Bu Hemeng,Xue Aoming,Zhang Fang

(School of Business Administration,Shenyang Pharmaceutical University,Shenyang 110016,China)

Abstract 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.

Keywords:TRIZ; new drug; biopharmaceutical; pharmaceutical technology; medical device

People usually face two types of problems:one has a known solution and the other has an unknown solution.Normally,the known solutions can be found by looking up books,technical literature,or relevant expert information.The other category is also called the invention problem.In response to the latter,a proven research method—TRIZ (Teoriya Resheniya Izobreatatelskikh Zadatch) theory was born.Since its formation in the late 1950s,TRIZ has played an increasingly important role in many scientific fields.Since the pharmaceutical industry is the thriving industry,continuous innovation and development are needed.However,after searching a large amount of literature,it is found that TRIZ is rarely used in the field of pharmacy.In this paper,the TRIZ theory is briefly analyzed,and then some methods of existing successful cases based on TRIZ theory are extended to the pharmaceutical field.This can help shorten the time for new drug innovation research and development,improve innovation performance and reduce the risks of research and development.

1 Brief introduction of TRIZ theory

In order to extend the innovative research theory of TRIZ to pharmaceutical field,we must understand TRIZ theory first.This article consults relevant literature and summarizes some content of TRIZ theory as follows.

1.1 Introduction of TRIZ theory

TRIZ is the Russian abbreviation of theory of inventive problem solving.It is a systematic approach to solve the problems of invention and innovation,which was proposed by Genrich S.Altshuller,an inventor and theorist of the former Soviet Union on the basis of researching more than 2.5 million patents[1]from 1946 to1985.And then the laws behind the invention and the solution of the problem were obtained[2].

TRIZ includes the following main system:8 major technological system evolution rules,IFR f inal ideal solution,40 invention principles,39 general parameters and conf lict matrix,physical contradiction and separation principle,substance-f ield analysis,76 standard solutions,ARIZ invention problem solving algorithms,scientific principles knowledge base,functional attribute analysis and resource analysis.

1.2 The ideas of TRIZ theory to solve problems

The following is the process of using TRIZ theory to solve problems.When a specific problem cannot be solved,f irst the problem should be analyzed and converted it into a TRIZ problem.Then a general solution can be obtained by using the concepts,methods,tools,and knowledge bases of TRIZ theory.The general solution indicates the direction of solving the problem.Finally,by adding constraints to the general solution,a specif ic solution to the problem can be gotten[2].

1.3 The advantages of using TRIZ theory

Genrich S.Altshuller once said:“You can wait for 100 years to obtain an epiphany,or you can use these principles to solve the problem in 15 minutes.” The traditional process of invention requires the inventor to brainstorm or repeat experiments indefinitely.Those correspond to “genius style” and“trial and error style” respectively.The brainstorming method is often affected by psychological inertia,resulting in subjective limitations.Meanwhile,the trial-and-error method will cause objective limitations due to the complexity of the problem and unpredictable number of attempts.TRIZ is a set of solution that is universally applicable to the same type of invention problems,focusing on the process of analyzing the problems (Fig.1).The data shows that when TRIZ is applied to product development and design,enterprises can improve the efficiency of product development by 60% to 70%,shorten the development cycle by 40% to 50%,and increase the number of patents by 70% to 80%[3].Just as “teaching people to fish is better than giving them the fish”,mastering the method of invention is more important than praising the inventor’s wisdom.

Fig.1 Comparison of TRIZ solution route and traditional method

2 Analysis of the status of TRIZ in the development and application of new drugs

In 2008,China set up a research group on innovative methods,and gradually increased the promotion and application of TRIZ theory in China[4].TRIZ is widely used in the field of machinery manufacturing design.In recent years,it has been used in crops fertilizer saving and pesticide reduction[5],chemical filters[6],as well as in biomedical engineering[7],chemical R&D[8]and other pharmaceutical-related fields.In addition to technology development and application,TRIZ is also applicable in hospital management[9]and pharmaceutical enterprise quality management[10].

