KR20190010212A - Method for preparation of resveratrol nano-capsue and the nano-capsule therefrom - Google Patents
Method for preparation of resveratrol nano-capsue and the nano-capsule therefrom Download PDFInfo
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- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 title claims abstract description 94
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 title claims abstract description 91
- 235000021283 resveratrol Nutrition 0.000 title claims abstract description 91
- 229940016667 resveratrol Drugs 0.000 title claims abstract description 91
- 239000002088 nanocapsule Substances 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 229920001661 Chitosan Polymers 0.000 claims abstract description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000463 material Substances 0.000 claims abstract description 14
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- 238000003756 stirring Methods 0.000 claims abstract description 5
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- 239000000203 mixture Substances 0.000 claims abstract 3
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- RUOKEYJFAJITAG-CUYWLFDKSA-N resveratroloside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C=C1)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 RUOKEYJFAJITAG-CUYWLFDKSA-N 0.000 description 1
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Abstract
Description
본 발명은 레스베라트롤의 캡슐화(encapsulation)를 통하여, 불안정한 유효성분을 빛, 산소, 수분, 온도 등의 외부요인으로부터 보호하는 기술로, 유효성분의 산화방지, 안정성 및 보존성 향상, 물성 및 제조공정 개선 등의 목적을 위한 발명으로서, 나노기술을 이용한 약물전달시스템(DDS : Drug Delivary System)을 이용하여 캡슐화를 시킴으로서, 나노단위의 작은 입자를 통해 용해도 향상, 체내 흡수 증가 및 표적기관으로의 안정적인 전달을 가능하게 하여 생체이용효율이 증가되는 기술에 관한 것이다.The present invention relates to a technique for protecting an unstable active ingredient from external factors such as light, oxygen, moisture, and temperature through encapsulation of resveratrol, which is effective for preventing oxidation of the active ingredient, improving stability and preservability, (DDS: Drug Delivary System), it is possible to improve the solubility through the small nano-sized particles, to increase the absorption into the body, and to make stable delivery to the target organ. Thereby increasing the bioavailability.
레스베라트롤(resveratrol, 3,4',5-trihydroxystilbene)은 최근 가장 주목받는 몰리페놀 중 하나로, 자연적으로 분비되는 강력한 항균물질로서, 항산화 효능이 탁월하고 항암, 항혈전 및 항염증 활성 등 여러가지 생리적 및 약리적 작용을 나타내어 식품과 화장품 등에 기능성 소재로 활용하려는 연구가 진행되고 있다.Resveratrol (3,4 ', 5-trihydroxystilbene) is one of the most remarkable molyphenols in recent years. It is a powerful antimicrobial substance secreted naturally. It has excellent antioxidant activity and various physiological and pharmacological activities such as anti-cancer, anti- Studies have been carried out to utilize them as functional materials for foods and cosmetics.
그러나, 하기의 이유로 다양한 생리 활성에 비해 산업적 활용도가 낮다.However, industrial utilization is low compared to various physiological activities for the following reasons.
레스베라트롤은Resveratrol
1) 난용성 성분으로 음료 등의 수용성 가공에 극히 제한적으로 사용되고 있으며, 2) 구조적인 불안정성으로 인해 빛, 열, 산소 등에 노출 시 trans형이 cis형으로 3) 대사가 빠르고 체내 반감기가 짧아 섭취 시 생체이용효율이 매우 낮은 문제점을 가지고 있다.2) Due to structural instability, trans type is cis type when it is exposed to light, heat, oxygen etc. 3) Its metabolism is fast and its half life is short. The bioavailability is very low.
특히, 주요 추출방법은 열수 추출방법이나, 이러한 열수 추출방법은 110℃의 고온에서 이루어지기 때문에 열에 의한 추출물의 변성 또는 레스베라트롤의 파괴가 일어나 추출물 중 레스베라트롤의 함량이 낮아지는 문제가 있다.Particularly, the main extraction method is a hot water extraction method, but since such a hot water extraction method is performed at a high temperature of 110 캜, there is a problem in that the content of resveratrol in the extract is lowered due to denaturation of the extract or destruction of resveratrol.
