KR100537954B1 - Composition activating and protecting brain fuctions - Google Patents
Composition activating and protecting brain fuctions Download PDFInfo
- Publication number
- KR100537954B1 KR100537954B1 KR10-2003-0066803A KR20030066803A KR100537954B1 KR 100537954 B1 KR100537954 B1 KR 100537954B1 KR 20030066803 A KR20030066803 A KR 20030066803A KR 100537954 B1 KR100537954 B1 KR 100537954B1
- Authority
- KR
- South Korea
- Prior art keywords
- composition
- present
- culture
- dementia
- corn
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title abstract description 106
- 210000004556 brain Anatomy 0.000 title description 11
- 230000003213 activating effect Effects 0.000 title description 2
- 230000002633 protecting effect Effects 0.000 title description 2
- 210000002569 neuron Anatomy 0.000 claims abstract description 38
- 230000000694 effects Effects 0.000 claims abstract description 34
- 229930195712 glutamate Natural products 0.000 claims abstract description 33
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 32
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 25
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 25
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims abstract description 21
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims abstract description 21
- 235000005822 corn Nutrition 0.000 claims abstract description 21
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229960004373 acetylcholine Drugs 0.000 claims abstract description 19
- 206010029350 Neurotoxicity Diseases 0.000 claims abstract description 16
- 206010044221 Toxic encephalopathy Diseases 0.000 claims abstract description 16
- 231100000228 neurotoxicity Toxicity 0.000 claims abstract description 16
- 230000007135 neurotoxicity Effects 0.000 claims abstract description 16
- 210000004958 brain cell Anatomy 0.000 claims abstract description 14
- 108090000371 Esterases Proteins 0.000 claims abstract description 13
- 241000289667 Erinaceus Species 0.000 claims abstract description 7
- 230000005779 cell damage Effects 0.000 claims abstract description 6
- 208000037887 cell injury Diseases 0.000 claims abstract description 6
- 240000008042 Zea mays Species 0.000 claims abstract 7
- 235000001674 Agaricus brunnescens Nutrition 0.000 claims description 20
- 208000024827 Alzheimer disease Diseases 0.000 claims description 20
- 239000000284 extract Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 12
- 235000007340 Hordeum vulgare Nutrition 0.000 claims description 11
- 241000209140 Triticum Species 0.000 claims description 11
- 235000013339 cereals Nutrition 0.000 claims description 11
- 235000021307 Triticum Nutrition 0.000 claims description 10
- 240000007594 Oryza sativa Species 0.000 claims description 8
- 235000007164 Oryza sativa Nutrition 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 235000009566 rice Nutrition 0.000 claims description 8
- 238000012258 culturing Methods 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 230000024245 cell differentiation Effects 0.000 claims description 5
- 230000002490 cerebral effect Effects 0.000 claims description 4
- 240000000588 Hericium erinaceus Species 0.000 claims description 2
- 235000007328 Hericium erinaceus Nutrition 0.000 claims description 2
- 241001556385 Sanghuangporus baumii Species 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 3
- 240000005979 Hordeum vulgare Species 0.000 claims 2
- 238000011321 prophylaxis Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000003925 brain function Effects 0.000 abstract description 25
- 230000004224 protection Effects 0.000 abstract description 15
- 230000004913 activation Effects 0.000 abstract description 14
- 210000004720 cerebrum Anatomy 0.000 abstract description 13
- 239000003814 drug Substances 0.000 abstract description 9
- 235000013305 food Nutrition 0.000 abstract description 7
- 206010012289 Dementia Diseases 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000004069 differentiation Effects 0.000 abstract description 5
- 230000036541 health Effects 0.000 abstract description 5
- 230000008929 regeneration Effects 0.000 abstract description 3
- 238000011069 regeneration method Methods 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 27
- 241000209149 Zea Species 0.000 description 15
- 230000003833 cell viability Effects 0.000 description 13
- 230000002964 excitative effect Effects 0.000 description 13
- 230000001681 protective effect Effects 0.000 description 13
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 12
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 11
- 210000003618 cortical neuron Anatomy 0.000 description 10
- 241000209219 Hordeum Species 0.000 description 9
- 238000010586 diagram Methods 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 239000002858 neurotransmitter agent Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108010010803 Gelatin Proteins 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 239000008273 gelatin Substances 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 6
- 210000003050 axon Anatomy 0.000 description 6
- 229930003270 Vitamin B Natural products 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 235000019156 vitamin B Nutrition 0.000 description 5
