Granted Patent B2

US 8,003,700 · App. 12/416,990 · Granted Aug 23, 2011

Abstract

Claims (36)

1. A solid complex, comprising:

colchicine and

a guest, wherein the guest is malic acid, oxalic acid, or para-toluenesulfonic acid; and

wherein the solid complex comprising colchicine and malic acid comprises a colchicine malic acid co-crystal comprising XRPD peak positions at 6.0, 7.2, 8.5, 11.1, 13.1, 16.3, 16.7, 18.4, 19.9, 22.0, and 24.6±0.2 degrees 2-theta;

wherein the solid complex comprising colchicine and oxalic acid comprises a colchicine oxalic acid co-crystal comprising XRPD peak positions at 7.4, 9.2, 9.4, 10.8, 12.0, 12.3, 14.4, 15.9, 17.8, 18.9, 20.5, and 23.7±0.2 degrees 2-theta or an XRPD pattern comprising the peaks of FIG. 5 ; and

wherein the solid complex comprising colchicine and para-toluenesulfonic acid comprises a colchicine para-toluenesulfonic acid co-crystal comprising XRPD peak positions at 6.6, 6.8, 9.6, 12.8, 14.3, 15.1, 17.1, 18.6, and 22.7±0.2 degrees 2-theta.

2. The solid complex of claim 1 , wherein the solid complex is colchicine malic acid co-crystal comprising one or more of the following:

XRPD peak positions listed in Table 1;

an XRPD pattern comprising the peaks of FIG. 1 ;

FT-Raman peaks at 2935, 1595, 1500, 1444, 1350, 1324, and 1287±4 cm −1 ;

FT-Raman peaks listed in Table 3;

FT-Raman spectrum comprising the peaks of FIG. 2 ;

an endotherm peak of about 70° C. by differential scanning calorimetry analysis; or

a ratio of about 1:1 malic acid:colchicine.

3. The solid complex of claim 1 , wherein the solid complex is colchicine oxalic acid co-crystal comprising one or more of the following:

XRPD peak positions listed in Table 4;

an XRPD pattern comprising the peaks of FIG. 3 ;

FT-Raman peaks at 2934, 1592, 1549, 1505, 1436,and 1401±4 cm −1 ;

FT-Raman peaks listed in Table 6;

FT-Raman spectrum comprising the peaks of FIG. 4 ;

an endotherm peak of about 144° C. by differential scanning calorimetry analysis; or

a ratio of about 1:2 oxalic acid:colchicine.

4. The solid complex of claim 1 , wherein the solid complex is colchicine oxalic acid co-crystal tetrahydrofuran solvate comprising

a ratio of about 1:2:1 oxalic acid:colchicine:tetrahydrofuran.

5. The solid complex of claim 1 , wherein the solid complex is colchicine para-toluenesulfonic acid co-crystal comprising one or more of the following:

XRPD peak positions listed in Table 8;

an XRPD pattern comprising the peaks of FIG. 6 ;

FT-Raman peaks at 1516, 1468, and 1322±4 cm −1 ;

FT-Raman peaks listed in Table 10;

FT-Raman spectrum comprising the peaks of FIG. 7 ;

an endotherm peak of about 198° C. by differential scanning calorimetry analysis; or

a ratio of about 1:1 para-toluenesulfonic acid:colchicine.

6. A composition, comprising:

a solid complex comprising colchicine and a guest, wherein the guest is malic acid, oxalic acid or para-toluenesulfonic acid according to claim 1 ; and

a pharmaceutically acceptable excipient.

7. The composition of claim 6 , wherein the composition is a solid oral dosage formulation.

Assignments (6)