U.S. patent application number 11/452663 was filed with the patent office on 2006-11-23 for pharmaceutical composition for treatment of emiction disorders caused by benign prostate hyperplasia (bph) and the method.
This patent application is currently assigned to Beijing Wonner Biotech Ltd. Co.. Invention is credited to Yufen Wang, Zouguang Zhang.
Application Number | 20060263457 11/452663 |
Document ID | / |
Family ID | 33035145 |
Filed Date | 2006-11-23 |
United States Patent
Application |
20060263457 |
Kind Code |
A1 |
Zhang; Zouguang ; et
al. |
November 23, 2006 |
Pharmaceutical composition for treatment of emiction disorders
caused by benign prostate hyperplasia (BPH) and the method
Abstract
A pharmaceutical composition with higher curative effect on
benign prostate hyperplasia and emiction disorders is disclosed. It
uses plants such as ginseng and gingko as well as cassia twig,
cinnamon and liquorices both for food and medicine as raw
materials. These raw materials are decocted or extracted separately
in ethanol solution or water, then concentrated and dried to make
the said pharmaceutical composition. Because this pharmaceutical
composition is not toxic and has no side effect, it can be prepared
as a medicament and healthy food to treat and improve benign
prostate hyperplasia and emiction disorders caused by benign
prostate hyperplasia.
Inventors: |
Zhang; Zouguang; (Beijing,
CN) ; Wang; Yufen; (Tianjin, CN) |
Correspondence
Address: |
HEDMAN & COSTIGAN P.C.
1185 AVENUE OF THE AMERICAS
NEW YORK
NY
10036
US
|
Assignee: |
Beijing Wonner Biotech Ltd.
Co.
|
Family ID: |
33035145 |
Appl. No.: |
11/452663 |
Filed: |
June 14, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10515910 |
Nov 24, 2004 |
|
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PCT/CN03/00243 |
Apr 4, 2003 |
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11452663 |
Jun 14, 2006 |
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Current U.S.
Class: |
424/757 |
Current CPC
Class: |
A61K 36/258 20130101;
A61K 36/484 20130101; A61P 13/08 20180101; A61K 36/16 20130101;
A61K 36/484 20130101; A61K 36/482 20130101; A61K 36/258 20130101;
A61K 2300/00 20130101; A61K 36/54 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 36/16 20130101; A61K 36/482 20130101; A61K 36/54
20130101 |
Class at
Publication: |
424/757 |
International
Class: |
A61K 36/48 20060101
A61K036/48 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 28, 2003 |
CN |
03121170.4 |
Claims
1-8. (canceled)
9. A pharmaceutical extract, characterized by that the extract is
obtained by the following steps of: soaking and extracting 9-45
weight shares of ginseng in ethanol or water, following by
separation and purification by means of chromatography and drying
to get a first extract; soaking and extracting 20-100 weight shares
of core of gingko in ethanol solution or water, following by
separation and purification by means of chromatography and drying
to get a second extract; mixing the first extract and the second
extract following by crushing and sieving to get said
pharmaceutical extract.
10. The pharmaceutical extract of claim 9, wherein said first
extract is obtained from 18-36 shares of ginseng and said second
extract is obtained from 40-80 shares of core of gingko based on
the weight ratio.
11. The pharmaceutical extract of claim 9, wherein said first
extract is obtained from 27 shares of ginseng and said second
extract is obtained from 60 shares of core of gingko based on the
weight ratio.
12. The pharmaceutical extract of claim 9, further comprising a
third extract obtained from the water or ethanol extract from
addition of 2-30 shares of cinnamon and 2-10 shares of
liquorices.
13. The pharmaceutical extract of claim 9, further comprising a
fourth extract obtained from the water or ethanol extract from 6-12
shares of cassia twig.
14. The pharmaceutical extract of claim 9, wherein the said extract
is prepared as any medicament type pharmaceutically.
15. The pharmaceutical extract of claim 9, comprising
pharmaceutically acceptable carriers.
16. (canceled)
17. A method of preparation of a pharmaceutical extract, comprising
the following steps of: soaking and extracting 9-45 weight shares
of ginseng in ethanol or water, following by separation and
purification by means of chromatography and drying to get a first
extract; soaking and extracting 20-100 weight shares of core of
gingko in ethanol solution or water, following by separation and
purification by means of chromatography and drying to get a second
extract; mixing the first extract and the second extract.
18. The method of claim 17, further comprising extracting 2-30
weight shares of cinnamon and 2-10 weight shares of liquorices in
water or ethanol to have a third extract, and mixing the first
extract and the second extract with the third extract.
19. The method of claim 18, further comprising extracting 6-12
weight shares of cassia twig in water or ethanol to have a fourth
extract, and mixing the first extract, the second extract and the
third extract with the fourth extract.
20-22. (canceled)
23. The use of the pharmaceutical extract of claim 9 in preparation
of medicament for improvement and treatment of emiction disorders
caused by BHP.
24. The use of the pharmaceutical extract of claim 9 in production
of food and healthy food.
25. (canceled)
26. The method of claim 17, wherein said first extract is obtained
from 18-36 weight shares of ginseng and said second extract is
obtained from 40-80 weight shares of core of gingko based on the
weight ratio.
27. The method of claim 17, wherein said first extract is obtained
from 27 weight shares of ginseng and said second extract is
obtained from 60 weight shares of core of gingko based on the
weight ratio.
Description
TECHNICAL FIELD
[0001] This Invention relates to a kind of pharmaceutical
composition with its main efficacy for improvement and treatment of
emiction disorders caused by benign prostate hyperplasia (BPH). It
can be used as medicament and healthy food.
[0002] This Invention also relates to a preparation method of the
pharmaceutical composition with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH).
BACKGROUND OF THE INVENTION
[0003] The emiction disorder caused by benign prostate hyperplasia
(BPH) is a kind of familiar and frequently-occurring disease that
harms and distresses the health of old and middle-aged men.
Especially with the increase of aged population in recent years,
its incidence rises continuously. Taking the United States of
America as an example, almost one third of American adult men have
BPH diseases statistically. In China, the BPH incidence trends to
go up swiftly. According to the investigation, up to now the
incidence of Chinese men above 41 years old has risen from 6.6% in
1936 to 30.5%.
