KR101616604B1 - a mbst composition of functon of athritis protection and treatment - Google Patents

a mbst composition of functon of athritis protection and treatment Download PDF

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KR101616604B1
KR101616604B1 KR1020130152785A KR20130152785A KR101616604B1 KR 101616604 B1 KR101616604 B1 KR 101616604B1 KR 1020130152785 A KR1020130152785 A KR 1020130152785A KR 20130152785 A KR20130152785 A KR 20130152785A KR 101616604 B1 KR101616604 B1 KR 101616604B1
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composition
extract
arthritis
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mbst
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KR20150067435A (en
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김동희
최학주
심부용
박지원
김은아
전지애
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대전대학교 산학협력단
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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
    • A61K36/17—Gnetophyta, e.g. Ephedraceae (Mormon-tea family)
    • 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)
    • A61K36/26—Aristolochiaceae (Birthwort family), e.g. heartleaf
    • 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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/714—Aconitum (monkshood)

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Abstract

본 발명은 관절염에 효능이 있는 약재 조성물로서 더욱 구체적으로는 마황, 부자, 세신을 이용한 조성물로 관절염에 예방 및 치료에 효과가 있는 조성물 및 이를 포함하는 약제학적 조성물에 관한 것이다.
본 발명은 마황 추출물, 부자 추출물, 세신 추출물을 혼합하여 조성한 관절염의 치료와 예방의 기능이 있는 조성물을 제공한다.
또한 마황 추출물 100중량부에 부자 추출물 50~100중량부, 세신 10~20중량부 혼합하여 조성한 것에 특징이 있는 관절염의 치료와 예방의 기능이 있는 조성물을 제공한다.
또한 상기의 조성물이 혼합된 관절염의 치료와 예방의 기능이 있는 약제학적 조성물을 제공한다.The present invention relates to a pharmaceutical composition having efficacy for arthritis, more specifically, to a composition using mahwang, rich, and cesin, which is effective for prevention and treatment of arthritis, and a pharmaceutical composition containing the same.
The present invention provides a composition having the function of treating and preventing arthritis, which is formed by mixing a magpie extract, a rich extract, and a cedma extract.
The present invention also provides a composition having the function of treating and preventing arthritis, which is characterized in that 100 to 10 parts by weight of a maggot extract is mixed with 50 to 100 parts by weight of an extract and 10 to 20 parts by weight of a sesquin.
Also provided is a pharmaceutical composition having the function of treating and preventing arthritis in which the composition is mixed.

Description

관절염에 효능이 있는 마황부자세신 조성물{a mbst composition of functon of athritis protection and treatment}[0001] The present invention relates to a mabst composition for the treatment of arthritis,

본 발명은 관절염에 효능이 있는 약재 조성물로서 더욱 구체적으로는 마황, 부자, 세신을 이용한 조성물로 관절염에 예방 및 치료에 효과가 있는 조성물 및 이를 포함하는 약제학적 조성물에 관한 것이다.
The present invention relates to a pharmaceutical composition having efficacy for arthritis, more specifically, to a composition using mahwang, rich, and cesin, which is effective for prevention and treatment of arthritis, and a pharmaceutical composition containing the same.

류마티스 관절염이 발병되면 여러 가지 염증 세포의 침윤과 관절 내의 만성 염증 반응이 일어나고 pannus의 형성으로 인하여 연골조직의 파괴와 관절 뼈조직의 부식 및 변형을 초래하게 된다 (Cai L et al . , Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16(1): 10-21).
When rheumatoid arthritis develops, inflammatory cell infiltration and chronic inflammatory reaction within the joints occur, resulting in destruction of cartilage tissue and erosion and deformation of joint bone tissue due to the formation of pannus (Cai L et al., Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16 (1): 10-21).

류마티스 관절염의 원인은 아직까지 정확하게 규명되지 않았으나, 어떤 항원 물질에 대한 생체 면역 반응의 결과 생산되는 cytokine을 비롯한 주요 면역 반응 매개 물질의 작용에 의해 지속적인 염증 반응이 나타남으로써 연골조직이 손상되고 뼈의 손상을 가져와 관절 기능을 제대로 할 수 없게 되는 것으로 알려져 있다 (Feldmann M et al ., Role ofcytokines in rheumatoid arthritis. Annu Rev Immunol. 1996, 14: 397-440).
Although the cause of rheumatoid arthritis has not yet been elucidated yet, the continuous inflammatory response due to the action of the major immune response mediators, including the cytokines produced as a result of bioimmune reactions to certain antigenic substances, (Feldmann et al., Role of cystokines in rheumatoid arthritis, Annu Rev Immunol 1996, 14: 397-440).

