KR20240030727A - Furyl thiazole compound and composition for preventing or treating sarcopenia comprising the same as an active ingredient - Google Patents
Furyl thiazole compound and composition for preventing or treating sarcopenia comprising the same as an active ingredient Download PDFInfo
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- KR20240030727A KR20240030727A KR1020220110127A KR20220110127A KR20240030727A KR 20240030727 A KR20240030727 A KR 20240030727A KR 1020220110127 A KR1020220110127 A KR 1020220110127A KR 20220110127 A KR20220110127 A KR 20220110127A KR 20240030727 A KR20240030727 A KR 20240030727A
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- sarcopenia
- preventing
- furylthiazole
- pharmaceutical composition
- treating
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
Abstract
본 발명은 화학식 1로 표시되는 퓨릴티아졸계 화합물을 유효성분으로 포함하는 근감소증 예방 또는 치료용 조성물에 관한 것으로, 상기 퓨릴티아졸계 화합물이 근아세포에서 형성된 근관의 위축을 개선시키는 효과를 나타내는 것을 확인함으로써, 근감소증 예방, 치료 또는 개선용 조성물로서 유용하게 활용될 수 있다.The present invention relates to a composition for preventing or treating sarcopenia containing a furylthiazole-based compound represented by Formula 1 as an active ingredient, and it was confirmed that the furylthiazole-based compound exhibits an effect of improving atrophy of root canals formed in myoblasts. By doing so, it can be usefully used as a composition for preventing, treating, or improving sarcopenia.
Description
본 발명은 퓨릴티아졸계 화합물 및 이를 유효성분으로 포함하는 근감소증 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a furylthiazole-based compound and a composition for preventing or treating sarcopenia containing the same as an active ingredient.
척수신경, 운동신경 또는 골격근 섬유의 퇴행에 의해 유발되는 근감소증은 아직까지 발병원인이 규명되지 않은 대표적인 난치성 질환의 하나이다. 지금까지 연구된 바에 의하면, 골격근의 수축을 유도하는 운동신경이 퇴행되어 골격근의 수축이 진행되지 않거나 또는 골격근 내에서 근육의 수축에 관여하는 단백질의 발현이 감소되거나(근감소증) 상기 단백질이 변형되어 정상적인 골격근의 수축이 진행되지 않으며, 장기적으로는 상기 운동신경 또는 골격근이 섬유성 조직으로 변형되는 것으로 알려져 있다.Sarcopenia, which is caused by degeneration of spinal nerves, motor nerves, or skeletal muscle fibers, is one of the representative incurable diseases whose cause has not yet been identified. According to research so far, the motor nerves that induce skeletal muscle contraction degenerate and skeletal muscle contraction does not proceed, or the expression of proteins involved in muscle contraction within skeletal muscles is reduced (sarcopenia), or the proteins are modified. It is known that normal skeletal muscle contraction does not proceed, and in the long term, the motor nerves or skeletal muscles are transformed into fibrous tissue.
근감소증 중에서 퇴행성 근감소증(Sarcopenia)은 노화와 관련한 근육량의 감소로 정의되며, 노년기에 삶의 질에 중요한 영향을 미치는 것으로 점차 인식되고 있다. 퇴행성 근감소증은 70세 이하의 사람들에게서 13~24%로 나타나나, 80세 이상에서는 50% 이상으로 발병하며, 근육감소와 연관된 근력저하는 피곤함, 작업수행능력의 감소, 대퇴골 골절과 같은 골절 위험의 증가와 관련이 있는 것으로 알려져 있다. 근감소증을 앓고 있는 환자는 골격근 지표가 기준치 이하이면서, 악력이나 보행속도가 떨어지는 등 일상생활에 어려움을 겪는다. 체성분상 근육의 양이 뚜렷하게 손실되는 반면, 체지방이 증가하는 경향을 나타낸다.Among sarcopenia, degenerative sarcopenia (sarcopenia) is defined as an age-related decrease in muscle mass, and is increasingly recognized as having a significant impact on quality of life in old age. Degenerative sarcopenia occurs in 13-24% of people under 70 years of age, but occurs in more than 50% of people over 80 years of age. Muscle weakness associated with muscle loss causes fatigue, reduced work performance, and risk of fractures such as femur fractures. It is known to be related to the increase in Patients suffering from sarcopenia have skeletal muscle indices below the standard value and experience difficulties in daily life, such as decreased grip strength and walking speed. In terms of body composition, while the amount of muscle is clearly lost, body fat tends to increase.
