1- Introduction about herbal and animal drugs and their preparations: Crud drugs are vegetable or animal drugs

that consist of natural substances that have undergone only the processes of collection and drying.

Natural substances:
1- Plant origin: leaves, flowers, seeds and barks. Or vegetable saps, extracts and secretions.
2-

Animal origin: whole animals, glands or organs, extracts and secretions.

Animal drugs are produced from wild animals (similar to wild plants) or domesticated animals (similar to cultivated plants). Wild animals must be:
1-

Hunted e.g., musk deer.

2- Fished for cod liver oil

Domesticated animals: I- When drugs consist of insects, the drugs are either: A-Collected from wild insects (cantharides) or B- Definite attempts are made to cultivate them to: 1- Furnish the insects with food and 2- Shelter To maintain optimum conditions for their propagation e.g., (honey bee). II- When drugs consist of animals: - Drugs such as hormones, endocrine products and some enzymes are obtained from domesticated hogs, sheep or cattle. - The slaughter house is the usual source of glandular products and enzymes.

I- Cantharides: Source: cantharides are the dried beatles Lytta vesicatoria, Meloide. Constituents: cantharides contain cantharidine. Uses: cantharides are an irritant and rubefacient. 1- If taken orally: it is excreted by kidney and irritates the urinary tract (aphrodisiac). 2- Topical application of solution containing cantharidine: it is effective in the removal of warts.
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3- Now D/C, used only in veterinary (toxic). II- Cochineal or coccus: Source: It consists of dried female insects, Dactylopius coccus. Constituents: it contains 10% glycosidic coloring principle carminic acid which is anthraquinone derivative. Uses: coloring agent in tooth pastes.

Source: musk is the dried distilled secretion from the preputial follicles of the small, male, musk deer animal found in china and himalaya. Constituents: The distilled musk yields 1.4% of the dark brown volatile oil muskone. Uses: high class perfumes.

Source: cleaned, dried and powdered thyroid gland obtained from domesticated animals e.g., Ox. Constituents: thyroids contains 0.17% - 0.23% of iodine. Uses: thyroid is used in goiter and obesity.

Source: pepsin is a substance containing a proteolytic enzyme obtained from glandular layer of the fresh stomach of the hog. Constituent: Pepsin is prepared by digesting the minced stomach lining with HCl. This solution is clarified and evaporated in vacuum. Uses: pepsin is used to assist gastric digestion.

Vegetable drugs are arranged for study as:

Alphabetic: The drugs are arranged in alphabetical order. Taxonomic: The drugs are arranged according to the plant source. Phyla, families, genera, species, variety (botanical classification). Morphological: The drugs are divided into:

1-

2-

3-

Organized drugs: Leaves, flowers, fruits, seeds, herbs and entire organisms, woods, barks, rhizomes and roots. Unorganized drugs: Dried lattices, gums, resins, oils, fats and waxes.
4-

Pharmacologic or therapeutic: Grouping of drugs according to the pharmacological action or therapeutic use.
4

5-

Chemical: the drugs are divided into groups according to their most important constituent: Carbohydrate: e.g., starch, agar, pectin. Glycosides: vanillin, barbaloin. Lipids:
a-

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Fixed oils and fats are glyceryl esters of fatty acids that are saponified by alkali: olive oil, peanut oil, sesame oil, caster oil.

b- Waxes are esters of fatty acids with high molecular weight monohydric alcohol e.g., bees wax. 4-Volatile oils (essential oils) e.g., peppermint oil, clove oil, cinnamon oil, anise oil, rose oil that responsible of odor of plants. 5- Steroids: are derivatives of cyclopentanophenanthrene e.g., estrogens, androgens, cholesterol, ergosterol.
6-

Alkaloids: they are nitrogenous, crystalline or oily compounds. Usually basic in nature e.g., atropine, morphine, quinine, cocaine and reserpine. Peptide hormones: these are active principles secreted by certain endocrine glands e.g., glucagons, insulin and oxytocin. Enzymes: organic catalysts that are produced by living organisms e.g., pepsin, pancreatin, rennin.

7-

8-

9-

Vitamins: chemical compounds that are necessary for normal growth and function of animals e.g., thiamine, riboflavin, ascorbic acid, vitamin E.

