KR20090019396A - Pharmaceutical compositions for preventing and treating allergy comprising small black soybean - Google Patents
Pharmaceutical compositions for preventing and treating allergy comprising small black soybean Download PDFInfo
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- KR20090019396A KR20090019396A KR1020070083789A KR20070083789A KR20090019396A KR 20090019396 A KR20090019396 A KR 20090019396A KR 1020070083789 A KR1020070083789 A KR 1020070083789A KR 20070083789 A KR20070083789 A KR 20070083789A KR 20090019396 A KR20090019396 A KR 20090019396A
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- pharmaceutical composition
- allergic
- preventing
- water extract
- rat
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- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
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- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/304—Foods, ingredients or supplements having a functional effect on health having a modulation effect on allergy and risk of allergy
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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Abstract
Description
본 발명은 알레르기성 질환의 예방 및 치료용 약학조성물에 관한 것으로서, 쥐눈이콩 물추출물을 유효성분으로 하며, 인체에 안전하고 독성이 없으며, 세포내에서 종양괴사인자-알파 (Tumor necrosis factor-α, TNF-α) 와 인터루킨-8 (Interleukin-8, IL-8)의 생성을 감소시키는 작용기전을 가지므로, 전신성 알레르기 반응과 국소 피부 알레르기 반응 등의 염증성 알레르기성 질환의 예방 및 치료에 우수한 효과를 나타내는 약학조성물에 관한 것이다. The present invention relates to a pharmaceutical composition for the prevention and treatment of allergic diseases, the rat eye water extract as an active ingredient, safe and non-toxic to humans, tumor necrosis factor-alpha in cells (Tumor necrosis factor-α, TNF-α) and Interleukin-8 (IL-8) have a mechanism of action to reduce the production of inflammatory allergic diseases, such as systemic allergic reactions and local skin allergic reactions are excellent effects It relates to a pharmaceutical composition that represents.
알레르기란 광범위하고 복잡한 병리적 현상의 총화로 면역반응에 근거한 생체의 전신적 또는 국소적인 장해이다. 인체에 나타나는 알레르기는 면역 기전에 따라 I, Ⅱ, Ⅲ 및 Ⅳ형으로 분류된다. Allergies are the summation of a wide range of complex pathological phenomena and are systemic or localized disorders of the living body based on immune responses. Allergies present in the human body are classified into I, II, III and IV types according to the immune mechanism.
상기한 알레르기 중 즉시형 과민반응에 속하는 I형 알레르기가 임상에 있어서 중요한 부분을 차지하고 있으며 아토피성 피부염, 알레르기성 비염, 기관지 천 식, 고초열 및 화분증 등이 여기에 속한다. Type I allergy, which belongs to immediate type hypersensitivity, is an important part of clinical practice, and includes atopic dermatitis, allergic rhinitis, bronchial asthma, hay fever and hay fever.
Ⅰ형 알레르기는 비만세포 (Mast cell)의 활성화에 의해 일어나며, 비만세포의 과립에 염증의 매개체인 히스타민 (Histamine)이 다량 함유되어 있음이 알려진 것은 1953년경이다. 알레르기 반응이 일어날 때 비만세포에서 히스타민이 방출되는 현상이 발견된 후에 이 기전을 구명하던 중, Ishizaka의 IgE의 발견은 비만세포가 즉시형 알레르기 반응에 관여함을 밝히는 중요한 계기가 되었다. 즉, 비만세포 표면에는 IgE 고친화성 수용체가 있으며 이 수용체에 IgE가 결합한 후 다시 항원이 결합하여 가교가 형성되면 탈과립반응이 유발되어, 과립 내용물인 히스타민, 세로토닌 (Serotonin), 브라드키닌 (Bradykinin) 등과 같이 합성되어 저장되어있던 매개물질 (Preformed mediator)과, 프로테아제 (Protease), 프로테오글리칸 (Proteoglycan) 등이 동시에 방출된다[Ishizaka 등, Histamine release from rat mast cells by antibodies against rat basophilic leukemia cell membrane. J. Immunol., 1977, 119: 1589-1596]. Type I allergy is caused by the activation of mast cells, and it is known that the granules of mast cells contain high amounts of histamine, a mediator of inflammation, around 1953. During the search for this mechanism after the discovery of histamine release from mast cells when an allergic reaction occurred, Ishizaka's discovery of IgE was an important opportunity to identify the mast cells involved in an immediate allergic reaction. In other words, the surface of mast cells has high IgE affinity receptors, and when IgE binds to these receptors, the antigens bind again to form cross-linking reactions, resulting in degranulation reactions such as histamine, serotonin, and bradykinin, which are granular contents. Preformed mediator, protease, and proteoglycan are simultaneously released [Ishizaka et al., Histamine release from rat mast cells by antibodies against rat basophilic leukemia cell membrane. J. Immunol., 1977, 119: 1589-1596.
