KR20070014395A - A composition of inhibiting thyroiditis - Google Patents
A composition of inhibiting thyroiditis Download PDFInfo
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- KR20070014395A KR20070014395A KR1020050069001A KR20050069001A KR20070014395A KR 20070014395 A KR20070014395 A KR 20070014395A KR 1020050069001 A KR1020050069001 A KR 1020050069001A KR 20050069001 A KR20050069001 A KR 20050069001A KR 20070014395 A KR20070014395 A KR 20070014395A
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- thyroiditis
- inhibiting
- hyperthyroidism
- herbal composition
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Abstract
Description
도 1은 실시예 2 흡광도 측정결과이다.1 is a measurement result of absorbance of Example 2.
본 발명은 자가면역 갑상선기능 항진증에 효과가 있는 생약 조성물에 관한 것으로 좀더 상세히는 감초, 흑두, 천궁 및 당귀를 포함하는 자가면역 갑상선기능 항진증에 효과가 있는 생약 조성물에 관한 것이다.The present invention relates to a herbal composition effective for autoimmune hyperthyroidism, and more particularly, to a herbal composition effective for autoimmune hyperthyroidism including licorice, dark bean, stool and Angelica.
갑상선은 요오드를 원료로 갑상선 호르몬을 만들어 내는 내분비 기관이며, 갑상선 호르몬은 우리 몸의 신진대사의 속도를 조절하는 역할을 한다. 갑상선 호르몬은 탄수화물, 지질 및 단백질을 포함한 대사를 조절한다. 이러한 작용의 결과로 갑상선 호르몬은 정상적인 성장과 발생 그리고 신경계통 성숙에 필수적이다. 갑상선은 자가항체가 생기기 쉬운 내분비기관이다. 갑상선 자극호르몬(TSH)의 작용을 받는 TSH 수용체에 대한 자가 항체도 생길 수 있으며, 이러한 항체가 갑상선을 자극하여 갑상선 기능항진증이 일어난다. 이렇게 TSH에 대한 자가항체로 갑상선 기능항진증 상태가 된 병을 그레이브스병(Graves' disease), 혹은 바세도우병이라고 한다. 반대로 갑상선 세포를 손상시킬 수 있는 면역 세포의 작용이 증가되어 갑상선에 염증을 일으키는 병이 만성 갑상선염 혹은 하시모토병(Hashimoto disease)이라고도 부른다. 그레이브스병과 만성 갑상선염은 갑상선병 중에서 가장 많은 병이다.The thyroid gland is an endocrine organ that produces thyroid hormones from iodine, and thyroid hormones regulate the rate of metabolism in our bodies. Thyroid hormones regulate metabolism, including carbohydrates, lipids, and proteins. As a result of these actions, thyroid hormones are essential for normal growth and development and nervous system maturation. The thyroid gland is an endocrine organ that is prone to autoantibodies. Autoantibodies to TSH receptors acting on thyroid stimulating hormone (TSH) can also occur, and these antibodies stimulate the thyroid gland, resulting in hyperthyroidism. The disease caused by hyperthyroidism due to autoantibodies to TSH is called Graves' disease, or Vasdou's disease. On the contrary, the disease that causes the thyroid gland to increase due to the increased action of immune cells that can damage the thyroid cells is called chronic thyroiditis or Hashimoto disease. Graves' disease and chronic thyroiditis are the most common thyroid diseases.
갑상선 기능 항진증은 갑상선에서 갑상선 호르몬이 정상보다 많이 나와 몸에 갑상선 호르몬이 너무 많은 상태를 말한다. 비정상적으로 대사속도가 빨라지고 열에 민감하며 비정상적으로 활발해질 뿐만 아니라 식욕이 왕성함에도 불구하고 체중은 감소한다.Hyperthyroidism is a condition in which the thyroid hormone is higher than normal in the thyroid gland and there is too much thyroid hormone in the body. Abnormally metabolic rate, heat-sensitive and abnormally active as well as weight loss despite a strong appetite.
