Phytopharmaceutical Technology

NATURAL MEDICINESNATURAL MEDICINES

TRADITIONAL Necessity of PRACTICAL INCREASING USAGE STOCK USAGE EFFECTIVENESS FRESH DRIED EXTRACT- ACTIVE PLANT PLANT PURIFIED CHEMICAL MATERIALS MATERIALS EXTRACT CONSTITUENTS

DIRECTLY INFUSION PHARMA- PHARMA- CONSUMED (DI GODOG) GEUTICAL CEUTICAL (Lalapan) (DI REBUS) DOSAGE DOSAGE JUICES (DI SEDUH) FORMS FORMS JAMU GENDONG

INSTABLE INPRACTICAL HYGROSCOPIC CONVENTIONAL VOLUMINOUS VOLUMINOUS INSOLUBLE DRUG

EXTRACTEXTRACTCONCENTRED PREPARATIONCONCENTRED PREPARATIONOBTAINED BY EXTRACTING ACTIVE CHEMICAL CONSTITUENTOBTAINED BY EXTRACTING ACTIVE CHEMICAL CONSTITUENTFROM PLANT OR ANIMAL MATERIALSFROM PLANT OR ANIMAL MATERIALSUSING APPROPRIATE SOLVENTUSING APPROPRIATE SOLVENTFOLLOWED BY EVAPORATION OF SOLVENTFOLLOWED BY EVAPORATION OF SOLVENTAND THE RESIDUAL MATERIAL ARE REEXTRACTEDAND THE RESIDUAL MATERIAL ARE REEXTRACTEDSO THAT THE COMBINED EXTRACT ACHIEVE REQUIRED STANDARDSO THAT THE COMBINED EXTRACT ACHIEVE REQUIRED STANDARD

STEPS OF EXTRACT PRODUCTION 1. PREPARATION OF STARTING MATERIALS2. EXTRACTION3. SEPARATION OF MENSTRUM FROM RESIDUAL MATERIAL4. CONCENTRATION OF MENSTRUM5. DRYING PROCESS

PREPARATION OFOFPREPARATION OFOF STARTING MATERIALSSTARTING MATERIALS

DRYING PROCESSDRYING PROCESS

LIVING PLANT HARVESTED ORGAN DRIED MATERIAL PHOTOSYNTHESIS DISCONTINOUS OF < 10% WATER BIOSYNTHESIS NUTRITIONAL SUPLY CONTENT

NATURAL > 10% WATER CONTENT DENATURATION ENZYMATIC ENZYME STILL ACTIVE OF ENZYME REACTION INHIBITION OF MICROBES CHEMICAL AND DECOMPOSITION OF STABILITY OF PHYSICAL ACT. CHEM. CONST. ACT. CHEM.CONST. STABILITY AND MICROBIAL AND PHYSICAL CONTAMINATION PROPERTIES

PULVERIZATIONPULVERIZATION

BORDER PHASE DISTANCEBORDER PHASE DISTANCE((TEBAL LAPISAN BATASTEBAL LAPISAN BATAS))

Required distaince of solvent penetration to achieve active Required distaince of solvent penetration to achieve active chemical constituents in the cells of powderchemical constituents in the cells of powder

