KR101132040B1 - Composition for alalgesic or neurophatic pain comprising extract of symplocos chinensis for. pilosa or its leaf - Google Patents
Composition for alalgesic or neurophatic pain comprising extract of symplocos chinensis for. pilosa or its leaf Download PDFInfo
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- KR101132040B1 KR101132040B1 KR1020110035476A KR20110035476A KR101132040B1 KR 101132040 B1 KR101132040 B1 KR 101132040B1 KR 1020110035476 A KR1020110035476 A KR 1020110035476A KR 20110035476 A KR20110035476 A KR 20110035476A KR 101132040 B1 KR101132040 B1 KR 101132040B1
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- South Korea
- Prior art keywords
- stink bug
- tree
- pain
- composition
- leaf
- Prior art date
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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Abstract
Description
본 발명은 노린재 나무 또는 노린재 나무 잎 식물 추출물을 유효성분으로 함유하는 진통제 또는 신경병증성 통증치료제의 조성물 및 이를 포함하는 통증 개선용 식품 조성물에 관한 것이다.The present invention relates to a composition of an analgesic or neuropathic pain medicament comprising a hemip tree or hemip tree leaf plant extract as an active ingredient and a food composition for pain improvement comprising the same.
현재, 진통제로는 아스피린이나 타이레놀 등의 소염진통제가 주류를 이루며, 심한 통증의 경우 모르핀 약물들이 대부분 사용되고 있다. 최근 새로운 통증 억제제를 개발하고 있는데, 외국의. 경우, 통증 치료제 전문 개발사 자벨린 파마슈티컬스(Javelin Pharmaceuticals) 비강내 모르핀 분무제 「릴로민」(Rylomine)이 후기 2상 임상에서 중등도에서 중증 수술후 통증의 치료에 정맥주사 모르핀과 대등한 진통효과를 나타내는 뿌리는 마약성 진통제를 개발하였으며, 중국에서는 상하이 싱롱 바오테크 제약회사에서 위와 이오테크 제약회사에서 위와장(腸), 유방, 폐, 신장과 관련된 암으로 인한 통증에 효능이 있는 신약 '아킬레스'를 개발하였다. 또한, 바다 달팽이 독에서 추출한 새로운 진통제 '프라이얼트(Prialt)'를 아일랜드 제약회사인 이랜(Elan)이 개발한 진통제로 영국에서 첫 시판됐었다.Currently, as analgesics, anti-inflammatory drugs such as aspirin and tylenol are the mainstream, and in case of severe pain, morphine drugs are mostly used. Recently I'm developing a new pain inhibitor, foreign. In this case, the drug developer, Javelin Pharmaceuticals' intranasal morphine spray `` Rylomine '', has a pain relief effect comparable to intravenous morphine in the treatment of moderate to severe postoperative pain in
국내에서는 캡사이신 길항물질을 개발하여 2004년 2월에 독일의 다국적 제약업체인 슈바르쯔 파마社가 이의 가치를 인정, 공동연구 및 라이선스 계약을 체결하였다. 노린재 나무 또는 노린재 나무 잎을 이용하여 통증제로 개발하거나 시도된 바는 없다.In Korea, Germany developed a capsaicin antagonist, and in February 2004, Schwarz Pharma, a German multinational pharmaceutical company, recognized the value and signed a joint research and licensing agreement. There have been no attempts to develop or attempt pain relief using stink bug trees or stink bug leaves.
만성 악성 종양성 통증은 물론 사회가 고령화됨에 따라 퇴행성 관절염, 요통 관련 질환 환자는 매년 증가 추세에 있으나 모르핀과 같은 기존의 아편제제는 일반인에게 마약작용으로 인하여 사용에 제한이 있고, 통증자체가 질병으로 여겨지며 이에 대한 관심이 어느 때보다 높고 확산되고 있어 통증완화제의 수요는 향후 훨씬 더 늘 것으로 예상되며 기존의 진통제에 반응하지 않는 통증에 대한 진통제 개발이 크게 요구되는 시점이며 기존의 마약성 및 비마약성 진통제들에 반응하지 않는 통증환자가 많이 보고될 뿐만 아니라 진통효과가 상대적으로 큰 것으로 알려진 기존의 아편유사제제 등이 마약성 및 심각한 부작용들로 인해 일반 환자가 편하게 사용할 수 없는 실정이므로 신청기술인 부작용이 없는 새로운 진통억제 효능이 있는 천연자원을 개발하고자 한다.As the society ages, as well as chronic malignant neoplastic pain, patients with degenerative arthritis and low back pain are increasing every year. However, existing opiates such as morphine have limited use due to narcotic action and the pain itself is a disease. The demand for pain relievers is expected to be much higher in the future, and the development of painkillers for pain that does not respond to existing painkillers is in high demand and existing narcotic and non-narcotic painkillers There are many reports of pain patients who do not respond to them, and existing opioids, which are known to have relatively high analgesic effects, cannot be used conveniently by general patients due to narcotic and serious side effects. Develop natural resources with new analgesic effects I would like to.
현재까지 진통제로는 아세트아미노펜, 아스피린 등이 사용되어 왔으나, 이들은 성인에게 1일 약 1g 내지 4g의 고용량으로 투여되어야 하고 이로 인해 위장장애, 알레르기, 간독성 등의 부작용이 있다. 이에, 저용량으로도 진통 효과가 우수하고 부작용이 없는 새로운 진통제의 개발이 절실히 요구되고 있다.To date, as analgesics, acetaminophen, aspirin, etc. have been used, but they should be administered to adults at high doses of about 1 g to 4 g per day, which causes side effects such as gastrointestinal disorders, allergies, and liver toxicity. Therefore, there is an urgent need for the development of new analgesic agents having excellent analgesic effects even at low doses and having no side effects.
본 발명자들은 노린재 나무 또는 노린재 나무 잎의 추출물에 대하여 다양한 통증에 대한 여러 가지 지표에 대한 테스트를 실시하여 우수한 진통억제 효과를 나타냄을 확인하여 본 발명을 완성하였다.The present inventors completed the present invention by confirming the excellent analgesic inhibitory effect by performing a test on various indicators for a variety of pain on the extract of stink bug tree or stink bug tree leaf.
