KR20220000186A - A pharmaceutical composition for the prevention or treatment of keratoconjunctivitis sicca comprising a mixture of quercetin and Polygonum cuspidatum stem extract - Google Patents
A pharmaceutical composition for the prevention or treatment of keratoconjunctivitis sicca comprising a mixture of quercetin and Polygonum cuspidatum stem extract Download PDFInfo
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- KR20220000186A KR20220000186A KR1020200077836A KR20200077836A KR20220000186A KR 20220000186 A KR20220000186 A KR 20220000186A KR 1020200077836 A KR1020200077836 A KR 1020200077836A KR 20200077836 A KR20200077836 A KR 20200077836A KR 20220000186 A KR20220000186 A KR 20220000186A
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- South Korea
- Prior art keywords
- quercetin
- mixture
- stem extract
- preventing
- keratoconjunctivitis
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Abstract
Description
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염의 예방 또는 치료용 약학 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of keratoconjunctivitis sicca, comprising a mixture of quercetin and a rhizome stem extract.
개 고양이에서 발생하는 건성각결막염 (Keratoconjuctivitis sicca, KCS)은 눈물의 구성성분 중 수분 부족으로 발생하는 수의 안과질환 중 하나이다. 건성각결막염이 있는 개, 고양이는 각막과 결막에 염증이 발생하고 결막 충혈과 각막의 상피가 두꺼워지고 색소가 침착되는 경우도 있다. 증상이 심할 경우에는 각막 궤양이 발생하고 실명하게 되는 경우도 있다. 면역매개성으로 인해 눈물샘이 파괴는 것이 개 고양이에서 건성각결막염이 발생하는 가장 큰 원인이다. 그 밖에 노화, 저갑상선질환, 당뇨, 아토피, 디스템퍼와 같은 전신질환에 의해서도 발생할 수 있고, 국소적인 안면부의 창상에 의해서도 발생할 수 있고, 건조한 실내환경의 과다노출과 같은 사육환경에 의해서도 발생할 수 있다. 그러나 대부분의 경우에 그 원인에 대해서는 정확히 알려진 바가 없다. Keratoconjuctivitis sicca (KCS), which occurs in dogs and cats, is one of the veterinary ophthalmic diseases caused by lack of water among the components of tears. In dogs and cats with keratoconjunctivitis sicca, the cornea and conjunctiva become inflamed, conjunctival hyperemia, and thickening and pigmentation of the corneal epithelium may occur. In severe cases, corneal ulceration may occur and blindness may occur. Immune-mediated destruction of the lacrimal gland is the biggest cause of keratoconjunctivitis sicca in dogs and cats. In addition, it can be caused by systemic diseases such as aging, hypothyroidism, diabetes, atopic dermatitis, and distemper, it can be caused by a local facial wound, or it can be caused by a breeding environment such as overexposure to a dry indoor environment. However, in most cases, the exact cause is not known.
한편, "호장근"이란, 우리나라 산야에서 자라는 마디풀과의 다년초 식물로 뿌리줄기는 굵고, 줄기는 높이 1.5 m가량이다. 잎은 어긋나고 달걀 모양, 길이 6~12 cm 이며 끝이 뽀죡하고, 잎자루는 길다. 어릴때 줄기의 생김새가 호피를 닮아서 호장근이라는 이름이 붙었다. 호장근은 민간에서 이뇨, 통경제, 진정제로 사용되어 왔으며, 완화, 이뇨, 통경, 화농성 피부염, 요도염, 방광염, 고혈압, 암, 동맥경화 등 여러 질병을 치료하기 위하여 우리나라를 비롯하여 동양권의 전통의학에서 이용되어 왔다.On the other hand, "Hojanggeun" is a perennial plant of the Knobaceae family that grows in the mountains of Korea. The rhizome is thick and the stem is about 1.5 m in height. The leaves are alternate phyllotaxis, egg-shaped, 6-12 cm long, with a sharp tip, and a long petiole. When young, the shape of the stem resembles a leopard, hence the name hojanggun. Hojang-geun has been used as a diuretic, analgesic, and sedative agent in folklore. has been used
케르세틴은 (Quercetin)은 식물에서 매우 흔한 플라보노이드 (polyphenolic flvonoid) 화합물의 광범위한 클래스에 속한다. 양파, 브로콜리, 사과 및 콩에서 고농도의 케르세틴이 발견되며, 사람에서 케르세틴은 수년간 식이 보충제로서 사용되어 왔다. Quercetin belongs to a broad class of polyphenolic flvonoid compounds that are very common in plants. High concentrations of quercetin are found in onions, broccoli, apples and beans, and in humans, quercetin has been used as a dietary supplement for many years.
