KR101660381B1 - Insect N-Glycans and Use Thereof - Google Patents
Insect N-Glycans and Use Thereof Download PDFInfo
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- KR101660381B1 KR101660381B1 KR1020140183127A KR20140183127A KR101660381B1 KR 101660381 B1 KR101660381 B1 KR 101660381B1 KR 1020140183127 A KR1020140183127 A KR 1020140183127A KR 20140183127 A KR20140183127 A KR 20140183127A KR 101660381 B1 KR101660381 B1 KR 101660381B1
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
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Abstract
본 발명은 하나 이상의 Hex 및/또는 HexGlcNAc로 구성된 특정 당쇄 구조를 가지는 귀뚜라미(Gryllus bimaculatus), 매미눈꽃동충하초(Isaria sinclairii), 강랑(Catharsius molossus), 맹충(Tabanus bivittatus) 또는 광대노린재(Poecilocoris lewisi) 유래 곤충 N-글라이칸(N-glycan), 이를 포함하는 약학 조성물, 기능성 식품 및 화장료용 조성물에 관한 것이다.
본 발명에 따른 하나 이상의 Hex 및/또는 HexGlcNAc로 구성된 특정 당쇄 구조를 가진 곤충 N-글라이칸(N-glycan) 및 이를 포함하는 글라이코자미노글라이칸의 분획물은 생물학적 활성이 알려짐에 따라 의약품, 화장품 및 기능성식품 소재로 사용할 수 있어, 제약 및 기능성 분자로서의 가치를 가지며, 특히 혈관신생 억제능 또는 혈관확장반응의 기능장애에 의한 질환 치료효과가 있어, 다양한 곤충유래 N-글라이칸(N-glycan) 의약품 개발을 가능케함으로써, 곤충사육농가 소득 보전 및 국민보건향상에 기여할 수 있다.The present invention relates to a method for screening for a compound of the present invention, which is based on a specific glycan structure consisting of one or more Hex and / or HexGlcNAc, such as Gryllus bimaculatus , Isaria sinclairii , Catharsius molossus , Tabanus bivittatus or Poecilocoris lewisi An insect N-glycan, a pharmaceutical composition containing the same, a functional food, and a composition for a cosmetic composition.
The insect N-glycan (N-glycan) having a specific sugar chain structure composed of one or more Hex and / or HexGlcNAc according to the present invention and the fraction of the glycocamminoglycan containing the same is known as a pharmaceutical, And can be used as a functional food material, and has a valuable value as a pharmaceutical and functional molecule. In particular, it has an effect of treating diseases caused by inhibition of angiogenesis or dysfunction of vasodilatation reaction. Thus, various insect-derived N-glycan drugs By enabling development, it can contribute to the conservation of income of insect farmers and the improvement of public health.
Description
본 발명은 특정 당쇄구조를 가지는 곤충 유래 N-글라이칸(N-Glycan) 및 이의 용도에 관한 것이다.The present invention relates to insect-derived N-glycans (N-Glycan) having a specific sugar chain structure and uses thereof.
글라이코자미노글라이칸(Glycosaminoglycan, GAG)은 반복하는 이당류 단위를 가진 음이온성 이형다당류로서, 산성당(uronic acid)과 아미노당(N-acetylglucoamine, N-acetylgalactosamine)의 결합을 통해 사슬이 무수히 반복되는 구조를 가지고 있으며, 당 잔기에 황산기(SO3-) 혹은 카르복실기(COO-) 가져 음전하를 띠고, 당 잔기들 간의 결합 형태와 sulfate의 수와 위치에 따라 그 특성이 분류된다. GAG는 황산기의 유무에 따라 황산화 다당과 비황산화 다당으로 크게 나누어지며, 대표적인 GAG는 hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin/heparan sulfate와 keratan sulfate를 들 수 있다. Glycosaminoglycan (GAG) is an anionic heterobifunctional polysaccharide with repeating disaccharide units, which is repeated numerous times through the linkage of uronic acid and amino sugar (N-acetylglucoamine, N-acetylgalactosamine) (SO 3 - ) or carboxyl group (COO - ) in the sugar residue and have a negative charge, and their characteristics are classified according to the type of bond between sugar residues and the number and position of sulfate. GAG is divided into sulfated polysaccharide and non-sulfur polysaccharide depending on the presence or absence of sulfate groups. Representative GAGs include hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin / heparan sulfate and keratan sulfate.
Hyaluronic acid를 제외한 GAG는 당단백질과는 다른 프로테오글리칸으로 존재하며, 음이온기가 많은 chondroitin sulfate와 keratan sulfate(또는 dermatan sulfate)의 콘드로이틴군(chondroitin family)과 헤파린군(heparin family)은 결합 부위에 중심단백질을 가지는 특징이 있다. GAG, except for hyaluronic acid, exists as a proteoglycan different from glycoprotein. Chondroitin sulfate and keratan sulfate (or dermatan sulfate) chondroitin family and heparin family, which have many anionic groups, There are features.
또한, 세포막에 존재하는 당단백질은 N-glycan과 O-glycan으로 나뉘어지며 그 중 N-glycan은 asparagine의 NH2 잔기에 N-acetylglucosamine이 결합하는 것을 시작으로 당쇄가 형성되며 N-X(아무 아미노산도 가능)-S(serine) /T(threonine)의 아미노산 서열을 가지는 경우의 Agr만 N-글라이칸(N-glycan)의 아미노산 부착이 가능하다. N-글라이칸(N-glycan)은 High mannose로 ER에서 미성숙형태로 합성되어, hybrid로 Golgi로 이동 후 성숙한 형태 complex로 되는데 mannose에 다시 N-glycosamine이 결합된 다양한 형태로 복잡하게 합성된 성숙한 형태로 되어간다. 이 과정은 매우 특이성이 높은 당전이효소들에 의해 조절되며 당쇄의 사소한 변화와 미묘한 차이에 의해 세포기능이 조절되고 변화할 수 있다.
In addition, the glycoprotein present in the cell membrane is divided into N-glycan and O-glycan. Among them, N-glycan is formed by binding of N-acetylglucosamine to the NH 2 residue of asparagine and NX ) -S (serine) / T (threonine), it is possible to attach amino acids of N-glycan only to Agr. N-glycan (N-glycan) is a high mannose, which is synthesized as an immature form in the ER and then transferred to the Golgi as a hybrid, resulting in a mature type complex. It is a mature form complexly synthesized in various forms in which N-glycosamine is combined with mannose . This process is regulated by highly specific glycosyltransferases and cell functions can be regulated and altered by subtle changes in sugar chains and subtle differences.
최근 GAG 또는 N-글라이칸(N-glycan)의 여러 가지 생물학적 활성이 알려짐에 따라 의약품, 화장품 및 기능성식품 소재로 사용하고 있어 제약 및 기능성 분자로서의 가치가 증가하고 있으며, 특히 성장 인자와 사이토카인 생성을 조절하고, 조직의 결합이나 특수한 조직의 성숙에 영향을 미치며, 생물학적인 필터로서 역할을 수행하고 콜라겐 섬유 합성과 피부의 인장강도를 조절하며 암세포의 성장과 침윤에도 영향을 미치는 것으로 알려져 있다.Recently, since various biological activities of GAG or N-glycan have been known, they have been used as medicines, cosmetics, and functional food materials. Thus, their value as pharmaceutical and functional molecules has been increasing. Especially, growth factors and cytokine production It affects tissue binding and maturation of specific tissues, acts as a biological filter, controls collagen fiber synthesis, skin tensile strength, and also affects the growth and invasion of cancer cells.
이의 주원료로 사용되고 있는 소, 돼지, 닭 등의 축육은 광우병, 돼지 인플루엔자, 콜레라, 구제역, 조류독감 등의 여러 가지 질병으로 인해 원료로서의 안전성 확보가 어렵고, 상어연골과 껍질, 고래, 참치와 같은 다랑어류는 개체수의 감소로 인해 멸종 방지를 위한 여러 가지 국제적 협약들이 맺어져 있으며, 이로 인해 연간 생산량이 한정되어 있다. 이 같은 자원 확보의 어려움 때문에 새로운 대체자원이 필요한 실정이다.
It is difficult to secure safety as a raw material due to various diseases such as mad cow disease, swine influenza, cholera, foot-and-mouth disease and avian influenza, which are used as main ingredients of cattle, pigs and chickens. There are several international agreements to prevent extinction due to the declining population, which limits annual production. Because of the difficulty of securing such resources, new alternative resources are needed.
이에 본 발명자들은 신규 GAG 공급원으로 곤충을 선택하였으며, 곤충알콜추출잔사에서 프로테오글라이칸이 포함된 글라이코자미노글라이칸을 제조 후, 단백질부분을 N-Glycosidase F처리하고, 당 이외 불순물을 다공성탄소흑연 카트리지를 이용하여 귀뚜라미, 매미눈꽃동충하초, 강랑, 맹충, 광대노린재로부터 N-글라이칸(N-glycan)을 분리한 다음, MS 및 MS/MS를 통한 당 서열 및 구조를 규명함으로써, 본 발명을 완성하였다.
Therefore, the present inventors selected insects as a new GAG source, prepared glycopolaminoglycans containing proteoglycans from insect alcohol extract residues, treated the protein portion with N-glycosidase F, By separating N-glycan from crickets, cicadas caterpillars, caterpillars, caterpillars and caterpillars using carbon graphite cartridges, the sugar sequences and structures were identified by MS and MS / MS, .
