PHARMACOGNOSY II PHAR306 6th Semester 5th Lecture

Prof. Dr. Müberra Koşar Ass. Prof. Dr. Aybike Yektaoğlu Eastern Mediterranean University Faculty of Pharmacy Department of Pharmacognosy PHARMACEUTICAL FIXED OILS AND ANIMAL FATS FIXED OILS & ANIMAL FATS

Amygdalae oleum

• “Almond oil” • obtained by crushing of the seeds of two varieties Prunus dulcis var. dulcis or P. dulcis var. amara (Rosaceae) in the cold • Almond oil is obtained in the Mediterranean countries (Italy, France, Spain and North Africa) where its culture is obtained • The only difference between the two varieties is the cyanogenic glycoside content of the var. amara FIXED OILS&ANIMAL FATS Amygdalae oleum

• seeds carries 40-55% fixed oil • the refined oil mainly contains oleic acid (62-86%), linoleic (20- 30%), palmitic (4-9%) • Amydalae oleum raffinatum (Almond oil, refined) (Eur.Pu.) • Amydalae oleum virginale (Almond oil, virgin) (Eur.Ph.) • major used in cosmetology and dermatology • used as a carrier in oily injectable preparations FIXED OILS&ANIMAL FATS Arachidis oleum

• “Arachis oil, Peanut oil” – “Peanut butter” • Arachis hypogaea (Fabaceae) • cultivated in South America, China, India, Australia, and West Africa • due to various genotypes they vary in fatty acid content • the seeds are cold-pressed • they have similar properties as olive oil • most suitable oil for added for embedding purposes into other oils (e.g. olive oil) FIXED OILS&ANIMAL FATS Arachidis oleum - content

• seeds carries 40-50% fixed oil • 50-65% oleic acid • 18-30% linoleic acid • 8-10% palmitic acid • stearic acid, arachidic acid • Arachidis oleum raffinatum (Arachis oil, refined) (Eur.Ph.) • Arachidis oleum hydrogenatum (Arachis oil, hydrogenated) (Eur.Ph.) FIXED OILS&ANIMAL FATS Arachidis oleum - application

• is one of the most consumed oil in the world • controlled release in IM (intramascular) injectable preparation as solvent • in topical preparations  vehicle • solvents for hormones and vitamins • in nutrition products for preparations of emulsions • liniment, ointment bases, at enema • in ear drops • in the food industry (margarine, cooking oil) FIXED OILS&ANIMAL FATS

Coconut oil

• “Coconut oil„ • Cocos nucifera (Palmae) • A drupe having fibrous fruit mesocarp and a hard endocarp • solid part of the endosperm of seeds is dried and squeezed where "coconut oil" is obtained • Coconut oil refined (Eur.Ph.) • A semi-solid fat, melts at 24 ᵒ C FIXED OILS&ANIMAL FATS

Coconut oil

• large amount of the composition is formed predominantly of unsaturated fatty acids (90%); lauric and myristic acid • lesser amounts of caproic, caprylic, oleic, palmitic and stearic acids • in particular, it contains high rates of medium chain fatty acid that is readily absorbed from the GIS (gastro intestinal system). Therefore the oil is used in the diet of patients with absorption problems FIXED OILS&ANIMAL FATS

Coconut oil

Fractionated coconut oil: • endosperm oil of fractionated and purified C. Nucifera • carries short and medium chain fatty acids (octanoic, decanoic acid, etc..) • its low viscosity continous until coming close to the melting point (0 °C). Therefore, it is used to create a nonacuse environment in certain oral drugs • Medium-chain triglycerides (Eur.Ph.) FIXED OILS&ANIMAL FATS Palm kernel oil

• Elaeis guineensis (Palmae) is obtained from the dried endosperm of seeds • used in the preparation of Medium-chain triglycerides (Eur.Ph.) • caprylic (50-80%), capric (20-50%), caprylic, lauric, myristic acid mp. 31-36 °C • used in the preparation of suppository as a base FIXED OILS&ANIMAL FATS Palm oil

