National Integrated Research Program on Medicinal Plants, Philippines

In 1974, the University of the Philippines Manila (UPM), several other universities and
governmental research agencies working under the Department of Science and
Technology (DOST) of the Republic of the Philippines (the Philippines) collaborated on
the formation of the National Integrated Research Program on Medicinal Plants
(NIRPROMP), with a mandate to distribute inexpensive medicine to the poor, to
propagate the use of herbal preparations with proven medicinal efficacy and identify
scientifically validated medicine that would improve the Filipino pharmaceutical
industry. NIRPROMP was established to address the rising costs of imported
pharmaceutical products, especially those used for frequent ailments such as the common
cold, fever and headaches. At the time, the Philippine pharmaceutical industry was not
self-sustaining in these medicines, and companies were spending approximately 150
million Philippine pesos (around US $22 million at the time) annually to import
medicine. These imported medicines were also prohibitively expensive and out of the
reach of many patients. With this in mind, NIRPROMP prioritized reducing the country’s
dependence on imports and offering people more affordable pharmaceutical products
through locally developed herbal medicine. One such innovation came in 1995, when
NIRPROMP isolated Vitex Negundo, a large, hardy, five-leaved aromatic shrub with
bluish-purple flowers, as a natural source for developing an effective herbal medicine.
Known in the Philippines as Lagundi, the plant thrives in both humid and arid regions
throughout Africa and Asia and has been used by local populations for hundreds of years
to effectively treat wounds, headaches, ulcers, skin diseases, diarrhea, and the common
cold, among many others. After successfully scientifically identifying the medicinal
properties of each part of the plant, NIRPROMP developed a Lagundi-derived formula
for a clinically proven cough and asthma medicine in tablet and syrup form.
Traditional knowledge
Lagundi has been used for centuries by local populations in the Philippines for its
medicinal properties, but these were not described in detail until a book by Spanish Jesuit
Father Colin that was published in 1900. In his book, Father Colin wrote that lagundi was
used regularly by Filipinos to treat wounds and as a pain medication. In addition, he also
found that they had vast traditional knowledge on the different medicinal properties of
each part of the plant. For example, while leaves are commonly used to ease headaches
and cleanse ulcers, seeds are used to treat skin diseases. The plant’s flowers are used to
treat numerous diseases such as diarrhea and cholera, and its black fruit is dried and eaten
to alleviate and regulate intestinal discomfort. Finally, Father Colin discovered that the
plant’s roots are used to treat rheumatism and dysentery. This traditional medicinal
knowledge surrounding lagundi is commonly disseminated through herbolaryos –
traditional healers who use their traditional knowledge to prepare and administer herbal
medicine. Herbolaryos have served as authority figures on medicine in many local
Filipino communities for generations, and have enjoyed a great deal of respect and trust
among many communities in the country.
Research and development
The development of modern lagundi-based medicine was the result of the herbal
medicine research and development (R&D) that has been continuously undertaken by
NIRPROMP. Headed by researchers primarily from UPM including Dr. Nelia Maramba
and Dr. Conrado Dayrit, R&D focused on clinically validating traditional medicine such
as lagundi for use in the development of symptomatic drugs (treatment that focuses on
the symptoms of an ailment, not the cause). This is done through isolating the active
ingredient and then developing the associated drug. When research started, lagundi was
not at the top of the list of potential candidates. In fact, after an initial review of various
research projects focusing on traditional medicine in the Philippines alone, the R&D team
discovered over 500 projects related to isolating active ingredients in plants, none of
which had been successfully commercialized.
Dr. Dayrit suspected that one of the main reasons why these active ingredients were
never commercialized into a product was because consumers were generally unaware of
the plants from which they originated and how the ingredients were prepared into an
herbal drug. Dr. Dayrit felt that this lack of knowledge bred distrust among consumers of
companies trying to develop new drugs based on relatively unknown plants, and that
R&D should be focused only on traditional medicine based on plants that are well known
and trusted among the population. After conducting a survey of consumers, the research
team learned that although people generally do not trust medicine based on a plant they
were unaware of and manufactured by an unknown company, many do trust herbolaryos.
The R&D focus therefore shifted from journal articles of various research programs to
herbolaryos, and NIRPROMP started collecting folkloric data and conducting scientific
tests to validate the herbolaryos’ claims.