특히, TNF- , IL-1 그리고 IL-6와 같은 염증성 cytokine이 염증 반응 및 관절 손상에 주요 역할을 하는 것으로 보고 되어 있고 실제로 류마티스 관절염이 유발된 환자들의 관절 부위에서 많이 발견된다. 관절 내 뼈의 손상은 pannus의 침습에 의하여 일어난다 (de Hooge AS et al ., Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis. Am J Pathol. 2000, 157(6): 2081- 2091; Cai L et al . , Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16(1): 10-21; Feldmann M et al ., Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996, 14: 397-440). Pannus는 여러 가지 염증 세포들의 덩어리로 연골을 파괴시키고 이어 연골하골을 손상시켜 관절의 변형을 가져오며 관절 주위에 있는 뼈 또한 약화시킨다 (Burr DB, The importance of subchondral bone in osteoarthrosis.Curr Opin Rheumatol. 1998, 10(3): 256-262).
In particular, inflammatory cytokines such as TNF-, IL-1 and IL-6 have been reported to play a major role in inflammatory responses and joint injuries, and are often found in the joints of patients with rheumatoid arthritis. Injury to the bones of the joint occurs by the invasion of the pannus (de Hooge AS et al., Involvement of IL-6, apart from its role in immunity, in chronic response to experimental arthritis. 6: 2081-2091; Cai L et al., Pathways by interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine 2001, 16 (1): 10-21; Feldmann M et al., Role of cytokines in rheumatoid arthritis, Annu Rev Immunol 1996, 14: 397-440). Pannus is a mass of inflammatory cells that destroys cartilage and damages cartilage, causing deformation of joints and also weakening the bone around joints (Burr DB, The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998 , 10 (3): 256-262).

또한 퇴행성 관절염이 발병되면 여러 가지 염증 세포의 침윤과 관절 내의 만성 염증 반응이 일어나고 pannus의 형성으로 인하여 연골조직의 파괴와 관절 뼈조직의 부식 및 변형을 초래하게 된다 (Cai L et al., Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16(1): 10-21). OA는 주로 체중부하 관절의 관절연골과 연부조직에서 만성적인 퇴 행성 변화를 가져오며, 퇴행성 변화에 의해 손상이 가속되는 양성질환으로 인식되어 왔다. 그러나 최근 유전적 인자, 개인적 또는 사회적 환경이 미치는 영향에 대탄 인식, 새로운 연구 기술의 발달 등으로 OA의 병인성 인자에 대한 연구가 활발하게 이루어지고 있다. (Haq Iet al., J. Osteoarthritis. Postgrad Med J. 2004,79(933) 377-383.)
In addition, when degenerative arthritis develops, various infiltration of inflammatory cells and chronic inflammatory reaction within the joint occurs, resulting in destruction of cartilage tissue and corrosion and deformation of joint bone tissue due to formation of pannus (Cai L et al., Pathways which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16 (1): 10-21). OA has been recognized as a benign disease that causes chronic degenerative changes in articular cartilage and soft tissue of weight-bearing joints, and accelerates damage by degenerative changes. However, recent studies on the pathogenicity factors of OA have been actively carried out due to the recognition of the genetic factor, the personal or social environment, and the development of new research techniques. (Haq Iet al., J. Osteoarthritis, Postgrad Med J. 2004, 79 (933) 377-383.)

이와 같은 류마티스 관절염 또는 퇴행성 관절염의 예방과 치료를 위한 양약이 많이 사용되고 있다. 그러나 이러한 양약은 간에 독성을 주는 부작용이 있어서 최근에서 한약재를 이용한 관절염 예방 및 치료제들이 많이 개발되고 있다.
Such medicines for prevention and treatment of rheumatoid arthritis or degenerative arthritis are widely used. However, since these medicines have side effects that give toxicity to the liver, there have been many developments in the prevention and treatment of arthritis using herbal medicines.

등록특허 10-1235238호(퇴행성 관절염에 대한 치료효과가 우수한 백작약 추출물 및 그를 포함하는 약제학적 조성물, 이하 선행기술)에서 "백작약 열수 추출물을 유효성분으로 함유하여 연골세포의 증식을 활성화시키는 것을 특징으로 하는 퇴행성 관절염 치료용 약제학적 조성물"을 제공하였다.
In a patent application No. 10-1235238 ("Veterinary extract having excellent therapeutic effect against degenerative arthritis, and pharmaceutical composition containing the same", hereinafter referred to as "prior art"), "a method of activating the proliferation of chondrocytes by containing a hot- Lt; RTI ID = 0.0 > a < / RTI > pharmaceutical composition for treating degenerative arthritis.

상기한 종래기술 및 선행기술은 여전히 간 및 신장에 독성이 있으며 관절염 치료에 미흡하였는바 본 발명은 이를 해결하고자 한다.The prior art and prior art described above are still toxic to the liver and kidney and are insufficient in the treatment of arthritis.

따라서 본 발명은 간 및 신장에 독성이 없으면서도 관절염의 예방과 치료에 매우 효과적인 약제 조성물을 제공하고자 한다.
Accordingly, the present invention provides a pharmaceutical composition which is highly effective for preventing and treating arthritis without toxicity in liver and kidney.

본 발명은 상기한 요구 및 문제점을 해결하기 위하여,In order to solve the above-mentioned needs and problems,

마황 추출물, 부자 추출물, 세신 추출물을 혼합하여 조성한 관절염의 치료와 예방의 기능이 있는 조성물을 제공한다.The present invention provides a composition having the function of treating and preventing arthritis, which is formed by mixing a magpie extract, a rich extract, and a sesquin extract.

또한 마황 추출물 100중량부에 부자 추출물 50~100중량부, 세신 10~20중량부 혼합하여 조성한 것에 특징이 있는 관절염의 치료와 예방의 기능이 있는 조성물을 제공한다.The present invention also provides a composition having the function of treating and preventing arthritis, which is characterized in that 100 to 10 parts by weight of a maggot extract is mixed with 50 to 100 parts by weight of an extract and 10 to 20 parts by weight of a sesquin.

