KR20240000071A - Osteoclast inhibitory composition of Aster glehni Extract and its Treatment - Google Patents
Osteoclast inhibitory composition of Aster glehni Extract and its Treatment Download PDFInfo
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- KR20240000071A KR20240000071A KR1020220076564A KR20220076564A KR20240000071A KR 20240000071 A KR20240000071 A KR 20240000071A KR 1020220076564 A KR1020220076564 A KR 1020220076564A KR 20220076564 A KR20220076564 A KR 20220076564A KR 20240000071 A KR20240000071 A KR 20240000071A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
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- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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Abstract
일 실시예는, 섬쑥부쟁이 추출물을 유효성분으로 포함하는 파골세포 억제 조성물 및 그 치료제를 제공한다. One embodiment provides an osteoclast-inhibiting composition and a therapeutic agent thereof containing an extract of Sagebrush as an active ingredient.
Description
본 발명은 섬쑥부쟁이 추출물의 파골세포 억제 조성물 및 그 치료제에 관한 것이다. The present invention relates to an osteoclast-inhibiting composition of an extract of Sagebrush and a therapeutic agent thereof.
섬쑥부쟁이(Aster glehni F.Schmidt)는 국화과 참취속의 여러해살이 풀이다. Aster glehni F.Schmidt is a perennial herb of the Asteraceae genus.
섬쑥부쟁이(Aster glehni F.Schmidt)는 비타민 A와 C가 풍부하고, 단백질과 인, 칼슘 등이 들어 있는 것으로 알려졌다. 섬쑥부쟁이에 들어있는 휘발성 향미성분은, 예를 들어, 알코올류 7종 8.5%, 에스테르류 3종 2.1%, 옥사이드류 1종 2.10%, 산류 1종 1.65% 및 알데히드류 1종 0.48%로 알려졌다. 섬쑥부쟁이의 주요 휘발성 향미성분은 알파-pinene, limonene, 감마-elemene, 베타-pinene, 시스-3-hexenol 및 myrcene이다. Aster glehni F.Schmidt is rich in vitamins A and C and is known to contain protein, phosphorus, and calcium. Volatile flavor components contained in sagebrush, for example, are known to be 8.5% of 7 alcohols, 2.1% of 3 esters, 2.10% of oxides, 1.65% of acids, and 0.48% of aldehydes. . The main volatile flavor components of sagebrush are alpha-pinene, limonene, gamma-elemene, beta-pinene, cis-3-hexenol, and myrcene.
섬쑥부쟁이는 개미취와 비슷한 약효를 가지고 있고, 사상의학 기준으로 호흡기가 약해서 기침이나 가래가 많은 태음인이 꾸준히 먹으면 효과가 있으나 소음인이 너무 많이 먹지 않는 것이 좋은 것으로 알려졌다. It has medicinal properties similar to that of ants, and according to Sasang medical standards, it is effective for Taeeum people who have a weak respiratory system and cough or have a lot of phlegm if they eat it regularly, but it is known that it is better for Soeum people not to eat too much of it.
섬쑥부쟁이는 튀겨서 먹기도 하며 국에 넣어 식용하기도 하고 묵나물로 저장하면서 이용되기도 한다. 섬쑥부쟁이는 다른 쑥부쟁이류와 마찬가지로 약간 쓰고 떫은 맛이 나지만, 예로부터 칼슘과 철분이 풍부하여 시금치 대용으로도 사용되었다. 섬쑥부쟁이는 식용뿐만 아니라 약용으로도 사용된 예들이 있다. Scallops are fried and eaten, added to soups, and stored as muknamul (muknamul). Like other sagebrush species, it has a slightly bitter and astringent taste, but since ancient times it has been used as a substitute for spinach because it is rich in calcium and iron. There are examples of sagebrush being used not only for food but also for medicinal purposes.
예를 들어, 한국공개특허 제2018-0020798호(발명의 명칭: 혈중요산감소를 위한 섬쑥부쟁이 추출물과 비타민을 포함하는 조성물)는 섬쑥부쟁이 추출물 및 비타민 B6의 혼합물을 유효성분으로 함유하는 혈중 요소 농도 저하용 조성물, 또는 통풍 또는 고요산혈증의 예방, 개선 및/또는 치료용 약학/식품 조성물, 및 이를 이용하는 통풍 또는 고요산혈증의 예방 및/또는 치료 방법을 개시하고 있다.For example, Korean Patent Publication No. 2018-0020798 (title of the invention: Composition containing Asterium aster extract and vitamins for reducing blood uric acid) is a blood clot containing a mixture of Asteria serrata extract and vitamin B6 as active ingredients. Disclosed is a composition for lowering urea concentration, or a pharmaceutical/food composition for preventing, improving, and/or treating gout or hyperuricemia, and a method for preventing and/or treating gout or hyperuricemia using the same.
한국공개특허 제2015-0135037호(발명의 명칭: 고요산혈증 또는 통풍에 유효한 섬쑥부쟁이 추출물, 이의 분획물 및 이로부터 분리된 활성화합물)는 섬쑥부쟁이 추출물, 이의 분획물, 그리고 상기 분획물로부터 분리된 활성화합물은 요산의 농도 증가로 인하여 유발되는 질환으로서 고요산혈증 또는 통풍의 치료, 예방 및 개선이 필요한 의약품, 건강식품 등의 활성 성분으로 유용하게 사용하는 것을 개시하고 있다. Korean Patent Publication No. 2015-0135037 (title of the invention: Asterium aster extract, fraction thereof, and active compound isolated therefrom effective for hyperuricemia or gout) is a Asterium aster extract, a fraction thereof, and an active compound isolated from the above fraction. The compound is disclosed to be useful as an active ingredient in medicines, health foods, etc. that require the treatment, prevention, and improvement of hyperuricemia or gout, which are diseases caused by an increase in the concentration of uric acid.
