The brain-derived neurotrophic factor in neuronal plasticity and neuroregeneration: new pharmacological concepts for old and new drugs

Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.

New drugs for the treatment of metastatic colorectal cancer

Colorectal cancer(CRC)represents one of the most frequent malignancies in terms of incidence and mortality,thus representing the third leading cause of cancer death worldwide.In the last decade,few drugs have enriched the treatment landscape of metastatic CRC and have significantly affected prognosis.Unlike other neoplasms,metastatic CRC patients who have exhausted treatment options often still maintain a good performance status.There are many challenges to increasing potential treatment options,notably a better understanding of disease biology and the mechanisms of resistance underlying cancer treatment failure.The development of new drugs for metastatic CRC certainly represents one of the most important challenges in medical oncology.This article discusses the main limitations in the development of new drugs and potential future scenarios.In particular,we addressed three questions:(1)The main limitations of targeted therapy in the treatment of metastatic CRC(mCRC);(2)New target armamentarium that could escape primary and secondary resistance and lead to more personalized mCRC therapy;and(3)Future directions.

PREDICTION OF THE THERAPEUTIC EFFECTIVENESS OF NEW DRUGS FROM CLINICAL PHARMACOLOGY STUDIES

The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-

Literature Review on the Development of New Drugs Based on TRIZ

Objective To promote the application of TRIZ theory in the new drug R&D and the innovative development of medical devices.Methods TRIZ can be literally translated as“theory of inventive problem resolving”,focusing on clarifying and solving contradictions in the system.This article introduces the TRIZ theory and the general process of new drug development.It collects literature in the field of new drug development and medical devices and refers to ideas for solving problems in some successful cases of applying TRIZ theory in other fields.Results and Conclusion After summarizing the general ideas of TRIZ to solve the problems,it is concluded that attention should be paid to applying TRIZ theory in the development of new drug and medical devices.

Regulatory evaluation of efficacy and safety of new drugs in China

Accessibility, availability, and rational use of medicines are widely recognized priorities for guaranteeing equity in health care. Commercial pressure can twist health policy if pharmaceutical companies are allowed to promote and impose their products beyond clear public-health interest. National regulatory

Developing new drugs from annals of Chinese medicine

Developing new pharmaceuticals requires massive amounts of time,money and efforts.The key step is how to find a safe and effective entity for a disease condition and how to develop it as new drug effectively.Unfortunately,the FDA’s rate of approving new entities has declined dramatically in the last three decades.There is a strong need to review the current strategy and to optimize process in developing new drugs,both to shorten the process and increase the success rate.Chinese medicine has used natural products to treat patients for thousands of years,and Chinese medicine practitioners have chronicled the patients and treatment methods for thousands of years.There is much information that has not yet been used.The success stories of artimisinin and arsentic trioxide are wonderful examples of how the annals of Chinese medicine can provide leads for discovering new drugs.This paper argues that the annals of Chinese medicine are valuable and describes how they can be used in modern drug discovery.The major topics addressed are:(i)why Chinese medicine is a rich resource for finding new drugs;(ii)how to identify a potential valuable record from Chinese medicine annals;(iii)when a potential valuable record is identified from annals,how to proceed;and(iv)both why and how the approach used for chemical drugs should be revised for drugs based on the historical documents related to herbal medicine.In conclusion,we argue here that the annals of Chinese medicine offer not only a rich resource for new drugs,but also several centuries of patient data with regard to safety and efficacy,that in effect represent pilot studies.Acknowledging and using these data can shorten new drug discovery time and improve efficiency of the drug development process,bringing more effective,safe drugs to market much more quickly and cheaply.

Opinion on pharmacology research and new drug development from precision medicine

Since President Obama announced the Precision Medicine Initiative from a national strategy perspective in his State of the Union address,precision medicine has rapidly become a world-wide hotspot and drawn global attention in the medical field.Precision medicine aims at applying genetic information of individual diseases to guide his or her diagnosis and treatment.

Real-World Evidence Supporting New Drug Review and Approval in European Union and Its Enlightenment to China

Objective To analyze the application of real-world evidence(RWE)in the field of medicine in European Union,and provide suggestions for RWE supporting the review and approval of new drugs in China.Methods The European Medicines Agency(EMA)and other databases were used to search relevant documents for analyzing the European Union’s new drug review and approval process with the support of RWE.Results and Conclusion The European Union carrying out new drug review and approval with the support of RWE has just begun.The decision-making process includes three stages such as new drug research and development,review,and approval.However,there are some challenges in data quality,research methods,evidence sufficiency,and research process of RWE supporting the European Union in reviewing and approving new drugs.At present,RWE can accurately grasp the clinical effects of drugs and improve the safety and effectiveness in the process of assisting the review and approval of new drugs.At the same time,RWE also can promote the development and application of Traditional Chinese Medicine(TCM)and help find out the potential value of TCM such as new indications.

Application Research of Earned Value Management in New Drug Research and Development Projects

Objective To help investors assess and control the costs of new drug development and reduce the risks of new drug development projects.Methods Cost analysis and financial forecasting were carried out with the integrated approach of earned value management.According to the principle of earned value management deviation analysis,the basic process of the new drug research and development project was combined with the hypothesis method from the research of Tufts Drug Development Research Center.Results and Conclusion If the project progress check was carried out in the clinical trial,the project costs were found overspent,the efficiency was low,the project progress was faster,and the resource investment was ahead.It is recommended that the adjustment should be made to reduce the input of resources,and increase the efficient key personnel to take the place of some less efficient staff.