근육감소증에 대한 치료법은 영양 접근법, 운동 훈련법이 연구되고 있다. 식욕자극제 및 테스토스테론과 같은 단백질 화합물을 이용한 치료가 제시되고 있으나, 그 치료 효과는 만족스러운 수준이 아니다. 운동 훈련법은 근감소증이 진행되고 있는 노인은 운동을 시도하는 것조차 쉽지 않은 경우가 많기 때문에 적절한 대안으로 보기 어렵다. 약제학적으로 근감소증의 진행을 둔화시키는 방법으로는 주로 근감소증의 일종인 근육세포의 퇴행 또는 진행성 변이에 의해 유발되는 근위축증을 억제하는 방법이 사용되고 있다.Nutritional approaches and exercise training methods are being studied as treatments for sarcopenia. Treatment using protein compounds such as appetite stimulants and testosterone has been proposed, but the treatment effect is not satisfactory. Exercise training is difficult to consider as an appropriate alternative because it is often difficult for elderly people with sarcopenia to even attempt exercise. Pharmaceutical methods to slow the progression of sarcopenia are mainly used to suppress muscular atrophy, a type of sarcopenia, caused by degeneration or progressive mutation of muscle cells.
상기와 같은 문제점을 해결하기 위해, 본 발명의 목적은 근감소증을 예방, 치료 또는 개선할 수 있는 새로운 약학 조성물을 제공하는 것으로, 퓨릴티아졸계 화합물을 근아세포에서 형성된 근관의 위축을 개선시키는 효과를 나타내는 것을 확인함으로써, 상기 퓨릴티아졸계 화합물을 근감소증의 예방, 치료 또는 개선을 위한 새로운 약제로 제공하는 것이다.In order to solve the above problems, the purpose of the present invention is to provide a new pharmaceutical composition that can prevent, treat or improve sarcopenia, and the furylthiazole-based compound has the effect of improving atrophy of root canals formed in myoblasts. By confirming this, the furylthiazole-based compound is provided as a new drug for preventing, treating, or improving sarcopenia.
본 발명은 하기 화학식 1로 표시되는 퓨릴티아졸계 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근감소증 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating sarcopenia comprising a furylthiazole-based compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Formula 1]
또한, 본 발명은 상기 화학식 1로 표시되는 퓨릴티아졸계 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근감소증 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving sarcopenia containing the furylthiazole-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 상기 약학 조성물을 근감소증이 발병된 개체에 약제학적으로 유효한 양으로 투여하는 단계를 포함하는 근감소증 치료방법을 제공한다.In addition, the present invention provides a method of treating sarcopenia comprising administering the pharmaceutical composition in a pharmaceutically effective amount to an individual suffering from sarcopenia.
본 발명에 따르면, 화학식 1로 표시되는 퓨릴티아졸계 화합물이 근아세포에서 형성된 근관의 위축을 개선시키는 것을 확인함에 따라, 근감소증의 예방, 치료 또는 개선용 조성물로서 유용하게 활용될 수 있다.According to the present invention, as it was confirmed that the furylthiazole-based compound represented by Formula 1 improves atrophy of root canals formed in myoblasts, it can be usefully used as a composition for preventing, treating, or improving sarcopenia.
도 1은 근아세포의 근관(myotube) 형성 과정에서 화학식 1로 표시되는 퓨릴티아졸계 화합물이 미치는 영향을 평가하기 위해, ICC(Immunocytochemistry)로 MYH(Myosin heavy chain) 및 핵을 염색한 결과이다.
