KR20210099911A - Pharmaceutical composition for preventing and treating neurological diseases comprising gossypol or derivatives thereof as an active ingredient - Google Patents
Pharmaceutical composition for preventing and treating neurological diseases comprising gossypol or derivatives thereof as an active ingredient Download PDFInfo
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- KR20210099911A KR20210099911A KR1020200013844A KR20200013844A KR20210099911A KR 20210099911 A KR20210099911 A KR 20210099911A KR 1020200013844 A KR1020200013844 A KR 1020200013844A KR 20200013844 A KR20200013844 A KR 20200013844A KR 20210099911 A KR20210099911 A KR 20210099911A
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- gosipol
- pharmaceutical composition
- gaba
- derivative
- disease
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Abstract
Description
본 발명은 고시폴, 또는 이의 유도체를 유효성분으로 포함하는 신경질환 예방 또는 치료용 약학조성물에 관한 것이다. The present invention relates to a pharmaceutical composition for preventing or treating neurological diseases, comprising gosipol or a derivative thereof as an active ingredient.
신경질환은 크게 신경전달물질에 의한 신경질환과 신경세포의 물리적 손상에 의한 신경질환으로 구분할 수 있다. 상기의 신경전달물질(neurotransmitter)이란 신경 세포에서 분비되는 신호 물질을 의미하는데, 아미노산, 펩타이드, 모노 아민 등이 있으며, 그 중 대표적인 아미노산 신경전달물질로는 흥분성 신경전달물질인 글루타메이트와 억제성 신경전달물질인 GABA(γ-aminobutyric acid, GABA)가 있다. 특히 GABA는 뇌 혈류 장애, 산소공급 감소, 뇌세포 대사 이상, 신경긴장, 스트레스, 기억력 감퇴, 혈압, 우울증, 중풍, 치매, 불면증, 비만, 갱년기 장애 등의 질환과 연관되는 것으로 알려져 있으며, 따라서 뇌 내 GABA 농도가 저해된 환자군에 GABA를 투여하면 치료 효과가 있음이 증명되었다. 또한 최근에는 GABA 투여가 뇌졸증 및 결장암, 대장암, 세포의 전이 및 증식 억제에도 효과가 있는 것으로 밝혀졌다(BioWave Vol. 9 No. 14 (2007). GABA의 생성과 이용).Neurological diseases can be largely divided into neurological diseases caused by neurotransmitters and neurological diseases caused by physical damage to nerve cells. The neurotransmitter means a signal substance secreted from nerve cells, and there are amino acids, peptides, monoamines, and the like. Among them, the representative amino acid neurotransmitters include glutamate, an excitatory neurotransmitter, and inhibitory neurotransmitter. There is a substance called γ-aminobutyric acid (GABA). In particular, GABA is known to be associated with diseases such as disorders of cerebral blood flow, decreased oxygen supply, abnormal brain cell metabolism, nervous tension, stress, memory loss, blood pressure, depression, stroke, dementia, insomnia, obesity, and menopausal disorders. It has been demonstrated that GABA has a therapeutic effect when administered to a group of patients whose GABA concentration is inhibited. In addition, it was recently found that GABA administration is effective in stroke, colon cancer, colorectal cancer, and inhibition of cell metastasis and proliferation (BioWave Vol. 9 No. 14 (2007). Generation and use of GABA).
GABA와 같은 신경전달물질은 체내 합성 효율을 조절하는 것이 매우 어렵기 때문에, 외부에서 신경전달물질을 투여하는 기술이 개발되고 있으며, 이에 따라 GABA를 함유한 다래나무 수액 음료 및 이의 제조방법(국내 공개특허 제 10-2018-0122780 호), GABA 생산 젖산균을 이용한 발효소세지의 제조방법(국내 공개특허 제 10-2018-0012477 호), 및 GABA 생성을 위한 김치 숙성 방법(국내 등록특허 제 10-1093531호) 등의 기술이 공지되었다.Since it is very difficult to control the synthesis efficiency of neurotransmitters such as GABA in the body, a technology for externally administering neurotransmitters is being developed. Patent No. 10-2018-0122780), a method for producing fermented sausage using lactic acid bacteria producing GABA (Korean Patent Publication No. 10-2018-0012477), and a method of aging kimchi for GABA production (Korean Patent No. 10-1093531) ) and the like are known.
본 발명은 신규한 GABA 증진용 유효성분으로서 고시폴, 또는 이의 유도체에 관한 것이다. 본 발명의 고시폴, 또는 이의 유도체를 유효성분으로 포함하는 약학조성물은 개체에 투여 시 뇌 내 GABA 농도 상승 효과가 현저하므로, GABA 농도 저하에 의해 발생하는 다양한 질환에 치료용으로 사용될 수 있을 것으로 기대된다.The present invention relates to gosipol, or a derivative thereof, as a novel active ingredient for enhancing GABA. Since the pharmaceutical composition comprising Gosipol or a derivative thereof of the present invention as an active ingredient has a remarkable effect of increasing the concentration of GABA in the brain when administered to an individual, it is expected that it can be used for treatment in various diseases caused by a decrease in the concentration of GABA. do.
본 발명은 상기와 같은 종래의 기술상의 문제점을 해결하기 위해 안출된 것으로, 고시폴, 또는 이의 유도체를 유효성분으로 포함하는 신경질환 예방 또는 치료용 약학조성물에 관한 것이다.The present invention has been devised to solve the problems in the prior art as described above, and relates to a pharmaceutical composition for preventing or treating neurological diseases comprising gosipol or a derivative thereof as an active ingredient.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당 업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical task to be achieved by the present invention is not limited to the tasks mentioned above, and other tasks not mentioned will be clearly understood by those of ordinary skill in the art from the following description.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세 사항, 예컨대, 특이적 형태, 조성물 및 공정 등이 기재되어 있다. 그러나, 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "한 가지 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현된 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, various specific details are set forth, such as specific forms, compositions and processes, and the like, for a thorough understanding of the present invention. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction with other known methods and forms. In other instances, well-known processes and manufacturing techniques have not been described in specific detail in order not to unnecessarily obscure the present invention. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, form, composition, or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, references to "in one embodiment" or "an embodiment" in various places throughout this specification do not necessarily refer to the same embodiment of the invention. Additionally, the particular features, forms, compositions, or properties may be combined in any suitable manner in one or more embodiments.
