Chapter 20 Carbohydrates

As the name implies, carbohydrates consist of carbon, hydrogen and oxygen with the last two elements usually present in the same proportions as in water. As we have previously noted, carbohydrates are among the first products to arise as a result of photosynthesis. They constitute a large proportion of the plant biomass and are responsible, as cellulose, for the rigid cellular framework and, as starch, for providing an important food reserve. Of special pharmacognostical importance is the fact that sugars unite with a wide variety of other compounds to form glycosides (Chapters 21–25). Mucilages, as found in marshmallow root and psyllium seeds, act as water-retaining vehicles, whereas gums, which are similar in composition and properties, are formed in the plant by injury or stress and usually appear as solidified exudates; both are typically composed of uronic acid and sugar units. The cell walls of the brown seaweeds and the middle lamellae of higher plant tissues contain polysaccharides consisting almost entirely of uronic acid components. All these groups are discussed more fully below, and the drugs and pharmaceutical necessities containing them are listed at the end of the chapter.

SUGARS (SACCHARIDES)

Monosaccharides

These sugars contain from three to nine carbon atoms, but those with five and six carbon atoms (pentoses, C₅H₁₀O₅, and hexoses, C₆H₁₂O₆) are accumulated in plants in greatest quantity.

The formulae of sugars and other carbohydrates are written in a number of different ways. The structure of glucose as a straight-chain pentahydroxy aldehyde was established by Kiliani in 1886. Emil Fischer, from 1884 onwards, was the most important of the early workers in this field. Their straight-chain formulae are still useful for illustrating the isomerism and stereochemical relationships and, as shown below, can be written in very abbreviated form. Many of the important biological properties of carbohydrates can, however, best be illustrated by ring formulae which show that the same sugar may exist either as a five-membered ring (furanose) or a six-membered ring (pyranose). Glucose has an aldehyde group and is therefore called an aldose or ‘aldo’ sugar; fructose has a ketone group and is therefore called a ketose. Terms such as ‘aldopentose’ and ‘ketohexose’ are self-explanatory. The formulae (Figs. 20.1, 20.2) illustrate these points.

Fig. 20.1 Hexose structures and representation.

Fig. 20.2 Examples of C₄ to C₇ monosaccharides (Fischer structures).

The furanose structure is comparatively unstable but may be stabilized on glycoside formation. The fructose phosphate of the furanose form illustrated in Fig. 20.1 is an intermediate in glycolysis, the anaerobic degradation of hexoses which provides energy for metabolism (see Fig. 18.5). Fructose in nature is always in the furanose form, but when isolated in crystalline form, it has a pyranose structure.

Uronic acids are produced by oxidation of the terminal groups to –COOH (e.g. glucuronic acid from glucose and galacturonic acid from galactose).

Biosynthesis of monosaccharides

Various monosaccharides arise from the photosynthetic cycle (q.v.). D-Fructose-6-phosphate and D-glucose-6-phosphate are universal in their occurrence. Free sugars may accumulate as a result of hydrolysis of the phosphorylated sugars or the latter may be utilized in respiration, converted to sugar nucleotides (e.g. uridine-diphosphoglucose—UDPG) or, by the action of various epimerases, give rise to other monosaccharides (e.g. galactose).

Di-, tri- and tetrasaccharides

These sugars may also be called bioses, trioses and tetroses. They are theoretically derived from two, three or four monosaccharide molecules, respectively, with the elimination of one, two or three molecules of water (Table 20.1). One of the commonest plant disaccharides is sucrose; it is formed in photosynthesis by the reaction of UDPG with fructose-6-phosphate (Fig. 20.3). Control mechanisms for the build-up of sucrose in leaves, and its breakdown for transport to storage organs, are achieved by metabolite effector control of the appropriate enzymes.

Table 20.1 Some di-, tri- and tetrasaccharides.

Fig. 20.3 Biosynthesis of sucrose.

The reverse process, hydrolysis, is brought about by suitable enzymes or by boiling with dilute acid. The same sugars may be linked to one another in various ways. Thus, the disaccharides maltose, cellobiose, sophorose and trehalose are all composed of two molecules of glucose joined by α-1,4-, β-1,4-, β-1,2- and α,α-1,1-(non-reducing) linkages, respectively.

