasemide, or spironolactone; beta-blockers, e.g., atenolol or propranolol; calcium channel blockers, e.g., diltiazem; ACE inhibitors, e.g., benazepril, ramipril, or enalapril; angiotensin receptor blockers, e.g., telmisalta Antiarrhythmic agents, e.g., flecainide; platelet aggregation inhibitors, e.g., clopidogrel; nonsteroidal anti-inflammatory drugs (NSAIDs), e.g., aspirin; anticoagulants, e.g., coumarin (vitamin K antagonist), (low molecular weight) heparin, factor Xa synthesis pentasaccharide inhibitors, and direct factor Xa inhibitors and / or direct thrombin inhibitors; DPP-IV inhibitors; and / or calcium channel sensitizers and / or positive inotropes, e.g., pimobendan and / or digitalis alkaloids.

[0019] Other solvents, excipients, buffers, flavorings and / or other additives, such as preservatives and / or solubilizers, may also be provided in the liquid pharmaceutical composition, as disclosed, for example, in WO2017 / 032799 and WO2023 / 227492 / EP 22175413.8. For example, one or more polar organic solvents, such as ethanol (e.g., in amounts of 0 to 20 g / 100 mL), propylene glycol (propane-1,2-diol) (e.g., in amounts of 0 to 60 g / 100 mL), and / or glycerol (propane-1,2,3-triol) (e.g., in amounts of 0 to 60 g / mL), may also be provided in the liquid pharmaceutical composition. In another embodiment, the liquid pharmaceutical composition may be substantially organic solvent-free, i.e., it may contain no organic solvents at all. For example, water or a buffered aqueous solution containing citric acid or phosphate may also be provided in the liquid pharmaceutical composition to achieve any desired pH of the composition (e.g., in amounts of 0 to 100 g / 100 mL, preferably 30 to 100 g / 100 mL). For example, the liquid pharmaceutical composition may be prepared to have a pH value in the range of 3 to 9.

[0020] Surprisingly, it has been found that solvents affect the palatability and applicability of liquid pharmaceutical compositions, and that certain solvents or combinations of solvents make the administration of very small volumes easier and more accurate. Particularly favorable results are achieved when the liquid pharmaceutical composition contains at least two or three organic polar solvents, and propylene glycol (propane-1,2-diol) is one of the at least two or three organic polar solvents. Such compositions are disclosed in WO2017 / 032799. Compositions 1 to 6 as disclosed in WO2017 / 032799 are incorporated herein by reference. Preferably, the liquid pharmaceutical composition contains propylene glycol in an amount ranging from 10 to 60 g / 100 mL, particularly in the range of 35 to 60 g / 100 mL, preferably in the range of 50 to 60 g / 100 mL, and at least one further organic polar solvent selected from ethanol and / or glycerol (propane-1,2,3-triol). With respect to further polar organic solvents, it is even more preferable that the liquid pharmaceutical composition contains ethanol in an amount ranging from 1 to 20 g / 100 mL, particularly in the range of 1 to 15 g / 100 mL, preferably in the range of 1 to 10 g / 100 mL, more preferably in the range of 1 to 8 g / 100 mL, and / or glycerol in an amount ranging from 1 to 60 g / 100 mL, particularly in the range of 1 to 52 g / 100 mL.

[0021] In a particularly preferred embodiment, the liquid pharmaceutical composition contains propylene glycol in an amount ranging from 10 to 60 g / 100 mL, especially in the range of 35 to 60 g / 100 mL, preferably in the range of 50 to 60 g / 100 mL, and ethanol in an amount ranging from 1 to 20 g / 100 mL, especially in the range of 2 to 15 g / 100 mL, preferably in the range of 3 to 10 g / 100 mL, particularly preferably in the range of 5 to 8 g / 100 mL. Composition 5 according to WO2017 / 032799, containing propylene glycol in an amount of 60 g / 100 mL and ethanol in an amount of 8 g / 100 mL, exhibits particularly accurate administration in the delivery system as described in paragraphs

[0078] to

[0107] of this specification (the specification as of the International Filing Date).

[0022] In another embodiment, the liquid pharmaceutical composition may contain ethanol as the sole organic polar solvent. According to this embodiment, the liquid pharmaceutical composition contains 20 g / 100 mL or less of ethanol, preferably 15 g / 100 mL or less, and more preferably 10 g / 100 mL or less. Preferably, ethanol is present in the liquid pharmaceutical composition in an amount in the range of 1 to 20 g / 100 mL, preferably 2 to 15 g / 100 mL, and more preferably 5 to 10 g / 100 mL. According to a particularly preferred embodiment, ethanol is present in the liquid pharmaceutical composition in an amount of 8 g / 100 mL. Examples of such compositions are disclosed as compositions 1 to 4 in EP22175413.8 and WO2023 / 227492. Compositions 1 to 4 as disclosed in EP22175413.8 and WO2023 / 227492 are incorporated by reference herein. In another embodiment, the liquid pharmaceutical composition does not contain any organic polar solvent, in particular organic solvents as described in paragraphs

[0046] to

[0051] . If an organic polar solvent is not present, the solvent of the liquid pharmaceutical composition is 100% water in the form of a buffered aqueous solution. Examples of suitable compositions that do not contain an organic polar solvent are described as compositions 5 to 12 in EP22175413.8 and WO2023 / 227492. Compositions 5 to 12 as disclosed in EP22175413.8 and WO2023 / 227492 are incorporated herein by reference.

[0023] Liquid pharmaceutical compositions may also include, without limitation, one or more solubilizers, including surfactants, anionic surfactants, nonionic surfactants, hydrogenated castor oil, polyoxyethylene-polyoxypropylene block copolymers, polyethylene glycol, and propylene glycol derivatives. Some specific non-limiting examples of suitable solubilizers include sodium dodecyl sulfate (SDS), Cremofer RH 40 (PEG-40 hydrogenated castor oil, macrogol glycerol hydroxystearate 40), polysorbate 20, Lutrol F68 (poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, and Kollidon 12 (povidone) (for example, in amounts of 0 to 50 g / 100 mL, preferably 1 to 50 g / 100 mL).

[0024] According to a preferred embodiment of this aspect, the liquid pharmaceutical composition contains one or more solubilizers, in particular, the solubilizers are selected from sodium dodecyl sulfate (SDS), Cremofer RH 40 (PEG-40 hydrogenated castor oil, macrogol glycerol hydroxystearate 40), polysorbate 20, Lutrol F68 (poloxamer 188), PEG 200, PEG 300, PEG 400, propylene glycol monolaurate, Kollidon 12 (povidone), and combinations thereof. Preferably, the total amount of solubilizer in the liquid pharmaceutical composition is 1 to 50 g / 100 mL, particularly 1 to 45 g / 100 mL, preferably 1 to 40 g / 100 mL, more preferably 1 to 35 g / 100 mL, even more preferably 1 g / mL to 30 g / mL, even more preferably 1 to 25 g / 100 mL, and most preferably 5 to 25 g / 100 mL.

[0025] In another embodiment, the liquid pharmaceutical composition as described herein contains two or more, preferably two, solubilizers. In this context, it is preferable that the solubilizers are Kollidon 12 (povidone) and PEG 200, PEG 300, or PEG 400, more preferably Kollidon 12 (povidone) and PEG 300. According to further embodiments, particularly if the composition is a suspension, the liquid pharmaceutical composition contains a liquid vehicle for holding solid particles comprising one or more SGLT-2 inhibitor compounds. The liquid vehicle may be aqueous or organic, preferably aqueous. According to a particularly preferred embodiment, the liquid vehicle is water or a buffered aqueous solution. In another embodiment, one or more suspending agents may be provided in the liquid pharmaceutical composition. Examples of suitable suspending agents include viscosity enhancers, such as cellulose derivatives or gel-forming agents, and / or thixotropic agents, such as gel-forming polysaccharides or natural gums. One or more viscosity enhancers may also be provided in the liquid pharmaceutical composition, including, but not limited to, inorganic gel-forming agents, organic gel-forming agents, and cellulose derivatives. Some specific, non-limiting examples of suitable viscosity enhancers include hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, carboxymethylcellulose, and silicon dioxide.

[0026] One or more thixotropic agents, including but not limited to synthetic or natural gums and mucus, may be provided in a liquid pharmaceutical composition. Some specific, non-limiting examples of suitable thixotropic agents include tragacanth, xanthan, or alginates. One or more flavoring agents (including flavors and / or sweeteners) may be provided in a liquid pharmaceutical composition (particularly for compositions used for oral administration). Non-limiting examples of flavoring agents that may be provided in such compositions include honey flavor, lime / salvia flavor, jasmine flavor, lavender flavor, peppermint flavor, raspberry flavor, lemon flavor, herbal flavor, meat flavor, artificial beef flavor, saccharin, stevia, and aspartame.

[0027] The concentration of APIs, including SGLT-2 inhibitors, in a liquid pharmaceutical composition can vary depending on a number of factors, including, but not limited to, the required daily dose for a specific type of patient, and the solubility characteristics of the API in the solution in combination with other components in the solution. The concentration of one or more SGLT-2 inhibitor compounds in a liquid pharmaceutical composition can range from 0.1 mg / mL to 20 mg / mL or higher, for example, 1.2 mg / mL to 15 mg / mL, or 1 mg / mL to 5 mg / mL, or 5 mg / mL to 20 mg / mL, or 10 mg / mL to 20 mg / mL, or 12 mg / mL to 18 mg / mL. In an example embodiment (for example, for the treatment of felines), the concentration of the SGLT-2 inhibitor compound in the liquid pharmaceutical composition may be 15 mg / mL. In a further example embodiment (for example, for the treatment of canines), the concentration of the SGLT-2 inhibitor compound in the liquid pharmaceutical composition may be 1.2 mg / mL. In another further embodiment (for example, for the treatment of equids), the concentration of the SGLT-2 inhibitor compound in the liquid pharmaceutical composition may be 15 mg / mL.

[0028] Dosage and administration The dosage of one or more SGLT-2 inhibitors to be administered to a patient can be determined based on a number of factors, including the patient / mammalian type, patient size / weight, the specific type of metabolic disorder, and / or other medical conditions to be prevented and / or treated. The liquid pharmaceutical compositions and delivery systems for administering such compositions as described herein are suitable for use in treating and / or preventing one or more metabolic disorders and / or other medical indications in subjects in any suitable patient. The patients are preferably animals, more preferably non-human mammals, such as equids (e.g., horses), canids (e.g., dogs), felines (e.g., cats), or ruminants (e.g., cows). The embodiments described herein are particularly useful for treatments involving smaller companion animals, such as felines and (small) canids. Generally, the dosage of one or more SGLT-2 inhibitors to be administered to a patient is in the range of 0.01 to 10 mg / kg BW (patient body weight) per day. The dosage can be administered once or multiple times per day, for example, twice a day (e.g., once every 12 hours), three times a day, etc. Depending on the patient's body weight and the concentration of one or more SGLT-2 inhibitor compounds in the liquid pharmaceutical composition, the dosage may be very small (e.g., less than 1 mL). Therefore, it is important to have an effective delivery system that can provide accurate dosage.

