KR100573375B1 - Composition having an extract of Akebia quinata Seed for treating or preventing cancer, and preparation method thereof - Google Patents
Composition having an extract of Akebia quinata Seed for treating or preventing cancer, and preparation method thereof Download PDFInfo
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- KR100573375B1 KR100573375B1 KR1020040013330A KR20040013330A KR100573375B1 KR 100573375 B1 KR100573375 B1 KR 100573375B1 KR 1020040013330 A KR1020040013330 A KR 1020040013330A KR 20040013330 A KR20040013330 A KR 20040013330A KR 100573375 B1 KR100573375 B1 KR 100573375B1
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- 240000008027 Akebia quinata Species 0.000 title claims description 5
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
Abstract
본 발명은 으름덩굴 종자 추출물을 포함하는 항암 조성물 및 그의 제조방법에 관한 것으로, 본 발명의 조성물은 우수한 항암성을 나타내며, 이에 추가적으로 전호, 인삼 및/또는 울금 추출물을 처방하여 보다 증강된 항암 효과를 얻을 수 있어, 암의 예방 및/또는 치료제로서 유용하게 사용할 수 있다. The present invention relates to an anticancer composition comprising a mash seed extract and a method for producing the same, the composition of the present invention exhibits excellent anticancer properties, in addition to the Jeonho, ginseng and / or turmeric extract to further enhance the anticancer effect It can be obtained and can be usefully used as a prophylactic and / or therapeutic agent of cancer.
으름덩굴, 항암 조성물Ivy, anticancer composition
Description
본 발명은 으름덩굴 종자 추출물을 포함하는 항암 조성물 및 그의 제조방법에 관한 것이다. The present invention relates to an anticancer composition comprising a mash seed extract and a method for producing the same.
으름덩굴은 으름덩굴과(Lardizabalaceae)과에 속하는 덩굴나무로 음지의 산골에 자라며 국내에는 으름덩굴[Akebia quinata (Thumb) Decne] 한 종이 자생한다. 중국에는 삼엽 목통(Akebia trifoliata)와 백목통(A.trifoliata (Thumb) Koidz. var. australis(Diels) Rehd)이 자라고 있으며 약용으로 사용되고 있다. 현재까지 이 종자 자체나 그로부터 분리된 성분에 대한 약리학적 연구는 행하여지지 않고 있다.The vine is a vine belonging to the family Laridazabalaceae, growing in the valley of the shade, and the vine in Korea [ Akebia quinata (Thumb) Decne ] A species grows wild. In China, Akebia trifoliata and A.trifoliata (Thumb Koidz. Var. Australis (Diels) Rehd ) grow and are used for medicinal purposes. To date, no pharmacological studies have been conducted on the seeds themselves or the components isolated therefrom.
한방에서는 수치라 하여 원 약재에 인위적인 조작을 가하여 약효의 상승, 독성의 감소등을 꾀하고 있다. 청매를 구어서 항회충 효과를 내게 하고, 부자를 열처리하여 독성을 감소시키는 예가 대표적이다. 또한 민간에서는 생약재 자체를 약으로 사용하기도 하지만 수치법을 사용하기도 한다. 생약을 술밥과 같이 숙성시켜 술로 만들어 마시는 방법도 있고, 식혜형식으로 발효시켜 사용하기기도 한다. 그럼으로 이와 같은 민간적 방법은 한방이 선호하는 탕의 개념과는 다르다. In oriental medicine, the artificial medicines are applied to the original medicine to increase the drug's efficacy and reduce toxicity. A typical example is the removal of a berry to give an anti-rounding effect and to heat the rich to reduce toxicity. In the private sector, the herbal medicine itself is used as a medicine, but the numerical method is also used. Some herbal medicines are matured like alcohol, and they are made into alcoholic beverages or fermented in the form of Sikhye. Therefore, such a private method is different from the concept of tang preferred by oriental medicine.
본 발명자는 생약제의 항암효과를 연구하던 중 으름덩굴 및 동속 식물(아케비아 트리폴리아타(A.trifoliata) 및 아케비아 바르 오스트랄리스(Akebia trifoliata var. australis))의 종자의 추출물이 항암성을 보임을 관찰하고, 이에 대한 연구를 행함으로써 본 발명을 완성하기에 이르렀다. The inventors of the present invention, while studying the anticancer effect of the herbal medicine extracts of the seeds of the ivy and the same plants ( Akebia trifoliata and Akebia trifoliata var. Australis ) show anticancer activity The present invention was completed by observing and conducting research on it.
본 발명에서는 보다 강력한 항암 조성물의 개발하기 위해, 민간의 수치법에 기초하여 열을 사용하지 않고 신선한 식물체 자체를 물과 혼합하여 숙성시키는 방법을 개발하였다. 민간의 수치법과 다른 점은 누륵이나 기타 발효제를 사용하지 않고 식물자체의 발효력을 이용하는 것이다. 말하자면 물 존재하에 식물체의 세포를 파괴함으로써 생화학적 변화를 일으켜 새로운 약효를 갖는 약물을 얻고자 하였다. 즉, 으름덩굴 종자에 이와 같은 단순한 수치법을 적용함으로써 새로운 항암제를 개발을 하고자 하였다. In the present invention, in order to develop a more powerful anti-cancer composition, a method of aging by mixing fresh plants themselves with water without using heat based on civilian numerical methods was developed. The difference from the civilian method is that it uses the fermentation power of the plant itself without using silkworm or other fermenting agents. In other words, by destroying the cells of the plant in the presence of water caused biochemical changes to obtain a drug with a new drug. In other words, by applying such a simple numerical method to the seeds of the creeper to develop a new anticancer drug.
본 발명의 목적은 으름덩굴 종자 추출물을 포함하는 항암 조성물을 제공하는 것이다. It is an object of the present invention to provide an anticancer composition comprising stalk seed extract.
또한 본 발명의 목적은 상기 추출물에 인삼, 전호 및/또는 울금 등의 항암생약을 추가적으로 포함하는 항암 조성물을 제공하는 것이다. It is also an object of the present invention to provide an anticancer composition further comprising an anticancer drug such as ginseng, Jeonho and / or turmeric in the extract.
