Compiled_Notes_in_Pharmacognosy_with_Plant_Chemistry(2).pdf

MODULE 1 INTRODUCTION TO PHARMACOGNOSY PREPARED BY: JESUSIMA P. MONSERATE, RPh & JOHN PAUL B. DEMONTEVERDE, RPh Pharmacognosy – from the Greek words… - “pharmakon” - drugs - ”gnosis”- knowledge or “gignosco” - to acquire a knowledge of - literally means,” knowledge of drugs or pharmaceutica...

MODULE 1 INTRODUCTION TO PHARMACOGNOSY PREPARED BY: JESUSIMA P. MONSERATE, RPh & JOHN PAUL B. DEMONTEVERDE, RPh Pharmacognosy – from the Greek words… - “pharmakon” - drugs - ”gnosis”- knowledge or “gignosco” - to acquire a knowledge of - literally means,” knowledge of drugs or pharmaceuticals” - has been a part of the healing arts and sciences since mankind first began to treat illnesses - science of natural drugs & other natural products affecting the health of humans & animals Pharmacognosy is an applied science that deals with the … - biologic (taxonomy, morphology, anatomy, physiology, genetics, biochemistry, etc) - chemical (isolation, purification, characterization of the active constituents) - economic features (commercial production and trade of natural drugs & their constituents) The most comprehensive idea of the scope of Pharmacognosy was presented by Fluckiger which states that … “It is a the simultaneous application of various scientific disciplines with the object of acquiring knowledge of drugs from every point of view.” In a broad sense, - pharmacognosy embraces a knowledge of the history, distribution, cultivation, collection, selection, preparation, commerce, identification, evaluation, preservation, and use of drugs and economic substances that affect the health of humans and other animals Plant Chemistry - deals with the study of plant constituents - a part of natural product and organic chemistry and includes biosynthesis which explains how plants synthesize these constituents from simple molecules Phytochemistry - study of the composition of plant principles with their extraction, biosynthesis and identification Scheele - father of modern Plant Chemistry Brief History of Pharmacognosy Earliest days - organized pharmaceutical & medical knowledge, all information pertaining to drugs and their usage in the western culture was designated “materia medica” (meaning medical matter) - Example: De materia medica libre cinque Early 19th century - as the amount of knowledge about drugs increased, specialized disciplines became a necessity so materia medica undergo division into; 1. Pharmacology - deals with the action of drugs 2. Pharmacognosy - deals with all aspects of drugs with lesser emphasis on actions - at the time, all medicines are derived from natural sources Late 19th century - chemist began to synthesize large number of organic compounds with structures of ever-increasing complexity, some of which were useful therapeutic agents. These products were considered to fall outside the realm of pharmacognosy, the discipline, medicinal chemistry which had remained dormant took an increase vigor - during this time, there came to be 3 basic disciplines devoted to drugs; 1. Pharmacology - deal with drug actions 2. Pharmacognosy - all information on drugs from natural sources 3. Medicinal chemistry - the science of synthetic drugs Value of Natural Drug Products 1. provide a number of extremely useful drugs that are difficult to produce synthetically - Examples: alkaloids of opium, of ergot, and solanaceous plants, digitalis glycosides, most antibiotics, serums, vaccines 2. natural source of basic compounds that may be modified slightly to render them more effective or less toxic - Examples: morphine derivatives 3. as prototypes or models for synthetic drugs possessing physiologic activities similar to the originals - Examples: atropine, cocaine, ephedrine etc. 4. can be modified by chemical or biological methods to produce potent drugs not easily obtained by other methods - Examples: production of hydrocortisone from stigmasterol Crude drugs - are vegetable/animal drugs that consist of natural substances that have undergone only the processes of collection & drying - as used in relation to natural products means any product that has not been advanced in value or improved in condition by shredding, grinding, chipping, crushing, distilling, evaporating, extracting, artificial mixing with other substances or by any process or treatment beyond what is essential to its proper packing to the prevention of decay or deterioration pending manufacture Pharmaceutically, Biological Drugs may be any of the ff; 1. Crude drugs - Examples: chondrus, cascara sagrada, cochineal, thyroid 2. Drug Constituents - chief constituents & their derivatives obtained from drugs of biologic origin or prepared synthetically or semisynthetically. - Examples: sucrose, menthol, progesterone 3. Other Natural Products 3.1. plant juices, exudates, secretions, extracts - Examples: aloe, acacia, orange oil 3.2. animal secretions & extracts - Examples: gelatin, chymotrypsin 3.3. microbial extracts & products - Examples: sutilains, xanthan gum 4. Biologics 4.1. products composed of antigenic matter or antibody preparations capable of developing a state of immunity in the patients - Examples: vaccines, toxoids, antitoxins, antirabies serum 4.2. diagnostic aids - Examples: mumps skin test antigen, tuberculin 4.3. biologics related to human blood - Examples: blood grouping serum, whole blood, human albumin ADDITIONAL INFORMATION Materia medica - medical matter/ medicinal substances - refers also to information pertaining to drugs and their usage - ancient science that dealt with all aspects of medicinal agents De Materia Medica - most famous commentary on drugs - a treatise concerning medical matter in 5 volumes written by the Greek pharmacobotanist Pedanios Dioscorides - covered some 600 plant drugs plus a number of animal drugs and mineral products - remains an authority for 15 centuries Pedanios Dioscorides - wrote “De Materia Medica” in 78 AD in which he described about 600 plants. - still used today are: belladonna, ergot, colchicum, aloe, hyocyamus, opium J.A. Schmidt - was first to introduce the word pharmacognosy in his title “Lehrbuch der Materia Medica” C.A. Seydler - the first to coined the word Pharmacognosy in his work “Analectica Pharmacognostica” Galen - greek pharmacist-physician described the method of preparing formulas containing plant & animal drugs (galenical preparations) - father of Galenical Pharmacy Pen-ts’ao kang mu - Chinese drug encyclopedia compiled by Li Shih-Chen & published in 1596 A.D. listed more than 2000 drugs of natural origin Vedas of India, a collection of hymns predating 1000 B.C. Includedmore than 1000 healing herbs Egyptian Papyrus Ebers - (1550 BC) - paper scroll, 110 pages, 20 m long - Georg Ebers - kept in University of Leipzig, Germany Pseudopharmacognostic writings - literature on natural drugs consisting of beliefs & opinions written by laymen & intended to inform other laymen. Drugs are used as such in their crude from or the principles (chemical entities or constituents) are extracted and employed as medicinal agents (active constituents) Methods of extraction/separation a) maceration e) percolation b) infusion f) distillation c) digestion g) expression d) decoction Solvents Commonly Used for Extraction a) petroleum ether - fats, fixed oils, waxes, pigments, resins b) ether/chloroform - alkaloids, resins, glycosides c) 95% EtOH - glycosides, tannins, saponins, resins d) 80% EtOH - same as 95% EtOH but preferred in phytochemical screening e) water - glycosides, sugar, salt, gums, proteins f) 1% HCl - alkaloids, salts of vegetable acids g) 5% NaOH - pentosans and hemicelluloses Plant Metabolites 1. Primary metabolites - abundant in plants but lower in value - Examples: CHON, CHO, lipids 2. Secondary metabolites - unique to a particular specie, usually possessing therapeutic value - Examples: alkaloids, steroids, flavonoids, See: Figure 1-6 on page 16 of PCog textbook Derivatives/extractives - principles separated from crude drugs by extraction; considered the chief constituent of the drug; product of the extraction process Menstruum - solvent used in the process of extraction which is selective in its action Marc - undissolved portion of the drug that remains after the extraction process Geographic source & habitat - refers to the region in which the plant/ animal yielding the drug grows Indigenous plants - are those growing in their native countries Naturalized - are those growing in foreign land aside from their country of origin PREPARATION OF DRUGS FOR THE COMMERCIAL MARKET 1. Collection - the most advantageous time is … a) when the drug is highest in its content of active principles, b) when the material will dry and give the maximum quality and appearance 2. Harvesting - maybe done by … - hand labor, or - use of mechanical device (cannot replace hand labor if skillful selection of plant parts is an important factor 3. Drying - either sun dried, use of artificial heat (40oC-60oC), or shade drying (to retain the color) a) removes moisture to ensure good keeping qualities, prevent decomposition b) facilitate comminution c) prevent the action of enzymes d) prevent molding and action of bacteria e) prevent chemical and other possible changes f) fixes the constituents g) convert the drug to a more convenient form for commercial handling (not all drugs are dried) Drying involves 2 main principles … a) control of temperature and b) regulation of air flow Curing - modified drying process that converts inert constituents to its active form. - Example: vanilla 4. Garbling - the final step in the preparation of crude drugs - the process of removing extraneous matter such as other plant parts, dirt & added adulterants 5. Packaging, storage & preservation - packaging depends on the final disposition of the drug - choose type of packaging that provides ample protection to the drug and gives economy of space - packaging and storage should protect the drug from moisture, light, air, insects & high temperature Insects that attacks drugs chiefly belongs to the orders LEPIDOPTERA, COLEOPTERA & DIPTERA. Methods used to destroy/prevent insect attacks; 1. expose to a temperature of 65 o C (most efficient) 2. fumigation with methyl bromide 3. store in tight, light resistant containers and add few drops of CHCl3 / CCl4 Evaluation of Drugs - to determine the quality & purity or - to identify drugs Quality - refers to the intrinsic value of the drug; amount of medicinal/active principles/constituents present Methods of Evaluating Drugs 1. Organoleptic - includes macroscopic appearance, odor & taste, sound of snap of fracture, & the feel of the drug 2. Microscopic - essential to the study of adulterants in powdered drugs & in the identification of powdered drugs 3. Pharmacologic/Biologic Assay/Bioassay - assays on living animals as well as on intact/excised organs (indicate the strength of the drug or its preparation) and also microorganism - it has been applied to the evaluation and standardization of drugs Methods of Evaluating Drugs 4. Chemical Assay - widely employed; the best method of determining the official potency of drugs - Example: color reaction tests 5. Physical test - application to crude drugs is rare but extensively applied to active principles of drugs such alkaloids, vol. oils, etc. - Examples: solubility, sp. gr., optical rotation, refractive index, congealing point, melting point, moisture determination 6. Instrumental - Examples: a) UV-VIS Spectroscopy - plant pigments b) IR Spectroscopy - finger printing device - functional group c) Mass Spectroscopy - molecular weight d) NMR Spectroscopy - structural formula CLASSIFICATION OF DRUGS (Vegetable drugs can be arranged for study under the following headings) 1. Alphabetical - either Latin or vernacular names may be used 2. Morphological classification - grouped according to the part of the plant/animal represented 3. Taxonomic classification – based on the accepted system of botanical classification or on relationship or phyllogeny among plants/animals 4. Pharmacologic/ therapeutic classification - based on their therapeutic use/pharmacological action of their most active constituent 5. Chemical/ Biogenetic classification - based on therapeutically/chemically active constituent New Families (Names) Old New Example 1. Cruciferae Brassicaceae Mustard 2. Graminae Poaceae Grasses 3. Labiatae Lamiaceae Mint 4. Palmae Arecaceae Palm 5. Umbelliferae Apiaceae Parsley 6. Leguminosae Fabaceae Beans 7. Compositae Asteraceae Sunflower 8. Guttiferae Clusiaceae Mangosteen Chemistry of Drugs Two Main Groups of Plant Constituents 1. Active Constituents- responsible for the therapeutic effect Examples: glycosides, alkaloids, terpenes 2. Inert Constituents- do not exert any therapeutic effect/have no definite pharmacologic activity - Examples: cellulose, lignin, suberin, cutin, starch, albumin and coloring matters in plants; - in animals keratin, chitin, muscle fiber and connective tissue Two Classes of Active Constituents 1. Pharmaceutically Active - cause precipitation/other chemical changes in a medicinal preparation - Example: tannin 2. Pharmacologically active - responsible for the therapeutic activity of the drug - Examples: glycosides, alkaloids Plant/Animal Constituents may be; 1. A single chemical substance - Examples: sugars, starches, plant acids, enzymes, glycosides, steroids, alkaloids, proteins, hormones & vitamins 2. Mixture of principles - Examples: fixed oils, fats, waxes, volatile oils, resins, oleoresins, oleo-gum-resins and balsams 3 Principal Factors that Influence Secondary Constituents of Drugs 1. Heredity (genetic composition) - induce qualitative and quantitative changes phenotypes - resemble in form & structure genotypes - same in genetic composition 2. Ontogeny (stage of development) - identity of the constituents vary according to the stage of development of the plant 3. Environmental factors - include soil, climate, associated flora, & methods of cultivation Drug Biosynthesis/Biogenesis - study of the biochemical pathway leading to the formation of secondary constituents used as drugs - to facilitate a general understanding of the pathways involved and their interrelationships See: Figure 1-6 on page 16 of PCog textbook  MODULE 2 CARBOHYDRATES PREPARED BY: JESUSIMA P. MONSERATE, RPh & JOHN PAUL B. DEMONTEVERDE, RPh CARBOHYDRATES - are aldehyde or ketone alcohols containing C, H & O in which H & O are generally in the same ratio as in water - first product formed in photosynthesis - most abundant organic molecule in nature - are organic compounds used to store energy 1. aliphatic polyhydric alcohols in which either the primary alcohol function has been oxidized to aldehyde/the secondary alcohol function has been oxidized to ketone. - frequently termed monosaccharides (or simply saccharides) - subclassified into aldoses & ketoses 2. condensation products of these partially oxidized polyalcohols - sometimes referred to as saccharide anhydrides - subclassified into: disaccharides, trisaccharides... polysaccharides according to the number of monosaccharide units Carbohydrates are Classified into Two Broad Groups (Tyler and Robbers) A. Sugars B. Polysaccharides A. Sugars - low molecular weight, crystalline, soluble in water, sweet tasting, yield simple saccharides on hydrolysis A.1. Monosaccharides - (CH2O)n - subclassified into aldoses & ketoses - subclassified according to the number of C atoms - glycoaldehyde/hydroxyacetaldehyde (diose) - parent molecule of aldoses - dihydroxyacetone (triose) - parent molecule of ketoses - hexoses - first detectable sugar synthesized by plants; - form units from which most of the polysaccharides are constructed - heptoses - of vital importance in the glucose metabolism of animals  CLASSIFICATION OF MONOSACCHARIDES No of C atoms Aldoses Ketoses hydroxyacetaldehyde/ Diose glycoaldehyde Triose L & D - glyceraldehyde dihydroxyacetone L & D - erythrose Tetroses D & L - erythrulose L & D - treose (D & L) ribose, arabinose, (D & L) ribulose, Pentoses xylose, lyxose xyloketose (D & L) fructose, (D & L) glucose, allose, talose, Hexoses psicose, tagatose, mannose, galactose, idose, altrose sorbose A.2 Disaccharides - can be hydrolyzed into two saccharide units Sucrose - only disaccharide that occur freely in plants - hydrolyzed to form equimolecular weight of glucose & fructose (invert sugars) - a non-reducing sugar Maltose - a reducing sugar Lactose - milk sugar - a reducing sugar Trehalose - a nonreducing sugar Cellobiose - a reducing sugar  CLASSIFICATION OF DISACCHARIDES Products of Name Occurrence