따라서, 본 발명의 일례는 노린재 나무 또는 노린재 나무 잎의 식물 추출물을 유효성분으로 함유하는 진통제 또는 신경병증성 통증 치료제의 조성물을 제공한다.Accordingly, one embodiment of the present invention provides a composition of an analgesic or neuropathic pain therapeutic agent containing a plant extract of Stink bug tree or Stink bug tree leaf as an active ingredient.
또 다른 예는 상기 노린재 나무 또는 노린재 나무 잎의 추출물을 포함하는 통증 개선용 식품 조성물에 관한 것이다.Another example relates to a food composition for pain improvement comprising the extract of the hemip tree or hemip tree leaf.
또 다른 예는 상기 노린재 나무 또는 노린재 나무 잎의 추출물을 유효성분으로 포함하는 진통제 또는 신경병증성 통증치료제의 조성물 제조 방법에 관한 것이다. Another example relates to a method for preparing a composition of an analgesic or neuropathic pain therapeutic agent comprising the extract of Stink bug tree or Stink bug tree leaf as an active ingredient.
본 발명자들은 노린재 나무 또는 노린재 나무 잎의 추출물에 대하여 노린재 나무 또는 노린재 나무 잎의 추출물을 이용한 라이딩(writhing) 억제 시험, 포르말린 통증 시험(Formalin test), 사이토 카인 통증 시험(cytokine test), 신경병증성 통증 시험(Neurophatic pain test), 꼬리 움직임 시험(tail-flick test), 뜨거운 바닥 시험(hot-plate test) 등의 다양한 통증 지표 테스트를 통하여 진통효과를 측정 규명하여 본 발명을 완성하였다.The inventors of the present invention, the extract of stink bug tree or stink bug tree leaves, the riding inhibition test (formulain test), formalin test, cytokine pain test (cytokine test), neuropathy The present invention was completed by measuring the analgesic effect through various pain index tests such as a pain test (Neurophatic pain test), a tail-flick test, and a hot-plate test.
이에, 노린재 나무 또는 노린재 나무 잎의 식물 추출물을 유효성분으로 함유하는 진통제 또는 신경병증성 치료제의 조성물이 제공된다.Thus, there is provided a composition of an analgesic or neuropathic therapeutic agent containing a plant extract of Stink bug tree or Stink bug tree leaf as an active ingredient.
또 다른 예에서, In another example,
건조된 노린재 나무 또는 노린재 나무 잎 식물을 준비하는 단계; 및Preparing a dried stink bug tree or stink bug tree leaf plant; And
상기 준비된 건조된 노린재 나무 또는 노린재 나무 잎 식물에 물, 탄소수 1 내지 4의 알코올로 이루어진 군에서 선택된 1종 이상의 용매를 가하여, 수용액상에서 추출하는 단계를 포함하는 상기 진통제 조성물의 제조 방법이 제공된다.Provided is a method for producing the analgesic composition comprising the step of extracting in an aqueous solution by adding at least one solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms to the dried stink bug tree or stink bug tree leaf plants.
이하, 이를 보다 상세히 설명한다. This will be described in more detail below.
노린재나무(Symplocos chinensis for. Pilosa (Nakai) Ohwi)는 노린재나무과(Symplocaceae)로 중국, 일본, 인도에 분포하며 우라나라 각처의 산과 들에 나는 낙엽 관목으로 키는 1-3m로 자라며 가지는 퍼지고, 작은 가지에는 털이 있다. 잎은 호생이며 난형 또는 긴 타원상 난형으로 양 끝이 뾰족하고, 보통 가장자리에 작은 톱니가 있으나 때로는 뚜렷하지 않고 호생하며 표면은 짙은 녹색이고 털이 없으며, 뒷면은 연두색으로 털이 있거나 없다. 열매는 길이 8mm로서 타원형이고 9월에 벽색(碧色)으로 익는다. Stinkwood Tree chinensis for. Pilosa (Nakai) Ohwi) is a species of Symplocaceae, distributed in China, Japan, and India. It is a deciduous shrub that grows in mountains and fields of Uranara, grows 1-3m in height, and has branched hairs. Leaves are eosinophilic, ovate or long oval ovate, pointed at both ends, usually with small sawtooth at edges, sometimes not clear and regenerated, surface is dark green, hairless, backside light green or without hair. Fruits are 8mm long, elliptical, and ripen in September.
원추화서는 길이 4~8cm로서 새로 난 가지 끝에 달리며 화경에 털이 있고 꽃잎은 긴 타원형이며 옆으로 터진다. 꽃은 지름 8~10mm이고 5월에 백색으로 핀다. 꽃잎은 장타원형으로 수술이 많고 약 보름간 감상할 수 있으며 은은한 향기가 있다.Cone inflorescence is 4 ~ 8cm long, hangs at the end of new branches, hairs are in the flower garden, petals are long oval and bursts to the side. The flower is 8-10mm in diameter and blooms white in May. The petals are long oval, with a lot of stamens, and can be enjoyed for about a full time with a subtle scent.
본 발명의 노린재 나무 추출물은 식물 전체를 추출하여 얻어진 것이거나, 식물 일부(뿌리, 잎, 꽃, 줄기 열매 등), 예컨대 식물이 지상부(잎, 꽃, 줄기, 열매 등), 바람직하게는 줄기 및 잎을 추출하여 얻어진 것일 수 있다. The stink bug tree extract of the present invention is obtained by extracting the entire plant, or a part of the plant (root, leaf, flower, stem fruit, etc.), for example, the plant is ground (leaf, flower, stem, fruit, etc.), preferably stem and It may be obtained by extracting the leaves.