도 2는 근아세포의 근관(myotube) 형성 과정에서 화학식 1로 표시되는 퓨릴티아졸계 화합물이 미치는 영향을 평가하기 위해, 근관 영역(myotube area), 근관 직경(myotube diameter) 및 융합 지수(fusion index)를 평가한 결과이다.Figure 1 shows the results of staining MYH (Myosin heavy chain) and nuclei by ICC (Immunocytochemistry) to evaluate the effect of the furylthiazole compound represented by Formula 1 on the myotube formation process of myoblasts.
Figure 2 shows the myotube area, myotube diameter, and fusion index to evaluate the effect of the furylthiazole compound represented by Formula 1 on the myotube formation process of myoblasts. This is the result of evaluating.
본 명세서에서 사용되는 용어는 본 발명에서의 기능을 고려하면서 가능한 현재 널리 사용되는 일반적인 용어들을 선택하였으나, 이는 당 분야에 종사하는 기술자의 의도 또는 판례, 새로운 기술의 출현 등에 따라 달라질 수 있다. 또한, 특정한 경우는 출원인이 임의로 선정한 용어도 있으며, 이 경우 해당되는 발명의 설명 부분에서 상세히 그 의미를 기재할 것이다. 따라서 본 발명에서 사용되는 용어는 단순한 용어의 명칭이 아닌, 그 용어가 가지는 의미와 본 발명의 전반에 걸친 내용을 토대로 정의되어야 한다.The terms used in this specification are general terms that are currently widely used as much as possible while considering the function in the present invention, but this may vary depending on the intention or precedent of a person skilled in the art, the emergence of new technology, etc. In addition, in certain cases, there are terms arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the relevant invention. Therefore, the terms used in the present invention should be defined based on the meaning of the term and the overall content of the present invention, rather than simply the name of the term.
다르게 정의되지 않는 한, 기술적이거나 과학적인 용어를 포함해서 여기서 사용되는 모든 용어들은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 일반적으로 이해되는 것과 동일한 의미를 가지고 있다. 일반적으로 사용되는 사전에 정의되어 있는 것과 같은 용어들은 관련 기술의 문맥상 가지는 의미와 일치하는 의미를 가지는 것으로 해석되어야 하며, 본 출원에서 명백하게 정의하지 않는 한, 이상적이거나 과도하게 형식적인 의미로 해석되지 않는다.Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the technical field to which the present invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related technology, and unless clearly defined in the present application, should not be interpreted in an ideal or excessively formal sense. No.
수치 범위는 상기 범위에 정의된 수치를 포함한다. 본 명세서에 걸쳐 주어진 모든 최대의 수치 제한은 낮은 수치 제한이 명확히 쓰여져 있는 것처럼 모든 더 낮은 수치 제한을 포함한다. 본 명세서에 걸쳐 주어진 모든 최소의 수치 제한은 더 높은 수치 제한이 명확히 쓰여져 있는 것처럼 모든 더 높은 수치 제한을 포함한다. 본 명세서에 걸쳐 주어진 모든 수치 제한은 더 좁은 수치 제한이 명확히 쓰여져 있는 것처럼, 더 넓은 수치 범위 내의 더 좋은 모든 수치 범위를 포함할 것이다.The numerical range includes the values defined in the range above. Every maximum numerical limit given throughout this specification includes all lower numerical limits as if the lower numerical limit were explicitly written out. Every minimum numerical limit given throughout this specification includes every higher numerical limit as if such higher numerical limit was clearly written. All numerical limits given throughout this specification will include all better numerical ranges within the broader numerical range, as if the narrower numerical limits were clearly written.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 하기 화학식 1로 표시되는 퓨릴티아졸계 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근감소증 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating sarcopenia comprising a furylthiazole-based compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Formula 1]
상기 화학식 1로 표시되는 퓨릴티아졸계 화합물은 IUPAC명이 4-[(디벤조[b,d]퓨란-2-일옥시)메틸]-2-(2-퓨릴)-1,3-티아졸 (4-[(Dibenzo[b,d]furan-2-yloxy)methyl]-2-(2-furyl)-1,3-thiazole)인 화합물이다.The furylthiazole-based compound represented by Formula 1 has the IUPAC name 4-[(dibenzo[b,d]furan-2-yloxy)methyl]-2-(2-furyl)-1,3-thiazole (4 It is a compound called -[(Dibenzo[b,d]furan-2-yloxy)methyl]-2-(2-furyl)-1,3-thiazole).
