Pharmaceutical composition, methods for treating and uses thereof

a technology of pharmaceutical compositions and sglt2 inhibitors, applied in the field of sglt2 inhibitors, can solve the problems of reducing the capacity of the kidneys to excrete waste products

Inactive Publication Date: 2016-02-11
BOEHRINGER INGELHEIM INT GMBH
View PDF2 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0288]The pharmaceutical compositions and methods according to this invention show advantageous effects in the treatment and prevention of those diseases and conditions as described hereinbefore. Advantageous effects may be seen for example with respect to efficacy, dosage strength, dosage frequency, pharmacodynamic properties, pharmacokinetic properties, fewer adverse effects, convenience, compliance, etc.
[0289]Methods for the manufacture of SGLT2 inhibitors according to this invention and of prodrugs thereof are known to the one skilled in the art. Advantageously, the compounds according to this invention can be prepared using synthetic methods as described in the literature, including patent applications as cited hereinbefore. Preferred methods of manufacture are described in the WO 2006 / 120208 and WO 2007 / 031548. With regard to empagliflozin an advantageous crystalline form is described in the international patent application WO 2006 / 117359 which hereby is incorporated herein in its entirety.
[0290]The active ingredients may be present in the form of a pharmaceutically acceptable salt. Pharmaceutically acceptable salts include, without being restricted thereto, such as salts of inorganic acid like hydrochloric acid, sulfuric acid and phosphoric acid; salts of organic carboxylic acid like oxalic acid, acetic acid, citric acid, malic acid, benzoic acid, maleic acid, fumaric acid, tartaric acid, succinic acid and glutamic acid and salts of organic sulfonic acid like methanesulfonic acid and p-toluenesulfonic acid. The salts can be formed by combining the compound and an acid in the appropriate amount and ratio in a solvent and decomposer. They can be also obtained by the cation or anion exchange from the form of other salts.
[0291]The active ingredients or a pharmaceutically acceptable salt thereof may be present in the form of a solvate such as a hydrate or alcohol adduct.
[0292]Pharmaceutical compositions or combinations for use in these therapies comprising the SGLT-2 inhibitor as defined herein optionally together with one or more other active substances are also contemplated.
[0293]Further, the present invention relates to the SGLT-2 inhibitors, optionally in combination with one, two or more further active agents, each as defined herein, for use in the therapies as described herein.

Problems solved by technology

Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Pharmaceutical composition, methods for treating and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Empagliflozin in Patients with Type 2 Diabetes Mellitus (T2DM) and Renal Impairment (RI)

[0352]A Phase III trial investigated the efficacy and safety of empagliflozin (EMPA) as add-on to existing therapy for 52 weeks in patients with T2DM and RI. Patients with mild RI (eGFR [MDRD equation]≧60 to 2) received EMPA 10 or 25 mg qd or placebo (PBO). Patients with moderate RI (eGFR 30 to 2) received EMPA 25 mg qd or PBO. Patients with severe RI (eGFR 5 to 2) received EMPA 25 mg qd or PBO.

[0353]In patients with type 2 diabetes and mild renal impairment, treatment with empagliflozin 10 and 25 mg at week 52 resulted in a small decrease in eGFR. However, mean eGFR increased to a value slightly above baseline at the 3-week follow up visit in the empagliflozin treatment groups; in contrast, in the placebo group, mean eGFR further decreased (Table 1A).

TABLE 1ADescriptive statistics for eGFR over time in patientswith mild renal impairmentEmpaEmpaPlacebo10 mg25 mgNumber of patients 32 (100.0)41 (10...

example 2

Empagliflozin in Hypertensive Patients with Type 2 Diabetes Mellitus (T2DM)

[0356]A Phase III trial investigated the efficacy and safety of empagliflozin (EMPA) administered orally, once daily over 12 weeks in hypertensive patients with T2DM (EMPA 10 or 25 mg, placebo (PBO)). Patients with a systolic blood pressure (SBP) of 130 to 159 mmHg and a diastolic blood pressure (DSP) of 80 to 99 mmHg were included in the trial.

[0357]Treatment with empagliflozin 10 and 25 mg at week 12 resulted in a small decrease in eGFR. However, mean eGFR increased to a value slightly above baseline at the 2-week follow up visit in the empagliflozin treatment groups; in contrast, in the placebo group, mean eGFR remained slightly below baseline (Table 2).

TABLE 2Descriptive statistics for eGFR (MDRD) over timeEmpaEmpaPlacebo10 mg25 mgBaseline eGFRN* (%)238 (100)241 (100)244 (100)Mean (SD) 84.47(17.06)83.01(16.43)83.97(17.85)[mL / min / 1.73 m2]Last value ontreatment eGFRN* (%)237 (99.6)238(98.8)240 (98.4)Mean (S...

example 3

Empagliflozin in Patients with Type 2 Diabetes Mellitus (T2DM) Receiving Treatment with Basal Insulin

[0358]A Phase IIb trial investigated the efficacy and safety of empagliflozin (EMPA 10 or 25 mg, placebo (PBO)) administered orally, once daily over 78 weeks in patients with T2DM receiving treatment with basal insulin (glargine, detemir, or NPH insulin only).

[0359]Treatment with empagliflozin 10 and 25 mg resulted in a small decrease in eGFR. However, mean eGFR increased to a value slightly below baseline at the 4-week follow up visit in the empagliflozin treatment groups; in contrast, in the placebo group, mean eGFR further slightly decreased (Table 3).

TABLE 3Descriptive statistics for eGFR (MDRD) over timeEmpaEmpa Placebo10 mg25 mgNumber of patients, 170 (100.0)169 (100.0)155 (100.0)N (%)Baseline eGFRN1 (%)170 (100.0)169 (100.0)155 (100.0)Mean (SD)83.89 (22.73)85.01 (23.63)82.88 (25.46)Week 18 eGFRN1 (%)134 (78.8)133 (78.7)113 (72.9)Mean (SD)80.07 (20.15)80.37 (23.03)79.11 (21.63)...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
waist circumferenceaaaaaaaaaa
waist circumferenceaaaaaaaaaa
waist circumferenceaaaaaaaaaa
Login to view more

Abstract

The present invention relates to certain SGLT-2 inhibitors for treating, preventing, protecting against and / or delaying the progression of chronic kidney disease in patients, for example patients with prediabetes, type 1 or type 2 diabetes mellitus.

Description

TECHNICAL FIELD OF THE INVENTION[0001]The present invention relates to certain SGLT-2 inhibitors for treating, preventing, protecting against and / or delaying the progression of chronic kidney disease in patients, for example patients with prediabetes, type 1 or type 2 diabetes mellitus.BACKGROUND OF THE INVENTION[0002]Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and chronic kidney disease is often diagnosed as a result of screening of people known to be at risk of kidney problems.[0003]Chronic kidney disease may be identified by a blood test, for example for creatinine. Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products.[0004]CKD has been classified into 5 stages, where stage 1 is kidney damage with normal GFR (mL / min / 1.73 m2) of ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/7048A61K45/06
CPCA61K45/06A61K31/7048A61K31/155A61K31/522A61K38/28A61K9/2018A61K9/2866A61P13/02A61P13/12A61P43/00A61P3/10A61K2300/00
Inventor BROEDL, ULI CHRISTIANJOHANSEN, ODD-ERIKMAYOUX, ERIC WILLIAMSSOLEYMANLOU, NIMAVON EYNATTEN, MAXIMILIANWOERLE, HANS-JUERGENCHERNEY, DAVID Z.I.PERKINS, BRUCE A.
Owner BOEHRINGER INGELHEIM INT GMBH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap