past, present and future of herb medicine in

PAST, PRESENT AND FUTURE OF
HERB MEDICINE IN RHEUMATOLOGY
Nyoman Kertia
Section of Rheumatology, Department of Internal Medicine
Faculty of Medicine Gadjah Mada University
Yogyakarta - Indonesia
WHO
Non western medicinal method
should be included
to the national health plan
for growing the primary health care
INTRODUCTION
Traditional Medicine Definition
(WHO,2010)
Original medicine in certain country used
for generations in that country or in
other countries.
Used at least in three generation and
proven to be beneficial and safe.
The main ingredient in traditional
medicine are herbs.
HERB MARKET IN THE WORLD (2000)
34%
22%
39%
5%
EUROPE
Source : Randy J. Dannin, 2001
NORTH AMERICA
ASIA
OTHER
PREVENTIVE
HERBS MEDICINE
PREVENTIVE
CURATIVE
CURATIVE
STANDARDIZED
EXTRACT
MODERN DRUGs
TRADITION / CULTURE
SCIENTIFIC APPROACH
TRADITIONAL
TIME
RESEARCHES AND DEVELOPMENT
THE TRADITIONAL AND MODERN
MEDICINE
Traditional treatment models
generally focused on relieving
symptoms of illnesses suffered by
patients (symptomatic).
In contrast, modern medicine is
more focused on the cause of the
illness
THE HERBS MARKET
The use of herbs in Asia Pacific
countries have a 2-dimensional
correlative aspects, that are
medical and economic aspects.
Herbal market in the developing
countries continue to increase
because most people use herbal
medicine.
HERBS MARKET IN THE WORLD (2000)
China
: US$ 9 B
West Europe
: US$ 6,6 B
USA
: US$ 3 B
Japan
: US$ 2 B
Canada
: US$ 1 B
The use of herbal medicine in the field
of Rheumatology in early time (before
1900 A.C.)
CAM (complementary and alternative
medicine) in rheumatology has been
known since long time ago in other
parts of the world, ranging from China,
India, Africa, and South America, since
2000 years B.C.
Script about the oldest herbal
medicine was found in Babylon more
than 60.000 years
In 11th century, in Scotland, had
been using the opium poppy
(Papaver somniferum) and
marijuana (Cannabis sativa) as
Painkillers and anesthetics (History
and development ofHerbal Medicine-Rajaa
Abuiedeh)
Papaver somniverum
India
Ayurvedic or the science of life is
an ancient holistic system for
diagnosis and treatment.
It has already existed since 1000
BC in India.
Ayurvedic is probably the oldest
system of medicine known by
human
CHINA
Herbal medicine was used since 5000 years ago
The oldest book of herbal medicine were Huang Di
Nei Jing (The Yellow Emperor) and WaiTai Mi Yao
(Secret Recipe).
The most famous old book is a compendium of
Materia Media, which was published in 1590. These
books was written by Li Shizhen and continued by
Zhan Xueim, contains 1,892 useful substances in
medical world.
The development of traditional medicine in
the country is relatively advanced because
of the government's fully supports
KOREA
The system of traditional medicine in
Korea has been known as Korean
Oriental Medicine (KOM) or more
popularly known as hangbang.
KOM development was visible from
many high schools that was
specialized for KOM. Not surprisingly,
that it is easy to find doctors and
pharmacists specialized in KOM
The Use of Herbal Medicine in
Rheumatology in Indonesia
Indonesia has about 35 thousand species of higher
plants, 3500 of which are reported as a medicinal
plant. As many as 90% of Asian medicinal plants
were grown in Indonesia. .
Jamu is a term, refers to the ingredients of the
herbal medicinal plants. Herbal medicine derived
from ancient Javanese language, spell or Usodo.
The utilization of natural herbs for health purposes
has existed since hundred years ago.
Healers and traditional healers are dispensing
various types of plants to cure diseases. Evidence of
herbal medicine use in the past can be seen through
the scripts in palm leaf, prasasti, and temple reliefs
(Sujarwanto, 2012).
USE OF HERBS MEDICINE IN POPULATION
DI NEGARA SEDANG BERKEMBANG SEBAGIAN BESAR MASYARAKAT
TERUS MENGGUNAKAN OT
USE OF HERBS MEDICINE IN
DEVELOPED COUNTRIES
Current Use of Herbal Medicine in
Rheumatology (1900-2013 A.C.)