[0004] The modern medical studies have proven that there are two
factors leading to lower urethra hamperness caused by prostate
hypertrophy, that is, dynamic and static factors. At present, two
major categories of medicaments are used clinically to treat BPH:
.alpha.1-adrenal receptor blocking agent and 5.alpha.-reductase
inhibitor (antiandrogen). The .alpha.1-adrenal receptor blocking
agent acts on smooth muscles of prostate gland and neck of bladder
to reduce their tension. Thus the dynamic factor of blocked exit of
urinary bladder is released to abate or remove the clinical
symptoms. Its representative medicaments are HARNAL, TERAZOSIN,
etc. The 5.alpha.-reductase inhibitor inhibits Prostate Hyperplasia
with inhibiting testosterone from being transformed into DHT, with
its representative medicaments such as PROSCAR. These two kinds of
medicaments have obvious curative effect in treatment and
improvement of BPH dysuria, but they have also different degrees of
side effects for patients. The frequently used compound medicaments
of pure plants for clinical treatment of BPH are CEFASABAL and
PROSTAT pollen preparation. The features of these medicaments are
secure, but usually with long period of treatment, e.g., with poor
immediate curative effect.
[0005] From the viewpoint of the Chinese Traditional Medicine, the
emiction disorder caused by BPH belongs to the category of dysuria
and blocking. The dysuria said in the Chinese Traditional Medicine
refers to difficult emiction, slim and fragile urine line and
blocked urine. When man pisses uneasily and difficultly with light
degree of seriousness, it is dysuria. When man can not piss or it
is blocked with a full lower abdomen and acute degree of
seriousness, it is called blocking. The medical principle of the
compound preparation of Chinese traditional medicaments for
treatment of BPH is a multiple targeting and multiple directing
treatments. Its advantage is that patients are treated as a whole
and it is safe. But its shortcoming is as same as the compound
medicaments of pure plants in the modern medicine.
[0006] In the prior art, the Chinese Patent No. 98113889.6
describes a kind of capsule and its preparation method. With that
method, the raw materials such as rough gentian, dried rehmannia
root, Tuckahoe, celery wormwood, root of Chinese thorowax, tulip,
cordate houttuynia and devilpepper are decocted in 8-fold water for
2 hours first, and the decoction is filtered. Secondly, it is
decocted in 5-fold water for a hour, and the decoction is filtered.
Thirdly, it is decocted in 3-fold water for a hour, and the
decoction is filtered. Then the three decoctions are combined,
decompressed, and concentrated as a dry extract. After it is dried,
it is comminuted and put in capsules. It has effects of clearing
away the heat-evil and expelling superficial evils, relieving
rheumatic pains; colds, etc and reducing swellings, relaxing the
liver-fire and dispelling melancholy, and activating blood
circulation to dissipate blood stasis. It is applicable for
diseases such as acute and chronic prostatitis, prostate
hypertrophy, etc. In the clinical observation, it has obvious
curative effects, and the symptom of dysuria is obviously improved.
And its efficiency rate reaches 90%. But its prescription is
relatively complicated, especially with uncertain effect on
emiction disorders.
SUMMARY OF THE INVENTION
[0007] In order to overcome the shortcomings in the prior art, the
object of this invention is to provide a kind of pharmaceutical
composition with its main efficacy for improvement and treatment of
emiction disorders caused by benign prostate hyperplasia (BPH),
especially a kind of medicament of plants, which can be used both
as medicament and healthy food.
[0008] This kind of pharmaceutical composition made of raw
materials both as medicament and food has no noxious effect (side
effect) and can be taken as a medicament for treatment of BPH
emiction disorders for a long time. And it can also be used as
healthy food for antiaging immunity-raising purposes.
[0009] Based on the principles, methods, prescriptions and
medicaments about dysuria and blocking in the Chinese traditional
medicine and combined with treatment mechanism of the modern
medicine, the solution of the pharmaceutical composition in this
invention is researched and developed and is a kind of Chinese
medicament of pure plants with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH). Its features are obvious curative effect and
safe with strong immediate curative effect. It can initially
improve the subjective and objective body symptoms of BPH patients
only after it is taken for a week. When taking for a long time, it
can also raise immunity and antiaging capability of patients.
[0010] The other object of this invention is to provide a
preparation method of the above mentioned pharmaceutical
composition with its main efficacy for improvement and treatment of
emiction disorders caused by benign prostate hyperplasia (BPH).
[0011] In order to reach the aim in this invention, this invention
provides the following technical solution.
[0012] In the first embodiment, this invention refers especially to
a pharmaceutical composition with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH), characterized by comprising 9-45 shares of
Ginseng and 20-100 shares of core of Gingko, preferably 18-36
shares of Ginseng and 40-80 shares of core of Gingko based on the
weight ratio.
[0013] The said pharmaceutical composition is more preferably
prepared with the components with the weight ratio of 27 shares of
Ginseng and 60 shares of core of Gingko.
[0014] In the second embodiment, 2-30 weight shares of cinnamon and
2-10 shares of liquorices can be further included in the
pharmaceutical composition with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH) to enhance the anti-inflammatory and inhibitive
effect on prostate hypertrophy.
[0015] In the third embodiment, on the basis of the second
embodiment, 6-12 weight shares of cassia twig can be further added
in the pharmaceutical composition with its main efficacy for
improvement and treatment of emiction disorders caused by benign
prostate hyperplasia (BPH) to strengthen the diuretic effect of the
pharmaceutical composition in this invention.
[0016] The said pharmaceutical composition in this invention
contains the pharmaceutically acceptable carriers or additives and
the said composition can be any pharmaceutical form, preferably
powder or tablets.
[0017] This invention also directs to an extract of the invented
pharmaceutical composition with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH). The said extract is obtained with the following
method, comprising: [0018] 1. soaking and extracting 9-45 weight
shares of ginseng in ethanol or water, following by separation and
purification by means of chromatography and dry to get the first
extract; [0019] 2. soaking and extracting 20-100 weight shares of
core of gingko in ethanol solution or water, following by
separation and purification by means of chromatography and dry to
get the second extract; [0020] 3. mixing the first extract obtained
from the step 1 and the second extract obtained from the step 2
following by crushing and sieving to get the invented extract.