hydrolysis 1. Sucrose glucose, fructose Sugarcane, Sugarbeets 2. Maltose glucose, glucose Enzymatic hydrolysis of starch 3. Lactose glucose, galactose Milk 4. Cellobiose glucose, glucose Enzymatic breakdown of celllulose 5. Trehalose glucose, glucose in fungi; a sweet-tasting substance constituting the pupal covering of a beetle 6. Sophorose glucose, glucose Sophora japonica; Hydrolysis of stevioside 7. Primeverose glucose, xylose Filipendura ulmaria; Hydrolysis of spiroein  CLASSIFICATION OF TRISACCHARIDES Name Products of hydrolysis Occurrence 1. Gentianose glucose, glucose, fructose Gentiana spp. Many seeds (Example: 2. Raffinose galactose, glucose, fructose cottonseed) galactose, galactose, 3. Manneotriose Manna of ash, Fraxinus ornus glucose 4. Scillatriose rhamnose, glucose, glucose Glycoside of squill 5. Planteose glucose, fructose, galactose Seed of Psyllium spp Example of Tetrasaccharides - Stachyose or manneotetrose yields -  galactose, galactose, glucose, fructose - from tubers of Stachys japonica and manna of Fraxinus ornus - Oligosaccharides - Greek “oligo” - few - containing 2 - 10 saccharide units B. Polysaccharides - also known as glycan (generic term) - carbohydrates that are complex with high molecular weight that vary in size & structure; containing many monosaccharide units joined in long linear/branched chain - are polymers of monosaccharides (sugars) linked together through glycosidic linkages - Two biological functions; a) storage form for fuel (starch) b) as structural elements (cellulose) Naturally Occurring Polysaccharides classified as; 1. Homoglycans - has only one type of monosaccharide unit present - Examples: starch, inulin, cellulose 2. Heteroglycans - has more than one kind of monosacchaaride units present - Example: gums Polysaccharides classified as to their monomers; 1. Hexosan - yields hexoses on hydrolysis 2 types a) Glucosan/Glucan - yields glucose - Example: starch b) Fructosan/Fructan - yields fructose - Example: inulin 2. Pentosan - yields pentoses on hydrolysis - Example: xylan PROPERTIES OF CARBOHYDRATES 1. Common monosaccharide (pentoses & hexoses) are white crystalline, when heated melts with simultaneous decomposition, readily soluble in water, less soluble in EtOH or MeOH & insoluble in ether 2. Common disaccharides, the hexobioses also display same characteristics 3. Polysaccharides are amorphous, do not melt sharply & much less water soluble 4. Soluble lower molecular weight carbohydrates – sweet taste Relative sweetness (sucrose - value 1 or 100) a) lactose – 1/6 0r 16% d) fructose – 1.7 or 143.3% b) glucose – ¾ or 73.3% e) invert sugar- 127-130% c) maltose – 1/3 or 38.5% xylitol - substitute for sugar in chewing gums; prevents dental plaque 5. All are optically active; specific rotation serves as a means of differentiation 6. Many display mutarotation (a continuing change in the value of the rotation until a final fixed value is attained) 7. The carbonyl (C=O) & adjacent alcohol will form phenylhydrazine derivatives known as osazones (give characteristic m. pts. & exhibit definite crystalline structure) 8. Ag & Cu are reduced in valence & the carbohydrate is oxidize (distinguished reducing from nonreducing sugar) 9. All polysaccharide are hydrolyzed to simple monosaccharide either by chemical/enzymatic procedure (the latter showing specificity) 10. Carbohydrates are hydrolyzed by many organisms to simple alcohols, ketones/acids with the production of CO2 (fermentation) Carbohydrate Containing Drugs 1. Sucrose – obtained from; a) sugarcane - Saccharum officinarum (Poaceae) b) sugarbeets - Beta vulgaris (Chenopodiaceae) c) sugar maple - Acer saccharum (Aceraceae) - sucrose is also known as saccharum, sugar - world production is equally divided between sugar cane and sugar beets In the production of sugar from sugarcane; - lime is to neutralize the plant acids - SO2 to decolorize the juice - molasses (residual dark colored syrup obtained from sucrose production) - cosettes (limp slivers from sliced sugar beets) 2. Dextrose - occurs naturally in grapes & other fruits - controlled enzymatic hydrolysis of starch 3. Dextrose excipient - crystalline dextrose monohydrate 4. Dextrates - controlled enzymatic hydrolysis of starch (NLT 93% dextrose) 5. Liquid Glucose - incomplete hydrolysis of starch, contains dextrose, dextrins, maltose, prepared by controlled enzymatic hydrolysis of corn starch 6. Fructose - fruit sugar - from inversion of aqueous solution of sucrose - naturally from sweet fruits & honey - high fructose sweeteners – prepared by controlled enzymatic isomerization of glucose 7. Lactose – from cow’s milk - Bos taurus (Bovidae) - contains 2.5 to 5% fat (butter) - cream (fat globules that rise to the top) - butter (fat globules that unite when milk is churned) - buttermilk (liquid left when butter is removed) - skimmed milk (liquid left after separation of cream) - coagulum (formed when skimmed milk is treated with rennin) - cheese (obtained after proper treatment of the coagulum) - whey (liquid separated from the coagulum) - contains lactose and inorganic salts - condensed milk (evaporation of milk in a vacuum & sterilization by autoclaving) - malted milk (evaporating milk with extract of malt) - kumyss (fermented milk) 8. Lactulose - alkaline rearrangement of lactose - yields fructose & galactose - laxative (metabolized to acetic & lactic acids that produces irritating effects) - therapeutic use is to decrease blood ammonia concentration in portal-systemic encephalopathy 9. Xylose - wood sugar - diagnostic agent to evaluate intestinal absorption 10. Cherry Juice - succus cerasi - Prunus cerasus (Rosaceae) - contains 1% malic acid DRUGS CONTAINING COMPOUNDS METABOLICALLY RELATED TO SUGAR 1. Products of Glycolytic and Oxidative Metabolism - plant acids, alcohol 2. Products of Reductive Metabolism - sugar alcohols 11. Plant acids - citric acid, lactic acid, tartaric acid - used as acidulants & components of buffer system to control acidity a) Citric acid – tricarboxylic acid - lemon juice (Scheele) - commercially from limes, lemons & pineapples - used as acidulant, systemic alkalinizer in buffer system b) Lactic acid - by lactic fermentation of sugars - used as a) acidulant in infant feeding formulas b) treatment of metabolic acidosis c) Tartaric acid – dicarboxylic acid - by-product of the wine ndustry - used in a) buffer system b) effervescent formulations 12. Alcohol – NLT 92.35% by weight; 94.9 % by volume at 15.56oC - 70% w/v local anti-infective - Diluted Alcohol - 48.4-49.5% by volume at 15.56oC - Alcoholic Beverages - Beer (fermented grain); NMT 14% alcohol - Wine (fermented grape juice); NMT 14% alcohol - mild stimulant & tonic - Brandy (from wine) 40-55% alcohol - Whiskey (from fermented malted grain) 40-55% alcohol - Rum (from fermented molasses) 40-55% alcohol - brandy & whiskey (classified as CNS depressants) 13. Sugar Alcohols – Dulcitol, Mannitol, Sorbitol a) Mannitol - a hexitol; reduction of mannose - isolation from manna (dried saccharine exudate of Fraxinus ornus (Oleaceae) - osmotic diuretic, laxative, diagnostic aid b) Sorbitol - D-glucitol; a hexitol from ripe berries of mountain ash of Sorbus aucuparia (Rosaceae) - by hydrogenation/electrolytic reduction of glucose - solution in combination with mannitol as urologic irrigation - taste approximately half as sweet as sucrose - has humectant properties Polysaccharides and Polysaccharide - Containing Drugs 14. Starch - amorphous powder, insoluble in water, tasteless; yields glucose on hydrolysis - most common carbohydrate reserve in plants - Examples: corn, wheat, potato tubers, rice, sorghum, marantha rhizome, cassava roots - Mixture of two structurally different polysaccharides: a) amylose & b) amylopectin - most starches have similar ratio of amylose to amylopectin (averaging about 25% to 75%)  Difference between amylose and amylopectin Amylose Amylopectin Branching, 1000 or more D- Linear, 250-300 D-glucopyranose glucopyranose units, linked by a- Structure units, linked by a-1,4 glucosidic 1,4 linkages with 1,6 links at bonds branch points (about 4% of the total linkages) Solubility More soluble in water Less soluble Color reaction with Deep blue Blue-violet or purple iodine Reaction with a- Mixture of branched and Mixture of glucose, maltose amylase unbranched oligosaccharides Reaction with b- Dextrins (product of incomplete Nearly pure maltose amylase hydrolysis) - waxy or glutinous starches contains either no amylose or small amounts (less than 6%) - separation by complexing & precipitating amylose with various alcohols/nitroparaffins Uses of Starch a) ingredient in dusting powders b) pharmaceutic aid (tablet filler, binder & disintegrant) c) suspension is used as antidote for I2 poisoning Sources of Starches used in Pharmaceutical Preparations a) corn - Zea mays (Poaceae) - grain b) wheat - Triticum aestivum (Poaceae) - grain c) potato - Solanum tuberosum (Solanaceae) - tubers NOTE: - starches form colloidal solutions rather than true solutions - agents that cause swelling & rupture of starch granules to form paste are cold concentrated solutions of; a) caustic alkalies, b) chloral hydrate, c) ammonium thiocyanate, d) HCl NOTE: - in amylose, glucopyranose units are linked by alpha-1,4 glucosidic bonds, same bonds - in amylopectin, however a number of alpha-1,6 links occur at branch points. 