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DEFINITION Applied science that deals with the biological, biochemical, and economic features of drugs of biological origin and their constituents Medicinal products in crude/unprepared form NOT just plants, but also animals (Sus scofa, etc) *focus on local sources HISTORYA. Babylonians Clay human m...

Description

Pharmacognosy DEFINITION

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Applied science that deals with the biological, biochemical, and economic features of drugs of biological origin and their constituents Medicinal products in crude/unprepared form NOT just plants, but also animals (Sus scofa, etc) *focus on local sources

HISTORY A.

Babylonians • Clay human models of human body • Medicinal effect of plants • Names ending with ‘-zar’ B. Ayurveda (India) • Traditional medicine • Literal meaning: “the science of life” • Mother of all healing arts • (2) texts: 1) Charaka § book on internal medicine (~Harrison’s) 2) Sushruta § Considered as “book of symptoms” § 184 chapters; 1120 illnesses § Many chapters because 1 chapter per human body part (e.g. palm) C. Egyptians • George Ebers – Papyrus Ebers • Introduced embalming – preservation of flesh (mummification) because they believed in afterlife • Human anatomy & use of plants D. Greeks 1. Dioscorides (78 AD) • Wrote De Materia Medica § Aka “The Medicinal Material” § 600+ plant descriptions with pressed plant samples (thick!) § Aloe, belladona, colchicum, ergot, opium 2. Claudius Galen (131-200 AD) • Descibed methods and processes of preparing formulas containing plant and animal drugs (“galenicals”) • Father of Pharmaceutical Compounding

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German 1. CA Seydler (1815) • Coined (but steal intellectual property) pharmacognosy from “pharmakon” (drug) & “gnosis” (knowledge) in Analecta Pharmacognostica 2. JA Schmidt (1811) • First used the word pharmacognosy in his Lehrbuch de Materia Medica (NOT yet a registered word) 3. Friedrich Serturner • Morphine Others 1. Fluckiger on Pharmacognosy • “Simultaneous application of scientific disciplines with the object of acquiring drugs from every point of view” 2. Pelletier & Caventou • Quinine

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Crude drugs • Vegetable/animal drugs of natural substances that had undergone only collection & drying Natural substances • Whole plants and their parts; animals and excised their organs • No molecular modifications made • e.g. oils Derivatives or Extractives • Chief principles/constituents of crude drugs that are separated and used in a specific manner • Solvent/Menstruum – liquid-liquid mixture used to extract active principles • Marc – undissolved portion of drug that remains after extraction is completed Indigenous plants • Grow in their native countries • e.g. balete, rafflesia Naturalized plants • grow in foreign land other than their native homes • e.g. blueberries

PREPARATION OF CRUDE DRUGS 1)

Collection • Collecting not just samples but also data/information (difference from harvesting, you don’t harvest data!) • Ensuring the true natural source of the drug

Pharmacognosy §

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Improper collection – if researcher does not know his plant sample, not enough data § Collection time o Flowers – dawn (when flower just starts to bloom or still a bud) o Bark – between spring (moist) & summer (dry) because very rich in constituents o Root crops (potato, carrots) – when upper ground portions are withered Harvesting • Specific or proper season • Manual labor (for delicate plants) vs. mechanical devices (e.g. tractors) o Coffee beans – floating (not good) à plant again o Strawberries – handpicked bec. succulent o Digoxin Drying • Most important step because it removes moisture to prevent bacterial & fungal growth and enzymatic degradation • Fixes constituents, facilitates grinding & milling • Convert plants to more convenient form • Types: a) Sun drying b) Oven drying c) Air drying Curing (not considered as a step in some references) • Could be under drying • Special drying process that enhances properties of plant’s active ingredients • Examples: a) Cascara sagrada § Anthraquinone glycosides (cathartic) § If NOT cured (fresh) à too irritating § Cured in MgO solution for 1 year à convert to reduced glycosides (active) b) Vanilla planifolia § Sweating – process of curing vanilla § Gray if cured, red if NOT § Wrapped in cloth at night, expose to sun during daytime. Repeat until it releases odor. Garbling • Final step in the preparation of crude drugs • Removal of extraneous matter

