Note: Descriptions are shown in the official language in which they were submitted.
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HERBAL COMPOSITIONS FOR TREATING GASTROINTESTINAL DISORDERS
TECHNICAL FIELD
This invention relates to new medicinal compositions and methods for treating
s gastrointestinal disorders, in particular the treatment of Irritable Bowel
Syndrome.
BACKGROUND ART
Irritable bowel syndrome (IBS) is a common functional bowel disorder
accounting for a significant proportion of patients seen in gastroenterology
practice. It
is characterised by chronic or recurrent abdominal pain and disturbed
defecation.
~o Studies in the U.S.A. and Australia suggest that between 10% and 20% of the
population suffer from this disorder.2'3'4'5 There is no single treatment
available that is
reliably effective for this condition.6'~ Patients use a variety of approaches
to assist in
its management including drugs, dietary modifications, counselling, and more
recently
Chinese herbal medicine (CHM).8
1s According to the fundamental principals of practice in traditional Chinese
medicine, treatment should be tailored to the individual clinical presentation
of patients,
even though they may all have the same western medical diagnosis.s'~4,~5
Furthermore, treatment needs to be modified at different stages of the
patient's illness
or recovery. However, such an approach to treatment of disease can be
cumbersome
2o and is not entirely compatible with conventional pharmaceutical and medical
practice.
Thus, there is a need for effective standardised Chinese herbal medicinal
preparations for the treatment of gastrointestinal disorders such as irritable
bowel
syndrome and for appropriately rigorous clinical study design for assessing
their
efficacy.
2s It is an object of the present invention to ameliorate at least some of the
disadvantages of the prior art therapies and methods, or at least provide
useful
alternatives.
SUMMARY OF THE INVENTION
A Chinese herbal formulation disclosed herein for treatment of
gastrointestinal
3o disorders, in particular Irritable Bowel Syndrome (IBS), was compared
against a
placebo (made to taste, smell and look like Chinese herbs) using a randomised,
double-blind, placebo controlled study design.
Substitute Sheet
Rule 26) RO/AU
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According to a first aspect there is provided a composition including the
herbs
Ledebouriellae Sesloidis, Bupleurum Chinense, Artemesiae Capillaris, Fraxini,
Plantaginis, Paeoniae Lactiflorae and Schizandrae.
According to a second aspect there is provided a composition including any two
herbs selected from the group consisting of Codonopsis Pilosulae, Atractylodis
Macrocephalae, Poriae Cocos and Glycyrrhizae Uralensis, any two herbs selected
from
the group consisting of Agastaches seu Pogostemi, Magnoliae Officinalis, Citri
Reticulatae and Saussureae seu Vladimiriae, any two herbs selected from the
group s
consisting of Phellodendri, Coptidis, Coicis Lachryma-jobi, Zingiberis
Offinicinalis and
Angelicae Dehuricae, and any two herbs selected from the group consisting of
Ledebouriellae Sesloidis, Bupleurum Chinense, Artemesiae Capillaris, Fraxini,
Plantaginis, Paeoniae Lactiflorae and Schizandrae.
According to a third aspect there is provided a composition including the
herbs
Codonopsis Pilosulae, Agastaches seu Pogostemi, Ledebouriellae Sesloidis,
Coicis
Lachryma-jobi, Bupleurum Chinense, Artemesiae Capillaris, Atractylodis
Macrocephalae, Magnoliae Officinalis, Citri Reticulatae, Zingiberis
Offinicinalis, Fraxini,
Poriae Cocos, Angelicae Dehuricae, Plantaginis, Phellodendri, Glycyrrhizae
Uralensis,
Paeoniae Lactiflorae, Saussureae seu Vladimiriae, Coptidis and Schizandrae.
Preferably, the compositions are formulated with powdered herbs. If the
2o moisture content of the herbs is high, the herbs can be baked before being
powdered
by for example grinding, or by other suitable means. Even more preferred are
formulations which include extracts of the herbs. For such formulations each
individual
herb can be extracted either with water or an organic solvent (eg. alcohol)
and the
extracts combined in an appropriate formulation. Alternatively all the dry
herbs can be
2s combined, boiled together and then concentrated by spray drying or other
means
known in the art, into a dry granulated formulation.
