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WO2019177327A1 - Composition comprenant un extrait de schisandra chinensis en tant que principe actif pour la prévention, le soulagement ou le traitement de l'arthrite - Google Patents

Composition comprenant un extrait de schisandra chinensis en tant que principe actif pour la prévention, le soulagement ou le traitement de l'arthrite Download PDF

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Publication number
WO2019177327A1
WO2019177327A1 PCT/KR2019/002819 KR2019002819W WO2019177327A1 WO 2019177327 A1 WO2019177327 A1 WO 2019177327A1 KR 2019002819 W KR2019002819 W KR 2019002819W WO 2019177327 A1 WO2019177327 A1 WO 2019177327A1
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WIPO (PCT)
Prior art keywords
arthritis
composition
extract
prevention
schisandra chinensis
Prior art date
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Ceased
Application number
PCT/KR2019/002819
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English (en)
Korean (ko)
Inventor
김동선
이윤미
손은정
육흥주
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Korea Institute of Oriental Medicine KIOM
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Korea Institute of Oriental Medicine KIOM
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Publication date
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Publication of WO2019177327A1 publication Critical patent/WO2019177327A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/79—Schisandraceae (Schisandra family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system

Definitions

  • the present invention relates to a composition for the prevention, improvement or treatment of arthritis containing Schizandra chinensis extract as an active ingredient.
  • inflammatory diseases including arthritis
  • Inflammatory diseases caused by these inflammatory reactions include gastritis, colitis, arthritis, nephritis, hepatitis, arteriosclerosis, cancer or degenerative diseases.
  • effective drugs or treatments for the prevention and treatment of arthritis diseases have not been developed.
  • Arthritis refers to the development of inflammatory changes in the joints due to various causes such as aging, mechanical damage, and immune disorders.
  • osteoarthritis is a type of arthritis, also called degenerative arthritis, and refers to arthritis caused by degenerative changes in cartilage and surrounding bone in lubricated joints.
  • osteoarthritis is a disease characterized by gradual loss of articular cartilage, hypertrophy of bone located below the cartilage, bone formation at the edge of the joint, and nonspecific synovial inflammation.
  • Osteoarthritis is a disease caused by cartilage damage caused by aging or excessive physical pressure (eg, obesity, trauma, etc.). Therefore, osteoarthritis represents severe pain and movement disorders such as knee joints, knee joints, hip joints, etc., which are heavily weighted, resulting in deformation of joints when left for a long time.
  • gouty arthritis is an inflammation caused by the deposition of uric acid in the spaces and tissues of the joints. Urate is increased by increasing the concentration of uric acid (the product of the body's metabolism of purine, which is obtained through food). (Uric acid is in the form of urate in the blood, body fluids, and joint fluids.) Crystals deposit in the cartilage, tendons, and surrounding tissue of the joint. This phenomenon causes inflammation of the joints, leading to recurrent attacks with extreme pain.
  • Schizandra chinensis is a dicotyledonous plant, a deciduous vine of Magnolia schizandra. Mainly growing in the valley, the trunk is brown and has the property of climbing trees. The leaves are alternate, wide oval, long oval or egg-shaped, with hairs on the rear leaf veins and tooth-shaped teeth on the edges. Flowers bloom in June-July, single flowers, slightly reddish yellowish white. After flowering, the female flower jaw grows 3 ⁇ 5cm long and the fruit runs with water. Fruits are berry ( ⁇ ), almost round, with several spikes. It ripens red in August-September and contains 1-2 reddish brown seeds. Young sprouts eat as herbs.
  • the fruit is mixed with five flavors of sour, sweet, bitter, salty and spicy. It is prescribed for nourishment, tonic, Jinhae, expectoration, and cold in Chinese medicine. It is prescribed for seawater, oil well, gugal, dohan, acute hepatitis. . In the private sector, Schisandra tea is made and drunk.
  • the prior art related to Schisandra chinensis No. 2007-0109004 discloses a pharmaceutical composition for the prevention and treatment of bone metabolism disease, oxidative stress, inflammatory diseases, including Schisandra chinensis extract, Korea Patent Publication No. 2005-09
  • 0019830 discloses a functional food for preventing autoimmune diseases containing Schizandra chinensis extract as an active ingredient, a composition for preventing, improving or treating arthritis containing Schizandra extract of the present invention as an active ingredient is not disclosed.