본 발명의 목적은 하나 이상의 Hex 및/또는 HexGlcNAc로 구성된 특정 당쇄구조를 가지는 곤충 N-글라이칸(N-glycan)을 제공하는데 있다.It is an object of the present invention to provide an insect N-glycan having a specific sugar chain structure composed of at least one Hex and / or HexGlcNAc.
본 발명의 다른 목적은 상기 곤충 N-글라이칸(N-glycan)을 유효성분으로 함유하는 혈관신생 억제용 또는 혈관확장반응의 기능장애로 인한 질환 치료용 약학 조성물을 제공하는데 있다.Another object of the present invention is to provide a pharmaceutical composition for inhibiting angiogenesis or treating a disease caused by a dysfunction of vasodilation reaction, which comprises the insect N-glycan as an active ingredient.
본 발명의 다른 목적은 상기 곤충 N-글라이칸(N-glycan)을 유효성분으로 함유하는 기능성 식품을 제공하는데 있다.Another object of the present invention is to provide a functional food containing the insect N-glycan (N-glycan) as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 Hex9GlcNAc2 당쇄 (1905 m/z)구조를 가지는 귀뚜라미(Gryllus bimaculatus) 유래 곤충 N-글라이칸(N-glycan)을 제공한다.To achieve the above object, the present invention provides an insect N-glycan derived from Gryllus bimaculatus having a Hex9GlcNAc2 sugar chain (1905 m / z) structure.
본 발명은 또한 Hex7 (1175.5 m/z)의 당쇄 구조를 가지는 매미눈꽃동충하초(Isaria sinclairii) 유래 곤충 N-글라이칸(N-glycan)을 제공한다.The present invention also provides an insect N-glycan derived from Isaria sinclairii having a glycan structure of Hex7 (1175.5 m / z).
본 발명은 또한 Hex3HexNAc2dHex1 (1079.4 m/z)의 당쇄 구조를 가지는 맹충(Tabanus bivittatus) 유래 곤충 N-글라이칸(N-glycan)을 제공한다.The present invention also provides an insect N-glycan derived from Tabanus bivittatus having a sugar chain structure of Hex3HexNAc2dHex1 (1079.4 m / z).
본 발명은 또한 Hex7 (1175.5 m/z) 및 Hex9 (1499.5 m/z)의 당쇄 구조를 가지는 강랑(Catharsius molossus) 유래 곤충 N-글라이칸(N-glycan)을 제공한다.The present invention also provides insect N-glycans from Catharsius molossus having a glycan structure of Hex7 (1175.5 m / z) and Hex9 (1499.5 m / z).
본 발명은 또한 Hex8 (1337.5 m/z)의 당쇄 구조를 가지는 광대노린재(Poecilocoris lewisi) 유래 곤충 N-글라이칸(N-glycan)을 제공한다.The present invention also provides an insect N-glycan derived from Poecilocoris lewisi having a sugar chain structure of Hex8 (1337.5 m / z).
본 발명은 또한 상기 곤충 N-글라이칸(N-glycan)을 유효성분으로 함유하는 혈관신생 억제용 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition for inhibiting angiogenesis, which comprises the insect N-glycan (N-glycan) as an active ingredient.
본 발명은 또한 상기 곤충 N-글라이칸(N-glycan)을 유효성분으로 함유하는 혈관확장반응의 기능장애로 인한 질환치료용 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition for treating a disease caused by a dysfunction of vasodilation reaction containing the insect N-glycan (N-glycan) as an active ingredient.
본 발명은 또한 상기 곤충 N-글라이칸(N-glycan)을 유효성분으로 함유하는 기능성 식품을 제공한다.The present invention also provides a functional food containing the insect N-glycan (N-glycan) as an active ingredient.
본 발명은 또한 귀뚜라미(Gryllus bimaculatus), 매미눈꽃동충하초(Isaria sinclairii), 맹충(Tabanus bivittatus), 광대노린재(Poecilocoris lewisi) 또는 강랑(Catharsius molossus) 유래 곤충 N-글라이칸(N-glycans)을 포함하는 프로테오글라이칸 및 그 분획물을 제공한다.The present invention also relates to a method for the production of insecticidal compositions comprising insect N-glycans derived from crickets ( Gryllus bimaculatus ), Isaria sinclairii , Tabanus bivittatus , Poecilocoris lewisi or Catharsius molossus Proteoglycans and fractions thereof.
본 발명에 따른 하나 이상의 Hex 및/또는 HexGlcNAc로 구성된 특정 당쇄구조를 가지는 곤충 N-글라이칸(N-glycan) 및 이를 포함하는 글라이코자미노글라이칸 분획물은 생물학적 활성이 알려짐에 따라 의약품, 화장품 및 기능성식품 소재로 사용할 수 있어, 제약 및 기능성 분자로서의 가치를 가지며, 특히 혈관신생 억제능 또는 혈관확장반응의 기능장애에 의한 질환 치료효과가 있어, 다양한 곤충유래 N-글라이칸(N-glycan) 의약품 개발을 가능케함으로써, 곤충사육농가 소득 보전 및 국민보건향상에 기여할 수 있다.The insect N-glycan (N-glycan) having a specific sugar chain structure composed of one or more Hex and / or HexGlcNAc according to the present invention and the glycocamminoglycan fraction containing the same is known as a pharmaceutical, It can be used as a functional food material, has a valuable value as a pharmaceutical and functional molecule, and particularly has an effect of treating diseases caused by inhibition of angiogenesis or dysfunction of vasodilatation reaction, and development of various insect-derived N-glycan drugs , Contributing to the maintenance of insect rearing farmers' income and the improvement of public health.
도 1은 조(crude) 글라이코자미노글라이칸에 대해 이온교환크로마토그라피(Sephadex DEAE A-25) 크로마토그램 결과이다(A: 맹충; B: 강랑; C: 귀뚜라미; D: 광대노린재)
도 2는 정제된 글라이코자미노글라이칸의 순도를 확인하기 위한 SAX-HPLC 결과이다.
도 3은 곤충 N-글라이칸의 질량분석 측정치이다(A: 귀뚜라미(Gryllus bimaculatus); B:매미눈꽃동충하초(Isaria sinclairii, 0.1 M); C: 맹충(Tabanus bivittatus, 0.1 M); D:강랑(Catharsius molossus, 0.5 M)).
도 4는 귀뚜라미(Gryllus bimaculatus) N-글라이칸(N-glycan)의 MALDI-TOF MS/MS 크로마토그래피 결과(A) 및, Hex9GlcNAc2 당쇄 (1905 m/z) 구조(B)이다.
도 5는 매미눈꽃동충하초(Isaria sinclairii, 0.1 M) N-글라이칸(N-glycans)의 MALDI-TOF MS/MS 크로마토그래피 결과(A)에 의한 당쇄 구조 분석결과(B)이다.
도 6는 강랑(Catharsius molossus, 0.5 M) N-글라이칸(N-glycan)의 MALDI-TOF MS/MS 크로마토그래피 결과이다.
도 7는 맹충(Tabanus bivittatus, 0.1 M) N-글라이칸(N-glycan)의 MALDI-TOF MS/MS 크로마토그래피 결과(A)에 의한 당쇄 구조 분석결과(B)이다.
도 8는 강랑(Catharsius molossus, 0 M) N-글라이칸(N-glycan)의 당쇄 구조 분석결과이다(A: Hex9 (1499.5 m/z); B: Hex7 (1175.5 m/z)).
도 9은 광대노린재(Poecilocoris lewisi)의 N-글라이칸(N-glycan)의 당쇄 구조 분석결과이다.BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a chromatogram of ion-exchange chromatography (Sephadex DEAE A-25) for crude glycosaminoglycan (A: manganese chloride, B: rutile, C: cricket, D:
Fig. 2 shows SAX-HPLC results for confirming the purity of the purified glycosaminoglycan.
Figure 3 is a mass spectrometry measurement of insect N-glycans (A: Gryllus bimaculatus ; B: Isaria sinclairii , 0.1 M); C: Tabanus bivittatus (0.1 M); D: Catharsius molossus , 0.5 M).
4 is a MALDI-TOF MS / MS chromatographic result (A) of Gryllus bimaculatus N-glycan (N-glycan) and a Hex9GlcNAc2 sugar chain (1905 m / z) structure (B).
5 is a result (B) of the sugar chain structure analysis by the MALDI-TOF MS / MS chromatography (A) of Isaria sinclairii (0.1 M) N-glycans.
Figure 6 is a MALDI-TOF MS / MS chromatographic result of Catharsius molossus (0.5 M) N-glycan.
7 is a graph (B) of a sugar chain structure analysis by MALDI-TOF MS / MS chromatography (A) of Tabanus bivittatus (0.1 M) N-glycan.
8 is a result of analysis of the sugar chain structure of Catharsius molossus (0 M) N-glycan (A: Hex9 (1499.5 m / z); B: Hex7 (1175.5 m / z)).
FIG. 9 shows the result of analysis of sugar chain structure of N-glycan of Poecilocoris lewisi .
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
최근 N-글라이칸(N-glycan)의 여러 가지 생물학적 활성이 알려짐에 따라 의약품, 화장품 및 기능성식품 소재로 사용할 수 있어, 제약 및 기능성 분자로서의 가치를 가지며, 공급원 확보의 어려움 때문에 원료로 사용할 수 있는 새로운 대체자원이 필요한 실정이다. 이에 본 발명자들은 신규 GAG 공급원으로 곤충을 선택하였으며, 이로부터 정제된 GAG의 N-글라이칸(N-glycan) 당서열을 규명함으로써, 본 발명을 완성하였다.