10- Antibiotics:

chemical

compounds

produced

biosynthetically that cause kill or inhibit microorganisms e.g., penicillin, tetracycline, erythromycin.. 11Biologics:

A- Antigens or antibody preparations are capable of developing a state of immunity in the patient e.g., hepatitis B vaccine, IG, diphtheria antitoxin. B- Biologics related to human food e.g., human albumin, anti-heamophilic factor.
12- Allergens

substances that causes unusual responses called

hypersensitivity in individuals, e.g., pollen grains, mold, spores, feathers, animal dander.
13- Poisonous

plants: some higher plants and fungi produce

toxic effects when introduced into the human body e.g., nightshade, water hemlock, amanita.

Pharmacopoeias:

They

are

books

recognized

by

the

governments as the legal authority for standard of drugs. The united states pharmacopoeia is revised and reprinted every five years. Official drug: is one that listed and described as definite therapeutic agent in pharmacopoeia. Unofficial drug: is one that have not recognized in pharmacopoeia. They are listed in unofficial books e.g., British pharmaceutical codex. The descriptive material pertaining to any of the drugs in the pharmacopoeia is known as the monograph. In the monograph of a crude drug, the following information are generally covered:
1-

Names English, Arabic, Italian, French.

2- Definition. 3- Description 4- Special conditions of collection or preparation for the market. 5- Identity test. 6- Tests for adulterant. 7- Method of assay.
8-

Special storage requirements.

9- dose

1-

Endogenous plant:

Plant is growing in native country, e.g., Hyoscyamus in Egypt, Cannabis sativa in India.

2- Naturalized plant:
Plants are cultivated in foreign land or in locality other than their native countries, e.g., cotton is naturalized in Egypt and endogenous to America.
3-

Exotic plant:

Plant is used in countries where neither cultivated nor growing wild, e.g., tea, digitalis.

4- Marine drug:
It is a pharmacological active compound of marine origin, e.g., agar, carageenan, code liver oil.
5-

Crude drug:

Drugs of animal or vegetable origin undergo processes of collection and drying only.

6- Commercial origin:
It is refers to its production and its channels trade, e.g., Alexandrian senna is the product growing in Khartom but it was shipped by way of Alexandria.

To evaluate a crude drug:

Can be established by actual collection of the drug from plants or animals origin +ve identified. How to determine the origin of the samples: 1- "Drug gardens' established by institutions engaged in pharmacognostical research. 2- Comparing unknown sample with a- a published description drug or b- with authentic drug samples.

It is refers to the intrinsic value of the drug, i.e., the amount of medicinal principle or active constituents present.

How obtain high grade of quality?

I- Collection of the drug from the correct natural source at the proper time and in proper manner. e.g1.,

Opium

(morphine,

codeine,

thebaine,

papaverine..etc). Origin: Papaver somniferum (induce sleep).

Time of collection: a- must collect from green unripe capsule (fruit). Why? b- 2-3 weeks after flowering. Why? Because at this time obtain a maximum morphine content (active constituent). But before this time, alkaloids content mainly thebaine which is inactive. Proper manner: capsules must be incision slowly in the morning, not deep and not allow aqueous juice to contaminate latex. e.g 2., clove: Origin: Myristica fragrance (nice aroma). Proper time: flower buds from clove tree. Because contain high % of A.C. Proper manner: absence of stalk. In official book say no more than 5% of stalk and mother clove to obtain high grade of quality. II- Preparation of the collected drug by proper cleaning, drying and garbling. e.g., 1- Ox thyroid gland 2- Under ground organs roots, rhizomes, corms and tubers. III- Proper preservation of the cleaned, dried, pure drugs against contamination with dirt, moisture, fungi, filth and insects.
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Occurrence on the market (commercial forms): I- Entire crude drugs as: A- Seeds (Coffee, fenugreek, nut meg, cardamom, caliber beans). B- Flowers as a- Bud (clove) b- Chamomile c- Santonica d- Safflower C- Fruits: Anise, cumen, coriander, fennel from family Umbellifereae. D- Leaves as tea, menthe, senna, digitalis, henna. E- Roots and rhizomes as licorice, ipeca, ginger, gensing. F- Bark as cinnamon, cascara, frangula, cinchona.

1- Cut, broken, sliced.

