KR20180003843A - Composition for Improving Retinal Diseases Using an Extract of Lithospermum erythrorhizon - Google Patents
Composition for Improving Retinal Diseases Using an Extract of Lithospermum erythrorhizon Download PDFInfo
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- KR20180003843A KR20180003843A KR1020160083497A KR20160083497A KR20180003843A KR 20180003843 A KR20180003843 A KR 20180003843A KR 1020160083497 A KR1020160083497 A KR 1020160083497A KR 20160083497 A KR20160083497 A KR 20160083497A KR 20180003843 A KR20180003843 A KR 20180003843A
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Abstract
Description
본 발명은 지치 추출물(Lithospermum erythrorhizon)을 이용한 망막질환 개선용 조성물에 관한 것이다.
The present invention relates to the use of an extract of Lithospermum erythrorhizon ) for improving retinal diseases.
망막(Retina)은 안구의 가장 안쪽을 덮고 있는 투명한 신경조직으로 구조적으로는 광수용체층, 신경절세포층(Retinal ganglion cell layer), 신경섬유층 등을 포함한 10개의 층으로 구성되어 있다. 안구로 들어온 빛이 광수용체세포(photoreceptor cell)에서 감지되어 전기적 신호로 전환되면, 신경절세포층에 존재하는 망막신경절세포(Retinal ganglion cell)가 이 전기적 신호를 뇌의 시신경 중추로 전달함으로써, 우리가 사물을 볼 수 있게 된다. 따라서 안압 상승, 고혈압, 당뇨, 혈전, 동맥경화 등에 의해 망막신경절세포가 사멸하게 되면 시력 왜곡이나 시력 상실이 야기될 수 있다. 색소성 망막염(RP), 시신경병증(선천성 레베르시신경병증, 허혈성 시신경병증), 녹내장, 황반변성(노인성, 습성 또는 건성 황반변성), 망막병증(퇴행성 망막병증, 당뇨병성 망막병증, 고혈압성 망박병증, 미숙아 망막병증, 허혈성 망막병증) 등이 이러한 망막신경절세포의 사멸을 수반하는 망막질환 등이다(Eye (Lond). 2004 Nov;18(11):1161-8; Mult Scler Relat Disord. 2016 Jan;5:66-9; Ophthalmol Clin North Am. 2005 Sep;18(3):383-95; European Ophthalmic Review, 2009,3(2):109-112; Brain Res. 2006 May 1;1086(1):191-200; Am J Pathol. 2014 Jun;184(6):1752-62; Invest Ophthalmol Vis Sci. 2010 Jul; 51(7): 3660-3665; Prog Retin Eye Res. 2002 Sep;21(5):465-84; Invest Ophthalmol Vis Sci. 2001 Mar;42(3):795-803; Arch Ophthalmol. 1997 Apr;115(4):511-5; Front Cell Neurosci. 2013 Jan 9;6:60). The retina is a transparent nerve tissue that covers the innermost part of the eye. It consists of ten layers structurally including the photoreceptor layer, the retinal ganglion cell layer, and the nerve fiber layer. When light entering the eye is detected in a photoreceptor cell and converted into an electrical signal, the retinal ganglion cell present in the ganglion cell layer transmits this electrical signal to the optic nerve center of the brain, . Thus, retinal ganglion cell death due to elevated intraocular pressure, hypertension, diabetes, thrombosis, arteriosclerosis, etc. can lead to visual distortions or loss of vision. (Retinopathy), retinopathy (degenerative retinopathy, diabetic retinopathy, hypertensive rickettsia, retinopathy of prematurity, retinopathy of prematurity, retinopathy of prematurity, retinopathy of prematurity Retinopathy, retinopathy of prematurity, ischemic retinopathy) are retinal diseases accompanied by the death of retinal ganglion cells (Eye (Lond) 2004 Nov; 18 (11): 1161-8; Mult Scler Relat Disord. 2005; 1 (3): 383-95; European Ophthalmology Review, 2009, 3 (2): 109-112; Brain Res. 2006 May 1; 1086 (1) (5): 191-200; Am J Pathol, 2014 Jun; 184 (6): 1752-62; Invest Ophthalmol Vis Sci. 2010 Jul; 51 (7): 3660-3665; Invest Ophthalmol Vis Sci 2001 Mar; 42 (3): 795-803; Arch Ophthalmol 1997 Apr; 115 (4): 511-5; Front Cell Neurosci.
특히 망막신경절세포 사멸을 수반하는 대표적 질환이 녹내장인데, 녹내장에서 나타나는 망막신경절세포의 사멸은 세포자살(Apoptosis)로 알려져 있으며, 이는 안압을 상승시킨 동물모델뿐만 아니라 사후 부검을 통해 녹내장 환자에서도 관찰된 바 있다(Invest Ophthalmol Vis Sci., 36, 774-786, 1995; Exp Eye Res., 61, 33-44, 1995). 세포자살(apoptosis)이란, 세포괴사(necrosis)와는 구별되는 세포 내의 자발적이고 계획된 세포사(programmed cell death)로, 망막신경절세포에서는 글루타메이트(glutamate), 사이토크롬 C(cytochrome c), TNF-α(tumor necrosis factor α), Bad(BCL2-antagonist of cell death) 등이 세포자살을 유도하는 것으로 알려져 있고, 산화적 스트레스도 중요한 원인으로 알려져 있다(Arch Ophthalmol., 123:458-463, 2005; J Cell Physiol., 180:182-189, 1999). In particular, glaucoma is a typical disease accompanied by retinal ganglion cell death. The death of retinal ganglion cells in glaucoma is known as apoptosis, which is observed not only in animal models with elevated intraocular pressure but also in glaucoma patients through post- (Invest Ophthalmol Vis Sci., 36, 774-786, 1995; Exp Eye Res., 61, 33-44, 1995). Apoptosis is a spontaneous and programmed cell death in the cell that is different from necrosis. In the retinal ganglion cell, glutamate, cytochrome c, TNF-α (JCL), which is known to induce cell apoptosis, is also an important cause of oxidative stress (Arch Ophthalmol, 123: 458-463, 2005; J Cell Physiol , ≪ / RTI > 180: 182-189, 1999).
