KOFOl cough syrup Pharmacological properties

summary

a) Clinical Pharmacology: Pharmacodynamics; Pharmacokinetics; bioavailability

Pharmacological group.
Combined preparation for catarrhal diseases and cough. ATC code R05X.

Pharmacological properties.
Pharmacodynamics. Kofol® is a herb-mineral preparation that acts against
cough, cold in the head, relieves expectoration. Pharmacological effect is
provided with the components of the preparation which combine in themselves a
few mechanisms.
Kofol® is a combination of medicinal herb extracts and Ammonium Chloride for
maintenance of normal respiratory function. It relieves from cough and
bronchospasms symptoms.

Active ingredients, which are in the composition of the syrup, have such actions
as:

➢ Malabar Nut, Yellow Berried Nightshade, Beetle Killer, Long Pepper

provide better stethocatharsis, act as a mucolytic agent.

➢ Licorice has emollient action, removes irritation.

➢ Sweet Violer, Turmeric, Cubeb Pepper, Ginger, Black Pepper also remove
irritation, and have sudorific, anti-inflammatory actions (the last also
makes better digestion).

➢ Beleric Myrobalan provides expectoration.

➢ Holy Basil is an anti-catarrhal & anti-infectious agent.

➢ Juniper provides expectorant & anti-septic actions.

➢ Pellitory has a sedative action.

 ➢ Ammonium Chloride provides phlegm liquefaction.

This composition of the formulation ensures a broad spectrum of action:

mucolytic action - faciftates liquefaction and easier excretion of secretions);
prevention of oedema - reduces hyperemia and oedema of the mucous
membranes in the respiratory tract; spasmolytic action - reduces bronchospasm;
antitussive action; anti-inflammatory action - reduces local inflammatory
processes in the bronchial mucous membranes; sedative action - normalises
psycho-physiological reactions, reduces anxiety and discomfort during
bronchospasms); antihistaminic, hypothermic and local antiseptic actions.

Pharmacokinetics. Whereas Kofol® is a multicomponent preparation, its kinetics

caused by an additive effect of its components and conducting trials is
impossible.

b) Efficacy: controlled studies; uncontrolled studies;

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1) REPORT ON LIMITED CLINICAL TRIALS OF KOFOL COUGH SYRUP

Manufactured by Charak Pharmaceuticals, India

Prof. L.O.Yashina D.Sc., Head of CIinical Testing

O.Ya.Lekan, In-Charge of testing
Kiev 2001

Limited clinical trials in an open parallel study on the effectiveness and

tolerance of Kofol cough syrup were conducted on 30 patients with chronic
obstructive bronchitis in the clinic of the Department of Diagnosis, Therapy
and Clinical Pharmacology of Pulmonary Diseases, F.G.Yanovsky Institute of
Phthisiology and Pulmonology, Academy of Sciences of Ukraine (Kiev).

MATERIALS AND METHODS

Limited clinical trials ofKofol syrup were conducted in the clinic of the
Department of Diagnosis, Therapy and Clinical Pharmacology of Pulmonary
Diseases, F. G. Yanovsky Institute of Phthisiology and Pulmonology, Academy
of Sciences of Ukraine (Kiev).

A group of patients was subjected to complex treatment including Kofol syrup

(100 ml bottle) manufactured by Charak Pharmaceutical, India.
The group consisted of 30 in-patients (age 40-60 years) with chronic obstructive
diseases.

All the patients include in the clinical trials had symptoms of chronic obstructive
diseases confirmed by clinical, functional and laboratory tests: breathlessness
under physical stress, cough with excretion of mucous or mucopurulent
secretions, sub- febrile temperature, and rapid fatigue.

ADMINISTRATION OF THE FORMULATION

The complex therapy included 2 teaspoons of Kofol syrup thrice daily.

The other elements of complex therapy included traditional treatment with

broncholytics - Atrovent, Berodual. In cases of infectious bonchitis the
treatment included antibiotics (Amoxyclav, Rovamycin).

The duration of treatment was 14 days.

