KR20160011329A - A Pharmaceutical composition comprising extract of Coptidis Rhizoma for enhancing the therapy of diabetes Mellitus and obesity - Google Patents
A Pharmaceutical composition comprising extract of Coptidis Rhizoma for enhancing the therapy of diabetes Mellitus and obesity Download PDFInfo
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- KR20160011329A KR20160011329A KR1020140092193A KR20140092193A KR20160011329A KR 20160011329 A KR20160011329 A KR 20160011329A KR 1020140092193 A KR1020140092193 A KR 1020140092193A KR 20140092193 A KR20140092193 A KR 20140092193A KR 20160011329 A KR20160011329 A KR 20160011329A
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- metformin
- extract
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- composition
- obesity
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Abstract
Description
본 발명은 당뇨병 치료효과 증진 및 비만개선용 약학적 조성물로서, 보다 구체적으로는 항당뇨병제인 메트포민(Metformin)의 당뇨병 치료효과를 증진시킴과 동시에 비만도 치료할 수 있는 황련(Coptidis Rhizoma) 추출물을 포함하는 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for improving the therapeutic effect of diabetes and for improving obesity, More particularly, the present invention relates to a composition comprising Metformin, an anti-diabetic agent, and a Coptidis Rhizoma extract capable of treating diabetes and treating obesity.
당뇨병은 인슐린의 절대적 또는 상대적 결핍 및 조직에서의 인슐린 작용성 저하에 기인하는 고혈당과 이에 수반되는 대사 장애를 특징으로 하는 질환이다. 인류문명의 발달에 따른 식이 형태와 생활양식의 변화로 인해 비만인구와 함께 증가추세에 있는 제 2형 당뇨병 (Type 2 Diabetes Mellitus)은 인슐린의 분비가 절대적으로 부족한 제 1형 당뇨병 (Type 1 Diabetes Mellitus)과는 달리 인슐린 저항성이 주요한 병태생리학적 특징이다. 인슐린 저항성은 유전적인 요인과 함께 말초조직에서 인슐린 감수성을 감소시키는 식이형태나 비만, 운동부족, 스트레스 등의 생활습관과 밀접한 관련이 있다. 인슐린 민감성의 감소는 비만과 매우 높은 연관성을 가지며, 비만 상태에서의 염증 반응이 인슐린 민감성을 감소시킨다는 연구들이 많이 보고되고 있다.Diabetes is a disease characterized by hyperglycemia resulting from the absolute or relative deficiency of insulin and a decrease in insulin action in tissues and concomitant metabolic disorders.
현재 제 2형 당뇨병 치료제로서, 인슐린 분비능을 증가시키는 sulfonlurea 계통의 약물이 있고, 인슐린 작용력을 향상시키는 peroxisome proliferator activated receptor gamma (PPAR γ) agonist인 pioglitazone과 rosiglitazone의 약물이 있다. 이 밖에도 간에서 당신생 합성을 감소시키는 Metformin 계통의 약물, 탄수화물의 소화흡수를 방해하여 식후 혈당의 상승을 방지하는 acarbose 계통의 약물이 있다.Currently, there are sulfonlurea drugs that increase insulin secretion, and pioglitazone and rosiglitazone, a peroxisome proliferator activated receptor gamma (PPAR γ) agonist that improves insulin action. In addition, there is a drug called acarbose, which prevents the increase of postprandial blood glucose by interfering with digestion and absorption of Metformin system drugs, carbohydrates, which reduce your biosynthesis in the liver.
이러한 약물 중에서도 Metformin은 다른 경구용 혈당강하제에 비해 저혈당 및 체중증가 등의 부작용이 적다는 장점이 있어 현재 제2형 당뇨병 환자의 1차적인 약물요법으로 사용되고 있다. 현재, Metformin은 이의 염산염으로서 글루코파지 (GLUCOPHAGE: 등록상표명, Bristol-Myers Squibb Company)의 정제 형태로 시판되고 있다. 시판되고 있는 글루코파지 정제는 500 mg, 850 mg, 또는 1000 mg의 염산 Metformin을 함유하고 있으며, 그 투여는 효능 및 내성의 양 측면을 고려하여 하루에 2,550 mg의 최대 요구 용량을 초과하지 않는 범위 내에서 이루어지고 있다.Among these drugs, Metformin has the advantage of less side effects such as hypoglycemia and weight gain than other oral hypoglycemic agents and is currently being used as the first drug therapy for
Metformin은 French lilac의 주요성분으로 1957년부터 유럽에서 사용되어 왔고, 미국에서는 1994년부터 사용이 허가되었으나 작용기전은 비교적 최근에 밝혀졌다. 이제까지 알려진 대표적인 작용기전은 세포의 에너지 조절에 관여하는 AMP-activated protein kinase (AMPK)의 활성화를 유도하여 간에서 당 신생작용을 억제하고 근육 및 간에서 지방산 산화를 촉진시키는 것으로 보고되었다. 최근 연구결과에 의하면 Metformin의 혈당저하작용에는 AMPK의 인산화 상위 kinase인 LKB1이 필요한 것으로 밝혀졌으며, LKB1에 의해 transcriptional co-activator인 TORC2의 인산화를 통한 당신생 억제작용을 나타내는 것으로 밝혀졌다.Metformin has been used in Europe since 1957 as a major component of French lilac and has been approved for use in the United States since 1994, but its mechanism of action has been relatively recent. It has been reported that the typical mechanism of action thus far is to induce activation of AMP-activated protein kinase (AMPK), which is involved in energy regulation of the cell, thereby suppressing the hepatogenic activity and promoting fatty acid oxidation in muscles and liver. Recent studies have shown that LKB1, an upper kinase for phosphorylation of AMPK, is required for the hypoglycemic action of Metformin, and it has been shown that LKB1 inhibits your life by phosphorylation of the transcriptional co-activator TORC2.
