KR101692546B1 - A Multivitamin Composition for Alleviating Thyroid Disorders - Google Patents
A Multivitamin Composition for Alleviating Thyroid Disorders Download PDFInfo
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- KR101692546B1 KR101692546B1 KR1020150110495A KR20150110495A KR101692546B1 KR 101692546 B1 KR101692546 B1 KR 101692546B1 KR 1020150110495 A KR1020150110495 A KR 1020150110495A KR 20150110495 A KR20150110495 A KR 20150110495A KR 101692546 B1 KR101692546 B1 KR 101692546B1
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- South Korea
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- vitamin
- selenium
- present
- composition
- thyroid
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- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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Abstract
Description
본 발명은 셀레늄, 비타민 C 및 비타민 E를 유효성분으로 포함하는 갑상선 질환의 예방, 완화, 개선 또는 치료용 복합비타민 조성물에 관한 것이다.The present invention relates to a multivitamin composition for preventing, alleviating, ameliorating or treating thyroid diseases comprising selenium, vitamin C and vitamin E as an active ingredient.
갑상선 관련 질환은 갑상선의 기능이 항진되어 갑상선 호르몬이 과도하게 생성되어 신체의 신진대사가 비정상적으로 증가하는 질환인 갑상선 기능 항진증과, 갑상선 호르몬의 결핍으로 인하여 전신의 대사 과정이 느려지는 질환인 갑상선 기능 저하증이 있다. 갑상선 기능 항진증의 경우 치료를 하지 않고 장시간 방치하는 경우 심장에 합병증을 초래하여 부정맥이나 심부전이 나타날 수 있으며, 폐경기 이후의 여성에서 골다공증을 악화시키는 원인이 된다. 갑상선 기능 저하증은 갑상선 자체의 이상으로 인한 일차성 갑상선 기능 저하증과 뇌하수체 이상으로 인한 이차성 갑상선 기능 저하증으로 나뉘며, 일차성 갑상선 기능 저하증의 경우 유전적 원인, 갑상선 적출 수술, 방사성 옥소의 투여, 만성 림프구성 갑상선 염증 등에 의해 갑상선 조직이 파괴되어 발생하며, 이차성 갑상선 기능 저하증의 경우 갑상선 호르몬의 분비를 자극하는 뇌하수체의 기능이 떨어진 경우에 발생한다. 이러한 갑상선 기능의 저하로 인해 대사 과정이 지나치게 느려지면 변비, 무기력, 부종, 피로, 기억력 감퇴, 월경과다, 근육통 등이 일어나고, 추위를 잘 견디지 못하며, 땀이 잘 나지 않고, 식욕은 감퇴되나 체중은 증가하게 된다.Thyroid-related diseases include hyperthyroidism, a disease in which the thyroid gland functions excessively and thyroid hormone is excessively produced and the metabolism of the body is abnormally increased, and thyroid gland function, which is a disease in which the metabolism of the whole body is slowed by the deficiency of thyroid hormone There is hypopnea. In the case of hyperthyroidism, if left untreated for a long time, it may cause cardiac complications, resulting in arrhythmia or heart failure, and it causes aggravation of osteoporosis in postmenopausal women. Hypothyroidism is divided into primary hypothyroidism due to hypothyroidism and hypothyroid hypothyroidism due to pituitary hypothyroidism. In the case of hypothyroid hypothyroidism, genetic cause, thyroidectomy, radioiodine administration, chronic lymphocytic Thyroid tissue is destroyed by thyroid inflammation and secondary hypothyroidism occurs when hypothyroid function that stimulates secretion of thyroid hormone is lost. If the metabolic process is slowed down by the loss of thyroid function, constipation, helplessness, edema, fatigue, memory loss, excessive menstruation, muscle aches, poor resistance to cold, poor appetite, .
최근 갑상선 관련질환 환자는 꾸준히 증가하는 추세이며, 국민건강보험공단 자료에 따르면 2002년부터 2009년까지 갑상선기능 저하증은 12만8천명에서 28만9천명으로 2.3배, 갑상선기능 항진증은 17만3천명에서 23만3천명으로 1.4배 증가하였으며, 기능 이상이 없더라도 자가면역 갑상선질환을 가지고 있는 환자들을 포함하면 그 수는 훨씬 많을 것으로 예상된다. Recently, the number of patients with thyroid-related diseases has been steadily increasing. According to the National Health Insurance Corporation data, from 2002 to 2009, the number of hypothyroidism was 2.3 times from 128,000 to 289,000, and the number of hyperthyroidism was 173,000 To 233,000. The number of patients with autoimmune thyroid disease is expected to be much higher, even if there are no abnormalities.
갑상선 기능이상을 유발하는 대표적인 질환으로 자가면역성 갑상선 질환인 그레이브스 병(Graves’disease) 및 하시모토 갑상선염(Hashimoto’s thyroiditis)이 있다. 이러한 질환의 병태생리학적 기전으로 자유 라디칼-매개 산화적 손상이 제시되고 있다. 이미 갑상선 기능 항진증 및 저하증 모두에서 체내 산화 대사물이 증가함과 동시에 항산화 물질인 비타민 E, A, 베타 카로틴 및 아스코르베이트가 감소함이 알려져 있고, 셀레늄은 갑상선 자가항체의 역가를 낮춰줌으로써 병의 경과를 호전시켜주는 것으로 알려져 있으나(Leonidas H. Duntas, J. Clin. Endocrinol. Metab., 95: 5180- 5188(2010)), 이러한 비타민 및 무기질 복합제를 복합 처리해야 하는지 또는 각각의 약물을 어느 범위에서 투여해야 항산화 효과로 인한 갑상선 질환 치료 효과가 있는지는 전혀 알려진 바 없다.The most common diseases that cause thyroid dysfunction are Graves' disease and Hashimoto's thyroiditis, which are autoimmune thyroid diseases. Free - radical - mediated oxidative damage has been suggested as a pathophysiological mechanism of these diseases. It is known that both the hyperoxia and hypothyroidism increase the body's oxidized metabolism and the vitamin E, A, beta carotene and ascorbate, which are antioxidative substances, are decreased. Selenium lowers the activity of the thyroid autoantibody, (Leonidas H. Duntas, J. Clin. Endocrinol . Metab., 95: 5180-5188 (2010)), but it is known that these vitamins and minerals should be combined, It is not known whether antioxidant effect is effective in treating thyroid disease.