또한 본 발명의 목적은 상기 추출물의 제조방법을 제공하는 것이다. It is also an object of the present invention to provide a method for preparing the extract.
본 발명은 으름덩굴 종자 추출물을 포함하는 항암 조성물을 제공한다. The present invention provides an anticancer composition comprising the mash seed extract.
본 발명에서 사용되는 으름덩굴은 바람직하게는 아케비아 퀴나타(Akebia quinata), 아케비아 트리폴리아타(A.trifoliata) 및 아케비아 바르 오스트랄리스(Akebia trifoliata var. australis)로 구성된 군에서 선택될 수 있다. Akebia used in the present invention preferably ahkebi Oh quinolyl displayed (Akebia quinata), ahkebi Oh Tripoli Atta (A.trifoliata) and ahkebi Avar Austral less can be selected from the group consisting of (Akebia trifoliata var. Australis) have.
본 발명의 조성물에 있어서, 상기 추출물은 예컨대, 으름덩굴 종자를 필요하다면 물의 존재하에 분쇄하고, 물을 첨가하여 물중에서 일정 온도하에서 일정 시간 동안 숙성시킨 후, C1-4 알코올 등으로 추출한 추출물일 수 있다. In the composition of the present invention, the extract is, for example, crushed crushed seeds in the presence of water if necessary, aged for a certain time in water by adding water, and then extracted with C 1-4 alcohol, etc. Can be.
본 발명에서 사용된 상기 C1-4 알코올은 예컨대, 메탄올, 에탄올, 프로판올, 부탄올, 이소부탄올 등일 수 있고, 특히 메탄올 또는 에탄올이 바람직하다. 상기 C1-4 알코올은 함수 알코올이 바람직하나, 특히 이에 한정되는 것은 아니다. The C 1-4 alcohol used in the present invention may be, for example, methanol, ethanol, propanol, butanol, isobutanol, and the like, and methanol or ethanol is particularly preferable. The C 1-4 alcohol is preferably a hydrous alcohol, but is not particularly limited thereto.
본 발명의 조성물에 있어서, 상기 으름덩굴 종자 추출물에 전호(Anthriscus sylvestris), 인삼 및 울금(Curcuma aromatica)의 추출물에서 선택된 하나 이상의 추출물을 추가적으로 첨가할 수 있고, 특히 전호의 에테르 분획, 인삼의 아세톤 분획 또는 부탄올 분획 및/또는 울금의 초산에칠 분획을 일정 비율로 포함할 수 있고, 이로서 항암성이 보다 향상된 조성물을 얻을 수 있다. In the composition of the present invention, one or more extracts selected from extracts of Jeonho ( Anthriscus sylvestris ), ginseng and Curcuma aromatica may be additionally added to the stalk seed extract, in particular the ether fraction of Jeonho, the acetone fraction of Ginseng Or butanol fraction and / or ethyl acetate fraction of turmeric may be included in a certain ratio, thereby obtaining a composition with improved anticancer properties.
본 발명의 조성물은 으름덩굴 종자를 물에서 숙성시키는 단계 및 상기 숙성된 종자 추출물을 C1-4 알코올로 추출하는 단계를 포함하는 방법에 의해 제조할 수 있다. 상기 방법에 있어서, 숙성 단계에서 으름덩굴 종자를 필요하다면 물의 존재 하에 분쇄하고, 적정량의 물을 첨가하여 숙성하는 것이 바람직하다. The composition of the present invention can be prepared by a method comprising the step of maturing the crushed seed in water and extracting the aged seed extract with C 1-4 alcohol. In the above method, it is preferable to grind the crushed seed in the presence of water if necessary in the aging step and to ripen by adding an appropriate amount of water.
본 발명의 제조방법에 있어서, 숙성 단계의 물의 양, 숙성 온도 및 숙성 시간이 본 발명의 조성물의 항암성을 결정하는데 특히 중요하며, 예컨대, 으름덩굴 종자의 1.5∼3배, 특히 바람직하게는 2∼3배의 물을 사용하여, 35∼40℃의 온도, 바람직하게는 38∼39℃의 온도에서, 2∼3시간동안 숙성시킴으로서 가장 유효한 항암성을 나타내는 추출물을 얻을 수 있다. In the preparation method of the present invention, the amount of water in the aging step, the aging temperature and the aging time are particularly important for determining the anticancer properties of the composition of the present invention, for example 1.5 to 3 times of the crushed seed, particularly preferably 2 The extract which exhibits the most effective anticancer property can be obtained by aging for 2-3 hours using the temperature of 35-40 degreeC, Preferably it is 38-39 degreeC using -3 times of water.
본 발명의 제조방법의 바람직한 실시예에서는, 으름덩굴 종자에 물을 첨가하여 분쇄하고, 총 물의 양이 분쇄물의 1.5∼3배가 되도록 물을 첨가하는 단계; 35∼40℃의 온도에서 2∼3시간 동안 숙성시키는 단계; 상기 숙성된 종자 추출물을 메탄올로 추출하는 단계; 및 상기 메탄올 추출물을 헥산, 초산에틸 및 아세톤으로 이루어진 군에서 선택된 용매를 가하여 분획하여, 남아 있는 메탄올 분획을 취하는 단계를 포함한다. In a preferred embodiment of the production method of the present invention, adding water to the crushed seed crushed, and adding water so that the total amount of water is 1.5 to 3 times the crushed powder; Aging for 2 to 3 hours at a temperature of 35 to 40 ℃; Extracting the aged seed extract with methanol; And fractionating the methanol extract by adding a solvent selected from the group consisting of hexane, ethyl acetate and acetone to take the remaining methanol fraction.
