KR101201549B1 - Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component - Google Patents

Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component Download PDF

Info

Publication number
KR101201549B1
KR101201549B1 KR1020090122833A KR20090122833A KR101201549B1 KR 101201549 B1 KR101201549 B1 KR 101201549B1 KR 1020090122833 A KR1020090122833 A KR 1020090122833A KR 20090122833 A KR20090122833 A KR 20090122833A KR 101201549 B1 KR101201549 B1 KR 101201549B1
Authority
KR
South Korea
Prior art keywords
extract
rheumatoid arthritis
preventing
present
bark
Prior art date
Application number
KR1020090122833A
Other languages
Korean (ko)
Other versions
KR20110066263A (en
Inventor
김영옥
차선우
김지강
이상원
김금숙
이승은
신유수
김옥태
박미희
Original Assignee
대한민국
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 대한민국 filed Critical 대한민국
Priority to KR1020090122833A priority Critical patent/KR101201549B1/en
Publication of KR20110066263A publication Critical patent/KR20110066263A/en
Application granted granted Critical
Publication of KR101201549B1 publication Critical patent/KR101201549B1/en

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/46Eucommiaceae (Eucommia family), e.g. hardy rubber tree
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • A23V2200/306Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Botany (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

본 발명은 항염증 활성과 파골세포 억제 효과를 갖는 두충 추출물, 상기 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 치료용 약학 조성물 및 상기 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 개선용 건강기능식품에 관한 것이다.The present invention is a worm extract having anti-inflammatory activity and osteoclast inhibitory effect, a pharmaceutical composition for preventing or treating rheumatoid arthritis containing the extract as an active ingredient and a health functional food for preventing or improving rheumatoid arthritis containing the extract as an active ingredient. It is about.

본 발명의 두충 추출물은 류마티스 관절염에 유용한 물질로서, 류마티스에 관련된 질병의 예방제 및 치료제로서 뛰어난 효능이 있다.Tofu extract of the present invention is a useful material for rheumatoid arthritis, has excellent efficacy as a preventive and therapeutic agent for diseases related to rheumatoid arthritis.

두충, 열수 추출물, 류마티스 관절염, 약학 조성물, 건강기능식품 Tofu, hot water extract, rheumatoid arthritis, pharmaceutical composition, dietary supplement

Description

두충 추출물을 유효성분으로 함유하는 류마티스 관절염의 예방 또는 치료용 약학 조성물 및 건강식품 조성물{Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component}Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis containing extracts of Eucommia ulmoides as effective component}

본 발명은 두충 추출물을 유효성분으로 함유하는 류마티스 관절염의 예방 또는 치료용 약학 조성물 및 건강식품 조성물에 관한 것으로, 보다 상세하게는 항염증 활성과 파골세포 억제 효과를 갖는 두충 추출물, 상기 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 치료용 약학 조성물 및 상기 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 개선용 건강기능식품에 관한 것이다.The present invention relates to a pharmaceutical composition and a health food composition for preventing or treating rheumatoid arthritis, which contains the worm extract as an active ingredient. More specifically, the worm extract having an anti-inflammatory activity and inhibitory effect on osteoclasts, the extract as an active ingredient It relates to a pharmaceutical composition for preventing or treating rheumatoid arthritis, and to a health functional food for preventing or improving rheumatoid arthritis containing the extract as an active ingredient.

염증이란 세균 유래의 농양으로서 조직에 침입하여 증식된 화농균류를 백혈구가 왕성히 탐식하여, 그 결과 생기는 백혈구의 사태, 균에 의해 장해를 받은 조직, 세포 파괴물 등이 조직 내 융해하여 농이 축적된 곳의 병리적 상태를 말하며, 소염작용이라 함은 침입균의 증식을 항균제 등에 의하여 억제하든가, 혹은 농양 중에 측정된 이물을 탐식하는 마크로파지(macrophage)를 활성화하여 그것들을 소화, 배설하는 기능을 높여서 농양의 치료과정이 촉진되는 것을 말한다. Inflammation is a bacterium-derived abscess that infiltrates tissues with purulent fungi, and white blood cells actively devour the resulting leukocytes, tissues that have been injured by bacteria, and cell debris. It refers to the pathological condition of the place, and the anti-inflammatory effect is to suppress the growth of invading bacteria by antibacterial agents, or to activate the macrophage that detects foreign substances measured during the abscess, and to increase the ability to digest and excrete them by abscesses. It means that the treatment process is accelerated.

