KR101454336B1 - Compositions for preventing and treating arthritis - Google Patents
Compositions for preventing and treating arthritis Download PDFInfo
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- KR101454336B1 KR101454336B1 KR1020130027207A KR20130027207A KR101454336B1 KR 101454336 B1 KR101454336 B1 KR 101454336B1 KR 1020130027207 A KR1020130027207 A KR 1020130027207A KR 20130027207 A KR20130027207 A KR 20130027207A KR 101454336 B1 KR101454336 B1 KR 101454336B1
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- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 239000001717 vitis vinifera seed extract Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 229940118573 xylitol 500 mg Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
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Abstract
본 발명은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모를 건조하고 적정비로 혼합한 후, 열수 추출법으로 얻은 천연 복합 추출물을 유효성분으로 함유하는 염증성 질환 개선 또는 치료용 조성물 및 이의 제조방법에 관한 것이다. 나아가 본 발명은 상기 어느 하나 이상의 상기 추출물을 유효성분으로 함유하는 골관절염 예방 또는 개선용 건강기능식품 조성물을 제공한다.
본 발명의 상기 추출물은 질소산화물(NO) 생성 억제, 염증성 사이토카인인 종양괴사인자-알파(TNF-α), 인터루킨-1 베타(IL-1β), 프로스타글란딘 E2(PGE2) 생성 억제 활성을 동시에 보유하여 염증성 질환 개선 및 치료용 효과를 나타내며, 세포독성은 없으므로, 염증성 질환의 개선 및 치료 또는 예방을 위한 의약품, 건강기능식품에 유용하게 사용될 수 있다.The present invention relates to a composition for improving or treating an inflammatory disease comprising an extract of natural complex obtained by mixing dried and appropriate ratio of Juniper berry, European grape skin, European grape seed, White rice, And a method for producing the same. Further, the present invention provides a health functional food composition for preventing or ameliorating osteoarthritis containing any one of the above extracts as an active ingredient.
The extract of the present invention has an inhibitory activity on the production of nitrogen oxides (NO), inhibition of inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and prostaglandin E 2 (PGE 2 ) And exhibits an effect for the improvement and treatment of inflammatory diseases. Since it has no cytotoxicity, it can be effectively used for medicines and health functional foods for the improvement and treatment or prevention of inflammatory diseases.
Description
본 발명은 관절염 예방 및 치료에 효과를 가지는 기능성 식품 및 천연물 신약 조성물에 관한 것으로, 보다 자세하게는 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모를 유효성분으로 함유하는 골관절염 예방 및 치료를 위한 약학 조성물 및 건강기능식품 조성물에 관한 것이다.
The present invention relates to a functional food and a natural substance new drug composition having an effect on prevention and treatment of arthritis. More specifically, the present invention relates to a composition for prevention and treatment of osteoarthritis comprising juniper berry, European grape skin, European grape seed, And to a health functional food composition.
최근 국민생활수준의 향상과 생명과학 및 의학기술의 발전으로 인간수명이 연장되어 향후 20년 이내에 평균수명이 85세 이상이 될 가능성이 크고, 2010년 이후에는 전체인구의 10~15%까지 노인인구가 증가하여 본격적인 노령화 사회가 될 것으로 예상하고 있다. 고령인구가 증가함에 따라 노인성 질환, 즉 치매, 동맥경화, 관절염 등의 퇴행성 질환 환자들이 증가하고 있고, 이는 본인과 가족들에까지 경제적, 정신적인 어려움을 가져와 사회적인 문제로 대두되고 있다.In recent years, life expectancy is likely to increase to 85 years or older within the next 20 years due to the improvement in people's standard of living and the development of life sciences and medical technology. In 2010 and beyond, 10 to 15% And it is expected to become an aging society in earnest. As the elderly population increases, the number of patients with degenerative diseases such as dementia, arteriosclerosis and arthritis is increasing. This causes economic and psychological difficulties for themselves and their families, and it is becoming a social problem.
노인인구의 증가로 퇴행성 질환 관련 의약품 및 기능성 식품 시장이 급속히 증가하는 추세이나, 퇴행성 질환에 대한 근원적인 치료 또는 예방의약의 개발은 아직 부족한 실정이다. 노화 및 관련 질환에 대한 예방과 치료는 주로 약물과 수술에만 치우쳐 있고, 예방의 차원에서 보건 기능성 식품은 거의 없다. 따라서 임상적인 측면에서 안전성이 확보된 식품성 천연물질을 이용한 기능성, 영향성을 가지고 있는 구체적인 노화질환 예방식품의 개발이 필요하고, 이러한 노화질환 예방식품의 관심은 노인계층의 증가와 더불어 증대되고 있다. Although the market for drugs and functional foods related to degenerative diseases is rapidly increasing due to the increase in the elderly population, there is still a lack of development of essential therapeutic or preventive medicines for degenerative diseases. Prevention and treatment of aging and related diseases are mainly devoted to drugs and surgery, and there are few health functional foods in terms of prevention. Therefore, it is necessary to develop a preventive food for aging disease which has functional and effect using food-grade natural substance which is secured from the clinical aspect, and the interest of such aging-prevention food is increasing with the increase of the elderly group .
생명과학의 발달로 민간에서 사용해오던 약용 및 식용 자원에서 기능성식품 소재 및 제품개발이 추진되어 산업계에 급속도로 파급되고 있으며, 특히 최근 우리나라는 노령화 사회로 진입함에 따라 55세 이상의 경우 80%, 75세 이상의 경우 거의 대부분이 골관절 질환을 가지고 있는 것으로 알려져 있다. 대표적인 퇴행성 질환인 관절염은 우리나라에도 최소 60만명 이상의 환자가 있는 것으로 알려져 있으며 전 세계적으로 골질환(골관절염, 골다공증) 관련 치료제가 가장 많이 판매가 되었다. Development of functional food materials and products has been promoted in medicinal and edible resources that have been used in the private sector due to the development of life sciences and has been rapidly spreading to industry. Especially recently, as Korea has entered into an aging society, 80% Most of these cases are known to have osteoarthritis. Arthritis, a typical degenerative disease, is known to have at least 600,000 patients in Korea, and the world has the largest number of treatments for osteoarthritis (osteoarthritis, osteoporosis).
이런 골관절염과 같은 퇴행성 질환은 나이와 식습관에 따라 증가하고 있고 여러 치료제의 개발에도 불구하고 인구 노령화와 서구적인 식습관으로 인해 여전히 심각한 질환으로 남아 있으며 치사율은 낮지만 운동성을 방해하고 생산성을 낮추는 등의 삶의 질을 낮추는 주요 요인으로 지목되고 있다. 퇴행성 질환 개선 소재 발굴 및 기능성식품의 개발을 위한 생리활성물질의 효능평가 및 연구 확립은 보다 많은 기능성식품 후보물질의 실용화 및 상품화를 앞당길 수 있으며, 이러한 질병은 유전적인 요인과 식생활 등의 환경적 요인 등에 의해 일어나므로 예방 효과가 있는 식품을 꾸준히 섭취함으로서 면역능력을 증진시킬 수 있으므로 생물소재에 함유된 생리활성을 가진 기능성 물질을 연구하는 것은 매우 의미가 있다. Degenerative diseases such as osteoarthritis are increasing with age and eating habits. Despite the development of various treatments, the aging population and western eating habits still remain serious diseases. The mortality rate is low, Which is a major factor in lowering the quality of life. The evaluation and study of the efficacy of physiologically active substances for the improvement of degenerative diseases and the development of functional foods are expected to accelerate the commercialization and commercialization of more functional food candidates. These diseases are caused by environmental factors such as genetic factors and dietary habits , It is very meaningful to study functional materials having physiological activity contained in biomaterials because they can increase immunity by steadily ingesting food having a preventive effect.
2008년 식품의약품안전청 자료에 의하면 2007년 우리나라에서 판매된 건강기능식품은 총 7,234억원이며, 이 가운데 홍삼제품이 3,270억원으로 전체 45.2%를 차지했으며 이어 알로에제품(797억원), 비타민/칼슘보충제(785억원), 인삼제품(350억원), 글루코사민함유 제품(269억원) 등이 판매되었다. 특히 글루코사민 함유 제품은 노인계층에 꾸준히 판매되고 있다. 그러나 관절염의 예방치료에 글루코사민이 정말 효과가 있는가에 대해서는 의학계와 관련업계간에 의견이 엇갈리고 있다. 제조업체들은 글루코사민이 연골을 구성하는 단백질 생성을 촉진하여 중장년층과 갱년기 여성에게 연골의 건강을 가져다준다고 주장하지만 대부분 의사들은 관절 통증을 완화시키는 진통제 효과는 있지만 관절염 예방이나 치료효과는 검증된 것이 없다는 입장이다. According to the 2008 Korea Food & Drug Administration (KFDA), health food products sold in Korea in 2007 accounted for a total of KRW 723.4 billion, of which red ginseng products accounted for 45.2%, totaling KRW 327.0 billion, followed by aloe products (KRW 79.7 billion), vitamin / 78.5 billion won), ginseng products (35 billion won), and glucosamine-containing products (26.9 billion won). In particular, glucosamine-containing products are steadily being sold to the elderly. However, there is a disagreement between the medical community and the industry about whether glucosamine is really effective in preventing arthritis. Manufacturers argue that glucosamine promotes cartilage protein production by promoting the production of cartilage proteins, but most physicians claim that they have analgesic effects that alleviate joint pain, but no evidence of arthritis prevention or treatment. .