15. Inulin - D-fructofuranose polymer - a fructosan, yields fructose on hydrolysis - subterranean organs of family Compositae or Asteraceae - abundant in taraxacum, inula, lappa, echinea & chicory - when extracted with alcohol --> inulin crystallizes in sphaerite aggregates Uses of inulin a) culture media as a fermentative identifying agent for certain bacteria b) special laboratory methods for the evaluation of renal function 16. Dextran - is an α -1,6-linked polyglucan from sucrose by the action of (dextran sucra) in Leuconostoc mesenteroides - desire size are prepared by controlled depolymerization (by acid hydrolysis, fungal dextranase or ultrasonic vibration) of native dextran or by controlled fermentation - Large Dextrans (70,000 & 75,000) - 6% solution-plasma expanders in shock caused by 1,6-linked, trauma/severe burns; is not a ubstitute for whole blood - Low Molecular Weight Dextran (40,000) in 10% solution - adjunct in the treatment of shock Note: Dextrans increase clotting time 17. Cellulose - most abundant organic compound in nature - composed of glucose units - primary structural material in plants; form the primary cell wall in plants - occurs as very fine threads called microfibrils - two other components of the cell wall; a) hemicellulose b) pectins - obtained from the hair of the seed of Gossypium hirsutum (Malvaceae) - ginned (remove seeds) - combed (remove gross impurities & short hairs) - weak alkali solution (remove fatty materials) - chlorinated soda (to bleach) Cellulose derivatives a) Methylcellulose - reaction of cellulose with caustic soda and methyl chloride - bulk laxative, suspending agent, topical protectant (artificial tears) b) Ethylcellulose - tablet binder, film coat c) Hydroxyethylcellulose - thickening agent d) Hydroxypropylcellulose - stabilizer, thickener, binder, film coat e) Hydroxypropyl methylcellulose - suspending agent, thickening agent, tablet excipient, topical protectant (artificial tears) f) Pyroxylin/Soluble Guncotton - action of nitric & sulfuric acids on cotton - mixture of cellulose nitrates - preparation of collodion & flexible ollodion (topical protectant) g) Oxidized Cellulose & Oxidized regenerated Cellulose - local hemostatics h) Cellulose Acetate Phthalate (CAP) - enteric coating i) Sodium CMC - suspending agent, thickening agent, tablet excipient, bulk laxative 18. Gums and Mucilages - are natural plant hydrocolloid - classified as anionic/nonionic polysaccharide/salts of polysaccharide - produced frequently in higher plants as a protective after injury - upon hydrolysis yields arabinose, galactose, glucose, mannose, xylose & various uronic acids that form salts with Ca , Mg, & other cations - gums are pathologic products that dissolves in water while mucilages are physiologic products that form slimy masses in water Sources of Commercially Useful Gums a) Shrub/ Tree Exudates - tragacanth, acacia, karaya b) Marine Gums - agar, carageenan, algin c) Seed Gums - guar, locust bean, psyllium d) Plant Extract - pectin e) Starch & Cellulose Derivatives - hetastarch, CMC, hydroxypropyl methylcellulose, methylcellulose, ethyl cellulose, oxidized cellulose f) Microbial Gums - dextran, xanthan A. Shrub/Tree Exudates 1. Tragacanth - Astragalus gummifer (Fabaceae) - vermiform tragacanth twisted into coils/wormlike - tragacanth sorts (irregular tears) - ribbon gum and flake gum (from transverse incisions made by a knife on main stem & older branches); a better grade - bassorin (70%); tragacanthin (30%) - tragacanth is employed as suspending agent, emulsifying agent, adhesive, demulcent & emolient (in lotions) - the most resistant hydrocololloid to acid hydrolysis (preferred in highly acidic conditions) 2. Acacia - aka gum arabic - Acacia senegal (Fabaceae) - principally arabin (complex mixture of Ca, Mg and K salts of arabic acid) - Stable at pH 2–10 - Uses: excellent emulsifying agent, suspending agent, demulcent, emollient, adhesive and binder in tablets 3. Karaya Gum - aka sterculia gum - Sterculia urens (Sterculiaceae) - high component of D-galacturonic & D-glucoronic acid residues - one of the least soluble exuded plant gums - Uses: bulk laxative, dental adhesive, in wave set lotions and skin lotions B. Marine Gums 1. Sodium Alginate - aka algin - from brown seaweeds with diluted alkali - Macrocystis pyrifera (Lessoniaceae) - chiefly Na salt of alginic acid (major component is mannuronic acid) - Uses: suspending agent, in the food industry (ice cream, chocolates) and in cosmetic preparations 2. Agar - aka japanese isinglas; from fresh seaweeds with diluted acid - sources… a) Gelidium cartilagineum (Gelidiaceae) b) Gracilaria confervoides (Sphaerococcaceae) c) related red algae (class Rodophyceae) - agarose & agaropectin - Uses: laxative, suspending agent, emulsifier, gelating agent, as surgical lubricants, tablet excipient & disintegrant, gel in bacteriologic culture media and in food processing. - agarose used as matrix for immunodiffusion, for electrophoretic separation of globulin & other proteins & in gel filtration & chromatography 3. Carageenan - aka chondrus/irish moss - from red algae or seaweeds of Chondrus crispus & Gigartina mamillosa (Gigartinaceae) - physically resemble agar - differ chemically from agar because of its higher sulfate ester content - Uses: form gel that stabilizes emulsion and suspensions, demulcent & bulk laxative, in toothpaste formulations 4. Furcellaran - aka danish agar - Furcellaria fastigiata (a red alga) - Uses: gelating agent, suspending agent C. Seed Gums 1. Plantago/Psyllium/Plantain Seed - Plantago psyllium (Plantaginaceae) - or P. indica (known as danish or french psyllium seed) or P.ovata (known as blonde psyllium of indian plantago seed) - Use: cathartic 2. Guar Gum/Guaran - Cyamopsis tetragonolobus (Fabaceae) - a galactomannan - Uses: bulk forming laxative, thickening agent, tablet binder & disintegrator 3. Locust Bean Gum – aka carob pulp/st. john’s bread - Ceratonia siliqua (Fabaceae) - a galactomannan - as thickener & stabilizer - in manufacturing processes where hydrocolloid is indicated 4. Cydonium - aka quince seed - Cydonia vulgaris (Rosaceae) - ingredient in wave set lotions D. Microbial Gum 1. Xanthan Gum - by the action of Xanthomonas campestris on suitable carbohydrates - has pseudoplastic properties used in toothpastes & ointments (enable them to hold their shape & spread easily) - excellent emulsifying and suspending properties 2. Dextran gum - formed from sucrose by the action a transglucosylase enzyme system (dextran sucrase) present in Leuconostoc mesenteroides (see slide #37) E. Plant Extract 1. Pectin - purified carbohydrate - dilute acid extract of the inner portion of the rind of citrus fruits/apple pomace - chiefly partially methoxylated polygalacturonic acid - standardized to “150 jelly grade” by addition of dextrose or other sugars - soluble pectin - in ripe fruits - pectic acid - in over ripe fruits - protopectin - insoluble form in unripe fruits - citrus peel is a rich source of pectin - Uses: protectant, ingredient in antidiarrheal preparations, suspending agent  Sources of pectin Plant Scientific name 1. Pomelo Citrus grandis 2. Orange Citrus aurantium 3. Dalanghita Citrus nobilis 4. Ponkan Citrus sinensis 