섬쑥부쟁이는 기침이나, 이뇨, 천식에 대한 약리작용을 가지고 있다고 알려진 것과 함께, 전술한 바와 같이 혈중 요산 농도 저하효과가 향상되어 통풍 또는 고요산혈증의 예방에 효과가 있는 것으로 알려졌다. 통풍은 관절의 염증에 관여하며 다른 관절 질환과 달리 면역시스템이 아닌 주로 인체 대사에 관여하는 것으로 알려졌다. In addition to being known to have pharmacological effects on coughing, diuresis, and asthma, it is also known to be effective in preventing gout or hyperuricemia by improving the effect of lowering blood uric acid concentration as mentioned above. Gout is known to be involved in joint inflammation, and unlike other joint diseases, it is mainly involved in human metabolism rather than the immune system.
본 발명은 파골세포 분화가 효과적으로 억제되는 파골세포 억제 조성물 및 그 치료제를 제공한다. The present invention provides an osteoclast inhibitory composition that effectively inhibits osteoclast differentiation and a therapeutic agent thereof.
일 실시예는, 섬쑥부쟁이 추출물을 유효성분으로 포함하는 파골세포 억제 조성물 및 그 치료제를 제공한다. One embodiment provides an osteoclast-inhibiting composition and a therapeutic agent thereof containing an extract of Sagebrush as an active ingredient.
일 실시예에 따른 파골세포 억제 조성물 및 그 치료제는 파골세포 분화가 효과적으로 억제될 수 있다. The osteoclast inhibitory composition and its therapeutic agent according to one embodiment can effectively inhibit osteoclast differentiation.
도 1은 RAW 264.7 세포에서 섬쑥부쟁이 물 추출물의 세포 생존율 및 NO 생성량 확인을 나타낸다.
도 2는 파골세포에서 섬쑥부쟁이 물 추출물의 염증성 사이토카인 억제 확인을 나타낸다.
도 3은 파골세포에서 섬쑥부쟁이 물 추출물의 파골세포 분화 관련 유전자 억제 확인을 나타낸다.
도 4는 파골세포에서 섬쑥부쟁이 물 추출물의 파골세포 활성화 관련 유전자 억제 확인을 나타낸다. Figure 1 shows the confirmation of cell viability and NO production of Aster water extract in RAW 264.7 cells.
Figure 2 shows the confirmation of inhibition of inflammatory cytokines by Aster water extract in osteoclasts.
Figure 3 shows the confirmation of suppression of genes related to osteoclast differentiation by Aster water extract in osteoclasts.
Figure 4 shows confirmation of the inhibition of osteoclast activation-related genes in osteoclasts by the Aster water extract.
이하, 본 발명의 일부 실시예들을 예시적인 도면을 통해 상세하게 설명한다. 각 도면의 구성요소들에 참조부호를 부가함에 있어서, 동일한 구성요소들에 대해서는 비록 다른 도면상에 표시되더라도 가능한 한 동일한 부호를 가지도록 하고 있음에 유의해야 한다. 또한, 본 발명의 실시예들을 설명함에 있어, 관련된 공지 구성 또는 기능에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명은 생략한다.Hereinafter, some embodiments of the present invention will be described in detail through illustrative drawings. When adding reference numerals to components in each drawing, it should be noted that identical components are given the same reference numerals as much as possible even if they are shown in different drawings. Additionally, when describing embodiments of the present invention, if it is determined that a detailed description of a related known configuration or function may obscure the gist of the present invention, the detailed description will be omitted.
본 발명에서 사용되는 용어 "치료", "억제" 및 "약화"란, 본 발명의 조성물을 개체에 사용하여, 특정 세포의 분화나, 특정 물질의 수준, 특정 질병 또는 질환의 진행을 감소시키거나 지연시키는 모든 행위를 의미한다. The terms “treatment,” “inhibition,” and “attenuation” as used in the present invention mean that the composition of the present invention is used on an individual to reduce the differentiation of specific cells, the level of a specific substance, or the progression of a specific disease or condition. It means any act of delay.
본 발명에서 사용되는 용어 "개체"란, 인간을 포함한 모든 동물을 의미한다.The term “individual” used in the present invention refers to all animals, including humans.
이하, 본 발명의 실시예들에 따른 관절에 사용하여 관절염에 우수한 치료 효과를 제공하는 관절염용 파골세포 억제 조성물 및 그 치료제에 대하여 설명한다.Hereinafter, an osteoclast inhibitory composition for arthritis and a therapeutic agent thereof that provide excellent therapeutic effects on arthritis when used in joints according to embodiments of the present invention will be described.
실시예: 약제학적 조성물 및 그 치료제Examples: Pharmaceutical compositions and therapeutic agents thereof
일 실시예는,섬쑥부쟁이 추출물을 유효성분으로 포함하는 파골세포 억제 조성물 및 그 치료제를 제공한다. 후술하는 실험예를 통해 알 수 있는 바와 같이, 섬쑥부쟁이 추출물은 31.25 μg/ml 이상 1,000 μg/ml의 농도의 물 추출물일 수 있으나, 이에 제한되지 않는다. One embodiment provides an osteoclast-inhibiting composition and a therapeutic agent thereof containing an extract of Asterium vulgaris as an active ingredient. As can be seen through the experimental examples described later, the Asterium aster extract may be a water extract at a concentration of 31.25 μg/ml or more and 1,000 μg/ml, but is not limited thereto.