일반적으로 염증반응은 생체의 세포나 조직에 어떠한 기질적 변화를 가져오는 침습이 가해질 때 그 손상부위를 수복재생하려고 하는 생체의 방어 반응과정이다. 따라서, 이러한 일련의 반응에는 국소의 혈관, 체액의 각종 조직세포, 면역관여 세포 등이 포함된다고 한다. In general, an inflammatory reaction is a defense process of a living body that attempts to repair and repair the damaged area when an invasion that causes some organic change in a living cell or tissue is applied. Therefore, such a series of reactions include local blood vessels, various tissue cells of body fluids, immune-involved cells, and the like.

현재까지 항염증 물질들은 급성염증에서만 치료효과를 가지고 있지만, 류마티스 관절염과 같은 만성염증에서는 1차적인 염증 현상만을 완화할 뿐이며, 면역학적 치료효과는 기대할 수 없다고 보고되어 있다. 한편 근래에는 하이드록시 에이코사테트라에노익산 (hydroxy-eicosatetraenoic acid: HETE), 류코트리엔 B4, 류코트리엔 C4 등에 관하여 연구가 진행되고 있으며 이는 만성 염증에서 약간의 효과를 나타내고 있다(Huskisson. E. D. et al. Inflammation, Mechanism and Treatment, MTP, Lancaster, England, p. 55 (1980)).To date, anti-inflammatory substances have therapeutic effects only in acute inflammation, but in chronic inflammation such as rheumatoid arthritis, it is reported that only the primary inflammatory phenomenon is alleviated, and immunological therapeutic effects cannot be expected. Recently, studies on hydroxy-eicosatetraenoic acid (HETE), leukotriene B4, and leukotriene C4 have been conducted, which has some effects on chronic inflammation (Huskisson. ED et al. Inflammation). , Mechanism and Treatment, MTP, Lancaster, England, p. 55 (1980)).

인체의 뼈는 매일 조금씩 분해되고, 분해된 양만큼 새로운 뼈로 채워짐으로써 항상성을 유지하는 매우 역동적인 기관이다. 뼈를 분해하는 파골세포 (Osteoclast)와 뼈를 재생하는 조골세포(Osteoblast)는 항상성을 유지하는데, RANKL(Receptor Activator of NF-κB Ligand)는 염증 전구 단백질이며 파골세포 표면 수용체 단백질이다. 뼈를 흡수하는 파골세포의 활성이 증가하게 되면, 뼈의 분해가 촉진, 뼈가 얇아지고 쉽게 부러지는 골다공증과 같은 질병이 일어나게 되며, 조골세포의 활성이 증가하게 되면, 골밀도의 증가로 뼈의 기형이나 골석화증이 일어나게 된다. 따라서 파골세포 분화와 활성의 증가는 치주염, 골다공증, 관절염 등과 같은 뼈의 파괴를 가져오게 된다. The bones of the human body are a very dynamic organ that maintains homeostasis by breaking down little by little each day and filling it with new bone in the amount broken down. Osteoblasts that break down bone (Osteoclast) and osteoblasts that regenerate bone maintain homeostasis, RANKL (Receptor Activator of NF-κB Ligand) is an inflammatory precursor protein and osteoclast surface receptor protein. Increased activity of osteoclasts, which absorb bones, promotes bone breakdown, thinner and more easily broken osteoporosis, and when osteoblast activity increases, bone density increases with bone density. Or osteoporosis will occur. Thus, osteoclast differentiation and increased activity result in bone destruction such as periodontitis, osteoporosis and arthritis.

류마티스 관절염을 위한 약물요법으로 다양한 경구용 치료제가 사용되고 있으나 약물에 의한 부작용이 보고되고 있고, 천연물로부터의 류마티스 관절염 치료를 위한 물질의 종류는 한정되어 있어, 이에 대해 천연물로부터 류마티스 관절염 치료를 위한 안전한 물질 개발에 대한 연구가 요구되고 있는 실정이다.Various oral therapeutics have been used as a pharmacotherapy for rheumatoid arthritis, but side effects due to drugs have been reported, and the types of substances for the treatment of rheumatoid arthritis from natural products are limited, which is a safe substance for treating rheumatoid arthritis from natural products. Research on development is required.