본 발명에 따른 추출물을 함유하는 항암 조성물은 임상적으로 이용시에 약제학적 분야에서 통상적으로 사용되는 담체와 함께 배합하여, 약제학적 분야에서 통상적인 제제, 예를 들면, 정제, 캅셉제, 트로키제, 액제, 현탁제 등의 경구투여용 제제, 주사용 용액 또는 현탁액, 또는 주사시에 주사용 증류수로 제조하여 사용할 수 있는 즉시 사용형 주사용 건조 분말 등의 형태인 주사용 제제, 연고제, 크림제, 액제 등의 국소적용형 제제 등의 다양한 제제로 제형화할 수 있다.The anticancer composition containing the extract according to the present invention may be combined with a carrier which is commonly used in the pharmaceutical field at the time of clinical use, such as conventional agents in the pharmaceutical field such as tablets, capsules, troches, Injectable preparations, ointments, creams, in the form of oral preparations such as solutions, suspensions, injectable solutions or suspensions, or ready-to-use injectable dry powders which can be prepared and used as injectable distilled water at the time of injection, It can be formulated into various formulations such as topical formulations such as liquids.
본 발명의 조성물 내에서 사용될 수 있는 담체는 약제학적 분야에서 통상적인 것으로, 예를 들면 경구투여용 제제의 경우에는 결합제, 활택제, 붕해제, 부형 제, 가용화제, 안정화제 등이 있고, 국소투여용 제제의 경우에는 기제, 부형제, 윤활제, 보존제 등이 있다. 이렇게 제조된 약제학적 제제는 경구적으로 투여하거나, 비경구적으로, 예를 들면, 정맥 내, 피하, 복강 내 또는 국소 적용할 수 있다. 또한 경구투여 시에 약제가 위산에 의해 분해되는 것을 방지하기 위하여 제산제를 병용하거나 정제 등의 경구투여용 고형 제제를 장용피로 피복된 제제로 제형화하여 투여할 수 있다.Carriers that can be used in the compositions of the present invention are conventional in the pharmaceutical field, for example, in the case of oral preparations, there are binders, lubricants, disintegrants, excipients, solubilizers, stabilizers and the like. In the case of the preparation for administration, there are a base, an excipient, a lubricant, a preservative. Pharmaceutical preparations thus prepared can be administered orally or parenterally, eg, intravenously, subcutaneously, intraperitoneally or topically. In addition, in order to prevent decomposition of the drug by gastric acid during oral administration, an antacid may be used in combination, or a solid preparation for oral administration such as tablets may be formulated into a formulation coated with enteric skin.
본 발명에 따른 조성물의 인체에 대한 투여량은 체내에서 활성 성분의 흡수도, 불활성화율 및 배설속도, 환자의 연령, 성별 및 상태, 치료할 질병의 증증도 등에 따라 적절히 선택되나, 일반적으로 성인에게 1일에 본 발명의 조성물을 신체조건, 병증의 정도에 따라 하루 10-30ml을 정맥 주사 할 수 있다. 이렇게 제형화된 단위투여형은 필요에 따라 약제의 투여를 감시하거나 관할하는 전문가의 판단과 개인의 요구에 따라 전문화된 투약법을 사용하거나, 일정 시간 간격으로 수회, 바람직하게는 1회 내지 6회 투여할 수 있다.The dosage of the composition according to the present invention to the human body is appropriately selected depending on the absorption rate, inactivation rate and excretion rate of the active ingredient in the body, the age, sex and condition of the patient, the severity of the disease to be treated, but generally 1 In one day, the composition of the present invention can be injected intravenously 10-30ml per day depending on the physical condition and the degree of the condition. The unit dosage forms thus formulated may use specialized dosing regimens, preferably one to six times at regular time intervals, according to the judgment of the expert who monitors or governs the administration of the drug as needed and the needs of the individual. May be administered.
본 발명을 위한 예비 실험에서 으름덩굴의 목부, 가지, 과육, 종자를 대상으로 항암성 스크리닝을 하였으나, 종자외에는 유효성을 입증할 수가 없었다. 그럼으로 본 발명에서는 으름덩굴의 종자에 대하여 집중적으로 연구를 행하였다. In the preliminary experiments for the present invention, screening was performed on the neck, branch, pulp, and seed of the creeper, but the efficacy could not be verified except for the seed. Thus, in the present invention, the seeds of the creeper vines have been intensively studied.
본 발명자들은 으름덩굴의 종자에서 가장 최적의 항암성 추출물을 얻기 위해, 하기 실시예에서와 같이, 우선 숙성을 위한 물의 양을 결정하고, 숙성온도, 숙성시간을 차례로 결정하여 숙성의 최적 조건을 찾아내고 이 조건하에서 생성된 유망 항암 약물을 발견하려 하였다.The present inventors first determine the amount of water for ripening, in order to obtain the most optimal anti-cancer extract from the seeds of the creeper, and then determine the ripening temperature, ripening time in order to find the optimum conditions for ripening We tried to find promising anticancer drugs produced under these conditions.
이하, 본 발명을 하기 실시예에 의하여 보다 구체적으로 설명하지만, 이들에 의해 본 발명의 범위가 어떤 식으로든 제한되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited by them in any way.
실시예Example
실시에 1. (추출물 1의 제조)1. in the implementation (preparation of extract 1)
으름덩굴 종자 36g을 유발에 가하고 40ml의 물을 가하고 분쇄하였다. 분쇄된 내용물을 250ml 크기의 비커에 넣고 유발은 물 14ml로 씻어서 다시 비이커에 넣었다. 비커 내용물 표면은 젖은 거즈로 덮고 실온(22도)에서 1시간 방치하였다. 1시간이 지나면 여기에 메탄올(98%이상의 순도) 80ml를 가한다음 30분간 교반하였다. 추출물을 여과하고 남은 식물체에는 80% 메탄올 150ml를 가하고 30분간 교반하였다. 메탄올 용해 분을 여과하여 얻고 1차분과 합쳤다. 합친 메탄올 용해 분을 감압 건고한 다음 여기에 98% 메탄올 30ml를 가하고 10분간 교반하였다. 메탄올 용분을 여과하고 불용분은 메탄올 10ml와 섞고 10분간 교반하였다. 여과후 1차분과 합쳤다. 합친 메탄올 용해 분은 작은 분액여두에 옮기고 여기에 헥산 40ml를 가하고 흔들어 준 다음 방치하여 상의 분리를 기다렸다. 하층의 메탄올 용액 층을 분리하고 헥산층은 버렸다. 메탄올 충에는 헥산 40ml를 가하여 흔들어 준 다음 방치하여 하층의 메탄올 용해부분을 취하였다. 메탄올 용액은 건고하였다. 건고물은 항암실험 직전에 생리 식염수 100ml에 용해하여 사용하였다. 36 g of vine seed was added to the mortar and 40 ml of water was added and ground. The pulverized contents were placed in a 250 ml beaker and the broth was washed with 14 ml of water and placed in the beaker again. The beaker contents surface was covered with wet gauze and left for 1 hour at room temperature (22 degrees). After 1 hour, 80 ml of methanol (purity of 98% or more) was added thereto, followed by stirring for 30 minutes. The extract was filtered and 150 ml of 80% methanol was added to the remaining plants and stirred for 30 minutes. Methanol dissolved fractions were obtained by filtration and combined with the first portion. The combined methanol dissolved powders were dried under reduced pressure, and then 30 ml of 98% methanol was added thereto, followed by stirring for 10 minutes. The methanol solution was filtered and the insolubles were mixed with 10 ml of methanol and stirred for 10 minutes. Combined with primary after filtration. The combined methanol dissolved portions were transferred to a small separatory filter, 40 ml of hexane was added thereto, shaken, and left to wait for phase separation. The lower methanol solution layer was separated and the hexane layer was discarded. 40 ml of hexane was added to the methanol filling, shaken, and left to take the methanol dissolved portion of the lower layer. The methanol solution was dried. The dried matter was used after dissolving in 100ml of saline solution immediately before the anticancer experiment.
