PHARMACOGNOSY ------------------------------------------------------------------------
PHARMACOGNOSY
CRUDE DRUGS
Applied science -> biological, biochemical and economic features of drugs of biological origin and their constituents Medicinal products in their crude or unprepared form
– vegetable or animal drugs consists of natural substances that had undergone only the processes of collection and drying; plant exudates
HISTORY OF PHARMACOGNOSY
Natural Substances – formed in nature; whole plants or parts; animals or organs; no molecular modifications had been made Derivatives of Extractives – chief principle or constituents of crude drugs that are separated and used in a specific manner Menstruum – solvent; liquid/liquid mixture used to extract active principle Marc – undissolved portion of the drug that remarks after extraction process is completed
Bablylonians Laws of Hammurabi (172 BC); clay models of human body; medicinal effects of 250 plants; mages and physician; wheat and barley Ayurveta (2500 BC) Traditional medicine; “Science of life”; Mother of all healing arts Charaka – text on internal medicine Sushruta – 184 chapters; 1120 illness Egyptians (Ebers papyrus – 1150 BC) Embalming; George Ebers; priest and doctors; human anatomy and use of plants Greeks Dioscorides – wrote “De Materia Medica” or The Medicinal material; aloe, belladonna, colchicum, ergot, opium; 600 plants Claudius Galen – described methods and processes of preparing formulas containing plant and animal drug; FATHER OF PHARMACEUTICAL COMPOUNDING Germans CA Seydler (1815) – coined the term, “pharmacognosy” from “pharmakon” and “gnosis” in Analecta Pharmacognistica JA Schidt (1811) – used the word, “pharmacognosy”; Lehrbuck de Materia Medica; described study of medicinal plants and their properties Fluckiger – simultaneous application of various scientific disciplines with the object of acquiring drugs from every point of view Pellitier and Caventou – Quinine Freidrich Serturner - Morphine
Methods of Extraction Infusion – hot water (ex. tea); short contact of action Maceration – soaked in solvent for long period of time Percolation – passage through percolate (ex. Simple Syrup USP) Digestion - <35-40oC Decoction – boiling water Liquid-Liquid Extraction Partitioning Distillation Indigenous Plants – plants growing in their native countries (ex. Rinorea niccolifera – metal eating plant; more on nickel) Naturalized Plants – plants that grow in foreign land other than their native homes Preparation of Crude Drugs 1. Collection – ensuring the true natural source of the drug: improper collection, collection time, highest content Harvesting – specific or proper season; manual labor vs mechanical devices 2. Drying – remove moisture to prevent bacterial and fungal growth with enzymatic degradation; fixed constituents, facilitates grinding and milling; converts plants to convenient form 3. Curing – special drying process that enhances properties of plants’ active ingredients 4. Garbling – final step in preparation of crude drugs; removal of extraneous matter *Last Packaging, Storage, Preservation – protection and marketability; maintain high degree of quality of drug
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Evaluation of Crude Drugs – determine quality and purity; qualitative (intrinsic value of drug; type of medicinal prinnciples) and quantitative (amount) Organoleptic Evaluation – organs of senses; evaluates macroscopic appearance of drug Microscopic – evaluate in a cellular level Pharmacologic Evaluation o Bioassays – assays using living animals or excised organs to evaluate effects of drugs Chemical Evaluation – assay of active constituents using chemicals (titration); best determination of official potency
CLASSIFICATION OF DRUGS 1. Morphology – forms; plant part used; convenient but no chemical correlation 2. Taxonomic (Lireus) – evolutionary development; no correlation on chemical and biological activity Phylogeny – natural relationship that occurs among plants and animals 3. Pharmacologic – based on therapeutic effect on body 4. Chemical – preferred method of classification – based-active constituents that are present; phytochemical studies but ambiguous at times Active Constituents – considered secondary metabolites; through drug biosynthesis or biogenesis
BIOGENESIS Ontogemy or Stage of Development Ex. Cannabis sativa (cannabidiol – plant is young; cannabinol – mature plant) Heredity – same but not the same Environment
I. CARBOHYDRATES Polyhydric aldehyde or ketone alcohols that contain C, H, and O H and O has same ratio as that of water, thus named CARBO + HYDRATES Photo First product of synthesis [C•H2O]n Xylem – H2O Phloem – nutrients – food (∆ source; ∆ storage; structure) Most abundant organic molecule in nature