From the literature and related scientific reports,it can be seen that TRIZ theory has rarely been applied in the scientific research and development of new drugs and even in the field of medical devices.The following is the analysis of possible reasons.(1) Drug production is subject to a variety of laws and regulations and has special characteristics.(2)Drug research and development has the features of “huge investment,high risk and long cycle with strong professionalism.Therefore,researchers are likely to form thinking patterns.(3) TRIZ requires that technicians have a certain understanding and application ability of basic physical principles.Therefore,how to more effectively solve the problems in the development of new drugs and reduce the risk of research and development has often become a problem for researchers.

3 Examples of applying TRIZ theory

TRIZ has the advantages of universality and efficiency.Problems encountered in different industries are solved by the same principle.The research on applications in the pharmaceutical field mainly focuses on the transformation and upgrading of related equipment in industrial production,such as the application of simulation modeling of excavation mechanism for deep-rooted Chinese medicinal materials[11].This article collects typical TRIZ cases in the biopharmaceutical field,and briefly describes the application in pharmaceutical preparations and medical devices to expand the thinking of TRIZ in the scientific research field of new drug development.Based on the above-mentioned TRIZ problem solving process,the thinking route of each example is analyzed.

3.1 Application of TRIZ in biopharmaceuticals

The development of new drugs is inseparable from the application of biotechnology.Discovering a mechanismin vivoand evaluating the non-clinical effects of new drugs are crucial links.This article introduces the improvements in PCR technology[12],actinomycete isolation[13],vaccine protection systems[14],and the applications in new biological fields.

3.1.1 Applying the principle of conflict matrix to solve PCR problems

PCR (polymerase chain reaction) is a molecular biology technique used to amplify specific DNA fragments.In order to solve the problem that multiple DNA samples cannot be used in the same thermal cycler during multi-index simulation CADMA analysis,the experiment uses conflict matrix to find the corresponding principles for improving and deteriorating common engineering parameters (that is,making some improvements at the cost of some undesired results,which is the contradiction is to be resolved) (Fig.2).Jiří Drábek’s technical progress in PCR technology shows that TRIZ can also play an important role in pharmacological research with relatively fixed processes and evaluation methods.

Fig.2 Analysis of conflict matrix principle

3.1.2 Improving actinomycete culture by TRIZ analysis

Actinomycetes are the main producers of antibiotics and are widely used in the biopharmaceutical industry.The main problems are the low culture efficiency of actinomycetes and the few isolates.Using the TRIZ system component analysis,causal analysis,and the standard solution of substance-field model,the scheme and the advantages are evaluated (Table 1).It is expected that the isolation efficiency of actinomycetes will be improved by more than 20%,which provides reference and ideas for the application of TRIZ theory in scientific experiments.

Table 1 Analysis of actinomycete culture scheme

3.1.3 Application of TRIZ to improve the performance of vaccine protection systems

The vaccine protection system is a protection device for aseptically transferring to the next operation process when the vaccine is not sealed.This system uses the substance-field analysis model to eliminate harmful effects and construct a complete substancefield model.It means an electrostatic field is added to the filter field to adsorb particles to eliminate pollution(Fig.3).

Fig.3 Substance-field analysis model

Conflict matrix 40 is queried to take the principles of composite materials as a conceptual solution.That is,the original homogeneous materials are replaced with composite materials (Fig.4).According to the law of system evolution,the system transits from expansion to simplification,which means simplifying the transition to the largest degree.Then increasing the motion track and the electrifying function of the guide rail and the universal wheel can solve the problem of the easy falling of unsealed vaccine bottles (Fig.5).