상기 화학식 1로 표시되는 퓨릴티아졸계 화합물 또는 이의 약학적으로 허용 가능한 염은 근감소증으로 인하여 감소된 체중, 골격근 중량, 악력 및 근육 단백질 관련 유전자의 발현 수준으로 이루어진 군에서 선택된 하나 이상의 근감소증 증상을 개선시킬 수 있으나, 이에 한정되는 것은 아니다.The furylthiazole compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may cause one or more sarcopenia symptoms selected from the group consisting of decreased body weight, skeletal muscle weight, grip strength, and expression levels of muscle protein-related genes due to sarcopenia. It can be improved, but it is not limited to this.
상기 근육 단백질 관련 유전자는 마이오디(MyoD) 또는 마이오제닌(Myogenin)을 코딩하는 유전자인 근육 단백질을 생성하는 유전자; 또는 마이오스타틴(Myostatin), 아트로진-1(Atrogin-1) 또는 MuRF1(Muscle RING-finger protein-1)을 코딩하는 유전자인 근육 단백질을 파괴하는 유전자일 수 있으나, 이에 한정되는 것은 아니다.The muscle protein-related genes include genes producing muscle proteins, which are genes encoding MyoD or Myogenin; Alternatively, it may be a gene that destroys a muscle protein, such as a gene encoding Myostatin, Atrogin-1, or MuRF1 (Muscle RING-finger protein-1), but is not limited thereto.
또한, 상기 화학식 1로 표시되는 퓨릴티아졸계 화합물 또는 이의 약학적으로 허용 가능한 염은 근관 위축을 개선시킬 수 있다.In addition, the furylthiazole-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof can improve root canal atrophy.
상기 근감소증은 퇴행성 근력 약화 또는 근위축증을 포함한다. 상기 근감소증은 퇴행성 근감소증(Sarcopenia)일 수 있으며, 노화 등의 다양한 이유로 근육 섬유의 수 및 단면적의 감소로 인한 골격근의 근육량 감소를 의미한다. 상기 근위축증은 근육이 위축되는 질환을 의미하며, 구체적으로, 사지의 근육이 거의 좌우대칭적으로 점점 위축되어 가는 질환으로, 근위축성 측삭경화증 또는 척수성진행성 근위축증을 포함할 수 있다.The sarcopenia includes degenerative muscle weakness or muscular dystrophy. The sarcopenia may be degenerative sarcopenia, and refers to a decrease in muscle mass of skeletal muscles due to a decrease in the number and cross-sectional area of muscle fibers due to various reasons such as aging. The muscular atrophy refers to a disease in which muscles atrophy. Specifically, it is a disease in which the muscles of the extremities gradually atrophy almost symmetrically, and may include amyotrophic lateral sclerosis or spinal progressive muscular atrophy.
본 발명에서, 상기 약학적으로 허용 가능한 염은 나트륨염, 칼륨염, 칼슘염, 리튬염, 마그네슘염, 세슘염, 아미늄(aminium)염, 암모늄염, 트리에칠아미늄염 및 피리디늄염으로 이루어진 군에서 선택된 하나 이상의 염기성 염일 수 있으나, 이에 한정되는 것은 아니다.In the present invention, the pharmaceutically acceptable salt consists of sodium salt, potassium salt, calcium salt, lithium salt, magnesium salt, cesium salt, aminium salt, ammonium salt, triethylaminium salt, and pyridinium salt. It may be one or more basic salts selected from the group, but is not limited thereto.