5. Kalamansi Citrus microcarpa 6. Lemon Citrus Iimon 7. Lime Citrus autantifolia  Tabulated Listing of Carbohydrates and Carbohydrate Containing Drugs A. Sugar and Sugar Containing Drugs Drug (Synonyms) Scientific name (Family) Constituent Uses Additional Info - part used - pharmaceutic sugar maple - Acer saccharum necessity for syrups (Aceraceae) - sap from - demulcent the trunk - nutrient 1. Sucrose (Sugar, - Saccharum officinarum - in sufficient concentration sucrose sugar cane Saccharum) (Poaceae) - stem bacteriostatic - Beta vulgaris - preservative (Chenopodiaceae) - - masks disageeable storage root taste sugar beets - retards oxidation - nutrient (PO, enema, SC inj, or naturally in grapes 2. Dextrose IV inj.) Vitis vinifera (Vitaceae) α-D(+)-glucopyranose/ dextrose - ingredient in Dextrose inj, Alc grapes by controlled enzymatic D-Glucose and Dextrose inj, Dextrose and hydrolysis of starch NaCl inj, etc  Scientific name Drug (Synonyms) (Family) Constituent Uses Additional Info - part used - how obtained - agent of pharmaceutic necessity - sweetening agent a crystalline dextrose 3. Dextrose excipient - substitute of sucrose in monohydrate syrups - tablet binders - coating agents - industrially, as pharmaceutic necessity prepared by controlled a purified mixture of - sweetening agent 4. Dextrates enzymatic hydrolysisof saccharides (NLT 93% - substitute of sucrose in starch dextrose) syrups - tablet binders - coating agents - product of incomplete primarily dextrose but hydrolysis of starch - agent of pharmaceutic 5. Liquid Glucose may contain dextrins, - by controlled acid necessity maltose and water hydrolysis of starch (US) - naturally-most sweet - food for diabetics fruits 6. Fructose NOTE: High fructose - inversion of aqueous - β-D(-)fructofuranose fructose sweeteners-prepared by - half as sweet as glucose solution of sucrose and - fruit sugar controlled enzymatic - separation of fructose isomerization of glucose - hydrolysis of inulin  Scientific name Drug (Synonyms) (Family) Constituent Uses Additional Info - part used - how obtained water (80-90%), fat (2.5- - nutrient 5%), casein (3%), lactose - source of lactose, yogurt 7. Cow’s Milk Bos taurus (Bovidae) (abt 5%), inorg salts azand kumyss (fermented ( 0.1-1%) and vitamins milk) - nutrient in infant food - pharmaceutic necessity 8. Lactose (milk sugar) sugar from milk lactose - tablet diluent (inert diluent for other drugs) - laxative (hydrolyzed into acetic and lactic acid in the colon and causes by alkaline - yields fructose and 9. Lactulose lactulose laxative effect) rearrangement of lactose galactose on hydrolysis - decrease blood NH3 in portal systemic encephalopathy a pentose obtained by boiling corn cobs, diagnostic agent to 10. Xylose (D-xylose, straw/similar materials xylose evaluate intestinal wood sugar) with dilute acid to absorption hydrolyze the xylan polymer  Tabulated Listing of Carbohydrates and Carbohydrate Containing Drugs B. Drugs Containing Compounds Metabolically Related to Sugar Products of Glycolytic and Oxidative Metabolism Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) 11. Cherry Juice (Succus Prunus cerasus - used in the prepration of cerasi) malic acid NLT 1% (Rosaceae) Cherry syrup - fruit obtained commercially - useful in buffering system 12. Citric acid from lemon, limes & citric acid - acidulant in effervescent isolated from lemon juice - a tricarboxylic acid pineapple formulations - by lactic fermentation - acidulant in infant feeding 13. Lactic acid of sugars lactic acid formulas - prepared synthetically a by-product of the wine - substitute for citric acid in 14. Tartaric acid industry tartaric acid buffer systems and in - a dicarboxylic acid effervescent formulations - NLT 92.3 by weight - 70% w/v local anti-infective - 94.9% by volume 15. Alcohol (Ethanol) - diluted alcohol - solvent - Diluted alcohol 48.4- 49.5% v/v at 15.56oC  Tabulated Listing of Carbohydrates and Carbohydrate Containing Drugs B. Drugs Containing Compounds Metabolically Related to Sugar Products of Reductive Metabolism Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) - hexahydric alcohol formed by reduction of mannose 16. Mannitol/D- - isolation from - diagnostic aid mannitol mannitol trunk exudate of - osmotic diuretic manna Fraxinus ornus (Oleaceae) - Sorbus aucuparia - well known - humectant (toothpaste, hexahydric alcohol (Rosaceae) 17. Sorbitol (D- chewing gums, & various - from glucose by glucitol or D-sorbitol sorbitol dietetic products hydrogenation or - berries (fruit) - with mannitol as electrolytic urologic irrigation reduction  Tabulated Listing of Carbohydrates and Carbohydrate Containing Drugs C. Pollysaccharides and Pollysaccharide-Containing Drugs Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) - Corn - Zea mays (Poaceae) - grain - Wheat -Triticum - ingredient in dusting powders aestivum (Poaceae) - - pharmaceutic aid (tablet 18. Starch starch grain filler, binder, disintegrant) - Potato - Solanum - antidote for iodine poisoning tubeosum (Solanaceae) - tuber starch that has been chemically or mechanically processed 19. Pregelatinized Starch - tablet excipient to rupture all or part of the granules in the presence of water - semisynthetic material 20. Sodium Starch - disintegrating agent in tablet - sodium salt of a Glycolate formulations carboxymethyl ether  Tabulated Listing of Carbohydrates and Carbohydrate Containing Drugs C. Pollysaccharides and Pollysaccharide-Containing Drugs Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) approximately 90% adjunct therapy in the amylopectin, and 7 or 8 treatment of shock hydroxyethyl - 6% solution used as plasma 21. Hetastarch caused by hemorrhage, constituents are present epander burns, surgery, sepsis, for every 10 glucose or other trauma units - in culture media 22. Inulin/hydrous inulin from subterranean - fermentative identifying agent extracted by alcohol ---> - a D-fructofuranose organs of embers of foer certain bacteria crystallizes as sphaerite polymer Asteraceae (Compositae) - used in sp lab method for the aggregates evaluation of renal function - from sucrose by the 2 types - 6% solution of Dextran 70 and - not a substitue for action of dextran 1. large dextran 75 - plasma expander in shock blood 23. Dextran sucrase (transglucosyse (mw 40,000, - 10% solution of LMW dextran - - interfere with - α-1,6-linked polyglucan enzyme system) in 70,000, 75,000) adjunct in the treatment of laboratory test (increase Leuconostoc 2. low mw dextran shock clotting time) messenteroides Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) 24. Purified - surgical dressing cellulose (β- Cotton/Absorbent - mechanical protection to Gossypium hirsutum linked linear cotton absorb blood, mucus or pus (Malvaceae) glucopyranosyl - hair of the seed - keep bacteria from infecting polymer) wounds mechanically, disintegrated cellulose prepared by processing - self-binding tablet diluent 25. Powdered Cellulose α-cellulose obtained as and disintegrating agent a pulp from fibrous plant materials - a partially dpolymerized cellulose - prepared by treating 26. Microcrystalline α-cellulose (obtained - diluent in tablets cellulose as a pulp from fibrous plant materials wih mineral acids) fibrous form of NMT 1.25% titanium 27. Purified rayon bleached regenerated - surgical aid dioxide cellulose  Tabulated Listing of Carbohydrates and Carbohydrate Containing Drugs D. Gums and Mucilages Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) - Bassorin (complex of - suspending agent 28. Tragacanth/ Gum Astragalus gummifer polymethoxylated - emulsifying agent Tragacanth - most resistant to acid (Fabaceae) acids 60-70% - adhesive - exudate hydrolysis - tragacanthin - demulcent (demethoxylated - emollient bassorin) - suspending agent 29. Acacia/Gum Arabic - Arabin (complex - unusually soluble for a Acacia senegal - emulsifying agent - exudate from stem and mixture of Ca, Ng hydrocolloid (Fabaceae) - adhesive and binder in tablets branches and K salts of - good stability over a - demulcent arabic acid) wide pH (2-10) - emollient - readily forms 30. Ghatti/Indian gum Anogeissus latifolia dispersion in cold water - exudate (Combretaceae) - substitute for acacia - more viscous than acacia Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) - acetylated branched - bulk laxative Sterculia urens, heteropolysacchari 31. Karaya/Sterculia gum - agent for forming eulsions and S.villosa, de with high - one of the least soluble - gummy exudate suspensions S. tragacantha component of D- plant gums - dental adhesives in wave set (Sterculiaceae) galacturonic acid lotions and glucoronic acid residues - sodium salt of alginic acid,a linear - Macrocystis pyrifera polymer of L- 32. Sodium Alginate/Algin (Lessoniaceae) guluronic and, - suspending agent - extract of brown - all species of mannuroric acid - tablet binder and thickening seaweeds (Phaeophyceae) - mannuronic acid is the major component - agarose (used as a matrix for - laxative - Gelidium cartilagineum immunodiffusion, - suspending agent (Gelidiaceae) for electrophoretic - emulsifier 33. Agar/Japanese Isinglas - Gracilaria confervoides separation of - gelating agent for suppository - extract of hydrophillic (Sphaerococcaeae) globulin and other - surgical lubricant colloidal substance - red algae proteins and gel - tablet excipient and disintegrant (class Rodophyceae) filtration and gel - gel in bacteriologic culture chromatography) media - agaropectin Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) - give stability to emulsions 34. galactans with and suspensions Carrageenan/Chondrus - Chondrus crispus sulfate esters - desirable in toothpaste /Irish Moss - Gigartina mamillosa - K-carrageenan formulations - from red algae and (Gigartinaceae) - i-carrageenan - demulent seaweeds - λ-czrrageenan - bulk laxative 35. Furcellaran Furcellaria fastigiata - similar to k- - gelating and suspending - extract of red algar carrageebnan agent - Plantago psyllium - Plantago indica 36. Plantago (Spanish/French - cathartic (swelling seed see/Psyllium psyllium seed) - hydrocolloid coat gives bulk and seed/Plantain Seed - Plantago ovata lubrication) - seed (blonde psyllium/Indian plantago) (Plantaginaceae) 37. Cydonium/ Quince Cydonia vulgaris Seed - ingredient in wave set lotion (Rosaceae) - seed Drug (Synonyms) Scientific name Constituent Uses Additional Info - part used (Family) - a galactomannan (1,4 linked-D- mannopyranosyl units form a linear form, - bulk forming laxative 38. Guar gum/ Guaran Cyamopsis tetragonolobus single 1,6 linked-D- - thickening agent - endosperm of the seed (Fabaceae) galactopyranosyl - tablet binder and disintegrator residues are attached to alternate mannose moieties - carob-flour or powder from the flesh of the of mature seed 39. Locust Bean Gum Ceratonia siliqua - a galactomannan and pods - powdered endosperm of the - thickener and stabilizer (Fabaceae) is similar to guar gum - resembles chocolates seed - aka carob pulp/St. John’s bread - a branched, partially acetylated - emulsifying and suspending agent - dissolves in hot and cold action of Xanthomonas 40. Xanthan Gum polysaccharide - pseudoplastic property water campestris on suitable - microbial gum containing D-glucose, - enable toothpaste and ointments to - viscosity independent of carbohydrates D-glucuronic acid and hold their shape and spread readily temperature between 10-70 o C D-mannose Pharmaceutic pectin differs - dilute acud extract of the - protectant from commercial pectin rind of citrus fruits or apple - partially - suspending agent because it does not contain 41. Pectin pomace methoxylated - ingredient in antidiarrheal preparation sugar or organic acids - citrus peel is a rich source of polygalacturonic acid - standardized to 150 jelly grade by the pectin addition of dextrose or other sugars - protopectin is the insoluble form of pectin in fruits  IDENTIFICATION TEST FOR CARBOHYDRATES TEST REAGENT POSITIVE RESULT CHO Tested A - copper sulfate solution Brick red ppt of cuprous 1. Fehling’s Test Reducing sugars B - KNaTartrate oxide solution 2. Molisch’s Test Alpha napthol in H2SO4 Purple/violet ring All carbohydrates 3. Osazone Test Phenylhydrazine, HAc, Yellow osazone crystals Ketoses & aldoses sodium acetate 4. Seliwanoff’s Test Resorcinol & HCl Cherry red color Ketones Brick red ppt (also Copper SO4, NaOH, green, yellow, orange 5. Benedict’s Test Reducing sugars Tartaric acid red, then brick red/brown Ammoniacal AgNO3 Gray to black ppt with 6. Tollen’s Test Reducing sugars solution Ag mirror  IDENTIFICATION TEST FOR CARBOHYDRATES TEST REAGENT POSITIVE RESULT CHO Tested Cupric acetate & acetic 7. Barfoed’s Test Brick red ppt Reducing sugars acid Anthrone reagent in 8. Anthrone Test Blue-green color Glucose & glucan conc. H2SO4 9. Bial-Orcinol Test Orcinol, HCl, FeCl3 Green color ppt Pentoses Alkaline solution of 10. Nylander’s Test Black ppt Reducing sugars Bismuth subnitrate Galactose & galactose 11. Mucic Acid Test HNO3 White sandy crystals containing CHO 2,4,6-trinitrophenol/ 12. Picric Acid Test Mahogany red solution Reducing sugars Picric acid  IDENTIFICATION TEST FOR CARBOHYDRATES TEST REAGENT POSITIVE RESULT CHO Tested 13. Trommer’s Test 10% NaOH, CuSO4 Orange red ppt Reducing sugars Deed blue color (in suspension) 14. Lugol’s Test Iodine T.S. Starch Purple color (in powder) 15. Tauber’s/Benzidine Benzidine reagent Violet color Pentoses Test 16. Phloroglucinol-HCl Phloroglucinol & HCl Cherry red color Pentoses Test Brown color with 17. Moore’s Test 10% NaOH CHO caramel-like odor 18. Iodine Test Iodine solution blue/black color Starch MODULE 3 GLYCOSIDES PREPARED BY: JESUSIMA P. MONSERATE, RPh & JOHN PAUL B. DEMONTEVERDE, RPh GLYCOSIDES - compounds that yields one or more sugars among the products of hydrolysis. - condensation products of sugars with various kinds of organic compounds with added restriction that the OH of the hemiacetal portion of the carbon must participate in the condensation. - chemically, are acetals in which the OH of the sugar is condensed with the OH of the nonsugar components and the 2nd OH is condensed within the sugar molecule itself to form an oxide ring. - are sugar ethers 2 components of Glycosides a) aglycone/genin - non sugar component - basis of classification - responsible for therapeutic action b) glycone - sugar component - beta D-glucose - most frequently occurring sugar (formerly referred to as glucoside) - both beta and alpha forms are possible but only the beta forms occur in plants CLASSIFICATION OF GLYCOSIDES 1. according to the identity of the sugar moiety - Examples: glucoside – glucose, fructoside – fructose 2. according to the complexity of the sugar moiety - Examples: monosides, biosides, etc. 3. according to the aglycone (feasible but intricate because of the large variety of aglycone) - Examples: tannins, sterols, carotenoids, anthocyanins 4. according to therapeutic activity - Examples: cardiotonics, cathartics 5. according to the chemical nature of the aglycone - Examples: anthraquinone, saponins, cyanophore Properties of Glycosides (when pure) 1. colorless/ white 2. optically active 3. soluble in alcohol & dilute alcohol Chemical Properties 1. susceptible to hydrolysis ----> yields sugar + nonsugar component Caused by; a) acid hydrolysis - hydrolyze both alpha & beta forms b) enzymatic hydrolysis - hydrolyze only the beta form - specific in their action Two enzymes that can hydrolyze a considerable number of glycosides a) emulsin - almond kernels - hydrolyze only beta-glycosides - aka beta-glucosidase b) myrosin - black mustard - these enzymes occur in different cells; exert hydrolytic effects when it contact with the glycosides when the plant … a) is damaged by grinding/other means b) during germination process c) other physiologic activities Functions of Glycosides in Plants 1. Regulatory 2. Sanitary 3. Protective I. Cardiac Glycosides - steroids characterized by a highly specific and powerful action on the cardiac muscle - occur as glycoside with sugars attached at the C3 of the steroid nucleus and a lactone ring at C17 Two types of aglycone genin 1. cardenolide- most prevalent in nature - a C23 steroid ( 5-membered lactone) 2. bufadienolide - a C24 steroid ( 6 membered lactone ring) - name is derived from the generic name for the toad, Bufo - the prototype compound bufalin was isolated from Bufo Cardiac glycosides increase the force of systolic contraction l more complete emptying of the ventricle & shortening in the length of the systole (the heart has more time to rest between contractions) (heart rate is decreased) l improve circulation