본 발명자들은 개 고양이의 건성각결막염 치료를 위한 연구를 한 결과, 케르세틴 및 호장근 줄기 추출물의 혼합물이 개 고양이 건성각결막염 치료에 효과가 있다는 것을 확인하고 본 발명을 완성하였다.As a result of the study for the treatment of keratoconjunctivitis sicca in dogs and cats, the present inventors confirmed that a mixture of quercetin and rhododendron stem extract was effective in treating keratoconjunctivitis sicca in dogs and cats, and completed the present invention.
본 발명은 상기의 문제를 해결하기 위해 안출한 결과, 케르세틴 및 호장근 줄기 추출물의 혼합물이 개 고양이 건성각결막염 치료 효과가 있다는 것을 확인하고 본 발명을 완성하였다. As a result of devising the present invention to solve the above problems, it was confirmed that a mixture of quercetin and rhizome stalk extract is effective in treating keratoconjunctivitis sicca in dogs and cats, and the present invention was completed.
본 발명의 목적은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 치료용 약학적 조성물을 제공하는 것이다. It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of keratoconjunctivitis sicca, comprising a mixture of quercetin and rhizome stem extract.
본 발명의 또 다른 목적은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 개선용 건강기능식품조성물을제공하는 것이다. Another object of the present invention is to provide a health functional food composition for preventing or improving keratoconjunctivitis keratoconjunctivitis, comprising a mixture of quercetin and Hojang root stem extract.
본 발명의 다른 목적은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 동물의 건성각결막염 예방 또는 치료용 수의학적 조성물을 제공하는 것이다. Another object of the present invention is to provide a veterinary composition for the prevention or treatment of keratoconjunctivitis sicca in animals, comprising a mixture of quercetin and a rhizome stem extract.
본 발명의 다른 목적은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 개선용 사료 첨가제를 제공하는 것이다.Another object of the present invention is to provide a feed additive for preventing or improving keratoconjunctivitis keratoconjunctivitis, comprising a mixture of quercetin and Hojang root stem extract.
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 치료용 악?e적 조성물을 제공할 수 있다. The present invention can provide a malignant composition for preventing or treating keratoconjunctivitis sicca, comprising a mixture of quercetin and Hojanggeun stem extract.
상기 호장근 줄기 추출물은 열수 추출물일 수 있다.The hojanggeun stem extract may be a hot water extract.
상기 케르세틴 및 호장근 줄기 추출물은 1:10 내지 1:1의 중량비율로 혼합되는 것일 수 있다.The quercetin and hojanggeun stem extract may be mixed in a weight ratio of 1:10 to 1:1.
상기 건성각결막염은 면역질환, 노화, 당뇨, 외상 및 환경성으로 이루어진 군으로부터 선택되는 어느 하나 이상 것으로 인할 수 있다.The keratoconjunctivitis sicca may be due to any one or more selected from the group consisting of immune diseases, aging, diabetes, trauma and environmental factors.
상기 케르세틴 및 호장근 줄기 추출물의 혼합물의 농도는 1 내지 1000mg/kg일 수 있다.The concentration of the mixture of the quercetin and hojanggeun stem extract may be 1 to 1000mg / kg.
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 개선용 건강기능식품조성을 제공할 수 있다. The present invention can provide a health functional food composition for preventing or improving keratoconjunctivitis sicca, comprising a mixture of quercetin and hojanggeun stem extract.
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 동물의 건성각결막염 예방 또는 치료용 수의학적 조성물을 제공할 수 있다. The present invention may provide a veterinary composition for preventing or treating keratoconjunctivitis sicca in animals, comprising a mixture of quercetin and rhizome stem extract.
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 개선용 사료 첨가제를 제공할 수 있다. The present invention may provide a feed additive for preventing or improving keratoconjunctivitis sicca, comprising a mixture of quercetin and rhizome stem extract.
본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물은 각막상피세포를 이용한 세포실험에서 건조스트레스로 유발되는 염증인자인 IL-1β, IL-8 및 TNF-α의 발현을 감소시키고, 개 임상시험에서 건성각결막염 증상을 보이는 환견의 눈물분비량을 증가시켜 건조증상을 완하하는 효과가 우수 하였다. The mixture of quercetin and rhizome stem extract of the present invention reduces the expression of inflammatory factors IL-1β, IL-8 and TNF-α, which are inflammatory factors induced by drying stress, in a cell experiment using corneal epithelial cells, and reduces dryness in a dog clinical trial. The effect of relieving dry symptoms was excellent by increasing tear secretion in patients with keratoconjunctivitis symptoms.
도 1은 케르세틴 및 호장근 줄기 추출물의 혼합물의 각막상피세포에서 건조스트레스로 유발된 세포손상 예방 및 염증인자인 IL-1β, IL-8 및 TNF-α의 발현 억제 효과를 확인한 결과이다.