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Packaging, Storage & Preservation • Protection and marketability • To avoid insect attacks: a) Simplest method: Expose the drug to 65℃ b) Fumigation with methyl bromide (CH3Br) c) Add a drop of chloroform or carbon tetrachloride

EVALUATION OF CRUDE DRUGS •

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Determines quality and quantity § Quality – intrinsic value of drug; types of AI present § Quantity – amount Involves qualitative and quantitative assays PARAMETERS: 1) Organoleptic Evaluation • Uses the organs of (5) senses (visual, odor, taste, sound, texture) • Evaluates the macroscopic appearance 2) Microscopic Evaluation • Plant samples under microscope • Crystals (rice, potato starch), cells, precipitate 3) Pharmacologic Evaluation • Bioassay – assays that uses living animals or excised organs to evaluate the effects of drugs § Rooster – oxytocin o Oxytocin for homeostasis, labor (uterine contraction), vasodilation o Tie crown à blue (vasoconstriction) à administer oxytocin to rooster’s crown § Pigeon – digitalis (heart rate) § Cat – atropine (easy to see mydriasis) 2+ § Dog – PTH à Ca (bones for dogs) 4) Chemical Evaluation • Assay of active constituents using chemicals (e.g. titration) • Best method of determining official potency 5) Physical evaluation • Determination of various physical characteristics/parameters with the use of physico-chemical techniques • e.g. solubility (sparingly, etc), flowability

Pharmacognosy

CLASSIFICATION OF DRUGS

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Morphology • “morph” – forms (named based on what thing does it resemble) • Plant part used • Leaf and flower arrangement Taxonomic • Carolus Linnaeus – Father of Taxonomy • “King Plays Chess On Fuzzy Green Stools” • Phylogeny § Natural relationship that occurs among plants and animals § Important for pharmacognosy Pharmacologic • Based on therapeutic effect on the body • NOT the most preferred Chemical • Preferred method of classification – more specific than pharmacological • Based on active constituents § Considered as secondary metabolites § Drug biosynthesis or biogenesis – process of producing secondary metabolites

CARBOHYDRATES [CH2O]n ● ● ●

Polyhydric aldehyde or ketone alcohols that contain C,H,O [C●H2O]n H & O has the same ratio as that of H2O, thus they are named as “carbo+hydrates” st 1 product of photosynthesis § Transport system: Xylem – water (l for liquid) Phloem – food (phood)

Classification of Sugars I) II) III) IV)

Monosaccharides Disaccharides Oligosaccharides Polysaccharides A) Homoglycans 1) Starch – glucosan (yields glucose units) 2) Inulin – fructosan (yields fructose units) 3) Cellulose – glucosan (yields glucose units) B) Heteroglycans 1) Gums and mucilages 2) Glycosides

Monosaccharides BIOGENESIS •

(3) Factors: 1) Ontogeny or Stage of Development • e.g. Cannabis sativa aka MJ, Mary Jane, Ashes, Marijuana § Tx of lung conditions (asthma, COPD) § Disposal: incineration or bury (never burn!) § Constituents: a) Cannabidiol – young plant b) Cannabinol – mature plant 9 9 c) 𝛥 -Tetrahydrocannabinol (𝛥 -THC) & nabilone 2) Heredity • Menthol content: Japanese peppermint – 50% > normal peppermint 3) Environment • Sunlight, soil, moisture • Periwinkle or chichirika (Catharanthus roseus) § Vinca alkaloids § Same sp., diff. environment à diff. colors o Wild – blue-violet o Domesticated – pink

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Monosaccharide § Simplest carbohydrate units § Cannot be hydrolyzed to simpler sugars § Names based on # of carbon atoms #C NAME EXAMPLE ATOMS 2 Diose Hydroxyacetaldehyde 3 Triose Dihydroxyacetone, glyceraldehyde 4 Tetrose Erythrose 5 Pentose Arabinose, xylose, ribose 6 Hexose*** Glucose, fructose, galactose 7 Heptose Sedoheptulose 8 Octose D-glycero-D-mannotulose*** Octoses have been synthetically prepared, they do NOT occur in nature 9 Nonose Neuraminic acid (Sialic acid)