갑상선 기능 항진증이 생기는 흔한 원인은 그레이브스 병, 갑상선 결절, 갑상선염 등이다. 이 중 그레이브스 병이 갑상선기능항진증의 가장 흔한 원인이다. 그레이브스 병은 일종의 자가면역 질환이다. 그레이브스 병의 경우에는 면역계통이 갑상선을 공격하는 것은 아니고 갑상선을 끊임없이 자극하여 호르몬을 만들어내도록 하는 것이 다른 자가면역질환과 약간 다르다.Common causes of hyperthyroidism include Graves' disease, thyroid nodules, and thyroiditis. Graves' disease is the most common cause of hyperthyroidism. Graves' disease is a type of autoimmune disease. In Graves' disease, the immune system does not attack the thyroid gland, but rather stimulates the thyroid gland to produce hormones, which is slightly different from other autoimmune diseases.
갑상선 기능 항진증 치료제로는 프로필티오우라실(propylthiouracil), 메티마졸(methimazol)이 있다. 그런데, 이들 치료제는 부작용을 수반한다. 항갑상선제의 부작용 중 가장 많은 것은 피부의 가려움증이다. 항갑상선제를 바꾸어도 계속 부작용이 있는 환자에서는 갑상선 절제수술이나 방사성 요오드로 치료해야 한다. 가려움증 외에도 관절통, 관절염, 발열, 피부의 발진, 간기능 장애, 황달, 백혈구 감소증 등의 여러 가지 부작용이 나타날 수 있다. 이러한 부작용 중에서 가장 위험한 것은 「백혈구 감소증」이다. 이렇게 되면 세균에 대한 저항력이 없어져 매우 위험하다.Treatments for hyperthyroidism include propylthiouracil and metimazol. However, these therapeutic agents carry side effects. The most common side effect of anti-thyroid drugs is itching of the skin. Patients who continue to have side effects after changing antithyroid drugs should be treated with thyroidectomy or radioactive iodine. In addition to itching, there are many side effects that can include joint pain, arthritis, fever, skin rash, liver failure, jaundice, and leukopenia. The most dangerous of these side effects is leukopenia. This is very dangerous because the resistance to bacteria is lost.
이와 같이, 갑상선기능 항진증 치료 용도로 사용해 오던 종래의 양약들은 갑상선 호르몬의 형성을 저해하기 때문에 전체 면역체계를 약화시켜 항진증의 치료효과가 있는 반면 부작용이 발생하는 문제점이 있다.As described above, conventional medicines used for the treatment of hyperthyroidism inhibit the formation of thyroid hormones, thereby weakening the entire immune system and thus causing side effects.
따라서, 본 발명은 부작용을 일으킬 가능성이 낮은 갑상선기능 항진증 치료제를 제공하려는 것을 그 목적으로 한다. 즉, 천연물을 이용함으로써 부작용이 없는 갑상선기능 항진증 치료를 위한 약제학적 조성물을 제공하려는 것이다.Accordingly, an object of the present invention is to provide a therapeutic agent for hyperthyroidism which is unlikely to cause side effects. In other words, by using natural products to provide a pharmaceutical composition for the treatment of hyperthyroidism without side effects.
위와 같은 목적을 달성하기 위하여 본 발명자들은 한방 약재 추출물에 대하여 갑상선 기능 항진증 억제 활성을 연구하여 본 발명에 이르게 되었다. 본 발명자들은 감초, 흑두, 천궁, 당귀의 추출물인 감궁탕이 자가면역 갑상선 기능 항진증(autoimmune thyroiditis)을 억제하는 효과가 있음을 확인하였다.In order to achieve the above object, the present inventors have led to the present invention by studying the antihyperthyroidism inhibitory activity against herbal extracts. The present inventors confirmed that the extract of licorice, black bean, cheongung, and Angelica tang extract has an effect of inhibiting autoimmune thyroiditis.
본 발명은 감초 10~40중량%, 흑두 20~30중량%, 당귀 20~30중량% 및 천궁 20~30중량%을 포함하는 갑상선 기능 항진증 억제활성을 나타내는 생약 조성물에 관 한 것이다.The present invention relates to a herbal composition that exhibits antihyperthyroidism inhibitory activity, including 10-40% by weight licorice, 20-30% by weight black bean, 20-30% by weight and Angelica 20-30% by weight.
또한, 본 발명은 상기 생약 조성물이 물, 수용액 또는 완충용액을 이용하여 추출, 여과하는 것을 특징으로 하는 갑상선 기능 항진증 억제활성을 나타내는 생약 조성물에 관한 것이다. 바람직하게는, 정제수, 메탄올, 에탄올, 글리세린, 에틸아세테이트, 부틸렌글리콜, 프로필렌글리콜, 디클로로메탄 및 헥산 중에서 선택된 1종을 추출용매로 사용한다.The present invention also relates to a herbal composition exhibiting antihyperthyroidism inhibitory activity, characterized in that the herbal composition is extracted and filtered using water, an aqueous solution or a buffer solution. Preferably, one selected from purified water, methanol, ethanol, glycerin, ethyl acetate, butylene glycol, propylene glycol, dichloromethane and hexane is used as the extraction solvent.