또한 상기의 조성물이 혼합된 관절염의 치료와 예방의 기능이 있는 약제학적 조성물을 제공한다.
Also provided is a pharmaceutical composition having the function of treating and preventing arthritis in which the composition is mixed.

본 발명에 따른 조성물은 간과 신장에 독성의 영향이 없는 효과를 창출한다.The composition according to the present invention produces an effect without toxicity on the liver and kidney.

또한 본 발명에 따른 조성물은 관절염의 항염증 효능이 현저히 높은 효과가 나타난다.In addition, the composition according to the present invention exhibits a remarkably high anti-inflammatory effect of arthritis.

또한 본 발명에 따른 조성물은 관절염의 연골조직손상의 치료에 현저히 높은 효과가 나타난다.
In addition, the composition according to the present invention exhibits a remarkably high effect for treating cartilage tissue damage of arthritis.

도 1은 본 발명에 따른 조성물 효능 실험을 위한 실험용 쥐의 사료 성분표.
도 2는 본 발명에 따른 조성물의 간 기능 실험 결과.
도 3a는 본 발명에 따른 조성물의 신장 기능 실험(creatinine 농도를 측정)결과.
도 3b는 본 발명에 따른 조성물의 신장 기능 실험(BUN 농도를 측정)결과.
도 4는 본 발명에 따른 조성물의 항염효과(Total Nitric oxide(NO) 생성 억제 효과) 측정 결과.
도 5는 본 발명에 따른 조성물의 항염효과(사이토카인 생성량) 측정 결과.
도 6a은 본 발명에 따른 조성물의 Cartilage volume에 미치는 영향을 보여주는 비교 사진.
도 6b는 본 발명에 따른 조성물의 Cartilage volume에 미치는 영향을 보여주는 결과 도표.FIG. 1 is a table showing feed composition of experimental rats for the efficacy of the composition according to the present invention.
FIG. 2 shows the liver function test results of the composition according to the present invention.
FIG. 3A shows the results of an experiment of renal function (measurement of creatinine concentration) of the composition according to the present invention.
FIG. 3b shows the results of the elongation test (measurement of BUN concentration) of the composition according to the present invention.
Fig. 4 shows the results of measuring the anti-inflammatory effect (total nitric oxide (NO) production inhibitory effect) of the composition according to the present invention.
Fig. 5 shows the anti-inflammatory effect (cytokine production amount) measurement result of the composition according to the present invention.
6A is a comparative photograph showing the effect of the composition according to the present invention on the cartilage volume.
Figure 6b is a plot showing the effect of the composition according to the invention on the cartilage volume.

이하 본 발명을 상세히 설명하고자 한다.
Hereinafter, the present invention will be described in detail.

본 발명은 마황 추출물, 부자 추출물, 세신 추출물을 혼합하여 조성한 관절염의 예방과 치료에 효과적인 조성물을 제공한다.The present invention provides a composition which is effective for prevention and treatment of arthritis, which is formed by mixing a magpie extract, a rich extract, and a sesquin extract.

(본 발명에서는 이와 같은 조성물을 Mahwangbujasesintang이라고 하고, 이하 실험 등의 설명에서는 MBST로 표기할 수 있다)
(In the present invention, such a composition is referred to as Mahwangbujasesintang, and hereinafter, it can be expressed as MBST in the description of experiments etc.)

상기한 추출물의 조성은 원재료를 함께 추출하는 방법 또는 각각 개별적으로 추출하여 섞는 방법 모두 사용할 수 있다.
The composition of the above extract may be either a method of extracting the raw materials together or a method of extracting and mixing them separately.

본 발명의 마황은 마황(麻黃. Ephedra sinica)은 마황과에 속하는 식물로, 그 성미는 맵고 쓰며 성질은 따뜻하다. 성분은 alkaloid가 1∼2%가 들어있는데, 그 중 40∼90%는 ephedrine이고 그 다음이 d-pseudoephedrine과 미량의 1-N- methylephedrine, d-N-pseudomethylephedrine, 1-norephedrine, ephedine, d-demethylpseudoephedrine이다. 또, catechu tanin 6%와 정유가 들어있다. 정유 속에는 1-a-terpineol이 들어있다. (김창민, 신민교, 안덕균, 이경순 : 中藥大辭典, 圖書出版 鼎談, 1997).
The ephedra sinica of the present invention is a plant belonging to the epidermis, and its mood is spicy, and its quality is warm. The composition contains 1 to 2% of alkaloids, of which 40 to 90% are ephedrine, followed by d-pseudoephedrine and trace amounts of 1-N-methylephedrine, dN-pseudomethylephedrine, 1-norephedrine, ephedrine and d-demethylpseudoephedrine . Also contains catechu tanin 6% and essential oil. Essential oil contains 1-a-terpineol. (Kim Changmin, Shin Min-gyo, Ahn Deok-gyun, Lee Kyung-Soon: 中 药 大 辭 典, 圖書 出版 鼎 談, 1997).

본 발명의 부자는 미나리아재비과에 속하는 다년생 초본식물로, 봄에 채취한 것은 오두, 자근(子根)이 형성된 9월에 채취하는 것은 부자라 한다. 또 오두에는 자근이 생기지 않고 형상이 긴 것은 천웅(天雄), 부자의 옆쪽에서 다시 작은 덩이뿌리가 나온 것은 측자(側子)라고 분류하기도 한다.The rich person of the present invention is a perennial herbaceous plant belonging to the buttercups family, and it is said that what is collected in spring is harvested in September, when odu and kimono are formed. In addition, it is classified as Chuang (longitude) in which the root is not formed in the duck, the long shape in the middle, and the side where the root of the small root again comes out from the side of the rich.

