WO2006123887A1 - Composition containing herb medicine for treating atopic dermatitis - Google Patents

Composition containing herb medicine for treating atopic dermatitis Download PDF

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Publication number
WO2006123887A1
WO2006123887A1 PCT/KR2006/001832 KR2006001832W WO2006123887A1 WO 2006123887 A1 WO2006123887 A1 WO 2006123887A1 KR 2006001832 W KR2006001832 W KR 2006001832W WO 2006123887 A1 WO2006123887 A1 WO 2006123887A1
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WIPO (PCT)
Prior art keywords
atopic dermatitis
linne
composition
herb medicine
treating atopic
Prior art date
Application number
PCT/KR2006/001832
Other languages
French (fr)
Inventor
Jeong-Jin Kim
Kyoo-Seok Ahn
Hee Kang
Original Assignee
Jeong-Jin Kim
Kyoo-Seok Ahn
Hee Kang
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Application filed by Jeong-Jin Kim, Kyoo-Seok Ahn, Hee Kang filed Critical Jeong-Jin Kim
Publication of WO2006123887A1 publication Critical patent/WO2006123887A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/482Cassia, e.g. golden shower tree
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284Atractylodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/532Agastache, e.g. giant hyssop
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/538Schizonepeta
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8964Anemarrhena
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders

Definitions

  • the present invention relates to a composition containing a herb medicine for
  • Atopic dermatitis is a disease in which inflammation is chronically caused in
  • T cell is associated with such an immune response, and cytokine secreted by the
  • ThI cytokine T cell is mainly classified into two types: ThI cytokine and Th2 cytokine.
  • ThI cytokine ThI cytokine
  • cytokine is associated with a cell-mediated immune response and the Th2 cytokine is
  • cytokines such as interleukin-4 (IL-4), IL-5, IL-13, etc. are excessively secreted, and
  • ThI cytokines such as interferon- y (IFN- Y ) secreted by the ThI
  • Immunoglobulin E continues to be
  • IL-4 the Th2 cytokine, functions to facilitate attachment of the bacteria to the skin
  • a steroid agent In order to treat such an atopic dermatitis, a steroid agent, an antihistaminic
  • the steroid agent such as an
  • agent may temporally alleviate the pruritus but develop various side effects if it is used for an extended time, and the antibiotic is used for treating a secondary infection by the
  • bacteria such as Staphylococcus sp., etc., but is not basically the remedy.
  • tacrolimus ProtopicTM
  • pimecrolimus ElidelTM
  • the skin may be weakened if they are used for an extended time.
  • the present invention is designed to solve the problems of the prior
  • cytokine compared to a secretion of the Th2 cytokine.
  • the present invention provides a
  • composition for treating atopic dermatitis including at least one herb medicine selected
  • Atractylodes japonica koidzumi Loranthus parasiticus (L) Merr., Foeniculum vulgare Miller, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Cimicifuga heracleifolia Komarov,
  • composition for treating atopic dermatitis will be described in detail, as follows.
  • composition for treating atopic dermatitis according to the present invention
  • composition for treating atopic dermatitis Preferably, the composition for treating atopic dermatitis
  • the present invention includes at least one herb medicine selected from the
  • the composition for treating atopic dermatitis according to the present invention includes at least one herb medicine selected from the group consisting of
  • the present invention is based on the finding that 150 herb medicines are
  • the ThI cytokine in comparison to a secretion of the Th2 cytokine, and therefore the
  • the present invention is based on the finding that the herb medicine having such a pharmacological effect is useful to treat atopic dermatitis.
  • the effect of treating atopic dermatitis For example, the effect of treating atopic dermatitis
  • atopic dermatitis patient may be determined by extracting blood from an atopic dermatitis patient, separating a
  • peripheral blood mononuclear cell from the blood, incubating the separated PBMC
  • the herb medicines used for the composition for treating atopic dermatitis according to the present invention may be included at various forms in the composition.
  • the herb medicine is thoroughly dried and ground into fine powder, and
  • the fine powder may be added to the composition of the present invention, and the
  • herb medicine is also extracted in a solvent, and then the extract may be added to the
  • composition of the present invention As the method for extracting the herb medicine
  • an enfleurage for exuding a herb medicine for a predetermined time at a relatively low temperature; a maceration similar to the enfleurage but exuding
  • composition for treating atopic dermatitis according to the present invention
  • a carrier may further include a carrier, a disintergrant, a binder, a lubricant, a wetting agent, an
  • composition may be any suitable suspending agent, an ointment, a cream, etc.