POLYSACCHARIDES

By condensation involving sugar phosphates and sugar nucleotides, polysaccharides are derived from monosaccharides in an exactly similar manner to the formation of di-, tri-and tetrasaccharides. The name ‘oligosaccharide’ (Greek oligo, few) is often applied to saccharides containing from two to 10 units. In polysaccharides the number of sugar units is much larger and the number forming the molecule is often only approximately known. The hydrolysis of polysaccharides, by enzymes or reagents, often results in a succession of cleavages, but the final products are hexoses or pentoses or their derivatives. The term ‘polysaccharide’ may usefully be taken to include polysaccharide complexes which yield in addition to monosaccharides their sulphate esters, uronic acids or amino sugars.

Table 20.2 indicates the character of some of the polysaccharides.

Table 20.2 The character of some polysaccharides.

Name	Occurrence and nature
Containing only monosaccharide units
1. Amylopectin or α-amylose	The main constituent of most starches (over 80%). The molecule has branched chains each consisting of 20–26 α-1,4-linked glucose residues. Several hundred of these chains are linked by α-1,6 glycosidic bonds to neighbouring chains giving a molecule containing some 50 000 glycosyl units. The branching pattern throughout the molecule is not uniform, resulting in some areas that are apparently amorphous (high degree of branching) and others probably crystalline (linear chains predominate with little branching)
1. Amylopectin or α-amylose
2. Amylose or β-amylose	Most starches contain up to 20%, but sometimes absent. Consists essentially of linear chains of α-1,4-linked glucose residues. Several thousand glucose units constitute a chain. It is now recognized that there is a very limited branching (α-1,6-linkages) to the extent of 2–8 branches per molecule
2. Amylose or β-amylose
3. Glycogen or animal starch	Important reserve carbohydrate of animal tissues. Molecule resembles that of amylopectin
4. Cellulose	Chief polysaccharide of plant cell walls. Linear chains of β-1,4-linked glucose residues
4. Cellulose
5. Inulin	A reserve carbohydrate particularly abundant in the Compositae. Linear chains of up to 50 β-1,2-linked fructofuranose units terminated by a single glucose unit
5. Inulin
6. Xylans, mannans and galactans	These are often associated with one another and with cellulose. They are difficult to isolate in a pure form. On hydrolysis they yield xylose, mannose and galactose, respectively
7. Hemicelluloses	These polysaccharides occur in the cell wall with cellulose and pectic substances. The nomenclature, dating from 1891, is deceptive because hemicelluloses are not components of cellulose but are formed mainly from hexose and pentose units. Hemicelluloses vary according to source and can be classified as xylans, mannans and galactans according to their principal components
8. Lichenin or lichen starch	A polysaccharide found in lichens. Resembles cellulose but molecule contains about 25% of β-1,3 glucosidic linkages
Polysaccharide complexes containing uronic acid or other units
1. Pectins	These occur in the middle lamellae of cell walls and are abundant in fruits (e.g. apples, oranges) and roots (beets and gentian). The parent substance protopectin is insoluble but is easily converted by restricted hydrolysis into pectinic acids (pectins). Pectins from different sources vary in their complex constitution, the principal components being blocks of D-galacturonic acid residues linked by α-1,4- glycosidic linkages and interspersed with rhamnose units; some of the carboxyl groups are methylated. These molecules are accompanied by small amounts of neutral arabinans (branched polymers of α-1,5-linked L-arabofuranose units) and galactans (largely linear chains of β-1,4- linked D-galactopyranose units)
1. Pectins
2. Algin or alginic acid	Alginic acid is the principal constituent of the cell walls of the brown algae. It was discovered by Stanford in 1880 and is now widely used for the manufacture of alginate salts and fibres (q.v.). The composition varies according to the biological source, thus providing a range of properties which are exploited commercially. It is a heteropolyuronide consisting of chains of β-1,4-linked D-mannuronic acid units interspersed with lengths of α-1,4-linked L-guluronic acid units together with sections in which the two monouronide units are regularly interspersed. In alginic acids from different sources the ratios of the two uronic acids vary from 2:1 to 1:2. The chain length varies with the method of preparation and molecular weight, and viscosity measurements suggest molecules of from 220 to 860 units
2. Algin or alginic acid
3. Polysaccharides with sulphuric acid esters	Certain algae, including those yielding agar and carrageen, contain a mixture of polysaccharides. Agar, sulphuric acid esters for example, contains a biose formed from D– and L-galactose but also a more complex agaropectin formed from galactose and uronic acid units partly esterified with sulphuric acid. Carrageen has a similar composition
4. Chitin	This is found in some of the lower plants, in insects and in crustaceans. The molecule consists of linear chains of β-1,4-linked N-acetyl-D-glycosamine residues. Its inclusion in the microfibrillar component of the fungal cell wall is analogous to that of the cellulose microfibril
4. Chitin
5. Gums and mucilages	Gums such as acacia and tragacanth and mucilages, such as those found in linseed, psyllium seeds and marshmallow root, are found in many plants, where they are usually formed from the cell wall or deposited on it in layers. They are essentially polyuronides consisting of sugar and uronic acid units. Some gums have methoxyl groups (e.g. tragacanth); in others the acidic complex is united with metals (e.g. acacia)