부자는 ≪신농본초경 神農本草經≫에 이미 약으로 쓴 기록이 있으며, 독성이 강하여 예로부터 가공처리하는 방법이 발달되어 있었다. 또 강한 독성 때문에 의료용으로보다 독을 화살에 묻혀 병기로 사용하였다. 그 성분은 알칼로이드로서 아코니틴·메사코니틴·히파코니틴 등을 함유한다. 약성은 뜨겁고, 맛은 맵고 쓴 것으로 이름이 높다.The rich man has already written a drug on the Divine Husbandman's Shonan Honsha 经 », and his method was developed from ancient times because of its strong toxicity. Also, because of its strong toxicity, poison was used as a weapon for medical purposes. Its components include alkaloids such as aconitine, mesaconitine, hipakonitin, and the like. The weakness is hot, the taste is spicy, and the name is high.

전신의 기능허약으로 몸이 차고 맥박이 미약하며, 허리와 무릎이 차고 저리며, 소변의 양이 많고 묽은 변을 보면서 얼굴이 창백하고 입술이 파란 사람에게 많이 쓰인다. 기능쇠약으로 인한 만성신장염과 심장부전으로 전신에 부종이 있을 때에도 응용되고 있다.The function of the whole body is fragile, the body is cold, the pulse is weak, the waist and the knee are cold, the urine is large, the face is pale and the lips are blue. It has also been applied to chronic nephritis due to functional impairment and edema in the whole body due to heart failure.

복부가 늘 차고 식욕이 없으며 설사를 자주 하는 사람에게는 식욕을 더하여 주며, 또 하복부가 늘 차고 성적 충동을 느끼지 못하며 소변의 색이 백색으로 나타날 때에 생식기능을 항진시켜주기도 한다.The abdomen is full of appetite, lack of appetite, appetite is added to those who frequent diarrhea, and the lower abdomen does not feel cold, sexual impulses, and the color of the urine appears white.

일시적인 쇼크로 졸도하여 손과 발, 피부가 차며 호흡이 미약할 때에 강심제로 사용되며, 허리와 무릎, 다리가 차면서 신경통이 빈발할 때에 진통제로도 쓰인다. 금기(禁忌)로는 발열성 질환에 사용하지 못하며 임산부와 간기능장애·심근염에도 쓰지 못한다. 민간에서는 부자에다 북어와 돼지족발을 같이 넣고 오랫동안 달여서 신경통·냉증에 먹는다. 대표적인 처방으로는 사역탕(四逆湯)이 있다.
It is used as a cardiopulmonary agent when the hand, feet and skin are cold and the respiration is weak. It is also used as an analgesic when the back, knee and legs are cold and neuralgia is frequent. It can not be used for febrile illness and can not be used for pregnant women, liver dysfunction or myocarditis. In the private sector, the rich and the pig and pigs are put together for a long time to eat the neuralgia and poor circulation. A typical prescription is the four-way hot water.

본 발명의 세신은 우리나라에서는 쥐방울덩굴과의 민족두리풀(Asiasarum heterotropoides F. Maekawa var. mandshuricum F. Maekawa) 또는 족두리풀(Asiasarum sieboldi F. Maekawa)의 뿌리 및 뿌리줄기를 말한다. 일본은 우리나라와 같으며 중국은 민족두리풀(북세신(北細辛)), 족두리풀(화세신(華細辛))을 비롯해 한성세신(Asiasarum sieboldi var. seoulense Nakai:漢城細辛)을 말한다. The seeds of the present invention are roots and rootstocks of Asiasarum heterotropoides F. Maekawa var. Mandshuricum F. Maekawa or Asiasarum sieboldi F. Maekawa in Korea. Japan is the same as our country, and China refers to Asiasarum sieboldi var. Seoulense Nakai, as well as Minjoshi (bean sprout), bamboo shrub (華 辛).

세신은 뿌리가 가늘고 맛이 매우 맵기 때문에 붙여진 이름이다.Seisin is a name given because it is thin and has a very high taste.

이 약은 특이한 냄새가 있고 혀를 약간 마비시키며 맛은 맵고 성질은 따듯하다.[辛溫]This medicine has a peculiar smell and slightly paralyzes the tongue, and the taste is spicy and temperate. [辛 温]

세신은 풍한습 두통, 사지마비동통, 복통, 외감성 두통, 오한, 발열, 전신통, 해수, 천식, 가래가 많은 증상, 축농증, 중풍 등에 쓰인다. Ssein is used for a variety of symptoms such as wet headache, limb paralysis, abdominal pain, headache, chills, fever, telegraph, seawater, asthma, sputum,

약리작용으로 해열, 진정, 진통, 국부마취, 항염, 면역억제작용, 기관지이완작용, 강심작용이 보고되었다. Pharmacological actions have been reported such as fever, sedation, analgesia, local anesthesia, anti-inflammation, immunosuppressive action, bronchodilatory action, and cardiac action.