이상의 점으로부터, 망막신경절세포에 대하여 보호 효과를 갖는 약물은 녹내장 등 망막신경절세포의 사멸을 수반하는 망막질환의 예방, 치료에 매우 유용할 것으로 기대되며, 실제 그러한 약물에 대한 연구가 활발히 이루어져 왔다(Invest Ophthalmol Vis Sci 45:2640-2651, 2004; Surv Ophthalmol 48:S47-S51, 2003; J Glaucoma 11:221-225, 2002; Curr Eye Res 28:153-157, 2004; Brain 128:550-558, 2005; Neurosci Lett 372:17-21, 2004).From the above, it is expected that a drug having a protective effect on retinal ganglion cells is very useful for the prevention and treatment of retinal diseases accompanied by the death of retinal ganglion cells such as glaucoma. Actually, such drugs have been actively studied Invest Ophthalmol Vis Sci 45: 2640-2651, 2004; Surv Ophthalmol 48: S47-S51, 2003; J Glaucoma 11: 221-225, 2002; Curr Eye Res 28: 153-157, 2004, Brain 128: 550-558, 2005, Neurosci Lett 372: 17-21, 2004).
한편 지치는 우리나라 각지에 야생하고 있는 다년생 초본으로, 그 뿌리는 대한민국약전에 자근(紫根)이란 약재로 수재되어 있으며, 식품공전에 식용 가능한 원료로도 등재되어 있다. 주요성분은 아세틸시코닌(Acetylshikonin), 베타-디메틸크릴시코닌(β-Dimethylcrylshikonin) 등의 시코닌 유도체이며, 양혈(凉血), 활혈(活血), 청열(淸熱), 해독(解毒), 강심(强心), 혈압강하(血壓降下), 항균(抗菌), 항진균(抗眞菌) 등의 효능이 알려져 있다(식약처 생약정보종합시스템, http://www.mfds.go.kr/herbmed/index.do). On the other hand, it is a perennial herb which is wild in various parts of Korea, and its roots are contained in the Korean pharmacopoeia as a medicinal substance called 根, and it is also listed as an edible raw material in the food circulation. The main ingredient is a shikonin derivative such as acetylshikonin and beta -dimethylcrylshikonin, and it is a derivative of a bichromal blood, an active blood, a cleansing heat, a detoxification, The efficacy of antithyroid drugs, such as strong heart, blood pressure drop, antimicrobial, and antifungal, has been known (see http://www.mfds.go.kr/) herbmed / index.do).
본 발명은 지치 추출물의 망막신경절세포의 보호 활성과, 망막신경절세포 사멸을 수반하는 망막질환 개선 활성 등을 개시한다.
The present invention discloses protective activity of retinal ganglion cells of retinal ganglion extract and retinal disease improving activity accompanied by retinal ganglion cell death.
본 발명의 목적은 지치 추출물을 이용한 망막질환 개선용 조성물을 제공하는 데 있다.It is an object of the present invention to provide a composition for improving retinal disease using an extract of Shigella.
본 발명의 다른 목적은 지치 추출물을 이용한 망막신경세포의 보호용 조성물을 제공하는 데 있다.It is another object of the present invention to provide a composition for protecting retinal nerve cells using a dentifrice extract.
본 발명의 다른 목적이나 구체적인 목적은 이하에서 제시될 것이다.
Other and further objects of the present invention will be described below.
본 발명은 아래의 실시예 및 실험예에서 확인되는 바와 같이, 지치 추출물이 시신경 부분 압착모델(partial optic nerve crush; PONC)의 동물실험에서 시신경 압착 손상에 의한 망막신경절세포층의 두께 감소와 망막신경세포의 사멸을 회복시킴을 확인함으로써 완성된 것이다. 상기 시신경 부분 압착모델은 망막신경절세포 자살(apoptosis) 억제 약물 및 시신경 보호 약물의 스크리닝에 널리 이용되고 있는 모델이다(Korean Ophthalmol Soc 51(5):746-750, 2010; Brain. 131:250-263, 2008; Exp Ther Med. 4(3):401-404, 2012). As shown in the following examples and experimental examples, the present invention is based on the finding that the dorsal root extract reduces the thickness of the retinal ganglion cell layer due to the optic nerve crush injury in the animal experiment of the partial optic nerve crush (PONC) And the restoration of the death of the dead. The optic nerve partial pressure model is a widely used model for the screening of retinal ganglion cell apoptosis inhibitory drugs and optic nerve protection drugs (Korean Ophthalmol Soc 51 (5): 746-750, 2010; Brain. 131: 250-263 , 2008; Exp Ther Med. 4 (3): 401-404, 2012).