기존의 종합 비타민 및 무기질 복합제는 갑상선 질환의 효율적인 치료를 위한 항산화 효과를 나타내지 못하며, 오히려 요오드 등 갑상선 기능에 영향을 줄 수 있는 성분이 포함된 경우 과량을 복용하였을 때 기능이상을 악화시킬 수 있는 위험이 있다. 따라서, 효율적으로 체내 산화적 손상을 감소시키면서 면역활성을 조절하여 자가면역성 갑상선 질환의 병태생리학적 기전을 전반적으로 억제하면서도 부작용이 없는 치료보조제의 개발이 요구되고 있다.Existing multivitamins and minerals do not exhibit antioxidant effects for effective treatment of thyroid disease. If they contain ingredients that can affect thyroid function, such as iodine, the risk of exacerbating dysfunction . Therefore, it is required to develop a therapeutic adjuvant which can suppress the pathophysiological mechanism of the autoimmune thyroid disease, while suppressing the oxidative damage in the body and controlling the immune activity, without side effects.
본 명세서 전체에 걸쳐 다수의 논문 및 특허문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
본 발명자들은 부작용이 없으면서도 우수한 항산화 효능 및 면역조절기능을 가지는 갑상선 질환의 예방, 개선, 완화 또는 치료용 조성물을 개발하기 위하여 예의 연구 노력하였다. 그 결과, 일정량의 셀레늄, 비타민 C 및 비타민 E를 1일 투여량으로 하여 투여하는 경우, 체내 산화적 손상을 크게 감소시키면서 면역활성을 조절하여 갑상선 질환을 완화할 수 있음을 확인함으로써, 본 발명을 완성하게 되었다.The present inventors have made intensive efforts to develop a composition for preventing, improving, alleviating or treating thyroid disease which has excellent antioxidant efficacy and immunomodulating function without side effects. As a result, it was confirmed that when a daily dose of selenium, vitamin C and vitamin E was administered, the thyroid disease could be alleviated by controlling the immune activity while greatly reducing the oxidative damage in the body, It was completed.
따라서 본 발명의 목적은 1일 투여량으로 일정량의 셀레늄, 비타민 C 및 비타민 E를 유효성분으로 포함하는 종합비타민 조성물을 제공하는 데 있다.Accordingly, an object of the present invention is to provide a multivitamin composition comprising a daily dose of selenium, vitamin C and vitamin E as an active ingredient.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 일 양태에 따르면, 본 발명은 셀레늄, 비타민 C 및 비타민 E를 유효성분으로 포함하며, 상기 셀레늄, 비타민 C 및 비타민 E는 1일 투여량이 다음과 같은 중량으로 구성된 종합비타민 조성물을 제공한다: (a) 100-200 μg 셀레늄; (b) 150-250 mg 비타민 C; 및 (c) 70-130 IU(International Unit) 비타민 E.According to one aspect of the present invention, there is provided a multivitamin composition comprising selenium, vitamin C and vitamin E as an active ingredient, wherein the daily dose of selenium, vitamin C and vitamin E is as follows: : (a) 100-200 [mu] g selenium; (b) 150-250 mg vitamin C; And (c) 70-130 IU (International Unit) vitamin E.
본 발명자들은 부작용이 없으면서도 우수한 항산화 효능 및 면역조절기능을 가지는 갑상선 질환의 예방, 개선, 완화 또는 치료용 조성물을 개발하기 위하여 예의 연구 노력하였다. 그 결과, 일정량의 비타민 C, 비타민 E 및 셀레늄을 1일 투여량으로 하여 투여하는 경우, 체내 산화적 손상을 크게 감소시키면서 면역활성을 조절하여 갑상선 질환을 완화할 수 있다는 사실을 확인하였다.The present inventors have made intensive efforts to develop a composition for preventing, improving, alleviating or treating thyroid disease which has excellent antioxidant efficacy and immunomodulating function without side effects. As a result, it was confirmed that when a daily dose of vitamin C, vitamin E and selenium is administered, thyroid disease can be alleviated by controlling immune activity while greatly reducing oxidative damage in the body.
본 발명에서 용어“갑상선 질환(thyroid gland disorder)”은 갑상선 기능의 이상으로 인하여 갑상선 호르몬의 분비가 과도하거나 또는 결핍되는 질환을 의미한다. 따라서 본 발명의 조성물로 치료되는 갑상선 질환은 갑상선 기능 항진증과 갑상선 기능 저하증을 모두 포함한다.The term " thyroid gland disorder " in the present invention means a disorder in which the secretion of thyroid hormone is excessive or deficient due to abnormal thyroid function. Accordingly, the thyroid disease treated with the composition of the present invention includes both hyperthyroidism and hypothyroidism.
갑상선 기능 항진증(hyperthyroidism)은 갑상선의 기능이 비정상적으로 활성화되어 갑상선 호르몬이 과도하게 생성됨으로서 신체의 신진대사가 비정상적으로 증가하는 질환이며, 갑상선 기능 저하증(hypothyroidism)은 갑상선 호르몬의 결핍으로 인하여 전신의 대사 과정이 느려지는 질환이다. 갑상선 기능 항진증 및 저하증 모두에서 체내 산화 대사물이 증가하며 항산화 물질인 비타민 A, 비타민 C, 비타민 E 및 베타 카로틴이 감소하므로, 본 발명의 조성물은 갑상선 기능 항진증 및 저하증 모두에 예방 및 치료 효과가 있다.Hyperthyroidism is a disorder in which the body's metabolism is abnormally increased due to abnormally activated thyroid function and excessive production of thyroid hormone. Hypothyroidism is caused by the deficiency of thyroid hormone, It is a disease that slows down the process. In both hyperthyroidism and hypothyroidism, the amount of oxidized metabolites in the body is increased and the antioxidant substances such as vitamin A, vitamin C, vitamin E and beta-carotene are reduced. Thus, the composition of the present invention has both prevention and therapeutic effects on hyperthyroidism and hypothyroidism .
본 발명에 따르면, 본 발명의 조성물에는 셀레늄, 비타민 C 및 비타민 E가 필수 구성으로 포함된다. 하기 실시예에서 입증한 바와 같이, 셀레늄, 비타민 C 및 비타민 E를 각각 투여하는 경우 및 셀레늄, 비타민 C 및 비타민 E 중 두 가지를 병행 투여하는 경우에는 활성산소종(ROS: reactive oxygen species)이 감소하지 않았으며, 셀레늄, 비타민 C 및 비타민 E를 모두 병행하여 투여하는 경우만이 유의적으로 활성산소종을 감소시킴을 확인할 수 있었다.According to the present invention, the composition of the present invention contains selenium, vitamin C and vitamin E as an essential constituent. As demonstrated in the following examples, when selenium, vitamin C and vitamin E are administered separately and when two kinds of selenium, vitamin C and vitamin E are administered in combination, reactive oxygen species (ROS) And it was confirmed that the simultaneous administration of selenium, vitamin C and vitamin E significantly reduced reactive oxygen species.