[0029] For example, one or more SGLT-2 inhibitor compounds may be 0.01-10 mg / kg BW, or 0.01-5 mg / kg BW, or 0.01-4 mg / kg BW, or 0.01-3 mg / kg BW, or 0.01-2 mg / kg BW, or 0.01-1.5 mg / kg BW, or 0.01-1 mg / kg BW, or 0.01-0.75 mg / kg BW, or 0.01-0.5 mg / kg BW, or 0.01-0.4 mg / kg BW, or 0.01-0.3 mg / kg BW; or 0.1-5.0 mg / kg BW, or 0.1-3.0 mg / kg BW, or 0.2-2.0 mg / kg BW, or 0.1-1 mg / kg BW, or 0.02-0.5 mg / kg It can be administered at a daily dose of BW, or 0.03-0.4 mg / kg BW, or 0.03-0.3 mg / kg BW.

[0030] SGLT-2 inhibitors can be administered in such a way that an appropriate plasma concentration of the SGLT-2 inhibitor is achieved (e.g., maximum plasma concentration, or plasma concentration after a given time, e.g., 4, 8, 12, or 24 hours after oral administration, preferably about 8 hours after oral administration). For example, for veragliflozin, the plasma concentration (e.g., maximum plasma concentration, or plasma concentration after the aforementioned given time after oral administration) may be in the range of 2 to 4000 nM, e.g., 20 to 3000, or e.g., 40 to 2000 nM. Preferably, following administration and the time required for the SGLT-2 inhibitor to reach the bloodstream, these levels are maintained in the blood for a time interval of at least 12 hours, more preferably at least 18 hours, and most preferably at least 24 hours. Preferably, the liquid pharmaceutical composition is administered orally according to the embodiments described herein. Using the delivery systems described herein, the liquid pharmaceutical composition containing the SGLT-2 inhibitor compound can be administered directly into the patient's mouth or together with the animal's food or beverage (e.g., its drinking water). Alternatively, the liquid pharmaceutical composition may be administered parenterally via the delivery systems described herein, or by any other suitable route of administration (e.g., rectally).

[0031] Metabolic disorders / other medical conditions Liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitors as described herein, in combination with a delivery system as described herein, can be used for the treatment and / or prevention of various metabolic disorders and / or other medical indications in various types of patients. For example, liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein can be used, without limitation, to treat and / or prevent one or more metabolic disorders (or conditions associated with such metabolic disorders) in equid patients (e.g., horses), including insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation including adipose tissue, obesity, localized steatosis, laminitis, vascular dysfunction, hypertension, hepatic lipidosis, atherosclerosis, hyperadrenocorticism, intermediate pituitary dysfunction, and / or equine metabolic syndrome.

[0032] Liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein may also be used, without limitation, to treat and / or prevent one or more metabolic disorders (or conditions associated with such metabolic disorders) in canine patients (e.g., dogs), including diabetes, prediabetes, obesity, and / or any disorders, diseases, conditions, or symptoms associated with one or more of these disorders. In particular, metabolic disorders may include hyperglycemia, impaired glucose tolerance, insulin resistance, insulin-dependent diabetes, and / or hepatic lipidosis. Further related metabolic disorders include hyperinsulinemia, impaired glucose tolerance, ketosis (especially ketoacidosis), hyperlipidemia, dyslipidemia, elevated blood levels of fatty acids and / or glycerol, syndrome X (metabolic syndrome), and / or pancreatic inflammation, mild systemic inflammation, and adipose tissue inflammation. Liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein may also be further used for the treatment and / or prevention of one or more other medical conditions in canine patients (e.g., dogs), including, but not limited to, one or more cardiac diseases. In particular, one or more cardiac diseases include, but not limited to, heart failure; congestive heart failure; asymptomatic / preclinical / latent heart failure; heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; congestive heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically manifest (primitive mesenchymal) mitral valve disease [(M) [MVD]; Asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; heart failure due to dilated cardiomyopathy (DCM); congestive heart failure due to dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent heart failure due 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).

[0033] Furthermore, liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein can be used, without limitation, to treat and / or prevent one or more metabolic disorders (or conditions associated with such metabolic disorders) in feline patients (e.g., cats), including diabetes, prediabetes, type 2 diabetes mellitus, acromegaly, diabetes mellitus with elevated IGF-1 levels, obesity, and / or any disorders, diseases, conditions or symptoms associated with one or more of these disorders, hyperglycemia, insulin resistance, diabetes and / or hepatic lipidosis, hyperinsulinemia, impaired glucose tolerance, ketosis (especially ketoacidosis), hyperlipidemia, elevated blood levels of fatty acids and / or glycerol, syndrome X (metabolic syndrome), atherosclerosis, pancreatic inflammation, adipose tissue inflammation, and / or loss of pancreatic beta-cell function. Liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein may be used, without limitation, for the treatment and / or prevention of one or more other medical conditions in feline patients (e.g., cats), including one or more heart diseases. In particular, one or more types of heart disease can include, without limitation, heart failure, heart failure due to one or more types of cardiomyopathy, 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 unclassified cardiomyopathy (UCM), heart failure due to arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), unclassified cardiomyopathy (UCM), and / or arrhythmogenic right ventricular cardiomyopathy (ARVC); preferably selected from the group consisting of: heart failure due to one or more types of cardiomyopathy, heart failure due to hypertrophic cardiomyopathy (HCM), and hypertrophic cardiomyopathy (HCM).

[0034] Furthermore, liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein can be used, without limitation, to treat and / or prevent one or more renal diseases in non-human mammals such as feline and / or canine patients (e.g., cats and / or dogs), including renal dysplasia, glomerulosis, polycystic kidney disease, amyloidosis, tubulonephritis / tubulointerstitial nephritis (TIN), acute kidney disease, and chronic kidney disease.

[0035] Furthermore, liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein may be used, without limitation, for the treatment and / or prevention of hypertension in non-human mammals such as feline and / or canine patients (e.g., cats and / or dogs), including circumstance-dependent hypertension, secondary hypertension and idiopathic hypertension, where secondary hypertension may be selected from the group consisting of chronic kidney disease (CKD), diabetes mellitus, obesity, heart disease, endocrine disorders such as Cushing's disease, hyperthyroidism, acromegaly, and hypertension associated with elevated blood pressure (BP) induced by pharmaceuticals, preferably glucocorticoids, mineralocorticoids, erythrocyte production stimulants, ephedrine and / or high-dose sodium chloride. Furthermore, liquid pharmaceutical compositions comprising one or more SGLT-2 inhibitor compounds as described herein may be used for dry milk in non-human mammals such as ruminants, including, but not limited to, improving and / or facilitating dry milk, reducing milk production, reducing milk accumulation and / or congestion in the mammary glands, reducing discomfort associated with mammary congestion, for example, increasing the reduction of daily recumbent time and / or stress, reducing post-dry milk leakage, and / or reducing the incidence of intramammary infections (IMIs), such as mastitis and / or endometritis.

[0036] Delivery system A delivery system for facilitating the administration of a liquid pharmaceutical composition to a patient as described herein includes a storage container for receiving and storing the composition, and a syringe for effectively drawing a precise dose volume of the composition from the container and delivering the dose volume to the patient (directly or indirectly). Referring to Figures 1-7, the delivery system 10 for the liquid pharmaceutical composition includes a container 20 and a syringe 50. The container 20 includes a storage tank 25 having a hollow interior, an open upper end 26, and an opposing lower closed end 27, where the storage tank 25 has a suitable geometry and sufficient internal volume to store a suitable number of doses of the liquid pharmaceutical composition before use. For example, the storage tank has a volume in the range of 10 mL to 60 mL, preferably 15 mL to 45 mL, so that a sufficient daily dose of the liquid pharmaceutical composition can be easily provided for at least 14 days, preferably at least 28 or 30 days, where the SGLT-2 concentration in the liquid pharmaceutical composition can range from 1.2 mg / mL to 15 mg / mL (e.g., 1.2 mg / mL for canids, 15 mg / mL for felines, and 15 mg / mL for equids).

[0037] The container 20 further includes a lid or cap 30 that is removably fixed to the open upper end 26 of the tank 25 (for example, via a screw connection between the cap and the tank opening end, as shown in the partial cross-sectional view of the cap as shown in Figure 2). Each of the storage tank 25 and the cap 30 is constructed of one or more polymers and / or other suitable materials that are relatively inert and nonreactive to any of the components of the liquid pharmaceutical composition stored in the container 20. For example, each of the storage tank and the cap may be constructed of one or more polyolefin materials. In the embodiment, the storage tank is constructed of a polymer material including, preferably consisting of, polyethylene (e.g., high-density polyethylene, or HDPE), while the cap is constructed of a polymer material including, preferably consisting of, polypropylene and polyethylene, particularly preferably polypropylene. As is known, high-density polyethylene (HDPE) has a linear polymer chain structure and is opaque, while low-density polyethylene (LDPE) has a branched polymer chain structure and is transparent or translucent. While HDPE and LDPE have similar properties, HDPE has higher hardness or rigidity and, in relation to LDPE, is more resistant to tearing / abrasion, while LDPE is a softer, more flexible material compared to HDPE.

[0038] The cap 30 comprises an outer portion 33, preferably made of polypropylene, and an inner portion 31, preferably made of polyethylene (e.g., high-density polyethylene, or HDPE). The inner portion 31 of the cap includes an inner helix that engages with the corresponding outer helix in a helical connection at the open upper end 26 of the tank 25. The inner portion 31 can be fixed or fused to the outer portion 33 in any suitable manner (e.g., via bonding, welding, and co-forming processes). A liner (e.g., made of polyethylene, preferably made of polyethylene) can be provided on the upper inner surface of the inner portion 31 to engage with the tank 25 and its open upper end 26 and to provide an effective fluid-tight seal at these interfaces. The cap may further include a tamper-evident element that provides an indication of whether the container has been opened (i.e., whether the cap has been partially or completely removed from the storage tank before the first use of the delivery system). In particular, the inner portion 31 of the cap 30 includes a detachable ring 32 that is detachably connected at the open end of the cap 30 directly below the inner helix of the cap (where the inner helix of the cap engages with the corresponding outer helix at the open upper end 26 of the groove 25). The detachable ring 32 can be connected at the lower end of the cap to the inner portion 31 of the cap 30, for example, via a release tab 34.