1970년대 이후 새로운 지질성의 염증 매개체에 대한 연구 결과가 보고되기 시작하였으며 이들은 세포의 활성화에 동반하여 세포막 인지질로부터 생산된 프로스타그란딘류 (Prostaglandins), 류코트리엔류 (Leukotriens), 트롬복산 (Thromboxane), 글리세로포스포리피드(Glycerophospholipids) 유도체인 혈소판 활성 인자 (Platelet activating factor, PAF) 등으로 다양한 생리활성을 나타내는 새로이 형성된 매개물질 (newly generated mediator)로서 Ⅰ형 알레르기 반응을 포함한 각종의 염증반응에 관여함이 밝혀졌다. 이러한 지질성 매개체는 IgE 수용체가 가교를 형성할 때 비만세포에서 탈과립 반응과 병행해서 생산, 방출된다. Since the 1970s, research on new lipid-mediated inflammatory mediators has begun to be reported. These include prostaglandins, leukotriens, thromboxane, and glycerol produced from cell membrane phospholipids, accompanied by cell activation. Platelet activating factor (PAF), a derivative of glycophospholipids, is a newly generated mediator that exhibits various physiological activities and has been shown to be involved in various inflammatory reactions, including type I allergic reactions. . These lipid mediators are produced and released in parallel with the degranulation reaction in mast cells when the IgE receptor forms a bridge.
또한 비만세포의 활성화에 동반하여 면역반응의 조절인자로 잘 알려진 사이토카인 (cytokine) 은 IL-3 (비만세포 증식인자), IL-4, IL-5 등이 있다 (Galli SJ 등, Cytokine production by mast cells and basophils. Curr. Opin. Immunol., 1991, 3:865-72, Bradding P 등, Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. J. Immunol., 1993, 151:3853-3865). Cytokines, well known as regulators of immune responses accompanied by activation of mast cells, include IL-3 (mastocyte proliferation factor), IL-4, and IL-5 (Galli SJ et al., Cytokine production by mast cells and basophils.Curr.Opin.Imunmun., 1991, 3: 865-72, Bradding P et al., Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects.The mast cell as a source of IL-4, IL -5, and IL-6 in human allergic mucosal inflammation.J. Immunol., 1993, 151: 3853-3865).
현재 임상에서 사용되고 있는 알레르기 치료약물은 작용기전에 따라 탈과립 저해제, 화학전달물질 작용억제제, 화학전달물질 합성저해제 등으로 대별할 수 있다. 이들 약물들 중 화학전달물질 작용억제제와 화학전달물질 합성저해제의 경우 약물작용점이 비교적 확실하지만 탈과립 저해제의 경우 그 작용기전이 불분명한 상태이다. Allergic drugs currently used in clinical practice can be classified into degranulation inhibitors, chemotransmitter inhibitors, and chemotransferase inhibitors depending on the mechanism of action. Among these drugs, chemical transport inhibitors and chemical transport inhibitors have a relatively certain drug action point, but degranulation inhibitors have an unclear mechanism of action.
또 이들 약물들은 장기간 투여에 의해 여러 가지 부작용을 초래할 수 있다. Ⅰ형 알레르기는 비만세포의 활성화에 의해 방출되는 과립내용물인 활성아민류와 프로테아제 (Protease)류, 세포막 인지질에서 생성되는 지질성 매개체, 전사의 활성화에 의해 생산되는 사이토카인 (Cytokine)류 등이 관련되어 일어나는 생체의 자연스러운 현상이라고 종합할 수 있다. These drugs can also cause various side effects by prolonged administration. Type I allergies include active amines, proteases, and lipid mediators produced by cell membrane phospholipids, and cytokines produced by activation of transcription. It can be summarized as a natural phenomenon of living organisms.
I형 알레르기의 치료를 위해서는 비만세포에서 이들 생리활성 물질의 생산 및 유리에 대한 작용기전을 밝히고 장기복용에 따른 부작용을 최소화할 수 있는 물 질의 개발이 대단히 중요하다고 할 수 있다. For the treatment of type I allergy, it is very important to develop a substance that can reveal the mechanism of action on the production and release of these bioactive substances in mast cells and minimize the side effects of long-term use.
따라서 비만세포에서 작용기전이 확실한 생리활성 물질의 생산 및 유리를 조절하는 약물을 개발한다면 알레르기의 예방 및 치료제가 될 것이다.Therefore, developing drugs that regulate the production and release of physiologically active substances with a certain mechanism of action in mast cells would be a preventive and therapeutic agent for allergies.