본 발명에 따르면, 본 발명의 조성물에는 (a) 135-400 μg 셀레늄; (b) 100-400 mg 비타민 C; 및 (c) 23-223 IU 비타민 E가 포함된다. IU는 인터네셔날 유닛(International Unit)으로 상기 비타민 E의 1 IU는 0.67 mg의 비타민 E를 의미한다. 따라서 본 발명의 조성물에 포함되는 상기 비타민과 셀레늄의 중량비를 계산하면 288.5:1-4069.7:1이다.According to the present invention, the composition of the present invention comprises (a) 135-400 μg selenium; (b) 100-400 mg vitamin C; And (c) 23-223 IU vitamin E. IU is an International Unit and 1 IU of Vitamin E means 0.67 mg of Vitamin E. Therefore, the weight ratio of the vitamin and selenium contained in the composition of the present invention is 288.5: 1-4069.7: 1.
1일 투여량으로 셀레늄을 135-400 μg 투여하는 경우의 60 kg 성인의 혈장 내 셀레늄 농도는 1.0-1.64 μM로 평가되고, 셀레늄, 비타민 C 및 비타민 E의 세 약물을 병행 투여하는 경우 하기 실시예에서 입증한 바와 같이, 셀레늄 농도가 1.0 및 5.0 μM인 경우 ROS 저감 효과가 있는바 1일 투여량으로 셀레늄을 135-400 μg 으로 투여하는 경우 갑상선 질환의 치료 효과가 있는 것으로 볼 수 있다.The selenium concentration in the plasma of 60 kg adults was estimated to be 1.0-1.64 μM when 135-400 μg of selenium was administered at a daily dose, and in the case of the simultaneous administration of three drugs of selenium, vitamin C and vitamin E, , There is a ROS reduction effect when the selenium concentration is 1.0 and 5.0 μM. When the daily dose of selenium is administered in the range of 135-400 μg, it can be considered to have a therapeutic effect of thyroid disease.
1일 투여량으로 비타민 C를 100-400 mg 투여하는 경우 혈장 내 비타민 C의 농도는 56-70 μM로 평가되고, 셀레늄, 비타민 C 및 비타민 E의 세 약물을 병행 투여하는 경우 하기 실시예에서 입증한 바와 같이, 비타민 C 농도가 50 및 70 μM인 경우 ROS 저감 효과가 있고 50 μM 이하의 농도에서는 ROS 저감 효과가 없다. 따라서 1일 투여량으로 비타민 C를 50-70 μM 투여하는 경우 갑상선 질환의 치료 효과가 있는 것으로 볼 수 있다.When 100-400 mg of vitamin C is administered at a daily dose, the concentration of vitamin C in the plasma is estimated to be 56-70 μM. When three drugs of selenium, vitamin C and vitamin E are administered concurrently, As shown above, vitamin C concentrations of 50 and 70 μM have ROS reduction effect and concentrations of 50 μM or less have no ROS reduction effect. Therefore, 50-70 μM of vitamin C at a daily dose can be considered as a therapeutic effect of thyroid disease.
1일 투여량으로 비타민 E를 23-223 IU(15.41-149.41 mg) 투여하는 경우 혈장 내 비타민 E의 농도는 10-30 μM로 평가되고, 셀레늄, 비타민 C 및 비타민 E의 세 약물을 병행 투여하는 경우 하기 실시예에서 입증한 바와 같이, 비타민 E 농도가 10 및 30 μM인 경우 ROS 저감 효과가 있고 10 μM 이하의 농도에서는 ROS 저감 효과가 없는바 1일 투여량으로 비타민 E를 10-30 μM 투여하는 경우 갑상선 질환의 치료 효과가 있는 것으로 볼 수 있다.When 23-223 IU (15.41-149.41 mg) of vitamin E is administered at a daily dose, the plasma vitamin E concentration is estimated to be 10-30 μM, and the three drugs selenium, vitamin C and vitamin E are administered concurrently As demonstrated in the following examples, there is an ROS reduction effect when the vitamin E concentration is 10 and 30 μM, and no ROS reduction effect when the concentration is 10 μM or less. In a daily dose of 10 to 30 μM vitamin E , It can be considered that there is a therapeutic effect of thyroid disease.
본 발명의 일 구현예에 따르면, 본 발명의 조성물에는 (a) 135-200 μg 셀레늄; (b) 100-220 mg 비타민 C; 및 (c) 85-150 IU 비타민 E가 포함된다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물에는 (a) 135-165 μg 셀레늄; (b) 150-220 mg 비타민 C; 및 (c) 85-120 IU 비타민 E가 포함된다. 본 발명의 어떠한 구현예에 따르면, 본 발명의 조성물에는 (a) 135-165 μg 셀레늄; (b) 180-220 mg 비타민 C; 및 (c) 90-110 IU 비타민 E가 포함된다. 본 발명의 특정 구현예에 따르면, 본 발명의 조성물에는 (a) 150 μg 셀레늄; (b) 200 mg 비타민 C; 및 (c) 100 IU 비타민 E가 포함된다.According to one embodiment of the present invention, the composition of the present invention comprises (a) 135-200 占 셀 selenium; (b) 100-220 mg vitamin C; And (c) 85-150 IU of vitamin E. According to another embodiment of the present invention, the composition of the present invention comprises (a) 135-165 占 셀 selenium; (b) 150-220 mg vitamin C; And (c) 85-120 IU of vitamin E. According to some embodiments of the present invention, the composition of the present invention comprises (a) 135-165 占 셀 selenium; (b) 180-220 mg vitamin C; And (c) 90-110 IU vitamin E. According to a particular embodiment of the invention, the composition of the present invention comprises (a) 150 [mu] g selenium; (b) 200 mg vitamin C; And (c) 100 IU of vitamin E.
본 발명의 조성물의 유효성분인 상기 셀레늄, 비타민 C 및 비타민 E는 상술한 범위의 1일 투여량으로 병행 투여됨으로써 자가면역 반응과 관련되어 있는 항산화 활성을 가진다(도 1).The selenium, vitamin C, and vitamin E, which are active ingredients of the composition of the present invention, have antioxidative activities associated with autoimmune reactions by being administered simultaneously in a daily dose in the above-mentioned range (Fig. 1).
본 발명의 일 구현예에 따르면, 본 발명의 종합비타민 조성물은 갑상선 질환의 예방, 완화, 개선 또는 치료용이다. 하기 실시예에서 입증한 바와 같이, 셀레늄, 비타민 C 및 비타민 E를 상술한 범위의 1일 투여량으로 투여하는 경우 매우 우수한 항산화 활성을 가져(도 1) 자가면역반응을 억제함을 확인하였으며, 따라서 본 발명의 조성물은 효율적인 갑상선 질환의 예방, 완화, 개선 또는 치료제로 이용될 수 있다.According to one embodiment of the present invention, the multivitamin composition of the present invention is for preventing, alleviating, improving or treating thyroid disease. As demonstrated in the following examples, it has been confirmed that administration of selenium, vitamin C and vitamin E at a daily dose in the above-mentioned range has a very excellent antioxidant activity (FIG. 1) The composition of the present invention can be used as an agent for preventing, alleviating, improving or treating an effective thyroid disease.
