KR101476761B1 - An antiobesitic composition comprising of extracts isolated from Piper retrofractum vahl - Google Patents
An antiobesitic composition comprising of extracts isolated from Piper retrofractum vahl Download PDFInfo
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Abstract
본 발명은 지방세포의 UCP 활성으로 인한 발열작용으로 항비만에 효과적인 식품 및 약제 조성물에 관한 것으로, 구체적으로는 파이퍼 레트로프락텀(Piper retrofractum Vahl)의 추출물을 함유하는 조성물의 신규 용도에 관한 것으로, 체중 및 체지방 감소를 통한 항비만에 효과적인 식품 조성물 또는 약제학적 조성물에 관한 것이다. The present invention relates to a food and pharmaceutical composition effective for anti-obesity by exothermic action due to UCP activity of adipocytes, and more particularly to a novel use of a composition containing an extract of Piper retrofractum Vahl, The present invention relates to a food or pharmaceutical composition effective for anti-obesity through weight reduction and body fat reduction.
Description
본 발명은 비만 예방 및 치료용 조성물, 더욱 상세하게는 파이퍼 레트로프락텀(Piper retrofractum Vahl)의 추출물을 함유하는 조성물의 신규 용도에 관한 것으로, 인체의 발열작용을 증대시켜 체중과 체지방을 감소시키는 항비만 기능성 식품 조성물 또는 약학적 조성물을 제공한다.
The present invention relates to a composition for preventing and treating obesity, and more particularly, to a new use of a composition containing an extract of Piper retrofractum Vahl. The present invention relates to a novel composition for preventing and treating obesity and an object of reducing the body weight and body fat An obesity functional food composition or a pharmaceutical composition.
2010년 경제협력개발기구(OECD)의 비만 보고서에 의하면 한국의 성인 비만율(BMI: 30이상)은 4% 이며, 30%는 과체중(BMI: 25~30)인 것으로 나타났다. 세계적으로 비만인구는 2억 5000만 명에 달하고, 오는 2025년에 이르면 3억 명 이상 될 것으로 예측되고 있다. 비만의 치료를 위해서는 섭취 열량 대비 소비되는 열량을 증가시켜 체내의 에너지를 소비할 수 있는 방법을 고안해야 한다. 체내에서 에너지를 소비할 수 있는 방법은 신체적 운동과 발열작용(thermogenesis)에 의해서다. 이 중 발열작용은 미토콘드리아 내에 존재하는 운반 단백질의 일종인 UCP(uncoupling protein)가 protein leak를 증가시켜 uncoupling oxidation을 통해서 ATP 생성 없는 열 생산을 발생시킨다. 이 중 언커플링 프로테인 1(UCP 1)은 갈색지방조직(BAT, Brown adipose tissue)에, 언커플링 프로테인 2(UCP 2)와 언커플링 프로테인 3(UCP 3)는 근육 및 지방조직에 존재하면서 신체 에너지의 항상성을 조절시키는 역할을 하고 있다. According to the Obesity Report of the Organization for Economic Cooperation and Development (OECD) in 2010, Korea's adult obesity rate (BMI: 30 or more) is 4% and 30% is overweight (BMI: 25 to 30). Globally, the estimated obesity population is 250 million, and by 2025 it is predicted to be over 300 million. For the treatment of obesity, it is necessary to devise a way to consume energy in the body by increasing the amount of calories consumed versus the calorie intake. The way in which the body can consume energy is by physical exercise and thermogenesis. The exothermic action of UCP (uncoupling protein), which is a kind of transport protein in mitochondria, increases the protein leakage and causes uncoupling oxidation to produce heat without ATP production. Uncoupling protein 1 (UCP 1) is bound to brown adipose tissue (BAT), uncoupling protein 2 (UCP 2) and uncoupling protein 3 (UCP 3) are present in muscle and adipose tissue But also regulates the homeostasis of body energy.