[0021] In the above mentioned method, 18-36 weight shares of
ginseng and 40-80 weight shares of core of gingko are preferable,
20 weight shares of ginseng and 60 weight shares of core of gingko
are more preferable.
[0022] In the above mentioned method, the extract out of the water
or ethanol solution of 2-30 weight shares of cinnamon and 2-10
weight shares of liquorices can also be added.
[0023] In the above mentioned method, the extract out of the water
or ethanol solution of 6-12 weight shares of cassia twig can also
be added.
[0024] The said extract can be processed as any types of medicament
in pharmacy. The said extract can contain the pharmaceutical
acceptable carriers or additives.
[0025] In addition, the present invention also relates to a method
for pharmaceutical extracts with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH). The method comprises the following steps of:
[0026] 1. soaking and extracting 9-45 weight shares of ginseng in
ethanol or water, following by separation and purification by means
of chromatography and dry to get the first extract; [0027] 2.
soaking and extracting 20-100 weight shares of core of gingko in
ethanol solution or water, following by separation and purification
by means of chromatography and dry to get the second extract;
[0028] 3. mixing the first extract obtained from the step 1 and the
second extract obtained from the step 2 following by crushing and
sieving to get the invented extract.
[0029] In accordance with the second embodiment of this invention,
2-30 weight shares of cinnamon and 2-10 weight shares of liquorices
are soaked and extracted in water or ethanol solution, concentrated
and dried to get extract. Then the obtained extract is further
crushed with the first and second extracts obtained in Step 1 and 2
together to get the extract of present invention.
[0030] In accordance with the third embodiment of this invention,
6-12 weight shares of cassia twig are in water or ethanol solution
extracted, concentrated and dried to obtain another extract. Then
it is crushed with the extract of this invention obtained in the
second embodiment together to get the other extract of this
invention.
[0031] In addition, the present invention also concerns a method,
by which extracts are made for a kind of pharmaceutical composition
with its main efficacy for improvement and treatment of emiction
disorders caused by benign prostate hyperplasia (BPH). The method
comprises the following steps, characterized by that 9-45 weight
shares of ginseng, 20-100 weight shares of core of gingko, 6-12
weight shares of cassia twig, 2-30 weight shares of cinnamon and
2-10 weight shares of liquorices are decocted in water or ethanol
solution to obtain their separate extracts. And the separated
extracts are concentrated separately to obtain their paste
extracts. Then they are dried separately to obtain the water or
ethanol extracts followed by mixing together and crushed.
[0032] In other words, it is well known by all the skilled person
in the art that all the raw materials said in this invention can be
extracted with the known methods to prepare and obtain their own
dry extracts separately. Then after they are dried, crushed, sifted
out and mixed, the mixture made of all the raw materials in this
invention is obtained.
[0033] According to the present invention, ginseng, its original
plant is Panax gineng C. A. Mey, and its rootstock can be used.
According to different processing methods, the medical commercial
garden ginsengs, also called the seedling ginsengs, include red
ginseng, strake ginseng, sugar-dipped ginseng, white ginseng,
sun-dried ginseng, suncured white ginseng root, nipped ginseng and
Dali ginseng. Additionally, it can include wild ginseng, migrated
ginseng, Korean ginseng and Korean red ginseng.
[0034] The core of gingko, its original plant is Ginkgo biloba L.
The medical part used in this invention is its dried seeds without
their crusts
[0035] The cassia twig is the young twig of the Cinnmomum cassia
Presl.
[0036] The cinnamon is the dried tree or twigs bark of the
Cinnmomum cassia Presl.
[0037] The liquorices are the roots and root-shaped stems of the
Glycyrrhiza uralensis Fisch.
[0038] The pharmaceutical composition or extracts of this invention
can be used to make healthy food or food complements.
[0039] The pharmaceutical composition or extracts of this invention
can be used as a medicament with its main efficacy for improvement
and treatment of emiction disorders caused by benign prostate
hyperplasia (BPH). It has antiaging functions. When man takes it
for a long time, it can not only improve emiction disorders, but
also enhance human immunity. The pharmaceutical composition or
extracts have the following features and advantages: [0040] 1. The
raw materials of the pharmaceutical composition or extracts said in
this Invention are all natural edible plants both for medicaments
and food. All the components apply with the regulations of the
"Management Methods of Healthy Food" and the "Medicine Act" of the
PRC. They have no toxic or side effect. And man can take it for a
long time. [0041] 2. In the field of improvement and treatment of
emiction disorders caused by benign prostate hyperplasia (BPH), the
pharmaceutical composition or extracts in this invention has
obvious efficacy and strong immediate curative effect. It can
initially improve the subjective and objective body symptoms of BPH
patients only after it is taken for a week. When it is taken for a
long time, it can also raise immunity and antiaging capability of
patients. [0042] 3. It has antiaging functions. When man takes it
for a long time, it can not only improve emiction disorders, but
also enhance human immunity. [0043] 4. The pharmaceutical
composition or extracts has not only proven in human and animal
tests that it can improve and treat effectively emiction disorders
caused by benign prostate hyperplasia (BPH), but also the contents
and action mechanism of its main functional factors (ginseng
saponin, cassia aldehyde, etc.) have been found out. [0044] 5. The
pharmaceutical composition or extracts need not to be decocted with
easy transportation and medicine-taking. It applies with the
regulations of the Health Act of the PRC. [0045] 6. The
pharmaceutical composition or extracts have the potential values
for further development of series of products (food, healthy food
and medicaments).
[0046] The application of the pharmaceutical composition or
extracts are given below: [0047] 1. This product can be used as
antiaging food and healthy food that improve emiction disorders
caused by benign prostate hyperplasia (BPH) and enhance human
immunity. [0048] 2. This product can be used as medicament that
improves and treats emiction disorders caused by benign prostate
hyperplasia (BPH)
DESCRIPTION OF THE DRAWINGS
[0049] FIG. 1 describes the processing procedures of this invented
method.
[0050] FIG. 2 describes another processing procedure of this
invented method.