  • the composition may be any suitable suspending agent, an ointment, a cream, etc.
  • a tablet preferably formulated in various forms together with a tablet, a granulating agent, a pill,
  • composition includes various additives in addition to the herb medicine components such as the herb medicine powder, the herb
  • FIGs. 1 and 2 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 3 and 4 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 5 and 6 show photographs taken before/after atopic dermatitis is treated
  • composition containing a Coiz lacryma-jobi Linne var. ma-yuen stapf extract according to the present invention.
  • FIGs. 7 and 8 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 9 and 10 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 11 and 12 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 13 and 14 show photographs taken before/after atopic dermatitis is treated using a composition containing an Asparagus cochinchinensls Merrill extract according
  • FIGs. 15 and 16 show photographs taken before/after atopic dermatitis is treated using a composition containing an Agastache rugosa O. Kuntze extract according to the present invention.
  • FIGs. 17 and 18 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 19 and 20 show photographs taken before/after atopic dermatitis is treated using a composition containing an Atractylodes japonica koidzumi extract according to
  • FIGs. 21 and 22 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 23 and 24 show photographs taken before/after atopic dermatitis is treated
  • FIGs. 25 and 26 show photographs taken before/after atopic dermatitis is treated
  • the freeze-dried powders were dissolved in phosphate-buffered saline (PSB)
  • PSB phosphate-buffered saline
  • Lymphoprep (Axis-Shield PoC AS, Oslo, Norway) and the blood were put
  • PSB phosphate-buffered saline
  • resultant cell pellet was suspended in a RPMI 1640 medium (Invitrogen, U.S.) containing 10% FBS (fetal bovine serum), 1% antibiotic and an antifungal agent.
  • FBS fetal bovine serum
  • the cell suspension and a trypan blue solution were thoroughly mixed at a ratio of 1 : 1 , kept
  • the cell suspension, in which the cell number was adjusted, was seeded at an
  • Example 2 prepared in Example 1 was added at an amount of 100 ⁇ g/ml. After 48-hour
  • the cell suspension was collected, centrifuged to remove a supernatant, and
  • ThI cytokine interferon- y (IFN- ⁇ )
  • Th2 cytokine interleukin-4
  • IL-4 was measured using an ELISA method. Firstly, Each well of a 96-well plate
  • biotinylated detection antibody (Pharmingen, U.S.) was added to each well of the
  • IL-4 and the IFN- y were measured at a wavelength of 450 to 570 nm using a
  • IFN- Y value is 1.5 as listed in the following Table 1, it is meant that an amount of the
  • cytokines in the well containing the herb medicines is higher than that of the cytokines
  • herb medicines having the high ratio of IFN- Y value/IL-4 value may be useful to treat
  • composition for treating atopic dermatitis according to the present invention are listed in Table 1, and the results of some of the herb medicines, which were excluded in the
  • ThI cytokine IFN- Y , thereby to increase a ratio of "ThI cytokine/Th2 cytokine".
  • the herb medicines may be useful to treat atopic dermatitis.
  • compositions according to the present invention were compared
  • present invention has an excellent efficiency in stimulating the secretion of the ThI
  • composition according to the present invention is more useful to treat atopic
  • a hydrophilic ointment containing the composition of the present invention was prepared, as follows.
  • Example 1 were added to the water bath, warmed to approximately 75 ° C , and then a
  • the total weight was adjusted to 1,000 g, vigorously stirred once more to obtain an
  • hydrophilic ointment containing the composition of the present invention prepared as described above was spread on the test sites of a patient' skin for 5 months
  • FIG. 15 show photographs taken
  • FIG. 2 Before the treatment of atopic dermatitis, and FIG. 2, FIG. 4, FIG. 6, FIG. 8, FIG. 10,
  • FIG. 12, FIG. 14, FIG. 16, FIG. 18, FIG. 20, FIG. 22, FIG. 24 and FIG. 26 show
  • composition of the present invention has an excellent efficiency in treating atopic
  • the present invention provides a composition containing a herb medicine for
  • composition being useful to treat atopic dermatitis
  • composition for treating atopic dermatitis is safe for human beings since the herb medicines, which have been generally used and proven to be safe, are used herein.