- 239000011720 vitamin B Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 210000000225 synapse Anatomy 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 3
- 230000006974 Aβ toxicity Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 101710138657 Neurotoxin Proteins 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 235000001785 ferulic acid Nutrition 0.000 description 3
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 3
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 3
- 229940114124 ferulic acid Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 239000002581 neurotoxin Substances 0.000 description 3
- 231100000618 neurotoxin Toxicity 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 235000019157 thiamine Nutrition 0.000 description 3
- 229960003495 thiamine Drugs 0.000 description 3
- 239000011721 thiamine Substances 0.000 description 3
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 3
- 238000003809 water extraction Methods 0.000 description 3
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 229920002498 Beta-glucan Polymers 0.000 description 2
- 102000009025 Endorphins Human genes 0.000 description 2
- 108010049140 Endorphins Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010019851 Hepatotoxicity Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000006931 brain damage Effects 0.000 description 2
- 231100000874 brain damage Toxicity 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000002932 cholinergic neuron Anatomy 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 208000002173 dizziness Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 230000007686 hepatotoxicity Effects 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000002438 stress hormone Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 210000002504 synaptic vesicle Anatomy 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- FYGDTMLNYKFZSV-WFYNLLPOSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,3s,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-WFYNLLPOSA-N 0.000 description 1
- CKAKVKWRMCAYJD-UHFFFAOYSA-N 1-(3-ethylphenyl)-1-methyl-2-naphthalen-1-ylguanidine;hydrochloride Chemical compound Cl.CCC1=CC=CC(N(C)C(N)=NC=2C3=CC=CC=C3C=CC=2)=C1 CKAKVKWRMCAYJD-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- UQNAFPHGVPVTAL-UHFFFAOYSA-N 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C1=C2C=CC=C1S(=O)(=O)N UQNAFPHGVPVTAL-UHFFFAOYSA-N 0.000 description 1
- ZMKBTZQKANQZSK-UHFFFAOYSA-N 2-(methylamino)-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid Chemical compound CNC(C(O)=O)CC1=C(C)ON=C1O ZMKBTZQKANQZSK-UHFFFAOYSA-N 0.000 description 1
- NTBLZMAMTZXLBP-UHFFFAOYSA-M 2-acetylsulfanylethyl(trimethyl)azanium;iodide Chemical compound [I-].CC(=O)SCC[N+](C)(C)C NTBLZMAMTZXLBP-UHFFFAOYSA-M 0.000 description 1
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- DMPGFSQMXITJPT-ZCKYJUNOSA-N Erinacine C Chemical compound C([C@@H]1C2=C(CC[C@]2(C)CC[C@@]1(C)[C@H]1O2)C(C)C)C=C(CO)[C@H]1O[C@H]1[C@H]2OC[C@@H](O)[C@@H]1O DMPGFSQMXITJPT-ZCKYJUNOSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 108010083687 Ion Pumps Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 229940123134 Nitric oxide inhibitor Drugs 0.000 description 1
- 206010033864 Paranoia Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- LPMRCCNDNGONCD-RITPCOANSA-N Selfotel Chemical compound OC(=O)[C@@H]1C[C@H](CP(O)(O)=O)CCN1 LPMRCCNDNGONCD-RITPCOANSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000001727 Tropicoporus linteus Species 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 229960001456 adenosine triphosphate Drugs 0.000 description 1
- 201000003352 adrenal gland pheochromocytoma Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 239000003282 amino acid receptor affecting agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 239000002956 ash Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007177 brain activity Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012092 media component Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000007625 mitochondrial abnormality Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 210000005155 neural progenitor cell Anatomy 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000004031 neuronal differentiation Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 229960004181 riluzole Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 229950009825 selfotel Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
- A61K36/8998—Hordeum (barley)
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/208—Fungi extracts
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/11—Preparation or pretreatment of starting material involving culturing conditions, e.g. cultivation in the dark or under defined water stress
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
본 발명은 뇌기능 활성화 및 뇌기능 보호용 조성물에 관한 것이다.The present invention relates to a composition for brain function activation and brain function protection.
본 발명의 조성물은 곡물배지에서 배양한 펠리누스 바우미의 배양물, 헤리시움 에리나세우스의 배양물 및 옥수수를 함유한다.The composition of the present invention is cultured in grain medium Cultures of Felinus Baumi, cultures of Hersidium erinaceus, and corn.