In addition to the well-established polysaccharide-containing pharmaceutical materials described later in this chapter there is now considerable interest in a number of polysaccharides with other pharmacological activities. These include immuno-modulating, antitumour, anti-inflammatory, anticoagulant, hypoglycaemic and antiviral properties. Specific examples are the glycyrrhizans of Glycyrrhiza uralensis and G. glabra and the glycans of ginseng and Eleutherococcus (q.v.). In general polysaccharides from fungi exhibit antitumour activity, those from higher plants are immunostimulatory and the algal polysaccharides, which often contain sulphate, are good anticoagulants.

Tests for carbohydrates

The following are some of the more useful tests for sugars and other carbohydrates.

1 Reduction of Fehling’s solution. To a heated solution of the substance add drop by drop a mixture of equal parts of Fehling’s solution No. 1 and No. 2. In certain cases reduction takes place near the boiling point and is shown by a brick-red precipitate of cuprous oxide. Reducing sugars include all monosaccharides, many disaccharides (e.g. lactose, maltose, cellobiose and gentiobiose). Non-reducing substances include some disaccharides (sucrose and trehalose, the latter a sugar found in some fungi) and polysaccharides. Non-reducing carbohydrates will on boiling with acids be converted into reducing sugars, but students are reminded to neutralize any acid used for hydrolysis before testing with Fehling’s solution, or cuprous oxide will fail to precipitate.

2 Molisch’s test. All carbohydrates give a purple colour when treated with α-naphthol and concentrated sulphuric acid. With a soluble carbohydrate this appears as a ring if the sulphuric acid is gently poured in to form a layer below the aqueous solution. With an insoluble carbohydrate such as cotton-wool (cellulose) the colour will not appear until the acid layer is shaken to bring it in contact with the material.

3 Osazone formation. Osazones are sugar derivatives formed by heating a sugar solution with phenylhydrazine hydrochloride, sodium acetate and acetic acid. If the yellow crystals which form are examined under the microscope they are sufficiently characteristic for certain sugars to be identified. It should be noted that glucose and fructose form the same osazone (glucosazone, m.p. 205°C). Before melting points are taken, osazones should be purified by recrystallization from alcohol. Sucrose does not form an osazone, but under the conditions of the above test sufficient hydrolysis takes place for the production of glucosazone.

4 Resorcinol test for ketones. This is known as Selivanoff’s test. A crystal of resorcinol is added to the solution and warmed on a water-bath with an equal volume of concentrated hydrochloric acid. A rose colour is produced if a ketone is present (e.g. fructose, honey or hydrolysed inulin).

5 Test for pentoses. Heat a solution of the substance in a test-tube with an equal volume of hydrochloric acid containing a little phloroglucinol. Formation of a red colour indicates pentoses.

6 Keller–Kiliani test for deoxysugars. Deoxysugars are found in cardiac glycosides such as those of Digitalis and Strophanthus spp. (see Chapter 23). The sugar is dissolved in acetic acid containing a trace of ferric chloride and transferred to the surface of concentrated sulphuric acid. At the junction of the liquids a reddish-brown colour is produced which gradually becomes blue.

