Volume 10

Medica! Journal of the Number 1

Islamic Republic of Iran Spring 1375
May 1996

PREPARATION AN D CLINICAL EVALUATION OF

SOME AN TI-ANORECTAL DISEASE DRUGS
OBTAINED FROM MEDICINAL PLANTS

SULEIMAN AFSHARYPOUR, KlANDOKHT SHAFII,

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MOHAMMAD ESMAIL AKBARY, * AND MOH.A.MM.A.D REZA

ZARGARZADEH

From the Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences,
Isfahan, and the *School ofMedicine, Isfahan University of Medical Sciences, Isfahan,
Islamic Republic of Iran.

ABSTRACT

The hydroalcoholic extracts of dried ligulate florets of Calendula ojficinalis

L., dried leaves of Plantago major L., and dried aerial parts of Vinca major L. were
prepared and used as the main active ingredients of two types of anti-anorectal
disease ointments and suppositories. Benzocaine was used in one of the
formulations, while a mixture of belladonna dry extract and ephedrine sulfate was
used in the other. The effects of both prepared formulations were investigated in
patients suffering from anorectal diseases, using relevant placebos for
comparison.
The results indicated that the prepared drugs were significantly effective in the
treatment of anorectal diseases. Formulations containing benzocaine proved to be
more effective in patients suffering from hemorrhoids, while formulations con­
taining belladonna dry extract and ephedrine sulfate were more effective in anal
fissure and proctitis.
Keywords: Anti-Anorectal Disease Plants; Calendula officinalis; Plantago major; Vinca major.

MJIRI, Vol. 10, No.1, 73-77,1996.

INTRODUCTION disorder may be masked. 1

The main pharmacologic agents used for relief of
In addition to hemorrhoids, anorectal disease en­ anorectal disease symptoms are: local anesthetics,
comp a s s e s other seri o us disor der s such as anal vasoconstrictor s, protectants, counterIrntants,
fis sure, anal fistula, proctitis, abscess, condyloma astringents, wound healing agent s , antiseptics,
latumi, condyloma acuminata, cryptitis, malignant neo­ keratolytics, and antichoIiner gics.1
plasm, and polypS.I-4 The common symptoms of In this research, considering the above mentioned
anorectal disorders are: itching, burning, pain, inflam­ types of pharmacological agents which are usually used
mation, irritation, swelling and discomfort which may fo r relief of anorectal disease symptoms, four
be relieved by self-medication if they are not manifesta­ formulations were designed, prepared, and their clinical
tions of more serious anorectal disease. Bleeding, seep­ effects investigated. The main active ingredients whicil
age, protrusion, prolapse and thrombosis are more seri­ have b een used in these formulations were the
ous symptoms of anorectal disease. These symptom::; hydroaJcoholic extracts of three standard medicinal
should not be self-medicated because a more serious plants, namely: Calendula officinalis, Plantago major,

73
 Anti-Anorectal Disease Drugs

and Vinca major. Table I. Classification of the patients according to

Calendula officinalis is an annual herb which is cul­ age and sex.

�
tivated widely in Iran.s It c ontains saponins,6.7 fla­
Male Female Total
vonoids,6.8 coumarins,9 carotenoid,lo and polysaccha­
rides.!1 It has spasmolytic, anti-inflammatory, anti-hem­ ge

orrhagic, styptic, and antiseptic properties.?

iAyear) No. % No. % No. %

Plantago major, a plant growing wild in different

0-5 0 0.00 1.04 1 0.59
parts of Europe, Asia (including Iran) and north of Af­
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rica, contains iridoids,12 mucilage,7.13 gum, and the glu­ 6-10 2 2.70 0 0.00 2 1.18
coside aucubin.13 It has anti-hemorrhagic activity.?13 11-15 0 0.00 1.04 0.59
Vinca major, which is a semi-procumbent shrub
16-20 1 1.35 8 8.33 9 5.29
with tailing or somewhat ascending stems,7 is cultivated
widely in different parts of Iran.s It contains alkaloids 2 1-25 2 2.70 11 1 1.46 13 7.65
and tannins with astringent and anti-hemorrhagic prop­ 26-30 13 17.57 16 16.67 29 17.06
erties'?
31-35 13 17.57 16 16.67 29 17.06 1
36-40 13 17.57 17 17.70 30 17.65
MATERIALS AND METHODS
4 1-45 6 8. 1 1 8 8.33 14 8.24