지금까지 Symplocos속 식물의 추출물에 대한 진통 효과에 대해서는 알려진 바가 없다. 특히, 본 발명에 따른 노린재 나무 및 잎의 추출물은 다른 유효성분과 병용되지 않고 단독으로 사용되는 경우에도 충분한 진통 효과를 얻을 수 있다는 이점이 있다.To date, no analgesic effects on extracts of plants of the genus Symplocos are known. In particular, the extracts of stink bug trees and leaves according to the present invention has the advantage that even when used alone without being used in combination with other active ingredients, a sufficient analgesic effect can be obtained.
본 발명에서 사용 가능한 노린재나무속 식물은 검노린재(Symplocos tanakana Nakai), 섬노린재(Symplocos coreana (H.Lev.) Ohwi), 흰노린재(Symplocos chinensis var. leucocarpa (Nakai) Ohwi)로 이루어진 군에서 선택된 1종 이상의 것일 수 있다. The hemipphyllum plant that can be used in the present invention is a gnome ( Symplocos) tanakana Nakai, Symplocos coreana (H.Lev.) Ohwi), white stink bug ( Symplocos chinensis var. leucocarpa (Nakai) Ohwi) may be one or more selected from the group consisting of.
상기 노린재나무 및 노린재나무 잎 추출물은 노린재나무 및 노린재 나무 잎을 물, 탄소수 1 내지 4의 알코올로 이루어진 군에서 선택된 1종 이상의 용매로 추출하여 얻어진 것일 수 있다. The bilberry and bilberry leaf extract may be obtained by extracting a bilberry and a hemberry leaf with one or more solvents selected from the group consisting of water and alcohols having 1 to 4 carbon atoms.
구체예에 있어서, 상기 노린재나무 및 노린재나무 잎 추출물은 노린재 나무 및 노린재 나무 잎을 물로 추출하여 얻어진 것일 수 있다.In a specific embodiment, the hemip tree and hemip tree leaf extract may be obtained by extracting the hemip tree and hemip tree leaf with water.
본 발명의 구체예에서는 노린재 나무 및 노린재 나무 잎을 물을 사용하여 100℃에서 3시간동안 환류(reflux) 추출하였으나, 이에 제한되는 것은 아니다.In the embodiment of the present invention, the stink bug tree and stink bug tree leaf was refluxed for 3 hours at 100 ° C. using water, but is not limited thereto.
노린재나무 식물 내의 유효성분이 충분히 추출될 수 있도록, 상기 추출용매의 사용량은 노린재나무 및 노린재 나무 잎의 중량 기준으로 약 5 내지 20배, 바람직하게는 약 7 내지 15배일 수 있으며, 추출 온도는 50 내지 120℃, 바람직하게는 80 내지 100℃ 범위로 하고, 추출 시간은 1 내지 10 시간, 바람직하게는 1 내지 5시간일 수 있으나, 이에 제한되는 것은 아니다.The amount of the extractant used may be about 5 to 20 times, preferably about 7 to 15 times, based on the weight of the hemip tree and stink bug tree leaves, so that the active ingredient in the hemip tree plant can be sufficiently extracted. 120 ° C, preferably 80 to 100 ° C, and the extraction time may be 1 to 10 hours, preferably 1 to 5 hours, but is not limited thereto.
본 발명의 조성물은 유효성분인 노린재 나무 또는 노린재 나무 잎의 추출물 외에, 영양제, 비타민, 전해질, 풍미제, 착색제, 중진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 추가로 함유할 수 있다. 상기 성분들은 독립적으로 또는 조합하여 추가될 수 있다. 상기 추가성분의 함량은 바람직하게는 상기 운향 추출물 100 중량부 당 0.01 내지 100 중량부 범위에서 추가할 수 있으나, 이에 제한되는 것은 아니다.The composition of the present invention, in addition to the extract of the hemip tree or stink bug leaf as an active ingredient, nutrients, vitamins, electrolytes, flavors, coloring agents, neutralizing agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like may further be contained. The components may be added independently or in combination. The content of the additional component is preferably added in the range of 0.01 to 100 parts by weight per 100 parts by weight of the fragrance extract, but is not limited thereto.
상기 조성물 내의 상기 노린재 나무 또는 노린재 나무 잎 추출물의 함량은 질환의 증상, 증상의 정도, 환자의 상태 등에 따라서 적절히 조절 가능하며, 예컨대, 전체 조성물 중량을 기준으로 0.0001 내지 99.9중량%, 바람직하게는 0.001 내지 50중량%인 것이 좋으나, 이에 한정되는 것은 아니다. 상기 함량비는 용매를 제거한 건조량을 기준으로 한 값이다. The content of the hemip tree or hemip tree leaf extract in the composition may be appropriately adjusted according to the symptoms of the disease, the degree of symptoms, the condition of the patient, and the like, for example, 0.0001 to 99.9% by weight, preferably 0.001 based on the total composition weight. It is preferably from 50% by weight, but is not limited thereto. The content ratio is a value based on the drying amount from which the solvent is removed.
상기 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있으며, 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액 등의 형태로 제형화하여 사용될 수 있다. The composition may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions, and oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like according to conventional methods It may be used in the form of a dosage form, an external preparation, a suppository, or a sterile injectable solution.
상기 조성물을 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 고형 제제는 적어도 한 가지 이상의 부형제 및/또는 윤활제 등을 포함할 수 있다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조제제, 좌제 등이 포함된다. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient 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 or more excipients and / or lubricants. Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like.
상기 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 보다 바람직한 효과를 위해서, 본 발명의 조성물의 투여량은 유효성분을 기준으로 1일 1 mg/kg 내지 100 mg/kg으로 하는 것이 좋으나 이에 제한되는 것은 아니다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 본 발명의 조성물은 동물, 바람직하게는 인간을 포함하는 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 정맥, 근육, 피하주사 등에 의해 투여될 수 있다. 본 발명의 조성물의 약학적 투여 형태는 유효성분의 약학적 허용 가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다. The preferred dosage of the composition depends on the condition and weight of the patient, the severity 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. For a more preferable effect, the dosage of the composition of the present invention is preferably 1 mg / kg to 100 mg / kg per day based on the active ingredient, but is not limited thereto. The administration may be carried out once a day or divided into several doses. The compositions of the present invention can be administered by various routes to an animal, preferably a mammal, including a human. All modes of administration can be envisaged, for example, by oral, intravenous, intramuscular, subcutaneous injection or the like. The pharmaceutical dosage form of the composition of the present invention may be used in the form of a pharmaceutically acceptable salt of the active ingredient, and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection.