본 발명의 조성물은 대뇌의 아세틸콜린 에스테라제의 활성을 효과적으로 억제하고, 글루타메이트에 의한 신경독성을 억제하며, 베타 아밀로이드에 의한 뇌세포손상을 억제하고, 신경세포의 재생 및 분화를 촉진하는 효과가 있으며, 별도의 부작용을 나타내지 않는다.The composition of the present invention effectively inhibits the activity of acetylcholine esterase in the cerebrum, inhibits neurotoxicity by glutamate, inhibits brain cell damage by beta amyloid, and promotes regeneration and differentiation of nerve cells. It does not show any side effects.
따라서 본 발명의 조성물은 성장기 어린이나 수험생을 위한 건강보조식품을 비롯하여 치매 치료용 의약품 등의 다양한 목적으로 사용될 수 있다.Therefore, the composition of the present invention can be used for a variety of purposes, such as health care foods for growing children or examinees, as well as drugs for treating dementia.
Description
본 발명은 뇌기능 활성화 및 뇌기능 보호용 조성물에 관한 것이다.The present invention relates to a composition for brain function activation and brain function protection.
인터넷의 보급과 산업의 발달로 인해 다양하고 많은 정보가 급속도로 보급됨에 따라, 현대인은 더 많은 자료와 더 정확한 정보를 수집하고 전달할 수 있는 빠른 인지 능력과 창의적인 활동으로 문제를 해결해 나가는 능력이 요구되고 있고, 이러한 지적능력은 미래의 경쟁자원으로 인식되고 있다.With the rapid dissemination of diverse and large amounts of information due to the spread of the Internet and the development of the industry, modern people are required to solve problems with fast cognitive ability and creative activities to collect and transmit more data and more accurate information. This intellectual ability is recognized as a competitive resource for the future.
또한 식생활과 의학의 발달로 평균 수명이 연장되어 사회가 노령화됨에 따라, 단지 오래 사는 것 자체보다는 치매와 같은 노인성 질환의 염려없이 건강하고 행복한 노후를 영위하고자 하는 인식이 높아지고 있다.In addition, as the life expectancy is extended due to the development of diet and medicine, the recognition of the desire to live a healthy and happy retirement without worrying about senile diseases such as dementia rather than just long life itself is increasing.
현대인이 원하는 우수한 지적능력과 행복한 노후생활은 육체적 건강과 정신적 건강이 조화를 이룰 때 최대로 발휘될 수 있으나, 각종 환경오염과 잘못된 식생활, 운동부족, 성공에 대한 정신적 스트레스로 영양불균형을 초래하고 신체 저항력이 약해지기 쉽다. The excellent intellectual ability and happy old life that modern people want can be maximized when physical health and mental health are harmonized, but it causes nutritional imbalance due to various environmental pollution, wrong diet, lack of exercise, and mental stress on success. It is easy to weaken the resistance.
과도한 스트레스는 뇌기능의 저하로 불면증, 기억력 감퇴, 학습 능력저하를 유발하며 나아가서는 스트레스 호르몬을 분비할 수 있다. 스트레스 호르몬에는 카테콜라민(catecholamines), 글루코코르티코이드(glucocorticoid)가 있으며, 이들의 분비는 뇌의 에너지를 감소시키고, 장기간 분비되면 신경세포 사이의 연결 (network)을 단절시킨다 (Sapolsky et al., Curr. Opini. Neurobiol., 5(2):205-216, 1995). 이러한 이유로 뇌 보호제 및 활성제의 개발이 시급한 실정이다.Excessive stress can lead to insomnia, memory loss, poor learning, and even release stress hormones. Stress hormones include catecholamines and glucocorticoids, whose secretion reduces brain energy and, over long periods of time, disrupts the network between nerve cells (Sapolsky et al., Curr. Opini). Neurobiol., 5 (2): 205-216, 1995). For this reason, development of brain protectors and active agents is urgent.
신경세포 사이의 흥분의 전달은 시냅스(synapse)를 통해 이루어진다. 한 뉴런(neuron)의 축색 돌기 말단과, 다른 신경세포의 수상 돌기 또는 신경 세포체는 약 20㎚의 극히 좁은 틈인 스냅스 틈을 두고 접속하여 시냅스를 형성하고 있다.The transmission of excitation between neurons is via synapses. The end of an axon of a neuron and the dendrites or nerve cell bodies of another neuron are connected through a snap gap, which is an extremely narrow gap of about 20 nm, to form a synapse.