Recently, since various biological activities of N-glycan are known, they can be used as medicines, cosmetics, and functional food materials. Therefore, they are valuable as pharmaceutical and functional molecules. New alternative resources are needed. Thus, the present inventors have selected insects as a novel GAG source and identified the sequences per N-glycan of purified GAG, thereby completing the present invention.
본 발명은 일 관점에서, Hex9GlcNAc2 당쇄 (1905 m/z)구조를 가지는 귀뚜라미(Gryllus bimaculatus) 유래 곤충 N-글라이칸(N-glycan)에 관한 것이다. In one aspect, the present invention relates to an insect N-glycan derived from Gryllus bimaculatus having a Hex9GlcNAc2 sugar chain (1905 m / z) structure.
본 발명에서 있어서, 상기 귀뚜라미(Gryllus bimaculatus) 유래 곤충 N-글라이칸(N-glycans)의 구조는 Hex 및 GlcNAc로 구성되며, 보다 상세하게는 Hex9GlcNAc2 (1905 m/z)의 당쇄 구조를 특징으로 하고, 구체적으로 도 4B의 구조를 가지며, 상기 당쇄를 포함하는 분획물에는 Hex6, Hex5GlcNAc2, Hex6GlcNAc2, Hex7GlcNAc2, Hex8GlcNAc2, 및 Hex10GlcNAc2 당쇄 구조를 가지는 N-글라이칸(N-glycan)이 혼합된 특징이 있다.In the present invention, the structure of the insect N-glycans derived from the cricket ( Gryllus bimaculatus ) is composed of Hex and GlcNAc, more specifically, a glycan structure of Hex9GlcNAc2 (1905 m / z) Specifically, the fraction having the structure of FIG. 4B is characterized in that N-glycans having Hex6, Hex5GlcNAc2, Hex6GlcNAc2, Hex7GlcNAc2, Hex8GlcNAc2, and Hex10GlcNAc2 glycans are mixed in the fractions containing the sugar chain.
본 발명에 있어서, 상기 귀뚜라미(Gryllus bimaculatus) 유래 곤충 글라이코자미노글라이칸으로 부터 N-글라이칸(N-glycan)을 정제하는데 있어서, 이온교환크로마토그라피(ion exchange chromatography) 과정에서 용출 시 사용되는 염화나트륨의 농도는 0 M인 것을 특징으로 한다.In the present invention, when purifying N-glycan from insect glycocalinoglycan derived from Gryllus bimaculatus , it is used in the elution in the ion exchange chromatography process And the concentration of sodium chloride is 0 M.
따라서, 본 발명은 다른 관점에서, Hex6, Hex5GlcNAc2, Hex6GlcNAc2, Hex7GlcNAc2, Hex8GlcNAc2, Hex10GlcNAc2 및 Hex9GlcNAc2 (1905 m/z)의 N-글라이칸(N-glycan) 당쇄 구조를 가지는 귀뚜라미(Gryllus bimaculatus) 유래 곤충 글라이코자미노글라이칸을 포함하는 0 M 분획물에 관한 것이다(도 3A).
Accordingly, the present invention provides, in a different aspect, an insect derived from a Gryllus bimaculatus having an N-glycan sugar chain structure of Hex6, Hex5GlcNAc2, Hex6GlcNAc2, Hex7GlcNAc2, Hex8GlcNAc2, Hex10GlcNAc2 and Hex9GlcNAc2 (1905 m / RTI ID = 0.0 > 0 M < / RTI > fraction comprising lycozaminoglycan (Figure 3A).
본 발명은 다른 관점에서, Hex7 (1175.5 m/z) 당쇄 구조를 가지는 매미눈꽃동충하초(Isaria sinclairii) 유래 N-글라이칸(N-glycan)에 관한 것이다. In another aspect, the present invention relates to N-glycan derived from Isaria sinclairii having a Hex7 (1175.5 m / z) sugar chain structure.
본 발명에 있어서, 상기 매미눈꽃동충하초(Isaria sinclairii) 유래 N-글라이칸은 도 5B에 나타난 바와 같이, Hex로 구성된 선형 구조를 가지는 특징이 있으며, 상기 당쇄를 포함하는 분획물에는 Hex8 (1337.5 m/z), Hex9 (1499.6 m/z), Hex10 (1681.7 m/z), 및 Hex11 (1823.7 m/z) 당쇄 구조를 가지는 N-글라이칸(N-glycan)이 혼합되어 있다.In the present invention, the N- glycan derived from Isaria sinclairii has a linear structure composed of Hex as shown in FIG. 5B, and the fractions containing the sugar chain have Hex8 (1337.5 m / z ), Hex 9 (1499.6 m / z), Hex 10 (1681.7 m / z), and Hex 11 (1823.7 m / z) glycans.
또한 상기 매미눈꽃동충하초(Isaria sinclairii) 유래 곤충 글라이코자미노글라이칸으로부터 N-글라이칸((N-glycans)을 정제하는데 있어서, 이온교환크로마토그라피(ion exchange chromatography) 과정에서 용출 시 사용되는 염화나트륨의 농도는 0.1 M인 것을 특징으로 한다.In addition, in the purification of N-glycans from the insect glycosaminoglycan derived from Isaria sinclairii , the amount of sodium chloride used in the elution in the ion exchange chromatography process And the concentration is 0.1 M.
따라서, 본 발명은 다른 관점에서, Hex7 (1175.5 m/z), Hex8 (1337.5 m/z), Hex9 (1499.6 m/z), Hex10 (1681.7 m/z), 및 Hex11 (1823.7 m/z) N-글라이칸(N-glycan) 당쇄 구조를 가지는 매미눈꽃동충하초(Isaria sinclairii) 유래 곤충 글라이코자미노글라이칸을 포함하는 0.1 M 분획물에 관한 것이다(도 3B).
Thus, the present invention provides, in a different aspect, Hex 7 (1175.5 m / z), Hex 8 (1337.5 m / z), Hex 9 (1499.6 m / z), Hex 10 (1681.7 m / z) The present invention relates to a 0.1 M fraction comprising an insect glycosaminoglycan derived from Isaria sinclairii having an N-glycan sugar chain structure (Fig. 3B).
본 발명은 다른 관점에서, Hex3HexNAc2dHex1 (1079.4 m/z) 당쇄 구조를 가지는 맹충(Tabanus bivittatus) 유래 곤충 N-글라이칸(N-glycan) 에 관한 것이다. In another aspect, the present invention relates to insect N-glycans derived from Tabanus bivittatus having Hex3HexNAc2dHex1 (1079.4 m / z) sugar chain structure.
본 발명에 있어서, 상기 맹충(Tabanus bivittatus) 유래 곤충 글라이코자미노글라이칸 중 Hex3HexNAc2dHex1 (1079.4 m/z)은 도 7B에 나타난 바와 같이, Hex, HexNAc 및 dHex로 구성된 당쇄 구조를 가지는 특징이 있으며, 상기 당쇄를 포함하는 분획물에는 Hex3HexNAc2 (933.4 m/z), Hex3HexNAc2dHex1 (1079.4 m/z), Hex4HexNAc2 (1095.4 m/z), Hex3HexNAc3 (1136.5 m/z), Hex4HexNAc2dHex1 (1241.5 m/z), Hex3HexNAc3dHex1 (1282.5 m/z), 및 Hex3HexNAc4dHex1 (1485.5 m/z) 당쇄 구조의 N-글라이칸(N-glycan)이 혼합되어 있다.In the present invention, Hex3HexNAc2dHex1 (1079.4 m / z) in the insect glycosaminoglycan derived from Tabanus bivittatus is characterized by having a sugar chain structure composed of Hex, HexNAc and dHex as shown in FIG. 7B, Hex3HexNAc2dHex1 (1274.4 m / z), Hex4HexNAc2 (1095.4 m / z), Hex3HexNAc3 (1136.5 m / z), Hex4HexNAc2dHex1 (1241.5 m / z), Hex3HexNAc3dHex1 m / z), and Hex3HexNAc4dHex1 (1485.5 m / z) glycans having a sugar chain structure.
따라서, 본 발명은 다른 관점에서, Hex3HexNAc2 (933.4 m/z), Hex3HexNAc2dHex1 (1079.4 m/z), Hex4HexNAc2 (1095.4 m/z), Hex3HexNAc3 (1136.5 m/z), Hex4HexNAc2dHex1 (1241.5 m/z), Hex3HexNAc3dHex1 (1282.5 m/z), 및 Hex3HexNAc4dHex1 (1485.5 m/z) N-글라이칸(N-glycan) 당쇄 구조를 가지는 맹충(Tabanus bivittatus) 유래 곤충 글라이코자미노글라이칸을 포함하는 0.1 M 분획물에 관한 것이다(도 3C).
Thus, the present invention provides, in another aspect, a Hex3HexNAc2dHex1, Hex3HexNAc2dHex1 (1079.4 m / z), Hex4HexNAc2 (1095.4 m / z), Hex3HexNAc3 (1136.5 m / z) And a 0.1 M fraction comprising insect glycocalinoglycans derived from Tabanus bivittatus having an N-glycan sugar chain structure of Hex3HexNAc4dHex1 (1485.5 m / z) (Fig. 3C).