With the help of the National Science and Technology Authority of the University of the
Philippines Los Baños, from 1977 to 1982 NIRPROMP conducted a detailed survey of
herbolaryos to identify those herbal preparations that have promising medicinal
properties. The survey included interviews with 1,000 herbolaryos and had detailed
accounts of the herbs they used and any side effects caused. Out of the 1,500 plants
identified, NIRPROMP scientifically validated that 480 of them contained beneficial
medicinal properties.

Another R&D project was carried out in tandem and based on the information provided
by the herbolaryos. Members of this project poured over the records of the Department of
Health to find out the leading cause of morbidity at the time. The gathered data was used
to prioritize the symptoms and/or diseases that herbal medicine would have the best
potential to treat. Researchers discovered that respiratory problems were among the most
common symptoms that held the potential to be treatable with traditional medicine.

Armed with this cache of data, the researchers developed five criteria with which to test
plants against: safety, efficacy, quality, availability of raw material, and propagation
studies of the raw herbs. The first three criteria were necessary to ensure that the
medicine would be safe and effective, while the last two would ensure the sustainability
of the supplies for R&D, clinical trials and eventual commercialization. Long and
detailed testing of each of the 480 plants ensued, and NIRPROMP identified ten plants
that were scientifically validated as safe, effective and sustainable.

Lagundi was one of these ten plants, and because respiratory problems were a primary
concern among the population, it was chosen to be the basis for a medicine to alleviate
cough and asthma symptoms. The beneficial properties of lagundi were first recognized
during the survey of the herbolaryos, in which 70% of them vouched for the plant’s
efficacy in treating cough. The lack of any reports of adverse side effects bolstered their
claims, and the abundance of the plant throughout the Philippines made lagundi R&D
even more attractive.