한편, 본 발명의 약학조성물에 사용되는 주성분인 쥐눈이콩small black soybean(Glycine max Merr.)은 여두 또는 서목태(鼠目太)라고도 한다. 콩과의 다년생 만초(蔓草)로 줄기와 잎은 갈색이다. 7월에 노란 꽃이 피어 타원형의 깍지 속에 지름 5 ∼ 7 ㎜ 정도의 검고 둥근 열매가 여물면 수확한다. 《본초강목》에 의하면 빛이 검으면서 반들반들하고 작은 수콩(雄豆)을 약으로 쓰는 것이 더 좋다고 한다. 유황을 뿌리고 재배하면 약성이 더욱 좋아지는 것으로 알려져 있다. 성질이 따뜻하고, 맛은 달며, 독이 없다. On the other hand, small black soybean (Glycine max Merr.), The main ingredient used in the pharmaceutical composition of the present invention is also called vulgaris or Seomoktae (鼠目 太). Perennial perennial plant (만 草) with stem and leaves brown. In July, yellow flowers bloom in the oval pods, and when black and round fruits of 5 to 7 mm in diameter grow, they are harvested. According to the Herb Wood, it is better to use it as a medicine while the light is black and soft. It is known that cultivation with sulfur will improve its weakness. It is warm in nature, tastes sweet and nonpoisonous.
동의보감 상에 약재로 사용하는 것으로 기재된 쥐눈이콩은 신장과 관련한 곡식이므로 신장병이 있을 때 먹으면 좋고, 삼초 중 중초를 고르게 하고, 기를 내려서 모든 풍열(風熱)을 억제하며, 맥이 막힌 것을 통하게 한다고 알려져 있다. 또한, 쥐눈이콩은 광물성 약재의 독을 비롯한 모든 독을 풀며, 혈액순환을 활발하게 한다고 기재되어 있다. The rat eye bean, which is described as a medicinal herb, is a grain related to kidneys, so it is good to eat when there is a kidney disease, to even out the middle of three seconds, reduce the wind and suppress all wind fever, and let the vein become blocked. have. In addition, rat eye has been described as releasing all poisons, including the poison of the mineral medicine, and active blood circulation.
쥐눈이콩의 성질은 평범하지만 법제하는 데 따라 적용하는 증세가 다른데, 이를 달인 물은 성질이 몹시 차갑기 때문에 몸에 열이 몹시 나고 가슴속이 답답하며 괴로운 증세에 효과가 있고, 모든 약의 독을 푸는 것으로 알려져 있다. 쥐눈이콩으로 만든 두부는 성질이 차갑기 때문에 기를 움직이고, 쥐눈이콩을 볶아서 먹으면 몸이 더워지며, 술에 담갔다가 먹으면 풍증(風症)에 효과가 있는 것으로 알려져 있다. 삶거나 찐 쥐눈이콩에 소금이나 새앙 따위를 섞어 띄워서 약을 만들면 성질이 몹시 차가워지는데, 이것으로 죽을 쑤어 먹으면 소갈증을 없애주며, 장을 만들면 성질이 평범해진다고 알려져 있다. The nature of the rat's eyes is normal, but the symptoms applied by the law is different. The decoction of water is very cold, so the body is very feverish, frustrating and painful, and it is effective to detoxify all medicines. Known. Tofu made with rat bean is cold because it is cold in nature, and it is known that the rat eye is fried and eaten, and the body gets hot. Boiled or steamed rats are mixed with salt or saenggi soybeans to make the medicine is very cold.
또한, 쥐눈이콩은 인체에 안전하고 독성이 없으며, 항산화작용, 항바이러스작용 등을 가짐이 보고되어 있어, 통상적으로 신경통, 신장질환, 노인성치매예방 등에 사용한다고 알려져 있다. In addition, rat eye is safe and non-toxic to the human body, has been reported to have antioxidant activity, antiviral action, etc., it is commonly known to be used for neuralgia, kidney disease, senile dementia prevention and the like.
따라서, 아직까지 쥐눈이콩의 알레르기성 질환에 대한 작용에 대해서는 개시된 것이 없다.Therefore, there is no disclosure about the effect on rat allergic disease.
본 발명자들은 전신성 알레르기와 국소 피부 알레르기 등과 같은 알레르기성 질환에 대한 치료제를 개발하고자 연구노력 하였으며, 쥐눈이콩 물추출물이 세포내에서 TNF-α 및 IL-8의 생성을 감소시키는 작용기전을 가짐을 확인하고 본 발명을 완성하였다.The present inventors have tried to develop a therapeutic agent for allergic diseases such as systemic allergy and topical skin allergy, and confirmed that rat bean water extract has a mechanism of action to reduce the production of TNF-α and IL-8 in cells. This invention was completed.
따라서, 본 발명은 전신성 알레르기 반응 및 국소 피부 알레르기 반응 등과 같은 알레르기성 질환의 예방 및 치료 효과가 탁월하면서도, 장기복용에 따른 부작용이 최소화된 약학조성물을 제공하는 것을 목적으로 한다.Accordingly, an object of the present invention is to provide a pharmaceutical composition that is excellent in preventing and treating allergic diseases such as systemic allergic reactions and local skin allergic reactions, and minimizes side effects due to long-term use.