후술하는 실험예를 통해 섬쑥부쟁이 추출물이 파골세포 억제 효능가 있는 것으로 확인할 수 있다. 따라서, 일 실시예에 따른 파골세포 억제 추출물 및 그 치료제가 전술한 섬쑥부쟁이 추출물을 유효성분으로 포함할 경우 파골세포 억제 효능를 가지는 것을 알 수 있다. 일 실시예에 따른 파골세포 억제 추출물 및 그 치료제가 파골세포 억제 효능을 가지기 때문에, 관절염 치료 효능을 나타내는 것을 알 수 있다. Through the experimental example described later, it can be confirmed that the Asterium vulgare extract has an osteoclast inhibitory effect. Therefore, it can be seen that the osteoclast inhibitory extract and its therapeutic agent according to one embodiment have osteoclast inhibitory effect when they include the above-mentioned Asterium vulgaris extract as an active ingredient. Since the osteoclast inhibitory extract and its therapeutic agent according to one embodiment have an osteoclast inhibitory effect, it can be seen that they exhibit arthritis treatment efficacy.
상기 파골세포 억제 치료제는 약제학적으로 허용 가능한 담체를 추가로 포함할 수 있으며, 상기 담체와 함께 제제화되어 식품, 의약품, 사료 첨가제 및 음용수 첨가제 등으로 제공될 수 있다. 본 발명에서 사용되는 용어 "약학적으로 허용 가능한 담체"란 생물체를 자극하지 않으면서, 투여되는 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 의미한다.The osteoclast inhibitory treatment may further include a pharmaceutically acceptable carrier, and may be formulated with the carrier and provided as food, medicine, feed additive, drinking water additive, etc. The term “pharmaceutically acceptable carrier” as used in the present invention refers to a carrier or diluent that does not irritate living organisms and does not inhibit the biological activity and properties of the administered compound.
본 발명에서 용어, "약학적으로 허용 가능한 담체"란 생물체를 자극하지 않고 투여 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 말한다. 액상 용액으로 제제화되는 조성물에 있어서 허용되는 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.In the present invention, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not irritate living organisms and does not inhibit the biological activity and properties of the administered compound. Acceptable pharmaceutical carriers in compositions formulated as liquid solutions include those that are sterile and biocompatible, such as saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these ingredients can be mixed and used, and other common additives such as antioxidants, buffers, and bacteriostatic agents can be added as needed. In addition, diluents, dispersants, surfactants, binders, and lubricants can be additionally added to formulate injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.
본 명세서의 파골세포 억제 조성물은 이를 유효성분으로 포함하는 어떠한 제형으로도 적용가능하며, 경구용 또는 비경구용 제형으로 제조할 수 있다. 본 명세서의 약학적 제형은 구강(oral), 직장(rectal), 비강(nasal), 국소(topical; 볼 및 혀 밑을 포함), 피하, 질(vaginal) 또는 비경구(parenteral; 근육내, 피하 및 정맥내를 포함) 투여에 적당한 것 또는 흡입(inhalation) 또는 주입(insufflation)에 의한 투여에 적당한 형태를 포함한다.The osteoclast inhibitory composition of the present specification can be applied in any formulation containing it as an active ingredient, and can be prepared as an oral or parenteral formulation. The pharmaceutical formulations herein may be administered orally, rectally, nasally, topically (including cheeks and under the tongue), subcutaneously, vaginally, or parenterally (intramuscularly, subcutaneously). and forms suitable for administration (including intravenously) or forms suitable for administration by inhalation or insufflation.
본 명세서의 조성물을 유효성분으로 포함하는 경구 투여용 제형으로는, 예를 들어 정제, 트로키제, 로렌지, 수용성 또는 유성현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캡슐, 시럽 또는 엘릭시르제로 제제화할 수 있다. 정제 및 캡슐 등의 제형으로 제제화하기 위해, 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제, 디칼슘 포스페이트와 같은 부형제, 옥수수 전분 또는 고구마 전분과 같은 붕괴제, 스테아르산 마스네슘, 스테아르산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유를 포함할 수 있으며, 캡슐제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를더 함유할 수 있다.Formulations for oral administration containing the composition of the present specification as an active ingredient include, for example, tablets, troches, lozenges, water-soluble or oily suspensions, powders or granules, emulsions, hard or soft capsules, syrups or elixirs. can do. For formulation into dosage forms such as tablets and capsules, binders such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, and stearic acid masene. It may contain a lubricant such as calcium, calcium stearate, sodium stearyl fumarate, or polyethylene glycol wax, and in the case of a capsule formulation, it may further contain a liquid carrier such as fatty oil in addition to the above-mentioned substances.
본 명세서의 조성물을 유효성분으로 포함하는 비경구 투여용 제형으로는, 피하주사, 정맥주사 또는 근육내 주사 등의 주사용 형태, 좌제 주입방식 또는 호흡기를 통하여 흡입이 가능하도록 하는 에어로졸제 등 스프레이용으로 제제화할 수 있다. 주사용 제형으로 제제화하기 위해서는 본 발명의 조성물을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알의 단위 투여용으로 제제화할 수 있다. 좌제로 주입하기 위해서는, 코코아버터 또는 다른 글리세라이드 등 통상의 좌약 베이스를 포함하는 좌약 또는 관장제와 같은 직장투여용 조성물로 제제화할 수 있다. 에어로졸제 등의 스프레이용으로 제형화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합될 수 있다.Formulations for parenteral administration containing the composition of the present specification as an active ingredient include injection forms such as subcutaneous injection, intravenous injection, or intramuscular injection, suppository injection, or sprays such as aerosols that allow inhalation through the respiratory tract. It can be formulated as: In order to formulate a formulation for injection, the composition of the present invention can be mixed in water with a stabilizer or buffer to prepare a solution or suspension, and the composition can be formulated for unit administration in ampoules or vials. For injection as a suppository, it can be formulated into a composition for rectal administration such as a suppository or enema containing a common suppository base such as cocoa butter or other glycerides. When formulating for spraying such as an aerosol, a propellant, etc. may be mixed with additives to disperse the water-dispersed concentrate or wet powder.