Abstract

Disclosed is a composition containing a herb medicine for treating atopic dermatitis. The composition according to the present invention is safe and may be useful to treat atopic dermatitis.

Description

COMPOSITION CONTAINING HERB MEDICINE FOR TREATING ATOPIC
DERMATITIS
TECHNICAL FIELD
The present invention relates to a composition containing a herb medicine for
treating atopic dermatitis.
BACKGROUND ART
Atopic dermatitis is a disease in which inflammation is chronically caused in
skin because the skin is hypersensitive to factors that are, otherwise, not harmful to
normal human. That is to say, it has been known that the atopic dermatitis is caused
due to the hypersensitiveness of immune system to infection by bacteria, virus, fungus,
etc., certain substances such as pollen, etc., foods, synthetic chemical substances, etc.
T cell is associated with such an immune response, and cytokine secreted by the
T cell is mainly classified into two types: ThI cytokine and Th2 cytokine. The ThI
cytokine is associated with a cell-mediated immune response and the Th2 cytokine is
associated with an antibody immune response, and atopic dermatitis or other allergic
diseases are all developed since, when a balance of the two cytokines is upset, the Th2
cytokines such as interleukin-4 (IL-4), IL-5, IL-13, etc. are excessively secreted, and
then secretion of the ThI cytokines such as interferon- y (IFN- Y ) secreted by the ThI
cell is decreased antagonistically (see, Jujo K. et al., Decreased interferone gamma and
increased interleukin-4 production in atopic dermatitis promotes IgE synthesis. J Allergy
CHn Immunol 1992; 90: 323-31 and Tang ML. et al., Interleukin-4 and interferone-γ production in atopic and non-atopic children with asthma. Clin Exp Allergy 1995; 25: 515-21).
Also, many Staphylococcus sp. are colonized in skin of most atopic dermatitis patients, and their cell number accounts for approximately 107 CFU/cm2 that is as much
as 200 times higher than the normal human. Immunoglobulin E (IgE) continues to be
secreted due to the bacterial infection, and ceramidase, which is known to be secreted by
these bacteria, degrades ceramide that maintains a moisturizing ability in a hypodermal
tissue, and therefore pruritus is continuously induced to aggravate the dermatitis. IL-4, the Th2 cytokine, functions to facilitate attachment of the bacteria to the skin, and
therefore, once the atopic dermatitis is developed, the Staphylococcus sp. is propagated
in an uncontrolled manner (see, Donald YM. et al, Infection in atopic dermatitis. Curr
Opin Pediatr 2003; 15: 399-404 and Chos SH. et al., Preferential binding of
Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J
Invest Dermatol 2001; 116: 658-63).
In order to treat such an atopic dermatitis, a steroid agent, an antihistaminic
agent, an antibiotic agent, etc. have been used, but the steroid agent such as an
adrenocortical hormone has an excellent effect on an anti-inflammatory response and an
immunosuppressive response but may develop severe skin side effects if it is used for an
extended time and be additionally infected by the bacteria. Also, the antihistaminic
agent may temporally alleviate the pruritus but develop various side effects if it is used for an extended time, and the antibiotic is used for treating a secondary infection by the
bacteria such as Staphylococcus sp., etc., but is not basically the remedy.
Recently, tacrolimus (Protopic™) or pimecrolimus (Elidel™) has been used as the therapeutic agent for the atopic dermatitis, and both of the drugs have disadvantages
that they have an effect of rapidly alleviating symptoms of the atopic dermatitis since they are used as the immunosuppressive agent for suppressing expression of the
inflammatory cytokines, but their effect is temporal, and a natural defense mechanism of
the skin may be weakened if they are used for an extended time.
DISCLOSURE QF INVENTION
Accordingly, the present invention is designed to solve the problems of the prior
art, and therefore it is an object of the present invention to provide a composition
containing a herb medicine for treating atopic dermatitis, the herb medicine being
generally used, proven to be safe for human beings and capable of being used for
treating atopic dermatitis. More particularly, it is an object of the present invention to
provide a composition containing a herb medicine for treating atopic dermatitis, the herb
medicine being capable of stimulating a relatively increased secretion of the ThI
cytokine, compared to a secretion of the Th2 cytokine.