뉴런을 따라 전달된 흥분이 축색 돌기 말단까지 전도되면 축색 말단에 있는 시냅스 소포에서 신경전달물질(neurotransmitter)이 방출된다. 신경전달물질은 시냅스 틈을 통해 확산되어, 다음 신경세포의 막 투과성을 변화시켜 전기 화학적 변화를 일으킨다. 이와 같이 화학적 방식에 의해 시냅스 틈을 건너 흥분이 전해지는 것을 흥분의 전달이라 한다. 시냅스 소포는 축색 돌기 말단에만 있기 때문에 흥분은 축색 돌기에서 다음 뉴런의 수상 돌기 쪽의 일방으로만 전달된다. 신경의 말단과 근육의 접속 부위도 화학 전달 물질에 의해 흥분이 전달된다.When the excitement transmitted along the neuron is conducted to the axon end, neurotransmitters are released from the synaptic vesicles at the axon end. Neurotransmitters diffuse through synaptic clefts, altering the membrane permeability of the next neuron, causing electrochemical changes. As such, the excitement is transmitted across the synaptic gap by the chemical method is called the transfer of excitement. Since the synaptic vesicles are only at the end of the axon, excitability is transmitted from the axon only to one side of the dendrites of the next neuron. Excitedness is also transmitted by the chemical transport material at the nerve endings and the muscle connections.
신경전달물질은 시냅스에서 신경세포사이, 또는 신경세포와 근육사이에 신호를 전달하며, 신경세포 말단(axon)에 저장되어 있다. 전기자극이 신경세포 말단에 전달되면 신경전달 물질이 분비되며 시냅스를 통하여 자극을 전달한다. 아세틸콜린, 노르에피네프린, 아데노신 트리포스페이트, 엔도르핀, 나이트릭 옥사이드를 포함하여 300개 이상의 신경전달물질이 있다. 이들은 뇌안에서, 또는 뇌와 신체의 자극전달에 관여한다. 헤로인이나 코카인과 같은 약물은 통증을 조절하는 엔도르핀의 수용기에 작용한다. 카페인의 자각작용은 뇌의 활성을 방해하는 아데노신 효과를 억제한다. 그러나 신경전달물질의 과다생산과 기능의 이상은 파킨스씨병, 근위축성 측삭 경화증 (amyotrophic lateral sclerosis), 디프레션(depression)을 유발한다.Neurotransmitters transmit signals between synapses, or between nerve cells and muscles, and are stored at the nerve cell axon. When electrical stimulation is delivered to the nerve cell ends, neurotransmitters are secreted and the stimulus is transmitted through synapses. There are more than 300 neurotransmitters, including acetylcholine, norepinephrine, adenosine triphosphate, endorphins, nitric oxides. They are involved in the transmission of stimuli in the brain or in the brain and body. Drugs like heroin and cocaine act on receptors for endorphins that control pain. The caffeine perception inhibits adenosine effects that interfere with brain activity. However, neurotransmitter overproduction and dysfunction cause Parkinson's disease, amyotrophic lateral sclerosis, and depression.
그 대표적인 예로 포유동물의 중추신경계에서 중요한 아미노산성 신경전달물질인 글루타메이트(glutamate)를 들 수 있다. 글루타메이트는 NMDA (N-메틸-D-아스파테이트) 수용체, AMPA (L-α-아미노-3-히드록시-5-메틸-4-이속사졸프로피오네이트) 수용체, 카이네이트(Kainate) 수용체 및 1S,3R-ACPD 수용체[Craig CR, Stitzel RE, Modern Pharmacology with Clinical Applications, p293-302, 1997]와 같은 다양한 흥분성 아미노산 리간드 이온 수용기 (ligand-gated ion channel)에 결합한다. 글루타메이트가 수용기에 결합하면 탈분극과 신경흥분을 일으키며, 정상적인 신경전달의 경우 그 효과는 순간적이다.A representative example is glutamate, an amino acid neurotransmitter important in the central nervous system of mammals. Glutamate is an NMDA (N-methyl-D-aspartate) receptor, AMPA (L-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor, Cainate receptor and 1S And bind to a variety of excitatory amino acid ligand-gated ion channels such as the 3R-ACPD receptor [Craig CR, Stitzel RE, Modern Pharmacology with Clinical Applications, p293-302, 1997]. Glutamate binds to receptors, resulting in depolarization and neuroexcitement. In normal neurotransmission, the effect is instantaneous.