뿐만 아니라, 본 발명은 생약조성물을 유효성분으로 하는 갑상선 기능 항진증 억제활성을 나타내는 약제학적 조성물에 관한 것이다.In addition, the present invention relates to a pharmaceutical composition exhibiting an antihyperthyroidism inhibitory activity comprising a herbal composition as an active ingredient.
상기 약제학적 조성물은 임상투여시에 경구 또는 비경구 투여가 가능하며 일반적인 의약품제제의 형태로 사용될 수 있다. 즉, 본 발명의 생약 추출물은 실제 임상투여시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 생약추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (Calcium carbonate), 수크로스 (Sucrose) 또는 락토오스 (Lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들 면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜 (Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The pharmaceutical composition may be administered orally or parenterally during clinical administration and may be used in the form of a general pharmaceutical preparation. That is, the herbal extract of the present invention may be administered in various oral and parenteral formulations during actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used, or Formulated using excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, or the like in one or more herbal extracts. (Sucrose) or lactose (Lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
상기 생약 추출물의 유효용량은 200∼600mg/kg이고, 바람직하게는 200∼500mg/kg 이며, 하루 1~3회 투여될 수 있다. 용량이 200mg/kg 미만이면 효과가 미비하며, 600mg/kg 초과하면 투여량에 대한 기대효과의 증가치가 적어 경제적이지 못하다.The effective dose of the herbal extract is 200 to 600 mg / kg, preferably 200 to 500 mg / kg, may be administered 1 to 3 times a day. If the dose is less than 200mg / kg the effect is insignificant, if it exceeds 600mg / kg the increase in the expected effect on the dosage is not economical.
본 발명에 사용된 약재는 각각 다음과 같은 효능과 특징이 있다.The medicines used in the present invention each have the following efficacy and characteristics.
당귀는 산형과(傘形科 Apiaceae)에 속하는 한약재인 당귀의 뿌리를 일컫는 것으로 효능은 보혈조경(補血調經：부족한 피를 보충하고 월경이상을 조절)·활혈지통(活血止痛：피를 활발하게 순환시켜 통증을 멈추게 함)·윤장(潤腸：대장을 윤택하게 하여 부드럽게 함) 등으로 대별된다. 당귀는 임상에서 가장 흔히 쓰이는 약물중의 하나이다. 특히 부인과의 주약(主藥)이며, 주로 월경조정에 사용한다. 생리통에도 효과가 있으며, 백작약(白芍藥)·연호삭延胡索)·향부자(香附子) 등을 배합하여 사용한다. 이외에 무월경, 생리불순에도 효과가 있다. Angelica refers to the root of Angelica, a Chinese herb belonging to the Apiaceae family, and its effect is to bolster blood circulation (補血 調經: lack of blood and control menstrual abnormalities), vigorous circulation (active 血 止痛: blood). To stop the pain), and lubrication (潤腸: makes the large intestine smooth and soft). Angelica is one of the most commonly used drugs in the clinic. In particular, it is the main medicine of gynecology and is mainly used for menstrual adjustment. It is also effective for menstrual cramps, and is used in combination with Baek Pak (白 芍藥), Yeon Ho Sak 延胡 索, and Hyangbuja. In addition to amenorrhea, menstrual impurities are also effective.
천궁은 중국 원산이며 약용 식물로 재배한다. 한방에서는 뿌리줄기를 진정 ·진통 ·강장에 효능이 있어 두통 ·빈혈증 ·부인병 등에 사용한다. 방향성 식물이며 민간에서는 좀을 예방하기 위해 옷장에 넣어 둔다. 천궁이란 중국 쓰촨성의 궁궁(芎샛)이라는 뜻이다. 죽어가는 소나무 뿌리에 천궁 삶은 물을 주면 나무가 회생한다는 말이 있다. Cheongung is native to China and is grown as a medicinal plant. In oriental medicine, root stem is effective for soothing, pain and tonic, and is used for headache, anemia and gynecological diseases. It is a directional plant and is stored in wardrobe in private to prevent moth. Cheongung means the palace of Chinese Sichuan Province. It is said that trees are regenerated when dying pine roots are boiled.
