From Herbal Folklore to Modern

Medicine
Go to:
 Traditional knowledge

 Research & development

 Invention

 Utility model

 Licensing & commercialization

 Trademarks
 Technology transfer

 Business results

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.
Traditional knowledge found its way to the metropolis of Manila (Photo: Flickr/Benson Kua)
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.

The lagundi plant (Photo: Flickr/Ahmad Fuad Morad)

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.
Lagundi was one of ten plants chosen for further research due to its properties at alleviating
cough and asthma symptoms (Photo: Flickr/Kristy Faith)
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

Dr. Neila Maramba, a founding member

of NIRPROMP (Photo:NIRPROMP)
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

Pascual's trademark
application (IP Philippines
Application No. 42011000094)
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.
Farmers in Palawan were able to benefit economically through a distribution agreeement with
Pascual (Photo: Flickr/CédricBuffler)
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.
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