최근, 전통의약이나 민간요법으로 사용되어 온 천연물로부터 관절염 관련 기능성 식품 및 천연물 신약을 발견하고자 하는 연구가 미국, 유럽 및 일본 등의 선진국을 중심으로 전 세계적인 각광을 받고 있다. 그리고 비교적 안정성이 높고 효과가 탁월한 천연 식품으로부터 건강기능식품 및 천연물 신약 개발을 추진하고자 세계 굴지의 제약회사들의 관심이 고조되고 있다. Recently, studies for discovering arthritis-related functional foods and natural product drugs from natural products that have been used as traditional medicines or folk remedies have received worldwide attention, particularly in developed countries such as the United States, Europe, and Japan. Interest in the world's leading pharmaceutical companies has been rising to promote the development of health functional foods and natural products from relatively stable and highly effective natural foods.
골관절염을 통틀어 모든 염증(inflammation)질환은 여러 가지 형태의 감염(infection)이나 생체 내 대사산물 중의 자극성 물질에 대한 생체 내 방어기전의 발현이라 할 수 있고, 다양한 화학적 매개체가 염증의 발현 기전에 관여하고 있으며, 그 병인도 매우 복잡하다. 기존의 항염증제는 크게 스테로이드성 및 비스테로이드성 항염증제로 구분되며, 이중 대부분의 합성 항염증제는 주작용 이외에 여러 가지 부작용을 수반하는 경우가 많으므로 효과가 탁월하며 부작용이 적은 항염증제의 개발이 절실히 요구되고 있는 실정이다. All inflammatory diseases, including osteoarthritis, are manifestations of various types of infection and pre-in vivo defense against irritants in vivo metabolites, and various chemical mediators are involved in the mechanism of inflammatory expression , The pathogen is also very complicated. Conventional anti-inflammatory agents are classified into steroidal and non-steroidal anti-inflammatory agents. Most of synthetic anti-inflammatory agents are accompanied with various side effects in addition to the main action. Therefore, there is a desperate need for the development of anti- It is true.
골관절염은 신진대사 및 세포 재생 능력이 저하되어 있는 고 연령층에서 일어나는 퇴행성 질환으로, 그 근본적 치료가 거의 불가능하며 외과적 수술, 약물 요법 및 물리 치료 등이 시행되고 있으나, 일부 보조 요법을 제외하면 많은 부작용의 위험을 감수해야 한다. Osteoarthritis is a degenerative disease that occurs in older age groups with decreased metabolism and cell regeneration ability. Its basic treatment is almost impossible, and surgery, medication and physical therapy are performed. However, except for some adjuvant therapies, You have to take risks.
골관절염은 관절의 점진적인 퇴행성 변화를 특징으로 하며, 체중 부하 관절에 흔히 침범한다. 또한 골관절염은 활액 관절에 발생하는 관절염 중 가장 흔한 형태로 노년에 흔히 나타난다 (McAlindon TE et al., Am J Med. 106, pp 151-157, 1999). 슬관절은 골관절염이 진행되면서 관절염과 관련된 증상을 가장 흔하게 나타내는 부분이며, 체중부하 관절이면서 운동에 관련되어, 삶의 질에 직접적으로 영향을 미치게 된다 (Felson DT et al., Arthritis Rheum. 30, pp 914-918, 1987). Osteoarthritis is characterized by gradual degenerative changes in the joints, often involving weight bearing joints. Osteoarthritis is also the most common form of synovial arthritis occurring in synovial joints (McAlindon TE et al., Am J Med 106, pp 151-157, 1999). Knee arthritis is the most common symptom of arthritis associated with osteoarthritis and is a weight-bearing joint, which affects exercise and directly affects quality of life (Felson DT et al., Arthritis Rheum. -918, 1987).
여성에서 더 흔하게 증상을 나타나게 되며 연령이 증가하면서 증상의 발현이 증가되어 65세에서 70세 사이 인구의 7%, 80세 이상 인구에서 11.2%에서 증상을 나타내게 되며, 증상이 없더라도 방사선 사진에서 65세에서 70세 사이 인구의 27.4%, 80세 이상 인구의 43.7%에서 골관절염이 진단된다 (Dougados M et al., J Rhemmatol. 19(3), pp 378-84, 1992). 60세 이상 인구의 약 10% 정도가 퇴행성 관절염으로 불편감을 느끼게 되며, 미국의 경우 2천만명 정도가 삶의 질에 영향을 받고 있으며, 매년 600억 달러 이상이 관절염의 치료를 위해 사용되고 있다 (Buckwalter JA et al., Clin Orthop Relat Res. 427S, pp6-15, 2004).Symptoms are more common in women, with an increase in the number of symptoms and an increased incidence of symptoms in 7% of the population aged 65 to 70 years and in 11.2% of those aged 80 years or older. Osteoarthritis is diagnosed in 27.4% of the population aged 70 to 70 years and 43.7% of the population aged 80 years or older (Dougados M et al., J Rhemmatol. 19 (3), pp 378-84, 1992). Approximately 10% of people aged 60 or older feel uncomfortable with degenerative arthritis. In the United States, 20 million people are affected by quality of life, and more than $ 60 billion annually is used to treat arthritis (Buckwalter JA et al., Clin Orthop Relat Res. 427S, pp6-15, 2004).
연령의 증가 이외에 방사선학적 변성을 동반하는 퇴행성 슬관절염의 위험인자로는 가족력, 골격이나 관절의 성장과 형태 발전에 영향을 미칠 수 있는 발생기의 문제들, 관절의 손상, 특정한 반복되는 동작들, 비만 등이 있다 (Dieppe PA et al., Lancet. 365, pp965-973, 2005; Felson DT., Clin. Orthop Relat Res. 427S, pp16-2, 2004). 이환 관절 주변의 활액막염이 관절의 통증, 관절의 염증 그리고 연골이 손상에 중요한 역할을 하는 것으로 보고되고 있으며, 프로스타그란딘 (prostaglandin E2, PGE2), 산화질소 (nitric oxide, NO) 등이 염증과 연골의 손상을 매개하는 것으로 보고되고 있다 (Brenner SS et al., Osteoarthritis Cartilage. 12, pp 469-475, 2003).Risk factors for degenerative knee osteoarthritis with radiographic degeneration other than increased age include family history, genetic problems that can affect skeletal or joint growth and morphogenesis, joint damage, specific repetitive movements, obesity (Dieppe PA et al., Lancet, 365, pp 965-973, 2005; Felson DT., Clin. Orthop Relat Res. 427S, pp 16-2, 2004). It has been reported that synovitis around the joints plays an important role in joint pain, joint inflammation and cartilage damage. Prostaglandin E2, PGE2, nitric oxide (NO) (Brenner SS et al., Osteoarthritis Cartilage. 12, pp 469-475, 2003).
현대에 와서 골관절염은 식습관 변화와 교통의 발달로 인한 비만 환자의 급증으로 그 연령층이 낮고 광범위해진 일반적인 질환인데 반해, 아직까지 관절염 발병기전이 밝혀지지 않아 선택적인 치료 약물 또한 없는 실정이다. 따라서 관절염의 치료 목적은 관절의 통증과 염증을 감소시키고, 관절의 변형을 방지하는데 있다. 골관절염에 대한 근본적인 치료법이 없으므로 기초 치료법으로 물리, 운동요법을 행하고, 적당한 비스테로이드성 항염증 약물(NSAIDs)을 사용하여 염증을 완화시키며, 염증이 심하면 금염(gold salt) 요법 또는 페니실라민(penicillamine)요법을 실시하고 있다. 상기의 방법이 효능이 없으면 스테로이드(steroid) 제제를 사용하며, 난치성인 경우 면역 억제제를 사용하고, 변형 관절염으로 이행되면 수술요법을 실시한다. 관절염에 대한 소염, 진통작용을 위해 사용되는 비스테로이드성 항염증약물(NSAIDs)은 주로 사이클로옥시게나아제(cyclooxygenase)를 억제하여 염증반응에 관여하는 프로스타글란딘(prostaglandin)의 생성을 억제함으로써 항염증 작용을 나타낸다. 그 중 인도메타신(indomethacin)과 페닐부타존(phenylbutazone)의 경우 다른 NSAIDs에 비해 강력한 항염증 효과를 가지고 있다. 인도메타신은 염증을 유발하는 프로스타글란딘의 생성을 가장 강력하게 억제하는 약물 중에 하나로 경구 투여로 잘 흡수되나, 이러한 약물은 NSAIDs에서 나타나는 일반적인 위장관에 대한 부작용 이외에 현기증, 정신 착란, 드물게는 환각증을 동반한 정신병이 보고되어 있을 만큼 심한 독성을 갖고 있어, 고용량에서 환자의 33%가 투약을 중지해야 하는 등 많은 부작용을 갖고 있다. 페닐부타존 역시 사용 초기 다른 NSAIDs에 비해 류마티스 관절염, 강직성 척추염, 급성 통풍성 관절염 치료에 효과적으로 사용되어 왔으나, 과립구 감소증이나 재생 불량성 빈혈 등을 일으키는 혈액학적 이상을 포함하는 심한 독성 때문에 현재 사용되지 않고 있다. 이런 NSAIDs에 비해 스테로이드 제제는 환자에게 사용할 수 있는 가장 빠른 방법으로, 항염증 효과가 빠르고 극적으로 나타나며 환자에게 쾌감을 주는 약물로 알려져 있다. 그러나 널리 알려진 것처럼 이 약물은 세균 감염에 대한 저항력을 약하게 하고, 당뇨병의 악화, 쿠싱(Cushing) 증후군, 부신 부전증, 정신 기능장애 등을 일으키는 것으로 독성이 매우 심각할 뿐만 아니라 치료를 시작하면 중지하기가 어렵기 때문에 사용상 주의를 요하며, 가능하면 금해야 하는 것으로 알려져 있다. 기존의 관절질환 치료 의약품은 심각한 부작용을 일으키며 효과도 작아서 부작용이 적은 기능성식품에 대한 소비자들이 선호도가 증가되고 있으며, 노인계층에 꾸준히 판매되고 있는 글루코사민 함유 제품은 부작용이 거의 없지만 의학계에선 관절 통증을 완화시키는 진통제 효과는 있지만 관절염 예방이나 치료효과는 검증된 것이 없다는 입장이기 때문에 효능이 뒷받침되는 새로운 기능성 소재 탐색은 고령화 사회로 접어들면서 관절질환에 대한 관심과 함께 골질환 개선 제품에 대한 수요가 급증할 것으로 예상된다. Osteoarthritis in the modern age is a common and generalized disease due to the rapid increase of obese patients due to changes in eating habits and traffic, but there is no selective treatment drug because the mechanism of arthritis is not known yet. Therefore, the purpose of treatment of arthritis is to reduce pain and inflammation of the joints, and to prevent deformation of the joints. Because there is no fundamental treatment for osteoarthritis, physical and exercise therapy is performed as the basic treatment method, and appropriate nonsteroidal antiinflammatory drugs (NSAIDs) are used to alleviate the inflammation. If inflammation is severe, gold salt therapy or penicillamine ). If the above method is not effective, a steroid preparation is used. In the case of refractory, an immunosuppressive agent is used. Nonsteroidal anti-inflammatory drugs (NSAIDs) used for