실시예 2. (추출물 2의 제조) Example 2. (Preparation of Extract 2)
종자 36g에 대하여 물 72ml를 가하고 숙성하는 것을 제외하고, 실시예 1과 같이 처리하였다. 36 g of seeds were treated as in Example 1 except that 72 ml of water was added and aged.
실시예 3. (추출물 3의 제조)Example 3. (Preparation of Extract 3)
종자 36g에 대하여 물 108ml를 하고 숙성하는 것을 제외하고, 실시예 1과 같이 처리하였다. 36 g of seeds were treated as in Example 1, except that 108 ml of water was aged and aged.
실시예 4. (추출물 4의 제조)Example 4 (Preparation of Extract 4)
종자 36g에 대하여 물 180ml로 하고 숙성하는 것을 제외하고, 실시예 1과 같이 처리하였다. 36 g of seeds were treated in the same manner as in Example 1, except that 180 ml of water was used for aging.
실시예 5. (추출물 21의 제조)Example 5 (Preparation of Extract 21)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 35도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, the aging time was fixed at 1 hour, and the treatment was carried out as in Example 1 except that the temperature was aged at 35 degrees.
실시예 6. (추출물 22의 제조)Example 6 (Preparation of Extract 22)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 36도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, and the aging time were fixed at 1 hour, and were treated in the same manner as in Example 1 except for aging at 36 degrees.
실시예 7 (추출물 23의 제조)Example 7 (Preparation of Extract 23)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 37도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, and the aging time were fixed at 1 hour, and were treated in the same manner as in Example 1 except for aging at 37 degrees.
실시예 8(추출물 24의 제조)Example 8 (Preparation of Extract 24)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 38도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, the maturation time were fixed at 1 hour, and the treatment was carried out as in Example 1 except that the fermentation was carried out at a temperature of 38 degrees.
실시예 9(추출물 25의 제조)Example 9 (Preparation of Extract 25)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 39도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, the aging time was fixed at 1 hour, and the treatment was carried out as in Example 1 except for aging at 39 degrees.
실시예 10(추출물 26의 제조)Example 10 (Preparation of Extract 26)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 40도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, and the aging time were fixed at 1 hour, and were treated in the same manner as in Example 1 except for aging at 40 degrees.
실시예 11(추출물 27의 제조)Example 11 (Preparation of Extract 27)
종자 36g, 물 첨가량 72ml, 숙성 시간을 1시간으로 고정하고 온도를 41도로 하여 숙성하는 것을 제외하고, 실시예1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, the ripening time was fixed at 1 hour and aged at 41 degrees, except that the treatment was carried out as in Example 1.
실시예 12(추출물 추출물 31의 제조)Example 12 (Preparation of Extract Extract 31)
종자 36g, 물 첨가량 72ml, 숙성 온도를 38도로 고정하고 2시간 숙성하는 것을 제외하고, 실시예 1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, and the maturing temperature were fixed at 38 ° C and aged for 2 hours were treated in the same manner as in Example 1.
실시예 13(추출물 32의 제조)Example 13 (Preparation of Extract 32)
종자 36g, 물 첨가량 72ml, 숙성 온도를 38도로 고정하고 3시간 숙성하는 것을 제외하고, 실시예 1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, and the maturing temperature were fixed at 38 degrees and aged for 3 hours were treated as in Example 1.
실시예 14(추출물 33의 제조)Example 14 (Preparation of Extract 33)
종자 36g, 물 첨가량 72ml, 숙성 온도를 38도로 고정하고 4시간 숙성하는 것을 제외하고, 실시예 1과 같이 처리하였다. 36 g of seeds, 72 ml of water addition amount, and the ripening temperature were fixed at 38 ° C and aged for 4 hours, except that the treatment was carried out as in Example 1.
실시예 15 (인삼, 전호를 가미한 처방구성)Example 15 (Prescription Composition with Ginseng and Whole Rice)
으름덩굴 종자 36g으로부터 얻은 상기 추출물 22, 전호 8g의 에테르 추출물 및 인삼 5g으로부터 얻은 아세톤 추출물을 혼합하고 여기에 크레모포어(Cremophore)를 10%가 되게 가한 다음 생리 식염수를 가하여 100ml로 만들었다.The extract 22 obtained from the crushed seed of 36 g, the ether extract of 8 g of Jeonho and the acetone extract obtained from 5 g of ginseng were mixed, and cremophore was added to 10%, and then saline was added to make 100 ml.
제제예 1. 캡슐제의 제조 Formulation Example 1 Preparation of Capsule
실시예 13의 조성물 100mg100 mg of the composition of Example 13
유당 100mgLactose 100mg
전분 93mgStarch 93mg
탈클 2mgTackle 2mg
스테아린산 마그네슘 적량Magnesium stearate proper amount
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충진하여 캡슐제를 제조한다.The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.