두충(Eucommia ulmoides)은 두충나무과(Eucommiaceae)에 속하는 낙엽교목으로, 중국사천성 부근이 원산지이며 은행나무처럼 암수 딴 그루이고 1과 1속 1종에 속하는 희귀한 수목이다. 두충의 약리 작용을 보면, 혈관 평활근에 직접적인 확장작용을 일으켜 혈압을 내리며, 항노화작용이 있고, 혈중 콜레스테롤치를 강화시키는데, 두충의 잎은 관상동맥 혈류량을 증가시킨다. 또한, 동물의 부신피질 호르몬을 증강시키며 항염증작용을 보이고, 진정 진통작용과 신체 면역 기능을 조절하여 세포면역의 억제와 증강작용을 보인다. 또한, 출혈시간을 단축시키고, 이뇨작용도 나타내며, 항알레르기 작용과 자궁수축 작용이 있다. Eucommia ulmoides ) is a deciduous tree belonging to the genus Eucommiaceae. It is native to Sichuan , China , and is a rare tree belonging to the genus 1 and 1 genus. The pharmacological action of the larvae leads to direct dilation of vascular smooth muscle, lowering blood pressure, anti-aging and strengthening blood cholesterol levels. The larva leaves increase coronary blood flow. In addition, it enhances the adrenal cortex hormone of the animal and shows anti-inflammatory action, and it shows the suppression and enhancement of cellular immunity by regulating calming analgesic and body immune function. In addition, the bleeding time is shortened, diuretic action is also shown, there are anti-allergic action and uterine contraction action.

한국특허공개 제2001-0018321호에는 류마티스 관절염 환자를 위한 건강식품 조성물이 개시되어 있으며, 한국특허공개 제2005-0078080호에는 관절염 치료용의 제약학적 조성물 및 그 제조방법이 개시되어 있다.Korean Patent Publication No. 2001-0018321 discloses a health food composition for rheumatoid arthritis patients, and Korean Patent Publication No. 2005-0078080 discloses a pharmaceutical composition for treating arthritis and a method of manufacturing the same.

본 발명은 상기와 같은 요구에 의해 도출된 것으로서, 본 발명은 이와 같은 점들을 감안하여 항염증 활성과 파골세포 억제 효과를 갖는 두충 추출물의 관절염에 대한 예방 또는 치료 효능을 규명함으로써 본 발명을 완성하였다.The present invention was derived by the above requirements, the present invention has completed the present invention by identifying the efficacy of preventing or treating arthritis of the worms extract having anti-inflammatory activity and osteoclast inhibitory effect in view of these points. .

상기 과제를 해결하기 위해, 본 발명은 항염증 활성과 파골세포 억제 효과를 갖는 두충 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 치료용 약학 조성물을 제공한다.In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of rheumatoid arthritis, containing as an active ingredient a worm extract having anti-inflammatory activity and osteoclast inhibitory effect.

또한, 본 발명은 항염증 활성과 파골세포 억제 효과를 갖는 두충 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 개선용 건강기능식품을 제공한다.The present invention also provides a health functional food for preventing or improving rheumatoid arthritis, which contains as an active ingredient a tofu extract having anti-inflammatory activity and osteoclast suppression effect.

본 발명에 따르면, 본 발명의 두충 추출물은 항염증 활성과 파골세포 억제 효과를 가지므로, 류마티스 관절염 환자를 위한 예방제 및 치료제 개발과 관련한 기능성 식품 및 약품 산업에 있어서 매우 유용하게 이용될 수 있다.According to the present invention, the worm extract of the present invention has anti-inflammatory activity and osteoclast inhibitory effect, and thus can be very useful in the functional food and pharmaceutical industry related to the development of preventive and therapeutic agents for rheumatoid arthritis patients.

본 발명의 목적을 달성하기 위하여, 본 발명은 항염증 활성과 파골세포 억제 효과를 갖는 두충 추출물을 제공한다.In order to achieve the object of the present invention, the present invention provides a worm extract having anti-inflammatory activity and osteoclast inhibitory effect.

