Pharmacognosy (1)

INTRODUCTION Pharmacognosy - applied science that deals with the biological, biochemical and economic features of drugs of biological origin and their constituents Focuses of Pharmacognosy  Identification of plants and animals  Chemistry  Evaluation, preservation and use of crude drugs  Toxicology  History, distribution, collection and selection  Preparation for commerce Brief History  Papyrus Ebers - Egyptian document - George Ebers - uses of plants and animals  Dioscorides - De Materia Medica - 600 medical plants  Claudius Galen - drugs from animals and plants - “galenicals” - documented methods of preparation of drugs  C.A. Seydler - introduced the term “pharmacognosy” - pharmakon – drug - gnosis – knowledge  Schmidt - first to use the term “pharmacognosy” Drug Constituents  Natural – directly obtained from nature (e.g. camphor tree  camphor)  Synthetic – manufactured o Semi-synthetic – natural raw material, chemically modified (e.g. pinene  camphor) o Totally synthetic – from chemicals (e.g. cyclopentadiene  camphor)

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Crude Drugs – vegetable or animal drugs that consist of natural substances that have undergone only the process of collection and drying Derivatives or Extractives – chief principles or constituents of crude drugs that are separated and used in a specific manner Naturalized Plants – grow in localities other than their native country Indigenous Plants – growing in their native country

Preparation of Crude Drugs 1) Collection – select the species to cultivate 2) Harvesting - gather the samples on a specific and proper period or season - can use manual labor or mechanical device 3) Drying - remove moisture to prevent fungal and microbial growth - fixes the constituent - converts the drug into a form more convenient for shipping and handling o temperature control o regulation of airflow 4) Curing - special drying process that enhances the property of the active ingredient o Cascara sagrada (fresh)  reduced glycoside which is irritating o Cascara sagrada (cured x 1 year with MgO)  oxidized glycoside which is less irritating 5) Garbling - final step - physical process of separating extraneous materials (dirt, soil, insects, other plants/ plant parts) 6) Preservation, Storage and Packaging - protect and market the drug

Classification of Drugs  Morphologic Classification – based on the plant or animal part used  Taxonomic Classification – based on natural relationship or phylogeny  Pharmacologic or Therapeutic Classification – based on the drug’s therapeutic effect  Chemical Classification - preferred in the method of study - based on the chemical class of the active ingredient CARBOHYDRATES AND RELATED COMPOUNDS Carbohydrates - most abundant group of organic molecules - first products of photosynthesis 6CO2 + 6H2O  C6H12O6 + 6O2 - general/ empirical formula (CH2O)n - polyhydric aldehydes and ketones

Functions of Carbohydrates  provide significant amount of energy (e.g. glucose)  storage of energy (e.g. starch, glycogen)  cell components (e.g. glycoproteins)  structural components (e.g. chitin) Classes of Carbohydrates 1) Sugars (monosaccharides, disaccharides, oligosaccharides) 2) Polysaccharides Monosaccharides - simplest CHO unit - cannot be [H2O] into simpler sugars - building blocks of CHO 1) Diose (2C) – e.g. hydroxyacetaldehyde (doesn’t occur in nature) 2) Triose (3C) – e.g. glyceraldehydes, dihydroxyacetone 3) Tetrose (4C) – e.g. erythrose

4) Pentose (5C)  Ribose - aldopentose - product of gum [H2O]  Ribulose – ketopentose  Xylose - aldopentose, diagnostic aid for intestinal absorption - wood sugar, absorbed but not metabolized - simplest sugar in plants - not found free, occur as xylan polymer  Xylulose – ketopentose 5) Hexose (6C)  Glucose (accepted chemical name) - Dextrose - aldohexose - most abundant form: -D glucose - grape sugar - physiologic sugar - obtained by controlled enzymatic [H2O] of starch - as nutrient by mouth, by injection (caloric agent)  Fructose - ketohexose - fruit sugar - sweetest sugar, bitter aftertaste - obtained by inversion of aqueous solution of sucrose or hydrolysis of inulin - as nutrient for DM patient  beneficial in acidosis - as nutrient in infant formulas - high fructose sweeteners  obtained from isomerization of glucose by glucose isomerise  Galactose - aldohexose - C4 epimer of glucose - found in milk (as lactose) - found in neuronal fibers (as galactosides

Gaucher’s Disease  inability to breakdown galactose - Mucic Acid Test (+) white ppt with oxidizing acid galactose  galactaric acid (mucic acid) o