본 명세서에서 용어“치료”는 (a)질환, 질병 또는 증상의 발전의 억제; (b)질환, 질병 또는 증상의 경감; 또는 (c)질환, 질병 또는 증상을 제거하는 것을 의미한다. 본 발명의 조성물은 갑상선 질환 또는 이의 증상의 발전을 억제하거나, 이를 제거하거나 또는 경감시키는 역할을 하며, 이에 본 명세서에서 용어“치료” 또는“치료제”는“치료 보조”또는“치료 보조제”의 의미를 포함한다. As used herein, the term " treatment " includes (a) inhibiting the development of a disease, disorder or condition; (b) relief of the disease, disorder or condition; Or (c) eliminating the disease, disease or condition. The composition of the present invention inhibits the development of thyroid disease or symptoms thereof, eliminates or alleviates the symptoms thereof, and thus the term "treatment" or "therapeutic agent" is used herein to mean "therapeutic aid" .
본 명세서에서, 용어“예방”은 질환 또는 질병을 보유하고 있다고 진단된 적은 없으나, 이러한 질환 또는 질병에 걸릴 가능성이 있는 대상체에서 질환 또는 질병의 발생을 억제하는 것을 의미한다.As used herein, the term " prophylactic " means inhibiting the development of a disease or disease in a subject who has never been diagnosed as having a disease or disease, but is likely to suffer from such disease or disease.
본 명세서에서, 용어 “완화” 및 “개선”은 질환 또는 질병의 증상이 호전되거나 이롭게 되는 모든 행위를 의미한다.As used herein, the terms " alleviation " and " improvement " refer to any action that alleviates or alleviates the symptoms of a disease or disease.
본 발명의 다른 구현예에 따르면, 본 발명의 갑상선 질환은 자가면역성 갑상선 질환이다. 본 명세서에서 용어“자가면역성 갑상선 질환”은 갑상선에 대한 자가항체가 매개하는 면역반응에 의하여 갑상선 호르몬이 과다 분비되거나 또는 결핍되는 질환을 의미한다. 갑상선 호르몬 수용체에 대한 자가항체(Thyroid stimulating hormone receptor antibody, TRAb)가 생성되면 갑상선 호르몬이 과다 생산되어 갑상선 기능 항진증으로 진행하며, 반대로 갑상선 세포를 파괴하는 자가면역 항체(Thyroid stimulatory blocking antibody, TSBAb)가 생성되면 호르몬 분비가 감소하여 갑상선 기능 저하증으로 발전한다. 본 발명의 조성물은 자가항체의 생성을 억제하거나 불활성화시킴으로써 효율적으로 자가면역반응을 조절, 자가면역성 갑상선 질환을 치료 또는 예방할 수 있다.According to another embodiment of the present invention, the thyroid disease of the present invention is an autoimmune thyroid disease. As used herein, the term " autoimmune thyroid disease " refers to a disorder in which the thyroid hormone is excessively secreted or deficient by an immune response mediated by autoantibodies to the thyroid. When thyroid stimulating hormone receptor antibody (TRAb) is produced, the thyroid hormone is overproduced and progresses to hyperthyroidism. In contrast, thyroid stimulating blocking antibody (TSBAb), which destroys thyroid cells, When it is produced, it decreases hormone secretion and develops hypothyroidism. The composition of the present invention can effectively treat or prevent autoimmune thyroid disease by controlling the autoimmune response by inhibiting or inactivating the production of autoantibodies.
본 발명의 어떠한 구현예에 따르면, 본 발명의 자가면역성 갑상선 질환은 그레이브스 병(Graves’ disease), 하시모토 갑상선염(Hashimoto’s thyroiditis), 갑상선안병증 및 산후갑상선염(postpartum thyroiditis)으로 구성된 군으로부터 선택된다. 본 발명의 특정 구현예에 따르면, 본 발명의 자가면역성 갑상선 질환은 갑상선안병증이다.According to some embodiments of the present invention, the autoimmune thyroid disease of the present invention is selected from the group consisting of Graves' disease, Hashimoto's thyroiditis, thyroid ophthalmopathy and postpartum thyroiditis. According to certain embodiments of the present invention, the autoimmune thyroid disease of the present invention is thyroid ophthalmopathy.
본 발명의 셀레늄은 당업계에서 셀레늄을 공급할 수 있는 셀레나이트, 셀레노메티오닌 및 효모가 모두 포함될 수 있으나, 이에 한정되지 않는다. 본 발명의 일 구현예에 따르면, 본 발명의 셀레늄은 셀레노메티오닌(selenomethionine)이다.The selenium of the present invention may include, but is not limited to, selenite, selenomethionine, and yeast capable of supplying selenium in the art. According to one embodiment of the present invention, the selenium of the present invention is selenomethionine.
본 발명의 일 구현예에 따르면, 본 발명의 비타민 E는 RRR-알파-토코페롤(RRR-alpha-tocopherol)이다.According to one embodiment of the present invention, the vitamin E of the present invention is RRR-alpha-tocopherol.
본 발명의 일 구현예에 따르면, 본 발명의 셀레늄, 비타민 C 및 비타민 E는 (a) 135-200 μg 셀레늄; (b) 100-300 mg 비타민 C; 및 (c) 23-112 IU 비타민 E를 1일 투여량으로 한다. 따라서 본 발명의 조성물에 포함되는 상기 비타민과 셀레늄의 중량비를 계산하면 577.1:1-2778.1:1이다.According to one embodiment of the present invention, the selenium, vitamin C and vitamin E of the present invention comprise (a) 135-200 [mu] g selenium; (b) 100-300 mg vitamin C; And (c) 23-112 IU vitamin E per day. Therefore, the weight ratio of the vitamin to selenium contained in the composition of the present invention is 577.1: 1-2778.1: 1.