도 2는 개 임상시험에서 건성각결막염을 보이는 환견에 케르세틴 및 호장근 줄기 추출물의 혼합물을 200mg/day의 농도로 6주일간 투여하면서 투여전, 투여 21일 후, 투여 42일 후 쉬머 눈물 검사 (Schirmer tear test)를 하는 결과이다.
도 3은 개 임상시험에서 건성각결막염을 보이는 환견에 케르세틴 및 호장근 줄기 추출물의 혼합물을 200mg/day의 농도로 6주일간 경구 투여한 뒤, 눈물 분비량을 측정한 결과이다. 1 is a result confirming the effect of a mixture of quercetin and a rhizome stem extract to prevent cellular damage induced by drying stress in corneal epithelial cells and to inhibit the expression of IL-1β, IL-8 and TNF-α, which are inflammatory factors.
2 is a shimmer tear test (Schirmer) before administration, 21 days after administration, and 42 days after administration, while administering a mixture of quercetin and rhizome spp. It is the result of the tear test).
3 is a result of measuring the amount of tear secretion after oral administration of a mixture of quercetin and rhododendron stem extract at a concentration of 200 mg/day for 6 weeks to a dog with keratoconjunctivitis sicca in a dog clinical trial.
이하에서 본 발명을 자세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명자들은 개 고양이 건성각결막염 예방 및 치료용 수의학적 약학 조성물을 연구하던 중, 케르세틴 및 호장근 줄기 추출물의 혼합물이 각막상피세포를 이용한 세포실험에서 건조스트레스에 의한 세포손상을 예방하고 염증인자인 IL-1β, IL-8 및 TNF-α의 발현을 억제하고 (도 1), 개 임상시험에서 건성각결막염 환견의 눈물분비량을 증가시키는 효능(도 2 및 도 3)을 확인하여 본 발명을 완성하였다. While the present inventors were studying a veterinary pharmaceutical composition for preventing and treating keratoconjunctivitis sicca in dogs and cats, a mixture of quercetin and rhizome stem extract prevented cellular damage caused by drying stress in a cell experiment using corneal epithelial cells and was an inflammatory factor. The present invention was completed by confirming the efficacy of inhibiting the expression of IL-1β, IL-8 and TNF-α (FIG. 1) and increasing the amount of tear secretion in dogs with keratoconjunctivitis sicca in dog clinical trials (FIGS. 2 and 3) did
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는, 건성각결막염 예방 또는 치료용 약학적 조성물을 제공하는 것이다.The present invention is to provide a pharmaceutical composition for preventing or treating keratoconjunctivitis keratoconjunctivitis, comprising a mixture of quercetin and Hojang root stem extract.
본 발명은 각막상피세포를 이용한 세포실험에서 건조스트레스에 의한 세포손상 및 염증인자인 IL-1β, IL-8 및 TNF-α의 발현을 케르세틴 및 호장근 줄기 추출물의 혼합물이 억제할 뿐만 아니라, 호장근 단독 및 케르세틴 단독으로 투여한 것 보다 효과가 우수하였으며 (도 1), 개 임상시험에서 건성각결막염 증상을 보이는 환견에 케르세틴 및 호장근 줄기 추출물의 혼합물을 200mg/day의 농도로 6주일간 경구 투여한 후 눈물분비량이 증가함 (도 2 및 도 3)을 확인하였다. 따라서 케르세틴 및 호장근 줄기 추출물의 혼합물이 개 고양이의 건성각결막염에 효과적인 것을 확인하였다. In a cell experiment using corneal epithelial cells, a mixture of quercetin and rhizome stem extract inhibits the cell damage caused by drying stress and the expression of inflammatory factors IL-1β, IL-8 and TNF-α, The effect was superior to that administered alone and quercetin alone (FIG. 1), and in a dog clinical trial, a mixture of quercetin and rhododendron stem extract was orally administered at a concentration of 200 mg/day to a dog showing symptoms of keratoconjunctivitis sicca for 6 weeks. After this, it was confirmed that the amount of tear secretion increased ( FIGS. 2 and 3 ). Therefore, it was confirmed that the mixture of quercetin and rhizome stem extract was effective for keratoconjunctivitis sicca in dogs and cats.
호장근은 예를 들면 학명 Polygonum cuspidatum인 호장근일 수 있으나, 이에 제한되는 것은 아니다.The rhomboid root may be, for example , an rhomboid root of the scientific name Polygonum cuspidatum , but is not limited thereto.
상기 각 약재의 추출 부위는 잎 및 줄기이며, 바람직하게는 줄기를 사용할 수 있다.The extraction site of each drug is a leaf and a stem, and preferably a stem may be used.