1-

Pressed drugs together by hydraulic pressure as in cannabis. Powdered and then molded into forms as rhubarb. Cinnamon bark, remove cork and cortex and packed in double quill of cigar length.

23-

4- Quillaia bark come to the market in large flat pieces.

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5-

Sennoside (4 types which A.C. of Senna leave used as laxative). Lanatoside, lanoxin from digitalis leave. Digoxin from digitalis leave. Atropine SO4 injection from Atropa belladonna. eye drops from caliber beans.

678-

9- Pilocarpine eye drops.

10- Physostigmine

II- A- Exudates: it is normal secretion or pathological

product of animal or plant (i.e., under microscope has no cellular structure, so called unorganized drug). Normal secretion: a- Latex: milky juice which is present normally in capsules of Papaver somniferum. b- Juice: liquid juice from aloe. c- Bee wax Pathological product: Underdone some special physical treatment e.g., gum, resin, oleo resin, oleo gum resin (myrrh). They occur in 1- Tears, small round masses e.g., Acacia. 2- Cylindrical pieces e.g., Gamboge.

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B- Galinical preparation:

a- Extract
Definition: concentrate preparation of liquid or dry or moderate consistence obtained from animal or plant source. It is prepared by masuration or percolation methods using any suitable solvent. Preparation One part of extract is equivalent to one part of original dried drug w/w, v/w. Dry drug (1 gm of drug extract 1 gm of original). Liquid (1 ml of drug extract 1 ml of original). Maceration: Herb reduced into pieces, add suitable solvent, allow to stand for 2-7 days in close container, decant the extract. Percolation: Herb reduced into pieces, add suitable solvent, allow to stand for few hours in pestle (percolator), the percolate allow to flow slowly through tap.

b-Tincture
1/10 from extract. Preparation 1 part of drug + 10 parts of extract solvent, macurate or percolate, extract, evaporation, residue. Potency: 1 ml tincture = 0.1 (1/10) weight of drug.
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c- Infusion
Used in: 1- Volatile oil containing drug thermolabile. 2- Drug containing water soluble constituent. Concentrate infusion: 1 volume of tea or coffee + 1 volume of water in pestle for few minutes to 2 hours (max).
123-

Cold water: cold infusion. Hot water: hot infusion. 25% alcohol (75% water): alcohol is help to prevent putrefaction.

Dilute infusion: 1 volume of conc infusion + 10 volume of water in pestle for 12 hours (max). Should add preservative why?

1- A.C. in the mixture form: Volatile oil of clove, anise, cinnamon, chamomile. 2- A.C. in the single form why? Bitter almond oil in benzaldehyde. Black mustard oil in allylisothiocyanate Winter green oil in methyl salicylate.

The evaluation of a drug involves a number of methods:

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Definition: The entire description of official crude drug

monographs.

= Organs of sense = Macroscopic appearance of drug. 1- Shape and size (for entire drugs not powdered).
Flowers: Floral parts: stigmas, corollas, anther, ovary, receptacle. Leaves and leaflets: Length, width, apex, margin, base, venation, the texture of the leaf and the hairs in upper and lower surface. The feel of the surface described as soft, hairy smooth. The bark: i- The barks occur in three shapes: 1- Flat or curved pieces.
2-

Single quills.

3- Double quills. ii- Barks have two surfaces, an outer and inner. iii- The inner surface is usually lighter in color than the outer surface.

2- Odor and taste.

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Odor:
1- distinct 2- indistinct [Depend on the amount of volatile constituents present in drug]. General terms used in describing odor are: 1-aromatic, 2-balsamic, 3- spicy, 4- comphoraceous.

Taste:
General terms used in describing taste are: 1- Acid (sour) 2- Saccharine (sweet): indicates sugar or sugar like substances e.g., liquorice. 3- Saline (salty) 4- Alkaline 5- Bitter: indicates presence of substances such as bitter principle, glycoside, alkaloids. 6- Tasteless (all substances insoluble in the salive).

7- Distinctive sensations to the tongue:

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a- mucilaginous and oily (soft feeling) e.g., linseed. b- astringent (contraction of the tissues oh the mouth) indicates presence of tannin. c- pungent (warm biting sensation) e.g., ginger. d- acrid (irritant sensation) e.g., Aconite, coca. e- nauseous (those tending to excite vomiting), Ipeca.

