Pharmaceutical compositions

Medicilon is the first CRO to offer preclinical animal testing service for the global pharmaceutical companies in China. We provide the IND filing for the preclinical services. Medicilon is the CRO that fulfill both the Chinese and US GLP standards. Medicilon could submit the application for both US FDA and CFDA for your new drug. Since 2004, we have successfully helped our clients to submit their new drug application to US FDA and CFDA and met the requirements of the US FDA and CFDA. We have undergone several inspections and passed all of them. Medicilon will provide an efficient, cost-effective and professional service to help our clients to achieve their goals.Email:[email protected] Web:www.medicilon.com
The present invention is directed to pharmaceutical compositions comprising: (a) a cyclopolysaccharide and (b) a compound of Formula (I) or its pharmaceutical acceptable salt: wherein X1, X2, Q, Z, and m are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compositions.
Example 5: Single Dose IV Toxicity Study in Mice with the NL-101 first generation formulation:
A single dose of NL-101 1st generaton formulation (20, 40, 60, 80 or 100 mg/kg) was slowly administered (iv, injection time>30 seconds), to mice and change in body weight was measured over 14 day to assess toxicity of the various doses of NL-101. We found that up to 60mg/kg of NL-101 did not result in a significant change in body weight.
However, we found that this first generation formulation has many disadvantages such as low pH value, potential precipitation after i.v. injection, and series side effects such as damaged mice tail after iv injection. More seriously, sometimes we observed that quick iv injection (e.g injection time <5 seconds) of NL-101 may lead to mice sudden death. Example 6: Single Dose IV Toxicity Study in Mice with the HP CD-based NL-101 formulation:
A single dose of HP CD-based NL-101 formulation (20, 40, 60, 80, 100, or 150 mg/kg) in 10% HP CD was administered (iv) to mice and change in body weight was measured over 14 day to assess toxicity of the various doses of NL-101. We found that up to 60mg/kg of NL-101 did not result in a significant change in body weight.
We are surprised to found that the HP CD-based NL-101 formulation can significantly reduce the cardiotoxicity in vivo. The mice even can survive under quick injection (t<5 seconds) of as high as 150mg/kg NL-101. More importantly, we didn't observe cardiorespiratory stress in mice at therapeutically effective dose of 60mg/kg. In addition, this formulation also has many other advantages, such as neutral pH, clear and stable injection solution, no precipitate issue after iv injection, and no damaged mice tail after iv injection. Therefore, HP CD-based NL-101 formulation will be an ideal formulation to be used in NL-101 MTD, PK, in vivo efficacy study, and IND enabling study. We are actively developing the HP CD-based NL-101 formulation for future human clinical trial.
Example 7: Single Dose IV Toxicity Study in Mice with the Captisol™-based NL-101 formulation:
A single dose of Captisol™-based NL-101 formulation (20, 40, 60, 80, 100, or 150 mg/kg) in 10% Captisol™ was administered (iv) to mice and change in body weight was measured over 14 day to assess toxicity of the various doses of NL-101. We found that up to 60mg/kg of NL-101 did not result in a significant change in body weight.
We are glad to found that the Captisol™-based NL-101 formulation can also significantly reduce the cardiotoxicity in vivo. The mice even can survive under quick injection (t<5 seconds) of as high as 150mg/kg NL-101. More importantly, we didn't observe cardiorespiratory stress in mice at therapeutically effective dose of 60mg/kg. In addition, this formulation also has many other advantages, such as neutral pH, clear and stable injection solution, no precipitate issue after iv injection, and no damaged mice tail after iv injection. Therefore, Captisol™-based NL-101 formulation will be also an ideal formulation to be used in NL-101 MTD, PK, in vivo efficacy study, IND enabling study, as well as in future human clinical trial. Example 8: Multiple Doses IV Toxicity Study in Mice with the HPpCD-based NL-101 formulation:
Multiple doses of HPpCD-based NL-101 formulation (60 mg/kg) in 10%
HP CD was administered (iv) to mice and change in body weight was measured to assess toxicity of the various doses of NL-101. We found that mice can well tolerate multiple doses of 60mg/kg of NL-101 without significant change in body weight. For example, the mice can be dosed at 60mg/kg at day 1, 4, 8, 11, 18, 25. Another feasible dosing scheme is 60mg/kg at day 1, 2, 8, 15, 22, 29.

10 images

0 comments
Only registered users can comment.