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4. Fermentation. — Pentoses do not ferment with yeast as all
other common simple sugars do. Maltose ferments directly, cane
sugar and lactose only after hydrolysis. To a 2 per cent, solution
of each of these sugars add a small particle of yeast and keep at a
temperature of 40°C. Results?

The Uses of Sugars. — They are used as flavoring and sweeten-
ing agents in medicines, and in strong solutions as preservatives.
Molasses is used in domestic medicine as a laxative. Lactose is
used in the preparation of infant foods and as an excipient or
vehicle in pharmacy. Levulose is sometimes given to diabetics
who cannot utilize glucose, but the advisability of this is question-
able since it is perhaps as difficult to oxidize in the body as
dextrose and other sugars. In cases of glycosuria it is often neces-
sary to distinguish between pentosuria, levulosuria, lactosuriaand
glucosuria. To determine this, diflFerences of rotation, fermenta-



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CARBOHYDRATES 139

tion, the melting point of the osazone and other tests must be
made.

CELLULOSE

Cellulose is a mixture of complex carbohydrates. Next to
water, it is the most abundant substance in plants where it consti-
tutes the greater part of the cell wall. Because it is not a pure
chemical, it is often called crude fiber. Celluloses are not diges-
tible except by strong reagents and the higher animals digest
but little cellulose, although some of the lower animals do.
This indigestibility renders cellulose valuable in the treatment of
chronic constipation. In such cases cellulose acts by stimulating
the bowel mechanically. Apparently some indigestible volume
is needed to elicit the normal function of the intestine. This is
one of the reasons why fruits and vegetables are so highly
recommended in cases of chronic constipation.

The celluloses include vegetable fibers, cotton, linen, hemp,
filter paper, etc. They are insoluble in water, alcohol and ether.
While they are indigestible, strong H2SO4 converts them into
dextrin and glucose. Treated with HNO3, cellulose yields gun-
cotton, cellulose hexanitrate, which is highly explosive. If the
HNO3 is allowed to act a short time only, the tetra and penta
nitrates are formed. These are not explosive, and dissolve
readily in a mixture of alcohol and ether with the formation of
collodion (see collodion and flexible collodion.)

Tests for Cellulose

1. Examine guncotton. Test its solubility in water and
alcohd.

2. Dip a piece of filter paper in a mixture of 4 volumes of
H2SO4 and one of water and immediately wash it oflf with water.
Let dry and apply the iodine test. Compare the test with the
original paper.

3. Crude Fiber. — The term fiber is applied to those carbo-
hydrate products in drugs or in food which are insoluble in
dilute acids and alkalies. Inasmuch as they are not pure cellu-
lose, they are often designated as crude fiber.

To determine the amount of crude fiber in a food or drug:
Weigh out 2 grams of the dry material. Extract with ether until



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140 CHEMICAL PHARMACOLOGY

all lipoids are extracted. Boil the residue with 200 cc. of 1.25
per cent. H2SO4 for 30 minutes, using a reflux condenser.
Filter through asbestos, wash with boiling water. Transfer the
asbestos, etc., to the flask again and repeat boiUng with 1.25 per
cent. NaOH 200 cc. Boil for 30 minutes, filter through a Gooch
crucible and wash free from alkali with hot water. Dry at
110*^0. until the weight is constant. Incinerate and weigh
again. The loss in weight is considered to be crude fiber.

HEMICELLULOSE

Hemi, pseudo, reserve cellulose, or paragalactane substances
are not well defined and seem to be mixtures of mannans, xylans,
arabans, galactans, or complexes which when treated with hot
dilute HCl or H2SO4 may yield galactose, rhaminose, mannose,
fructose, arabinose, or xylose, whereas ordinary cellulose does
not, except when treated with strong acids. The seeds of many
plants, especially nut shells and stony seeds, cocoanut rind, and
young plant tissues, contain the reserve carbohydrate which is
called hemicellulose. It serves as reserve food or supporting
tissue. From its reactions hemicellulose is considered simpler
than cellulose in composition. When boiled with acid the only
product of hydrolysis is a hexose. Hemicellulose is also dissolved
by dilute alkali and by means of enzymes, and may be converted
into gums. The formation of galactose on hydrolysis suggests
a relationship to the gums.