In order to accomplish the above object, the present invention provides a
composition for treating atopic dermatitis, including at least one herb medicine selected
from the group consisting of Cassia obtusifolia Linne, Angelica tenuissima Nakai, Agastache rugosa O. Kuntze, Platycodon grandiflorum A. De candole, Phragmites
communis Trinius, Salvia miltiorrhiza Bunge, Angelica gigas Nakai, Liriope platyphylla Wang et Tang, Hordeum vulgare Linne, Saussurea lappa Clarke, Saposhnikovia divaricata Schiskin, Dictamnus albus Linne, Angelica dahurica Bentham et Hooker,
Atractylodes japonica koidzumi, Loranthus parasiticus (L) Merr., Foeniculum vulgare Miller, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Cimicifuga heracleifolia Komarov,
Massa Medicata Fermentata, Cistanche deserticola Y. C. Ma, Coiz lacryma-jobi Linne
var. ma-yuen stapf, Hoelen rubra, Anemarrhena asphodeloides Bunge, Cnidium
officinale Makino, Gastrodia elata Blume, Asparagus cochinchinensls Merrill,
Trichosanthes kirilowii Maximowicz, Celosia argentia Linne, Alisma orientale
Juzepczuk, Cyperus rotundus Linne, Corydalis ternata Nakai, Schizonepeta tenuifolia
Briquet, Sesamum indicum Linne and Scutellaria baicalensis Georgi.
Hereinfater, the composition for treating atopic dermatitis according to the present invention will be described in detail, as follows.
The composition for treating atopic dermatitis according to the present invention
includes at least one herb medicine selected from the group consisting of Cassia
obtusifolia Linne, Angelica tenuissima Nakai, Agastache rugosa O. Kuntze, Platycodon
grandiflorum A. De candole, Phragmites communis Trinius, Salvia miltiorrhiza Bunge,
Angelica gigas Nakai, Liriope platyphylla Wang et Tang, Hordeum vulgare Linne,
Saussurea lappa Clarke, Saposhnikovia divaricata Schiskin, Dictamnus albus Linne, Angelica dahurica Bentham et Hooker, Atracty lodes japonica koidzumi, Loranthus
parasiticus(L) Merr., Foeniculum vulgare Miller, Dipsacus asperoides C. Y. Cheng et T.
M. Ai, Cimicifuga heracleifolia Komarov, Massa Medicata Fermentata, Cistanche
deserticola Y. C. Ma, Coiz lacryma-jobi Linne var. ma-yuen stapf, Hoelen rubra,
Anemarrhena asphodeloides Bunge, Cnidium officinale Makino, Gastrodia elata Blume, Asparagus cochinchinensls Merrill, Trichosanthes kirilowii Maximowicz, Celosia
argentia Linne, Alisma orientale Juzepczuk, Cyperus rotundus Linne, Corydalis ternata
Nakai, Schizonepeta tenuifolia Briquet, Sesamum indicum Linne and Scutellaria baicalensis Georgi. Preferably, the composition for treating atopic dermatitis
according to the present invention includes at least one herb medicine selected from the
group consisting of Agastache rugosa O. Kuntze, Angelica gigas Nakai, Atractylodes
japonica koidzumi, Anemarrhena asphodeloides Bunge, Asparagus cochinchinensls
Merrill, Schizonepeta tenuifolia Briquet and Scutellaria baicalensis Georgi. More
preferably, the composition for treating atopic dermatitis according to the present invention includes at least one herb medicine selected from the group consisting of
Atractylodes japonica koidzumi, Anemarrhena asphodeloides Bunge, Schizonepeta
tenuifolia Briquet and Scutellaria baicalensis Georgi.
The present invention is based on the finding that 150 herb medicines are
screened so as to find herb medicines for stimulating a relatively increased secretion of
the ThI cytokine in comparison to a secretion of the Th2 cytokine, and therefore the
herb medicines as listed above stimulates a relatively increased secretion of the ThI
cytokine. Also, the present invention is based on the finding that the herb medicine having such a pharmacological effect is useful to treat atopic dermatitis.
Various in vivo, ex vivo or in vitro methods may be used for determining an
effect of treating atopic dermatitis. For example, the effect of treating atopic dermatitis
may be determined by extracting blood from an atopic dermatitis patient, separating a
peripheral blood mononuclear cell (PBMC) from the blood, incubating the separated
PBMC, followed by reacting the incubated PBMC with the herb medicines to measure changes of secreted cytokines, but is not limited thereto.