본 발명은 또 다른 관점에서, Hex3HexNAc3dHex1 (1282.5 m/z) 및 Hex8 (1337.5 m/z) N-글라이칸(N-glycan) 당쇄 구조를 가지는 강랑(Catharsius molossus) 유래 곤충 글라이코자미노글라이칸을 포함하는 0.5 M 분획물에 관한 것이다(도 3D). In another aspect, the present invention provides an insect glycosaminoglycan derived from Catharsius molossus having a Hex3HexNAc3dHex1 (1282.5 m / z) and Hex8 (1337.5 m / z) N-glycan glycan structure (Fig. 3D).
또한 강랑(Catharsius molossus) 유래 곤충 글라이코자미노글라이칸을 포함하는 0 M는 분획물 3K Da 미만 fraction에서 Hexose로 이루어진 glycan으로 m/z1175.5 Hex7, m/z 1499.5이 있다(도 6)
Also, 0 M, which contains the insect glycocalinoglycan derived from Catharsius molossus, is a glycan composed of hexose at fraction less than 3 K Da fraction, with m / z 1175.5 Hex 7 , m / z 1499.5 (Figure 6)
본 발명에서의 용어 '크로마토그래피(chromatography)'는 다공성 흡착제 입자를 충전시킨 일정한 길이의 관(column)에 용질이 들어 있는 혼합물을 통과시켜 흡착제 입자에 대한 용질의 흡착 특성의 차이를 근거하여 분리하는 방법이다. 크로마토그래피 공정은 이동상(mobile phase) 및 고정상(stationary phase)로 이루지면, 고정상은 흡착제, 이온교환수지, 다공성 물질 또는 겔을 사용할 수 있다. 다성분 혼합시료의 분리 분석에 유용한 액체 크로마토그래피는 고압액체 크로마토그래피(high-pressure liquid chromatography), 이온교환 크로마토그래피(ion-exchange chromatography) 및 친화성 크로마토그래피(affinity chromatography)로 대표적으로 분류될 수 있으며, 본 발명에서는 이온 또는 전기적으로 전화를 띠는 화합물, 즉 곤충의 글리칸(N-glycan)의 극성이 크다는 점을 이용하여, 전기적 힘에 의하여 충진제와의 흡착원리를 이용한 이온교환 크로마토그래피(ion-exchange chromatography)를 이용하는 것이 바람직하다.The term " chromatography " in the present invention refers to a method of separating the adsorbent particles based on the difference in adsorption characteristics of the solute to the adsorbent particles by passing a mixture containing a solute in a column of a predetermined length packed with the porous adsorbent particles Method. If the chromatographic process consists of a mobile phase and a stationary phase, the stationary phase can use an adsorbent, an ion exchange resin, a porous material or a gel. Liquid chromatography, which is useful for the separation analysis of multi-component mixed samples, can be typified by high-pressure liquid chromatography, ion-exchange chromatography and affinity chromatography. In the present invention, ion-exchange chromatography (ion-exchange chromatography) using an adsorption principle with a filler by means of an electric force is carried out by taking advantage of the fact that the polarity of an ion or an electrically- ion-exchange chromatography.
본 발명에서의 용어 '용출'은 '용리(elution)과 혼용될 수 있으며,이온교환 크로마토그래피(ion-exchange chromatography)에 사용된 이온교환수지에 결합된 글리칸(N-glycan)의 극성이 서로 다르다는 점을 활용하여 염 구배에 의하여 염 농도를 달리한 버퍼를 사용하여 산성당(uronic acid) 함량이 높은 분획물을 수득하는 과정이다.The term " elution " in the present invention can be used in combination with 'elution, and the polarity of the N-glycan bonded to the ion exchange resin used in ion-exchange chromatography And a fraction having a high uronic acid content is obtained by using a buffer having a different salt concentration by a salt gradient taking advantage of the difference.
본 발명에서, 각 곤충 N-글라이칸(N-glycans)을 수득하기 위하여 염화나트륨을 사용한 염 구배 용출을 수행하며, 각 곤충별 산성당(uronic acid) 함량이 높은 분획을 선택하여, 이의 당쇄 구조를 규명하였다.
In the present invention, a salt gradient elution using sodium chloride is carried out to obtain each insect N-glycans, and a fraction having a high uronic acid content for each insect is selected, Respectively.
본 발명은 또 다른 관점에서, Hex7 (1175.5 m/z) 또는 Hex9 (1499.5 m/z) 당쇄 구조를 가지는 강랑(Catharsius molossus) 유래 곤충 N-글라이칸(N-glycans)에 관한 것이다. In another aspect, the present invention relates to insect N-glycans derived from Catharsius molossus having a Hex7 (1175.5 m / z) or Hex9 (1499.5 m / z) glycan structure.
상기 각각의 강랑 유래 N-글라이칸(N-glycans)은 구체적으로 도 8B 및 도 8A에 나타난 바와 같이, Hex로 구성된 선형구조를 가진다.
Each of the tribologically-derived N-glycans has a linear structure composed of Hex, specifically as shown in Figs. 8B and 8A.
본 발명은 또 다른 관점에서, Hex8 (1337.5 m/z) 당쇄 구조를 가지는 광대노린재(Poecilocoris lewisi) 유래 곤충 N-글라이칸(N-glycan)에 관한 것이다.In another aspect, the present invention relates to an insect N-glycan derived from Poecilocoris lewisi having a Hex8 (1337.5 m / z) sugar chain structure.
상기 N-글라이칸(N-glycan)은 구체적으로 도 9에 나타난 바와 같이, Hex로 구성된 선형구조를 가진다.
The N-glycan specifically has a linear structure composed of Hex as shown in FIG.
본 발명에 따른 곤충 N-글라이칸(N-glycan)은 (a) 곤충에 아세톤, 헥산, 에틸아세테이트, 메틸알콜, 에틸알콜, 프로판올, 부탄올, 아세토니트릴, 클로로포름 및 디클로로메탄으로 이루어진 군에서 선택된 하나 이상의 유기용매에 1 내지 4일간 침지하여 지방류를 제거하고, (b) 이로부터 단백질을 제거한 다음, (c) 침전과 투석과정을 통해 산성당이 포함된 N-글라이칸(N-glycan) 분획을 수집하여, (d) 이온교환크로마토그라피(ion exchange chromatography) 과정에서의 염화 나트륨을 이용한 염구배 용출과정을 통해, 정제되는 것을 특징으로 한다.The insect N-glycan according to the present invention can be prepared by a method comprising the steps of: (a) adding insect N-glycan to insects by adding an insecticide selected from the group consisting of acetone, hexane, ethyl acetate, methyl alcohol, ethyl alcohol, propanol, butanol, acetonitrile, chloroform and dichloromethane (B) removing the protein from the solution, (c) separating the N-glycan fraction containing the acid group by precipitation and dialysis, And (d) is purified through a salt gradient elution process using sodium chloride in the course of ion exchange chromatography.
상기 (b) 단계에서의 단백질 제거는 바실러스 유래(Bacillus licheniformis 등) 단백분해효소인 알카라제, Aspergillus oryzae 유래 protease 등을 포함하는 단백분해제를 사용하여 수행할 수 있으며, 이 때 단백분해에 필요한 소요 시간은 3~7일로, 실온 이상에서 단백질 분해를 촉진할 수 있고, 44℃ 가온시 반응을 촉진할 수 있다. 상기 단백분해제를 2 ~ 5중량% 사용함으로써, 곤충 껍질의 단백질을 효과적으로 제거할 수 있다. The protein removal in step (b) can be carried out using a proteolytic cleavage method including a protease derived from Bacillus licheniformis , protease such as alkaline protease, Aspergillus oryzae , etc. In this case, The required time is 3 to 7 days. It can accelerate protein decomposition at room temperature or higher, and can accelerate reaction at 44 ℃. By using 2 to 5% by weight of the protein disintegration, protein of the insect bark can be effectively removed.
본 발명에 있어서, 상기 이온교환크로마토그라피(ion exchange chromatography)는 Sephadex DEAE A-25를 충전제로 사용하며, 이에 한정된 것은 아니다.
In the present invention, the ion exchange chromatography uses Sephadex DEAE A-25 as a filler, but is not limited thereto.
본 발명은 또 다른 관점에서, 상기 곤충 N-글라이칸(N-glycan) 또는 이를 포함하는 분획물을 유효성분으로 함유하는 혈관신생 억제용 약학 조성물에 관한 것이다. In another aspect, the present invention relates to a pharmaceutical composition for inhibiting angiogenesis containing the insect N-glycan or a fraction containing the insect N-glycan as an active ingredient.
상기 혈관신생에 의해 매개되는 질환은 종양, 암전이, 혈관종, 혈관섬유종, 관절염, 당뇨병성 망막증, 조숙아의 망막증, 신생혈관성 녹내장, 신생혈관에 의한 각막질환, 퇴화반, 반점의 변성, 익상편, 망막변성, 후수정체 섬유증식증, 과립성 결막염, 건선, 모세관 확장증, 화농성 육아종, 지루성 피부염, 또는 여드름일 수 있으며, 이에 한정된 것은 아니다. 본 발명의 약학 조성물은 상기 혈관신생을 억제함으로써, 치료효과를 기대할 수 있다.The disease mediated by the angiogenesis may be selected from the group consisting of tumor, metastasis, angioma, angiofibroma, arthritis, diabetic retinopathy, retinopathy of prematurity, neovascular glaucoma, corneal disease caused by neovascularization, degeneration, But are not limited to, degenerative, posterior capsular hyperplasia, granulomatous conjunctivitis, psoriasis, capillary dilatation, pyogenic granuloma, seborrheic dermatitis, or acne. The pharmaceutical composition of the present invention can be expected to have a therapeutic effect by inhibiting angiogenesis.