다만, Metformin에 의해 유발되는 부작용으로서, 복용 환자의 20 내지 30 ％에서, 식욕 감퇴, 복부 팽만감, 구역, 설사 등이 보고된바 있다. 또한, 드물게 젖산증 (lactic acidosis)을 유발하는 것으로 보고되었고, 이로 인해 신질환, 간질환, 저산소증, 심각한 감염, 알코올중독증 등이 동반된 경우에는 주의를 필요로 한다. 이러한 부작용은 최소 및/또는 지속 용량을 감소시키거나 투약 횟수를 줄이거나 다른 약제와 병용 투여하는 방법에 의해 부분적으로 해결될 수 있다.However, as a side effect caused by Metformin, anorexia, abdominal bloating, nausea and diarrhea have been reported in 20 to 30% of patients taking it. It is rarely reported to cause lactic acidosis, and caution should be exercised when accompanied by renal disease, liver disease, hypoxia, severe infection, alcoholism, and the like. Such side effects can be partially resolved by reducing the minimum and / or sustained dose, by reducing the number of dosing regimens, or by co-administering with other drugs.
따라서, 약제의 병용 또는 혼합을 통한 Metformin의 당뇨병 치료효과 상승 및 부작용 감소가 주요한 과제의 대상 되고 있고, 관련 연구가 이루어지고 있으나(한국 특허공개번호 10-2011-0123908), 아직 미비한 실정이다. Therefore, the increase of the therapeutic effect of Metformin through the combination of drugs or the mixing thereof and the reduction of side effects are the main problems, and related studies have been made (Korea Patent Publication No. 10-2011-0123908).
본 발명은 상기와 같은 문제점을 해결하기 위해 안출된 것으로서, 본 발명자들은 항당뇨병제인 Metformin과 황련 추출물의 병용에 의한 항당뇨 효과의 증진, 부작용 감소 및 지방축적 억제 효과를 확인하고, 이에, 기초하여 본 발명을 완성하게 되었다.Disclosure of the Invention The present invention has been conceived to solve the problems as described above. The present inventors have confirmed the antidiabetic effect, the side effect reduction and the fat accumulation inhibitory effect of Metformin, which is an anti-diabetic agent, Thereby completing the present invention.
이에, 본 발명의 목적은 항당뇨병제인 Metformin과 병용되는, 황련 추출물을 포함하는 항당뇨 치료 효과 증진용 약학적 조성물을 제공하는 것이다.
Accordingly, it is an object of the present invention to provide a pharmaceutical composition for enhancing the antidiabetic therapeutic effect, which comprises the extract of Chrysanthemum japonica, in combination with Metformin, an anti-diabetic agent.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.
상기와 같은 본 발명의 목적을 달성하기 위하여, 본 발명은 항 당뇨병제인 Metformin과 병용되는, 황련 추출물을 포함하는 항당뇨 치료 효과 증진용 약학적 조성물을 제공한다.In order to achieve the object of the present invention as described above, the present invention provides a pharmaceutical composition for enhancing an antidiabetic therapeutic effect comprising a Chinese persimmon extract, which is used in combination with Metformin, an anti-diabetic agent.
본 발명의 일 구현예로서, 상기 조성물은 상기 항 당뇨병제인 Metformin과 동시에(simultaneous), 별도로(separate) 또는 순차적(sequential)으로 투여되는 것을 특징으로 한다.In one embodiment of the present invention, the composition is administered simultaneously, separately or sequentially with Metformin, the anti-diabetic agent.
본 발명의 다른 구현예로서, 상기 조성물은 항당뇨 치료 효과 증진과 동시에 비만을 예방 또는 치료하는 것을 특징으로 한다.In another embodiment of the present invention, the composition is characterized by preventing or treating obesity at the same time as enhancing the antidiabetic therapeutic effect.
본 발명의 또 다른 구현예로서, 상기 황련 추출물은 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 이루어진 군으로부터 선택된 1종 이상 용매로 추출한 것을 특징으로 한다.In another embodiment of the present invention, the Huanghui extract is characterized by being extracted with at least one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.
본 발명의 또 다른 구현예로서, 상기 조성물은 AMPK-α, PPAR-α 및 PPAR-γ로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자 발현을 증가시키는 것을 특징으로 한다.In another embodiment of the present invention, the composition is characterized in that the expression of one or more genes selected from the group consisting of AMPK-alpha, PPAR-alpha and PPAR-y is increased.
본 발명의 또 다른 구현예로서, 상기 조성물은 XBP-1 유전자 발현을 감소시키는 것을 특징으로 한다. In another embodiment of the present invention, the composition is characterized by reducing XBP-1 gene expression.
본 발명은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는 당뇨병 치료효과 증진 및 비만 치료방법을 제공한다.The present invention provides a method of treating hyperlipemia and an obesity treatment method comprising the step of administering the pharmaceutical composition to a subject.
본 발명은 황련 추출물을 포함하는 조성물의 당뇨병 치료효과 증진 및 비만의 치료 용도를 제공한다.The present invention provides a therapeutic effect of a composition containing an extract of Angelica keiskei, which is effective for treating diabetes, and for the treatment of obesity.
