WO2018212548A1 - Composition comprenant un extrait de zédoaire en tant que substance active pour la prévention, le soulagement ou le traitement de la vascularite - Google Patents

Composition comprenant un extrait de zédoaire en tant que substance active pour la prévention, le soulagement ou le traitement de la vascularite Download PDF

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Publication number
WO2018212548A1
WO2018212548A1 PCT/KR2018/005536 KR2018005536W WO2018212548A1 WO 2018212548 A1 WO2018212548 A1 WO 2018212548A1 KR 2018005536 W KR2018005536 W KR 2018005536W WO 2018212548 A1 WO2018212548 A1 WO 2018212548A1
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WIPO (PCT)
Prior art keywords
vasculitis
extract
composition
high cholesterol
preventing
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PCT/KR2018/005536
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English (en)
Korean (ko)
Inventor
김기모
채성욱
김윤희
임아랑
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한국 한의학 연구원
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Priority claimed from KR1020180054269A external-priority patent/KR102096345B1/ko
Application filed by 한국 한의학 연구원 filed Critical 한국 한의학 연구원
Publication of WO2018212548A1 publication Critical patent/WO2018212548A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form

Definitions

  • the present invention relates to a composition for the prevention, improvement or treatment of vasculitis containing an extract of the extract as an active ingredient, and more specifically to the prevention of vasculitis containing an extract of the extract which can be used as a functional food or pharmaceutical composition as an active ingredient. , To improve or treat compositions.
  • Vasculitis is one of the intractable conditions commonly recognized for autoimmune diseases and is characterized by inflammation of the blood vessel wall and thus tissue damage. Inflammation of the vessel wall causes ischemia in tissues that have been fed through the vessels, resulting in tissue damage. Since all types of blood vessels and blood vessels of all organs can be invaded, the symptoms and symptoms vary depending on the location and characteristics of the involved vessels. It may occur primary without underlying disease, or secondary with rheumatic arthritis such as rheumatoid arthritis or systemic lupus erythematosus.
  • Vasculitis includes diseases such as vasculitis, irritable vasculitis, giant cell arteritis (temporal arteritis) and Behcet's vasculitis.
  • vasculitis The cause of vasculitis is thought to be due to immune dysfunction or allergic reaction of our body.
  • the process of vasculitis begins when the immune system that recognizes its cells as an antigen first releases antibodies in a steady state.
  • the binding of an antibody to an antigen is called an immunocomplex, which is attached to the blood vessel wall, causing inflammation of the blood vessel wall.
  • vasculitis Patients with vasculitis have systemic symptoms such as fever, weight loss, loss of appetite, and weakness, and symptoms such as spots or nodules on the skin, pain in the limbs caused by exercise, difficulty breathing, kidney failure, gastrointestinal bleeding, and neurological disorders. appear. Clinical findings and course vary greatly depending on the type of vasculitis, and even the same vasculitis appears in various ways depending on the patient. Complications can include vision disorders, heart disease, myocardial infarction, dyspnea, pulmonary hemorrhage, nephritis, intestinal bleeding, intestinal necrosis, skin necrosis, and infection.
  • Curcuma zedoaria is dried root stem of Curcuma phaeocaulis of Zingiberaceae, and has been traditionally used for indigestion, gusts, colic, menstrual irregularities, stomach and digestive action, anticancer Action, hepatocyte protective action, etc. have been reported. It is also known to be effective in controlling pepper anthrax, and to have macrophage activating activity and pancreatic lipase inhibitory activity.
  • Korean Patent No. 1710081 discloses a composition and its use, including the extract of Achul which can increase the activity of TLR4 and TLR7 / 8, and induce the production of interferon ⁇
  • Korean Patent Publication No. 1287688 Although a composition for treating atopic dermatitis using a natural substance including azu is disclosed, there is no disclosure regarding a composition for preventing, improving or treating vasculitis containing the azu extract of the present invention as an active ingredient.
  • the present invention has been made by the above-described requirements, and provides a composition for the prevention, improvement or treatment of vasculitis, which contains the extract of Achul as an active ingredient, the expression of cathepsin known as the atherosclerosis-induced vascular inflammation markers
  • the present invention was completed by inhibiting vascular plaque formation and lipid accumulation in the aorta, and inhibiting the expression of vascular inflammatory factors.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of vasculitis, which contains the extract extract as an active ingredient.
  • the present invention provides a health functional food composition for preventing or improving vasculitis, which contains the extract of Ashal as an active ingredient.
  • the present invention relates to a composition for the prevention, improvement or treatment of vasculitis containing the extract of Achul as an active ingredient, the extract of the present invention inhibited plaque formation of blood vessels and lipid accumulation of the aorta increased by a high cholesterol diet, It is effective in reducing cathepsin expression in the aorta, suppressing the expression of the vascular inflammation marker HMGB1, and inhibiting the expression of the vascular inflammation factors CX3CL1, VCAM-1, ICAM-1, TNF- ⁇ and IL-6.