상기한 과제를 해결하기 위한 일례로서 본 발명은, 쥐눈이콩 물추출물을 유효성분으로 함유하는 알레르기성 질환 예방 및 치료용 약학조성물을 특징으로 한다.As an example for solving the above problems, the present invention is characterized by a pharmaceutical composition for the prevention and treatment of allergic diseases containing rat bean water extract as an active ingredient.
이하, 본 발명을 상세하게 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본 발명의 약학조성물은 쥐눈이콩small black soybean(Glycine max Merr.) 물추출물을 유효성분으로 함유한다.The pharmaceutical composition of the present invention contains small black soybean (Glycine max Merr.) Water extract as an active ingredient.
이하, 쥐눈이콩 물추출물을 수득하는 방법에 대하여 상세하게 설명한다.Hereinafter, the method for obtaining the rat bean water extract will be described in detail.
본 발명의 쥐눈이콩 물추출물은, 쥐눈이콩을 건조 및 분쇄한 분말 중량의 5 ~ 10 배, 바람직하기로는 약 5 배에 달하는 부피의 물을 사용하여, 수욕상에서 3 ~ 6 시간씩 2 ~ 5 회 반복 추출한 후, 여지로 여과한 여액을 증발 농축하고 잔사를 동결건조하여 얻을 수 있다. 상기와 같은 방법으로 얻어진 쥐눈이콩 물추출물은 -20 ℃ 에 보관하면서 실험에 이용한다. 상기 쥐눈이콩 물추출물의 건조분말은 식염수(saline) 또는 티로이드 완충용액 A(Thyroid buffer A: 10 mM HEPES, 130 mM NaCl, 5 mM KCl, 1.4 mM CaCl2, 1 mM MgCl2, 5.6 mM glucose, 0.1% bovine serum albumin)에 사용 전에 용해하여 일정한 농도로 조제하여 사용한다.The rat bean water extract of the present invention is 5 to 10 times, preferably about 5 times the weight of the powder weight of dried and ground mouse eye, using 2 to 5 times in water bath for 3 to 6 hours. After repeated extraction, the filtrate filtered through filtrate can be evaporated and concentrated and the residue can be obtained by lyophilization. The mouse eye water extract obtained by the above method is used for experiments while being stored at -20 ° C. The dry powder of the rat bean water extract was saline or thyroid buffer A (Thyroid buffer A: 10 mM HEPES, 130 mM NaCl, 5 mM KCl, 1.4 mM CaCl 2 , 1 mM MgCl 2 , 5.6 mM glucose, Dissolve in 0.1% bovine serum albumin) and prepare to a constant concentration.
상기에서 수득된 쥐눈이콩 물추출물의 알레르기성 질환에 대한 활성을 확인하기 위하여, 전신성 알레르기 질환에 대한 농도별 및 투여 시간별 활성을 측정하였으며, 국소 피부 알레르기에 대한 수동 국소 피부 알레르기 반응(PCA)에 대한 활성 및 염증 유발성 사이토카인 분비에 대한 실험을 수행한 결과, 그 뛰어난 효과를 확인할 수 있었다.In order to confirm the activity of allergic diseases of the rat eye water extract obtained above, the activity of each concentration and time of administration for systemic allergic diseases was measured, and for manual local skin allergic reaction (PCA) to local skin allergy. Experiments on active and proinflammatory cytokine secretion showed excellent effects.
이러한 쥐눈이콩 물추출물은 전체 약학조성물 중 5 ~ 90 중량% 범위, 바람직하기로는 10 ~ 80 중량% 범위로 포함될 수 있다.Such rattle water extract may be included in the range of 5 to 90% by weight, preferably 10 to 80% by weight of the total pharmaceutical composition.
본 발명의 약학조성물은 바람직하게는, 본 발명에 따른 조성물은 약제학적으로 허용 가능한 담체를 더 포함할 수 있으며, 상기 약제학적으로 허용 가능한 담체로는, 이에 제한되는 것은 아니지만, 부형제, 결합제, 활택제, 붕괴제, 피복제, 유화제, 현탁제, 용제, 안정화제, 흡수조제, 주사용수 및 등장화제 등으로 이루어진 군으로부터 선택된 1 종 또는 2 종 이상의 혼합물을 사용할 수 있다.The pharmaceutical composition of the present invention, preferably, the composition according to the present invention may further comprise a pharmaceutically acceptable carrier, the pharmaceutically acceptable carrier, including but not limited to excipients, binders, lubricants One kind or a mixture of two or more kinds selected from the group consisting of agents, disintegrating agents, coating agents, emulsifiers, suspending agents, solvents, stabilizers, absorption aids, water for injection, and isotonic agents can be used.
본 발명의 약학조성물은 경구형 제제, 외용제 및 주사제 등으로써 제형화 될 수 있으며 경구형 제제와 외용제의 제형이 보다 바람직하다. 경구형 제제로는, 과립제, 정제, 캡슐제, 환제, 현탁액, 에멀젼, 시럽 등을 예시할 수 있으며 외용제로는 연고제, 로션제, 에어로졸 등을 예시할 수 있다.The pharmaceutical composition of the present invention may be formulated as an oral preparation, an external preparation, an injection, and the like, and more preferably, an oral preparation and an external preparation. Examples of oral formulations include granules, tablets, capsules, pills, suspensions, emulsions, syrups, and the like, and external preparations include ointments, lotions, aerosols, and the like.