본 발명의 두충 추출물의 상기 파골세포 억제는 RANKL(Receptor Activator of NF-κB Ligand)의 발현을 억제함으로써 수행될 수 있다.The osteoclast inhibition of the larvae extract of the present invention can be carried out by inhibiting the expression of Receptor Activator of NF-κB Ligand (RANKL).

또한, 본 발명은 본 발명의 두충 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating rheumatoid arthritis, containing the extract of the present invention as an active ingredient.

본 발명의 두충 추출물은 바람직하게는 두충 수피를 추출한 것이며, 더욱 바람직하게는 두충 수피를 열수 추출한 것이며, 더 더욱 바람직하게는 두충 수피 550-650 g을 물 10,000-14,000 ml에 넣고 90-100℃에서 2-4시간 동안 열수 추출한 다음 진공 농축기로 40-50℃에서 고형분이 25-35%가 될 때까지 농축하고, 농축물을 동결건조하여 수득할 수 있으며, 가장 바람직하게는 두충 수피 600 g을 물 12,000 ml에 넣고 100℃에서 3시간 동안 열수 추출한 다음 진공 농축기로 45℃에서 고형분이 30%가 될 때까지 농축하고, 농축물을 동결건조하여 수득할 수 있다.The larvae extract of the present invention is preferably extracted from the larva bark, more preferably from the hydrothermal extract of the larva bark, more preferably 550-650 g of the larva bark in 10,000-14,000 ml of water at 90-100 ℃ Hot water extraction for 2-4 hours, then concentrated in a vacuum concentrator at 40-50 ℃ until the solid content is 25-35%, and the concentrate can be obtained by lyophilization, most preferably 600 g of Peel bark It can be obtained by pouring into 12,000 ml, hot water extraction at 100 ° C. for 3 hours, and then concentrating at 45 ° C. until a solid content of 30% is obtained in a vacuum concentrator, and freezing-drying the concentrate.

본 발명은 또한, 두충 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 개선용 건강기능식품을 제공한다.The present invention also provides a health functional food for preventing or improving rheumatoid arthritis, which contains the worm extract as an active ingredient.

본 발명의 건강기능식품에서, 두충 추출물은 바람직하게는 두충 수피를 추출한 것이며, 더욱 바람직하게는 두충 수피를 열수 추출한 것이며, 더 더욱 바람직하게는 두충 수피 550-650 g을 물 10,000-14,000 ml에 넣고 90-100℃에서 2-4시간 동안 열수 추출한 다음 진공 농축기로 40-50℃에서 고형분이 25-35%가 될 때까지 농축하고, 농축물을 동결건조하여 수득할 수 있으며, 가장 바람직하게는 두충 수피 600 g을 물 12,000 ml에 넣고 100℃에서 3시간 동안 열수 추출한 다음 진공 농축기로 45℃에서 고형분이 30%가 될 때까지 농축하고, 농축물을 동결건조하여 수득할 수 있다.In the dietary supplement of the present invention, the larvae extract is preferably extracted from the bark of the larvae, more preferably from the hydrothermal extract of the larvae bark, more preferably 550-650 g of the larva bark in 10,000-14,000 ml of water Hot water extraction at 90-100 ° C. for 2-4 hours and then concentrating at 40-50 ° C. with a vacuum concentrator until 25-35% solids, the concentrate can be obtained by lyophilization, most preferably tofu 600 g of bark may be added to 12,000 ml of water, hot water extracted at 100 ° C. for 3 hours, and then concentrated at 45 ° C. until the solid content reaches 30%, and the concentrate may be obtained by lyophilization.

이하, 본 발명을 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail.

본 발명의 두충 추출물은 류마티스 관절염뿐만 아니라 다양한 염증질환과 뼈의 조직의 강성에도 유용하게 사용될 수 있다.The worm extract of the present invention can be usefully used not only for rheumatoid arthritis, but also for stiffness of various inflammatory diseases and bone tissues.

본 발명의 류마티스 관절염 예방 또는 치료용 약학 조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.02 내지 80 중량%, 바람직하게는 0.02 내지 50 중량%로 포함할 수 있다.The pharmaceutical composition for preventing or treating rheumatoid arthritis of the present invention may include 0.02 to 80% by weight of the extract, preferably 0.02 to 50% by weight, based on the total weight of the composition.