  • the composition of the present invention containing the extract extract as an active ingredient can be used as a functional material for preventing, improving or treating vasculitis.
  • FIG. 1 is a schematic diagram of an animal test method for confirming the vascular inflammation inhibitory effect by the administration of Achul extract in ApoE deficient mice induced with vasculitis through a high cholesterol diet.
  • Control is a normal diet group
  • HCD is a high cholesterol diet group
  • C2E is a high cholesterol diet and Achul extract group
  • statin is a high cholesterol diet and statin (positive control group).
  • Figure 3 is a result of oil-red-O (Oil-Red-O) staining the tissue in the aorta of the ApoE deficient mice induced vasculitis through a high cholesterol diet.
  • A is a micrograph
  • B is a result of quantifying a staining site.
  • Control is a normal diet group
  • HCD is a high cholesterol diet group
  • C2E is a high cholesterol diet and Achul extract administration group.
  • # Indicates that the fat accumulation of the high cholesterol diet group was significantly increased compared to the general diet group, p ⁇ 0.05.
  • * Indicates that the fat accumulation of the high cholesterol diet and the Achul extract group was significantly reduced compared to the high cholesterol diet group, p ⁇ 0.05.
  • Figure 4 is an image of the expression level of cathepsin in the aorta of ApoE deficient mice induced with vasculitis through a high cholesterol diet.
  • Control is a general diet group
  • HCD is a high cholesterol diet group
  • C2E-1 ⁇ 3 is a high cholesterol diet and Achul extract administration group
  • statin is a high cholesterol diet and statin (positive control group).
  • Control is a general diet group
  • HCD is a high cholesterol diet group
  • C2E-1 ⁇ 3 is a high cholesterol diet and Achul extract administration group
  • statin is a high cholesterol diet and statin (positive control group).
  • Figure 6 is a result of confirming the expression of the vascular inflammation marker HMGB1 by immunohistostaining by extracting the aorta of ApoE deficient mice induced by vasculitis through a high cholesterol diet.
  • A is a micrograph
  • B is a result of quantifying a staining site.
  • Control is a normal diet group
  • HCD is a high cholesterol diet group
  • C2E is a high cholesterol diet
  • Achul extract administration group # Indicates that the expression of HMGB1 in the high cholesterol diet group was significantly increased compared to the general diet group, p ⁇ 0.05.
  • * Indicates that the expression of HMGB1 in the high cholesterol diet and the Achul extract administration group was significantly decreased compared to the high cholesterol diet group, p ⁇ 0.05.
  • Figure 7 is a result of confirming the expression of vascular inflammatory factors (CX3CL1, VCAM-1, ICAM-1, TNF- ⁇ and IL-6) by extracting the aorta of the ApoE-deficient mouse induced vasculitis through a high cholesterol diet.
  • (A) is the result of developing protein expression through Western blot
  • (B) is the result of quantifying VCAM-1 protein expression.
  • Con is a general diet group
  • HCD is a high cholesterol diet group
  • C2E is a high cholesterol diet and Achul extract administration group
  • statin is a positive control group administered a high cholesterol diet and statin (statin).
  • * Indicates a significant increase in VCAM-1 expression in the high cholesterol diet group compared to the normal diet group, p ⁇ 0.05.
  • # Indicates that VCAM-1 expression was significantly decreased in the high cholesterol and achal extract or high cholesterol and statin-administered groups compared to the high cholesterol diet group, p ⁇ 0.05.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of vasculitis, which contains the extract of Achul as an active ingredient.
  • Ahchul to the extract it is preferable to extract using a lower alcohol, water or a mixture of C 1 to C 4 as a solvent, more preferably, of extracting with water.
  • the vasculitis of the present invention is preferably a vasculitis induced by a high cholesterol diet, and a vasculitis caused by a high cholesterol increases the concentration of blood cholesterol through a high cholesterol diet, resulting in a hypercholesterolemia state, and vascular endothelial cells are damaged. May be vasculitis caused by deposition of fat.
  • the vasculitis includes rheumatoid vasculitis, lupus vasculitis, multiple nodular arteritis, microscopic multiple vasculitis, Wegener's granulomatosis, Chuck-Strauss syndrome, Takayasu's arteritis, Henoch-Scholine purpura, urticaria vasculitis, irritable vasculitis, giant cell arteritis and Behcet's vasculitis It may be any one selected from the group consisting of, but is not limited thereto.
  • the composition may inhibit the expression of cathepsin or HMGB1.
  • composition may further comprise a suitable carrier, excipient or diluent commonly used in the manufacture of pharmaceutical compositions.
  • the pharmaceutical composition according to the present invention may be used in the form of capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols and the like, oral formulations, suppositories, and sterile injectable solutions, respectively, according to a conventional method.
  • Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate And various compounds or mixtures including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like in the pharmaceutical composition. Mix is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
  • Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • utopsol macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • Suitable dosages of the pharmaceutical compositions of the present invention may be prescribed in various ways depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be.
  • the pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration and the like.
  • the present invention also relates to a nutraceutical composition for the prevention or improvement of vasculitis, which contains the extract of Ashal as an active ingredient.
  • the dietary supplement composition of the present invention may be one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.
  • the health functional food composition of the present invention When used as a food additive, the health functional food composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method.
  • the active ingredient may be appropriately used depending on the purpose of use (prevention or improvement).
  • the nutraceutical composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less with respect to the raw material.
  • the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
  • dietary supplement there is no particular limitation on the type of dietary supplement.
  • foods to which the health functional food composition may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products, including ice cream, various soups, drinks, tea Drinks, alcoholic beverages and vitamin complexes, and the like includes all of the health food in the conventional sense.
  • the nutraceutical composition of the present invention may be prepared as a food, in particular a functional food.
  • the functional food of the present invention may include ingredients that are commonly added. Examples include proteins, carbohydrates, fats, nutrients and seasonings.
  • natural carbohydrates or flavors may be included as additional ingredients in addition to the active ingredient.
  • the natural carbohydrates can be monosaccharides (e.g. glucose, fructose, etc.), disaccharides (e.g. maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g. dextrins, cyclodextrins, etc.) or sugar alcohols (e.g.
  • the flavourant may be a natural flavourant (eg, taumartin, stevia extract, etc.) and a synthetic flavourant (eg, saccharin, aspartame, etc.).
  • the carbonation agent etc. which are used for a drink can be contained further.
  • the ratio of the above-mentioned ingredients is not critical, it is generally selected from 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.
  • the dried extract was pulverized by drying, and then, by adding reflux of 10 L to 1 kg of extract, and reflux-cooled once at 100 ° C. for 3 hours. Thereafter, the filtrate obtained using the filter paper was prepared by extracting the solvent by using a vacuum condenser to remove the solvent.
  • ApoE deficient mice that induced vasculitis in a high cholesterol diet ApoE deficient mice administered with a high cholesterol diet and the Achul extract of Preparation Example 1 or statin, a positive control, and ApoE deficient mice that did not induce vasculitis in a normal diet
  • Morphology of the aorta and liver was confirmed by H & E staining, and the degree of lipid accumulation was confirmed by oil-red-O staining.
  • ApoE deficient mice were subjected to a high cholesterol diet or a general diet for a total of 12 weeks, as shown in FIG. 1, and the daily extracts of Achul extract (100 mg / kg / day) or statin (10 mg / kg / day) of Preparation Example 1 Oral administration.
  • mice were anesthetized with ketamine and xylazine after the diet, and the aortic vessels and livers were removed from the anesthetized mice, and the tissues were fixed with 4% (v / v) formaldehyde. Thereafter, the immobilized tissue was embedded with paraffin to make a block, and then the tissue was sectioned with a microtome for H & E (haematoxylin and eosin) staining or oil-red-O staining. was carried out.
  • H & E haematoxylin and eosin
  • ApoE deficient mice that induced vasculitis in a high cholesterol diet ApoE deficient mice administered with a high cholesterol diet and the Achul extract of Preparation Example 1 or statin, a positive control, and ApoE deficient mice that did not induce vasculitis in a normal diet
  • the expression level of cathepsin in the aortic vessels was analyzed using a probe.
  • HMGB1 as an inflammatory marker in the blood vessels of ApoE deficient mice that induced vasculitis in a high cholesterol diet
  • ApoE deficient mice that received the high cholesterol diet and the Achul extract of Preparation Example 1 and ApoE deficient mice that did not induce vasculitis in a normal diet was confirmed through immunohistostaining.
  • HMGB1 increased by high cholesterol diet (HCD) was concurrently administered with the extract (C2E). When it was confirmed that significantly reduced.
  • ApoE deficient mice that induced vasculitis in a high cholesterol diet ApoE deficient mice administered with a high cholesterol diet and the Achul extract of Preparation Example 1 or statin, a positive control, and ApoE deficient mice that did not induce vasculitis in a normal diet
  • the protein was extracted by dissolving the tissue through a tissue mill. The extracted protein was confirmed the expression level of vascular inflammatory factors through Western blot. As a result, the expression of vascular inflammatory factors (CX3CL1, VCAM-1, ICAM-1, TNF- ⁇ and IL-6) increased by the high cholesterol diet as shown in FIG. Decreased.
  • the extract of the present invention can effectively improve vasculitis induced by a high cholesterol diet.