A. CLASSIFICATION OF CARBOHYDRATES I. MONOSACCHARIDES – simplest carbohydrate unit; cannot be hydrolyzed; identification test: Benedicts and Barfoed’s = brick red ppt.; *neuramonic – aka sialic PENTOSES Xylose – “wood sugar”; obtained from boiling corn cobs, straw; diagnostic aid for intestinal malabsorption; absorbed but not metabolized o Xylan -> Xylose (aldehyde) -> xylulose (ketoses) HEXOSES – most important monosaccharide Glucose – aldohexose; aldehyde group is present in C1; reducing sugar as determined by Benedict’s Test; occurs as linear and cylic; o β-D-Glucose – most abundant o D-Glucose – aka Dextrose, Blood Sugar, Grape Sugar, Physiologic Sugar o Uses: Parenteral – rigorously purified; as nutrient Pharmaceutic necessity – less rigorous purification; Liquid Glucose – syrupy liquid; incomplete acid hydrolysis of starch; almost colorless and taste sweet; Dextrose excipient – crystalline sweetening agent (Oral Glucose Tolerance Test – 75g) Fructose – ketohexose = (+)Seliwanoff’s Test: pink/red; ketone group is present in C2; reducing sugar; fruit sugar; sweet fruits and honey; aka Levulose (sweetest monosaccharide); obtained from inversion of aq. sucrose solution; honey (mostly sucrose) o High Fructose Sweeteners – isomerization of glucose isomers from Streptomyces sp. o Uses: Food for diabetic Ingredient in infant feeding formula Ingredient in Fructose injection nutruient Galactose – aldohexose; “Brain Sugar”; C4 epimer of glucose (C2 – mannose); milk:lactose::neuronal fibers:galactosides; Gaucher’s Disease; (+) Mucic acid and Phenylhydralazine = crystal formation (osazone crystals) II. DISACCHARIDES – composed of two monosaccharide units; formed via dehydration synthesis; glycosidic bond Sucrose – “table sugar”; obtained from: o Saccharum officianarum (sugar cane) – (+) lime = decreased albumin; use SO2 clear = clarification o Beta vulgaris (sugar beets) – cossettes (“cut limps livers” – chop finely) o Acer saccharum (sugar maple) - non-reducing sugar: (-)Benedict’s Test - glucose + fructose, α-1,2 bond - uses: demulcent, sweetening agent to mask taste, coating agent, preservative (85%), production of syrups, retards oxidations
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- Molasses – residual dark colored syrup after complete crystallization of sucrose; only disaccharide in free state; food and ethanol industry Maltose – malt sugar; produced-germination of barley; glucose + glucose, α-1,4 bond; major degradation product of starch; reducing sugar (beer, ovaltine, cereal drinks); glu + glu + glu = maltotriose (oligosaccharide – 3-10C) Lactose – milk sugar (cow’s milk); glucose + galactose, β-1,4 bond; reducing sugar; milk products: 1. Whole milk –(sit)-> butter 2. Butter milk –(churn)-> cream 3. Skimmed milk -> whey (rennin – young calf) coagulum –(tx)-> cheese * Kamyss – fermented spoiled milk * Condensed Milk – partial condense autoclave, evapo Lactulose – fructose + galactose, β-1,4 bond; alkaline rearrangement of lactose; converted by lactose to lactic and acetic acid, which causes irritation of the intestines and subsequent cathartics – ideally used with MI and stroke PRODUCTS OF OXIDATIVE METABOLISM Cherry Juice – ripe fruit of Prunus cerasus (Rosaceae); contains pectin and 1% malic acid; cherry syrup Plant Acids – uses: acidulants in effervescent formulations; component of buffer systems o Citric Acid – Scheele – lemon juice (1784); citric – Tricarboxylic acid (TCA) –(Deniges Test)-> tartaric (by product, dicarboxylic) = wine o Lactic Acid – acidulant – infant feeding formula, feminine wash (0.2% chlohexidine – vaginal; 0.6% - mouth) – (INSERT) Alcohol/Ethanol – 95% ethanol by volume 15.56oC; product of fermentation; undergo process of distillation to concentration the alcohol content to 40-55%; low conc. – CNS stimulant; high conc. – CNS depressant o Brandy - wine o Whiskey – malted grain o Rhum - molasses o Diluted Alcohol – 48.4-49.5% ethanol at 15.56% oC PRODUCTS OF REDUCTIVE METABOLISM Mannitol – from manna, dried exudate of Franxinus ornus; osmotic diuretic and osmotic laxative, GFR; used in people with neurological trauma Sorbitol – from berries of mountain ash, Sorbus aucuparia; aka D-glucitol; tastes ½ sweet as sugar; used in manufacture of toothpaste and chewing gum xylitol as alternative
III. POLYSACCHARIDES Homoglycans – polysaccharides that yield one type of monosaccharide unit upon hydrolysis o Starch – temporary storage form of photosynthetic products from: Zea mays – corn Triticum aestivum – wheat Solanum tuberosum – potato Oryza sativa – rice Maranta arundinacea – arrowroot Constituents: Bases of Differences Structure
Solubility in water Iodine test
Amylose Linear/Helical 250-300 units α-1,4
Amylopectin
Insoluble
Branched (every 25-30 mins) 1000 or more α-1,4 and α-1,6 Soluble
Deep/Dark blue
Blue violet/purple