본 발명의 다른 구현예에 따르면, 본 발명의 종합비타민 조성물은 60 kg 성인을 기준으로 투여 후 혈장 내 셀레늄, 비타민 C 및 비타민 E의 농도가 (a) 1-5 μM 셀레늄; (b) 50-70 μM 비타민 C; 및 (c) 10-30 μM 비타민 E이다. 하기 실시예에서 입증한 바와 같이, 상기 농도의 셀레늄, 비타민 C 및 비타민 E를 세포에 처리한 경우 및 상기 세 유효성분 중 두 유효성분을 조합하여 병행 처리한 경우 ROS 감소 효과가 없었으나, 본 발명과 같이 상기 농도의 셀레늄, 비타민 C 및 비타민 E를 모두 병합하여 세포에 처리한 경우 유의한 ROS 감소 효과를 확인할 수 있었다. 본 발명의 일 구현예에 따르면, 상기 셀레늄 농도는 투여 후 16주 후의 농도이다. 본 발명의 일 구현예에 따르면, 상기 비타민 E 농도는 투여 후 0-72시간 후의 농도이다.According to another embodiment of the present invention, the multivitamin composition of the present invention has a concentration of selenium, vitamin C and vitamin E in plasma after administration of 60 kg of adult (a) 1-5 μM selenium; (b) 50-70 [mu] M Vitamin C; And (c) 10-30 < RTI ID = 0.0 > uM < / RTI > As demonstrated in the following examples, there was no effect of reducing ROS when cells were treated with selenium, vitamin C and vitamin E at the above concentrations, or when two active ingredients were used in combination, , It was possible to confirm a significant ROS reduction effect when the above concentrations of selenium, vitamin C and vitamin E were all incorporated into the cells. According to one embodiment of the present invention, the selenium concentration is the concentration after 16 weeks of administration. According to one embodiment of the present invention, the vitamin E concentration is 0-72 hours after administration.
본 발명의 일 구현예에 따르면, 본 발명의 종합비타민 조성물은 비타민 B-12 및 β-카로틴을 추가적으로 포함한다. 본 발명의 다른 구현예에 따르면, 상기 비타민 B-12 및 β-카로틴은 30-70 μg 비타민 B-12 및 2.6-4.6 mg β-카로틴을 1일 투여량으로 하여 추가적으로 포함된다. 본 발명의 어떠한 구현예에 따르면, 상기 비타민 B-12 및 β-카로틴은 40-60 μg 비타민 B-12 및 3.1-4.1 mg β-카로틴을 1일 투여량으로 하여 추가적으로 포함된다. 본 발명의 특정 구현예에 따르면, 상기 비타민 B-12 및 β-카로틴은 45-55 μg 비타민 B-12 및 3.3-3.8 mg β-카로틴을 1일 투여량으로 하여 추가적으로 포함된다. 본 발명의 다른 특정 구현예에 따르면, 상기 비타민 B-12 및 β-카로틴은 50 μg 비타민 B-12 및 3.6 mg β-카로틴을 1일 투여량으로 하여 추가적으로 포함된다.According to one embodiment of the present invention, the multivitamin composition of the present invention further comprises vitamin B-12 and? -Carotene. According to another embodiment of the present invention, the vitamin B-12 and? -Carotene are additionally contained in a daily dose of 30-70 μg vitamin B-12 and 2.6-4.6 mg β-carotene. According to some embodiments of the present invention, the vitamin B-12 and? -Carotene are additionally included in a daily dose of 40-60 μg vitamin B-12 and 3.1-4.1 mg β-carotene. According to a particular embodiment of the invention, the vitamin B-12 and beta -carotene are additionally included in a daily dose of 45-55 [mu] g vitamin B-12 and 3.3-3.8 mg [beta] -carotene. According to another particular embodiment of the invention, the vitamin B-12 and beta -carotene are additionally included in a daily dose of 50 [mu] g vitamin B-12 and 3.6 mg [beta] -carotene.
본 발명의 일 구현예에 따르면, 본 발명의 종합비타민 조성물은 1일 투여량을 하루에 2회로 나누어 투여한다.According to one embodiment of the present invention, the multivitamin composition of the present invention is administered in two daily doses per day.
본 발명의 조성물은 약제학적 조성물, 기능성 식품 조성물 또는 식품 조성물이다.The composition of the present invention is a pharmaceutical composition, a functional food composition or a food composition.
본 발명의 조성물이 약제학적 조성물로 제조되는 경우, 본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. 본 발명의 약제학적 조성물에 포함되는 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences(19th ed., 1995)에 상세히 기재되어 있다.When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약제학적 조성물은 경구 또는 비경구 투여할 수 있으며, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있다. 본 발명의 일 구현예에 따르면, 본 발명의 약제학적 조성물은 경구 투여한다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration or the like. According to one embodiment of the invention, the pharmaceutical composition of the present invention is administered orally.
본 명세서에서 용어“투여”는 어떠한 적절한 방법으로 환자에게 본 발명의 조성물을 도입하는 것을 의미한다.As used herein, the term " administering " means introducing a composition of the present invention to a patient in any suitable manner.
본 명세서에서 용어“대상체”는 제한없이 인간, 마우스, 래트, 기니아 피그, 개, 고양이, 말, 소, 돼지, 원숭이, 침팬지, 비비 또는 붉은털 원숭이를 포함한다. 바람직하게는, 본 발명의 대상체는 인간이다. As used herein, the term " subject " includes without limitation humans, mice, rats, guinea pigs, dogs, cats, horses, cows, pigs, monkeys, chimpanzees, baboons or rhesus monkeys. Preferably, the subject of the present invention is a human.
본 명세서에서 용어“유효량”은 대상체에게 투여했을 때 대상체가 고통받거나 고통받을 것이 예상되는 상태를 치료하거나, 최소한 이를 개선할 수 있는 있을 만큼 유효한 조성물의 양을 의미한다. As used herein, the term " effective amount " means an amount of a composition that is effective enough to treat, or at least ameliorate, a condition in which a subject is expected to suffer or suffer from pain when administered to the subject.
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명의 조성물이 기능성 식품 조성물로 제조되는 경우, 특별히 이에 제한되지 않으나, 음용수, 건강 기능성 식품, 영양 보조제, 영양제, 파머푸드(pharmafood), 건강 식품, 뉴트라슈티칼(nutraceutical), 디자이너 푸드, 식품 첨가제 등의 모든 형태의 식품이 될 수 있다. 바람직하게는, 광천수, 음료수, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 차, 드링크제, 알콜 음료 및 비타민 복합제 등의 형태일 수 있으며, 또한, 당업계에 알려진 통상의 식품 제조 시 첨가될 수 있다.When the composition of the present invention is manufactured from a functional food composition, it may be used in the form of a food composition such as a drinking water, a health functional food, a nutritional supplement, a nutrient, a pharmafood, a health food, a nutraceutical, Additives, and the like. It is preferably in the form of mineral water, beverage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, tea, And may also be added during the manufacture of conventional foods known in the art.
본 발명의 조성물이 식품 조성물로 제조되는 경우, 유효성분 뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라 이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트 린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스 파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 유효성분인 피페로날 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.When the composition of the present invention is prepared with a food composition, it includes not only the active ingredient, but also ingredients normally added during the manufacture of the food, including, for example, proteins, carbohydrates, fats, nutrients, flavoring agents and flavoring agents . Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared as a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract and licorice extract are added in addition to the active ingredient of the present invention .