그러나 글루타메이트에 의한 수용기의 흥분이 과다하거나 길어지면, 신경세포가 손상되어 알츠하이머성 치매, 파킨슨병, 뇌졸증 및 근위축성 측삭 경화증(amyotrophic lateral sclerosis) 등의 퇴행성 신경질환(neurodegenerative disorders)을 유발한다 [Haloween, B., Reactive oxygen species and the central nervous system. J. Neurochem. 59, p1609-1623, 1992; Coyle, J. T. 및 Puttfarcken, P., Oxidative stress, glutamate, and neurodegenerative disorders. Science 262, p689-695, 1993; Olanow, C. W., A radical hypothesis for neurodegeneration. Trends Neurosci. 16, p439-444, 1993].Excessive or prolonged excitation of the receptor by glutamate, however, damages the nerve cells, leading to degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, stroke and amyotrophic lateral sclerosis. , B., Reactive oxygen species and the central nervous system. J. Neurochem. 59, p 1609-1623, 1992; Coyle, JT and Puttfarcken, P., Oxidative stress, glutamate, and neurodegenerative disorders. Science 262, p 689-695, 1993; Olanow, CW, A radical hypothesis for neurodegeneration. Trends Neurosci . 16, p 439-444, 1993.
글루타메이트에 의한 신경세포의 사멸을 글루타메이트 흥분성 신경독성이라 하며, 이 경우 세포내 칼슘 농도의 증가와 미토콘드리아의 손상이 일어나며, 신경세포 에너지 대사의 이상으로 신경 세포사멸을 일으키게 된다. 또한 신경세포 사멸과정에서 활성산소(reactive oxygen species)가 발생되는데, 활성산소는 미토콘드라아에서 싸이토크롬 c(cytochrome C)를 분출한다.Neuronal cell death by glutamate is called glutamate excitatory neurotoxicity. In this case, an increase in intracellular calcium concentration and damage of mitochondria occurs, and neuronal cell death is caused by abnormal neuron energy metabolism. In addition, reactive oxygen species are generated during neuronal cell death, which releases cytochrome c from mitochondria.
특히 뇌허혈과 같은 자극이 있을 경우 뇌세포에 산소공급이 감소하여, 해당작용이 증가하며, 조직내의 에너지원인 ATP가 줄어 들어 이온펌프의 작용이 감소하게 되고, 세포 외의 포타슘 이온의 양이 증가하여 신경세포막이 탈분극된다. 이렇게 되면 흥분성 신경전달물질이 분비되어 NMDA, AMPA, 카이네이트 수용체가 활성화됨으로써 뇌손상이 일어난다.In particular, when there is a stimulus such as cerebral ischemia, oxygen supply to brain cells is reduced, and glycolysis is increased, and ATP, which is an energy source in tissues, is reduced, so that the action of ion pump is decreased, and the amount of extra potassium ions in the cells increases The cell membrane is depolarized. In this case, excitatory neurotransmitters are secreted to activate NMDA, AMPA, and kinate receptors, resulting in brain damage.
이러한 흥분성 신경세포 사멸의 원리는 생체 내(in vivo)와 시험관 내(in vitro)에서 아미노산을 투여함으로 쉽게 연구하게 되면서 신경세포의 퇴화를 일으키는 기작이 연구되어 이를 억제할 수 있는 방법이 제시되었다. 이 방법 중의 하나가 글루타메이트에 의한 신경흥분을 억제할 수 있는 물질의 연구이며, 이러한 물질은 질병을 치료하는데 도움을 줄 수 있다. 최근에 항글루타메이트 물질인 릴루졸(riluzole)이 근위축성 측삭 경화증, 파킨슨씨병, 헌팅턴증후군과 같은 미토콘드리아의 이상에 의한 질환에 효과가 있는 것으로 보고되었다.The principle of the excitatory neuron killing is easily studied by administering amino acids in vivo and in vitro, and the mechanisms by which neuronal degeneration is studied has been suggested. One of these methods is the study of substances that can inhibit neurostimulation by glutamate, which can help treat diseases. Recently, anti-glutamate substance riluzole has been reported to be effective in diseases caused by mitochondrial abnormalities such as amyotrophic lateral sclerosis, Parkinson's disease and Huntington's syndrome.
한편 뇌의 해마 부위는 인지, 학습, 및 기억과 연관된 기능을 가지는 것으로 알려져 있다. 알츠하이머성 치매 환자들의 해마에서는 콜린작동성 뉴런의 수치가 현저히 감소되는 것으로 나타났으며, 이러한 콜린작동성 뉴런의 진행성 손상은 기억 및 인지 기능에 있어서 진행성 손상을 나타낸다.The hippocampal region of the brain is known to have functions related to cognition, learning, and memory. The hippocampus of Alzheimer's dementia patients has been shown to significantly reduce the levels of cholinergic neurons, and progressive damage of these cholinergic neurons indicates progressive impairment in memory and cognitive function.