The herb medicines used for the composition for treating atopic dermatitis according to the present invention may be included at various forms in the composition. For example, the herb medicine is thoroughly dried and ground into fine powder, and
then the fine powder may be added to the composition of the present invention, and the
herb medicine is also extracted in a solvent, and then the extract may be added to the
composition of the present invention. As the method for extracting the herb medicine
of the present invention, an enfleurage for exuding a herb medicine for a predetermined time at a relatively low temperature; a maceration similar to the enfleurage but exuding
a herb medicine at 35 to 45 °C ; a heating extraction method for exuding a herb
medicine at 60 to 120 °C ; a percolation method using a percolater; a distillation/cooling
extraction method, etc. may be used herein, but is not limited thereto. The composition for treating atopic dermatitis according to the present invention
may further include a carrier, a disintergrant, a binder, a lubricant, a wetting agent, an
emulsifying agent, a suspending agent, etc. for the purpose of its easy formulation, in
addition to the powder and extract of the herb medicine as described above, or be
formulated in various forms together with a tablet, a capsule, a granulating agent, a pill,
a solution, a suspending agent, an ointment, a cream, etc. The composition may be
preferably formulated in various forms together with a tablet, a granulating agent, a pill,
a solution, ointment, a cream, etc., wherein the composition includes various additives in addition to the herb medicine components such as the herb medicine powder, the herb
medicine extract, etc.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other features, aspects, and advantages of preferred embodiments of
the present invention will be more fully described in the following detailed description, taken accompanying drawings. In the drawings:
FIGs. 1 and 2 show photographs taken before/after atopic dermatitis is treated
using a composition containing an Alisma orientale Juzepczuk extract according to the present invention.
FIGs. 3 and 4 show photographs taken before/after atopic dermatitis is treated
using a composition containing a Cnidium officinale Makino extract according to the present invention.
FIGs. 5 and 6 show photographs taken before/after atopic dermatitis is treated
using a composition containing a Coiz lacryma-jobi Linne var. ma-yuen stapf extract according to the present invention.
FIGs. 7 and 8 show photographs taken before/after atopic dermatitis is treated
using a composition containing an Angelica dahurica Bentham et Hooker extract
according to the present invention.
FIGs. 9 and 10 show photographs taken before/after atopic dermatitis is treated
using a composition containing a Liriope platyphylla Wang et Tang extract according to
the present invention.
FIGs. 11 and 12 show photographs taken before/after atopic dermatitis is treated
using a composition containing a Platycodon grandiflorum A. De candole extract
according to the present invention.
FIGs. 13 and 14 show photographs taken before/after atopic dermatitis is treated using a composition containing an Asparagus cochinchinensls Merrill extract according
to the present invention.
FIGs. 15 and 16 show photographs taken before/after atopic dermatitis is treated using a composition containing an Agastache rugosa O. Kuntze extract according to the present invention.
FIGs. 17 and 18 show photographs taken before/after atopic dermatitis is treated
using a composition containing an Angelica gigas Nakai extract according to the present invention.
FIGs. 19 and 20 show photographs taken before/after atopic dermatitis is treated using a composition containing an Atractylodes japonica koidzumi extract according to
the present invention.
FIGs. 21 and 22 show photographs taken before/after atopic dermatitis is treated
using a composition containing a Schizonepeta tenuifolia Briquet extract according to the present invention.
FIGs. 23 and 24 show photographs taken before/after atopic dermatitis is treated
using a composition containing a Scutellaria baicalensis Georgi extract according to the
present invention.
FIGs. 25 and 26 show photographs taken before/after atopic dermatitis is treated
using a composition containing an Anemarrhena asphodeloides Bunge extract according
to the present invention.
BEST MODES FOR CARRYING OUT THE INVENTION Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, it should be understood
that other equivalents and modifications could be made thereto without departing from
the spirit and scope of the invention. Example 1: Preparation of Herb Medicine Sample
Each of the herb medicines was weighed, put into distilled water, kept overnight,
and then extracted. Subsequently, supernatants were freeze-dried and ground into
powders. The freeze-dried powders were dissolved in phosphate-buffered saline (PSB)
to a concentration of 100 //g/ml, and then filtered through a 0.2 μm filter to prepare test
samples.