• Elaeis guineensis (Palma) is prepared by squeezing of the mesocarp of the fruit • major compounds palmitic and oleic acid • mp. 30 °C • margarine preparation and soap industry FIXED OILS&ANIMAL FATS Gossypii oleum

• “Cottonseed oil„ • is obtained from several Gossypium (Malvaceae) by squeezing from the seeds • after removal of seed testae the inner part is kept hot • used refined • semi-dry oil (depending on the absorbtion of oxygen from air) • the hydrogenated oil is offisinal FIXED OILS&ANIMAL FATS Gossypii oleum- content

• seeds carries 15% fixed oil • 45% linoleic acid • 30% oleic acid • 20% palmitic acid • 3% myristic acid • 1% stearic acid, 1% arachidic acid • gossypol has a polyphenolic structure that are toxic FIXED OILS&ANIMAL FATS Gossypii oleum- application

• used as a solvent in IM injection • in nutrition products in the preparation of IV (intravenous) emulsions • Gossypol, during administration of the IV emulsions mild bradycardia, may cause drop in blood pressure • as a cooking oil in the food industry and in margarine preparation FIXED OILS&ANIMAL FATS Lini oleum

• “Linseed oil„ • is obtained from Linum usitatissimum (Linaceae) by squeezing the seeds in hot medium • seeds carries 30-40% fixed oil 36-50% α-linolenic acid 23-24% linoleic acid 10-18% oleic acid 5-11% unsaturated fatty acid (myristic, stearic, palmitic acid) • in contact with air, the oxygen absorbent is dried and forms a thin film on the surface • paint industry FIXED OILS&ANIMAL FATS Lini oleum

• Linseed oil, virgin (Eur.Ph.) • is used in the preparation of liniment • hydrolysed linseed oil; is effective against strains of antibiotic-resistant Staphyllococcus aureus. Due to this effect it is used in the topical preparations for its antibacterial effect FIXED OILS&ANIMAL FATS Olivae oleum

• “Olive oil„ • Olea europae (Oleaceae) • it is cultivated in the Mediterranean countries and in the south-western United States and also in other subtropical countries • is obtained by extraction from the mature fruit • the residue is named "pomace" • Olivae oleum raffinatum (Eur.Ph.) • Olivae oleum virginale (Eur. Ph.)

FIXED OILS&ANIMAL FATS Olivae oleum- content

• the composition of the oil obtained from different sources is different • Fruit carries 15% fixed oil; 65-75% oleic acid 9-15% linoleic acid 10-15% palmitic and stearic acid • cholagogue and has a laxative effect • externally emollient • in parenteral preparations solvent, carrier • liniments, ointments, plasters and soap making • as topical emollients in eczema and psoriasis • used as edible oils in the food industry FIXED OILS&ANIMAL FATS Brassicae oleum

• “Rapeseed oil„ • its fixed oil is obtained from the seeds of Brassica napus and B. campestris (Brassicaceae) by extraction or mechanic expression (40%) • in the composition; oleic (61%), linoleic (21%), α-linolenic (11%), erucic (0.2-2%) acid, saturated fatty acid (7%) • is normally obtained from seeds. It contains 20-40% erucic acid FIXED OILS&ANIMAL FATS Brassicae oleum

• animal experiments have shown that erucic acid has myocardial toxicity • erucic acid content more than 2% in cooking oil is undesirable • Thus, oil from genetically modified varieties are prepared • used in the preparation of biodiesel FIXED OILS&ANIMAL FATS Sesami oleum

• “Sesame oil, gingelly oil, teel oil” • its fixed oil is obtained from the seeds of Sesamum indicum (Pedaliaceae) by extraction or squeezing • is cultivated in India, China, Japan, and also in many tropical countries • Sesami oleum raffinatum (Eur.Ph.) FIXED OILS&ANIMAL FATS Sesami oleum- content