생김새는 고르지 않게 구부러진 노끈 모양을 이루고 황갈색의 마디가 진 뿌리줄기에 뿌리가 많이 달려 있다. 그 바깥면은 엷은 갈색이나 어두운 갈색으로 밋밋하거나 극히 얕은 세로주름이 있다. 뿌리줄기의 위쪽 끝에는 엽병, 화병 또는 싹눈이 붙어 있는 경우가 있으며 각 마디에는 엽병과 화병 자국이 있고 그 마디 사이에 가늘고 긴 뿌리가 여러 개 붙어 있다. 이 약은 꺾어지기 쉽고 꺾은 면은 황백색으로 평탄하지 않다.
Its appearance is uneven and has a rope shape with many roots on the roots of yellowish brown nodes. Its outer surface is light brown or dark brown with flat or extremely shallow vertical wrinkles. At the upper end of the rootstock is a petiole, vase, or gland. In each node there are petiole and vase marks, and there are several elongated roots between the nodes. This medicine is easy to break, and the folded surface is yellowish white and uneven.

본 발명은 상기한 마황 추출물, 부자 추출물, 세신 추출물을 혼합하여 조성물을 제공한다.
The present invention provides a composition by mixing the above-mentioned magpie extract, rich extract and cedma extract.

본 발명은 상기한 재료들을 개별적으로 추출할 수도 있도 함께 혼합하여 추출하는 방법도 사용할 수 있다.
In the present invention, the above materials may be separately extracted or mixed and extracted.

본 발명의 조성물은 마황 추출물 100중량부에 부자 추출물 50~100중량부, 세신 추출물 10~20중량부 혼합하여 조성한다.
The composition of the present invention is prepared by mixing 50 to 100 parts by weight of the Extract Extract and 10 to 20 parts by weight of the Seshin extract in 100 parts by weight of the Radix extract.

본 발명은 상기한 재료를 건조시켜 사용하는 것이 좋으나, 건조시키지 않은 것을 사용하여도 무방하다.
In the present invention, it is preferable to dry and use the above-mentioned material, but it is also possible to use it without drying.

본 발명의 추출물은 상기한 재료를 물에 침지시키고 가열하여 추출물을 수득하는 방법이 사용될 수 있다.
The extract of the present invention can be obtained by immersing the aforementioned materials in water and heating them to obtain an extract.

또한 본 발명에서는 더욱 고농도의 추출물을 수득하기 위하여 상기의 재료를 흐르는 증류수에 잘 세척한 후, 동일 부피의 증류수를 채워 충분히 불리고 반응전열기를 사용하여 열탕 추출한다. Further, in the present invention, in order to obtain a higher concentration of the extract, the above materials are thoroughly washed with distilled water, filled with distilled water of the same volume, and extracted with hot water using a reaction electric heater.

0.45μm와 0.1μm의 filter paper를 연속적으로 사용하여 추출액을 여과하고 약전 소금을 이용하여 여과액 내의 무기염류들을 침전시켜 제거하고 citric acid와 Na3PO4를 이용하여 pH 7.3으로 조절한 후, 고압 살균하여 제조하는 방법을 사용할 수 있다.
The filtrate was filtered using 0.45 μm and 0.1 μm filter paper continuously, and the inorganic salts in the filtrate were removed by precipitation with pharmacopoeial salt, adjusted to pH 7.3 with citric acid and Na 3 PO 4, Can be used.

또한 본 발명은 재료 100~150g을 80%의 주정(알코올, 1리터)에 넣고 2~4시간 동안 환류추출하는 방법으로 추출물을 수득할 수 있다.
In addition, the present invention can be obtained by adding 100 to 150 g of a material to 80% alcohol (1 liter) and refluxing for 2 to 4 hours.

본 발명은 상기한 마황 추출물 100중량부에 부자 추출물 50~100중량부, 세신 10~20중량부 혼합하여 관절염 예방과 치료에 효능이 있는 마황부자세신 조성물(MBST)을 제공한다.
The present invention provides a saccharin rich succinic composition (MBST) which is effective for prevention and treatment of arthritis by mixing 50-100 parts by weight of a rich extract and 10-20 parts by weight of sesquin in 100 parts by weight of the above-mentioned mahwang extract.

또한 본 발명은 상기한 관절염 예방과 치료에 효능이 있는 마황부자세신 조성물(MBST)을 포함하는 약제학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition comprising a magenta rich succinic composition (MBST) effective for preventing and treating arthritis.

상기의 약제학적 조성물은 관절염의 예방과 치료를 위한 약을 의미하며, 여기에 본 발명의 마황부자세신 조성물(MBST)이 포함된 것을 의미한다.
The above pharmaceutical composition means a drug for the prevention and treatment of arthritis, and it means that the present invention contains the Maggot Rich Sequin Composition (MBST).

본 발명은 상기한 방법으로 제조한 마황부자세신 조성물(MBST)을 동물 실험을 통하여 관절염의 예방과 치료에 효과가 있음을 알 수가 있었다.
The present invention was found to be effective in the prevention and treatment of arthritis through animal experiments with the Maqulipu rich suzin composition (MBST) prepared by the above method.

하기할 동물실험은 마황 4g, 부자 3g, 세신 0.5g을 혼합한 것(이를 "1첩"이라 한다)을 단위로 하여 15첩을 상기한 80%의 주정(1리터)을 통하여 3시간 동안 환류추출한 주정 추출물(MBST 조성물)을 사용한다. Animal experiments to be performed were carried out for 15 hours through a 80% alcohol (1 liter) containing the mixture of 4 g of mahwah, 3 g of rich ginseng and 0.5 g of sesquin as a unit Extracted alcohol extract (MBST composition) is used.