본 발명은 또 다른 관점에서, 상기 곤충 N-글라이칸(N-glycan) 또는 이를 포함하는 분획물을 유효성분으로 함유하는 혈관확장반응의 기능장애로 인한 질환치료용 약학 조성물에 관한 것이다. In another aspect, the present invention relates to a pharmaceutical composition for treating a disease caused by a dysfunction of vasodilation reaction containing the insect N-glycan or a fraction containing the insect N-glycan as an active ingredient.
본 발명에 있어서, 상기 혈관확장반응의 기능장애로 인한 질환은 고혈압, 뇌졸중, 뇌출혈, 허혈성 심질환 또는 레이노병일 수 있으며, 이에 한정된 것은 아니다. In the present invention, the disease caused by the functional disorder of the vasodilation reaction may be hypertension, stroke, cerebral hemorrhage, ischemic heart disease, or Raynaud's disease, but is not limited thereto.
본 발명에 있어서, 상기 곤충 N-글라이칸(N-glycan) 또는 이의 분획물을 유효성분으로 함유하는 약학 조성물은 상기 질환 외에도 소염, 항당뇨, 항응혈 등에 효과를 나타낼 수 있다.
In the present invention, the pharmaceutical composition containing the insect N-glycan or its fractions as an active ingredient may exhibit effects such as anti-inflammation, anti-diabetic, anticoagulant and the like in addition to the above-mentioned diseases.
본 발명에 있어서, 상기 약학 조성물의 유효성분인 곤충 N-글라이칸(N-glycan) 또는 이의 분획물은 귀뚜라미(Gryllus bimaculatus), 매미눈꽃동충하초(Isaria sinclairii), 강랑(Catharsius molossus), 맹충(Tabanus bivittatus), 또는 광대노린재(Poecilocoris lewisi) 유래인 것을 특징으로 하며, 단독 또는 혼합의 조성으로 구성될 수 있다.In the present invention, the insect N-glycan or its fractions, which is an active ingredient of the above pharmaceutical composition, can be used as an effective ingredient for preventing and treating insects such as Gryllus bimaculatus , Isaria sinclairii , Catharsius molossus , Tabanus bivittatus ) Or Poecilocoris lewisi , and may be composed of a single composition or a mixture.
본 발명의 약학 조성물은 상기 곤충 유래 N-글라이칸(N-glycan) 또는 이의 분획물에 대해 추가로 호박벌(Bombus ignitus) 여왕벌 또는 서양뒤영벌(Bombus terrestris) 여왕벌 유래의 N-글라이칸(N-glycan) 또는 이를 포함하는 글라이코자미노글라이칸을 포함할 수 있다.The pharmaceutical composition of the present invention further comprises N-glycan derived from Bombus ignitus queen bee or Bombus terrestris queen bee for the insect-derived N-glycan or its fractions, Or a glycosaminoglycan comprising the same.
본 발명은 또 다른 관점에서, 상기 곤충 N-글라이칸(N-glycan) 또는 이의 분획물을 유효성분으로 함유하는 기능성 식품에 관한 것이다. In another aspect, the present invention relates to a functional food containing the insect N-glycan or a fraction thereof as an active ingredient.
본 발명은 또 다른 관점에서, 상기 곤충 N-글라이칸(N-glycan) 또는 이를 포함하는 분획물을 유효성분으로 함유하는 화장품용 조성물에 관한 것이다.
In another aspect, the present invention relates to a cosmetic composition containing the insect N-glycan or a fraction containing the insect N-glycan as an active ingredient.
본 발명에 있어서, 발명에서 ‘쇠똥구리’는 Catharsius 계열 즉 Catharsius molossus 및 애기뿔쇠똥구리 등 Copris 계열을 포함한다(생약명 강랑의 정의에 준함, 곤충류 약물도감, 최정, 안미영등, 도서출판 신일). In the present invention, the "dung beetle" comprises Catharsius sequence that is Catharsius molossus and Arabidopsis horn dung beetle such Copris series in the invention (according to the definition of saengyakmyeong gangrang, insects Drug Encyclopedia, Choi, Jung, anmiyoung etc., published by Shinil).
본 발명에 있어서, '귀뚜라미'는 약용곤충으로 솔슬(곤충류 약물도감, 최정, 안미영들, 도서출판 신일)로 불리는 곤충, Gryllus bimaculatus(아열대산 귀뚜라미), Teleogryllus emme (국내산 귀뚜라미) 등을 포함한다.In the present invention, 'cricket' is a medicinal insect and includes insects called insects (insect drug guide, Choi Jeong, An Mi-yong, Shin-il Publishing Co.), Gryllus bimaculatus (subtropical crickets) and Teleogryllus emme (domestic crickets).
또한, 본 발명에 있어서, '쇠등에(소등에)'는 생약명으로 맹충(Tabanus, 곤충류약물도감, 신일출판, 최정, 안미영 등)에 준하는 등에(Tabanus bivittatus)를 포함하며, 분류학적으로 등에과(Family Tabanidae)인 것을 특징으로 한다.In the present invention, and as is saengyakmyeong (on off) of iron or the like, including maengchung (Tabanus bivittatus) or the like, pursuant to (Tabanus, insects Drug Encyclopedia, Shinil Publishing, Choi, Jung, anmiyoung etc.), deungegwa taxonomically ( Family Tabanidae ).
상기 쇠똥구리는 생약명으로 강랑이며, 상기 강랑은 쇠똥구리를 수세하여 건조시킨 것이고, 상기 쇠등에는 생약명 맹충으로, 상기 맹충은 쇠등에를 수세하여 건조시킨 것이다.
The dung beetle is a dung beetle with a generic name, the dung beetle is washed with water and dried, and the dung beetle is washed with water, and the bumblebees are washed with water.
본 발명의 약학 조성물 또는 기능성 식품은 투여를 위해서 유효성분 이외에 추가로 약학, 식품학적 및/또는 미용학적으로 허용되는 담체를 1종 이상 포함하여 제제화 할 수 있다.The pharmaceutical composition or the functional food of the present invention may be formulated to contain at least one pharmaceutical, foodstuff and / or cosmetically acceptable carrier in addition to the active ingredient for administration.
약학, 식품학적 및/또는 미용학적으로 허용되는 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 하나 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 용매, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제를 부가적으로 첨가할 수 있다. 더 나아가 당 분야의 적절한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화 할 수 있다.The pharmacy, foodstuff and / or cosmetically acceptable carrier may be a mixture of one or more of saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, , Other conventional additives such as an antioxidant, a buffer solution, a bacteriostatic agent and the like may be added. In addition, diluents, dispersants, surfactants, solvents, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, lubricants or flavors may additionally be added. Further, it can be suitably formulated according to each disease or ingredient, using methods disclosed in the art or by methods disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA.
본 발명의 약학 조성물은 제약상 적합한 부형제인 고상, 준고상 또는 액상희석제, 충전제 및 모든 유형의 제형보조물을 첨가하여 제제화 가능하며, 바람직한 제형으로는 정제, 피복정제, 캡슐제, 환제, 과립제, 좌약, 액제, 현탁액제 및 에멀전제, 페이스트제(pastes), 연고제, 겔제, 크림제, 로션제, 산제, 시럽, 즙, 점적제, 주사 가능한 액제, 서방출형 제제 및 분무제 등이 포함된다.The pharmaceutical compositions of the present invention can be formulated by the addition of pharmaceutically acceptable excipients, such as solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of any type, and preferred formulations include tablets, coated tablets, capsules, pills, granules, Suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, syrups, juices, drops, injectable solutions, sustained-release preparations and sprays.
정제, 피복 정제, 캡슐제, 환제 및 과립제는 통상의 부형제, 예를 들면 (a) 충진제 및 중량제(예: 전분, 락토스, 슈크로스, 글루코오스, 만니톨과 규산) (b) 결합제(예: 카르복시메틸 셀룰로오스, 알긴산염, 젤라틴 및 폴리비닐피롤리돈) (c) 흡습제(예: 글리세롤), (d) 붕해제(예: 한천, 탄산칼슘 및 탄산나트륨), (e) 용해지연제(예: 파라핀) (f) 흡수촉진제(예: 4급 암모늄 화합물), (g) 습윤제(예: 세틸알코올 및 글리세롤모노스테아레이트), (h) 흡착제(예:고령토 및 벤토나이트), 및, (i) 윤활제(예: 활석, 스테아르산 칼슘, 스테아르산 마그네슘, 마그네슘 스타레이트 탈크 및 고체 폴리에틸렌 글리콜), 또는 상기(a) 내지 (i)에서 기재한 물질의 혼합물 이외에 유효화합물 또는 화합물들을 함유할 수 있다. 정제, 캡슐제, 환제 및 과립제는 피막을 입힐 수 있으며, 장관 특정부위에 유효화합물만 방출시키도록 할 수 있으며, 필요한 경우 고분자 등을 사용하여 서방형으로 제제화할 수도 있고 미세캡슐화할 수도 있다.Tablets, coated tablets, capsules, pills and granules may contain conventional excipients such as (a) fillers and weighting agents such as starch, lactose, sucrose, glucose, mannitol and silicic acid; (b) binders (C) humectants such as glycerol, (d) disintegrants such as agar, calcium carbonate and sodium carbonate, (e) dissolution retardants such as paraffin, (g) wetting agents such as cetyl alcohol and glycerol monostearate; (h) adsorbents such as kaolin and bentonite; and (i) lubricants (for example, For example, talc, calcium stearate, magnesium stearate, magnesium stearate talc and solid polyethylene glycols), or a mixture of the substances described in (a) to (i) above. Tablets, capsules, pills, and granules can be coated to release the effective compound only at a specific site of the intestinal tract. If necessary, the composition can be formulated into a sustained release form using a polymer or the like, or microencapsulated.