제제예 2. 캡슐제의 제조 Formulation Example 2 Preparation of Capsule
실시예 14의 조성물 200mg200 mg of the composition of Example 14
유당 100mgLactose 100mg
전분 93mgStarch 93mg
탈클 2mgTackle 2mg
스테아린산 마그네슘 적량Magnesium stearate proper amount
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충진하여 캡슐제를 제조한다.The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.
제제예 3. 캡슐제의 제조 Formulation Example 3 Preparation of Capsule
실시예 15의 조성물 200mg200 mg of the composition of Example 15
유당 100mgLactose 100mg
전분 93mgStarch 93mg
탈클 2mgTackle 2mg
스테아린산 마그네슘 적량Magnesium stearate proper amount
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충진하여 캡슐제를 제조한다.The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.
제제예 4. 액제의 제조 Formulation Example 4 Preparation of Liquid
실시예 13의 조성물 300mg300 mg of the composition of Example 13
설탕 20g20 g of sugar
이성화당 20g20 g of isomerized sugar
레몬향 적량Lemon flavor
정제수를 가하여 전체 100mlAdd 100 ml of purified water
상기의 성분을 통상의 액제의 제조방법에 따라서 혼합하고 100ml의 갈색병에 충진하고 멸균시켜서 액제를 제조한다.The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml brown bottles and sterilized to prepare a liquid.
제제예 5. 액제의 제조 Formulation Example 5 Preparation of Liquid
실시예 15의 조성물 300mg300 mg of the composition of Example 15
설탕 20g20 g of sugar
이성화당 20g20 g of isomerized sugar
레몬향 적량Lemon flavor
정제수를 가하여 전체 100mlAdd 100 ml of purified water
상기의 성분을 통상의 액제의 제조방법에 따라서 혼합하고 100ml의 갈색병에 충진하고 멸균시켜서 액제를 제조한다.The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml brown bottles and sterilized to prepare a liquid.
실험예. LL/2 세포를 이용한 동물실험Experimental Example Animal testing with LL / 2 cells
LL/2 세포와 배양액LL / 2 Cells and Cultures
배양액은 멸균 주사용 증류수에 L-glutamine이 포함된 RPMI 1640 medium 한 pack, 56C 수조에서 30분간 가열하여 불활성화시킨 fetal bovine serum (FBS) 100 mL, sodium bicarbonate 2 g, penicillin 10만 단위, streptomycin 100 mg을 넣어 용해시킨 후 0.1N HCl으로 pH를 조절하여 전체를 1 L가 되게 한 후 세균 여과하여 제조하였으며, 4℃에서 보관하면서 사용하였다. 세포를 3일에 한 번씩 계대하여 유지하였으며, 세포를 부착면으로부터 분리하기 위하여 phosphate buffered saline 용액에 0.5% trypsin과 2% EDTA를 녹인 용액을 사용하였다.The culture solution was a pack of RPMI 1640 medium containing L-glutamine in sterile injectable distilled water, 100 mL of fetal bovine serum (FBS) inactivated for 30 minutes in a 56C water bath, 2 g of sodium bicarbonate, 100,000 units of penicillin, streptomycin 100 After dissolving mg and adjusting the pH with 0.1N HCl to make the whole to 1 L was prepared by bacterial filtration, it was used while storing at 4 ℃. The cells were passaged and maintained every three days, and a solution of 0.5% trypsin and 2% EDTA in phosphate buffered saline solution was used to separate the cells from the adherent surface.
LL/2 세포를 이용한 동물실험Animal testing with LL / 2 cells
시험관내에서 배양한 LL/2세포를 멸균된 냉 생리식염수를 사용하여 충분히 세척한 후 세포를 혈구계 (haemacytometer)로 세어 5ㅧ106 cells/mL의 농도로 세포 부유액을 만들고 이 부유액을 0.2 mL 씩 마우스의 겨드랑이에 피하로 이식하였다. 이식 24 시간 후에 각 군을 7 마리로 분류하였다. 시료는 주사하기 바로 직전에 생리식염수에 용해시켜 제조하고, 실험동물의 복강 내에 0.2 mL씩 주사하였다. 음성대조군에는 생리식염수만을 시료 투여량과 같은 용량으로 투여하였으며 양성 대 조군으로는 etoposide (36 mg/kg/day)를 암세포 이식 후 1, 5, 9 일째에 주사하였으며, 주사일정은 시료에 따라 다르나 통상적으로 암세포 이식 후 24 시간이 지난 후에 시작하여 3, 5, 7, 9, 11 일, 투여하다가 16, 17 일 다시 투여하여 전체 9 회 투여하였다 [Teruhiro, U. 등, Cancer Res., 56, 2809 14 (1996) 참조].After culturing in vitro, LL / 2 cells were thoroughly washed with sterile cold saline solution, and the cells were counted with a hemocytometer to make a cell suspension at a concentration of 5 ㅧ 10 6 cells / mL, and the suspension was 0.2 mL. The mice were implanted subcutaneously into the armpits. Twenty four hours after transplantation, each group was divided into seven animals. Samples were prepared by dissolving in physiological saline immediately before injection, and injected 0.2 mL into the abdominal cavity of the experimental animal. In the negative control group, only saline was administered at the same dose as the sample dose. The positive control group was injected with etoposide (36 mg / kg / day) 1, 5, and 9 days after cancer cell transplantation. Typically, 24 hours after cancer cell transplantation, starting 3, 5, 7, 9, 11 days, and then again 16, 17 days to administer a total of nine times [Teruhiro, U., et al., Cancer Res ., 56, 2809 14 (1996).
마우스에 대한 각각의 시료의 독성을 측정하기 위해 2 일에 1 회 몸무게를 측정하였으며, 항암효과는 약물투여 11 일∼19 일에 대조군과 약물처리군의 암괴의 부피를 측정 후 다음 식에 따라 계산하였다.To determine the toxicity of each sample to mice, weight was measured once every 2 days, and the anticancer effect was calculated according to the following equation after measuring the volume of the mass of the control and drug treatment groups from 11 to 19 days of drug administration. It was.