또 다른 예에서, 상기 노린재 나무 또는 노린재 나무 잎의 식물 추출물을 포함하는 통증 개선용 식품 조성물이 제공된다.In another example, there is provided a food composition for pain improvement comprising the plant extract of the hemip tree or hemip tree leaf.
본 발명에서 식품은 영양소를 한 가지 또는 그 이상 함유하고 있는 천연물 또는 가공품을 의미하며, 바람직하게는 어느 정도의 가공 공정을 거쳐 직접 먹을 수 있는 상태가 된 것을 의미하며, 통상적인 의미로서, 각종 식품, 건강기능 식품, 음료, 식품 첨가제 및 음료 첨가제를 모두 포함하는 의미로 사용된다. 상기 식품의 예로서 각종 식품류, 음료, 껌, 차, 비타민 복합제, 기능성 식품 등이 있다. 추가로, 본 발명에서 식품에는 특수영양식품(예, 조제유류, 영,유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류(예, 라면류, 국수류 등), 건강보조식품, 조미식품(예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류(예, 스넥류), 유가공품(예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임식품(각종 김치류, 장아찌 등), 음료(예, 과실,채소류 음료, 두유류, 발효음료류, 아이스크림류 등), 천연조미료(예, 라면 스프 등), 비타민 복합제, 알코올 음료, 주류 및 그 밖의 건강보조식품류를 포함하나 이에 한정되지 않는다. 상기 건강기능식품, 음료, 식품첨가제 또는 음료첨가제는 통상의 제조방법으로 제조될 수 있다.In the present invention, the food means a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through a certain processing process. , Dietary supplements, beverages, food additives and beverage additives. Examples of the foods include various foods, beverages, gums, teas, vitamin complexes, and functional foods. In addition, the food in the present invention includes special nutritional products (e.g., prepared oils, infants, baby food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), health supplements, seasoned foods ( For example, soy sauce, miso, red pepper paste, mixed soy sauce), sauces, confectionery (e.g. snacks), dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickles (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruits, vegetable drinks, soy milk, fermented beverages, ice cream, etc., natural seasonings (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages, and other health supplements. The health functional food, beverages, food additives or beverage additives may be prepared by a conventional manufacturing method.
상기 식품 조성물은 식품학적으로 허용 가능한 식품 보조 첨가제를 포함할 수 있으며, 기능성 식품의 제조에 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더욱 포함할 수 있다.The food composition may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.
또한, 상기 식품에 있어서, 상기 노린재 나무 또는 노린재 나무 잎 추출물의 양은 전체 식품 중량의 0.00001 중량% 내지 50 중량%로 포함될 수 있으며, 상기 식품이 음료인 경우에는 식품 전체의 부피 100 ml 를 기준으로 0.001 g 내지 50 g, 바람직하게는 0.01 g 내지 10 g의 비율로 포함될 수 있으나, 이에 한정되는 것은 아니다.In addition, in the food, the amount of hemip tree or hemip tree leaf extract may be included as 0.00001% to 50% by weight of the total food weight, if the food is a beverage based on the volume of 100 ml of the total food content of 0.001 g to 50 g, preferably 0.01 g to 10 g, but is not limited thereto.
본 발명은 진통제 및 신경병증성 통증 치료제의 조성물에 관한 것으로 노린재 나무 또는 노린재 나무 잎의 추출물을 이용한 진통효과를 얻는 것을 그 특징으로 하며 이는 천연물에서 유래한 진통제 또는 신경병증성 통증 치료제의 조성물이라는 측면에서 그 의의가 있으며 이를 적극적으로 활용할 경우 다양한 질병에 대한 진통제 및 신경병증성 통증 치료제의 조성물로서 널리 활용될 수 있으며 나아가 국민 건강에 기여 할 수 있다.The present invention relates to a composition of an analgesic agent and a neuropathic pain treatment, characterized in that it obtains an analgesic effect using an extract of Stink bug tree or Stink bug tree leaf, which is a composition of an analgesic agent or a neuropathic pain therapeutic agent derived from natural products. If it is meaningful, it can be widely used as a composition for analgesics and neuropathic pain treatments for various diseases and can contribute to national health.
도 1은 노린재 나무 물 추출물 실험결과 (writhing test - 농도별)
- 노린재 나무 물 추출물을 농도별로 마우스에 경구 투여한 30분 후, 1% Acetic acid를 복강 투여하여 writhing test를 진행한 결과, 0.1 mg/kg의 저농도부터 200 mg/kg의 고농도까지 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 2는 노린재 나무 물 추출물 실험결과 (Formalin test - 농도별)
- 노린재 나무 물 추출물을 농도별로 마우스에 경구 투여한 30분 후, 5% Formalin을 마우스의 왼쪽 발바닥에 투여하여 실험을 진행한 결과, 2nd phase에서 0.1 mg/kg의 저농도부터 200 mg/kg의 고농도까지 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 3은 노린재 나무의 물 분획물 실험결과 (writhing test)
- 노린재 나무의 물 분획물을 농도별로 마우스에 경구 투여한 30분 후, 1% Acetic acid를 복강 투여하여 writhing test를 진행한 결과, 5 mg/kg 부터 25 mg/kg까지 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 4는 노린재 나무 물 분획물 층별 물질 실험결과 (writhing test)
- 노린재 나무의 물 분획물의 다양한 층을 200 mg/kg로 마우스에 경구 투여한 30분 후, 1% Acetic acid를 복강 투여하여 writhing test를 진행한 결과, 모든 물 분획물의 층별 물질에서 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 5는 노린재 나무 물 추출물의 진통효과 관련 기전 연구
- Norepinephrine 수용체 억제제인 Phentolamin과 Yohimbine, Serotonie 수용체 억제제인 Methysergide, Opioid 수용체 억제제인 Naloxone을 복강내로 전처리한 10분 후, 노린재 나무의 물 추출물을 100 mg/kg로 마우스에 경구 투여하여 그로부터 30분 후에 1% Acetic acid를 복강 투여하여 writhing test를 진행한 결과, Naloxone을 전처리한 그룹에서 노린재 나무의 진통효과가 대조군 수준으로 돌아가는 것을 확인 함. 이로보아, 노린재 나무의 진통효과는 Opioid 관련 기전과 연관이 있다고 생각된다.
