MAKALAH PLENARY DISCUSSION

BLOK FITOFARMAKA

SKENARIO IN ENGLISH

TUTORIAL 7 2019

Disusun oleh:

Nabila Khaula Rahma :20180350003

Anifa Zuhanna Wiratna Putri :2080350010

Dwi Ayuningrum :20180350020

Nurul Inaayah Prasistaratri :20180350035

Feby Puspitasari :20180350040

Bella Nugraini :20180350056

Hilmi Adil Pangarso :20180350063

Tasya Okta Permata B :20180350065

Mohamad Hilman Nurhakim :20180350066

 M. Fanka Hajriantipo :20180350078

Fanny Rohimatul Azizah Putri :20180350096

Novita Zulaekhah :20180350103

Fitri Rahmayanti :20180350109

CHAPTER I INTRODUCTION

A. Background

Indonesia is the second richest country in the world in terms of biodiversity. There are around
30,000 species that have been identified and 950 of them are known to have biopharmaca
functions, namely plants, animals, and microbes that have potential as medicines, health food,
nutraceuticals, both for humans, animals and plants.

With this wealth, Indonesia has a great opportunity to become one of the largest countries in the
traditional medicine and natural cosmetics industry with plant-based raw materials whose market
opportunities are quite large.

As an alternative to the development of biopharmaca, fitofarmaka or better known as medicinal

plants, has great potential in the development of Indonesia's traditional medicine and cosmetics
industry. During this time, the industry developed by utilizing plants obtained from natural forests
and very little has been cultivated by farmers. If as for, the technique of cultivation and processing
of raw materials has not applied the raw material requirements desired by the industry, which is
free of chemicals and not contaminated with mold or other impurities.

In promoting the development of phytopharmaca-based agribusiness at the farm level, it is very

important to increase the ability of farmers in terms of medicinal plant cultivation. In addition to
cultivation, the post-harvest and marketing aspects also need to be improved in an effort to spur
the development of Indonesia's traditional medicine and cosmetics industry.

Medicinal natural ingredients that were originally widely used by countries in Asia, South America
and Africa, now extends to developed countries in Australia and North America. Initially natural
medicinal ingredients are used as a hereditary tradition. With the advancement of science and the
development of technology, both production and information, preclinical and clinical trials are
conducted to gain confidence in the efficacy of natural medicine.

B. AIM

students are able to develop the phytopharmaca immunostimulator formula derived from
Morindae citrifolia / Echinacea sp.

C. SCENARIO

RZ works in an RnD natural materials industry. He was tasked with developing the
phytopharmaca immunostimulator formula derived from Morinda citrifolia / echinacea sp. To
meet Halal requirements, the halal production process must also be guaranteed.

CHAPTER II CONTENT

What is definition of Morindae citrifolia L / Echinacea sp?

Morinda citrifolia L has regional names: Eodu, noni, bengkudu, (Sumatra); kudu,
cengkudu, kemudu, pace (Javanese); wangkudu, manakudu, bakulu (Nusa Tenggara); andin
Kalimantan known as mangkudu, wangkudu, and labanan (Wijayakusuma, 1995).
Division: Spermatophyta
Subdivision: Angiosperms
Class: Dicotyledone
Class children: Sympatalae
Nation: Rubiales
Tribe: Rubiaceae
Genus / genus: Morinda
Type / species: Morinda citrifolia L.
Plant morphology
This plant is shaped tree with a height of 4-8 cm. Woody stems, rounded, rough skin, monopoidal
branches. Single leaf, ovoid, pointed tip and base. 10-40 cm long. Compound interest, humped
shape, stemmed, stamens 5. Humped fruit, irregular surface, fleshy, 5-10 cm long, yellowish green
(Syamsul hidayat and Hutapea, 1991).