본 발명에 따른 조성물은 황련 추출물을 유효성분으로 포함하며, 상기 황련 추출물과 항당뇨병제인 Metformin을 병용함으로써, 당뇨병, 전당뇨 치료 효과 증진 및 부작용 감소를 확인하였는바, 당뇨병을 치료효과를 증진시키기 위한 약학 조성물로 유용하게 사용될 수 있을 것으로 기대된다. 아울러, 상기 당뇨병 치료효과와 함께 지방축적 억제효과를 확인하였는바, 당뇨병 치료와 함께 비만의 예방 또는 치료 효과를 기대할 수 있다.The composition according to the present invention contains the extract of Rhododendron as an active ingredient and the combination of the Rhodiola extract and Metformin, an anti-diabetic agent, has been shown to improve diabetic and pre-diabetic therapeutic effects and reduce side effects. And is expected to be useful as a pharmaceutical composition. In addition, as a result of confirming the fat accumulation inhibitory effect as well as the diabetic therapeutic effect, it can be expected to prevent or treat obesity together with the treatment of diabetes.
도 1은 RAW 264.7 세포에서 정상군 (N), metformin 처리군 (M), Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE), Metformin + 황련 추출물(water 100%) 처리군(M+HLW)의 AMPK-α 유전자 발현을 확인한 결과이다.
도 2는 RAW 264.7 세포에서 정상군 (N), metformin 처리군 (M), Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE), Metformin + 황련 추출물(water 100%) 처리군(M+HLW)의 PPAR-α 유전자 발현을 확인한 결과이다.
도 3은 RAW 264.7 세포에서 정상군 (N), metformin 처리군 (M), Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE), Metformin + 황련 추출물(water 100%) 처리군(M+HLW)의 PPAR-γ 유전자 발현을 확인한 결과이다.
도 4는 RAW 264.7 세포에서 정상군 (N), metformin 처리군 (M), Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE), Metformin + 황련 추출물(water 100%) 처리군(M+HLW)의 XBP-1 유전자 발현을 확인한 결과이다. FIG. 1 is a graph showing the results of treatment of RAW 264.7 cells with normal (N), metformin (M), Metformin + Rhodiola extract (ethanol 30%), M + HLE, Metformin + + HLW) expression of the AMPK-alpha gene.
FIG. 2 is a graph showing the results of treatment of RAW 264.7 cells with normal group (N), metformin treated group (M), Metformin + chrysanthemum extract (ethanol 30%) treated group (M + HLE), Metformin + + HLW) expression of PPAR-alpha gene.
FIG. 3 shows the results of treatment of RAW 264.7 cells with normal (N), metformin treated (M), Metformin + Rhodiola extract (ethanol 30%) treated group (M + HLE), Metformin + + HLW) expression of PPAR-γ gene.
FIG. 4 is a graph showing the results of treatment of RAW 264.7 cells with normal (N), metformin treated (M), Metformin + Rhodiola extract (ethanol 30%) treated group (M + HLE), Metformin + + HLW) expression of the XBP-1 gene.
본 발명에서, Metformin 및 황련(Coptidis Rhizoma) 추출물의 병용에 의한 항당뇨 및 지방축적 억제효과와 관련된 AMPK-α(AMP-activated protein kinase-α), PPAR-α(Peroxisome proliferator-activated receptor-alpha), PPAR-γPPAR-γ(Peroxisome proliferator-activated receptor-gamma) 유전자 발현의 증가를 확인하였다. 또한, Metformin의 부작용과 관련된 XBP-1(X-box binding protein 1) 유전자 발현의 감소를 확인하고, 이에 기초하여 본 발명을 완성하였다.
In the present invention, AMP-activated protein kinase-alpha (AMPK-alpha), Peroxisome proliferator-activated receptor alpha (PPAR-alpha) associated with anti-diabetic and fat accumulation inhibitory effects by the combination of Metformin and Coptidis Rhizoma extract, , And PPAR-gamma PPAR-gamma (Peroxisome proliferator-activated receptor-gamma) gene expression. In addition, the decrease of expression of XBP-1 (X-box binding protein 1) gene associated with adverse effects of Metformin was confirmed, and the present invention was completed based on this finding.
이하 본 발명을 상세히 설명한다.
Hereinafter, the present invention will be described in detail.
본 발명은 항 당뇨병제인 Metformin과 병용되는, 황련 추출물을 포함하는 항당뇨 치료 효과 증진용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for enhancing the antidiabetic therapeutic effect comprising a Chinese chrysanthemum extract, which is used in combination with Metformin, an anti-diabetic agent.
본 발명에서, 황련 추출물은 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예컨대, 본 발명에서 황련 추출물은 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 이루어진 군으로부터 선택된 1종 이상 용매를 사용하여 추출할 수 있으며, 바람직하게는 에탄올을 사용할 수 있다. 또한, 황련으로부터 추출물을 추출하는 방법은 열수 추출, 냉침 추출, 환류 추출, 초음파 추출 등의 다양한 방법을 통하여 추출할 수 있지만, 이것으로 제한되는 것은 아니다.In the present invention, the Huangyan extract can be extracted using a conventional solvent known in the art for extracting an extract from a natural product, that is, under ordinary temperature and pressure conditions. For example, in the present invention, the Huangyan extract may be extracted using at least one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably ethanol. In addition, the method for extracting the extract from Huanglin can be extracted by various methods such as hot water extraction, cold extraction, reflux extraction, and ultrasonic extraction, but the present invention is not limited thereto.
상기 제조된 추출물은 이후 여과하거나 농축 또는 건조과정을 수행하여 용매를 제거할 수 있으며, 여과, 농축 및 건조를 모두 수행할 수 있다. 예컨대, 여과는 여과지를 이용하거나 감압여과기를 이용할 수 있으며, 농축은 감압 농축기, 건조는 동결건조법 등을 수행할 수 있으나, 이것으로 제한되는 것은 아니다.The extract thus prepared may be filtered, concentrated or dried to remove the solvent, and may be subjected to both filtration, concentration and drying. For example, the filtration can be performed using a filter paper or a vacuum filter, the concentration can be carried out using a vacuum concentrator, and the lyophilization can be carried out, but the present invention is not limited thereto.