6) Heptose (7C)  Sedoheptulose – ketoheptose 7) Nonose (9C)  Neuraminic acid/ sialic acid Disaccharides - composed of 2 monosaccharides linked by glycosidic bond 1) Sucrose - table sugar - glucose + fructose - -1,2 bond (reducing groups are linked together) - non-reducing sugar - sources: o beet (Beta vulgaris)  cut into limp slivers (cossettes) o sugarcane (Saccharum officinalum) o sugar maple (Acer saccharum) o sugarcane juice boiled with lime (neutralize plant acids, coagulate albumins)  sucrose – decolorized with SO2  molasses – residual dark-colored syrup after the complete crystallization - only disaccharide that occurs free in nature - undergo inversion sucrose  glucose + fructose - pharmaceutic necessity in preparation of Syrup, NF  85% (sufficiently bacteriostatic, self-preserving) masks disagreeable taste of drugs - demulcent, nutrient

2) Maltose - malt sugar - major degradation product of starch - glucose + glucose - -1,4 bond - reducing sugar 3) Lactose - milk sugar - glucose + galactose - -1,4 bond - reducing sugar - from cow’s milk (cow - Bos taurus) - uses: o tablet diluents (because it is inactive) o infant feed (important to establish normal flora in the gut Lactobacillus sp.) 4) Milk products  Butter – formed when fat globules unite  Buttermilk – liquid left when fat globules unite  Skimmed milk – milk left after the separation of cream  Coagulum – formed when skimmed milk is treated with rennin  Cheese – treated coagulum  Whey – liquid left after separation of coagulum  Condensed milk – partial evaporation of milk in a vacuum with subsequent sterilization usually by autoclaving  Malted milk – milk evaporated with malt extract  Kumyss – fermented milk 5) Lactulose - Duphalac®, Lilac® - fructose + galactose - -1,4 bond - semi-synthetic sugar lactose  lactulose (alkaline rearrangement) - laxative/ stool softener

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MOA o not absorbed in small intestine o fermented in large intestine into lactic acid and acetic acid (laxative effect)

Oligosaccharides - 3 or more monosaccharides 1) Maltotriose - 3 glucose units - intermediate product of starch hydrolysis 2) Dextrin - several glucose units - responsible for browning of bread - product of partial [H2O] of starch (acid/ heat) starch  dextrin  maltotriose  maltose  glucose

Polysaccharides - glycans - complex, high molecular weight polymers of monosaccharides linked by glycosidic bonds  Heteroglycan – different monosaccharides  Homoglycan – same monosaccharides Homoglycans 1) Cellulose - structural polysaccharide in plants - homopolyglycan - -1,4 bond  Purified cotton (Gossypium hirsutum)  Powdered cellulose – mechanically disintegrated -cellulose (disintegrant)  Microcrystalline cellulose – partially depolymerised -cellulose (diluents)  Pyroxylin - cellulose nitrate (nitric and sulphuric acid) - soluble gun cotton - preparation of collodions 2) Chitin - structural polysaccharide in animals

in arthropods (exoskeleton) and molluscs (shells) homoglycan of N-acetylglucosamine

3) Starch - storage polysaccharide in plants - components: Amylose Amylopectin more branched Linearity linear (q 25-30 units) -1,4 Bonds -1,4 -1,6 Solubility in H2O less soluble more soluble Size 250-300 units > 1000 units Iodine dark blue color blue-violet color  glutens – tacky proteins that retard the free flow of starch - official sources: o corn (Zea mays) o potato (Solanum tuberosum) o rice (Oryza sativa) o wheat (Triticum aestivum) - other sources: arrowroot (Maranta arundinacea) - uses: o dusting powder o diluents o binder o disintegrant o antidote for iodine poisoning  starch paste – dispersing starch in cold water, boiling until the granules swell and burst forming a translucent solution  heta starch - contains ≥ 90% amylopectin - more soluble - plasma expander in shock patient 4) Glycogen - storage polysaccharide for animals - more branched than starch (q 10 units) - supplies energy (glucose) 8-12 hrs - Glycogen Storage Diseases: o GSD Type I - Von Gierke’s Disease - deficiency of glucose-6phosphatase glycogen  glucose-6-PO4  glucose - mental retardation

5) Inulin - polyfructan - -2,1 bond - abundant in family Asteraceae (compositae) e.g. sunflower - improve digestion - diagnostic aid to estimate GFR (inulin clearance), not secreted not reabsorbed 6) Dextran - homopolyglycan - -1,6 bond - from sucrose by action of a transglycolase enzyme system (dextran sucrose) found in Leuconostoc mesenteroides - used as a plasma expander - preparation: Iron dextran  hematinic (IV/IM) Heteroglycans (more than 1 type of sugar) 1) D-gluco-D-mannan – glucose + mannose Metabolically Related 1) Acids a. Citric acid - tricarboxylic acid - discovered by Scheele in lemons - acidulant in effervescent preparations - salts: o systemic alkalizers o anticoagulants b. Tartaric acid - dicarboxylic acid - byproduct of wine industry - buffer and acidulant in effervescent preparation  Denige’s Test – differentiate citric and tartaric acid c. Lactic acid - lactic fermentation of sugars - acidulant in feeding formulas