현재 개발된 대표적인 항비만 의약품인 리덕틸과 제니칼의 경우 목마름, 어지럼증 혹은 복부 팽만감, 지방변 등의 다양한 부작용을 보이고 있어, 최근에는 이러한 화학적 합성품이 아닌 식물 추출물과 같이 부작용은 적으면서 안전성이 높은 천연물을 이용한 기능식품을 개발하고자 하는 연구가 활발히 진행되고 있다.Reductil and Xenical, which are representative anti-obesity drugs currently developed, show various side effects such as thirst, dizziness or bloating and fat spread. In recent years, they have been shown to have low side effects such as plant extracts Research into the development of functional foods is actively under way.
이에 전통적으로 동남아시아에서 사용되고 있는 약용식물 중 파이퍼 레트로프락텀(Piper retrofractum Vahl)의 추출물을 비만 유도 동물에게 장기간 섭취시킨 후 체중 및 체지방량을 측정한 결과, 유의적으로 감소하였고, 이는 지방세포의 UCP 활성으로 인한 열 발생으로 사료된다. The results of body weight and body fat measurement after the long-term ingestion of Piper retrofractum Vahl extract in the medicinal plants used in Southeast Asia for obesity induction animals were significantly decreased, indicating that UCP activity of adipocytes Is considered to be the heat generation due to heat.
항비만 약용식물 추출물 중 보이차 조성물은 10-2001-22510호에, 박과식물 추출물은 10-2003-87280호에, 홍삼추출물은 10-2006-115006호에, 해국지상부추출물은 10-2007-56192호에, 누룩치추출물은 10-2006-38254호에, 포도나무수피추출물은 10-2007-82438호, 결명자추출물은 10-2006-91698호에 각각 공지되었다.Among the anti-obesity medicinal plant extracts, the viscera composition was 10-2001-22510, the root extract was 10-2003-87280, the red ginseng extract was 10-2006-115006, 56192, Nurukchi extracts 10-2006-38254, Vine bark extracts 10-2007-82438 and Cucumber extracts 10-2006-91698, respectively.
본 발명의 약용식물 파이퍼 렉트로프럭탐은 후추과(piperaceae family) 식물로서, 동남 아시아에서 자생하는 식물로서 본 발명에서는 열매부분을 사용하였다. The medicinal plant of the present invention, piperaceae family, is a plant native to Southeast Asia and used as a fruit part in the present invention.
상기 식물은 전통적으로 향신료, 조미료, 복부 및 장 질환의 치료제 및 추위 노출시의 발열효과에 의한 체온 보존제로 사용되고 왔다. 파이퍼 렉트로프럭탐의 아마이드(amide)성분으로는 레트로프락타마이드 A(retrofractamide A), 레트로 프락타마이드 B(retrofractamide B,pipericide), 레트로프락타마이드 C(retrofractamide C), 피페린 (piperine), 구이닌신(guineensine), 메틸 피페레이트(methyl piperate), 펠리토린(pellitorine), 파이퍼 롱귀미닌 (piperlongumininie) 등이 함유되어 있으며, 항산화, 항균, 살충효과, 약물의 생체이용성 증진 및 혈관확장에 의한 발열 효과를 나타내는 것으로 보고된 바 있다.The plant has traditionally been used as a therapeutic agent for spices, seasonings, abdominal and intestinal diseases, and as a body temperature preservative due to the exothermic effect of cold exposure. The amide components of piperactotropham include retrofractamide A, retrofractamide B, retrofractamide C, piperine, It contains guineensine, methyl piperate, pellitorine and piperlongumininie. It has antioxidant, antibacterial, insecticidal effect, drug bioavailability enhancement and vasodilation. Have been reported to exhibit fever effects.
그러나 본 발명에서와 같이 UCP활성으로 인한 발열작용에 의한 체중 및 체지방 감소효과에 대한 보고는 전무하다.However, as in the present invention, there is no report on the effect of the exothermic action due to the UCP activity on body weight and body fat reduction.