명세서에서 특별한 정의가 없으면 본 명세서에 사용된 모든 과학적 및 기술적인 용어는 본 발명이 속하는 기술분야에서 당업자에 의하여 통상적으로 이해되는 것과 동일한 의미를 가진다.Unless otherwise defined in the specification, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
본 발명에 있어서 “신경전달물질(neurotransmitter)”이란, 시냅스(synapse)에서 화학적 신호(chemical signal)를 전달하기 위해 신경세포에서 분비되는 신호 물질이다. 신경세포 사이의 접합부인 시냅스에는 신경세포의 축삭말단(axon terminal)과 또 다른 신경세포의 수상돌기(dendrite)가 존재한다. 다양한 분자가 신경전달물질로 작용하는데, 그 예로는 콜린 아세틸기전달효소(choline acetyltransferase)에 의해서 아세틸조효소A(acetyl CoA)와 콜린(choline)으로부터 합성되는 아세틸콜린(acetylcholine)이 있고, 아미노산인 글리신(glycine), 글루탐산(glutamate) 등이 있다. 많은 신경전달물질은 아미노산 유도체인 아민(amine)인데, 아미노산 티로신(tyrosine)은 도파민(dopamine), 에피네프린(epinephrine)과 같은 카테콜아민(catecholamine)류를 만들어내고, 글루탐산의 탈카복시화(decarboxylation) 반응은 억제성 신경전달물질인 가바(γ-aminobutyrate, GABA)를 만들어낸다. 세로토닌(serotonin)은 아미노산 트립토판(tryptophan)으로부터 두 단계 반응을 거쳐 만들어지는데, 두 번째 반응이 탈카복시화 반응이다. 또한, 아미노산 히스티딘(histidine)의 탈카복시화 반응은 히스타민(histamine)을 만들어낸다. 일반적으로 하나의 신경세포는 한 종류의 신경전달물질을 분비한다.In the present invention, a “neurotransmitter” is a signal substance secreted from a nerve cell to transmit a chemical signal at a synapse. In the synapse, the junction between neurons, there are axon terminals of neurons and dendrites of other neurons. Various molecules act as neurotransmitters, such as acetyl CoA by choline acetyltransferase and acetylcholine, which is synthesized from choline, and the amino acid glycine. (glycine) and glutamate. Many neurotransmitters are amino acid derivatives called amines. The amino acid tyrosine produces catecholamines such as dopamine and epinephrine, and the decarboxylation reaction of glutamic acid Produces the inhibitory neurotransmitter γ-aminobutyrate (GABA). Serotonin is produced from the amino acid tryptophan through a two-step reaction, the second reaction being decarboxylation. In addition, the decarboxylation reaction of the amino acid histidine produces histamine. In general, one neuron secretes one type of neurotransmitter.
본 발명에 있어서 “GABA(γ-aminobutyric acid, GABA)”란, 억제성 신경전달물질이다. GABA는 신경계에서 신경의 흥분을 조절하는 역할을 맡고 있으며, 인간의 경우 γ-아미노뷰티르산은 근육의 상태를 직접적으로 조절하며, 곤충의 경우엔 신경 수용체의 흥분에만 관여한다. GABA는 엄밀하게 말하면 아미노산의 일종이지만, 알파 아미노산이 아니기 때문에 GABA는 단백질을 구성하는 데는 사용되지 않는다. In the present invention, “GABA (γ-aminobutyric acid, GABA)” is an inhibitory neurotransmitter. GABA plays a role in regulating nerve excitation in the nervous system, and in humans, γ-aminobutyric acid directly regulates the state of muscles, and in insects, it is only involved in the excitation of nerve receptors. GABA is technically a type of amino acid, but since it is not an alpha amino acid, GABA is not used to make proteins.
GABA는 뇌에서 포도당 분해를 촉진하고 뇌의 기능을 활발하게 한다. 뇌내의 GABA 농도 저하는 경련을 유발시킨다. 병태와의 관련도 주목되고 있는데, GABA의 농도를 상승시킴으로서 뇌 혈류 장애, 산소공급 감소, 뇌세포 대사 이상, 신경긴장, 스트레스, 기억력 감퇴, 혈압, 우울증, 중풍, 치매, 불면증, 비만, 갱년기 장애, 뇌졸중, 및 결장암, 대장암, 세포의 전이 및 증식 억제 효과를 얻을 수 있는 것으로 알려져 있다. 또한, GABA의 농도 저하는 간질, 발작, 경련, 우울증, 파킨슨씨병과 같은 질환을 유발하며, 특히 경련/발작 발생과는 밀접한 관련이 있어, GABA의 상승제를 사용하거나 뇌 GABA 농도를 올림으로써 경련이 조절됨이 증명되었다(J Neurosci, 12:4151-4172, 1992).GABA promotes the breakdown of glucose in the brain and activates brain functions. Decreased GABA levels in the brain cause convulsions. The relationship with pathology is also being noted, and by increasing the concentration of GABA, cerebral blood flow disorder, oxygen supply decrease, brain cell metabolism abnormality, nervous tension, stress, memory loss, blood pressure, depression, stroke, dementia, insomnia, obesity, menopausal disorder , stroke, and colon cancer, colorectal cancer, is known to be able to obtain the effect of inhibiting metastasis and proliferation of cells. In addition, a decrease in the concentration of GABA causes diseases such as epilepsy, seizures, convulsions, depression, and Parkinson's disease, and is particularly closely related to the occurrence of seizures/convulsions. This regulation has been demonstrated (J Neurosci, 12:4151-4172, 1992).