본 발명의 추출물을 포함하는 약학조성물은 약학적 조성물의 제조에 통상적으로 사용하여 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical composition comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions.

본 발명의 추출물의 약학적 투여 형태는 이들의 약학적 허용 가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.The pharmaceutical dosage forms of the extract of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in suitable aggregates.

본 발명에 따른 추출물을 포함하는 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한 다양한 화 합물 혹은 혼합물을 들 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 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 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. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate Various compounds or mixtures, including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. 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 preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate and sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 추출물은 1일 0.0001 내지 100 mg/kg으로, 바람직하게는 0.001 내지 100 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어 떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. The administration may be carried out once a day or divided into several times. The dosage does not limit the scope of the invention in any aspect.

본 발명의 추출물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.The extract of the present invention can be administered to mammals such as rats, mice, livestock, humans and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

또한, 본 발명은 류마티스 관절염 예방 또는 개선 효과를 나타내는 상기 두충 추출물 및 식품학적으로 허용 가능한 식품보조첨가제를 포함하는 건강기능식품을 제공한다. 상기 두충 추출물은 바람직하게는 열수 추출물이다. 상기 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등이 있다.In addition, the present invention provides a health functional food comprising the worm extract and food acceptable food supplements exhibiting an effect of preventing or improving rheumatoid arthritis. The larvae extract is preferably a hot water extract. Examples of the food to which the extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

또한, 당뇨병의 예방 또는 개선 효과를 목적으로 식품 또는 음료에 첨가될 수 있다. 이때, 식품 또는 음료 중의 상기 추출물의 양은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다.It may also be added to foods or beverages for the purpose of preventing or improving diabetes. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml. have.

본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물, 예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention has no particular limitation on the other ingredients other than the above-mentioned extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract, for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. . The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

상기 외에 본 발명의 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 추출물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있으며, 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 추출물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the extract of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components may be used independently or in combination, and the proportion of such additives is not so critical but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

실시예Example 1: 두충 추출물의 제조 1: Preparation of Tobacco Extract

두충 수피 600 g을 물 12,000 ml에 넣고 100℃에서 3시간 열수 추출한 다음 진공농축기로 45℃에서 고형분이 30%가 될 때까지 농축하고, 그 농축물을 동결건조하여 분말 150g을 수득하였다.600 g of Tobacco bark was added to 12,000 ml of water, extracted with hot water at 100 ° C. for 3 hours, and concentrated at 45 ° C. until the solid content reached 30%. The concentrate was lyophilized to obtain 150 g of powder.

실시예Example 2: 본 발명의 두충 추출물의 부종억제 효과 2: edema inhibitory effect of the worm extract of the present invention

윈터 등의 방법으로 카라지난 부종 억제 작용을 조사하였다. 150~200 g 수컷 흰쥐의 발바닥에 1%의 카라지난 0.1 ml를 피하주사하여 부종을 유발하고 검체는 카라지난 주사 30분 전에 경구투여하였다. 카라지난 주사 후 1시간 간격으로 4회에 걸쳐 부종의 용적을 용적측정기로 측정한 다음 주사 전의 용적을 기준으로 하여 그 증가율을 윈터 등의 방법(Winter, C. A. et al., Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs, Proc. Soc. Exp. Biol. Med., 111, 544 (1962))에 따라서 계산하여 부종 정도를 검정하였다. 대조약물 이부로펜 200 mg/kg을 경구투여하여 비교실험하였다. 실험결과 평균값과 표준오차를 사용하여 계산하였고 각 군간의 비교는 수튜던트 t-test를 사용하여 P값이 5% 미만일 때 통계학적으로 유의성이 있다고 판정하였다. The action of inhibiting carrageenan edema was investigated by the method of Winter et al. Edema was induced by subcutaneous injection of 0.1 ml of 1% carrageenan into the soles of 150-200 g male rats. Samples were orally administered 30 minutes before carrageenan injection. Measure the volume of edema four times at an interval of 1 hour after carrageenan injection, and then increase the rate based on the volume before injection (Winter, CA et al., Carrageenan-induced edema in hind). The degree of edema was calculated according to paw of the rat as an assay for anti-inflammatory drugs, Proc. Soc.Exp. Biol.Med., 111, 544 (1962)). Comparative experiment was performed by oral administration of the control drug ibulopene 200 mg / kg. The experimental results were calculated using the mean value and the standard error, and the comparison between each group was statistically significant when the P value was less than 5% using the Student's t-test.