7 Enzyme reactions. Since certain carbohydrate reactions are only brought about by certain specific enzymes, such enzymes may be used for identification.

8 Chromatography. Chromatographic methods are particularly suited to the examination of drug extracts, which may contain a number of carbohydrates often in very small amounts. Not only are they applicable to carbohydrates originally present in the sample (see pharmacopoeial TLC test for honey), but also they may be used to study the products of hydrolysis of polysaccharide complexes such as gums and mucilages. As standards for comparison many pure sugars, uronic acids and other sugar derivatives are commercially available.Experimental details and R_f values of sugars in different systems are to be found in standard books on chromatography. The carbohydrate spots obtained after separation are identified by their positions and by reagents. It may be useful to examine them in ultraviolet light. A non-specific reagent for reducing sugars is a freshly prepared ammoniacal silver nitrate solution. More specific reagents giving coloured spots with different sugars include aniline hydrogen phthalate (in water-saturated n-butanol) and naphthoresorcinol (in acetone, water and phosphoric acid). These are applied to the chromatogram with a spray. Although sugars are non-volatile, it is possible by suitable treatment to render them satisfactory for gas chromatography (q.v.)

COMMERCIAL PLANT-DERIVED FIBRES AND PRODUCTS

The biological origin and the structure of plant fibres is discussed in Chapter 42; many have important commercial uses and for a review on their botany, chemistry and processing see McDougall et al., J. Sci. Food, Agric., 1993, 62, 1.

A number of vegetable fibres have importance in pharmacy, particularly as components of surgical dressings and for the manufacture of artificial fibres and haemostatic dressings. The subject of surgical dressings was, and in many Schools still is, regarded as pharmacognosy-related. However with the more recent advances in the management and concept of wound-healing, many materials of non-vegetable origin are now used which, for an in-depth coverage, bring the topic outside the scope of this book. Described below are the more important primary carbohydrate materials involved.

COTTON, RAW COTTON

Cotton consists of the epidermal trichomes of the seeds of Gossypium herbaceum and other cultivated species of Gossypium (Malvaceae). The plants are shrubs or small trees which produce three- to five-celled capsules containing numerous seeds. The USA produces about half of the world’s cotton, other important sources being Egypt, India and South America. The chief American cottons are derived from G. barbadense (Sea Island cotton) and G. herbaceum (Upland, Texas or New Orleans cotton).

The hairs of the different species vary in length or ‘staple’. The staples of important commercial varieties of cotton are as follows: (1) Sea Island, up to 54.5 mm; (2) Egyptian, 31–38 mm; (3) Brazilian and Peruvian, 29–30 mm; (4) American Upland, about 25.9 mm; (5) Indian, 21.4–29.2 mm.

ABSORBENT COTTON WOOL, ABSORBENT WOOL

Cotton wool is mainly prepared from linters, card strips, card fly and comber waste. Bales of these short-fibred cotton wastes pass from the yarn manufacturers to the makers of cotton wool. For best-quality cotton wool the comber waste of American and Egyptian cottons is preferred. In this the fibres are reasonably long and twisted and thus suitable for producing a cotton wool having an average staple that will offer appreciable resistance when pulled and not shed a significant quality of dust when shaken gently.

The preparation may be outlined as follows. The comber waste (which arrives in bales) is loosened by machinery and then heated with dilute caustic soda and soda ash solution at a pressure of 1–3 atmospheres for 10–15 h. This removes much of the fatty cuticle and renders the trichome wall absorbent. It is then well washed with water, bleached with dilute sodium hypochlorite solution and treated with very dilute hydrochloric acid. After washing and drying it is in a matted condition and is therefore opened up by machines and then ‘scutched’; that is, it is converted into a continuous sheet of fairly even thickness with the fibres loosened ready for the carding machine. The carding machine effects a combing operation and forms a thin continuous film of cotton wool. Several such films are superimposed on one another, interleaved with paper and packaged in rolls.

Tests

For tests on cotton wool, see under ‘Cotton, Raw Cotton’.