본 발명에 있어서 “고시폴”이란, 고시피움(gossypium)속 식물과 아욱과(Malvaceae) 식물의 일부의 씨앗, 잎, 줄기, 뿌리의 분리성 색소선에 포함되어 있는 폴리페놀 화합물의 일종으로, 폴리페놀릭 고시폴(polyphenolic gossypol) 또는 면실색소라고도 한다. 하기 화학식 1로 표현된다. 식물에게 해충에 대한 내성을 제공한다. 가금사료에 고시폴을 첨가할 때, 사료 이용성, 계란생산성 저하와 저장된 계란의 난황탈색 등이 보고된 바 있다. 반면 반추가축은 발효에 의해 고시폴을 비활성화시킨다. 유리 고시폴은 생리적으로 유독성인 반면 결합 고시폴은 비활성이다. 면실 중 비단백질 성분도 고시폴과 결합하여 비용해성 및/또는 비소화성 복합체를 형성한다. 이 결합은 면실박내 고시폴을 해독시키긴 하지만 단백질 및 생물학적 가치를 감소시킨다. 유리 고시폴에 대해 철을 2:1 혹은 3:1의 비율로 첨가하면 간에서 고시폴의 독성을 효과적으로 감소시킬 수 있다. 중국에서는 이러한 고시폴이 남성의 정자 기능을 억제하는 것을 발견하여, 남성 경구 피임약으로 연구되고 있다. 본 발명에 있어서의 고시폴은 (+)-고시폴, (-)-고시폴, (+)고시폴, (-)고시폴, 또는 이들의 연결형 고시폴이나, 헤미고시폴, 아포고시폴 등 고시폴의 유도체를 모두 포함하는 의미이다.In the present invention, "gossipol" is a kind of polyphenol compound contained in the separable pigment glands of seeds, leaves, stems, and roots of plants of the genus Gossypium and plants of the Malvaceae family, Also called polyphenolic gossypol or cotton thread pigment. It is represented by the following formula (1). Gives plants resistance to pests. When Gossypol is added to poultry feed, it has been reported that feed availability, egg productivity, and egg yolk discoloration of stored eggs have been reported. On the other hand, ruminant cattle inactivate gossypol by fermentation. Free gosypol is physiologically toxic, whereas bound gosipol is inactive. Non-protein components in cotton also bind with gossypol to form insoluble and/or non-digestible complexes. This binding detoxifies gossypol in cottonseed meal, but reduces its protein and biological value. The addition of iron in a ratio of 2:1 or 3:1 to free gossypol can effectively reduce the toxicity of gossypol in the liver. In China, it has been found that gosipol inhibits male sperm function and is being studied as an oral contraceptive for men. Gossypole in the present invention is (+)-gosipol, (-)-gosipol, (+)gosipol, (-)gosipol, or their connection type gosipol, hemigosipol, apogosipol, etc. It is meant to include all derivatives of gossypol.
본 발명에 있어서 상기 고시폴 유도체는 이에 제한하는 것은 아니나, 하기 화학식 2인 것이 바람직하다.In the present invention, the gossypol derivative is not limited thereto, but is preferably represented by the following formula (2).
[화학식 1][Formula 1]
[화학식 2][Formula 2]
본 발명의 일 구체예에서 “치료”란, 목적하는 질병의 완화 또는/및 개선을 위해 수행되는 일련의 활동을 의미한다. 본 발명의 목적상 치료는 뇌 내 GABA 농도의 저하에 의해 유발되는 다양한 질환에 있어서 GABA 농도를 높임으로서 증상을 정상화하거나, 개선시키는 활동을 포괄적으로 포함한다.In one embodiment of the present invention, “treatment” refers to a series of activities performed for alleviation and/or amelioration of a desired disease. For the purpose of the present invention, treatment comprehensively includes activities for normalizing or ameliorating symptoms by increasing the GABA concentration in various diseases caused by the lowering of the GABA concentration in the brain.
본 발명의 일 구체예에서 “약학조성물”이란, 특정한 목적을 위해 투여되는 조성물을 의미한다. 본 발명의 목적상, 본 발명의 약학조성물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여 시간, 투여 경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있고, 상기 약학 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약물 형태, 투여 경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있다. 본 발명에 따른 약학 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형화될 수 있다. 또한 본 발명에 따른 약학 조성물은 조성물 총 중량에 대하여 본 발명의 유효성분을 0.1 내지 50 중량%로 포함한다. 암을 예방 또는 치료하는 것이며, 이에 관여하는 화합물 및 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함할 수 있다. 본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있으나, 이에 제한되는 것은 아니다.In one embodiment of the present invention, "pharmaceutical composition" refers to a composition administered for a specific purpose. For the purposes of the present invention, the pharmaceutical composition of the present invention is used to determine the activity, age, weight, general health, sex, diet, administration time, administration route, excretion rate, drug formulation and the severity of the specific disease to be prevented or treated of the specific compound used. It may vary depending on several factors including, and the dosage of the pharmaceutical composition may vary depending on the patient's condition, weight, degree of disease, drug form, administration route and period, but may be appropriately selected by those skilled in the art. The pharmaceutical composition according to the present invention may be formulated as pills, dragees, capsules, solutions, gels, syrups, slurries, and suspensions. In addition, the pharmaceutical composition according to the present invention comprises 0.1 to 50% by weight of the active ingredient of the present invention with respect to the total weight of the composition. It is to prevent or treat cancer, and may include a compound involved therein and a pharmaceutically acceptable carrier, excipient or diluent. Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
본 발명의 일 구체예에서 “투여”란, 어떠한 적절한 방법으로 환자에게 본 발명의 조성물을 도입하는 것을 의미하며, 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 경구 투여, 복강 내 투여, 정맥 내 투여, 근육 내 투여, 피하 투여, 피내 투여, 비내 투여, 폐내 투여, 직장내 투여, 강내 투여, 복강 내 투여, 경막 내 투여가 이루어질 수 있으나, 이에 제한되지는 않는다. 본 발명에서 유효량은 질환의 종류, 질환의 중증도, 조성물에 함유된 유효 성분 및 다른 성분의 종류 및 함량, 제형의 종류 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료 기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 성인의 경우, 상기 치료용 약학조성물을 1회 50ml 내지 500ml의 양으로 체내에 투여 가능하며, 화합물일 경우 0.1ng/kg 내지 10㎎/kg, 모노클로날 항체일 경우 0.1ng/kg 내지 10㎎/kg의 용량으로 투여될 수 있다. 투여 간격은 1일 1회 내지 12회로 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 1일 12회 투여할 경우에는 2시간마다 1회씩 투여할 수 있다. 또한 본 발명의 약학조성물은 목적하고자 하는 암 줄기세포의 치료를 위해 단독 또는 당업계에 공지된 다른 치료법, 예를 들어 화학요법제, 방사선 및 수술과 같이 투여될 수 있다. 또한 본 발명의 약학조성물은 면역 반응을 증진하기 위하여 고안된 다른 치료, 예를 들어 당업계에 주지된 것과 같은 어쥬번트 또는 사이토카인(또는 사이토카인을 코딩하는 핵산)과 혼합하여 투여될 수 있다. 