Note: Descriptions are shown in the official language in which they were submitted.
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ANALGESIC COMPOSITION
[Technical Field]
The present invention relates to an analgesic composition comprising extract
of
Pulsatillae Radix as active ingredient. Specifically, the present invention
relates to the
analgesic composition which alleviates pain of cancer patient and has low side
effects.
More specifically, the present invention relates to the analgesic composition
comprising extract of Pulsatillae radix as active main ingredient and if
necessary, more
comprising one or more extracts selected from the group consisting extract of
Ginseng Radix,
extract of Glycyrrhizae Radix, extract of pericarp of Akebia quinata and
extract of the bark of
Couex Ulmi as auxiliary ingredient(s).
Various cancer cells which grow in cancer patients affect various influences
to hosts.
Growing cancer induces hyperthermia, anorexia, loss of weight, microbiosis,
anemia,
destruction of hormone balance, neurosis, pressure to marginal tissue or
organ, occlusion of
intestinal tract or blood vessel, indifferent invasion, destruction of tissue,
influence to ter-
tissue by metastasis, blood circulation of virulent material, etc., to induce
of severe pain to
host to come to death.
Therefore, the pain of cancer patient is commonly very severe and difficult to
be
controlled and clinically intensive toxic analgesic should be used. An example
of pain by
destruction of tissue is ostalgia. The ostalgia is induced by an irritation
which induced by
cancer cell which is irrupted or transferred into bone tissue or by fracture.
A cancer patient is
very sensitive to microbiosis by loss of protective power of the patient, by
destruction of
protective mechanism through cancer therapy and by retention of fluid through
obstruction.
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An example of obstruction of blood vessel by tumor occurred in limited tissue
is
brain tumor and pain is induced by pressing blood vessel and meninx because of
occurrence
of tumor in brain blood vessel.
Tumor growing in intestinal tract stretches andlor presses and/or obstructs
the tract
and induces pain. However, tumor gradually growing in the tract is sometimes
already
progressed before complaint of pain. For example, stomach cancer, pancreas
cancer, rectal
cancer and liver cancer, etc. often do not induce pain until considerable
progress of the
cancers. In another case, pain does not arise at the very site of the cancer
but arise at another
site. For example, in the case of cancer occurred in the intestinal tract,
because irritation
transfer enters through sympathetic nerve into spiral marrow, pain sometimes
occurred a very
distant area from the site of the cancer.
As for analgesic for the treatment of the pain of cancer or tumor, a very
intensive
analgesic is used sometimes together with auxiliary ingredient. The mostly
used analgesic is
morphine or derivative derived from morphine. As for such auxiliary material,
calcium
channel agonist and antagonist including N-methyl-D-aspartate(NMDA) antagonist
and
topical and general anesthetics are used.
However, analgesics used until now can not reduce 100% of pain of cancer
patient
and have drug tolerances and side effects. Therefore, In order to treat pain
of cancer, it is ideal
that an analgesic which has antitumor activity and less side effect and
analgesic effect at the
same time is developed.
[Background Art]
The development of analgesic based upon roots of plants (Pulsatillae Radix) of
Pulsatillae species has merit that Pulsatillae Radix is a powerful anticancer
material. In fact, in
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case any cancer or tumor is treated, pain is naturally disappeared. According
to experiences of
the inventors, patients who were administered preparation of Pulsatillae Radix
felt reductions
of pains and even though cancers were not treated perfectly and became to
death, during the
state that patients were not treated with Pulsatillae preparation, the
patients declared that pains
were reduced substantially.
Pulsatillae Radix is the root of Pulsatillae species which belong to
Ranunculaceae
plant. All the roots can be used in the present invention. In oriental
medicine, Pulsatillae
Radix is used for the purpose of treating child bed fever, detoxification,
antidiarhea,
bactericide, amebicide, fungicide (Chinese medicine encyclopedia).