Chemical content

Noni contains scopoletin, routine, polysaccharides, ascorbic acid, β-carotene, 1-arginine,

proxironin, and proxeroninase, iridoid, asperolusid, iridoid anthraxone, fatty acids, calcium,
vitamin B, amino acids, glycosides, and also glucose (Sjabana) and Bahalwan, 2002;
Wijayakusuma and Dalimartha, 1995). It also contains compounds such as, morindon, rubiadine,
and flavonoids (Bangun and Sarwono, 2002).
Noni fruit extract also contains xeronin and proxeronin which function to normalize damaged cell
function, so that the immune system increases. Xeronin also plays a role in activating the thyroid
and thymus glands that function in the body's immunity
Noni Active Substance Content

Almost all parts of the noni plant contain a variety of chemical compounds that are useful for
human health and medicine. Compound -
compounds that play a role in traditional medicine are compounds found in the fruit, including
xeronine, proxeronine, proxeronase, serotonin, dammacanhtal, (anti-cancer substances),
scopoletin, vitamin C, anti-oxidants, minerals, proteins, carbohydrates, enzymes, alkaloids, plant
cofactors and other very active phytonutrients that are very powerful in strengthening the immune
system, improving cell function and accelerating the regeneration of damaged cells. The chemical
content of noni leaves and fruits generally contains alkaloids, saponins, flavonoids, terpenoids,
and antraquinone, besides that the leaves also contain polyphenols.
One of the important alkaloids found in noni is xeronine. Xeronine is also produced by the human
body in limited quantities which functions to activate enzymes and regulate protein function in
cells. Xeronine was first discovered by Dr. Ralph Heinicke (biochemist). Although noni fruit
contains only a small amount of xeronine, it contains xeronine precursor ingredients, namely
proxeronine in large quantities.
According to Bangun (2002), noni contains proxeronine which is a molecule. Compared to other
alkaloid molecules, proxeronine does not contain sugar, amino acids, or nucleic acids. Winarno
(2003) further argues that alkaloids are secondary metabolites as a result of the continuous flow of
photosynthetic metabolism (proteins, starches, lipids) in plants in low concentrations that can
provide certain physiological effects on an organism.

what is the mechanism of Morindae citrifolia L?

Its mechanism of action damages bacterial cell walls, destroys the cytoplasmic membrane and
inhibits the work of enzymes in bacterial cells. While the alkaloid compound, has the ability as an
antibacterial by disrupting the constituent components of peptidoglycan in bacterial cells so that
the cell wall layer is not formed intact and imperfect because it does not contain peptidoglycan
and the cell wall only covers the cell membrane.

what are the sympathetic test methods?

1. Alkaloid test
2. Steroid test
3. Flavonoid test
4. Tanin test
5. Antrakuinon test
6. Saponin test

What IS THE DEFINITION OF ECHINACEA?

Echinacea is one of Coneflowers, a group of wildflowers originating in North America, including

the Daisy family (Asteraceae). The shape of this plant is characterized by spiny flowering heads,
with an elevated receptacle which froms the "cone". Of the 9 extant species, 3 have been developed
into medicinal plants and have been commercialized, namely: Echinacea purpurea (L.) Moench.,
or purple coneflower, E. pallida (Nutt.) Nutt., or pale coneflower and the DC. angustifolia E., or
Narrow-leaved Echinacea. The history of Echinacea use can be seen in American Indians, who
have used it to heal wounds, snakebites, headaches, and common cold. In herbal medicine,
Echinacea has been used for sinusitis, otitis media, lower urinary tract infections, additional
treatment for recurrent vaginal infections by Candida albican, skin infections and carbunkel,
wound healing, anti-inflammatory, in Europe and The United States is reportedly effective for the
prevention and treatment of common cold although in some studies the product used not only
consisted of Echinacea, but also other crops. The most uses are for the prevention and treatment
of common cold, through its ability to stimulate the immune system.

History of Echinacea use can be seen in the American Indian tribe, who had used it to heal wounds,
snake bites, headaches, and common cold. In herbal medicine, Echinacea has been used for
sinusitis, otitis media, lower urinary tract infections, additional treatment for recurrent vaginal
infections by Candida albican, skin infections and carbunkel, wound healing, anti-inflammatory,
in Europe and The United States is reportedly effective for the prevention and treatment of
common cold although in some studies the product used not only consisted of Echinacea, but also
other crops. The most uses are for the prevention and treatment of common cold, through its ability
to stimulate the immune system.Common cold treatment although on some product studies used
not only consist of Echinacea, but also other crops. Use for prevention and common cold treatment,
through its ability to stimulates the immune system.