Preferably, the compositions are prepared in a capsule dosage form, however it
will be understood by those skilled in the art that other dosage forms may
also be
suitably prepared by known methods, for example tablets, powders, pastes,
liquids and
3o similar dosage forms. Also it will be understood that the compositions of
the present
invention may also contain one or more conventional pharmaceutically
acceptable
excipients, adjuvants, solvents or carriers and may also include flavours,
colourings,
coatings, etc.
According to a fourth aspect there is provided a method of treating
35 gastrointestinal disorders including the administration to a subject
requiring such
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treatment a composition according to any one of first to third aspects.
Preferably, the gastrointestinal disorder to be treated is Irritable Bowel
Syndrome (IBS). The treatment is preferably administered orally and may be
therapeutic or prophylactic. The treatment may be delivered in a single bolus
dose,
multiple doses or via a slow release device.
The term "herb" as used herein includes the whole herb or tuber, as well as
the
root, stem, flower or fruit of the herb.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In a preferred embodiment of the invention, the composition of the invention
1o includes a combination of any two herbs selected from Groups 1, 2 and 3 and
any three
herbs selected from Group 4, depicted in Table 5. The herbs may each be
included in
concentration of from 1 % to 30% of the total weight of the herbal
composition.
In another preferred embodiment the composition of the invention includes the
herbs Ledebouriellae Sesloidis, Bupleurum Chinense, Artemesiae Capillaris,
Fraxini,
Plantaginis, Paeoniae Lactiflorae and Schizandrae, each herb included in a
concentration of from 1 % to 30%, the balance being made up for example by
other
herbs, preferably Codonopsis Pilosulae, Agastaches seu Pogostemi, Coicis
Lachryma-
jobi, Atractylodis Macrocephalae, Magnoliae Officinalis, Citri Reticulatae,
Zingiberis
Offinicinalis, Poriae Cocos, Angelicae Dehuricae, Phellodendri, Glycyrrhizae
Uralensis,
2o Saussureae seu Vladimiriae and Coptidis.
Although the administration of compositions including a selection of herbs
from
each of the four groups depicted in Table 5, or the key herbs discussed above
and
depicted in Table 6, are useful in the treatment of Irritable Bowel Syndrome,
the
synergism between all the herbs renders the administration of a combination
containing
each of the herbs mentioned desirable.
Thus, in a more preferred embodiment, the composition of the present invention
includes each herb combined in the proportions given in Table 2.
In addition to providing for the first time an effective and well tolerated
treatment
for Irritable Bowel Syndrome, the availability of the herbs and ease of
formulation
(powdering, extraction, etc.) provides a less costly alternative medicament.
The
treatment may also be individualised as well as prepared as a standard
formulation,
making the treatment more broadly applicable and effective over both short and
long
term administration.
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The invention will now be described with reference to the following examples
to
illustrate preferred embodiments only and does not serve to limit the
invention.
EXAMPLE 1. Herbs and preparation of formulations
For the purpose of conducting a clinical study, all herbs were used in the
dried
powdered form and encapsulated before administration. If sufficiently dry, the
herbs
were powdered using a grinder or similar device. If the moisture content of
the herbs
was high, the herbs were baked before being powdered.
The components of the standard herbal formulation according to one
embodiment of the present invention are listed in Table 1. The key herbs are
listed in
1o Table 2 and the grouping of the herbs for a particular selection according
to one
embodiment of the present invention is shown in Table 3. The placebo
preparation was
prepared and encapsulated by a pharmaceutical contractor. It was designed to
taste,
smell and look like a Chinese herb formula and, after testing on a number of
independent volunteers, it was deemed indistinguishable from raw powdered
Chinese
herbs.
The herbs may also be formulated by one of the following methods:
(a) concentrating either a water or an organic solvent (eg. alcohol) extract
of each herb
and then combining the extracts;
(b) all the raw herbs can be boiled together and then concentrated by spray
drying or
other known methods into a dry granulated formulation. The extracts can be
concentrated before or after combining and may be processed into tablets or
capsules.