이러한 뉴런의 감소에 대한 원인 중 하나는 신경전달물질인 아세틸콜린의 손상 또는 기능 저하에 있다. 따라서 뇌의 아세틸콜린 양을 증가시키기 위하여 아세틸콜린 에스테라제 억제제(acetylcholine esterase inhibitor)들이 널리 이용되고 있다. 이외에도, 이러한 뇌손상을 억제하기 위한 많은 연구가 이루어지고 있으며[Gagliardi RJ, Neuroprotection, excitotoxicity and NMDA antagonists, Arq. Neuro-Psiquiatr. p58, 2000], NMDA 길항제, AMPA 길항제, GABA 효능제, 세포내 칼슘감소제, 산화질소(nitric oxide) 억제제, 유리 라디칼 제거제(free radical scavenger), 나트륨 채널 억제제, 글루타메이트 유리 억제제, 성장인자, 산성화(acidosis), 저체온법(hypothermia), 칼륨 채널 활성제(potassium channel activators)등의 개발이 시도되고 있다.One of the causes for the reduction of these neurons is the damage or deterioration of the neurotransmitter acetylcholine. Therefore, acetylcholine esterase inhibitors are widely used to increase the amount of acetylcholine in the brain. In addition, many studies have been conducted to suppress such brain damage [Gagliardi RJ, Neuroprotection, excitotoxicity and NMDA antagonists, Arq. Neuro-Psiquiatr. p58, 2000], NMDA antagonists, AMPA antagonists, GABA agonists, intracellular calcium reducers, nitric oxide inhibitors, free radical scavengers, sodium channel inhibitors, glutamate free inhibitors, growth factors, acidification (acidosis), hypothermia, and potassium channel activators have been attempted.
그러나, NMDA 길항제로 도조사일핀(dozocyilpin) (MK 801), 셀포텔(selfotel), 세레스테이트(cerestat), 덱스트로메톨판(dextrometorfan) 등이 개발되었으나, 이 약물들은 저용량으로 투여시, 지각인지의 변화, 불쾌감, 안구진탕증(nystagmus), 저혈압 등을 유발하며, 고용량으로 투여시 흥분, 집착(paranoia), 환각과 같은 정신적인 부작용을 나타낸다. 또한, AMPA 길항제로 NBQX가 개발되었으나, 심각한 신장독성의 발현으로 의약품으로서의 실용가능성이 아주 낮다.However, dozocyilpin (MK 801), selfotel, cerestat, dextrometorfan, etc. have been developed as NMDA antagonists. Changes, discomfort, nystagmus, hypotension, etc., and mental side effects such as excitement, paranoia, and hallucinations when administered at high doses. In addition, NBQX has been developed as an AMPA antagonist, but due to the development of severe renal toxicity, its practical utility as a drug is very low.
아세틸콜린 에스테라제는 뇌에서 아세틸콜린의 양을 증가시키며, 알쯔하이머병의 초기에 아세틸콜린 에스테라제 억제제는 효과적인 치료제로 사용되나, 대부분이 비특이적인 작용으로 인하여 말초신경의 콜린성 부작용이 있고, 반감기가 너무 짧으며, 간독성 등의 심각한 부작용이 나타난다는 문제가 있다(Br. J. Psychiatry, 138, 46, 1981, "Goodman and Gilman's, The Pharmacological Basis of Therapeutics", Ed. Gilman, et al., Pergamon Press, 8th Ed., Chap. 7, 1990). Acetylcholine esterase increases the amount of acetylcholine in the brain, and in the early stages of Alzheimer's disease, acetylcholine esterase inhibitors are used as effective treatments, but most of them have cholinergic side effects of peripheral nerves due to their nonspecific action, and half-life Is too short and there are serious side effects such as hepatotoxicity (Br. J. Psychiatry, 138, 46, 1981, "Goodman and Gilman's, The Pharmacological Basis of Therapeutics", Ed. Gilman, et al., Pergamon Press, 8th Ed., Chap. 7, 1990).
코넥스(Cognex)의 성분화합물 9-아미노-1,2,3,4-테트라하이드로아크리딘 (THA)는 가장 널리 사용되고 있는 약품으로, 실제 알츠하이머성 치매 환자에게 경구 투여한 결과 상당한 지각능력의 향상결과를 얻을 수 있었다(N. Engl. J. Med., 315, 1241, 1986). 그러나, 이 제품은 떨림증, 어지럼증, 간독성 등의 심각한 부작용을 수반하는 문제점이 있다.Conn's ingredient compound 9-amino-1,2,3,4-tetrahydroacridine (THA) is the most widely used drug, and it has a significant perceptual ability as a result of oral administration to patients with Alzheimer's dementia. Improvements were obtained (N. Engl. J. Med., 315, 1241, 1986). However, this product has problems with serious side effects such as dizziness, dizziness and hepatotoxicity.