Structure of fibre

Like the cell wall in general, that of cotton consists of a primary and secondary wall. The formation of the former is modified to embrace the enormous longitudinal development of the cell, some thousands of times greater than the width. The microfibrils themselves are unexpandable and are initially laid down in hoops around the fibre, restricting its lateral growth. However, because of their different orientation at the fibre end, longitudinal extension can take place. Owing to the build-up of pressure from successive layers of cellulose the original orientation becomes lost as the fibre matures. Matrix polysaccharides and proteins derived from the Golgi apparatus are also present in the primary wall. The secondary wall, some 5–10 μm thick and consisting almost entirely of pure cellulose, constitutes the main bulk of the mature cotton fibre.

Chemical nature

Raw cotton consists of cellulose approximately 90% and moisture 7%, the remainder being wax, fat, remains of protoplasm and ash.

Absorbent cotton is a very pure form of cellulose and its chemical and physical properties have been extensively studied. The cellulose molecule is built up of glucose residues united by 1,4-β-glucosidic links (contrast starch). The wall of the cotton fibre, like that of plant cells in general, shows anisotropic properties. When swollen in water, the swelling is in a direction at right angles to the long axis. In the direction of the long axis it shows considerable tensile strength. Examined in polarized light, it shows birefringence, the value of the double refraction depending on the liquid in which the fibre is immersed. This phenomenon, characteristic of mixed bodies with rod-like structural elements, has been termed rodlet-double refraction. Stained with chlor-zinc-iodine and examined microscopically in polarized light (analyser removed), the fibre shows greater absorption when orientated with its long axis parallel to the plane of polarization than when orientated with the long axis at right angles (dichroism). These physical properties suggest that the fibre wall is built up of elongated structural units orientated in some definite manner. The study of the cotton fibre by X-ray analysis has confirmed this and has shown that its cell wall is composed of elongated chain-like molecules (built up of repeating units 1.03 nm long) and orientated in a spiral manner, the spiral making an angle of 30° with the long axis of the fibre. The length of the repeating unit of structure corresponds to that of two glucose residues fully extended. This unit is the ‘cellobiose unit’, many of which are united in the polysaccharide molecule of cellulose (Table 20.2).

The biosynthesis of cellulose in the cotton trichome would appear to involve UDP-glucose originating from sucrose.

Jute

Jute consists of the strands of phloem fibres from the stem bark of Corchorus capsularis, C. olitorius and other species of Corchorus (Tiliaceae). These are annual plants about 3–4 m high which are cultivated in Bengal, in the delta region of the Ganges and Brahmaputra rivers, and in Assam, Bihar and Orissa.

The fibres are separated from the other plant material by retting and then spun into yarn which can be made up into hessian and sacking. Short fibres left over from the preparation of the yarns and ropes constitute tow and in pharmacy the term ‘tow’ refers to jute, although it can also be applied to hemp and flax. The commercial strands are 1–3 m long and about 30–140 μm in diameter. Each consists of a bundle of phloem fibres composed of lignocellulose. The heavily lignified middle lamella is destroyed by oxidizing agents; a mixture of nitric acid and potassium chlorate may therefore be used to disintegrate the bundles, the individual fibres being then teased out and sketched. Prepared transverse sections should also be examined and compared with those of hemp and flax.

Flax

Flax is prepared from the pericyclic fibres of the stem of Linum usitatissimum (Linaceae).

The commercial fibres show fine transverse injuries received during the preparation. Good-quality flax fibre is non-lignified except for the middle lamella. Lignification of the secondary wall, however, takes place as the stem matures, starting at the base, and if the stems are too old before retting, the fibre is coarse and harsh in texture.

Hemp

Hemp is prepared from the pericyclic fibres of the stem of Cannabis sativa (Cannabinaceae). The fibre is composed chiefly of cellulose, but some lignification has usually taken place and the percentage of cellulose is lower than in flax.

The fibre ends, in contrast to those of flax, are bluntly rounded. Some of the fibre ends are forked, this bifurcation arising from injuries to the stem. The lumen of the hemp fibre is flattened or oval, in contrast to the small round lumen of flax. Transverse striations seen in commercial fibres arise from beating, the fibres being prepared by partial retting.

Jute, hemp and flax fibres are compared in Table 20.3.