[0039] During the initial installation or connection of the cap 30 to the open upper end 26 of the tank 25, the cap 30 is connected to the upper end of the tank via a corresponding spiral, where the cap is rotated (for example, clockwise) and moved downward onto the upper end of the tank to close the container 20. The removable ring 32 also moves downward along the upper end of the tank and moves over or rides onto the ledge 28 at the open upper end 26 of the tank. The removable ring 32 further includes one or more inwardly extending and upwardly bent (i.e., bent towards the closed end of the cap) stop members 36. The ring 32 and one or more stop members 36 are three-dimensionally configured to allow the ring 32 and stop members 36 to ride over and pass over the ledge 28 when rotated downward onto the tank 25 (for example, clockwise). However, if the ring 32 is positioned below the ledge 28 (i.e., between the ledge of the tank 25 and the lower closing end 27), the stop member 36 prevents the ring 32 from moving upward beyond the ledge 28. The cap 30 can also be rotated upward (e.g., counterclockwise) and then detached from the open upper end 26 of the tank 25 by a release tab 34 that disengages the ring 32 from the inner portion 31 of the cap 30 after the cap has been rotated a distance selected for removal from the tank 25 (e.g., partially or completely detached / removed from the tank). The separation of the ring 32 from the cap 30 provides an indication that the container 20 has been at least partially opened and therefore used (at least once) or tampered with in some manner before the first use (potentially damaging the liquid pharmaceutical composition inside the container).

[0040] The container 20 may further include an adapter 40 fixed to the upper or upper open end of the tank 25. The adapter may be constructed of a polymer or other suitable material, such as a polyolefin material. In the embodiment, the adapter 40 is constructed of a polymer material, preferably including, polyethylene (e.g., low-density polyethylene, or LDPE). Referring to Figures 3A and 3B, the adapter 40 includes a hollow and elongated (e.g., generally cylindrical) main member 42 that is appropriately sized to substantially fit into the open upper end 26 of the tank 25. At least a portion of the main member 42 of the adapter 40 has an outer diameter that is substantially the same as, and may be slightly larger than, the inner diameter (ID) at the open upper end 26 of the tank 25. The dimensions of the adapter and open upper end of the container tank, combined with the construction materials for both components (e.g., the adapter made of LDPE and the container tank made of HDPE), ensure friction and fluid tight fitting between the two components when the adapter 40 is mounted in the open upper end 26 of the tank, with the outer wall portion of the main member 42 engaging with the inner wall portion of the tank 25 at its open upper end. The main member 42 includes an open upper end 44 and an end wall with an opposing lower end 45. A circular flange 46 is positioned at the open upper end 44 of the main member 42, where the flange 46 has a larger cross-sectional dimension relative to the main member 42. The flange 46 extends outward at the upper end 44 of the main member and has a diameter that roughly corresponds to the outer diameter of the tank 25 at the open upper end 26. Thus, when the adapter 40 is connected to the tank 25, the flange 46 is fixed at and rests on the open upper end 26 of the tank 25. The adapter 40 is further connected to the tank 25 in a suitable manner to provide a fluid-tight seal between the two components at the tank opening end.

[0041] The end walls at the opposing lower ends 45 of the main member 42 include a central opening 47, which is smaller in size in relation to the opening at the upper end 44. Extending longitudinally from the end wall at the lower end 45 into the hollow main member 42 is an elongated and hollow (e.g., cylindrical) inner connecting member 48, which communicates in a fluid-tight manner (i.e., is aligned) with the central opening at the lower end wall of the lower end 45, and further extends into the open upper end 44 within the outer hollow main member 42. The inner connecting member 48 opens at its upper end, and the upper end of the inner connecting member is generally coplanar or on the same surface as the flange 46, or alternatively, extends beyond it. Thus, when the adapter 40 is fixed to the tank 25 at the tank open upper end 26, the adapter provides an outlet through which the liquid pharmaceutical composition is drawn out of the tank via the elongated inner connecting member 48. As described herein in relation to the syringe 50, the cross-section (e.g., diameter) of the hollow inner connecting member 48 is appropriately sized to engage with the corresponding end of the syringe in a releaseable friction and fluid-tight manner.

[0042] Referring to Figures 4 and 5, the syringe 50 of the delivery system 10 includes a barrel 60 and a plunger 80, where the plunger 80 is appropriately sized to facilitate the drawing of fluid from the container into the barrel and the flow of fluid from the barrel through the plunger during use, such that a portion of the plunger is slidably housed and movable in a snap-fit ​​manner within the barrel. Each of the syringe barrel and plunger can be constructed of any suitable polymer and / or other material that is relatively inert and non-reactive to any components of the liquid pharmaceutical composition with which the syringe interacts during use. For example, each of the syringe barrel and plunger can be made of the same or different polyolefin material. In a preferred embodiment, the syringe barrel is constructed of a polymer material including, preferably consisting of, polyethylene (e.g., low-density polyethylene or LDPE), while the syringe plunger is constructed of a polymer material including, preferably consisting of, polystyrene. The choice of material for the plunger and barrel has a remarkable effect on the drug delivery characteristics of the syringe. The combination of a syringe barrel constructed from LDPE and a plunger constructed from polystyrene leads to improved, and in particular, more precise, application or delivery of very small volumes of liquid pharmaceutical compositions.

[0043] The syringe barrel 60 is hollow and has an elongated and generally cylindrical three-dimensional structure including a lower or front end 62 from which the solution is drawn (via the plunger 80) from the tank 25 of the container 20. The barrel 60 further has an upper or rear end 64 of the opening which is appropriately sized to accommodate a portion of the plunger 80. The cross-sectional dimensions or diameter of the barrel 60 vary along its length, where the barrel includes a first portion 66 extending from the front end 62 to the moving section 68, where the barrel's cross-sectional dimensions or diameter increase in the moving section. A second portion 70 of the barrel 60 extends from the moving section 68 to the rear end 64 of the opening. The second portion 70 has a cross-sectional dimension or diameter (i.e., second cross-sectional dimension) that is larger than the cross-sectional dimensions or diameter (i.e., first cross-sectional dimension) of the first portion 66. A finger grip flange 72 is provided at the rear end 64 of the opening and has a cross-sectional dimension that is larger than the cross-sectional dimensions of the rear end 64 of the opening.

[0044] The barrel front end 62 includes an end wall 74 having a small central opening via the end wall 74. The opening provided via the end wall 74 at the barrel front end 62 is smaller in size than the opening at the barrel rear end 64. The barrel first portion 66 has a suitable outer wall diameter (OD) which may be substantially similar to, and slightly larger than, the inner diameter (ID) of the elongated inner connecting member 48 of the adapter 40 at the upper end of the adapter. This facilitates friction and fluid tight connection between the barrel first portion 66 and the adapter inner connecting member 48 when the barrel front end 62 is inserted into the inner connecting member 48. This prevents fluid leakage between these two components while facilitating the effective movement of the liquid pharmaceutical composition from the container 20 into the hollow interior of the barrel 60. In certain embodiments, the barrel first portion at the barrel front end may have a unique outer cross-sectional geometry (e.g., tapered, polyhedral, etc.) that matches the internal cross-sectional geometry of the elongated inner connecting member for the adapter.

[0045] The close dimensional correspondence between the OD of the first portion of the barrel at the front end of the barrel and the ID of the adapter's internal connecting member, as well as any corresponding or matching geometry at the engagement surface between the front end of the barrel and the adapter's internal connecting member, provides a key-like connection required for the use of syringe 50 with container 20 to ensure a secure and fluid tight connection at their interface and effective transfer of the liquid pharmaceutical composition into the syringe barrel. In other words, the key-like connection between the syringe barrel and container via the adapter ensures that only a specific syringe can be effectively used with a container containing a particular liquid pharmaceutical composition, and that another syringe cannot be interchanged with a syringe stereo-configured for use with the pharmaceutical provided in the corresponding container. Such key-like features may be specific to a particular syringe and its paired container having a specified liquid pharmaceutical composition. This restricts or prevents the use of a particular syringe in a delivery system with another container that may contain a different liquid pharmaceutical composition not stereo-configured for use with a particular syringe.

[0046] The plunger 80 is appropriately sized to be substantially housed within the barrel 60 via the rear end 64 of the opening and includes an elongated member to facilitate the sliding engagement of the plunger within the barrel during use. The plunger 80 includes an upper or rear end 84 and a lower or front end 82, where the front end 82 is provided within the barrel and may extend together with the hollow interior of the barrel within the first portion 66 and the second portion 70 of the barrel. The plunger includes a first portion 86 extending from the front end 82 to the moving section 88, and a second portion 90 extending from the moving section 88 to the rear end 84 of the plunger. Similar to the barrel 60, the second portion 90 of the plunger has a larger cross-section (e.g., diameter) than the cross-section of the first portion 86 of the plunger. A finger grip flange 92 is provided at the rear end 84 of the plunger, where the flange 92 extends laterally beyond the cross-sectional dimensions of the rear end 84 of the plunger, thereby providing a grip surface during use of the syringe 50 (e.g., when moving the plunger within the barrel).

[0047] The plunger 80 has a longitudinal or vertical dimension that is at least substantially the same as, preferably greater than, the longitudinal or vertical dimension of the barrel 60. This facilitates the full relocation of the plunger into the barrel, where the front end of the plunger can engage with the front end wall of the barrel. In addition, if the plunger is longer than the barrel, a small portion of the plunger at its rear end extends beyond the rear end of the barrel when the plunger is fully relocated within the barrel (i.e., the front end of the plunger contacts the front end of the barrel). In such embodiments, the plunger flange always extends beyond the barrel flange by a suitable distance (thus allowing for easy gripping of the plunger flange to pull a portion of the plunger out of the barrel).