anti-inflammatory and analgesic effects on arthritis mainly inhibit cyclooxygenase and inhibit the production of prostaglandins (inflammation) . Among them indomethacin and phenylbutazone have strong anti-inflammatory effects compared to other NSAIDs. Indomethacin is one of the most potent inhibitors of inflammation-inducing prostaglandin production, and is well absorbed by oral administration, but these drugs have been associated with dizziness, delirium, and, in rare cases, with hallucinations, as well as side effects on the common gastrointestinal tract Psychosis has been reported to be so toxic that 33% of patients at high dose have many side effects such as discontinuation of medication. Phenylbutazone has also been used effectively in the treatment of rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis compared to other early NSAIDs, but is currently not used due to severe toxicity including hematologic abnormalities such as granulocytopenia or aplastic anemia. Compared to these NSAIDs, steroids are the fastest method available to patients, and they are known to be a drug that shows rapid and dramatic anti-inflammatory effects and pleasure to the patient. However, as is widely known, this drug is less resistant to bacterial infections and causes worsening diabetes, Cushing's syndrome, adrenal insufficiency, mental dysfunction, and is very toxic, It is known that it is difficult to use, and it should be avoided if possible. Conventional treatments for joint disease have serious side effects and are less effective, consumers are increasing their preference for functional foods with fewer side effects. Glucosamine-containing products, which are regularly sold to the elderly, have few side effects, but the medical community alleviates joint pain However, since there is no evidence that arthritis prevention or therapeutic effects have been proven, the search for new functional materials that are backed by efficacy will become an aging society, and there will be a surge in demand for bone disease-improving products as well as interest in joint diseases It is expected.
본 발명자들은 오랜 기간 동안 부작용 없이 사용되어 온 민간요법을 토대로 전통생물 자원으로부터 유용성분을 검색하고, 보다 효과적인 골관절 보호 및 골질환 예방 기능성식품을 개발할 수 있는 자료를 마련하고자, 전통 한방 조성물 가공식품들이 건강기능성 식품으로서의 전환 사례를 제시하고, 기능성소재 기술의 경쟁력 향상과 전통 소재의 유용성분에 대한 개별 약효 인증기법을 개발하기 위해 예의 연구를 거듭한 결과, 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모를 유효성분으로 함유하는 염증관련 질환 예방 및 치료를 위한 약학조성물 및 식품조성물을 제공하는 것이다. The present inventors have searched for useful ingredients from traditional biological materials based on folk remedies that have been used for a long time without adverse effects and have prepared traditional herbal composition processed foods As a result of intensive researches to improve the competitiveness of functional material technologies and to develop individual medicinal certification methods for useful ingredients of traditional materials, we have found that the use of Juniper berry, European grape skin, European grape seed And a pharmaceutical composition and a food composition for the prevention and treatment of inflammation-related diseases which contain white rice, wheat, and ginseng as active ingredients.
주니퍼베리 (노간주나무 열매)는 동의학사전 기록에 의하면 노가지나무과에 속하는 상록성 교목인 노간주나무 (또는 노가지나무(Juniperus rigida Sieb. dt Zucc.))의 익은 열매를 말린 것이다라고 나와있으며 풍습을 없애고 소변이 잘 나오게 한다. 약리실험에서 건위작용, 거담작용, 억균작용이 밝혀졌으며, 부종, 방광과 요도의 병, 류머티즘성 관절염, 아메바성 이질 등에 쓰인다.Juniper berry is said to have dried ripe berries from Juniperus rigida Sieb. Dt Zucc.), An evergreen tree belonging to the family Porphyra, according to prehistoric records. Let urine come out well. In pharmacological experiments, it has been shown that it works in the form of dry matter, gadolinium, and bacillus, and is used for edema, bladder and urethral diseases, rheumatoid arthritis and amoebic dysentery.
또한 유럽종 포도를 포함한 모든 포도류는 항산화물질을 포함하고 있는데 특히 포도씨 추출물은 바이오플라보노이드의 일종인 프로안토시아니딘을 다량 함유하고 있으며 결합조직의 기능을 향상시키고 심혈관계 질환, 관절염, 암을 유발하는 발생기 산소를 소거시킴으로써 조직손상을 막는다. 또한 포도씨와 껍질에 있는 프로안토시아니딘(proanthocyanidin)은 항바이러스, 항박테리아, 항염증, 항알러지 기능을 가지고 있다. 포도씨 추출물은 인체내에서 약 3일간 효과를 발휘할 수 있으며, 그 효과는 비타민 C의 20배, 비타민 E의 50배에 달한다. All grapes, including European grapes, contain antioxidants. Grape seed extracts contain a large amount of proanthocyanidins, a type of bioflavonoid, which improve the function of the connective tissues and improve cardiovascular disease, arthritis and cancer. It prevents tissue damage by eliminating the generator oxygen that is triggered. In addition, proanthocyanidin in grape seeds and skin has antiviral, antibacterial, anti-inflammatory and anti-allergic properties. The grape seed extract can be effective for about 3 days in the human body, and the effect is 20 times of vitamin C and 50 times of vitamin E.
백미는 백미꽃(Cynanchum atratum Bunge) 및 만생백미(C. versicolor Bunge)(박주가리과 Asclepiadaceae)의 뿌리를 건조한 것이다. 성상으로는 엷은 황갈색의 가늘고 긴 뿌리가 짧은 뿌리줄기에 모여서 나며, 길이 10~25㎝, 지름 1~2㎜이다. 뿌리는 부러지기 쉬우며, 특이한 냄새가 있고, 맛은 조금 맵다. 규명된 성분으로는 스테로이드 글리코사이드(Steroid glycoside), 네오리그난(Neolignan), 아세토페논(Aetophenone) 등이 있으며 약리작용으로는 항암작용, 항염증작용 및 해열, 이뇨약으로 열병의 중기 및 말기의 발열, 뇌졸중환자의 사지 부종 등에 쓰인다.White rice is the dried root of Cynanchum atratum Bunge and C. versicolor Bunge (Aspergillus and Asclepiadaceae). Appearance is light yellow-brown, elongated roots gathered in short rootstock, length 10 ~ 25㎝, diameter 1 ~ 2㎜. The roots are easy to break, have a peculiar smell, and taste a bit spicy. Steroid glycosides, Neolignan, and Aetophenone have been identified. Their pharmacological actions include anti-cancer, anti-inflammatory and antipyretic effects, diuretics, fever and fever of fever , And limb swelling in stroke patients.
우슬은 쇠무릎(Achyranthes japonica)의 뿌리를 말린 것으로, 당우슬 및 천우슬의 뿌리 두 가지가 상용된다. 당우슬의 뿌리에는 트리테르페노이드 사포닌이 함유되어 있고, 다량의 칼륨염도 함유되어 있다. 예로부터 우슬은 정혈작용, 이뇨효과, 혈압강하 효과, 진통작용이 알려져 있고, 보간, 보신하고, 근골을 튼튼하게 하는 효능이 있다고 알려져 있다(정보섭; 향약대사전, 영림사, pp340-341, 1998).It is dried with the roots of Achyranthes japonica. Two sprouts are used. The root of the sugarcane contains triterpenoid saponin and contains a large amount of potassium salt. It has been known for a long time that blood circulation, diuretic effect, blood pressure lowering effect and analgesic action are known, and it is known that it has an effect of interpolating, watching and strengthening muscular strength (Jung Hyun Suh, Yeonglim Corp, pp340-341, 1998) .
지모는 중국이 원산지이고, 한국에서는 중부지방에서 재배되는 다년초이다. 본 발명에서는 지모의 근경을 건조하여 사용하였으며, 그의 대표적인 것은 백합과의 지모(Anemarrhena asphodelorides BUNGE)로 이의 근경은 약전(KP, JP)에서 소염, 해열, 지사, 이뇨, 요통, 진정에 사용되고 있다. 이 약용식물에는 아스포닌(Asphonin) 6% 이외에도 살사사포닌(Sarsasaponin), 마르코게닌(Markogenin; 2-hydroxy sarsasapogenin) 등의 스테로이드 사포게닌, 플라보노이드, 탄닌 등이 함유되어 있다. 동의보감이나 본초강목 등에서는 지모를 골증노열에 사용하였는데, 골증노열이란 용어를 해석하면 골즈에서 골소송증이 발증되어 만성적인 동통을 호소하는 것을 의미한다.It is a perennial plant that is grown in Central China and origin in China. In the present invention, the rhizome is dried and used. Typical examples thereof are Anemarrhena asphodelorides BUNGE, which is used for anti-inflammation, fever, diarrhea, diuretic, back pain and sedation in the pharmacopoeia (KP, JP). This medicinal plant contains steroid sapogenins, flavonoids and tannins, such as sarsasaponin and 2-hydroxy sarsasapogenin, as well as 6% asphonin. In the case of Dong-Bo-bo-gyung and Hwa-gok gangmyeon, the hair was used for osteoporotic fever. The interpretation of the term osteoporosis means that the osteoporosis is manifested in the bone and the patient complains of chronic pain.