그러나, 동남아시아에서 자생하고 있는 약용식물 중 파이퍼 레트로프락텀(Piper retrofractum Vahl) 열매의 추출물을 비만유도동물에게 장기간 섭취한 후 체중 및 체지방량을 측정한 결과 유의적으로 감소시킨 사실을 확인하였다. 즉, 7주간 High Fat diet를 실험동물에 급이하여 비만 상태를 유도한 후, 8주동안 파이퍼 레트로프락텀을 투여한 결과, 체중 및 체지방 감소효과를 관찰할 수 있었으며, 이러한 결과는 비만 예방 및 치료제로서 항비만 기능성 식품 조성물 또는 약학적 조제물로서 사용 가능함을 시사하였다.
However, among the medicinal plants native to Southeast Asia, Piper retrofractum Vahl) fruit was significantly reduced after long-term intake of obesity-inducing animals after body weight and body fat measurement. In other words, we could observe body weight and body fat reduction effect by feeding Piperretrofurcum for 8 weeks after inducing obesity by feeding high fat diet for 7 weeks to experimental animals. Suggesting that it can be used as an anti-obesity functional food composition or as a pharmaceutical preparation as a therapeutic agent.
따라서, 본 발명의 목적은 파이퍼 레트로프럭탐(Piper retrofractum Vahl) 열매의 추출물을 유효성분으로 함유하는 조성물 및 이를 포함하는 약제학적 조성물을 제공하는 데 있다.
It is therefore an object of the present invention Pfeiffer retro loop reoktam (Piper retrofractum Vahl) extract as an active ingredient and a pharmaceutical composition comprising the same.
본 발명의 상기 목적은 파이퍼 레트로프럭탐의 열매로부터 추출물을 얻는 단계와; 상기 추출물을 비만 동물모델 쥐에 투여하여 항비만효과를 실험, 평가하는 단계를 통하여 달성하였다.
The above object of the present invention is achieved by a method for producing an extract from a plant, comprising the steps of: obtaining an extract from the fruit of Piperretrofluram tam; The above extract was administered to obese animal model rats to test and evaluate anti-obesity effect.
본 발명에 따른 파이퍼 레트로프럭탐 추출물을 함유한 조성물은 체중 및 체지방을 감소시켜 비만을 예방 및 치료할 수 있는 뛰어난 효과가 있다.
The composition containing the piperetoropuramtam extract according to the present invention has an excellent effect of preventing and treating obesity by decreasing body weight and body fat.
도 1은 본 발명에 따른 파이퍼 레트로프럭탐 추출물의 처리 여부에 따른 마우스 체중 감소 효과를 나타내었다. 그래프 위에 ** 로 표시한 것은 one-way ANOVA의 사후검정인 Tukey's Multiple Comparison Test 를 통해 * p<0.05, ** p<0.01 에서 유의함을 나타낸다.
도 2는 본 발명에 따른 파이퍼 레트로프럭탐 추출물의 처리 여부에 따른 마우스의 체지방 감소를 나타낸 것이다. 막대그래프 위에 ** 로 표시한 것은 one-way ANOVA의 사후검정인 Tukey's Multiple Comparison Test 를 통해 * p<0.05, ** p<0.01 에서 유의함을 나타낸다.
도 3은 본 발명에 따른 파이퍼 레트로프럭탐 추출물의 처리 여부에 따른 마우스 지방 세포(3T3-L1)에서 웨스턴 블랏을 이용하여 언커플링 프로테인 3(uncoupling protein 3, 이하 UCP 3라 한다.) 단백질의 활성 증진 여부를 나타낸 것이다.FIG. 1 shows a mouse weight reduction effect according to whether or not the extract of Piperretrofuramtam according to the present invention is treated. The ** marking on the graph shows significance at p <0.05, ** p <0.01 through Tukey's Multiple Comparison Test, a post-test of one-way ANOVA.
FIG. 2 shows reduction of body fat in mice according to whether or not the extract of piperafluoropropam according to the present invention is treated. ** Marked ** on the bar graph indicates significance at the p <0.05, ** p <0.01 through Tukey's Multiple Comparison Test, which is a post-test of one-way ANOVA.
FIG. 3 is a graph showing the effect of the uncoupling protein 3 (hereinafter referred to as UCP 3) protein in mouse adipocytes (3T3-L1) according to whether or not the pipererotropam protein extract of the present invention has been treated by Western blotting Activity enhancement.