Recently, the Pulsatillae Radix is reported to have antitumor activity and is
now
under clinical trial. Prior arts are illustrated as follows:
1. Hsu et al.,: Oriental Materia Medica pp 226-227, Oriental Healing Art
Institute.
1986, CA, USA,
2. Korea Patent Nos. 72,982 and 312,622.
Panax Ginseng has various pharmaceutical activities such as anti-stress and
anti-
diabetes activities. Specifically, according to mouse writhing test,
ginsenoside Rf among
ginsenosides which Ginseng Radix has was reported to have analgesic
activity(1). In addition,
though US Patent No. 5,417,979 teaches that a raw plant drug composition
comprising
Glycyrrhizae Radix as main component has analgesic activity, the said patent
only teaches
that the composition can be used as auxiliary. However, the selectivity of
main plant drug,
specialty of anticancer analgesic or preparation method thereof is different
fiom the present
invention.
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1. Mogil JS, Shin YH, McCleskey EW, Kim SC, Na Sy, Brain Res 792, 218-
228(1998).
2. US Patent No. 5,417,979.
Glycyrrhizae Radix is used as tonic, neutralization, analgesic,
detoxification, cough
medicine or resolutive in oriental medicine. Various studies for protection of
liver, anticancer
property etc. were carried out.
Pericarp of Alcebia quinata is a fruit of Akebia quinata and is used as
lumbago,
intercostal neuralgia, gastralgia, urethra calculosis, menoxenia or diarrhea.
The Pericaip of
Akebia quinata has akebia saponin. But, no literatures that Pericarp of Akebia
quinata is used
as analgesic have published until now.
Ulmi cortex is a bark of Ulmus species or a bark of root of the Ulmus species
and is
used resolutive in oriental medicine. Recently, a literature reports that
extract of the Ulmi
cortex prevents local or systemic anaphylaxis (1).
1. Kim HM, Shin HY, Choi IY, Lee EH, Lee EJ, Action of Ulmi radicis cortex
extract on systemic and local anaphylaxis on rats. Gen. Pharmacol. 31, 483-488
(1998).
(Disclosure of Invention]
One object of the present invention is to provide an analgesic composition
comprising an extract of Pulsatillae Radix as active ingredient.
The other object of the present invention is to provide an analgesic
composition
comprising an extract of Pulsatillae Radix as active ingredient and one or
more ingredients)
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selected from the group consisting extract of Ginseng Radix, extract of
Glycyrrhizae, extract
of Radix Pericarp of Akebia quinata and extract of Ulini cortex as auxiliary
ingredient(s).
It is not known until now which compound of Pulsatillae Radix has analgesic
effect.
In spite of that, in case any preparation comprising the Pulsatillae Radix has
good anticancer
5 effect, it is natural that pain reduces. Accordingly, the present inventors
determined that it is
important that raising of concentration of anticancer material of the
Pulsatillae Radix is
important.
Korean Patent Nos. 72,982 and 312,622 teach that solvent fractions were
prepared
from Pulsatillae Radix in order to prepare anticancer preparations. However,
there were some
uncertainties of establishment of formation conditions of anticancer materials
and were used
mainly first fractions of extracts. Hederagenin-3-O-a-L-rhamnopyranosyl(1-~2)-
[(3-D-
glucopyranosyl(1-~4]-a-L-arabinopyranoside(Code No. SB365) was isolated as
anticancer
material from the Pulsatillae Radix. The inventors tried to improve analgesic
effect of the
Pulsatillae Radix by preparing preparation in which SB365 is accumulated in
high
concentration.