Table 1: Standard formula (capsule ingredients)
Chinese name Pharmaceutical name Powdered
herb
Dang Shen Codonopsis Pilosulae, radix 7%
Huo Xiang Agastaches seu Pogostemi, herba4.5%
Fang Feng Ledebouriellae Sesloidis, radix3%
Yi Yi Ren Coicis Lachryma-jobi, semen 7%
Chai Hu Bupleurum Chinense 4.5%
Yin Chen Artemesiae Capillaris, herba 13%
3o Bai Zhu Atractylodis Macrocephalae, 9%
rhizoma
Hou Po Magnoliae Officinalis, cortex 4.5%
Chen Pi Citri Reticulatae, pericarpium3%
Pao Jiang Zingiberis Offinicinalis, rhizoma4.5%
Qin Pi Fraxini, cortex 4.5%
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Fu Ling Poriae Cocos, sclerotium (Hoelen)4.5%
Bai Zhi Angelicae Dehuricae, radix 2%
Che Qian Zi Plantaginis, semen 4.5%
Huang Bai Phellodendri, cortex 4.5%
Zhi Gan Cao Glycyrrhizae Uralensis, radix 4.5%
Bai Shao Paeoniae Lactiflorae, radix 3%
Mu Xiang Saussureae seu Vladimiriae, 3%
radix
Huang Lian Coptidis, rhizoma 3%
Wu Wei Zi Schizandrae, fructus 7%
1o Table 2: Key herbs
Chinese name Pharmaceutical name Powdered herb
Fang Feng Ledebouriellae Sesloidis,3%
radix
Chai Hu Bupleurum Chinense 4.5%
Yin Chen Artemesiae Capillaris, 13%
herbs
Qin Pi Fraxini, cortex 4.5%
Che Qian Zi Plantaginis, semen 4.5%
Bai Shao Paeoniae Lactiflorae, 3%
radix
Wu Wei Zi Schizandrae, fructus 7%
Table 3: Herb combinations (any two herbs from group 1 can be combined with
any
2o two herbs from group 2, with any two herbs from group 3, with any three
herbs from
group 4)
Chinese name Pharmaceutical name Powdered
herb
Group 1
Dang Shen Codonopsis Pilosulae, radix 7%
Bai Zhu Atractylodis Macrocephalae, 9%
rhizoma
Fu Ling Poriae Cocos, sclerotium (Hoelen)4.5%
Zhi Gan Cao Glycyrrhizae Uralensis, radix 4.5%
Group 2
Huo Xiang Agastaches seu Pogostemi, herbs4.5%
3o Hou Po Magnoliae Officinalis, cortex 4.5%
Chen Pi Citri Reticulatae, pericarpium3%
Mu Xiang Saussureae seu Vladimiriae, 3%
radix
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Group 3
Huang Bai Phellodendri, cortex 4.5%
Huang Lian Coptidis, rhizoma 3%
Yi Yi Ren Coicis Lachryma-jobi, semen 7%
Pao Jiang Zingiberis Offinicinalis, 4.5%
rhizoma
Bai Zhi Angelicae Dehuricae, radix 2%
Group 4
Fang Feng Ledebouriellae Sesloidis, 3%
radix
Chai Hu Bupleurum Chinense 4.5%
Yin Chen Artemesiae Capillaris, herba 13%
Qin Pi Fraxini, cortex 4.5%
Che Qian Zi Plantaginis, semen 4.5%
Bai Shao Paeoniae Lactiflorae, radix 3%
Wu Wei Zi Schizandrae, fructus 7%
The concentrations of individual herbs depicted in Tables 1 to 3 may vary by
about ~50%.
EXAMPLE 2: Selection and recruitment of patients
The majority of patients were recruited from gastroenterology units in two
teaching hospitals in Sydney, Australia and through private
gastroenterologists. Patient
2o screening and subsequent review occurred in these centers. Patients were
further
diagnosed (according to Chinese medicine principles) and then treated by
Chinese
medicine practitioners.
