Jack He MD, MSc, RAc
Canadian Integrative Cancer Therapies Association
Why human beings are losers in fighting against cancer? Why the current anticancer drugs have little therapeutic effect? We believe that the main reason could be related to several factors, such as the genetic instability and non-homogeneity of tumor cells, namely the heterogeneity of cancer cells, the multi-drug resistance of cancer cells and imperfect concept of the current rational anticancer drug design etc. Because the design of current anticancer drugs is all based on tumor cell’s certain biological characteristics, so only a part of the identical cancer cells can be killed, but other cancer cells are insensitive. Furthermore, considering the multidrug resistance of tumor cells, it can be imagined that the effect of chemotherapeutics is limited and clinically unsatisfactory. The defect of the current anticancer drugs design based on single mechanism; single target has fully revealed through the clinical-proven evidence. In the R & D process of novel anticancer botanical drug, CARESENG line of products adopted the compounding strategies and herbal formulation from the basic principles of Traditional Chinese Medicine in combination with the principle of modern evidence-based medicine. As a result, this novel anticancer drug with multiple mechanisms, multi-targets, omni-directional-attack tumor cells properties has been developed.
CARESENG line of anticancer preparations is a complex mixture derived from a group of Dammarane Sapogenins, including principle ingredients PAM200 and PBM300. The PAM200 is a fast inducer of specific-tumor cells apoptosis (eliminating the pathogenic factor effect), which can activate multiple caspases pathways to induce apoptosis in cancer cells, inhibit Akt phosphorylation, which in turn inhibits the survival pathways in cancer cells, increase free radical’s superoxide anion within cancer cells leading to apoptosis. Meanwhile, the PBM300 is a potent antitumor immunostimulating agent (strengthening the body resistance effect), which can enhance dendritic cells activation and differentiation as well as NK cells proliferation. It also can induce interferon release to kill the tumor cells. Therefore, the design of CARESENG line of anticancer products complies with both the TCM treatment principles of “Strengthening the body resistance and eliminating the pathogenic factors” and the latest trends of contemporary strategies for cancer therapy.
1. Modernization of TCM: inspiration of CARESENG line of anticancer products R & D
Dr. William Jia, a tenure professor at the University of British Columbia, is one of the inventors of CARESENG line of anticancer products. Based on his over 10 years studies on anticancer activities of the Dammarane Sapogenins derived from Chinese herbal medicine and collaboration with other scientists in the R & D process of CARESENG, he profoundly realized that the modernization of TCM is not simply to be modern drug dosage forms for Chinese patent medicine, and not to be highly purified drugs either. The globalization of TCM absolutely does not mean its “Westernization”. He is eventually attempting to explore a new approach for modernization of TCM, which is a fully integration of the TCM fundamentals with the modern new drug discovery and development protocols. In terms of the concepts of modern medical science, the fundamentals and philosophy of TCM treatment are about to apply multi-components, multi-systems, multi-levels, and multi-targets as well as multi-mechanisms for achieving desired therapeutic outcomes. Therefore, the well-established TCM formulations and logical combination rationale have become the essence and mainstream in healing paradigm of TCM. To date, the TCM healing paradigm has not been well-recognized by the prevailing biomedical mainstream though, there is no doubt that recently much more attention has been paid in TCM. It is well known that the conventional new drug research and development is focusing on screening molecules of lead-like and drug-like properties, especially more specific drug targets exclusive for therapeutics. However, how to employ the holistic and systemic healing logic and well-established formulations rationale to today’s Chinese herbal medicine development and modernization still faces challenges that will need to be resolved. The reason is that the TCM including Chinese patent medicines have many inherent problems, for example its complex nature, the active constituent in a herb is not identified, nor is its biological activity well characterized and chemical constituents is not of consistency and can not be more readily chemically quantified; standard pharmacokinetic measurements to monitor the absorption, distribution, metabolism of active constituent in a botanical drug may be technically infeasible, and so on. The TCM globalization was greatly hampered by these existed matter issues and modernization of TCM faces challenges and concerned issues.