[0048] Each of the plunger and barrel is appropriately sized to facilitate the extraction of a sufficient amount of liquid from the barrel, thereby ensuring that an appropriate dose of the liquid pharmaceutical composition is delivered to the patient. The front end 82 of the plunger 80 includes a stopper member 94, which is sized to provide friction-tight and fluid-tight engagement along the inner wall of the first portion 66 of the barrel. The stopper member 94 can be formed from the same material (e.g., polystyrene) as the rest of the plunger 80, including the first portion 86, the moving section 88, and the second portion 90. The stopper member 94 has a cross-section larger than the internal cross-section (e.g., inner diameter) of the barrel moving section 68. During the installation of the plunger in the barrel, the plunger 80 can be inserted into the barrel 60 together with the plunger front end 82, and the stopper member 94 is pushed downward through the barrel moving section 68 and toward the barrel front end 62. During the withdrawal of the plunger from the barrel, the barrel movement section 68 provides a slight base for the forward end 82 of the plunger with a stopper member 94 to provide the user with an indication of the stop point where the plunger should not be further withdrawn from the barrel. Thus, the maximum fluid volume in the barrel 60 is limited to the volume defined by the first part 66 of the barrel.

[0049] Syringe 50 is stereoscopically configured to provide certain beneficial features for drawing very small, individual, and precise doses of liquid pharmaceutical composition from container 20, depending on the dosage required by the patient. For example, if the patient has a relatively low body weight (e.g., a feline or a small canid), the volume of liquid pharmaceutical composition to be administered may need to be very small. The volume of liquid pharmaceutical composition depends on the dosage required for treatment (based on the patient's active ingredient in mg / kg BW), the concentration of the active ingredient in the liquid pharmaceutical composition (e.g., an SGLT-2 inhibitor), and the patient's body weight. If a feline is being treated for a metabolic disorder, and we assume the feline weighs approximately 2 kg, then the single dose required is 1.0 mg / kg BW, and the concentration of the liquid pharmaceutical composition is 15 mg / mL. For this example, the single dose to a feline (e.g., administered orally) is approximately 0.133 mL. Providing such small volumetric doses within the barrel of a conventional syringe is extremely difficult.

[0050] Syringe 50 can be stereostructured such that the barrel volume defined in the first part 66 is 3 mL or less, preferably 2 mL or less, more preferably 1 mL or less, for example, 0.9 mL or less, or 0.8 mL or less, or 0.7 mL or less, or 0.6 mL or less, or 0.5 mL or less, or preferably 0.4 mL or less. In particular, syringe 50 can be stereostructured such that the barrel volume defined in the first part 66 is in the range of 0.01 mL to 3 mL, preferably 0.01 mL to 2 mL, more preferably 0.01 mL to 1 mL, especially in the range of 0.02 mL to 0.9 mL, even more preferably in the range of 0.03 mL to 0.8 mL, even more preferably in the range of 0.04 mL to 0.7 mL, and most preferably in the range of 0.05 mL to 0.6 mL. The dose increment of the syringe based on the patient's weight can be on a graduated scale with 10 or more increments. Therefore, the dose volume may be 0.05 mL smaller or even lower. In a preferred embodiment, the dose volume is in the range of 0.01 mL to 3 mL, preferably 0.01 mL to 2 mL, more preferably 0.01 mL to 1 mL, particularly 0.02 mL to 0.9 mL, even more preferably 0.03 mL to 0.8 mL, more preferably 0.04 mL to 0.7 mL, and most preferably 0.05 mL to 0.6 mL. In the embodiment, the dose volume of the syringe is in the range of 0.05 mL to 0.6 mL. The stereochemical configuration of the syringe 50 is such that each dose increment can be easily selected depending on the specific outline of the treatment for the patient.

[0051] Nevertheless, the barrel volume defined in the first part 66 can be selected depending on the patient's weight, size, and the required dose. Therefore, in yet another embodiment, the syringe 50 can be configured such that the barrel volume defined in the first part 66 is in the range of 5 mL to 40 mL, preferably 10 mL to 30 mL, and more preferably 15 mL to 25 mL. According to this embodiment, the dose volume is in the range of 5 mL to 40 mL, preferably 10 mL to 30 mL, and more preferably 15 mL to 25 mL. Such dose volumes and configurations of the syringe 50 are particularly suitable for the treatment of equids.

[0052] In particular, the first barrel portion 66, which defines the maximum volume that can be drawn from the container 20 into the syringe 50, is much longer than its inner diameter (ID) or internal cross-section. Increasing the length of the internal volume portion in relation to the inner diameter of the barrel portion that contains the fluid allows the plunger to draw the fluid from the barrel in very small volume measurement increments with high precision and particle size, because the amount of fluid drawn from the barrel into the internal volume portion of the barrel with each increment of movement of the plunger can be minimized while the plunger is drawn further out of the barrel. Preferably, the first barrel portion 66 has a length-to-inner diameter (or internal cross-section) ratio, referred to as L / D, of at least 5. For example, the first barrel portion 66 can have an L / D ratio of 5 to 20, or 7 to 15, or 9 to 14. In a specific embodiment, the L / D ratio for the first barrel portion is about 12.2 (L / D = 12.2). This can also have the effect of increasing the distance between divisions that define volumetric measurement increments on the scale provided as a marking on the syringe (i.e., making it easier for the user to visually interpret the exact amount of fluid being drawn from the syringe barrel).

[0053] The construction materials for the plunger and barrel also enhance the very small increments of liquid pharmaceutical composition drawn into the barrel in very individual and small volume measurements. For example, the combination of forming the plunger from a polymer material including, preferably composed of, polystyrene, and forming the barrel from a polymer material including, preferably composed of, polyethylene (e.g., LDPE), provides a very smooth and gliding interaction between these two components at their frictional and fluid-tight interface (e.g., between the plunger stopper member 94 and the inner wall surface area of ​​the first part 66 of the barrel). This facilitates the smooth and easy drawing of the plunger from the barrel in very precise small volume increments (e.g., less than 0.05 mL) when drawing fluid from the fluid chamber of the barrel (as defined in the first part of the barrel). Furthermore, the stereochemical configuration of the adapter and barrel facilitates the ease of drawing out the very small portion remaining in the container during use.

[0054] Further enhancements to the syringe 50 include providing markings (e.g., printed and / or etched markings) along the exposed surface wall section of the plunger 80, preferably on the second part 90 of the plunger, where the markings include a dose scale 100 of stepped marks including lines and / or corresponding numbers (see, e.g., Figure 7) aligned in a direction corresponding to the longitudinal dimension of the plunger (e.g., substantially parallel thereto), where each stepped mark and / or corresponding number indicates a specific dose drawn into the front end 62 of the barrel (when the barrel 60 is connected to the container 20 in the manner described herein). Typically, volumetric markings or dose scales for conventional syringes are provided along the barrel rather than the plunger, where the front end of the plunger is aligned with scale marks provided on the barrel (when the barrel is transparent or at least partially translucent) during the drawing of fluid into the barrel to obtain a desired volume of fluid in the barrel. The syringe 50 as described herein is operable to obtain the exact volume (and therefore the exact dose) of the liquid pharmaceutical composition in the barrel 60 by withdrawing the plunger 80 from the barrel 60 until the desired stepped marks on the dosage scale 100 on the plunger are visible at a designated position along the second barrel portion 70 or on a portion of the second plunger portion 90 that is exposed (i.e., outside the barrel). Referring to Figure 6, the exact indication (i.e., the exact dose) of the volume of the fluid in the first barrel portion 66 is determined based on the stepped marks on the scale 100 along the second plunger portion 90 that is exposed and outside the barrel 60. In particular, during the withdrawal of the liquid pharmaceutical composition from the container 20, the plunger 80 can be moved away from the barrel 60 until a particular stepped mark from the scale 100 aligns (e.g., substantially coplanar) with the rear surface 73 (as part of the barrel flange 72) that defines the rear end 64 of the barrel. Alternatively, the plunger can also be aligned with the barrel in any other manner such that specific stepwise marks from the dosage scale align with any other part of the syringe.In another embodiment, the barrel includes a window or other indicator (e.g., a cutout portion located along the second portion of the barrel and / or a printed mark along the second portion of the barrel) that provides a position for aligning specific stepped marks of a dosage scale provided on a surface wall section of the second portion of the plunger to indicate that an accurate volumetric measurement / dosage has been drawn into the barrel in the first portion of the barrel. The dosage scale is provided along the second portion of the plunger at a precise position so as the movement of the plunger from the barrel aligns the indicator position along the barrel with the specific stepped marks, the precise volume of fluid drawn into the first portion of the barrel is established.

[0055] The stepped markings on the dosage scale 100 for the plunger 80 can be provided in volumetric measurements (e.g., in milliliters or milliliters), or alternatively, in any other numerical markers that facilitate the use of the syringe when administering accurate doses to the patient. In an example embodiment (as shown in Figure 7), the dosage scale 100 for the plunger 80 may include stepped markings numerically ordered based on the body mass or weight of the patient (e.g., a feline), where the body mass or weight can be provided in any suitable type of unit, e.g., SI units, or in kg (kilograms), or in imperial units or lb (pounds). This enhances the simplicity or ease of the delivery system in providing the patient with an appropriate dose based on the patient's weight and the concentration of the SGLT-2 inhibitor (and / or other API) in the liquid pharmaceutical composition used. In particular, this minimizes the potential for user error in dosage by converting the dosage scale to patient weight, which is especially advantageous for end users who may not be healthcare or medical professionals (e.g., veterinarians) but instead caregivers for the patient (e.g., pet owners for feline or other animal patients).

[0056] For example, if the required dose of an SGLT-2 inhibitor to a feline patient for the treatment of a specific metabolic disorder is 0.1 mg / kg BW, the dose scale 100 provides the user with a convenient conversion to administer an accurate volumetric dose from the syringe 50 by simply withdrawing the liquid pharmaceutical composition from the container 20 into the syringe barrel 60 by moving the plunger 80 from the barrel 60 until the stepped marks on the scale 100, representing the feline patient's weight in kilograms (kg), are aligned with the corresponding indicator on the syringe (e.g., the stepped marks on the plunger are aligned with or substantially coplanar with the rear surface 73 of the barrel flange 72). It is described that such markings on the patient's weight require a dose scale corresponding to the concentration of the SGLT-2 inhibitor (and / or other API) in the liquid pharmaceutical composition to be administered (e.g., 15 mg / mL as shown in Figure 7). A pre-described key-like connection between the syringe and the container (via an adapter for the container) ensures that the appropriate syringe with a dosage scale corresponds to the precise liquid pharmaceutical composition being drawn from the container.