본 발명의 파골세포 억제 조성물 및 그 치료제의 투여방법은 특별히 제한되는 것은 아니나, 목적하는 방법에 따라 정맥 내, 피하, 복강 내, 흡입, 피부도포, 패치제 또는 국소적용과 같이 비경구 투여하거나 경구 투여할 수 있다.The method of administration of the osteoclast inhibitory composition and its therapeutic agent of the present invention is not particularly limited, but is administered parenterally or orally, such as intravenously, subcutaneously, intraperitoneally, inhalation, skin application, patch, or topical application, depending on the desired method. It can be administered.
투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 그 범위가 다양하다. 일일 투여량은 치료를 필요로 하는 개체에 투여됨으로써 경감된 질병 상태에 대한 치료에 충분한 본 발명의 치료용 물질의 양을 의미한다. 치료용 물질의 효과적인 양은 특정 화합물, 질병 상태 및 그의 심각도, 치료를 필요로 하는 개체에 따라 달라지며, 이는 당업자에 의해 통상적으로 결정될 수 있다. 비제한적 예로서, 본 발명에 의한 조성물의 인체에 대한 투여량은 환자의 나이, 몸무게, 성별, 투여 형태, 건강 상태 및 질환 정도에 따라 달라질 수 있다. The dosage range varies depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of the disease. Daily dosage refers to the amount of therapeutic agent of the invention sufficient to treat the disease condition alleviated by administration to an individual in need of treatment. The effective amount of a therapeutic agent will depend on the particular compound, the disease state and its severity, and the individual in need of treatment, and can be routinely determined by a person skilled in the art. As a non-limiting example, the dosage for the human body of the composition according to the present invention may vary depending on the patient's age, weight, gender, dosage form, health status, and disease severity.
전술한 실시예에 따른 파골세포 억제 조성물 및 그 치료제는 아래 실험예들을 통해 확인된 바와 같이 파골세포 분화가 효과적으로 억제되는 것을 확인할 수 있다. It can be confirmed that the osteoclast inhibitory composition and its therapeutic agent according to the above-described examples effectively inhibit osteoclast differentiation, as confirmed through the experimental examples below.
이하, 실험예들을 기술함으로써 본 발명을 보다 상세히 설명한다. 다만, 하기의 실험예는 본 발명의 일 예시에 불과하며, 본 발명의 내용이 이에 한정되는 것으로 해석되어서는 아니된다.Hereinafter, the present invention will be described in more detail by describing experimental examples. However, the following experimental example is only an example of the present invention, and the content of the present invention should not be construed as limited thereto.
아래 실험예에서 섬쑥부쟁이 추출물의 제조방법을 예시적으로 설명하나, 본 발명의 실시예들은 일반적으로 식물 추출물의 제조방법(추출 용액이나 추출 조건의 변경 등)을 통해서도 섬쑥부쟁이 추출물을 제조할 수 있다. 특히 섬쑥부쟁이를 물을 이용하여 추출한 것을 섬쑥부쟁이 물 추출물이라고 지칭하나, 다른 일반적인 추출용매를 이용하여 삼쑥부쟁이 추출물을 제조할 수 있다. In the experimental examples below, the method for producing the Asterium aster extract is illustratively described, but the embodiments of the present invention generally allow the aquila extract to be prepared through a method for producing a plant extract (change of extraction solution or extraction conditions, etc.). You can. In particular, the extract of Aster aster using water is referred to as a Aster aster water extract, but a Aster aster extract can be prepared using other common extraction solvents.
실험예: 약제학적 조성물Experimental Example: Pharmaceutical Composition
1. 실험방법1. Experimental method
1) 섬쑥부쟁이의 제조1) Production of sagebrush
섬쑥부쟁이는 울릉도에서 자란 것을 구하여 사용하였다. 섬쑥부쟁이 100 g의 중량을 정확히 측정한 뒤 증류수 1 L와 함께 넣은 뒤 탕액이 끓는 시점으로부터 2시간 동안 가열하여 추출한 다음 추출액을 여과지(filter paper) No. 4를 이용하여 감압 여과하였다. 동결건조기(FDU-1200, EYELA, Tokyo, Japan)를 이용하여 건조된 분말을 획득하였으며, 그 수율은 32%였다. The sagebrush grown on Ulleungdo was obtained and used. After accurately measuring the weight of 100 g of Aster, add it with 1 L of distilled water, heat and extract it for 2 hours from the time the decoction boils, and then filter the extract using filter paper No. Filtered under reduced pressure using 4. Dried powder was obtained using a freeze dryer (FDU-1200, EYELA, Tokyo, Japan), and the yield was 32%.
2) RAW 264.7 세포의 배양 및 파골세포로의 분화2) Culture of RAW 264.7 cells and differentiation into osteoclasts
RAW 264.7 파골 전구세포는 한국세포주은행(Korean Cell Line Bank)으로부터 구입하였다. RAW 264.7 세포는 10% fetal bovine serum (FBS)과 100 uint/ml penicillin-stretomycin이 함유된 Dulbecco's Modified Eagle Medium (DMEM) 배지를 사용하여 37℃, 5% CO2 incubator에서 배양하였다. RAW 264.7 osteoclast progenitor cells were purchased from the Korean Cell Line Bank. RAW 264.7 cells were cultured in a 5% CO 2 incubator at 37°C using Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS) and 100 uint/ml penicillin-stretomycin.
파골 전구세포를 파골세포로 분화시키기 위해 10% FBS와 100 uint/ml penicillin-stretomycin이 함유된 α-Minimum Essential Media (MEM) 배지에 50 ng/mL의 Receptor activator of nuclear factor kappa-B ligand (RANKL)를 처리하여 배양하였다. To differentiate osteoclast precursor cells into osteoclasts, 50 ng/mL of Receptor activator of nuclear factor kappa-B ligand (RANKL) was added to α-Minimum Essential Media (MEM) medium containing 10% FBS and 100 uint/ml penicillin-stretomycin. ) was treated and cultured.