According to the above understanding, Dr. William Jia boldly proposed the new concept of the drug design, Selective Multi-compound Drug (SMD), and is willing to provide a new approach and idea for the current modernization of TCM. This concept, which is a fully integration of well-established TCM formulations and combination rationale logic and healing paradigm of multi-targets and multi-mechanisms modulation with the modern pharmaceutical standards and evidence-based medicine’s principles, was emphasized on the rational, potent, and optimized combination of selective compounds available on the basis of scientific evidence, other than randomly mixed many unidentified chemical components of TCM, that is to say, it must conform to international accepted quality standards in respect of “Safety, Efficacy, Quality, Consistency” of the medicine. This proposed concept is the high-level integration and sublimation of TCM and modern medicine and is considered to be sublation- “developing the good and discarding the bad”. The definition of SMD is a compounding drug with therapeutic properties for specific disease, which is composed of several identified compounds with well-characterized pharmacological activities. The rationale is firstly, currently the TCM formulations are paid more attention in Chinese new drug research and development. The interest emphasizes on relative amount of all herb compositions in the multi-herb formulation and previous clinical-proven efficacy, other than quantities of active constituent in the formulation. Utilizing rationale of combination of all herb compositions to enhance efficacy and reduce toxicity, namely through the compatibility effects of herbs “mutual enhancement (xiang xu) and mutual assistance (xiang shi)” leading to enhance efficacy, and the “mutual counteraction (xiang wei) and mutual suppression (xiang sha)” leading to reduce its toxicity. Therefore, according to the medical indications, the SMD proposed that selective potent combination of a few of medicinal ingredients with established pharmacological actions may be present and use their multi-targets and multiple mechanisms to enhance the therapeutic effects synergistically. The extensive studies have revealed that CARESENG line of anticancer compounding products were superior to individual active constituents in the treatment for cancer, which is the best example. And in order to meet different demands in the drug market, the different new products can be developed by modifying the relative proportion of individual active constituents. Secondly, SMD requires that the active ingredients of the compounding drug must chemically identified and quantified, as well as the manufacturing process should be well defined, with adequate in-process controls to ensure the finished product is of consistently good quality. Globalization of TCM requests compliance with current pharmaceutical practices and international harmonization of requirements to achieve the modernization of TCM with sufficient scientific evidence to interpret the reason why TCM can cure the diseases. This is the only way that TCM can be recognized by the mainstream in the international medical society. Thirdly, SMD requires that the principle active ingredients may be possible to perform standard pharmacokinetic studies by monitoring absorption, distribution and metabolism of active ingredients that should be fully understood. Moreover, using modern scientific methodologies, the mutual relationship between the active ingredients and the drug targets as well as the interrelationship between all individual medicinal ingredients should be investigated, and make SMD truly become “safety, efficacy, quality and consistency”. Fourthly, “clinical-proven effectiveness is the solid ground for drugs”, SMD proposed that in the process of developing Chinese new drugs, we should completely change the phenomenon of emphasizing basic research and ignoring clinical research during the development and the drug evaluation process and consider the TCM clinical research to be a central stage on the development of new drugs. Fifthly, “No patent, No drug development”. TCM is one of the most intellectual property treasures to the Chinese nation, but the fact is that the sales of herbal medicine share only about 5% of the international market makes us feel embarrassing indeed. The lessons of Qinghaosu (Artemisinin) and Yin Xing Ling (Ginkgo GBE50) we have learned should be kept in mind, and patent applications of TCM and related products should facilitate to protect the intellectual property rights of the Chinese medicine. CARESENG line of anticancer products are based on several patents and developed under the strict protection of intellectual property rights. It’s the only way, Chinese herbal medicine can go out of “the China Town” toward internationalization.
