WO2012036446A2 - 천연물질을 이용한 아토피 치료용 조성물 - Google Patents

천연물질을 이용한 아토피 치료용 조성물 Download PDF

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WO2012036446A2
WO2012036446A2 PCT/KR2011/006754 KR2011006754W WO2012036446A2 WO 2012036446 A2 WO2012036446 A2 WO 2012036446A2 KR 2011006754 W KR2011006754 W KR 2011006754W WO 2012036446 A2 WO2012036446 A2 WO 2012036446A2
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weight
parts
composition
rhizoma
atopic dermatitis
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PCT/KR2011/006754
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English (en)
French (fr)
Korean (ko)
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WO2012036446A3 (ko
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송용원
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Song Yong-Won
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Priority to JP2012534130A priority Critical patent/JP5176008B2/ja
Priority to KR1020127022740A priority patent/KR101287688B1/ko
Publication of WO2012036446A2 publication Critical patent/WO2012036446A2/ko
Publication of WO2012036446A3 publication Critical patent/WO2012036446A3/ko

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9064—Amomum, e.g. round cardamom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • the present invention hot water by mixing rhubarb, barrel, gardenia, chajeonja, veins and single axis 3 to 15 parts by weight, 3 to 10 parts by weight, 3 to 10 parts by weight, 8 parts by weight, 8 parts by weight, 8 parts by weight, respectively It relates to a composition for treating atopy containing the extracted active ingredient.
  • the present invention the construction worker, Baekdugu, cloves, Mokyang, health, ginseng, Dongguk, Baekbokyeong, Baekchul, Gilgyeong, dermis, Gwakyang, nutmeg, founded, Seokchangpo, Shiho, Betelang, Hwangnyeon, Windproof, Osuyu, Hubak, Rhubarb, Cheonmundong , Crust, baekbaek, astragalus, cheoncho, vigor, resources, hyangbuja, licorice, small fennel, keg, makmundong, samseong, earl, broiler, gardenia, gardenia, tea, malt, constriction, green skin It relates to a composition for treating atopy containing an active ingredient.
  • the range of skin diseases includes atopic dermatitis, contact dermatitis, seborrheic dermatitis, molar eczema, tachycardia, congestive dermatitis, heterogeneous eczema, sebaceous eczema, and self-sensitizing eczema. Etc. are included.
  • environmental factors, genetic predispositions, immunological reactions, and abnormalities of the skin barrier may be the main causes, and in large part, it may be considered that skin diseases are caused by exogenous stimulants and / or endogenous secretions.
  • inflammatory factors such as excess NO (nitric oxide) and PGE 2 (prostaglandin E 2 ) are formed by inducible NO synthase (iNOS, NOS-II) and COX2 (cyclooxygenase2) in the inflammatory process in the body. do.
  • excess NO nitric oxide
  • PGE 2 prostaglandin E 2
  • COX2 cyclooxygenase2
  • NOS-II is expressed when exposed to lipopolysaccharide (LPS) and various inflammatory-induced cytokines, and NOS-II is the most important and pathologically important function of NOS-II. Known.
  • immunoglobulin E acts on proteins secreted from keratinocytes, causing autoimmune hypersensitivity reactions and exacerbating skin diseases.
  • Langerhans cells present in the skin when IgE and the receptor FcRI bind to the antigen invading from the outside, MCP-1 (monocyte chemotactic protein 1) and interleukin-16 (interleukin-16) Will secrete.
  • MCP-1 monocyte chemotactic protein 1
  • interleukin-16 interleukin-16
  • Langerhans cells also deliver antigens to T-cells to induce Th 2 (helper T cell 2) proliferation.
  • monocytes are collected into the skin and monocytes are differentiated into inflammatory dendritic cells (IDECs), which are inflammatory cytokines TNF- ⁇ and IL-1 (Interleukin-1). And excessive secretion of IL-6 leads to a process of exacerbating skin diseases.
  • IDECs inflammatory dendritic cells
  • TNF- ⁇ and IL-1 Interleukin-1
  • the IL-1 family includes IL-1 ⁇ , IL-1 ⁇ , IL-1RA, and IL-1 ⁇ is known to be bioactive in precursors, but IL-1 ⁇ is bioactive only in mature bodies.
  • steroids There are steroids as immunosuppressive agents, and IFN- ⁇ and antihistamine are typical bioregulators.