The extracting procedures are as follows: To certain parts of powder of the
Pulsatillae Radix is added a certain parts of solvent and the mixture is
extracted at a certain
temperature for various hours) and measures the contents of SB365. The
extracting
temperature is under 60 C, desirably 20-50 C, more desirably 25-35 C. 2-10
parts of solvent,
desirably 2-3 parts are used per 1 part of the Pulsatillae Radix. Maintaining
paste state of the
mixture is desirable method, for the sides of kinetics or easiness of work up
method because
chemical reaction is comparative to concentrations of substrates and catalysis
(enzymes)
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(under the condition that hydrolysis by hydrolase). Based upon the change with
the passage of
time, reaction time is most desirable at about 30 C.
As for work up method after extraction, common evaporation of solvent, drying
method or lyophilization can be used. Lyophilization is most desirable.
As for solvent for extracting plant substances, water, methanol, ethanol,
propanol,
butanol, methylenechloride, acetone or mixture thereof can be used. Water,
methanol, ethanol
or mixture thereof is more desirable. Water or 50 % (V/V) alcoholic solution
is most desirable.
The composition of the present invention can be prepared in the forni of
solution,
injection, powder, tablet, capsule with vehicle commonly used in the
pharmaceutical field.
[Brief Description of the Drawing]
Fig. 1 shows TLG of extract of Pulsatillae Radix (PKW).
[Best Mode for Carrying Out the Invention]
The present invention is explained in more detail with the examples and
experiments
below.
General examples
General example 1
Preparation of basic extract from Pulsatillae Radix
1) 1 weight part of Pulsatillae Radix is mixed with 1 - 100 weight parts) of
water or
lower alcohol solution of water of 50%(vlv) and the mixture is covered with
gauze or filter
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paper and with cover. The mixture is reacted at or under 60 C for about 30min
and the
mixture is filtered. Filtrate is stored and remaining residue is mixed with 2-
10 weight parts of
lower alcohol of 20-80 % (v/v). The mixture is stirred for about 15 min and
filtered. The
combined filtrate is evaporated under reduced pressure to obtain residue. To
the residue is
added 2-10 weight parts of methanol or ethanol and the mixture is stand for
about 10 min.
Insolubles are filtered to obtain a solution. The solution is evaporated to
obtain an extract of
yellowish brown (PKW fraction).
Yield of the PKW fraction is 28-35 weight %. The PKW fraction can be used as
anticancer agent or analgesic of the present invention or can be used as basic
ingredient for
further composition. The PKW fraction has much SB365 contents than that which
is extracted
from any other solvent such as organic solvent, water-containing organic
solvent.
2) The combined solution of 1 ) of the general example 1 is instantly
lyophilized to
obtain an extract of yellowish brown.
1 S General example 2
Preparation of extract of Ginseng Radix (PKG)
1) 1 weight part of Ginseng Radix is mixed with 5 - 100 weight paa.-ts of
water and
extracted at room temperature for about 2hrs and the mixture is filtered.
Filtrate is stored and
remaining residue is mixed with alcoholic water of 20-80 % (v/v) and filtered.
The combined
solution is evaporated to obtain an extract. The extract is titled to PKG.
2) The combined solution of 1 ) of the general example is instantly
lyophilized to
obtain an extract of Ginseng Radix.
General example 3
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Preparation of extract of Glycyrrhizae Radix (PKIy)
1 ) 1 weight part of powder of Glycyrrhizae Radix is mixed with 2-500 weight
parts
of water and extract at room temperature for 2hours, filtered and dried to
obtain extract of
Glycyrrhizae Radix (PKIy).
2) The filtrate obtained from 1) is instantly lyophilized to obtain an extract
of
Glycyrrhizae Radix (PKIy).
General example 4
Preparation of extract of Pericarp of Akebia quinata (PKake)
1) 1 weight part of powder of Pericarp of Akebia quinata is mixed with 10-50
weight
pants of alcoholic water of 20-50%(V/V) and extracted at room temperature for
2hours,
filtered and evapor ated under reduced pressure to obtain extract of Pericarp
of Alcebia
quinata(PKake).