2. Modernization of TCM: concern issues and consideration of the succeeded CARESENG line of anticancer products commercialization
The pharmaceutical industry is a vital, promising, and prospective high-tech-intensive industry, and it has been recognized the internationalized industry and is one of the most rapidly developing industries today. “Harvard Business Review” in 2003 had predicted that the modernization of Chinese herbal medicine will be the most important one of the four major industries in the next 20 years. According to the United Nations Organization’s statistics, the global herbal medicine market is estimated up to 60 billion U.S. dollars annually, which will occupy about 20% of the global drug market. In the 21st century, the “Back to Nature” trend of the world in the development of the life sciences leads to breakthrough of TCM and it is possible to become one of the new major contributions which the Chinese nation given to the whole humanity. However, China only occupies 5% shares in such a large and fast growth international herbal market, which does not match its several thousand year’s history in the application of herbal medicine. There are very rich and abundant resources of medicinal herbs in China, and the export of TCM is mainly based on the botanical raw materials resources for many years. Foreigners make full use of these relatively cheap medicinal resources to produce high value-added herbal products, and then go back to occupy the international drug market including China to obtain the high profits. However, China has the most to loss in ecology and environment and the least to gain in economic return. What is most concerned issue, TCM was adopted in east Asia neighbor countries Japan and Korea in ancient time, thereby setting up the foundation of Kampo and Korean Medicine. Japan and Korea import raw herbal materials from China and export finished products “Kampo medicine” and “Korean medicine” to occupy about 90% of the entire international drug market including China. In recent years, many European and US companies also joined the “Gold Rush” herbal industries. As a result of the absolute superiority of US and European pharmaceutical companies, such as funds, technologies, packaging, marketing and so on, they not only occupy the international market, but also straightly aim to China, a country with a long history of using Chinese herbal medicine. Therefore, the modernization of TCM faces enormous challenges and historic opportunities.
We believe that the modernization of TCM calls for the modernization of ideas and concepts in advance. The research of TCM should emancipate the mind and insist on the principle of “letting a hundred flowers blossom and a hundred schools contend”. Efficacy-driven approach is the solid ground and golden standard for drugs. We should abandon the superficial model of the modernization of TCM and reach a consensus that the efficacy-driven approach is the unique standard to assess the successful or unsuccessful of the modernization of TCM. No matter what the model of the chemical drug or the botanical drug adopted, the approach may not be directly associated with development of TCM theory, nevertheless it has advanced technology to ensure quality, consistency and efficacy with a market competitiveness and becomes a successful model for the Traditional Medicine and modern pharmaceutical globalization. In some sense, it represents the developmental direction of medicinal productive forces and eventually promotes to develop the entire enterprise of TCM. Therefore, regarding to choose the model to achieve the modernization of TCM, we should not only “make old things serve today”, but also “make foreign things serve China”, as well as absorb the mode of the developmental of the chemical drugs and the botanical drugs, “adopt superiority and avoid weakness”. It’s the only way we can truly achieve the modernization of TCM and possess appropriate market share in the stringent international market as a great country with abundant medicinal herb resources.
To achieve the modernization of TCM, we should begin from two aspects, namely, to achieve a modern scientific TCM and promote the internationalization and industrialization of TCM. On the one hand, we should be committed to great funding for scientific research, collaboration of expertise and task forces to resolve hot issues and challenges on the research of TCM and break through the bottlenecks restricting the development of the modernization of TCM, as well as establish the common technical platforms including the extraction, isolation, and analysis of Chinese herbal medicine. On the other hand, we ought to increase commercialization for herbal industries. The industrialization of TCM must insist on a high starting point and comply with the current national standards and regulations in every aspect of the research, development, manufacture, operation, application, and management of TCM. If comparing the modernization of TCM to two-wheel cart, the scientific research and the industrial development are independent two wheels of the cart, while the operator is the market. The competitive market is stringent and crucial. As long as following the marketing rules, the modernization of TCM will come true.
The development process of CARESENG line of anticancer product has fully employed and adopted the well-established TCM formulations and logical combination rationale, and ingeniously applied the development model of the botanical drug and the chemical drug. The products are not only complied with the pharmaceutical standards of modern drug, but also follow the TCM formulations strategies. CARESENG line of anticancer products derived from the Chinese medicinal herb, and it is also superior to the general standard of Chinese patent medicine in many aspects. We believe that the successful research and development of CARESENG line of anticancer products will not only bring about the meaningful inspiration for the modernization of TCM, but also provide the gospel for the majority of cancer patients.