Pharmacognosy A) PENTOSE 1) Xylose aka “Wood sugar” • Obtained from boiling corn cobs straw • Diagnostic aid in intestinal malabsorption • Aldehyde § *Note: for ketone form, just add ‘u’ o Xylose à xylulose o Ribose à ribulose

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B) HEXOSE – most important monosacch; can’t oseàulose 1) Glucose aka “Blood, Grape, Physiologic Sugar”(bec. common in body) • Aldohexose • Aldehyde group in C1 • Reducing sugar as det. by Benedict’s test • Occurs as linear & cyclic • 𝛽-D-Glucose – most abundant and important § D-glucose aka dextrose § Use: source and storage of energy, structure of plants • Uses of glucose: 1) Parenteral • Rigorously purified/sterile • Nutrient

Disaccharides Disaccharides – composed of 2 monosaccharides formed via dehydration synthesis which forms glycosidic bonds (dictate what bond - ɑ, β, 1,3, etc) A) Sucrose aka “Table Sugar” • Glucose + Fructose, 𝛼-1,2 bond • Sources of sucrose: 1) Sugar cane – Saccharum officinarum § Boil with dilute acid (to ppt albumin) à pure sucrose § + SO2 – to remove color 2) Sugar beet – Beta vulgaris § Cosettes – limp slivers (very fine) 3) Sugar maple – Acer saccharum § Indigent in Canada • Non-reducing, unlike its components (gluc, fruc) • Uses of fructose: 1) Demulcent 2) Sweetening agent; masks taste 3) Coating agent 4) Preservative (85% sugar) 5) Production of syrups

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Pharmaceutic necessity – less rigorous (just a sweetener) a) Liquid glucose aka syrup • Syrupy liquid, almost colorless, tastes sweet • Incomplete acid hydrolysis of starch b) Dextrose excipient aka sugar/glucose powder • Crystalline sweetening agent • For oral glucose tolerance test (OGTT): 75 g Fructose aka “Levulose, Fruit Sugar” • Aka Levulose, the sweetest monosaccharide but bitter aftertaste • Fruit sugar – sweet fruits and honey § Mango – highest fructose content § *Grape – highest glucose content • ɑ-Ketohexose • Ketone group in C2 • Reducing sugar as det. by Seliwanoff’s test • Uses of fructose: (but glucose is used more) 1) For diabetic Pt 2) Ingredient in infant feeding formula

3) Ingredient in fructose injection nutrient Galactose • Aldohexose • C4 epimer of glucose (C2 epimer – mannose) • Gaucher’s disease – cannot metab. galactose • *Lactose intolerant – cannot metab. lactose • milk : lactose :: neuronal fibers : galactosides

Pharmacognosy 6)

Retards oxidation § Honeys don’t expire (found in pyramids) § Light yellow – baby, NOT therapeutic § Darker – more therapeutic • Molasses § Residual dark colored syrup after complete crystallization of sucrose § Food and EtOH industry § Burnt taste § Horse’s comfort food B) Maltose aka “Malt sugar” • Produced during the germination of barley • Glucose + Glucose, 𝛼-1, 4 bond (*3 Glucose – maltotriose) • Major degradation product of starch • Reducing sugar • e.g. Milo, Nesvita, Energen, cereals, beer, Colt 45 C) Lactose aka “Milk Sugar” • Glucose + Galactose, 𝛽-1,4 bond • Obtained from cow’s milk (Bos taurus) • Reducing sugar • Milk products

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Products of Oxidative Metabolism 1)

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Cherry juice • Ripe fruit of Prunus cerasus (Rosaceae) • Contains pectin & malic acid • Use: cherry syrup as flavorant to mask salty taste (e.g. PCT & cough syrup) Plant Acids • Uses of plant acids: a) Acidulant in effervescent formulations b) Component of buffer systems a) Citric acid (aka TCA)* - isolated by Scheele from lemon juice in 1784 + b) Lactic acid – acidulant in infant feeding formula, feminine wash ( masculine wash – Freshman®) c) Tartaric acid (DCA)* - by-product of wine industry d) Ferrous fumarate - hematinic 2 • *Differentiation test: Denige’s test & TaWi Alcohol or Ethanol • 95% ethanol by volume @ 15.56℃ • •