3- Color and external markings. May help in revealing the nature of the herb.
1- White: e.g., starch, flours, gums, talk) 2- Pale yellow (yellowish white) e.g., ginger, squill, white pepper. 3- Deep yellow: e.g., peeled liquorice, calumba, hydrastis. 4- Light pale brown e.g., lupulin, nux vomica, fennel, coriander, anise. 5- Dark brown: e.g., cloves. 6- Dark reddish brown: cinchona, nutmeg. 7- Red: Kamala. 8- Pale green e.g., lobelia. 9- Greenish brown: most of the leaf herbs.

4- Fracture and internal color. Dealing with microscopic appearance of the herb in sectional view and in powdered form. 17

Microscopical evaluation is useful in the study of:

1- Histologic elements of herbs. 2- Detection of adulterant. 3- Quantitative microanalysis of admixed or adulterated powders. Histology refers to the character and arrangement of these tissues as they are present in the herb. Histologic studies are made from very thin transverse (radial) or longitudinal (tangential) sections (entire organ) properly mounted in suitable stains, reagents or mounting media. Powdered herbs posses very few macroscopic features of identification outside of color, odor and taste. Microscopically, the cells are broken, except those with lignified walls, but the cell contents are scattered in the powder and become very evident in the mounted specimen e.g., starch, calcium oxalate crystals, aleurone, phloem, glandular and nonglandular hair, pollen grain.

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For the identification of powdered crude drugs 1- leaves:

a- Trichomes (glandular and nonglandular) b- Crystals of calcium oxalate c- Stomata, resin. d- Epidermis cells, palisade, e- Vessels

2- flower:
a- Trichomes (glandular and nonglandular) b- Epidermis, stigma, anther. c- Pollen grain d- Volatile oil

3- Fruits and seeds:

Starch Aleurone Sclerenchyma Vitta Endocarp

Bark & wood:

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Phloem, xylem Trachedes, Parenchyma, wood Parenchyma Fibers, medullary rays, cork, cambium. In some cases, the drug may have the same diagnostic element, they are known as closely related species. So, microscope is

not the method of choice.

It is used to identify closely related species.

1-Microscopical linear measurement

Used only in

Root Rhizomes Bark

E.g1., Different between Cinnamon as quill and Cassia as flat [Both have same diagnostic element]. So differentiate between both by:
Microscopical linear measurement

Cinnamon < 8 m 30 m

Cassia > 10m 30-45 m

1- Diameter of starch granules 2- Width of phloem fiber

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Active constituent Volatile oil Cinnamic aldehyde Phenolics Eugenol Tast Cost

Cinnamon 0.7-1% v/w 60-75% 4-10% 10% Astringent Cheap

Cassia 1-2%v/w Not less than 85% More astringent Cheaper

E.g2., Ipecacuanha
Starch granule Rio Ipecacuanha 15 m Cartagena Ipecacuanha 17-20 m

Why we need to differentiate between Rio and Cartagena Ipeca? Because Rio Ipeca contains more emetine alkaloid.

E.g3., Contain clusters of CaOx American podophyllum 60-100 m

Indian podophyllum
30-40 m

If closely related species are leaves: We need to

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2- Ratio value: 1- Palisade ratio. 2- Stomata index. 3- Vein islet number. 4- Vein islet terminate number 1- Palisade ratio: Def: numbers of palisade cell under one epidermal cell using four continuous epidermal cells for the count. To do the ratio value is determined by camera lucida can transfer the microscopic field to microscopic stage by using mirror. Surface preparation: Take leave, T.S., count and draw 4 epidermal cells, then count and draw palisade cells under 4 epidermal cells. 2- Stomatal index (%):

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Def: it is the percentage of the number of stomata to the total number of epidermal cells including the stomata, each stoma being counted as one cell. Stomatal index= S/E+S x 100 (S) Number of stomata per unit area (E) Number of epidermal cells in the same unit area. The figure obtained is constant for any species and can be used for the differentiation between the closely related species. 3- Vein islet number: Def of vein islet: The small areas of green tissue outlined by the veinlets are temrmed vein islet. Def of vein islet number: is the number of vein islet per mm2. This value has been shown to be constant for any species and unaffected by the age of the plant or the size of the leaves.