따라서, 레스베라트롤 산업의 확장 발전을 위해서는 레스베라트롤 소재의 가용성과 생체이용률을 증가시키기 위한 기술 개발이 절실히 요청되고 있는 실정이다.Therefore, in order to expand the development of the resveratrol industry, it is urgently required to develop a technique for increasing the availability and bioavailability of resveratrol.
이러한 문제점을 해결하기 위한 본 발명은 레스베라트롤의 니노캡슐화를 통해 이를 개선하고자 하는 것이다.In order to solve such a problem, the present invention aims to improve this through ninocapsulation of resveratrol.
캡슐화(encapsulation)는 불안정한 유효성분을 빛, 산소, 수분, 온도 등의 외부요인으로부터 보호하는 기술로, 이로 인하여, 유효성분의 산화방지, 안정성 및 보존성 향상, 물성 및 제조공정 개선하고자 하는 것이다.Encapsulation is a technique for protecting an unstable active ingredient from external factors such as light, oxygen, moisture, and temperature, thereby improving oxidation property, stability and preservability of the active ingredient, and improving physical properties and manufacturing process.
나노기술을 이용한 약물전달시스템(DDS : Drug Delivary System)을 통하여, 나노단위의 작은 입자를 통해 용해도 향상, 체내 흡수 증가 및 표적기관으로의 안정적인 전달을 가능하게 하여 생체이용효율이 증가시키고자 한다.Through the use of nanoparticle drug delivery system (DDS), it is intended to increase solubility through small particles in the nano unit, increase absorption into the body, and enable stable delivery to target organs, thereby increasing bioavailability.
본 발명의 목적을 위하여,For purposes of the present invention,
나노캡슐의 기본 피복물질로 수용성 키토산(chitosan)과 폴리글루탐산(poly-γ-glutamic acid, PGA)을 이용하여 키토산/PGA 나노입자를 제조하였다. Chitosan / PGA nanoparticles were prepared using water-soluble chitosan and poly-γ-glutamic acid (PGA) as basic coating materials for nanocapsules.
레스베라트롤 용액은 100% 유기용매, 바람직하게는 에탄올에 녹여 제조하였다. 레스베라트롤 함유 키토산/PGA 나노캡슐을 제조하기 위하여 키토산 용액에 레스베라트롤 용액을 충분히 분산시킨 후 계속 교반하면서, PGA 용액을 키토산과 레스베라트롤 혼합용액에 일정 속도로 떨어뜨려 레스베라트롤 함유 나노캡슐을 제조하였다 (도 1 참조).Resveratrol solution was prepared by dissolving in 100% organic solvent, preferably ethanol. To prepare resveratrol-containing chitosan / PGA nanocapsules, resveratrol solution was thoroughly dispersed in chitosan solution, and then the solution was dropped into chitosan and resveratrol mixed solution at a constant rate while stirring continuously to prepare resveratrol-containing nanocapsules (see FIG. 1) ).
이때, 교반속도는 1,000 rpm, PGA 혼합속도는 1.0 mL/min 인 것이 바람직하고, PGA 혼합시는 peristaltic pump를 사용하는 것이 바람직하다.At this time, it is preferable that the agitation speed is 1,000 rpm and the PGA mixing rate is 1.0 mL / min, and it is preferable to use peristaltic pump for PGA mixing.
따라서, 본 발명은 이러한 나노기술을 적용하여 레스베라트롤의 캡슐을 제조함으로, 레스베라트롤의 용해도를 개선시키고, 항산화 및 항노화활성, 생체이용효율을 극대화 시킨 고기능성 레스베라트롤 소재를 개발하고자 하는 것이다.Accordingly, the present invention is to develop a resveratrol material having improved solubility of resveratrol, maximizing antioxidant, anti-aging activity and bioavailability by preparing capsules of resveratrol by applying such nanotechnology.
이러한 레스베라트롤 나노캡슐은 이를 이용한 기능성 식품, 의약품 및 화장품의 제조에 유용하게 사용할 수 있는 효과가 있다.Such resveratrol nanocapsules can be advantageously used for the production of functional foods, medicines and cosmetics using the same.