2) The filtrate obtained from 1) is lyophilized to obtain an extract of
Pericarp of
1 S Akebia quinata(PKake).
General example 5
Preparation of extract of Ulmi cortex (PKu)
1) 1 weight part of powder of Glycyrrhizae Radix is mixed with 5-50 weight
parts
of water or alcoholic ethanon of 20-80%(V/V) and extracted at room temperature
for 2hours,
filtered and dried to obtain extract of extract of Ulmi cortex(PKu).
2) The filtrate obtained from 1) is instantly lyophilized to obtain an extract
of Ulmi
cortex (PKu).
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Examples
Example 1
Preparation of extract from Pulsatillae Radix(PKV~
1) In a beaker of 100m1, there added 30g of powder of Pulsatillae Radix said
60m1 of
water and is mixed to obtain a paste. The paste is covered with gauze which is
wetted with
water and the paste is stand at 30 C for lhour. The paste is added to a beaker
of 300m1 and
240m1 of methanol is added thereto and stirred with magnetic stirrer. After
stirring, the
mixture is filtered and the remaining on the filter is added to the beaker and
300m1 of
alcoholic water of 50% (V/V) is added thereto and the mixture is stirred for
20min., filtered.
The combined filtrate evaporated under reduced pressure to dryness. To the
dried residue
there added 200m1 of methanol, stirred, stood for lhour and filtered. The
obtained filtrate is
dried to obtain 11.3g of pale yellow residue which is titled to PKW of which
TLC is shown to
Fig. 1. In the Fig. l, left is developed with methanol solution (PKE), center
is developed with
Methanol insoluble material and right is developed with SB 365.
2) The last filtrate is immediately lyophilized to obtain the same contents of
extract
of which TLC is the same with that of Fig. l .
Example 2
Preparation of extract of Ginseng Radix (PKG)
1) 15g of powder of dried fine roots of Ginseng Radix is mixed with 100m1 of
water
and the mixture is stirred at room temperature for about lhr and filtered. To
the filter cake
there added 100m1 of ethanolic water of 50% (V/V), stirred for 1 hr and
filtered. The
combined filtrate is evaporated to obtain 5.4g of brown tar (PKG).
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2) The combined solution of 1) of the example 2 is instantly lyophilized to
obtain the
same amount of extract of Ginseng Radix.
Example 3
5 Preparation of extract of Glycyrrhizae Radix (PKIy)
1) 4.Sg of powder of Glycyrrhizae Radix is dispersed with SOmI of water and
extract at room temperature for lhour, filtered and dried to obtain 1.9g of
extract of
Glycyrrhizae Radix (PKIy).
2) The filtrate obtained from 1) is instantly lyophilized to obtain the same
amount of
10 extract of Glycyrrhizae Radix (PKIy).
Example 4
Preparation of extract of Pericarp of Akebia quinata (PKake)
1) lOg of powder of Pericarp of Akebia quinata is mixed with 100m1 of
alcoholic
water of 50%(V/V) and extract at room temperature for 2hours and filtered. The
residue is
extracted with the same way and filtered. The combined filtrate is evaporated
to obtain 3.2g of
extract of Pericarp of Akebia quinata(PKake) of brown color.
2) The combined filtrate obtained from 1 ) is instantly lyophilized to obtain
the same
amount of extract of Pericarp of Akebia quinata (PKake).
Example 5
Preparation of extract of Ulmi cortex (PKu)
1) lOg of powder of Ulmi cortex is mixed with 100m1 of methanolic water of 50%
(V/V) and is extracted for lhour and filtered. The residue is extracted with
the same way and
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filtered. The combined filtrate is evaporated to obtain 2.Sg of extract of
extract of Ulmi cortex
(PKu).
2) The combined filtrate obtained from 1) is instantly lyophilized to obtain
the same
amount of the extract of Ulmi cortex (PKu).
