Abstract

Objective: This article is intended to demonstrate the development of new Chinese drugs. Methods: To explore the shortcuts in developing new drug in terms of traditional Chinese medicine through retrospective reviews. Result: Shortcuts have been found within eight studies. Conclusion: Re-development of traditional Chinese medicine is the shortcut for effectively developing new drug.

Drug is very important in guaranteeing the health of human being, so the development of new drug is the hot spot frequently discussed. The profit from a new drug is compromised by high risk. To exploit a chemical drug needs eight or ten years costing about 0.3-- 1 billion USD. Therefore it is very urgent to look for such a way as more success rate, less investment and time saving to develop new drug.

TCM has made a great contribution to Chinese people for thousands of years and received a welcome by our neighbors. But TCM has not been popularly accepted by Countries yet because of the historical reason and the differences of medical culture between Countries. Any way, TCM is the only one that possesses perfect theoretical system among the four mainstreams of traditional medicine all over the world, together with its abundant and strong foundation of clinical practices for thousands of years. So we believe that new TCM drug must be come out in the way of less investment in a timely manner based on the principle that TCM development combines with modern scientific technologies.

A. To develop new TCM drug starting with individual medicinal material

China is rich in natural herbal resources due to a vast territory, complex geographies and climate conditions. According to the investigation in 1990, there are 12,807 kinds of Chinese medicinal materials in total. 12,694 kinds therein have been included into “Chinese Medicinal Resources Compendium” among which, 11,020 kinds are medicinal plants in 2313 genus in 383 families, 1590 medicinal animals in 879 genus in 414 families and 84 medicinal minerals. Another great work called “ Chinese Materia Medica” collects more than 8980 varieties of materia medica with the references citation of more than 10,000 literatures both modern and ancient. This great work in 22 million’s letters was published in the latest of 1999, collected all the valuable herbs from the ancient time to nowadays, written by more than 500 specialists in ten years. By reference of the traditional species, we select and sort out the materials as follows in this great work: a. Good quality homogeneous herbs such as the local caladiums in Anhui and Hubei province of China we found out in support of developing class I new traditional medicine; b. Newly medicinal plant parts such as extract ginsenoside from the stem or leaf of ginseng to produce them into class II new traditional medicine; c. Active ingredients such as extracting arteannuin from southernwood to come out the newly anti-malaria medicine in the forms of high efficacy, quick result and less toxicity etc. and that have aroused a great respect by the world medicinal field. Moreover, a series of the southernwood product has been developed at the basis of the structural reconstruction of arteannuin such as southernwood methyl ether, southernwood aether, artesunate, arteannuin succinate, dihydroarteannuin etc. and all these demonstrate the huge potential in developing new Chinese medicine; d. Artificial product (artifact). In consideration of scarcity of resource, the modern scientific technological methods such as bioengineering and chemical synthesis should be fully employed into developing class I new traditional medicine. For examples, use artificial fermentation technology to develop out artificial aweto in place of natural one; Use the culture technology of armillaria mellea to produce artificial gastrodia elata instead of natural one; Use artificial implantation technology to get bezoar and Use the technology of chemical synthesis to produce artificial muskiness and so on.

B. Optimize from old and proved recipes to develop new traditional medicine

TCM has a long history with more than 10,000 categories of books both ancient and modern preserved. The prescriptions recorded are countless such as “The peaceful Holy Benevolent Prescriptions” published in Song dynasty, collecting 16,834 formulas; “Prescriptions for Universal Relief” in Ming dynasty, collecting 61779 formulas; A series of the book called “China Folk Simple Recipe ” edited by China Medicinal Material Company selects and includes more than 20,000 contemporary folk recipes. We give the several examples here to show what a huge content they have! For instance, The decoction of Ephedra, cassia twig, Chinese thorowax, root of kudzuvine, Chengqi and resuscitation etc. has been used for about 2000 years not only in China but also in Japan, Korea and our other neighbors. The most of current Chinese patent medicines are from the ancient and proved prescription having a great potential for developing new medicines. As far as we know, it needs to take three years, costing three million pounds to develop out a new patent herbal medicine in England. However, its profit is surely calculated at one billion USD’ basis.