추출 용매는 특별히 한정되지 않으며, 예를 들면, 물 또는 유기용매를 사용할 수 있고, 유기용매로는 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol) 등을 포함하는 탄소수 1 내지 4의 알코올, 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylene chloride), 헥산(hexane) 및 시클로헥산 (cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있으나, 이에 제한되지는 않는다. 바람직하게는 물을 사용할 수 있다.The extraction solvent is not particularly limited, and for example, water or an organic solvent may be used, and the organic solvent is methanol, ethanol, propanol, isopropanol, butanol, etc. containing 1 to 4 alcohols, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclo Various solvents, such as hexane (cyclohexane), may be used alone or in combination, but is not limited thereto. Preferably, water can be used.
추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법 중 어느 하나를 선택하여 사용할 수 있으며, 바람직하게는 열수추출법일 수 있다. 또한, 목적하는 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다. 본 발명에 따른 추출물의 제조방법에는 제한이 없으며, 공지되어 있는 어떠한 방법도 이용될 수 있다. 열수 추출의 경우의 구체적인 예를 들자면, 약재 중량의 3 내지 20배, 구체적으로 10배의 물을 가하여, 온도 80 내지 100℃, 구체적으로 90℃로 1시간 내지 24시간, 구체적으로 8시간 추출할 수 있으나, 이에 제한되는 것은 아니다.As the extraction method, any one of methods such as hot water extraction method, cold extraction method, reflux cooling extraction method, solvent extraction method, steam distillation method, ultrasonic extraction method, elution method, compression method, etc. can be selected and used, and it may be preferably a hot water extraction method. In addition, the desired extract may be further subjected to a conventional fractionation process, and may be purified using a conventional purification method. There is no limitation on the method for preparing the extract according to the present invention, and any known method may be used. As a specific example in the case of hot water extraction, 3 to 20 times, specifically, 10 times the weight of the drug is added, and the temperature is 80 to 100 ° C., specifically 90 ° C. for 1 hour to 24 hours, specifically for 8 hours. However, the present invention is not limited thereto.
발명에 따른 추출물은 상기 추출 이후에 필요에 따라 여과, 농축, 건조 등의 공정을 행한 것일 수 있다. 그러나 조건은 한정되지 않고 당 분야에 공지된 방법, 통상적으로 행해지는 조건으로 수행될 수 있다.The extract according to the present invention may be subjected to a process such as filtration, concentration, drying, etc. as needed after the extraction. However, the conditions are not limited and may be carried out by methods known in the art, and conditions commonly used.
케르세틴은 하기의 화학식을 가지는 화합물 또는 약학적으로 허용되는 염을 포함할 수 있다. Quercetin may include a compound having the following formula or a pharmaceutically acceptable salt.
[화학식][Formula]
상기 케르세틴 및 호장근 줄기 추출물의 함량비는 특별히 한정되지 않으나, 케르세틴 및 호장근 줄기 추출물은 1:10 내지 1:1의 중량비율로 혼합되는 것이 바람직하고, 1:3의 중량비율로 혼합하는 것이 가장 바람직하다.The content ratio of the quercetin and the rhizome extract is not particularly limited, but the quercetin and the rhododendron stem extract are preferably mixed in a weight ratio of 1:10 to 1:1, and mixing in a weight ratio of 1:3 Most preferred.
상기 건성각결막염은 면역질환, 노화, 당뇨, 외상 및 환경성으로 이루어진 군으로부터 선택되는 어느 하나 이상 것으로 인할 수 있고, 바람직하게는 노화일 수 있으나, 이에 제한되는 것은 아니다.The keratoconjunctivitis sicca may be due to any one or more selected from the group consisting of immune diseases, aging, diabetes, trauma and environmental factors, and may preferably be aging, but is not limited thereto.
상기 케르세틴 및 호장근 줄기 추출물의 혼합물의 농도는 특별히 한정되지 않으며, 바람직하게는 1 내지 1000 mg/kg일 수 있고 더 바람직하게는 200 mg/kg일 수 있다.The concentration of the mixture of the quercetin and hojanggeun stem extract is not particularly limited, and may preferably be 1 to 1000 mg/kg, and more preferably 200 mg/kg.
상기 조성물은 그 용도에 따라 상기 혼합물을 유효한 양, 또는 유효 성분으로서 포함할 수 있다. 상기 유효한 양은 개체에 따라 적절하게 선택할 수 있다. 질환 내지 상태의 중증도, 개체의 연령, 체중, 건강, 성별, 개체의 추출물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 투여 기간, 상기 조성물과 배합 또는 동시 사용되는 다른 조성물을 포함한 요소 및 기타 생리 내지 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.The composition may contain the mixture in an effective amount or as an active ingredient according to its use. The effective amount can be appropriately selected depending on the individual. the severity of the disease or condition, the subject's age, weight, health, sex, the subject's sensitivity to the extract, the time of administration, the route of administration and the rate of excretion, the duration of administration, factors including other compositions used in combination with or concurrently with the composition, and others It may be determined according to factors well known in the field of physiology or medicine.