Analysis of the results showed that the patients who took Kofol syrup had
positive changes in the clinical symptoms. Thus, there was a reduction in
breathlessness under normal physical stress, while there was an increase in the
number of patients who became breathless under severe stress. There was a
significant reduction in the number of patients with severe cough, while there
was a significant increase in the number of patients with insignificant cough.
All the patients experienced improved expectoration within 4 days after the start
of treatment (cough was milder, expectoration was easier) and significant
improvement after using the test formulation for 12 days. There was also a
change in the nature and quantity of secretions: not a single patient had purulent
secretions after the course of treatment and the number of patients with mucous-
purulent secretions reduced by 50%. The quantity of secretion expectorated
became less by 60%. The results of objective examinations also flowed positive
changes in patients using Kofol syrup. Thus, there was a reduction in the number
of patients with harsh respiration (by 33.3%), while the number of patients with
vesicular respiration increased by 33.3%.

Dispersed dry rates were found in 26.7% of the patients, while 16.6% had moist
rates before treatment. None of the patients had such rates after the course of
treatment. The number of patients who had individual dry rates became less.
The parameters of external respiratory function (ERF) did not change
significantly during treatment, but there was a trend towards normalization of
most of the parameters.

Analysis of the changes in the clinical symptoms and functional tests show that
Kofol syrup causes favorable shift in these parameters.

Sixteen patients -were subjected to bronchoscopy before and after the course of
treatment.

By the end of the course of treatment none of the patients had bronchial
inflammation of levels 18.8% or 50%; inflammation of level 18.8% in 4 patients
before treatment reduced to level 25%; only one patient remained with
inflammation of level 6.3%.

Analysis of the data shows that all the parameters of blood analysis became
normal after treatment.

Analysis of the data shows that the test formulation, Kofol syrup, did not have
an adverse effect on the kidneys and liver.

The results in terms of effectiveness of treatment were as follows:

Very high effectiveness in 7 (23.3%) patients

High effectiveness in 21 (70.0%) patients

Satisfactory effectiveness in 2 (6.7%) patients who had purulent-obstructive

bronchitis for more than 10 years. Clinical symptoms of bronchitis remained after
the course of treatment. These patients were advised to continue the complex
treatment.

The test formulation was well tolerated by the patients and gave a positive
clinical effect. Complications and side effects were absent. It is worth noting that
there were no reports of individual intolerance during the clinical trials. This
indicates that the formulation has low toxicity.

Thus, the clinical trials show that the Kofol cough syrup is a highly effective,
nontoxic therapeutic formulation.
The expectorant, mucolytic and anti-inflammatory actions of Kofol make it
useful for treatment of chronic obstructive bronchitis. The results of these trials
show that Kofol has an expectorant and anti-inflammatory effect, is well
tolerated by patients and does not induce pathological changes in the laboratory
and biochemical parameters of the patients with chronic obstructive bronchitis.

The ingredients include Malabar But (200 mg), Yellow Berried Nightshade (120
mg), Beetle Killer (40 mg) and Long Pepper (30 mg) which facilitate
expectoration of secretions and act as spasmolytics; Licorice(150 mg) has a
softening action and reduces irritation; Sweet Violet (50 mg). Turmeric (20 mg),
Cubeb Pepper (10 mg), Ginger (10 mg). Black Pepper (10 mg) also reduce
irritation and moreover have a sudorific, anti-inflammatory action (the last
substance also improves digestion); Beleric Myrobalan (100 mg) facilitates
expectoration; Holy Basil (60 mg) is an anticatarrhal and antiinfective; Juniper (50
mg) facilitates expectoration and has an antiseptic action; Ammonium chloride
(15 mg) helps to liquefy the mucus; Pellitory has a sedative action. This
composition of the formulation ensures a broad spectrum of action: mucolytic
action - faciftates liquefaction and easier excretion of secretions); prevention of
oedema - reduces hyperemia and oedema of the mucous membranes in the
respiratory tract; spasmolytic action - reduces bronchospasm; antitussive action;
anti-inflammatory action - reduces local inflammatory processes in the bronchial
mucous membranes; sedative action - normalises psychophysiological reactions,
reduces anxiety and discomfort during bronchospasms); antihistaminic,
hypothermic and local antiseptic actions.