도 1은 레스베라톨 함유 나노켑슐 제조의 모식도이다.
도 2는 피복물질 농도에 따른 나노입자의 입자 크기에 관한 그래프이다.
도 3은 피복물질 농도에 따른 나노입자의 분산도 (PDI)에 관한 그래프이다.
도 4는 8.3% 에탄올에서의 레스베라트롤 함유 나노분산액과 유리 레스베라트롤의 용해도 그래프이다.
도 5는 레스베라트롤 함유한 키토산/PGA캡슐의 세포투과율이다.
도 6는 키토산 및 PGA 농도에 따른 입자크기의 3차 그래프이다.
도 7은 키토산 및 PGA 농도에 따른 용해도의 3차 그래프이다.
도 8은 키토산 및 PGA 농도에 따른 UV안정성의 3차 그래프이다.1 is a schematic diagram of preparation of resveratol-containing nano-capsule.
2 is a graph showing the particle size of the nanoparticles according to the concentration of the coating material.
FIG. 3 is a graph showing the dispersion of nanoparticles (PDI) according to the concentration of the coating material.
4 is a graph of solubility of resveratrol-containing nanodispersions and glass resveratrol in 8.3% ethanol.
5 is the cell permeability of resveratrol-containing chitosan / PGA capsules.
6 is a third-order graph of particle size according to chitosan and PGA concentration.
FIG. 7 is a tertiary graph of solubility according to the concentration of chitosan and PGA.
Figure 8 is a tertiary graph of UV stability with chitosan and PGA concentration.
본 발명에서, 레스베라트롤의 용해도 및 불안정성을 극복하기 위한 나노캡슐화 방법에 사용되는 피복소재로 키토산과 γ-PGA를 선정하였다. 나노캡슐을 화장품이나 식품에 적용하기 위해 안전한 피복소재의 선정은 중요한 요소인데, 키토산과 PGA는 식의약 분야에 널리 쓰이는 물질로 그 안전성이 이미 검증된 물질이며 섭취 후에도 인체 내에서 생분해 가능하며 무독성이라고 알려져 있다. 또한 키토산은 양전하를 띄고 PGA는 음전하를 띄므로 가교제 없이 두 물질만을 이용한 이온결합 방법으로 나노캡슐화가 가능하므로 두 물질을 피복소재로 선정하였다.In the present invention, chitosan and γ-PGA were selected as coating materials used in the nanocapsulation method to overcome the solubility and instability of resveratrol. The selection of safe coating materials for application of nanocapsules to cosmetics or foods is an important factor. Chitosan and PGA are widely used in the food and medicine field, and its safety has already been proved. It is biodegradable and non-toxic in the human body after ingestion It is known. In addition, since chitosan has a positive charge and PGA has a negative charge, it can be nano-encapsulated by using only two substances without a cross-linking agent.
본 발명의 레스베라톨나노 캡슐에 있어서, In the resveratol nanocapsule of the present invention,
포도에서 레스베라톨을 추출하였고, 레스베라트롤의 추출율을 높히기 위하여 효소처리를 할 수 있다.Resveratol is extracted from grapes and enzymes can be processed to increase the rate of resveratrol extraction.
처리 효소는 효모추출물로서 생효모보다 유용함을 연구실험 결과 확인되어 효모 추출물을 처리하는 것으로 하며 농도는 1.0% 처리보다 0.5% 처리군에서 함량 증진 효과가 더 큰 것으로 나타났다. 따라서 효모추출물 (Yeast Extract) 는 0.5% 농도를 사용하는 것이 바람직하다. (표 1 참조)The treatment enzymes were found to be more useful than yeast extracts. Yeast extracts were treated with 0.5% of the yeast extract. Therefore, the yeast extract (Yeast Extract) is preferably used at a concentration of 0.5%. (See Table 1)
효모 추출물 처리농도
Yeast extract treatment concentration
resveratrol의 함량(㎍/g)
The content of resveratrol (㎍ / g)
상기와 같이 제조된 레스베라트롤 나노캡슐은 이를 이용한 기능성 식품, 의약품 및 화장품의 제조에 유용하게 사용할 수 있다. The resveratrol nanocapsules prepared as described above are useful for the production of functional foods, medicines and cosmetics using the same.