All herbal medicines used were administered within standard dosage levels and
are all available over the counter throughout Australia.
(i) Subjects
Patients between the ages of 18 and 75 (inclusive) were screened by a
gastroenterologist. This involved a routine clinical work-up for IBS patients
with tests as
determined appropriate by the specialist, including a colonoscopy or barium
enema in
the last five years (for 18-60yrs) or within the previous 3 years (for 61-
75yrs). Patients
3o were assessed according to the Rome criteria, an established standard for
diagnosis of
IBS - (3 months continuous or recurrent abdominal pain/discomfort including
some pain
present within the last two weeks AND two of the following - altered stool
frequency,
altered stool form, altered stool passage, passage of mucous, and abdominal
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distension).~6,~~ If diarrhoea was a prominent symptom lactose intolerance was
excluded (by hydrogen breath testing or over a two week lactose exclusion
period). A
full list of inclusion and exclusion criteria are presented in Table 4
Table 4: Inclusion and exclusion criteria
Inclusion criteria Exclusion
criteria
1. Age 18-75 years inclusive Pregnancy or breast feeding
2. Colonic evaluation (colonoscopy Liver disease
or barium
enema) within the previous 5 years Medications: anticholinergics,
(for lactulose,
18-60yrs) or within the previous smooth muscle relaxants, motility
3 years
(for 61-75yrs) stimulants, antidepressants.
3. IBS by criteria: Usage of these is accepted
provided
At least 3 months of continuous patient is still symptomatic
or recurrent of IBS,
symptoms of: medications have been used
for 3
Abdominal pain or discomfort with months, and effects of medications
at least are
some discomfort present within stable.
the last
two weeks. Current alcoholism or drug
abuse
and Current psychiatric illness
or dementia
two or more of the following on Allergies to food additives
at least
one quarter of occasions or days: Lactose intolerance - no obvious
clinical
i. abdominal distension that is indications
visible
or felt by tight clothing Inflammatory bowel disease
(ulcerative
ii. pain relief with bowel action colitis, Crohn's)
iii. more frequent stools with Gastric and duodenal ulcers
onset of
pain Cancers of the gastrointestinal
tract
iv. looser stools with onset of Celiac disease
pain
v. mucous in stools Diabetes mellitus
vi. feeling of incomplete evacuation
4. At least one marking on the
Visual
Analogue Scales for IBS symptoms
to be at
least 20mm from the 'not present'
end of the
scale.
5. Normal liver function tests
and full blood
count, urea and creatinine (within
the last two
weeks).
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_g_
Written informed consent was obtained from all patients before entering the
study. Patients were free to withdraw from the study at any time.
ii) Treatment schedule
After initial gastroenterological screening (Week 0) all patients entered a
two
s week run-in period. A Bowel Symptom Scale (BSS) was completed at the
beginning
and end of the two week period to assess measurement reliability, and to
account for
any degree of improvement based simply on admission to the study. Patients
were
seen on specified days by one of three herbalists during the study period and
were not
permitted to change herbalist during the course of the treatment. The first
consultation
1o with the Chinese herbalist occurred at Week 2, at which time the patient
was
randomised (by an assistant) into placebo or standard treatment groups. The
patient
was reviewed by the Chinese herbalist at fortnightly intervals on two
occasions and
then monthly intervals on two further occasions. Sixteen weeks continuous
treatment
was administered. All patients were reviewed by their gastroenterologist after
eight
1s weeks of treatment (and precautionary liver function tests performed), and
reviewed
again at the end of the 16 week treatment period. Patients were closely
monitored for
any side effects or worsening of symptoms. Follow-up questionnaires were sent
to all
patients 14 weeks after completion of the treatment period. Treatment codes
were only
broken and revealed to patients after completion of the follow-up
questionnaires.
20 (iii) Herbal preparation and dispensing
All herbs and the placebo formulation used in the clinical study were supplied
in
the same opaque capsules. Patients in both groups were required to take the
same
dosage levels (5 capsules thrice daily). All patients were treated in an
equivalent
fashion. Compliance was assessed by an item included in the Bowel Symptom
Scale
25 (BSS) and by pill count.