l improve renal circulation l relieves edema (associated with heart failure) Digitalis - Digitalis/foxglove - Digitalis pupurea (Scrophulariaceae) - adjusted to final potency by admixture of sufficient lactose exhausted marc of digitalis starch or powdered drug of digitalis with lower or higher potency - digitoxin, gitaloxin and gitoxin (important glycosides from medicinal viewpoint) - pigeon - animal employed in the assay procedure - digitalis in tablets or capsules is used to treat CHF, paroxysmal atrial tachycardia, atrial flutter and atrial fibrillation Digitoxin - cardiotonic glycoside obtained from D. purpurea , D. lanata and other suitable species of digitalis - a highly potent drug - the most lipid-soluble of the cardiac glycosides used in therapeutics - has complete oral absorption (distinguishes it from other cardiac glycosides) - has same uses and precautions as digitalis Digitalis lanata or Grecian Foxglove - source of digoxin and desacetyllatoside C - nearly 70 different glycosides have been detected 19 of the most important are derivatives of 5 aglycones 3 of which (digitoxigenin, gitoxigenin and gitaloxigenin) also occur in D. lanata - the 5 types of primary glycosides are designated lanatosides A,B,C D and E - lanatosides are also referred to as digilanids Digoxin - the most widely used of the cardiotonic glycosides - highly potent drug (should be handled with exceptional care) - short-acting and rapidly eliminated (compared with digitoxin) Deslanoside (desacetyllnatoside C) - frequently used to attain rapid initial loading by parenteral administration - highly potent  Drugs Containing Cardiac Glycosides Drugs (part used) Scientific Name and Family Important Constituents Important Uses treat CHF, paroxysmal atrial Digitalis purpurea 1. Digitalis/Foxglove (leaves) digitoxin, gitoxin, gitaloxin tachycardia, atrial flutter, (Scrophulariaceae) atrial fibrillation digoxin & 2. Digitalis lanata/Grecian Digitalis lanata desacetyllanatoside C have digoxin, dsacetyllanatoside C Foxglove (leaves) (Scrophulariaceae) the same uses and precautions as digitalis 3. Convallaria/Lily-of-the- Convallaria majalis convallatoxin, convallatoxol, cardiotonic, diuretic valley (roots) (Liliaceae) convallatoside 4. Apocynum/indian hemp, Apocynum cannabinum, dog bane, Canadian hemp A. androsaemifolium cymarin cardiotonic anti-arrhythmia (rhizome and roots) (Apocynaceae) 5. Adonis/pheasant’s eye Adonis vernalis adonitoxin, cymarin, K- cardiotonic (overground portion) (Ranunculaceae) strophanthin  Drugs Containing Cardiac Glycosides Drugs (part used) Scientific Name and family Constituents Important Uses 6. Cactus grandiflorus/night Selenicereus grandiflorus stimulating tonic, cardiac blooming cereus, queen of resinous glycosides (Cactaceae) restorative, diuretic the night (stem) 7. Black Hellebore/ Helleborus niger Christmas rose (rhizome and hellebrin cardiac stimulant (Ranunculaceae) roots) for heart problems and high Strophanthus kombe K-strophanthosside blood pressure, used by the 8. Strophanthus (seed) S. hispidus (Apocynaceae) /strophoside native Africans in the preparation of arrow poisons 9. Squill/ squill bulb (fleshy, expectorant, emetic, Urginea maritima (Liliaceae) scillaren A inner scales of the bulb) cardiotonic, diuretic 10. Red Squill (bulb or bulb U. maritima red variety rat poison (rodenticide) scales) Other Cardiac Glycosides Oleandrin - leaves of Nerium oleander (Apocynaceae) - treat cardiac insuffciency Ouabain - seeds of Strophanthus gratus / wood of Acokanthera schimperi (Apocynaceae) - also known a G-strophanthin - cardiac stimulant (and in the teatment of peptic ulcer and snake bites) II. Anthraquinone glycosides (aglycones related to anthracene...anthraquinones, anthranols and anthrones) Drugs … a) cascara sagrada e) chrysarobin b) frangula f) rhubarb c) aloe g) danthron d) Senna - employed as stimulant cathartic except chrysarobin - the free anthraquinone aglycones exhibit little therapeutic activity; the sugar residue facilitate absorption and translocation of the aglycone to the site of action  Drugs Containing Anthraquinone Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family Barbaloin - cathartic 1. Cascara sagrada/ Rhamnus purshianus Chrysaloin (correction of habitual Rhamnus purshiana (Rhamnaceae) Note: bitter taste constipation) (bark) reduced by MgO 2. Frangula/Buck- Rhamnus frangula Note: MOVICOL is - cathartic Thorn Bark (Rhamnaceae) frangula + karaya gum 3. Aloe/Curacao - cathartic Aloe barbadensis Barbaloin (aloe-emodin Aloe/Cape Aloe (latex - pharmaceutical aid of (Liliaceae) anthrone) of the leaves) compound benzoin tr.  Drugs Containing Anthraquinone Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family Cassia acutifolia Dimeric glycosides cathartic 4. Senna (leaves) C. angustifolia (aglycones are aloe- UD: 2g (Fabaceae) emodin & rhein 5. Chrysarobin Andira araroba keratolytic (treatment (Anthralin) (Fabaceae) chrysarobin of psoriasis, eczema, (neutral principles - hot benzene etc.) from Goa powder 6. Rhubarb/ Rheum officinale rhein enthrones cathartic (drastic) Rheum (Polygonaceae) 1,8-dihydroxy- 7. Danthron/chrysazin cathartic anthraquinone III. Saponin glycosides (sapogenin) Drugs: glycyrrhiza/ licorice, ginseng, Dioscorea (widely distributed in higher plants) - Important characteristics of saponin glycosides a) form colloidal solutions with water that foams upon shaking b) bitter acrid taste c) sternutatory (irritating to the mucous membrane) d) destroy RBC by hemolysis (toxic to cold-blooded animals fish poison) sapotoxins - more poisonous saponins - Two types of saponin glycosides (based on the chemical structure of the aglycones) 1. neutral saponins - derivatives os steroids with spiroketal side chain 2. acid saponins - possess triterpenoid structures  Drugs Containing Saponin Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family 1. Glycyrrhiza/ Glycyrrhiza glabra glycyrrhizin/glycyrrhizi - demulcent Licorice (Fabaceae) c acid - expectorant (50x as sweet as - flavoring agent (mask sugar) the taste of bitter drugs) 2. Dioscorea/Yam Dioscorea spp Dioscin + HOH  D. floribunda - best diosgenin (precursor of source of steroids glucocoorticoids) 3. Ginseng Panax ginseng (Asian) ginsenosides - adaptogenic/ or P. quinquefolius panaxosides antistress (American) - chikusetsusaponins - tonic (Araliaceae) - stimulant - diuretic - carminative IV. Cyanophore/Cyanogenic glycosides (HCN) Common cyanophore glycosides… a) derivatives of mandelonitrile (benzaldehyde- cyanohydrin) Example: Amygdalin (bitter almonds, kernels of pricots & other seeds of Rosaceae) b) prunasin - Prunus serotina c) sambunigrin - Sambacus nigra - widely employed as flavoring agents - anticancer claims (Laetrile/ Vit B17- amygdalin containing preparation  Drugs Containing Cyanophore Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family - prunasin (L- 1. Wild Cherry/ mandelonitrile - sedative expectorant Prunus Virginiana Prunus serotina glucoside from partial - flavored vehicle in Wild Black Cherry Tree (Rosaceae) hydrolysis of cough remedies (stem bark) amygdalin) - HCN  V. Isothiocyanate Glycosides - (isothiocyanates) - from the seeds of cruciferous plants Glycosides … a) sinigrin - black mustard - hydrolyze to form allylisothiocyanate (volatile mustard oil) b) sinalbin - white mustard - hydrolyze to form acrinyl isothiocyanate c) gluconapin - rape seed Isothiocyanate glycoside - also known as glucosinolates (represent a group of bound poisons like the cyanogenic glycosides - the S atom is conjugated with glucose as the S-glycoside - characteristic constituents of the mustard family (Brassicaceae) as rapeseed, mustard, horseradish, broccoli, cabbage, turnips - feeding deterrent (insects) and found to have anticarcinogenic property  Drugs Containing Isothiocyanate Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family 1. Black Mustard/ Brassica njgra - sinigrin (glycosside) - local irritant Sinapis Nigra/ (Brassicaceae) - myrosin (enzyme) - emetic Brown Mustard - rubefacient - vesicant - condiment 2. WhiteMustard/ Brassica alba - sinalbin commercially Sinapis Alba (Brassicaceae) important as black mustard 3. Garlic Allium sativum Alliin + HOH  Allicin-antibacterial, (Liliaceae) Allicin  (E) ajoene + responsible for odor & (Z) ajoene flavor Garlic - garlic