바이오리스틱(biolistic) 전달 또는 생체 외(ex vivo) 처리와 같은 다른 표준 전달 방법들이 사용될 수도 있다. 생체 외 처리에서 예를 들어 항원제시세포들(APCs), 수지상세포들, 말초혈액 단핵구세포들, 또는 골수세포들을 환자 또는 적당한 공여자로부터 얻어서 본 약학조성물로 생체 외에서 활성화된 후 그 환자에게 투여될 수 있다.In one embodiment of the present invention, "administration" means introducing the composition of the present invention to a patient by any suitable method, and the administration route of the composition of the present invention is through any general route as long as it can reach the target tissue. may be administered. Oral administration, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, intranasal administration, intrapulmonary administration, rectal administration, intraperitoneal administration, intraperitoneal administration, intrathecal administration may be made, but is not limited thereto does not In the present invention, the effective amount refers to the type of disease, the severity of the disease, the type and content of the active ingredient and other ingredients contained in the composition, the type of formulation and the age, weight, general health status, sex and diet, administration time, route of administration of the patient. And it can be adjusted according to various factors including the secretion rate of the composition, the duration of treatment, and drugs used simultaneously. For adults, the therapeutic pharmaceutical composition can be administered into the body in an amount of 50ml to 500ml at a time, 0.1ng/kg to 10mg/kg in the case of a compound, 0.1ng/kg to 10mg in the case of a monoclonal antibody It can be administered at a dose of /kg. The administration interval may be administered once a day to 12 times a day, or may be administered in several divided doses. When administered 12 times a day, it can be administered once every 2 hours. In addition, the pharmaceutical composition of the present invention may be administered alone or with other therapies known in the art, for example, chemotherapeutic agents, radiation and surgery for the treatment of desired cancer stem cells. In addition, the pharmaceutical composition of the present invention may be administered in admixture with other treatments designed to enhance the immune response, for example, adjuvants or cytokines (or nucleic acids encoding cytokines) as well known in the art. Other standard delivery methods may be used, such as biolistic delivery or ex vivo treatment. In ex vivo treatment, for example, antigen-presenting cells (APCs), dendritic cells, peripheral blood mononuclear cells, or bone marrow cells obtained from a patient or an appropriate donor can be activated in vitro with the present pharmaceutical composition and then administered to the patient. there is.
본 발명의 일 구체예에서 “식품 조성물”이란, 본 발명에서 목적으로 하는 적응증의 예방 또는 개선을 위해 다양하게 이용되는 것으로서, 본 발명의 조성물을 유효성분으로 포함하는 식품조성물은 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 분말, 과립, 정제, 캡슐, 과자, 떡, 빵 등의 형태로 제조될 수 있다. 본 발명의 식품조성물은 독성 및 부작용이 거의 없는 기존의 식품용 섭취물로부터 개량되어 구성된 것이므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있다. 본 발명의 조성물이 식품조성물에 포함될 때 그 양은 전체 중량의 0.1 내지 100%의 비율로 첨가할 수 있다. 여기서, 상기 식품조성물이 음료 형태로 제조되는 경우 지시된 비율로 상기 식품조성물을 함유하는 것 외에 특별한 제한점은 없으며 통상의 음료와 같이 여러가지 향미제 또는 천연탄수화물 등을 추가 성분으로서 함유할 수 있다. 즉, 천연탄수화물로서 포도당 등의 모노사카라이드, 과당 등의 디사카라이드, 슈크로스 등의 및 폴리사카라이드, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜 등을 포함할 수 있다. 상기 향미제로서는 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등) 등을 들 수 있다. 그 외 본 발명의 식품조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성풍미제 및 천연풍미제 등의 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 통상적으로 본 발명의 조성물 100 중량부 당 0.1 내지 100 중량부의 범위에서 선택되는 것이 일반적이나, 이에 제한되는 것은 아니다.In one embodiment of the present invention, "food composition" is used in various ways for the prevention or improvement of indications for the purpose of the present invention. For example, it may be prepared in the form of beverage, gum, tea, vitamin complex, powder, granule, tablet, capsule, confectionery, rice cake, bread, and the like. Since the food composition of the present invention is improved from the existing food intake with little toxicity and side effects, it can be safely used even when taken for a long period of time for the purpose of prevention. When the composition of the present invention is included in the food composition, the amount may be added in a proportion of 0.1 to 100% of the total weight. Here, when the food composition is prepared in the form of a beverage, there is no particular limitation other than containing the food composition in the indicated ratio, and it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in a conventional beverage. That is, as natural carbohydrates, monosaccharides such as glucose, disaccharides such as fructose, polysaccharides such as sucrose, and common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol are included. can do. Examples of the flavoring agent include natural flavoring agents (taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.). Others of the present invention of various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH regulators, It may contain stabilizer, preservative, glycerin, alcohol, carbonation agent used in carbonated beverage, etc. These components can be used independently or in combination.The proportion of these additives is usually per 100 parts by weight of the composition of the present invention. It is generally selected in the range of 0.1 to 100 parts by weight, but is not limited thereto.
본 발명의 일 구체예에서, 하기 화학식 2의 화합물 또는 이의 약리학적으로 허용되는 염, 수화물 또는 용매화물을 제공한다.In one embodiment of the present invention, there is provided a compound of Formula 2 or a pharmacologically acceptable salt, hydrate or solvate thereof.