도 6은 노린재 나무의 신경병증성 통증 모델인 CCI von Frey 실험 결과
- 신경병증성 통증(Neuropathic Pain)은 상처로 입은 신경손상 이후로 병을 일으키는 계속되는 아픔 (persistent pain that develops after nerve damage caused by injury)을 말함. 신경병증성 통증에 대한 노린재 나무의 진통효과를 알아보고자 CCI von Frey 실험을 진행하였고, 그 결과 노린재 나무은 신경 병증성 통증에도 효과가 있음을 확인할 수 있다.
도 7은 노린재 나무의 신경병증성 통증 모델인 SNI von Frey 실험 결과
- 신경병증성 통증에 대한 노린재 나무의 진통효과를 알아보고자 SNI von Frey 실험을 진행하였고, 그 결과 노린재 나무은 신경 병증성 통증에도 효과가 있음을 확인할 수 있다.
도 8은 노린재 나무의 Glutamate 및 Substance P Test의 결과
- 노린재 나무를 농도별로 마우스에 경구 투여한 30분 후, Glutamate를 척수강 내에 투여하여 통증 실험을 진행한 결과, 5 mg/kg과 10 mg/kg의 농도에서 유의성 있는 진통 효과를 보이는 것으로 확인 함. 그리고, 노린재 나무를 농도별로 마우스에 경구 투여한 30분 후, Substance P를 척수강 내에 투여하여 통증 실험을 진행한 결과, 0.1 mg/kg과 1 mg/kg의 농도를 제외한 대부분의 농도에서 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 9는 노린재 나무의 다양한 Cytokines test 결과
- 노린재 나무를 농도별로 마우스에 경구 투여한 30분 후, 다양한 Cytokine을 척수강 내에 투여하여 통증 실험을 진행한 결과, TNF-a는 1 mg/kg과 5 mg/kg의 농도에서 유의성 있는 진통 효과를 보이는 것으로 확인 하였고, IL-1b는 0.1 mg/kg과 1 mg/kg의 농도에서 유의성 있는 진통 효과를 보이는 것으로 확인하였으며, IFN-g는 0.1~5 mg/kg의 농도에서 유의성있는 진통 효과를 보이는 것을 확인하였다.
도 10은 노린재 나무의 Tail flick test 결과
- 노린재 나무를 200 mg/kg으로 마우스에 경구 투여한 30분 후, Tail flick test 통증 실험을 진행한 결과, 유의성있는 진통 효과를 보이는 것을 확인 하였다.
도 11은 노린재 나무의 Hot plate test 결과
- 노린재 나무를 200 mg/kg으로 마우스에 경구 투여한 30분 후, Hot plate test 통증 실험을 진행한 결과, 진통 효과를 보이는 것을 확인하였다.
도 12는 노린재 나무 잎의 writhing test 결과
- 노린재 나무 잎의 물 추출물을 10 mg/kg의 농도로 마우스에 경구 투여한 30분 후, 1% Acetic acid를 복강 투여하여 writhing test를 진행한 결과, 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 13은 노린재 나무 잎의 Glutamate 및 Substance P Test의 결과
- 노린재 나무 잎을 10 mg/kg의 농도로 마우스에 경구 투여한 30분 후, Glutamate를 척수강 내에 투여하여 통증 실험을 진행한 결과 진통 효과를 보이는 것으로 확인 함. 그리고, 노린재 나무 잎의 물 추출물을 10 mg/kg의 농도로 마우스에 경구 투여한 30분 후, Substance P를 척수강 내에 투여하여 통증 실험을 진행한 결과, 유의성 있는 진통 효과를 보이는 것으로 확인하였다.
도 14는 노린재 나무 잎의 Cytokines test 결과
- 노린재 나무 잎을 10 mg/kg의 농도로 마우스에 경구 투여한 30분 후, Cytokine을 척수강 내에 투여하여 통증 실험을 진행한 결과 진통 효과를 보이는 것으로 확인하였다.1 is a test result of stink bug tree water extract (writhing test-by concentration)
-30 minutes after oral administration of stink bug tree water extract to mice, the writhing test with 1% Acetic acid intraperitoneally showed significant analgesic effect from the low concentration of 0.1 mg / kg to the high concentration of 200 mg / kg. It was confirmed to show.
Figure 2 is a test result of Stink bug tree water extract (Formalin test-by concentration)
-30 minutes after oral administration of Stink bug tree water extract to mice by concentration, 5% Formalin was administered to the left foot of the mouse. Up to a significant analgesic effect was confirmed.
3 is a water fraction test results of stink bug trees (writhing test)
-After 30 minutes of oral administration of water fraction of stink bug tree to mice by concentration, writhing test with 1% Acetic acid intraperitoneally showed significant analgesic effect from 5 mg / kg to 25 mg / kg. Confirmed.
Figure 4 is a test result of the stinkwood tree water fraction layered material (writhing test)
-30 minutes after oral administration of various layers of water fractions of stink bug trees to mice at 200 mg / kg, a writhing test was performed with 1% Acetic acid intraperitoneally, and the analgesic effect of all the water fractions was significantly increased. It was confirmed to show.
5 is a mechanism study related to the analgesic effect of Stink bug tree water extract
10 minutes after intraperitoneal pretreatment with Norepinephrine receptor inhibitors, Phentolamin, Yohimbine, Serotonie receptor inhibitor, Methysergide, and Opioid receptor inhibitor Naloxone, orally administered 100 mg / kg water extract of Stink bug tree to
6 shows the results of CCI von Frey experiment, a neuropathic pain model of stink bug trees.