또한, 상기 용매로 추출한 추출물은 이후, 헥산, 메틸렌클로라이드, 아세톤, 에틸아세테이트, 에틸 에테르, 클로로포름, 물 및 이들의 혼합물로 이루어진 군으로부터 선택된 용매로 분획과정을 더욱 실시할 수도 있다. 상기 분획 시 온도는 4℃ 내지 120℃일 수 있으나, 이에 제한되지는 않는다.Further, the extract extracted with the solvent may be further fractionated with a solvent selected from the group consisting of hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, and mixtures thereof. The fractionation temperature may be 4 캜 to 120 캜, but is not limited thereto.
본 발명에서 사용되는 용어, "치료"란 본 발명에 따른 약학적 조성물의 투여에 의해 당뇨병에 대한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "treatment" refers to any action that improves or alters the symptoms of diabetes by administration of the pharmaceutical composition according to the present invention.
본 발명의 조성물에 의한 예방, 치료 대상 질병인 "당뇨병(diabetes Melitus)"은 만성 대사성 질환으로 오랜 시간이 경과함에 따라 혈관장애와 신경, 신장 및 망막 등의 기능이상을 초래하고 이로 인해 생명까지 잃게 하는 질환이다. 당뇨병은 크게 발생하는 기전에 따라 인슐린 의존형 당뇨병(제1형 당뇨병)과 인슐린 비의존형 당뇨병(제2형 당뇨병)으로 구분되며, 본 발명에서는 바람직하게는 인슐린 비의존형 당뇨병을 의미한다. 상기 인슐린 비의존형 당뇨병은 일반적으로 인슐린에 대하여 저항성을 나타내며 인슐린의 작용부전으로 인하여 과혈당 상태가 지속되는 것이 보통이다. 만성적 고혈당은 췌장 베타 세포에 손상을 일으켜 세포 사멸을 야기하므로 제2형 당뇨병의 치료를 위해서는 효과적인 혈당 조절을 필요로 한다."Diabetes Melitus", a preventive and therapeutic disease to be prevented and treated by the composition of the present invention, is a chronic metabolic disease that causes a vascular disorder and dysfunction such as nerve, kidney, and retina, . Diabetes mellitus is divided into insulin-dependent diabetes mellitus (
본 발명의 조성물과 병용되는 항당뇨병제로서, gliclazide, glibenclamide, repaglinide, nateglinide, mitiglinide, rosiglitazone, pioglitazone, acarbose, voglibose 등일 수 있으며, 바람직하게는 Metformin일 수 있으나, 이로써 제한되는 것은 아니다.The antidiabetic agent used in combination with the composition of the present invention may be gliclazide, glibenclamide, repaglinide, nateglinide, mitiglinide, rosiglitazone, pioglitazone, acarbose, voglibose and the like, preferably Metformin, but is not limited thereto.
예컨대, 본 발명에서 사용되는 항당뇨병제인 "메트포민(Metformin)"은 바이구아나이드(biguanide)계열 약물로서, 2형 당뇨병 환자의 1차적인 치료약물로 이용되고 있으나, 식욕 감퇴, 복부 팽만감, 구역, 설사, 피부 발진등의 부작용이 있는바, 이에 대한 각별한 주의가 요구되는 실정이다. For example, the anti-diabetic agent "Metformin" used in the present invention is a biguanide-based drug, which is used as a first-line treatment for patients with
따라서, 본 발명에 따른 조성물은 항당뇨병제 투여에 의한 항당뇨 효과의 증진 및 부작용 경감을 위하여, 항당뇨병제와 동시에(simultaneous), 별도로(separate) 또는 순차적(sequential)으로 투여되는 것을 특징으로 한다.Accordingly, the composition according to the present invention is characterized in that it is administered simultaneously, separately or sequentially with an anti-diabetic agent in order to enhance the anti-diabetic effect and reduce the side effects by the administration of the anti-diabetic agent .
또한, 본 발명에 따른 조성물은 항당뇨 치료 효과 증진과 동시에 비만을 예방 또는 치료하는 것을 특징으로 한다.In addition, the composition according to the present invention is characterized in that the effect of treating diabetes is improved and at the same time obesity is prevented or treated.
본 발명의 조성물에 의한 예방, 치료 대상 질병인 "비만(obesity)"은 대사 장애로 인하여 체내에 지방세포가 증식 분화하고 이로 인하여 지방이 과잉으로 축적된 상태를 의미하며, 에너지 흡수량이 소비량에 비해 상대적으로 증가하는 경우, 지방세포의 수와 부피가 증가되는 과정을 거쳐 결과적으로 지방조직의 질량이 증가된다. 세포 수준에서의 비만은 지방세포의 증식 및 분화의 촉진으로 인한 지방세포의 수와 부피의 증가를 의미한다.The term "obesity" which is a preventive and therapeutic disease caused by the composition of the present invention means a state in which the fat cells multiply and differentiate in the body due to metabolic disorders and the fat is accumulated excessively, In the case of relative increase, the number and volume of adipocytes are increased, resulting in an increase in the mass of adipose tissue. Obesity at the cellular level means an increase in the number and volume of adipocytes due to promotion of proliferation and differentiation of adipocytes.
비만은 제2형 당뇨병의 주요한 병태생리학적 특징인 인슐린 저항성 증가와 밀접한 연관성을 가지고 있다. 인슐린 저항성은 다량의 인슐린 주사에 의해서도 혈당강하가 일어나지 않는 상태로써, 인슐린 민감도 감소를 의미한다. 이러한 인슐린 민감도 감소는 아디포카인들(adipokines)과 유리지방산(free fatty acid)의 불규칙적인 분비로 인하여 지방산이 베타세포나 신장, 간, 심장 등 인슐린 민감성 조직내에 쌓여 지방 독성(lipotoxicity)을 나타내기 때문에 발생하는 것으로 알려져 있다. Obesity is closely associated with increased insulin resistance, a major pathophysiological feature of
또한, 본 발명에 따른 조성물은 AMPK-α, PPAR-α 및 PPAR-γ로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자 발현을 증가시키는 것을 특징으로 한다. In addition, the composition according to the present invention is characterized in that the expression of one or more genes selected from the group consisting of AMPK-alpha, PPAR-alpha and PPAR-y is increased.