EXAMPLE 3 Assessment and data analysis
(i) The Bowel Symptom Scale (BSS)
The BSS was designed as the major instrument to assess change in IBS
symptoms during the course of the treatment. It consists of visual analogue
scales
3o related to each individual symptom and an overall severity scale. Both
patients and
gastroenterologists were required to complete this scale independently at the
beginning
and end of the treatment period. Patients were also monitored during the
course of the
trial using this scale. A small number of additional items, assessing rate of
stool
passage and interference with life activities, and recording changes in
medications
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usage and fibre consumption, were included in the BSS for all patients to
complete.
Tests for validity and reliability of the scale are reported below.
(ii) Treatment credibility rating scale
In order to assess the success of patient blinding a brief questionnaire was
administered regularly throughout the treatment period. This four item scale
was
originally used to test credibility of different forms of psychological
treatment~8 but has
also been successfully used in acupuncture trials.l9'2o It has been shown to
have good
internal consistency and test-retest reliability. Tests for reliability,
internal consistency,
and construct validity are also reported here.
to (iii) Statistical anal rLsis
Pearson product moment correlation was employed in the analysis of reliability
and validity data. Factor analysis was also used to determine construct
validity of the
credibility scale. Outcome measures with categorical responses were analysed
using
Chi-square and Fisher's exact tests. For the bowel symptom scales analysis of
variance was used to determine the differences between groups at baseline, at
end of
treatment and on follow-up. In each case the statistical assumptions were
carefully
considered, p values were all 2-tailed unless otherwise indicated, a level of
significance
was set at 0.05. Missing scale and item scores were not replaced.
Data are presented below according to an 'intention to treat' protocol, where
2o patients who withdrew from the trial are recorded as having worsened (if
appropriate)
for categorical items only. Data for all other outcome measures are presented
as per
protocol analysis.
EXAMPLE 3 Results of the study
A total of 78 subjects were recruited over an 18 month period: 35 were
randomised into the placebo group and 43 into the standard treatment group.
Fifteen
patients (13%) withdrew during the four month course of the trial. A further
two patients
were withdrawn from the trial for commencing a variety of relevant medications
during
the treatment period. Patient data on entry is summarised in Table 5.
Table 5: Patient population characteristics pre-treatment and mean total bowel
3o symptom scores as reported by patients and gastroenterologists at start and
end of
treatment period, and at a follow-up. (Standard deviation in brackets,
n=subject
numbers). "p<0.10, '°'p<0.05, """p<0.01, #p=0.75.
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Placebo Standard F statistic
group group
(n=35) (n=43)
Characteristic
Weight 72.1 (12.8) 66.7(16.8) 1.27
Age 45.0(13.9) 47.6(15.1) 0.39
Gender 0.46 0.65 NS#
(male:female)
Baseline data
Gastroenterologist 182.7(65.4) 172.2(72.6) 0.52
total BSS score
Patient total BSS 191.2 (69.4) 189.7 (64.8) 0.40
score
End of treatment
Gastroenterologist147.2 (86.6)70.9 (63.2) 7.92''
total BSS score(n=30) (n=35)
Patient total 150.0 (81.6)106.1 (73.7) 3.79''
BSS
score (n=32) (n=38)
At follow-up
Patient total 155.7 (84.2)132.6 (90.2) 2.41"
BSS
score (n=18) (n=35)
Patient groups were similar in terms of age, weight and gender distributions.
There were no significant differences between patients in the two treatment
groups on
entry in terms of total severity of symptoms as judged independently by both
the patient
and gastroenterologist, and no significant differences in duration of the
disease as self-
reported by patients. However, patients allocated to the placebo group did
register a
higher mean score for constipation, whilst patients allocated to the standard
treatment
group registered a higher mean score for diarrhoea. Compliance with medication
was
high as measured by a questionnaire item and by random pill counts, and did
not differ
between groups. Fibre and medication consumption did not alter significantly
for any
1o group during the treatment period.