본 발명에 따른 상기 추출물을 포함하는 의학적 약학 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 점안제 (eye drop), 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition comprising the extract according to the present invention, each of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. oral dosage forms, eye drops, external preparations, It can be formulated and used in the form of suppositories and sterile injectable solutions.
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 개선용 건강기능식품 조성물을 제공할 수 있다. 상기 케르세틴 및 호장근 줄기 추출물은 상기 약학적 조성물에서 사용된 것과 같으므로 상기 기재로 설명을 대신한다. The present invention may provide a health functional food composition for preventing or improving keratoconjunctivitis sicca, comprising a mixture of quercetin and hojanggeun stem extract. Since the quercetin and rhizome stem extract are the same as those used in the pharmaceutical composition, the description is replaced with the above description.
본 발명에 따른 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 일반 식품으로는 이에 한정되지 않지만 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마아말레이드 등), 어류, 육류 및 그 가공식품(예: 햄, 소시지 콘비이프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게이트, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치이즈 등), 식용 식물 유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물을 첨가하여 제조할 수 있다. 또한, 영양보조제로는 이에 한정되지 않지만 캡슐, 타블렛, 환 등에 본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물을 첨가하여 제조할 수 있다. 또한, 건강기능식품으로는 이에 한정되지 않지만 예를 들면, 본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용(건강음료)할 수 있도록 액상화, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다. 또한, 본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물과 건성각결막염 예방 또는 개선 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다. The food composition according to the present invention can be prepared in various forms according to conventional methods known in the art. Common foods include, but are not limited to, beverages (including alcoholic beverages), fruits and their processed foods (eg, canned fruit, bottled, jam, marmalade, etc.), fish, meat and their processed foods (eg, ham, sausages) Corn beef, etc.), breads and noodles (eg udon noodles, soba noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, syrup, dairy products (eg butter, cheese, etc.), edible vegetable oils and fats, margarine , vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.) can be prepared by adding a mixture of quercetin and hojang root stem extract of the present invention. In addition, the nutritional supplement is not limited thereto, but it can be prepared by adding a mixture of quercetin and rhizome stem extract of the present invention to capsules, tablets, pills, and the like. In addition, the health functional food is not limited thereto, but for example, the mixture of quercetin and rhizome extract of the present invention is prepared in the form of tea, juice, and drink, and liquefied and granulated so that it can be consumed (health drink). , can be ingested by encapsulating and powdering. In addition, in order to use the mixture of quercetin of the present invention and the rhizome extract of the present invention in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate. In addition, it can be prepared in the form of a composition by mixing a mixture of quercetin and rhizome stem extract of the present invention and a known active ingredient known to be effective in preventing or improving keratoconjunctivitis sicca.
본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물을 건강음료로 이용하는 경우, 상기 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연탄수화물의 비율은 본 발명의 조성물 100 mL 당 일반적으로 약 0.01 ～ 0.04 g, 바람직하게는 약 0.02 ～ 0.03g 이다.In the case of using the mixture of quercetin of the present invention and the rhizome stem extract as a health drink, the health drink composition may contain various flavoring agents or natural carbohydrates as additional ingredients, as in a conventional drink. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol. Sweeteners include natural sweeteners such as taumatine, stevia extract; A synthetic sweetener such as saccharin or aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물은 건성각결막염 예방 또는 개선용 식품 조성물의 유효성분으로 함유될 수 있는데, 그 양은 건성각결막염 예방 및 개선 작용을 달성하기에 유효한 양으로 특별히 한정되는 것은 아니나, 전체 조성물 총 중량에 대하여 0.01 내지 100 중량%인 것이 바람직하다. 본 발명의 식품 조성물은 케르세틴 및 호장근 줄기 추출물의 혼합물과 함께 건성각결막염 예방 및 개선용 조성물에 효과가 있는 것으로 알려진 다른 활성 성분과 함께 혼합하여 제조될 수 있다. The mixture of quercetin and Hojang root stem extract of the present invention may be contained as an active ingredient in a food composition for preventing or improving keratoconjunctivitis sicca, and the amount is particularly limited to an effective amount to achieve the prevention and improvement action of keratoconjunctivitis sicca. However, it is preferably 0.01 to 100% by weight based on the total weight of the entire composition. The food composition of the present invention may be prepared by mixing with a mixture of quercetin and rhizome stem extract with other active ingredients known to be effective in the composition for preventing and improving keratoconjunctivitis sicca.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid, pectic acid salts, alginic acid, alginic acid salts, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, It may contain glycerin, alcohol or a carbonation agent and the like. In addition, the health food of the present invention may contain fruit for the production of natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명은 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 동물의 건성각결막염 예방 또는 치료용 수의학적 조성물을 제공할 수 있다. The present invention may provide a veterinary composition for preventing or treating keratoconjunctivitis sicca in animals, comprising a mixture of quercetin and rhizome stem extract.