C. To develop a new herbal medicine by way of breaking up recipe

The traditional doctors usually prescribe herbal medicine by way of compatibility of herbs in which, at least several herbals put together or at most dozens of herbals putting together. All these recipes are made in accordance with the principle of compatibility of herbs under the guidance of TCM theory. But occasionally some recipes are not reasonable. For example, some herbs with the same function and an unreasonable combination contain heavy metals that are beyond the standard and some recipes contain national protected species and so on. In regard to all these unreasonable recipes, break up them, research with a modern scientific technology and find out their active components in aspects of pharmacology, pharmacodynamics and chemistry etc.. In that case, we may find out and develop some new herbal drugs that not only keep their original efficacy but also turn out to be a simple recipe and even find out active ingredients or other purposes. For examples: Storax pill is consisted of 15 ingredients originally. After breaking up, only five ingredients (storax, borneol, frankincense, sandalwood and radix aristolochiae) are left and form an improved recipe called “Storax pill for treating coronary heart disease”. The rest of ten ingredients such as rhinoceros horn (from wild protected animal), vermilion (containing heavy metals), muskiness and gharu-wood (belonging to costly medicine) etc. are taken out by breaking up recipe. Its efficacy on coronary heart disease or angina shows no obvious difference compared with Storax pill. The Storax pill for treating coronary heart disease has been re-broken up into Subing dripping which is only consisted of Storax and borneol and has a better effect on pain because dripping can enlarge its contact area, easy to absorb and play a quick action. Another example is the mixed pill of radix gentianae, Chinese angelica and aloe. It is consisted of 11 ingredients originally. After breaking-up, only natural indigo has been found to produce the pharmacological action on chronic granular leukaemia and its active constituent is called indirubin. The potency of the new drug developed based on indirubin is far beyond the mixed pill of radix gentianae, Chinese angelica and aloe as well as natural indigo. In addition to this, it has some other advantages like a small dose, quick action and less side-effect. As we know, the second generation of the new drug called “ isomethindigo” to be based on indirubin has already been come out. So, through these examples, you could see what a great prospect it is to break up recipes to develop new drug!

D. Improving the production process and old dosage, developing new medical products

Chinese medical industry stresses on medical raw materials rather than stressing on preparation chronically. It is a quite right way to go at that time, however, it is not adjusted timely, so, it causes some problems obstructing the development of preparation, especially TCM preparation. For past 20 years, TCM industry has developed rapidly, however, its production scale is still small, together with low technical level, low quality equipment, nonstandard management and low quality staffs, so only 10% of TCM enterprise reached requirement of GMP. Old production process has being adopted to produce outmoded products with coarse appearance, and it can’t meet consumers’ requirement. Though the dosage form increases to a high level, still not break through the old dosage form. Compared with the advanced production process & dosage form, there is still a big gap to current TCM products. Because TCM production facilities and production process, such as distilling, separation, concentration, drying and packaging, together with production management, are similar to Western Medicine’s, the advanced production process, facilities and management of Western Medicine can be used in TCM production. If so, there must be a big breakthrough in TCM production. Since Outline for New Drug Application being released by Chinese Government in 1985, nearly one thousand new TCM products have been developed.

E. Developing new products by utilizing new supplementary materials

Supplementary materials is very important to medical production, in other word, the significance of inventing a new supplementary material exceeds the significance of a new drug’s invention. The supplementary material not only make the drug in certain forms, is also in the key position to maintain the preparation’ stability and increase efficacy of drug. For past 20 years, medical industry in developed countries has developed rapidly, profiting from the development and utilization of new supplementary material. Till now, many TCM manufacturers in China still use old traditional supplementary material utilized in 1940’ to 1950’ to make modern TCM products. In recent years, dozens of new supplementary material have been introduced from foreign countries and produced, but their using scope is limited. The active ingredient in many TCM products is uncertain, so it is very difficult to produce the advanced dosage form used in release controlled system & targetable dosed system. If the new supplementary material can be introduced into production, i.e. leaking booster, flocculant, material former, adsorbent, filter and osmotic agent, TCM preparation will achieve a new level.

