STEROID TETROL SOLID STATE FORMS - 2
The invention relates to solid state forms of androst-5-ene-3α,7β,16β,17β-tetrol, formulations containing or prepared from such solid state forms and use of these materials for modulating unwanted inflammation including acute and chronic non-productive inflammation. The formulations can be used to prevent, treat or slow the progression of conditions related to autoimmunity and metabolic disorders such as arthritis, multiple sclerosis, ulcerative colitis, Type 1 diabetes and Type 2 diabetes.
1 . Crystalline androst-5-ene-3α,7β,16α,17β-tetrol.
2 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 1 wherein crystalline androst-5-ene-3α,7β,16α,17β-tetrol is a crystalline anhydrate.
3 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 1 wherein crystalline androst-5-ene-3α,7β,16α,17β-tetrol is Form Iα or Form IIα 3α-tetrol.
4 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 3 wherein crystalline androst-5-ene-3α,7β,16α,17β-tetrol is Form Iα 3α-tetrol characterized by (1) an XRPD pattern having three or more peaks selected from the group consisting of about 7.6, 16.1, 17.8, 19.8 and 22.2 degree 2-theta or (2) DTA thermogram, obtained with a temperature ramp of 10° C./min, having a prominent endotherm centered at about 224° C. and an exotherm centered at about 154° C. or (1) and (2).
5 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 4 wherein the XRPD pattern further has one or more peaks selected from the group consisting of about 13.7, 15.3, 16.5, 17.0 and 20.9 degree 2-theta.
6 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 4 wherein the 224° C. DTA endotherm has an onset temperature of about 216° C.
7 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 4 wherein crystalline androst-5-ene-3α,7β,16α,17β-tetrol is further characterized by TGA thermogram, obtained with a temperature ramp of 10° C./min, having (1) negligible weight loss from about 60° C. to about 140° C. or (2) about 2% wt loss from about 60° C. to about the onset of the prominent endotherm or (1) and (2).
8 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 3 wherein crystalline androst-5-ene-3α,7β,16α,17β-tetrol is Form IIα 3α-tetrol characterized by (1) DTA thermogram, obtained with a temperature ramp of 10° C./min, having a prominent endotherm centered at about 243° C.
9 . The crystalline androst-5-ene-3α,7β,16α,17β-tetrol of claim 8 wherein the 243 oC DTA endotherm has (1) an onset temperature of about 229° C. or (2) a shoulder between about 230 to 240° C. or (1) and (2).
10 . Amorphous androst-5-ene-3α,7β,16α,17β-tetrol.
11 . The amorphous androst-5-ene-3α,7β,16α,17β-tetrol of claim 10 characterized by (1) XRPD pattern having a broad band from about 11 degree 2-theta to about 20 degree 2-theta or a broad band centered between about 16 to 17 degree 2-theta or (2) DTA thermogram, obtained with a temperature ramp of 10° C./min, having a prominent exotherm centered at about 166° C. or (1) and (2).
12 . The amorphous androst-5-ene-3α,7β,16α,17β-tetrol of claim 11 wherein the DTA thermogram further has an endotherm centered at about 225° C.
13 . The amorphous androst-5-ene-3α,7β,16α,17β-tetrol of claim 12 wherein the 225° C. DTA endotherm has a shoulder at about 220° C.
14 . The amorphous androst-5-ene-3α,7β,16α,17β-tetrol of claim 11 further characterized by TGA thermogram with negligible % weight loss between about 60° C. to about 140° C.
15 . A composition comprising one or more excipients and a solid state form of androst-5-ene-3α,7β,16α,17β-tetrol.
16 . The composition of claim 15 wherein the solid state form is crystalline androst-5-ene-3α,7β,16α,17β-tetrol.
17 . The composition of claim 15 wherein the solid state form is a crystalline anhydrate.
18 . The composition of claim 17 wherein the crystalline anhydrate is Form Iα 3α-tetrol.
19 . The composition of claim 17 wherein the crystalline anhydrate is Form IIα 3α-tetrol.
20 . A method of preparing a liquid formulation comprising admixing a solid state form of androst-5-ene-3α,7β,16α,17β-tetrol with a liquid excipient.
21 . The method of claim 20 wherein the solid state form is crystalline androst-5-ene-3α,7β,16α,17β-tetrol.
22 . The method of claim 20 the solid state form of androst-5-ene-3α,7β,16α,17β-tetrol is a crystalline anhydrate.
23 . The method of claim 13 wherein the crystalline anhydrate is Form Iα or Form IIα 3α-tetrol.
24 . The method of claim 20 wherein the solid state form is amorphous 3α-tetrol.
25 . A method of treating unwanted inflammation, comprising administering an effective amount of a solid formulation to a subject in need thereof wherein the solid formulation comprises a solid state form of androst-5-ene-3α,7β,16α,17β-tetrol and one or more excipients.
26 . The method of claim 25 wherein the solid state form is crystalline androst-5-ene-3α,7β,16α,17β-tetrol.
27 . The method of claim 25 wherein the solid state form is a crystalline anhydrate.
28 . The method of claim 27 wherein the crystalline anhydrate is Form Iα or Form IIα 3α-tetrol.
29 . The method of claim 25 wherein the solid state form is amorphous 3α-tetrol.
30 . The method of claim 25 wherein the unwanted inflammation is a condition or disease associated with chronic, non-production inflammation.
31 . The method of claim 30 wherein the condition or disease is an autoimmune condition or disease.
32 . The method of claim 30 wherein the condition or disease is a metabolic condition or disease.
33 . The method of claim 31 wherein the autoimmune disease is Type 1 diabetes.
34 . The method of claim 31 wherein the autoimmune disease is a lupus condition, systemic lupus erythematosus or discoid lupus
35 . The method of claim 30 wherein the condition or disease is an arthritis condition or rheumatoid arthritis.
36 . The method of claim 30 wherein the condition or disease is an inflammatory bowel disease, ulcerative colitis or Crohn's disease (regional enteritis).
37 . The method of claim 30 wherein the condition or disease is a lung inflammation condition, cystic fibrosis, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, acute asthma, chronic asthma, emphysema, acute bronchitis, allergic bronchitis, chronic bronchitis, a fibrosing alveolitis (lung fibrosis) condition or subepithelial fibrosis in patients having chronic bronchitis, asthma and/or COPD.
38 . The method of claim 30 wherein the condition or disease is a neurodegenerative condition, Parkinson's disease or Alzheimer's disease.
39 . The method of claim 30 wherein the condition or disease is a hyperproliferation condition or cancer.
40 . The method of claim 30 wherein the condition or disease is a liver cirrhosis condition, nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver disease.
41 . The method of claim 32 wherein the metabolic condition or disease is type 2 diabetes, obesity, insulin resistance, hyperglycemia, impaired glucose utilization or tolerance, or impaired or reduced insulin synthesis.