  • Korean Patent Application No. 10-2007-0010080 discloses an atopic therapeutic agent of natural ingredients, including Root, Root root, Yogurt, Angelica, and Jaso.
  • Korean Patent Publication No. 2006-0058530 describes a mixed extract of burdock, xinhua, thistle, turmeric, and Schizandra chinensis which exhibits itching effect.
  • Korean Patent Publication No. 2007-0095588 discloses a special herbal composition for the treatment of atopic dermatological diseases and eoseongcho, donkey, wormwood, cheongung, fresh vinegar, firewood, pine needles, mint, green bean, apricot Seeds, rosin, edible mushrooms, ginger, hyeonsam, jepi, green tea, marigold, bellflower, black beans are described.
  • Korean Patent Laid-Open Publication No. 2006-0074038 describes a mixed extract of gold and silver, Angelica, Bupyeongcho, dew, marigold, aloe, and gold in a composition having a prophylactic effect of atopic dermatitis.
  • the present invention hot water by mixing rhubarb, barrel, gardenia, chajeonja, veins and single axis 3 to 15 parts by weight, 3 to 10 parts by weight, 3 to 10 parts by weight, 8 parts by weight, 8 parts by weight, 8 parts by weight, respectively
  • a composition for treating atopy containing the extracted active ingredient it is intended to solve the technical problem.
  • the present invention the construction worker, Baekdugu, cloves, Mokyang, health, ginseng, Dongguk, Baekbokyeong, Baekchul, Gilgyeong, dermis, Gwakyang, nutmeg, founded, Seokchangpo, Shiho, Betelang, Hwangnyeon, Windproof, Osuyu, Hubak, Rhubarb, Cheonmundong , Crust, baekbaek, astragalus, cheoncho, vigor, resources, hyangbuja, licorice, small fennel, keg, makmundong, samseong, earl, broiler, gardenia, gardenia, tea, malt, constriction, green skin
  • a composition for treating atopy containing an active ingredient it is intended to solve the technical problem.
  • composition for treating atopic dermatitis of the present invention has a remarkable effect of improving and treating atopic dermatitis by continuously taking it without bringing side effects.
  • Example 1 is a view showing the results of experiments on the cytotoxicity of the sample according to Example 1.
  • Example 2 is a view showing the results of experiments DPDP scavenging ability of the sample according to Example 1.
  • Example 3 is a view showing the results of experiments in the NO production inhibition of the sample according to Example 1.
  • Example 4 is a view showing the results of experiments on the effect of IL-1 ⁇ production of the sample according to Example 1.
  • Example 5 is a view showing the results of experiments on the effect of IL-6 production of the sample according to Example 1.
  • Example 6 is a view showing the results of experiments affecting the production of MCP-1 sample according to Example 1.
  • Example 7 is a view showing the results of experiments on the effect on the TNF- ⁇ production of the sample according to Example 1.
  • Example 8 is a view showing the results of experiments on the TNF- ⁇ gene expression of the sample according to Example 2.
  • FIG. 9 is a view showing the results of experiments affecting the expression of the IL-6 gene of the sample according to Example 2.
  • FIG. 10 is a view showing the results of experiments on the effect on COX2 gene expression of the sample according to Example 2.
  • FIG. 11 is a view showing the results of experiments on the effect on the expression of NOS-II gene of the sample according to Example 2.
  • Example 12 is a view showing the results of experiments on the effect of the production of MCP-1 sample according to Example 2.
  • Example 13 is a view showing the results of experiments on the effect of IL-6 production of the sample according to Example 2.
  • Example 14 is a view showing the results of experiments affecting the production of IL-8 sample according to Example 2.
  • the present applicant interpreted atopic disease from the viewpoint of oriental medicine, and devised a therapeutic composition.
  • a therapeutic composition As a main component of the composition, rhubarb, neck, gardenia, chajeon, veins, and short axis are examined.
  • Atopic dermatitis is also commonly referred to as febrile fever, and atopic dermatitis patients commonly know that the body has a lot of fever.
  • rhubarb, throat and gardenia function to communicate the heat of the small intestine and large intestine.
  • the chason, axial axis, gardenia, and vein communicate with the bladder to remove toxins from the body.
  • the bladder is not simply an organ for urine discharge, but is located at the bottom of the human body and is an important organ covering the whole body.