[화학식 2][Formula 2]
본 발명의 또 다른 구체예에서, 고시폴, 또는 이의 유도체를 유효성분으로 포함하는 억제성 신경전달물질 저하성 질환의 예방 또는 치료용 약학조성물을 제공하고, 상기 억제성 신경전달물질은 GABA(γ-aminobutyric acid)인 것인 억제성 신경전달물질 저하성 질환의 예방 또는 치료용 약학조성물을 제공하며, 상기 고시폴은 하기 화학식 1로 표현되는 것인 억제성 신경전달물질 저하성 질환의 예방 또는 치료용 약학조성물을 제공하며, 상기 고시폴 유도체는 (+)-고시폴, (-)-고시폴, (+)고시폴, (-)고시폴, 또는 이들의 연결형 고시폴이나, 헤미고시폴, 및 아포고시폴로 구성되는 그룹에서 선택되는 어느 하나 이상을 포함하는 것인 억제성 신경전달물질 저하성 질환의 예방 또는 치료용 약학조성물을 제공하며, 상기 고시폴 유도체는 하기 화학식 2로 표현되는 것인 억제성 신경전달물질 저하성 질환의 예방 또는 치료용 약학조성물을 제공하며, 상기 억제성 신경전달물질 저하성 질환은 간질, 발작, 경련, 우울증, 불안증, 강박증, 파킨슨씨병, 뇌졸중, 뇌경색, 스트레스 장애, 혈압 장애, 기억력 감퇴, 알츠하이머병, 불면증, 비만, 갱년기 장애, 및 암으로 구성되는 그룹에서 선택되는 어느 하나인 것인 억제성 신경전달물질 저하성 질환의 예방 또는 치료용 약학조성물을 제공한다.In another embodiment of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of an inhibitory neurotransmitter-degrading disease comprising Gossypol or a derivative thereof as an active ingredient, wherein the inhibitory neurotransmitter is GABA (γ -aminobutyric acid), which provides a pharmaceutical composition for the prevention or treatment of inhibitory neurotransmitter-decreasing diseases, wherein the gosipol is represented by the following formula (1). It provides a pharmaceutical composition for use, wherein the gosipol derivative is (+)-gosipol, (-)-gosipol, (+)gosipol, (-)gosipol, or their linked gosipol, hemigosipol, And it provides a pharmaceutical composition for the prevention or treatment of inhibitory neurotransmitter-decreasing disease comprising any one or more selected from the group consisting of apogosipol, wherein the gosipol derivative is represented by the following formula (2) It provides a pharmaceutical composition for the prevention or treatment of inhibitory neurotransmitter-decreasing diseases, wherein the inhibitory neurotransmitter-decreasing diseases are epilepsy, seizures, convulsions, depression, anxiety, obsessive compulsive disorder, Parkinson's disease, stroke, cerebral infarction, stress disorder , Blood pressure disorder, memory loss, Alzheimer's disease, insomnia, obesity, menopausal disorders, and provides a pharmaceutical composition for preventing or treating inhibitory neurotransmitter-decreasing disease which is any one selected from the group consisting of cancer.
[화학식 1][Formula 1]
[화학식 2][Formula 2]
본 발명의 다른 구체예에서, 고시폴, 또는 이의 유도체를 유효성분으로 포함하는 억제성 신경전달물질 저하성 질환의 예방 또는 개선용 식품조성물을 제공하고, 상기 억제성 신경전달물질은 GABA(γ-aminobutyric acid)인 것인 억제성 신경전달물질 저하성 질환의 예방 또는 개선용 식품조성물을 제공하며, 상기 고시폴은 하기 화학식 1로 표현되는 것인 억제성 신경전달물질 저하성 질환의 예방 또는 개선용 식품조성물을 제공하며, 상기 고시폴 유도체는 (+)-고시폴, (-)-고시폴, (+)고시폴, (-)고시폴, 또는 이들의 연결형 고시폴이나, 헤미고시폴, 및 아포고시폴로 구성되는 그룹에서 선택되는 어느 하나 이상을 포함하는 것인 억제성 신경전달물질 저하성 질환의 예방 또는 개선용 식품조성물을 제공하며, 상기 고시폴 유도체는 하기 화학식 2로 표현되는 것인 억제성 신경전달물질 저하성 질환의 예방 또는 개선용 식품조성물을 제공하며, 상기 억제성 신경전달물질 저하성 질환은 간질, 발작, 경련, 우울증, 불안증, 강박증, 파킨슨씨병, 뇌졸중, 뇌경색, 스트레스 장애, 혈압 장애, 기억력 감퇴, 알츠하이머병, 불면증, 비만, 갱년기 장애, 및 암으로 구성되는 그룹에서 선택되는 어느 하나인 것인 억제성 신경전달물질 저하성 질환의 예방 또는 개선용 식품조성물을 제공한다.In another embodiment of the present invention, there is provided a food composition for preventing or ameliorating an inhibitory neurotransmitter-decreasing disease comprising gossypol or a derivative thereof as an active ingredient, wherein the inhibitory neurotransmitter is GABA (γ- aminobutyric acid), which provides a food composition for the prevention or improvement of inhibitory neurotransmitter-decreasing diseases, wherein the gosipol is for the prevention or improvement of inhibitory neurotransmitter-decreasing diseases that are represented by the following formula (1) It provides a food composition, wherein the gosypol derivative is (+)-gosipol, (-)-gosipol, (+)gosipol, (-)gosipol, or their linked gosipol, hemigosipol, and It provides a food composition for preventing or ameliorating an inhibitory neurotransmitter-degrading disease comprising at least one selected from the group consisting of apogosipol, wherein the gosipol derivative is expressed by the following formula (2) It provides a food composition for the prevention or improvement of sexual neurotransmitter-degrading diseases, wherein the inhibitory neurotransmitter-decreasing diseases include epilepsy, seizures, convulsions, depression, anxiety, obsessive compulsive disorder, Parkinson's disease, stroke, cerebral infarction, stress disorder, It provides a food composition for preventing or ameliorating an inhibitory neurotransmitter-decreasing disease, which is any one selected from the group consisting of blood pressure disorders, memory loss, Alzheimer's disease, insomnia, obesity, menopausal disorders, and cancer.
[화학식 1][Formula 1]
[화학식 2][Formula 2]
이하 상기 본 발명을 단계별로 상세히 설명한다.Hereinafter, the present invention will be described in detail step by step.
억제성 신경전달물질인 GABA의 농도 저하는 간질, 발작, 경련, 우울증, 파킨슨씨병과 같은 질환을 유발한다. 본 발명은 고시폴, 또는 이의 유도체를 유효성분으로 포함하는 신경질환 예방 또는 치료용 약학조성물에 관한 것으로, 본 발명의 약학조성물은 개체에 투여 시 뇌 내 GABA 농도 상승 효과가 현저하므로, GABA 농도 저하에 의해 발생하는 다양한 질환에 치료용으로 사용될 수 있을 것으로 기대된다.Decreased levels of the inhibitory neurotransmitter GABA lead to diseases such as epilepsy, seizures, convulsions, depression, and Parkinson's disease. The present invention relates to a pharmaceutical composition for the prevention or treatment of neurological diseases comprising gossypol or a derivative thereof as an active ingredient. It is expected that it can be used for treatment of various diseases caused by
도 1은 본 발명의 일 실시예에 따른, GABA 증진 후보 약물을 1주간 투여한 전후의 실험동물의 체중 변화를 나타낸 도이다.