Experimental example 1 : Measurement of Cytokine Secretion
<Culture of Peripheral Blood Mononuclear Cell >
Blood was extracted from an atopic dermatitis patient and put into a heparinized
tube. Then, Lymphoprep (Axis-Shield PoC AS, Oslo, Norway) and the blood were put
into a centrifugal tube at a ratio of 1 :2, and then centrifuged for 20 minutes at a rotary
speed of 1,000 rpm to separate a middle fraction containing the cell. Subsequently,
phosphate-buffered saline (PSB) was added, and centrifuged 3 additional times. The
resultant cell pellet was suspended in a RPMI 1640 medium (Invitrogen, U.S.) containing 10% FBS (fetal bovine serum), 1% antibiotic and an antifungal agent. The cell suspension and a trypan blue solution were thoroughly mixed at a ratio of 1 : 1 , kept
for approximately 5 minutes, and then the numbers of dead cell dyed with the trypan
blue solution and the total cell were counted. Cell viability was determined using such
a trypan blue assay, and then the cell number was adjusted to 1.5 X 106/m£.
The cell suspension, in which the cell number was adjusted, was seeded at an
amount of 0.5 ml into each of 48 wells, and PHA (phytohemagglutinin, Sigma, Cat. #L-8902, U.S.) was added at an amount of 50 βg/ml and simultaneously the sample
prepared in Example 1 was added at an amount of 100 μg/ml. After 48-hour
incubation, the cell suspension was collected, centrifuged to remove a supernatant, and
then stored in -20 °C until it is used later in the following cytokine assay.
<Cytokine Assay>
The ThI cytokine, interferon- y (IFN- γ ), and the Th2 cytokine, interleukin-4
(IL-4) was measured using an ELISA method. Firstly, Each well of a 96-well plate
was coated with capture antibodies against IL-4 and IFN- Y (Pharmingen, U.S.) at 4°C
overnight. Then, the 96-well plate was washed 3 times, and then phosphate-buffered
saline containing 10 % FBS was put into each well of the 96-well plate at an amount of
200 //fVwell and kept for 1 hour to carry out a blocking reaction. The 96-well plate
was washed 3 times again to remove a blocking buffer completely, and then the sample
diluted with the blocking buffer was added at an amount of 100 μi and incubated at
4 °C overnight. The resultant 96-well plate was washed 5 times, and then a
biotinylated detection antibody (Pharmingen, U.S.) was added to each well of the
96-well plate, incubated for 1 hour at a room temperature, and then washed 7 times.
Then, 100 ≠ of streptavidin-HRP was added, and 50 μl of IM H2SO4 was added at
30 minutes after the streptavidin-HRP addition. Subsequently, optical densities of the
IL-4 and the IFN- y were measured at a wavelength of 450 to 570 nm using a
microplate reader (Tecan, Austria).
As a control, the samples, prepared in Example 1 using the same blood sample,
were not added but only PHA was added to each of the herb medicine, and then an optical density of the samples was measured. Because the cytokine secretion is
different according to each of the herb medicines, the measurement results of the IL-4
and IFN- Y on each of the herb medicines are represented by increase ratios of the
corresponding cytokines to the IL-4 and IFN- Y of the control. For example, if an
IFN- Y value is 1.5 as listed in the following Table 1, it is meant that an amount of the
cytokines in the well containing the herb medicines is higher than that of the cytokines
in the well devoid of the herb medicines as much as 1.5 times (when the same blood
sample was used in both the cases).
The herb medicines exhibiting undesirable results in the first measurement were
excluded, and then the same experiment was repeated using the remaining herb
medicines, except that a blood sample of another patient was used herein. The
experiments were also repeated in the same manner as described above until the reliable
results were obtained, except that blood samples of other patients were used very time.