[0051] FIG. 3 describes another processing procedure of this
invented method.
DETAILED DESCRIPTION OF THE INVENTION
[0052] In combination with the FIGS. 1, 2 and 3, the present
invention is explained in details as follows.
EXAMPLE 1
[0053] Referring to FIG. 1, 27 kg of ginseng was soaked and
extracted in 70% ethanol solution. And then it was chromatographed,
purified and dried to get the ethanol extract. 60 kg core of gingko
was decocted in water, filtered, concentrated and dried to get the
water dry extracts. The ethanol extract and water dry extract
obtained in the above mentioned steps were mixed together and
crushed, sifted with a 80-mesh screen to obtain the extract of the
present invention.
EXAMPLE 2
[0054] Repeating the same procedures in Example 1 except that 9 kg
of ginseng and 20 kg of core of gingko were soaked and extracted in
the ethanol solution separately.
EXAMPLE 3
[0055] Repeating the same procedures in Example 1 except that 45 kg
of ginseng and 100 kg core of gingko were decocted in water
separately.
EXAMPLE 4
[0056] Referring to FIG. 1, 27 kg of ginseng was soaked and
extracted in 70% ethanol solution. And then it was chromatographed,
purified and dried to obtain ethanol extract.
[0057] 60 kg of core of gingko, 3 kg of cinnamon, 3 kg of
liquorices and 9 kg of cassia twig were decocted in water,
filtered, concentrated and dried to obtain dry water extracts.
[0058] The ethanol and dry water extracts obtained in the above
mentioned steps were mixed together and crushed, sifted with a
80-mesh screen to obtain the extract of the invention. The
composition of this invention was prepared directly into capsules
with the method known by person skilled in the art.
EXAMPLE 5
[0059] Repeating the same procedures in Example 4 except that 45 kg
of ginseng, 100 kg core of gingko, 2 kg of cinnamon, and 2 kg of
liquorices were extracted in ethanol solution or water separately.
Then they were mixed and crushed to obtain the extract of the
invention.
EXAMPLE 6
[0060] Repeating the same procedures in Example 4, except that 9 kg
of ginseng, 20 kg of core of gingko, 30 kg of cinnamon, and 10 kg
of liquorices were extracted in ethanol solution or water
separately. Then they were mixed and crushed to obtain the extract
of the invention. The composition of the invention was prepared
directly into powder with the method known by person skilled in the
art.
EXAMPLE 7
[0061] Repeating the same procedure in Example 6 except that 12 kg
of cassia twig was added.
EXAMPLE 8
[0062] Repeating the same procedures in Example 5 except that 6 kg
of cassia twig was added.
EXAMPLE 9
[0063] Referring to FIG. 3, 27 kg of ginseng was soaked and
extracted in 70% ethanol solution. And then it was chromatographed,
purified and dried to obtain the ethanol extract. 60 kg of core of
gingko was soaked and extracted in water. It was filtered,
concentrated, and dried to obtain the dry water extract. Then the
ethanol and dry water extracts obtained in the above mentioned
steps were mixed and crushed to obtain the extract.
[0064] 24 kg of cinnamon and 6 kg of liquorices were mixed and
decocted in 95% ethanol solution. After it was filtered and
concentrated, it is absorbed with a proper amount of officinal
calcium hydrogen phosphate, and then dried to obtain the dry
ethanol extract.
[0065] The dry ethanol extract of ginseng and the dry water extract
of core of gingko obtained in the above steps were mixed with the
dry ethanol extracts of cinnamon and liquorices together, crushed
and filtered with 80-mesh screen to obtain the extract said in this
invention. The combination or composition of this invention was
prepared directly into powder with the method known by person
skilled in the art.
EXAMPLE 10
[0066] Again referring to FIG. 3, repeating the same procedures in
Example 9 except that 18 kg of ginseng, 40 kg of core of gingko, 2
kg of cinnamon and 2 kg of liquorices were decocted and extracted
in water.
[0067] The dry water extracts of ginseng and gingko were dried
together with the dry water extracts of cinnamon and liquorices to
make the dry extract of the combination.
EXAMPLE 11
[0068] 27 kg of ginseng, 60 kg of core of gingko, 9 kg of cassia
twig, 3 kg of cinnamon and 3 kg of liquorices were taken. Then the
said ginseng, gingko, cassia twig, cinnamon and liquorices were
decocted in water or 70% ethanol solution and filtered separately
to obtain their own extracts. They were concentrated to obtain
their dry extracts, and then were dried to obtain their own dry
water or ethanol extracts separately. Finally, the obtained dry
extracts were crushed and filtered with an 80-mesh screen to be
mixed together to obtain the extract of the invention.
EXAMPLE 12
[0069] 9 kg of ginseng and 20 kg of core gingko were taken. With
the method known by the person skilled in the art, they were
directly crushed and filter with an 80-mesh screen to obtain the
pharmaceutical composition of the invention. Accordingly with the
method known by the person skilled in the art, they were directly
pressed and made into tablets.
EXAMPLE 13
[0070] 45 kg of ginseng, 100 kg of core of gingko, 30 kg of
cinnamon and 10 kg of liquorices were taken. With the method known
by the person skilled in the art, they were directly crushed and
filtered with an 80-mesh screen to obtain the pharmaceutical
composition of the invention. Then with the method known by the
person skilled in the art, they were directly pressed and made into
tablets.
EXAMPLE 14
[0071] Repeating the same procedures in Example 13 except that 12
kg of cassia twig was added, crushed and sifted out.
EXAMPLE 15
[0072] Repeating the same procedure in Example 13 except hat 18 kg
of ginseng, 40 kg of core of gingko, 3 kg of cinnamon, 4 kg of
liquorices and 6 kg of cassia twig were crushed into powder. Then
with the method known by the person skilled in the art, the
composition of the invention is made into capsules.
EXPERIMENTING EXAMPLE 1
[0073] Impacts on prostate hyperplasia of rats caused by
testosterone propionate by medicaments of anti prostate hyperplasia
and the extracts of this invention were done as below.