이에 본 발명가들은 상기 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 천연 복합 추출물을 제조하고, 본 발명의 추출물들이 질소산화물(NO) 생성 억제, 염증성 사이토카인인 종양괴사인자-알파 (TNF-α), 인터루킨-1 베타 (IL-1β), 프로스타글란딘 E2 (PGE2) 생성 억제활성을 보여줌으로써 우수한 염증성 질환 예방 또는 치료용 효과를 가짐을 확인하였고, 또한 세포독성이 없음을 밝힘으로써 본 발명을 완성하였다.
Accordingly, the inventors of the present invention prepared a natural complex extract of Juniper berry, European grape skin, European grape seed, White rice, Wasser and Zymo, and found that the extracts of the present invention inhibit the production of nitrogen oxides (NO), tumor necrosis factor (TNF-α), interleukin-1 beta (IL-1β) and prostaglandin E 2 (PGE 2 ), and thus has excellent prophylactic or therapeutic effects against inflammatory diseases and has no cytotoxicity To complete the present invention.
상기 과제를 해결하기 위한 본 발명의 적절한 실시 형태에 따르면, 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모로 이루어진 천연 복합 추출물을 유효성분으로 함유하는 골관절염 예방에 효과적인 한방 조성물을 제공하는 것이다.According to a preferred embodiment of the present invention for solving the above problems, there is provided a herbal composition which is effective for preventing osteoarthritis comprising, as an active ingredient, a natural compound extract comprising Juniper berry, European grape skin, European grape seed, White rice, .
나아가 본 발명은 상기 어느 하나 이상의 상기 추출물을 유효성분으로 함유하는 골관절염 예방 또는 개선용 건강기능식품 조성물을 제공한다.
Further, the present invention provides a health functional food composition for preventing or ameliorating osteoarthritis containing any one of the above extracts as an active ingredient.
본 발명은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모로 이루어진 천연 추출물 및 상기 천연 추출물 중 어느 하나 이상이 포함된 천연 복합 추출물로 이루어지는 군으로부터 선택된 어느 하나를 유효성분으로 함유하는 것을 특징으로 하는 염증성 질환의 예방 또는 치료용 조성물을 제공한다.The present invention relates to a pharmaceutical composition containing, as an active ingredient, any one selected from the group consisting of Juniper berries, European grape skin, European grape seed, natural extract consisting of white rice, Or a pharmaceutically acceptable salt thereof. The present invention also provides a composition for preventing or treating an inflammatory disease.
본 발명의 바람직한 실시 형태에 따르면, 상기 추출물 양이 전체 조성물의 0.01~95% 중량비를 갖는 것을 특징으로 한다.According to a preferred embodiment of the present invention, the amount of the extract is 0.01 to 95% by weight of the total composition.
본 발명의 다른 바람직한 실시 형태를 따르면, 상기 천연 복합 추출물은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 조성비가 1 : 1 : 1 : 1 : 1 : 1의 중량비로 혼합된 것을 특징으로 한다.According to another preferred embodiment of the present invention, the natural complex extract is mixed with a composition ratio of 1: 1: 1: 1: 1: 1: 1 ratio of juniper berry, European grape skin, European grape seed, .
또한, 본 발명은 상기의 조성물을 유효성분으로 함유하는 염증성 질환의 예방 또는 치료용 건강기능식품을 제공한다.The present invention also provides a health functional food for the prevention or treatment of inflammatory diseases containing the above composition as an active ingredient.
본 발명의 바람직한 실시 형태에 따르면, 상기 건강기능식품은 식품학적으로 허용 가능한 식품 첨가제를 포함하고, 정제, 캡슐제, 환제 또는 액제 중 어느 하나의 형태를 포함하며, 식품, 음료, 껌, 차, 비타민 복합제, 건강기능성식품의 형태를 더 포함하는 것을 특징으로 한다.According to a preferred embodiment of the present invention, the health functional food comprises a foodstuff acceptable food additive and is in the form of any one of tablet, capsule, pill or liquid, and is in the form of food, beverage, gum, tea, Vitamin complex, and health functional food.
또한, 본 발명은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 각각의 천연물을 건조하는 단계; 상기 건조된 각각의 천연물을 동일 중량비로 합하여 합한 천연물의 5~20배 부피 또는 중량의 물을 가해 80~100℃의 추출온도에서 3~5시간 동안 열수 추출법으로 2~5회 동안 추출하는 단계; 상기 단계로부터 수득한 추출물을 여과한 후, 40~80℃에서 감압 농축하여 얻어진 엑기스를 엑기스 총량의 10~60배의 물로 1~5회 공비 농축하는 단계; 및 상기 공비 농출한 엑기스를 동결건조 또는 진공건조를 통하여 분말엑기스로 제조하는 단계를 포함하는 것을 특징으로 하는 골관절염 예방 및 개선용 조성물의 제조방법을 제공한다.
The present invention also relates to a method for producing a nutritional composition, comprising the steps of: drying each natural product of Juniper berry, European grape skin, European grape seed, White rice, Adding the dried natural products at the same weight ratio, adding 5 to 20 times volume or weight of the natural product, extracting the product for 2 to 5 times at a temperature of 80 to 100 캜 for 3 to 5 hours by hot water extraction; Filtering the extract obtained from the step, concentrating the extract at a reduced pressure at 40 to 80 ° C, and azeotropically concentrating the obtained extract 1 to 5 times with 10 to 60 times the total amount of the extract; And preparing an extract of the azeotropic mixture as a powdery extract through lyophilization or vacuum drying. The present invention also provides a method for preparing a composition for preventing and improving osteoarthritis.
본 발명은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모로 이루어진 천연 복합 추출물을 함유하는 염증성 질환 개선 또는 치료용 조성물에 관한 것으로, 본 발명의 상기 추출물은 질소산화물(NO) 생성 억제, 염증성 사이토카인인 종양괴사인자-알파 (TNF-α), 인터루킨-1 베타 (IL-1β), 프로스타글란딘 E2 (PGE2) 생성 억제 활성을 동시에 보유하여 염증성 질환 개선 및 치료용 효과를 나타내며, 세포독성은 없으므로, 염증성 질환의 개선 및 치료 또는 예방을 위한 의약품, 건강기능식품에 유용하게 사용될 수 있다.
The present invention relates to a composition for improving or treating an inflammatory disease, which comprises a natural compound extract consisting of Juniper berry, European grape skin, European grape seed, white rice, (TNF-α), interleukin-1 beta (IL-1β), and prostaglandin E 2 (PGE 2 ) Since it has no cytotoxicity, it can be usefully used for medicines and health functional foods for the improvement and treatment or prevention of inflammatory diseases.
도 1은 본 발명의 천연 복합 추출물을 통한 세포독성평가를 BALB/c 마우스 유래의 RAW 264.7 대식세포주에 실험하여 측정한 자료이다.
도 2는 본 발명의 천연 복합 추출물을 통한 일산화질소(NO)의 생성 억제효과를 BALB/c 마우스 유래의 RAW 264.7 대식세포주에 실험하여 측정한 자료이다.
도 3은 본 발명의 천연 복합 추출물을 통한 종양괴사인자(TNF-α) 생성 억제효과를 BALB/c 마우스 유래의 RAW 264.7 대식세포주에 실험하여 측정한 자료이다.
도 4는 본 발명의 천연 복합 추출물을 통한 인터루킨 1-베타(IL-1β) 생성 억제효과를 BALB/c 마우스 유래의 RAW 264.7 대식세포주에 실험하여 측정한 자료이다.
도 5는 본 발명의 천연 복합 추출물을 통한 프로스타글란딘 E2(PGE2) 생성 억제효과를 BALB/c 마우스 유래의 RAW 264.7 대식세포주에 실험하여 측정한 자료이다.FIG. 1 is a data obtained by measuring the cytotoxicity of RAW 264.7 macrophage cell line derived from BALB / c mouse using the natural compound extract of the present invention.
FIG. 2 is a data obtained by measuring the inhibitory effect of the natural combination extract of the present invention on the production of nitrogen monoxide (NO) by RAW 264.7 macrophage cell line derived from BALB / c mouse.
FIG. 3 is a graph showing the inhibitory effect of the natural compound extract of the present invention on tumor necrosis factor (TNF-α) production in RAW 264.7 macrophage cells derived from BALB / c mice.
FIG. 4 is a data obtained by measuring the inhibitory effect of the natural compound extract of the present invention on the production of interleukin 1-beta (IL-1β) by RAW 264.7 macrophage cell line derived from BALB / c mouse.
FIG. 5 shows experimental results of inhibiting the production of prostaglandin E 2 (PGE 2 ) by the natural combination extract of the present invention in RAW 264.7 macrophage line derived from BALB / c mouse.
이하 본 발명을 상세히 설명한다.
Hereinafter, the present invention will be described in detail.