3) 세포독성 분석3) Cytotoxicity analysis
Raw 264.7 세포를 96well plate에 1×105의 밀도로 분주하고 24시간 동안 37℃, 5% CO2 incubator에서 배양한 후, 0, 15.625, 31.25, 62.5, 125, 250, 500, 및 1,000 μg/ml 농도의 섬쑥부쟁이 물 추출물을 세포에 처리하였다. 24시간 이후 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) 용액을 처리하였으며, 4시간 후 상등액을 제거하고 dimethyl sulfoxide (DMSO)을 이용하여 비수용성 formazan product을 용해하였다. Raw 264.7 cells were distributed in a 96 well plate at a density of 1 Cells were treated with a ml concentration of Aster water extract. After 24 hours, 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) solution was treated, and after 4 hours, the supernatant was removed and non-aqueous formazan was removed using dimethyl sulfoxide (DMSO). The product was dissolved.
Cell viability는 Epoch®microvolume spectrophotometer system (BioTek Instruments Inc., Winooski, VT, USA)을 이용하여 540 nm 흡광도에서 측정하였다.Cell viability was measured at absorbance at 540 nm using an Epoch ® microvolume spectrophotometer system (BioTek Instruments Inc., Winooski, VT, USA).
4) Nitric oxide (NO) 생성량 분석4) Nitric oxide (NO) production amount analysis
Raw 264.7 세포를 24well plate에 1×105의 밀도로 분주하고 24시간 동안 37℃, 5% CO2 incubator에서 배양하였다. 0, 15.625, 31.25, 62.5, 125, 250, 500, 및 1,000 μg/ml 농도의 섬쑥부쟁이 물 추출물과 20 μM의 NIL을 1시간 동안 전처리한 후, 1 μg/ml의 LPS를 처리하여 48시간 동안 배양하였다. 그다음 배양 상등액을 분리하여 96 well palte에 옮겨준 후, 동량의 Griess 시약을 처리하여 실온에서 반응시킨 후 540 nm 흡광도에서 측정하였다.Raw 264.7 cells were distributed at a density of 1×10 5 in a 24-well plate and cultured in a 37°C, 5% CO 2 incubator for 24 hours. After pretreatment with Aster water extract and 20 μM NIL at concentrations of 0, 15.625, 31.25, 62.5, 125, 250, 500, and 1,000 μg/ml for 1 hour, treatment with 1 μg/ml LPS for 48 hours. cultured for a while. Next, the culture supernatant was separated and transferred to a 96 well plate, treated with an equal amount of Griess reagent, reacted at room temperature, and absorbance was measured at 540 nm.
5) RNA 분리 및 realtime PCR 분석5) RNA isolation and real-time PCR analysis
RAW 264.7 세포를 3 x 105의 밀도가 되도록 DMEM 배지에 희석하여 6well plate에 분주하고 24시간 동안 37℃, 5% CO2 인큐베이터(incubator)에서 배양하였다. 그다음 α-MEM 배지로 교환하였고 50 ng/mL의 RANKL을 처리하기 30분 전에 섬쑥부쟁이 물 추출물(250, 500, 및 1,000 μg/ml)로 전처리한 뒤 3일 동안 배양하였다. 전체 RNA(Total RNA)의 분리는 Trizol reagent (Invitrogen, Carlsbad, CA, USA)를 사용하여 추출하였다. 추출된 total RNA (2 ug)와 d(T)16 프라이머(primer) 및 AMV 역전사효소(reverse transcriptase)를 사용하여 cDNA를 얻었다. RAW 264.7 cells were diluted in DMEM medium to a density of 3 x 10 5 and distributed in 6-well plates and cultured in an incubator at 37°C and 5% CO 2 for 24 hours. Then, the medium was changed to α-MEM, and the cells were pretreated with Asterium astera water extract (250, 500, and 1,000 μg/ml) 30 minutes before treatment with 50 ng/mL RANKL and cultured for 3 days. Total RNA was extracted using Trizol reagent (Invitrogen, Carlsbad, CA, USA). cDNA was obtained using extracted total RNA (2 ug), d(T)16 primer, and AMV reverse transcriptase.
유전자들의 상대적인 양은 SYBR Primix ExTaq (Takara) 을 사용한 realtime RT-PCR법 (Real Time PCR System7500, Applied biosystems, Foster, CA)에 의해 정량하였다. IL-1β, IL-6, RANKL, RANK, TRAF6, NFATc1, c-Fos, ATP6v0d2, Cathepsin K, MMP9, 및 MITF 유전자의 Ct 값을 β-actin 유전자의 Ct 값으로 gene express 2.0 프로그램 (Applied biosystems)을 이용하여 보정하였다. 또한 녹는점 곡선(melting curve) 분석을 통하여 증폭된 PCR 산물의 특이성을 확인하였다.The relative amounts of genes were quantified by real-time RT-PCR (Real Time PCR System7500, Applied biosystems, Foster, CA) using SYBR Primix ExTaq (Takara). Ct values of IL-1β, IL-6, RANKL, RANK, TRAF6, NFATc1, c-Fos, ATP6v0d2, Cathepsin K, MMP9, and MITF genes were converted to Ct values of β-actin gene using gene express 2.0 program (Applied biosystems). It was corrected using . Additionally, the specificity of the amplified PCR product was confirmed through melting curve analysis.
6) 통계 분석6) Statistical analysis
모든 수치는 mean ± SEM (n=3)으로 나타냈다. 데이터는 one-way analysis of variance (ANOVA) 와 Dunnett’s test를 사용하였다. 통계학적 분석은 Statistical Package for the Social Sciences (SPSS; version 19.0)을 이용하였다.All values are expressed as mean ± SEM (n=3). Data were analyzed using one-way analysis of variance (ANOVA) and Dunnett’s test. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS; version 19.0).