The CAS System of New Drug Research and Its Key Results

The Chinese Academy of Science (CAS), the top national research hub for natural sciences, has always been committed itself to the national target of research and development (R&D) of new medicines. During the past several decades, a great number of R&D achievements have been attained. During the period from 1986 to 1999, for example, 135 pharmacutical projects won prizes of the CAS awards for natural sciences, inventions and S&T progress (roughly ac-

A New Anticancer Drug

After some six years of hard work, a research team headed by Prof. Liu Zhivu (Z.Y. Liu) at the Shanghai Institute of Organic Chemistry, CAS, has scored major progress in independently generating a novel cancer killer called epothilone. Their findings have been granted three patents, and their research paper Total Synthesis of Epothilone: A Thorough Stereospecific Expoxidation of the 3-0-(4-methoxy) Benzyl Ether of Epothilone C has been accepted for publication in the Chemistry - European Journal.

Current stage in inflammatory bowel disease: What is next?

In recent years,the incidence of inflammatory bowel disease(IBD) has been on the rise,extending to countries where it was infrequent in the past. As a result,the gap between high and low incidence countries is decreasing. The disease,therefore,has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently,new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD.

Innovative immunosuppression in kidney transplantation:A challenge for unmet needs

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries,new innovative drugs in kidney transplantation are difficult to be encountered.The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market.These unmet needs are the prevention of delayed graft function(DGF),the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection.These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts.The first are particularly exposed to DGF,the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur.Particular caution is needed in treating these drugs.First,they are described in very recent studies and the follow-up of their effect is of course rather short.Second,some of these drugs are still in an early phase of study,even if in well-conducted randomized controlled trials.Particular caution and a careful check need to be used in trials launched 2 or 3 years ago.Indeed,is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.

Progress in approved drugs from natural product resources

Natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impactson the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs orindirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United States,and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, centralnervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

Physical-Chemical Aggressiveness of Solutions of Medicines as a Factor in the Rheology of the Blood inside Veins and Catheters

In experiments in vitro and observations in the clinic in vivo studied the state of the lumen of subcutaneous veins and blood rheology of patients after their interaction with vascular catheters and solutions of medicines based on the values of temperature, volume, concentration, osmotic activity and pH. It is shown that heparin injection in blood not prevent, but solution of 4% sodium bicarbonate injection prevents blood clotting, blood clots and blockage blood clots of veins and of catheters. It is shown that the heating to a temperature of＋42 ℃ with the solution of 4% sodium bicarbonate provides softening action on old dry blood clots in 1 min, and their subsequent irrigation with a warm solution of 4% sodium bicarbonate and 3% hydrogen peroxide provides complete destruction and discoloration of the remaining spots of blood during 2 s. Proposed new medicines and hygiene products for the protection of the veins and installed in them vascular catheters from blockage of blood clots, and for removing blood stains from clothes and body surface patients.

Clinical Trial Participant Willingness and Influencing Factors Study of Patients with Inflammatory Bowel Disease

Objective: The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the clinical trial participation of patients with IBD. A clinical experiment guidance will be proved by this study to maximized the benefits to patients and to help the clinical trial to conduct successfully. Method: An anonymous questionnaire was designed and was administrated to the patients with IBD who were randomly delivered in the inpatient or outpatient departments. The survey result was analyzed. Result: Total 372 available questionnaires were returned. Among these patients, 26.3% patients with IBD indicated willingness to participate, 57.3% indicated a situation dependence, and 41.04% indicated unwillingness. Among the potential factors that may influence the patient’s willingness to participate the clinical, trusted physician’s recommendation, no proved drugs to use and accessing to free medication to release financial burden were statistically significant. Conclusion: The overall willingness of IBD patients to participate in drug clinical trials is not high. Among the patients who are willing to participate in clinical trials, the main reasons for their participation are that they trust doctors’ recommendation, can get free medication and examination, and can reduce the economic burden. Efficacy and safety were the main influencing factors in patients who were case-dependent and unwilling to participate in clinical trials.

A follow-up study on newer anti-epileptic drugs as add-on and monotherapy for partial epilepsy in China

Background Recently,new anti-epileptic drugs （AEDs） have been more frequently selected to treat epilepsy.In the present study,we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.Methods Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine （OXC）,lamotrigine （LTG） or topiramate （TPM） therapy.Each group included monotherapy and add-on therapy subgroups.We followed all patients for one year and recorded the indexes of efficacy and safety in detail.Results A total of 909 patients finished the follow-up observation.No significant difference was found in proportion of patients with 〉 or =50% reduction,〉 or =75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months.In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with 〉 or =50% reduction （P=-0.002）,〉 or =75% reduction （P 〈0.0001） and 100% seizure reduction （P=0.009） in the monotherapy subgroup,and about 〉 or =75% reduction and 100% seizure reduction in the add-on therapy subgroup （P 〈0.0001）.The efficacy between the add-on and monotherapy subgroups showed a statistical difference.The safety of the three newer AEDs was good.Conclusions The three newer AEDs all showed good efficacy and tolerability for partial epilepsy.And the efficacy can be maintained for at least one year.

~PEKING UNIVERSITY

Type of Company： Government institution. New Preparartions and Late-Model Drug Delivery System Technical Plaform of Peking University School of Pharmaceutical Sciences is a national technical plaform for developing new and important drugs. The person in charge for the platform is a pharmaceutical science professor of Peking University School of Pharmaceutical Sciences. The plaform selects the following as the main research areas： late-model carrier drug delivery system, biotechnological drug delivery system, mucous and transdermal drug delivery system, oral controlled-release drug delivery system, and four corresponding research teams are set up to study in depth the main problems and key issues.

INTRODUCTION OF THE HIGH THROUGHPUT SCREENING SYSTEM

In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.