Prescriptions
General Prescription 1
Prescription composed with 2 kinds of extracts
0.3, 0.6, 0.8 and 1.0 weight parts of PKG are respectively added to 1 weight
part of
PKW and mixed to obtain respective compositions. The compositions are
respectively titled
to PKWG-0.3, PKWG-0.6, PKWG-0.8 and PKWG-1Ø
General Prescription 2
1 S Prescription composed with 2 kinds of extracts
0.1, 0.2, 0.3, 0.4 and 0.5 weight parts of PKgly are respectively added to 1
weight
part of PKW and mixed to obtain respective compositions. The respective
compositions are
respectively titled to PKgly 0.1, PKgly 0.2, PKgly 0.3, PKgly 0.4 and PKgly
0.5.
General Prescription 3
Prescription composed with 2 kinds of extracts
0.1, 0.3, 0.5, 0.7 and 0.9 weight parts of PKake are respectively added to 1
weight
part of PKW and mixed to obtain respective compositions. The respective
compositions are
respectively titled to PKalce 0.1, PKake 0.3, PKake 0.5, PKake 0.7 and PKake
0.9.
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General Prescription 4
Prescription composed with 2 kinds of extracts
0.2, 0.5, 0.8, 1.1 and 1.5 weight parts of PKu are respectively added to 1
weight part
of PKW and mixed to obtian respective compositions. The respective
compositions are
respectively titled to PKu 0.2, PKu 0.5, PKu 0.8, PKu l .l and PKu 1.5.
Prescriptions composed with 3 kinds of extract
The following prescriptions are composed with 3 kinds of extracts based upon
animal experiments.
General prescription 5
Prescriptions composed with PKW, PKG and PKgly(Prescription PGgly)
0.8 weight part of PKG and 0.4 weight part of PKgly are added to 1 weight part
of
PKW and mixed to obtain prescription PGgly.
General prescription 6
Prescriptions composed with PKW, PKG and PKake(Prescription PGake)
0.8 weight part of PKG and 0.5 weight part of PKake are added to 1 weight part
of
PKW and mixed to obtain prescription PGake.
General prescription 7
Prescriptions composed with PKW, PKG and PKu(Prescription PGu)
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0.8 weight part of PKG and 1.1 weight part of PKu are added to 1 weight part
of
PKW and mixed to obtain prescription PGu.
In fact, in the case of prescriptions composed of 2 kinds of extracts, all
eight parts of
PKG, PKgly, PKake and PKu to 1 weight part of PKW can be composed based on the
above
prescriptions. In the same way, various prescriptions composed of 3 kinds of
extracts can be
composed based on the above prescriptions. In fact, all weight parts are based
on l Og of PKW.
Preparation Examples are illustrated as follows.
The above prescriptions are prepared as injections, oral preparations, etc.
Injections: Injections are prepared by dissolving the said prescriptions in
physiological sodium chloride solution, Ringer's solution or other nutritive
solution and
bacterial-filtration or any other bactericidal measures.
Oral preparations: oral preparations are prepared with the said prescriptions
by
conventional preparation methods.
Preparation examples
Preparation example 1
Preparation of PKW 0.8
lOg of PKW is dissolved in lliter of physiological sodium chloride solution
and
bacteria-filtered to prepare solution.
Preparation example 2
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Preparation of PKWG 0.8
lOg of PKW and 8g of PKG are dissolved in lliter of physiological sodium
chloride
solution and bacteria-filtered to prepare solution.
Preparation example 3
Preparation of PKWgIy 0.4
l Og of PKW and 4g of PKgly are dissolved in l liter of physiological sodium
chloride
solution and bacteria-filtered to prepare solution.
Preparation example 4
Preparation of PKWake 0.5
lOg of PKW and Sg of PKake are dissolved in lliter of physiological sodium
chloride solution and bacteria-filtered to prepare solution.
Preparation example 5
Preparation of PKWu 0.8
lOg of PKW and 8g of PKu are dissolved in Miter of physiological sodium
chloride
solution and bacteria-filtered to prepare solution.