2. 실험결과2. Experiment results
1) RAW 264.7 세포에서 섬쑥부쟁이 물 추출물의 세포 생존율 및 NO 생성량 측정1) Measurement of cell viability and NO production of Asterium aster water extract in RAW 264.7 cells
파골 전구세포로부터 염증 매개 물질의 억제 효과는 세포독성으로 인해 RAW 264.7 세포가 사멸되는 것에 의해 나타날 수 있으므로 이러한 가능성을 배제하고자 MTT assay를 수행하였다. Since the inhibitory effect of inflammatory mediators from osteoclast precursor cells may be caused by the death of RAW 264.7 cells due to cytotoxicity, MTT assay was performed to rule out this possibility.
섬쑥부쟁이 물 추출물을 0, 15.625, 31.25, 62.5, 125, 250, 500, 및 1,000 μg/ml의 농도로 첨가하여 배양한 결과, 세포의 생존율은 모든 처리 농도에서 80% 이하의 감소율을 보이지 않음을 관찰하였다(도 1A 참조). As a result of culturing with the addition of water extract of Asterium dulcis at concentrations of 0, 15.625, 31.25, 62.5, 125, 250, 500, and 1,000 μg/ml, the survival rate of cells did not decrease below 80% at all treatment concentrations. was observed (see Figure 1A).
더 나아가, 섬쑥부쟁이 물 추출물이 파골 전구세포에서 염증 매개 물질을 억제시키는지를 확인하고자, NO 생성량을 확인한 결과 31.25 μg/ml 이상의 농도부터 NO 생성량을 유의미하게 억제시켰다(도 1B 참조). 이에 세포독성이 없으면서 유의미한 염증 억제 효과를 보이는 250, 500, 및 1,000 μg/ml의 농도를 선택하여 파골세포 분화 억제능을 확인하고자 하였다.Furthermore, in order to confirm whether the water extract of Sagebrush suppresses inflammatory mediators in osteoclast precursor cells, the amount of NO production was checked, and the amount of NO production was significantly suppressed starting at a concentration of 31.25 μg/ml or higher (see Figure 1B). Accordingly, we attempted to confirm the ability to inhibit osteoclast differentiation by selecting concentrations of 250, 500, and 1,000 μg/ml, which showed a significant anti-inflammatory effect without cytotoxicity.
2) 파골세포에서 섬쑥부쟁이 물 추출물의 염증성 사이토카인 억제 효과 확인2) Confirmation of the inflammatory cytokine inhibition effect of Aster water extract on osteoclasts
섬쑥부쟁이 물 추출물이 파골세포 형성 과정에서 중요한 요인인 염증성 사이토카인에 미치는 영향을 알아보기 위해 qRT-PCR을 이용하여 IL-1β 및 IL-6의 mRNA 발현을 확인하였다. In order to determine the effect of Aster water extract on inflammatory cytokines, which are important factors in the osteoclast formation process, the mRNA expression of IL-1β and IL-6 was confirmed using qRT-PCR.
도 2에 나타낸 바와 같이, 대조군에 비해 RANKL 처리 군에서 IL-1β 및 IL-6의 mRNA 발현이 급격히 증가한 반면, 섬쑥부쟁이 물 추출물 처리에 의해 IL-1β 및 IL-6의 mRNA 발현이 효과적으로 억제되었음을 확인하였다. As shown in Figure 2, the mRNA expression of IL-1β and IL-6 rapidly increased in the RANKL-treated group compared to the control group, while the mRNA expression of IL-1β and IL-6 was effectively suppressed by treatment with Aster water extract. It was confirmed that it was done.
3) 파골세포에서 섬쑥부쟁의 파골세포 분화 관련 유전자 억제 효과 확인3) Confirmation of the effect of suppressing genes related to osteoclast differentiation of Sagebrush on osteoclasts
섬쑥부쟁이 물 추출물이 파골세포 분화 관련 유전자의 발현에 미치는 영향을 알아보기 위해 qRT-PCR을 이용하여 RANKL, RANK, 및 TRAF6의 mRNA 발현을 확인하였다. In order to determine the effect of water extract of Sagebrush on the expression of genes related to osteoclast differentiation, the mRNA expression of RANKL, RANK, and TRAF6 was confirmed using qRT-PCR.
RANKL 처리에 의해 RANKL, RANK, 및 TRAF6의 mRNA 발현이 급격히 증가한 반면, 섬쑥부쟁이 물 추출물 처리에 의해 RANKL, RANK, 및 TRAF6의 mRNA 발현이 효과적으로 억제되었음을 확인하였다(도 3 참조).It was confirmed that the mRNA expression of RANKL, RANK, and TRAF6 was rapidly increased by treatment with RANKL, while the mRNA expression of RANKL, RANK, and TRAF6 was effectively suppressed by treatment with the Aster water extract (see Figure 3).
4) 파골세포에서 섬쑥부쟁의 파골세포 활성화 관련 유전자 억제 효과 확인4) Confirmation of the effect of suppressing genes related to osteoclast activation of Sagebrush on osteoclasts
섬쑥부쟁이 물 추출물이 파골세포 활성화 관련 유전자의 발현에 미치는 영향을 알아보기 위해 qRT-PCR을 이용하여 NFATc1, c-Fos, ATP6v0d2, Cathepsin K, MMP9, 및 MITF의 mRNA 발현을 확인하였다. In order to determine the effect of Asterium astera water extract on the expression of genes related to osteoclast activation, qRT-PCR was used to confirm the mRNA expression of NFATc1, c-Fos, ATP6v0d2, Cathepsin K, MMP9, and MITF.