1. Pharmacology

The chemical components contained in Echinacea include carbohydrates: polysaccharides

(Arabinogalaktan, Xyloglycan, echinacin), inulin; Glycosides: Kafeat acid and its derivate
(chichoric acid, echinacoside, chlorogenic acid), Cynarin; Alkaloids: Isotussilagine, tussilagine;
Alkylamides (alkamides) such as Echinacein; Polyacetylenes; Germacrene sesquiterpene alcohol;
Other components: glycoproteins, flavonoids, resins, fatty acids, essential oils, phytosterols and
minerals. Kafeat acid derivatives, Cynarin, polysaccharides and glycoproteins are polar while
alkylamides and Polyacetylenes are lipophilic.

What is mechanism of Echinacea as Immunostimulator?

Echinacea affects the immune system, especially Non-specific immune system. Administration of
Echinacea Improve the early phase immune response and adaptive immune response. Burger A.
Roger et al. Conducting in vitro experiments using fresh pressed juice and dried juice Echinacea
with a concentration of 10μg/ml-0,012 μg/ml mixed with the macrophages of human edge blood
that has been isolated and compared with the control group (endotoxin are stimulated and not
stimulated). The calculation of cytokine production is average. From the results it is derived that
the macrophage cultures that have been mixed with Echinacea mean increasing the production of
IL-1, IL-6, IL-10 and TNFα (P < 0.05), at all concentrations used. The mechanism of activation of
the immune system through this cytokine line by Echinacea is not yet known. Besides that
Echinacea is also known to be activating Natural Killer (NK) cells and antibodydependendent
cellular cytotoxicity by mononuclear cells.

What are the Benefits of Echinacea sp?

1. Help prevent cancer

2. Strengthens the body's immune system

3. Pain relief

4. As a natural laxative

5. Anti-inflammatory drugs

What are the stages of drug development?

So that fitofarmaka can be accounted for its safety and efficacy in use in humans, then the
development of traditional medicine must be covers various stages of testing and development
systematically. These stages include:
1. SELECTION STAGE (SELECTION)
Selection of the type of traditional medicine that will experience
testing and development towards fitofarmaka
based on priorities outlined by the Department
Health of the Republic of Indonesia Selection priorities
Presented to:
a. Type of traditional medicine that is expected to have
efficacy for occupying diseases
upper order in morbidity (pattern of disease).
b. The type of traditional medicine that is thought to have
efficacy for certain diseases based
inventory of usage experience.
c. The type of traditional medicine that is estimated is
rare alternative (or the only alternative)
for certain diseases. For example for urination
stone (calculi).
Further provisions regarding the priority of the choice of drug
traditional to be tested and developed in the direction
Fitotarmaka will be determined by the Director General
Drug and Food Control, Ministry of Health
Republic of Indonesia. At this time the test is done
drug candidates that are not narcotics.

2. PHARMACOLOGICAL TESTING STAGE

Screening of the pharmacological effects of Fitofarmaka is aimed at see and pharmacological work
on the biologic system can be a clue to the benefits therapeutic. Testing can be done in vivo or in
vitro in animals try accordingly. Clues about the efficacy of candidates fitofarmaka should be
obtained from in vivo experiments in suitable mammals, wherever possible associated with the
model of the disease in humans. No all therapeutic efficacy of a prospective drug can be estimated
directly from animal experiment models. Some properties that might be estimated from the test
screening with animal testing models such as power analgesics, sleep power, anti hypertension,
anti diabetes, anti arthritis etc. Use of pharmacological screening tests actually is to avoid deep
waste further test phase. Positive results can be used for an estimate of the possible effects on
humans.

3. STAGE OF TESTING TOXICITY

An acute toxicity test involves administering several doses single that increases regularly on
several groups of animals of the same type. Observation of death within 24 hours is used to
calculate LD50, and animals kept for 14 day. An acute toxicity test is a formal prerequisite safety
of fitofarmaka candidates for use on human. Ideally the acute toxicity test is performed on some
types of animals, at least animal types a rodent and one type of non-rodent animal. However due
to various considerations of acute toxicity testing at the time This is quite adequate, when done in
rats from both sexes, using a minimum of animals from each sex per dose. Things to look for here
are: a. Acute toxicity spectrum The most biological system sensitive to candidates Fitofarmaka. b.
Mode of death (mode of death). c. Median lethal dose (LD50) values calculated by standard
statistical methods.