본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 수의학적 조성물은 통상의 방법에 따른 적절한 부형제 및 희석제를 더 포함할 수 있다. 본 발명의 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 수의학적 조성물에 포함될 수 있는 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 세탄올, 스테아릴알콜, 유동파라핀, 솔비탄모노스테아레이트, 폴리소르베이트 60, 메칠파라벤, 프로필파라벤 및 광물유를 들 수 있다.The veterinary composition comprising a mixture of quercetin and rhizomes stem extract of the present invention may further include an appropriate excipient and diluent according to a conventional method. Excipients and diluents that may be included in the veterinary composition comprising a mixture of quercetin and rhizome stem extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum , alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearate aryl alcohol, liquid paraffin, sorbitan monostearate,
본 발명에 따른 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 수의학적 조성물은 충진제, 항응집제, 윤활제, 습윤제, 향신료, 유화제, 방부제 등을 추가로 포함할 수 있는데, 본 발명에 의한 수의학적 조성물은 동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 잘 알려진 방법을 사용하여 제형화될 수 있고, 제형은 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 용액, 시럽, 에어로졸, 연질 또는 경질 젤라틴 캅셀, 좌제, 멸균 주사용액, 멸균 외용제, 점안제 (eye drop) 등의 형태일 수 있다.The veterinary composition comprising a mixture of quercetin and rhizome stem extract according to the present invention may further include a filler, an anti-aggregant, a lubricant, a wetting agent, a spice, an emulsifier, a preservative, and the like. Can be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to an animal, the formulations being powders, granules, tablets, capsules, suspensions, emulsions, solutions , syrup, aerosol, soft or hard gelatin capsules, suppositories, sterile injection solutions, sterile external preparations, eye drops, and the like.
본 발명에 의한 수의학적 조성물은 그 용도에 따라 상기 추출물을 유효한 양, 또는 유효 성분으로서 포함할 수 있다. 상기 유효한 양은 동물의 개체에 따라 적절하게 선택할 수 있다. 질환 내지 상태의 중증도, 개체의 연령, 체중, 건강, 성별, 개체의 추출물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 투여 기간, 상기 조성물과 배합 또는 동시 사용되는 다른 조성물을 포함한 요소 및 기타 생리 내지 수의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.The veterinary composition according to the present invention may contain the extract in an effective amount or as an active ingredient, depending on its use. The effective amount can be appropriately selected depending on the individual of the animal. the severity of the disease or condition, the subject's age, weight, health, sex, the subject's sensitivity to the extract, the time of administration, the route of administration and the rate of excretion, the duration of administration, factors including other compositions used in combination with or concurrently with the composition, and others It may be determined according to factors well known in the field of physiology or veterinary medicine.
본 발명은 또한 케르세틴 및 호장근 줄기 추출물의 혼합물을 포함하는 건성각결막염 예방 또는 개선용 기능성 사료 첨가제를 제공할 수 있다. The present invention may also provide a functional feed additive for preventing or improving keratoconjunctivitis keratoconjunctivitis, comprising a mixture of quercetin and rhizome stem extract.
상기 조성물이 기능성 사료 첨가제인 경우, 당해 기술분야에 공지되어 있는 통상적인 사료의 제형으로 제제화될 수 있다. 상기 사료용 조성물은 예를 들어 산제, 과립제, 정제, 환제, 캅셀제, 현탁액, 유제, 시럽제, 침제, 액제, 엑스제 등의 일반적인 제형으로 제조될 수도 있고, 임의의 사료 형태로 제조될 수도 있다. 상기 사료의 제제화를 위해 수의영양학적으로 허용 가능한 첨가제를 사용할 수 있으며, 제조하고자 하는 제형의 제조에 당해 기술분야에서 사용 가능한 것으로 공지되어 있는 임의의 첨가제가 이용될 수 있다. When the composition is a functional feed additive, it may be formulated in a formulation of a conventional feed known in the art. The composition for feed may be prepared in general formulations such as powders, granules, tablets, pills, capsules, suspensions, emulsions, syrups, needles, liquids, extracts, etc., or may be prepared in any form of feed. A veterinary and nutritionally acceptable additive may be used for formulating the feed, and any additive known to be usable in the art may be used for the preparation of the dosage form to be prepared.