이러한 실험 결과는 지치 추출물이 망막신경절세포(또는 망막신경세포)의 보호 용도로 유용하게 사용될 수 있고 나아가 망막신경세포의 사멸을 수반하거나 이에 따른 시신경 손상을 수반하는 망막질환에도 유용하게 사용될 수 있음을 보여주는 것이라 할 수 있다. The results of this experiment suggest that the extract can be useful for the protection of retinal ganglion cells (or retinal nerve cells) and may be useful for retinal diseases accompanied by the death of retinal nerve cells or accompanying optic nerve damage It can be said that it shows.
전술한 바를 고려할 때, 일 측면에서 본 발명은 지치 추출물을 유효성분으로 포함하는 망막신경세포의 사멸을 수반하는 망막질환 개선용 조성물로 파악할 수 있고, 다른 측면에 있어서는 지치 추출물을 유효성분으로 포함하는 망막신경세포 보호용 조성물로 파악할 수 있다. In view of the foregoing, in one aspect, the present invention can be understood as a composition for improving retinal diseases accompanied by the death of retinal nerve cells comprising an immunoglobulin extract as an active ingredient, and in another aspect, And a composition for protecting retinal nerve cells.
본 명세서에서, "지치 추출물"이란 추출 대상인 지치 전초, 줄기, 잎, 열매, 꽃, 뿌리, 또는 이들의 혼합물 등을 물, 알콜 특히 탄소수 1 내지 4의 저급 알콜(메탄올, 에탄올, 부탄올 등), 메틸렌클로라이드, 에틸렌, 아세톤, 헥산, 에테르, 클로로포름, 에틸아세테이트, 부틸아세테이트, N,N-디메틸포름아미드(DMF), 디메틸설폭사이드(DMSO), 1,3-부틸렌글리콜, 프로필렌글리콜 또는 이들의 혼합 용매를 사용하여 침출하여 얻어진 추출물, 이산화탄소, 펜탄 등 초임계 추출 용매를 사용하여 얻어진 추출물 또는 그 추출물을 분획하여 얻어진 분획물을 의미하며, 추출 방법은 활성물질의 극성, 추출 정도, 보존 정도를 고려하여 냉침, 환류, 가온, 초음파 방사, 초임계 추출 등 임의의 방법을 적용할 수 있다. 분획된 추출물의 경우 추출물을 특정 용매에 현탁시킨 후 극성이 다른 용매와 혼합·정치시켜 얻은 분획물, 상기 조추출물을 실리카겔 등이 충진된 칼럼에 흡착시킨 후 소수성 용매, 친수성 용매 또는 이들의 혼합 용매를 이동상으로 하여 얻은 분획물을 포함하는 의미이다. 또한 상기 추출물의 의미에는 동결건조, 진공건조, 열풍건조, 분무건조 등의 방식으로 추출 용매가 제거된 농축된 액상의 추출물 또는 고형상의 추출물이 포함된다. 바람직하게는 추출용매로서 물, 에탄올 또는 이들의 혼합 용매를 사용하여 얻어진 추출물, 더 바람직하게는 추출용매로서 물과 에탄올의 혼합 용매를 사용하여 얻어진 추출물을 의미한다.In the present specification, the term "drench extract" means water, alcohols, especially lower alcohols having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.) (DMF), dimethylsulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixture thereof. The solvent is preferably selected from the group consisting of methylene chloride, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, Refers to an extract obtained by leaching using a mixed solvent, an extract obtained by using a supercritical extraction solvent such as carbon dioxide or pentane, or a fraction obtained by fractionating the extract, and the extraction method includes considering the polarity, extraction degree, and preservation degree of the active substance Any method such as cooling, reflux, heating, ultrasonic irradiation, supercritical extraction, and the like can be applied. In the case of the fractionated extract, a fraction obtained by suspending the extract in a specific solvent and mixing and leaving with a solvent having a different polarity, the crude extract is adsorbed on a column packed with silica gel, and then a hydrophobic solvent, a hydrophilic solvent, Quot; means fractions obtained as a mobile phase. Also, the meaning of the extract includes a concentrated liquid extract or a solid extract in which the extraction solvent is removed by a method such as freeze drying, vacuum drying, hot air drying, spray drying and the like. Preferably an extract obtained by using water, ethanol or a mixed solvent thereof as an extraction solvent, and more preferably an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.
또 본 명세서에서 "유효성분"이란 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.In the present specification, the term " active ingredient "alone means an ingredient which exhibits the desired activity or which can exhibit activity together with a carrier which is not itself active.
또 본 명세서에서, "망막질환"은 망막신경세포의 사멸을 수반하거나 그에 의한 시신경의 손상을 수반하는 질환으로 정의되며, 색소성 망막염(RP), 시신경병증(선천성 레베르시신경병증, 허혈성 시신경병증), 녹내장, 황반변성(노인성, 습성 또는 건성 황반변성), 망막병증(퇴행성 망막병증, 당뇨병성 망막병증, 고혈압성 망박병증, 미숙아 망막병증, 허혈성 망막병증) 등을 포함하는 의미이다.In the present specification, the term "retinal disease" is defined as a disease accompanied by or accompanied by the death of the retinal nerve cell, including retinitis pigmentosa (RP), optic neuropathy (congenital Leberish neuropathy, ischemic optic neuropathy ), Glaucoma, macular degeneration (senile, mood or dry macular degeneration), retinopathy (degenerative retinopathy, diabetic retinopathy, hypertensive retinopathy, prematurity retinopathy, ischemic retinopathy).