도 2는 본 발명의 일 실시예에 따른, 동물에 GABA 증진 후보 약물을 투여 후 뇌 조직의 GABA 함량을 측정한 결과를 나타낸 도이다.
도 3은 본 발명의 일 실시예에 따른, 동물에 GABA 증진 후보 약물을 투여 후 뇌 조직 내의 젖산 함량을 측정한 결과를 나타낸 도이다.
도 4는 본 발명의 일 실시예에 따른, 동물에 GABA 증진 후보 약물을 투여 후 근육 조직 내의 젖산 함량을 측정한 결과를 나타낸 도이다.
도 5는 본 발명의 일 실시예에 따른, 동물에 GABA 증진 후보 약물을 투여 후 혈청 내의 젖산 함량을 측정한 결과를 나타낸 도이다.
도 6은 본 발명의 일 실시예에 따른, GABA 증진 후보 약물을 투여 후 뇌 조직 내의 LDH 활성을 측정한 결과를 나타낸 도이다.
도 7은 본 발명의 일 실시예에 따른, GABA 증진 후보 약물을 투여 후 뇌 조직 내의 ALDH 활성을 측정한 결과를 나타낸 도이다.1 is a diagram showing changes in body weight of experimental animals before and after administration of a GABA-enhancing candidate drug according to an embodiment of the present invention for 1 week.
2 is a diagram showing the results of measuring the GABA content in brain tissue after administration of a GABA enhancement candidate drug to an animal, according to an embodiment of the present invention.
3 is a diagram showing the results of measuring the lactic acid content in brain tissue after administration of a GABA enhancement candidate drug to an animal, according to an embodiment of the present invention.
4 is a diagram showing the results of measuring the lactic acid content in muscle tissue after administration of a GABA enhancement candidate drug to an animal, according to an embodiment of the present invention.
5 is a diagram showing the results of measuring the lactic acid content in the serum after administration of a GABA enhancement candidate drug to an animal, according to an embodiment of the present invention.
6 is a diagram showing the results of measuring LDH activity in brain tissue after administration of a GABA-enhancing candidate drug according to an embodiment of the present invention.
7 is a diagram showing the results of measuring ALDH activity in brain tissue after administration of a GABA-enhancing candidate drug according to an embodiment of the present invention.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예.Example.
GABA 증진 시험을 위한 실험동물은 샘타코바이오코리아(경기도 성남, 한국)로부터 ICR 마우스(7주령, 수컷)을 분양 받아, (주)동남의화학연구원 동물사(동물시설등록증: 제 412호)에서 일주일간 검역과 순화/사육을 거친 후 실험하였다. 사육 시 조명시간은 12시간 (07:00∼19:00)으로 설정하였고, 식이와 급수는 자유섭취시켰다. 사료는 실험동물용 고형사료(하나바이오, 경기도 성남, 한국)를 제공하고, 체중 변화는 3회 측정하였다. 실험동물은 일정 시간(오전 10:00-12:00) 내에 처치하였다. 모든 동물을 이용한 시험은 (주)동남의화학연구원 동물실험위원회(SEMI-19-009, Institutional Animal Care and Use committee)의 방침 및 법규에 따라 진행하였다.Experimental animals for the GABA enhancement test were acquired ICR mice (7 weeks old, male) from Samtaco Bio Korea (Seongnam, Gyeonggi-do, Korea), After a week of quarantine and acclimatization/breeding, it was tested. During breeding, the lighting time was set to 12 hours (07:00 to 19:00), and food and water were freely consumed. For the feed, solid feed for experimental animals (Hana Bio, Seongnam, Gyeonggi-do, Korea) was provided, and the change in body weight was measured three times. Experimental animals were treated within a certain period of time (10:00-12:00 am). All animal tests were conducted in accordance with the policies and regulations of the Dongnam Medical Research Institute's Animal Experiment Committee (SEMI-19-009, Institutional Animal Care and Use committee).
GABA 증진 후보 약물은 하기 표 1과 같이 1주간 투여하였다(n=7).GABA enhancement candidate drugs were administered for 1 week as shown in Table 1 below (n=7).
(mg/kg)dosing concentration
(mg/kg)
(50mA, 0.2초)1convulsions induction
(50mA, 0.2 sec)1
시험예 4와 시험예 5의 고시폴, 또는 고시폴 유도체의 정보는 하기 표 2에 기재하였다.Information on gosipol or a gosypol derivative of Test Example 4 and Test Example 5 is shown in Table 2 below.
양성대조군으로 사용한 프레가발린(pregabalin)은 중추 신경의 전위 의존성 칼슘 채널에 결합하여 글루타메이트, 노에피네프린의 분비를 억제하여 진통 작용을 일으키는 약물이다(J Korean Med Assoc, 55(6): 582-592, 2012). 선행 문헌에 따르면, 프레가발린 투여 시 전기 자극으로 뇌 조직 내 줄어든 GABA의 함량이 유의적으로 증가한다.Pregabalin, used as a positive control, is a drug that binds to the potential-dependent calcium channel of the central nerve and inhibits the secretion of glutamate and norepinephrine to cause analgesic action (J Korean Med Assoc, 55(6): 582-592) , 2012). According to the prior literature, when pregabalin is administered, the content of GABA, which is reduced in brain tissue due to electrical stimulation, is significantly increased.
상기 표 1의 GABA 증진 후보 약물을 1주간 투여한 전후의 체중은 모든 시험군에서 정상적인 체중의 변화를 보였다. 이를 표 3과 도 1에 나타내었다.The body weight before and after administration of the GABA enhancement candidate drug of Table 1 for 1 week showed a change in normal body weight in all test groups. This is shown in Table 3 and FIG. 1 .
GABA 증진 후보 약물 투여 30분 후, ECT Unit (UGO Basline, Italy)을 사용하여 경련을 유도하였다. 실험동물의 양눈에 식염수를 떨어뜨린 후 50mA, 0.2초간 전기 자극을 주었다. 뒷 다리를 비롯한 몸통에 나타나는 강직성 경련의 유/무를 항경련 활성의 기준으로 설정하였다. 전체 개체 중에서 전기 자극으로 유도된 경련이 나타난 개체수를 계산하여 결과를 정리하였다. 상기 결과를 표 4에 나타내었다.Thirty minutes after administration of the GABA-enhancing candidate drug, convulsions were induced using an ECT Unit (UGO Basline, Italy). After saline was dropped on both eyes of the experimental animals, electrical stimulation was applied at 50 mA for 0.2 seconds. The presence/absence of tonic spasm in the trunk including the hind legs was set as the criterion for anticonvulsant activity. The results were summarized by counting the number of subjects who had seizures induced by electrical stimulation among all subjects. The results are shown in Table 4.