또한, 상기 약학적으로 허용 가능한 염은 염산, 브롬산, 황산, 아황산, 인산, 구연산, 초산, 말레산, 퓨마르산, 글루코산, 메탄설폰산, 벤젠설폰산, 캠퍼설폰산, 옥살산, 말론산, 글루타릭산, 아세트산, 글리콘산, 석신산, 타타르산, 4-톨루엔설폰산, 갈락투론산, 엠본산, 글루탐산, 시트르산 및 아스파르탄산으로 이루어진 군에서 선택된 하나 이상의 산성 염일 수 있으나, 이에 한정되는 것은 아니다.In addition, the pharmaceutically acceptable salts include hydrochloric acid, hydrobromic acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, acetic acid, maleic acid, fumaric acid, glucolic acid, methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, oxalic acid, and malonic acid. , glutaric acid, acetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid, and aspartic acid. It is not limited.
본 발명에 따른 약학 조성물은 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다.The pharmaceutical composition according to the present invention can be manufactured in unit dose form by formulating using a pharmaceutically acceptable carrier according to a method that can be easily performed by those skilled in the art, or by placing it in a multi-dose container. there is.
상기 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸 히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘, 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약학 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다.The pharmaceutically acceptable carriers are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.
본 발명에 있어서, 상기 약학 조성물에 포함되는 첨가제의 함량은 특별히 한정되는 것은 아니며 통상의 제제화에 사용되는 함량 범위 내에서 적절하게 조절될 수 있다.In the present invention, the content of additives included in the pharmaceutical composition is not particularly limited and can be appropriately adjusted within the content range used in conventional formulations.
상기 약학 조성물은 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립, 정제, 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제로 이루어진 군에서 선택된 하나 이상의 외용제 형태로 제형화될 수 있다.The pharmaceutical compositions include injectable formulations such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, tablets, creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, paste agents, and cataplasmase agents. It may be formulated in the form of one or more external preparations selected from the group consisting of.
본 발명의 약학 조성물은 제형화를 위해 추가로 있는 약학적으로 허용 가능한 담체 및 희석제를 포함할 수 있다. 상기 약학적으로 허용 가능한 담체 및 희석제는 전분, 당, 및 만니톨과 같은 부형제, 칼슘 포스페이트 등과 같은 충전제 및 증량제, 카르복시메틸셀룰로오스, 히드록시프로필셀룰로오스 등과 같은 셀룰로오스 유도체, 젤라틴, 알긴산염, 폴리비닐 피롤리돈 등과 같은 결합제, 활석, 스테아린산 칼슘, 수소화 피마자유 및 폴리에틸렌 글리콜과 같은 윤활제, 포비돈, 크로스포비돈과 같은 붕해제, 폴리소르베이트, 세틸알코올, 글리세롤 등과 같은 계면활성제를 포함하나, 이에 한정되지 않는다. 상기 약학적으로 허용 가능한 담체 및 희석제는 대상체에게 생물학적 및 생리학적으로 친화적인 것일 수 있다. 희석제의 예로는 염수, 수용성 완충액, 용매 및/또는 분산제(dispersion media)를 들 수 있으나, 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention may additionally contain pharmaceutically acceptable carriers and diluents for formulation. The pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar, and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, gelatin, alginate, and polyvinyl pyrrolidone. It includes, but is not limited to, binders such as copper, lubricants such as talc, calcium stearate, hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone and crospovidone, and surfactants such as polysorbate, cetyl alcohol, glycerol, etc. The pharmaceutically acceptable carrier and diluent may be biologically and physiologically friendly to the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents, and/or dispersion media.
본 발명의 약학 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있다. 경구 투여일 경우, 정제, 트로키제(troches), 로젠지(lozenge), 수용성 현탁액, 유성 현탁액, 조제 분말, 과립, 에멀젼, 하드 캡슐, 소프트 캡슐, 시럽, 엘릭시르제 등으로 제형화될 수 있다. 비경구 투여일 경우, 주사액, 좌제, 호흡기 흡입용 분말, 스프레이용 에어로졸제, 연고, 도포용 파우더, 오일, 크림 등으로 제형화 될 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally, or topically) depending on the desired method. For oral administration, it can be formulated as tablets, troches, lozenges, aqueous suspensions, oily suspensions, powders, granules, emulsions, hard capsules, soft capsules, syrups, elixirs, etc. In the case of parenteral administration, it can be formulated as an injection, suppository, powder for respiratory inhalation, aerosol for spray, ointment, powder for application, oil, cream, etc.