또 본 명세서에서, "망막질환 개선"은 망막질환 증상의 경감, 치료, 그러한 질환의 예방(발병 억제 또는 지연)을 포함하는 의미이다.In this specification, "retinal disease improvement" is meant to include alleviation, treatment, prevention of the disease (inhibiting or delaying onset)
또 본 명세서에서, "망막신경세포의 보호"란 글루타메이트, 산화적 스트레스 등 망막신경세포의 세포자살을 유도하는 내·외적 인자에 의한 망막신경세포의 사멸을 억제하거나 그 사멸을 회복한다는 의미이다. In this specification, the term " protection of retinal nerve cells "means inhibiting or restoring the death of retinal nerve cells by internal or external factors that induce apoptosis of retinal nerve cells such as glutamate and oxidative stress.
본 발명의 망막질환 개선용 조성물 또는 망막신경세포 보호용 조성물(이하 "본 발명의 조성물")에서 그 유효성분은 망막질환의 개선 효과, 망막신경세포의 보호 효과 등 나타낼 수 있는 한, 용도, 제형 등에 따라 임의의 양(유효량)으로 포함될 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 15 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 그 적용 대상인 포유동물 바람직하게는 사람에게 의료 전문가 등의 제언에 의한 투여 기간 동안 본 발명의 조성물이 투여될 때, 망막질환의 개선 효과, 망막신경세포의 보호 효과 등 의도한 의료적·약리학적 효과를 나타낼 수 있는, 본 발명의 조성물에 포함되는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.The effective ingredient of the composition for improving retinal disease or composition for protecting retinal nerve cell (hereinafter, referred to as "composition of the present invention") of the present invention may be used as far as it can show such as improvement effect of retinal disease, protective effect of retinal nerve cell, (Effective amount), and a typical effective amount will be determined within the range of from 0.001 wt% to 15 wt% based on the total weight of the composition. The term "effective amount" as used herein refers to an amount of an effective amount of the composition of the present invention to be administered to a mammal, preferably a human, Refers to the amount of the active ingredient contained in the composition of the present invention, which can exhibit antiphlogistic effects. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.
본 발명의 조성물은 유효성분 이외에, 망막질환의 개선 활성, 망막신경세포의 보호 활성의 상승·보강을 위하여 또는 눈의 피로도 개선 활성, 안구건조증 개선 활성 등 유사활성의 부가를 통한 복용이나 섭취의 편리성을 위하여, 당업계에서 이미 안전성이 검증되고 해당 활성이 확인된 임의의 화합물이나 천연 추출물을 추가로 포함할 수 있다. The composition of the present invention may be used not only for the effective ingredient but also for improving the retinal disease or for enhancing or enhancing the protective activity of the retinal nerve cell or for improving the fatigue of the eyes or improving the dryness of the eye, May further comprise any compound or natural extract that has already been tested in the art for its safety and has been identified for its activity.
이러한 화합물 또는 추출물에는 각국 약전(한국에서는 "대한민국약전"), 각국 건강기능식품공전(한국에서는 식약처 고시인 "건강기능식품 기준 및 규격"임) 등의 공정서에 실려 있는 화합물 또는 추출물, 의약품의 제조·판매를 규율하는 각국의 법률(한국에서는 "약사법"임)에 따라 품목 허가를 받은 화합물 또는 추출물, 건강기능식품의 제조·판매를 규율하는 각국 법률(한국에서는 "건강기능식품에관한법률"임)에 따라 개별적으로 기능성을 인정받은 화합물 또는 추출물이 포함된다. 예컨대 한국 건강기능식품공전 상의 루테인, 헤마토코쿠스(Haematococcus pluvialis) 추출물, 한국 "건강기능식품에관한법률"에 따라 개별적으로 인정받은 빌베리 추출물, 들쭉 열매 추출물, 루테인과 지아잔틴의 복합 추출물, 루테인 복합물, 마리골드추출물, 지아잔틴추출물 등이 이러한 화합물 또는 추출물에 해당할 것이다.Such compounds or extracts include compounds or extracts listed in the official pamphlet of each country's pharmacopeia ("Korea Pharmacopoeia" in Korea), each country's health functional foods (in Korea, "Health Functional Food Standards and Specifications" (The "Act on Health Functional Foods" in Korea), which regulates the manufacture and sale of compounds or extracts and health functional foods approved by the respective countries under the laws of the respective countries ("Pharmaceutical Affairs Law" in Korea) "). ≪ / RTI > For example, lutein, hematococcus ( Haematococcus pluvialis extract, a bilberry extract, a complex extract of lutein and giazanthin, a lutein complex, a marigold extract and a giazanthin extract, which are individually recognized according to the Korean Health Functional Food Act, .
이러한 화합물 또는 추출물은 본 발명의 조성물에 그 유효성분과 함께 하나 이상 포함될 수 있다.Such compounds or extracts may be included in the composition of the present invention in combination with one or more thereof.
본 발명의 조성물은 구체적인 양태에 있어서 식품 조성물로서 파악할 수 있다.The composition of the present invention can be identified as a food composition in a specific embodiment.