The antitussive, expectorant, antibacterial, spasmolytic and anti-inflammatory

actions of Kofol syrup make it suitable for treating all types of productive and
unproductive coughs caused by infections of the upper respiratory tract,
bronchitis, acute pneumonia, bronchiectasis, asthma, tuberculosis and coughs
after colds; coughs caused by professional and ecological factors or conditions of
work; smoker's cough; in local eosinophilia, during treatment of
tracheobronchitis, chronic obstructive bronchitis (including bronchitis of
infectious origin), mucoviscidosis, chronic bronchiectatic disease, disorders of
formation of bronchial secretions and pathological increase in viscosity of the
secretions. Kofol syrup is also recommended for symptomatic relief and faster
recovery from colds, angina; rhinitis, laryngitis, pharyngitis, tonsillitis and
sinusitis.

As Kofol does not contain alcohol, soporific and narcotic substances; it can be
used by patients of any age.

The formulation rapidly relieves and eliminates all types of cough. It can be used
as a safe, alcohol-free treatment for children with cough caused by infections of
 the upper respiratory tract, bronchitis, asthma, allergic bronchitis, whooping
cough or cough after measles.

Kofol did not cause any side effects during clinical trials in India or in the
Ukraine.

The results of the study make it possible to draw the following conclusions:

1. Kofol cough syrup, manufactured by Charak Pharmaceuticals, India, is an

effective mucolytic and expectorant for treatment of patients with chronic
obstructive bronchitis.

2. Kofol cough syrup, manufactured by Charak Pharmaceuticals, India, is well

tolerated by patients and does not induce pathological changes in the clinical
analytical parameters. The formulation did not have any toxic effects on the
patients. The absence of side effects during use of the syrup indicates that the
formulation is safe.

3. Kofol cough syrup, manufactured by Charak Pharmaceuticals, India, can be

used in complex therapy of patients with chronic obstructive bronchitis along
with other anti-inflammatory drugs, antibiotics and broncholytics.

4. Kofol cough syrup, manufactured by Charak Pharmaceuticals, India, can be

recommended for use in medical practice.

2) Clinical Evaluation of an Herbal Cough Treatment Kofol Syrup

Dr. Praful Vakil of Charak Clinic, India

MATERIAL & METHODS:

62 patients who came for the treatment of one of their chief complaints as cough
were treated at our clinic in the year 1991-1992. Their complaints were noted.
Their origin, duration and progress of the complaints, treatment taken if any,
benefit, side effects, noted. Their personal history as to diet, habit, exertion,
addiction to smoking cigarettes noted.

Their past history of illness, operation, family noted. They were examined for
general health, weight, blood pressure, ear, nose, throat, tonsils, DNS, polyp,
chest, heart, lungs, spleen, liver, bones, joints, nervous system, skin pruritus,
pigment changes, eczema, etc. noted. Laboratory tests of urine for sugar, stool
(ova, worms) blood for routine WBC eosinophilia, blood chemistry, sputum for
tuberculosis. X-ray chest done where necessary.
 DOSAGE & OBSERVATION: All were given specific treatment of diseases
found, antibiotics for severe-infection, anti T.B. for tuberculosis, broncho dilators
for severe asthma along with Kofol Syrup in dose of 1 teaspoonful t.d.s. for a
period of I to 2 weeks depending on response. They were examined twice a week
for relief in symptoms, diminution in physical findings, general good, side effect
of drug if any. There were 12 drop outs and were excluded from study leaving us
50 cases. Their response was as under:

Complete relief from cough 36% in the first week,

dry/wet in 18 cases Classed as good.

Good relief for cough dry/ 40% in two weeks,

wet in 20 cases classed as fair.

No relief in two weeks in 24 % m two weeks,

12 cases classed as poor.

No side effect was noted in any case and drug did not have to be stopped prior
to schedule due to side effects like drowsiness, insomnia, constipation, dryness
of mouth, spincture disturbance, etc.