항경련 시험 결과, C군에서는 전기 자극을 통해 7마리 중 6마리의 개체가 경련이 일어났으며 그 중 1마리는 사망하였다. 그러나 고시폴(SA)을 투여한 실험군에서는 모든 개체가 경련이 유도되지 않았다. 이는 양성대조군으로 사용한 프레가발린과 비교하여도 항경련 효과가 우수한 것이다.As a result of the anticonvulsant test, in group C, 6 out of 7 animals had convulsions through electrical stimulation, and one of them died. However, no convulsions were induced in all subjects in the experimental group administered with gosipol (SA). This is superior to the anticonvulsant effect compared to pregabalin used as a positive control.
경련 유도 후 1시간 이내에 실험동물을 CO2로 마취하고, 1 mL 주사기를 이용하여 복부대정맥에서 채혈하였다. 또한 뇌, 간, 신장, 근육, 및 비장 조직을 수득하였다.Within 1 hour after induction of convulsions, the experimental animals were anesthetized with CO 2 , and blood was collected from the abdominal vena cava using a 1 mL syringe. Brain, liver, kidney, muscle, and spleen tissues were also obtained.
상기 뇌 조직으로부터 GABA를 측정한 결과를 표 5, 및 도 2에 나타내었다. 실험 결과, 전기 자극을 유도한 C군의 뇌 조직 내 GABA 함량이 감소하였지만, 고시폴(SA), 또는 고시폴 유도체(SB)를 투여한 군에서는 C군 대비 p<0.05 유의 수준으로 증가되어 경련을 조절하는 것을 확인하였다.The results of measuring GABA from the brain tissue are shown in Table 5 and FIG. 2 . As a result of the experiment, the GABA content in the brain tissue of group C induced by electrical stimulation decreased, but in the group administered with gosipol (SA) or gosipol derivative (SB), it increased to a significance level of p<0.05 compared to group C, resulting in convulsions. was confirmed to be controlled.
간질은 뇌에서 포도당과 산소의 대사가 증가하여 초기에 뇌 혈류가 증가하고 혈류 보상이 충분하지 않을 때 발생한다. 이 때 무산소 대사가 증가하면 젖산이 증가하고 인산크레아틴이 감소한다(J Korean Radiol Soc, 42:4, 2000).Epilepsy occurs when the metabolism of glucose and oxygen in the brain increases, which initially results in increased cerebral blood flow and insufficient blood flow compensation. When anaerobic metabolism increases, lactic acid increases and creatine phosphate decreases (J Korean Radiol Soc, 42:4, 2000).
상기 수득한 실험동물의 조직과 혈액으로부터 젖산(lactate)의 함량을 확인하였다. 그 결과, 하기 표 6과 도 3 내지 도 5에서와 같이, 뇌, 근육 조직, 및 혈청 모두에서 젖산의 함량이 C군 대비 N군에서 유의적으로 감소하였다. 이는 전기 자극으로 인해 젖산이 축적된 것임을 알 수 있다. 프레가발린(Pre), 고시폴(SA), 또는 고시폴 유도체(SB)를 투여한 실험군 또한 젖산의 함량이 C군 대비 유의 수준으로 감소하였다. 특히 고시폴, 또는 고시폴 유도체의 젖산 완화 효과는 프레가발린보다 우수한 것으로 나타났다.The content of lactate was confirmed from the obtained tissue and blood of the experimental animal. As a result, as shown in Table 6 and FIGS. 3 to 5 below, the content of lactic acid in all of the brain, muscle tissue, and serum was significantly reduced in group N compared to group C. It can be seen that lactic acid is accumulated due to electrical stimulation. In the experimental group administered with pregabalin (Pre), gosipol (SA), or a gosipol derivative (SB), the content of lactic acid was also reduced to a significant level compared to group C. In particular, it was found that the lactic acid relief effect of gosipol or a gosipol derivative was superior to that of pregabalin.
어떤 자극으로 인해 뇌 혈류가 감소되며 손상된 세포나 염증 세포의 대사가 활발해지면 젖산 탈수소효소(lactate dehydrogenase; LDH)나 알데하이드 탈수소효소(Aldehyde dehydrogenase; ALDH) 활성이 증가하게 된다(Eur J Cancer, 50(1):137-49, 2014).When cerebral blood flow is reduced due to any stimulus and metabolism of damaged or inflammatory cells becomes active, lactate dehydrogenase (LDH) or aldehyde dehydrogenase (ALDH) activity increases (Eur J Cancer, 50 (Eur J Cancer, 50 (Eur J Cancer, 50) 1):137-49, 2014).
상기 수득한 실험동물의 조직과 혈액으로부터 LDH, 및 ALDH의 함량을 확인하였다. 실험 결과, 하기 표 7, 도 6 내지 도 7에서와 같이, 전기 자극으로 유도된 경련이 발생한 C군 대비 전기 자극을 주지 않은 N군에서는 효소 활성이 유의적으로 감소하였다. 프레가발린(Pre), 고시폴(SA), 또는 고시폴 유도체(SB)를 투여한 실험군 또한 ALDH의 함량이 C군 대비 유의 수준으로 감소하였다.The contents of LDH and ALDH were confirmed from the obtained tissues and blood of the experimental animals. As a result of the experiment, as shown in Table 7 and FIGS. 6 to 7 below, the enzyme activity was significantly reduced in group N, which did not receive electrical stimulation, compared to group C, in which electrical stimulation-induced convulsions occurred. In the experimental group administered with pregabalin (Pre), gosipol (SA), or a gosipol derivative (SB), the ALDH content was also reduced to a significant level compared to group C.
상기 모든 시험의 결과는 평균치와 표준편차로 나타내었으며, 각 군의 유의성 검정은 Statview program의 Anova t-test를 이용하여 확인한 것이다.The results of all the tests were expressed as the mean and standard deviation, and the significance test of each group was confirmed using the Anova t-test of the Statview program.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.As described above in detail a specific part of the present invention, for those of ordinary skill in the art, this specific description is only a preferred embodiment, and it is clear that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (13)
[화학식 2]
A compound of Formula 2 or a pharmaceutically acceptable salt, hydrate or solvate thereof.