Experimental Materials
Medicaments:
[0074] 1. PROSCAR: tablets, produced by Merck & Co., Inc., (UK)
Co. The medicament was prepared into 0.5 mg/ml medicament. [0075]
2. Saw Palmett tablets, produced by Zhejiang Conba Pharmaceutical
Co. Ltd. It was prepared with distilled water into 0.5 mg/ml
medical liquid. [0076] 3. Longbishu Capsules: produced by
SHIJIAZHUAN KEDI Pharmaceutical Co., Ltd. It was prepared with
distilled water into 0.18 g/ml medical liquid. [0077] 4. The
extract was taken from Example 9. The extract was prepared into 6
g/ml medical liquid. [0078] 5. Estradiol Benzoate Injection [0079]
6. Testosterone propionate Injection Test Method and Results
[0080] The 130 g-150 g male Wistar rats were taken as test animals
and anaesthetized with ether. Both of their testis were removed
under axenic conditions and bred for a week after operation. The
rats were divided at random into 6 groups, 6 in each group. All
groups of animals were hyped with 5 mg/Kg testosterone propionate
dissolved in prepared peanut oil per day. And they were
simultaneously medicated, that is, the contrast groups were drunk
by force with physiological salt solution. The medicine-taking
groups were drunk by force with 5 mg/Kg PROSCAR, 5 g/Kg Saw
Palmetto, 1.8 g/Kg longbishu, 6 g/Kg extract obtained from Example
9 in this invention, with the medicine-taking 1 ml/100 g volume;
and for hypodermic injection of 50 .mu.g/Kg estradiol benzoate, the
volume was 0.05 ml/Kg, once a day and continuously for 30 days. In
24 hours after the last medicine-taking, all the rats were killed.
The whole prostate glands were anatomized. The prostate glands were
placed in formalin. All the fat were removed away after the
prostate glands were taken out. The liquid on the surface was dried
with filter papers. They were weighed with a tissue balance to
calculate the weight (factors) of prostate glands. Table 1 shows
the results. TABLE-US-00001 TABLE 1 Impact on Prostate Gland
Factors (mg/100 g) of Rats by medicaments of anti prostate
hyperplasia x .+-. SD Sum of three lobes Dosage/volume (anterior,
g/kg Number head and weight of Anterior Inhibition posterior
Inhibition Medicament g/kg animals lobe rate % lobes) rate %
Contrast -- 10 284.7 .+-. 75.7 721.2 .+-. 129.7 group estradiol 50
.mu.g/Kg 10 180.1 .+-. 55.8 36.7** 585.3 .+-. 80.5 18.8** benzoate
PROSCAR 5 mg/Kg 10 164.2 .+-. 31.4 42.3** 453.4 .+-. 59.1 37.1**
Saw Palmett 5 g/Kg 10 250.6 .+-. 40.9 11.9** 656.5 .+-. 88.1 4.7**
Longbishu 1.8 g/Kg 10 231.4 .+-. 37.0 18.7** 650.2 .+-. 68.1 9.8**
The extract 6 g(crude 10 190.2 .+-. 30.3 33.2** 497.9 .+-. 81.1
30.9** drug)/Kg Note: compared with the contrast groups: *P <
0.05, **P < 0.01
EXPERIMENTING EXAMPLE 2
Study on the Action of Anti Prostate Hyperplasia by the Extract in
this Invention
[0081] In order to evaluate the action of anti prostate hyperplasia
by the extract in this Invention, the anti-inflammatory action of
the extract in this intention and its impact on prostate
hyperplasia caused by Testosterone Propionate were observed in this
experiment.
Experimental Materials
1. Animals: 1) Wistar rats and 2) mice of Kunming origin
2. Medicaments:
2.1 The extract obtained in Example 9 in this invention
2.2 Estradiol benzoate Injection
2.3 Testosterone Propionate injection
2.4 Hydrocortisone acetate injection
Experimental Method and Results
[0082] 1. Impact on Otic Swelling caused by Mixed Inflammatory
Solution of Croton Oil
[0083] 60 18-22 g male mice were selected and divided in 6 groups
randomly, 10 in each group: a contrast group of physiological salt
solution, a group of hydrocortisone, a group of Saw Palmett, and
three dosage groups of the extract obtained in Example 9 in this
invention (1.5, 3.0 and 6.0 g/kg). They were drunk by force with
the medicaments in the stomachs, once a day, and continuously for 5
days. After the last medicament, the mixed inflammatory solution of
croton oil (2% croton oil, 20% anhydrous ethanol, 5% distilled
water and 73% ether) was applied on the both front and rear sides
of the left ears of animals, 0.05 ml each mouse. Four hours after
inflammation, the mice were killed with a disjointed cervical
vertebra method. The two ears were cut along the auricle baseline.
The equal parts of the two ears with the same area were cut off and
weighed on weighing scales to test twisting force. When the weight
of the right ear was subtracted from the weight of the left ear of
each mouse, it got the swelling degree. The swelling degrees
between the contrast groups and the medicine-taking groups were
processed statistically; the swelling inhibition rate was got.
Table 2 shows the results. TABLE-US-00002 TABLE 2 Impact on otic
swelling degrees caused by mixed inflammatory solution of croton
oil by the extract in this Invention Swelling degree Inhab- Number
of (mg) itation Groups Dosage animals (x .+-. SD) P rate % Contrast
10 17.85 .+-. 2.05 group The said 1.5 g/kg 10 15.25 .+-. 2.26
<0.05 14.56 extract The said 3 g/kg 10 13.10 .+-. 1.45 <0.01
26.61 extract The said 6 g/kg 10 11.55 .+-. 2.38 <0.01 35.29
extract Saw Palmett 2.5 g/kg 10 12.65 .+-. 1.30 <0.01 29.13
Hydrocortisone 20 mg/kg 10 9.50 .+-. 2.93 <0.01 46.77
[0084] The results have shown that the high, middle and low dosages
of the extract in this invention can all obviously reduce the
swelling degrees of mouse otic inflammation caused by the mixed
inflammatory solution of croton oil. The extract in this Invention
has an anti-inflammatory action.