Plant materials 46-50 4 5.40 9 9.38 13 7.65

Dried l ig u late florets of standard Calendula 5 1-55 6 8. 1 1 4 4.17 10 5.88

officinalis L. (family: Compositae) and dried leaves of
56-60 11 14.86 3 3.13 14 8.24
standard Plantago major L. (family: Plantaginaceae)
6 1-65 2 2.70 0 0.00 2 1.18
were obtained commercially from Isfahan, Iran. Aerial
parts of standard Vinca major L. (family: Apocynaceae) 66-70 1 1.35 2 2.08 3 1.76
were collected from the Agricultural Experimental
Station of the Faculty of Pharmacy and Pharmaceutical
Table II. Percentages of symptom relief with type
Sciences-Isfahan Univ er s i t y of Medical Sciences,
A formulations.
Isfahan, Iran.
The identity of the above mentioned standard plant Results Very good Good Total

materials was confi r m e d by examining them Symptoms % of

macroscopically and microscopically and analyzing Relieved No. % No. % relief

their active ingredients according to pharmacopoeial Pain 25 4 1.67 23 38.33 80.00

procedures.?
Bleeding 27 55.10 15 30.62 85.72

Preparation of plant extracts Burning 22 43.14 16 3 1.37 74.51

HYdroalcoholic extracts o f plant materials were pre­ Discomfort 15 44.12 13 38.24 82.36
pared by perculation method.l4 Each extract was then
Itching 15 48.39 10 32.26 80.65
evaporated under reduced pressure until its concentra­
tion was equivalent to one part of plant material (by Inflammation 11 39.29 10 35.71

�
weight) per one part of menstruum (by volume). Swelling 4 23.53 8 47.06

Seepage 5 41.67 2 16.67 58.34

Ointments
Two types of oint m e nt formulations were de­
signed,IS and then prepared by fusion method.l6.17 A bees wax (6.7 gm) (total weight 100 gm). =

placebo for each formulation was also prepared by the Packaging: Collapsible tin tubes, each containing
same method. Formulations of the ointments and their 15 gm ointment.
placebos were as follows: Placebo of Ointment Formulation Type A:
Ointment Formulation Ty pe A: Concentrated Hydroalcoholic solution of an approved brown color
hydroalcoholic extracts of: dried ligulate florets of (30 ml); benzocaine (3.3 gm); white soft petrolatum
Calendula officinalis (10 ml), dried leaves of Plantago (45.5 gm); cholesterol (3 gm); stearyl alcohol (12 gm);
major (10 mI), and dried aerial parts of Vinca major (10 white bees wax (6.7 gm) (total weight 100 gm). =

ml); benzocaine (3.3 gm); white soft petrolatum (45.5 Packaging: Collapsible tin tubes, each containing 15
gm); cholesterol (3 gm); stearyl alcohol (12 gm); white gm ointment.

74
 Suleiman Afsharypour, et al.

Percentage Percentage
60 ,,-------, 80rl

60

40
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20

Fissures Procti ti s Hemorrhoids Fissures Proctitis Hemorrhoids

Ver y good 40.68 14.3 33.33 Very good 58.33 25 20

Good 37.29 42.9 55.56 Good 30.56 75 40
Moderate 11.86 42.9 11.11 Moderate 5.56 0 13.33
No change 10.17 o o No change 5.56 0 26.67

- Very good � Good _ Very good � Good

[]]I Moderate .. No change []I] Moderate _ No change
Figure 1. Effects of type A preparations on different anorectal Figure 2. Effects of type B preparations on different anorectal
diseases. diseases.

Ointment Formulat ion Type B: Concentrated major (0.2 ml), and dried aerial parts of Vinca major
hydroalcoholic extracts of: dried ligulate florets of (0.2 ml); benzocaine (75 mg); cetostearyl alcohol (50
Calendula officinalis mg); white bees wax (50 mg); cocoa butter (1.16 gm)
major (10 ml), and dried aerial parts of Vinca major (10 (total weight 1.55 gm).
=

ml); ephedrine sulfate (0.2 gm); belladonna dry extract Packaging: Plastic (P.V.C.) molds, each containing
(0.7 gm); white soft petrolatum (45.5 gm); cholesterol 1.55 gm of the formulation.
(3 gm); stearyl alcohol (12 gm); white bees wax (6.7 Placebo of Suppository Formulation Type A:
gm) (total weight 100 gm).
=
Hydroalcoholic solution of an approved brown color
Packaging: Collapsible tin tubes, each containing (0.6 ml); benzocaine (75 mg); cetostearyl alcohol (50
15 gm ointment. mg); white bees wax (50 mg); cocoa butter (1.16 gm)
Placebo of Ointment Formulat ion Type B: (total weight 1.55 gm).
=