In the following Tables 1 and 2, the term "Ratio " represents a ratio of an
IFN- Y value/an IL-4 value, and an amount of the secreted ThI cytokine is increased in
comparison to that of the secreted Th2 cytokine as the ratio increases, and therefore the
herb medicines having the high ratio of IFN- Y value/IL-4 value may be useful to treat
atopic dermatitis. The results of the herb medicines, which can be included in the
composition for treating atopic dermatitis according to the present invention, are listed in Table 1, and the results of some of the herb medicines, which were excluded in the
mentioned-above experiments, are listed in Table 2. Table 1
Figure imgf000013_0001
Figure imgf000014_0001
Table 2
Figure imgf000014_0002
Figure imgf000015_0001
Figure imgf000016_0001
Figure imgf000017_0001
Figure imgf000018_0001
Figure imgf000019_0001
Figure imgf000020_0001
As listed in Tables 1 and 2, it was understood that the herb medicines, selected
from the group consisting of Cassia obtusifolia Linne, Angelica tenuissima Nakai,
Agastache rugosa O. Kuntze, Platycodon grandiflorum A. De candole, Phragmites
communis Trinius, Salvia miltiorrhiza Bunge, Angelica gigas Nakai, Liriope platyphylla
Wang et Tang, Hordeum vulgare Linne, Saussurea lappa Clarke, Saposhnikovia
divaricata Schiskin, Dictamnus albus Linne, Angelica dahurica Bentham et Hooker,
Atractylodes japonica koidzumi, Loranthus parasiticus(L) Merr., Foeniculum vulgare
Miller, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Cimicifuga heracleifolia Komarov,
Massa Medicata Fermentata, Cistanche deserticola Y. C. Ma, Coiz lacryma-jobi Linne
var. ma-yuen stapf, Hoelen rubra, Anemarrhena asphodeloides Bunge, Cnidium
officinale Makino, Gastrodia elata Blume, Asparagus cochinchinensls Merrill,
Trichosanthes kirilowii Maximowicz, Celosia argentia Linne, Alisma orientale
Juzepczuk, Cyperus rotundus Linne, Corydalis ternata Nakai, Schizonepeta tenuifolia
Briquet, Sesamum indicum Linne and Scutellaria baicalensis Georgi, stimulate secretion
of the ThI cytokine, IFN- Y , thereby to increase a ratio of "ThI cytokine/Th2 cytokine".
As a result, the herb medicines may be useful to treat atopic dermatitis.
Experimental example 2: Comparison of Cytokine Secretion
Some of the compositions according to the present invention were compared
with pimecrolimus which is a main component of Elidel Cream™ (Novartis Korea, Korea) as the therapeutic agent of atopy. The experiment was repeated in the same manner as described above in Experimental example 1, except that a 1 nM
pimecrolimus solution was used as a comparative control. The results are listed in the
following Table 3. Table 3
Figure imgf000021_0001
Figure imgf000022_0001
As listed in Table 3, it was revealed that the composition according to the
present invention has an excellent efficiency in stimulating the secretion of the ThI
cytokine, IFN- γ , to increase a ratio of "ThI cytokine/Th2 cytokine" in comparison to
the pimecrolimus that is the therapeutic agent of atopy. Accordingly, it was considered
that the composition according to the present invention is more useful to treat atopic
dermatitis.
Experimental example 3: Measurement of Effect on Treatment of Atopic
Dermatitis
<Preparation of Hydrophilic Ointment >
In order to measure an effect on the treatment of atopic dermatitis, a hydrophilic ointment containing the composition of the present invention was prepared, as follows.
250 g of white vaseline and 200 g of stearyl alcohol were added to a water bath,
heat-melted, mixed, and then kept at 75 °C . Then, 1 g of methyl p-hydroxybenzoate, 1
g of propyl p-hydroxybenzoate, 120 g of prophylene glycol, 10 g of glyceryl
monosterate, 40 g of polyoxyethylene hydrogenated castor oil 60 and 5 g of the
freeze-dried powder of the herb medicine of the present invention as prepared in
Example 1 were added to the water bath, warmed to approximately 75 °C , and then a
suitable amount of the prepared distilled water was added thereto and stirred vigorously.
The total weight was adjusted to 1,000 g, vigorously stirred once more to obtain an
emulsifying solution, and then stirred while cooling until the emulsifying solution
became hard.
< Measurement of Effect on Treatment of Atopic Dermatitis >
The hydrophilic ointment containing the composition of the present invention prepared as described above was spread on the test sites of a patient' skin for 5 months
to measure whether or not the atopic dermatitis is alleviated. The results obtained
using Alisma orientale Juzepczuk were shown in FIGs. 1 and 2; the results obtained using Cnidium officinale Makino were shown in FIGs. 3 and 4; the results obtained
using Coiz lacryma-jobi Linne var. ma-yuen stapf were shown in FIGs. 5 and 6; the
results obtained using Angelica dahurica Bentham et Hooker were shown in FIGs. 7 and
8; the results obtained using Liriope platyphylla Wang et Tang were shown in FIGs. 9 and 10; the results obtained using the results obtained using Platycodon grandiflorum A.