본 발명의 약학 조성물의 투여량은 환자의 상태 및 체중, 연령, 성별, 건강상태, 식이 체질 특이성, 제제의 성질, 질병의 정도, 조성물의 투여시간, 투여방법, 투여기간 또는 간격, 배설율 및 약물 형태에 따라 그 범위가 다양할 수 있으며, 이 분야 통상의 기술자에 의해 적절하게 선택될 수 있다. 예컨대, 약 0.1 내지 10,000mg/kg의 범위일 수 있으나 이제 제한되지 않으며, 하루 일회 내지 수회에 나누어 투여될 수 있다. The dosage of the pharmaceutical composition of the present invention is determined by the patient's condition and weight, age, gender, health, dietary constitution specificity, nature of the preparation, degree of disease, administration time of the composition, administration method, administration period or interval, excretion rate, and The range may vary depending on the drug form and can be appropriately selected by a person skilled in the art. For example, it may range from about 0.1 to 10,000 mg/kg, but is not limited and may be administered once to several times a day.
상기 약학 조성물은 목적하는 방법에 따라 경구 투여되거나 비경구 투여(예를 들면, 정맥 내, 피하 내, 복강 내 또는 국소에 적용)될 수 있다. 본 발명의 약학 조성물의 약학적 유효량, 유효 투여량은 약학 조성물의 제제화 방법, 투여 방식, 투여 시간 및/또는 투여 경로 등에 의해 다양해질 수 있으며, 당해 기술 분야에서 통상의 지식을 가진 자는 목적하는 치료에 효과적인 투여량을 용이하게 결정하고 처방할 수 있다. 본 발명의 약학 조성물의 투여는 하루에 1회 투여될 수 있고, 수회에 나누어 투여될 수도 있다.The pharmaceutical composition may be administered orally or parenterally (eg, intravenously, subcutaneously, intraperitoneally, or topically applied) depending on the desired method. The pharmaceutically effective amount and effective dosage of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, and/or administration route of the pharmaceutical composition, and those skilled in the art will be able to determine the desired treatment. Effective dosage can be easily determined and prescribed. The pharmaceutical composition of the present invention may be administered once a day, or may be administered in several divided doses.
또한, 본 발명은 상기 화학식 1로 표시되는 퓨릴티아졸계 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 근감소증 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving sarcopenia containing the furylthiazole-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명은 통상적으로 이용되는 식품으로써 일반적으로 사용될 수 있다.The present invention can be generally used with commonly used foods.
본 발명의 식품 조성물은 건강기능식품으로서 사용될 수 있다. 상기 "건강기능 식품"이라 함은 건강기능 식품에 관한 법률에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention can be used as a health functional food. The term “health functional food” refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with the Health Functional Food Act, and “functional” refers to food that is related to the structure and function of the human body. It means ingestion for the purpose of controlling nutrients or obtaining useful health effects such as physiological effects.
본 발명의 식품 조성물은 통상의 식품 첨가물을 포함할 수 있으며, 상기 "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The food composition of the present invention may contain common food additives, and its suitability as a “food additive” is determined in accordance with the general provisions and general test methods of the food additive code approved by the Ministry of Food and Drug Safety, unless otherwise specified. The decision is made based on the specifications and standards for the item.
상기 "식품 첨가물 공전"에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류들을 들 수 있다.Items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as subchromic pigment, licorice extract, crystalline cellulose, high-liquid pigment, and guar gum; Examples include mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations.
본 발명의 식품 조성물은 정제, 캡슐, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다.The food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc.
예를 들어, 캡슐 형태의 건강기능 식품 중 경질캡슐제는 통상의 경질캡슐에 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합 및 충진하여 제조할 수 있으며, 연질캡슐제는 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합하고 젤라틴 등 캡슐기제에 충진하여 제조할 수 있다. 상기 연질캡슐제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.For example, among health functional foods in the form of capsules, hard capsules can be manufactured by mixing and filling the composition according to the present invention with additives such as excipients in ordinary hard capsules, and soft capsules can be manufactured by mixing and filling the composition according to the present invention. It can be manufactured by mixing with additives such as excipients and filling it with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary.