Table 20.3 Characters of jute, hemp and flax fibres.

REGENERATED CARBOHYDRATE MATERIAL AND CHEMICALLY MODIFIED FIBRES

Regenerated fibres are those produced from naturally occurring, long-chain molecules which have been isolated, controlled and, if necessary, modified to give a suitable fibre form. The term ‘rayon’, as in viscose, acetate and cuprammonium rayon, is applied to those derived from the polysaccharide cellulose. The term ‘artificial silk’ is now out of date. Also in this class is alginate fibre, derived from alginic acid (q.v.).

Viscose (regenerated cellulose, rayon)

This has been developed from a process introduced by three British chemists (Beadle, Bevan and Cross) in 1892, and accounts for the bulk of the world rayon output today. It is also the principal type used in surgical dressings.

The starting material is a cellulose prepared either from coniferous wood, particularly spruce, or scoured and bleached cotton linters. The wood is usually delignified at source (Canada, Scandinavia, etc.) by a process similar to that used for cellulose wadding. It reaches the rayon manufacturers as boards of white pulp, containing 80–90% of cellulose and some hemicellulose (mainly pentosans). The latter, being alkali-soluble, are removed in the first stage of the process, which consists of steeping in sodium hydroxide solution. After most of the excess alkaline liquor has been pressed out, alkali-cellulose (sodium cellulosate) remains. This is dissolved by treatment with carbon disulphide and sodium hydroxide solution to give a viscous (whence the name ‘viscose’) solution of sodium cellulose xanthate. After ‘ripening’ and filtering, the solution is forced through a spinneret, a jet with fine nozzles, immersed in a bath which includes dilute sulphuric acid and sodium sulphate, when the cellulose is regenerated as continuous filaments. These are drawn together as a yarn, which is twisted for strength, desulphurized by removing free sulphur with sodium sulphide, bleached, washed, dried and conditioned to a moisture content of 10%.

The viscose yarn may be left as such (i.e. continuous filament rayon) for use in such things as blouse fabrics, or it may be cut up to give staple rayon (‘Fibro’) of fixed length from 1 to 8 in. That used in surgical dressings and many other fabrics is made to resemble cotton in dimensions. Suitable spinnerets are used to give a diameter of 15–20 μm and the fibre is cut into lengths usually of 4.8 cm. This staple can be processed on types of spinning and weaving machines used for cotton dressings or it may be left in a loose fibre form as viscose rayon absorbent wool.

Viscose rayon is a very pure form of cellulose. It yields a trace of ash which contains sulphur. The cellulose molecules of the original natural material, whether wood or cotton, become more separated from one another in the viscose solution than in the vegetable material and in the regenerated fibre are still less closely packed. Radiography has shown that the side-to-side aggregation of the long-chain molecules is different from that in natural celluloses. The size of the molecules is also reduced, wood cellulose having molecules of the order of 9000 glucose residue units, while those of viscose rayon have only about 450.

Viscose rayon gauze and other rayon dressings have the advantage over cotton dressings in that they show no loss of absorbency on storage.

Macroscopical characters

As normally produced, this rayon is a white, highly lustrous fibre (natural or glossy viscose). Its tensile strength varies from two-thirds to one-and-a-half times that of cotton. When wetted it loses about 60% of its tensile strength, a proportionately greater loss than is found with cotton. Where more than a certain amount of rayon is used in a dressing, the fabric may be required to be rendered water-repellent (e.g. cotton crêpe bandage).

Microscopical characters

The fibres are solid and transparent and 15–20 μm in diameter. They have a slight twist, and show grooves along their length which are principally caused by the spinnerets being immersed in the regenerating solution (compare nylon). The grooves give a characteristic appearance to the transverse section. The ends of the fibres are abrupt and characteristic. The fibres are clearly seen in chloral hydrate solution or in lactophenol, but are almost invisible in cresol (having the same refractive index of 1.53). They appear bright in polarized light with crossed Nicols.

Chemical tests

1 The fibres give the general tests for vegetable and regenerated carbohydrate fibres.

2 On ignition they behave like cotton; distinction from acetate rayon and alginate yarn (also wool, silk, nylon and glass).