상기 알레르기성 질환은 염증성 알레르기 질환일 수 있으며, 이러한 염증성 알레르기 질환으로는 전신성 알레르기 반응 또는 국소 피부 알레르기 반응이 있다. 구체적으로 상기한 염증성 알레르기 질환을 예시하면, 과민증(anaphylaxia), 알레르기성 비염(allergic rhinitis), 천식(asthma), 알레르기성 결막염, 알레르기성 피부염, 아토피성 피부염(atopic dermatitis), 접촉성 피부염, 두드러기(urticaria), 곤충 알레르기, 식품 알레르기 및 약품 알레르기 등이 있으며, 본 발명의 약학조성물은 상기한 질환에 유효하다.The allergic disease may be an inflammatory allergic disease. Such inflammatory allergic diseases include systemic allergic reactions or local skin allergic reactions. Specific examples of the inflammatory allergic diseases include anaphylaxia, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, atopic dermatitis, contact dermatitis, urticaria (urticaria), insect allergies, food allergies, drug allergies, and the like, and the pharmaceutical composition of the present invention is effective for the above diseases.
본 발명의 쥐눈이콩 물추출물은, 오래도록 식용되어져온 식물로서, 인체에 어떠한 독성도 유발시키지 않음은 자명하며, 따라서, 장기간 투여에 따른 부작용이 없는 장점을 가진다.The rat bean water extract of the present invention is a plant that has been edible for a long time, it is obvious that it does not cause any toxicity to the human body, and thus has the advantage that there is no side effect of long-term administration.
본 발명의 약학조성물의 바람직한 투여량은 환자의 나이, 성별, 체중과, 질병의 정도, 약물의 형태, 투여경로 및 기간에 따라 달라질 수 있으나, 이러한 투여량은 당업자에 의하여 적절히 조절될 수 있다. 그러나, 바람직한 효과를 발현하기 위해서, 본 발명의 쥐눈이콩 물추출물은 2 ~ 100 mg/kg/day, 바람직하기로는 5 ~ 50 mg/kg/day이 효과적이다. 상기 투여는 하루에 한번 투여할 수도 있고, 수회 나누어서 투여할 수 있으므로, 이러한 투여량이 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the pharmaceutical compositions of the present invention may vary depending on the age, sex, weight, and severity of the patient, the form of the drug, the route of administration, and the length of time. Such dosages can be appropriately adjusted by those skilled in the art. However, in order to express the desired effect, the rat bean water extract of the present invention is 2 to 100 mg / kg / day, preferably 5 to 50 mg / kg / day is effective. The administration may be administered once a day, or may be administered several times, such a dose does not limit the scope of the present invention.
이러한 본 발명의 쥐눈이콩 물추출물을 유효성분으로 하는 약학조성물은 다양한 식품류에도 이용될 수 있으며, 본 발명의 조성물이 첨가될 수 있는 식품으로는 예컨대, 차, 술, 음료, 건강보조 식품류 등을 예로 들 수 있고, 외용제로서 화장품류에도 적용가능하며, 개, 토끼, 고양이 등의 온혈동물 치료에도 사용이 가능하다.The pharmaceutical composition using the rat bean extract of the present invention as an active ingredient may be used in various foods. Examples of the foods to which the composition of the present invention may be added include, for example, tea, alcohol, beverages, health supplements, and the like. The present invention can be applied to cosmetics as an external preparation, and can be used to treat warm-blooded animals such as dogs, rabbits and cats.
본 발명에 따른 쥐눈이콩 물추출물을 유효성분으로 하는 알레르기성 질환의 예방 및 치료용 약학조성물은 인체에 안전하고 독성이 없으며, 세포내에서 TNF-α 및 IL-8의 생성을 감소시키는 작용 기전을 가지므로, 전신성 알레르기 반응과 국소 피부 알레르기 반응 등의 예방 및 치료에 우수한 효과를 나타낸다.The pharmaceutical composition for the prevention and treatment of allergic diseases, comprising the extract of the rat eye, according to the present invention as an active ingredient, is safe and nontoxic to the human body, and has a mechanism of action to reduce the production of TNF-α and IL-8 in cells. Therefore, it shows an excellent effect on the prevention and treatment of systemic allergic reactions and local skin allergic reactions.
이하, 실시예에 의거하여 본 발명을 더욱 구체적으로 설명하겠는바, 다음 실시예에 의하여 본 발명이 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by the following Examples.