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Abstract

La présente invention concerne une composition pharmaceutique comprenant un extrait de zéodaire en tant que substance active efficace pour prévenir, soulager ou traiter la vascularite. Un extrait de zédoaire selon la présente invention présente l'effet remarquable de supprimer la formation de plaque induite par un régime riche en cholestérol dans les vaisseaux sanguins et le stockage de lipides dans l'aorte, diminuer l'expression de cathepsine dans l'aorte, supprimer l'expression du marqueur d'inflammation vasculaire HMGB1 et supprimer l'expression de facteurs d'inflammation vasculaire, de sorte que la composition comprenant un extrait de zédoaire en tant que substance active selon la présente invention puisse être utile en tant qu'agent thérapeutique contre la vascularite ou aliment fonctionnel de santé pour prévenir ou soulager la vascularite.
PCT/KR2018/005536 2017-05-15 2018-05-15 Composition comprenant un extrait de zédoaire en tant que substance active pour la prévention, le soulagement ou le traitement de la vascularite WO2018212548A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20170060000 2017-05-15
KR10-2017-0060000 2017-05-15
KR1020180054269A KR102096345B1 (ko) 2017-05-15 2018-05-11 아출 추출물을 유효성분으로 함유하는 혈관염의 예방, 개선 또는 치료용 조성물
KR10-2018-0054269 2018-05-11

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011093880A (ja) * 2009-10-02 2011-05-12 Geo Co Ltd 抗炎症組成物ならびにそれを含有する皮膚外用剤、化粧料および健康食品
KR20160047329A (ko) * 2014-10-22 2016-05-02 한국생명공학연구원 아출의 추출물을 포함하는 조성물 및 그의 용도
KR20160067614A (ko) * 2014-12-04 2016-06-14 한국생명공학연구원 아출 추출물을 유효성분으로 포함하는 어류의 스쿠티카충 감염 질환 예방 또는 치료용 조성물
KR101743617B1 (ko) * 2015-11-26 2017-06-05 한국식품연구원 봉출 추출물을 포함하는 염증성 질환 치료용 약학 조성물

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011093880A (ja) * 2009-10-02 2011-05-12 Geo Co Ltd 抗炎症組成物ならびにそれを含有する皮膚外用剤、化粧料および健康食品
KR20160047329A (ko) * 2014-10-22 2016-05-02 한국생명공학연구원 아출의 추출물을 포함하는 조성물 및 그의 용도
KR20160067614A (ko) * 2014-12-04 2016-06-14 한국생명공학연구원 아출 추출물을 유효성분으로 포함하는 어류의 스쿠티카충 감염 질환 예방 또는 치료용 조성물
KR101743617B1 (ko) * 2015-11-26 2017-06-05 한국식품연구원 봉출 추출물을 포함하는 염증성 질환 치료용 약학 조성물

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KAUSHIK, M. L. ET AL.: "Evaluation of Anti-intlammatory Effect of Ethanolic and Aqueous Extracts of Curcuma Zedoaria Rose Root", INTERNATIONAL JOURNAL OF DRUG DEVELOPMENT & RESEARCH, vol. 3, no. 1, 2011, pages 360 - 365, XP055559484 *
ULLAH, A. ET AL.: "Evaluation of Antinociceptive, in-vivo & in-vitro Anti-inflammatory Activity of Ethanolic Extract of Curcuma Zedoaria Rhizome", BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, vol. 14, 2014, pages 1 - 12, XP021199426 *

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