본 발명은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모로 이루어진 천연 복합 추출물로 이루어지는 군으로부터 선택되는 어느 하나 이상의 상기 추출물을 유효성분으로 함유하는 염증성 질환 예방 또는 치료용 약학적 조성물을 제공한다.The present invention relates to a pharmaceutical composition for the prevention or treatment of inflammatory diseases containing, as an active ingredient, any one or more of the above extracts selected from the group consisting of Juniper berries, European grape skin, European grape seed, Lt; / RTI >
상기 추출물은 채취한 것, 양식한 것 또는 시판되는 것 등 제한 없이 사용할 수 있으며, 일례로 채취한 후 물로 세척하여 이물질을 제거한 후 건조하여 사용하는 것이 바람직하다.The extract can be used without limitation such as collected, cultured, or marketed. For example, it is preferable to collect the extract and wash it with water to remove foreign matter and dry it.
또한, 본 발명은 상기 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 군으로부터 선택되는 어느 1종 이상의 추출물을 염증을 억제할 정도의 양으로 투여하는 단계를 포함하는 염증의 예방 또는 개선하는 방법을 제공하는데 이용될 수 있다.The present invention also relates to a method of treating inflammation, comprising administering an extract of at least one selected from the group consisting of Juniper berry, European grape skin, European grape seed, rice white, Prevention or amelioration of a disease or condition.
이 때, 염증을 억제할 정도의 양이란 이에 제한되는 것은 아니나 바람직하게는 0.1 내지 500 mg/kg 더욱 바람직하게는 1 내지 100 mg/kg이다. 상기 투여량은 특정 환자의 체중, 연령, 성별, 건강상태, 식이, 투여기간, 투여방법, 제거율, 질환의 중증도 등에 따라 변화될 수 있다.In this case, the amount to inhibit inflammation is not particularly limited, but is preferably 0.1 to 500 mg / kg, more preferably 1 to 100 mg / kg. The dose may vary depending on the weight, age, sex, health condition, diet, administration period, administration method, elimination rate, severity of disease, etc. of the specific patient.
본 발명에 따른 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 군으로부터 선택되는 어느 1종 이상의 추출물의 염증성질환 예방 또는 개선용 효과를 측정하기 위하여 BALB/c 마우스 유래의 RAW 264.7 대식세포주를 대상으로 질소산화물(NO) 생성 억제, 염증성 사이토카인인 종양괴사인자-알파 (TNF-α), 인터루킨-1 베타 (IL-1β), 프로스타글란딘 E2(PGE2) 생성 억제 및 세포독성 평가 실험을 수행하였다.
In order to determine the effect of at least one extract selected from the group consisting of Juniper berry, European grape skin, European grape seed, Japanese white rice, oyster and Japanese oyster according to the present invention for the prevention or amelioration of inflammatory diseases, RAW 264.7 Inhibition of nitric oxide (NO) production in macrophage cell lines, inhibition of inflammatory cytokines TNF-α, interleukin-1 beta, prostaglandin E2 (PGE2) Experiments were performed.
본 발명의 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 천연 복합 추출물에 대한 항염증 생리활성 실험결과는 도1 내지 5를 통해 나타내었다. The results of the anti-inflammatory physiological activity tests on the natural compound extracts of Juniper berry, European grape skin, European grape seed, White rice, Wasser and Zymo of the present invention are shown in FIGS.
따라서 본 발명은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모로 이루어진 천연 복합 추출물은 질소산화물(NO) 생성 억제, 염증성 사이토카인 종양괴사인자-알파(TNF-α), 인터루킨-1 베타(IL-1β) 및 프로스타글란딘 E2(PGE2) 생성 억제 효과를 나타냄으로써 이로부터 유발되는 염증성 질환, 구체적으로는 부종, 피부염, 알레르기, 아토피, 천식, 결막염, 치주염, 비염, 중이염, 인후염, 편도염, 폐렴, 위궤양, 위염, 크론병, 대장염, 치질, 통풍, 간직성 척추염, 류마티스 열, 루푸스, 섬유근통(fibromyalgia), 건선관절염, 골관절염, 류마티스관절염, 견관절주위염, 건염, 건초염, 건주위염, 근육염, 간염, 방광염, 신장염, 쇼그렌 증후군(sjogren’s syndrome), 다발성 경화증 및 급성 또는 만성 염증 질환 등을 예방 또는 개선용 의약품, 건강기능식품에 매우 유용하게 사용될 수 있다.Accordingly, the present invention provides a natural combination extract consisting of Juniper berry, European grape skin, European grape seed, White rice, Wasser and Zymo, which is effective for inhibiting NO production, inhibiting inflammatory cytokine tumor necrosis factor- Inflammatory diseases, such as edema, dermatitis, allergies, atopy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sphincteritis, and the like, which exhibit an inhibitory effect on the production of IL-1 beta (IL-1?) And prostaglandin E2 Osteoarthritis, rheumatoid arthritis, shoulder inflammation, tendonitis, hay fever, tendinitis, myalgia, osteoarthritis, arthritis, osteoarthritis, osteoarthritis, osteoarthritis, osteoarthritis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, , Drugs for preventing or improving hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis and acute or chronic inflammatory diseases, Can be usefully used.
또한, 본 발명의 추출물 및 식품학적으로 허용 가능한 식품 첨가제를 포함하는 연골재생 효과와 염증, 진통 개선을 위한 건강 기능식품을 제공한다. 본 발명의 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명의 화합물을 첨가할 수 있는 식품으로는, 예를 들어 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등이 있다. 상세하게는, 본 발명의 추출물을 유효성분으로 함유하는 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 연골재생 효과와 염증, 진통 개선용 건강 기능식품을 제공한다. Also provided is a cartilage regeneration effect comprising the extract of the present invention and a pharmaceutically acceptable food additive, and a health functional food for improving inflammation and pain. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids. Examples of the foods to which the compound of the present invention can be added include various foods, beverages, gums, tea, And health functional foods. In detail, the present invention provides a cartilage regeneration effect and an anti-inflammatory and analgesic health functional food comprising an extract containing the extract of the present invention as an active ingredient and a pharmaceutically acceptable food-aid additive.
본 발명의 약학적 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다.The pharmaceutical composition of the present invention may be various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
비수성용제, 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
본 발명의 적절한 실시 형태에 따르면, 추출물 양이 전체 조성물의 0.01~95% 중량비를 갖는 것이 바람직하다.According to a preferred embodiment of the present invention, it is preferred that the amount of extract has a weight ratio of 0.01 to 95% of the total composition.
본 발명의 적절한 실시 형태에 따르면, 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 조성비가 1 : 1 : 1 : 1 : 1 : 1의 중량비로 혼합된 것이 바람직하다.According to a preferred embodiment of the present invention, it is preferable that the composition ratio of juniper berry, European grape skin, European grape seed, White rice, Wasser and Zymo are mixed in a weight ratio of 1: 1: 1: 1: 1: 1.
본 발명의 적절한 실시 형태에 따르면, 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 각각의 천연물을 건조한 후, 각 천연물을 동일 중량비로 합하여 합한 천연물의 5~20배 부피/중량의 물을 가해 80~100℃의 추출온도에서 3~5시간 동안 열수 추출법으로 2~5회 동안 추출하여, 상기 단계로부터 수득한 추출물을 여과한 후, 40~80℃에서 감압 농축하여 얻어진 엑기스를 엑기스 총량의 10~60배의 물로 1~5회 공비 농축한 다음, 동결건조 또는 진공건조를 통하여 분말엑기스를 제조하는 제 2단계 등을 포함하는 것을 특징으로 하는 골관절염 예방 및 개선용 약학적 조성물의 제조방법을 제공한다.
According to a preferred embodiment of the present invention, each natural product of Juniper berries, European species grape skin, European species grape seed, white rice, wool and plum is dried, and then 5 to 20 times by volume / The extract is extracted with water for 2 to 5 times by hot water extraction at an extraction temperature of 80 to 100 ° C for 3 to 5 hours. The extract obtained from the above step is filtered and concentrated under reduced pressure at 40 to 80 ° C. And a second step of azeotropically concentrating the extract concentrate 1 to 5 times with 10 to 60 times the total amount of extract and then lyophilizing or vacuum drying the extract to prepare a powdery extract, and a pharmaceutical composition for preventing and improving osteoarthritis Of the present invention.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
단, 하기 실시예, 참고예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 이에 의해 한정되는 것은 아니다.
However, the following examples, reference examples and experimental examples are illustrative of the present invention, and the present invention is not limited thereto.
실시예 1. 본 발명에 따른 골관절염 예방 및 개선용 천연 복합 생약 추출물의 제조
Example 1. Preparation of natural herbal medicine extracts for prevention and improvement of osteoarthritis according to the present invention
1-1. 천연 복합 생약의 조성1-1. Composition of natural complex herbal medicine
본 실시예 에서는 하기 표 1의 천연 복합 생약의 조성으로 골관절염 예방 및 개선용 천연 복합 생약 조성물을 제조하였다.
In this Example, a natural combination herbal composition for prevention and improvement of osteoarthritis was prepared by the composition of the natural combination herbal medicine shown in Table 1 below.
1-2. 천연 복합 생약 추출물 (열수 추출물)1-2. Natural herbal medicine extract (hot water extract)
상기 표 1의 비율에 따라 주니퍼베리 16 중량%, 유럽종 포도씨 16 중량%, 유럽종 포도껍질 16 중량%, 백미 16 중량%, 우슬 18 중량% 및 지모 18 중량%를 혼합하여 천연 복합 생약 추출물을 제조하였다. 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모로 이루어진 천연물을 건조한 후, 천연물에 천연물의 5~20배 부피/중량의 물을 가하여 80~100℃의 추출온도에서 3~5시간 동안 열수 추출법으로 2~5회 동안 추출하여, 상기 단계로부터 수득한 추출물을 여과한 후, 40~80℃에서 감압 농축하였다.