본 발명의 식품 조성물은 어떠한 형태로도 제조될 수 있으며, 예컨대 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구루트 등의 가공 유류(乳類), 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 정제, 캡슐, 환, 과립, 액상, 분말, 편상, 페이스트상, 시럽, 겔, 젤리, 바 등의 건강기능식품 제제류 등으로 제조될 수 있다. 또 본 발명의 식품 조성물은 법률상·기능상의 구분에 있어서 제조·유통 시점의 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 한국 "건강기능식품에관한법률"에 따른 건강기능식품이거나, 한국 "식품위생법"의 식품공전(식약처 고시 "식품의 기준 및 규격"임)상 각 식품유형에 따른 과자류, 두류, 다류, 음료류, 특수용도식품 등일 수 있다.The food composition of the present invention can be prepared in any form and can be used in various forms such as beverages such as tea, juice, carbonated beverage, ionic drink, processed milk such as milk and request route, gum, rice cake, Such as confectionery, cotton, etc., tablets, capsules, rings, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars and the like. In addition, the food composition of the present invention may be classified into any product category as long as it meets the laws and regulations on the time of manufacture and distribution in the legal and functional category. For example, it is a health functional food according to the "Health Functional Food Act" in Korea or the food standard (standard and standard of food notices) of the Food Sanitation Act of Korea. Beverages, special-purpose foods, and the like.
본 발명의 식품 조성물에는 그 유효성분 이외에 식품첨가물이 포함될 수 있다. 식품첨가물은 일반적으로 식품을 제조, 가공 또는 보존함에 있어 식품에 첨가되어 혼합되거나 침윤되는 물질로서 이해될 수 있는데, 식품과 함께 매일 그리고 장기간 섭취되므로 그 안전성이 보장되어야 한다. 식품의 제조·유통을 규율하는 각국 법률(한국에서는 "식품위생법"임)에 따른 식품첨가물공전에는 안전성이 보장된 식품첨가물이 성분 면에서 또는 기능 면에서 한정적으로 규정되어 있다. 한국 식품첨가물공전(식약처 고시 "식품첨가물 기준 및 규격)에서는 식품첨가물이 성분 면에서 화학적 합성품, 천연 첨가물 및 혼합 제제류로 구분되어 규정되어 있는데, 이러한 식품첨가물은 기능 면에 있어서는 감미제, 풍미제, 보존제, 유화제, 산미료, 점증제 등으로 구분된다. The food composition of the present invention may contain food additives in addition to the active ingredients thereof. Food additives are generally understood to be substances that are added to foods and mixed or infiltrated into food in the manufacture, processing or preservation of food, and their safety must be ensured since they are ingested daily with food and for long periods of time. Food additives according to national laws regulating the manufacture and distribution of food (in Korea, the "Food Sanitation Act") are stipulated as safety-guaranteed food additives in terms of ingredients or function. In the Food Additives Ordinance of the Republic of Korea (Food Additives Standards and Standards), the food additives are classified into chemical compounds, natural additives, and mixed preparations in terms of ingredients. These food additives are classified into sweeteners, , Preservatives, emulsifiers, acidulants, and thickeners.
감미제는 식품에 적당한 단맛을 부여하기 위하여 사용되는 것으로, 천연의 것이거나 합성된 것 모두 본 발명의 식품 조성물에 사용할 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다. The sweetener is used for imparting a sweet taste suitable for food, and both natural and synthetic sweeteners can be used in the food composition of the present invention. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.
풍미제는 맛이나 향을 좋게 하기 위한 용도로 사용되는 것으로, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 대잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제로서는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다. Flavors are used to improve taste and flavor, and natural and synthetic flavors can be used. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. If desired, a synthetic flavor agent may be used. As the synthetic flavor agent, esters, alcohols, aldehydes, terpenes and the like may be used.
보존제로서는 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등이 사용될 수 있고, 또 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등이 사용될 수 있으며, 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등이 사용될 수 있다. 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다. 점증제로서는 현탁화 구현제, 침강제, 겔형성제, 팽화제 등이 사용될 수 있다.As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid) and the like can be used, and as the emulsifier, acacia gum, carboxymethyl cellulose, xanthan gum, pectin And acidulant, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid and the like may be used as the acidulant. The acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste. Examples of the thickening agent include suspending agents, sedimentation agents, gel-forming agents, bulking agents and the like.
본 발명의 식품 조성물은 전술한 바의 식품첨가물 이외에, 기능성과 영양성을 보충·보강할 목적으로 당업계에 공지되고 식품첨가물로서 안정성이 보장된 생리활성 물질이나 미네랄류를 포함할 수 있다.The food composition of the present invention may contain physiologically active substances or minerals which are known in the art and which are stable as a food additive, for the purpose of supplementing and reinforcing the functionality and nutrition, in addition to the above-mentioned food additives.
그러한 생리활성 물질로서는 녹차 등에 포함된 카테킨류, 비타민 B1, 비타민 C, 비타민 E, 비타민 B12 등의 비타민류, 토코페롤, 디벤조일티아민 등을 들 수 있으며, 미네랄류로서는 구연산칼슘 등의 칼슘 제제, 스테아린산마그네슘 등의 마그네슘 제제, 구연산철 등의 철 제제, 염화크롬, 요오드칼륨, 셀레늄, 게르마늄, 바나듐, 아연 등을 들 수 있다. Examples of such physiologically active substances include catechins contained in green tea and the like, vitamins such as vitamin B1, vitamin C, vitamin E and vitamin B12, tocopherol, dibenzoyl thiamine, etc. Examples of minerals include calcium preparations such as calcium citrate, magnesium stearate , Iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc and the like.