그 결과, 부종 수치는 두충 추출물 투여군이 대조군에 비해서 낮은 수치를 보여, 두충 추출물이 부종억제 효능이 있음을 확인할 수 있었다 (도 1).As a result, the edema values showed a lower value than the control group to the worm extract extract, it was confirmed that the worm extract is effective in suppressing edema (Fig. 1).

실시예Example 3: 본 발명의 두충 추출물의  3: of the worm extract of the present invention 류마티스Rheumatism 관절염 억제 효과 Arthritis Inhibitory Effect

두충 추출물에 대한 류마티스 관절염 항염증작용을 알아보기 위해 DBA/1J 마우스 (6주령 25g, 수컷 (중앙실험동물))에 16주간 투여하였다. 관절염의 유발은 제2형 콜라겐(Sigma, USA)을 2 mg/ml의 농도로 0.1M 아세트산에 녹인 후 Freund's incomplete adjuvant (Sigma, USA)에 유화시켜 만들었다. 그 후 100㎕를 흰쥐의 우측 족척에 피하주사하였다. 일차 주사 후 7일 후 다시 꼬리기시부에 동량을 추가 접종하였고, 대조군에는 동량의 생리식염수를 접종하였다. 마지막 접종 일로부터 21일째에 육안으로 관절주위 발적, 부종 및 팽창을 형성하는 개체를 선별하여 실험하였다. 두충 추출물 투여시에는 두충 추출물 200 mg/kg을 0.9% 생리식염수에 녹여 membrane filter(pore size 0.2㎛, Whatman)로 여과한 후 1일 1회씩 16주 동안 경구 투여하였다.In order to investigate the anti-inflammatory effect of rheumatoid arthritis on the extract of the worms, DBA / 1J mice (6 weeks old 25g, males (Central experimental animals)) were administered for 16 weeks. Arthritis was induced by dissolving collagen type 2 (Sigma, USA) in 0.1 M acetic acid at a concentration of 2 mg / ml and then emulsifying it in Freund's incomplete adjuvant (Sigma, USA). 100 μl was then injected subcutaneously into the right foot of the rat. Seven days after the first injection, the same amount was further inoculated in the tail portion and the control group was inoculated with the same amount of saline. Individuals forming periarticular redness, edema and swelling were visually selected on day 21 after the last inoculation. When the worm extract was administered, 200 mg / kg of the worm extract was dissolved in 0.9% physiological saline, filtered through a membrane filter (pore size 0.2㎛, Whatman), and orally administered once a day for 16 weeks.

그 결과, 류마티스지수는 두충 추출물 투여군이 대조군에 비해서 낮은 수치를 보여, 이로 보아 두충 추출물이 류마티스 관절염 억제 효능이 있음을 확인할 수 있었다 (도 2).As a result, the rheumatoid index showed a lower value than the control group of the worm extract extract, it can be seen that the worm extract extracts are effective in inhibiting rheumatoid arthritis (Fig. 2).

실시예Example 4: 본 발명의 두충 추출물의 관절염무릎관절에서  4: arthritis knee joint of the present invention RANKLRANKL 억제 효과  Inhibitory effect

상기 실시예 3의 마우스를 16주 후에 에테르 마취하에서 혈액을 채취하고 무릎조직을 채취하여 탈회시킨 후 면역조직화학법을 실시하였다.After 16 weeks, the mice of Example 3 were subjected to immunohistochemistry after blood was collected under ether anesthesia, and knee tissue was collected and demineralized.

도 3은 두충 추출물의 RANKL의 저해 효과이다. 그림 A는 대조군으로 관절염무릎관절에서 RANKL의 발현을 보여주며, 그림 B는 두충 추출물을 투여한 군으로 관절염무릎관절에서 RANKL의 발현이 억제된 것을 알 수 있었다 (도 3).Figure 3 is an inhibitory effect of RANKL of the larvae extract. Figure A shows the expression of RANKL in the arthritis knee joint as a control, Figure B shows that RANKL expression was suppressed in the arthritis knee joint group to the group of administration of the extract of the worms (Fig. 3).