AGAR

Agar (agar-agar) is a carbohydrate extracted with hot water
from certain marine algae which grow mainly along the eastern
coast of Asia and Japan. The extract is evaporated and the
product sold in bundles of shreds, or as a powder. It consists
practically of the hemicellulose, gelose, (CeHioOg), and dissolves
in 500 parts of water. When boiled with about 600 parts of
water* for 10 minutes, it yields a stiff jelly on cooling. It is used
principally in the preparation of bacterial culture media, and
because of its indigestibility has been recommended as a cathartic.
In this respect it acts like bran and vegetables rich in cellulose.
Phenolphthalein agar, is agar impregnated with 3 per cent, phenol-



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CARBOHYDRATES 141

phthalein to increase its laxative effect. Regulin is another
preparation of agar with cascara.

Agar, because, of its cheapness and good jelling properties, has
been employed as a "coagulator" in the manufacture of cheap
jellies. To detect agar in such jelUes the product is heated with
5 per cent, sulphuric acid, a little permanganate is added, and
after the material settles, diatoms in large numbers will be found
if agar has been used.

GUMS

Gums are desiccated exudations of certain plants, obtained by
incising the limbs or branches. They are somewhat transparent
carbohydrates, isomeric with starch. Acacia and tragacanth are
the most important. They have a physical action only and are
used mainly as excipients or vehicles (see mucilages and demul-
cents). Their use is objectionable in cases where they are hydro-
lyzed by bacteria and the products remain as irritating
substances. They are but little used externally for this reason.
Pectin or vegetable jelly is closely related to the gums and causes
fruit to set or "gel". Gums lessen the irritation of medicines
and are used in enemata where it is desirable to retain the solution
in the rectum for some time. The taste of acids or salts is also
lessened by being mixed with colloids, as in fruits. Raspberries
contain more acid than currants but taste less acid because they
contain colloid. These effects are due to lessened absorption
and also to protection of the sensory nerve endings by the
colloidal material.

Tests for Gums

1. Test the solubility of gum acacia and tragacanth in water
and alcohol.

2. Mix watery, solution of acacia with an equal volume of
alcohol. Result? What has happened? Compare with glu-
cosides under the same treatment. What is the difference?

3. Test a water solution of acacia or tragacanth with Fehling's
solution.

4. Test a water solution of a gum with iodine solution.
Compare results with starch solution. Note differences.

5. To a solution of acacia in a test tube add a few drops of



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142 CHEMICAL PHARMACOLOGY

H2SO4. Boil for two or three minutes. Neutralize with KOH
or NaOH and test with Fehling's solution.

6. Compare the taste of a 1 per cent, citric acid in water with
1 per cent, citric acid in 10 per cent, mucilage of acacia.
Explain.

7. Mix a small quantity of cottonseed oil with 3 volumes
mucilage of acacia and shake until an emulsion is formed. Add
alcohol to the mixture and note results. Explain.

8. State the differences between starches, sugars, and gums;
between gums and glucosides; glucosides and alkaloids.

PECTINS

Pectins are carbohydrate bodies whose composition is known
but slightly. They are associated with cellulose in the plant.
It is due to pectin that fruit juices ''gel''. The phenomenon of
gelling is similar to the setting of gelatin, but the composition of
the gelUng body is different in the two cases. In the case of
gelatin it is a protein, while pectin is a carbohydrate.

Pectin is especially abundant in apples, pears, gooseberries
and currants. It is also found in abundance in carrots, beet
roots, etc., as pectose, which as ripening proceeds is converted
into pectin.