상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다. 상기 식품의 종류에는 특별한 제한이 없으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.Definitions of terms such as excipients, binders, disintegrants, lubricants, coagulants, flavoring agents, etc. are described in literature known in the art and include those with the same or similar functions. There is no particular limitation on the type of food, and it includes all health functional foods in the conventional sense.
본 발명에서 용어“예방”은 본 발명에 따른 조성물의 투여로 근감소증을 억제 또는 지연시키는 모든 행위를 말한다. In the present invention, the term “prevention” refers to all actions that inhibit or delay sarcopenia by administering the composition according to the present invention.
본 발명에서 용어 “치료”는 본 발명에 따른 조성물의 투여로 근감소증을 호전시키거나 이롭게 변경하는 모든 행위를 말한다. In the present invention, the term “treatment” refers to any action that improves or beneficially changes sarcopenia by administering the composition according to the present invention.
본 발명에서 용어 “개선”은 본 발명에 따른 조성물의 투여로 근감소증의 나쁜 상태를 좋게 하는 모든 행위를 말한다.In the present invention, the term “improvement” refers to all actions that improve the bad condition of sarcopenia by administering the composition according to the present invention.
또한, 본 발명은 상기 약학 조성물을 근감소증이 발병된 개체에 약제학적으로 유효한 양으로 투여하는 단계를 포함하는 근감소증 치료방법을 제공한다.In addition, the present invention provides a method of treating sarcopenia comprising administering the pharmaceutical composition in a pharmaceutically effective amount to an individual suffering from sarcopenia.
상기 약제학적으로 유효한 양은 질병의 치료에 유효한 양으로, 예컨대 치료하고자 하는 대상에게 투여되는 조성물의 양으로, 재발을 예방하거나, 증상을 완화시키거나, 직접 또는 간접적인 병리학적 결과를 저해시키거나, 전이를 예방하거나, 진행 속도를 감소시키거나, 상태를 경감 또는 일시적 완화시키거나, 예후를 개선시키는 조성물의 양을 모두 포함할 수 있다.The pharmaceutically effective amount is an amount effective for the treatment of a disease, such as the amount of the composition administered to the subject to be treated, preventing recurrence, alleviating symptoms, inhibiting direct or indirect pathological results, It may include any amount of the composition that prevents metastasis, reduces the rate of progression, alleviates or temporarily alleviates the condition, or improves the prognosis.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, the present invention will be described in detail through examples to aid understanding. However, the following examples only illustrate the content of the present invention and the scope of the present invention is not limited to the following examples. Examples of the present invention are provided to more completely explain the present invention to those skilled in the art.
[실시예 1] 근관세포의 분화 활성 효과 확인[Example 1] Confirmation of differentiation activity effect of myotube cells
화학식 1로 표시되는 퓨릴티아졸계 화합물의 근감소증 치료 효과를 확인하기 위해, 근아세포의 근관(myotube) 형성 과정에서 화학식 1로 표시되는 퓨릴티아졸계 화합물이 미치는 영향을 평가하였다. 퓨릴티아졸계 화합물은 상업적으로 입수하였다. 1% 페니실린/스트렙토마이신(penicillin/streptomycin) 및 10% FBS(Fetal Bovine Serum)를 포함하는 DMEM(Dulbecco's Modified Eagle's Medium)을 성장배지(Growth medium)로 사용하고, 1% 페니실린/스트렙토마이신(penicillin/streptomycin) 및 2% NHS(Normal Horse Serum)를 포함하는 DMEM(Dulbecco's Modified Eagle's Medium)을 분화배지(Differentiation medium)로 사용하였다. 0.1% 젤라틴 용액으로 96 웰 플레이트에 코팅하였다. 50~60% 밀도의 4 계대 마우스 근아세포주인 C2C12 세포를 트립신을 이용하여 수집하고, 젤라틴으로 코팅된 96 웰 플레이트에 성장 배지와 함께 5000개의 세포를 깔아주었다. 24시간 동안 배양하고, 배지를 분화 배지로 교체하고, 48시간 동안 배양하여 근관(myotube) 형성을 유도하였다. 이 후, 음성 대조군 및 시험군에는 덱사메사손(dexamethasone) 150μM을 처리하여 근관의 위축을 유도하였다. 24시간 후, 시험군에는 5~25μM 농도의 화학식 1로 표시되는 퓨릴티아졸계 화합물을 처리하고, 양성 대조군 및 음성 대조군에는 0.1% DMSO를 처리하였다. 