SUMMARY & CONCLUSION:

Kofol is a valuable addition in the relief of cough of dry unproductive, wet

productive, as well as spasmodic origin while the causative factor of the disease
is being given required treatment.

3) KOFOL SYRUP
INDIGENOUS COUGH REMEDY
CLINICAL EVALUATION IN YOUNG AGE GROUP

The investigator of clinical study :-

DR. C.M. HAZARI, M.D. D.CH,
HAZARI HOSPITAL, JOGESHWARI (WEST), BOMBAY.
HON. PAEDIATRICIAN, ESIS HOSPITAL, MAROL, BOMBAY.

Kofol a herbal cough syrup was evaluated in younger age group of patients
suffering from cough, running nose, fever, expectoration, breathlessness - aches -
pains, in 89 indoor and outdoor cases in this year, with antibiotics or other
medications where necessary. A majority of them benefited in a weeks time
without any side effects.

MATERIAL & METHODS: 89 cases attending our clinics in the year 1992-93
with a complaint of cough were studied. Some had fever, breathlessness, aches
and pains etc. along with cough. Those requiring in-patient treatment were
admitted while the rest were treated in outpatient department.

Detailed history of the complaints, onset, duration, treatment taken was noted.
Personal, family, past history relevant to present sickness was taken. They were
all examined for general condition, fever, rash, breathing and detailed
examination of chest RS, CVS, AS, URO genital, CNS, bones, joints, etc. done.
Laboratory examination of blood, urine, stools, sputum, x-ray chest done when
necessary.

DOSAGE & OBSERVATION:

Consent was taken from patients or their guardians for trial of the drug. They
were put on Kofol Syrup ½ tsf 4 times a day for children less than 2 years. 1
teaspoonful 4 times a day for older children. 2 tsf 4 times a day for adults: Other
medications were given as required for fever, asthma, etc.

1. Good: complete relief from dry or wet cough in a week: 46 cases: 51.5%

2. Fair: complete relief from cough in a fortnight: 33 cases: 36.5% = 88%

3. Poor: no relief: 10 cases: 12%

No side effect was found in any - all accepted the taste.

Kofol gave good results in 88% cases without side effects. It was palatable and
was accepted by all. Action seem to be anti - catarrhal, anti - allergic, anti -
histaminic Holy Basil, antipyretic – Black Pepper, expectorant – Malabar Nut,
demulcent - Licorice, laxative – Beleric Myrobalan, antispasmodic – Yellow
Berried Nightshade, antispasmodic – Pellitory etc.

Results were good in 45 cases ( 51.5% ): fair in 33 ( 36.5% ) making total benefit in
88% with failures in 10 ( 12% ) cases.

Maximum were good in cough - dry and wet with upper respiratory tract
infection, tonsillitis, adenoiditis, pharyngitis, rhinitis, running nose. Next to
benefit were cases of bronchitis, whooping cough and bronchial asthma,
 Eosinophilia. KOFOL gave relief in many cases while specific illness was being
treated with appropriate drugs.

THE SUMMARY AND CONCLUSION OF CLINICAL STUDY: -

89 patients of cough with illnesses acute and chronic associated with fever, rash,
breathing difficulties and cough dry/wet were treated with an indigenous
formulation - Kofol along with other medicines where necessary for a period of 1
to 3 weeks. Benefit was seen in 46 + 33 = 79 cases (88%) without side effect. Mode
of action is discussed.

KOFOL Syrup is thus a valuable addition to the existing formulations available

in market for cough. KOFOL is palatable, acceptable, and economical without
side effects of modern allopathic remedies and is thus worth trying.

c) Safety: adverse drug reactions in volunteers and where a new chemical moiety
has been marketed for less than five (5) years, adverse drug reactions in patients.

As Kofol does not contain alcohol, soporific and narcotic substances; it can be
used by patients of any age. The formulation rapidly relieves and eliminates all
types of cough. It can be used as a safe, alcohol-free treatment for children with
cough caused by infections of the upper respiratory tract, bronchitis, asthma,
allergic bronchitis, whooping cough or cough after measles.

Kofol did not cause any side effects during clinical trials in India or the Ukraine.