따라서 상기한 추출물을 rotary evaporator를 이용하여 50ml로 감압, 농축하여 동결건조 하였고 완전 건조된 MBST 조성물(11.5g)를 냉동 보관하여 시료로 사용하였다.
Thus, the above extract was lyophilized to 50 ml using a rotary evaporator, concentrated, and the completely dried MBST composition (11.5 g) was stored frozen and used as a sample.

1. 동물실험1. Animal experiments

(1) 수컷 6 주령의 SD-Rat(170-200g)을 라온바이오(Korea)사에서 골관절염 유발물질인 MIA : Monosodium iodoacetate (Sigma. Chemical Co. Ltd, Cat. No. I2512)를 오른쪽 무릎 관절강 내에 50 ul(60 mg/mL)씩 투여한 후 유발된 쥐만을 공급받아 실험하였다. (1) A 6-week-old male SD-Rat (170-200 g) was intraperitoneally injected with MIA: Monosodium iodoacetate (Sigma Chemical Co. Ltd, Cat. No. I2512), an osteoarthritis inducing substance, in the right knee joint And 50 μl (60 mg / ml), respectively.

동물은 실험 당일까지 일반 고형사료(퓨리나)를 충분히 공급하고 온도 22±2℃, 습도 55±5%, 12 시간(light-dark cycle)의 환경에서 1 주간 적응시킨 후 실험에 사용하였다. 본 실험은 대전대 동물실험윤리 위원회의 승인(동물사용 윤리위원회 승인번호 - DJUARB2013-006)을 받아 동물윤리준칙에 의거하여 실험하였다. 일반 사료의 당 조성내용과 분량은 [도 1](Table II)과 같다.
The animals were fed the general solid feed (purina) until the day of the experiment and were adapted for 1 week in an environment of temperature 22 ± 2 ° C, humidity 55 ± 5%, light-dark cycle for 12 weeks. This experiment was conducted in accordance with the animal ethics code of the Daejeon National Animal Experimentation Ethics Committee (Animal Use Ethics Committee Approval Number - DJUARB2013-006). The content and amount of sugar in the general diet are shown in [Figure 1] (Table II).

(2) SD-Rat에 MIA를 주사하여 관절염을 유발시킨 후, 일주일이 경과된 이후부터 각 실험군별로 매일 1회 2(200 mg/kg) 씩 오전 10시에 4주 동안 경구투여 하였다. MBST 조성물 투여량은 1첩을 성인 체중 60 kg에 1회 투여용량으로 하고, 1첩으로부터 얻은 시료를 마우스 체중 30 g으로 기준하여 산출하였다.
(2) MIA was injected into SD-Rat to induce arthritis. After one week, 2 (200 mg / kg) was orally administered to each experimental group every day for 10 days at 10 am for 4 weeks. The dose of the MBST composition was calculated on the basis of 30 g of a mouse body weight obtained from a single administration at a dose of 1 dose per 60 kg adult body weight.

2. 간기능에 미치는 영향2. Effect on liver function

(1) 혈청 내에서 AST, ALT 활성도를 측정하기 위해 실험 종료 후 심장 천자법을 이용하여 혈액을 채취하였다. 혈액을 30분간 상온에서 굳힌 뒤 3,000 rpm에서 15분간 원심분리 후 혈청을 분리하여, 서울의과학연구소에 분석 의뢰 하였다. AST, ALT 활성도는 JSCC UV method의 원리를 이용하여 생화학 자동분석기로 측정하였다.
(1) To measure AST and ALT activity in the serum, blood was collected using the cardiac puncture method after the end of the experiment. The blood was solidified at room temperature for 30 minutes, centrifuged at 3,000 rpm for 15 minutes, and the serum was separated and analyzed for analysis by Seoul National University Science Laboratory. AST and ALT activities were measured by a biochemical automatic analyzer using the principle of JSCC UV method.

(2) ALT(alanine transaminase)의 경우 대조군(36.1± 2.8 U/L)이 정상군(23.3±0.9 U/L)에 비하여 높았으며, MBST 투여군(27.3±2.4 U/L)은 대조군에 비해 24.4% 감소를 나타내었다. AST(aspartate transaminase)의 경우 대조군(139.7±9.5 U/L)이 정상군(92.7±2.3 U/L)에 비하여 높았으며, MBST 투여군(118.0±5.6 U/L)은 대조군에 비해 15.5% 감소를 나타내었다 (도 2).
(2) In the case of alanine transaminase, the control group (36.1 ± 2.8 U / L) was higher than the normal group (23.3 ± 0.9 U / L) and the MBST group (27.3 ± 2.4 U / L) % Reduction. In the case of AST (aspartate transaminase), the control group (139.7 ± 9.5 U / L) was higher than the normal group (92.7 ± 2.3 U / L) and the MBST group (118.0 ± 5.6 U / L) (Fig. 2).