본 발명에 사용된 레스베라트롤(>99%, RES)은 Sigma-Aldrich Co.(St Louis, MO, USA)에서 구입하여 사용하였다. 포도추출물은 단국대 (Gyeonggi, Korea)에서 제공 받아 사용하였다. 피복물질로 사용된 키토산 (chitosan, M.W. 1,000~3,000) 과 폴리글루탐산(poly-γ-glutamic acid, PGA, M.W. 50 kDa)는 각각 Kittolife Co. (Seoul, Korea) 과 BioLeaders Corp. (Daejeon, Korea)에서 구입하여 사용하였다.Resveratrol (> 99%, RES) used in the present invention was purchased from Sigma-Aldrich Co. (St Louis, MO, USA). The grape extract was used in Dankook University (Gyeonggi, Korea). Chitosan (M.W. 1,000-3,000) and poly-γ-glutamic acid (PGA, M.W. 50 kDa) used as coating materials were purchased from Kittolife Co. (Seoul, Korea) and BioLeaders Corp. (Daejeon, Korea).
나노캡슐의 기본 피복물질로 수용성 키토산(chitosan)과 폴리글루탐산(poly-γ-glutamic acid, PGA)을 이용하여 키토산/PGA 나노입자를 제조한 후, 레스베라트롤 용액은 100% 에탄올에 녹여 제조하였다. 레스베라트롤 함유 키토산/PGA 나노캡슐을 제조하기 위하여 키토산 용액에 레스베라트롤 용액을 충분히 분산시킨 후 계속 교반(1,000 rpm)하면서 PGA 용액을 peristaltic pump를 이용하여 키토산과 레스베라트롤 혼합용액에 일정 속도(1.0 mL/min)로 떨어뜨려 레스베라트롤 함유 나노캡슐을 제조하였다.Chitosan / PGA nanoparticles were prepared by using water-soluble chitosan and poly-γ-glutamic acid (PGA) as the basic coating material of nanocapsules. Resveratrol solution was prepared by dissolving resveratrol in 100% ethanol. To prepare resveratrol-containing chitosan / PGA nanocapsules, the resveratrol solution was thoroughly dispersed in chitosan solution, and the PGA solution was continuously poured into the chitosan and resveratrol mixed solution at a constant rate (1.0 mL / min) while stirring (1,000 rpm) To prepare resveratrol-containing nanocapsules.
레스베라트롤 함유 키토산/PGA 나노캡슐의 크기가 100-150 nm로 측정되었다.The size of resveratrol-containing chitosan / PGA nanocapsules was measured at 100-150 nm.
레스베라트롤 함유 나노캡슐의 물리적 특성Physical properties of resveratrol-containing nanocapsules
키토산과 PGA 농도변화에 따른 레스베라트롤 함유 키토산/PGA 나노입자의 물리적 특성을 측정하기 위하여 6가지 제조조건을 설정하였다. 이 제조조건에서 나노캡슐의 입자크기와 입자분산도(PDI) 등의 입자특성을 분석하였다 (도 2 및 3 참조). Six manufacturing conditions were established to measure the physical properties of resveratrol - containing chitosan / PGA nanoparticles with varying chitosan and PGA concentration. Particle characteristics such as particle size and particle dispersity (PDI) of nanocapsules were analyzed under these manufacturing conditions (see FIGS. 2 and 3).
나노캡슐의 나노입자크기(particle size)를 비롯하여 입자의 분산도(polydispersity index, PDI), 산란강도(derived count rate, DCR) 및 제타전위(zeta potential) 등의 입자특성은 나노입도분석기(Marvern Zetasizer Nano ZS)를 이용하여 측정하였다.Particle properties such as particle size of nanocapsules, polydispersity index (PDI), derived count rate (DCR), and zeta potential were measured using a nano particle size analyzer (Marvern Zetasizer Nano ZS).