Neuropathic Pain is the persistent pain that develops after nerve damage caused by injury. CCI von Frey experiment was conducted to investigate the analgesic effect of Stink bug tree on neuropathic pain. As a result, Stink bug tree has effects on neuropathic pain.
7 is a SNI von Frey experiment results of neuropathic pain model of stink bug trees
-SNI von Frey experiment was conducted to investigate the analgesic effect of Stink bug tree on neuropathic pain. As a result, Stink bug tree has effects on neuropathic pain.
8 is a result of Glutamate and Substance P Test of stink bug tree
-30 minutes after oral administration of stink bug trees to mice by concentration, Glutamate was administered in the spinal cavity to conduct a pain experiment. In addition, after 30 minutes of oral administration of stink bugs to mice by concentration, a pain test was conducted by administering Substance P into the spinal cavity, and significant analgesia was observed at most concentrations except 0.1 and 1 mg / kg The effect was confirmed to be.
9 shows various Cytokines test results of stink bug trees
-After 30 minutes of oral administration of stink bug trees to mice at different concentrations, a variety of cytokines were administered in the spinal cavity to test the pain. TNF-a had significant analgesic effects at concentrations of 1 mg / kg and 5 mg / kg. IL-1b showed significant analgesic effects at concentrations of 0.1 mg / kg and 1 mg / kg, and IFN-g had significant analgesic effects at concentrations of 0.1-5 mg / kg. It was confirmed.
10 is Tail flick test results of stink bug trees
-30 minutes after oral administration of stink bug trees to the mouse at 200 mg / kg, the tail flick test pain test results, it was confirmed that showing a significant analgesic effect.
11 is a hot plate test results of stink bug wood
-30 minutes after oral administration of stink bug trees to the mouse at 200 mg / kg, Hot plate test pain test results, it was confirmed that showing the analgesic effect.
12 is writhing test results of stink bug tree leaves
-30 minutes after oral administration of water extract of Stink bug tree leaf to the concentration of 10 mg / kg, 1% Acetic acid was intraperitoneally administered writhing test, and showed a significant analgesic effect.
13 is a result of Glutamate and Substance P Test of stink bug tree leaves
-30 minutes after oral administration of stink bug leaves to mice at a concentration of 10 mg / kg, Glutamate was administered into the spinal cavity to confirm pain relief. In addition, 30 minutes after oral administration of water extract of stink bug tree leaves to the mouse at a concentration of 10 mg / kg, Substance P was administered into the spinal cavity, and as a result of the pain test, it was confirmed that it showed a significant analgesic effect.
14 is a result of Cytokines test of stink bug tree leaves
-30 minutes after oral administration of stink bug tree leaves to the mice at a concentration of 10 mg / kg, Cytokine was administered in the spinal cavity to confirm the analgesic effect.
이하, 실시예를 통하여 본 발명을 보다 상세히 설명하도록 한다. 그러나, 이들 실시예는 본 발명을 대표적으로 예시하기 위한 것일 뿐이며, 본 발명의 범위가 이들 실시예에 의하여 제한되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are only intended to illustrate the present invention, but the scope of the present invention is not limited by these examples.
제조예Manufacturing example 1: 노린재나무 추출물 제조 1: hemipteran extract manufacture
노린재나무 1 kg에 물 20L를 넣고 반응조(MS-CM709) 100℃에서 3시간동안 환류(reflux) 추출하였다. 상기의 방법에 의해 제조된 노린재나무 열수 추출물을 감압회전농축(Eyela N-1000, Tokyo, Japan) 을 이용하여 감압농축하여 얻은 조 추출물 중 활성평가를 위해 일부를 분취 후 동결건조하여 43.5 g을 얻었다.20 kg of water was added to 1 kg of stink bug trees, and reflux was extracted for 3 hours at 100 ° C of a reaction tank (MS-CM709). A portion of the crude extract obtained by the above method was extracted under reduced pressure using a reduced pressure rotary concentrate (Eyela N-1000, Tokyo, Japan), and then freeze-dried to obtain 43.5 g. .
나머지 농축된 노린재나무 물 추출물은 분획깔대기를 이용하여 노르말 헥산(n-hexane), 에틸아세테이드, 부탄올 등으로 용매분획하여 농축 후 동결건조하여 분말상으로 제조하였으며 얻은 양은 메틸렌클로라이드(CH2Cl2) 용성 분획물 0.58 g, 에틸아세테이트 용성 분획물 0.27 g, 부탄올 용성 분획물 3.28 g, 물 분획물 32.14 g을 얻었다.
The remaining extract of Stink Bugs tree water was prepared using a fraction funnel with solvent fractionation with normal hexane (n-hexane), ethyl acetate, butanol, etc., concentrated and freeze-dried to obtain a powder. The amount obtained was methylene chloride (CH 2 Cl 2). ) 0.58 g of soluble fraction, 0.27 g of ethyl acetate soluble fraction, 3.28 g of butanol soluble fraction and 32.14 g of water fraction were obtained.
제조예Manufacturing example 2: 노린재나무 잎 추출물 제조 2: stink bug leaf extract manufacture
노린재 나무 잎 1 kg 물 15 L를 넣고 반응조(MS-CM709) 100℃에서 3시간동안 환류(reflux) 추출하였다. 상기의 방법에 의해 제조된 노린재나무 잎 열수 추출물을 감압회전농축(Eyela N-1000, Tokyo, Japan) 을 이용하여 감압농축하여 얻은 조 추출물 중 활성평가를 위해 일부를 분취 후 동결건조하여 141.3g을 얻었다.15 kg of stink bug tree leaves were put in water and reflux was extracted for 3 hours at 100 ° C in a reaction tank (MS-CM709). A portion of the crude extract obtained by the above method was extracted under reduced pressure using a reduced pressure rotary concentrated extract (Eyela N-1000, Tokyo, Japan), and then freeze-dried. Got it.