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D) Lactulose (Lilac®, Duphalac®) • From alkaline rearrangement of lactose • Cathartic & laxative • Converted to lactic & acetic acid, which causes irritation of the intestines and subsequent catharsis • Initially used for MI/stroke Pt to help them poop with no stress thus, Px another MI/stroke • Lactulose + omeprazole – most abused

Normal dose: 30 cc OD HS *Omeprazole § For PPI (stressed-induced gastritis) § 20 md OD PO § Prescribed to all hospital Pt (abused) § Just standard bowel time (evening)

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Product of fermentation Undergo the process of distillation to concentrate the alcohol content to 4055% § Brandy (Brown) – distillation of wine § Whiskey – Malted grain (W à M) § Rum – molasses Concentrations: § 70% (aka rubbing alcohol) – disinfectant o Isopropyl – more effective o EtOH – less irritation § 48.4-49.5% EtOH @ 15.56℃(aka dilute alcohol) Uses of alcohol: § LOW concentration – CNS stimulant § HIGH concentration – CNS depressant Drink caffeine (energy) or alcohol (concentration)?

Pharmacognosy Products of Reductive Metabolism

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Polysaccharides A)

HOMOGLYCANS: yield one type of monosaccharide unit upon hydrolysis 1) Starch • Temporary storage form of photosynthetic products • (Official) sources of starch: a) Corn – Zea mays b) Wheat – Triticum aestivum c) Potato – Solanum tuberosum d) Rice – Oryza sativa • (Unofficial) source - arrowroot (rootcrop) - aka Kuraro (Marinduque) - aka Maranta arundinacea • Starch constituents: DIFFERENCE ON: AMYLOSE AMYLOPECTIN Structure • Linear • Branched • 250-300 D• ≥1000 glucose units glucose units • α-1, 4 and α-1, 6 • α-1, 4 glycosidic glycosidic bonds at bonds every 25 glucose unit Solubility in H2O Insoluble Soluble Iodine test Deep/dark blue Blue violet/purple Ratio 25% 75% •

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Enzymes that break down starches: a) 𝛼-amylase § Present in pancreatic juice and saliva § Metabolism/breakdown of carbohydrates starts in the mouth b) 𝛽-amylase § Hydrolyses starch to nearly pure maltose § Only in fungi, NOT found in humans Uses of starch: a) Tablet filler, binder and disintegrant

b) Antidote for iodine poisoning Starch preparations: a) Pre-gelatinized starch § Chemically or mechanically processed to rupture all or part of the granules § Tablet binder b) Sodium starch glycollate § Disintegrating agent c) Hetastarch (Voluven®) § Plasma expander for shock, hypovolemia (low blood volume) § Hydroxyethyl starch: 6% on the market § 99% amylopectin • Glutens § If starch has glutens à poor angle of repose (poor flowability) bec. it has tacky proteins § Meat substitute, NOT easily digested Glycogen • Storage polysaccharide in animals • Stored in liver and skeletal muscles (glycogen can provide 8-12 hr of energy) • More branched than starch (every 10) • Red color with iodine Inulin • Chicory root – Chicorum intybus (Asteraceae) • Polyfructan of fructofuranose • Uses of inulin: a) Ingredient in culture media b) Evaluation of renal function c) Component of Nutrilin® - appetite stimulant d) Improves digestion Dextran • Leuconostocme senteroides • Glucosan • Plasma expander • Diff. from dextrin (bread turns brown) Cellulose • Most abundant organic matter • Structural polysaccharide in plants a) Purified/absorbent cotton § From the hair of the seeds of Gossypium hirsutum (has toxic constituents) b) Soluble guncotton/pyroxylin § Formed by the action of HNO3 and H2SO4 on cotton •

Mannitol • From manna (means life), Fraxinus orus • Osmotic diuretic, osmotic laxative, assess GFR Sorbitol aka “D-glucitol” • From berries of mountain ash, Sorbus aucuparia • Taste half as sweet as sucrose • Manufacture of toothpastes and chewing gums

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Pharmacognosy §

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Other ingredients: i) Castor oil – flexibility ii) Camphor – waterproof § Use of pyroxylin: topical protectant Other cellulose derivatives i) Cellulose acetate phthalate (CAP) § coating agent ii) Methyl cellulose and ethyl cellulose § Theratears® § Artificial tears § *Eye-Mo® & Vicine® o phase out due to non-GMP compliance (can cause glaucoma) o all: irrigating NSS

Chitin • Structural polysaccharide in animals • Exoskeleton: mollusks and arthropods • Homoglycan of N-acetylglucosamine • Mushrooms, arthropods (cockroach), crustaceans (chitin turns them orange when cooked)

B) HETEROGLYCANS • Polysaccharides that yield >1 type of monosaccharide unit upon hydrolysis • e.g. glycoproteins, glycolipids, etc.