F. Developing new drug by enforcing quality control

It is very difficult for TCM manufacturers to control the quality of TCM, because its raw material is natural, and its quality is not stable, together with its complicated ingredient. Now, the quality control on TCM production is still the weakness. For last 20 years, the quality control on TCM has developed, for instance, the first section of China Pharmacopiea published in 1995 collects 552 species Chinese medicinal materials, in which 411 of them have qualitative analysis methods and 104 of them have quantitative analysis methods, and 398 varieties of set prescription preparation of TCM, in which 371 of them have qualitative analysis methods and 51 of them have quantitative analysis methods. All of the new TCM products have qualitative & quantitative analysis methods. Currently, TLC & Microidentification are in the majority in respect of qualitative analysis methods on TCM, and TLC-scanning & spectrophotometric method are in the majority in the respect of quantitative analysis methods. But still there are some problems in them, such as not enough indicatrix or indicatrix with narrow scope, not exclusive and undiversified analysis method. The manufacturers don’t stress on the production process from raw material to preparation and quality control enough. Introducing into advanced analysis facilities and related technique, selecting more workable examination standard and stressing on the production process from raw materials to final products, It will further improve the quality of TCM products, also is an important and absolutely necessary way to develop new products.

G. Developing the dietary supplement conforming to requirements of US law

To exert an effect of the natural medicine, to reduce the high expense spent on medical care and to satisfy the people’s demand on guard against disease & medical care, US government issued the law of Dietary Supplement, Health and Education in 1994, which loosens the requirements on marketing herbal medicine, permitting the products containing vitamin, mineral matter, herbal medicine or other plant, amino acid as the dietary supplement to enter the US market. Furthermore, the troghic function of products can be listed on the label. It provides an excellent opportunity for TCM products to enter the US market, so after being improved, the TCM products made by Chinese enterprises can enter the US market as the dietary supplement without any misgivings in a short time. In recent years, Sinoking Development & Management Group (USA) takes up with the project enabling TCM products as the dietary supplement to enter the US market, and, with the support of Sinoking, 310 varieties of TCM products manufactured by 231 Chinese enterprises have been exported to USA successfully. Sinoking has built its own Web Site [http://www.sinoking-herb.com(English)& http://www.sinoking.com.cn (Chinese)], which have been counted the first Web Site in TCM line by noted international search engine-YAHOO, and they have been the most authoritative TCM Web Site in the world. It is obvious that the TCM products have bright future on entering US market as the dietary supplement.

H. Developing OTC products conforming to US requirement

Three hundred thousand OTC products are sold in US market. According to OTC products’ ingredient of therapeatic action and indication, they have been classified into over 80 species and some 700 kinds of active ingredient by FDA, in which a certain amount of plant medical products or extract products or active ingredient are similar to TCM products, such as, genseng, liguorice, clove, coriander, rhubarb, groundsel, plantain seed, bark of elm, mint oil and ephedrin. Some of their usage is same with TCM products’, such as, rhubarb and aloe used for treating diarrhea, and other of their usage is not same, i.e. groundsel used for treating menoxenia, liquorice used for aphrodisiac and regulating the menstruation. Based on the FDA requirements, by modifying production techniques, some TCM products selected from off-the-shelf can receive FDA approval within short period. With the support of Sinoking, TCM products manufactured by major Chinese TCM enterprises have received approval as OTC products from FDA. These TCM products are on the US market. Currently, several TCM products are in the review cycle for OTC approval from FDA. There are always some difficulties, however, TCM products can enter the US market and be finalized within certain scope and guidelines.