De candole were shown in FIGs. 11 and 12; the results obtained using Asparagus cochinchinensls Merrill were shown in FIGs. 13 and 14; the results obtained using Agastache rugosa O. Kuntze were shown in FIGs. 15 and 16; the results obtained using
Angelica gigas Nakai were shown in FIGs. 17 and 18; the results obtained using
Atractylodes japonica koidzumi were shown in FIGs. 19 and 20; the results obtained
using Schizonepeta tenuifolia Briquet were shown in FIGs. 21 and 22; the results
obtained using Scutellaria baicalensis Georgi were shown in FIGs. 23 and 24; and the
results obtained using Anemarrhena asphodeloides Bunge were shown in FIGs. 25 and
26, respectively. In the drawings, FIG. 1, FIG. 3, FIG. 5, FIG. 7, FIG. 9, FIG. 11, FIG.
13, FIG. 15, FIG. 17, FIG. 19, FIG. 21, FIG. 23 and FIG. 25 show photographs taken
before the treatment of atopic dermatitis, and FIG. 2, FIG. 4, FIG. 6, FIG. 8, FIG. 10,
FIG. 12, FIG. 14, FIG. 16, FIG. 18, FIG. 20, FIG. 22, FIG. 24 and FIG. 26 show
photographs taken after the treatment of atopic dermatitis.
As seen from each of the photograph results, it was revealed that the
composition of the present invention has an excellent efficiency in treating atopic
dermatitis.
INDUSTRIAL APPLICABILITY
The present invention provides a composition containing a herb medicine for
treating atopic dermatitis, the composition being useful to treat atopic dermatitis, and
the composition for treating atopic dermatitis is safe for human beings since the herb medicines, which have been generally used and proven to be safe, are used herein.

Claims

What is claimed is;
1. A composition for treating atopic dermatitis, comprising at least one herb
medicine selected from the group consisting of Cassia obtusifolia Linne, Angelica
tenuissima Nakai, Agastache rugosa O. Kuntze, Platycodon grandiflorum A. De candole,
Phragmites communis Trinius, Salvia miltiorrhiza Bunge, Angelica gigas Nakai, Liriope platyphylla Wang et Tang, Hordeum vulgare Linne, Saussurea lappa Clarke,
Saposhnikovia divaricata Schiskin, Dictamnus albus Linne, Angelica dahurica Bentham
et Hooker, Atractylodes japonica koidzumi, Loranthus parasiticus(L) Merr., Foeniculum
vulgare Miller, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Cimicifuga heracleifolia
Komarov, Massa Medicata Fermentata, Cistanche deserticola Y. C. Ma, Coiz
lacryma-jobi Linne var. ma-yuen stapf, Hoelen rubra, Anemarrhena asphodeloides
Bunge, Cnidium officinale Makino, Gastrodia elata Blume, Asparagus cochinchinensls
Merrill, Trichosanthes kirilowii Maximowicz, Celosia argentia Linne, Alisma orientale
Juzepczuk, Cyperus rotundus Linne, Corydalis ternata Nakai, Schizonepeta tenuifolia
Briquet, Sesamum indicum Linne and Scutellaria baicalensis Georgi.
2. The composition for treating atopic dermatitis according to claim 1 ,
wherein the herb medicine is at least one selected from the group consisting of Agastache rugosa O. Kuntze, Angelica gigas Nakai, Atractylodes japonica koidzumi, Anemarrhena asphodeloides Bunge, Asparagus cochinchinensls Merrill, Schizonepeta
tenuifolia Briquet and Scutellaria baicalensis Georgi.
3. The composition for treating atopic dermatitis according to claim 2,
wherein the herb medicine includes at least one selected from the group
consisting of Atractylodes japonica koidzumi, Anemarrhena asphodeloides Bunge,
Schizonepeta tenuifolia Briquet and Scutellaria baicalensis Georgi.
4. The composition for treating atopic dermatitis according to any of claims
I to 3, wherein the atopic dermatitis is treated by enhancing an amount of the secreted
Th2 cytokine, compared to the secreted ThI cytokine.
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