나머지 농축된 노린재나무 잎 물 추출물은 분획깔대기를 이용하여 노르말 헥산(n-hexane), 에틸아세테이드, 부탄올 등으로 용매분획하여 농축 후 동결건조하여 분말상으로 제조하였으며 건조 후 얻은 양은 노르말헥산 용성 분획물 0.01 g, 메틸렌클로라이드(CH2Cl2) 용성 분획물 6.66g, 에틸아세테이트 용성 분획물 3.74 g, 부탄올 용성 분획물 12.77g, 물 분획물 106.17g을 얻었다.
The remaining concentrated Stink bug leaf water extract was fractionated by solvent fractionation with normal hexane (n-hexane), ethyl acetate, butanol, etc., using a fraction funnel, concentrated and freeze-dried to obtain a powdery form. 0.01 g, methylene chloride (CH 2 Cl 2 ) soluble fraction 6.66 g, ethyl acetate soluble fraction 3.74 g, butanol soluble fraction 12.77 g, and water fraction 106.17 g were obtained.
실시예Example 1: 노린재 나무 및 노린재 나무 잎의 1: of stink bug tree and stink bug tree leaf 라이딩Riding (( writhingwrithing ) 억제 시험Suppression test
제조예1, 2에서 얻은 천연물(노린재 나무 및 노린재 나무 잎)을 4주령 ICR 생쥐(체중 약 25g)에게 여러가지 농도로 경구투여 하였다. 이어서 생쥐의 복강에 1 % 초산 0.25 ㎖를 투여한 다음 30 분 동안 라이딩 반응(writhing response)을 조사하였다. 이때 대조군으로서 천연물(노린재 나무)이 투여되지 않은 생쥐를 사용하여 동일하게 시험하였다.
Natural products obtained from Preparation Examples 1 and 2 (stink bug tree and stink bug tree leaf) were orally administered to 4 week old ICR mice (weight about 25 g) at various concentrations. Subsequently, 0.25 ml of 1% acetic acid was administered to the abdominal cavity of mice, and then the riding response was examined for 30 minutes. At this time, as a control, the same test was performed using mice that did not receive the natural product (stink bug tree).
실시예Example 2: 노린재 나무 및 노린재 나무 잎의 포르말린 시험 2: formalin test of stink bug tree and stink bug tree leaf
제조예 1, 2 에서 얻은 천연물(노린재 나무 및 노린재 나무 잎)을 4주령 ICR 생쥐(체중 약 25g)에게 여러가지 농도로 경구투여 하였다. 이 후 30 분이 경과한 때에, 각각의 생쥐의 뒷 발바닥에 5% 포르말린 수용액을 투여한 후, 처음 5분 동안의 제 1 기 및, 20 내지 40 분의 동안의 제 2 기에 생쥐가 발바닥을 핥거나 흔드는 등의 통증 반응을 보이는 시간을 측정하였다. 이때 대조군으로서 천연물(노린재 나무)이 투여되지 않은 생쥐를 사용하여 동일하게 시험하였다.
Natural products obtained from Preparation Examples 1 and 2 (stink bug tree and stink bug tree leaf) were orally administered to 4 week old ICR mice (weight about 25 g) at various concentrations. At the end of 30 minutes, 5% formalin aqueous solution was administered to the rear paws of each mouse, and then the mice licked the paws in the first stage for the first 5 minutes and the second stage for 20 to 40 minutes. The time of showing pain response of shaking back was measured. At this time, as a control, the same test was performed using mice that did not receive the natural product (stink bug tree).
실시예Example 3: 신경 3: nerves 병증성Pathogenic 통증 모델 Pain model
이전의 rat에서 시행한 (Seltzer et al., 1990)모델을 참고하여 마우스의 좌골신경 부분 손상 모델을 응용한다. 신경병증성 통증의 유발을 위하여 할로탄(2-3%)으로 마취된 마우스는 9-0 silk를 이용하여 좌골신경의 직경 1/2 내지 1/3가량이 매듭지어짐. 대조군으로는 좌골신경을 노출만 시킨 후 매듭을 짓지 않은 것을 이용한다. 시술후 3일, 7일, 10일 후 각각 von Frey hair를 이용한 기계적 자극과, Radiant Heat 을 이용한 Paw withdrawal latency를 측정하여, 기계적 혹은 온도유발 통감의 변화를 측정함으로서 신경병증성 통증의 발생여부를 판단하게 된다.
A model of sciatic nerve injury in mice is applied, referring to the previous model of rats (Seltzer et al., 1990). Mice anesthetized with halotan (2-3%) to induce neuropathic pain are knotted with 1 / 2-0 / 3 of the sciatic nerve diameter using 9-0 silk. As a control, only the sciatic nerve is exposed and no knot is used. 3 days, 7 days, and 10 days after the procedure, mechanical stimulation using von Frey hair and Paw withdrawal latency using Radiant Heat were measured, and neuropathic pain was measured by measuring changes in mechanical or temperature-induced pain. You will be judged.
실시예Example 4: 노린재 나무 및 노린재 나무 잎의 글루타민 산과 물질 P 및 다양한 4: Glutamic acid and substance P and various of stink bug trees and stink bug leaves 사이토 카인들의Of the cytokines 통증 시험 Pain test
제조예 1, 2에서 얻은 천연물(노린재 나무 및 노린재 나무 잎)을 4주령 ICR 생쥐(체중 약 25g)에게 여러가지 농도로 경구투여 하였다. 이 후 30 분이 경과한 때에, 각각의 생쥐의 척수강(intrathecal)에 글루타민 산 20 ㎍ 또는 물질 P(Substance P) 0.7 ㎍ 또는 다양한 사이토 카인을 100 ㎍의 양으로 각각 투여한 후, 30 분 동안 생쥐가 꼬리 및 하반신 쪽을 핥거나 흔드는 등의 통증 반응을 보이는 시간을 측정하였다. 이때 대조군으로서 천연물(노린재 나무)이 투여되지 않은 생쥐를 사용하여 동일하게 시험하였다.