Currently, traditional medicine has
been developed to modern medicine
using standards of scientific testing as
modern medicine.
This modernized traditional herbal
medicine can be used as an alternative
way to treat rheumatic diseases
The Examples of AntiInflammatory Plants
Curcuma domestica Val. and Curcuma
longa L (tumeric)
Curcuma xanthorrhiza Roxb. (temoelawaq)
Zingiber officinale Rosc. (Zingiberaceae)
Colocassia esculenta (Shah et al.,2007)
Momordica charantia (Shah et al.,2008).
The use of herbal medicine,
complementary and alternative
medicine (CAM) have been increased in
rheumatologic patients.
Approximately 47% of patients
sufferred from osteoarthritis use CAM
to treat their illness, and they feel
comfortable using those treatment.
The Legalization of Herbal
Medicine
Republic of China: Chinese government has
integrated TCM (Traditional Chinese Medicine) in
mainstream health services. Chinese government
supports the load TCM herbal medicine in their
constitution. TCM clinical trials have been
conducted in 40 local hospitals.
Japan: Japan is one of the example of developed
countries that utilize herbal medicine in their
healthcare system. A total of 140 herbal remedies
were included in health insurance’s drug list, so that
physicians can give herbal medicine prescriptions.
Korea: Korean Government mandates
herbal medicine through the National
Health Act since 1952. Herbal medicine
was included into the health insurance’s
drug list since 1967.
ASEAN: The governments in ASEAN
countries has harmonized the regulation of
herbal medicines.
USA: American government make the
legalization of medicinal herbal through
including herbal medicine as dietary
supplement group. Those regulation were
stated in Dietary Supplement Health and
Education Act (Oshea).
European Union: regulation of
herbal medicine was
conducted in herbal medicine
pharmacopoeia assessment
through Europe and EMEA
(European Medicine Agency) in
London (WHO, 2002).
HERBAL CLINIC OF
DR. SARDJITO HOSPITAL
YOGYAKARTA - INDONESIA
DR SARDJITO HOSPITAL
THE “A CLASS” (HIGH LEVEL) HOSPITAL
WHAT LEVEL IS THE HERB MEDICINE ??
CAM CLINICs ARE IN FRONT OF
HOSPITAL
TWO TYPES OF MEDICINE
KONVENTIONAL
VS
TRADITIONAL
KONVENTIONAL
CALM
KONVENTIONAL
CONCEITED
CONVENTIONAL
CALM
TRADISIONAL
HURT
TRADITIONAL
CALM
TRADITIONAL
CALM
TRADITIONAL
CONCEITED
CONVENTIONAL
HURT
NATURAL MEDICINE DEVELOPMENT TEAM OF DR. SARDJITO H0SPITAL
ADVISOR
KETUA PFT
(ex officio)
HEAD
Dr.dr. Nyoman Kertia,SpPD-KR
CONSULTANTS
Prof.Dr Samekto W.P.Far.K.,Sp.FK(K),Sp.S(K)
Prof.DR.phil.nat.Sudarsono, Apt
Prof. DR.Suwijiyo Pramono, Apt
Prof.dr.Moh.Hakimi,PhD,SpOG(K)
Prof.dr.H.A.H.Asdie SpPD-KEMD
Prof.dr. Ngatijan,MSc,SpFK(K)
DEPUTY
Dr. Sumadiono, PhD, SpA (K)
Quality Assurance
System
Prof.DR.phil.nat.