3 With N/50 iodine and sulphuric acid, 80%, they give a blue colour similar to that given by cotton; distinction from acetate rayon, alginate yarn, jute, hemp (also wool, silk, nylon).

4 With ammoniacal copper oxide they behave like absorbent cotton; distinction from acetate rayon, jute (also wool, nylon).

5 Cold sulphuric acid, 60% w/w, dissolves the fibre; distinction from cotton, oxidized cellulose, alginate yarn, flax, jute, hemp (also wool).

6 Warm (40°C) Hydrochloric Acid BP does not cause solution; distinction from acetate rayon (also silk, nylon).

7 Boiling potassium hydroxide solution, 5%, insoluble; distinction from oxidized cellulose (also wool, silk).

8 Shirlastain A produces a bright pink; distinction from cotton, oxidized cellulose, acetate, rayon (also wool, silk, nylon).

9 Phloroglucinol and hydrochloric acid produce no red stain; distinction from jute, hemp and kapok.

10 The fibres, like cotton, are insoluble in acetone, formic acid 90% or phenol 90%; distinction from acetate rayon (also nylon).

Delustring and dyeing of fibres

Rayon and other artificial fibres with a natural lustrous appearance may be delustred by addition of the white pigment titanium oxide to the solution (e.g. viscose) or to the melt (e.g. nylon) before extrusion of the filaments. In this way the pigment is evenly distributed inside each filament and delustring is permanent. These fibres may be similarly ‘spun-dyed’ by addition of an appropriate dye instead of the titanium oxide. The method results in an exceptional degree of colour fastness.

Matt Viscose (delustrated viscose rayon) is the form normally used in the manufacture of surgical dressings; hence, in general appearance these are very similar to those manufactured from cotton. The individual filaments have the appearance already described, except for the matt white colour and on microscopical examination the pigment particles, which appear black by transmitted light and are scattered throughout the filament. The amount of pigment is controlled by the ash value. Titanium is detected in the ash by dissolving in sulphuric acid, diluting and adding hydrogen peroxide, 3%, when a yellow colour is produced.

Cellulose ethers

These are prepared from purified alkali cellulose derived from cotton linters or delignified wood pulp by the action of caustic soda, as in the initial stages of the production of viscose rayon.

Methylcellulose BP/EP is a whitish, fibrous powder prepared by the action of methyl chloride under pressure on an alkali cellulose, when hydroxyl groups become methylated. A useful grade is that in which two of the three hydroxyl groups of the glucose residue units of the cellulose chain are methylated, and this has the optimum solubility in water. In pharmacy a grade giving a low viscosity is used both to increase the viscosity and to stabilize lotions, suspensions, pastes and some ointments and ophthalmic preparations; one giving a high viscosity is used as a tablet disintegrant. In medicine it is used as a hydrophilic colloid laxative in chronic constipation and can be used in obese persons to curb the appetite, because it gives a feeling of fullness. Ethylcellulose is similarly prepared and has like applications.

Carmellose Sodium EP/BP (sodium carboxymethylcellulose) is an odourless and tasteless white hygroscopic powder or granules prepared by the action of monochloroacetic acid on alkali cellulose and removal of the byproduct salts. Substitution of hydroxyl groups by carboxymethyl groups occurs over a range depending on the conditions and the cellulose used; there are prescribed limits for the sodium content. It is water-soluble, and a grade giving a medium viscosity contains 0.7 carboxymethyl groups per glucose residue unit. It is insoluble in organic solvents. Its pharmaceutical and medical uses are similar to those of methylcellulose, but as well as being used as a laxative it is a useful antacid.

Carmellose calcium is also official.

Pyroxylin BP (Cellulose nitrate)

Pyroxylin is prepared by the action of nitric and sulphuric acids on wood pulp or cotton linters that have been freed from fatty materials. When dry it is explosive and must be carefully stored, dampened with not less than 25% its weight of isopropyl alcohol or industrial methylated spirits. It is used for making Flexible Collodion BP.

Absorbable haemostatic dressings

The control of bleeding is of vital concern in surgery, and the great disadvantage of the old-type dressing such as a cotton gauze plug is that it has to be removed after bleeding has been checked with a consequent danger of a recurrence of the haemorrhage. Gelatin sponge, oxidized cellulose and alginate dressings overcome this, in that there is no need to remove them after the bleeding has been checked, since they are absorbed by the tissues.