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How to determined the mm2 ? By using Eye-peice micrometer and stage micrometer. 4- Veinislet terminate number: Def: it is the number of veinlet termination per mm2 of leaf surface. A veinlet termination is the ultimate free termination of a veinlet or branch of a vienlet. It can be used to distinguish between leaves of closely related species.

It is the study of active constituents by the application of chemical and physical methods to small quantities (a few milligrams) of the drug in powdered form or to histologic sections of the drug. It offers a means by which constituents of many drugs may be isolated and purified. It includes steps: I- Isolation of A.C.: A- By chemical solvents: 1- Micro-extraction 2- Micro-filtration

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3- Micro-crystallization B- By micro-sublimation II- Identification of constituents: 1- By crystallography 2- By melting point determination 3- By confirmative test 1- Chemical test. 2- Physical test Microextraction: Def: It is a separation of the constituents from a small quantity of the drug and depends on the solubility of the constituents in a solvent. During microextraction procedures, various factors must be considered, such as: 1- State of division of the drug (whole, broken, powdered)

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2-

Type of solvent used with increase polarity [Pet.ether, chloroform, ethylacetate, butanol, ethanol, methanol, water].

3- Temperature: [increase temperature lead to increase solubility between solvent and extract].
4-

Nature of impurities e.g., if impurities soluble in certain solvent do not used this solvent. Nature of substances e.g., volatile oil, fixed oil, sterol, triterpenes, anthracene, coumarin, flavonoids, alkaloids, etc. If soluble in polar solvent means it is a polar compounds. If soluble in non-polar solvent means it is a non-polar compounds.

5-

All substances soluble in 90-95% alcohol.

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alcoholic extract [hydroalcoholic extract] evaporation residue methanol : water (70-30%) pet.ether 1- fixed oil 2- v.o. 3- sterol chloroform 1- triterpenes 2- cardiac glycosides aqueoues saponine sugar

butanol 1-saponine 2-sugar

ethylacetate 1- flavonoids 2- alkaloids 3- coumarin 4- all glycosides

Why we need to add dilute acid on the aqueous extract? Hydroalcoholic solution, evaporation, residue, soluble in methanol:water (70-30%), add dilute acid. 1- To convert alkaloid to salts. 2- Ionized form of phenol (phenate) converted to unionized form of phenate. ******************** Why we add NH4OH instead of NaOH?
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NaOH is very strong base and it is not used because:

1-

It is hydrolyzed ester alkaloids e.g., vinca alkaloids (vincrystine and vinblastine), atropine alkaloid and coca alkaloids. Can open lactone ring in some alkaloids such as pilocarbine. Form water soluble un-extracted phenate of phenolic alkaloids as morphine & psychotrine, emetine and cephaeline in Ipeca alkaloids.

2-

3-

4- Break down glycosydic linkage in glycoside compounds. To secure small quantities of the extracted substances in a clear solution generally requires microfiltration methods to obtain the extracted constituent in a pure form necessitates crystallization and re-crystallization. Micro-crystallization: If substances is soluble in methanol and insoluble in ethylacetate. How can be crystallization? Microsublimation:

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1- It is refer to a method of obtaining a constituent of a drug by heating the drug to vaporize its chief constituent to a gaseous state and then condensing the vapor back into a solid form. 2- This method is employed only when the drug or its constituents are not decomposed by heat. 3- When the constituent condenses on a cool place, the resulting crystals develop in a pure form. 4- Caffeine is sublimed from powdered Kola or from powdered coffee. II- Identification of constituents: 1- By crystallography: It is a science dealing with: i- Classification of crystals ii- Form iii- Structure iv- Properties of crystals e.g., crystal is:

Isotropic Anisotropic

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Uniaxial Biaxial Its type of extinction Optic sign Sign of elongation

Refractory index 2- By melting point determination: It is very important as a means of identifying pure substances. 3- By confirmative test: 1- Chemical test. 2- Physical test e.g., menthol is isolated from peppermint oil. It occurs as colorless, hexagonal crystals, usually needle like. The melting point of l-menthol from natural sources is between 41 and 43 C. when l-menthol is triturated with an equal weight of camphor, chloral hydrate or phenol, the mixture liquefies, thus confirming the identity.

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