  • Example 1 In order to prepare a composition for treating atopic dermatitis to be used in Example 1, 3 to 15 g of rhubarb, 3 to 10 g of neck, 3 to 10 g of gardenia, 8 g of tea, 8 g of veins and 8 g of shrunken were heated in 1 L of water for 2 to 4 hours. An extract was obtained.
  • the extract was filtered and then lyophilized to prepare an extract powder.
  • the filtration process of the extract was used gauze and / or filter paper (filter paper), it was lyophilized by adding water to the concentrated.
  • Example 2 is made clear in advance that the composition was focused on the removal of heat poisoning as well as the balance of the five viscera.
  • Mokhyang, Dongguk, Siho, Samneung, Seongjak, Baekjak, Cheongpi, and Hyangbuja perform the functions of raising the anger of the liver and raising the energy of the scattered liver.
  • rhubarb, gardenia, windproof, rhubarb, strong bow, keg, nutmeg communicate the energy of the small intestine, large intestine.
  • licorice is used to harmonize each ingredient to make it stronger and detoxify the poison.
  • rhubarb 3 ⁇ 15g, neck 3 ⁇ 10g, gardenia 3 ⁇ 10g, charcoal 8g, gut 8g, single axis 8g which is the composition of the composition for treating atopy used in Example 1 Phosphorus, Baekdugu, Clove, Mokyang, Health, Ginseng, Angelica, Baekbokyeong, Baekchul, Gilgyeong, Dermis, Gwakhyang, Nutmeg, founded, Seokchangpo, Shiho, Betelang, Hwangnyeon, Windproof, Osuyu, Hubak, Cheonmun-dong, Crust, Hwangbaek, Hwanggi, Cheoncho, vigor, resources, Hyangbuja, licorice, Sohyang, Mcmundong, Samseong, Baekjak, broiler, Cheongpi, it is also possible to extract the composition by mixing 1
  • composition for treating atopy according to Example 1, rhubarb, keg, gardenia, chacha, veins, and shrunk, respectively, was prepared into 90 to 120 mesh powder, respectively, 3 to 15 parts by weight, 3 to 10 parts by weight, and 3 to 5 parts by weight. 10 parts by weight, 8 parts by weight, 8 parts by weight, and 8 parts by weight of mixed dough to prepare a 0.3-0.5cm diameter ring (pill).
  • An atopy treatment composition according to Example 2 Baekdugu, Clove, Mokyang, Health, Ginseng, Angelica, Baekbokyeong, Baekchul, Gilkyung, Dermis, Gwakyang, Nutmeg, Bulgogi, Seokchangpo, Shiho, Betelang, Hwangnyeon, Windproof, Osuyu , Bakbak, rhubarb, astronomical dong, crust, baekbaek, astragalus, cheoncho, vigor, resources, hyangbuja, licorice, small fennel, neck, makmundong, samseong, count, broiler, gardenia, tea, gumac, pyeonyak, cheongpi each 90 It is prepared from mesh to 120 mesh powder and mixed and mixed into 1 to 15 parts by weight to prepare a pill (pill) having a diameter of 0.3 to 0.5 cm.
  • Example of taking the composition of Example 1 and the pills of Example 3-1 Example of taking the composition of Example 1 and the pills of Example 3-1
  • compositions and pills according to Examples 1 to 3 are administered orally, it is revealed that the dosage of the composition controls the appropriate amount according to the age, sex, weight, degree of atopic dermatitis of the patient.
  • the administration period of the compositions and pills according to Examples 1 to 3 takes about 2 to 6 months.
  • Pills are recommended to take 7 rings for 5-10 years old, 15 rings for 10-15 years old, 18 rings more than that, and pills 30 minutes after meals, preferably with water. If there is, dilute the sugar or honey.
  • Patients under 5 years old are easy to take in liquid form, take three times a day to take about 120cc 30 minutes after meals, patients over 5 years old is preferably about 200cc.
  • Pills are 5 to 10 years old 30 ring, 10 to 15 years old 40 ring, more preferably take 50 rings.
  • Raw 264.7 cells were incubated in 96 well plates at 10 4 cells / well for 24 hours, and then the samples were incubated at 25, 50, 100 and 200 ug / ml for 24 hours. After incubation, 10ul of WST solution was added, followed by reaction for 30 minutes in a CO 2 incubator (37 ° C., 5% CO 2 ), and the change in absorbance at 450 nm was measured to express the cell viability of the control group as a percentage.
