Taking great pains with a closed scientific project from botanical research to plantation, technology of cultivation and formulation, Dr. Nguyen Thi Ngoc Tram has invented Crila® for tumor treatment.
Holding a few-week-old leaf of Crinum latifolium L. in her hand, Dr. Nguyen Thi Ngoc Tram enthusiastically made an explanation of how to care this unique cultivar to obtain the most stable bioactive content. Her decade-lasting research demonstrated that this medicinal plant is only suitable for the soil in Southern Vietnam, and its bioactive substances will lose in other regions of Vietnam. “Fortunately, there is no need to worry that this Vietnamese variety is taken away”, she said.
“Vietnamese Crinum latifolium L var. crilae Tram & Khanh” – a new proprietary variety of Vietnamese Crinum latifolium species – is used by Thien Duoc Limited Company, founded by Dr. Nguyen Thi Ngoc Tram, as raw materials to produce Crila® for the treatment of uterine fibroids and benign prostatic hypertrophy. At present, Crila’s price is only one third of imported products’, providing Dr. Tram’s company with domestic revenue of 45 billion VND and has been authorized to be sold in American market.
Crinum latifolium L. has been associated with Dr. Nguyen Thi Ngoc Tram since 1990 when she began her study on genetic polymorphism of Crinum latifolium species and discovered that one of seven species contains alkaloids and flavonoids which are considered as inhibitors against tumor growth. The research group on Vietnamese Crinum latifolium L. conducted by Dr. Nguyen Thi Ngoc Tram and her colleagues in 2010 was evaluated as a great achievement for Vietnamese traditional medicine by the National Council of Sciences. Previously, she was also awarded Kovalevskaya Prize in honour of female scientists.
In 1990, Dr. Tram upheld her doctoral thesis on the determination of compositions and structures of 45 compounds present in the essential oils of Vietnamese Cardamon in Bulgaria and then continued defending her Doctor of Science thesis. She worked as an assistant professor at the Technical University of Sofia and scientific collaborator with the Bulgarian Academy of Sciences in a research team on Asian medicinal plants for cancer and tumor treatment. Her findings of beneficial effects of Crinum latifolium L. plants as well as her great belief in probability of producing medicine for tumor treatment inspired her to embark on an arduous journey of bringing her research to market.
She acknowledged “it’s full of difficulties” in specific market like healthcare industry. She also recognized that there was not any venture capital investment from the government or private companies, so “We have to invest by ourselves to make our belief come true”. She sold her spacious house in Hanoi, formerly bought with her savings from many years of working as a scientific collaborator in foreign countries to buy another one with less money in Saigon. “The remainder of my money was used for doing research, hiring people to travel everywhere to bring varieties for cultivation, many years of collecting leaves for testing, getting failure, then testing again”, she recalled.
Her first “business benefactor” was Agribank branch in District 5, Ho Chi Minh City, Vietnam, who provided her with a loan of 200 million VND in 1997 to buy teabag packing machines. “At that time, there were not any banks that could make a loan to those who didn’t have land documents, but Agribank did respect me as a scientist in terms of reliability”, she said. The clinical trial of Crinum latifolium L. tea was also conducted in Vietnam – Soviet Friendship Hospital thanks to the confidence of the hospital leader at that time. The launch of Crinum latifolium L. tea in 1997 was soon accepted by consumers, which provided Dr. Tram with a basic accumulated sum to help her go deep into medicine production.
“The last stage for medicine to be on the market is the assessment result of clinical trials. It’s the only thing that can prove we have conducted the research in accordance with right process from botany, cultivation, chemical composition, extraction and formulation”, she said. In 2004, Crila® capsules were clinically tested on over 1,000 patients in healthcare facilities such as: Vietnam National Institute of Gerontology (VNIG), Central Traditional Medicine Hospital, HCMC Traditional Medicine Hospital, Tu Du Obstetrics Hospital and National Hospital of Obstetrics and Gynecology (NHOG). The results showed that high treatment efficacy of Crila® for prostatic hypertrophy reached 89.18% and 79.5% for uterine fibroids, and this product is safe to patients without side effects such as dizziness, menstrual disorders, or reduction of sexual abilities, etc. Crila® medicine was allowed for nationwide circulation by the Ministry of Health for the treatment of benign prostatic hypertrophy in 2005 and uterine fibroids in 2007.
Dr. Tram acknowledged that scientists’ way of thinking was completely different from business practices. “Initially, I thought that the price of my own medicine would be cheaper than that of other products on the market, and I still got some money for my research”, she said. In fact, the market was much harsher. Low price resulted in an insufficient budget for promotion as well as difficulty in creating accumulation funds for reinvestment in R&D. Fortunately, according to Dr. Tram, her product originates from scientific research work, so it could draw the attention of communication circle and win quick recognition from the public. “If my product lacked quality stability, it couldn’t keep its foothold on the market for the last 10 years.” she said proudly.
Products from Crinum latifolium L. var. crilae Tram & Khanh account for 50% of the market share of this medicine line on the market according to the estimation by Thien Duoc Limited Company in 2013. Revenue of nearly 45 billion VND is a large number when calculated on herbal product line but a very small number in the market of imported medicine. Natural medicine products are more and more popular all over the world, which will provide a great opportunity to herbal products.
Crila® attracted great attention from the public in America when Healing Quest, a famous television channel specializing in integrative health, came to Vietnam for making reportage on Dr. Tram’s research work, which inspired many researchers to travel to VN to find out. In 2011, Crinum Health officially distributed Crila® in America after it was certified in accordance with FDA safety standards by Eurofins laboratory (University of Illinois, USA) and allowed for circulation. Dr. Sue McKinney, Managing Director of Crinum Health, told that Crila® was preferably chosen because it is produced in a closed system from raw materials collected from the standard plantation. She shared, “We do not have to face any risk of the origin or the variety of herbs in these products.”