According to the ratio shown in Table 1, 16% by weight of Juniper berries, 16% by weight of European seed grains, 16% by weight of European grape skin, 16% by weight of white rice, 18% by weight of astaxanthin and 18% . Dried water is added to natural products at a ratio of 5 to 20 times volume / weight of natural product, and the product is dried at an extraction temperature of 80 to 100 ° C for 3 to 5 times For 2 to 5 times. The extract obtained from the above step was filtered, and then concentrated under reduced pressure at 40 to 80 ° C.
참고예 1. 실험재료의 준비Reference Example 1. Preparation of experimental material
세포 배양액인 세포배양용 배지(Dulbecco's Modified Eagle Medium, Cat # 11995, 이하, 'DMEM'라고 한다.), 소태아혈청(Fetal Bovine Serum, Cat # 16000-044, 이하, 'FBS'라고 한다.), 스트렙토마이신-페니실린(Streptomicin-penicillin, Cat # 15140-122) 등의 세포배양용 시약들은 깁코(Gibco) BRL사 (NY, USA)에서 구입하였다. 실험에 사용된 시약 중 세포증식 분석(Aqueous One Solution Cell Proliferation Assay)(MTS) 키트와 그리스 시약(Griess Reagent System, Cat # G3580)은 프로메가(Promega)사(WI, USA)에서 구입하였다. 세포배양용액 내 싸이토카인(cytokine) 측정을 위한 ELISA 키트는 (TNF-α, Cat #88-7324 ; IL-1β, Cat #88-7013)는 이바이오사이언스(eBioscience)사 (CA, USA)에서 구입하였으며, PGE2 분석 키트(Cat # SKGE004B)는 R&D 시스템사 (MN, USA)에서 구입하였다. 실험에 사용된 모든 시약은 분석용 등급 이상으로 사용하였다.
(Dulbecco's Modified Eagle Medium, Cat # 11995, hereinafter referred to as 'DMEM') and fetal bovine serum (Cat # 16000-044, hereinafter referred to as 'FBS') which is a cell culture medium. , And Streptomycin-penicillin (Cat # 15140-122) were purchased from Gibco BRL (NY, USA). The Aqueous One Solution Cell Proliferation Assay (MTS) kit and the Griess Reagent System (Cat # G3580) were purchased from Promega (WI, USA). An ELISA kit (TNF-α, Cat # 88-7324; IL-1β, Cat # 88-7013) for cytokine measurement in cell culture solutions was purchased from eBioscience Inc. (CA, USA) And the PGE 2 assay kit (Cat # SKGE004B) was purchased from R & D Systems, Inc. (MN, USA). All reagents used in the experiment were used for analytical grade or higher.
참고예 2. 세포배양Reference Example 2. Cell culture
마우스의 대식세포주인 RAW264.7 세포 (한국세포주은행 (KCLB))를 10% FBS과 1% 페니실린-스트렙토마이신(penicillin-streptomycin)을 포함하는 DMEM 배지에 37℃, 5% CO2의 조건에서 배양하여 하기 실험에 사용하였다. 또한 모든 실험결과는 평균과 표준편차로 표시하고 유의성 검증은 시그마 플롯 (Sigma Plot, Window용 version 7.0)을 이용하여 스튜던트의 T 검정(student's t-test)(p<0.001)을 실시하여 실험군과 대조군 또는 염증유발 성분인 지질다당체(Lipopolysaccharide, 이하, 'LPS'라고 한다.)간의 유의성을 표기하였다.
RAW264.7 cells (Korean Cell Line Bank (KCLB)), a macrophage cell line of mouse, was cultured in DMEM medium containing 10% FBS and 1% penicillin-streptomycin under the conditions of 37 ° C and 5% CO 2 And used in the following experiments. In addition, all the test results were expressed as means and standard deviation. The significance test was performed by Student's t-test (p <0.001) using Student's t-test (Sigma Plot, version 7.0 for Window) Or Lipopolysaccharide (hereinafter referred to as 'LPS'), which is an inflammation-inducing component.
실험예 1. MTS 분석Experimental Example 1. MTS analysis
상기 실시예 1-2에서 수득한 추출물의 세포에 대한 독성을 측정하기 위해 문헌(Desai, A, Vyas T, Amiji M. Cytotoxicity and apoptosis enhancement in brain tumor cells upon coadministration of paclitaxel and ceramide in nanoemulsion formulations. J. Pharm. Sci. 97(7): 2745-56, 2008)에 기재된 5-(3-카르복시페닐)-2H-테트라-졸륨 분자내 염(5-(3-carboxyphenyl)-2H-tetra-zolium inner salt, 이하 'MTS'라고 한다.) 분석 방법을 이용하여 하기와 같이 실험을 수행하였다.
To determine the toxicity of the extracts obtained in Example 1-2 above to cells, Desai, A, Vyas T, Amiji M. Cytotoxicity and apoptosis enhancement in brain tumor cells coadministration of paclitaxel and ceramide in nanoemulsion formulations J (3-carboxyphenyl) -2H-tetra-zolium inner (3-carboxyphenyl) -2H-tetrazolium salt described in salt, hereinafter referred to as " MTS ").
상기 참고예 2의 방법으로 배양된 RAW264.7 세포를 96 웰 플레이트(well plate)에 1×104세포/웰로 분주하고, 상기 실시예 1에서 수득한 추출물을 각각 농도별(5, 10, 20, 50㎍/㎖)로 24시간 동안 처리하였다. 웰당 20 ㎕의 MTS 용액을 첨가하여 37℃, 5% CO2 배양기에서 4시간 동안 반응시킨 후, 마이크로 플레이트 리더 (ELISA reader, Tecan, Austria)를 이용하여 450 ㎚에서 흡광도의 변화를 측정하여 추출물을 처리하지 않은 대조군에 대한 세포생존율을 백분율로 표시하였다. 각 농도별 약재가 갖는 흡광도를 보정하기 위하여 세포를 뺀 배지를 같이 배양하여 대조군과 실험군의 흡광도를 비교 보정하여 세포 생존율을 백분율 (평균값± 표준편차)로 표시하였다.
RAW 264.7 cells cultured by the method of Reference Example 2 were dispensed into a 96-well plate at 1 × 10 4 cells / well, and the extracts obtained in Example 1 were diluted with 5, 10, 20 , 50 [mu] g / ml) for 24 hours. After adding 20 μl of MTS solution per well, the reaction was carried out in a 5% CO 2 incubator at 37 ° C. for 4 hours. The absorbance at 450 nm was measured using a microplate reader (ELISA reader, Tecan, Austria) Cell viability for the untreated control was expressed as a percentage. In order to calibrate the absorbance of the medicinal materials at each concentration, the medium in which the cells were removed was cultured together, and the absorbance of the control group and the experimental group was compared and expressed, and the cell survival rate was expressed as a percentage (mean value ± standard deviation).
실시예 1-2의 천연 복합 생약 추출물을 각 농도별 (5, 10, 20, 50ug/ml)로 24hr 동안 처리한 결과, 도 1에서 도시한 바와 같이 실시예 1-2의 고농도 실험군인 50㎍/㎖의 농도까지는 90% 이상의 세포생존율을 나타냈으며, 셀레콕시브 군들은 74~80%의 세포생존율을 보였다.
As shown in FIG. 1, the natural herbal medicine extract of Example 1-2 was treated with each concentration (5, 10, 20, 50 ug / ml) for 24 hours. As a result, / Ml, cell survival rate of 90% or more was observed. Celecoxib group showed cell survival rate of 74 ~ 80%.
실험예 2. 일산화질소(NO)의 생성량 측정Experimental Example 2. Measurement of nitrogen monoxide (NO) production amount
일산화질소(Nitric Oxide, NO)의 생성량을 측정하기 위해 문헌(Wang S et al., J. Ethnopharmacol., 114(3), pp458-462, 2007)에 기재되어 있는 방법을 이용하여 하기와 같이 실험하였다. 상기 참고예 2의 방법으로 배양된 RAW264.7 세포에 상기 실시예 1-2에서 수득한 복합 생약 추출물을 전처리 하고 1시간 후 1 ng/㎖의 LPS를 처리하여 24시간 동안 배양하였다. 배양액 50 ㎕와 같은 양의 그리스 반응액 (Griess Reagent)을 넣어주고 10분간 상온에서 반응시킨 후 마이크로 플레이트 리더(ELISA reader)를 이용하여 흡광도 540 ㎚에서 측정하였다. 아질산 나트륨 (sodium nitrite)의 농도별 표준곡선을 이용하여 배양액 내의 일산화 질소의 농도를 결정하였다.To measure the amount of nitric oxide (NO) produced, a method described in Wang S et al., J. Ethnopharmacol., 114 (3), pp 458-462, 2007, Respectively. RAW264.7 cells cultured by the method of Reference Example 2 were pre-treated with the herbal extracts obtained in Example 1-2 and treated with 1 ng / ml of LPS for 1 hour and cultured for 24 hours. The same amount of grease reagent as that of the culture solution (50 μl) was added, and the reaction was carried out at room temperature for 10 minutes. Then, the absorbance was measured at 540 nm using an ELISA reader. The concentration of nitrogen monoxide in the culture medium was determined using a standard curve of the concentration of sodium nitrite.
실험결과, 도 2에 나타난 바와 같이, LPS 1 ng/㎖의 농도로 처리하였을 때, 아무 처리도 하지 않은 대조군에 비하여 일산화질소(NO)의 생성량이 약 36배 증가됨을 확인할 수 있었다. 또한 복합 생약 추출물 50 ㎍/㎖의 농도를 1시간 동안 전 처리하였을 때, LPS-유도된 일산화질소(NO)의 생성감소율이 저농도인 5ug/ml에서는 약 62%, 고농도인 50 ㎍/㎖의 농도에서는 75%로 뚜렷한 감소효과를 확인할 수 있었다.
