Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-11-13
1998-04-14
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 21, A61K 3800, A61K 3813
Patent
active
057391050
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/KR95/00059, filed 19 May 1995.
FIELD OF THE INVENTION
The present invention relates to a composition comprising a cyclosporin, and to a process for the preparation thereof.
DESCRIPTION OF THE PRIOR ART
Cyclosporins, a group of cyclic polypeptides comprised of 11 amino acids having the structural formula (I), are useful as an immunosuppressive which suppresses allogenic transplant rejection which may occur in the transplantation of organs of animals including human beings. ##STR1## Cyclosporin A: R=CH.sub.2 CH.sub.3 ; Cyclosporin B: R=CH.sub.3 ; containing cyclosporins have seen limited applications because of their extremely low solubility in water(20-30 .mu.g/ml).
U.S. Pat. No. 4,388,307 describes pharmaceutical compositions containing cyclosporins (SANDIMMUN or SANDIMMUNE) in the form of a solution for injection or oral administration, or a soft capsule filled with the solution. The solution is prepared by dispersing a cyclosporin into a vegetable oil by using an ethoxylated castor oil (obtained from a reaction between natural or hydrogenated castor oil and ethylene oxide) or a transesterification product of a natural vegetable oil triglyceride and a polyalkylene polyol as an emulsifier, and ethanol as a solubilizing agent. However, the process has certain drawbacks. For example, when the oily composition is contacted with an aqueous solution in mouth or intestine, the drug component is often separated as a solid, thereby reducing its bioavailability to a level of, e.g., below 30%. Moreover, in case of a long period storage, cyclosporins tend to be crystallized as the ethanol content decreases by evaporation; and patients suffer from the unpleasant odor of the ethoxylated castor oil.
Accordingly, many attempts have been made in search for a cyclosporin containing formulation with improved stability and bioavailability. For example, Japanese Patent No. 89-38029 describes a method of dissolving a cyclosporin in an organic solvent with a surfactant and then drying the resultant; German Patent Nos. 295,765 and 295,766 offer a method of dissolving cyclosporins in ethanol with a surfactant and lyophilizing the resultant; PCT international publication No. WO 90-00389 discloses a method of solubilizing cyclosporins by using a liposome and lyophilizing the resultant; and German Patent No. 293,499 presents a method of dissolving cyclosporins in propylene glycol, suspending the solution with a polymeric polysaccharide, and solidifying the suspension with a solid carrier.
Even though the above processes may have achieved some success in improving the stability of the formulation through minimizing the ethanol content therein, they still suffer from various deficiencies. For example, the use of surfactants having a complicated composition is not practically suitable or desirable for preparing the formulation; liposome makes the whole process complicated and the reproducibility of particle size or inclusion rate is hard to control; and the use of a polymeric polysaccharide may turn the total volume of the formulation to be too bulky for administration. Further, the prior art methods still fail to produce cyclosporin containing compositions which have a satisfactory dissolution rate in an aqueous solution.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a cyclosporin containing composition having improved stability as well as a high dissolution rate and blood concentration of cyclosporin.
It is another object of the present invention to provide a process for the preparation of the inventive composition.
In accordance with one aspect of the present invention, there is provided a composition comprising 1.0 to 40 wt. % of a cyclosporin A, 0.1 to 30 wt. % of an emulsifier and 5 to 80 wt. % of a porous dextrin, based on the total weight of the composition.
In accordance with another aspect of the present invention, there is provided a process for preparing a cyclosporin containing composition comprising the steps of dissolving the cyclospori
Choi Jae Yoon
Choi Sung Wook
Kim Hyun Soo
Lee Hye Weon
Park Young Keun
Touzeku P. Lynn
Tsang Cecilia J.
Yuhan Corporation
LandOfFree
Cyclosporin containing composition and process for the preparati does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cyclosporin containing composition and process for the preparati, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cyclosporin containing composition and process for the preparati will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-634568