상기 AMPK-α, PPAR-α 및 PPAR-γ은 항당뇨 및 지방축적 억제효과와 관련성이 있는 유전자로서, AMPK(AMP-activated protein kinase)는 세포 내 에너지가 부족한 상황(ATP에 비해 AMP가 증가하는 상황)에서 활성화 되어 정상 에너지 균형을 회복시키기 위해 ATP를 소비하는 과정(지방산, 콜레스테롤 등의 합성을 억제하고 반대로ATP를 생산하는 과정), 즉 지방산 산화, 해당과정을 활성화하며, PPAR-α는 중성지방의 분해에 관여하는 당지질 대사를 조절하고, lipoprotein lipase (LPL)을 통해 triglyceride(TG)의 level을 낮추는 역할을 한다. 또한, PPAR-γ는 지방세포의 전사조절분자 중의 하나로서, 지방세포의 분화 및 지방합성과 저장에 관여하는 효소들의 발현을 조절하는 역할을 할 뿐만 아니라, 인슐린 민감도를 항진시키는데 있어서 중요한 기능을 가지고 있다. The AMPK-alpha, PPAR-alpha and PPAR-gamma are genes associated with anti-diabetic and fat accumulation inhibitory effects. AMP-activated protein kinase (AMPK) (Ie, the process of producing ATP by inhibiting the synthesis of fatty acids and cholesterol, and conversely by activating ATP) to activate the normal energy balance, ie, activating the fatty acid oxidation process, and PPAR-α is neutral It regulates the metabolism of glycolipids involved in lipolysis and lowers the level of triglyceride (TG) through lipoprotein lipase (LPL). In addition, PPAR-γ is one of the transcriptional regulatory molecules of adipocytes, and plays an important role in regulating the expression of enzymes involved in adipocyte differentiation and lipid synthesis and storage, as well as in enhancing insulin sensitivity have.
또한, 본 발명에 따른 조성물은 XBP-1 유전자 발현을 감소시키는 것을 특징으로 한다.In addition, the composition according to the present invention is characterized by decreasing XBP-1 gene expression.
상기 XBP-1 유전자는 metformin의 부작용과 관련성이 있는 유전자로서, XBP-1 유전자는 소포체 스트레스에 관여하는 것으로 알려져 있다.The XBP-1 gene is a gene associated with adverse effects of metformin, and the XBP-1 gene is known to be involved in endoplasmic reticulum stress.
본 발명의 일시예에서는 Metformin 및 황련 추출물을 처리한 RAW 264.7 cell을 세포배양시켰으며(실시예 1 참조), AMPK-α, PPAR-α 및 PPAR-γ 유전자 발현의 증가(실시예 2 참조)를 통해 항당뇨 효과의 증진 및 지방축적 억제효과를 확인하였으며, XBP-1 유전자 발현의 감소(실시예 3 참조)를 통해 Metformin에 의하여 유발되는 부작용 감소를 확인하였다. In a temporal example of the present invention, RAW 264.7 cells treated with Metformin and Rhodiola extracts were cell cultured (see Example 1), and the increase of AMPK-a, PPAR-a and PPAR-y gene expression (see Example 2) And inhibited lipid accumulation. Further, the decrease in the expression of XBP-1 gene (see Example 3) confirmed the reduction of side effects caused by Metformin.
본 발명에 따른 약학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체를 포함할 수 있다. 이때, 약제학적으로 허용되는 담체는 제제 시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세 결정성셀룰로스, 폴리비닐피로리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필 히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일등을 포함하나, 이에 한정되는 것은 아니다. 또한, 상기성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다.The pharmaceutical composition according to the present invention may contain, in addition to the active ingredient, a pharmaceutically acceptable carrier. Herein, pharmaceutically acceptable carriers are those conventionally used at the time of formulation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose But are not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Further, in addition to the above components, a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like may be further included.
본 발명의 약제학적 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 시간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다.The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may vary depending on the condition and weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.
본 발명의 약제학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명에 다른 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, The sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
구체적으로 본 발명의 약제학적 조성물의 유효량은 환자의 연령, 성별, 상태, 체중, 체내에 활성 성분의 흡수도, 불활성율 및 배설속도, 질병종류, 병용되는 약물에 따라 달라질 수 있으며, 일반적으로는 체중 1kg 당 0.001 내지 150mg, 바람직하게는 0.01 내지 100mg을 매일 또는 격일 투여하거나, 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, body weight, absorbency, inactivation rate and excretion rate of the active ingredient in the body, type of disease, 0.001 to 150 mg, preferably 0.01 to 100 mg, per 1 kg of body weight may be administered daily or every other day, or one to three divided doses per day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
본 발명의 다른 양태로서, 본 발명은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는 당뇨병 치료 방법을 제공한다. 본 발명에서 "개체"란 질병의 치료를 필요로 하는 대상을 의미하고, 보다 구체적으로는, 인간 또는 비-인간인 영장류, 생쥐(mouse), 개, 고양이, 말 및 소 등의 포유류를 의미한다.
In another aspect of the present invention, the present invention provides a method for treating diabetes comprising administering the above pharmaceutical composition to a subject. The term " individual "as used herein refers to a subject in need of treatment for a disease, and more specifically refers to a mammal such as a human or non-human primate, mouse, dog, cat, horse and cattle .
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.
Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
실시예 1. 황련 추출물의 처리 및 세포의 배양 Example 1. Treatment of Huanglung extract and cultivation of cells
Macrophage cell line인 RAW 264.7 세포는 한국 세포주 은행(KCLB, Seoul, Korea)에서 분주 받아 사용하였고, 세포배양은 DMEM에 10% FBS와 2 mML-glutamine, 100 U/ml penicillin, and 100 lg/ml streptomycin이 함유된 배지를 사용하였다. CO2 incubator 37℃, 5% CO2 -95% O2 조건하에서 배양하였다. 실험에 사용된 황련 추출물(water 100%, ethanol 30%)은 동국대학교 약학대학에서 제공받아 사용하였다.RAW 264.7 cell line, a macrophage cell line, was used in a Korean cell line bank (KCLB, Seoul, Korea). Cell culture was performed in DMEM supplemented with 10% FBS, 2 mM glutamine, 100 U / ml penicillin, and 100 lg / ml streptomycin Was used. CO 2 incubator 37 캜, 5% CO 2 -95% O 2 Lt; / RTI > The water extracts (water 100%, ethanol 30%) used in the experiment were supplied by the College of Pharmacy, Dongguk University.
각각의 세포를 정상군 (N), metformin 처리군 (M), Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE), Metformin + 황련 추출물(water 100%) 처리군(M+HLW)으로 6군을 만들었으며, 이후 각각의 세포군에 24hr 동안 100㎍/㎖ 약물처리를 하고, 1 mM Metformin을 처리했다.(M + HLW), Metformin + Rhodiola extract (water 100%) treated group (M + HLW), and Metformin + , And each cell group was treated with 100 μg / ml of drug for 24 hours and treated with 1 mM of Metformin.
RAW 264.7 cell은 DMEM에 10% FBS와 2 mML-glutamine, 100 U/ml penicillin, and 100 lg/ml streptomycin이 함유된 배양액을 사용하여 37℃, 5% CO2, 90% humidity의 조건하에서 배양되었다. 배양된 세포는 2~3일에 한 번씩 배양액을 바꾸어 주면서 배양하여 세포분화가 최대에 도달하였을 때 phosphate buffered saline(PBS)으로 세포를 세척한 후, trypsin-EDTA 용액으로 부착된 세포를 분리한 뒤 원심분리하여 세포를 모은 다음, 세포와 배지를 잘 혼합하여 계대 배양하여 사용하였다.
RAW 264.7 cells were cultured in DMEM with culture medium containing 10% FBS, 2 mML-glutamine, 100 U / ml penicillin, and 100 lg / ml streptomycin at 37 ° C, 5% CO 2 , and 90% humidity . The cultured cells were cultured with the culture medium changed every 2-3 days. When the cell differentiation reached its maximum, the cells were washed with phosphate buffered saline (PBS), and the cells adhered with trypsin-EDTA solution were separated Cells were collected by centrifugation, and cells and medium were mixed well and subcultured.
실시예 2. Metformin과 황련 추출물의 병용에 의한 항당뇨 효과 관련 유전자 발현의 확인Example 2. Confirmation of gene expression related to anti-diabetic effect by the combination of Metformin and Rhodiola extract
Metformin과 황련 추출물의 병용이 항당뇨 효과와 관련 유전자의 발현에 어떠한 영향을 주는지 확인하기 위하여 단독으로 Metformin을 처리(M)한 RAW 264.7 세포와 Metformin + 황련 (ethanol 30% 또는 water 100%)을 처리한 RAW 264.7 세포간의 AMPK-α, PPAR-α, PPAR-γ 유전자 발현을 Real-time PCR을 통하여 비교하였다.To determine the effect of the combination of Metformin and Rhizome extracts on the antidiabetic effect and the expression of the related genes, RAW 264.7 cells treated with Metformin alone and Metformin + Rhizobium (ethanol 30% or water 100%) were treated AMPK-α, PPAR-α, and PPAR-γ gene expression in RAW 264.7 cells were compared by real-time PCR.
total RNA는 Trisure (Bioline, USA)를 사용하여 protocol에 따라 분리 정제하였다. 1㎍의 total RNA를 cDNA synthesis kit (SprintTMRTCompleteOligo-(dT)18, Clontech, MountainView, CA, USA)를 이용하여 protocol에 따라 역전사 반응을 수행하여 first strand cDNA를 얻었다. RT-PCR 샘플은 Light Cycler-Fast Start DNA Master SYBR Green(Roche Applied Science, Indianapolis, ID, USA)을 이용하여 최종 반응 용량을 20 μL로 하여 Light Cycler instrument(Roche Applied Science)에서 진행하였다. Total RNA was isolated and purified according to the protocol using Trisure (Bioline, USA). 1 μg of total RNA was reverse-transcribed according to the protocol using cDNA synthesis kit (SprintTMRTCompleteOligo- (dT) 18, Clontech, MountainView, CA, USA) to obtain first strand cDNA. RT-PCR was performed on a Light Cycler instrument (Roche Applied Science) with a final reaction volume of 20 μL using Light Cycler-Fast Start DNA Master SYBR Green (Roche Applied Science, Indianapolis, ID, USA)
상기 실시예에서 사용된 Primer의 DNA sequence는 다음과 같다. The DNA sequence of the primer used in the above example is as follows.
