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US 5,665,760 AGranted
Lyophilized thioxanthenone antitumor agents
AssigneeSanofi Winthrop, Inc.
InventorsStephen Brown, Gurdial Singh Sandhu
Life of this patent
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Abstract
Disclosed are reconstituted lyophilized formulations for the treatment of mammalian tumors comprising a thioxanthenone antitumor agent in combination with mannitol or sucrose as a stabilizer in a lactate buffer.
Claims10
A reconstituted lyophilized formulation for the treatment of mammalian tumors comprising:
- a) of from about 1 to about 50 mg/ml of an antitumor agent having the formula ##STR4## wherein n is 2 or 3;
- R.sup.1 and R.sup.2 are independently lower-alkyl;
- Q is a residue chosen from the group consisting of CH.sub.2 NHR.sup.3, CH.sub.2 N (R.sup.4) SO.sub.2 R.sup.7, CH.sub.2 NHCHO, CH.dbd.N--Ar, C(O) NR.sup.5 R.sup.6, CH.sub.2 N(R.sup.4) C(O)R.sup.7, CH.sub.2 N (C.sub.2 H.sub.5) CHO, CH.sub.2 N(R.sup.4)P(O)(O-lower-alkyl).sub.2, CH.sub.2 N.dbd.CH--N (R.sup.9)(R.sup.10), CH.sub.2 N (R.sup.4)C(O)CF.sub.3 and CH.sub.2 N (R.sup.4) C (O) OR.sup.7 ;
- R.sup.3 is hydrogen or lower-alkyl;
- R.sup.4 is hydrogen, lower-alkyl or Ar;
- R.sup.5 is hydrogen, lower-alkyl or Ar;
- R.sup.6 is hydrogen or lower-alkyl;
- R.sup.7 is lower-alkyl, or Ar;
- R.sup.8 is hydrogen, lower-alkyl, lower-alkoxy, or hydroxy;
- Ar is phenyl or phenyl substituted with methyl, methoxyl, hydroxy, halogen or nitro, with the proviso that when n is 2, R.sup.1 and R.sup.2 are ethyl, R.sup.8 is hydrogen and Q is CH.sub.2 NHSO.sub.2 Ar, the Ar group cannot be 4-monosubstituted by methyl or halogen;
- and
- R.sup.9 and R.sup.10 are independently lower-alkyl;
- or a pharmaceutically acceptable acid-addition salt or solvate thereof;
- b) of from about 10 to about 125 mg/ml of a stabilizer selected from the group consisting of mannitol and sucrose;
- and
- c) of from about 0.025 to about 0.25M of a lactate buffer, said formulation having a pH of from about 3.0 to about 4.5.
13 more elements
A reconstituted lyophilized formulation for the treatment of mammalian tumors comprising:
- a) from about 1 to about 20 mg/ml of an antitumor agent having the formula ##STR5## wherein n is 2 or 3;
- R.sup.1 and R.sup.2 are independently lower-alkyl;
- Q is a residue chosen from the group consisting of CH.sub.2 NHR.sup.3, CH.sub.2 NHCHO, CH.dbd.N--Ar, C(O)NR.sup.5 R.sup.6, CH.sub.2 N(R.sup.4)C(O)R.sup.7, CH.sub.2 N(C.sub.2 H.sub.5)CHO, CH.sub.2 N(R.sup.4)P(O)(O-lower-alkyl).sub.2, CH.sub.2 N.dbd.CH--N(R.sup.9) (R.sup.10), CH.sub.2 N(R.sup.4)C(O)CF.sub.3 and CH.sub.2 N(R.sup.4)C(O) OR.sub.7 ;
- R.sup.3 is hydrogen or lower-alkyl;
- R.sup.4 is hydrogen, lower-alkyl or Ar;
- R.sup.5 is hydrogen, lower-alkyl or Ar;
- R.sup.6 is hydrogen or lower-alkyl;
- R.sup.7 is lower-alkyl, or Ar;
- R.sup.8 is hydrogen, lower-alkyl, lower-alkoxy, or hydroxy;
- Ar is phenyl or phenyl substituted with methyl, methoxyl, hydroxy, halogen or nitro, and
- R.sup.9 and R.sup.10 are independently lower-alkyl;
- or a pharmaceutically acceptable acid-addition salt or solvate thereof;
- b) of from about 30 to about 100 mg of a stabilizer selected from the group consisting of mannitol and sucrose;
- c) of from about 0.025 to about 0.25M of a lactate buffer, said formulation having a pH of from about 3.5 to 4.5.
11 more elements
A reconstituted lyophilized formulation for the treatment of mammalian tumors comprising:
- a) 1-50 mg of N-[[1-[[2-(di-methylamino)ethyl]amino]-9-oxothioxanthene-4-yl]methyl]metha nesulfonamide;
- b) 0.025 to about 0.25M of sodium lactate buffer;
- c) of from about 10 to 125 mg of sucrose;
- d) of from about 1.0 to about 10 mg sodium chloride;
- and
- e) water to 1.0 ml,
- said formulation having a pH of from about 3.0 to about 4.5.
4 more elements
Dependencies are inferred from the claim text.