  • the present invention is derived from the above demands, Schisandra ( Schisandra) chinensis) provides a composition for the prevention, improvement or treatment of arthritis containing leaf or stem extract as an active ingredient, Schisandra of the present invention ( Schisandra chinensi s) leaf or stem extract is not cytotoxic, has the effect of inhibiting the production of inflammation-induced NO, and statistically significantly reduces the increased foot thickness caused by gouty arthritis, as well as the content of IL-1 ⁇ The effect of reducing was superior to the Schisandra chinensis fruits, and when the Schisandra chinensis extract was administered in an osteoarthritis animal model, the present invention was completed by confirming that the weight loss rate was statistically significantly increased.
  • the present invention Schizandra ( Schisandra) chinensi s) It provides a health functional food composition for the prevention or improvement of arthritis containing leaf or stem extract as an active ingredient.
  • the present invention also provides a pharmaceutical composition for the prevention or treatment of arthritis, containing Schizandra leaf or stem extract as an active ingredient.
  • Schisandra ( Schisandra) chinensi s) relates to a composition for the prevention, improvement or treatment of arthritis containing a leaf or stem extract as an active ingredient, specifically, Schisandra of the present invention ( Schisandra chinensi s) leaf or stem extract is not cytotoxic, has the effect of inhibiting the production of NO induced by inflammation, and statistically significantly reduces the thickness of the feet increased by gouty arthritis, as well as the content of IL-1 ⁇ In the osteoarthritis animal model, administration of the Schisandra chinensis leaf extract of the present invention has a statistically significant effect of reducing the weight-bearing rate.
  • NMMA is a positive control group, N-Monomethyl arginine.
  • FIG. 2 shows that the production of NO increased by the treatment of LPS (lipopolysaccharide) in RAW 264.7 cells, the result of confirming that the production of NO increased by LPS by treating the Schizandra leaf or stem extract of the present invention.
  • Con is LPS-treated RAW264,7 cells, *, **** is a statistically significant NO production reduction compared to Con, * is p ⁇ 0.05, **** is p ⁇ 0.0001.
  • Figure 3 is a result confirming the effect of reducing the foot thickness (foot thickness) in C57BL6 mice induced gouty arthritis by MSU (monosodium ureate).
  • Con is a control group that did not induce gouty arthritis
  • MSU is a group that caused gouty arthritis by administration of MSU, Schisandra chinensis-Schisandra chinensis, Schisandra chinensis-Schisandra chinensis, MSU + Schisandra chinensis fruit, leaf or stem extract
  • MSU monosodium ureate
  • Figure 4 is a result confirming the reducing effect of IL-1 ⁇ in C57BL6 mice induced gouty arthritis by MSU (monosodium ureate).
  • Con is a control group that did not induce gouty arthritis
  • MSU is a group that caused gouty arthritis by administration of MSU, Schisandra chinensis-Schisandra chinensis, Schisandra chinensis-Schisandra chinensis, MSU + Schisandra chinensis fruit, leaf or stem extract
  • MSU monosodium ureate
  • Figure 5 is the result showing the hind limb weight load rate (%) of the SD rat.
  • Con is a negative control group
  • MIA monosodium iodoacetate
  • Indomethacin is a positive control group
  • Schisandra chinensis leaf-300 is a group of 300 mg / kg MIA and Schisandra chinensis extract
  • #### means that the weight-bearing rate of the osteoarthritis-induced group by MIA was significantly reduced compared to the negative control group, which means p ⁇ 0.0001.
  • *, **, ***, **** is an experimental group of MIA and Schisandra chinensis extract (300mg / kg, 150mg / kg) in parallel treatment; Alternatively, the weight-bearing rate (%) of the positive control group treated with MIA and indomethacin increased compared to the osteoarthritis-induced group treated with MIA, where * is p ⁇ 0.05, ** is p ⁇ 0.01, and *** Is p ⁇ 0.001 and **** means p ⁇ 0.0001.
  • Schisandra ( Schisandra) chinensi s) relates to a nutraceutical composition for the prevention or improvement of arthritis containing leaf or stem extract as an active ingredient.
  • the arthritis is osteoarthritis or gouty arthritis, but is not limited thereto.
  • the composition may be characterized by inhibiting inflammatory cytokines and pain, and the pain may be pain due to arthritis.
  • the Schisandra chinensis leaf or stem extract may be prepared by a method comprising the following steps, but is not limited thereto:
  • the extraction solvent in step 1) is preferably water, lower alcohols of C 1 ⁇ C 4 or mixtures thereof, more preferably 70% (v / v) ethanol extract, but is not limited thereto.
  • the extraction of Schisandra chinensis leaves or stems may use all conventional methods known in the art, such as filtration, hot water extraction, dipping extraction, reflux cooling extraction, and ultrasonic extraction.
  • Concentration under reduced pressure of step 3) is preferably a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto.
  • the drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.
  • composition is preferably, but not limited to, prepared in any one formulation selected from powders, granules, pills, tablets, capsules, candy, syrups and beverages.
  • the Schizandra leaf or stem extract may be added as it is, or may be used together with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment).
  • the composition of the present invention is added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight based on the raw materials.