• it contains 50% of oil in its seeds • Refined sesame oil: 43% oleic acid, 43% linoleic acid 9% palmitic acid, 4% stearic acid 0.8% arachidic acid • In very small amounts; in 1% lignan structure the hydrolysis product phenolic compound SESAMOL of sesamin and sesamolin FIXED OILS&ANIMAL FATS Sesami oleum

• Sesamol is determined by Baudouin test • 1% sucrose in conc. HCl is added to sesame oil and shaken where a formation of pink color sesami oil presence proves (sesamol hydroxymethyl furfural) • This reaction allows the determination of sesame oil among all oils

sesamol FIXED OILS&ANIMAL FATS Sesami oleum- application

• in oral or rectal capsules • in ophthalmic preparations • in suspension and emulsion formulations • as liniments, ointment bases and porous-pflaster bases • expecially in controlled release IM preparations as a solvent (: valerate, hydroxyprogesterone caproate, enanthate, decanoate and other fat-soluble pharmaceutical crude materials- like fluphenazine decanoate and enanthate esters) • in subcutaneous injectable preparations as a solvent FIXED OILS&ANIMAL FATS Sojae oleum

• “Soya oil” • its fixed oil is obtained from the seeds of Glycine soja ve G. max (Fabaceae) • homeland East Asia • cultivated in U.S.A., South America, in India • its seeds carries 20% fixed oil • mainly linoleic (50%), oleic (30%), linolenic (7%) and saturated fatty acids (14%) FIXED OILS&ANIMAL FATS Sojae oleum-application

• refined soybean oil; • as a source of fat in parenteral nutritional products, in the preparation of emulsions • as a carrier in oral and IV preparations • in the preparation vitamins, steroids that are poorly water soluble, diazepam, emulsions of fluorocarbons • in the formulations of liposomes FIXED OILS&ANIMAL FATS Sojae oleum-application

• is an important source of proteins. Sediment carries 45-65% protein • after oil is obtained from seeds, lecithin is obtained from the residue • regulates lecithin lipid and cholesterol metabolism • stigmasterol in seeds are used in the semi-synthesis of steroidal hormones • cultivated in Marmara and the East Black Sea in Turkey FIXED OILS&ANIMAL FATS Helianthi oleum

• “Sunflower oil” • its fixed oil is obtained from the seeds of Helianthus annuus (Compositae) • major: linoleic (48-74%), oleic acid (10-14%) • carrier in injectable preparations • nutritional support • in cosmetics

FIXED OILS&ANIMAL FATS Cacao oleum

• “Cocoa butter” • “Theobroma oil” • Theobroma cacao (Sterculiaceae) • contains about 40-50 seeds in its elliptical crops(fruits) that are 20-25 cm tall • homeland Mexico, cultivated in South and Central America in the tropical forests • 4-6 m, small trees FIXED OILS&ANIMAL FATS Cacao oleum

• ripe fresh seeds are left for fermentation about 10 days • during the fermentation the seeds turns to brown and its aroma changes • testa is separated after parched/roasted, the rest of the seed (embryo cotyledon) is pressed and gives the cocoa butter. Seeds carries 45-53% fat • composition; 37% oleic acid, 34% stearic acid, 26% palmitic acid 2% linoleic acid glycerides FIXED OILS&ANIMAL FATS Cacao oleum-application

• Cocoa butter is solid at room temperature, melts at 30-35 °C • suppository excipient • in cosmetic (sun oils) and food industry • used in the obtaining of stearic acid. Stearic acid is used as a lubricant in Mg salt tablets FIXED OILS&ANIMAL FATS

Maydis oleum

• “Maize oil, Corn oil” • Zea mays (Poaceae) • cultivated in Mediterranean • the seed is separated from the embryos and are squeezed in cold • oil is used refined FIXED OILS&ANIMAL FATS

Maydis oleum-composition

• seeds contains 50% fixed oil; • 50% linoleic acid • 37% oleic acid • 10% palmitic acid • 3% stearic acid • 0.4% arachidic acid • 0.2% lignoceric acid FIXED OILS&ANIMAL FATS Maydis oleum-application