A valuable advantage was provided to Thien Duoc Company Limited when Dr. Richard van Breemen and his colleagues in Eurofins continued to perform an in-depth study on Crinum Health after calibration and came to a conclusion that “the compounds of Crinum latifolium L. do not contain estrogen”. This conclusion means Crila® is safe for people with breast or prostate cancer. Crinum Health then labeled “Estrogen Free” on Crila® product for its circulation in the United States.
Thien Duoc Company Limited has determined its development path by integrating into global market. One box of 40 Crila® capsules costs 75,000 VND - one third of the price of imported products but higher competitiveness due to not having side effects. Dr. Tram told that once her product was standard enough to go through US market, it would be easier to expand the market. One box of 180 Crila® capsules is now being sold at the price of 99.99 USD in the United States. According to Dr. Sue McKinney’s estimation, just in the United States, annual sales growth of natural products reaches 100 million USD. Dr. Sue McKinney also said, “This will be a good opportunity for Vietnamese enterprises if they pay more attention to quality. Large companies in the United States no longer want to buy herbal materials from China because of their toxic chemicals.”
According to Dr. Tram, it is challenging to keep up with the trend but the most important thing is to take advantage of this opportunity to turn the abundant source of precious herbs in Vietnam into products which can enter into the international pharmaceutical market. “Land, soil and climate naturally synthesize new beneficial compounds by themselves better than human being”, she analyzed. The fact that Vietnam has more than 4,000 species of medicinal plants and thousands of medicinal sea creatures, but still use imported products mostly is considered as “a challenge for Vietnamese intellectuals.” In order to deal with this, it is important to have policies, mechanisms for scientific research and medicine development as well as the introduction of medicine to hospitals so that our abundant and diverse source of herbs can develop conformably to its potential.
The closed model from botanical research to manufacture makes Crila® more preeminent. After her successful domestication of the variety, Dr. Tram developed 20 hectares of Crinum latifolium L. plantation in Long Thanh, Dong Nai province into the first clean medicinal materials plantation in Vietnam according to GACP (Good Agricultural and Collection Practices) – World Health Organization. She conducted reclamation of fallow land by thickening the ground bed with clean soil transported from forests so as to make the plants’ roots longer than normal level of about 15 cm. In order to avoid toxic chemicals or synthetic fertilizers, she bought cow manure from livestock ranches in Ninh Thuan province, composted with extracted leaves of Crinum latifolium L., fermented by microbes, then remanured to the land. For disinfestation of pests, odorizing compounds were used to lure male caterpillars into jars, preventing the fertilization of female caterpillars.
Another important thing is to apply international standards including GMP, GLP, GSP for whole factory. She also pays special attention to copyright protection, patent protection and proprietary utility solutions.
Dr. Tram’s scientific research career was strongly influenced by her father’s research career, scientist Nguyen Van Truong. Prof. Dr. Truong began his career as a forestry engineer during the period of French domination. He was proficient in many languages and was also the first Editor-in-Chief of Vietnam’s Encyclopedia. Dr. Tram’s career orientation was based on her father’s advice “There are many precious medicinal plants in Vietnam, you should try your best to study and research to invent new herbal medicines for our people.”
It was her father’s valuable advice that gave her confidence and strong motivation. After graduating from college in 1972, she formulated a children cough syrup extracted from Plectranthus amboinicus, which was considered as the first self-produced medicinal product of Vietnam. “Hereditary passion for scientific research from my father helped me grow up in science”. She said what she learned from her father was his perseverance, optimism, confidence in his work as well as the way he managed by himself to find financial resources for the pursuit of his career in scientific research.
Her career also had the support from her husband – a former lecturer of Department of Chemistry at Vietnam University of Commerce – when he decided to “take a step back” from his career to take care of their family during her years of hard abroad study. “Now, living in retirement, we discuss with each other about scientific issues and he always helps me things that my secretary can not do”, she said.
The last days of July, the 65-year-old doctor has been busy with her plans for the introduction of a new line of functional foods named “Thien hoang sa”, which was commercialized from the research of three kinds of Vietnamese herbal plants for haemorrhoids treatment. She has also been conducting two projects of conservation and exploitation of genetic sources from Polyscias fruticosa (L.) Harms and Portulaca Oleracea L. as raw materials for medicine production. Five hectares of Polyscias fruticosa (L.) Harms for conservation are assessed through harvest seasons to yield 17% of root components in comparison with the average level of only 7%. She told that she was preparing for the acceptance of national-level project for her successive study of new substances to make medicines for the treatment of hypertension and heart rate disorders.
Despite at the age of 65, the way she talked about Vietnamese medicinal plants was full of passion “everything is just beginning”. She is conducting intensive study to produce Crilinte, which supports cancer treatment by method of immune stimulation, prevention of angiogenesis and cancer cells. This medicinal product is successfully tested on lung cancer, benign and malignant brain tumor, pending the Ministry of Health’s permission to be clinically tested on lung and prostate cancer in collaboration with scientists from Bulgarian Academy of Sciences and Medical University of Innsbruck (Austria).
“Of all the things I achieved in both scientific career and finance, the most precious one is the point of honour. I believe, with my great effort for scientific research, it will be sustainable”, Dr. Tram said. In regard to forthcoming research, she said, “I am no longer young enough to follow up the results of my research to the bitter end, but I believe in its success. My colleagues and next generations will proceed my footsteps at Thien Duoc Company in order to preserve the previous achievements for posterity”.