Unlock instant, AI-driven research and patent intelligence for your innovation.

Process for the Preparation of Dicycloplatin

a dicycloplatin and process technology, applied in the field of process for the preparation of dicycloplatin, can solve the problems of toxic and severe side effects, inability to stabilize cisplatin as an aqueous solution, and myelosuppression still exists, and achieves mild reactive conditions, short reaction time, and easy operation

Active Publication Date: 2016-10-13
SYN NAT PROD ENTERPRISE LLC +1
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]The present invention provides a surprisingly discovered new process for preparing dicycloplatin with the benefits of easy operation, mild reactive conditions, short reaction times and high reproducibility.

Problems solved by technology

Although a drug of this type exhibits therapeutic effects in cancers such as genitourinary cancer, nasopharyngeal cancer, cephalocircular cancer and lung cancer, it is toxic and leads to severe side effects.
Some undesirable effects, such as nephrotoxicity, neurotoxicity, ototoxicity, nausea, and vomiting, are all constraints to its dosage and long term use.
Although the toxicity and associated side effects of carboplatin is significantly less than that of cisplatin, myelosuppression still exists, and cisplatin is not stable as an aqueous solution.
However, the processes disclosed in U.S. Pat. No. 6,699,901, which were tested by the inventors of the present invention, cannot produce satisfying results and are difficult to scale up for industrial-scale production.
The preparation of dicycloplatin according to the method of U.S. Pat. No. 6,699,901 produced a mixture of carboplatin and dicycloplatin, resulting in high toxicity and unacceptable products.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for the Preparation of Dicycloplatin
  • Process for the Preparation of Dicycloplatin
  • Process for the Preparation of Dicycloplatin

Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation Procedures for Dicycloplatin

[0066]1) Charged 5.0 g of carboplatin (13.47 mmol) and 2.232 g of 1,1-cyclobutane dicarboxylic acid (15.50 mmol) into a 20-mL glass vial.[0067]2) Added 12.5 mL of deionized water into the same vial and stirred the mixture at RT (room temperature) to form uniform suspension while keeping the vial away from light.[0068]3) Cooled the mixture to 5° C. at a rate of 0.33° C. / min and aged at 5° C. for 20 hours to form a precipitation cake.[0069]4) Vacuum filtered and washed the cake with 5 mL of deionized water, and then vacuum dried the wet cake.[0070]5) Collected the solids from the dried cake and measured the amount of dicycloplatin.[0071]6) 6.49 g dicycloplatin was obtained with an overall yield of 93.2%.

[0072]The product was analyzed by XRPD, DSC, TGA and 1H NMR.

[0073]1H NMR results: (400 MHz, DMSO-d6) δ 12.63 (s, 2H), 4.09 (s, 6H), 2.67 (t, J=7.9 Hz, 4H), 2.37 (t, J=8.0 Hz, 4H), 1.95-1.76 (m, 2H), 1.73-1.55 (m, 2H).

[0074]The XRPD data are liste...

example 2

Preparation Procedures for Dicycloplatin

[0075]1) Charged 1.0 g of carboplatin (2.69 mmol) and 776.4 mg of 1,1-cyclobutane dicarboxylic acid (5.39 mmol) into a 20-mL glass vial.[0076]2) Added 5 mL of deionized water into the same vial and stirred the suspension at RT for 6 hours while keeping the vial away from light to form a precipitation cake.[0077]3) Vacuum filtered and washed the cake with 2.8 mL of deionized water rapidly, and then vacuum dried the wet cake.[0078]4) Collected the solids from the dried cake and measured the amount of dicycloplatin.

[0079]The product was analyzed by XRPD, DSC, TGA and 1H NMR.

[0080]1H NMR results: (400 MHz, DMSO-d6) δ 12.65 (s, 2H), 4.09 (s, 6H), 2.67 (t, J=7.9 Hz, 4H), 2.37 (t, J=8.0 Hz, 4H), 1.92-1.77 (m, 2H), 1.72-1.57 (m, 2H).

[0081]The XRPD data are listed in Table 2.

TABLE 22-thetad-spacingintensity %7.611.7100.015.15.966.316.55.411.816.85.323.618.54.817.120.84.315.321.54.112.122.14.017.822.83.933.824.03.734.226.53.412.329.83.011.630.62.918.631...

example 3

Preparation Procedures for Dicycloplatin

[0082]1) Charged 5.0 g of carboplatin (13.47 mmol) and 2.523 g of 1,1-cyclobutane dicarboxylic acid (17.52 mmol) into a 100-mL glass vial.[0083]2) Added 25 mL of deionized water into the same vial and stirred the suspension at RT for 5 hours while keeping the vial away from light to form a precipitation cake.[0084]3) Vacuum filtered and washed the cake with 5 mL of deionized water rapidly, and then vacuum dried the wet cake.[0085]4) Collected the solids from the dried cake and measured the amount of dicycloplatin.[0086]5) 5.88 g of dicycloplatin was obtained with an overall yield of 84.2%.

[0087]The product was analyzed by XRPD, DSC, TGA and 1H NMR.

[0088]1H NMR results: (400 MHz, DMSO-d6) δ 12.63 (s, 2H), 4.09 (s, 6H), 2.67 (t, J=7.9 Hz, 4H), 2.37 (t, J=8.0 Hz, 4H), 1.90-1.80 (m, 2H), 1.70-1.59 (m, 2H).

[0089]The XRPD data are listed in Table 3.

TABLE 32-thetad-spacingintensity %7.511.8100.015.05.990.916.45.413.816.85.324.218.54.822.921.14.210.82...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molar ratioaaaaaaaaaa
reaction temperatureaaaaaaaaaa
reaction temperatureaaaaaaaaaa
Login to View More

Abstract

The present invention relates to a process to prepare dicycloplatin under mild reactive conditions and at fast reaction rates. The process is reproducible and easy to scale up for industrial application.

Description

FIELD OF THE INVENTION[0001]This invention relates to a new process for preparing an antitumor derivative of a double dicarboxylic acid diaminoplatin complex, named as dicycloplatin.BACKGROUND OF THE INVENTION[0002]Cisplatin has been used widely in clinical medicine as an antitumor drug since an antitumor effect was discovered for cis-dichlorodiaminoplatin. Rosenberg et al. Nature, 1965, 205: 698; Nature, 1972, 222: 385. Although a drug of this type exhibits therapeutic effects in cancers such as genitourinary cancer, nasopharyngeal cancer, cephalocircular cancer and lung cancer, it is toxic and leads to severe side effects. Some undesirable effects, such as nephrotoxicity, neurotoxicity, ototoxicity, nausea, and vomiting, are all constraints to its dosage and long term use. Carboplatin, one of the second-generation antitumor drugs of platin analogues, has an antitumor spectrum similar to that of cisplatin and is susceptible to cross drug-resistance. The therapeutic effect of carbop...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): C07F15/00
CPCC07B2200/13C07F15/0093A61K31/282
Inventor LIU, XIAOZHONGXI, JIRUIZHAO, YEZHANG, LIANG
Owner SYN NAT PROD ENTERPRISE LLC