또한 치매의 주원인은 뇌에 베타 아밀로이드가 축적되기 때문인 것으로 알려져 있어, 베타 아밀로이드의 작용을 억제할 수 있는 물질에 대한 관심도 급증하고 있다.In addition, the main cause of dementia is known to be due to the accumulation of beta amyloid in the brain, so there is an increasing interest in substances that can inhibit the action of beta amyloid.
다른 한편에서는 신경세포 자체를 재생시키거나, 전구세포로부터 분화시킬 수 있는 물질에 대한 연구도 진행되고 있다.On the other hand, research is being conducted on substances that can regenerate neurons themselves or differentiate from progenitor cells.
따라서, 뇌기능의 활성화 및 보호를 위해 글루타메이트 흥분성 신경독성, 아세틸콜린 에스테라제 활성, 베타 아밀로이드의 작용을 억제하고 신경세포 분화를 촉진하면서도 부작용을 수반하지 않는 조성물에 대한 발명이 필요하다.Therefore, there is a need for the invention of a composition that inhibits the action of glutamate excitatory neurotoxicity, acetylcholine esterase activity, beta amyloid and promotes neuronal differentiation but does not involve side effects for activation and protection of brain function.
본 발명에서는 곡류에 약용 버섯을 접종하여 배양한 균사체와 옥수수를 함유하며, 부작용 없이 뇌기능 활성화 및 보호 효과를 나타내는 조성물을 제공하고자 한다.The present invention contains a mycelia and corn cultured by inoculating medicinal mushrooms in cereals, and to provide a composition showing the brain function activation and protective effect without side effects.
본 발명은 뇌기능 활성화 및 뇌기능 보호용 조성물을 제공한다.The present invention provides a composition for brain function activation and brain function protection.
본 발명의 조성물은 곡물배지에서 배양한 펠리누스 바우미(Phellinus baumii)의 배양물(culture), 헤리시움 에리나세우스(Hericium erinaceus)의 배양물 및 옥수수(Zea may)로 이루어진다.The composition of the present invention is cultured in grain medium It consists of a culture of Phellinus baumii , a culture of Hericium erinaceus and Zea may .
본 발명에서 배양물이란 버섯 균사체를 곡물배지에 접종하고 배양한 후 얻어진 배양혼합물(cultured products)을 의미한다.In the present invention, the culture means a cultured product obtained after inoculating the mushroom mycelium on a grain medium and culturing.
본 발명에서 배양물은 버섯 균사체 뿐 아니라 배지 자체, 그리고 균사체가 자라면서 생성하는 여러가지 유용물질을 함께 포함한다.In the present invention, the culture includes not only the mushroom mycelium, but also the medium itself, and various useful substances generated as the mycelium grows.
본 발명에서 곡물배지는 보리, 밀, 쌀 배아, 쌀, 옥수수, 조, 미강 중 선택된 하나 이상의 삶은 곡물을 사용할 수 있다.Grain medium in the present invention may use one or more boiled grain selected from barley, wheat, rice germ, rice, corn, crude, rice bran.
본 발명의 조성물의 각 성분은 열수 추출 또는 유기용매 추출하여 얻은 추출물 형태로 함유될 수 있다. 또한 본 발명의 조성물은 필요에 따라 천연물 그 자체를 건조시켜 얻는 건조물, 또는 상기 건조물을 분쇄하여 얻은 분말 등의 형태를 함유될 수 있다.Each component of the composition of the present invention may be contained in the form of extract obtained by hot water extraction or organic solvent extraction. In addition, the composition of the present invention may contain a form such as a dried product obtained by drying the natural product itself, or a powder obtained by pulverizing the dried product, if necessary.
본 발명의 조성물은 구체적으로 펠리누스 바우미 배양물의 열수 추출물, 헤리시움 에리나세우스 배양물의 열수 추출물 및 옥수수 분말로 이루어진다.The composition of the present invention specifically consists of a hydrothermal extract of a Felinus Baumi culture, a hydrothermal extract of a Hersidium erinaceus culture and a corn powder.