실시예 1 : 쥐눈이콩 물추출물의 제조Example 1 Preparation of Rat Bean Water Extract
전라북도 임실에서 구입한 쥐눈이콩을 실험에 사용하였으며, 분쇄된 쥐눈이콩 분말 100 g을 0.5 ℓ의 증류수를 가하여 잘 교반한 다음 수욕상에서 5시간 동안 2회 출한 후 여액을 분리하였고 농축한 후 동결건조시켜 쥐눈이콩 물추출물의 분말 11.3 g을 수득하였다.The rat eye bean purchased from Imsil, Jeollabuk-do was used for the experiment, and 100 g of the ground mouse eye bean powder was stirred well by adding 0.5 L of distilled water, and then extracted twice in a water bath for 5 hours, and the filtrate was separated, concentrated and freeze-dried. 11.3 g of powder of rat bean water extract was obtained.
실험예 1 : 전신성 알레르기 반응에 대한 쥐눈이콩 물추출물의 농도에 따른 효과Experimental Example 1: Effect of rat eye extract on the systemic allergic reaction
쥐눈이콩 물추출물이 생쥐의 전신성 알레르기 반응에 미치는 효과를 확인하기 위하여 치사율 실험을 하였으며, 다음 표 1에 전신성 알레르기 반응에 대한 쥐눈이콩 물추출물의 농도에 따른 효과를 나타내었다.To determine the effect of rat eye water extract on systemic allergic reactions in mice, mortality experiments were conducted. Table 1 shows the effects of rat eye water extracts on systemic allergic reactions.
비만세포 탈과립제인 compound 48/80을 생쥐(대한 바이오링링크에서 구입한 4 주령의 수컷 ICR 종, 평균체중 20 ~ 24 g)의 복강에 투여하기 60분 전에 쥐눈이콩 물추출물의 분말을 증류수에 0.01 ~ 1.0 mg/g의 용량으로 용해시켜 복강 내에 주사하였으며, 치사율은 아나필락시를 유발시킨 후 1시간 동안 관찰하였다. 생리식염수 200 μl를 투여한 대조군은 100 % 치사율을 보였지만 쥐눈이콩 물추출물의 분말을 0.05 mg/g 농도로 투여하였을 때는 60 %, 0.1 mg/g 농도로 투여하였을 때는 30 %, 0.5 mg/g 농도로 투여하였을 때는 0 %로 농도 의존적으로 치사율이 억제됨을 알 수 있었다 .Methanol water extract powder was added to distilled water 0.01 minutes before administration of compound 48/80, a mast cell degranulator, into the abdominal cavity of mice (4 weeks old male ICR species purchased from Daehan Bioringlink, average weight 20-24 g). Dissolved at a dose of ˜1.0 mg / g and injected intraperitoneally, lethality was observed for 1 hour after inducing anaphylaxis. The control group treated with 200 μl of saline showed 100% mortality, but 60% with 0.05 mg / g powder of rat bean water extract, 30% with 0.5 mg / g, and 0.5 mg / g. When administered as, the mortality rate was suppressed to 0%.
실험예 2 : 전신성 알레르기 반응에 대한 쥐눈이콩 물추출물의 시간에 따른 효과Experimental Example 2 Effect of Rats Eye Water Extracts on Systemic Allergic Reaction over Time
쥐눈이콩 물추출물이 생쥐의 전신성 알레르기 반응에 미치는 효과를 확인하기 위하여 시간에 따른 치사율 실험을 하였으며, 다음 표 2는 전신성 알레르기 반응에 대한 쥐눈이콩 물추출의 시간에 따른 효과를 나타내었다.To determine the effect of rat eye water extract on systemic allergic reactions in mice, mortality experiments were conducted over time. Table 2 shows the effects of rat eye water extraction on systemic allergic reactions over time.
비만세포 탈과립제인 compound 48/80을 생쥐(대한 바이오링링크에서 구입한 4 주령의 수컷 ICR 종, 평균체중 20 ~ 24 g)의 복강에 투여한 후 쥐눈이콩 물추출물의 분말 1.0 mg/g을 5분, 10분, 15분 및 20분에 각각 복강 내에 주사하였으며 치사율은 아나필락시를 유발시킨 후 1시간 동안 관찰하였다. 탈과립제인 compound 48/80을 생쥐의 복강에 투여한 5분 후에 쥐눈이콩 물추출물을 투여하였을 때 치사율은 0 %, 10분 후에 투여하였을 때는 70 %, 15분 후에 투여하였을 때는 80 %로 치사율이 시간 의존적으로 증가함을 알 수 있었다Magnesium cell degranulation compound 48/80 was injected into the abdominal cavity of mice (4 weeks old male ICR species purchased from Daehan Bioringlink, average weight 20-24 g), and then 1.0 mg / g Minutes, 10 minutes, 15 minutes and 20 minutes were injected intraperitoneally, respectively, and lethality was observed for 1 hour after inducing anaphylaxis. After 5 minutes of degranulation, Compound 48/80 was injected into rat abdominal cavity, and the mortality rate was 0% when rat bean water extract was administered, 70% after 10 minutes, and 80% after 15 minutes. Increased dependently
실험예 3 : 국소 피부 알레르기 반응에 대한 쥐눈이콩 물추출물의 효과Experimental Example 3 Effects of Water Extracts from Rats' Eyes on Local Skin Allergic Reactions
알레르기 치료효과를 갖는 약물을 개발할 때 많이 사용되는 수동 국소 피부 알레르기 반응 (Passive Cutaneous Anaphylaxis, PCA)을 이용하여 쥐눈이콩 물추출물의 피부 알레르기에 대한 효과를 실험하였다. Passive cutaneous anaphylaxis (PCA), which is widely used when developing drugs with allergic effects, was used to examine the effects of rat eye water extract on skin allergy.