상기 기능성사료 조성물 중의 상기 혼합물의 함량은 사용 목적(예방 또는 개선)에 따라 적합하게 결정될 수 있다. 일반적으로, 전체 사료 중량의 1 내지 20 중량%로 포함할 수 있다. The content of the mixture in the functional feed composition may be suitably determined according to the purpose of use (prevention or improvement). In general, it may be included in 1 to 20% by weight of the total feed weight.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예 1. 케르세틴 및 호장근 줄기 추출물의 혼합물의 제조Example 1. Preparation of a mixture of quercetin and rhododendron stem extract
케르세틴은 Sigma aldrich (USA)에서 구입하였으며, 호장근 줄기는 영천영농조합 (영천, 경상북도, 한국)에서 구입하여 사용하였다. 용기에 호장근 (Polygonum cuspidatum) 줄기 100중량부를 넣고, 물 1000 중량부를 넣었다. 이후 70℃로 3시간 동안 열수 추출하여 추출물을 얻고, 상기 추출물을 추출액의 2/3까지 농축한 후 동결건조하여 추출물을 얻었다. 이후 케르세틴과 호장근 줄기 추출물을 중량비 1:3으로 혼합하여 케르세틴+호장근 혼합물을 얻었다. Quercetin was purchased from Sigma aldrich (USA), and the stems of rhododendrons were purchased from the Yeongcheon Agricultural Cooperative (Yeongcheon, Gyeongsangbuk-do, Korea). Hojanggeun ( Polygonum cuspidatum ) 100 parts by weight of the stem was put in a container, and 1000 parts by weight of water was added. Then, hot water extraction was performed at 70° C. for 3 hours to obtain an extract, and the extract was concentrated to 2/3 of the extract and then freeze-dried to obtain an extract. Thereafter, quercetin and rhododendron stem extract were mixed at a weight ratio of 1:3 to obtain a mixture of quercetin + rhododendron.
실시예 2. 각막상피세포에서 건조스트레 의한 염증인자 발현에 케르세틴 단독, 호장근 줄기 추출물 단독 또는 케르세틴+호장근 혼합물이 미치는 효과 확인Example 2. Confirmation of the effect of quercetin alone, rhododendron stem extract alone, or quercetin + rhizome mixture on the expression of inflammatory factors caused by drying strain in corneal epithelial cells
상기 실시예 1에서 제조한 케르세틴+호장근 혼합물이 건조스트레스로 유도한 각막상피세포의 염증인자 발현에 미치는 영향을 확인하기 위하여, 다음의 세포실험을 실시하였다. 각막 상피 세포 (PCS-700-010, American Type Culture Collection, Manassas, VA, USA)를 성장 보충제를 포함하는 각막 상피 세포 기본 배지에서 배양하였다. 건조스트레스를 유발하기 전 케르세틴 단독, 호장근 추출물 단독, 케르세틴+호장근 혼합물을 24시간 동안 사전 처리하였다. 그 후 배지를 제거하여 25분간 공기에 노출 시켜 건조 스트레스를 유도하였다. 그 후에 MTS 분석 키트((Promega Corporation)를 이용하여 세포 생존을 실험한 결과, 케르세틴+호장근 혼합물이 용량 의존적으로 건조 스트레스에서 세포 생존력을 증가시켰으며, 케르세틴 단독 또는 호장근 추출물 보다 동일한 농도에서 세포생존력을 더 많이 증가시켰다 (도 1A). 또한 각막상피세포에서 mRNA를 추출하여 염증유발인자 IL-1β, IL-8, TNF-α의 발현을 PCR을 통해 확인하였다. Trizol 시약 (Invitrogen, Carlsbad, CA, USA)을 사용하여 각막상피세포의 총 RNA를 추출하고, M-MLV 역전사 효소 (Bioneer, 대전, 한국)를 사용하여 cDNA를 합성하였다. PCR은 2x SYBR Green PCR Master Mix (SYBR Premix Ex Taq, TaKaRa, Tokyo, Japan)와 함께 iQ5 Continuous Fluorescence Detector System (Bio-Rad, CA, USA)을 사용하여 수행되었다. 모든 절차는 제조업체의 지시에 따라 수행되었다. 프라이머 서열은 하기 표 1과 같다. 그 결과 IL-1β, IL-8 및 TNF-α의 mRNA 발현은 유의하게 건조 상태에서 증가하였고, 케르세틴 + 호장근 혼합물에 의해 감소하였으며, 케르세틴 단독 또는 호장근 줄기 추출물 보다 동일한 농도에서 더 많이 감소시켰다. (도 1B). 이를 통해 본 케르세틴 및 호장근 줄기 추출물의 혼합물이 건조스트레스에 의해 각막상피세포에 유발된 염증을 억제한다는 것을 알 수 있었다.In order to confirm the effect of the mixture of quercetin + rhizome prepared in Example 1 on the expression of inflammatory factors in the corneal epithelial cells induced by drying stress, the following cell experiment was performed. Corneal epithelial cells (PCS-700-010, American Type Culture Collection, Manassas, VA, USA) were cultured in corneal epithelial cell basal medium containing growth supplements. Before inducing drying stress, quercetin alone, rhododendron extract alone, and a mixture of quercetin + rhododendron were pre-treated for 24 hours. After that, the medium was removed and exposed to air for 25 minutes to induce drying stress. After that, cell viability was tested using the MTS assay kit ((Promega Corporation). As a result, the quercetin + ligamentous root extract dose-dependently increased cell viability under dry stress. Viability was further increased (Fig. 1A).In addition, by extracting mRNA from corneal epithelial cells, the expression of proinflammatory factors IL-1β, IL-8, TNF-α was confirmed by PCR.Trazol reagent (Invitrogen, Carlsbad, CA, USA) was used to extract total RNA from corneal epithelial cells, and cDNA was synthesized using M-MLV reverse transcriptase (Bioneer, Daejeon, Korea) PCR was performed using 2x SYBR Green PCR Master Mix (SYBR Premix Ex Taq). , TaKaRa, Tokyo, Japan) together with iQ5 Continuous Fluorescence Detector System (Bio-Rad, CA, USA) was carried out.All procedures were performed according to the manufacturer's instructions.The primer sequence is shown in Table 1 below. Results The mRNA expression of IL-1β, IL-8, and TNF-α was significantly increased in the dry state, decreased by the quercetin + rhizome mixture, and was decreased more at the same concentration than quercetin alone or rhizome stem extract. (FIG. 1B) From this, it was found that the mixture of quercetin and rhizome stem extract inhibited inflammation induced in corneal epithelial cells by drying stress.