(i) Reliability testing
The reliability of the BSS (ie the consistency of the measure) was determined
by
a test-retest assessment during the run-in period prior to treatment
commencing (week
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0 to week 2). Patients were invited to complete the BSS during the initial
interview with
the gastroenterologist and then two weeks later at the clinical treatment
centers prior to
treatment commencing. Correlation between the first completion of the bowel
symptom
scale (BSS1 ) and the second (BSS2) was high for the total score (r=0.7,
p<0.01, two-
s tailed) and for each individual symptom (bloating (r=0.8), pain (r=0.6),
diarrhoea (r=0.8)
and constipation (r=0.7)). The high test-retest reliability between the two
scale scores
indicates the test is reliable on repeated administration and that the
patients'
presentation of their condition was relatively stable.
The credibility scale was also examined for test-retest reliability.
Correlation
to between the first and second administration of this scale was significant
(r=0.6, p<0.01,
two-tailed). The correlation coefficients for each of the four scale items
fell in the range
of 0.47 to 0.65. The internal consistency of the credibility scale was
explored by
examining inter-item correlations on each of the first two occasions. Inter-
item
correlations on both occasions were uniformly high and Cronbach's coefficient
alpha
15 (representing average inter-item correlations) was 0.87 and 0.86 for the
first and
second occasions, respectively.
ii) Validity testing
The visual analogue scales within the BSS had high face validity (100mm lines
with severity marked at the extreme right and absence of symptom marked at the
2o extreme left), and have high content validity (in that they incorporate the
key domains
of interest - pain and discomfort, bloating, constipation and diarrhoea). The
items in the
scale were also tested for concurrent validity against the gastroenterologist
assessment
at the commencement and at the end of the treatment period. At these times
both
patients and gastroenterologists completed the visual analogue scales
independently.
2s The gastroenterologist assessment of the patient correlated highly with the
patient's
own perception of severity of symptoms. (On both occasions Pearson's
correlation
coefficient was in the range of r=0.63 to r=0.84 for any one item (symptom) or
for the
total symptom score) (p<0.01 on all occasions).
The credibility scale was assessed for construct validity through a principal
3o components factor analysis based on the first administration. The results
revealed only
one factor with an eigenvalue greater than 1 (2.89). This factor accounted for
72.2% of
variance in this data set. All items had a high correlation with this first
factor. This
suggests that there was a satisfactory level of construct validity of this
scale.
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(iii) Main outcome measures
Five distinct outcome measures are reported here - total mean bowel symptom
scales and global improvement as recorded by patients and gastroenterologists,
and
interference with life as recorded by patients. On all measures, patients
receiving the
standard herbal formulation of the present invention responded significantly
better than
patients in the placebo group.
(iv) Bowel symptom scales
The bowel symptom scales were completed by patients at various stages during
the course of treatment including upon completion of the trial. An analysis of
variance
(ANOVA) test performed at the end of treatment demonstrated a significant
difference
between the mean total symptom scores for patients in each group, the standard
herbal
treatment patients responding significantly better compared to placebo (F=3.8;
df 2, 96;
p<0.05) (Table 5).
The bowel symptom scale was also completed by the gastroenterologist on
~ 5 reviewing the patient at the end of the treatment period. Analysis of
variance showed a
significant difference between the mean total symptom scores for patients in
each
group, with standard herbal treatment patients responding significantly better
compared
to placebo (F=7.9; df 2, 87; p<0.05).
Patients receiving the standard herbal formulations improved by 44% (according
2o to patients) and 59% (according to gastroenterologists), in contrast to
patients in the
placebo group who improved 22% (according to patients) and 19% (according to
gastroenterologists).
(v) Interference with life
An item was included in the BSS asking patients to assess the degree of
25 interference with life and activities. Responses allowed for a grade of
severity of
interference to be recorded. This item was included on each occasion the
patient
completed the BSS. Change in the severity score for this item was calculated
for each
patient. A significant association was found between the treatment groups and
the
change in grade of interference by the end of treatment (p=0.03, df=4,
X2=10.6). 63%
30 of patients receiving the standard formulation stated treatment resulted in
less
interference in their lives and activities, in contrast to 37% of placebo
patients.
wi) Global improvement
At the end of the trial both gastroenterologists and patients were asked
whether
they felt the IBS symptoms had improved, stayed the same or worsened (Table
6).