Enzymes that breaks down starches: 1. Alpha amylase – present in pancreatic juice and saliva; *metabolism/breakdown of carbohydrates starts in mouth 2. Beta amylase – hydrolyses starch to nearly pure maltose Uses: tablet filler, binder and disintegrant; antidote for iodine poisoning Starch Preparations: 1. Pregelatinized starch – chemically or mechanically processed to rupture all or part of granules; tablet binder 2. Sodium starch glycollate – disintegrating agent 3. Hetastarch - >90-99% amylopectin; plasma expander; hydroxyethylstarch; Voluben® 4. Glutens – tacky proteins that impedes flow of starch o Glycogen – storage polysaccharide in animals; more branched than starch (every 10); red color with iodine o Inulin – polyfructan of fructofuranose; Chicorium intybus (Asteraceae) – chicory root; improve digestion; Uses: ingredient in culture media; evaluation of renal function o Dextran – glucosan; Leuconostoc mesenteroides; plasma expander o Cellulose – structural polysaccharide in plants (from the hair of seeds of Gossypium hirsutum) Purified/Absorbent Cotton – surgical dressing Soluble Guncotton/Pyroxylin – formed by action of nitric and sulfuric acid on cotton; Other ingredients: castor oil (flexibility); camphor (water-proof); Use: topical protectant Other Cellulose Derivatives – cellulose acetatephthalate (CAP) – coating agent; methylcellulose and ethycellulose – artificial tears
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o Chitin – structural polysaccharides in animals; exoskeleton: mollusks and arthropods; homoglycan of Nacetylglucosamine Chitosan – deacetylation of chitin; water purification Glucosamine – acid deacetylation and hydrolysis of chitin Heteroglycans – polysaccharides that yield more than one types of monosaccharide units upon hydrolysis
natural plant hydrocolloids that may be classified as anionic or non-ionic polysaccharides produced by plants as a protective after injury; upon hydrolysis, they yield arabinose, galactose, glucose, mannose, xylose and other uronic acid derivatives Pb acetate and alcohol Solubility Stability Use
Production
GUMS Pathologic (injury)
Solubility in water
Readily soluble
BRANCHED More More Gelating agents MUCILAGES Physiologic (natural) Slimy mass
PLANT EXUDATES Acacia - Gum Arabic -> arabin -> K, Ca, Mg, Arabic acid; mucilage; emulsifier; suspending agent (33-35%); 12% H2O content; <60% alcohol
BOTANICAL SOURCE Acacia Senegal
Tragacanth Types: vermiform (worm); taragacanth sorts (tear) Constituents: Bassorin (swells: 2/3); traganthin (dissolves: 1/3) SA: 5-6% K: galactomannan -> bulk laxative Karaya – most fetid gum Sterculia gum Indian – Ghatti; alternative fro acacia
Astragalus gummifer
Carageenan or Irish Moss
Danish Agar
SOURCE Algae Gelidium cartilagineum Gracilaria confervoides Brown Seaweeds Macrocystis pyrifera Red Algae Chondrus crispus Gigartina mamillosa
Furcellaria fastigiata
Cydonium/Quince Seed Guar Gum or Guaran
SOURCE Seed coat of: Plantago psyllium – Spanish Plantago ovata – Blonde Ripe seed of Cydonia vulgaris Endosperm of Cyamopsis tetragonolobus Endosperm of the seed of Ceratonia siliqua Chocolate substitute
MICROBIAL GUM GUM Xanthan Gum
SOURCE Action of Xanthomonas campestris on carbohydrates
NOTES Has a pseudoplastic activity enable toothpastes and ointments to spread easily
C. PLANT EXTRACTIVES Pectin – intracellular cementing materials; partially methoxylated galacturonic acid (swelling); extract of inner portion of rind of citrus fruits (pomelo, grapefruit, orange, ponkan, lemon, calamansi, dalanghita, apple) and apple pomace; antidiarrheal agent; o Kaopectate – Kaolin + Pectin -> antidiarrheal preparation o Protopectin – unripe o Pectin (sol) – just ripe o Pectic acid – overripe
D. GLYCOSIDES
Sterculia urens Anogeissus latifolia
MARINE GUMS GUM Agar or Japanese Isinglas Algin
GUM Psyllium
Locust Bean Gum/Carob Pulp or St. John’s Bread
B. GUMS AND MUCILAGES
LINEAR Less Less Viscosity enhancers
SEED GUMS
CONSTITUENTS
Heteroglycans; “sugar ethers”; BETA form occur in plants; N-, S-, C-, O, alpha or beta; regulatory, protective and sanitary compounds Components: glycone (acts as vehicle; inactive) and aglycone (genin; basis for classification; active) CARDIAC GLYCOSIDES o Unsaturated steroidal aglycone tests Libermann-Burchard = blue/green; yellow for saturated Salkowski = red/violet o 2-deoxy sugar glycone test Keller-Killanii test = reddish brown) o CARDENOLIDES vs BUFADIENOLIDES (C235-B246)
Agarose Agaropectin Mannuronic acid
CARDENOLIDES - Common (active) - C-23 α and β unsaturated 5membered lactone ring
Kappa-gelling component Iota-gelling component Lambda – non-gelling component Kappa
BUFADIENOLIDES - Rare (Bufo sp); (inactive) - C-24 doubly unsaturated 6membered lactone ring
o Digoxin – H2O; Digitoxin – lipid; Desllanatoside – digitalization = rapid o Convallaria – Convallatoxin – Lily of the Valley o Apocynum – Dogbane – cymarine o Adonis – Pheasant’s Eye – adonitoxin o Black Hellebore – Xmas Rose – hellebrin o Strophantus – K strophantin (good) G strophantin (bad) – (toxic)- Oubain o Sqiuill – Scillarenin -> expectorant (bufadienolides)
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ANTHRAQUINONE GLYCOSIDES o Aglycone: Anthracene o Use: cathartic
o Derivative color: orange o Identification Test: Borntranger’s Test o Cascara Sagrada – Rhamnus purshianus i. Constituents: Cascarosides A and B – optical isomers of barbaloin Cascarosides C and D – optical isomers of chrysaloin ii. LANE’s Pill – casanthol, purifiesd mix of anthranol glycosides iii. Cured in MgO for 1 year o Frangula or Buckthorn Bark – Rhamnus frangula i. Present in Movicol® – Karaya (laxative) + Frangula (cathartics); for constipation o Aloe – dried latex or juice of Aloe barbadensis or Aloe vera ; hybrids of Aloe ferox with Aloe Africana and Aloe spicata ; (cathartics and BURNS) i. Constituents: barbaloins and aloe emodin o Rhubarb – glucohein Rheum or Chinese Rhubarb (Therapeutic) Rheum officinale Rheum palmatum