실시예 3. 개 임상시험에서 케르세틴+호장근 혼합물이 건성각결막염 환견 눈물 분비량에 미치는 영향 확인Example 3. Confirmation of the effect of quercetin + sphincter muscle mixture on tear secretion in dogs with keratoconjunctivitis sicca in a dog clinical trial
동물병원에 내원한 건성각결막염 증상을 보이는 환견을 무작위로 무처치군과 케르세틴+호장근 혼합물 투여군 두 군으로 나누었다. 혼합물 투여전 모든 환견에서 쉬머르 눈물량 검사(Schirmer tear test)를 실시하였다. 눈물량 검사지를 눈꺼풀 외측 끝 부위 안구표면에 접촉시킨 후 30초 후 눈물에 의해 검사지의 색이 변한 길이를 측정하였다. 이후 6주간 케르세틴+호장근 혼합물 200mg/day을 1일 1회씩 경구투여 하였다. 약물 투여후 3주후 및 6주후에 눈물 분비량을 쉬머르 눈물량 검사를 통해 다시 측정하여 분석하였다. 그 결과, 도 2 및 도 3A에 나타난 바와 같이 시험군인 케르세틴+호장근 혼합물 투여군의 좌안 및 우안 모두 눈물 분비량이 증가하는 경향이 나타났으며, 도 3B에 나타난 바와 같이 약물 투여전 눈문분비량을 O%으로 하고 약물 투여후 늘어난 눈물량의 비율로 환산한 결과 무처치군인 대조군 우안은 눈물양이 0.4%가량 감소하였지만, 케르세틴+호장근 혼합물 투여군인 시험군의 우안에서는 눈물양이 1.5% 증가함이 확인되었고, 좌안은 2%가량 눈물분비량이 증가되는 것을 확인하였다. 이를 통해 케르세틴+호장근 혼합물이 건성각결막염 환견에서 눈물분비량을 촉진하여 증상을 개선하는 효과가 있음을 확인하였다. Dogs with symptoms of keratoconjunctivitis sicca who visited the veterinary hospital were randomly divided into two groups: an untreated group and a group administered with a quercetin+hojang muscle mixture. Before administration of the mixture, Schirmer tear test was performed on all dogs. After contacting the tear quantity test strip to the ocular surface at the outer edge of the eyelid, the length of the test strip's color change due to tears was measured 30 seconds later. After that, 200 mg/day of a mixture of quercetin + rhizomes was orally administered once a day for 6 weeks. After 3 weeks and 6 weeks after drug administration, the amount of tear secretion was measured and analyzed again through the Schimer tear test. As a result, as shown in FIGS. 2 and 3A , both the left and right eyes of the test group administered with a mixture of quercetin + sphincter showed a tendency to increase tear secretion, and as shown in FIG. As a result of converting to the ratio of increased tear volume after drug administration, the tear volume decreased by 0.4% in the untreated control right eye, but it was confirmed that the tear volume increased by 1.5% in the right eye of the test group administered with the quercetin + hojanggeun mixture. It was confirmed that the tear secretion was increased by 2% in the left eye. Through this, it was confirmed that the mixture of quercetin + rhizome sicca was effective in improving symptoms by promoting tear secretion in dogs with keratoconjunctivitis sicca.
Claims (9)
[화학식 1]
[Formula 1]
A feed additive for preventing or improving keratoconjunctivitis keratoconjunctivitis, comprising a mixture of quercetin and Hojang root stem extract.
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