RANKL 처리에 의해 NFATc1, c-Fos, ATP6v0d2, Cathepsin K, MMP9, 및 MITF의 mRNA 발현이 급격히 증가한 반면, 섬쑥부쟁이 물 추출물 처리에 의해 이들의 발현이 효과적으로 억제되었음을 확인하였다(도 4 참조).It was confirmed that the mRNA expression of NFATc1, c-Fos, ATP6v0d2, Cathepsin K, MMP9, and MITF was rapidly increased by RANKL treatment, while their expression was effectively suppressed by treatment with Aster water extract (see Figure 4).
종합하면, 실험예를 통해, 섬쑥부쟁이의 추출물이 파골세포 억제 효능을 갖는 것을 알 수 있었다. 실험예를 통해, 일 실시예에 따른 파골세포 억제 추출물 및 그 치료제가 파골세포 억제 효능을 가지기 때문에, 관절염 치료 효능을 나타내는 것을 알 수 있다. In summary, through the experimental examples, it was found that the extract of Asterium vulgaris has an osteoclast inhibitory effect. Through experimental examples, it can be seen that the osteoclast-inhibiting extract and its therapeutic agent according to one embodiment have an osteoclast-inhibiting effect and thus exhibit an arthritis treatment effect.
이하 실시예 및 실험예에 따른 약제학적 조성물을 포함하는 치료제 및 건강식품의 제조예들을 설명한다. Hereinafter, examples of manufacturing therapeutic agents and health foods containing pharmaceutical compositions according to examples and experimental examples will be described.
<제조예 1> : 치료제의 제조<Preparation Example 1>: Preparation of therapeutic agent
<1-1> 산제의 제조<1-1> Production of powder
섬쑥부쟁이 추출물 300 ㎎300 mg of Asterium aster extract
유당 100 ㎎Lactose 100 mg
탈크 10 ㎎ Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled into an airtight bubble to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of tablets
섬쑥부쟁이 추출물 50 ㎎50 mg of Cordycepsia extract
옥수수전분 100 ㎎Corn starch 100 mg
유당 100 ㎎Lactose 100 mg
스테아린산 마그네슘 2 ㎎Magnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제 를 제조한다.After mixing the above ingredients, tablets are manufactured by compressing them according to a typical tablet manufacturing method.
<1-3> 캡슐제의 제조<1-3> Manufacturing of capsules
섬쑥부쟁이 추출물 50 ㎎50 mg of Cordycepsia extract
옥수수전분 100 ㎎Corn starch 100 mg
유당 100 ㎎Lactose 100 mg
스테아린산 마그네슘 2 ㎎Magnesium stearate 2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.Capsules are prepared by mixing the above ingredients and filling them into gelatin capsules according to a typical capsule manufacturing method.
<1-4> 주사제의 제조<1-4> Preparation of injections
섬쑥부쟁이 추출물 50 ㎎50 mg of Cordycepsia extract
주사용 멸균 증류수 적량Proper amount of sterile distilled water for injection
pH 조절제 적량Appropriate amount of pH adjuster
통상의 주사제의 제조방법에 따라 1 앰플 당(2 ㎖) 상기의 성분함량으로 제조한다.It is prepared with the above ingredients per ampoule (2 ml) according to the usual manufacturing method for injections.
<1-5> 액제의 제조<1-5> Preparation of liquid
섬쑥부쟁이 추출물 1,000 ㎎Sagebrush extract 1,000 mg
설탕 20 g20 g sugar
이성화 당 20 g20 g isomerized sugar
레몬향 적량Lemon flavor appropriate amount
정제수를 가하여 전체 1000 ㎖로 맞추었다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조하였다.Purified water was added to bring the total volume to 1000 ml. The above ingredients were mixed according to a typical liquid preparation method, then filled into a brown bottle and sterilized to prepare a liquid.
<제조예 2> : 건강 식품의 제조<Production Example 2>: Production of health food
섬쑥부쟁이 추출물 1,000 ㎎Sagebrush extract 1,000 mg
비타민 혼합물 적량Vitamin mixture dosage
비타민 A 아세테이트 70 ㎍Vitamin A acetate 70 μg
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍Vitamin B12 0.2 ㎍
비타민 C 10 ㎎Vitamin C 10 mg
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 ㎎Nicotinamide 1.7 mg
엽산 50 ㎍Folic acid 50 μg
판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture appropriate amount
황산 제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Monobasic Potassium Phosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎Calcium carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.The composition ratio of the above vitamin and mineral mixture is a mixture of components relatively suitable for health food in a preferred embodiment, but the mixing ratio may be modified arbitrarily. The above ingredients are mixed according to a typical health food manufacturing method, and then , granules can be manufactured and used to manufacture health food compositions according to conventional methods.
<제조예 3> : 건강 음료의 제조<Preparation Example 3>: Preparation of health drink
섬쑥부쟁이 추출물 1000 ㎎1000 mg of Asterium vulgaris extract
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 g2 g plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 ㎖ 통상의 건강 음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동 안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강 음료 조성물 제조에 사용한다.Purified water was added to make a total of 900 ml. The above ingredients were mixed according to the usual health drink manufacturing method. After stirring and heating at 85°C for about 1 hour, the resulting solution was filtered, placed in a sterilized 2-liter container, sealed, and sterilized. It is then refrigerated and used to prepare the health drink composition of the present invention.
전술한 치료제 및 건강식품도 약제학적 조성물을 포함하므로 실험예에서 전술한 바와 같이 파골세포 억제 효능을 갖는 것을 확인할 수 있다. Since the above-mentioned therapeutic agents and health foods also contain pharmaceutical compositions, it can be confirmed that they have osteoclast inhibition effects as described above in the experimental examples.