Indian Rhubarb or Himalayan Rhubarb (Ornamental) Rheum emodi Rheum webbianum
o Senna – dried leaflet of Cassia acutifolia ; Cassia angustifolia <Tinnevelly>; cultivated in wat lands resembling rice paddies; derivative color: blue green Constituents: Sennosides A, B, C, and D o Chrysarobin – from Goa powder, Andira araroba; only anthraquinone glycoside that is NOT used as cathartic because it is very irritating; used as keratolytic; hot benzene is used to extract this substance SAPONINS – foam upon shakin (froth test); bitter, acrid taste; sternutatory (may irritate mucous membrane = sneezing); destroy RBCs of cold blooded animals -> fish poisons; froth, hemolysis, capillary o Glycyrrhiza or Licorice – dried roots of Glycyrrhiza glabra; increase foaminess of beer Constituents: glycrrrhizia, glycyrrhziac acid o Dioscorea or Yam Dioscorea spiculiflora – contains diosgenin which is a glucocorticoid precursor; Dioscorea floribunda – best source of steroids; Diosgenin – anti-inflammatory o Ginseng – Panax ginseng (Asia); Panax quinquefolius (American); aphrodisiac and an adaptogen Constituents: panaxosides, ginsenosides, chikusetsusaponins CYANOPHOIC OR CYANOGENIC GLYCOSIDES o Amygdalin (H2O and amygdalase) mandelonitrile glucose (H2O and prunase) mandelonitrile + glucose benzaldehyde +HCN o Rosaceae
o Emulsin – amygdalase and prunase (collectively) o APE = A+P+E o Guingard’s Test = brick red/red coloration Bitter almond – Prunus amygdalus; source of Laetrile (Vit B17) – controversial treatment for sickle cell anemia Wild cherry – Prunus serotina; flavored vehicle, expectorant and sedative Apricots – Prunus armeniaca ISOTHIOCYANATE GLYCOSIDES o Rapeseed – Brassicca napus; gluconapin o Watercress – Nastutium officinale; gluconasturtiin o Odor test mustard smell (volatile); garlic (allicin) o Ferric chloride test blood red (non-volatile) o Black Mustart or Sinapis Nigra – Brassica nigra – sinigrin Sinigrin/sinalbin –(myrosinase)-> allyl/acrinyl o White Mustard – Brassica alba – sinalbin FLAVONOL GLYCOSIDES – flavonoids or bioflavonoids from citrus fruits and soya o Rutin and Hesperidin – vitamin P or permeability factors; treatment of capillary bleeding secondary to capillary fragility o Hesperitin, Diosmin, and Naringen – treatment of symptoms of common colds o Yellow Pigment – rutin and quercetin o Milk Thistle – Silybum marianum; silibinin, silymarin, hepatoprotective o Gingko – Ginggko biloba; gingkolides, bilolabides; memory enhancement ALCOHOL GLYCOSIDES – Salicin – salix and populous o Salix purpurea and Salix fragilis o Aglycone: saligenin o Anti-inflammatory; anti-rheumatic o Tests: Fehling’s – brick red Nessler’s – gray Tollen’s – silver mirror Schiff’s – recolorization ALDEHYDE GLYCOSIDES o Vanilla – cured fruit of Vanilla planifolia (orchidaceae) – Mexican, Vera Cruz, Bourbon Constituent: vanillin Use: flavoring agents PHENOL GLYCOSIDES o Urva ursi – dried leaf of Arctostaphylos urva ursi Constituents: arbutin (hydroquinone + sugar) Use: astringent and diuretic o Poison Ivy (Rhus radicans) and Poison Oak (Rhus toxicondendron); uroshiol – delayed contact dermatitis (type IV)
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LACTONE GLYCOSIDES o Coumarin – from Tonka beans, Dipteryx odorata; constitutents: dicoumarol bishydroxycoumarin anticoagulant, Warfarin; Test for unsaturated lactone: Kedde’s = blue-violet o Cantharides – from dried insect, Cantharis vesicatoria; Russian/Spanish fly; Blistering fly Constituents: cantharidin-irritant, vesicant and rubefacient Causes priaprism – sustained erection o Psoralens – photosensitizing furocoumarins; from Bishop’s flower, Ammi majus Methoxsalen – repigmentation in vitiligo Trioxsalen
II. TANNINS Complex substances or polypeptides that are difficult to separate because they do not crystallize Phenolic in nature; non-crystallizable polyphenols; protein precipitant (astringent); found in barks and leaves Local sources: o Guava – Psidium guajava o Kamachile – Pithecolobium dulce o Duhat – Syzigium cumini Characteristics: o Acidic o Sharp puckering taste o Causes precipitation of alkaloids o Industrial – leather and ink o Clinical – astringents – GI or skin, treatment of burns Chemical classes: (True tannins vs Pseudo tannins – chlorogenic acid and catechins) A. True Tannins – animal skin leather; (+) Gold Beater’s Skin Test i. Hydrolyzable – readily hydrolyzed to yield phenolic acids and sugars Pyrogallol Leather: bloom FeCl3 = blue-black; Br2 test = (-) ii. Non-hydrolyzable (aka Condensed Tannins/ Phlobatannins) – results from condensation of catechin and leucocyanidin tend to polymerize phlobaphenes (red colored product) Leather: tanners red FeCl3 = green-black; Br2 test = (+) B. Pseudo Tannin Hamamelis Leaf – Witch Hazel Leaf, dried leaf of Hamamelis viriniana; constituent: hamamelitanin; used for hemorrhoids Nutgall – excrescence obtained from young twigs of Quercus infectoria, Fagacea (when Cynips tinctoria bores a hole to