As shown in FIG. 2, when the concentration of LPS was 1 ng / ml, the amount of nitrogen monoxide (NO) was increased about 36 times as compared with the control without any treatment. When the concentration of 50 ㎍ / ㎖ of complex herbal extracts was pretreated for 1 hour, the reduction rate of the production of LPS - induced NO was about 62% at the low concentration of 5 ug / ml and the concentration of the high concentration of 50 ㎍ / And 75%, respectively.
실험예 3. Mouse TNF-α, mouse IL-1β cytokine 생성량 측정Experimental Example 3. Measurement of Mouse TNF-α, mouse IL-1β cytokine production
염증을 나타내는 지표로써, 세포 배양액 내의 염증성 사이토카인 (proinflammatory cytokine) 종양괴사인자-알파(mouse TNF-α), 인터루킨-1 베타 (mouse IL-1β)의 양을 측정하기 위해 면역효소분석 키트를 이용하여 ELISA 분석법 (Enzyme-Linked Immunosorbent Assay) 실험을 수행하였다. As an indicator of inflammation, an immunoenzymatic assay kit was used to measure the amount of proinflammatory cytokine tumor necrosis factor-alpha (mouse TNF-α) and interleukin-1 beta (mouse IL-1β) And then subjected to ELISA (Enzyme-Linked Immunosorbent Assay).
상기 참고예 2의 방법으로 배양된 RAW264.7 세포에 상기 실시예 1에서 수득한 천연 복합 생약 추출물을 5, 10, 20, 50ug/ml의 농도로 1시간 동안 전 처리 한 후 1 ng/㎖의 LPS를 처리하였다. 24시간 동안 5% CO2, 37℃로 배양한 후 세포 배양액을 적절한 농도로 희석하였다. 각각의 사이토카인 항체(cytokine capture antibody)로 코팅된 96 웰플레이트(well plate)에 100 ㎕씩 첨가하여 4℃에서 하룻밤 동안 방치시켰다. 워싱 완충액(washing buffer)로 5회 세척하고, 각각의 사이토카인(cytokine) 비오티닐화 항체 반응액(biotinylated antibody reagent)을 100 ㎕를 각각의 웰에 처리하여 1시간 동안 상온에서 반응시킨 후 5회 세척한 다음, 100 ㎕의 스트렙타비딘-HRP 용액(streptavidine-HRP solution)을 각각의 웰에 처리하여 1시간 동안 상온에서 반응시킨 후 다시 세척 완충용액(washing buffer)로 5회 세척하였다. 여기에 디(2-에틸헥실)-2,4,5-트리메톡시벤자말로네이트(di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate, TMB) 기질을 100 ㎕씩 처리하여 5~30 분간 반응시킨 후 100 ㎕의 반응 정지용액(stop solution)을 처리한 후 450 ㎚에서 흡광도를 측정하였다. The RAW264.7 cells cultured by the method of Reference Example 2 were pretreated with the natural herbicidal extracts obtained in Example 1 at concentrations of 5, 10, 20 and 50 ug / ml for 1 hour, and then treated with 1 ng / ml LPS was treated. After culturing for 24 hours at 5% CO 2 at 37 ° C, the cell culture was diluted to an appropriate concentration. 100 [mu] L was added to a 96 well plate coated with each cytokine capture antibody, and the plate was allowed to stand overnight at 4 [deg.] C. 100 μl of each cytokine biotinylated antibody reagent was treated in each well and reacted at room temperature for 1 hour, followed by 5 times washing with washing buffer After washing, streptavidin-HRP solution (100 μl) was added to each well, reacted at room temperature for 1 hour, and then washed 5 times with washing buffer. 100 μl of di (2-ethylhexyl) -2,4,5-trimethoxybenzalmalonate (TMB) substrate was treated with 5 ~ 30 After incubation for one minute, 100 μl of stop solution was treated and absorbance was measured at 450 nm.
실험결과, 도 3에 나타난 바와 같이 LPS에 의해 유도되는 종양괴사인자-알파 (TNF-α)의 생성량은 천연 복합 생약 추출물의 저농도인 5 ㎍/㎖, 고농도인 50 ㎍/㎖ 농도처리군에서 각각 39%, 63% 감소하였다. 또한 도 4에 나타난 바와 같이, LPS에 의해 유도되는 인터루킨-1 베타 (IL-1β)의 생성량은 천연 복합 생약 추출물의 저농도인 5 ㎍/㎖, 고농도인 50 ㎍/㎖ 농도처리군에서 각각 40%, 67% 감소하였다. As shown in FIG. 3, the amount of tumor necrosis factor-alpha (TNF-α) induced by LPS in the treatment group of low concentration of 5 μg / ml and a high concentration of 50 μg / 39% and 63%, respectively. In addition, as shown in FIG. 4, the amount of IL-1β induced by LPS was 40% at the low concentration of 5 ㎍ / ml and at the high concentration of 50 ㎍ / , And 67%, respectively.
본 발명의 복합 생약 추출물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
The preparation examples of the composition containing the herbal extract of the present invention will be described below, but the present invention is not intended to be limited thereto but is specifically explained.
실험예 4. PGE2 생성량 측정Experimental Example 4. Measurement of PGE 2 production amount
염증을 나타내는 또 다른 지표인 PGE2의 양을 측정하기 위해 상용 경쟁적 효소 면역분석 키트(commercial competitive enzyme immunoassay kit, R&D systems, MN)를 이용하여 하기와 같이 실험을 수행하였다. In order to measure the amount of PGE 2 , another indicator of inflammation, an experiment was conducted using the commercial competitive enzyme immunoassay kit (R & D systems, MN) as follows.
상기 참고예 2의 방법으로 배양된 RAW264.7 세포에 상기 실시예 1-2에서 수득한 천연 복합 생약 추출물을 5, 10, 20, 50ug/ml의 농도로 1시간 동안 전 처리한 후 1 ng/㎖의 LPS를 처리하였다. 24 시간 후 세포 배양액을 goat anti-mouse로 코팅된 96 웰플레이트에 각각의 배양액을 100 ㎕씩 주입한다. 여기에 1차 항체용액(primary antibody solution) 50 ㎕와 PGE2 conjugate 50 ㎕씩 첨가하여 4℃에서 하룻밤 정치시켰다. 세척 완충용액(washing buffer)로 5회 세척하고 기질 용액(substrate solution)을 200 ㎕씩 처리하여 5~20분간 반응시킨 후, 50 ㎕의 반응정지 용액(stop solution)을 처리한 후 450 ㎚에서 흡광도를 측정하였다. The RAW264.7 cells cultured by the method of Reference Example 2 were pretreated with the natural herb extracts obtained in Example 1-2 at concentrations of 5, 10, 20 and 50 ug / ml for 1 hour, Ml < / RTI > of LPS. After 24 hours, the cell culture solution is injected into a 96-well plate coated with goat anti-mouse in an amount of 100 μl of each culture. 50 μl of the primary antibody solution and 50 μl of PGE 2 conjugate were added thereto, and the mixture was allowed to stand overnight at 4 ° C. After washing 5 times with washing buffer, 200 μl of substrate solution was treated for 5 ~ 20 minutes, 50 μl of stop solution was treated, and absorbance at 450 nm Were measured.
실험결과, 도 5 에 나타난 바와 같이 LPS 1 ng/ml을 첨가한 농도에서 아무 처리도 하지 않은 대조군에 비해 PGE2 생성량이 약 17배 증가됨을 확인할 수 있었다. 또한 실시예 1-2의 천연 복합 생약 추출물을 처리한 실험군은 저농도인 5 ㎍/㎖ 의 농도에서는 53%의 감소효과, 고농도인 50 ㎍/㎖의 농도에서는 88%의 감소효과를 확인할 수 있었다.
As shown in FIG. 5, the amount of PGE 2 produced was about 17 times higher than that of the control without any treatment at a concentration of 1 ng / ml of LPS. In addition, the experimental group treated with the natural herb extract of Example 1-2 showed a reduction effect of 53% at the low concentration of 5 ㎍ / ㎖ and a reduction effect of 88% at the high concentration of 50 ㎍ / ㎖.
제제예 1. 산제의 조제Formulation Example 1. Preparation of powder
복합 생약 추출물 20mgHerbal medicine extract 20mg
유당 100mgLactose 100mg
탈크 10mgTalc 10mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 조제한다.
The above ingredients are mixed and filled in airtight bags to prepare powders.
제제예 2. 정제의 제조Formulation Example 2. Preparation of tablets
복합 생약 추출물 10mgComplex herbal medicine extract 10mg
옥수수 전분 100mg
유당 100mgLactose 100mg
스테아린산 마그네슘 2mgMagnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예 3. 캅셀제의 제조Formulation Example 3. Preparation of capsules
복합 생약 추출물 10mgComplex herbal medicine extract 10mg
결정성 셀룰로오스 3mgCrystalline cellulose 3 mg
락토오스 14.8mgLactose 14.8 mg
마그네슘 스테아레이트 0.2mg0.2 mg of magnesium stearate
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충진하여 캡슐제를 제조한다.
The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection
복합 생약 추출물 10mgComplex herbal medicine extract 10mg
만니톨 180mg180 mg mannitol
주사용 멸균 증류수 2974mgSterile sterilized water for injection 2974 mg
Na2HPO412H2O 26mgNa 2 HPO 4 12 H 2 O 26 mg
통상 주사제의 제조방법에 따라 1 앰플당 (2ml) 상기의 성분 함량으로 제조한다.
It is usually prepared by the above-mentioned component content per 1 ampoule (2 ml) according to the method of injection preparation.