  • the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
  • Examples of foods to which the extract or fractions thereof may be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, drinks, tea , Drinks, alcoholic beverages and vitamin complexes, and includes all the health functional foods in the conventional sense.
  • composition of the present invention When the composition of the present invention is used as a health beverage, various flavors, natural carbohydrates, and the like may be contained as additional components, as in general beverages.
  • natural carbohydrates are sugars such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as textine and cyclotenstrin, xylitol, sorbitol and erythritol.
  • sweetening agent natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used.
  • the ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention.
  • the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages.
  • the composition of the present invention may contain a pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical, but the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.
  • the present invention also relates to a pharmaceutical composition for the prevention or treatment of arthritis, containing Schizandra leaf or stem extract as an active ingredient.
  • the arthritis is preferably, but not limited to, osteoarthritis or gouty arthritis.
  • composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredient, and may be various oral or parenteral formulations.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid preparations for oral administration include capsules, powders, granules, tablets, pills, and the like, which may comprise at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
  • lubricants such as magnesium stearate, talc and the like are also used.
  • Liquid preparations for oral administration include suspensions, emulsions, syrups, aerosols and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc., 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 the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • suppository As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycero gelatin and the like can be used.
  • parenteral administration it is desirable to select either external or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dura or cerebrovascular injections.
  • composition according to the invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, the effective amount of the level of the disease, the severity, the drug activity of the patient , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of the drug, and other factors well known in the medical arts.
  • the compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.
  • the dosage of the composition of the present invention varies depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the disease of the patient, the daily dosage of Schisandra chinensis leaf or stem extract 0.01-2,000 mg / kg, preferably 30-500 mg / kg, more preferably 50-300 mg / kg, based on the amount, can be administered 1-6 times per day.
  • the compositions of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers.
  • RAW 264.7 cells which are mouse macrophage lines, were dispensed in 96-well plates, followed by incubation for 24 hours or 48 hours by treatment of Schizandra ethanol extract prepared in Example 1 by concentration (25, 50 ⁇ g / ml) It was. After culturing the cells, the MTT solution was added and reacted for 4 hours, and then the absorbance of 540 nm was measured using an ELISA reader. The relative cell viability was calculated by comparison with the control group.
  • LPS 500 ng / ml
  • the Schisandra chinensis ethanol extract prepared in Example 1 was treated by concentration (25, 50 ⁇ g / ml) for 24 hours. Incubated. After taking the culture supernatant, the amount of NO was measured according to the manufacturer's method using Griess reagent.
  • the paw tissue obtained by the autopsy was immersed in RIPA buffer solution, and the tissue was crushed to measure the expression level of IL-1 ⁇ protein, which is an inflammatory marker in the supernatant, by ELISA, and cholchicine as a positive control.
  • IL-1 ⁇ protein which is an inflammatory marker in the supernatant, by ELISA, and cholchicine as a positive control.
  • MIA monosodium iodoacetate -Induced Effects of Schizandrae Fructus Extract on Body Weight in Osteoarthritis-Induced Osteoarthritis
  • Hind limb weight load was measured using a foot weigher (Incapacitance tester, Linton instrument Co., UK, Ser No. 01/45/25). In osteoarthritis-induced rats in the tester's holder, the pain of the osteoarthritis stood on the normal foot without MIA, so the weight of both feet was unbalanced and the weight of the MIA-treated foot was relatively light. When measuring the weight of the foot, the weight (g) of both feet was measured without the SD rat's belly touching the sensor of the device.
  • the weight load rate (%) was calculated by the method of Equation 1 below.
  • the weight load is the force supported by the foot, and in the normal case, the weight of both feet is balanced so that the weight load ratio of one foot is shown as 50%, but as the pain increases due to osteoarthritis, the weight load rate (%) of the hind limbs in which osteoarthritis is induced is increased. Lowers.
  • % Weight load [weight of osteoarthritis-induced hind limb / (weight of hind limb of foot)] ⁇ 100