흑두는 검은콩을 말하며, 검정콩은 약효 작용은 여러 가지 독을 없애주고, 신장계통의 대사 촉진에 좋은 효과를 보인다고 한다. 신장계통이 약한 사람은 몸이 냉하고 신진대사가 원활하지 않아 몸에 여분의 수분이나 지방이 쌓이게 되는 것이다. 검은콩을 먹으면 신장의 작용이 활발해져 수분과 지방이 축적되지 않는 몸으로 체질이 개선된다. 또한 검은콩은 당뇨병이나 귀울림, 백발 등의 증상을 개선하는 것으로 알려지고 있다. 검은콩은 양질의 단백질과 지질, 비타민 B1,B2가 많이 들어 있는 영양이 풍부한 우수 식품이다. 그 중에 한가지는 검정콩과 검정 깨를 섞어 미숫가루처럼 물에 타서 먹는데, 이것으로 식사를 대신하는 방법이 있다. 검정콩은 각종 질병에 효능이 있어서 약으로 많이 이용되어 왔다.Black bean refers to black soybeans, and black soybeans are effective in removing various poisons and promoting the metabolism of the kidney system. People with weak kidneys are cold body and metabolism is not smooth, so the body will accumulate extra moisture or fat. When you eat black beans, the kidneys are active, so the body does not accumulate moisture and fat, improving the constitution. In addition, black beans are known to improve symptoms such as diabetes, tinnitus and white hair. Black soybeans are high quality, rich in protein, lipids and vitamins B 1 and B 2 . One of them is a mixture of black beans and black sesame seeds, which are eaten in water like wheat flour. Black soybean has been used as a medicine because it is effective in various diseases.
감초는 동의보감에는 "감초는 5장6부의 한열(寒熱)과 사기(邪氣)를 다스리며 눈, 코, 입, 귀와 대소변의 생리를 정상으로 되게 하고 모든 혈맥을 소통시키며 근육과 뼈를 튼튼하게 하고 영양 상태를 좋게 할 뿐만 아니라, 모든 약의 독성을 해독하고 72가지 석약(石藥)과 1200가지 초약(草藥)을 서로 조화하여 약효를 잘 나타나게 하므로 별명을 국노(國老)라 한다."고 적혀 있다. 시베리아산(G. glabra var. glandulifera), 에스파냐산(G. glabra) 등이 있다. 비슷한 종으로 개감초(G. pallidiflora)가 있다. 이는 단맛이 적고 감초와 달리 약용으로 쓰이지 않으며, 털이 적고 열매가 타원형이며 끝이 뾰족하다. 중국 동북부와 시베리아, 몽골 등지에 분포한다. Licorice agrees that "Licorice controls the heat and fraud of chapter 5 and 6, normalizes the physiology of the eyes, nose, mouth, ears and faeces, communicates all blood veins, strengthens muscles and bones, and nourish Not only does it improve the condition, but also detoxify the toxicity of all medicines, and 72 kinds of stone (石 藥) and 1200 kinds of herbs (草藥) harmonize with each other to make the medicine appear well, so the nickname is called Kukno (國 老). " have. Siberian acid (G. glabra var. Glandulifera) and Spanish acid (G. glabra). A similar species is G. pallidiflora. It is less sweet, unlike licorice, not used for medicinal purposes, and has little hair, fruit is oval, and has a sharp tip. It is distributed in northeastern China, Siberia and Mongolia.
이하, 본 발명의 구성을 실시예를 통하여 구체적으로 설명한다. 그러나, 실시예는 예시적인 기재일뿐이며, 본 발명의 범위가 실시예에만 한정되는 것은 아니다.Hereinafter, the configuration of the present invention in detail through the embodiment. However, the examples are merely illustrative and the scope of the present invention is not limited only to the examples.
