The application for listing of the sustained release tablets of silymarin group is proposed to be included in the priority review

Wen Jie DOPINE According to the CDE website, on January 19, the listing application of the sustained-release tablets of Paris piperone of Petrochemicals Group was proposed to be included in the priority review varieties Shiyao group is the second company to apply for the listing of 4 generic drugs of piperone sustained-release tablets and sustained-release tablets Pariprasidone, also known as paparenone and 9-hydroxyrisperidone, is the active metabolite of risperidone in the liver and a derivative of benzoisoxazole As a new atypical antipsychotic drug, the mechanism of action of pariprasidone is not clear It is generally believed that it is mediated by the combined action of antagonism to dopamine 2 (D2) receptor and 5-hydroxytryptamine 2 (5HT2A) receptor in the central nervous system In addition, it is also an antagonist of α 1 and α 2 adrenergic receptor and H1 histamine receptor Palipexone sustained-release tablets were originally developed as Johnson & Johnson, the second generation of antipsychotic drugs They were first approved by the FDA in December 2006, and then approved by nmpa in 2008 for the treatment of adult schizophrenia The trade name is Rida, and then approved by nmpa in 2017 for the treatment of adolescents (12-17 years old, weight ≥ 29 kg) with schizophrenia It is worth mentioning that Rida is the first drug approved for use in adolescent patients through this process since the release of CDE "technical guidelines for extrapolation of adult drug use data in pediatric clinical trials and the use of relevant information" Up to now, pariprasidone has been listed in more than 100 countries in the world for the treatment of schizophrenia, and has been approved for the treatment of adolescent schizophrenia in more than 50 countries and regions In fact, palipexone can be said to be obtained from the transformation and upgrading of risperidone Risperidone is also developed by Johnson & Johnson The oral tablet was approved for marketing in the United States in December 1993, and its trade name is risperidal However, due to the poor compliance of tablets (according to statistics, 30% of patients feel that tablets and capsules are difficult to swallow or swallow, especially the elderly and children), Johnson launched risperidone oral liquid in 1996, followed by Risperdal in 2003 Consta, once a week), in which orally disintegrating tablets are introduced based on their ability to improve compliance in patients with treatment resistance (e.g., vomiting) or oral dysphagia During the development of risperidone, it was found that 9-hydroxyrisperidone, the metabolite of risperidone, also has certain pharmacological activity Johnson started the development of 9-hydroxyrisperidone Finally, in December 2006, it launched the sustained-release tablet of palipexone in the United States, which was used for the treatment of acute schizophrenia The sustained-release tablet uses OROS technology and consists of three layers (see the figure below for detailed structure) However, Johnson & Johnson did not stop the upgrading and transformation of palipexone, and cooperated with EDT company to develop palipexone palmitate injection by using nano crystal technology In 2009, the monthly invega sustenn was launched in the United States, and in 2015, the monthly invega trinza was launched in the United States The upgrading and transformation of risperidone and palipexone by Johnson & Johnson can be regarded as a model in the pharmaceutical industry, which also brings huge profits See the figure below for details (the data is based on the financial statements of Johnson & Johnson in recent years, and the annual sales of palipexone sustained-release tablets in 2017 and 2018 are not found) At present, only the original developed sustained-release tablets and injections have been approved for listing in China However, according to insight database, seven enterprises have begun to lay out the field (see the table below), among which Jiangsu Haosen and Shiyao group have put forward the listing application of sustained-release tablets, and the other five have been approved for clinical use Although Haosen of Jiangsu Province is earlier than the production of petrochemicals, if petrochemicals are included in the priority review in the future, it is not clear who will take the first imitation of palipexone sustained-release tablets in the future reference material: [1] J & J's financial report in recent years