FINER IS THE POWDER SHORTER IS THE BORDER PHASE DISTANCE

EASIER IS THE SOLVENT PENETRATION

IN ACHIEVING ACTIVE CHEMICAL CONSTITUENTS

MORE EFFECTIVE IS THE EXTRACTION PROCESS

IN REALITY

IT IS NOT ALWAYS THE CASE

SOME DISADVANTAGES OF TOO FINESS POWDERSOME DISADVANTAGES OF TOO FINESS POWDEROF PLANT MATERIALOF PLANT MATERIAL

1. EVAPORATION OF VOLATILE OIL DUE TO BROKEN CELLS In THE POWDER

2. INSOLUBLE BALLAST SUBSTANCES DISCHARGE THE MENSTRUM

WATER INSOLUBLE SUBSTANCES : LIPIDS

CHLOROPHYL

RESINS

ETHANOL INSOLUBLE SUBSTANCES : CARBOHYDRATES

PROTEINS

3. VERY FINE INTERCELLULAR SPACE CAUSES CLOGGING IN PERCOLATION PROCESS

4. RHIZOMES AND SEEDS CONTAINING STARCH WILL GELATINIZE IN THE PRESENT OF WARM WATER 　 =>

　　 THE MIXTURE BECOME STICKY AND FORMS PORRIDGE

STEPS OF EXTRACTIONSTEPS OF EXTRACTION

１． SOLVENT PENETRATION INTO CELLS

Border phase distance – Powder finess

Hardness of cells – Leaves, flowers, rhizomes Soft

　　　　　　　　　　　　　　 Woods, certain fruits Hard

　　 Solvent – Biger is the percentage of OH group,

stronger is the penetration capability of solvent

Water > Glycerol > Methanol > Ethanol > Eter

2. DEVELOPMENT OF INTRA AND INTERCELLULAR SPACE

3. CONTACT BETWEEN SOLVENT AND ACTIVE CHEMICAL CONSTITUENTS

STEP OF EXTRACTION (Continued)STEP OF EXTRACTION (Continued)

4. DISSOLUTION OF ACTIVE CHEMICAL CONSTITUENTS Polarity of solvent and active chemical constituents – Like and Dislike Solvent saturation – Percolation (supply of new solvent) > Maceration Heating process – Decrease viscosity of solvent – Increase capability in dissolving active chemical constituents Stirring and shaking - Increase dissolution of active chemical

constituents

5. DIFFUSION OF ACTIVE CHEMICAL CONSTITUENTS TO OUTSIDE CELLS

Different concentration of solute in solvent between outside and inside cells – Concentration equilibrium – Percolation > Maceration

Pressure – Percolation (liquid flow of addition solvent) > Maceration Created by addition of pressure or vacum

SOLVENTS SOLVENTS DISSOLVED CHEMICAL CONSTITUENT GROUPSDISSOLVED CHEMICAL CONSTITUENT GROUPS

HEXANE Terpenoids (volatile oil), Triterpenes, Steroids, Coumarins, Benzene, Toluene Polymethoxy flavones, Lipid, Resin, Chlorophylls, Xanthophylls

CHLOROFORM All above mentioned groups, Anthraquinones, Free alkaloids, Dichloromethane Curcuminoids, Free phenols

DIETHYL ETHER All above mentioned groups, Flavonoid aglycones, Phenolic acids

ETHYL ACETATE All above mentioned groups, Flavonoid monoglycosides, Acetone Quasinoids, Other glycosides

ETHANOL All above mentioned groups, Flavonoid diglycosides, Tannin, And other alcohols

HOT WATER All above mentioned groups starting from those dissolved in diethyl ether, Alkaloid salts, Flavonoid polyglycosides, Mono- and Disaccharides, Amino acids and Proteins

STABILITY OF ACTIVE CONSTITUENTSSTABILITY OF ACTIVE CONSTITUENTSEsters : Methyl salicylate Gaultheria fragrantissima Wall Counter irritant Hydrolysis : Methanol and

Salicylic acid Benzyl acetate Jasminum officinale L. Aromatherapy Hydrolysis : Benzyl alcohol and Acetic acid

OC

OH3C

C

O

OCH3

OH

Ethyl p-methoxy cinnamate

Kaempferia galanga L.

Expectorant and Analgesic

Hydrolysis : Etanol and

p -Methoxy cinnamic acid

Linalyl acetate

Ocimum basilicum L.

Aromaterapi

Hydrolysis : Linalyl alcohol and

Acetic acid

O

C CH3

O

OCH3

C CH

CO

OC2H5

H

GLYCOSIDEGLYCOSIDE

Apium graveolens L.