PCR amplification은 C/EBPα에서 95℃에서 10분 동안 prior incubation 후, 45 cycle의 amplification(95℃에서 10초간 denaturation, 52℃에서 10초간 annealing, 72℃에서 15초간 extension) 하였고 beta-actin에서는 95℃에서 10분 동안 prior incubation 후, 35 cycle의 total RNA는 Trisure (Bioline, USA)를 사용하여 protocol에 따라 분리 정제하였다. 1㎍의 total RNA를 cDNA synthesis kit (Sprint TMRTCompleteOligo-(dT)18, Clontech, MountainView, CA, USA)를 이용하여 protocol에 따라 역전사 반응을 수행하여 first strand cDNA를 얻었다. RT-PCR 샘플은 Light Cycler-Fast Start DNA Master SYBR Green(Roche Applied Science, Indianapolis, ID, USA)을 이용하여 최종 반응 용량을 20 μL로 하여 Light Cycler instrument(Roche Applied Science)에서 진행하였다.
PCR amplification was carried out at 95 ° C for 10 min in C / EBPα for 10 min, followed by 45 cycles of amplification (denaturation at 95 ° C for 10 sec, annealing at 52 ° C for 10 sec, extension at 72 ° C for 15 sec) After 10 minutes of prior incubation, 35 cycles of total RNA were isolated and purified according to the protocol using Trisure (Bioline, USA). 1 μg of total RNA was reverse-transcribed according to the protocol using cDNA synthesis kit (Sprint TMRTCompleteOligo- (dT) 18, Clontech, MountainView, CA, USA) to obtain first strand cDNA. RT-PCR was performed on a Light Cycler instrument (Roche Applied Science) with a final reaction volume of 20 μL using Light Cycler-Fast Start DNA Master SYBR Green (Roche Applied Science, Indianapolis, ID, USA)
AMPK-α 유전자 발현은 도 1에 나타난 바와 같이, 정상군 (N)은 0.80, metformin 처리군 (M)은 0.76으로 측정되었다. Metformin + 황련 추출물(ethanol 30%) 처리군,(M+HLE)에서 AMPK-α 유전자의 발현의 증가를 확인하였다, As shown in Fig. 1, the AMPK-alpha gene expression was measured as 0.80 in the normal group (N) and 0.76 in the metformin treated group (M). The expression of AMPK-α gene was confirmed in Metformin + HuangYin extract (ethanol 30%) treated group and (M + HLE)
PPAR-α 유전자 발현은 도 2에 나타난 바와 같이, 정상군 (N)은 1.01, metformin 처리군 (M)은 0.68로 측정되었다. Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE)은 1,57로 측정되었으며, PPAR-α 유전자의 발현의 증가를 확인하였다.As shown in Fig. 2, PPAR-a gene expression was measured as 1.01 in the normal group (N) and 0.68 in the metformin treated group (M). Metformin + HuangYin extract (ethanol + 30%) treated group (M + HLE) was measured as 1,57, and the increase of expression of PPAR-α gene was confirmed.
PPAR-γ 유전자 발현은 도 3에 나타난 바와 같이, 정상군 (N)은 1.03, metformin 처리군 (M)은 0.83으로 측정되었다. Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE)은 1.05로 측정되었으며, PPAR-α 유전자의 발현의 증가를 확인하였다.
As shown in Fig. 3, PPAR-gamma gene expression was measured to be 1.03 for the normal group (N) and 0.83 for the metformin treated group (M). Metformin + HuangYin extract (ethanol + 30%) treated group (M + HLE) was 1.05 and the expression of PPAR-α gene was increased.
실시예 3. Metformin과 황련 추출물의 병용에 의한 Metformin의 부작용 관련 유전자 발현의 확인Example 3. Confirmation of Adverse Effect-Related Gene Expression of Metformin by Combination of Metformin and Chinese Rhizome Extract
Metformin과 황련 추출물의 병용이 Metformin에 의해 유발되는 부작용과 관련 유전자의 발현에 어떠한 영향을 주는지 확인하기 위하여 Real-time PCR을 통하여, 단독으로 Metformin을 처리(M)한 RAW 264.7 세포와 Metformin + 황련 (ethanol 30% 또는 water 100%)을 처리한 RAW 264.7 세포간의 XBP-1 유전자 발현을 비교하였다.To investigate the effect of Metformin and Huang Rin extract on Metformin-induced side effects and expression of related genes, RAW 264.7 cells treated with Metformin alone and Metformin + Hyperlipidemia (Real-time PCR) ethanol 30% or water 100%) were compared between the RAW 264.7 cells treated with XBP-1 gene.
XBP-1 유전자 발현을 확인하기 위하여, Primer를 제외하고 상기 실시예 3에 기재된 방법과 동일한 방법으로, Real-time PCR을 실시하였다.To confirm the expression of XBP-1 gene, real-time PCR was performed in the same manner as described in Example 3 except for the primer.
상기 실시예에서 사용된 Primer의 DNA sequence는 다음과 같다.The DNA sequence of the primer used in the above example is as follows.
XBP-1 유전자 발현은 도 4에 나타낸 바와 같이, 정상군 (N)은 1.00, metformin 처리군 (M)은 1.01로 측정되었다. Metformin + 황련 추출물(ethanol 30%) 처리군(M+HLE)은 0.18, Metformin + 황련 추출물(water 100%) 처리군(M+HLW)은 0.39로 측정되었으며, XBP-1 유전자 발현의 감소를 확인하였다.
XBP-1 gene expression was measured as 1.00 in the normal group (N) and 1.01 in the metformin treated group (M) as shown in Fig. (M + HLW) and Metformin + Rhodiola extract (M + HLW) were 0.18 and 0.39, respectively, and the expression of XBP-1 gene was decreased Respectively.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.
It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.