키토산과 PGA의 농도비율이 약 5:1 ~10:1의 비율 일때 비교적 균일한 크기의 나노캡슐이 형성되었으며, 그 이외의 비율에서는 침전물이 형성되거나 입자크기가 불균일하게 형성되었다. 즉, 키토산 0.5 mg/mL 일 때 PGA 0.05, 0.10 mg/mL 조건, 키토산 1.0 mg/mL 일 때 PGA 0.10, 0.20 mg/mL 조건, 키토산 2.0 mg/mL 일 때 PGA 0.20, 0.40 mg/mL 조건일 때 입자 분산도가 낮은 우수한 특성의 나노입자가 제조됨을 확인하였다.When the concentration ratio of chitosan to PGA was about 5: 1 to 10: 1, relatively uniform nanocapsules were formed. In other ratios, precipitates were formed or the particle size was unevenly formed. In the case of chitosan 0.5 mg / mL, PGA 0.05, 0.10 mg / mL, PGA 0.10 and 0.20 mg / mL when chitosan 1.0 mg / mL and PGA 0.20 and 0.40 mg / mL when chitosan 2.0 mg / It was confirmed that nanoparticles having excellent properties with low particle dispersion were produced.
나노캡슐의 입자크기는 0.5에서 2.0 mg/mL까지의 키토산 농도변화에 의해서는 유의적 차이를 나타내지 않았으나 키토산/PGA 비율이 증가됨에 따라서는 유의적으로 증가되었다. 키토산 농도와 상관없이 키토산/PGA 비율이 10일 때, 입자크기는 약 500 nm로 측정되었고 비율이 5일때, 약 150 nm의 나노캡슐이 형성되었다. 또한, PDI는 키토산이나 PGA 농도 및 키토산/PGA 비율과 상관없이 모든 조건에서 0.1 이하로 측정되어 매우 균일한 입자크기 분포를 가짐을 알 수 있었다. The particle size of the nanocapsules was not significantly different by the change of chitosan concentration from 0.5 to 2.0 mg / mL, but it was significantly increased with increasing chitosan / PGA ratio. Regardless of chitosan concentration, the particle size was measured at about 500 nm when the chitosan / PGA ratio was 10, and about 150 nm nanocapsules were formed when the ratio was 5. PDI was measured to be 0.1 or less under all conditions regardless of chitosan, PGA concentration and chitosan / PGA ratio, and it was found that PDI had a very uniform particle size distribution.
따라서 상대적으로 작은 입자크기를 형성하는 키토산/PGA 비율 5일 때의 조건에서 나노입자를 제조하여 이 후 실험에 이용하였다.Therefore, nanoparticles were prepared at a chitosan / PGA ratio of 5, which forms a relatively small particle size, and then used in the experiment.
- 용해도 평가- Solubility assessment
나노캡슐화에 따른 용해도 변화를 측정하기 위하여 레스베라트롤을 함유한 나노캡슐 분산액과 대조군인 나노캡슐화하지 않은 레스베라트롤 용액을 제조하였다. 두 용액에 최대한 녹는 레스베라트롤의 양을 측정하기 위해 혼합해주는 레스베라트롤의 농도를 점차 높이며 제조하였다. 에탄올에 대한 간섭효과를 제거하기 위해 두 용액 모두 에탄올 함량을 8.3%로 동일하게 유지하였다. 물에 대한 용해도를 측정하In order to measure the solubility change by nanocapsulation, a dispersion of nanocapsules containing resveratrol and a non-nanocapsulated resveratrol solution as a control group were prepared. To measure the amount of resveratrol dissolved in the two solutions, the concentration of resveratrol was gradually increased. The ethanol content of both solutions was kept the same at 8.3% in order to eliminate interference effect on ethanol. To measure the solubility in water
기 위하여 두 용액을 같은 조건에서 동결건조 후 물에 재분산하여 물에 대한 용해도를 측정하였다. 각 분산액을 0.45 μm MCE syringe filter를 통하여 여과한 후, HPLC를 이용하여 레스베라트롤을 정량분석하였다.The two solutions were lyophilized under the same conditions and redispersed in water to determine their solubility in water. Each dispersion was filtered through a 0.45 μm MCE syringe filter and resveratrol was quantitatively analyzed by HPLC.