3. 신(신장)기능에 미치는 영향3. Impact on renal function

(1) 혈청 내에서 creatinine, BUN 활성도를 측정하기 위해 실험 종료 후 심장 천자법을 이용하여 혈액을 채취하였다. 혈액을 30분간 상온에서 굳힌 뒤 3,000 rpm에서 15분간 원심분리 후 혈청을 분리하여, 서울의과학연구소에 분석 의뢰 하였다. Creatinine의 함량은 Creatinine Jaffe Method 의 원리, BUN의 함량은 Kinetic UV assay for urea/urea nitrogen의 원리를 이용하여 생화학 자동분석기로 측정하였다
(1) To measure creatinine and BUN activity in the serum, blood was collected using the cardiac puncture method after the end of the experiment. The blood was solidified at room temperature for 30 minutes, centrifuged at 3,000 rpm for 15 minutes, and the serum was separated and analyzed for analysis by Seoul National University Science Laboratory. The content of creatinine was measured by a biochemical automatic analyzer using the principles of Creatinine Jaffe Method and the content of BUN using the principle of Kinetic UV assay for urea / urea nitrogen

(2) Creatinine에 미치는 영향(2) Influence on Creatinine

혈청 중의 creatinine 농도를 측정한 결과 정상군은 0.54±0.02 mg/dl, 대조군은 0.59±0.04 mg/dl, MBST 투여군은 0.54±0.02 mg/dl로 나타나, 대조군에 비해 8.5% 감소를 나타내었다 (도 3a).
The creatinine concentration in the serum was 0.54 ± 0.02 mg / dl in the normal group, 0.59 ± 0.04 mg / dl in the control group and 0.54 ± 0.02 mg / dl in the MBST group, showing a decrease of 8.5% 3a).

(3) BUN에 미치는 영향(3) Influence on BUN

혈청 중의 BUN 농도를 측정한 결과, 정상군은 16.76±1.59 mg/dl, 대조군은 17.87±0.80 mg/dl, MBST 투여군은 17.27±0.97mg/dl로 나타나, 대조군과 투여군에 많은 차이는 나타나지 않았다 (도 3b).
The BUN concentration in the serum was 16.76 ± 1.59 mg / dl in the normal group, 17.87 ± 0.80 mg / dl in the control group and 17.27 ± 0.97 mg / dl in the MBST group, and there was no significant difference between the control group and the administration group 3b).

4. 항염증 효능에 미치는 영향 4. Effect on anti-inflammatory efficacy

(1) Total Nitric oxide(NO) 생성 억제 효과 측정 (1) Measurement of total nitric oxide (NO) production inhibitory effect

NO의 농도는 배양액 내의 nitrite 농도를 Griess Reagent System을 이용하여 측정하였다. Raw 264.7 cells은 96well plates에 104 cells/well로 분주하여 24시간 동안 배양 한 후, MBST 주정 추출물을 1, 10, 100 (μg/ml)의 농도로 처리하고, LPS 1 μg/ml을 처리하여, 다시 24시간 동안 배양하였다. N1 buffer를 50 ul를 각 well에 처리한 후, 10분간 상온에서 암소 반응 후, N2 buffer 50 ul를 각 well에 처리하고, 10분간 반응시킨 후, 540 nm에서 흡광도를 측정하였다. Nitrite standard의 농도별 표준곡선을 이용하여 배양액의 NO 농도를 결정하였다.
NO concentration was measured by using Griess Reagent System. Raw 264.7 cells were cultured in 96 well plates at 10 4 cells / well and cultured for 24 hours. MBST extract was treated with 1, 10, 100 μg / ml LPS and treated with 1 μg / ml LPS , And cultured for another 24 hours. 50 μl of N1 buffer was added to each well. After 10 min of incubation at room temperature, 50 μl of N2 buffer was added to each well, incubated for 10 min, and absorbance was measured at 540 nm. The concentration of NO in the culture medium was determined using the standard curve of concentration of nitrite standard.

MBST 주정 추출물의 NO 생성량은 대조군을 100±3.7%로 나타냈을 때, 정상군은 28.4±4.4%, MBST 투여군은 1 μg/ml 농도에서 98.9±5.1%, 10 μg/ml 농도에서 95.9±8.5%, 100 μg/ml 농도에서 92.8±5.7%로 나타나, 대조군에 비해 100 μg/ml 농도에서 7.2% 감소를 나타내었다 (도 4).
The NO production of MBST extract was 28.9 ± 4.4% in normal group, 98.9 ± 5.1% in 1 μg / ml and 95.9 ± 8.5% in 10 μg / ml of MBST group, respectively, when the control group was 100 ± 3.7% And 92.8 ± 5.7% at the concentration of 100 μg / ml, respectively, and decreased by 7.2% at the concentration of 100 μg / ml compared to the control (FIG. 4).

(2) 사이토카인 생성량 측정     (2) Measurement of cytokine production amount

1) Raw 264.7 cells을 12 well plates에 1.5×105 cells/이 되도록 분주하고, 24시간 동안 배양한 후, MBST 주정 추출물을 1, 10, 100 (μg/ml)의 농도로 처리하고, LPS 1 ug/ml을 처리하였다. 24시간 동안 배양한 후 세포배양액을 수거하여 배양액에 함유된 IL-1β IL-6, TNF-a 등을 custom-made 4-plex cytokine Milliplex panel을 이용하여 측정하였다.
1) Raw 264.7 cells were plated in 12 well plates at a density of 1.5 × 10 5 cells / and cultured for 24 hours. MBST extract was treated at concentrations of 1, 10, 100 (μg / ml) lt; / RTI > / ml. After culturing for 24 hours, cell culture medium was collected, and IL-1β IL-6 and TNF-a contained in the culture were measured using a custom-made 4-plex cytokine Milliplex panel.