본 발명의 특징 및 이점을 요약하면 다음과 같다:The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 1일 투여량으로 일정량의 셀레늄, 비타민 C 및 비타민 E를 유효성분으로 포함하는 종합비타민 조성물을 제공한다.(a) The present invention provides a multivitamin composition comprising a daily dose of selenium, vitamin C and vitamin E as an active ingredient.
(b) 본 발명의 조성물은 산화반응을 크게 감소시키고 갑상선 세포에 대한 자가면역 반응을 효율적으로 억제함으로써, 부작용 없고 치료 효능이 우수한 갑상선 질환 예방, 완화, 개선 또는 치료용 조성물로 유용하게 이용될 수 있다.(b) The composition of the present invention can be effectively used as a composition for preventing, alleviating, improving or treating a thyroid disease without side effects and excellent therapeutic effect by effectively reducing the oxidation reaction and effectively suppressing the autoimmune reaction to thyroid cells have.
(c) 본 발명의 조성물은 이미 갑상선 기능이상을 가지거나, 또는 정상적인 갑상선 기능을 유지 중인 자가면역성 갑상선염 환자들의 질병 경과에 보조적인 도움을 주는 치료 보조제 또는 기능성 식품으로도 응용될 수 있다.(c) The compositions of the present invention may also be used as therapeutic supplements or functional foods that assist the disease progression in patients with autoimmune thyroiditis that already have thyroid dysfunction or are maintaining normal thyroid function.
도 1은 안와 섬유모세포에 셀레늄, 비타민 C 및 비타민 E를 특정 농도로 각각 또는 병합 처리한 경우의 세포 내 ROS 생성 결과를 나타낸다. α-T: 비타민 E(alpha-tocopherol), Se: 셀레늄(selenium), AA: 비타민 C(ascorbic acid). *: P<0.05 vs. H2O2 처리에 의하여 자극된 안와 섬유모세포.
도 2는 본 발명의 실험에 사용된 농도의 셀레늄, 비타민 C 및 비타민 E의 독성 테스트 결과를 나타낸다.1 shows the results of intracellular ROS production when orbital fibroblasts are treated with selenium, vitamin C and vitamin E at specific concentrations or, respectively. α-T: alpha-tocopherol, Se: selenium, AA: ascorbic acid. *: P <0.05 vs. Orbital fibroblasts stimulated by H 2 O 2 treatment.
Figure 2 shows the toxicity test results of selenium, vitamin C and vitamin E at the concentrations used in the experiments of the present invention.
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 with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예Example
실시예 1: 세포 내 ROS(reactive oxygen species) 측정Example 1: Measurement of intracellular reactive oxygen species (ROS)
갑상선안병증 환자의 안와내 지방에서 추출한 안와모세포를 6 cm 디쉬에서 배양한 후 FBS(Fetal Bovine Serum)를 뺀 DMEM 배지(Hyclone Laboratories, Inc., 미국)로 갈아주었다. 상기 배지에 부착된 세포에 다음의 약물을 각각 처치하여 37℃ 및 5% CO2에서 24시간 배양하였다: 5 μM RRR-알파-토코페롤(α-T: alpha-tocopherol, Sigma-Aldrich Co, 미국), 10 μM RRR-알파-토코페롤; 30 μM RRR-알파-토코페롤; 0.5 μM 셀레노메티오닌(Se: selenium, Sigma-Aldrich Co); 1 μM 셀레노메티오닌; 5 μM 셀레노메티오닌; 10 μM 비타민 C(AA: ascorbic acid, Sigma-Aldrich Co); 50 μM 비타민 C; 70 μM 비타민 C; 및 세 약물의 조합(5 μM RRR-알파-토코페롤, 0.5 μM 셀레노메티오닌, 10 μM 비타민 C; 10 μM RRR-알파-토코페롤, 1 μM 셀레노메티오닌, 50 μM 비타민 C; 및 30 μM RRR-알파-토코페롤, 5 μM 셀레노메티오닌, 70 μM 비타민 C). 이후, 37℃, 5% CO2에서 10 μM DCFH-DA(Sigma Chemical Co., 미국)를 첨가한 PBS(pH 7.4)로 세포를 30분간 처치하고 PBS(pH 7.4)로 DCFH-DA를 1회 세척한 후 PBS(pH 7.4)에 100 μM H2O2를 처리하여 30분간 유지하였다.The orbital cells extracted from orbital fat of patients with thyroid ophthalmopathy were cultured in a 6 cm dish and changed to DMEM medium (Hyclone Laboratories, Inc., USA) without FBS (Fetal Bovine Serum). The cells were incubated with the following drugs at 37 ° C and 5% CO 2 for 24 hours: 5 μM RRR-alpha-tocopherol (Sigma-Aldrich Co, USA) , 10 [mu] M RRR-alpha-tocopherol; 30 [mu] M RRR-alpha-tocopherol; 0.5 [mu] M selenomethionine (Se: selenium, Sigma-Aldrich Co); 1 [mu] M selenomethionine; 5 [mu] M selenomethionine; 10 μM vitamin A (ascorbic acid, Sigma-Aldrich Co); 50 [mu] M Vitamin C; 70 [mu] M Vitamin C; And a combination of the three drugs (5 μM RRR-alpha-tocopherol, 0.5 μM selenomethionine, 10 μM vitamin C; 10 μM RRR-alpha-tocopherol, 1 μM selenomethionine, 50 μM vitamin C and 30 μM RRR-alpha - tocopherol, 5 [mu] M selenomethionine, 70 [mu] M vitamin C). Cells were then treated with PBS (pH 7.4) supplemented with 10 μM DCFH-DA (Sigma Chemical Co., USA) at 37 ° C and 5% CO 2 for 30 min and DCFH-DA After washing, PBS (pH 7.4) was treated with 100 μM H 2 O 2 and kept for 30 minutes.
음성대조군은 H2O2를 처치하지 않았으며, 비교예로 100 μM H2O2를 30분 동안 처치하여 ROS 증가를 평가하였다. 트립신으로 세포를 분리하고 PBS(pH 7.4)로 2회 씻어낸 후 유동세포계수법(Flow Cytometry, FACSverse, BD Biosciences, 미국)을 이용하여 형광을 측정하였으며, 비교예 대비 약물처치군의 ROS 생성을 비교하여 나타내었다.Negative controls were not treated with H 2 O 2 , and comparative examples were treated with 100 μM H 2 O 2 for 30 minutes to assess ROS increase. Cells were isolated with trypsin and washed twice with PBS (pH 7.4). Fluorescence was measured using flow cytometry (FACSverse, BD Biosciences, USA), and the ROS production in the drug treatment group Respectively.