Preparation example 6
Preparation of PGgly
lOg of PKW, 8g of PKG and 4g of PKgly are dissolved in lliter of physiological
sodium chloride solution and bacteria-filtered to prepare solution.
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Preparation example 7
Preparation of PGake
lOg of PKW, 8g of PKG and Sg of PKake are dissolved in lliter of physiological
sodiwn chloride solution and bacteria-filtered to prepare solution.
5
Preparation example 8
Preparation of PGu
lOg of PKW, 8g of PKG and 8g of PKu are dissolved in lliter of physiological
sodium chloride solution and bacteria-filtered to prepare solution.
Preparation example 9
O.Sg of PKW and 0.2g of PKgly are mixed with conventional vehicle and pressed
to
prepare tablet.
Preparation example 10
O.Sg of PKW and 0.3g of PKake axe mixed with conventional vehicle and
encapsulated to prepare capsule.
Preparation example 11
O.Sg of PKW and 0.2g of PKu are dissolved in distilled water for injection,
filled into
ampoule and sterilized to prepare injection.
Preparation example 12
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O.Sg of PKW, 0.4g of PKG and 0.2g of PKgly are mixed with conventional vehicle
and pressed to prepare tablet.
Preparation example 13
1 g of PKW, 0.2g of PKG and 0.2g of PKal~e are mixed with conventional vehicle
and sealed in envelope coated with polyethylene resin into prepare powder.
The present invention is explained in more detail with experimental examples
as
follows.
Analgesic effects for the said prescriptions were firstly screened by using
animals.
By representatively selecting prescriptions which show superior analgesic
effects clinical
trials were carried out.
Experimental examples
Experimental example with animals
It is regarded that though measuring pains of tumor patients by using animals
is
impossible, the mechanisms of reducing or eliminating pains for persons and
animals are
same.
RCI mice were used as animals. After administration of composition of the
present
invention to the animals, acetic acid is injected into abdominal cavity of the
animals. After the
administration of the injection into abdominal cavity, the number of times of
writhing is
recorded. Test results obtained with several representative prescriptions are
explained below.
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Experimental example 1
1) Measurement of analgesic effect on mouse
17 groups including 3 mice of body weight of 20-25g per one group are divided
and
1 group is used as control group. To remaining 16 groups test materials are
injected into
abdominal cavities of each mouse following doses and times listed on the Table
1. First from
control group, to each group each 0.2m1 of acetic acid of 0.6% is injected
into abdominal
cavities. Number of times of writhing of each mouse of each group is measured
for 10 min.
Inhibition rates are recorded as percent rate of writhing of groups
administered of test
materials to those of control group. The results are shown on the Table 1.
As shown from the Table 1, PKW, the extract of Pulsatillae Radix its has
powerful
analgesic effect on mouse model. PKWG of the combination of PKW and PKG and
PGgly
of the 3 combinations of PKW, PKW and PKgly show inhibition rates of 95% or
over.
20
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Table 1 : Inhibition rates of mice on writhing test based on PKW prescriptions
Prescri dose ml/k number of writhininhibition rate
tion
Control saline 17.6 0
0.5 1.33 92.4
P~
1 0.66 92.2
0.5 2.33 86.7
PKWG0.8 -
1.5 0.66 92.2
0.5 6.3 64.2
PKWg1y0.4
1.5 1.33 92.4
0.5 10.3 41.
4
_
PKWake0.5 1.5 4.6 _
73.8
0.5 10.6 39.7
PKu0.8 _
1.5 7.3 58.5
0.5 1 94.3
PGgly
1.5 0.33 98.1
1 11 37.5
PGake
2 5.6 68.1
1 13.3 24.4
PGu
2 3.6 79.5
Acetaminophene 0.2mg/kg in saline 0.9~ 0.05
2) Analgesic effect with volunteers
By selecting prescriptions having good analgesic effects from the above animal
tests,
the test materials of the prescriptions are administered to volunteers of
cancer patients and
evaluated analgesic effects of the test materials. As for the test materials,
we selected and used
PKW and PGalce which are effect from the animal tests. Amounts of the test
materials are
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0.25m1/kg of PKW and 0.25m1/kg of PGgly. The test materials are administered
once/day for
4 days (first injections) and evaluated through asking the degrees of pains to
the volunteers.