[Formula 2]
A pharmaceutical composition for the prevention or treatment of an inhibitory neurotransmitter-decreasing disease, comprising gosipol, or a derivative thereof, as an active ingredient.
상기 억제성 신경전달물질은 GABA(γ-aminobutyric acid)인 것인, 약학조성물.
3. The method of claim 2,
The inhibitory neurotransmitter is GABA (γ-aminobutyric acid), the pharmaceutical composition.
상기 고시폴은 하기 화학식 1로 표현되는 것인, 약학조성물.
[화학식 1]
3. The method of claim 2,
The gossypol is represented by the following formula (1), a pharmaceutical composition.
[Formula 1]
상기 고시폴 유도체는 (+)-고시폴, (-)-고시폴, (+)고시폴, (-)고시폴, 또는 이들의 연결형 고시폴이나, 헤미고시폴, 및 아포고시폴로 구성되는 그룹에서 선택되는 어느 하나 이상을 포함하는 것인, 약학조성물.
3. The method of claim 2,
The gosipol derivative is (+)-gosipol, (-)-gosipol, (+)gosipol, (-)gosipol, or a group consisting of a linked type of gosipol, hemigosipol, and apogosipol A pharmaceutical composition comprising any one or more selected from.
상기 고시폴 유도체는 하기 화학식 2로 표현되는 것인, 약학조성물.
[화학식 2]
6. The method of claim 5,
The gosipol derivative is represented by the following formula (2), a pharmaceutical composition.
[Formula 2]
상기 억제성 신경전달물질 저하성 질환은 간질, 발작, 경련, 우울증, 불안증, 강박증, 파킨슨씨병, 뇌졸중, 뇌경색, 스트레스 장애, 혈압 장애, 기억력 감퇴, 알츠하이머병, 불면증, 비만, 갱년기 장애, 및 암으로 구성되는 그룹에서 선택되는 어느 하나인 것인, 약학조성물.
3. The method of claim 2,
The inhibitory neurotransmitter-degrading disease includes epilepsy, seizures, convulsions, depression, anxiety, obsessive compulsive disorder, Parkinson's disease, stroke, cerebral infarction, stress disorder, blood pressure disorder, memory loss, Alzheimer's disease, insomnia, obesity, menopausal disorder, and cancer Any one selected from the group consisting of, a pharmaceutical composition.
A food composition for preventing or improving an inhibitory neurotransmitter-decreasing disease, comprising gosipol, or a derivative thereof, as an active ingredient.
상기 억제성 신경전달물질은 GABA(γ-aminobutyric acid)인 것인, 식품조성물.
9. The method of claim 8,
The inhibitory neurotransmitter is GABA (γ-aminobutyric acid), the food composition.
상기 고시폴은 하기 화학식 1로 표현되는 것인, 식품조성물.
[화학식 1]
9. The method of claim 8,
The gossypol is represented by the following formula (1), a food composition.
[Formula 1]
상기 고시폴 유도체는 (+)-고시폴, (-)-고시폴, (+)고시폴, (-)고시폴, 또는 이들의 연결형 고시폴이나, 헤미고시폴, 및 아포고시폴로 구성되는 그룹에서 선택되는 어느 하나 이상을 포함하는 것인, 식품조성물.
9. The method of claim 8,
The gosipol derivative is (+)-gosipol, (-)-gosipol, (+)gosipol, (-)gosipol, or a group consisting of a linked type of gosipol, hemigosipol, and apogosipol A food composition comprising any one or more selected from.
상기 고시폴 유도체는 하기 화학식 2로 표현되는 것인, 식품조성물.
[화학식 2]
10. The method of claim 9,
Wherein the gosipol derivative is represented by the following formula (2), a food composition.
[Formula 2]
상기 억제성 신경전달물질 저하성 질환은 간질, 발작, 경련, 우울증, 불안증, 강박증, 파킨슨씨병, 뇌졸중, 뇌경색, 스트레스 장애, 혈압 장애, 기억력 감퇴, 알츠하이머병, 불면증, 비만, 갱년기 장애, 및 암으로 구성되는 그룹에서 선택되는 어느 하나인 것인, 식품조성물.
9. The method of claim 8,
The inhibitory neurotransmitter-degrading disease includes epilepsy, seizures, convulsions, depression, anxiety, obsessive compulsive disorder, Parkinson's disease, stroke, cerebral infarction, stress disorder, blood pressure disorder, memory loss, Alzheimer's disease, insomnia, obesity, menopausal disorder, and cancer Any one selected from the group consisting of, a food composition.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020200013844A KR20210099911A (en) | 2020-02-05 | 2020-02-05 | Pharmaceutical composition for preventing and treating neurological diseases comprising gossypol or derivatives thereof as an active ingredient |
| PCT/KR2021/001506 WO2021158046A1 (en) | 2020-02-05 | 2021-02-05 | Pharmaceutical composition comprising gossypol or derivative thereof as active ingredient for prevention or treatment of neurological disorder |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020200013844A KR20210099911A (en) | 2020-02-05 | 2020-02-05 | Pharmaceutical composition for preventing and treating neurological diseases comprising gossypol or derivatives thereof as an active ingredient |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20210099911A true KR20210099911A (en) | 2021-08-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020200013844A KR20210099911A (en) | 2020-02-05 | 2020-02-05 | Pharmaceutical composition for preventing and treating neurological diseases comprising gossypol or derivatives thereof as an active ingredient |
Country Status (2)
| Country | Link |
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| KR (1) | KR20210099911A (en) |
| WO (1) | WO2021158046A1 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100579494B1 (en) * | 2004-04-07 | 2006-05-12 | 학교법인 한림대학교 | Anticonvulsant Composition containing Pyridoxal-?-aminobutyrate |
| CN102395268A (en) * | 2009-04-15 | 2012-03-28 | 桑福德-伯纳姆医学研究院 | Naphthalene-based inhibitors of anti-apoptotic proteins |
| KR101579371B1 (en) * | 2014-02-27 | 2015-12-22 | 국립암센터 | Anti-cancer composition comprising gossypol and phenformin |
| CN104910041B (en) * | 2014-03-12 | 2017-09-26 | 南开大学 | Aromatic amine Schiff base derivatives of gossypol and preparation method thereof and Antiphytoviral application |
-
2020
- 2020-02-05 KR KR1020200013844A patent/KR20210099911A/en unknown
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| WO2021158046A1 (en) | 2021-08-12 |
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