deposit ova); constituent: tannic acid (Gallic + Ellagic = Tannic [GET]) astringent Chinese/Japanese Gall – Rhus chinensis; Aphis sp. – gallic acid (Bismuth subgallate – protectant; deodorizer for flatulence)
III. LIPIDS FIXED OILS Long chain fatty acids + glycerol From vegetables Liquid at room temp EXCEPTIONS: Solid FO – Theobroma, Myristica USE: storage
FATS Long chain fatty acids + glycerol From animals Sold at room temp EXCEPTIONS: Liquid F: Cod liver oil
USE: storage
WAXES Long chain fatty acids + high molecular weight alcohol (cetyl alcohol, stearyl alcohol) EXCEPTIONS: Liquid W: Jojoba oil USE: protectant
Fatty Acids o Saturated – capric, lauric, myristic, palmitic, stearic, arachidic o Unsaturated (=) – palmitoleic, oleic, linoleic, linolenic, arachodonic Uses: emollients; vehicles for IM injection (COCOPESE); cathartic (castor oil); soap production; increase caloric value (TPN) USP Tests: o Acid value or Acid number – mg of KOH needed to neutralize free FAs o Saponification value – mg of KOH needed to saponify the esters o Iodine value – g of iodine absorbed in 100g of sample Expression – cold-pressed oil; hot-pressed oil; only from fixed oils Rendering – fats Solvent extraction – fats; hexane – best solvent for extracting fats Types of oils – ability to absorb oxygen; oxygen saturates double bonds forming oxides that polymerize to form films; paint industry Non-drying Semi-drying Drying
IODINE VALUE RANGE <100 100-120 >120
EXAMPLES Olive; Almond Cottonseed; Sesame Linseed; Cod liver oil
Reactions of Lipids o Hydrogenation – liquid oil to semi-solid fat; passing of H with Pd/Ni in 160-200oC; shortening and cooking fat o Sulfation – reaction with sulfuric acid; temp at chilling; sulfates adds to double bonds, surfactants
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IV. FIXED OILS SEED OILS FIXED OIL Cottonseed Oil – IM injection; not edible; constituent: gossypol –x-> male sterility; ID test: Halphen/Bevan Sesame Seed Oil – Benne/Teel Oil; uses: IM injection, edible; constituent: sesamol (phenol) – self-preserving + lignin sesamolin & pyrethrin insecticides; ID test: Bauduoin Coconut Oil – constituents: lauric, myristic, triclycerides Castor Oil – tangan-tangan; ricinoleic (good) - cathartic trcinoleic (good) ricin (toxic) = abrin (jequirity bean) Peanut Oil – peanut oil cake; peanut butter; afflotoxin aspergillus (due to improper storage and drying) Soybean Oil – stigmasterol - steroid; lecithin – regulate cholesterol; antilipemic agents Corn Oil – germ oil cake – IM injection; antilipemic agents; Hydrogenated volatile oils = sergers Safflower Oil – antilipemic agents Sunflower Oil – antilipemic agents Ethiodized Oil Injection
BOTANICAL SOURCE Gossypium hirsutum
Sesmum indicum
VI. WAXES
Glycine soja
Spremaceti – head of spermwhale, Physeter macrocephalus; synthetic spermaceti – cetyl ester wax Jojoba Oil – seeds of Simmondsia chinensis, Buxaceae; hydrogenated form resembles spermaceti; eicosenoic acids: eicosenol and docosenol Beeswas or Yellow Wax – honeycomb of bees, Apis mellifera; stiffening agent in plasters and cerates; White Wax – bleached yellow wax; myricyl pamitate Carnuba Wax – leaves of Copernicia prunifera; myricyl cerotate
Zea mays
VII. VOLATILE OILS
Cocos nucifera Ricinus communis
Arachis hypogaea
Carthamus tinctoria Helianthus anuus Iodine addition product of ethyl ester of fatty acid of Poppy seed
PERICARP OILS FIXED OIL Olive Oil – ID test: Milon’s
BOTANICAL SOURCE Olea europaea
Cod Liver Oil – from Gadus morrhua; sclerosing agent to obliterate varicose veins; source of vitamin A and D (Scott’s emulsion) Undecylenic Acid – pyrolysis of ricinoleic acid from castor oil; has antifungal property Azelaic Acid – onolysis of Castor oil; anti-acne
NOTES Grades: 1. First Grade Virgin Olive Oil – extracted with less pressure 2. Second Grade Virgin Olive Oil – pulp in #1 is extracted with more pressure 3. Technical Oil – extracted with hot water 4. Sulfur Grade – extracted with Carbon disulfide; inferior quality 5. Tournant Oil – fallen and decomposing fruits
V. FATS AND RELATED COMPOUNDS Theobroma Oil – Theobroma cocao; food for the gods o Uses: cocoa syrup – beverage; cocoa butter – suppository base (melts at 30-35oC) o Nibs prepared cacao/breakfast cacao Lanolin – purified fatlike substance from wool of sheep Ovis aries, Boviidae; contains 25% water; Uses: water absorbable ointment base; emollient o Anhydrous lanolin – woolfat (contains 0.25% water)
Odorous principle in carious plants Colorless and photosensitive; light resistant tight container in a cool and dry place Undergoes auto-oxidation and resinification Plant families: o Glandular hairs or trichomes (lamiaceae labiatae) o Modified parenchymal cells piperaceae o Oil tubes or vittae apiacea (umbelliferae) o Lysigenous and schizogenous passages pinaceae and rutaceae Physical characteristics: o Possess characteristic odors, high refractive index, optically active, immiscible in H2O but can be sufficiently be soluble to impart odor in water aromatic water VOLATILE OILS Distillation Resinification (-) Grease Spot
FIXED OILS Saponification Rancidity (+) Grease Spot