PCA는 면역 글로블린 E(IgE)에 의해 매개되는 알레르기 반응으로 항체를 국소 피부에 피내주사하고 48시간 후 항원을 생쥐의 꼬리 정맥으로 투여하여 인위적으로 알레르기 반응을 일으키는 실험 방법이다. PCA is an allergic reaction mediated by immunoglobulin E (IgE), which is an experimental method of artificially causing an allergic reaction by intravenously injecting an antibody into topical skin and administering the antigen to the tail vein of the mouse 48 hours later.
다음 표 3은 국소 피부 알레르기 반응에 대한 쥐눈이콩 물추출물의 효과를 나타내고 있는데, 항원과 항체를 생쥐에 투여하면 항체 주입 부위에 국소적으로 발적이 일어나 그 부위에 존재하는 비만세포가 활성화 되어 국소적으로 알레르기 반응이 나타난다. 여기에 쥐눈이콩 물추출물의 분말을 농도별로 증류수에 용해한 용액을 투여한 결과 쥐눈이콩 물추출물의 농도 의존적으로 국소 피부 알레르기 반응이 억제됨을 알 수 있었다.The following Table 3 shows the effect of water extract of rat eye on local skin allergic reaction. When antigen and antibody are administered to mice, local redness occurs at the injection site of the antibody, which activates the mast cells present in the site. As allergic reactions occur. In addition, the result of administering a solution in which the powder of the rat bean water extract was dissolved in distilled water for each concentration showed that the skin allergic reaction was suppressed depending on the concentration of the rat bean water extract.
실험예 3 : 염증 유발성 사이토카인의 분비에 대한 쥐눈이콩 물추출물의 효과Experimental Example 3 Effect of Rat Eye Extract on the Secretion of Inflammatory Cytokines
TNF-α, IL-8과 같은 염증 유발성 사이토카인은 비만세포에서 유리되거나 새로 합성되어 분비됨으로서 염증성 알레르기를 유발하는 중요한 생리활성 물질이다. 다음 표 4 및 표 5는 염증 유발성 사이토카인의 분비에 대한 쥐눈이콩 물추출물의 저해 효과를 나타내고 있다. Inflammatory cytokines such as TNF-α and IL-8 are important bioactive substances that cause inflammatory allergies by being released from mast cells or newly synthesized. Tables 4 and 5 show the inhibitory effect of the rat bean water extract on the secretion of inflammatory cytokines.
단백질 키나제 C(Protein kinase C) 활성화 인자인 포르볼 12-미리스테이트 13-아세테이트(Phorbol 12-myristate 13-acetate, PMA)와 칼슘 채널 활성화 인자인 칼슘 이오노포어 A23187(Calcium ionophore A23187, A23187)은 비만세포를 활성화 하여 염증 유발성 사이토카인의 분비를 촉진한다는 것이 널리 알려져 있으며, 이들을 인체 비만세포주 (Human mast cell lime, HMC-1 )인 세포에 투여한 결과 TNF-α 및 IL-8의 분비량이 증가하였다. Protein kinase C activator phorbol 12-myristate 13-acetate (PMA) and calcium channel activator calcium ionophore A23187 (Calcium ionophore A23187, A23187) It is widely known that activating mast cells promotes the secretion of inflammatory cytokines, and the amount of TNF-α and IL-8 secreted as a result of administration to human mast cell lime (HMC-1) cells Increased.
여기에 쥐눈이콩 물추출물의 분말을 농도별로 증류수에 용해한 용액을 투여한 결과 쥐눈이콩 물추출물의 농도 의존적으로 PMA와 A23187에 의한 TNF-α (표 4) 및 IL-8 (표5) 분비량이 감소됨을 알 수 있었다.As a result of administering a solution in which the powder of the rat bean water extract was dissolved in distilled water by concentration, the secretion of TNF-α (Table 4) and IL-8 (Table 5) by PMA and A23187 was reduced depending on the concentration of the rat bean water extract. And it was found.
이하, 본 발명에 따른 알레르기의 예방 및 치료용 조성물을 다양한 제형으로 제제화한 제조예를 설명하기로 한다. 이하에서 사용된 쥐눈이콩 물추출물은 별도의 기재가 없는 한 쥐눈이콩 물추출물의 건조분말을 의미한다. Hereinafter, the preparation examples of the composition for preventing and treating allergy according to the present invention in various dosage forms will be described. As used herein, rat eye water extract means a dry powder of rat eye water extract unless otherwise stated.