비경구 투여를 위한 제제에는 주사제, 현탁제, 유제, 동결건조제, 좌제 등이 포함된다. 좌제는 유제화합물 이외에 통상의 수용성 또는 수불용성 부형제, 예를 들면 폴리에틸렌 글리콜, 카카오지방 등의 지방, 고급에스테르(예: C16-지방산을 갖는 C14-알코올), 위텝솔, 마크로골, 트윈61, 라우린지 및 글리세롤젤라틴 물질의 혼합물을 함유할 수 있다.Formulations for parenteral administration include injections, suspensions, emulsions, lyophilisers, suppositories, and the like. Suppositories may contain conventional water-soluble or water-insoluble excipients such as fats such as polyethylene glycol, cacao fat, higher esters (e.g., C14-alcohol with C16-fatty acid), witepsol, macrogol, Lt; RTI ID = 0.0 > gelatin < / RTI >
연고제, 페이스트제, 크림제 및 겔제는 유효화합물 이외 통상의 부형제, 락토오스, 활석, 규산, 수산화알루미늄, 규산칼슘 및 폴리아미드 분제, 또는 이들 물질들의 혼합물을 함유할 수 있다. 분무제로는 통상의 포사제, 예를 들면 클로로풀루오로히드로카본을 더 함유할 수 있으며, PEG-4000과 글리세린을 함유하는 비강 분무제로도 제제화할 수 있다.The ointments, pastes, creams and gels may contain conventional excipients other than the active compound, lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder, or a mixture of these materials. The spraying agent may further contain a conventional propellant, for example, chlorofluorohydrocarbons, and may be formulated into a nasal spray agent containing PEG-4000 and glycerin.
액제 및 에멀젼제는 유효 성분 이외에 통상의 부형제, 예를 들면 용매, 가용화제 및 유화제, 예를 들면, 물, 에칠알콜, 이소프로필 알코올, 에틸카보네이트, 에칠아세테이트, 벤질알코올, 벤질벤조에이트, 프로필렌글리콜, 1,3-부틸렌글리콜, 디메틸포롬아미드 오일, 특히 면실유, 낙화생유, 옥수수 배종유, 올리브유, 피마자유 및 참깨유, 글리세롤, 테티라히드로푸로푸릴 알코올, 포리에틸렌 글리콜 및 소르비탄의 지방산 에스테르, 또는 이들물질의 혼합물을 포함할 수 있다. 비경구 투여용 액제 및 에멀젼제는 혈액과 등장성인 멸균형태로 제제할 수 있다.The liquid agent and the emulsion agent may contain, in addition to the active ingredient, conventional excipients such as solvents, solubilizing agents and emulsifiers such as water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 1,3-butylene glycol, dimethylformamide oil, fatty acid esters of cottonseed oil, peanut oil, corn steep liquor, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycol and sorbitan , Or a mixture of these materials. The liquid preparation for parenteral administration and the emulsion preparation may be formulated in a sterile form which is isotonic with blood.
현탁제는 유효 화합물 이외에 통상의 부형제, 예를 들면 액상희석제(예: 물, 에틸알코올, 프로필렌글리콜, 폴리에틸렌 글리콜) 및 현탁제(예: 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 및/또는 소르비탄 에스테르), 미세결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 한천 및 트라가칸트, 에틸올레이트와 같은 주사 가능한 에스테르 또는 이들 물질의 혼합물을 함유할 수 있다.In addition to the active compound, the suspending agent may contain conventional excipients such as liquid diluents (e.g., water, ethyl alcohol, propylene glycol, polyethylene glycol) and suspending agents (such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and / Lactose esters), microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, injectable esters such as ethyl oleate, or mixtures of these materials.
상기 제형들은 또한 발색제, 방부제 및 냄새나 맛을 개선시키는 첨가제, 예를 들면 박하유 및 유칼리유 및 감미제(예: 사카린)를 함유할 수 있으며, 본 발명에 의한 화합물 이외에 다른 제약상의 유효한 화합물을 함유할 수 있다.The formulations may also contain coloring agents, preservatives and additives which improve the odor or taste, for example, peppermint oil and eucalyptus oil and sweeteners such as saccharin, and may contain other pharmaceutical active compounds other than the compounds according to the invention .
상기 제형은 공지된 방법, 예를 들면 유효성분을 부형제와 혼합하는 통상의 방식으로 제조된다. 유효성분은 상기 제형에 있어서 전체 혼합물의 약 0.1 내지 99.5 중량%, 바람직하게는 0.5 내지 95 중량%의 양으로 함유된다.The formulations are prepared in a conventional manner, for example by mixing the active ingredient with excipients. The active ingredient is contained in the formulation in an amount of about 0.1 to 99.5% by weight, preferably 0.5 to 95% by weight of the total mixture.
본 발명에 있어서, 곤충 N-글라이칸(N-glycan) 또는 이를 포함하는 분획물을 포함하는 약학 조성물은 목적에 따라 정맥내, 동맥내, 복강내, 근육내, 흉골내, 경피, 비측내, 흡입, 국소, 직장, 경구, 안구내 또는 피내 경로 등을 통해 통상적인 방식으로 투여할 수 있다.In the present invention, the pharmaceutical composition comprising insect N-glycan or a fraction containing the insect N-glycan may be administered intravenously, intraarterially, intraperitoneally, intramuscularly, intrasternally, percutaneously, , Topically, rectally, orally, intra-ocularly or intradermally, and the like.
본 발명에 있어서, 각각의 곤충 N-글라이칸(N-glycan) 및 이를 포함하는 분획물의 약학 조성물은 유효성분 양을 기준으로 투여량은 체중 60 kg 성인기준으로 1일 0.1 mg/kg ~ 900 mg/kg의 범위 내에서 조절할 수 있다. 다만, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 질환의 종류, 질환의 중증도, 약학 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로, 치료기간, 및 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다.
In the present invention, the pharmaceutical composition of each insect N-glycan (N-glycan) and fractions containing the same is administered in an amount of 0.1 mg / kg to 900 mg per day / kg. < / RTI > However, the optimal dose to be administered can be easily determined by a person skilled in the art, and can be easily determined by a person skilled in the art and depends on the kind of the disease, the severity of the disease, the content of the active ingredient and other ingredients contained in the pharmaceutical composition, Health condition, sex and diet, time of administration, route of administration, duration of treatment, and concurrent medication.
본 발명의 기능성 식품의 제형은 통상의 방법에 따라 제조하며, 담체와 함께 건조한 후 캡슐화하거나 기타 정제, 과립, 분말, 음료, 죽 등의 형태로 제형화할 수 있으며, 상기 기재한 것 외에도 모든 식품 형태로 제조가능하다The formulations of the functional food of the present invention may be prepared by conventional methods and may be formulated into capsules or other tablets, granules, powders, beverages, pills, etc. after drying with the carrier, Can be manufactured by
본 발명의 화장품 조성물의 제형은 통상의 방법에 따라 제조하며, 적당한 담체를 이용하여 로션제, 크림제 등의형태로 제형화 할 수 있으며, 상기 기재한 것 외에도 모든 화장품 형태로 제조 가능하다.The formulation of the cosmetic composition of the present invention is prepared according to a conventional method, and can be formulated into a form such as lotion, cream, etc. using a suitable carrier.
본 발명은 하기의 실시예에 의하여 더욱 구체적으로 설명한다. 그러나, 하기 실시예는 본 발명의 이해를 돕기 위한 것일 뿐, 어떤 의미로든 본 발명의 범위가 이러한 실시예에 의하여 한정되는 것은 아니다. The present invention will be described in more detail with reference to the following examples. However, the following examples are provided to aid understanding of the present invention, and the scope of the present invention is not limited by these examples in any sense.
이 때, 사용되는 기술 용어 및 과학 용어에 있어서 다른 정의가 없다면, 이 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 통상적으로 이해하고 있는 의미를 가지며, 하기의 설명 및 첨부 도면에서 본 발명의 요지를 불필요하게 흐릴 수 있는 공지기능 및 구성에 대한 설명은 생략한다.
In this case, unless otherwise defined, technical terms and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the following description and the accompanying drawings, A description of known functions and configurations that may unnecessarily obscure the description of the present invention will be omitted.