- 용해도 평가 결과- Solubility evaluation results
키토산/PGA 나노캡슐화에 따른 레스베라트롤의 용해도 변화를 관측하기 위하여, 캡슐에 함유하는 레스베라트롤 농도를 점차적으로 높이면서 레스베라트롤의 용해도를 측정하였다. 나노캡슐화 되지 않은 유리 레스베라트롤도 같은 농도에서 용해도를 측정했으며, 나노캡슐 제조시에 함유되는 에탄올에 의한 간섭효과를 없애기 위하여 나노캡슐과 유리 레스베라트롤 모두 에탄올 농도를 8.3%로 고정하였다.In order to observe the change of solubility of resveratrol following chitosan / PGA nanoencapsulation, resveratrol solubility was measured while gradually increasing resveratrol concentration in the capsules. Nano-encapsulated glass resveratrol also measured the solubility at the same concentration. In order to eliminate the interference effect of ethanol contained in the preparation of nanocapsules, the concentration of ethanol in both nanocapsules and glass resveratrol was fixed at 8.3%.
나노캡슐화가 레스베라트롤의 용해도에 미치는 영향을 정량분석과 육안관측을 통하여 비교하였다. (도 4 참조) The effects of nanocapsulation on the solubility of resveratrol were compared by quantitative analysis and visual observation. (See Fig. 4)
캡슐화되지 않은 유리 레스베라트롤 분산액의 경우, 레스베라트롤 농도 80 μg/mL까지는 첨가 레스베라트롤양이 증가할수록 용해도도 증가하였으나 그 이상에서는 더 이상 녹을 수 있는 레스베라트롤의 양은 증가하지 않고 그 값이 유지되었다. 그러나 나노캡슐의 경우 레스베라트롤 농도 200 μg/mL까지 용해되는 것을 확인했으며, 이는 캡슐화되지 않은 유리 레스베라트롤 용해도의 2.5배에 해당하는 수치이다. 따라서 나노캡슐화 됨에 따라 난용성인 레스베라트롤의 용해도가 증가했음을 확인하였다. 그러나 피복물질 농도별간의 용해도 차이는 나타나지 않았다.In the case of the unencapsulated glass resveratrol dispersion, the solubility was increased with increasing amount of resveratrol up to 80 μg / mL of resveratrol concentration, but the amount of resveratrol, which could be melted further, remained unchanged. However, nanocapsules have been shown to dissolve up to 200 μg / mL resveratrol, which is 2.5 times the solubility of non-encapsulated glass resveratrol. Therefore, it was confirmed that solubility of resolubilized resveratrol increases with nanocapsule formation. However, there was no difference in solubility between the concentrations of the coating materials.
육안관측 결과, 레스베라트롤 농도 80 μg/mL 까지는 캡슐화 유무에 따른 육안상의 차이가 관측되지않았으나, 레스베라트롤의 농도가 점차 증가됨에 따라 레스베라트롤 캡슐은 뚜렷한 변화없이 약간 뿌연 반투명한 상태를 유지한 반면, 유리 레스베라트롤의 경우 레스베라트롤 농도 증가에 따라 분산액이 탁해지면서 200 μg/mL의 농도에서는 거의 불투명한 성상을 나타냈다.As a result of visual observation, there was no visual difference according to the presence or absence of encapsulation up to the resveratrol concentration of 80 μg / mL. However, as the concentration of resveratrol gradually increased, resveratrol capsules remained slightly cloudy translucent without any change, In the case of the resveratrol concentration, the dispersion became cloudy and showed almost opaque property at the concentration of 200 μg / mL.
- 저장 안정성 평가 - Storage stability evaluation
레스베라트롤 함유 키토산/PGA 나노캡슐의 저장안정성을 평가하기 위하여 15일 동안 25℃에서 시료를 저장하면서 용해도를 측정하였다.To evaluate the storage stability of resveratrol-containing chitosan / PGA nanocapsules, the solubility of the resveratrol-containing chitosan / PGA nanocapsules was measured at 25 ° C for 15 days.