  • the free radical scavenging activity test was performed using a stable free radical DPPH, mixing 150 ul of 0.2 mM DPPH solution dissolved in ethanol and 100 ul of samples (25, 50, 100, 200, 400, 800 ug / ml), respectively, at 37 ° C. After reacting for 30 minutes at, the absorbance at 517 nm was measured. For the control group, distilled water was added instead of the sample solution, and ethanol was added instead of the DPPH solution to obtain a correction value. Free radical scavenging rate was calculated according to the following equation, and the result is expressed as a concentration (IC50) capable of eliminating 50% of free radicals.
  • IC50 concentration
  • % Clearance ⁇ (absorbance of control-absorbance of sample addition) / absorbance of control ⁇ x100
  • the sample according to Example 1 in the Raw 264.7 cell line showed high scavenging ability in a concentration-dependent manner, and the sample according to Example 1 showed an antioxidant effect.
  • Raw 264.7 cells were inoculated in 96 well plates at 10 4 cells / well, incubated for 24 hours, treated with 25, 50, 100 and 200 ug / ml of each sample, and treated with LPS 1 ug / ml for another 24 hours. Incubated for After 50ul of N1 buffer was treated in each well, after 10 minutes of dark reaction at room temperature, 50ul of N2 buffer was treated in each well, and reacted for 10 minutes, and the absorbance was measured at 540 nm. NO concentration of the culture was determined using the concentration-specific standard curve of the nitrite standard.
  • LPS Lipopolysaccharide
  • TNF- ⁇ Tumor necrosis factor- ⁇
  • IL-6 Interleukin-6
  • IL- It is known to increase inflammation-induced cytokines such as 1 [beta] (Interleukin-1 [beta]).
  • the sample according to Example 1 in the Raw 264.7 cell line reduced total NO production induced by LPS in a concentration-dependent manner, indicating that the sample according to Example 1 showed an anti-inflammatory effect. Able to know.
  • Raw 264.7 cells were dispensed into 6 well plates at 3 ⁇ 10 5 cells / ml, incubated for 24 hours, and then the samples were treated at concentrations of 25, 50, 100 and 200 ug / ml, respectively, and treated with LPS 1 ug / ml. .
  • cell culture medium was collected, and IL-1 ⁇ , IL-6, MCP-1, and TNF- ⁇ contained in the culture solution were measured using a custom-made 4-plex cytokine Milliplex panel. The analysis was done by a Milliplex analyst.
  • the sample according to Example 1 in the Raw 264.7 cell line reduced IL-1 ⁇ production induced by LPS in a concentration-dependent manner, and the sample according to Example 1 showed an anti-inflammatory effect. It can be seen.
  • the sample according to Example 1 in the Raw 264.7 cell line reduced TNF- ⁇ production induced by LPS in a concentration-dependent manner, and the sample according to Example 1 showed an anti-inflammatory effect. It can be seen.
  • Experimental Examples 1 to 7 showed that the sample according to Example 1 exhibited high DPPH scavenging ability in a concentration-dependent manner in Raw 264.7 cell line, and induced total NO, IL-1 ⁇ and TNF- ⁇ induced by LPS. As a result, it can be seen that the sample according to Example 1 shows antioxidant and anti-inflammatory effects.
  • 100 mg of the extract powder of the composition for treating atopic dermatitis according to Example 2 was dissolved in 10 ml of sterile distilled water and used by filtration.
  • Raw 264.7 cell lines were divided into 1 ⁇ 10 6 cells in a 24 well plate, treated with 100 and 50 ⁇ g / mL of each sample, and after 1 hour, LPS 2 ⁇ g / mL was added to each well and incubated for 6 hours. It was centrifuged for 5 minutes at 2,000 rpm. After centrifugation, the supernatant was removed, and 500 ⁇ l of RNAzolB was added thereto and mixed until dissolved. 50 ⁇ l of chloroform (CHCl3) was added to the mixed suspension, and then mixed again for 15 seconds.