암의 부피(mm3) = 길이 (mm) × 폭2(mm2) / 2Arm volume (mm 3 ) = length (mm) × width 2 (mm 2 ) / 2
암성장저해율 (inhibition ratio, %) = (C - T) × 100 / CInhibition rate (%) = (C-T) × 100 / C
(상기 식에서, C : 대조군의 평균 암부피 (mm3), T : 시료투약군의 평균 암부피 (mm3)를 나타낸다.)(In the above formula, C: mean cancer volume of the control group (mm 3 ), T: mean cancer volume of the sample administration group (mm 3 ).)
본 발명에서 나타낸 각 추출물의 암성장저지율은 3회 측정한 평균치로 나타내었다. The cancer growth inhibition rate of each extract shown in the present invention is represented by the average value measured three times.
비교예. 용매 분획의 항암성(숙성 단계 없음)Comparative example. Anticancer activity of solvent fraction (no maturation step)
본 비교예의 용매 분획은 종자를 분쇄하여 세포파괴가 일어나는 즉시 용매로 추출함으로써 효소등 생화학적 반응을 차단하려는 목적으로 제조되었다. 하기 실험에서 알 수 있는 바와 같이 상기 분획은 항암성을 보이 않는다. 그 반면, 물에서 숙성시켜 추출한 하기 실시예의 분획에서는 항암성을 보임으로써 종자의 항암작용 이 숙성을 통하여 생성된다는 사실이 증명되었다. 이하 용매분획의 제조 방법과 항암성 측정결과를 기술한다;The solvent fraction of this comparative example was prepared for the purpose of blocking biochemical reactions such as enzymes by grinding seeds and extracting them with a solvent as soon as cell destruction occurred. As can be seen in the experiment below, the fraction does not show anticancer activity. On the other hand, in the fractions of the following examples, which were extracted by aging in water, it was proved that anticancer activity of seeds was generated through aging by showing anticancer activity . The following describes the preparation method of solvent fractions and the results of anticancer activity;
종자 36g을 80% 메탄올 100ml와 같이 작은 분쇄기에 가하고 분쇄한 후 여과하였다. 여지에 남은 식물체는 작은 비커에 옮기고 여기에 메탄올 80% 50ml를 가하고, 10분간 교반한 후 여과하였다. 이 조작을 한번 더 반복하였다. 메탄올 추출물을 합한 후 건고하였다. 건고물에는 98% 메탄올 10ml를 가하고 30분간 교반한 후 방치하고 불용분을 제거하였다. 메탄올 용해분은 건고하여 메탄올 추출물을 얻었다. 메탄올 추출물에 헥산, 초산에칠, 아세톤등을 가하여 흔들어 준 다음 용매를 제거하고 남아 있는 물질을 생리식염수 100ml에 용해한 후, 동물암종으로는 Lewis Lung Carcinoma Cell을 이식한 BDF1 마우스를 사용하여 항암성을 측정하였다. 36 g of seeds were added to a small grinder such as 100 ml of 80% methanol, triturated and filtered. The remaining plants were transferred to a small beaker, and 50 ml of methanol 80% was added thereto, stirred for 10 minutes, and filtered. This operation was repeated once more. Methanol extracts were combined and then dried. 10 ml of 98% methanol was added to the dried product, stirred for 30 minutes, and left to remove insoluble matters. The methanol melt was dried to obtain a methanol extract. After shaking with adding hexane, ethyl acetate, acetone, etc. to the methanol extract, the solvent was removed, and the remaining material was dissolved in 100 ml of physiological saline, and as an animal carcinoma, BDF1 mouse transplanted with Lewis Lung Carcinoma Cell was used. Measured.
위 액 0.2ml씩을 복강 주사한 후의 암성장 저해율은(Inhibition rate, IR) 21%였다. 이는 사실상 유효성이 인정되지 않는 수치이다.Inhibition rate of cancer growth (inhibition rate, IR) after intraperitoneal injection of 0.2 ml of gastric juice was 21%. This is in fact a valid figure.
최적 숙성 조건의 수립Establishment of Optimum Ripening Conditions
본 발명의 수치법의 기전은 효소의 작용이 필수적임은 자명하다. 그럼으로 효소반응의 최상의 조건을 찾아냄으로써 최대의 항암효과에 이를 수 있다. 우선 물의 양은 일정량의 효소 활성의 농도와 직결된다. 물의 양이 많으면 효소반응 속도가 느리게 되고, 물의 양이 적으면 그 농도가 높아진다. 실로 물의 양은 최소로 하는 것이 제일 좋을 것이다. 그러나 식물체 분말이 물에 완전히 습윤이 되는 정도의 물량이라야 반응이 이상적으로 일어 날 것이다. 둘째, 효소의 반응에는 적정 온도 는 매우 중요하다. 적정 온도를 찾기 위하여 여러 온도에서 얻은 추출물의 유효성을 비교하였다. 마지막으로 반응시간의 조절이다. 적정 온도와 물의 양에서도 장시간 숙성시키면 효소의 불화성화, 생성물질의 2차적 파괴 등이 일어 날 것이다. It is apparent that the mechanism of the numerical method of the present invention is essential for the action of an enzyme. Therefore, the best anticancer effect can be reached by finding the best conditions for the enzyme reaction. First, the amount of water is directly related to the concentration of a certain amount of enzyme activity. The higher the amount of water, the slower the enzyme reaction rate, and the lower the amount of water, the higher the concentration. Indeed, it is best to minimize the amount of water. However, the reaction will occur ideally when the amount of plant powder is completely wetted with water. Second, the optimum temperature is very important for the enzyme reaction. To find the proper temperature, the effectiveness of extracts obtained at various temperatures was compared. Finally, the reaction time is controlled. Long-term aging, even at appropriate temperatures and water levels, will result in enzyme inactivation and secondary destruction of the product.