[0057] As previously described, liquid pharmaceutical compositions and delivery systems (containers with syringes), particularly those containing one or more SGLT-2 inhibitor compounds, may be combined as a single kit-in-part and made available together for commercial or other end-use by being provided in a single package as a kit-in-part. The kit-in-part may include a single package structure comprising the liquid pharmaceutical composition and the container with syringe. Each of these components may be subpackaged within the single kit-in-part package (i.e., provided in separate packages). The kit-in-part may further include appropriate instructions, such as those provided in a package insert or brochure, containing information regarding the administration of the liquid pharmaceutical composition and the use of the delivery system for the treatment and / or prevention of metabolic disorders and / or other medical indications as described herein for identified patients.

[0058] The delivery system can be stereoconfigured for administering liquid pharmaceutical compositions to animal patients such as equids, ruminants, canids, and felines. The route of administration may be oral or parenteral, but is preferred. The delivery system 10 as described herein comprises a needleless syringe, in which the liquid pharmaceutical composition is drawn into the syringe barrel 60 via engagement between the front end 62 of the barrel and an adapter 40 of the container 20. However, it is described that the delivery system may also include a needle for parenteral administration for certain embodiments. In particular, an example embodiment demonstrating the operation of the delivery system 10 for the treatment and / or prevention of metabolic disorders or other medical indications in a patient by administering a liquid pharmaceutical composition containing one or more SGLT-2 inhibitors to the patient is described herein. In this example embodiment, the patient is a feline, and the dosage scale 100 for syringe 80 is as shown in Figure 7 (the graded marks for scale 100 correspond to body weight in kg for felines).

[0059] Before the syringe 50 engages with the container 20, the plunger 80 is fully inserted into the barrel 60 so that the plunger front end 82, including the stopper member 94, contacts the inner surface at the barrel front end 62. After the cap 30 is removed from the container 20, the syringe 50 (including, for example, the plunger 80 mounted inside the barrel 60 as shown in Figures 1 and 6) is connected to the container 20 by inserting the barrel front end 62 into the inner connecting member 48 of the adapter 40 sufficiently to ensure friction and a tight fluid engagement. The container 20 with the engaged syringe 50 can then be inverted (for example, by oriented vertically, the upper end 26 of the container is below the lower end 27, and the syringe 50 is positioned below the container 20). This results in a liquid pharmaceutical composition positioned inside the container 20 at the upper end 26 with substantially no air gaps or voids at the interface between the inner surface portion of the adapter 40 inside the container 20 and the liquid pharmaceutical composition in contact with these inner surface portions. Furthermore, as can be seen, for example, in Figures 5 and 6, the stepped markings on the dosage scale 100 can be inverted (e.g., upside down) in relation to the front end 82 of the plunger 80. This facilitates the ease of reading the dosage scale 100 when the syringe 50 is inverted and the liquid pharmaceutical composition is drawn into the barrel 60 (for example, the stepped markings are on the upper right).

[0060] The rear end 92 and front end 82 of the plunger are moved by a selected distance from the rear end 72 and front end 62 of the barrel, respectively, until the specified stepped marks along the dosage scale 100 on the second part 90 of the plunger, corresponding to the weight (in kg) of the feline patient, are appropriately aligned (e.g., coplane) with the rear surface 73 of the barrel flange 72. For example, if the weight of the feline is 4 kg, the plunger 80 is moved from the barrel until the stepped mark for the number 4 on the dosage scale 100 is aligned (e.g., coplane) with the barrel flange surface 73 (e.g., as illustrated in Figure 6). This movement of the plunger 80 from the barrel 60 results in the withdrawal of the liquid pharmaceutical composition from the container 20 through the internal connecting member 48 of the adapter 40 and through the opening in the end wall 74 of the front end 62 of the barrel into the first part 66 of the barrel. The movement of the plunger 80 from the barrel 60 to align the specified stepwise marks from scale 100 with the rear surface 73 of the barrel flange ensures that a precise dose of liquid pharmaceutical composition is drawn from the container 20 into the first portion 66 of the barrel. The three-dimensional configuration of the plunger together with the barrel, as well as the friction and fluid tight fit between the front end 66 of the barrel and the inner connecting member 48 of the adapter 40, ensure that sufficient vacuum force is generated within the first portion 66 of the barrel when the rear end 84 of the plunger is moved by a selected distance from the rear end 64 of the barrel, resulting in a substantially total volume defined by the interior of the first portion 66 of the barrel between the front end 62 of the barrel and the stopper member 94 of the syringe 80, corresponding to the volume of liquid pharmaceutical composition drawn into the barrel.

[0061] The specified dose of the liquid pharmaceutical composition, withdrawn into the syringe barrel of the delivery system, can be administered orally to the feline patient directly by injecting the composition from the barrel 60 into the mouth of the feline patient (i.e., by moving the plunger 80 back into the barrel 60 to push the composition through the opening in the end wall 74 at the front end 62 of the barrel). Alternatively, the dose can be administered indirectly orally by providing the liquid pharmaceutical composition from the syringe 50 to a liquid (e.g., water) or food for ingestion by the feline patient. The accompanying leaflet or brochure will provide end-users with information regarding the daily dose (e.g., the number of daily doses) to be provided to the feline patient based on the characteristics of the metabolic disorder or other medical indication being treated.

[0062] Accordingly, the embodiments described herein facilitate the administration of liquid pharmaceutical compositions, particularly those containing one or more SGLT-2 inhibitor compounds, in very small individual doses for the treatment and / or prevention of one or more metabolic disorders and / or one or more other medical indications. The delivery system having key features can ensure that a suitable syringe (having specific dosage indications for a particular composition, a particular patient type, and / or a particular medical treatment) is matched with a suitable container containing the particular composition for administration to the patient. In particular, embodiments of the present invention are described herein by means of the following clauses, which are part of the disclosure and are included by the spirit and scope of the present invention:

[0063] 1. A system for administering a liquid pharmaceutical composition to a patient, the system comprising a syringe, wherein the syringe is A barrel including a hollow, elongated member that includes an open barrel front end and an open barrel rear end, wherein the hollow, elongated member is A first portion extending from the front end of an open barrel to a moving section arranged along a hollow, elongated member, the first portion having a first cross-sectional dimension; and A second portion extending from the moving section to the rear end of the open barrel, the second portion having a second cross-sectional dimension that is larger than the first cross-sectional dimension. barrels including; and A plunger including an elongated member that includes the front end and rear end of the plunger. Includes, Here, The plunger and barrel are sized such that a portion of the plunger, including its front end, can be inserted into the hollow, elongated member of the barrel at the rear end of the open barrel, and the plunger can extend into the barrel until its front end engages with the inner surface portion of the hollow, elongated member at the front end of the barrel; The confinement of the liquid pharmaceutical composition within the barrel of the syringe via the open barrel front end is limited to a volume defined within a first portion of the barrel, where the volume is adjustable by adjusting the movement of the plunger front end away from the barrel front end; The surface wall section of the plunger includes a marking that includes a dosage scale indicating the volume of the liquid pharmaceutical composition contained within the first portion of the barrel, based on the corresponding movement of the front end of the plunger away from the front end of the barrel.

[0064] 2. A system according to Clause 1, wherein the barrel is formed of a polymer material containing polyethylene, preferably a polymer material consisting of polyethylene, most preferably a polymer material consisting of low-density polyethylene, and the plunger is formed of a polymer material containing polystyrene, preferably a polymer material consisting of polystyrene. 3. A system in accordance with any one of clauses 1 or 2, wherein the second part of the barrel has a length-to-diameter (L / D) ratio of 5-20, 7-15, or 9-14. 4. A system that conforms to any one of clauses 1 to 3, defining the volume within a hollow, elongated member of the second part of the barrel, which is 1 mL or less, or 0.9 mL or less, or 0.8 mL or less, or 0.7 mL or less, or 0.6 mL or less, or 0.5 mL or less, or 0.4 mL or less. 5. The dosage scale on the surface wall section of the plunger includes multiple marks aligned in a direction corresponding to the longitudinal dimension of the plunger; In the operation, the volume of the liquid pharmaceutical composition contained within the first portion of the barrel in response to the movement of the front end of the plunger away from the front end of the barrel is indicated by the alignment of the corresponding marks on the dosage scale with the outer surface of the barrel at the rear end of the barrel. A system that complies with any one of clauses 1 through 4.

[0065] 6. Container containing liquid pharmaceutical composition A system that includes, in addition, any one of clauses 1 to 5. 7. A system in accordance with Clause 6 in which the liquid pharmaceutical composition comprises one or more SGLT-2 inhibitor compounds selected from the group consisting of: (1) The following formula: [ka] (In the formula, R 1 This represents cyano, Cl, or methyl (most preferably cyano), R 2 This represents H, methyl, methoxy, or hydroxy (most preferably H), R 3These include cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy -3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; Here, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; most preferably, R 3 (It is cyclopropyl.) A glucopyranosyl-substituted benzene derivative or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups; (2) The following formula: [ka] Veragliflozin, represented by; (3) The following equation: [ka] Dapagliflozin, represented by; (4) The following formula: [ka] Canagliflozin, represented by; (5) The following equations: [ka] Empagliflozin, represented by; (6) The following equation: [ka] Luseogliflozin, represented by; (7) The following equation: [ka] Tofogliflozin, represented by; (8) The following equations: [ka] Ipragliflozin, represented by [the symbol]; (9) The following equation: [ka] Erzggliflozin, represented by; (10) The following equations: [ka] Atigliflozin, represented by; (11) The following equation: [ka] Remogliflozin, represented by [the symbol]; (11A) The following equation: [ka] Lemogliflozin ethanolate, represented by [the specified method]; (12) The following equation: [ka] (In the formula, R represents methoxy or trifluoromethoxy.) Thiophene derivatives represented by; (13) The following equation: [ka] 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by: (14) The following formula: [ka] (In the formula, R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl) Spirochetal derivatives represented by; (15) The following equation: [ka] (In the formula: R 1 C 1-3 - Indicates an alkoxy, L 1 , L 2 These independently represent either H or F. R 6 H, (C 1-3 -alkyl)carbonyl, (C 1-6 (-Alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl) Pyrazole-O-glucoside derivatives represented by; (16) The following equation: [ka] Sotagliflozin, represented by; (17) The following equation: [ka] Cergliflozin, represented by; (18) The following equation: [ka] (In the formula: R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy-3- Methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; where R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; where R 3 (Most preferably, it is cyclopropyl.) A compound or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups; (19) The following equation: [ka] Bexagliflozin, represented by; (20) The following equation: [ka] Janagliflozin, represented by; (21) Long liflozin; [ka] (22) Wampagliflozin; (23) The following equation: [ka] Enabogliflozin, represented by; and (24) The following equation: [ka] TFC-039 is represented by [this symbol].

