1. Research on the Formula and Small-scale Test Process of CHA for Injection:

From 2001 to 2003, Sichuan Jiuzhang Biotech designed the process route and pharmaceutical parameters of the lyophilized powder for injection of CHA according to the physical and chemical properties and stability characteristics of the CHA as the active pharmaceutical ingredient. It also entrusted the West China School of Pharmacy, Sichuan University to complete the verification of the small-scale experiment. Principal responsible person: Zhang Liang, Li Xinquan. Person in charge of the trustee party: He Yingju. Main participants: Zeng Xiaoyu, Li Jianping, Lin Liyang. (Contract Name: Process Research of CHA-001 for Injection, Contract No.: JZ2003002-JS)

2. Research on the Pilot-scale Test Process of CHA for Injection:

From 2003 to the present, Sichuan Jiuzhang Biotech, based on the research results of the small-scale trial process of CHA for injection,  took the lead in formulating the pilot-scale research plan for the lyophilized powder injection of CHA for injection. It also entrusted Chengdu Tongde Pharmaceutical Co., Ltd. to complete the verification. Principal responsible person: Zhang Jie. Main participants: Zhang Liang, Huang Wang, Zhang Chao, Zhang Fei, Zhang Ya. (Contract Name: Contract for Commissioned Drug Processing)

3. Research on the Quality and Stability of CHA for Injection:

From 2003 to 2012, Sichuan Jiuzhang Biotech, based on the quality control indexes of CHA raw materials, its stability characteristics and the preparation process of CHA for injection, took the lead in constructing the quality control index system for CHA for injection. It also entrusted the West China School of Pharmacy, Sichuan University to complete the verification of the analytical methods and the inspection of the quality indexes. Principal responsible person: Zhang Jie. Main participants: Zhang Liang, Li Xinquan, Huang Wang. Person in charge of the trustee party: Xu Xiaoping. Main participants: Tian Chenxu, Liu Jing, He Wenwen, Liang Guilun, Su Dongfeng, Li Zukun. (Contract Name: Research on the Quality Standards of CHA-001 and Its Injection, Contract No.: JZ2004003-JS)

4. Research on the Pharmacokinetics of CHA for Injection:

From 2003 to 2006, Sichuan Jiuzhang Biotech, based on the pharmacodynamic test results of CHA, the proposed human dosage and administration route of CHA for injection, took the lead in constructing the pharmacokinetic research system of CHA for injection. It also entrusted the West China School of Pharmacy, Sichuan University to complete the pre-clinical pharmacokinetic tests. Principal responsible person: Zhang Jie. Main participant: Liao Juan. Person in charge of the trustee party: Xu Xiaoping. Main participants: Liu Jing, He Wenwen and Wu Xiaodong.(Contract Name: Research on the Animal Pharmacokinetics of CHA-001 for Injection, Contract No.: JZ2002001-JS)

5. Research on the Pharmacology of CHA for Injection:

In 2004, Sichuan Jiuzhang Biotech determined the general pharmacological research content and plan of CHA for injection according to the proposed indications, human dosage and administration route of CHA for injection. It also entrusted the West China School of Pharmacy, Sichuan University to conduct the general pharmacological tests. Principal responsible person: Zhang Jie. Main participant: Zhang Liang. Person in charge of the trustee party: Bao Xu. Main participants: Xiao Yu, Liu Boyang and Zhang Haiying. (Contract Name: Research on the Long-term Toxicity, General Pharmacology, Allergic Reaction, Hemolysis, Local Irritation and Teratogenicity, Carcinogenicity and Mutagenicity Tests of CHA-001 and Its Injection, Contract No.: JZ2003001-JS)