Methods of Obtaining Volatile Oils Distillation o Water Distillation – dry sample; turpentine oil o Water and Steam Distillation – dry sample; clove and cinnamon oil o Steam Distillation - peppermint and spearmint o Destructive Distillation – empyreumatic oils (heat without access of air); pinaceae and cuppressiaceae – only family to use destructive distillation (“char”) Enzymatic Actions – mustards Expressions o Ecuellle and Piquer – rolling a fruit in a trough line with sharp tiny projections enough to puncture the rind – citrus fruit
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o Enfleurage – flower petals (or small plant part) on a fatty pomade followed by EtOH extraction Components of Volatile Oil STEREOPTENE - Solid oxidized hydrocarbon portion - Menthol - Amenthol - Thymol
1. Camphor – Cinnamomum camphora; natural camphor: (+); synthetic camphor: racemic (-); anti pruritic, rubefacient, anti-infective 2. Spearmint – Mentha spicata; carvone (-); (+) carvone – same odor as caraway (Carum carvi) 3. Buchu Oil – Berosma betulina; diosphenol; menstrual problem, carminative, anti-rheumatic 4. Wormwood/Quinghaosu – Artemia annua; Artemisia ketone and camphor; anti-malarial artemisinin, artenether, artesunate Phenol Volatile Oil 1. Clove Oil – Engenia caryophyllus; eugenol; toothache drops, dental analgesic 2. Thyme – Thymus vulgaris; thymol antifungal and antibacterial 3. Creosole Oil – Fagus grandiflorus; creosole disinfectant, guiacol 4. Jupiter Tar – Juniperus oxycedrus; cadinene; antiexzema Polytar® Phenolic Ether Volatile Oil 1. Nutmeg/Myristica Oil – Myristica fragrans; constitentuents: safrole and myristicin; halloahogen 2. Anise Pimpenella – Pimpenella anisum – anisaldehyde, transanethol 3. Fennel – Freniculum vulgare; fendiole, transanethole
ELEOPLENESES - Liquid hydrocarbon portion - Methysalicylate - Encalyptol - Eugenol
Medicinal and commercial use: fabrication of perfumes o Top Notes – (smell – minute to hour); most volatile product; leave skin readily – lemon (limonene – most used flavorant), lavender, anise oil o Middle Notes – (3-6 hours); intermediate tenacity and volatility – thyme, neroli and rose oil o Base Notes – (long hours); low volatility and high tenacity; aka Fixatives = staying power Musk – dried secretion from the preputial follicles of the male musk deer of Asia, Moschus spp – muskane Civet – glandular secretion appearing in an outwardly discharging pockets of civet cat, Paracloxutus hermaphrodites Amber gris – most valuable material; pathologic product formed in stomach of spermwhale when if feeds on squid or cattlefish (ambrein) Constituents of Volatile Oils: o Terpenes – natural products whose structure are made up of isoprene units: Monoterpene – 2 Hydrocarbon Volatile Oils 1. Turpentine Oil – Pinus palustris; rectified tuperntine; terpinhydrate/terpinol – expectorant; α and β pinene ** turpentine oil + NaOH = rectified turpentine ** RT + HNO3 = terpinhydrate/terpinol 2. Peppermint Oil – Mentha piperita; menthol (antipruritic) (+) synthetic, (-) natural; Japanese Peppermint Oil – Mentha arvensis; increase menthol concentration; flavorant, carminative, stimulant counter – irritant *****INSERT HERE********* Aldehyde Volatile Oil 1. Cinnamon Oil – Cinnamomum loureiril; Cinnamomum zeylanicum; Cinnamomum cassia (aka cassia oil); constituent: cinnamaldehyde; uses: flavoring, carminative, antiseptic 2. Lemon Peel Oil – rind of the fruit Citrus limon; lemon oil; citral and limonene 3. Citronella Oil – leaves of Cymbopogon winterianus – tanglad; citronellal; insect repellant 4. Hamamelis Oil – Hamamelis virginiana; 2-hexanal; hemorrhodal preparation Ketone Volatile Oil
Sesquiterpene - 3 Diterpene - 4 Triterpene - 6 Tetraterpene – 8 o Acetate-Mevalonate Pathways o Shikimic Pathway – aromatic compound
VIII. RESIN AND RESIN COMBINATION RESINS – amorphous products with complex chemical nature; hard transparent or translucent and when heated they soften and melt; complex mixtures of: Resin acids Resin alcohols Resinotannols Esters Resenes – B-complex neutral substances devoid of characteristics RESIN Rosin/Colophony Podophyllum
SOURCE Pinus palustris Podophyllum peltatum
Eriodictyon/Yerba Santa
Eriodictyon californicum
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CONSTITUENTS/NOTES Podophyllin – caustic agent for warts Peltatin – purgative Podophyllotoxin – etoposide, tenoposide
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Jalap
Exogonium purge Pistacia lentiscus Piper methysticum Tops of Cannabis sativa
Mastic Kava/Kava-kava Cannabis/Indian Hemp/ Marijuana/Pot
Jalapin and purganol – drastic purgative Masticin and mastichic acid Styrylpyrones – yangonin, kawaiin, methysticin Resin: Hashish Constituets: THC, Cannabidiol, nabilone Duquenois Test: violet on chloroform layer
RESIN COMBINATIONS: Oleoresins – volatile oils + resin
X. ALKALOIDS
OLEORESINS Turpentine/ Gum Turpentine Capsicum/ Cayenne Pepper – African chilles Ginger
SOURCE Pinus palustris
CONSTITUENTS
Capsicum frutescence C. annum var longum (Louisiana long pepper) Zingiber officinale
Capsaicin – vesicant; irritant
White Pine Balsam Comaiba
Pinus strobus Copaifera spp.