저장기간동안 나노캡슐화 되지 않은 유리상태의 레스베라트롤과 나노캡슐화 된 레스베라트롤의 용해도를 5일마다 관측하였다. 저장 직전 시료들의 레스베라트롤 용해도는 모두 같았다. 저장 5일후 유리 레스베라트롤의 용해도는 30% 감소한 반면 나노캡슐화된 레스베라트롤의 용해도는 5-15% 감소하였다. During the storage period, the solubility of non-nanocapsulated resveratrol in glass and resveratrol in nanocapsules was observed every 5 days. Resveratrol solubility of all samples before storage was the same. After 5 days of storage, the solubility of glass resveratrol was reduced by 30%, while the solubility of nanocapsulated resveratrol was reduced by 5-15%.
이는 나노캡슐화된 레스베라트롤이 친수성인 키토산과 PGA의 영향을 받아 유리 레스베라트롤보다 용해도가 증가했기 때문으로 생각된다.This is probably due to the increased solubility of resorbable nanocapsulated resveratrol compared to glass resveratrol due to the influence of hydrophilic chitosan and PGA.
시료들 중에서는 입자크기가 가장 작은 CS0.5 PGA0.1 나노입자가 pH 3.5, pH 5.5에서 저장기간동안 유의적으로 가장 큰 용해도를 나타냈다. 또한 입자크기가 클수록 저장기간동안 용해도가 더 낮아지는 경향을 보였고, 이를 통해 입자크기가 용해도에 영향을 미쳤을 것으로 판단하였다.Among the samples, CS0.5 PGA0.1 nanoparticles with the smallest particle size showed the greatest solubility at pH 3.5 and pH 5.5 during the storage period. Also, the larger the particle size, the lower the solubility during the storage period, and the particle size influenced the solubility.
- 세포투과율 평가 - Cellular permeability evaluation
Confocal 형광 현미경을 이용하여 레스베라트롤의 장세포 투과정도를 확인하였다. Confocal fluorescence microscopy was used to confirm the intestinal cell permeability of resveratrol.
confocal 현미경 사진에서 형광세기가 클수록 세포 내로 흡수된 레스베라트롤이 많다는 것을 의미하는데, 나노캡슐화하지 않은 유리 레스베라트롤의 형광세기가 나노캡슐화된 레스베라트롤보다 작았다. 이를 통해 나노캡슐화에 의해 세포투과력이 증진됨을 확인할 수 있었으나, 시료 간에 가시적인 차이를 보지 못해 정량분석을 진행하였다. (도 5 참조).In confocal microscope photographs, the larger the fluorescence intensity, the more resveratrol was absorbed into the cells, the fluorescence intensity of the nanoscopically unresponsive glass resveratrol was smaller than that of the nanocapsulated resveratrol. Through this, it was confirmed that the cell permeability was enhanced by nano-encapsulation, but the quantitative analysis was carried out because no visible difference was observed between the samples. (See FIG. 5).
나노캡슐화하지 않은 유리 레스베라트롤의 세포투과율은 3.5% 였으나, 나노캡슐화된 레스베라트롤의 세포투과율은 5-7%를 나타냈다. 피복물질농도가 낮을수록 세포투과율이 증가하는 경향을 보였으며 이는 용해도와 유사한 경향을 보인다. 따라서 tight junction을 열어준다고 알려져있는 키토산 뿐만 아니라 용해도도 세포투과에 영향을 끼친다고 판단된다.The cell permeability of nano-encapsulated glass resveratrol was 3.5%, but the nanocapsulated resveratrol showed a cell permeability of 5-7%. The lower the concentration of the coating material, the higher the cell permeability, which is similar to the solubility. Therefore, it is considered that not only chitosan, which is known to open a tight junction, but also solubility affects cell permeation.
- 실험결과 - Experiment result
입자크기는 키토산/PGA 비율이 3 이상부터 키토산/PGA 비율이 증가함에 따라 입자크기가 증가하는 경향이 관측되었다 (도 6 참조). The particle size was observed to increase as the chitosan / PGA ratio increased from 3 or higher to the chitosan / PGA ratio (see FIG. 6).