그 결과, 비교예는 음성대조군에 비해 ROS가 700%로 의미있게 증가하였다. H2O2 자극 하에서 RRR-알파-토코페롤, 셀레늄 및 비타민 C를 각각 단독으로 처치한 경우 실험한 모든 농도에서 유의한 ROS 감소효과는 없었다(도 1).As a result, the ROS of the comparative example was significantly increased to 700% as compared with the negative control. H 2 O 2 When RRR-alpha-tocopherol, selenium and vitamin C were individually treated under stimulation, there was no significant ROS reduction effect at all the concentrations tested (Fig. 1).
세 약물을 병행 처치한 경우에 있어 0.5 μM 셀레노메티오닌, 5 μM RRR-알파-토코페롤 및 10 μM 비타민 C를 병행 처치한 경우 유의한 ROS 감소효과가 없었다. 그러나, 1 μM 셀레노메티오닌, 10 μM RRR-알파-토코페롤 및 50 μM 비타민 C를 병행 처치한 경우 및 5 μM 셀레노메티오닌, 30 μM RRR-알파-토코페롤 및 70μM 비타민 C를 병행 처치한 경우에는 의미있는 ROS 감소효과가 있음을 확인하였다(도 1). 따라서 셀레노메티오닌, RRR-알파-토코페롤 및 비타민 C를 병행처리함과 동시에, 상기 세 약물이 일정 농도 이상(셀레노메티오닌 1 μM, RRR-알파-토코페롤 10 μM 및 비타민 C 50 μM)이어야만 ROS 감소효과가 있음을 알 수 있었다.The concurrent treatment of the three drugs with 0.5 μM selenomethionine, 5 μM RRR-alpha-tocopherol and 10 μM vitamin C did not significantly reduce ROS. However, when concurrent treatment of 1 μM selenomethionine, 10 μM RRR-alpha-tocopherol and 50 μM vitamin C, and 5 μM selenomethionine, 30 μM RRR-alpha-tocopherol and 70 μM vitamin C, (Fig. 1). Therefore, concurrent treatment of selenomethionine, RRR-alpha-tocopherol and vitamin C, and reduction of ROS only when the three drugs are above a certain concentration (1 μM of selenomethionine, 10 μM of RRR-alpha-tocopherol and 50 μM of vitamin C) It was found that there was an effect.
실시예 2: 세포 독성 테스트Example 2: Cytotoxicity test
알파-리포산(α-Lipoic acid)의 세포 독성 테스트는 MTS 분석으로 확인하였다. MTS 분석은 각 웰에 안와 섬유모세포를 배양하고, 본 발명의 셀레노메티오닌, 비타민 C 및 알파-토코페롤을 농도별로 48시간 또는 72시간 동안 처리함으로써 수행하였다. 배양 후 MTS 용액 20 μl를 투여하고 4시간 경과 후 ELISA 플레이트 리더에서 490 nm 파장의 UV로 광밀도(OD)를 측정하여 세포성장 억제를 비교하였다. 대사가 왕성한 세포에서 발견되는 디하이드로게네이즈(dehydrogenas) 효소에 의해서 MTS가 포르마잔으로 바뀌며, 490 nm 자외선으로 측정되는 흡광도의 정도가 배양 시 살아있는 세포의 수와 직접 비례한다.The cytotoxicity test of alpha-lipoic acid was confirmed by MTS analysis. MTS analysis was performed by culturing orbital fibroblasts in each well and treating the selenomethionine, vitamin C and alpha-tocopherol of the present invention for 48 hours or 72 hours by concentration. After incubation, 20 μl of MTS solution was administered. After 4 hours, the optical density (OD) was measured at 490 nm wavelength in an ELISA plate reader to compare cell growth inhibition. The dehydrogenase enzyme found in intense metabolized cells converts MTS to formazan and the degree of absorbance measured at 490 nm ultraviolet light is directly proportional to the number of living cells in culture.
그 결과, 본 발명에서 실험을 실시한 셀레노메티오닌, 비타민 C 및 알파-토코페롤의 농도는 안와섬유모세포에 독성이 없음을 확인하였다(도 2).As a result, it was confirmed that the concentrations of selenomethionine, vitamin C and alpha-tocopherol which were tested in the present invention were not toxic to the orbital fibroblast (Fig. 2).
실시예 3: 약물함량 결정Example 3: Determination of drug content
셀레늄 함량 결정Determine selenium content
135 μg-400 μg의 셀레늄을 셀레노메티오닌으로 복용하였을 경우, 성인(체중: 60 kg)은 2.256.67 μg/kg로 복용하는 것으로 평가할 수 있고, 이는 약동학적 자료1의 도 2에 따라 혈장농도 196.1322.1 μg/L로 평가할 수 있으며, 이는 약 1.0-1.64 μmol/L(셀레노메티오닌 분자량 196.1로 계산)에 해당된다.If hayeoteul taking selenium of 135 μg-400 μg as selenomethionine, an adult (body weight: 60 kg) may be evaluated by taking into 2.256.67 μg / kg, the plasma concentration which in accordance with Figure 2 of pharmacokinetic data 1 196.1322.1 μg / L, which corresponds to approximately 1.0-1.64 μmol / L (calculated as molecular weight of selenomethionine 196.1).
실시예 1의 실험에 의하여 셀레노메티오닌 농도 1 및 5 μmol/L이 유효한 농도임을 확인하였으며, 셀레노메티오닌이 0.5 μmol/L인 경우 세 약물을 병합 처치하여도 ROS 감소 효과가 없었는바(도 1), 세 약물 병합 처치에 있어 셀레노메티오닌의 최소 유효 농도는 1 μmol/L임을 알 수 있었다.Selenomethionine concentrations of 1 and 5 μmol / L were found to be effective concentrations by the experiment of Example 1, and when selenomethionine was 0.5 μmol / L, there was no ROS reduction effect even when the three drugs were combined (FIG. 1 ), It was found that the minimum effective concentration of selenomethionine in the three drug combination treatments was 1 μmol / L.
비타민 C 함량 결정Determining Vitamin C Content
비타민 C를 100-400 mg 투여하는 경우의 혈장 내 비타민 C의 농도는 약동학적 자료2의 표 1에 따라 56-70 μM로 평가된다.The concentration of vitamin C in plasma when 100-400 mg of vitamin C is administered is estimated to be 56-70 μM according to Table 1 in Pharmacokinetic Data 2 .
실시예 1의 실험에 의하여 비타민 C의 농도가 10 μmol/L인 경우 세 약물을 병합 처치하여도 ROS 감소 효과가 없었고, 50 및 70 μmol/L인 경우 유의한 ROS 감소 효과를 확인하였는바(도 1), 세 약물 병합 처치에 있어 비타민 C의 최소 유효 농도는 50 μmol/L임을 알 수 있었다. 따라서 본 발명의 비타민 C 범위인 56-70 μM이 유효농도에 포함됨을 확인할 수 있었다.According to the experiment of Example 1, when the concentration of vitamin C was 10 μmol / L, no effect of ROS reduction was obtained even when the three drugs were combined, and a significant ROS reduction effect was observed at 50 and 70 μmol / L 1), the minimum effective concentration of vitamin C in the three drug combination treatments was found to be 50 μmol / L. Therefore, it was confirmed that the effective concentration of vitamin C of the present invention contained 56-70 [mu] M.