Hydroalcoholic solution of an approved brown color Packaging: Plastic (P.V.C.) molds, each containing
(30 ml); ephedrine sulfate (0.2 gm); belladonna dry ex­ 1.55 gm of the formulation.
tract (0.7 gm); white soft petrolatum (45.5 gm); choles­ Suppos itory Formulation Type B: Concentrated
terol (3 gm); stearyl alcohol (12 gm); white bees wax hydroalcoholic extracts of: dried ligulate florets of
(6.7 gm) (total weight 100 gm).
=
Calendula officinalis
Packaging: Collapsible tin tubes, each containing major (0.2 mI), and dried aerial parts of Vinca major
15 gm ointment. (0.2 ml); ephedrine sulphate (3 mg); belladonna dry ex­
tract (9 mg); cetostearyl alcohol (50 mg); white bees
Suppositories wax (50 mg); cocoa butter (1.25 gm) (total weight
Two types of suppository formulations were =1.55 gm).
prepared by fusion method.16•17 A placebo of each Packaging: Plastic (P.V.C.) molds, each containing
formulation was also prepared by the same method. 1.55 gm of the formulation.
Formulations of the suppositories and their placebos Placebo of Suppository Formulation Type B:
were as follows: Hydroalcoholic solution of an approved brown color
Suppository Formulation Type A: Concentrated (0.6 ml); ephedrine sulfate (3 mg); belladonna dry
hydroaicoholic extracts of: dried ligulate florets of extract (9 mg); cetostearyl alcohol (50 mg); white bees
Calendula off icin wax (50 mg); cocoa butter (1.25 gm) (total weight =

75
 Anti-Anorectal Disease Drugs

Percentage Table III. Percentages of symptom relief with type

1 00rl ----�----------------------, B formulations.

aOf- ································ Results Very good Good Total

Symptoms % of
, Relieved No. % No. % relief
60f--
Pain 21 55.26 12 31.58 86.84

40 Bleeding 2 60.00 9 25.71 85.71

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Burning 25 69.44 7 19.44 88.88

20
Discomfort 18 64.29 4 14.29 78.58

Itching 10 43.48 8 34.78 78.26

0
Preparation A Preparation B 12 54.55 7 31.82 86.37
Inflammation
Very good 37.33 43.86 Swelling 7 70.00 0 0.00 70.00
Good 38.67 36.84
Total Seepage 4 66.67 2 33.33 100
76 80.7
Moderate 14.67 8.77
No ch ange 9.33 10.53 Previously, subjects 20-50 years of age have been
_ Very good � Good claimed to own the greatest frequency of disease.!
IT3 M oderate HI No change From an occupational point of view, the greatest
mmTotal frequency of these disorders was among women house­
Figure 3. Overall efficacy of type A and B preparations on keepers (49.41 %). Pregnancy and labor were by far
anorectal disorders. among the most important etiologic factors in women.
The gravid uterus causes increased pressure in the
1.55 gm.) middle and inferior hemorrhoidal vessels, while labor
Packaging: Plastic (P.V.C.) m olds, each containing intensifies the hemorrhoidal condition, producing in­
1.55 gm of the formulation. tense symptoms after delivery.!
Patients who received the prescribed formulations
Evalua tion of clinical effects of the prepared for treatment were mostly suffering from anal fissures,
fomulations followed in order of frequency by hemorrhoids and
The prepared formulations and their placebos were proctitis.
prescribed to 170 patients suffering from anorectal The common symptoms of anorectal disorders were,
disease. The patients were examined by a specialist in order of frequency, pain (71.76%), bleeding
before and after treatment at the Vijeh Clinic of (66.47%), burning (65.88%), discomfort (50.59%), itch­
Khorshid Hospital in Isfahan, Iran. Out of 144 patients ing (46.47%), inflammation (35.29%), swelling
who cooperated with us, 75 patients used type A (20.59%) and seepage (13.53%).
ointment and suppository formulations, 57 patients used Type A formulations of both ointment and supposi­
type B ointment and suppository formulations, and 12 tory forms were more effective in patients suffering
patients used the placebos of these formulations. from hemorrhoids (see Fig. 1). This efficacy can be at­
Duration of treatment was at least 6-7 days, and the tributed to the presence of benzocaine which acts as a
patients used either one tube of ointment or six supposi­ local anesthetic by preventing the transmission of nerve
tories. Ointments were appl ied locally twice daily impulses,19 On the other hand, type B formulations of
(b.i.d.), and suppositories as one suppository h.s. both drug forms were more effective in anal fissures
and proctitis (see Fig. 2). In the latter formulations,
benzocaine was replaced with ephedrine sulfate and
RESULTS AND DISCUSSION belladonna dry extract. Ephedrine sulfate is a vasocon­
strictor which acts on both alpha- and beta-adrenergic
Out of 170 patients who received the prepared receptors.19.20 When applied locally in the anorectal
formulations, 96 patients ( 5 6 5 %) were women and 74
. area, it causes arteriolar constriction. It relieves local
patients (43. 5%) men. The prevalence of anorectal itching because of its slight anesthetic effect, caused by
disease in women has been reported previously by other an unknown mechanism.! Belladonna dry extract which
investigators.l8 These disorder s appear with greatest has anticholinergic action, has been employed previ­
frequency in subjects 26-40 years of age (see Table I). ously to relieve the discomfort of hemorrhoids and anal