• as a solvent in IM injectable preparations • in topical preparations as a vehicle • in oral feeding products up to 67% of corn oil emulsions are prepared • food industry FIXED OILS&ANIMAL FATS Ricini oleum

• “Castor oil” • Ricinus communis (Euphorbiaceae) • one year life in temperate climates, perennial in the tropics, a plant which can grow up to 15 m • homeland India

• grown in all tropical and subtropical countries • mainly in Africa, South America, East Asia and the Mediterranean countries FIXED OILS&ANIMAL FATS

Ricini semen

• fruit is 3 lobed capsules, each lobe 1 seed • seeds ellipsoid, testa colourful and hard FIXED OILS&ANIMAL FATS Ricini oleum

• hard testa of seeds breaks by pressing/squeezing, and then endosperm and embryo are separated, endosperm is squeezed in cold • seeds contain 45-55% fixed oil, 20% protits (ricin) • steam is passed through the oil where toxic proteins (ricin) are denatured • used refined (does not contain ricin) • Ricini oleum virginale (Eur.Ph.) • Ricini oleum raffinatum (Eur.P.) • Ricini oleum hydrogenatum (Eur.Ph.)

FIXED OILS&ANIMAL FATS Ricini oleum-composition

• seeds; 45-55% fixed oil  75% trisinole • trisinole is hydrolysed by lipase in duodenum and transformed into free ricinoleic acid and its isomers which have purgative effect. 85-90% of ricinoleic acid (12-OH of oleic acid) • 3-7% linoleic acid, 2-5% oleic acid, 1-3% stearic acid, 0.5-2% palmitic acid, a small amount of linoleic and gadoleic acid

ricinoleic acid FIXED OILS&ANIMAL FATS Ricini oleum-application

• it has purgative effet because of ricinoleic acid is effective purgative; preoperatively used in several radiographic examinations • undecylenic acid source. Ricinoleic acid gives undecylenic acid by pyrolysis • Undecylenic acid is the starting material of polymer chemistry. Plastic raw material • used in cosmetology because of its antifungal effect • castor oil gave sulphonated castor oil with sulfuric acid (Turkey red oil) and was used as surface active agent. Today not obtained FIXED OILS&ANIMAL FATS Castor oil-hydrogenated (Castor wax)

• Hydrogenated castor oil (Eur.Ph.) • Hydrogenated castor oil is prepared by the help of a catalyst • is used as excipient • carries 12-hydroxystearic acid triglycerides as a major compound • mp 83-88 °C • practically insoluble in water • can remain stable at temperatures up to 150 °C. Has different types FIXED OILS&ANIMAL FATS Castor oil-hydrogenated (Castor wax)-application

• the hard types with high melting points are used in oral and topical pharmaceutical formulations • in topical formulations to ensure the rigidity of creams and emulsions • in the preparation of sustained release oral formulations and in the preparation of capsules • as solid matrix or coating material • in tablets and in the food as lubricants • in cosmetic FIXED OILS&ANIMAL FATS Castor oil-hydrogenated (Castor wax)-polyethylene derivatives

• Polyoxyl castor oil (Eur.Ph.) • Hydrogenated polyoxyl castor oil (Eur.Ph.) • is prepared by the reaction of castor oil with ethylene oxide

Cremophor EL 1 mol HCO + 35-40 mol ethylene oxide Cremophor RH 40 1 mol HCO + 40-45 mol ethylene oxide Cremophor RH 60 1 mol HCO + 60 mol ethylene oxide FIXED OILS&ANIMAL FATS

Cremophor

• synthetic non-ionic surfactant (surface active agent) • in aqueous systems used to stabilize the emulsions of nonpolar compounds • solubility enhancing • dispersing FIXED OILS&ANIMAL FATS

Cremophor

• Miconazole (antifungal) • Paclitaxel (anticancer) • Aci-Gel (acetic acid/oxychinolin/ricinoleic acid - vaginal) • Cyclosporin injection • Nelfinavir mesylate (antihiv) • Propofol (IV. anesthetic agents, as original Cremophor is applied, now in a lipid emulsion application) • Injectable diazepam (in lipid emulsion) • Vitamin K injection • Ixabepilone (anticancer) FIXED OILS&ANIMAL FATS

