Patent application EP16163764A (EP), filed 2016-04-04
Publication number: EP3228306A1
Title: COMPLEX COMPOUND COMPRISING OBETICHOLIC ACID AND CYCLODEXTRIN AND PHARMACEUTICAL FORMULATION COMPRISING THE COMPLEX COMPOUND
Abstract: The present invention relates to a complex compound comprising obeticholic acid and cyclodextrin and a pharmaceutical formulation comprising it. The invention further relates to a process for producing said pharmaceutical formulation. Finally, the invention relates to the therapeutic use of the complex compound in the treatment of a farnesoid X receptor (FXR) mediated disease or condition.
IPC codes: A61K  47/    69            A I
A61K   9/    00            A I
Claims: number: 1
text: A complex compound comprising:
number: 2
text: The complex compound according to claim 1, which is an inclusion complex.
number: 3
text: The complex compound according to claim 1 or 2, wherein the molar ratio of obeticholic acid to cyclodextrin is about 1:1.
number: 4
text: The complex compound according to any one of the previous claims, wherein cyclodextrin is selected from β-cyclodextrin, (2-hydroxypropyl)-β-cyclodextrin, (2-hydroxypropyl)-γ-cyclodextrin, random methyl-β-cyclodextrin and sodium sulfobutylether-β-cyclodextrin.
number: 5
text: The complex compound according to any one of claims 1 to 4, which is present in amorphous form.
number: 6
text: The complex compound according to any one of claims 1 to 4, which is present in crystalline form.
number: 7
text: The complex according to claim 6, in which the crystalline form is characterized by an X-ray diffraction pattern including characteristic peaks at about 5.5, 7.6; 10.9; 12.4; and 18.2 degrees 2-theta ± 0.2 degrees 2-theta.
number: 8
text: A crystalline complex compound comprising:
number: 9
text: The crystalline complex compound of claim 8, which is is characterized by an X-ray diffraction pattern including characteristic peaks at about 5.5, 7.6; 10.9; 12.4; and 18.2 degrees 2-theta ± 0.2 degrees 2-theta.
number: 10
text: An amorphous complex compound comprising:
number: 11
text: A pharmaceutical formulation, comprising the complex compound according to any one of claims 1 to 10, and optionally one or more pharmaceutical excipient(s).
number: 12
text: The pharmaceutical formulation according to claim 11, which is a tablet or capsule.
number: 13
text: The complex compound according to any one of claims 1 to 10 for use in the medical treatment of a farnesoid X receptor (FXR) mediated disease or condition.
number: 14
text: The complex compound for use according to claim 13, in which the FXR mediated disease or condition is a hepatic or biliary disease or condition.
number: 15
text: The complex compound for use according to claim 13 or 14, wherein the disease or condition is selected from biliary atresia, cholestatic liver disease, chronic liver disease, nonalcoholic steatohepatitis (NASH), hepatitis C infection, alcoholic liver disease, primary biliary cirrhosis (PBC), liver damage due to progressive fibrosis, liver fibrosis, and cardiovascular diseases including atherosclerosis, arteriosclerosis, hypercholesteremia, and hyperlipidemia.
Office action: search_report, dated 2017-10-11
Rejection reasons: inventive_step_epc_56
Prior art cited: ref_id: WO2013192097A1
ref_type: patent
severity: background
ref_id: WO02072598A1
ref_type: patent
severity: background
ref_id: - L. GREENSPAN, JOURNAL OF RESEARCH OF THE NATIONAL BUREAU OF STANDARDS, vol. 81A, 1977, pages 89
ref_type: npl
severity: background
ref_id: - A. WEXLER; S. HASEGAWA, JOURNAL OF RESEARCH OF THE NATIONAL BUREAU OF STANDARDS, vol. 53, 1954, pages 19
ref_type: npl
severity: background
ref_id: - H.P. FIELDER: "Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende Gebiete"
ref_type: npl
severity: background
ref_id: - A.H. KIBBE: "Handbook of Pharmaceutical Excipients", AMERICAN PHARMACEUTICAL ASSOCIATION, WASHINGTON
ref_type: npl
severity: background
ref_id: WO02072598A1
ref_type: patent
severity: background
ref_id: - C A VENTURA ET AL: "Improvement of water solubility and dissolution rate of ursodeoxycholic acid and chenodeoxycholic acid by complexation with natural and modified beta-cyclodextrins", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 149, 1 January 1997 (1997-01-01), pages 1 - 13, XP055300022
ref_type: npl
severity: background
ref_id: WO02072598
ref_type: patent
severity: obviousness
ref_id: - C A VENTURA ET AL, "Improvement of water solubility and dissolution rate of ursodeoxycholic acid and chenodeoxycholic acid by complexation with natural and modified beta-cyclodextrins", INTERNATIONAL JOURNAL OF PHARMACEUTICS, (19970101), vol. 149, pages 1 - 13, XP055300022 [Y] 1-15 * the whole document and in particular the abstract *
ref_type: npl
severity: obviousness
Final disposition: pending (2017-10-11)