Sudarsono, Apt
SERVICES
Dr. I Dewa Putu Pramantara
SpPD-KGer
Dr. Ishandono, SpBP
SECRETARY
Dra. Eni Purwaningtyastuti,Apt
EDUCATIONAL &
RESEARCH
Dr. Cecep Kristanto, SpKJ
Dr. Luthfan SpPD-KEMD
Dr. Rukmono Siswihanto, MKes, SpOG(K)
Prof.Dr Samekto
W.P.Far.K.,Sp.FK(K),Sp.S(K)
Dr. Paryono, SpS
Dr. Fajar Waskito, SpKK, MKes
Dr. Bambang Jarwoto SpPD-KGH (Peny
Dalam)
Dr. Diah Rumekti SpOG
Dra. Rosita Mulyaningsih, Apt, SpFRS
Dra. Nurul Ambariyah, Apt
Dr. Cecep Kristanto, SpKJ
Dr. Retno Sutomo, PhD SpA
Yeni Prawiningdyah,SKM,MKes
Drg. Goeno Soebagyo, SpPM
Dr. Umi S. Intansari, Mkes, SpPK
Prof.Dra. Mae Sri Hartati, Apt, MSc,
Prof.Dr. Sunartini PhD, SpA(K)
Dr. Mahar Agusno, SpKJ(K)
Dr. Sulanto Saleh Danu, SpFK
Prof.Drs. Mustofa Apt,MKes, PhD
Dr.Med.dr.Indwiani Astuti
Dr. Rustamaji, MKes
DR med. Dr. Putrika PRG
Dr. Ahsanudin SpOG
Dr. Setyo Purwono MKes, SpPD
DOCUMENTATION
PUBLICATION &
MARKETING
Dr. H.Sunardi Radiono,
SpKK(K)
Dr. Suharsana
Drs. Trisno Heru MKes
Dra. Sri Kadarinah, Apt
Dr. Bambang Sigit R. SpPD-KP
Dr. Irwan TR SpOG
Dr. Rizka Humardiyanti, SpPDKPTI
HERBS SERVICES BASED RESEARCH
1.
informed consent
2.
Name tag of the doctors using herb
3.
Herbs Formularium Book
4.
Herbs Medical Services Standard
Book
5.
Herbs Standard Operational
Procedure
6.
Herbs training for doctors and
pharmacists
THE HERBS FORMULARIUM
FIGURE 6
CHANGE OF THE SYNOVIAL FLUID BIOCHEMISTRY
AND IMFLAMMATORY
IN THE TREATMENT OF PIROXICAM VS CURCUMA
16
14
12
PRE PIROXICAM
10
POST PIROXICAM
DELTA PIROXICAM
VALUES
8
PRE CURCUMA
6
POST CURCUMA
4
DELTA CURCUMA
2
0
V IS C O S IT Y ( C M )
LE UC O C Y T E
C OUN T ( X 1 0 0/ uL)
P M N (%)
LY M P H OC Y T E
( X 1 0 %)
M O N OC Y T E ( %)
-2
-4
VARIABLES
M A C R OP H A G
( %)
P R OT E OG LY C A N
( X 1 0 M G/ L)
M DA
(N .M O L/ M L)
FIGURE 1
AIMS SCORES IN THE TREATMENT OF
PIROXICAM VS CURCUMA
4.5
4
3.5
3
AIMS SCORES
PRE PIROXICAM
POST PIROXICAM
2.5
DELTA PIROXICAM
PRE CURCUMA
POST CURCUMA
2
DELTA CURCUMA
1.5
1
0.5
0
PHYSICAL
ACTIVITY
SOCIAL
ACTIVITY
AFFECTIVE
VARIABLE OF AIMS
PAIN
ABILITY TO
WORK
FIGURE 3
EFFECT OF PIROXICAM VS CURCUMA
ON AST, ALT, UREA & CREATININE
LEVEL
40
35
30
25
PRE PIROXICAM
20
POST PIROXICAM
LEVEL
DELTA PIROXICAM
PRE CURCUMA
15
POST CURCUMA
DELTA CURCUMA
10
5
0
AST (U/L)
ALT (U/L)
UREA (MG/DL)
-5
-10
VARIABLES
CREATININE ( :10
MG/DL)
FIGURE 4
GAIN AND RISK OF THE PIROXICAM VS
CURCUMA TREATMENT
PROXICAM
CURCUMA
12
FREQUENCY (%)
10
8
6
4
2
0
DISPEPSIA
CONSTIPATION
INCREASE
APATITE
EXCITING
GAIN AND RISK
FEELING
FRESH
FEELING
WARM
URETER
COLIC
RATIONAL DRUG
/ HERBALS
HERBALS
MEDICINE
QUALITY
TO ENSURE THE RELIABILITY & REPEATABILITY
EVIDENCE BASED MEDICINE
QUALITY ASSURANCE OF THE
TRADITIONAL MEDICINE
GOOD AGRICULTUREAL PRACTICE
GOOD MANUFACTURING PARCTICE
FOR HERBS MEDICINE
Five key strategies to be conducted by
WHO for the development of herbal
medicine
1. Included traditional medicine into national
healthcare system
2. Promoted safety and efficacy in using
traditional drug
3. Improved access to get safety and efficacy
information about herbal medicine
4. Promoted protection against the use of
traditional drug
5. Strengthened cooperation in rheumatologic
field between science development and
traditional treatment
MUST WE DO THIS SCENARIO ?