본 발명의 식품 조성물에는 전술한 바의 식품첨가물이 제품 유형에 따라 그 첨가 목적을 달성할 수 있는 적량으로 포함될 수 있다.The food composition of the present invention may contain an appropriate amount of the above-mentioned food additives according to the product type so as to achieve the purpose of addition thereof.
본 발명의 식품 조성물에 포함될 수 있는 기타의 식품첨가물과 관련하여서는 각국 법률에 따른 식품공전이나 식품첨가물공전을 참조할 수 있다.With regard to other food additives that may be included in the food composition of the present invention, reference may be made to the Food Code or the Food Additive Code of the respective country.
본 발명의 조성물은 다른 구체적인 양태에 있어서는 약제학적 조성물로 파악될 수 있다.In another specific embodiment, the composition of the present invention can be identified as a pharmaceutical composition.
본 발명의 약제학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체를 포함하여 당업계에 공지된 통상의 방법으로 투여 경로에 따라 경구용 제형 또는 비경구용 제형으로 제조될 수 있다. 여기서 "약제학적으로 허용되는" 의미는 유효성분의 활성을 억제하지 않으면서 적용(처방) 대상이 적응 가능한 이상의 독성을 지니지 않는다는 의미이다.The pharmaceutical composition of the present invention may be prepared into oral formulations or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.
본 발명의 약제학적 조성물이 경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 분말, 과립, 정제, 환제, 당의정제, 캡슐제, 액제, 겔제, 시럽제, 현탁액, 웨이퍼 등의 제형으로 제조될 수 있다. 이때 약제학적으로 허용되는 적합한 담체의 예로서는 락토스, 글루코스, 슈크로스, 덱스트로스, 솔비톨, 만니톨, 자일리톨 등의 당류, 옥수수 전분, 감자 전분, 밀 전분 등의 전분류, 셀룰로오스, 메틸셀룰로오스, 에틸셀룰로오스, 나트륨 카르복시메틸셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 셀룰로오스류, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트, 광물유, 맥아, 젤라틴, 탈크, 폴리올, 식물성유 등을 들 수 있다. 제제화활 경우 필요에 따라 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 및/또는 부형제를 포함하여 제제화할 수 있다.When the pharmaceutical composition of the present invention is prepared into an oral formulation, it may be formulated into powder, granules, tablets, pills, sugar tablets, capsules, solutions, gels, syrups, suspensions, wafers And the like. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, xylitol, starch such as corn starch, potato starch and wheat starch, cellulose, methylcellulose, ethylcellulose, Cellulose derivatives such as sodium carboxymethyl cellulose and hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, And the like. In case of formulation, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and / or an excipient may be formulated according to need.
본 발명의 약제학적 조성물이 비경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 점안제, 주사제, 경피 투여제, 비강 흡입제, 좌제의 형태로 제제화될 수 있다. 점안제로 제제화활 경우 적합한 담체로서는 멸균수, 식염수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있으며 필요에 따라 염화벤잘코늄, 메필파라벤, 에틸파라벤 등을 방부 목적으로 첨가할 수 있다. 주사제로 제제화할 경우 적합한 담체로서는 멸균수, 에탄올, 글리세롤이나 프로필렌 글리콜 등의 폴리올 또는 이들의 혼합물을 사용할 수 있으며, 바람직하게는 링거 용액, 트리에탄올 아민이 함유된 PBS(phosphate buffered saline)나 주사용 멸균수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있다. 경피 투여제로 제제화할 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태로 제제화할 수 있다. 비강 흡입제의 경우 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 등의 적합한 추진제를 사용하여 에어로졸 스프레이 형태로 제제화할 수 있으며, 좌제로 제제화할 경우 그 기제로는 위텝솔(witepsol), 트윈(tween) 61, 폴리에틸렌글리콜류, 카카오지, 라우린지, 폴리옥시에틸렌 소르비탄 지방산 에스테르류, 폴리옥시에틸렌 스테아레이트류, 소르비탄 지방산 에스테르류 등을 사용할 수 있다.When the pharmaceutical composition of the present invention is prepared into a parenteral dosage form, it may be formulated in the form of eye drops, injections, transdermal drug delivery, nasal aspirates, suppositories according to methods known in the art together with suitable carriers. In the case of formulation with eyedrops, sterile water, saline, isotonic solution such as 5% dextrose may be used. If necessary, benzalkonium chloride, mepilparaben, ethylparaben and the like may be added for preservative purposes. As the carrier suitable for injection preparation, sterilized water, ethanol, polyol such as glycerol or propylene glycol, or a mixture thereof, may be used, and preferably, a solution of Ringer's solution, phosphate buffered saline containing triethanolamine or sterilized by injection Water, or isotonic solution such as 5% dextrose may be used. When formulated with a transdermal preparation, it can be formulated in the form of ointments, creams, lotions, gels, external liquids, pastes, liniments, and air-lozenges. The nasal inhalant may be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. When formulated as a suppository, witepsol, tween 61, polyethylene glycols, cacao butter, laurin, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and sorbitan fatty acid esters.
약제학적 조성물의 구체적인 제제화와 관련하여서는 당업계에 공지되어 있으며, 예컨대 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)] 등을 참조할 수 있다. 상기 문헌은 본 명세서의 일부로서 간주 된다.The formulation of pharmaceutical compositions is well known in the art and can be found, for example, in Remington ' s Pharmaceutical Sciences (19th ed., 1995). This document is considered part of this specification.