24시간 후, ICC(Immunocytochemistry) 방법을 통해 MYH(Myosin heavy chain) 및 핵을 염색하고, 근관 영역(myotube area), 근관 직경(myotube diameter) 및 융합 지수(fusion index)를 평가하였다.In order to confirm the effectiveness of the furylthiazole compound represented by Formula 1 in treating sarcopenia, the effect of the furylthiazole compound represented by Formula 1 on the myotube formation process of myoblasts was evaluated. Furylthiazole-based compounds were obtained commercially. DMEM (Dulbecco's Modified Eagle's Medium) containing 1% penicillin/streptomycin and 10% FBS (Fetal Bovine Serum) was used as a growth medium, and 1% penicillin/streptomycin (penicillin/streptomycin) was used as a growth medium. DMEM (Dulbecco's Modified Eagle's Medium) containing streptomycin) and 2% NHS (Normal Horse Serum) was used as a differentiation medium. A 96-well plate was coated with 0.1% gelatin solution. C2C12 cells, a 4th passage mouse myoblast cell line, at a density of 50-60% were collected using trypsin, and 5000 cells were spread on a 96-well plate coated with gelatin along with growth medium. After culturing for 24 hours, the medium was replaced with differentiation medium, and cultured for 48 hours to induce myotube formation. Afterwards, the negative control and test groups were treated with 150 μM of dexamethasone to induce atrophy of the root canals. After 24 hours, the test group was treated with a furylthiazole compound represented by Formula 1 at a concentration of 5 to 25 μM, and the positive and negative control groups were treated with 0.1% DMSO. 24 hours later, MYH (Myosin heavy chain) and nuclei were stained using the ICC (Immunocytochemistry) method, and myotube area, myotube diameter, and fusion index were evaluated.
도 1, 도 2 및 표 1에 나타난 바와 같이, 음성 대조군에서는 근관(myotube)이 형성된 세포에 덱사메사손(dexamethasone)을 처리하자 근관이 위축되고, 관의 직경이 감쇠되는 것으로 나타났고, 화학식 1로 표시되는 퓨릴티아졸계 화합물을 처리하는 경우, 처리 농도가 증가함에 따라 근관 위축 현상이 개선되는 것으로 나타났다. 상기의 결과는 덱사메사손(dexamethasone)에 의해 유도되는 근관에서의 근감소 현상을 화학식 1로 표시되는 퓨릴티아졸계 화합물이 개선시키는 것을 입증하며, 화학식 1로 표시되는 퓨릴티아졸계 화합물이 근감소증을 개선 및 치료할 수 있는 효과가 있다는 것을 시사한다.As shown in Figures 1, 2, and Table 1, in the negative control group, when the cells in which myotubes were formed were treated with dexamethasone, the myotubes were atrophied and the diameter of the tubes was reduced. Formula 1 When treated with a furylthiazole-based compound represented by , root canal atrophy was shown to improve as the treatment concentration increased. The above results demonstrate that the furylthiazole-based compound represented by Formula 1 improves the muscle loss phenomenon in root canals induced by dexamethasone, and the furylthiazole-based compound represented by Formula 1 reduces sarcopenia. This suggests that there is an effect that can be improved and treated.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 즉, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다.As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred embodiments and do not limit the scope of the present invention. do. That is, the practical scope of the present invention is defined by the appended claims and their equivalents.
Claims (7)
[화학식 1]
A pharmaceutical composition for preventing or treating sarcopenia comprising a furylthiazole-based compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 1]
[화학식 1]
A health functional food composition for preventing or improving sarcopenia comprising a furylthiazole compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 1]
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