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Table 6: Perception of improvement by treatment group (percentages of
respondents in
brackets)
Compared to Placebo groupStandard group
- before trial
Patient Improved 11 (33%) 29 (76%)
response
Chi-square Stayed the 19 (57%) 8 (21 %)
p=0.007 same
Worsened 3 (9%) 1 (3%)
GastroenteroloImproved 9 (30%) 29 (78%)
gist response
Chi-square Stayed the 19 (63%) 7 (19%)
p=0.002 same
Worsened 2 (7%) 1 (3%)
A significant association between the treatment group and how patients felt at
the end of treatment was observed (p=0.007, df=4, X2=14.3). 76% of patients
receiving
the standard formulation stated they had improved during treatment. In
contrast, only
33% of patients receiving placebo stated they had improved during treatment.
The gastroenterologists' responses also demonstrated a significant association
between the treatment group and how patients felt at the end of treatment
(p=0.002,
df=4, X2=17.1 ). 78% of patients receiving the standard formulation were
identified as
1o having improved during treatment. In contrast, only 30% of patients
receiving placebo
perceived having improved during treatment.
There was significant correlation between patients' and gastroenterologists'
assessment of global improvement and of total BSS scores at the beginning and
end of
the trial (all r>0.5, all significant to 0.01 level, 2-tailed).
(vii) Follow-up assessment
The BSS was administered to patients one final time 14 weeks after completion
of the course of treatment. Treatment codes were not revealed to patients
until after
completion of this final follow-up questionnaire, hence patients were still
blinded.
Blinding of patients was verified.
2o Patients still responded as having made notable improvement when compared
to before the trial. A chi-square test performed on the patient responses
demonstrated
a significant association between the treatment group and how patients felt at
the point
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of follow-up (p=0.02, df=4, X2=11.5). 63% of patients who had received the
standard
formulation stated they still felt improved. Notably, 32% of patients who had
received
placebo stated they still felt improved.
Herbalism, acupuncture, homeopathy and manual therapies (eg osteopathy)
s frequently rely on a second diagnostic process distinct from western
medicine and an
high degree of interaction between the patient and practitioner during the
treatment.
The former leads to a clinical distinction between what seem to be similar
diagnostic
cases in western medicine (individualisation of therapy). The latter demands
that the
therapeutic intervention be continuously modified in response to patient
feedback.
1o Treatment needs to be tailored to the individual at the outset and also
modified at
differing stages of the patient's illness. Rigorous clinical trial methodology
frequently
imposes standardisation of treatment for trial subjects.
The present study has demonstrated that Chinese herbal medicine is effective
in the management of irritable bowel syndrome with, in some cases, effects
lasting up
Is to 14 weeks after completion of treatment. At the outset of the study there
were no
significant differences between patients in each group. They were well matched
for
age, gender, weight, severity and duration of illness. Patients receiving
standard herbal
treatment demonstrated significantly better outcomes (both clinically and
statistically)
than patients receiving the placebo treatment on all five key outcome
measures.
2o A conclusion can be drawn that Chinese herbal formulations of the present
invention may offer substantial assistance to patients with irritable bowel
syndrome and
constitute an alternative treatment option for the management of IBS.
A person skilled in the art will understand that the therapeutic effects of
the
compositions result from a plurality of active agents in each herb which when
combined,
2s act synergistically to enhance efficacy. It will also be understood that
compositions
comprising all or a selection of such active agents, preferably in pure form,
are also
contemplated herein, as are liquid formulations of the composition and
formulations
which are suitable for slow release administration. Thus it will be understood
that the
compositions of the invention can be administered orally, intravenously,
topically or by
30 other known means.
The invention may be embodied in various other forms which are understood by
those skilled in the art.
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