After 14 days from the first injections, the same way of administrations is
carried out for 4
days (2nd injections). After 2nd injections, the degrees of pains are
evaluated through asking
the degrees of pains to the volunteers.
Experimental example 2
Clinical trials with cancer patients
12 patients suffering from various cancers are entered to the trials. The
patients
whose cancers are already advanced are appealing cancer pains. PKW and PGgly
which are
effect from the animal tests are selected and injected intravenously. Other
analgesics which
had been being administered to the patients are stopped. 2 days after of
stopping of
administration of the other analgesics, 0.25m1/kg of the test materials are
injected
intravenously once a day for 4 days (first injections) and evaluated through
asking the degrees
of pains to the patients. After 14 days from the first injections, the same
way of
administrations is carried out(2nd injections). After the 2nd injections,
a~ialgesic effects of the
test materials are evaluated through asking the degrees of pains to the
patients. The test results
are shown on the Table 2.
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Table 2 : Evaluations of pains for cancer volunteers
PKW infections
Volunteers efore Admin.fter 1st fter 2nd
in'ect. in'ect.
Kim, O.H.
severe alleviativeno pain
female, eso ha
eal cance
Kim, D.O.
very severealleviativealleviative
female, liver cancer
Shim, O.C.
severe alleviativeno pain
female, lar a int.
cancer
Park, J.S
very severealleviativeno pain
. male, stomach
cancer
Park, S.M.
moderate no pain no pain
male, arotid cancer
Whang, J. S.
severe alleviativealleviative
male, lun cancer
PG~Iy infections
After 1st After 2nd
Volunteers Before
Admin.
in'ect. in'ect.
Kwon, T.Y.
severe alleviativeno pain
female, uterine
caner
Lee, C.H.
severe alleviativealleviative
female, stomach
cancer
Chung, K.C.
very severealleviativeno pain
male, metastasis
cancer
YouJ.I.
moderate no pain no pain
male, lun cancer
Kim, O.G.
very severealleviativealleviative
female, th roid
cancer
Kim, D.C.
very severeno pain no pain
male, metastasis
cancer
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As shown on the Table 2, all prescriptions of the extract of Pulsatillae Radix
and
prescriptions based on the extract of Pulsatillae Radix show excellent
analgesic effects. These
prescriptions have characteristics of having analgesic effect and anti cancer
effect
simultaneously. For instance, it is regarded that synergistic analgesic
effects of the present
compositions are achieved, because emphraxis by tumor, damage of tissue and
the size of
tumor are lessened and at the same time analgesic effect are exhibited as
pharmacological
effects of the composition.
Experimental example 3
Acute toxicity
Each Sml of preparation example 11 are injected intraperitoneally to 10 ICR
mice of
25-30g of body weight. No animals are died.
[Industrial Applicability]
The most excellence of the present composition shows characteristics of having
analgesic effect and anti cancer effect simultaneously. These effects are
different from the
existing control methods of pain in which anticancer agent and analgesic agent
are used
separately. In addition, the analgesic effect of the present composition has
prolonged duration
of effect. As seen from the Table 2, cancer patients do not complain from pain
even though 15
days have past from the beginning. In the case of the terminal stage of
cancer, though
administration of the composition of the present invention has stopped,
patients (Kim, O.G.,
Kim, D.C., and Whang, J. S.) did not complain from pains until they died.
Therefore, the
present composition can be used as analgesic agent in alleviating or treating
pain of cancer
patient.