피복물질의 농도는 입자크기에 영향을 미치며 키토산 농도가 증가,The concentration of the coating material influences the particle size and increases the chitosan concentration,
PGA 농도가 감소할수록 입자크기가 증가한다고 판단된다.It is considered that particle size increases with decreasing PGA concentration.
용해도는 키토산농도 1.1-2.5mg/mL 범위에서 키토산 농도가 감소, PGA 농도가 증가할수록 증가하는 경향을 보였다 (도 7 참조). Solubility tended to increase with decreasing chitosan concentration and PGA concentration at chitosan concentration 1.1-2.5 mg / mL (see FIG. 7).
입자크기가 감소할수록 용해도가 증가하는 것을 확인했다. 입자크기와 피복물질의 물리화학적 특성이 용해도에 영향을 미친 것으로 추정된다.It was confirmed that the solubility increases with decreasing particle size. The particle size and physical and chemical properties of the coating material are thought to have affected solubility.
UV 안정성은 키토산 농도가 증가할수록 증가하는 경향이 관측되었다 (도 8 참조). 키토산 농도 0.5-1.5mg/mL 범위에서 PGA 농도 감소함에 따라 UV 안정성이 증가하였으나 키토산 농도 1.5-2.5mg/mL 범위에서는 PGA 농도변화에 따른 뚜렷한 경향이 관측되지 않았다. 키토산의 최저 농도와 PGA의 최대 농도에서 가장 낮은 UV안정성을 나타냈으며, UV안정성과 입자크기는 비슷한 경향을 보임을 알 수 있었다. 입자크기가 클수록 UV안정성은 증가하고 용해도는 감소하는 것으로 판단된다.UV stability was observed to increase with increasing chitosan concentration (see FIG. 8). The UV stability increased as the concentration of chitosan decreased from 0.5 to 1.5 mg / mL. However, no significant trend was observed with the concentration of chitosan in the range of 1.5-2.5 mg / mL. The lowest UV stability was obtained at the lowest concentration of chitosan and the highest concentration of PGA, and UV stability and particle size showed similar tendency. The larger the particle size, the higher the UV stability and the lower the solubility.
Claims (8)
Wherein the coating material is chitosan and? -PGA.
레스베라트롤 용액은 100% 유기용매에 녹여 제조하는 단계;
레스베라트롤 함유 키토산/PGA 나노캡슐을 제조하기 위하여 키토산 용액에 레스베라트롤 용액을 충분히 분산시킨 후 계속 교반하는 단계; 및
동시에 PGA 용액을 키토산과 레스베라트롤 혼합용액에 일정 속도로 떨어뜨리는 단계.
The method for preparing resveratrol nanocapsules according to claim 1, comprising the following steps:
Resveratrol solution is prepared by dissolving in 100% organic solvent;
Sufficiently dispersing the resveratrol solution in the chitosan solution to prepare the resveratrol-containing chitosan / PGA nanocapsule, and then continuing to stir; And
And simultaneously dropping the PGA solution into the chitosan and resveratrol mixed solution at a constant rate.
키토산과 PGA의 농도비율이 약 5:1 ~10:1의 비율인 것을 특징으로 하는 레스베라트롤 나노캡슐 제조방법.
3. The method according to claim 1 or 2,
Wherein the concentration ratio of chitosan to PGA is about 5: 1 to 10: 1.
포도에 0.5% 농도의 효모추출물 (Yeast Extract)을 추가하여 레스베라트롤을 추출하는 것을 특징으로 하는 레스베라트롤 나노캡슐 제조방법.
3. The method of claim 1 or 2, wherein the resveratrol
A method for preparing resveratrol nanocapsules, which comprises extracting resveratrol by adding 0.5% yeast extract to grapes.
The method for preparing resveratrol nanocapsules according to any one of claims 1 to 5, wherein the resveratrol nanocapsules have a size of 100-150 nm.
3. The method of claim 2, wherein the organic solvent is 100% ethanol.
2. The method for preparing resveratrol nanocapsules according to claim 2, wherein the stirring speed is 1000 rpm, the PGA addition rate is 1.0 mL / min, and a peristaltic pump is used when added.
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