<110> Dongguk University Gyeongju Campus Industry-Academy Cooperation Foundation <120> Pharmaceutical composition comprising extract of Coptidis Rhizoma for enhancing the therapy of diabetes Mellitus <130> PB14-12067 <160> 10 <170> KopatentIn 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta actin primer_forward <400> 1 gcaagtgctt ctaggcggac 20 <210> 2 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> beta actin primer_reverse <400> 2 aagaaagggt gtaaaacgca gc 22 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> AMPK alpha1 primer_forward <400> 3 aagccgaccc aatgacatca 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> AMPK alpha1 primer_reverse <400> 4 cttccttcgt acacgcaaat 20 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> PPAR-alpha primer_forward <400> 5 gcctgtctgt cgggatgt 18 <210> 6 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> PPAR-alpha primer_reverse <400> 6 ggcttcgtgg attctcttg 19 <210> 7 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> PPAR-gamma primer_forward <400> 7 gccctttggt gactttatgg a 21 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PPAR-gamma primer_reverse <400> 8 gcagcaggtt gtcttggatg 20 <210> 9 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> XBP-1 primer_forward <400> 9 tggccgggtc tgctgagtcc g 21 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> XBP-1 primer_reverse <400> 10 gtccatggga agatgttctg g 21 <110> Dongguk University Gyeongju Campus Industry-Academy Cooperation Foundation <120> Pharmaceutical composition comprising extract of Coptidis Rhizoma for enhancing the therapy of diabetes Mellitus <130> PB14-12067 <160> 10 <170> Kopatentin 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta actin primer_forward <400> 1 gcaagtgctt ctaggcggac 20 <210> 2 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> beta actin primer_reverse <400> 2 aagaaagggt gtaaaacgca gc 22 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> AMPK alpha1 primer_forward <400> 3 aagccgaccc aatgacatca 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> AMPK alpha1 primer_reverse <400> 4 cttccttcgt acacgcaaat 20 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> PPAR-alpha primer_forward <400> 5 gcctgtctgt cgggatgt 18 <210> 6 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> PPAR-alpha primer_reverse <400> 6 ggcttcgtgg attctcttg 19 <210> 7 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> PPAR-gamma primer_forward <400> 7 gccctttggt gactttatgg a 21 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PPAR-gamma primer_reverse <400> 8 gcagcaggtt gtcttggatg 20 <210> 9 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> XBP-1 primer_forward <400> 9 tggccgggtc tgctgagtcc g 21 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> XBP-1 primer_reverse <400> 10 gtccatggga agatgttctg g 21
Claims (6)
상기 조성물은 황련(Coptidis Rhizoma) 추출물을 포함하고, 상기 항 당뇨병제는 메트포민(Metformin)인, 조성물.
A pharmaceutical composition for enhancing the antidiabetic therapeutic effect in combination with an anti-diabetic agent,
Wherein the composition comprises Coptidis Rhizoma extract and the anti-diabetic agent is Metformin.
상기 조성물은 상기 항당뇨병제와 동시에(simultaneous), 별도로(separate) 또는 순차적(sequential)으로 투여되는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein said composition is administered simultaneously, separately or sequentially with said anti-diabetic agent.
상기 조성물은 항당뇨 치료 효과 증진과 동시에 비만을 예방 또는 치료하는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition is characterized by preventing or treating obesity at the same time as enhancing the antidiabetic therapeutic effect.
상기 황련 추출물은 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 이루어진 군으로부터 선택된 1종 이상 용매로 추출한 것을 특징으로 하는, 조성물.
The method according to claim 1,
The Rhodiola extract Wherein the composition is extracted with at least one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof.
상기 조성물은 AMPK-α(AMP-activated protein kinase-alpha), PPAR-α(Peroxisome proliferator-activated receptor-alpha) 및 PPAR-γ(Peroxisome proliferator-activated receptor-gamma)로 이루어진 군으로부터 선택되는 어느 하나 이상의 유전자 발현을 증가시키는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition is selected from the group consisting of AMP-activated protein kinase-alpha, peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and peroxisome proliferator-activated receptor gamma RTI ID = 0.0 > expression, < / RTI >
상기 조성물은 XBP-1 (X-box binding protein 1) 유전자 발현을 감소시키는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein said composition reduces XBP-1 (X-box binding protein 1) gene expression.
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| KR1020140092193A KR20160011329A (en) | 2014-07-21 | 2014-07-21 | A Pharmaceutical composition comprising extract of Coptidis Rhizoma for enhancing the therapy of diabetes Mellitus and obesity |
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| Application Number | Priority Date | Filing Date | Title |
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| KR1020140092193A KR20160011329A (en) | 2014-07-21 | 2014-07-21 | A Pharmaceutical composition comprising extract of Coptidis Rhizoma for enhancing the therapy of diabetes Mellitus and obesity |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109157558A (en) * | 2018-11-01 | 2019-01-08 | 郑老海 | A kind of Chinese medicine and preparation method thereof for treating diabetes |
| KR20190074755A (en) | 2017-12-20 | 2019-06-28 | 동국대학교 경주캠퍼스 산학협력단 | A Composition for Prevention and Treatment of Thyroid Disease including Coptidis Rhizoma Extract |
| KR20230046054A (en) | 2021-09-29 | 2023-04-05 | 한국한의약진흥원 | Composition for the prevention or treatment of obesity comprising Scutellariae Radi and Coptidis Rhizoma extract as an active ingredient |
-
2014
- 2014-07-21 KR KR1020140092193A patent/KR20160011329A/en not_active Application Discontinuation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190074755A (en) | 2017-12-20 | 2019-06-28 | 동국대학교 경주캠퍼스 산학협력단 | A Composition for Prevention and Treatment of Thyroid Disease including Coptidis Rhizoma Extract |
| CN109157558A (en) * | 2018-11-01 | 2019-01-08 | 郑老海 | A kind of Chinese medicine and preparation method thereof for treating diabetes |
| KR20230046054A (en) | 2021-09-29 | 2023-04-05 | 한국한의약진흥원 | Composition for the prevention or treatment of obesity comprising Scutellariae Radi and Coptidis Rhizoma extract as an active ingredient |
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