PLEASE REMEMBER THE GENOMIC PATERNS !
INTEGRATED
MEDICINE
(HARMONIZATION)
WESTERN
MEDICINE
STANDARDIZATION,
PRE CLINICAL & CLINICAL TRIAL
EASTERN
MEDICINE
MOVE EASILY WITH HERBS
THANK YOU VERY MUCH
INCREASING THE DIURETIC EFFECT
Familia : Gramineae
Effects : Antipiretic, diuretic, haemostatic
Using : Root for fever, Urinary tract infection,
Hematuria, Hemaptoe, Epistaxis
SIDE EFFECT OF PARACETAMOL <<
Family : Acanthaceae
Effects : Analgetic, anti inflammatory, antipiretic
The Use of Herbal Medicine in
the Field of Rheumatology
Inflammatory diseases - including various
rheumatologic diseases - can cause morbidity
and daily activity disturbance, that often called
as King of Human miseries (Shahet al.,2006)
Curcuma longa
The active substances contained inCurcuma
longa Lis curcumin.
Its clinical potential in inflammation treatment
was by inhibiting COX andNitric Oxide
Synthetase(NOS) activity (Shahet al.,2011)
Curcuma longa
Aristolochia
The anti-inflammatory effect of Aristolochia
species is resulted from direct interaction
between aristolochic acid and phospholipase
A2 derivatives.
Aristolochia indicaL, andAristolochia
Aristolochia kaempferi recurvilabra are now
used in anti-inflammatory conditions.
Aristolochia indica L
Medicinal caprifoliaceae
Caprifoliaceae family consists of approximately
400 species, some of which are used as antiinflammatory therapy in Asia and Pacific region,
Lonicera japonica, Lonicera affinis, Lonicera
confusa, Sambucus javanica, Sambucus
sieboldiana, and Weigela floribunda. Further
researchs will be conducted by expanding other
species that have the possibility of inhibiting
phospholipase A2 with biflavonoid content. One
herb that has been studied is ochnaflavone of
Lonicera japonica
Lonicera japonica
Lonicera japonica:anti-inflammatory and
antipyretic agent ofLonicera japonicaare found
in their active substance including biflavonoid
and ochnaflavone, that are strongly inhibiting
phospholipase enzyme activity
COX Inhibitor
Some types of plants in Apocynaceaefamily in
Asia are commonly used for the treatment of
inflammation but not all of them have been
studied whether they have COX inhibition
mechanism or not.
The example of these plants are Alstonia
scholaris, Plumeria rubra, Ervatamia divaricata,
Trachelospermum jasminoides and
Trachelospermum asiaticum
Alstonia scholaris
Zingiber officinaleinhibits TNF-α,
prostaglandin, and leukotriene synthesis, and
currently still has limited efficacy in
osteoarthritis therapy
Zingingiber officinale
Research of herbal medicine use in
rheumatology
In a study involving 232rheumatologic
patients, one thirdof them had been using
CAM during6-12 months during research
period.Forty-four procents of themstillused
CAM, 12% of them werenew user, 22% of
them used CAM as maintenance, and 22% of
them hadstopped using CAM (Setty, 2005).
Suyanto Hadi, 2011
Hadi Suyanto (2012) had studied the benefit
of herbal extract derived from black cumin
(Nigella sativa),bay leaves(Syzigum
polyanthum)and celery (Celedri folia) for four
weeks in patients with hyperuricemia.
The patients in this study were divided into 3
groups; 32 patients used herbal medicine, 28
patients used allopurinol, and 31 patients used
placebo.
This study concluded that herbal extract could
lowered uric acid level better than allopurinol
and placebo at week-4.Herbal extracts could
also decrease the value of musculoskeletal
pain compared to placebo.The side effects of
herbal extracts were notsignificantly different
thanallopurinoland placeboatweek-4 of this
study (Kertia, 2011).