[[ 실시예Example 1] 곤충 글라이코자미노글라이칸의 제조 1] Production of Insect Glycosaminoglycan
1. 조(crude) 글라이코자미노글리칸의 제조1. Preparation of crude glycosaminoglycan
① 강랑(쇠똥구리)(중국 연길 구입), ② 귀뚜라미(충북 음성 사육농가에서 구입), 및 ③ 매미눈꽃동충하초, ④ 맹충(쇠등에), 및 ⑤ 광대노린재를 포함하는 3종의 곤충(농촌진흥청 국립농업과학원에서 입수함)을 각각 ① 1.3 kg, ② 2 Kg, ③ 2.5kg, ④ 2 kg, ⑤100 g을 마쇄 후 동량 이상의 부피의 에탄올 또는 아세톤에 3일간 침지하여 지방류를 제거한 다음, 여과하여 걸러지지 않는 잔사(곤충껍질 등)를 건조시켰다. 건조된 잔사를 분쇄기(ball mill 또는 hammer mill)로 분쇄(100~300메쉬)하고, 바실루스 유래(bacillus lichenformis)의 시그마 알카라제(pH 9.0)를 2.5% 중량으로 첨가하여 44℃에서 4일간 효소처리로 단백질을 분해시켰다.(3) insects, including caterpillars (purchased from China Yanji), (2) crickets purchased from a farm owned by the Chungcheongbuk-do farmers, and (3) cicadidae, caterpillars, and caterpillars (Obtained from the National Institute of Agricultural Science and Technology), respectively, were ground for 3 days in ethanol or acetone having a volume equal to or more than the same amount, followed by filtration and filtration. Residues (such as insect bark) that did not survive were dried. The dried residue was pulverized (100 to 300 mesh) with a ball mill or a hammer mill, added with 2.5% by weight of Sigma Alkalase (pH 9.0) derived from bacillus lichenformis , The protein was degraded by treatment.
냉장보관한 50% 트리클로로아세트산 (Trichloroacetic acid)을 5%되도록 상기 효소처리액에 첨가하여 4℃에서 3시간 동안 방치하여 단백질을 침전시킨 다음 원심분리(8000 rpm)방법으로 수득된 잔사 부피에 대해 2배의 에탄올(100%)과 potassium acetate로 당을 공침시키고, 다시 침전물을 배량의 cetylpyridinium(5 중량%)에 침전시킨 후, 다시 침전물을 2 배량의 에탄올에 침전시킨 후, 증류수로 분자 량3500 이상의 투석막을 사용하여 투석하고, 동결건조하여 각각 ① 1.1g, ②3.4g, ③ 3,9g, ④0.617g, ⑤ 0.27g의 곤충 유래 조(crude) 글라이코자미노글라이칸을 수득하였다.
50% trichloroacetic acid was added to the enzyme-treated solution so that 5% of the solution was stored at 4 ° C for 3 hours to precipitate the proteins, followed by centrifugation (8000 rpm) After the precipitate was precipitated into cetylpyridinium (5% by weight), the precipitate was again precipitated in two times of ethanol, and the molecular weight was 3500 Dialyzed using the above dialysis membrane, and lyophilized to obtain 1.1 g, 3.4 g, 3.9 g, 4.617 g, and 0.27 g insect origin crude glycosaminoglycan, respectively.
2. 곤충 N-글라이칸(N-glycan) 분획의 제조2. Preparation of insect N-glycan fractions
상기 과정을 반복하여 추출된 조(crude) 글라이코자미노글라이칸에 대해 이온교환크로마토그라피(Sephadex DEAE A-25)를 사용하여 염 경사(salt gradient; 0, 0.1, 0.5, 1, 2.5 M NaCl in phosphate buffer)로 정제하였으며, 산성당(Uronic acid)을 가지는 분획물을 수집한 후, 분자량 3500 cutoff 투석 막(dialysis)을 사용 염분을 제거한 후 동결건조후 곤충 글라이코자미노글라이칸의 당쇄 분석 대상으로 선택하였다(도 1). The crude glycosaminoglycan extracted was repeatedly subjected to the above procedure and then subjected to salt gradient (0, 0.1, 0.5, 1, 2.5 M NaCl) using ion exchange chromatography (Sephadex DEAE A-25) in phosphate buffer, and fractions having Uronic acid were collected and then subjected to a molecular weight of 3500 cutoff dialysis to remove salt. After lyophilization, the glycoconjugate of the insect glycosaminoglycan was analyzed (Fig. 1).
순도확인은 글라이칸 분해효소(헤파리나제I,II,III, 콘드로이친 ABCase) 처리 후 저분자하여 SAX(강이온교환, 페노멕스, 250x 10 mm)-HPLC, 232 nm를 실시하여 단일 Peak가 검출되는지를 확인함으로써 순도를 확인하였다(도 2). 이 때 도 2는 SAX-HPLC 결과(귀뚜라미 글라이코자미노글라이칸 최종 저분자 SAX-HPLC 크로마토그램)로서, 곤충의 글라이코자미노글라이칸은 주요 SAX-HPLC peak가 하나로 존재한다.The purity was confirmed by a single molecule of SAX (strong ion exchange, phenomex, 250 x 10 mm) -HPLC, 232 nm after treatment with glycansolytic enzyme (heparinase I, II, III, chondroitin ABCase) To confirm the purity (Fig. 2). At this time, FIG. 2 shows the result of SAX-HPLC (cricket glycocalinoglycan final low-molecular SAX-HPLC chromatogram), and insect glycosaminoglycan has one main SAX-HPLC peak.
[실시예 2] 곤충 N-글라이칸(N-glycan)의 당서열 분석[Example 2] Saccharification of insect N-glycan (N-glycan)
1. 곤충 N-글라이칸(N-glycan) 농축1. Insect N-glycan enrichment
곤충엑기스 추출 후 조추출물로부터 분리한 프로테오글라이칸으로부터 N-글라이칸(N-glycan)만을 방출시켜, 이들의 당서열을 분석하기 위하여 다음의 과정을 수행하였다.After extracting insect extract, only N-glycan was released from the proteoglycans isolated from the crude extract, and the following procedure was performed to analyze their sugar sequences.
상기 프로테오글리칸에 denaturing 버퍼를 혼합하여 100℃ 10분간 끓여 단백질부분을 불활성화하고 2 ㎕ N-glycosidase F(1000 U, 제조사, 국가)를 사용하여 37℃에서 20시간동안 처리하여 당과 단백질을 연결이 절단되도록 하여, 단백질 부분을 제거한 다음, 최종적으로 수득된 N-글라이칸(N-glycan)을 진공건조하여 보관하였다.The denaturation buffer was added to the proteoglycans, and the protein fractions were inactivated by boiling at 100 ° C for 10 minutes. The protein fractions were inactivated by treatment with 2 μl of N-glycosidase F (1000 U, manufacturer, National) at 37 ° C. for 20 hours, The protein portion was removed, and the finally obtained N-glycan was vacuum-dried and stored.
N-글라이칸(N-glycan)을 분리하기 위하여, 다공성탄소흑연 카트리지(porous carbon graphite cartridge, PGC(제품명; Extract-clean columns carbograph, 제조사 ; Grace)를 80% acetonitirle/0.1% trifluoroacetic acid(v/v) 혼합 용액으로 세척한 후, 초순수로 조건을 맞추고, 상기 N-글라이칸(N-glycan)을 상기 카트리지에 로딩하고, 10분 동안 대기한 다음, 4 mL의 초순수로 세척하고 염과 완충액을 제거하였다. To separate N-glycan, a porous carbon graphite cartridge (PGC, product name: Extract-clean columns carbograph, manufactured by Grace) was dissolved in 80% acetonitrile / 0.1% trifluoroacetic acid (v / v) mixed solution, the conditions were set with ultrapure water, the N-glycan was loaded onto the cartridge, and the cartridge was allowed to stand for 10 minutes, then washed with 4 mL of ultrapure water, Respectively.
그 후, 40% acetonitirle/0.05% trifluoroacetic acid를 사용하여 용출한 후, 과메칠레이션(permethylation)시키고, 진공 건조 후 50% acetonitrile 10 ㎕에 10 mg/ml의 농도로 혼합된 2,5-dihydroxybenzoic acid(DHB) 함유 용액에 용해시킨 다음 Matrix assisted laser ionization(MALDI) Time of flight(TOF) analyzer(AXIMA Resonance, Shimadzu), positive polarity를 실시하였으며, 상기 MALDI-TOF의 분석 조건은 표 1에 나타난 바와 같다.After elution with 40% acetonitrile / 0.05% trifluoroacetic acid, the mixture was allowed to undergo over-methylation, vacuum-dried, and then added to 10 μl of 50% acetonitrile at a concentration of 10 mg / ml to obtain 2,5-dihydroxybenzoic acid (TOF) analyzer (AXIMA Resonance, Shimadzu) and positive polarity. The analysis conditions of the MALDI-TOF were as shown in Table 1 .
그 결과, 표 2에 나타난 바와 같이, MS로 분자량 패턴을 확인한 후, MS/MS를 실시하고 이로부터 수득된 데이터에 대해 glycan data base library program을 실시하여 당서열 분석을 확인하였으며, 이를 근거로 각 곤충으로부터의 N-글라이칸(N-glycan) 당서열 및 구조를 동정하였다(표 2, 도 3 ~ 8).
As a result, as shown in Table 2, the MS / MS was performed after confirming the molecular weight pattern by MS, and the glycan data base library program was performed on the data obtained therefrom to confirm the sequence analysis. The sequence and structure of N-glycan (N-glycan) from insects were identified (Table 2, Figs. 3 to 8).