EXPERIMENTING EXAMPLE 3
Impact on Permeability of Mice Celiac Capillary Vessels
[0085] The same experimental materials and animals as in
Experimenting Example 2 were used. But it was different that 60
18-22 g male mice were selected and divided in 6 groups in
accordance with their weight, 10 in each group: a contrast group of
physiological salt solution, a group of hydrocortisone, a group of
Saw Palmett, and three dosage groups of the extract obtained in
Example 9 in this invention (1.5, 3.0 and 6.0 g/kg). They were
drunk by force with the medicaments in the stomachs once a day, and
continuously for 5 days. One hour after the last medicament, they
were intravenously injected with 0.5% Evans blue in a 5 ml/kg
dosage. After 5 minutes, 0.7% acetic acid in a dose of 10 ml/mg was
injected in their abdomens. After 30 minutes, they were killed with
a disjointed cervical vertebra method. Their abdomens were washed
many times with distilled water. The washing solution was changed
to the total amount of 10 ml/mg, and 0.1N NaOH 0.1 mL was added.
After it was placed for 30 minutes, the light density of mice
celiac transudate was measured with a colorimetry of a 721
spectrophotometer. Table 3 shows the results. TABLE-US-00003 TABLE
3 impact on permeability of capillary vessels by the extract in
this Invention Number Evans blue Inhibi- of transudate (OD tion
rate Groups Dosage animals x .+-. SD) P (%) Contrast 10 0.166 .+-.
0.04 The said 1.5 g/kg 10 0.133 .+-. 0.030 >0.05 19.87 extract
The said 3 g/kg 10 0.117 .+-. 0.031 <0.01 29.52 extract The said
6 g/kg 10 0.100 .+-. 0.027 <0.01 39.75 extract Saw Palmett 2.5
g/kg 10 0.122 .+-. 0.033 <0.05 26.51 Hydrocortisone 20 mg/kg 10
0.092 .+-. 0.019 <0.01 44.58
[0086] The results have shown that the high, middle and low dosages
of the extract in this invention can all obviously reduce the
permeability of mice celiac capillary vessels and make the Evans
blue transudate decline. It shows that the extract in this
Invention has an anti-inflammatory action.
EXPERIMENTING EXAMPLE 4
Impact on Tampon Granuloma of Rats
[0087] The same experimental materials and animals as in
Experimenting Example 2 were used. But it was different that 60
150-180 g male rats were used. Under the ether anaesthesia and
normal disinfection, two .+-.1 mg sterilized tampons were embedded
under the inguinal skins on the both sides. On the same day of
operation, the 60 rats were randomly divided in 6 groups, 10 in
each group: a contrast group of physiological salt solution, a
group of hydrocortisone, a group of Saw Palmett, and three dosage
groups of the extract obtained in Example 9 in this invention. They
were drunk by force with the medicaments in the stomachs once a
day, and continuously for 7 days. On the eighth day, they were
killed with a disjointed cervical vertebra method. The tampons were
taken out and placed in a 60.degree. C. oven for 12 hours and then
weighed. Table 4 shows the results. TABLE-US-00004 TABLE 4 impact
on tampon granuloma of rats Weight of tampon Number granuloma of
(mg Inhibition Groups Dosage animals x .+-. SD) P rate % Contrast
10 45.95 .+-. 9.03 The said 1.5 g/kg 10 40.30 .+-. 7.32 >0.05
12.30 extract The said 3 g/kg 10 38.05 .+-. 6.17 <0.05 17.19
extract The said 6 g/kg 10 32.15 .+-. 5.41 <0.01 30.03 extract
Saw Palmett 2.5 g/kg 10 42.30 .+-. 6.36 >0.05 7.94
hydrocortisone 20 mg/kg 10 26.45 .+-. 2.61 <0.01 42.43
[0088] The results have shown that the high and middle dosages of
the extract in this Invention can all obviously inhibit the
hyperplasia of tampon granuloma of rats. t shows that the extract
in this invention has an anti-inflammatory action.
EXPERIMENTING EXAMPLE 5
Impact on Rat Prostate Hyperplasia caused by Testosterone
Propionate
[0089] The same experimental materials and animals as in
Experimenting Example 2 were used. But it was different that 60
130-150 g male Wistar rats were used. Under the conditions of ether
anaesthesia and sterilization, the testis of both sides were
removed. They were bred for a week after the operation. The rats
were randomly divided in 5 groups, 10 in each group. Each group of
animals were hyped with 5 mg/kg testosterone propionate dissolved
in prepared oil once a day. And at the same time they were treated
with medicaments. For the contrast group, they were drunk by force
with physiological saline solution; for the medicine-fed group,
they were drunk by force with 1.5, 3 and 6 g/kg extract obtained in
Example 9 in this invention separately with a medicine-taking
volume of 1 m/100 g. For the positive contrast group, they were
hyped with 50 ug/kg estradiol benzoate with a volume of 0.05 ml/100
g, once a day and continuously for 30 days. After the last
medicament, the rats were killed. The whole prostate glands were
anatomized. The prostate glands were placed in formalin. All the
fat was removed away after the prostate glands were taken out. The
liquid on the surface were dried with filter papers. And the
prostate glands were placed in 70% ethanol and fixed for 24 hours.
Then they were taken out and placed on filter papers. The anterior,
head and posterior lobes of prostate glands were separated and
weighed a weighing scale to test twisting force to calculate the
factors of all the lobes of prostate glands. The transverse
diameter, diameter and height of the anterior lobes of prostate
glands were measured with a two-foot vernier. When the three
dimensions multiply, the volume of the anterior lobe of a prostate
gland was got. Lastly, all the anterior lobes were examined with
tectology, and the diameter of prostate gland cavity and the height
of glandular epithelium cells were measured. The non-pairing t
examinations among the groups were made for all the indexes. The
obviousness of average difference were compared between the
medicine-taking and contrast groups. Table 5 and 6 show the
results.
[0090] 1. Impact on Weight of Prostate Glands of Rats
[0091] 30 days after the rats took the medicament, in comparison
with the contrast group, the 1.5 g, 3 g and 6 g crude drug/kg of
the extract in this invention have the inhibition rates of 23.2%
(P<0.01), 31.26% (P<0.01), and 34.46% (P<0.01) for
prostate anterior lobe separately, and the inhibition rate of
estradiol is 35.3% (P<0.01); the inhibition rates for head lobes
are 13.5%, 36.5% (P<0.01), and 46.0% (P<0.01) separately, the
group of estradiol is 30.2% (P<0.05); the inhibition rates for
posterior lobe are 9.6%, 15.3%, and 20.8% separately, the
inhibition rate of estradiol is 12.5%. The results have shown that
the extract in this invention has an obvious inhibitive action on
the weight of anterior and head lobes with no obvious influence on
posterior lobe.