2) 혈청 내의 IL-1β 생성량을 측정한 결과 정상군은 2.6±0.5 pg/ml, 대조군은 138.1±16.9 pg/ml, MBST 투여군은 100.7±18.8 pg/ml으로 나타나, 대조군에 비해 MBST 투여군에서 유의성 있는(* P < 0.05) 감소를 나타내었다 (도 5).
2) The amount of IL-1β produced in the serum was 2.6 ± 0.5 pg / ml in the normal group, 138.1 ± 16.9 pg / ml in the control group and 100.7 ± 18.8 pg / ml in the MBST group. (* P < 0.05) (Fig. 5).

5. Cartilage volume에 미치는 영향5. Effect on Cartilage Volume

(1) Micro-CT 측정은 연세대학교(원주캠퍼스)측에 의뢰하여 실시하였으며, 조형제인 헥사브릭스(HEXABRICS 320)를 꼬리 정맥에 주사 후 μCT-arthrograpy를 사용하여 무릎관절의 연골양 (cartilage volumne) 등을 측정 및 분석하였다.
(1) Micro-CT was performed by Yonsei University (Wonju Campus). The cartilage volume (cartilage volume) of the knee joint was measured using μCT-arthrograpy after injection of HEXABRICS 320, Were measured and analyzed.

(2) 무릎관절의 연골 파괴정도를 측정 한 결과 정상군을 1.39±0.16 mm3 으로 나타냈을 때, 대조군은 0.28±0.05 mm3, MBST 투여군은 0.81±0.13 mm3 으로 나타나, 대조군에 비해 MBST 투여군에서 유의성 있는(*** P < 0.001) 감소를 나타내었다(도 6a, 도 6b).
(2) The degree of cartilage destruction of the knee joint was found to be 1.39 ± 0.16 mm 3 in the normal group, 0.28 ± 0.05 mm 3 in the control group and 0.81 ± 0.13 mm 3 in the MBST group, (*** P < 0.001) (Fig. 6 (a) and (b)).

본 발명의 상기한 조성물은 상기한 바와 같이 간과 신장에 독성이 없으면서도 관절염의 예방과 치료에 매우 효과적인 것을 알 수가 있다.
As described above, the composition of the present invention is highly effective for prevention and treatment of arthritis even when it is not toxic to liver and kidney.

본 발명은 이와 같이 간과 신장에 독성이 없으면서도 관절염의 예방과 치료에 매우 효과적인 마황부자세신 조성물 및 이를 포함하는 약제학적 조성물을 제공한다.
The present invention thus provides a magpie supplement suzicin composition and a pharmaceutical composition containing the same, which are very effective for preventing and treating arthritis without toxicity in liver and kidney.

본 발명은 생약, 약초를 이용하여 관절염을 치료하는 기능성 식품, 약제 등을 생산, 가공, 유통, 판매하는 산업에 매우 유용하다.
INDUSTRIAL APPLICABILITY The present invention is very useful in an industry for producing, processing, distributing and selling functional foods and medicines for treating arthritis using herbal medicines and herbs.

Claims (3)

마황 추출물, 부자 추출물, 세신 추출물을 혼합하여 조성한 관절염 예방의 기능이 있는 조성물.
A composition having the function of preventing arthritis, which is prepared by mixing a magic extract, a rich extract, and a sesamin extract.
제1항에 있어서,
마황 추출물 100중량부에 부자 추출물 50~100중량부, 세신 추출물 10~20중량부 혼합하여 조성한 것에 특징이 있는 관절염 예방의 기능이 있는 조성물.
The method according to claim 1,
A composition having the function of preventing arthritis, which is characterized in that 50 to 100 parts by weight of a rich extract and 10 to 20 parts by weight of a sesamin extract are mixed in 100 parts by weight of a mahwang extract.
제1항 또는 제2항의 조성물이 포함된 관절염 예방의 기능이 있는 약제학적 조성물.
A pharmaceutical composition having the function of arthritis prevention comprising the composition of any one of claims 1 or 2.
KR1020130152785A 2013-12-10 2013-12-10 a mbst composition of functon of athritis protection and treatment KR101616604B1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104983823A (en) * 2015-07-29 2015-10-21 四川金堂海纳生物医药技术研究所 Traditional Chinese medicine pills for treating tuberculous osteomyelitis and preparation method thereof

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CN103272064A (en) * 2013-06-17 2013-09-04 贵州鸿德中药开发有限公司 Traditional Chinese medicine for treating rheumatoid arthritis and preparation method of traditional Chinese medicine
KR101321754B1 (en) 2013-03-29 2013-10-28 유한회사한풍제약 A composition for treating rheumatoid arthritis and osteoarthritis

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KR20010084485A (en) * 2000-02-25 2001-09-06 정두순 Method of preparing herbal relievers for neuralgia and arthritis.
KR20090025469A (en) * 2007-09-06 2009-03-11 삼성생약주식회사 Pharmaceutical composition for the prevention and treatment of inflammatory diseases or the alleviation of pain containing extract of gastrodia elata

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KR101321754B1 (en) 2013-03-29 2013-10-28 유한회사한풍제약 A composition for treating rheumatoid arthritis and osteoarthritis
CN103272064A (en) * 2013-06-17 2013-09-04 贵州鸿德中药开发有限公司 Traditional Chinese medicine for treating rheumatoid arthritis and preparation method of traditional Chinese medicine

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104983823A (en) * 2015-07-29 2015-10-21 四川金堂海纳生物医药技术研究所 Traditional Chinese medicine pills for treating tuberculous osteomyelitis and preparation method thereof

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