제제예 5. 액제의 제조Formulation Example 5. Preparation of a liquid preparation
복합 생약 추출물 20mgHerbal medicine extract 20mg
이성화당 10g10g per isomerization
만니톨 5gMannitol 5 g
정제수 적정량Purified water titration
통상 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component is added to purified water in accordance with the usual preparation method of the liquid preparation and dissolved, and the lemon flavor is added in an appropriate amount. Then, the above components are mixed, and purified water is added to adjust the total volume to 100 ml. The solution is filled in a brown bottle and sterilized to prepare a liquid preparation .
제제예 6. 환의 제조Formulation Example 6. Preparation of the Ring
복합 생약 추출물 1000mgComplex herbal medicine extract 1000mg
유당 1500mgLactose 1500mg
글리세린 1000mg
자일리톨 500mgXylitol 500mg
상기의 성분을 혼합한 후, 통상의 방법에 따라 1환 당 4000mg이 되도록 제조한다.
After the above components are mixed, they are prepared to be 4000 mg per one ring according to a conventional method.
제제예 7. 과립의 제조Preparation Example 7. Preparation of granules
복합 생약 추출물 150mgComplex herbal medicine extract 150mg
대두 추출물 50mgSoybean extract 50mg
포도당 200mg200 mg of glucose
전분 600mgStarch 600mg
상기의 성분을 혼합한 후, 30% 에탄올 100ml을 첨가하여 섭씨 60℃에서 건조하여 과립을 형성한 후 포에 충진한다.
After mixing the above components, 100 ml of 30% ethanol is added and the mixture is dried at 60 ° C to form granules, which are then filled into a capsule.
제제예 8. 티백의 제조Formulation Example 8. Preparation of tea bag
복합 생약 추출물의 조성물인 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모를 깨끗한 물로 씻은 후, 고압스팀 살균솥에 넣어 120℃의 고온 증기로 1시간 증숙하였다. 상기 증숙한 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모를 내부 온도가 80℃인 건조기에서 3시간 정도 건조시키고, 상기 6가지 생약들의 수분함량을 상압가열건조법으로 측정한 결과, 모두 수분 함량이 5% 이하를 유지함을 확인한다. The compositions of the herbal extracts were washed with clean water and then steamed for 1 hour at 120 ° C. in a high pressure steam sterilization pot. The moisture content of the above-mentioned six herbals was measured by the atmospheric pressure heating drying method, and the moisture content of the above-mentioned six herbal medicines was measured by drying at a temperature of 80 [deg.] C for about 3 hours in the dried juniper berry, European grape skin, European grape seed, , It is confirmed that all the moisture content is maintained at 5% or less.
상기 건조시킨 복합 생약의 조성물인 주니퍼베리 160g, 유럽종 포도껍질 160g, 유럽종 포도씨 160g, 백미 160g, 우슬 180g 및 지모 180g 을 혼합하고, 분쇄기를 통하여 입자들의 크기가 1 내지 2mm가 되도록 분쇄한다. 다시 혼합 교반기에 넣어 10분 이상 잘 혼합한 후, 상기 분쇄된 혼합 원료를 20g씩 티백 포장용 호퍼에 넣고 포장하여 침출차 티백을 완성한다.
160 g of Juniper berries, 160 g of European species grape skin, 160 g of European grape seeds, 160 g of white rice, 180 g of oyster and 180 g of gum are mixed together and pulverized to a particle size of 1 to 2 mm through a pulverizer. After mixing well for 10 minutes or longer, 20 g of the pulverized mixed raw material is put in a hopper for packing the tea bag and packed to complete the tea bag.
제제예 9. 건강기능식품의 제조Formulation Example 9. Preparation of Health Functional Foods
복합 생약 추출물 1000mgComplex herbal medicine extract 1000mg
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70㎍70 비 of vitamin A acetate
비타민 E 1.0mgVitamin E 1.0mg
비타민 B1 0.13mg0.13 mg of vitamin B1
비타민 B2 0.15mg0.15 mg of vitamin B2
비타민 B6 0.5mgVitamin B6 0.5mg
비타민 B12 0.2㎍0.2 g of vitamin B12
비타민 C 10mgVitamin C 10mg
비오틴 10㎍10 μg of biotin
니코틴산아미드 1.7mgNicotinic acid amide 1.7 mg
엽산 50㎍50 엽 of folic acid
판토텐산 칼슘 0.5mgCalcium pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75mg1.75 mg ferrous sulfate
산화아연 0.82mg0.82 mg of zinc oxide
탄산마그네슘 25.3mgMagnesium carbonate 25.3 mg
제1인산칼륨 15mg15 mg of potassium phosphate monobasic
제2인산칼슘 55mgCalcium phosphate diphosphate 55 mg
구연산칼륨 90mgPotassium citrate 90mg
탄산칼? 100mgCarbonate knife? 100 mg
염화마그네슘 24.8mg24.8 mg of magnesium chloride
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above components may be mixed , Granules may be prepared and used in the manufacture of a health functional food composition according to a conventional method.
제제예 10. 건강 음료의 제조Formulation Example 10. Preparation of Health Drink
복합 생약 추출물 1000mgComplex herbal medicine extract 1000mg
구연산 1000mgCitric acid 1000mg
올리고당 100gOligosaccharide 100 g
매실농축액 2gPlum concentrate 2g
타우린 1gTaurine 1g
정제수 전체 900mlTotal purified water 900ml
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L container, ≪ / RTI >
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.
Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
Claims (6)
Wherein the active ingredient is a natural combination extract comprising Juniper berries, European species grape skin, European species grape seeds, white rice, whiskey, and radish.
상기 천연 복합 추출물 양이 전체 조성물의 0.01~95% 중량비를 갖는 것을 특징으로 하는 항염증 조성물.
The method according to claim 1,
Wherein the amount of the natural complex extract has a weight ratio of 0.01 to 95% of the total composition.
상기 천연 복합 추출물은 주니퍼베리, 유럽종 포도껍질, 유럽종 포도씨, 백미, 우슬 및 지모의 조성비가 1 : 1 : 1 : 1 : 1 : 1의 중량비로 혼합된 것을 특징으로 하는 항염증 조성물.
The method according to claim 1,
Wherein the natural combination extract is mixed at a weight ratio of 1: 1: 1: 1: 1: 1 in the composition ratio of juniper berry, European grape skin, European grape seed, white rice,
An anti-inflammatory health functional food comprising the composition of any one of claims 1 to 3 as an active ingredient.
상기 건강기능식품은 식품학적으로 허용 가능한 식품 첨가제를 포함하고, 정제, 캡슐제, 환제 또는 액제 중 어느 하나의 형태를 포함하며, 식품, 음료, 껌, 차, 비타민 복합제, 건강기능성식품의 형태를 더 포함하는 것을 특징으로 하는 항염증 건강기능식품.
5. The method of claim 4,
The health functional food comprises a food acceptable food additive and is in the form of any one of tablets, capsules, pills or liquids, and is in the form of food, beverage, gum, tea, vitamin complex, ≪ / RTI > further comprising an anti-inflammatory health functional food.
상기 건조된 각각의 천연물을 동일 중량비로 합하여 합한 천연물의 5~20배 부피 또는 중량의 물을 가해 80~100℃의 추출온도에서 3~5시간 동안 열수 추출법으로 2~5회 동안 추출하는 단계;
상기 단계로부터 수득한 추출물을 여과한 후, 40~80℃에서 감압 농축하여 얻어진 엑기스를 엑기스 총 부피의 10~60배의 물로 1~5회 공비 농축하는 단계; 및
상기 공비 농출한 엑기스를 동결건조 또는 진공건조를 통하여 분말엑기스로 제조하는 단계를 포함하는 것을 특징으로 하는 골관절염 예방 및 개선용 조성물의 제조방법.Drying each natural product of Juniper Berry, European grape skin, European species grape seed, white rice, whisker, and brine;
Adding the dried natural products at the same weight ratio, adding 5 to 20 times volume or weight of the natural product, extracting the product for 2 to 5 times at a temperature of 80 to 100 캜 for 3 to 5 hours by hot water extraction;
Concentrating the extract obtained by concentrating under reduced pressure at 40 to 80 ° C by azeotropic distillation 1 to 5 times with 10 to 60 times the total volume of the extract; And
The method for preparing a composition for prevention and remedy of osteoarthritis according to claim 1, wherein the extract is prepared by freeze drying or vacuum drying.
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KR101099021B1 (en) * | 2009-04-24 | 2011-12-28 | 에이치 엘 지노믹스(주) | Pharmaceutical composition for preventing or treating osteoarthritis comprising Vitis vinifera pip extract |
KR20130012298A (en) * | 2011-07-25 | 2013-02-04 | 주식회사 엔유씨전자 | Fermented achyranthes extract for the prevention and treatment of osteoarthritis or rheumatoid arthritis and a method for preparation thereof |
JP5167461B2 (en) | 2005-09-16 | 2013-03-21 | 国立医薬品食品衛生研究所長 | Inflammatory bowel disease preventive |
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KR20070088940A (en) * | 2006-02-27 | 2007-08-30 | 신일제약주식회사 | Amaranthaceae extracts compositions for treating or preventing inflammatory diseases |
KR101099021B1 (en) * | 2009-04-24 | 2011-12-28 | 에이치 엘 지노믹스(주) | Pharmaceutical composition for preventing or treating osteoarthritis comprising Vitis vinifera pip extract |
KR20130012298A (en) * | 2011-07-25 | 2013-02-04 | 주식회사 엔유씨전자 | Fermented achyranthes extract for the prevention and treatment of osteoarthritis or rheumatoid arthritis and a method for preparation thereof |
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