Through scientific and clinical tests, the research team identified four active ingredients
of lagundi and found the effect of each: (1) as a relaxant of the air passages in the lungs;
(2) as an anti-histamine; (3) as an anti-inflammatory; and (4) as an anti-asthmatic. While
each ingredient acted weakly when administered on its own, they produced a powerful
cough suppression effect when used together, and without any adverse side effects. With
these promising results in hand, NIRPROMP developed a lagundi-based cough medicine
in tablet form and launched clinical trials in the late 1980s, with 119 patients suffering
from mild to moderate cough participating. Each patient was given either a placebo or the
lagundi medicine, and those who received the lagundi medicine exhibited substantial
positive medical responses without any adverse reactions or side effects. By 1993,
researchers had successfully developed a lagundi-based cough medicine in tablet form. In
October 1995, the Philippine Department of Health released a list of officially endorsed
plants that exhibit effective natural medicinal properties with proven therapeutic value.
Lagundi was among the plants listed, along with the nine other plants NIRPROMP
isolated through its earlier R&D.
Invention
Following the successful development of lagundi cough tablets, NIRPROMP researchers
worked to also develop the medicine in a syrup form. Children and the elderly make up a
significant portion of the demand for cough medicine, but tablets can be difficult for them
to take. In 1999, NIRPROMP successfully altered the formulation for lagundi cough
tablets into a lagundi cough syrup, which retains all the medicinal properties of the
tablets, but is in a form that is easier to administer.
The new syrup formulation uses decoction to extract the organic compounds from
lagundi leaves. Decoction involves drying the lagundi leaves and grinding them through a
mesh until a fine powder is formed. Distilled water is then added to moisten this powder,
and it is then boiled for approximately fifteen minutes with occasional stirring in a low to
medium heat (which prevents possible degradation of the active ingredient). The resulting
lagundi decoction is set aside to cool and then filtered or strained. Sucrose is then
dissolved in the prepared decoction using a turbine mixer, after which the compound is
aged for about three days. A small amount of methyl and propylparaben (a preservative)
is ground into a fine powder, and propylene gylco (an organic compound used as a
solvent) is added until the propylparaben is completely dissolved. This is introduced into
the aged sucrose and lagundi decoction compound. After mixing well, a small amount of
citric acid and orange oil is added. Lastly, a sufficient amount of distilled water is mixed
in to obtain the required volume. This is thoroughly mixed together until a syrup solution
is formed in the appropriate consistency.
Utility model
Because NIRPROMP’s research was funded by DOST and was a collaboration between
UPM and PCHRD, a sectoral council of DOST, all intellectual property (IP) is managed
and owned by DOST. In order to protect the IP behind lagundi cough syrup formula and
promote commercialization, in 1999 DOST therefore applied for a utility model with the
Intellectual Property Office of the Philippines (IP Philippines) for an herbal
pharmaceutical composition that is based on lagundi. The utility model was approved
and issued in February 2001.
Licensing and commercialization
Although NIRPROMP was responsible for the R&D and clinical trials of the lagundi
cough medicine in tablet form, PCHRD was responsible for coordinating and facilitating
commercialization. When the lagundi cough tablet formulation was ready for
commercialization, PCHRD organized informational forums to gauge interest from local
pharmaceutical companies. Many of them expressed interest and as such in 1993 PCHRD
developed and announced a non-exclusive licensing agreement system. Under this
agreement, the licensee pays an upfront fee for the technology and royalties based on
gross revenues less value added tax and the typical volume discount given to large drug
store chains. As the funding entity of PCHRD and NIRPROMP, all royalties and fees are
paid to DSOT. Each licensee is responsible for registering their derived products with the
Philippine Food and Drug Administration (then known as the Bureau of Food and
Drugs). An important part of the license is the provision of the results of the clinical
studies which verify the safety and effectiveness of the drug. Without these, the drug
cannot be sold as a legal medicine in the Philippines.

The first licensee for the lagundi tablet technology was Herbafarm, a Filipino
pharmaceutical company which used lagundi grown from its own farms and at an in-
house manufacturing facility at a DOST compound. Herbafarm launched its lagundi
products in 1994. Other licensees soon followed, one of which was Pascual Laboratories
(Pascual), a large Filipino pharmaceutical company that would go on to become the most
successful licensee of lagundi technology. Pascual’s product based on the PCHRD
lagundi formula was approved by the Bureau of Food and Drugs in 1996 and continues to
be on sale in the Filipino pharmaceutical market.

Despite the successful commercialization of the lagundi cough medicine formulation, it