The clotting of plant juices is said to be due to an enzyme
pectase, but that it will occur without enzyme action is apparent
from the gelation after prolonged cooking which destroy enzymes.
According to Duclaux and others the clotting of pectin is due to
the presence of calcium salts and the presence of an enzyme is
unnecessary. The clotting therefore would seem similar in
nature to the clotting of blood. According to Freimy (Jour.
Pharm. et chim., 1840, 26, 368) the hardness of unripe fruit is
due to pectose. When this is boiled with dilute acids or alkalies,
pectin, parapectin, metapectin, and pectic acid are formed.
Some of these exist in the plant combined with calcium, in the same
sort of union as that which occurs in guma.

No very characteristic tests for pectins can be given. Methyl-
ene blue and some other substances stain pectins but not pure
cellulose, while crocein, napthol black and orseille, stain cellulose,
but not pectin. Pharmacologically pectins may exert a vitamin
effect, but this is not proven.



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FATS AND OILS 143

METHOD OF PREPARING PECTIN

(C. H. Hunt, Science, 48, 201, 1918)

The object in view was to prepare pectin, so that it could be
added to fruit juices which are low in pectin, and so cause a
gelling of non-gelatinating juices: The method was as follows:

Dried apple pomace (60 g.) was boiled with 3 successive
portions (200 cc. each) of H2O, and filtered after each boiling.
For each 100 cc. of filtrate, 25 g. (NH4)2S04 were added; the re-
sulting solution was heated to 70°; the pectin separated as 'a
grayish white flocculent precipitate which was collected on a
filter, dissolved in hot H2O, again precipitated with (NH4)2S04
and collected on a filter, dried at 60 to 70°, then washed several
times with cold H2O to remove adhering (NH4)2S04, and again
dried. The product was tested for gelatinizing power "by adding
to a 1 per cent, solution of the pectin 0.5 per cent, solution of
citric acid and 65 g. of sugar. This solution was boiled for 10 to
20 minutes and upon cooling a nice stiff jelly was produced.
The taste did not indicate the presence of (NH4)2S04 and upon
dissolving the jelly in hot H2O only a slight milkiness was pro-
duced when tested for sulphates." If wet pomace be used, in
addition to the 25 g. (NH4)2S04 per 100 cc. of filtered extract,
that salt must be added in extra portions 5 g. each until precipita-
tion of the pectin occurs; it may also be precipitated by saturation
of the filtered extract in the cold (NH4)2S04. '^ The (NH4)2S04
method gave a yield of 6.33 per cent, pectin, the alcohol method a
jdeld of 6.91 per cent. Concentration of the pectin extract either
at a temperature below the boiling point or by freezing did not
impair the quality of the pectin and reduced the amount of (NH4)2
SO4 required.

XVn. FATS AND FIXED OILS

Fats and fixed oils are salts of glycerine with fatty acids, the
acids being principally palmitic, stearic, and oleic, or mixtures
of these. The oils are liquid fats. The consistency of fat
depends upon the relative amount of the acids present: if
stearic acid only is present, the fat is hard (e.g., oil of theobroma-
cocoa butter) ; if oleic acid is the principle one present, the fat is
soft or oily (as in all the ordinary fixed oils). Tallow is the fat
from beef and mutton suet, while lard is hog fat. To obtain these



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144



CHEMICAL PHARMACOLOGY



relatively pure, the fats are sometimes kneaded in a muslin bag
under hot water. The pure fat separates and floats on the sur-
face, while the connective tissue is held in the bag. High heat
decomposes fats with a resultant formation of irritating sub-
stances (acrolein — acrid oil). Vegetable oils are obtained by
expression of the seeds, which, when the fats are solid, are often
heated to liquefy the oil and facilitate the process. The fixed
oils are entirely different from the volatile oils (g.t;.).
• Fats are sometimes called glycerides, glycerine esters, or etheral
salts. Glycerine with stearic acid alone is called stearin, or
glyceryl stearate; with pahnitic acid, pahnitin, and with oleic
acid, olein. The combination is represented by the following
formulas — where R represents any fatty acid radical:



CHaOiH HOiOC.R

I ZZZZ^

CHOIH HOIOC.R



CHaOiH HOJOC.R

Glycerine + fatty acid
Stearic acid
Stearin
Palmitic #acid
Palmitin
Oleic acid
Olein



CH2O.OCR

I

CH.O.OCR + 3H2O

I
CH2O.OCR

Fat + water
CitHsbCOOH

C3H6(Ci8H3602)3

CibHsiCOOH

C3Hb(Ci6H8i02)8
G17H33COOH
C3Hb(Ci8H33 02)3



CLASSIFICATION OF OILS

Oils are divided into drying and non-drying. Some oils which
contain Unolenic and linoUc acids when exposed to the air absorb
oxygen and become resinous and leave a hard elastic film. This
process is hastened by catalytic agents such as Utharge, manga-'
nese dioxide and the acetates and borates of lead, manganese, and
zinc. These agents are known as "driers.'* Oleic acid does not
absorb oxygen. The drying oils are less viscous and less stable
than the non-drying. This drying and unstable property is due
to the unsaturated fatty acids. The drying vegetable oils are:



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FATS AND OILS 145

I. The linseed oil group which includes:

Linseed

Hempseed

Wahiut

Sunflower

Poppyseed

Nigerseed

The semi-drying or cottonseed oil group includes:

Cottonseed

Sesame

Beechnut

Maize

Rape

Brazil nut

This group is composed mainly of the glycerides of oleic and
linolic acids.

II. The non-drying or castor oil group includes:

Castor
Croton

The non-4rying olive oil group includes :

Olive
Almond
Rape
Peanut
Mustard oils

Most animal fats and waxes are non-drying, but the fats of the
rattlesnake and ice bear are drying, while horse fat is semi-drying.

Both animal and vegetable fats and oils are used in medicine.
The most important animal fats are lard or swine fat, suet or
mutton fat, tallow or beef fat, and butter fat.

The relative amount of the various fatty acids in these differ-
ent fats varies widely, not only with the species but also with the
food of the animal. Lard may contain 90 per cent, olein and
melt as low as 28°C. when the diet is corn-meal, or as high as 35°C.
when the animal is fed on oats, peas and barley; the fat in this
case contains less olein than when the animal is corn fed. Fat

10



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146 [ CHEBOCAL PHARMACOLOGY

from diflferent parts of the same animal may vary in melting
point due to differences in composition. Human fat melts as
low as 17.5°C. because it is rich in olein, tallow melts at about
45°C., and suet at 45-50°C. If a fat contains only oleic acid
with glycerine it is an olein or triolein and is a liquid at 0*^C.,
while palmitin (tripalmitin) melts at 62*^0. and stearin (tri-stearin)
at 71.6°C.

Butter fat is a mixture of palmitin, stearin and olein, and in ad-
dition it contains 6 to 8 per cent, of volatile fatty acids combined
with glycerine. These are butyric, caproic, capryllic, capric,
with traces of lauric and myristic. No other fat except cocoa-
nut oil contains so high a percentage of vdatile fatty acids.
This fact aids in the recognition of an adulteration of butter with
other fats as in oleomargarine, which consists chiefly of the higher
fatty acids. Butter is little if at all used as a medicine, but it is
extremely valuable as a food and contains vitamines essential to
normal growth, which few if any other fats can adequately
supply.

Fats and oils are widely distributed in the vegetable kingdom,
chiefly as the glycefides of palmitic, stearic and oleic acids, but
the following fatty acids are frequently found :

CHav
I. Isobutyl acetic or caproic )>CH.CH2.CH2.COOH

CHs^

Caprylic CH3(CH2)6COOH

Capric CH3(CH2)8COOH -

Lauric CH3(CH2) loCOOH

Myristic CH3(CH2) 12COOH

Pahnitic CHsCCHj) uCOOH

Stearic CH3(CH2)i6COOH

Arachidic CH3(CH2) isCOOH

Behenic CH3(CH2)2oCOOH

These acids all conform to the general formula

(C,H2n02).