2) Alcohols a. Ethanol - ≥ 92.3% or ≥ 94.9% EtOH at 15.56˚C - 70% local anti-infective  Diluted alcohol – 48.4-49.5% ~ 50% alcohol  Brandy – wine  Whisky – fermented malted grain  Rum – fermented molasses b. Mannitol - manna (dried saccharine exudates of Fraxinus ornus) - laxative (osmotic), not absorbed - also used to estimate GFR - sugar alcohol (from mannose)

c. Sorbitol or Glucitol - moutain ash (Sorbus aucuparia) - reduction product of glucose - humectants - non-caloric sweetener d. Dulcitol or Galactitol – reduction product of galactose Gums and Mucilages Gums - natural hydrocolloids that maybe anionic or non-ionic as their salts - translucent and amorphous - typically heteropolysaccharides - occur as salts of Ca++ and Mg++ - protective for plant injury Linear Branched less soluble more soluble less stable more stable less gelling (viscosity gelating agent enhancers) - general uses: o ingredient in dental and other adhesive o bulk laxatives o pharmaceutic necessity: binder, emulsifying/ suspending agent, viscosity enhancer, gelling agent - precipitated from solution by lead acetate or alcohol (e.g. acacia gum)

1) Shrub and Tree Exudates a. Tragacanth - gum tragacanth - Astragalus gummifer - composed of: o bassorin - ⅔ H2O  swells in water o tragacanth - ⅓ H2O  dissolves in water - most acid-resistant hydrocolloid - suspending agent (5-6%) - emulsifying agent - 3 forms: o Vermiform - worm-like, coiled - natural injuries - yellowishbrown o Tragacanth sorts - irregular tearshaped - natural injuries - yellowishbrown o Ribbon and Flake Gum - ribbon/ flaked - from manmade transverse incision of the bark - preferred form/ grade b. Acacia - Egyptian gum - Gum Arabic - Acacia senegal - Arabin  Ca, Mg, K salt or Arabic acid - stable below 60% alcohol - 12-15% H2O - stable at pH 2-10 - suspending agent (35-38%)

c. Ghatti Gum - Indian gum - Anogiessus latifolia - branched hydrocolloid - discontinuous mucilage substitute for acacia d. Karaya Gum - Sterculia gum - Sterculia urens, S. villosa, S. tragacantha - has a fetid odor - one of the least soluble plant gums - discontinuous mucilage 2) Marine Gums a. Algin - Na alginate (Na salt of alginic acid), suspending agent - Macrocystis pyrifera Laminaria spp. Ascophyllum spp. Ecklonia spp. Nereocystis spp. b. Agar - Japanese isinglass - Gellidum cartilagineum Gracilaria confervoides Rhodophycaceae - composed of: o agarose (SO4) o agaropectin (SO4) - uses: o laxative o suspending and gelling agent o culture medium c. Carrageenan - highly sulphated - Chondrus (Chrondrus crispus) - Irish moss ( Gigartina memillosa) - stabilizer, gelling agent, demulcent, bulk laxative - ingredient in toothpaste

Kappa () stable helix

Iota () stable helix

gelling property gelling property

Lambda () no stable helix non-gelling property (viscosity enhancer)

d. Danish Agar - Furcellaran - Furcellara fastiglata - similar to K-carrageenan - gelling, suspending agent 3) Seed Gums a. Plantago Seeds - Metamucil®, C-lium® - Psyllium seed, Plantain seed - Spanish or French (Plantago psyllium, Psyllium indica) - Indian or Blonde (Plantago ovata) - gum is present in the seed coat - bulk-forming laxative b. Guar Gum - endosperm of Guaran - Cyamopsis tetragonolobus - Galactomannan - bulk laxative c. Locust Bean Gum - endosperm of Carob (Ceratonia siliqua) - St. John’s Bread - Galactomannan - thickener, stabilizer - chocolate substitute 4) Plant Extractives a. Pectin - intracellular cementing material - dilute acid extraction from rind of fruits - Pomelo (Citrus grandis) Orange (C. aurantium) Dalanghita (C. nobilis) Ponkan/ Tangerine (C. sinensis) Kalamansi (C. microcarpa) Grapefruit (C. paradisi) Lemon (C. limon) Apple pomace (Pyrus malus)

- forms: o protopectin (unripe fruits) o pectin (ripe fruits) o pectinic acid (overripe fruits) - uses: o protectant o suspending agent o anti-diarrheal (Kaolinpectin) 5) Starch and Cellulose Derivatives 6) Microbial Gums a. Xanthan Gum - high molecular weight gum from the action of bacterium Xanthomonas campestris on a suitable carbohydrate - pseudoplastic flow  responsible for ability of toothpaste and ointments to retain form and be able to spread readily b. Dextran Gum