동충하초cicada
Cordyceps
Hex8 Hex 3 HexNAc 3 dHex 1,
Hex 8
m/z1282.5, Hex3HexNAc3dHex1,
m/z1485.5, Hex3HexNAc4dHex1
진한글시는 major peakm / z 933.4, Hex 3 HexNAc 2 , m / z 1079.4, Hex 3 HexNAc 2 dHex 1 , m / z 1095.4, Hex 4 HexNAc 2 , m / z 1136.5, Hex 3 HexNAc 3 , m / 5, Hex 4 HexNAc 2 dHex 1 ,
m / z 1282.5, Hex 3 HexNAc 3 dHex 1 ,
m / z 1485.5, Hex 3 HexNAc 4 dHex 1
The major peak
m/z1282.5, Hex3HexNAc3dHex1,
m/z1485.5, Hex3HexNAc4dHex1 m / z 933.4, Hex 3 HexNAc 2 , m / z 1079.4, Hex 3 HexNAc 2 dHex 1 , m / z 1095.4, Hex 4 HexNAc 2 , m / z 1136.5, Hex 3 HexNAc 3 , m / 5, Hex 4 HexNAc 2 dHex 1 ,
m / z 1282.5, Hex 3 HexNAc 3 dHex 1 ,
m / z 1485.5, Hex 3 HexNAc 4 dHex 1
m/z1499.5, Hex9 m / z 1175.5, Hex 7,
m / z 1499.5, Hex 9
Claims (21)
Hex7 (1175.5 m/z), Hex8 (1337.5 m/z), Hex9 (1499.6 m/z), Hex10 (1681.7 m/z) 및 Hex11 (1823.7 m/z)의 각각의 당쇄 구조를 가지는 매미눈꽃동충하초(Isaria sinclairii) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
Hex3HexNAc2 (933.4 m/z), Hex3HexNAc2dHex1 (1079.4 m/z), Hex4HexNAc2 (1095.4 m/z), Hex3HexNAc3 (1136.5 m/z), Hex4HexNAc2dHex1 (1241.5 m/z), Hex3HexNAc3dHex1 (1282.5 m/z) 및 Hex3HexNAc4dHex1 (1485.5 m/z)의 각각의 당쇄 구조를 가지는 맹충(Tabanus bivittatus) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
Hex7 (1175.5 m/z), Hex9 (1499.5 m/z), Hex3HexNAc3dHex1 (1282.5 m/z) 및 Hex8 (1337.5 m/z)의 각각의 당쇄 구조를 가지는 강랑(Catharsius molossus) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
또는,
Hex8 (1337.5 m/z)의 당쇄 구조를 가지는 광대노린재(Poecilocoris lewisi) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
중에서 선택되는 한가지의 혼합물을 함유하는 것을 특징으로 하는,
고혈압, 뇌졸중, 뇌출혈, 허혈성 심질환 및 레이노병으로 이루어진 군에서 택일되는 혈관확장반응의 기능장애의 예방 또는 치료용 약학적 조성물.
An insect N-glycan mixture from Gryllus bimaculatus having a sugar chain structure of Hex6, Hex5GlcNAc2, Hex6GlcNAc2, Hex7GlcNAc2, Hex8GlcNAc2, Hex10GlcNAc2 and Hex9GlcNAc2 (1905 m / z);
The cicadas have the sugar chain structure of Hex7 (1175.5 m / z), Hex8 (1337.5 m / z), Hex9 (1499.6 m / z), Hex10 (1681.7 m / z) Isaria sinclairii- derived insect N-glycan mixture;
Hex3HexNAc2dHex1 (1283.5 m / z), Hex3HexNAc2dHex1 (1079.4 m / z), Hex3HexNAc2dHex1 (1079.4 m / z), Hex3HexNAc2dHex1 (1079.4 m / z), Hex3HexNAc2dHex1 1485.5 m / z), an insect N-glycan mixture derived from Tabanus bivittatus ;
Hex7 (1175.5 m / z), Hex9 (1499.5 m / z), Hex3HexNAc3dHex1 (1282.5 m / z) and Hex8 (1337.5 m / z) each having a sugar chain structure gangrang (Catharsius molossus) derived from insect N- article Mau of ( N-glycan) mixture;
or,
An insect N-glycan mixture derived from Poecilocoris lewisi having a sugar chain structure of Hex8 (1337.5 m / z);
≪ RTI ID = 0.0 > 1, < / RTI >
A pharmaceutical composition for preventing or treating dysfunction of an angiogenic response selected from the group consisting of hypertension, stroke, cerebral hemorrhage, ischemic heart disease, and Raynaud's disease.
Hex7 (1175.5 m/z), Hex8 (1337.5 m/z), Hex9 (1499.6 m/z), Hex10 (1681.7 m/z) 및 Hex11 (1823.7 m/z)의 각각의 당쇄 구조를 가지는 매미눈꽃동충하초(Isaria sinclairii) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
Hex3HexNAc2 (933.4 m/z), Hex3HexNAc2dHex1 (1079.4 m/z), Hex4HexNAc2 (1095.4 m/z), Hex3HexNAc3 (1136.5 m/z), Hex4HexNAc2dHex1 (1241.5 m/z), Hex3HexNAc3dHex1 (1282.5 m/z) 및 Hex3HexNAc4dHex1 (1485.5 m/z)의 각각의 당쇄 구조를 가지는 맹충(Tabanus bivittatus) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
Hex7 (1175.5 m/z), Hex9 (1499.5 m/z), Hex3HexNAc3dHex1 (1282.5 m/z) 및 Hex8 (1337.5 m/z)의 각각의 당쇄 구조를 가지는 강랑(Catharsius molossus) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
또는,
Hex8 (1337.5 m/z)의 당쇄 구조를 가지는 광대노린재(Poecilocoris lewisi) 유래 곤충 N-글라이칸(N-glycan) 혼합물;
중에서 선택되는 한가지의 혼합물을 함유하는 것을 특징으로 하는 고혈압, 뇌졸중, 뇌출혈, 허혈성 심질환 및 레이노병으로 이루어진 군에서 택일되는 혈관확장반응 기능장애의 예방 또는 개선용 건강기능식품.
Insect N-glycan mixture from Gryllus bimaculatus having a sugar chain structure of Hex6, Hex5GlcNAc2, Hex6GlcNAc2, Hex7GlcNAc2, Hex8GlcNAc2, Hex10GlcNAc2 and Hex9GlcNAc2 (1905 m / z);
The cicadas have the sugar chain structure of Hex7 (1175.5 m / z), Hex8 (1337.5 m / z), Hex9 (1499.6 m / z), Hex10 (1681.7 m / z) Isaria sinclairii- derived insect N-glycan mixture;
Hex3HexNAc2dHex1 (1283.5 m / z), Hex3HexNAc2dHex1 (1079.4 m / z), Hex3HexNAc2dHex1 (1079.4 m / z), Hex3HexNAc2dHex1 (1079.4 m / z), Hex3HexNAc2dHex1 1485.5 m / z), an insect N-glycan mixture derived from Tabanus bivittatus ;
Hex7 (1175.5 m / z), Hex9 (1499.5 m / z), Hex3HexNAc3dHex1 (1282.5 m / z) and Hex8 (1337.5 m / z) each having a sugar chain structure gangrang (Catharsius molossus) derived from insect N- article Mau of ( N-glycan) mixture;
or,
An insect N-glycan mixture derived from Poecilocoris lewisi having a sugar chain structure of Hex8 (1337.5 m / z);
Or a pharmaceutically acceptable salt, solvate, or prodrug thereof, which is selected from the group consisting of hypertension, stroke, cerebral hemorrhage, ischemic heart disease, and Raynaud's disease.
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| KR1020140183127A KR101660381B1 (en) | 2014-12-18 | 2014-12-18 | Insect N-Glycans and Use Thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200071421A (en) | 2018-12-11 | 2020-06-19 | 대한민국(농촌진흥청장) | An anti-microbial peptide, Teleogryllusine 3 isolated from Teleogryllus emma and its synthetic composition |
| KR20200071416A (en) | 2018-12-11 | 2020-06-19 | 대한민국(농촌진흥청장) | Poecilocorisin-1 peptide isolated from Poecilocoris lewisi or antimicrobial, antimycotic and antiinflammatory composition comprising it |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR101869793B1 (en) * | 2018-04-17 | 2018-06-21 | 대한민국 | N-Glycan Purifed from BIC: clony shell of B. ignitus or B. terrestris worker and theirs Use Thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR100847889B1 (en) | 2007-03-02 | 2008-07-25 | 대한민국 | Glycosaminoglycans derived from insect and a process for purification of the same |
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| KR20110013074A (en) * | 2009-07-31 | 2011-02-09 | 대한민국(농촌진흥청장) | Novel use of glycosaminoglycans derived from insect and a preparation method of the glycosaminoglycans |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR100847889B1 (en) | 2007-03-02 | 2008-07-25 | 대한민국 | Glycosaminoglycans derived from insect and a process for purification of the same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200071421A (en) | 2018-12-11 | 2020-06-19 | 대한민국(농촌진흥청장) | An anti-microbial peptide, Teleogryllusine 3 isolated from Teleogryllus emma and its synthetic composition |
| KR20200071416A (en) | 2018-12-11 | 2020-06-19 | 대한민국(농촌진흥청장) | Poecilocorisin-1 peptide isolated from Poecilocoris lewisi or antimicrobial, antimycotic and antiinflammatory composition comprising it |
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| KR20160074796A (en) | 2016-06-29 |
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