본 발명의 약제학적 조성물의 바람직한 투여량은 환자의 상태, 체중, 성별, 연령, 환자의 중증도, 투여 경로에 따라 1일 0.001mg/kg ~ 10g/kg 범위, 바람직하게는 0.001mg/kg ~ 1g/kg 범위일 수 있다. 투여는 1일 1회 또는 수회로 나누어 이루어질 수 있다. 이러한 투여량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 해석되어서는 아니 된다.
The preferred dosage of the pharmaceutical composition of the present invention is 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g / day, depending on the patient's condition, body weight, sex, age, / kg < / RTI > The administration can be carried out once or several times a day. Such dosages should in no way be construed as limiting the scope of the invention.
전술한 바와 같이, 본 발명에 따르면 지치 추출물을 이용한 망막질환 개선용 조성물을 제공할 수 있다. 본 발명의 조성물은 식품, 의약품 등으로 제품화될 수 있다.INDUSTRIAL APPLICABILITY As described above, the present invention can provide a composition for ameliorating a retinal disease using a dentifrice extract. The composition of the present invention can be commercialized into foods, medicines and the like.
본 발명의 조성물에 유효성분으로 사용되는 지치 추출물은 시신경 부분 압착모델의 동물실험에서 시신경 압착 손상에 의한 망막신경절세포층의 두께 감소와 망막신경세포의 사멸을 회복시키는 효과를 갖는다.
The dentifrice extract used as an active ingredient in the composition of the present invention has the effect of restoring the retinal ganglion cell layer thickness reduction and the retinal nerve cell death by the optic nerve compression damage in the animal experiment of the optic nerve partial compression model.
도 1 및 도 2는 각각 지치 추출물이 시신경 부분압착모델의 동물실험에서 시신경 압박에 의한 망막신경절세포층의 두께 감소와 망막신경세포의 사멸 회복 효과를 보여주는 결과이다.FIGS. 1 and 2 show the results of the reduction of the retinal ganglion cell layer thickness and the restoration of retinal nerve cell death by optic nerve compression in an animal experiment of the optic nerve partial compression model, respectively.
이하 본 발명을 실시예 및 실험예를 참조하여 설명한다. 그러나 본 발명의 범위가 이러한 실시예 및 실험예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.
<< 실시예Example > > 지치Shag 추출물의 제조 Preparation of extract
건조된 지치 뿌리 세절물 30g에 250mL의 95% 에탄올을 가하고 3시간 동안 60-80℃에서 온침 추출한 후 추출액을 여과하였다. 추출액을 여과한 후 남은 잔사에 다시 250 mL의 에탄올을 가하고 60-80℃에서 3시간 동안 온침 추출하는 방법을 추가로 1회 반복하였다. 총 추출액을 40℃에서 감압 농축하여 에탄올 추출물 4.3g을 수득하였다. 상기 추출물은 디메틸설폭사이드(Dimethyl sulfoxide; DMSO)에 녹인 후, 하기 실험에 이용되었다.To 30 g of dried three pieces of dentifrice, 250 mL of 95% ethanol was added, the mixture was warmed at 60-80 ° C for 3 hours, and the extract was filtered. After filtration of the extract, 250 mL of ethanol was added to the remaining residue, and the resultant was subjected to warm-up extraction at 60-80 ° C for 3 hours. The total extract was concentrated under reduced pressure at 40 占 폚 to obtain 4.3 g of an ethanol extract. The extract was dissolved in dimethyl sulfoxide (DMSO) and used in the following experiment.
<< 실험예Experimental Example > > 시신경 부분 압착모델로 유도한 Optic nerve partial compression model C57BLC57BL /6J 쥐 망막 / 6J Rat retina 시신경세포의Optic nerve cell 사멸 억제 효과 측정 Measurement of inhibition of death
상기 실시예의 지치 추출물의 시신경 부분 압착모델(partial optic nerve crush ; PONC)로 유도한 C57BL/6J 쥐 망막 시신경세포의 사멸 억제효과를 다음과 같이 확인하였다. The inhibitory effect of C57BL / 6J mouse retinal optic nerve cells induced by partial optic nerve crush (PONC) in the denture extract of the above Example was confirmed as follows.
실험 일주일 전부터 C57BL/6J 쥐에 농도에 따라 실시예의 지치 추출물과 대조군인 0.01M PBS를 경구투여 하였다. 2% 럼푼 주사액과 졸레틸을 혼합하여 1ml/kg 근육 주사하여 마취시킨 후 결막 뒤쪽을 혈관을 다치지 않도록 조심스럽게 절개하여 시신경을 노출시킨 후 안구에서 2mm 뒤쪽의 시신경에 크로스 액션 포셉을 이용하여 5초간 압착 손상을 적용하였다. 수술 후 감염을 예방하기 위해 0.5% 비가목스 점안액(ALcon Laboratoriss, Inc. USA)을 한 방울 점안하였다. 실험군에는 지치 추출물 10 mg/kg, 50 mg/kg를 일 1회 경구 투여하였고 대조군에서는 같은 용량의 0.01M PBS를 경구 투여하였다. One week before the experiment, C57BL / 6J rats were orally administered with the dorsal root extract of Example and 0.01 M PBS as a control group according to the concentration. A 2% rumon injection and Zoletil were mixed and anesthetized with 1 ml / kg intramuscular injection. The optic nerve was exposed to the back of the conjunctiva to prevent injury to the blood vessels. Second, compression damage was applied. To prevent infection after surgery, a drop of 0.5% non-Gagus eyedrop (ALcon Laboratoriss, Inc. USA) was applied. In the experimental group, 10 mg / kg and 50 mg / kg of dentifrice extract were orally administered once a day, and 0.01 M PBS of the same dose was orally administered to the control group.