본 발명에 따른 파이퍼 레트로프락텀 추출물을 포함하는 조성물은 체중 및 체지방 감소효과에 의하여 비만을 예방 및 치료할 수 있다.The composition comprising the piperafluorophyll extract according to the present invention can prevent and treat obesity by the body weight and body fat reducing effect.
본 발명에 따른 다른 실시예로서, 상기 파이퍼 레트로프락텀 열매추출물은 유기 용매 추출물이나 단독 이산화탄소 혹은 이산화탄소와 유기용매를 함께 사용한 초임계 추출물로서 얻을 수 있다.
In another embodiment of the present invention, the Piper Retroviral Fruit extract can be obtained as an organic solvent extract, a sole carbon dioxide, or a supercritical extract using carbon dioxide and an organic solvent together.
<실시예> 추출방법EXAMPLES Extraction method
건조시킨 파이퍼 레트로프락텀 열매분말을 4배 내지 10배의 추출 용매와 함께 추출장치에 넣고 12시간 이상 방치하여 하거나 초임계 추출하고 이를 농축기로 농축 및 건조하여 추출물을 얻는다.The dried Piper Retroviral Fruit Powder is put into an extraction device together with an extracting solvent 4 to 10 times, and left for 12 hours or more, or it is subjected to supercritical extraction, followed by concentration with a concentrator and drying to obtain an extract.
상기 추출용매로는 정제수(water), 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판 올(isopropanol), 부탄올(butanol), 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름 (chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylenechloride), 헥산(hexane), 시클로헥산(cyclohexane), 석유 에테르(petroleum ether) 또는 이들의 혼합물 등의 다양한 용매들이 가능하며, 바람직하게는 에탄올을 사용할 수 있다. 이외에도 상기 파이퍼 레트로프락텀 열매 성분을 유효 성분으로 추출하기에 적절한 용매는 별다른 제한 없이 사용 가능하다.
Examples of the extraction solvent include water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene Various solvents such as chloroform, ethyl acetate, methylenechloride, hexane, cyclohexane, petroleum ether or mixtures thereof are possible, Ethanol can be used. In addition, a solvent suitable for extracting the above-mentioned Piper retroviral compound as an active ingredient can be used without limitation.
본 발명은 또한 상기 조성물을 이용한 항비만 기능성 건강식품 및 약제 조성물을 제공한다. 상기 건강식품 및 약제 조성물은 본 발명에 따른 파이퍼 레트로프럭텀 열매추출물을 포함하기 때문에, 인체지방세포의 언커플링 프로테인 3(UCP 3) 활성기전으로, 체중 및 체지방을 감소시켜 비만을 예방 및 치료할 수 있다.
The present invention also provides an anti-obesity functional health food and pharmaceutical composition using the composition. Since the health food and pharmaceutical composition contains the fruit extract of Piperrethrophatum according to the present invention, it is possible to prevent and treat obesity by decreasing body weight and body fat by the mechanism of the uncoupling protein 3 (UCP 3) activity of human adipocytes .
본 발명의 항비만 기능성 건강식품 및 약학적 조성물을 경구 투여하는 경우, 경구 투여용 담체와 함께 당업계에 공지된 방법에 따라 분말, 과립, 정제, 환제, 당의 정제, 캡슐제, 액제, 겔제, 시럽제, 현탁액, 웨이퍼등의 형태로 제형화될 수 있다. 적합한 담체의 예로는 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨 및 말티톨 등을 포함하는 당류와 옥수수 전분, 밀 전분, 쌀 전분 및 감자 전분 등을 포함하는 전분류 셀룰로즈, 메틸 셀룰로즈, 나트륨 카르복시메틸셀룰로도즈 및 하이드록시 프로필메틴-셀룰로즈 등을 포함하는 셀룰로즈류 젤라틴, 폴리비닐피롤리돈 등과 같은 충전제가 포함될 수 있다. 또한 경우에 따라 가교결합 폴리비니리롤리돈, 한천, 알긴산 또는 나트륨 알지네이트 등을 붕해제로 첨가할 수 있다. 나아가 상기 약학적 조성물은 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.