실시예Example 1: 생약 조성물의 추출물 제조 1: Preparation of extract of herbal composition
감초 15g, 흑두 15g, 당귀 15g 및 천궁 15g에 증류수 400㎖를 가하여 3시간 동안 진탕하여 추출하고, 여과한 후 여액을 회전식증발기(rotary evaporator)로 전량이 200㎖가 되도록 감압농축하였다. 여기에 에탄올을 가하여 각각 75%, 85%, 95% 에탄올 용액으로 되게 하여 단계적으로 추출한 다음, 저온에서 방치하여 생성된 침전물을 여과하고 여액을 pH 7.4로 조절하여 전량이 200㎖가 되게 한 다음, 저온에서 24시간 방치한 후 여과막(membrane filter; 0.22㎛, 직경 25mm)으로 여과, 멸균하여 여액 1㎖당 30㎎의 추출물을 얻었다.15 g of licorice, 15 g of black bean, 15 g of Angelica 15g, and 15 g of Cheongung were added to extract 400 ml of distilled water for 3 hours, followed by filtration. The filtrate was concentrated under reduced pressure to a total amount of 200 ml using a rotary evaporator. Ethanol was added thereto to make 75%, 85%, and 95% ethanol solutions, respectively, and extracted in stages. Then, the precipitate was left to stand at low temperature, filtered, and the filtrate was adjusted to pH 7.4 so that the total amount was 200 ml. After standing at low temperature for 24 hours, the mixture was filtered and sterilized with a membrane filter (0.22 µm, diameter 25 mm) to obtain an extract of 30 mg per 1 ml of the filtrate.
실시예Example 2: 생약 조성물의 실험적 면역질환 발생에 대한 억제효과 2: Inhibitory effect of herbal composition on experimental immune disease development
실시예 1에서 제조한 생약 추출물을 음용수에 희석하여 3일 전(day-3), 당일(day 0), 3일 후(day 3) 3가지 조건으로 200mg/kg/day의 양으로 CBA/J 생쥐 연구방 법에 기술된 대로 투여하였다. 당일(day 0)군의 생쥐들을 50㎍ dgpTg(mouse deglycosylated thyroglobulin)/CFA(complete Freunds adjuvant)를 마우스 꼬리부분 기저막에 면역주사하고 같은 양을 7일 후(day 7)에 발뒷꿈치에 다시 주사하였다. 대조군(control mice)은 면역주사 후 음용수만 섭취시켰다. 모든 생쥐는 피를 완전히 제거한 후에 14일째에 갑상선을 분리하였다. 그리고 분광기(spectrophotometer)를 이용하여 490nm에서 각각의 흡광도를 측정하고 도 1에 나타내었다.The herbal extract prepared in Example 1 was diluted in drinking water, and 3 days before (day-3), 3 days after (day 0), 3 days after (day 3) CBA / J in an amount of 200mg / kg / day Administration was as described in the mouse study method. Mice in the
도 1에서 dgpTg를 투여하였을 때 투입한 생약 조성물이 유의성 있게 갑상선수치를 감소시키는 것을 확인하였다.It was confirmed that the herbal composition injected when dgpTg was administered in FIG. 1 significantly reduced thyroid value.
따라서, 본 발명의 조성물을 3일 전에 투여한 군에서 효과적인 결과를 보임으로서, 본 발명의 조성물이 갑상선 기능 항진증에 있어서 예방적 효과가 있음을 확인할 수 있었다.Therefore, by showing an effective result in the group administered three days before the composition of the present invention, it was confirmed that the composition of the present invention has a prophylactic effect in hyperthyroidism.
본 발명의 생약 조성물은 자가면역 갑상선기능 항진증에서 면역조절제(immunomodulator)로써 활성을 나타내어 자가면역질환을 억제시키므로, 상기 생약 조성물을 함유하는 약제학적 조성물 또는 건강보조식품으로 개발하여 제공할 수 있다.Since the herbal composition of the present invention exhibits activity as an immunomodulator in autoimmune hyperthyroidism and suppresses autoimmune diseases, it can be developed and provided as a pharmaceutical composition or dietary supplement containing the herbal composition.
또한, 본 발명의 생약조성물은 천연물로부터 추출한 것으로 인체에 부작용이 거의 없는 갑상선 기능 항진증 치료제를 제공할 수 있다.In addition, the herbal composition of the present invention is extracted from natural products can provide a therapeutic agent for hyperthyroidism with little side effects to the human body.
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| CN104436061A (en) * | 2014-12-15 | 2015-03-25 | 徐小琳 | Oral medicine for treating thyroiditis |
| CN105362821A (en) * | 2015-12-18 | 2016-03-02 | 夏修菲 | Traditional Chinese medicine pill used for treating postpartum thyroiditis and preparation method |
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| CN105362821A (en) * | 2015-12-18 | 2016-03-02 | 夏修菲 | Traditional Chinese medicine pill used for treating postpartum thyroiditis and preparation method |
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