Black Pepper
Nyoman Kertia, et al
Kertia et al (2009) studied about the anti-
inflammatory activities and safety of Curcuminoid
from Curcuma domestical Val. rhyzome extract
compared to diclofenac sodium for osteoarthritis
treatment in 80 patients with osteoarthritis.
Administration of 30 mg three times daily of
curcuminoid from Curcuma domestica Val. extract
significantly reduced the secretion of COX-2 and ROI
by synovial fluid monocytes, leucocyte count, MDA
level and joint pain score, while no significant
difference compared to 25 mg three times daily of
diclofenac sodium treatment. There was no significant
difference in adverse events during the study in both
groups, either on head, chest, gastrointestinal tract or
urinary tract complaints.
Ginger rhizome
Curcuma longa Linn
Further researchs are needed to systematically and
scientifically validate the effectiveness of CAM
(Complementary and Alternative Medicine) in clinical
practice.
The knowledge of the mechanism of action of CAM
therapies required by physicians for deciding and
explaining the effectiveness, indications, contraindications,
drug interactions, side effects and anticipate their toxicity.
CAM therapies are widely use, especially in rheumatic
diseases.
Herbal remedies are often used without much knowledge
or information from physicians. Future research is expected
to find the new molecular targets for therapeutic efficacy of
herbal medicine in rheumatic diseases.
Most people believethatherbal medicines
were safer, because of their naturality and
considered safer than conventional treatment.
Mostpatients using CAM thought that herbal
medicine use for long periodremainedsafe,
withoutthe knowledgeabout their clinical
benefit and side effects.
Someherbal products may contain heavy metal or
harmful drugs which were not mentioned in their
composition lists, like glyburide, sildenafil, colchicines,
ephedrine,phenacetin or phenilbutazone.
The concommitant use of herbal medicines with other
conventional drugcanraise their side effectand drug
interaction, especially in elderly patients who oftenget
polypharmacy.
The knowledge aboutherbal medicine andtheir
interaction with conventional drugis veryimportantto
beunderstanded (Setty. 2005).
Table 3. The use of CAM research in Rheumatology
The Future Use of Herbal Medicine
in Rheumatology
The development of traditional medicine use in
rheumatology depends on regulation framework,
wisdom, and government development programs.
The use of herbal medicine must be implemented
from standard practice and production rules, quality
assesmentguide, safety, andefficacy, education and
training, a fair attitude toward herbal medicine
products, monitoring of herbal products safety in one
countries.
The threat for most countries in using herbal medicine
is lack of financial supports and limitation of capable
human resources (WHO, 2012).
Omic Methodologies
Omic future methodology will evolve rapidly to
address the need for information, strategy
development of molecular biology, and can be applied
to research on CHM for standardization and quality
control of herbal formulas, and the characteristics of
the target mediated downstream effect, identification
of molecular mechanisms to predict side effects and
interactions with other drugs (Buriani, 2012)
.
Thank You
.
Powerpoint Templates
STRATEGI WHO PERLU
DIJABARKAN DALAM
KEBIJAKS
NASIONAL YG
KOMPREHENSIF