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Abstract

La présente invention concerne une composition contenant un extrait de feuilles ou de tiges de Schisandra chinensis en tant que principe actif pour la prévention, le soulagement ou le traitement de l'arthrite. Plus particulièrement, l'extrait de feuilles ou de tiges de Schisandra chinensis selon la présente invention n'est pas cytotoxique, a pour effet d'inhiber la production de NO induite par l'inflammation, réduit l'épaisseur d'un pied gonflé par l'arthrite goutteuse, et diminue une teneur en IL-1β. L'extrait de feuilles de Schisandra chinensis selon la présente invention a pour effet d'augmenter la mise en charge réduite dans un modèle animal d'arthrose avec une signification statistique. Ainsi, l'extrait peut être utilisé utilement pour la prévention, le soulagement ou le traitement de l'arthrite.
PCT/KR2019/002819 2018-03-12 2019-03-12 Composition comprenant un extrait de schisandra chinensis en tant que principe actif pour la prévention, le soulagement ou le traitement de l'arthrite Ceased WO2019177327A1 (fr)

Applications Claiming Priority (2)

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KR20180028632 2018-03-12
KR10-2018-0028632 2018-03-12

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WO2019177327A1 true WO2019177327A1 (fr) 2019-09-19

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KR102668703B1 (ko) * 2022-12-28 2024-05-24 주식회사 웰레스트 오미자와 발아녹두를 유효성분으로 함유하는 염증질환 개선, 예방 또는 치료용 조성물

Citations (5)

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KR20050014615A (ko) * 2003-07-30 2005-02-07 학교법인 인하학원 오미자 추출물을 유효성분으로 함유하는 관절염 예방 및치료용 조성물
KR20110036317A (ko) * 2009-10-01 2011-04-07 재단법인 제주테크노파크 항염증성 조성물
KR20150067585A (ko) * 2013-12-10 2015-06-18 동의대학교 산학협력단 오미자 추출물을 포함하는 항염 활성 증진용 조성물과 그 제조방법
KR20150115414A (ko) * 2014-04-04 2015-10-14 한국생명공학연구원 오미자 추출물의 에틸아세테이트 분획물을 유효성분으로 포함하는 염증 질환의 예방 및 치료용 약학적 조성물 또는 상처치유용 약학적 조성물
KR20170045463A (ko) * 2015-10-17 2017-04-27 동의대학교 산학협력단 오미자 추출물을 유효성분으로 포함하는 IL-1β에 의한 관절염의 예방 또는 개선용 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050014615A (ko) * 2003-07-30 2005-02-07 학교법인 인하학원 오미자 추출물을 유효성분으로 함유하는 관절염 예방 및치료용 조성물
KR20110036317A (ko) * 2009-10-01 2011-04-07 재단법인 제주테크노파크 항염증성 조성물
KR20150067585A (ko) * 2013-12-10 2015-06-18 동의대학교 산학협력단 오미자 추출물을 포함하는 항염 활성 증진용 조성물과 그 제조방법
KR20150115414A (ko) * 2014-04-04 2015-10-14 한국생명공학연구원 오미자 추출물의 에틸아세테이트 분획물을 유효성분으로 포함하는 염증 질환의 예방 및 치료용 약학적 조성물 또는 상처치유용 약학적 조성물
KR20170045463A (ko) * 2015-10-17 2017-04-27 동의대학교 산학협력단 오미자 추출물을 유효성분으로 포함하는 IL-1β에 의한 관절염의 예방 또는 개선용 조성물

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