There are other fatty acids of the oleic or acrylic series that
conform to the general formula

(CnH 20-202).



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FATS


AND


OILS




II. These are Tiglic acid






CbHsO^


Oleic






C18H34O2


Elaidic






C16H84O2


Iso-oleic •






C18H34O2


Erucic






C22H42O2


Brassidic






C22H42O2



147



The most/important of these in medicine are oleic and tiglic —
foiind in croton oil.

III. The linolic series

(CnH2n - 4O2)

1. open series linolic acid C18H32O2

2. Chaulmoogric acid C18H32O2

a cycliq ccnnpound, from chaulmoogra oil, which is used in the
treatment of leprosy.

IV. A linolenic acid series of the general formula

CnH2ii-602

is also known but not important in medicine.

V. A clupanodonic series with the general formula

CnH2n-8 O2

VI. A iicinoleic oleic series, general formula

CnH2n-203

of which the acid from castor oil is the important representative.
While many of these are unimportant in medicine, they illustrate
because of their unsaturated condition, what is meant by the
iodine number — described below. Unsaturated compounds as
a rule are also more active physiologically than saturated
compounds.

The chief vegetable fats used in medicine are:

Palm oil, which consists almost entirely of palmitin and cocoa
butter, contains about

40 per cent, stearin, 20 per cent, palmitin,

30 per cent, olein, 6 per cent, linolein.

Linseed oil consists mainly of oleins — a mixture of oleic, Unolic,
linolenic, and isolinolenic acids.



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148 CHEMICAL PHARMACOLOGY

Cottonseed oil consists chiefly of olein, palmitin, and linolein,
with small amounts of linolenic acid.

Olive oil, consists of 72 per cent, of Uquid glyeerides, made
up of olein 94 parts, linolein 6 parts, and about 28 per cent,
palmitin.

Castor oil consists mainly of the glyeerides of triricinolein,
together with ricinisolein, palmitin and dioxystearin.

Croton oil: The composition of croton oil is very complex.
The glyeerides of at least 10 acids have been found, namely —
oleic, palmitic, stearic myristic, lauric, valeric, formic, butyric,
acetic, tiglic and croton oleic. It is a violent jpurgative, a single
drop being a dose. When rubbed on the skin croton oil may also
produce rubefaction and pustulation. It yields about half as
much volatile fatty acids as butter, among these volatile acids are
formic, acetic, and valerianic. While these acids areirritating,
and it was formerly thought that the irritant and purgative
action is due to the irritation caused by the acids liberated on
saponification of the oil, it is now believed that these actions of
croton oil are due to an acrid resin C13H18O4 contained in the oil.

Most oils are insoluble in alcohol, castor and croton oils are
exceptions to this rule. Croton is somewhat soluble and castor
is soluble in absolute alcohol. Both are soluble in ether.

A distinguishing property of castor oil is its insqlubiUty in
petroleum ether. It is Ukewise one of the heaviest fats having a
ispecific gravity of 0.960 as against a range of 0.85 to 0.95 for
other fats.

Fats are extracted from seeds, or tissues after these have been
thoroughly desiccated. They are then placed in extractors and
the fat is drawn out with ether, light petroleum, carbon bisulphide
or carbon tetrachloride. Ether is the usual laboratory solvent.

These solvents extract also cholesterol, lecithin, essential oils,
and the indefinite group of bodies known as lipoids, and the extract
for this reason is known as the ether extract. A process of puri-
fication must be employed if a pure product is desired.

GENERAL PROPERTIES OF FATS

1. The physical properties depend on the composition — oleins
are Uquid, stearins are solid, palmitins of a vaseline or tallow
consistency.



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ACTION OF SOAP 149

2. Pats are insoluble in water and but slightly soluble in cold
alcohol.

3. They are soluble in ether, benzine, benzene, chloroform,
carbon bisulphide, carbon tetrachloride.

4. Fats can be heated from 200*^ to 250°C. without decomposi-
tion. Higher heat may decompose them with the formation of
the irritating volatile product of glycerine — acrolein

CH2 = CH- CHO

This change is hastened by the addition of (KHSO4) — potas-
sium bisulphate, and is a test for true fats, or anything containing
glycerine.