[0092] 2. Impact on the Volume of Prostate Anterior Lobe of Rats
TABLE-US-00005 TABLE 5 Impact on rat prostate factors (mg/100 g) of
all lobes by the extract in this invention x .+-. SD Dosage Number
of Groups (g/Kg body weight) animals Anterior lobe Head lobe Rear
lobe Contrast 10 196.7 .+-. 41.1 73.4 .+-. 22.3 54.1 .+-. 12.8 The
said 1.5 g/kg 10 151.0 .+-. 28.1** 63.5 .+-. 7.3 48.9 .+-. 11.9
extract The said 3.0 g/kg 10 135.2 .+-. 40.9** 46.6 .+-. 16.5**
45.8 .+-. 15.3 extract The said 6.0 g/kg 10 128.9 .+-. 26.3** 39.6
.+-. 13.5** 42.7 .+-. 12.3 extract Estradiol 50 .mu.g/kg 10 127.2
.+-. 23.4** 51.2 .+-. 10.7* 47.3 -+ 14.4 benzoate Note: in
comparison with the contrast group: *P < 0.05, **P < 0.01
[0093] 30 days after the rats took the medicament, in comparison
with the contrast group, the 1.5 g, 3 g and 6 g of crude drug/kg of
the extract in this invention have the inhibition rates of 18.2%,
31.1% (P<0.01), and 40.3% (P<0.01), and the inhibition rate
of estradiol is 45.5% (P<0.01). The results have shown that the
extract in this Invention has an obvious inhibitive action on the
volume of prostate gland. TABLE-US-00006 TABLE 6 Impact on the
volume of prostate anterior lobe of rats by the extract in this
invention X .+-. SD Volume of anterior Dosage (g/kg Number lobe
Medicament weight) of animals (cm3) Contrast group 10 0.77 .+-.
0.21 The said extract 1.5 g/kg 10 0.63 .+-. 0.17 The said extract
3.0 g/kg 10 0.53 .+-. 0.13** The said extract 6.0 g/kg 10 0.46 .+-.
0.13** Estradiol 50 .mu.g/kg 10 0.42 .+-. 0.12** Note: in
comparison with the contrast group: *P < 0.05, **P < 0.01
[0094] 3. Impact on the Diameter of Prostate Gland Cavity and the
Height of Glandular Epithelium Cells of Rats
[0095] 30 days after the rats took medicament continuously, the
microscopic examination has shown that the prostate gland body of
the anterior, head and posterior lobes has obvious hyperplasia with
enlarged acinus. There were epithelioid papillas going into gland
cavity. On the hyperplastic glandular epithelium, an active
excreting activity could be seen. The glandular epithelium cells
appeared in high column-form or multi-layer form without clear cell
boundaries. The nucleus was placed on the base with parts of cell
plasm in a grain form. The glandular cavity was full of secretion.
The hyperplasia of connective tissue between acini can also be
observed. The histological changes in the medicine-taking groups
were nearly the same. The hyperplasia of anterior and head
glandular body was not so obvious as the contrast group. The
hyperplasia of posterior lobe could still be observed with the
similar pathologic changes as in the contrast group. But in
comparison with the contrast group, the extract in this invention
can obviously inhibit the hyperplasia of the diameter of the
glandular cavity of prostate anterior and head lobes. The estradiol
can also obviously inhibit the hyperplasia of the diameter of
prostate anterior and head glandular cavity. In all the groups, no
obvious influence was observed on the diameter of posterior
glandular cavity and the height of glandular epithelium cells of
all the lobes. The results have shown that the extract in this
invention can inhibit hyperplasia of diameter of prostate anterior
and head glandular cavity.
EXPERIMENTING EXAMPLE 6
Impact on Prostate Hypernlasia caused by Implantation of Urine
Genital Sinus of Mice
[0096] 60 30-35 g male mice with the age of 7-10 weeks were
selected. Under the injected celiac anaesthesia with 50 mg/kg
pentobarbital, the inferior belly was cut open and the prostate
gland was separated carefully. A small hole was made in the celiac
prostate gland with a needle. Then three urine genital sinus
tissues with 16-day fetal age were implanted in the celiac anterior
lobe. Another mouse was taken and its celiac prostate gland was
probed twice with a needle as a blank contrast of false operation.
Then the belly was sutured. On the same day, taking the 10 animals
as the blank contrast group of false operation, the other 50
animals were divided in 5 groups, 10 in each group: a contrast
group, three dosage groups of the extract in Example 9 in this
invention, and a group of positive contrast Saw Palmett. They were
drunk by force with the medicament in the stomachs once a day and
continuously for 30 days. After the last medicament, the mice were
killed and paunched. The prostate glands were taken out and weighed
with a tissue scale. The results were used to examine the
obviousness of difference between the medicine-taking group and the
contrast group with the t examination method and to calculate the
inhibition rate. (see Table 7) TABLE-US-00007 TABLE 7 Impact on
prostate hyperplasia caused by implantation of urine genital sinus
of mice by the extract in this invention Weight of prostate gland
Number of (mg/10 g Inhibition Groups Dosage animals x .+-. SD) P
rate % Blank 10 17.9 .+-. 6.32 contrast Contrast 10 63.4 .+-. 11.4
The said 1.5 g/kg 10 53 .+-. 7.4 <0.05 16.4 extract The said 3
g/kg 10 45.8 .+-. 4.8 <0.01 27.8 extract The said 6 g/kg 10 41
.+-. 6.6 <0.01 35.3 extract Saw Palmett 2.5 g/kg 10 49.6 .+-.