of
Zingebol and bisabolene – stomachic; antibacterial
Oleo-Gum-Resin – volatile oil + gum + resin o Myrrh/Gum Myrrh – Commipholra molmol; use: astringent (Astring-o-sol®) o Asafetida – Devil’s dung; Ferula asafetida Balsams – mixtures that contain cinnamic acid, benzoinc acid or both or esters of these acids BALSAM Storax/Styrax – wound healing; perfumery; storesin (α and β – Levant’s storax 50:50); pharmaceutic and compound benzoic tincture (benzoin, storax, tolu balsam, aloe, ethyl alcohol) Peru Balsam – parasiticide Tolu Balsam – flavorant, expectorant; compound benzoic tincture (benzoin, storax, tolu balsam, aloe, ethyl alcohol) Benzoin – Sumatra; Siam topical compound benzoin tincture
o Secondary – fermentation of primary bile acids by intestinal flora; desoxycholic acid, litocholic acid Steroid Hormones o Glucocorticoids – carbohydrate metabolism; antiinflamatory; cortisone, cortisol o Mineralocorticoids – electrolyte and water balance; aldosterone o Sex Hormones – Males: androgens, testosterone; Females: estrogen, progestin
SOURCE Liquidambar orientalis
Myroxylon pereirae Myroxylon balsamum
Styrax benzoin
Resin Acids – oxyacids (-COOH and phenik) Glycoresin – resin + carbohydrate
IX. STEROIDS Compounds with CPPP; metabolites of mevalonic pathways Sterols o Cholesterol – animals o Ergosterol – fungi o Phytosterol – plants Bile Acids o Primary – directly from cholesterol (liver); cholic acid, chenodeoxycholic acid
Bitter, basic nitrogenous compounds; physiologically active; most of them ends in –ine; Nitrogen can be: Primary amine – RNH2; Secondary amine – R2NH; Tertiary amine – R3N All are solids except for: [CANS] o Coniine – Coniium maculatum; poison hemlock (Socrates) o Arecoline – scotchbroom (Cysticus coparius), lupin – Lupinus mutabilis – anti-arrhythmic o Nicotine o Sparteine Alkaloidal Reagents – form double salts with compounds of mercury, gold, platinum, and other heavy metals o Wagnner’s Reagent – iodine in KI (red-brown) o Mayer’s Reagent – potassium mercuric iodide (cream) o Valser’s Reagent – mercuric iodide (white) o Dragendorff’s Reagent – potassium bismuth iodide (orange) o Bouchdart’s Reagent – iodine in KI, most sensitive o Marme’s Reagent – K cadmium iodide o Sonnencheims’s Reagent – phosphotungstic acid o Hager’s Reagent – picric acid o Gold compounds o Tannic acid
A. PYRIDINE-PIPERIDINE ALKALOIDS Nicotine – leaves of Nicotiana tabacum; use: CNS stimulant; smoking deterrent (Nicoret®) Areca, Areca Nut or Betel Nut – dried ripe seed of Areca catechu; arecoline – anthelminthic-taenicid; tannin content causes oropharengeal cancer; catechutannin cancer causing Lobella – Indian tobacco; Lobella inflata; Lobeline – CNS stimulant and smoking deterrent (Bantron®)
B. TROPANE ALKALOIDS (Solaneous alkaloids) Belladona – Atropa belladonna; anticholinergic, mydriatic; (-) hyoscyamine atropine] Hyocyamus or Henbane – leaves of Hyscyamus niger, 0.04%; hog +bean toxic to swine Egyptian Hyoscyamus or Egyptian Henbane – hyoscyamus muticus, 1.5%
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Duboisia – Duboisia myoporoides Withania – Withania somnifera; commercial sources of atropine3 Stramonium or Jimson Weed/Jamestown Weed – Datura stramonium Solanaceae; Talumpunay; used for asthma and COPD burned then vapors are obtained Mandragora or European Mandrake/Satan’s Apple – roots of Mandragora officinarum; mandragorine; potent poison Cocaine – Huanuco coca – Erythroxylon coca; Truxillo coca – E. truxillense; crack/coke; psychomotor stimulant, local anesthetic; Brompton’s cocktail Atropine – antispasmodic; antisialogogue; mydriatic and cycloplegic; antidote for cholinesterase inhibitors; (+) inotropic agent Scopolamine or Hyoscine – treatment form motion sickness; Trans-scop® or Transderm®
C. QUINOLINE ALKALOIDS Cinchona – Red cinchona bark – Cinchona succirubra; Yellow cinchona bark – C. calisaya; “cinchonism”; Quinine, Quinidine – antimalarial; Thalleioquin test = fine blue fluorescence then green ppt Cuprea – Remijia purdieana, Cupreaceae; commercial source of quinidine