6. Research on the Toxicology of CHA for Injection:

From 2004 to 2005, Sichuan Jiuzhang Biotech took the lead in constructing the safety evaluation system of CHA for injection according to the safety characteristics of CHA as the active pharmaceutical ingredient, the proposed clinical indications, the intended dosage and the mode of administration of CHA for injection. It entrusted the West China School of Pharmacy of Sichuan University and the Institute of Laboratory Animals of Sichuan Academy of Medical Sciences to complete the verification of acute toxicity and long-term toxicity tests. Principal responsible person: Zhang Jie. Main participant: Liao Juan. Person in charge of the trustee party: Wang Hongxing. Main participants: He Yongliang, Yang Feng, Yu Xiaojun, Zhang Weilan and Yan Zhifeng. (Contract Name: Pre-clinical Trial Research of CHA-001 for Injection, Contract No.: JZ2005002-JS); Person in charge of the trustee party: Bao Xu. Main participants: Liu Boyang, Xiao Yu, Zhang Haiying, Zhou Cuiying, Zhong Zhendong and Ai Yingxian. (Contract Name: Research on the Acute Toxicity and Pharmacodynamics of CHA-001 and Its Injection, Contract No.: JZ2003003-JS)

In 2005, Sichuan Jiuzhang Biotech determined the research plan for the three types of toxicity (teratogenicity, carcinogenicity, and mutagenicity) of chlorogenic acid for injection according to the safety characteristics of chlorogenic acid for injection, the proposed clinical indications, the intended dosage and the mode of administration. It entrusted the West China School of Pharmacy, Sichuan University to complete the verification of reproductive toxicity and mutagenicity tests. Principal responsible person: Zhang Jie. Main participant: Liao Juan. Person in charge of the trustee party: Bao Xu and Hu Yuhua. Main participants: Meng Xianmin, Zhou Sha, Zhao Zhengzhong, Zhang Zunzhen, Li Hong and Ran Yun.  (Contract Name: Research on the Long-term Toxicity, General Pharmacology, Allergic Reaction, Hemolysis, Local Irritation and Teratogenicity, Carcinogenicity and Mutagenicity Tests of CHA-001 and Its Injection, Contract No.: JZ2003001-JS)

7. Pharmacodynamic Tests of CHA for Injection:

From 2004 to 2008, Sichuan Jiuzhang Biotech took the lead in constructing the animal pharmacodynamic evaluation system of CHA for injection according to the proposed clinical indications, the intended dosage and the mode of administration of CHA for injection, and entrusted the West China School of Pharmacy, Sichuan University to complete the verification of in-vivo pharmacodynamic experiments. Principal responsible person: Zhang Jie. Main participants: Yang Huarong, Zhang Liang and Liao Juan. Person in charge of the trustee party: Bao Xu. Main participants: Liu Jie, Qiu Guo and Wei Dapeng. (Contract Name: Research on the Acute Toxicity and Pharmacodynamics of CHA-001 and Its Injection, Contract No.: JZ2003003-JS)

In 2007, Sichuan Jiuzhang Biotech took the lead in constructing an in vitro molecular pharmacodynamic evaluation system for CHA for injection based on the proposed clinical indications, intended dosage, and mode of administration of CHA for injection. Principal responsible person: Zhang Jie. Main participant: Yang Huarong. Person in charge of the trustee party: Xu Xiaoping. Main participants: Wan Yi and Liu Jie. (Contract Name: Supplementary Agreement on the Research Test of In Vivo and In Vitro Antitumor Pharmacodynamics and Mechanism of CHA, Contract No.: JZ2007001-JS)

From 2011 to 2012, Sichuan Jiuzhang Biotech, based on the research results of the pharmacodynamics of CHA for injection both in vitro and in vivo, Sichuan Jiuzhang Biology further took the lead in constructing the pharmacodynamic evaluation system for the single use and combined use of CHA for injection, and entrusted the Institute of Materia Medica, Chinese Academy of Medical Sciences to complete the verification of the in vivo pharmacodynamic experiments. Principal responsible person: Zhang Jie. Main participant: Yang Huarong. Person in charge of the trustee party: Chen Xiaoguang. Main participants: Zhang Furong, Zhou Wanqi, Li Yan. (Contract Name: Research on the Antitumor Pharmacodynamics of CHA Used Alone and in Combination with Other Drugs, Contract No.: JZ2011005-JS)