Germ oil

• “Wheat germ oil” • Triticum aestivum (Poaceae) is obtained by squeezing the cold embryo • major compounds; linoleic (52-59%), palmitic (14-19%), oleic (12-23%), linolenic (3-10%), and stearic, eicosanoic acid • as food supplements • in cosmetology FIXED OILS&ANIMAL FATS g-Linolenic (GLA) acid Bearing Oils

• n-6 PUFA necessary for the body • the first metabolite that is formed in the liver during the metabolization of AA which is the essential precursors of eicosanoid by activation of Δ6 desaturase enzyme of LA

GLA (C18: 3 n-6)

FIXED OILS&ANIMAL FATS g-Linolenic (GLA) acid Bearing Oils

• Δ6 desaturase enzyme may lack as hereditary or may lack in various situations (age, diabetes, high alcohol consumption, poor nutrition, stress, high cholesterol levels, viral infections) • in these cases GLA support required

• GLA supplementation has been shown to reduce the incidence and symptoms atopic eczema • GLA rich vegetable oils such as borage seed oil (Borago officinalis), evening primrose oil (Oenothera biennis), and black currant seed oil (Ribes nigrum) are used in the symptomatic treatment of atopic eczema

FIXED OILS&ANIMAL FATS Oenothera sp. (Onagraceae)

• “Evening primrose oil” • is obtained from the seeds of O. biennis, O. lamarkiana by squeezing/pressing or extraction • cultivated mainly made ​​in UK • O. biennis  7-9% GLA • Evening primrose oil refined (Eur.Ph.) • in the treatment of atopic eczema • as food support • cosmetic purposes • for diabetic neuropathy and those with rheumatoid arthritis FIXED OILS&ANIMAL FATS Borago officinalis (Boraginaceae)

• “Borage oil, Borage seed oil” • fixed oil is obtained from its seeds by extraction (SFE) • Starflower (borage) oil refined (Eur.Ph.) • cultivated mainly made ​​in UK • contains less linoleic acid and more GLA than O. biennis • linoleic 30-41%, 17-27% GLA, 12-22% oleic, 9-12% palmitic acid • in the treatment of atopic eczema • as food supplement, cosmetic purposes • is not suggested for diabetic neuropathy and in rheumatoid arthritis FIXED OILS&ANIMAL FATS Ribes nigrum (Grossulariaceae)

• “black currant oil” • Ribes nigrum seeds; % 15-20 • Ribes rubrum seeds contain GLA FIXED OILS&ANIMAL FATS Hydnocarpi oleum

• “Hydnocarpus oil, Chaulmoogra oil” • grows in tropical trees • is obtained by the squeezing/pressing of the fresh fruits of Hydnocarpus wightiana and its other types and of Taraktogenos kurzii species (Flacourtiacea) • contains hydnocarpic and chailmoogric acid • have bactericidal activity. Ethyl esters (ethyl hidnokarpat) and salts are effective against Mycobacterium leprae FIXED OILS&ANIMAL FATS

Morrhuae oleum

• “Oleum Jecoris Aselli, Cod-liver Oil” • is obtained from the liver of Gadus morrhua by extraction (liquid oil) • major compound jecolein and therapin (jecoleic acid and therapic acid glycerides) other components; palmitic (glycerides), iodine, acetic, butyric, valeric and capric acid glycerides • small amounts of iron, manganese, , and sodium • To deodorize the odoriferous substances are removed by polymerization • used during periods of convalescence and weakness • in children and young people during periods of growth FIXED OILS&ANIMAL FATS

Adeps suillus

• “Pork fat” • purified internal fat of Sus scrofa (Suidae) • 40% solid glycerides (myristic, stearic and palmitic acid glycerides) • 60% liquid glyceride mixtures (such as oleic acid) forms • at 0 °C these fractions are separated by pressure ("Lard oil" and "stearin") • lard is a soft, white oil, mp 34-41 °C • used as ointment bases WAXES