Fig.4 Schematic diagram of system problem solving based on the principle of composite materials

Fig.5 Schematic diagram of problem solving based on evolutionary path system

3.1.4 Applications of TRIZ in new biological fields

Successful transfer of ideas in the fields of biology and engineering design requires the application of abstractions and analogies,thus stimulating a biological model that improves the principles of TRIZ innovation.Mansoorian and Naini listed 40 biological models of TRIZ invention principles,combining TRIZ with biology[15].

For the treatment of cancer,the author applies the principle of TRIZ segmentation to the development of drugs for radiation source and locally acting particles.A new idea is proposed for the radiation therapy of tumors because the formation of cancer is an automatic catalytic process similar to nuclear fission.TRIZ biological combination system can be used for the treatment[16].Besides,since the long-term inhalation of new antibacterial nano-silver can cause liver damage,new ecological products based on TRIZ theory can be developed to achieve the purpose of minimizing the use of nano silver and maximizing the sterilization effect[17].

3.2 Application of TRIZ in pharmaceutical preparations

Drug release microcapsule technology uses microcapsules to release drugs that are unstable in the body directly to specific sites.Based on the TRIZ conflict matrix 28 (2),instead of mechanical system,the electric,magnetic and electromagnetic fields are used to complete the interaction with the objects.Replacing the driving force of the motor with direct electromagnetic force can solve the problem of large capsule volume and low reliability problem[18].

In the process of researching and improving the efficiency of separating granules,combined with multiple principles of TRIZ (Table 2),a highly efficient granule separator was designed[19].

Table 2 Design principle of pellet separator

3.3 Application of TRIZ in medical devices

As a powerful method in the design of mechanical products,TRIZ has been applied in the design process of medical devices,and has become a research hotspot in medical device design and innovative methodologies in recent years.

3.3.1 Innovative design and development of prehospital infusion pump with TRIZ

Based on the analysis of the quality house of TRIZ theory,five pairs of major technical characteristics conflicts (including one physical conflict and four technical conflicts) in the innovative design of the pre-hospital emergency infusion pump are identified.Based on the 39 general engineering parameters of TRIZ,the conflicts among five pairs of technical characteristics are converted into five pairs of TRIZ standard problems.Using the conflict matrix and separation principles,that is,the periodic action of TRIZ invention principle No.19 can solve the core technical bottleneck of the maximum rate of the infusion pump between volume and weight[20].

3.3.2 Improving infusion bag system by TRIZ

The functional model of the innovation engine is applied to analyze the function of the infusion technology system.According to TRIZ’s typical trimming principle C,when other carriers are running effectively,this carrier can be trimmed.It means a spring can be introduced between the infusion bag and the hook.The spring is used to connect the infusion bag and the alarm contact.As the medicine in the infusion bag becomes less and less,the length of the spring becomes shorter.There is a point that brings the two together.At this time,an alarm function is performed to remind the caregiver to change the infusion bag[21].

4 Conclusions

TRIZ has successfully revealed the inherent laws and principles of innovative inventions.It is based on the study of the entire design and development process to obtain the laws of technological development and evolution.After this,inventions are no longer random behaviors.Practice has proved that the use of TRIZ can speed up the process of people’s invention and obtain high-quality innovative products.Researchers should summarize the thinking and methods in their field and share such knowledge.

Innovative method is a forward-looking,basic,and non-profit scientific and technological capacitybuilding work,which requires strong support from the national finance.In developed countries,a certain percentage of public funding is dedicated to supporting research on scientific methods and instruments.Therefore,our government should also increase such investment to ensure that good ideas and methods in various fields are tapped and developed.

It is expected that this research can promote the popularization and application of TRIZ in the research and development of new drugs.In this way,TRIZ innovation theory will be accepted by more and more researchers to accelerate the technological progress of the industry.In addition,the application and promotion of TRIZ in the field of new drug research and development will push this discipline to a new height and enrich the application of TRIZ.With the widespread application of TRIZ theory in the research and development of new drugs,the pharmaceutical industry will definitely accelerate the pace of innovation.