알파-토코페롤 함량 결정Determination of alpha-tocopherol content
23-223 IU의 알파-토코페롤을 복용하는 경우, 약동학적 자료3에 따라 혈중 총 알파-토코페롤의 농도는 10-30 μmol/L 범위이다. 본 실험에서 사용한 알파-토코페롤은 식물성 유지로부터 추출한 것으로 1g 당 약 670 mg의 RRR-알파-토코페롤이 함유되어 있다.When taking alpha-tocopherol of 23-223 IU, the total alpha-tocopherol concentration in the blood is in the range of 10-30 μmol / L according to Pharmacokinetic Data 3 . Alpha-tocopherol used in this experiment was extracted from vegetable oils and contained about 670 mg of RRR-alpha-tocopherol per gram.
실시예 1의 실험에 의하여 알파-토코페롤 10 및 30 μmol/L이 유효농도임을 알 수 있었으며, 알파-토코페롤의 농도가 5 μmol/L인 경우 세 약물을 병합 처치하여도 ROS 감소 효과가 없는바(도 1), 세 약물 병합 처치에 있어 알파-토코페롤의 최소 유효 농도는 10 μmol/L임을 알 수 있었다.According to the experiment of Example 1, it was found that alpha-
종합비타민 함량 결정Determination of total vitamin content
상기 각 약물의 최소 유효 농도 확인 결과 ROS 감소에 의하여 갑상선 질환을 예방, 완화, 개선 또는 치료하기 위한 본 발명의 종합 비타민 조성물의 1일 투여량은 150 μg 셀레늄, 200 mg 비타민 C 및 100 IU 비타민 E로 결정하였다.The daily dose of the multivitamin composition of the present invention for preventing, alleviating, ameliorating, or treating thyroid disease by reducing the ROS as a result of the minimum effective concentration of each of the above drugs is 150 μg selenium, 200 mg vitamin C and 100 IU vitamin E Respectively.
참고문헌references
1. Burk RF, Norsworthy BK, Hill KE, Motley AK, Byrne DW. Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol Biomarkers Prev 2006;15:804-10.1. Burk RF, Norsworthy BK, Hill KE, Motley AK, Byrne DW. Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol Biomarkers Prev 2006; 15: 804-10.
2. Graumlich JF, Ludden TM, Conry-Cantilena C, Cantilena LR, Jr., Wang Y, Levine M. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm Res 1997;14:1133-9.2. Graumlich JF, Ludden TM, Conry-Cantilena C, Cantilena LR, Jr., Wang Y, Levine M. Pharmacokinetic model of ascorbic acid in healthy volunteers during depletion and repletion. Pharm Res 1997; 14: 1133-9.
3. Traber MG, Rader D, Acuff RV, Ramakrishnan R, Brewer HB, Kayden HJ. Vitamin E dose-response studies in humans with use of deuterated RRR-alpha-tocopherol. Am J Clin Nutr 1998;68:847-53.3. Traber MG, Rader D, Acuff RV, Ramakrishnan R, Brewer HB, Recording HJ. Vitamin E dose-response studies in humans with deuterated RRR-alpha-tocopherol. Am J Clin Nutr 1998; 68: 847-53.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (9)
(a) 135-400 μg 셀레늄;
(b) 100-400 mg 비타민 C; 및
(c) 23-223 IU(International Unit) RRR-알파-토코페롤(RRR-alpha-tocopherol).
A1 The present invention relates to a multivitamin composition for the prevention, alleviation, amelioration or treatment of thyroid ophthalmopathy which comprises as an active ingredient selenium, vitamin C and RRR-alpha-tocopherol as an active ingredient, wherein said selenium, vitamin C and RRR- Tocopherol (RRR-alpha-tocopherol) is a composition wherein the daily dose is the following weight:
(a) 135-400 [mu] g selenium;
(b) 100-400 mg vitamin C; And
(c) 23-223 IU (International Unit) RRR-alpha-tocopherol (RRR-alpha-tocopherol).
The composition of claim 1, wherein the selenium is selenomethionine.
(a) 135-200 μg 셀레늄;
(b) 100-300 mg 비타민 C; 및
(c) 23-112 IU RRR-알파-토코페롤(RRR-alpha-tocopherol).
The composition according to claim 1, wherein the daily dose of selenium, vitamin C and RRR-alpha-tocopherol is the following weight:
(a) 135-200 [mu] g selenium;
(b) 100-300 mg vitamin C; And
(c) 23-112 IU RRR-alpha-tocopherol.
(a) 1-5 μM 셀레늄;
(b) 50-70 μM 비타민 C; 및
(c) 10-30 μM RRR-알파-토코페롤(RRR-alpha-tocopherol).
The composition according to claim 1, wherein the multivitamin composition is a composition comprising selenium, vitamin C and RRR-alpha-tocopherol in plasma after administration on a 60 kg adult basis at the following concentrations: :
(a) 1-5 [mu] M selenium;
(b) 50-70 [mu] M Vitamin C; And
(c) 10-30 [mu] M RRR-alpha-tocopherol.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20010020541A (en) * | 1997-06-27 | 2001-03-15 | 티오네 인터내셔날 인코포레이티드 | Intra-oral antioxidant preparations |
JP2008516948A (en) * | 2004-10-15 | 2008-05-22 | イブレット・ラボラトリーズ・インコーポレーテッド | Methods and compositions for supplementation of nutritional deficiencies in kidney patients |
KR20090114457A (en) * | 2007-02-15 | 2009-11-03 | 와이어쓰 | Improved stability in vitamine and mineral supplements |
KR20120131956A (en) * | 2011-05-27 | 2012-12-05 | 연세대학교 산학협력단 | A Composition for Treating or Preventing Thyroid Disorders |
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Publication number | Priority date | Publication date | Assignee | Title |
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KR20010020541A (en) * | 1997-06-27 | 2001-03-15 | 티오네 인터내셔날 인코포레이티드 | Intra-oral antioxidant preparations |
JP2008516948A (en) * | 2004-10-15 | 2008-05-22 | イブレット・ラボラトリーズ・インコーポレーテッド | Methods and compositions for supplementation of nutritional deficiencies in kidney patients |
KR20090114457A (en) * | 2007-02-15 | 2009-11-03 | 와이어쓰 | Improved stability in vitamine and mineral supplements |
KR20120131956A (en) * | 2011-05-27 | 2012-12-05 | 연세대학교 산학협력단 | A Composition for Treating or Preventing Thyroid Disorders |
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