Further toxicity testing includes:

a. Sub-acute Toxicity The design of the sub acute toxicity test is based on acute toxicity test results.
Sub acute toxicity test. Can give an idea about the toxicity of phytopharmaca candidates for use
repeat over a relatively long period of time. Trends in cumulation and reversibility of toxic effects
fitofarmaka candidates can be stated from the test results sub acute toxicity. - Ideal animals try
three types, namely 2 rodents and 1 non rodent, temporarily adequate use one type, namely mice,
at least 3 dose, one dose is the equivalent dose will be used in humans, 10 animals per dose, two
sexes. - The giving route is the same as the route used in humans. - The duration of the test for
giving fitofarmaka candidates in sub acute toxicity 3 (three) months. Examination of vital organs
such as the liver, kidneys, lung, brain, hematologic system, done with standard (standard) method,
including inspection histopathology. Technical implementation of the test must done in standard
(standard) ways meet scientific requirements. When on Observation Acute toxicity test shows
symptoms toxic to the liver and or kidneys then parameters need to be supplemented with
biochemical parameters regarding liver and kidney.

b. Chronic Toxicity Chronic toxicity tests are prioritized for candidates phytopharmaca whose use
is repeated / continued in a very long period of time (more than 6 months). Chronic toxicity test
provides an overview of toxicity or safety of fitofarmaka candidates on repeated use of common
doses for life animal. - Chronic toxicity test design is based on Sub acute toxicity test results. - The
number of animals used must be sufficient a lot, at least 20 animals per dose, so that the test results
chronic toxicity can still be interpreted with careful, despite the death of an animal not related to
the technical matters of the experiment during the testing time.
c. Specific Toxicity
This toxicity test is for example a teratogenicity test, test
carcinogenicity, mutagenicity test, toxicity test
on the fetus, a test of reproductive functions
and others. Whether or not these tests need to be done
depends on the possibility of effects
toxicology, in connection with its use
in humans. For example teratogenicity test or test
fetal toxicity must be worked out if
Fitofarmaka clinic use will later be given to
periods of organogenesis and pregnancy.
Mutagenicity and carcinogenicity tests must be
done when phytopharmaca is used chronically,
penguiian implementation, must meet the methods
common (standard) standards. For preparations
which is used topically is required for
Topical toxicity testing, for example
skin irritation with animal model experiments
corresponding.
4. PHARMACODYNAMIC TESTING STAGE
This stage is intended to be more knowledgeable
straightforward pharmacological effects on various systems
biologically. If needed, research is carried out on
suitable experimental animals, both invitro or invivo.
If a fitofarmaka candidate has undergone a screening test
biologic (stage 2) and is seen as not yet biased or not yet
maybe to do pharmacodynamic testing,
then this should not be a barrier
for more. The pharmacodynamic testing phase will be
depends more on the facilities and infrastructure
exist, both software and hardware.
5. STAGE OF DEVELOPMENT
(FORMULATION)
The development of the preparation is intended to be the dosage form
fitofarmaka which will be given to humans later
meet quality requirements as well
aesthetics. Quality requirements according to the way
gifts both immoral and other ways of giving must be
pay special attention.
Those who need attention are the candidates
fitofarmaka given must:
1. Does not give the smell and taste that it causes
failure of testing (example on garlic).
2. have good bioavailability, test results
pharmacology and clinical trials are dubious, sometimes
sometimes due to the availability of biological candidates
inadequate fitofarmaka.
6. FITOKIMIA SCREENING AND STANDARDIZATION
AVAILABLE
if before the active ingredients are known, the first stage
which must be done in conjunction with clinical testing
in making a chromatogram profile in stages with
non-polar, semi-polar and polar solvents.
Then the standard preparations are carried out with
using identity substances.
Further phytochemical research is determination
active chemical content. If the chemical content is active
preparations are known, it can be done
standardization of preparations based on content
the active.
7. CLINICAL TESTING STAGE
Requirements for fitofarmaka candidate clinical trials
such as :
a. There are basic considerations in the implementation of the Basics
consideration of doing a clinical test on a
fitofarmaka candidates are:
- There is an empirical experience that a candidate has
fitofarmaka has clinical benefits
in the prevention and treatment of diseases or
symptoms of the disease.
- Presence of pharmacological data in testing
against animals that show phytopharmaca
it has a pharmacological activity
relevant.
b. Requirements for clinical trials on fitofarmaka
Clinical trials can be performed on humans if
has been proven safe based on research
toxicological and declared eligible
security for testing in humans.
c. Criteria for carrying out clinical trials
- Fitofarmaka clinical trials must meet the scientific and methodological requirements of a clinical
trial for
development and evaluation of a new drug.
- Fitofarmaka clinical trial protocol must be done
approved by a Scientific Committee
independent
- Fitofarmaka clinical trials can only be done by
several people (teams) of researchers who have
expertise, experience, authority and responsibility
responsible for clinical testing and drug evaluation.
- Fitofarmaka clinical trials must meet ethical principles from the planning stage
until the completion of clinical trials
- Every test must obtain eligibility permission
Ethics (Ethical clearance) from the Ethics Committee
Biomedical research in humans.