• TCM MEMPUNYAI AKAR SEJARAH JAUH LEBIH
TUA DIBANDING WESTERN MEDICINES
• TELAH PULUHAN ABAT MENYEBAR LUAS
KESELURUH DUNIA (CHINESE OVERSEASE)
DLM KONTEKS PENGGUNAAN OBAT HERBAL YG TERUS MENINGKAT WHO
MENGELUARKAN STRATEGI OBAT TRADISIONAL:
1) INTEGRASI SECARA TEPAT OT DLM SISTEM PELAYANAN KES. NASIONAL
2) MENINGKATKAN SAFETY, EFFICACY DAN MUTU DG MEMPERKUAT KNOWLEDGE
BASED, REGULASI DAN QA STANDARD
3) KETERSEDIAAN & KETERJANGKAUAN TERUTAMA UNTUK MASY TIDAK MAMPU
4) MEMPROMOSIKAN PENGGUNAAN OT SECARA TEPAT KPD PROFESIONAL MEDIK
MAUPUN KONSUMEN
BERDASARKAN PENGGUNAAN DAN PENGAKUAN OBAT TRADISIONAL
PADA SISTEM PELAYANAN KESEHATAN, MENURUT WHO ADA 3
SISTEM YANG DIANUT OLEH NEGARA-NEGARA DI DUNIA:
SISTEM INTEGRATIF
SISTEM INCLUSIVE
SISTEM TOLERAN
•
RRC
: INTEGRASI TCM DALAM MAINSTREAM YANKES
KONSTITUSI RRC MEMUAT TCM
UJI KLINIK TCM DI 40 RS
•
JEPANG ; NEGARA MAJU YG MEMANFAATKAN OT DALAM
MAINSTRAEM YANKES
140 OBAT HERBAL DLM LIST OBAT ASKES
DOKTER MENGGUNAKAN OBAT HERBAL
•
KOREA : UU KESEHATAN NASIONAL 1952 MENGAMANATKAN
OBAT TRADISIONAL
SEJAK 1967 OBAT TRADISIONAL MASUK LIST ASKES
•
ASEAN : HARMONISASI REGULASI OBAT TRADISIONAL
•
USA
•
UNI EROPA: ASSESMENT OT MELALUI FARMAKOPE EROPA DAN
EMEA DI LONDON
; DIETARY SUPPLEMENT DIATUR DALAM DIETARY
SUPPLEMENT HEALTH AND EDUCATION ACT (DSHEA)
RANKING PASAR DUNIA
AGROMEDISIN
EKSTRAK NABATI TUNGGAL TAHUN 1999
Gingko
Ginseng
Garlic
Echinaceae
St. John’s Wort
Saw Palmetto
Grape Seed Extract
Evening Primrose Oil
Cranberry
Valerian
Bilberry
Milk Thistle
Kava-kava
Source : Randy J. Dannin,2000
USD
USD
USD
USD
USD
USD
USD
USD
USD
USD
USD
USD
USD
90,197,288
86,048,080
71,474,288
49,189,576
47,774,792
18,381,592
9,965,772
7,299,353
6,182,210
6,104,450
4,555,723
3,037,672
2,950,132
STRATEGI WHO PERLU
DIJABARKAN DALAM
KEBIJAKS
NASIONAL YG
KOMPREHENSIF
• TCM MEMPUNYAI AKAR SEJARAH JAUH LEBIH
TUA DIBANDING WESTERN MEDICINES
• TELAH PULUHAN ABAT MENYEBAR LUAS
KESELURUH DUNIA (CHINESE OVERSEASE)
DLM KONTEKS PENGGUNAAN OBAT HERBAL YG TERUS MENINGKAT WHO
MENGELUARKAN STRATEGI OBAT TRADISIONAL:
1) INTEGRASI SECARA TEPAT OT DLM SISTEM PELAYANAN KES. NASIONAL
2) MENINGKATKAN SAFETY, EFFICACY DAN MUTU DG MEMPERKUAT KNOWLEDGE
BASED, REGULASI DAN QA STANDARD
3) KETERSEDIAAN & KETERJANGKAUAN TERUTAMA UNTUK MASY TIDAK MAMPU
4) MEMPROMOSIKAN PENGGUNAAN OT SECARA TEPAT KPD PROFESIONAL MEDIK
MAUPUN KONSUMEN
Negara-negara Penghasil Herbal di dunia
Cina
•Sejak 5000 th silam, kitab tertua : Huang Di Nei Jing (Kitab Kaisar Kuning) dan Wai Tai Mi Yao (Resep
Rahasia).
•Kitab tua yang paling terkenal adalah Kompendium Materia Media, yang diterbitkan pada tahun 1590. Buku
yang ditulis oleh Li Shizhen dan diteruskan oleh Zhan Xueim ini memuat 1.892 zat medis yang berguna
dalam dunia pengobatan.
•Perkembangan pengobatan tradisional di negara ini relatif maju karena pemerintahnya mendukung penuh
India
•Ayurveda atau ilmu tentang kehidupan adalah sistem holistik kuno untuk mendiagnosis serta
mengobati, sudah ada sejak 1.000 SM di India.
•Ayurveda mungkin merupakan sistem kedokteran tertua yang dikenal manusia.
Korea
• Sistem pengobatan tradisional di Korea dikenal dengan nama Korean Oriental Medicine (KOM)
atau lebih populer dengan sebutan hangbang.
•Perkembangan KOM terlihat dari banyaknya sekolah lanjutan tinggi yang khusus
mempelajarinya. Tak heran jika di Korea mudah dijumpai dokter dan apoteker khusus KOM
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