When the anti-obesity functional health food and the pharmaceutical composition of the present invention is orally administered, it may be formulated into a powder, a granule, a tablet, a pill, a sugar, a tablet, a capsule, a liquid, a gel, Syrups, suspensions, wafers, and the like. Examples of suitable carriers include all kinds of sugars including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, etc. and corn starch, wheat starch, rice starch and potato starch, Cellulose gelatin, polyvinylpyrrolidone and the like, including cellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose and hydroxypropylmethylcellulose, and the like. In addition, crosslinked polyvinylidrolidone, agar, alginic acid or sodium alginate may optionally be added as a disintegrant. Further, the pharmaceutical composition may further comprise an anti-coagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent.
이하, 실험예 등을 통해 본 발명을 더욱 상술하지만, 하기 실험예 등은 본 발명을 예시하기 위한 것이며, 본 발명의 권리범위가 이들만으로 한정되는 것은 아니다.
Hereinafter, the present invention will be described in further detail with reference to experimental examples. However, the following experimental examples are for illustrating the present invention, and the scope of the present invention is not limited thereto.
[실험예 1] 동물모델에서 체중 및 체지방 측정[Experimental Example 1] Measurement of body weight and body fat in an animal model
<1-1> 실험동물 및 사료 <1-1> Experimental animals and feed
본 실험에서 사용된 고지방 식이는 40% fat calorie이며, 파이퍼 레트로프럭텀 추출물은 마우스 체중 kg당 100mg (EXT 100)으로 포함시켰다. The high fat diet used in this experiment was 40% fat calorie, and the piperetoroproteum extract was included as 100 mg (EXT 100) per kg body weight of the mouse.
5주령의 수컷 C57BL/6J 마우스를 고지방 대조군(HFD군)과 섭취용량에 따른 추출물 투여군(EXT군) 임의 배치한 후, 1주일간 실험 동물실 환경에 적응시켰다. 7주 동안 High Fat Diet 를 급여 시킨 후, 8주 동안 Vehicle 혹은 Vehicle로 분산시킨 추출물을 강제급여 시켰다.
Five week old male C57BL / 6J mice were randomly assigned to the high fat control group (HFD group) and the extract administration group (EXT group) according to the intake dose, and were then adapted to the experimental animal room environment for one week. High Fat Diet was fed for 7 weeks, and the extracts were dispersed in Vehicle or Vehicle for 8 weeks.
<1-2> 체중 및 체지방 측정 <1-2> Measurement of body weight and body fat
8주 동안 Vehicle 혹은 Vehicle로 분산시킨 추출물을 강제급여 후 희생직전 체중을 측정하였으며, 희생 후 부고환지방을 적출하여 무게를 측정하였다.
After 8 weeks of feeding, the body weight was measured immediately before sacrifice, and the epididymal fat was sacrificed and weighed.
[실험예 2] 열발생과 관련된 유전자의 단백질 발현 증진 효과[Experimental Example 2] Enhancement of protein expression of genes involved in heat generation
3T3-L1 지방세포에 열흘 정도 인슐린, Dexamethasone, IBMX 를 처리하여 지방이 형성되게 분화시킨 후, 파이퍼 레트로프럭텀 추출물 처리 후, 웨스턴 블랏(western blot)을 통해 언커플링 프로테인 3(UCP 3) 단백질 발현을 확인하였으며, α-tublin 으로 단백질 로딩량이 각 시료 별로 일정함을 나타내었다.
3T3-L1 adipocytes were treated with insulin, Dexamethasone, and IBMX for 10 days to induce fat formation. After treatment with piperretrofumptum extract, the uncomplexed protein 3 (UCP3) protein And the amount of protein loading by α-tublin was constant for each sample.