[0066] 8. A system in accordance with Clause 7, wherein the concentration of one or more SGLT-2 inhibitor compounds in the liquid pharmaceutical composition is 0.1 mg / mL to 20 mg / mL. 9.1 A system according to Clause 8, comprising veragliflozin, wherein one or more SGLT-2 inhibitor compounds, preferably veragliflozin, is the only SGLT-2 inhibitor contained in the liquid pharmaceutical composition. 10. A system in accordance with Clause 9, wherein the concentration of veragliflozin in the liquid pharmaceutical composition is 1.2 mg / mL or 15 mg / mL.

[0067] 11. A system in accordance with any one of clauses 1-10, including the following: An adapter connected to an opening in a container, the adapter includes a hollow connecting member that facilitates coupling between the front end of the barrel and the connecting member in order to facilitate the transfer of a liquid pharmaceutical composition to a first portion of the barrel, wherein a portion of the hollow connecting member of the adapter has an outer diameter substantially similar to the inner diameter of the opening in the container in order to establish a frictional and fluid-tight connection between the adapter and the container, and the hollow connecting member of the adapter has an inner diameter substantially similar to the outer diameter of the front end of the barrel in response to the insertion of the front end of the barrel into the hollow connecting member in order to establish a frictional and fluid-tight connection between the adapter and the barrel. 12. A system according to any one of clauses 1 to 11, wherein the adapter is formed of a polymer material containing, preferably consisting thereof, low-density polyethylene, and the container is formed of a polymer material containing, preferably consisting thereof, high-density polyethylene.

[0068] 13. One or more SGLT-2 inhibitor compounds for use in a method of treating and / or preventing metabolic disorders and / or other medical conditions in a patient by administering a dose of a liquid pharmaceutical composition containing one or more SGLT-2 inhibitor compounds to the patient, wherein the method is To provide a syringe and a container for a liquid pharmaceutical composition, wherein the syringe includes a barrel and a plunger, The barrel includes a hollow, elongated member having an open barrel front end and an open barrel rear end; a first portion extending from the open barrel front end to a movable section positioned along the hollow, elongated member, having a first cross-sectional dimension; and a second portion extending from the movable section to the open barrel rear end, having a second cross-sectional dimension larger than the first cross-sectional dimension; The plunger includes an elongated member and a dosage scale, the elongated member including the front end and rear end of the plunger, and the dosage scale includes multiple marks positioned on the surface wall section of the plunger and aligned in a direction corresponding to the longitudinal dimension of the plunger; The plunger and barrel are sized such that a portion of the plunger, including its front end, can be inserted into the hollow, elongated member of the barrel at the rear end of the open barrel, and the plunger can extend within the barrel until its front end engages with the inner surface portion of the hollow, elongated member at the front end of the barrel; To draw a desired dose of liquid pharmaceutical composition from a container into the first part of the syringe barrel by moving the front end of the plunger a selected distance from the front end of the barrel until a selected mark of multiple marks for the dosage scale aligns with the outer surface of the barrel at the rear end of the barrel; and Administering a desired dose of liquid pharmaceutical composition to the patient from a syringe. One or more SGLT-2 inhibitor compounds, including [the specified compound]. (The corresponding methods for treating and / or preventing metabolic disorders and / or other medical conditions in a patient by administering a dose of a liquid pharmaceutical composition containing one or more SGLT-2 inhibitor compounds to the patient, and the corresponding use of one or more SGLT-2 inhibitor compounds for the preparation of pharmaceuticals for treating and / or preventing metabolic disorders and / or other medical conditions in a patient, are also intended to be included by the present invention.)

[0069] 14. One or more SGLT-2 inhibitor compounds for use in a manner in accordance with Clause 13, including oral or parenteral administration to a patient, preferably oral administration, by administering a desired dose of a liquid pharmaceutical composition from a syringe to a patient. 15. One or more SGLT-2 inhibitor compounds for use in any one of clauses 13 to 14, including oral administration to a patient by direct transfer of the liquid pharmaceutical composition from the syringe to the patient orally, or by indirect transfer of the liquid pharmaceutical composition from the syringe to food or liquid for ingestion by the patient.

[0070] 16. One or more SGLT-2 inhibitor compounds for use in a manner according to any one of clauses 13 to 15, wherein the desired dose is 1 mL or less, or 0.9 mL or less, or 0.8 mL or less, or 0.7 mL or less, or 0.6 mL or less, or 0.5 mL or less, or 0.4 mL or less. 17. One or more SGLT-2 inhibitor compounds for use in a manner according to any one of clauses 13 to 16, wherein the desired dose is in the range of 0.05 mL to 0.6 mL.

[0071] 18.1 or more SGLT-2 inhibitor compounds selected from the group consisting of the following, for use in a manner in accordance with any one of clauses 13 to 17: (1) The following formula: [ka] (In the formula, R 1 This represents cyano, Cl, or methyl (most preferably cyano), R 2 This represents H, methyl, methoxy, or hydroxy (most preferably H), R 3These include cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy -3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; Here, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; most preferably, R 3 (It is cyclopropyl.) A glucopyranosyl-substituted benzene derivative or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups; (2) The following formula: [ka] Veragliflozin, represented by; (3) The following equation: [ka] Dapagliflozin, represented by; (4) The following formula: [ka] Canagliflozin, represented by; (5) The following equations: [ka] Empagliflozin, represented by; (6) The following equation: [ka] Luseogliflozin, represented by; (7) The following equation: [ka] Tofogliflozin, represented by; (8) The following equations: [ka] Ipragliflozin, represented by [the symbol]; (9) The following equation: [ka] Erzggliflozin, represented by; (10) The following equations: [ka] Atigliflozin, represented by; (11) The following equation: [ka] Remogliflozin, represented by [the symbol]; (11A) The following equation: [ka] Lemogliflozin ethanolate, represented by [the specified method]; (12) The following equation: [ka] (In the formula, R represents methoxy or trifluoromethoxy.) Thiophene derivatives represented by; (13) The following equation: [ka] 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by: (14) The following equation: [ka] (In the formula, R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl) Spirochetal derivatives represented by; (15) The following equation: [ka] (In the formula: R 1 C 1-3 - Indicates an alkoxy, L 1 , L 2 These independently represent either H or F. R 6 H, (C 1-3 -alkyl)carbonyl, (C 1-6 (-Alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl) Pyrazole-O-glucoside derivatives represented by; (16) The following equation: [ka] Sotagliflozin, represented by; (17) The following equation: [ka] Cergliflozin, represented by; (18) The following equation: [ka] (In the formula: R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy-3- Methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; where R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; R 3 (Most preferably, it is cyclopropyl.) A compound or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups; (19) The following equation: [ka] Bexagliflozin, represented by; (20) The following equation: [ka] Janagliflozin, represented by; (21) Long liflozin; [ka] (22) Wampagliflozin; (23) The following equation: [ka] Enabogliflozin, represented by; and (24) The following equation: [ka] TFC-039 is represented by [this symbol].

[0072] 19.1 One or more SGLT-2 inhibitor compounds for use in accordance with Clause 18, wherein the SGLT-2 inhibitor compounds include veragliflozin, and preferably veragliflozin is the only SGLT-2 inhibitor compound administered.

[0073] 20. One or more SGLT-2 inhibitor compounds for use in a manner in accordance with any one of the provisions 13 to 19, with a dosage of 0.01 to 10 mg / kg patient body weight. 21. One or more SGLT-2 inhibitor compounds for use in a manner according to any one of clauses 13 to 20, wherein the patient is a non-human mammal selected from the group of equids, ruminants, felines and canids, preferably felines or (small) canids.

[0074] 22. One or more SGLT-2 inhibitor compounds for use in accordance with any one of clauses 13 to 21, selected from the group consisting of: (i) Metabolic disorders in equids (preferably, the metabolic disorder is one or more disorders selected from insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, obesity, and / or local steatosis; preferably, the metabolic disorder is insulin resistance, hyperinsulinemia, and / or clinical conditions associated with insulin resistance and / or hyperinsulinemia; preferably, the clinical conditions are one or more conditions selected from impaired glucose tolerance, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, obesity, and / or local steatosis); (ii) Metabolic disorders in equids (a metabolic disorder is one or more disorders selected from laminitis, vascular dysfunction, hypertension, hepatic lipidosis, atherosclerosis, hyperadrenocorticism, intermediate pituitary dysfunction and / or equine metabolic syndrome, preferably a clinical condition / sign associated with insulin resistance and / or hyperinsulinemia, and the clinical condition / sign is preferably one or more conditions selected from laminitis, vascular dysfunction, hypertension, hepatic lipidosis, atherosclerosis, hyperadrenocorticism, intermediate pituitary dysfunction and / or equine metabolic syndrome); (iii) Metabolic disorders in felines (preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes mellitus, insulin resistance, acromegaly, diabetes mellitus with elevated IGF-1 levels, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta-cell function, and / or remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained); (iv) Metabolic disorders in canids (preferably, the metabolic disorder is 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, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, hepatic lipidosis, pancreatic inflammation, metabolic disorder events, such as hypertension, renal insufficiency and / or musculoskeletal disorders, and / or syndrome X (metabolic syndrome), preferably one or more selected from the group consisting of prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus and insulin resistance, preferably the onset of hyperglycemia-induced cataract formation is prevented or remission is achieved, and / or preferably the onset of metabolic disorder events such as hypertension, renal insufficiency and / or musculoskeletal disorders is prevented, or the progression is delayed, or remission is achieved); (v) Cardiac diseases in felines (preferably, the cardiac disease is selected from the group consisting of heart failure, heart failure due to one or more cardiomyopathy, 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 unclassified cardiomyopathy (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), unclassified cardiomyopathy (UCM), and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably, one or more selected from the group consisting of heart failure due to one or more cardiomyopathy, heart failure due to hypertrophic cardiomyopathy (HCM), and hypertrophic cardiomyopathy (HCM)); (vi) Dryness of non-human mammals, preferably ruminants (preferably one or more selected from the group consisting of improving and / or facilitating dryness of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or milk secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or congestion in the mammary glands, preferably mammary glands, of non-human mammals, preferably ruminants; reducing discomfort associated with mammary congestion; for example, increasing the daily recumbent time and / or stress reduction of non-human mammals, preferably ruminants; reducing milk leakage after dryness of non-human mammals, preferably ruminants; and reducing the incidence of intramammary infections (IMI), preferably mastitis and / or endometritis, in non-human mammals, preferably ruminants); (vii) Cardiac diseases in non-human mammals, especially canids, excluding felines (preferably, cardiac diseases include heart failure; congestive heart failure; asymptomatic / preclinical / latent heart failure; heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; congestive heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically manifest (primitive mesenchymal) mitral valve disease [(M)MVD]; Asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; Heart failure due to dilated cardiomyopathy (DCM); Congestive heart failure due to dilated cardiomyopathy (DCM); Asymptomatic / preclinical / latent heart failure due to dilated cardiomyopathy (DCM); Dilated cardiomyopathy (DCM); Clinically overt dilated cardiomyopathy (DCM); Asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); One or more selected from the group consisting of aortic stenosis (valvular, supravalvular and / or subvalvular); (viii) Hypertension in non-human mammals, preferably carnivores, more preferably cats or dogs (preferably, hypertension is one or more selected from the group consisting of circumstance hypertension, secondary hypertension and idiopathic hypertension, where preferably, secondary hypertension is selected from the group consisting of chronic kidney disease (CKD), diabetes mellitus, obesity, heart disease, endocrine disorders, e.g., Cushing's disease, hyperthyroidism, acromegaly hypertension, and hypertension associated with elevated blood pressure (BP) induced by pharmaceuticals, preferably glucocorticoids, mineralocorticoids, erythrocyte production stimulants, ephedrine and / or high-dose sodium chloride); (ix) Renal diseases in non-human mammals, preferably carnivores, more preferably cats or dogs (preferably, the renal disease is one or more selected from the group consisting of renal dysplasia, glomerulosis, polycystic kidney disease, amyloidosis, tubulonephritis / tubulointerstitial nephritis (TIN), acute kidney disease, and chronic kidney disease).