possesses antihyperlipidemic and enhances blood fibrinolytic activity and inhibits platelet aggregation - (E) ajoene & (Z) ajoene formed from allicin have antithrombotic property with the Z-isomer being more bioactive VI. Flavonol Glycosides (together with their aglycones are generally termed flavonoids) - occur as yellow pigments in higher plants - best known flavonoid constituents … a) rutin b) quercitrin c) citrus bioflavonoids (hesperidin, hesperitin, diosmin, naringen) - rutin and hesperidin - referred to as vit. P or Permeability factors - treatment of capillary bleeding - citrus bioflavonoids - for the treatment of common colds VII. Alcohol Glycosides (alcohol) - Example: Salicin - from species of salix & populus - willow & poplar barks yield salicin - principal sources: Salix purpurea & Salix fragilis - hydrolyze into D-glucose & saligenin (salicyl alcohol) - has antirrheumatic properties VIII. Aldehyde Glycosides – (aldehyde) Drug... a) Vanilla (vanillin develops during the curing process) - vanillin is 4-hydroxy-methoxybenzaldehyde or methylprotocathechuicaldehyde - vanillin is semisynthetically prepared from … a) coniferin from cambium sap of pine trees b) eugenol a phenol from clove oil c) lignin a byproduct of the pulp industry (from where most of vanillin in commerce is made) - vanillin is used as flavoring agent (ethyl vanillin a synthetic analog of vanillin is also used as flavoring agent)  Drugs Containing Aldehyde Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family 1. Vanilla/Vanilla bean V. planifolia - glucovanillin - the tincture as (fruit) (Mexican/Bourbon) - glucovanillic alcohol flavoring agent V. tahitensis (Tahiti) - - pharmeutical aid (Orchidaceae) - source of vanillin IX. Lactone Glycosides (coumarin) - Examples: glycosides with hydroxylated coumarin derivatives skimmin (Japanese Star Anise), aesculin (Horse Chestnut tree), daphnin (mezereum), fraxin(ash bark), scopolin (Belladonna, limettin (citrus trees) - none is of paricular medicinal importance - some use have been made o natural nonglycosidic coumarin and other lactone substances( coumarin and tonka beans, coumarin containng seeds of Dipteryx odorata and D. oppositifolia (Fabaceae) were formerly used as flavoring agents - other uses anticoagulant (some coumarin der.), antispasmodic(scopoletin), uterine sedatives, dermatologic purposes (cantharidin and methoxalen), anthelmentic (santonin) Uses of Coumarin & Coumarin Derivatives a) flavoring agent (pharmaceutically) b)anticoagulant(dicumarol/bishydroxycoumarin) c) antispasmodic d) uterine sedatives e) for dermatologic purposes (cantharidin & methoxsalen) f) anthelmintic (santonin)  Drugs Containing Lactone Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family - Tonka beans, Dipterex odorata (Fabaceae) - Sweet Vernal grass, Anthoxanthum odoratum (Poaceae) - Sweet Clover, Melilotus - formerly used as 1. Coumarin albus (Fabaceae) coumarin flavoring agent - Sweet-Scented Bedstraw, Galium triflorum (Rubiaceae) - Red Clover, Trifolium pratense (Fabaceae) 2. - Melilotus officinalis Dicumarol/Bishydroxycou (Fabaceae) (leaves and dicumarol anticoagulant marin flowering tops)  Drugs Containing Lactone Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family - irritant - vesicant 3. Cantharides/ - rubefacient Spanish Flies/ Cantharis vesicatoria cantharidin - aphrodisiac Blistering Flies/ (Meloidae) (whole insect) - removal of warts Russian Fliies (0.7%cantharidin in collodion) 4. Methoxalen / xanthotoxin/ - facilitate repigmentation 8-methoxy-psoralen in idiopathic vitiligo Ammi majus 8-methoxy-psoralen (leukoderma) Note: Trioxalen (synthetic (Umbelliferae) - symptomatic control of furocoumarin s available severe psoriasis for the treatment of vitiligo) X. Phenol Glycosides (phenol) - Examples: Arbutin (uva ursi, chimapila, etc.), hesperidin (citrus fruits), phloridzin ( rootbark of rosaceous plants) baptisin (baptisia), iridin) Drug … a) uva ursi/bearberry - diuretic & astringent  Drugs Containing Phenol Glycosides Scientific Name and Drugs (part used) Important Constituents Important Uses Family Arctostaphylos uva - astringent 1. Uva ursi/bearberry arbutin –ursi (Ericaceae) - diuretic Hespiridin Citrus fruit Phlofridzin Root bark of Rosaceous plants Examples of phenolic glycosides Name Examples of sources Products of hydrolysis 1. Salicin Salix and Populus spp. Salicyl alcohol, glucose Viburnum prunifolium 2. Populin (benzoyl-salicin) Populus tremula Salicyl alcohol, benzoic acid, glucose 3. Arbutin Ericaceae and Rosaceae Hydroquinone, glucose 4. Phloridzin Rosaceae, including spp. of Malus Phloretin, glucose 5. Trilobatin Malus, Spiraea Phloretin, glucose 6. Coniferin Coniferae Coniferyl alcohol, glucose 7. Gaultherin Gaultheria, Betula and Monotropa Methyl salicylate, primeverose 8. Syringin Particularly in Oleaceae Methoxyconiferyl alcohol, glucose 9. Glucovanillin Vanilla spp. and some Gramineae Vanillin, glucose 10. Gein Geum spp. Eugenol, vicianose (glucose + arabinose) 11. Glucogallin Rheum spp. Gallic acid, glucose 12. Hamamelitannin Hamamelis virginiana Gallic acid (2 mols), hamamelose 13. Meadowsweet MODULE 4 TANNINS PREPARED BY: JESUSIMA P. MONSERATE, RPh & JOHN PAUL B. DEMONTEVERDE, RPh TANNINS - are complex substances usually occur as mixtures of polyphenols that are difficult to separate because they do not crystallize - also referred to as “tannin extracts” - the term “tannin” was first used by Seguin in 1796 to denote substances present in plant extracts which were able to combine with proteins of animal hides, prevent their putrefaction and convert them into leather - most true tannins have molecularweight from 1000 to 5000 - found in greatest quantity in dead or dying cells Tannins are customarily divided into two chemical classes (based on the identity of the phenolic nuclei) 1. hydrolyzable tannins/pyrogallol tannins - consist of gallic acid and hexahydroxydiphenic acid and their derivatives esterified with glucose. - readily hydrolyze to yield phenolic acids (gallic acid/related polyhydric compounds) & sugar (glucose units) - gives blue/blue-black color with FeCl3 reagent - Examples: Gallitannins, ellagitannins Tannins are customarily divided into two chemical classes (based on the identity of the phenolic nuclei) 2. nonhydrolyzable tannins/condensed tannins/catechol tannins - contain only phenolic nuclei but frequently are linked to carbohydrates/proteins - proanthocyanidin is used alternatively for condensed tannins (when treated with hot acids ---> anthocyanidin monomers - when treated with hydrolytic agents  polymerize  red colored compounds (phlobaphenes) - gives blue–green color with FeCl3 reagent (brownish green by Trease and Evans) - Example: proanthocyanidins  Pseudotannins - simple phenolic copounds often (often of low molecular weight) present with tannin - they may at certain conditions give precipitates with gelatin but do not respond to goldbeater’s skin test. - Examples: Gallic acid, cathechins, chlorogenic acid, ipecacuanhic acid NOTE: - both classes of tannins are widely distributed - both are present although one type tends to predominate - tannins are usually localized in specific plant parts as stems, leaves, fruits and barks “Complex tannins” - term applied by Okuda to a newly-discovered group of tannins which are biosynthesized from both hydrolyzable and a condensed tannin - have not great relevance to mainstream pharmacognosy - have been isolated from Combretaceae, Fagaceae, Myrtaceae, Polygonaceae, and Theaceae Properties of Tannins a) non-crystallizable b) form colloidal solution with water possessing acid reaction with sharp puckering taste c) precipitate solutions of gelatin & alkaloids d) form dark blue/greenish black soluble compounds with Fe salts e) forms deep red color with K ferricyanide & ammonia f) precipitated by salts of Cu, Pb, Tin, strong aqueous K dichromate Uses of Tannins a) astringent (GIT & skin abrasions) b) trx of burns c) vegetable tanning (convert animal hides to leather) : “bloom leather” - hydrolyzable tannin “tanners red leather” - nonhydrolyzable tannin d) manufacture of inks e) reagent in the detection of gelatin, proteins & alkaloids f) antidote for alkaloidal poisoning g) may have potential value as cytotoxic/antineoplastic agents Medicinal and Biological Prope