Patent EA-001760-B1 (EA)
Title: Microgranulescontaining cisplatin
Inventor: DEBREGEAS PATRICE
IPC: A61K33/243
Filed: 1998-02-10
Abstract: 1. Microgranules containing cisplatin with controlled release for oral administration, average size of said microgranules is from 0,4 to 1,5 mm, and more specifically, from 1 to 1,25 mm. 2. Microgranules according to Claim 1, characterised in that each microgranule contains active microgranule which is covered with coat, which comprises covering agent providing controlled release of cisplatin and/or other active principles, said active microgranule includes either a mixture comprising excipients, cisplatin and, possibly, other active principles, or neutral granule-carrier, coated with mixture comprising excipients, cisplatin and, possibly, other active principles. 3. Microgranules according to Claim 2, characterised in that covering agent providing controlled release of cisplatin and, possibly, other active principles is selected from cellulose polymers or methacrylic acid copolymers. 4. Microgranules according to Claim 3, characterised in that covering agent is selected from ethylacrylate and methylmethacrylate copolymers. 5. Microgranules according to any of Claims 2-4, characterised in that the coat comprises covering agent, which consists of one polymer or a mixture of polymers and/or several layers of polymers. 6. Microgranules according to any of Claims 2-5, characterised in that lubricating agent is added to the covering agent, said lubricating agent is such as talc, and/or plasticizing agent, such as triethylcitrate, and/or surface-active agent, such as polysorbate 80. 7. Microgranules according to any of Claims 2-6, characterised in that between active microgranule and the coat, which comprises a covering agent, the protective layer is applied. 8. Microgranules according to any of Claims 2-7, characterised in that the mixture of excipients comprises sodium chloride. 9. Microgranules according to any of Claims 2-8, characterised in that cisplatin constitutes from 25 to 350 mg/g therein. 10. Microgranules according to Claim 9, characterised in that cisplatin constitutes from 50 to 60 mg/g therein. 11. A method for producing of microgranules according to any of Claims 2-10, characterised in that cisplatin is applied on carrier neutral granules by means of pulverisation of suspension, which contains cisplatin in hydro-alcoholic, alcoholic, or aqueous medium. 12. A method according to Claim 11, characterised in that the suspension is predominantly aqueous and comprises a stabilising agent, such as sodium chloride, one or more sticker agents, such as hydroxypropylmethylcellulose or polyethyleneglycol, and/or surfactant agent. 13. A method according to Claim 11 or 12, characterised in that active microgranules are covered with a coat, containing covering agent, and are lubricated with talc. 14. A pharmaceutical remedy, characterised in that it comprises microgranules according to any of Claims 1-10, obtained by means of a method according to any of Claims 11-13, in the amount which provides obtaining of single dose, comprising from 10 to 50 mg of cisplatin. 15. A pharmaceutical remedy according to Claim 14, characterised in that it comprises a mixture of cisplatin microgranules and an anticancer agent as a combined product for simultaneous, separate or time-phased use in anticancer therapy. 16. A pharmaceutical remedy according to Claim 14, characterised in that anticancer agent is fluorouracil, anticancer remedy which is a mixture of tugafur with 5-chloro-2,4-dihydroxypyridin and oxonic acid in ratio 1:0, 4:1 (S1), a mixture of vinblastine with bleomycine, or a mixture of etoposide with bleomycine or paclitaxel. 17. The use of microgranules according to Claims 1-10, obtained by means of a method according to any of Claims 11-13 for preparation of medicament for oral administration in minor doses, in particular, less or equal to 20 mg/m<2> per 24 hours. 18. The use according to Claims 17, characterised in that the medicament is used for polychemotherapy or in association with radiotherapy. 19. The use according to Claim 17 or 18, wherein the average cisplatin concentration in blood is from 0,5 to 1, 0 μg/ml.