도 1은 두충 추출물의 부종 저해 효과이다.1 is the edema inhibitory effect of the larvae extract.

도 2는 두충 추출물의 류마티스지수 저해 효과이다.Figure 2 is a rheumatoid index inhibitory effect of the worms extract.

도 3은 두충 추출물의 RANKL의 저해 효과이다.Figure 3 is an inhibitory effect of RANKL of the larvae extract.

A: 대조군, B: 두충 추출물 투여군.A: control group, B: toxin extract administration group.

Claims (10)

삭제delete 삭제delete 두충 수피 550-650 g을 물 10,000-14,000 ml에 넣고 90-100℃에서 2-4시간 동안 열수 추출한 다음 진공 농축기로 40-50℃에서 고형분이 25-35%가 될 때까지 농축하고, 농축물을 동결건조하여 수득한 두충 수피의 열수 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 치료용 약학 조성물.550-650 g of Tobacco bark was added to 10,000-14,000 ml of water, extracted by hot water at 90-100 ° C. for 2-4 hours, and concentrated at 40-50 ° C. until the solid content was 25-35% by vacuum concentrator. A pharmaceutical composition for preventing or treating rheumatoid arthritis, containing the hydrothermal extract of the larva bark obtained by lyophilization as an active ingredient. 삭제delete 삭제delete 삭제delete 두충 수피 550-650 g을 물 10,000-14,000 ml에 넣고 90-100℃에서 2-4시간 동안 열수 추출한 다음 진공 농축기로 40-50℃에서 고형분이 25-35%가 될 때까지 농축하고, 농축물을 동결건조하여 수득한 두충 수피의 열수 추출물을 유효성분으로 함유하는 류마티스 관절염 예방 또는 개선용 건강기능식품.550-650 g of Tobacco bark was added to 10,000-14,000 ml of water, extracted by hot water at 90-100 ° C. for 2-4 hours, and concentrated at 40-50 ° C. until the solid content was 25-35% by vacuum concentrator. A functional health food for preventing or improving rheumatoid arthritis, containing the hydrothermal extract of the bark bark obtained by lyophilization. 삭제delete 삭제delete 삭제delete
KR1020090122833A 2009-12-11 2009-12-11 Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component KR101201549B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020090122833A KR101201549B1 (en) 2009-12-11 2009-12-11 Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020090122833A KR101201549B1 (en) 2009-12-11 2009-12-11 Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component

Publications (2)

Publication Number Publication Date
KR20110066263A KR20110066263A (en) 2011-06-17
KR101201549B1 true KR101201549B1 (en) 2012-11-15

Family

ID=44399125

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020090122833A KR101201549B1 (en) 2009-12-11 2009-12-11 Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component

Country Status (1)

Country Link
KR (1) KR101201549B1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160121032A (en) 2015-04-09 2016-10-19 주식회사 중헌제약 Pharmaceutical composition comprising 2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol for treating and preventing inflammation and arthritis diseases
KR20240096003A (en) 2022-12-19 2024-06-26 이진호 Pharmaceutical health supplement composition for treating and preventing degenerative arthritis.
KR20240095994A (en) 2022-12-19 2024-06-26 이진호 Pharmaceutical health supplement composition for treating and preventing degenerative arthritis.

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101248378B1 (en) * 2012-09-26 2013-04-02 대한약품공업 주식회사 Pharmaceutical composition for arthritis treatment and prevention
CN104473998B (en) * 2014-11-28 2018-07-20 河南恒瑞源实业有限公司 A method of extraction Cortex Eucommiae fine powder simultaneously prepares activated carbon
CN104490984A (en) * 2014-12-25 2015-04-08 井冈山大学 Preparation method of eucommia bark superfine powder

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Arch. Pharm. Res., Vol.26, No.11, pages 929-936 (2003).
Carbohydrate Research, Vol.344, pages 1319-1324.