76
 Suleiman Afsharypour, et al.

fistula. 19.20 5. Zargary A: Medicinal Plants, Vol. 3, 5th edition, Tehran

When the efficacy of different formulations on the University Publications, pp. 188,402, 1992.
common symptoms of anorectal disorders were com­ 6. Djurdjica T, Ivanka D: Antimicrobial substances in Flos
pared, type A formulations were shown to be less effec­ Calendulae. Farm Vestn (Ljubljana) 40(2): 117-120,
tive on burning, pain, discomfort, inflammation and 1989.
seepage, while type B formulations were less effective 7. British Herbal Medicine Association: British Herbal
on itching and swelling. On the other hand, the effects Pharmacopoeia, Bournemouth: Megaron Press Ltd., pp.
of both formuiations were similar on bleeding, since the 44, 163,232, 1983.
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proportions of anti-hemorrhagic plant extracts were 8. Piergiorgio P , Annamaria E, Pierluigi M, Angelo R: Sepa­
equal in all types of formulations (see Tables II and III). ration of flavonol-2-0-glycosides from Calendula
Placebo ointments and suppositories of both types A officinalis
and B were ineffective in treatment, but temporarily re­ uid and micellar electrokinetic capillary chromatography.
lieved some of the symptoms, such as pain or itching, I Chromatogr 593 (1,2): 165-170,1992.
depending on the presence of either benzocaine or 9. Derkach AI, Komissarenko NF, Chernobia VT:
ephedrine sulfate and belladonna dry extract in the Coumarins from inflorescences of Calendula officinalis
formulations used. and Helichrysum arenarium. Khim Prir Soedin 6: 777,
The overall results obtained from the use of the 1986.
prepared drugs in this investigation are shown in Figure 10. Chiej R: The MacDonald Encyclopedia of Medicinal
3. It i s notable that the ointment and suppository forms Plants. London: MacDonald and Co. (Publishers) Ltd., p.
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in the treatment of anorectal disorders. 11.ladranka V, Andras L, Hildebert W: Structural analysis of
Out of 92 patients who used the "antihemorrhoid" a rhamnoarabinogalactan and arabinogalactans with

formulations which are available in the commercial immuno-stimulating activity from Calendula of
f icina
market of Iran, 23 patients (25%) experienced no Phytochemistry 28(9): 2379-83, 1989.

change in symptoms, while out of 132 patients who 12. Afifi MS, Salama OM, Maatooq GT: Phytochemical study

used our prepared forn:miations, this number dropped to of two Plantago species, Part II: Iridoid glucosides.

14 (10.60%). The differences between the above Mansoural Pharm Sci 6(4): 16-25, 1990.

mentioned percentages are statistically significant. 13. Zargari A: Medicinal Plants. Vol. 4, 4th edition, Tehran
University Publications,p. 197, 1990.
14. British Pharmacopoeia, Vol. 2. London: HMSO Publica­
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