Natural products obtained from Preparation Examples 1 and 2 (Stink bug tree and Stink bug tree leaf) were orally administered to 4 week old ICR mice (body weight about 25 g) at various concentrations. After 30 minutes, each mouse was given an intrathecal dose of 20 μg of glutamic acid or 0.7 μg of Substance P or 100 μg of various cytokines, respectively. The time of pain response such as licking or shaking the tail and lower body was measured. At this time, as a control, the same test was performed using mice that did not receive the natural product (stink bug tree).
실시예Example 5: 노린재 나무의 꼬리 움직임 시험( 5: Test of tail movement of stink bug tree tailtail -- flickflick testtest ))
제조예 1에서 얻은 천연물(노린재 나무)을 4주령 ICR 생쥐(체중 약 25g)에게 여러가지 농도로 경구투여 하였다. 이어서, 각각의 생쥐의 꼬리에 빛(radient heat)을 쪼인 후 이러한 작열성 동통 수용기(thermal nociceptor) 자극으로 인한 통증으로 꼬리 움직임 반응을 보이는 시간을 측정하여 진통 기간(초)을 결정하였다. 이 검사법은 척수동통 회로에 대한 약물의 진통 효과를 확인해준다. 이 때 대조군으로서 천연물(노린재 나무)이 투여되지 않은 생쥐를 사용하여 동일하게 시험하였다.
The natural product (Stinkwood) obtained in Preparation Example 1 was orally administered to various concentrations of 4 weeks old ICR mice (about 25g body weight). Subsequently, the duration of analgesia (seconds) was determined by measuring the time at which the tail movement response was caused by pain of the thermal nociceptor stimulation after radiating heat to the tail of each mouse. This test confirms the analgesic effect of the drug on the spinal pain circuit. At this time, the same test was conducted using mice that did not receive the natural product (stink bug) as a control.
실시예Example 6: 노린재 나무의 뜨거운 바닥 시험( 6: hot floor test of stink wood ( HotHot -- plateplate testtest ))
제조예 1에서 얻은 천연물(노린재 나무)을 4주령 ICR 생쥐(체중 약 25g)에게 여러가지 농도로 경구투여 하였다. 이어서, 각각의 생쥐를 55도씨의 뜨거운 바닥에 올려 놓은 후 이러한 작열성 동통 수용기(thermal nociceptor) 자극으로 인한 통증으로 발바닥 움직임 반응을 보이는 시간을 측정하여 진통 기간(초)을 결정하였다. 이 검사법은 말초에서 중추로의 회로에 대한 약물의 진통 효과를 확인해준다. 이 때 대조군으로서 천연물(노린재 나무)이 투여되지 않은 생쥐를 사용하여 동일하게 시험하였다.The natural product (Stinkwood) obtained in Preparation Example 1 was orally administered to various concentrations of 4 weeks old ICR mice (about 25g body weight). The duration of labor (seconds) was then determined by placing each mouse on a hot floor at 55 degrees C and then measuring the time for the plantar movement response to pain due to this thermal nociceptor stimulus. This test confirms the analgesic effect of the drug on the peripheral to central circuit. At this time, the same test was conducted using mice that did not receive the natural product (stink bug) as a control.
Claims (6)
상기 준비된 건조된 노린재 나무 및 노린재 나무 잎에 물을 상기 건조된 노린재 나무 및 노린재 나무 잎을 중량 기준으로 5 내지 20배의 가하고, 수용액상에서 추출하는 단계를 포함하는 제1항의 급성 및 만성 통증에 관련된 진통제 또는 신경병증성 통증치료제의 조성물의 제조 방법.Preparing dried stink bug trees and stink bug tree leaves; And
5 to 20 times the weight of the dried stink bug tree and stink bug tree leaves by weight to the prepared dried stink bug tree and stink bug tree leaves, and extracting in aqueous solution related to the acute and chronic pain of claim 1 A method for preparing a composition of analgesic or neuropathic pain treatment.
The method of claim 5, wherein the extraction step is performed for 1 to 10 hours at a temperature range of 50 to 100 ℃.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101483647B1 (en) | 2014-11-18 | 2015-01-16 | (주) 와이디생명과학 | Composition for preventing and treating arthritis comprising extract of symplocos chinesis for. pilosa and astragalus membranaceus and method for preparing the same |
| KR20190036904A (en) | 2017-09-28 | 2019-04-05 | (주)휴럼 | Litsenolide used as an active ingredient for pain relief, and A composition comprising the same as an active ingredient |
| KR20200086207A (en) | 2019-01-08 | 2020-07-16 | 서울대학교산학협력단 | Composition for prevention or treatment of diabetic related disease comprising extract of Symplocos spp. or compound isolated from thereof |
| KR20220090815A (en) | 2020-12-23 | 2022-06-30 | 대한민국(산림청 국립산림과학원장) | Composition for preventing or improving skin cell damage caused by ultraviolet rays containing Symplocos chinensis f. pilosa (Nakai) Ohwi fruits extracts |
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| Title |
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| 논문:J ETHNOPHARMACOL. * |
| 논문:J ETHNOPHARMACOL.* |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101483647B1 (en) | 2014-11-18 | 2015-01-16 | (주) 와이디생명과학 | Composition for preventing and treating arthritis comprising extract of symplocos chinesis for. pilosa and astragalus membranaceus and method for preparing the same |
| WO2016080691A1 (en) * | 2014-11-18 | 2016-05-26 | (주) 와이디생명과학 | Pharmaceutical composition comprising extracts of symplococs chinesis and astragalus membranaceus for preventing and treating arthritis, and method for preparing same |
| KR20190036904A (en) | 2017-09-28 | 2019-04-05 | (주)휴럼 | Litsenolide used as an active ingredient for pain relief, and A composition comprising the same as an active ingredient |
| KR20200086207A (en) | 2019-01-08 | 2020-07-16 | 서울대학교산학협력단 | Composition for prevention or treatment of diabetic related disease comprising extract of Symplocos spp. or compound isolated from thereof |
| KR20220090815A (en) | 2020-12-23 | 2022-06-30 | 대한민국(산림청 국립산림과학원장) | Composition for preventing or improving skin cell damage caused by ultraviolet rays containing Symplocos chinensis f. pilosa (Nakai) Ohwi fruits extracts |
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