faced numerous difficulties penetrating the market early on. At the time, medical
professionals and some in the public did not consider herbal medicine to be an effective
form of medical therapy. To counter this problem, Pascual launched a marketing
campaign to improve the image of herbal treatments and lagundi cough medicine. The
company’s first strategy was to promote the drug to medical practitioners directly,
especially those at Rural Health Units (RHUs). RHUs are small government funded
clinics in rural areas, and as such they were very open to using lagundi cough medicine
because it was developed through a government funded program. To further verify the
effectiveness of the drug, in 1997 Pascual submitted it to the International Exhibition of
New Products, Inventions and Techniques in Geneva, Switzerland, where it was awarded
the silver certificate for R&D. The company took this award back home and used it
extensively in advertising and developing awareness, and it helped change the opinions
of medical professionals and skeptical consumers.
Pascual and other pharmaceutical companies marketing lagundi cough medicine picked
up the pace of their advertising campaigns in the late 1990s and 2000s. By 2006, Pascual
was running television commercials during popular morning shows and advertising on
the radio and billboards. Other companies followed suit, and their successes increased
interest in licensing the technology. In 2009, Herbs and Nature Corporation entered into a
licensing agreement and launched its own lagundi cough medicine, and in 2010 New
Market Link Pharmaceutical Corporation, Herbcare and Pharmacare all did the same and
introduced lagundi cough medicine products to the market.
Trademarks
An integral part of the success of the efforts of Pascual and other companies was the
renewed brand image they helped create for lagundi, and this was facilitated by the strong
brand names the companies created for their respective products. Recognizing the need to
protect its popular brand names, in January 2011 Pascual applied for trademarks with IP
Philippines for Ascof, Ascof Lagundi, and a stylized logo that includes an image of a
lagundi leaf. Pascual’s efforts paid off, as by early 2011 the company’s lagundi cough
medicines became the second most popular cough medications in the Philippines. In
February 2009, Trevenodd Corporation (Trevenodd), a newcomer to the industry, applied
for a trademark registration for its Plemex brand lagundi cough medicine, which was
registered in August of that same year.
Technology transfer
Until 2009, the technology for lagundi tablets and syrup was transferred through
licensing agreements between PCHRD, a government entity, and the private sector.
However, according to Republic Act 10055, otherwise known as the “Philippine
Technology Transfer Act of 2009” (the Act), technology developed backed by
government funding must be completely transferred to entities such as universities or
companies that can translate this technology into useful products and services. The goal
of the Act is to promote and facilitate the transfer, dissemination, and effective use,
management and commercialization of IP, technology and knowledge resulting from
R&D funded by the government for the benefit of the national economy and all Filipino
people.
Based on this new policy, PCHRD formally transferred the lagundi cough medicine syrup
formula to UPM, which would then be tasked with further R&D, licensing and
commercialization activities. In October 2010, Azarias Pharmaceutical Laboratories, Inc.
(Azarias) made an application to UPM to become the first licensee of lagundi syrup under
this new framework. Following the evaluation and recommendation of PCHRD, the
agreement was officially signed in January 2011. The licensing agreement was the first of
its kind between a public R&D organization (UPM) and a private corporation (Azarias)
in the Philippines since the Act was ratified in 2010.
Business results
When lagundi cough medicine was first launched on the market in 1994, it faced an
uphill battle of consumer skepticism. However, through a consecutive series of lucrative
licensing agreements and concerted efforts to improve the image of herbal medicine and
lagundi derived products, the drug has been a success for the many companies that have
commercialized it as well as NIRPROMP, PCHRD and DSOT. This is evident in the
rapid increase in royalties received by DSOT, which rose from PHP 160,000
(approximately US $4,000) in 1997 to PHP 9,751,000 (approximately US $210,000) in
2009.
The successful commercialization of lagundi has also been beneficial for the many
farmers that grow and sell the shrub to manufacturers. One such example is the case of
the lagundi farmers on the southwestern island of Palawan. With the help of a non-
governmental organization, the farmers were able to secure a distribution deal with
Pascual to produce lagundi. Under the terms of the deal, Pascual lent money to the
farmers to install solar powered dryers and mills so that they could produce the lagundi in
powdered form. With the help of this new equipment, the farmers were able to produce
more lagundi than before and improve their processing ability. Within two years the
farmers not only paid Pascual back, but also became an important supplier of lagundi,
which significantly improved the livelihood for the farmers, their families and
communities.
Championing technology transfer and herbal medicine
Passed down for generations, the traditional knowledge of lagundi has been transformed
into a safe, scientifically validated herbal drug. With the help of the Philippine
government and collaborations between universities and pharmaceutical companies, the
technology was transferred and smart use IP structures such as utility models and
trademarks ensured its success. Once only in the domain of herbolaryos, the lagundi plant
now uplifts the livelihood of local farmers and brings an affordable, safe and effective
medicine for all.

References:
Wipo.int. 2013. From Herbal Folklore to Modern Medicine. [online] Available at:
<https://www.wipo.int/ipadvantage/en/details.jsp?id=3661> [Accessed 13 October 2013].