What is MUI Menu Halal Requirements?

 Material Requirements in Halal Certification
1. All materials (raw materials, auxiliary materials and auxiliary materials) used must meet
the halal standard of ingredients
2. Materials in the form of intermediates or raw products may not be produced from
production facilities which are also used to make products that use pigs or their derivatives
as one of the ingredients.
3. Companies that implement the coding of ingredients or products must be able to guarantee
traceability (ingredients, producers, halal status). Coding must also guarantee that the
material with the same code has the same halal status.
 Material Standards for Halal Certification
1. Does not contain pigs or piglets
2. Does not contain alcoholic drinks (khamr) and its derivatives
3. All material from animals (not fish / animals that live in water) must be from halal animals
and slaughtered according to Islamic rules (proven by MUI halal certificate or from
institutions recognized by MUI)
4. does not contain unclean substances such as carcasses, blood and parts of the human body
 Examples of Halal Materials According to MUI
1. Gelling Agent Type of product (Type of product):
a. Gelatin
b. Agar Flour (Agar Powder)
c. Gum (guar gum, arabic gum, carob bean gum, etc.)
d. Carrageenan (Carrageenan)
e. Seaweed Flour (Sem, veed Powder)
f. Konyaku (Konjac)
g. CMC (Carboxymethyl cellulose)
h. Pectin (Pectin)
i. Alginate (Alginate)
j. Qelly Powder Jelly Powder)
2. Oil, Fat and Processed Product Groups (Oil, Fat and Processed Products) Product type (Type of
product):
a. Oils (sawil, sesame, jagurrg, hazelnut, cotton seeds, olives, canola, peanuts, soybeans, etc.) I Oil
(palm, coconut, sesame, corn, candle nut, cottonseed, olive, canola, xrx ground nut, soya bean, etc)
b. Animal Fat (chicken fat, beef fat, tallow, etc.) / Animal Fat (Chicken Fat, Beef Fat, Tallow, etc)
c. Processed Oil / Fat (Processed Oil / Fat)
d. Oleochemicals (glycerin, triacetin, fatty acids, fatty acid esters, stearin, olein, etc.) /
Oleochemicals (glycerin, triacetin, fatty acids, esters offatty acids, stearin, olein, etc)
e. Samin oil (Vegetable Ghee)
f. Crude / RBD Oil: CPO, CPKO, RBDPO, RBDPKO, crude palm olein, crude palm stearin, RBD
palm olein, RBD palm stearin, etc.
g. Margarine (Margarine)
h. Reroti Fats (Shortening)
i. Substitute Butter Oil (Butter Oil Substitute)
j. Pan Grease
k. Specialty Fats
l. Oil industry byproducts (palm oil cake, palm fiber, etc.) / By Product of Oil Industry (palm
kernel expeller, palmfiber, etc)
3. Extract Group (Ertract)
Product type (Type of product):
a. Plant Extract
b. Animal Extract (Animal Extract)
CHAPTER III CONCLUSION

 The stages of drug development are selection stage, pharmacological testing stage, stage of
testing toxicity, pharmacodynamic testing stage, stage of development, and fitokimia screening
and standardization available.
 Material Requirements in Halal Certification All materials (raw materials, auxiliary
materials and auxiliary materials) used must meet the halal standard of ingredients, and
Companies that implement the coding of ingredients or products must be able to guarantee
traceability (ingredients, producers, halal status).

References

Halosehat.com 5 Manfaat Bunga Echinacea untuk Kesehatan Tubuh

http://ccrc.farmasi.ugm.ac.id/?page_id=389

https://www.academia.edu/7055500/Fitofarmaka