제조예 1: 정제Preparation Example 1 Tablet
하기의 조성에 따라 통상의 정제 제조방법으로 제조하였다.According to the following composition was prepared by a conventional tablet manufacturing method.
정제 조성물Tablet composition
쥐눈이콩 물추출물 600.0 mgRat bean water extract 600.0 mg
유당 500.0 mgLactose 500.0 mg
탈크 5.0 mgTalc 5.0 mg
마그네슘 스테아레이트 1.0 mgMagnesium Stearate 1.0 mg
제조예 2 : 캡슐제Preparation Example 2 Capsule
하기와 같은 방법에 따라 다음과 같은 조성으로 캡슐제를 제조하였다. 이때, 쥐눈이콩 물추출물을 체질하여 부형제와 혼합한 후 젤라틴 캡슐 중에 충전하여 캡슐을 제조하였다.According to the following method was prepared a capsule with the following composition. At this time, sieve bean water extract was sieved and mixed with excipients and then filled into gelatin capsules to prepare capsules.
캡슐제 조성물Capsule Composition
쥐눈이콩 물추출물 600.0 mgRat bean water extract 600.0 mg
전분 1500 10.0 mgStarch 1500 10.0 mg
스테아르산마그네슘 100.0 mgMagnesium stearate 100.0 mg
제조예 3 : 과립제Preparation Example 3 Granules
하기의 성분을 통상의 과립제의 제조방법으로 과립제를 제조하였다.The granules were prepared by the following method for preparing the granules.
과립제 조성물Granule composition
쥐눈이콩 물추출물 600.0 mgRat bean water extract 600.0 mg
유당 100.0 mgLactose 100.0 mg
탈크 5.0 mgTalc 5.0 mg
제조예 4 : 주사제Preparation Example 4 Injection
하기의 성분을 통상의 주사제의 제조방법으로 10.0 ml의 앰플에 충전하고 멸균시켜 근육주사제를 제조하였다.The following components were filled in 10.0 ml of ampoules and sterilized by a conventional method for preparing an injection, thereby preparing an intramuscular injection.
주사제 조성물Injectable Composition
쥐눈이콩 물추출물 600.0 mgRat bean water extract 600.0 mg
산성아황산나트륨 10.0 mg10.0 mg of acid sodium sulfite
메틸파라벤 6.0 mgMethylparaben 6.0 mg
푸로펜파라벤 4.0 mgFuropenparaben 4.0 mg
제일인산나트륨 12.0 mgSodium phosphate 12.0 mg
제이인산나트륨 8.0 mgSodium diphosphate 8.0 mg
수산화나트륨 10.0 mgSodium hydroxide 10.0 mg
주사용 수 10.0 ml10.0 ml water for injection
제조예 5 : 크림제Preparation Example 5 Cream
하기의 성분을 통상의 크림제의 제조방법으로 1,000 g을 제조하였다.The following components were prepared 1,000 g by the conventional method for preparing a cream.
크림제 조성물Cream composition
쥐눈이콩 물추출물 50.0 gRat bean water extract 50.0 g
백색바셀린 250.0 gWhite Vaseline 250.0 g
스테아린알코올 200.0 g200.0 g of stearin alcohol
프로피렌그라이콜 120.0 gPropylene glycol 120.0 g
스테아린산모노글리세린 60.0 g60.0 g of stearic acid monoglycerin
피마자유 0.08 g0.08 g of castor oil
메틸파라벤 0.06 g0.06 g of methyl paraben
정제수 적량Purified water
제조예 6 : 로션제Preparation Example 6 Lotion Agent
하기의 성분을 통상의 로션제의 제조방법으로 1,000 ml를 제조하였다.The following components were prepared in 1,000 ml by a conventional method for preparing a lotion.
로션제 조성물Lotion composition
쥐눈이콩 물추출물 50.0 gRat bean water extract 50.0 g
글리세린 80.0 gGlycerin 80.0 g
올레인산 20.0 g20.0 g of oleic acid
트리에탄올아민 5.0 g5.0 g of triethanolamine
정제수 적량Purified water
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2018190638A1 (en) * | 2017-04-12 | 2018-10-18 | 한국과학기술연구원 | Composition for preventing or treating corneal diseases, containing glycine max extract |
EP3590522A1 (en) * | 2018-07-05 | 2020-01-08 | Korea Institute of Science and Technology | Composition for preventing or improving inflammation including extract of seed of new soybean cultivar scel-1 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2018190638A1 (en) * | 2017-04-12 | 2018-10-18 | 한국과학기술연구원 | Composition for preventing or treating corneal diseases, containing glycine max extract |
EP3590522A1 (en) * | 2018-07-05 | 2020-01-08 | Korea Institute of Science and Technology | Composition for preventing or improving inflammation including extract of seed of new soybean cultivar scel-1 |
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