1) 물량의 결정과 용매 추출 1) Determination of quantity and solvent extraction
신선한 종자 일정량을 분쇄한 후 상기 실시예에 따라 여러 용량의 물을 가한 후 우선 실온에서 1시간 숙성하였다. 숙성 후 이를 용매처리하여 용매 추출물을 얻고 Lewis Lung Carcinoma(LLC, LL/2)에 걸린 마우스에 대한 항암성을 측정하였다. 상세히 설명하면 물의 양은 식물체에 1에 대하여 1.5배량-3배량이 적당하였으며, 2배량의 경우가 가장 좋았다. 유기용매로는 함수 알코올류이며, 메탄올의 수용액이 가장 적합하였다, 숙성물에 메탄올을 가하여 메탄올양이 첨가 물의 양에 따라 50%내지 80%가 되게 한 후 추출하는 것이 가장 효과적이다. 메탄올 추출물을 건고한 다음 건고물 1에 대하여 98%의 메탄올 5-10배량을 가하고 흔들어 준 다음 방치하여 불용분은 여과하여 제거하였다. 메탄올 용해 분은 감압 농축하여 건고물을 얻고 여기에 아세톤, 초산에칠, 헥산등을 가하고 흔들어 준다음 여과하여 여액은 버리고 남은 부분을 하기 실험예에 따라 항암실험에 사용하였다. 헥산으로 탈지하는 경우 메탄올 용액에 헥산을 직접가하고 흔들어 탈지하는 방법을 사용할 수도 있다.After crushing a certain amount of fresh seed, various volumes of water were added according to the above example, and then aged for 1 hour at room temperature. After aging, the resultant was solvent treated to obtain a solvent extract, and anticancer activity was measured for mice with Lewis Lung Carcinoma (LLC, LL / 2). In detail, the amount of water was 1.5 times to 3 times the amount of 1 for the plant, and 2 times was the best. As organic solvents, water-soluble alcohols were most suitable. Aqueous solutions of methanol were most suitable. The most effective extraction was to add methanol to the aging product so that the amount of methanol is 50% to 80% depending on the amount of the additive. Methanol extract was dried, and then 5-10 times of 98% methanol was added to the dried product 1, shaken, and left to stand. The insolubles were filtered out. Methanol dissolved components were concentrated under reduced pressure to obtain a dried product, and acetone, ethyl acetate, hexane, and the like were added thereto, shaken, filtered, and the filtrate was discarded. The remaining portion was used for anticancer experiments according to the following experimental example. In the case of degreasing with hexane, a method of directly adding hexane to the methanol solution and shaking to degreasing may be used.
이렇게 탈지된 추출물은 물에 쉽게 용해되어 주사제로 사용하기에 적합하였다. 여기서 얻어진 추출물과 그 암성장저지율은 하기 표 1과 같다.This degreasing extract was easily dissolved in water and suitable for use as an injection. The extract obtained here and its growth inhibition rate are shown in Table 1 below.
표 1Table 1
(주) 추출물 1=종자 1부분에 대하여 물의 양을 1.5배 가하여 실온에서 1시간 숙성한 것; 추출물 2=종자 1부분에 대하여 물의 첨가량을 2배를 가하고 실온에서 1시간 숙성한 것; 추출물 3=종자 1부분에 대하여 물 3부분을 가하고, 실온에서 1시간 숙성한 것; 추출물 4=종자 1부분에 대하여 물 5부분을 가하고 실온에서 1시간 숙성한 것. (Note) extract 1 = 1 part of seeds, 1.5 times the amount of water and aged at room temperature for 1 hour; Extract 2 = one part of seed, added twice the amount of water, and aged at room temperature for 1 hour; Extract 3 = Adding 3 parts of water to 1 part of seed and aging for 1 hour at room temperature; Extract 4 = Five parts of water were added to one part of seed and matured at room temperature for 1 hour.
2) 적정 숙성온도의 결정2) Determination of the optimum ripening temperature
위에서 적정 물의 양이 종자 1부분에 대하여 2 부분이 적합한 것으로 결정 되었다. 그럼으로 여기에서는 물의 양은 종자 1에 대하여 2배량으로 고정하고 온도를 변화와 항암성의 관계를 보고자하였다. 숙성시간은 임의로 1시간으로 하였다. 예비 실험에서 정한 온도 범위가 35도에서 40도 사이 인 것이 판명되었음으로 35도를 출발 온도로 하여 1도씩 상승시키면서 숙성의 관정과 항암성의 변화를 관찰하였고, 그 결과를 하기 표 2에 나타내었다. 숙성 후 처리는 상기 추출물 1의 경우와 같다.Above, the titration amount was determined to be suitable for two parts for one part of the seed. Therefore, here, the amount of water was fixed at twice the amount of seed 1, and the relationship between temperature change and anticancer activity was examined. Aging time was arbitrarily set to 1 hour. Since the temperature range determined in the preliminary experiments was found to be between 35 degrees and 40 degrees, the change of fermentation and anticancer activity was observed while increasing the temperature by 35 degrees as the starting temperature by 1 degree, and the results are shown in Table 2 below. Post-aging treatment is the same as that of the extract 1.
표 2TABLE 2
(주) 추출물 21=물 72ml를 가하고, 35도에서 1시간 숙성한 것; 추출물 22=물 72ml를 가하고, 36도에서 1시간 숙성한 것; 추출물 23=물 72ml를 가하고, 37도에서 1시간 숙성한 것; 추출물 24=물 72ml를 가하고, 38도에서 1시간 숙성한 것; 추출물 25=물 72ml를 가하고, 39도에서 1시간 숙성한 것; 추출물 26=물 72ml를 가하고, 40도에서 1시간 숙성한 것; 추출물 27=물 72ml를 가하고, 41도에서 1시간 숙성한 것.(Note) add 72 ml of extract 21 = water, and aged at 35 degrees for 1 hour; 72 ml of extract 22 = water was added and aged at 36 degrees for 1 hour; 72 ml of extract 23 = water was added and aged at 37 degrees for 1 hour; 72 ml of extract 24 = water was added and aged at 38 degrees for 1 hour; 72 ml of extract 25 = water was added and aged at 39 degrees for 1 hour; 72 ml of extract 26 = water was added and aged at 40 degrees for 1 hour; 72 ml of extract 27 = water was added, and the mixture was aged at 41 degrees for 1 hour.