비교예Comparative example
한국공개특허 제2018-0020798호(발명의 명칭: 혈중요산감소를 위한 섬쑥부쟁이 추출물과 비타민을 포함하는 조성물)의 섬쑥부쟁이 추출물 한국공개특허 제2015-0135037호(발명의 명칭: 고요산혈증 또는 통풍에 유효한 섬쑥부쟁이 추출물, 이의 분획물 및 이로부터 분리된 활성화합물)의 섬쑥부쟁이 추출물은, 본 발명의 실시예에 따른 약제학적 조성물과 용매 추출 방법 및 구체적인 화합물을 분리한 것에 대한 차이점이 있다. Korean Patent Publication No. 2018-0020798 (Title of the invention: Composition containing Asterium extract and vitamins for reducing blood uric acid) Korean Patent Publication No. 2015-0135037 (Title of the invention: Composition containing Asterium aster extract and vitamins for reducing blood uric acid) There is a difference between the Asteria extract (effective for gout, the Asterium aster extract, its fractions, and the active compound isolated therefrom) and the pharmaceutical composition according to an embodiment of the present invention in terms of a solvent extraction method and separation of specific compounds. .
특히, 한국공개특허 제2018-0020798호(발명의 명칭: 혈중요산감소를 위한 섬쑥부쟁이 추출물과 비타민을 포함하는 조성물)의 섬쑥부쟁이 추출물 한국공개특허 제2015-0135037호(발명의 명칭: 고요산혈증 또는 통풍에 유효한 섬쑥부쟁이 추출물, 이의 분획물 및 이로부터 분리된 활성화합물)의 섬쑥부쟁이 추출물은 요산 저하 기능만 확인하여 통풍 치료 및 예방에 사용될 수 있다고 기재하고 있을 뿐이다 In particular, Korean Patent Publication No. 2018-0020798 (title of the invention: Composition containing Asterium aster extract and vitamins for reducing blood uric acid) extract of Asterium vulgaris extract, Korean Patent Publication No. 2015-0135037 (name of the invention: Goyo) It is only stated that the uric acid lowering function of the euphorbia extract (effective for acidosis or gout, its fractions, and active compounds isolated therefrom) can be used for the treatment and prevention of gout.
본 발명의 실시예에 따른 약제학적 조성물은 파골세포 억제 효능을 가지고 있기 때문에, 전술한 바와 같이 파골세포에 의해서 영향을 받는 관절염의 진행에 중요한 염증성 사이토카인 및 파골세포의 분화를 억제시킬 수 있는 것을 확인하였다.Since the pharmaceutical composition according to an embodiment of the present invention has an osteoclast inhibitory effect, it can inhibit inflammatory cytokines and differentiation of osteoclasts, which are important in the progression of arthritis affected by osteoclasts, as described above. Confirmed.
사용예Example of use
전술한 본 발명의 실시예에 따른 약제학적 조성물은 관절염 치료제 뿐만 아니라 건강식품이나 영상진단용 구성물로 사용될 수 있다. 예를 들어, 전술한 본 발명의 실시예에 따른 약제학적 조성물은 파골세포 억제 조성물로 초음파 촬영에 사용하는 초음파 젤에 혼합되어 사용될 수 있다. 이를 통해 초음파 촬영 중 사용되는 초음파 젤을 통해 파골세포 억제 효과를 추가로 달성할 수 있다. The pharmaceutical composition according to the above-described embodiment of the present invention can be used not only as a treatment for arthritis but also as a health food or composition for imaging diagnosis. For example, the pharmaceutical composition according to the above-described embodiment of the present invention can be used as an osteoclast inhibitory composition mixed with ultrasonic gel used in ultrasonic imaging. Through this, an additional osteoclast inhibition effect can be achieved through the ultrasound gel used during ultrasound imaging.
이상 도면을 참조하여 실시예들을 설명하였으나 본 발명은 이에 제한되지 않으며, 상기 설명은 본 발명의 기술 사상을 예시적으로 설명한 것에 불과한 것으로서, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자라면 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 다양한 수정 및 변형이 가능할 것이다. 따라서, 본 발명에 개시된 실시예들은 본 발명의 기술 사상을 한정하기 위한 것이 아니라 설명하기 위한 것이고, 이러한 실시예에 의하여 본 발명의 기술 사상의 범위가 한정되는 것은 아니다. 본 발명의 보호 범위는 아래의 청구범위에 의하여 해석되어야 하며, 그와 동등한 범위 내에 있는 모든 기술 사상은 본 발명의 권리범위에 포함되는 것으로 해석되어야 할 것이다.Although the embodiments have been described above with reference to the drawings, the present invention is not limited thereto, and the above description is merely an illustrative explanation of the technical idea of the present invention, and those skilled in the art will understand the present invention. Various modifications and variations may be made without departing from the essential characteristics of the invention. Accordingly, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention, but are for illustrative purposes, and the scope of the technical idea of the present invention is not limited by these embodiments. The scope of protection of the present invention should be interpreted in accordance with the claims below, and all technical ideas within the equivalent scope should be construed as being included in the scope of rights of the present invention.
Claims (4)
상기 섬쑥부쟁이 추출물은 31.25 μg/ml 이상 1,000 μg/ml의 농도의 물 추출물인 파골세포 억제 조성물.According to paragraph 1,
The osteoclast inhibitory composition is a water extract wherein the Sagebrush extract is a water extract at a concentration of 31.25 μg/ml or more and 1,000 μg/ml.
약제학적으로 허용 가능한 담체를 포함하는 파골세포 억제 치료제.A composition containing Asteria extract as an active ingredient;
An osteoclast-inhibiting therapeutic agent comprising a pharmaceutically acceptable carrier.
상기 섬쑥부쟁이 추출물은 31.25 μg/ml 이상 1,000 μg/ml의 농도의 물 추출물인 파골세포 억제 치료제.According to paragraph 3,
The Asterium vulgaris extract is an osteoclast inhibitory treatment agent that is a water extract at a concentration of 31.25 μg/ml or more and 1,000 μg/ml.
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