시신경 손상 6일 후, 다시 쥐를 마취시킨 후 두피를 절개하였다. 시신경 세포 염색을 위해 시신경과 연결되어 있는 뇌의 상구부위에 수술용 드릴을 이용하여 타공하고 3% FluoroGold를 주입하였다. 절개부위를 봉합하고, 항생연고를 발라주어 감염을 예방하였다. 시신경 손상 12일 후, Phoenix사의 micron4를 이용하여 망막안저 촬영 및 망막단층을 촬영하여 망막신경절세포층의 손상정도를 확인하였다. 또한 안구를 적출하여 4% parafromaldehyde에 4시간 동안 고정하였다. 고정한 안구는 맥락막으로부터 망막을 분리하여 4개의 방사상 절개를 하고, 슬라이드위에 클로버잎 모양으로 마운트하였다. 각 실험군 슬라이드는 형광현미경을 이용하여 형광을 띄는 시신경 세포를 확인하고 40배, 200배 촬영하였다.Six days after injury of the optic nerve, the mice were anesthetized again and the scalp was incised. For the optic nerve cell staining, 3% FluoroGold was injected into the upper part of the brain connected to the optic nerve using a surgical drill. The incision was sutured and antibiotic ointment was applied to prevent infection. Twelve days after the optic nerve damage, retinal angiography and retinal layer were photographed using a micron4 from Phoenix to confirm the degree of damage of the retinal ganglion cell layer. Eyes were removed and fixed in 4% parafromaldehyde for 4 hours. Fixed eyeballs were separated from the choroid by 4 radial incisions and mounted on a slide in the shape of a cloverleaf. Fluorescence microscopy was used to observe the fluorescence of the optic nerve cells.
망막신경절세포층(GCL)D의 두께를 측정한 결과를 [도 1]에 나타내었고, 망막신경세포 보호 효과를 측정한 결과를 [도 2]에 나타내었다.The results of measuring the thickness of the retinal ganglion cell layer (GCL) D are shown in FIG. 1, and the protective effect of retinal nerve cell is measured (FIG. 2).
[도 1]을 참조하여 보면 시신경 압착 손상에 의해 망막신경절세포층(GCL)의 두께가 음성대조군(Control)에 비해 감소하였으나 지치 추출물을 처리할 경우 농도 의존적으로 유의성 있게 회복되었음을 알 수 있으며, [도 2]를 참조하여 보면 망막신경세포도 시신경 압착 손상에 의해 감소하나 지치 추출물 처리에 의해 농도 의존적으로 유의성 있게 회복되었음을 알 수 있다.
Referring to FIG. 1, the thickness of the retinal ganglion cell layer (GCL) was decreased by the compression of the optic nerve compared to the negative control (Control). However, 2], the retinal nerve cell was also decreased by the compression of the optic nerve, but it was significantly restored by the treatment with the lipid extract.
Claims (9)
A composition for improving retinal diseases accompanied by the death of retinal nerve cells comprising an extract of Zhiwi as an active ingredient.
상기 망막질환은 색소성 망막염, 시신경병증, 녹내장, 황반변성 또는 망막병증인 것을 특징으로 하는 망막질환 개선용 조성물.
The method according to claim 1,
Wherein the retinal disease is pigmentary retinitis, optic neuropathy, glaucoma, macular degeneration or retinopathy.
상기 지치 추출물은 지치를 물, 에탄올 또는 이들의 혼합용매로 추출하여 얻어진 것을 특징으로 하는 망막질환 개선용 조성물.
The method according to claim 1,
Wherein the dermis extract is obtained by extracting dermis with water, ethanol or a mixed solvent thereof.
상기 조성물은 식품 조성물인 것을 특징으로 하는 망막질환 개선용 조성물.
4. The method according to any one of claims 1 to 3,
Wherein the composition is a food composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는 망막질환 개선용 조성물.
4. The method according to any one of claims 1 to 3,
Wherein the composition is a pharmaceutical composition.
A composition for protecting retinal nerve cells, comprising an extract of Shiitake as an active ingredient.
상기 지치 추출물은 지치를 물, 에탄올 또는 이들의 혼합용매로 추출하여 얻어진 것을 특징으로 하는 망막신경세포 보호용 조성물.
The method according to claim 6,
Wherein the dermis extract is obtained by extracting dermis with water, ethanol or a mixed solvent thereof.
상기 조성물은 식품 조성물인 것을 특징으로 하는 망막신경세포 보호용 조성물.
8. The method according to claim 6 or 7,
Wherein the composition is a food composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는 망막신경세포 보호용 조성물.
8. The method according to claim 6 or 7,
Wherein the composition is a pharmaceutical composition.
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| KR1020160083497A KR101860510B1 (en) | 2016-07-01 | 2016-07-01 | Composition for Improving Retinal Diseases Using an Extract of Lithospermum erythrorhizon |
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| JP6026719B2 (en) | 2010-08-31 | 2016-11-16 | 株式会社ダイセル | Visual function preventive / improving agent |
| JP5893438B2 (en) | 2012-02-27 | 2016-03-23 | 株式会社ダイセル | Retinopathy preventive or ameliorating agent |
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