이상에서 명백한 바와 같이, 본 발명은 레트로프럭텀 열매추출물 유래의 항비만 기능성 조성물을 제공하는 효과가 있으며, 지방세포의 언커플링 프로테인 3(UCP 3) 활성에 의한 열발생 기전을 특징으로 하는 체중 및 체지방 감소효능이 있는 기능성 조성물과 특히, 언커플링 프로테인 3(UCP 3) 활성에 의한 열발생 기전을 특징으로 하는 항비만 기능성 식품 및 약제학적 조성물을 제공하는 뛰어난 효과가 있으므로 생물의약상 매우 유용한 발명인 것이다.As is apparent from the above, the present invention provides an anti-obesity functional composition derived from Retrofloccum fruit extract and has a weight-average molecular weight And an anti-obesity functional food and a pharmaceutical composition characterized by a heat-generating mechanism due to the activity of uncoupling protein 3 (UCP 3), in particular, it is very useful in biological medicine It is an invention.
Claims (8)
The present invention relates to an uncoordinated protein 3 of an adipocyte, which comprises, as an active ingredient, an extract of a Piper retrofractum Vahl fruit prepared according to any one of extraction method of purified water, organic solvent extraction or supercritical extraction UCP 3) A pharmaceutical composition for prevention and treatment of obesity having a mechanism of heat generation by protein activity.
The present invention relates to an uncoordinated protein 3 of an adipocyte, which comprises, as an active ingredient, an extract of a Piper retrofractum Vahl fruit prepared according to any one of extraction method of purified water, organic solvent extraction or supercritical extraction UCP 3) An obesity-improving functional food composition having a heat-generating mechanism by protein activity.
A pharmaceutical composition for preventing or treating obesity, which comprises an extract of Piper retrofractum Vahl fruit according to claim 3 in an amount of 0.001 to 80% by weight based on the total weight of the composition.
The pharmaceutical composition according to claim 3, wherein the composition is a powder, a granule, a tablet, a capsule, a syrup, or a beverage.
The composition for improving obesity-improving functional food according to claim 4, wherein the extract of Piper retrofractum Vahl fruit is contained in an amount of 0.001 to 80% by weight based on the total weight of the composition, and has a body weight and a body fat decreasing mechanism.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020110052191A KR101476761B1 (en) | 2011-05-31 | 2011-05-31 | An antiobesitic composition comprising of extracts isolated from Piper retrofractum vahl |
| JP2014513442A JP2014516983A (en) | 2011-05-31 | 2012-05-31 | A composition for treating obesity and diabetes, and for improving exercise capacity by increasing muscle mass, comprising an extract of PIPERRETROFRACTUMVAHL.FRUITS as an active ingredient |
| CN201410842636.0A CN104547059B (en) | 2011-05-31 | 2012-05-31 | Composition containing extract of fruit of Piper longum for preventing obesity, diabetes, increasing muscle mass and improving athletic ability |
| US14/122,752 US20140186473A1 (en) | 2011-05-31 | 2012-05-31 | Composition for treating obesity and diabetes and for increasing muscle mass and improving capacity for exercise, comprising extracts of piper retrofractum vahl. fruits as active ingredients |
| PCT/KR2012/004325 WO2012165888A2 (en) | 2011-05-31 | 2012-05-31 | Composition for treating obesity and diabetes and for increasing muscle mass and improving capacity for exercise, comprising extracts of piper retrofractum vahl. fruits as active ingredients |
| CN201280027034.9A CN103717229A (en) | 2011-05-31 | 2012-05-31 | Composition for treating obesity and diabetes and for increasing muscle mass and improving capacity for exercise, comprising extracts of piper retrofractum vahl. fruits as active ingredients |
| HK15105136.7A HK1204566B (en) | 2011-05-31 | 2015-05-29 | Composition for treating obesity and diabetes and for increasing muscle mass and improving capacity for exercise, comprising extracts of piper retrofractum vahl. fruits as active ingredients |
| JP2016045156A JP6255432B2 (en) | 2011-05-31 | 2016-03-09 | A composition for treating obesity and diabetes, and for improving exercise capacity by increasing muscle mass, comprising an extract of PIPERRETROFRACTUMVAHL.FRUITS as an active ingredient |
| US15/433,552 US20170209511A1 (en) | 2011-05-31 | 2017-02-15 | Composition for treating obesity and diabetes and for increasing muscle mass and improving capacity for exercise, comprising extracts of piper retrofractum vahl. fruits as active ingredients |
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