D. ISOQUINOLINE ALKALOIDS Ipecac – dried rhizome and rood of Cephaelis ipecacuanha; constituent: emetine or methylcephaeline; use: ipecac syrup – emetic o Ipecac fluidextract is 14 times more potent o Ipecac + Opium = Dover’s Powder (diaphoretic) o Paregoric – camphorated opium tincture o Laudanum – deodorized opium tincture Sanguinaria or Bloodrood – Sanguinaria Canadensis; constituents: saguinarine; use: stimulating expectorant and emetic Tubocurarine Chloride – aka curare or south American arrow poison; Strychnos castelnaei; constituent: tubocurarine – skeletal muscle relaxant o Pot – clay o Tube – bamboo o Calabash – gourd o Standardization of Tubocurarine – Head Drop Assay in Rabbits – least amount of drug capable of producing muscle relaxation so that head of animal drops in a characteristic manner Opium or Gum Opium – unripe poppy seed capsules of Papaver somniferum; only legal source is India; stone of immortality; Marquis Test: opiods (purple); synthetic o Diacetlymorphine – Heroin; acetylation of morphin; increase danger of habit formation (very potent)
o Hydromorphone – more potent analgesic; less frequent SE o Apomorphine – condensation of morphine + HCl; use: emetic o Hydrocodone - antitussive o Opiates – natural source Morphine – Serturner; most important, most abundant, narcotig analgesic Codeine – P. Robiquet; most widely used opium alkaloid; obtained from methylation of morphine; methymorphine – antitussive Noscapine – non-narcotic opium alkaloid; antitussive; anarcotin/narcotine Papeverine – smooth muscle relaxant, antitussive Thebane
E. INDOLE ALKALOIDS (Tryptophan) Rawolfia Serpentina – dried root of Raubolfia serpentina; constituent: reserpine – treatment of snake bites to insanity, hypotensive effects, sedative and tranquilizong properties Chichirica/Catharanthus/Vinca – Cantharanthus roseus; constituents: vinscristine and vinblastine; lymph, hodgkins; aka Periwinkle Nux Vomica – dried ripe seed Strychnos nux vomica; Strychnos Ignatii (St. Ignatius Bean) – commercial source of strychnine; constituents: strychnine (toxic central stimulant) Mandelin’s Test = violet; Brucine (alcohol denaturant) Physostigmine/Eserine – local sources: calabar, ordeal, or Esere Bean; from Physostigma venenosum; treatment of Glaucoma Ergot – dried sclerotium of Claviceps purpurea on rye, secale cereal; constituents: ergonovine (ergometrine & metylsergide – prophylaxis for migraine) – oxytoxic agent, ergotamine o Lysergic Acid Diethylacmide – most active and most specific psychomimetic drugs
F. IMIDIZOLE ALKALOIDS Pilocarpine – leaflets of Pilocarpus jaborandi; treatment of glaucoma
G. STEROIDAL ALKALOIDS Green Hellebore/Veratum viride – roots of Veratrum viride; use: cardiac depressant; (-) inotrope Black Hellebore – cardiac stimulant; (+) inotrope White Hellebore/European Hellebore – roots of Veratum album; insectesies
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H. ALKALOIDAL AMIDES Ephedra/Ma Huang – ephedrine; overground portion of Ephedra sinica; nasal decongestant; bronchodilator Colchicine – Colchicum autumnale, Liliaceae; used in plant genetics because it can double the chromosomes Khat/Abyssynian Tea – fresh leaces of Catha edulis; constituents: cathinone amphetiamine like effects Peyote/Mescal Buttons – aka “shrooms”dried tops of Lophophora williamsii; hallucinogenic and euphoric agent; constituent: mescaline (psilycybe psilocybine)
I. PURINE ALKALOIDS/METHYLXANTHNES Cannot be precipitated by any alkaloidal reagents Caffeine – 1,3,7-trimethylxanthine *INSERT STRUCTURES* o Kola, Cola or Kolanuts – dried cotyledon of Cola nitida o Coffee Bean – dried seeds of Coffea Arabica o Amaic Acid Test: Red-brown/transient purple o C. robusta; C. liberica Chlorogenic acid + caffeine (+ caffeole) –(∆) Decaffenieted coffee – 0.08% o Phosphodiesterase Inhibitors – diuresis; increase gastric secretions; inhibit uterine contraction; weak (+) chronotropic and inotropic effects Theophylline – 1,3-dimethylxanthine; leaf buds of Camellia sinensis; treatment of bronchial asthma; tocolytic agent o Aminophylline – semi-synthetic theophylline derivative – treatment of bronchial asthma Green Tea (Fresh) – China and Japan Black Tea (Fermented) – India and Sri Lanka (Ceylon) Theobromine – 3,7-dimethylxanthine; seeds of Theobroma cacao; diuretic in cardiac and pulmonary edema
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