  • CHCl3 chloroform
  • DEPC diethyl pyrocarbonate
  • Reverse transcription reaction was performed by reacting 3 ⁇ g of prepared total RNA with DNase I (10 U / ⁇ l) 2 U / tube for 30 minutes in a 37 ° C. heating block, then denatured at 75 ° C. for 10 minutes, and thus 2.5 ⁇ l 10 mM dNTPs mix, 1 ⁇ l random sequence hexanucleotides (25 pmole / 25 ⁇ l), 1 ⁇ l RNase inhibitor (20 U / ⁇ l) as RNA inhibitor, 1 ⁇ l 100 mM DTT, 4.5 ⁇ l 5 ⁇ RT buffer (250 mM, Tris-HCl, After addition of pH 8.3, 375 mM KCl, 15 mM MgCl 2), 1 ⁇ l of M-MLV RT (200 U / ⁇ l) was added again to a final volume of 20 ⁇ l with DEPC treated distilled water.
  • DNase I 10 U / ⁇ l 2 U / tube for 30 minutes in a 37 ° C
  • the 20 ⁇ l reaction mixture was mixed well and centrifuged at 2,000 rpm for 5 seconds to react for 60 minutes in a 37 ° C. heating block to synthesize first-strand cDNA, and then left at 95 ° C. for 5 minutes to obtain M-MLV RT. After inactivation, the synthesized cDNA was used for polymerase chain reaction (PCR).
  • PCR polymerase chain reaction
  • Real time PCR was performed for 2 minutes at 50 ° C. and 10 minutes at 94 ° C. for pre-denaturation. The reaction was repeated 40 times for 15 seconds at 95 ° C. and 1 minute at 60 ° C.
  • the sample administration group and the control group measured the RQ (relative quantitative) value by quantifying the quantitative PCR of the target group using the following formula using GAPDH as the internal standard.
  • Example 2 reduces the TNF- ⁇ gene expression induced by LPS in the Raw 264.7 cell line.
  • Example 2 reduced IL-6 gene expression induced by LPS in a raw 264.7 cell line in a concentration-dependent manner.
  • Example 2 reduces COX2 gene expression induced by LPS in the Raw 264.7 cell line.
  • Example 2 reduced NOS-II gene expression induced by LPS in a Raw 264.7 cell line in a concentration-dependent manner.
  • Experimental Examples 13 to 14 reveals that the experiment preparation process of Experimental Example 12 was performed in the same manner.
  • Example 2 reduces the production of MCP-1 induced by house dust mite in the THP-1 cell line.
  • Example 2 reduces the production of IL-6 induced by house dust mites in the THP-1 cell line.
  • Example 2 reduces the production of IL-8 induced by house dust mite in the THP-1 cell line.
  • Example 2 reduces the production of MCP-1, IL-6 and IL-8 induced by house dust mite in THP-1 cell line.
  • Example 2 exhibited an anti-inflammatory effect by inhibiting gene expression of inflammatory cytokines and generation of inflammatory cytokines.

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PCT/KR2011/006754 2010-09-14 2011-09-10 천연물질을 이용한 아토피 치료용 조성물 WO2012036446A2 (ko)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2012534130A JP5176008B2 (ja) 2010-09-14 2011-09-10 アトピー治療用組成物
KR1020127022740A KR101287688B1 (ko) 2010-09-14 2011-09-10 천연물질을 이용한 아토피 피부염 치료용 조성물

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KR20100090022 2010-09-14
KR10-2010-0090022 2010-09-14

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CN103656413A (zh) * 2013-12-19 2014-03-26 青岛友铭辰生物技术有限公司 一种治疗荨麻疹的中药组合物
CN104042978A (zh) * 2014-06-28 2014-09-17 蚌埠明日欣医药有限公司 一种治疗玫瑰糠疹的中药混合物
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KR20190002775A (ko) * 2017-06-29 2019-01-09 주식회사두웰바이오 으름 추출물 또는 이의 분획물을 유효성분으로 함유하는 아토피성 피부염 예방 또는 치료용 조성물
CN116019862A (zh) * 2023-02-21 2023-04-28 云南云科特色植物提取实验室有限公司 一种具备多功效位点的祛痘组合物及其制备方法与应用

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KR102222362B1 (ko) * 2014-07-01 2021-03-04 주식회사 엘지생활건강 한약재 추출물을 포함하는 항염 또는 트러블 개선용 화장료 조성물
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KR102095621B1 (ko) * 2017-10-25 2020-03-31 이충식 식품 첨가물의 제조방법
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