상기 표 2에서 알 수 있듯이, 온도의 영향을 보면 38도와 39도를 정점으로 더 높은 온도에서는 감소하는 경향을 보인다. 이는 온도가 높으면 효소의 불활성화 등으로 항암물질의 생성이 저해되기 때문인 것으로 생각된다.As can be seen in Table 2, the effect of temperature shows a tendency to decrease at higher temperatures with a peak at 38 degrees and 39 degrees. This is considered to be because when the temperature is high, the production of anticancer substances is inhibited by inactivation of the enzyme.
3) 적정 숙성시간의 결정 3) Determination of proper ripening time
위 두 실험에서 물의 양은 종자의 2배량, 숙성 온도는 38도가 적합함을 알았다. 이를 기초로 하여 숙성시간과 항암성의 관계를 규명하고자 하였다.In the above two experiments, it was found that the amount of water was twice the seed and the ripening temperature was 38 degrees. On the basis of this, the relationship between ripening time and anticancer activity was attempted.
분쇄한 종자 1에 대하여 물 2배량을 가하고 혼합한 다음 비커를 38도의 항온조에 담그고 시간별 변화를 관찰하였다. 예비 실험의 결과를 토대로 하여 시간을 1시간, 2시간, 3시간, 4시간으로 나누었다. 숙성된 물건은 상기 추출물 1의 경우와 같이 처리하여 항암 조성물을 만들었다. 그 결과를 하기 표 3에 나타내었다. 2 times of water was added to the ground seed 1, mixed, and the beaker was immersed in a thermostat at 38 degrees, and the change in time was observed. Based on the results of the preliminary experiments, the time was divided into 1 hour, 2 hours, 3 hours and 4 hours. Aged article was treated as in the case of extract 1 to make an anticancer composition. The results are shown in Table 3 below.
표 3TABLE 3
(주) 추출물 22=물 72ml와 38도로 고정시키고 1시간 숙성한 것; 추출물 31=물 72ml와 38도로 고정시키고 2시간 숙성한 것; 추출물 32=물 72ml와 38도로 고정시키고 3시간 숙성한 것; 추출물 33=물 72ml와 38도로 고정시키고 4시간 숙성한 것(Note) extract 22 = 72 ml of water and fixed to 38 degrees and aged for 1 hour; Extract 31 = 72 ml of water and 38 deg. Extract 32 = 72 ml of water and fixed at 38 degrees and aged for 3 hours; Extract 33 = 72 ml of water and 38 deg.
상기 표 3에서 알 수 있듯이, 숙성시간은 2시간과 3시간이 최적이며 4시간이 넘으며 항암성이 감소한다. 이는 장기간의 숙성으로 인하여 효소의 활성이 감소되든지 생성된 항암 물질이 변화된 것이 윈인이라 생각된다.As can be seen in Table 3, the ripening time is 2 hours and 3 hours is optimal, more than 4 hours and anticancer properties are reduced. It is thought that the cause of the long-term aging is that the enzyme activity is reduced or the anticancer substance produced is changed.
또한 실시예 15의 추출물, 즉, 으름덩굴 종자로부터 얻은 추출물과 인삼, 전호의 추출물을 혼합하여 만든 처방의 경우, 암성장저지율 97%를 보였다. 특기할 것은 7마리 마우스 중 3마리에서는 암이 자라지 않았다는 것이다. In addition, in the case of the formulation of the extract of Example 15, that is, a mixture made from the extract of the crushed seed, ginseng, Jeonho, showed 97% cancer growth inhibition. Of note, three of the seven mice had no cancer.
위 실험에서 얻을 수 있는 중요한 성과는 식물자체를 물과 같이 숙성시킴으로써 새로운 약리 효과를 갖게 한다는 것이다. 으름덩굴 종자의 메탄올 추출물은 사실상 항암성을 보이지 않는데 비하여, 물과 같이 숙성시켜 얻은 추출물은 좋은 항암성을 보인다는 것이 이를 증명한다. 으름덩굴 종자 추출물의 암성장 저해율은 물의 양, 숙성 시간 및 숙성 온도에 의하여 영향을 받으며, 종자 1에 대하여 두배량의 물을 사용하고 38도 또는 39도에서 2시간에서 3시간동안 숙성시키는 것이 최 적임을 알 수 있었다. 또한 추가적으로 다른 항암성이 있다고 알려진 생약을 가함으로써 생약간의 상승 또는 상가 작용에 의해 임상적으로 유용한 신규 함암제를 얻을 수 있다. An important achievement from the above experiments is that the plants themselves have a new pharmacological effect by aging the plants like water. Methanol extract of the vine seed shows virtually no anticancer activity, whereas the extract obtained by aging with water shows good anticancer activity. Inhibition of cancer growth of lamella seed extract is influenced by the amount of water, ripening time and ripening temperature, and it is best to ripen for 2 to 3 hours at 38 or 39 degrees using twice the amount of water for seed 1 I could see the enemy. In addition, by adding another herbal drug known to be anti-cancer, it is possible to obtain a novel clinically useful cancer drug by synergistic or additive action between the herbal drugs.
이상에서 알 수 있듯이, 본 발명의 조성물은 우수한 항암 작용을 갖고 있을 뿐만 아니라, 생약을 식물 자체의 발효력을 사용하여 숙성시킴으로써 인체에 부작용을 최소화할 수 있어, 암의 예방 및/또는 치료제로서 유용하게 사용할 수 있다. As can be seen from the above, the composition of the present invention not only has an excellent anticancer action, but also can minimize side effects on the human body by aging the herbal medicine using the fermentation power of the plant itself, which is useful as a preventive and / or therapeutic agent for cancer. Can be used.
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| KR20230160977A (en) | 2022-05-17 | 2023-11-27 | 에이치앤오바이오시스(주) | Extracts of Five or More Herbal Plants Used for Anticancer Therapy |
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| CN103977014B (en) * | 2014-06-10 | 2016-10-05 | 刘丽宏 | A kind of medicine being applied to treat metabolic syndrome |
| CN104871900A (en) * | 2015-05-26 | 2015-09-02 | 孙君策 | Wild akebia trifoliate seed seedling culturing method |
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| KR20230160977A (en) | 2022-05-17 | 2023-11-27 | 에이치앤오바이오시스(주) | Extracts of Five or More Herbal Plants Used for Anticancer Therapy |
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