QUIZ #1 1) 2) 3) 4) 5) 6) 7) 8) 9) 10)

Coined the term “pharmacognosy” Storage of glycogen in the body Hydrolytic product of sucrose Milk left after separation of cream Skimmed milk from coagulum when treated with ______. T/F: Lactulose is a trisaccharide. Aka wood sugar Aka dextrose Used as 6% plasma expander Cut limp silvers of Beta vulgaris

GUMS & MUCILAGES • •

Natural plant hydrocolloids that may be classified as anionic or nonionic polysaccharides Produced by plants as protective after injury (~platelets)

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Upon hydrolysis, they yield arabinose, galactose, glucose, mannose, xylose and other uronic acid derivatives Lead acetate and alcohol – solubilizers Gum + water à dissolves Mucilage + water à sticky/paste Pectin + water à gel

A) PLANT EXUDATES PLANT BOTANICAL EXUDATES SOURCE Acacia senegal Acacia aka Gum arabic Tragacanth aka Gum tragacanth

Astrolagus gummifer

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• • yellowbrown Karaya aka Sterculia gum Indian aka Indian gum Ghatti gum

Sterculia urens

Anogeissus latifolia

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Constituent: Arabin Suspending agent (33-35%) Stable at 60% w/ alcohol Constituent: 1) Tragacanthin (⅓, dissolves) 2) Bassorin (⅔, swells) Suspending agent (5-6%) 3 grades: 1) Vermiform - worm 2) Sorts - tear shaped 3) Flakes - man made, preferred bec. clear Most fetid gum Laxative

• Substitute for acacia

B) MARINE GUMS GUM SOURCE Algae Agar aka Japanese • Gelidium cartilagineum Isinglas • Gracilaria confervoides Algin Carageenan aka Irish moss

Brown seaweeds • Macrocystis pyrifera Red algae • Chondrus crispus • Gigartina mamillosa

CONSTITUENTS • Agarose § high SO4 • Agaropectin § higher SO4 • Mannuronic acid • Kappa & Iota § Gelling component § Stable helix & straight chain • Lambda § Non-gelling component

Pharmacognosy

§ No stable chain & helix § Dissolves

Danish agar

Furcellaria fastigiata

C) SEED GUMS GUM Psyllium

Cydonium aka Quince seed Guar gum aka Guaran Locust bean gum aka Carob pulp, St. John’s Bread

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Citrus microcarpa Citrus limon Pyrus malus

GLYCOSIDES aka “SUGAR ETHERS” SOURCE NOTES Seed coat of: • Plantago psyllium – Spanish! • Plantago ovate – Blonde Ripe seed of Cydonia vulgaris Thixotropic agent Endosperm of Cyamopsis tetragonolobus Endosperm of the seed of Sub. for chocolate Ceratonia siliqua

D) MICROBIAL GUM GUM SOURCE Action of Xanthomonas Xanthan campestris on carbohydrates gum

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Calamansi Lemon Apple

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Heteroglycans (produces sugar upon hydrolysis) § Glycone – non-sugar portion § Aglycone aka Genin o Sugar portion; vehicle/base o Dictates what type of glycoside o e.g. CPPP – saponin, cardiac, steroidal (diff. R) Beta forms occur in plants N-, S-, C-, O, alpha or beta Regulatory, protective and sanitary compounds

A) Cardiac or Cardioactive Glycosides NOTES • Has pseudoplastic activity • Enables toothpastes and ointments to spread readily

PLANT EXTRACTIVES 1) Pectin • Intercellular cementing material • Partially methoxylated galacturonic acid (reason why it swells) • Extract of the inner portion of the rind of citrus fruits and apple pomace (e.g. pomelo has the highest pectin content bec. ↑↑ rind) • Antidiar...