Apigenin-7-O-apiosyl-glucoside

Apiin Apigenin

Polar Semi polar

Water soluble Ethanol soluble

Apiosil-glukosil-O O

O

OH

OH

O

O

OH

OH

HO

POLYSACCHARIDESPOLYSACCHARIDES

Plantago major L. seedsGuazuma ulmifolia Lamk. leavesPOLYSACCHARIDE MONO/DISACCHARIDE- Water soluble fiber - Glucose, galactose- Mucilage - Sucrose, lactose- Big molecule - Small molecule - Difficult to be absorbed - Easy to be absorbed

- Facilitating defecation - Source of energy - Decrease appetite - Increase body weight - Slimmer

OXIDATION & POLYMERIZATIONOXIDATION & POLYMERIZATION

Mono and sesqui terpene

(component of volatile oils)

oxydation

Become darker

polymerization

Resin

Insoluble

Increase toxicity

ULTRAVIOLET LIGHTULTRAVIOLET LIGHT

Azulene - Curcuma aeruginosaChamazulene – Matricaria chamomilla Unsaturated sesquiterpene Blackish blue color Decoloration by UV lightCurcuminoid or Diarylheptanoid Indirect exposure of UV light Prohibited disinfection by radiation

HEATING FACTORHEATING FACTOR

Volatile oils- Terpenoid hydrocarbon with low boiling point

evaporated, disappear- Sesquiterpene lacton - thermolabile

Poly unsaturated compounds- Carotenes- Curcuminoid- Poly unsaturated fatty acid (PUFA)

pH FACTORpH FACTOR

Inactivation of enzyme by boiling of Curcuma

rhizomes in water containing Calcium Bright

brownish yellow

Big mistake

Disappearance of Volatile oil by water steam

Decomposition of Curcumin to become ferulic

acid

NECESSITY OF STANDARDIZATIONNECESSITY OF STANDARDIZATION

CHEMICAL CONSTITUENTS : - Active chemical constituents – Dose influencing

therapeutic effect

- Ballast substances- carbohydrate, protein, lipid, chlorophyll, resin, tannin - Saturation of extract Influence the solubility of active constituents - Influence absorption of active constituents

- Starting materials, extracts, and products must be standardized

PRODUCTION OF PURIFIED EXTRACTPRODUCTION OF PURIFIED EXTRACT

- DELIPIDATION and FRACTIONATION

- SAPONIFICATION

- RESIN ELIMINATION

- DISTILLATION

- PRECIPITATION BY :

- Different solvent polarities

- Heavy metal – Poly phenol reaction

- Protein – Tannin reaction

- ALKALOID SEPARATION

DELIPIDATION AND FRACTIONATIONDELIPIDATION AND FRACTIONATION

PLANT POWDER PLANT POWDER PETROLEUM ETHANOL ETHER RESIDUE EXTRACTNON POLAR RESIDUE ETHANOLSUBSTANCES Chloroform Evaporation; /Ether + Hot Water

SUSPENSIONRESIDUE EXTRACT CHCl3 Ether: Ethanol /ETHER Ethyl acetate: Butanol

EXTRACT ETHANOL DIFFERENT FRACTIONS

SAPONIFICATIONSAPONIFICATION

NON POLAR / LIPID EXTRACT KOH Solution

SOAP WATER FRACTION

Ether

WATER ETHER FRACTION FRACTION (TRITERPENE

STEROID CAROTENOID)

RESIN ELIMINATIONRESIN ELIMINATION

ETHANOLIC EXTRACT ETHANOLIC EXTRACT

Petroleum ether KOH ethanolic

/Hexane

PE/Hexanic INSOLUBLE PRECIPITATE SOLUBLE

FRACTION FRACTION (RESIN) FRACTION

CURCUMIN PIPERINE

DISTILLATIONDISTILLATION

NON POLAR/ LIPID EXTRACT

+ WATER DISTILLATION

ESSENTIAL OIL NON VOLATILE FRACTION