Oxidized cellulose

Oxidized cellulose originated in the USA as a result of the work published by Yackel and Kenyon in 1942. Cotton wool or gauze is treated with nitrogen dioxide until the number of carboxyl groups formed by the oxidation of the primary alcohol groups of the glucose residue units of the cellulose molecules reaches 16–22%. The original cellulose now has glucuronic acid residue units (compare alginic acid) as well as some glucose residue units.

Appearance

Gauze, lint or knitted material, very similar to normal cotton but with an off-white colour, a harsher texture, charred odour and an acid taste. It does not go pasty on chewing. The wool tends to disintegrate on handling. In microscopical appearance the fibres are very similar to those of absorbent cotton.

Tests

1 Does not give the tests for animal fibres and animal source-haemostatics.

2 On ignition it behaves like normal cotton.

3 With iodine and sulphuric acid or ammoniacal copper oxide solution it behaves like absorbent cotton.

4 Slowly soluble in 80% sulphuric acid.

5 Insoluble in warm hydrochloric acid BP.

6 Soluble in the cold in 5% potassium hydroxide solution.

Complete solubility in aqueous alkali is made the basis of a test for absence of unchanged cotton and foreign particles. The solution in alkali gives with excess acid a white flocculent precipitate (former BP test for identity).

7 It reduces Fehling’s solution.

8 Shirlastain A gives a pale blue to mauve colour.

9 Shirlastain C gives a brown to olive green.

Uses

It is used as an absorbable haemostatic in many types of surgery, but is incompatible with pencillin, delays bone repair and cannot be sterilized by heat. It has found some application in chromatography.

Alginate fibres

These originated about 1938 in Britain and were further developed during World War II.

The fibres are prepared by a process similar to that for viscose rayon. An aqueous solution of sodium alginate (see this chapter) is pumped through a spinneret immersed in a bath of calcium chloride solution (acidified with hydrochloric acid), when water-insoluble calcium alignate is precipitated as continuous filaments. These are collected, washed and dried. For use in surgical dressings and bacteriological swabs they are reduced to a staple form which may then be processed to a calcium alginate wool or a fabric (e.g. gauze) in the same manner as used for viscose staple or cotton.

As indicated in Table 20.2, alginic acid is composed of polymers of both mannuronic and guluronic acids. The properties of the two are variable and alginates of different origin have different compositions and properties. This is illustrated by the two commercial haemostatic dressings—Kalostat (BritCair Limited) and Sorbsan (Steriseal—Pharmaplast Limited). The former is derived from the seaweed Laminaria hyperborea collected off the Norwegian coast and yields an alginate with a guluronic:mannuronic ratio of 2:1; the latter is prepared from Laminaria and Ascophyllum species collected off the west coast of Scotland and gives an alginate with a guluronic:mannuronic acid ratio of about 1:2. On a wound surface the α-linkages of the guluronic acid polymer are not easily broken so that fibre strength is retained and a strong gel is formed on contact with the wound exudate. A high ratio of mannuronic acid polymer (β-linkages) yields a product giving a weaker gel and less retention of fibre strength. In practice this means that the Kalostat dressing can be removed from the wound with forceps and Sorbsan is removed by irrigation with, for example, sodium citrate solution.

Calcium alginate fibres of commerce contain substantial traces of substances used to inhibit mould and bacterial growth in the sodium alginate spinning solution. Spinning lubricants such as lauryl or cetyl pyridinium bromide (antibacterial) are also applied to the filaments. These substances must not be used or must be removed in the case of calcium alginate staple for use in, for example, bacteriological swabs.

Before use as an absorbable haemostatic dressing some calcium alginate dressings must be immersed in sodium chloride to give a fibre of the calcium alginate covered by sodium alginate. The degree of conversion is conditioned to give the desired rate of absorption when in use; the greater the proportion of sodium alginate the faster the absorption rate.

Alginate filaments are composed of salts of the long-chain molecules of alginic acid (see Table 20.2) and there is little cross-linking between the chains in the fibre.