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160121032A (en) 2015-04-09 2016-10-19 주식회사 중헌제약 Pharmaceutical composition comprising 2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol for treating and preventing inflammation and arthritis diseases
US10265276B2 (en) 2015-04-09 2019-04-23 Chungbuk National University Industry-Academic Cooperation Foundation Pharmaceutical composition for preventing or treating arthritis or inflammatory disease containing 2-methoxy-4-(3-(4-methoxyphenyl)propyl-1-en-1-yl)phenol as active ingredient
US10918609B2 (en) 2015-04-09 2021-02-16 Chungbuk National University Industry-Academic Cooperation Foundation Pharmaceutical composition for preventing or treating arthritis or inflammatory disease containing 2-methoxy-4-(3-(4-methoxyphenyl)propyl-1-en-1-yl)phenol as active ingredient
KR20240096003A (en) 2022-12-19 2024-06-26 이진호 Pharmaceutical health supplement composition for treating and preventing degenerative arthritis.
KR20240095994A (en) 2022-12-19 2024-06-26 이진호 Pharmaceutical health supplement composition for treating and preventing degenerative arthritis.

Also Published As

Publication number Publication date
KR20110066263A (en) 2011-06-17

Similar Documents

Publication Publication Date Title
KR101201549B1 (en) Pharmaceutical and health food composition for preventing or treating rheumatoid arthritis comprising extracts of Eucommia ulmoides as effective component
KR101898688B1 (en) Composition for preventing, treating or improving muscle atrophy comprising complex extracts
KR102064651B1 (en) Composition for preventing or improving diabetes mellitus comprising momrdica charantia (l.) extract, chrysanthemum zawadskii var. latilobum and paeonia lactiflora extract as an effective ingredient
KR101341693B1 (en) Composition comprising the extract of herbs for preventing or treating neurodegenerative disorders
KR102123832B1 (en) Composition comprising herbal mixture extract for treating or preventing inflammatory disease
KR100927101B1 (en) Composition comprising Acer tegmentosum Maxim. extract or salidroside isolated from the same for preventing or treating gastritis and peptic ulcer
KR20160006812A (en) Compositions for preventing and curing diabetes comprising extract of Paeonia lactiflora
KR101783119B1 (en) Composition comprising the combined extracts of Schisandra chinensis, Eucommia ulmoides and Lycium barbarum for preventing or treating bone metabolism diseases
KR102275492B1 (en) Composition for Prevention or Treatment of Gastritis and Gastric ulcer Comprising Steamed Ginger Extract or 1-Dehydro-6-gingerdione Isolated therefrom as an Active Ingredient
KR101016837B1 (en) Composition comprising the extract of Lonicera japonica THUNB. preventing and treating arthritis
KR102277057B1 (en) Pharmaceutical composition comprising the extraction of cattail pollen as an effective component for prevention or treatment of thrombosis and health functional food comprising the same
KR102159686B1 (en) Pharmaceutical composition comprising the extract of acorn pollen as an effective component for prevention or treatment of diabetes and health functional food comprising the same
KR101606773B1 (en) Composition comprising oriental herbal extract for preventing or treating gastrointestinal disorder
KR102114978B1 (en) A Composition for Prevention and Treatment of Thyroid Disease including Coptidis Rhizoma Extract
KR20120008366A (en) A composition comprising the compound isolated from schisandra chinensis for preventing and treating colitis disease
KR101332824B1 (en) Pharmaceutical Compositions for Preventing or Treating Arthritis Comprising Euphorbia ebracteolata Extracts
KR101787082B1 (en) Composition comprising the extract of Platycodon grandiflorum enhanced effective saponin contents for treatment of rheumatoid arthritis
KR100750873B1 (en) A pharmaceutical composition comprising the extract of Rubiae Radix for treating or preventing allergic disease
KR20160089930A (en) A composition for memory enhancement, comprising 5-HMF, paeoniflorin and betaine
KR101899086B1 (en) Composition for preventing, improving or treating liver damage
KR20080094982A (en) Composition comprising powder of tangerine peel or the extract thereof for treating and preventing gastrointestinal disease
KR102463297B1 (en) Novel use of extract of Artemisia annua
KR102216221B1 (en) Pharmaceutical composition comprising the extract of pine pollen as an effective component for prevention or treatment of thrombosis and health functional food comprising the same
KR20090089672A (en) Composition comprising the extract of anemarrhena asphodeloides bunge. preventing and treating arthritis
KR101219736B1 (en) Composotion for facilitate secretion of testosterone comprising silk worm dry powder and its use

Legal Events

Date Code Title Description
A201 Request for examination
AMND Amendment
E601 Decision to refuse application
AMND Amendment
X701 Decision to grant (after re-examination)
GRNT Written decision to grant