[0075] If any modifications and variations of this invention fall within the scope of the appended claims and their equivalents, then the present invention is intended to encompass such modifications and variations. Relative terms such as “top,” “bottom,” “front,” “rear,” “side,” “height,” “length,” “width,” “upper,” “lower,” “inside,” and “outside,” as used herein, should be understood to merely describe points of reference and not to limit the present invention to any particular orientation or three-dimensional configuration.

Claims

1. A system for administering a liquid pharmaceutical composition to a patient, wherein the system includes a syringe, and the syringe is A barrel including a hollow, elongated member, which includes an open barrel front end and an open barrel rear end, wherein the hollow, elongated member is A first portion extending from the front end of an open barrel to a moving section arranged along a hollow, elongated member, the first portion having a first cross-sectional dimension; and A second portion extending from the moving section to the rear end of the open barrel, the second portion having a second cross-sectional dimension that is larger than the first cross-sectional dimension. barrels including; and A plunger including an elongated member that includes the front end and rear end of the plunger. Includes, Here, The plunger and barrel are sized such that a portion of the plunger, including its front end, can be inserted into the hollow elongated member of the barrel at the rear end of the open barrel, and the plunger can extend into the barrel until its front end engages with the inner surface portion of the hollow elongated member at the front end of the barrel; The capacity of the liquid pharmaceutical composition in the barrel of the syringe via the open barrel front end is limited to a volume defined within a first portion of the barrel, where the volume is adjustable by adjusting the movement of the plunger front end away from the barrel front end; The surface wall section of the plunger includes a marking that includes a dosage scale indicating the volume of the liquid pharmaceutical composition contained within the first portion of the barrel based on the corresponding movement of the front end of the plunger away from the front end of the barrel. system.

2. The system according to claim 1, wherein the barrel is formed of a polymer material containing polyethylene, preferably a polymer material consisting of polyethylene, most preferably a polymer material consisting of low-density polyethylene, and the plunger is formed of a polymer material containing polystyrene, preferably a polymer material consisting of polystyrene.

3. The system according to any one of claims 1 to 2, wherein the first portion of the barrel has a length-to-diameter (L / D) ratio of 5 to 20, or 7 to 15, or 9 to 14.

4. The first part of the barrel defines the volume within a hollow, elongated member having a volume of 3 mL or less, or 2 mL or less, or 1 mL or less, or 0.9 mL or less, or 0.8 mL or less, or 0.7 mL or less, or 0.6 mL or less, or 0.5 mL or less, or 0.4 mL or less; and / or The first portion of the barrel defines the volume within a hollow, elongated member in the range of 0.01 mL to 3 mL, preferably 0.01 mL to 2 mL, more preferably 0.01 mL to 1 mL, particularly 0.02 mL to 0.9 mL, even more preferably 0.03 mL to 0.8 mL, even more preferably 0.04 mL to 0.7 mL, and most preferably 0.05 mL to 0.6 mL. The system according to any one of claims 1 to 3.

5. The dosage scale on the surface wall section of the plunger includes multiple marks aligned in a direction corresponding to the longitudinal dimension of the plunger; In the operation, the volume of the liquid pharmaceutical composition contained within the first portion of the barrel in response to the movement of the front end of the plunger away from the front end of the barrel is indicated by the alignment of the corresponding marks on the dosage scale with the outer surface of the barrel at the rear end of the barrel. The system according to any one of claims 1 to 4.

6. Container containing liquid pharmaceutical composition The system according to any one of claims 1 to 5, further comprising:

7. Liquid pharmaceutical composition, (1) The following formula: 【Chemistry 1】 (In the formula, R 1 This represents cyano, Cl, or methyl (most preferably cyano), R 2 This represents H, methyl, methoxy, or hydroxy (most preferably H), R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxypropyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy -3-methylbuta-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, difluoromethyloxy, trifluoromethyloxy, 2-methyloxy-ethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; Here, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; most preferably, R 3 (It is cyclopropyl.) A glucopyranosyl-substituted benzene derivative or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -Alkyl)carbonyl, (C 1-18 -Alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 (Acylated with a group selected from -alkyl-carbonyl); (2) The following formula: 【Chemistry 2】 Veragliflozin, represented by; (3) The following formula: 【Transformation 3】 Dapagliflozin, represented by; (4) The following formula: 【Chemistry 4】 Canagliflozin, represented by; (5) The following formula: 【Transformation 5】 Empagliflozin, represented by; (6) The following formula: 【Transformation 6】 Luseogliflozin, represented by; (7) The following formula: 【Transformation 7】 Tofogliflozin, represented by; (8) The following formula: 【Transformation 8】 Ipragliflozin, represented by; (9) The following formula: 【Chemistry 9】 Erzgliflozin, represented by; (10) The following formula: 【Chemistry 10】 Atigliflozin, represented by; (11) The following formula: 【Chemistry 11】 Remogliflozin, represented by; (11A) The following equation: 【Chemistry 12】 Lemogliflozin ethanolate, represented by: （１２） The following formula: 【Chemistry 13】 (In the formula, R represents methoxy or trifluoromethoxy.) Thiophene derivatives represented by; (13) The following equation: 【Chemistry 14】 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by: (14) The following formula: 【Chemistry 15】 (In the formula, R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl) Spirochetal derivatives represented by; (15) The following equation: 【Chemistry 16】 (In the formula: R 1 represents C 1-3 -alkoxy, and L 1 , L 2 These independently represent either H or F. R 6 H, (C 1-3 -Alkyl)carbonyl, (C 1-6 (-Alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl) Pyrazole-O-glucoside derivatives represented by; (16) The following formula: 【Chemistry 17】 Sotagliflozin, represented by; (17) The following formula: [Chemistry 18] Cergliflozin, represented by; （１８） The following formula: 【Chemistry 19】 (In the formula: R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxypropyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy-3- Methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; where R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; R 3 (Most preferably, it is cyclopropyl.) A compound or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -Alkyl)carbonyl, (C 1-18 -Alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 (Acylated with a group selected from -alkyl-carbonyl); (19) The following formula: 【Chemistry 20】 Bexagliflozin, represented by; (20) The following equation: 【Chemistry 21】 Janagliflozin, represented by; (21) Long liflozin; 【Chemistry 22】 (22) Wampagliflozin; (23) The following equation: 【Chemistry 23】 Enabogliflozin, represented by; and (24) The following equation: 【Chemistry 24】 TFC-039 is represented by The system according to claim 6, comprising one or more SGLT-2 inhibitor compounds selected from the group consisting of the following.

8. The system according to claim 7, wherein the concentration of one or more SGLT-2 inhibitor compounds in the liquid pharmaceutical composition is 0.1 mg / mL to 20 mg / mL.

9. The system according to claim 7 or 8, wherein one or more SGLT-2 inhibitor compounds comprise veragliflozin, preferably veragliflozin is the only SGLT-2 inhibitor contained in the liquid pharmaceutical composition, and more preferably the concentration of veragliflozin in the liquid pharmaceutical composition is 1.2 mg / mL or 15 mg / mL.

10. The system according to any one of claims 6 to 9, wherein the liquid pharmaceutical composition comprises one or more SGLT-2 inhibitor compounds in the form of a solution or suspension, preferably in a solution form, and / or the liquid pharmaceutical composition is in the form of a solution or suspension, preferably in a solution form.

11. The system according to any one of claims 6 to 10, wherein the liquid pharmaceutical composition comprises one or more organic polar solvents, preferably one or more organic polar solvents selected from ethanol and / or propylene glycol and / or glycerol, and in particular, the liquid pharmaceutical composition comprises propylene glycol and at least one further organic polar solvent selected from ethanol and / or glycerol as the organic polar solvent.

12. The present invention further includes an adapter connected to an opening in a container, the adapter comprising a hollow connecting member that facilitates coupling between the front end of the barrel and the connecting member in order to facilitate the transfer of a liquid pharmaceutical composition to a first portion of the barrel, wherein a portion of the hollow connecting member of the adapter has an outer diameter substantially similar to the inner diameter of the opening in the container to establish a frictional and fluid-tight connection between the adapter and the container, and the hollow connecting member of the adapter has an inner diameter substantially similar to the outer diameter of the front end of the barrel to establish a frictional and fluid-tight connection between the adapter and the barrel in response to the insertion of the front end of the barrel into the hollow connecting member. The system according to any one of claims 1 to 11.

13. The system according to claim 12, wherein the adapter is formed of a polymer material containing low-density polyethylene, preferably a polymer material consisting of low-density polyethylene, and the container is formed of a polymer material containing high-density polyethylene, preferably a polymer material consisting of high-density polyethylene.