8. Special Safety Tests of CHA for Injection:

In 2004, Sichuan Jiuzhang Biotech designed and completed the special safety test plan according to the proposed human dosage and administration mode of CHA for injection, and entrusted the West China School of Pharmacy, Sichuan University to conduct the hemolysis and local irritation tests. Principal responsible person: Zhang Jie. Main participant: Zhang Liang. Person in charge of the trustee party: Bao Xu. Main participants: Wei Li, Wang Xiaoqing, Song Pingping. (Contract Name: Research on the Long-term Toxicity, General Pharmacology, Allergic Reaction, Hemolysis, Local Irritation and Teratogenicity, Carcinogenicity and Mutagenicity Tests of CHA-001 and Its Injection, Contract No.: JZ2003001-JS)

From 2004 to 2009, Sichuan Jiuzhang Biotech took the lead in constructing the safety evaluation system for the sensitization of CHA for injection based on the preparation process characteristics of CHA as the active pharmaceutical ingredient and CHA for injection as the preparation. It entrusted the West China School of Pharmacy of Sichuan University and the Safety Evaluation Center of the Institute of Natural Medicine of Sichuan Province to complete the verification of the allergy tests. Principal responsible person: Zhang Jie. Main participants: Yang Huarong, Liao Juan. Person in charge of the trustee party: Bao Xu, Xu Xiaoping. Main participants: Wang Xiaoqing, Zhang Jie (female), Zhou Sha, Luo Fei.  (Contract Name: Research on the Long-term Toxicity, General Pharmacology, Allergic Reaction, Hemolysis, Local Irritation and Teratogenicity, Carcinogenicity and Mutagenicity Tests of CHA-001 and Its Injection, Contract No.: JZ2003001-JS; Research on the Allergic Test of CHA for Injection, Contract No.: JZ2009001-JS)

In 2012, Sichuan Jiuzhang Biotech took the lead in formulating the research plan for the sensitizing substances during the preparation process of chlorogenic acid, based on the preparation process of chlorogenic acid as the active pharmaceutical ingredient, the research results of sensitization safety and the findings of literature research. It entrusted the West China School of Pharmacy, Sichuan University to complete the verification of the research on the allergic substances. Principal responsible person: Zhang Jie. Main participant: Yang Huarong. Person in charge of the trustee party: Xu Xiaoping. Main participants: Ren Jie, Wang Jing. (Contract Name: Isolation and Identification of Allergenic Impurities in CHA Extracts, Contract No.: JZ2011004-JS)

9. Clinical Approval of CHA for Injection:

In 2013, Sichuan Jiuzhang Biotechnology Co., Ltd., the applicant, obtained the clinical trial approval for anti-tumor drugs from the NMPA (formerly CFDA) (Class 1 chemical drug, Approval No. for CHA for Injection: 2013L01855).

10. Research on the Mechanism of Action of CHA for Injection:

From 2013 to the present, the sponsor, Sichuan Jiuzhang Biology, took the lead in designing an in-depth research plan for the mechanism of action, such as the action targets of CHA for injection, based on the results of pre-clinical pharmacodynamic studies. It entrusted the Institute of Materia Medica, Chinese Academy of Medical Sciences to complete the relevant verification. Principal responsible person: Zhang Jie. Main participants: Yang Huarong, Zhu Lina, Liao Juan. Person in charge of the trustee party: Jiang Jiandong, Chen Xiaoguang, Zhang Jinlan. (Contract Name: Exploratory Research Cooperation Agreement on the Antitumor Mechanism of CHA, Contract No.: JZ2016026-JS)

11. Pharmaceutical Research on the Production Process and Quality Optimization of CHA for Injection:

From 2013 to the present, it has been independently completed by Sichuan Jiuzhang Biotech, effectively controlling the impurity level. Person in charge of the sponsor: Zhang Jie. Main participants: Huang Wang, Zhang Liang, Zhang Fei, Zhang Ya, Yan Yongjiang, Ning Ling.

12. Research on the Industrialization Transformation and Application of CHA for Injection:

From 2013 to the present, Jiuzhang Biotech, the holder, took the lead in constructing the research system for industrial transformation and entrusted Chengdu Tongde Pharmaceutical Co., Ltd. to conduct the verification. Person in charge of the entrusting party: Zhang Jie. Main participants: Zhang Liang, Huang Wang, Zhang Chao, Zhang Fei, Zhang Ya. (Contract Name: Entrusted Production of Clinical Injectables by Tongde Pharmaceutical Co., Ltd.)