8.6 <0.01 21.8
[0097] The experimental results have proven that the prostate
hyperplasia is obviously caused with the implantation of urine
genital sinus of mice. 30 days after the mice took the extract in
this Invention, the high, middle and low dosage groups can reduce
the weight of prostate glands of mice with obvious difference in
comparison with the contrast group. It has shown that the extract
can obviously inhibit the prostate hyperplasia caused by the
implantation of urine genital sinus of mice.
EXPERIMENTING EXAMPLE 7
Curative Effect on Senile BPH Patients with the Extract in this
Invention
Method:
[0098] In June-August 2002, the inventor treated 46 cases of BPH
patients with the age of above 51-70 with the extract obtained in
Example 4 in this invention. It was taken with warm water in the
morning and evening with an empty stomach in a dose of 1.0
g/tablet, once a tablet, twice a day. They were treated and
observed for one week and 4 weeks.
Results:
[0099] Patients: The subjective symptoms were obviously improved.
One week and 4 weeks after the treatment, the IPSS was averagely
reduced by 16.6% and 30% separately. And the MFR was averagely
increased by 14.2% and 33% separately. After four-week treatment,
according to the measurement with an ultrasonic wave scanning Type
B, the average residue urine was reduced by 36%. The extract in
this invention has no impact on the pulse and blood pressure of the
patients who take the extract in this Invention.
CONCLUSION
[0100] The extract in this invention is safe and effective for
senile BPH patients. It can make the subjective symptoms and
objective body symptoms of patients as well as their life improve
obviously without obvious serious side effect.
1. Data and Methods
1.1 Clinical Data
[0101] There were 46 cases of male patients with an age of 51-78,
averaging 63.2. In accordance with their chief complaints, they
suffered from dysuria. After finger examination of anus,
examination with an ultrasonic wave scanner Type B, etc., the
diseases such as sclerosis of neurogenic urinary bladder and neck
of bladder, carcinoma of prostate, etc. and other diseases that
have impact on emiction. In accordance with the clinical diagnose,
they are suffered from BPH: IPSS>22 in average; MFR=10.6 ml/s
(one urine volume>152 ml); and bladder residue urine=51.6 ml in
average in accordance with the ultrasonic wave scanner Type B.
1.2 Treatment Methods
[0102] 2 weeks before treatment, they were not allowed to take
diuretic medicaments. In the treatment, they took the extract in
this Invention, once a tablet, twice a day, and they should take it
in the morning and evening with a empty stomach and drink warm
water together. They were treated and observed for one week and
four weeks. Before the treatment, 1 week and 4 weeks after
medicament supply, IPSS, urine flow rate, bladder residue urine,
pulse and blood pressure were measured separately. During the
treatment, all the other curative BPH medicaments and medicaments
that have influence on emiction were stopped. The side effects were
recorded. The examination and evaluation were processed with the t
check statistics.
2. Results
2.1 IPSS Evaluation
[0103] Before the treatment, one week and four weeks after the
treatment, the average IPSS value was 24.6.+-.3.4, 20.5.+-.3.2,
17.2.+-.4.1 in average separately. The IPSS values have obvious
difference between the values of one week and four weeks after the
treatment (P<0.01), and the IPSS was reduced by 16.6% and 30%
separately. (see Table 8)
2.2 Maximum Flow Rate (MFR)
[0104] Before the treatment, one week and four weeks after the
treatment, the recorded MFR was (10.6.+-.4.1)ml/s,
(12.1.+-.4.4)ml/s, and (14.1.+-.3.8)ml/s separately. The difference
before and after the treatment was obvious (P<0.01), and the MFR
were increased by 14.2% and 33% in average separately. (see Table
8)
2.3 Bladder Residue Urine
[0105] Before the treatment and one week and four weeks after the
treatment, in accordance with the celiac measurement with a
ultrasonic wave scanner Type B, the bladder residue urine was
(51.6.+-.38)ml, (41.+-.32)ml, and (33.+-.26)m1 separately with
obvious difference (P<0.01), and the average residue urine was
reduced by 20.5% and 36%. (see Table 8)
2.4 Side Effects
[0106] Before the treatment, one week and four weeks after the
treatment, no obvious changes occurred in the pulse and blood
pressure of patients, and also without depressed blood pressure.
TABLE-US-00008 TABLE 8 Comparison of improved urine flow before and
after taking the extract in this invention Before 1 week after 4
weeks after Time treatment treatment treatment P I-PSS value 24.6
.+-. 3.4 20.5 .+-. 3.2 17.2 .+-. 4.1 <0.01 (.dwnarw. 16.6%)
(.dwnarw. 30%) MFR(ml/s) 10.6 .+-. 4.1 12.1 .+-. 4.4 14.1 .+-. 3.8
<0.01 (.uparw. 14.2%) (.uparw. 33%) Residue urine 51.6 .+-. 38
41 .+-. 32 33 .+-. 26 <0.01 (ml) (.dwnarw. 20.5%) (.dwnarw.
36%)
[0107] 3. Discussion
[0108] From the viewpoint of the Chinese Traditional Medicine, the
emiction disorder caused by BPH belongs to the category of dysuria
and blocking. The dysuria said in the Chinese Traditional Medicine
refers to difficult emiction, slim and fragile urine line and
blocked urine. When man pisses uneasily and difficultly with light
degree of seriousness, it is dysuria. When man can not piss or it
is blocked with a full lower abdomen and acute degree of
seriousness, it is called blocking. Based on the principles,
methods, prescriptions and medicaments about dysuria and blocking
in the Chinese traditional medicine and combined with treatment
mechanism of the modern medicine, the solution of the
pharmaceutical composition in this invention is researched and
developed and is a kind of Chinese medicament of pure plants with
its main efficacy for improvement and treatment of emiction
disorders caused by benign prostate hyperplasia (BPH). Its features
are obvious curative effect and safe with strong immediate curative
effect.
[0109] The clinical experiments have shown that the said extract in
this invention can improve the subjective and objective symptoms of
senile BPH patients with its strong immediate curative effect. One
week after treatment, it can reduce patients' IPSS by 16.6% in
average, and increase patients' MFR by 14.2% in average, and reduce
patients' residue urine by 20.5% in average. In addition, side
effects occur very rarely when the extract of the Chinese
traditional medicament is taken to treat emiction disorders caused
by BPH.
* * * * *