14. One or more SGLT-2 inhibitor compounds for use in a method of treating and / or preventing metabolic disorders and / or other medical conditions in a patient by administering a dose of a liquid pharmaceutical composition containing one or more SGLT-2 inhibitor compounds to the patient, wherein the method is The present invention provides a syringe and a container for a liquid pharmaceutical composition, wherein the syringe comprises a barrel and a plunger, The barrel includes a hollow, elongated member having an open barrel front end and an open barrel rear end, a first portion extending from the open barrel front end to a movable section positioned along the hollow, elongated member, having a first cross-sectional dimension, and a second portion extending from the movable section to the open barrel rear end, having a second cross-sectional dimension larger than that of the first portion; The plunger includes an elongated member and a dosage scale, the elongated member including the front end and rear end of the plunger, and the dosage scale includes multiple marks positioned on the surface wall section of the plunger and aligned in a direction corresponding to the longitudinal dimension of the plunger; The plunger and barrel are sized such that a portion of the plunger, including the front end of the plunger, is insertable into the hollow elongated member of the barrel at the rear end of the open barrel, and the plunger is extendable into the barrel until the front end of the plunger engages with the inner surface portion of the hollow elongated member at the front end of the barrel; and The desired dose of liquid pharmaceutical composition is drawn from the container into the first portion of the syringe barrel by moving the front end of the plunger a selected distance from the front end of the barrel until a selected mark of multiple marks for the dosage scale aligns with the outer surface of the barrel at the rear end of the barrel. One or more SGLT-2 inhibitor compounds, including [the specified compound].

15. One or more SGLT-2 inhibitor compounds for use in the method of claim 14, wherein administering a desired dose of a liquid pharmaceutical composition to a patient from a syringe comprises oral or parenteral administration to the patient, preferably oral administration, and more preferably oral administration to the patient, wherein administering a desired dose of a liquid pharmaceutical composition to a patient from a syringe comprises oral administration to the patient by direct transfer of the liquid pharmaceutical composition from the syringe to the patient or by indirect transfer of the liquid pharmaceutical composition from the syringe to food or liquid for ingestion by the patient.

16. One or more SGLT-2 inhibitor compounds for use in the method according to any one of claims 14 to 15, wherein the desired dose is 3 mL or less, or 2 mL or less, or 1 mL or less, or 0.9 mL or less, or 0.8 mL or less, or 0.7 mL or less, or 0.6 mL or less, or 0.5 mL or less, or 0.4 mL or less, or the desired dose is in the range of 0.05 mL to 0.6 mL; and / or the desired dose is in the range of 0.01 mL to 3 mL, or the range of 0.01 mL to 2 mL, or the range of 0.01 mL to 1 mL, or the range of 0.02 mL to 0.9 mL, or the range of 0.03 mL to 0.8 mL, or the range of 0.04 mL to 0.7 mL, or the range of 0.05 mL to 0.6 mL.

17. At least one SGLT-2 inhibitor compound, (1) The following formula: 【Chemistry 25】 (In the formula, R 1 This represents cyano, Cl, or methyl (most preferably cyano), R 2 This represents H, methyl, methoxy, or hydroxy (most preferably H), R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxypropyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy -3-methylbuta-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, difluoromethyloxy, trifluoromethyloxy, 2-methyloxy-ethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; Here, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; most preferably, R 3 (It is cyclopropyl.) A glucopyranosyl-substituted benzene derivative or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -Alkyl)carbonyl, (C 1-18 -Alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 (Acylated with a group selected from -alkyl-carbonyl); (2) The following formula: 【Chemistry 26】 Veragliflozin, represented by; (3) The following formula: 【Chemistry 27】 Dapagliflozin, represented by; (4) The following formula: 【Chemistry 28】 Canagliflozin, represented by; (5) The following formula: 【Chemistry 29】 Empagliflozin, represented by; (6) The following formula: 【Transformation 30】 Luseogliflozin, represented by; (7) The following formula: 【Chemistry 31】 Tofogliflozin, represented by; (8) The following formula: 【Chemistry 32】 Ipragliflozin, represented by; (9) The following formula: 【Transformation 33】 Erzgliflozin, represented by; (10) The following formula: 【Transformation 34】 Atigliflozin, represented by; (11) The following formula: 【Chemistry 35】 Remogliflozin, represented by; (11A) The following equation: 【Transformation 36】 Lemogliflozin ethanolate, represented by: (12) The following formula: 【Chemistry 37】 (In the formula, R represents methoxy or trifluoromethoxy.) Thiophene derivatives represented by; (13) The following equation: 【Transformation 38】 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, represented by: (14) The following formula: 【Chemistry 39】 (In the formula, R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl) Spirochetal derivatives represented by; (15) The following equation: 【Chemistry 40】 (In the formula: R 1 C 1-3 - Indicates alkoxy, L 1 , L 2 These independently represent either H or F. R 6 H, (C 1-3 -Alkyl)carbonyl, (C 1-6 (-Alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl) Pyrazole-O-glucoside derivatives represented by; (16) The following formula: 【Chemistry 41】 Sotagliflozin, represented by; (17) The following formula: 【Chemistry 42】 Cergliflozin, represented by; (18) The following formula: 【Chemistry 43】 (In the formula: R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxypropyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy-3- Methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano; where R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy; R 3 (Most preferably, it is cyclopropyl.) A compound or derivative thereof represented by (where one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -Alkyl)carbonyl, (C 1-18 -Alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 (Acylated with a group selected from -alkyl-carbonyl); (19) The following formula: 【Chemistry 44】 Bexagliflozin, represented by; (20) The following equation: 【Chemistry 45】 Janagliflozin, represented by; (21) Long liflozin; 【Chemistry 46】 (22) Wampagliflozin; (23) The following equation: 【Chemistry 47】 Enabogliflozin, represented by; and (24) The following equation: 【Chemistry 48】 TFC-039 is represented by Selected from the group consisting of, Here, preferably, one or more SGLT-2 inhibitor compounds include veragliflozin, and more preferably, veragliflozin is the only SGLT-2 inhibitor compound administered. One or more SGLT-2 inhibitor compounds for use in the method according to any one of claims 14 to 16.

18. Metabolic disorders and / or other medical conditions (i) Metabolic disorders in equids (preferably, the metabolic disorder is one or more disorders selected from insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, obesity, and / or local steatosis; preferably, the metabolic disorder is insulin resistance, hyperinsulinemia, and / or clinical conditions associated with insulin resistance and / or hyperinsulinemia; preferably, the clinical conditions are one or more conditions selected from impaired glucose tolerance, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, obesity, and / or local steatosis); (ii) Metabolic disorders in equids (a metabolic disorder is one or more disorders selected from laminitis, vascular dysfunction, hypertension, hepatic lipidosis, atherosclerosis, hyperadrenocorticism, intermediate pituitary dysfunction and / or equine metabolic syndrome, preferably a clinical condition / sign associated with insulin resistance and / or hyperinsulinemia, and preferably one or more conditions selected from laminitis, vascular dysfunction, hypertension, hepatic lipidosis, atherosclerosis, hyperadrenocorticism, intermediate pituitary dysfunction and / or equine metabolic syndrome); (iii) Metabolic disorders in felines (preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes mellitus, insulin resistance, acromegaly, diabetes with elevated IGF-1 levels, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta-cell function, and / or remission of the metabolic disorder, preferably remission of diabetes, is achieved and / or maintained); (iv) Metabolic disorders in canids (preferably, the metabolic disorder is 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, asymptomatic inflammation, systemic inflammation, mild systemic inflammation, hepatic lipidosis, pancreatic inflammation, metabolic disorder events, e.g., hypertension, renal insufficiency and / or musculoskeletal disorders, and / or syndrome X (metabolic syndrome), preferably one or more selected from the group consisting of prediabetes, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus and insulin resistance, preferably the onset of hyperglycemia-induced cataract formation is prevented or remission is achieved, and / or preferably the onset of metabolic disorder events such as hypertension, renal insufficiency and / or musculoskeletal disorders is prevented, or the progression is delayed, or remission is achieved); (v) Cardiac diseases of felines (preferably, the cardiac disease is selected from the group consisting of heart failure, heart failure due to one or more cardiomyopathy, 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 unclassified cardiomyopathy (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), unclassified cardiomyopathy (UCM), and / or arrhythmic right ventricular cardiomyopathy (ARVC); preferably, one or more selected from the group consisting of heart failure due to one or more cardiomyopathy, heart failure due to hypertrophic cardiomyopathy (HCM), and hypertrophic cardiomyopathy (HCM)); (vi) Dryness of non-human mammals, preferably ruminants (preferably one or more selected from the group consisting of improving and / or facilitating dryness of non-human mammals, preferably ruminants; reducing milk production, preferably milk production and / or milk secretion, in pregnant and / or lactating non-human mammals, preferably ruminants; reducing milk accumulation and / or congestion in the mammary glands, preferably mammary glands, of non-human mammals, preferably ruminants; reducing discomfort associated with mammary congestion; for example, increasing the daily recumbent time and / or stress reduction of non-human mammals, preferably ruminants; reducing post-dryness milk leakage of non-human mammals, preferably ruminants; and reducing the incidence of intramammary infections (IMI), preferably mastitis and / or metritis, in non-human mammals, preferably ruminants); (vii) Cardiac diseases in non-human mammals, especially canids, excluding felines (preferably, cardiac diseases are: heart failure; congestive heart failure; asymptomatic / preclinical / latent heart failure; heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; congestive heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically manifest (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; heart failure due to dilated cardiomyopathy (DCM); congestive heart failure due to dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent heart failure due to dilated cardiomyopathy (DCM); dilated cardiomyopathy (DCM); clinically overt dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); one or more selected from the group consisting of aortic stenosis (valvular, supravalvular and / or subvalvular); (viiii) Hypertension in non-human mammals, preferably carnivores, more preferably cats or dogs (preferably, hypertension is one or more selected from the group consisting of circumstance hypertension, secondary hypertension and idiopathic hypertension, where preferably, secondary hypertension is selected from the group consisting of chronic kidney disease (CKD), diabetes mellitus, obesity, heart disease, endocrine disorders, e.g., Cushing's disease, hyperthyroidism, acromegaly hypertension, and hypertension associated with elevated blood pressure (BP) induced by pharmaceuticals, preferably glucocorticoids, mineralocorticoids, erythrocyte production stimulants, ephedrine and / or high-dose sodium chloride); (ix) Renal diseases in non-human mammals, preferably carnivores, more preferably cats or dogs (preferably, the renal disease is one or more selected from the group consisting of renal dysplasia, glomerulosis, polycystic kidney disease, amyloidosis, tubulonephritis / tubulointerstitial nephritis (TIN), acute kidney disease, and chronic kidney disease). Selected from the group consisting of, Preferably, the dosage is 0.01 to 10 mg / kg patient body weight. One or more SGLT-2 inhibitor compounds for use in the method according to any one of claims 14 to 17.

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