Waxes

• products of straight-chain high molecular weight acids with high molecular weight alcohols and esters • alcohols;

aliphatic alcohols (C26-28) or sterols (C18-22) • esters "wax esters" formed by high molecular weight aliphatic alcohols (cetyl alcohol) • esters formed by sterols are called "wax ester-sterols or wax ester/sterol ester" WAXES Waxes

• 16 C cetyl alcohol (palmitic acid) • 18 C stearyl alcohol (stearic acid) • 26 C ceryl alcohol (cerotic acid) • 30 C myricyl alcohol (melissic acid)

• aliphatic primary alcohols corresponding to these acids also combines with these acids forming wax esters WAXES Waxes

• waxes are found on the surface of fruits and leaves of plants • secretions of certain insects have waxes in the structure

• they are solid at room temperature; hardening of pomades, coating of dragees, used in the preparations of some stiff pomades (hard-pomades) WAXES Cera Carnauba

• Carnauba wax (Eur.Ph.) • Copernicia cerifera (Palma) • grows in Brazil • leaves and leaf buds are dried, are shredded in strips. Is heated with hot water. Wax layer on the leaf melts. When cooled the wax is separated above the layer from the water WAXES Cera Carnauba

• mp 83-86 °C, greenish-white wax

• cerotic acid (C26) + myricyl alcohol (C30)

Application • lacquering/coating of dragees • slow-release tablet formulations • in cosmetics as cream bases WAXES Cera Flava

• Yellow beeswax (Eur.Pp.) • Apis mellifera (Apidae) - Honey bee

Obtaining: • Honey comb is heated with water. The top layer is rescued from the water by squeezing the wax. Water is separated by centrifugation WAXES

Cera Flava

• mp 62-65 °C • brown-yellow

Application • hardener (5-20% in ointments and creams) • lacquering/coating of dragees • emulsion stabilizer WAXES

Cera Alba

• White beeswax (Eur.Ph.)

Preparation: • Yellow wax is melted and filtered. By treatment with oxidizing and bleaching agents or with the help of water vapor in the sun the wax is oxidized WAXES

Cera Alba-application

• thickener in creams and ointments • thickener in w/o (water in oil) type emulsions • lacquering/coating of dragees • emulsion stabilizer • in calibration of the melting point of suppositories WAXES Cetaceum

• Spermaceti (TF) • a white waxy substance consisting of various esters of fatty acids • Physeter macrocephalus (Pyseteridae) • Sperm whale fish, Atlantic and Indian oceans

• in the head of the fish space is holed in the region near to the nose • flowing oily liquid portion is left out in the cold • the precipitate is pressed/squeezed in a diaper bag • washed with KOH solution and is recovered from the oil • washed again, centrifugated and is recovered from the water WAXES

Cetaceum

• has a structure of wax ester and cetyl palmitate • melting point: 45-54 °C

Application • lacquering/coating of dragees • used to increase the viscosity creams and ointments WAXES Adeps Lanae (Eur.Ph.)

• "Anhydrous lanolin, Wool fat" • Ovis aries (Bovidae)

Obtaining: • sheep wool is heated with boiling water • lanolin collected in the upper part is decolorized with KMnO4 • separated from the water and dried

• or nonwovens/wools are consumed with CS2 or ether where lanolin is obtained WAXES

Lanolin

lanopalmitic acid (C16H32O3) + ceryl alcohol esters

cholesterol + ceryl alcohol esters lanosterol WAXES

Adeps Lanae Anhydricus

• mp 36-40 °C • is yellow, can get/absorb water twice

Adeps lanae cum aqua (Eur.Ph.): • anhydrous lanolin is melted, water is added little by little where the mixture is stirred • absorbed more easily through the skin

Adeps lanae hydrogenatus (Eur.Ph.) • anhydrous lanolin is hydrogenated at high pressures or high temperatures. An emollient base for creams and ointments