5. Lipases hydrolyze fats into fatty acids and glycerine. This
change may also be accomplished by bacteria and by superheated
steam. Acids and alkalies greatly accelerate the reaction. This
hydrolysis is known as saponification.

6. When boiled with alkalies fats are hydrolyzed, and the
combination of the alkali metal with the fatty acid is known as a
soap. Green soap is the potassium or soft soap, and is so-called
because the oils formerly used contained chlorophyll which gave
the soap a green color.

In medicine and pharmacy, antiseptics and other substances
are frequently added to, or incorporated in the soap. These are
the so-called medicated soaps. Cresol, thymol, tar, sulphur,
mercury, salicylic acid, etc. are among the substances added.
Castile soap is made from olive oil and sodium hydroxide; green
soap from linseed oil and potassium hydroxide. Lead plaster is a
lead soap. Resin and sodium silicate are added to soaps mainly
as adulterants. Such soaps hold a great deal of water, hence
weigh more than a pure soap, and this is the principal reason for
the addition.

Explanation of the Cleansing Action of Soap

Ordinary soaps are the sodium potassium salts of fatty acids.
These are weak acids, and their salts are decomposed to some
extent by water just as sodium carbonate is, and soap solutions
are alkaline in reaction for the same reason that sodium carbonate
is alkahne. In water soap is hydrolyzed according to the formula :



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160



CHEMICAL PHARMACOLOGY



1. CH,(CH,)i6COONa-^CH,(CH-0i6COO + Na+

2. CHs(CH2),6COO - + Na+ + HOH ->

Na+ + OH CH8(CH2)i6COOH +
Stearate ion Stearic acid

Since stearic acid is insoluble in water, it is removed from solu-
tion, and the NaOH ions react alkaline. The amount of free
alkali depends on the dilution. In strong solution a soap that
will cause just a pink color with phenolphthalein, may be dis-
tinctly alkaline on dilution. These hydrolyzed products readily
emulsify fats, and such emulsion is readily soluble in or removable
by water. This briefly explains the mechanism of soap in wash-
ing. Mathews explains the formation of these colloidal solutions
as follows:







O



1. Na - - C - (CH2)i6 - CHa^ ^ ||

Na+ + O- - C - (CH2)f6 - CH3
Sodium stearate ?:± Sodium ion + stearate ion

2. Na - - C - (CH2)i6 - CHa + HaO^

II NaOH+ H - - C - (CH2)i6 - CH3

O II

o

stearic acid

3. Na+ - O - C - (CH2)i. - CHa + 2H0 - C - (CH,)u

II . II -CH,^

o o



+

Na +



O

II
-0 - G - (CH2),e - CH3
2H0 - C - (CH2)i, - CH,

II
O



Colloidal soap.

This negatively changed colloidal soap is held in solution by
the great attraction of the positively changed sodium ion, for



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FAT CONSTANTS 151 '

water, and it (colloidal soap) has a great attraction for the fatty
acids of neutral fat or grease. Consequently when put on the
skin, the fats of the skin adhere to the colloidal soap particles
and are held in colloidal solution by the attraction of the sodium
ion for water. Large easily removable aggregates may thus be
formed. Vaseline, liquid petrolatum and other Upoids that do not
form emulsions readily, are for this reason hard to remove.

THE CHARACTERIZATION OF FATS

The following methods are used for the recognition and the
evaluation of fats.

1. The melting point is determined. This shows the general
nature of the fats — whether they are composed mainly of stearin,
palmitin or olein.

2. The acid number. This is the number of milligrams of
KOH required to neutralize the free acid contained in one gram
of the fat. This is determined by dissolving 1 or 2 grams of the
fat in about 20 cc. of a mixture of 1 part alcohol and two parts
of ether. Titrate the solution with N/10 solution of KOH in



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