본 발명의 조성물은 펠리누스 바우미 배양물의 열수 추출물 50∼70 중량%, 헤리시움 에리나세우스 배양물의 열수 추출물 10∼30 중량%, 옥수수 분말 10∼30 중량%로 이루어진다.The composition of the present invention is composed of 50 to 70% by weight of hydrothermal extract of Felinus Baumi culture, 10 to 30% by weight of hydrothermal extract of Herridium erinaceus culture, and 10 to 30% by weight of corn powder.
본 발명의 조성물의 가장 바람직한 실시예는 펠리누스 바우미를 밀에 배양하여 얻은 배양물의 열수 추출물 60 중량%, 헤리시움 에리나세우스를 보리에 배양하여 얻은 배양물의 열수 추출물 20 중량% 및 옥수수 분말 20 중량%로 이루어진다.The most preferred embodiment of the composition of the present invention is 60% by weight of hydrothermal extract of the culture obtained by culturing Felinus Baumi on wheat, 20% by weight of hydrothermal extract of the culture obtained by culturing Hersidium erinaceus on barley and corn powder It consists of 20% by weight.
이하 본 발명의 조성물이 함유하는 각 성분에 대해 상세히 설명한다.Hereinafter, each component contained in the composition of the present invention will be described in detail.
본 발명의 조성물이 함유하는 펠리누스 바우미는 현재 '장수상황'이라는 명칭으로 품종등록되어 있으며, 그 특징은 노란색을 띄며 해를 거듭할수록 나이테 무늬를 만들며 성장하기도 하며 성장이 무척 빨라 현재 가장 널리 인공재배되고 있다.Felinus Baumi contained in the composition of the present invention is currently registered varieties under the name of 'longevity situation', its characteristic is yellow and grows year after year as the ring pattern grows and grows very fast and is currently the most widely cultivated It is becoming.
펠리누스 속 버섯은 목질진흙버섯, 마른진흙버섯, 말똥진흙버섯, 검은진흙버섯, 낙옆소충버섯 등 크게 다섯 군으로 분류되며, 우리나라에는 세계적으로 존재하는 50여개 중 8종이 자연상태에서 자생하는 것으로 알려져 있다. The mushrooms of the genus Pellinus are classified into five groups: woody mud mushrooms, dried mud mushrooms, horse mud mushrooms, black mud mushrooms, and fungus fungi. In Korea, 8 out of 50 species are known to grow wild in nature. have.
펠리누스 바우미는 그 중에서 목질진흙버섯 속에 해당하며, 펠리누스 린테우스(Phellinus linteus)와 함께 '상황버섯'으로 일컬어진다.Felinus Baumi is among the woody mud mushrooms and is called 'situation mushroom' along with Phellinus linteus .
일반적으로 버섯류는 칼륨, 칼슘, 마그네슘, 비타민B2, B3, C, 섬유소, 아미노산 등을 함유하는데, 특히 펠리누스 바우미는 상기 성분 외에 인체 내의 면역기능을 증강시키는 것으로 알려진 다당류(Polysaccharide)를 다량 함유하고 있다. In general, mushrooms contain potassium, calcium, magnesium, vitamin B2, B3, C, fibrin, amino acids, etc. In particular, Felinus Baumi contains a large amount of polysaccharides known to enhance immune function in the human body in addition to the above components. have.
펠리누스 바우미의 단백질 함량은 4.2% 정도인 반면, 다당체 함량은 97.5%에 달한다. 펠리누스 바우미의 다당체는 글루코스 58%, 만노스12.1%, 갈락토스4.9%와 자이로스, 아라비노스로 이루어진다. 펠리누스 바우미의 단백질은 주로 발린, 알라닌, 글리신을 위시한 15종으로 이루어진다. 상기 성분들은 체내에 흡수되어 인체의 면역체계를 활성화시켜주며, 약해진 신체의 각종 기능을 도와 주는 것으로 알려져 있다.Felinus Baumi's protein content is around 4.2%, while the polysaccharide content is up to 97.5%. Felinus Baumi's polysaccharide consists of 58% glucose, 12.1% mannose, 4.9% galactose, gyros and arabinose. Felinus Baumi's proteins consist mainly of 15 species, including valine, alanine and glycine. The components are absorbed into the body to activate the body's immune system, it is known to help various functions of the weakened body.
본 발명의 조성물이 함유하는 헤리시움 에리나세우스는 지방 함량이 낮은 반면 섬유질을 비롯하여 기타 무기물과 비타민 B군, D군이 풍부하다. 특히 베타 글루칸(ß-D-glucan)의 함량이 매우 높으며, 신경세포 성장인자(nerve growth factor)의 합성을 활성화시키는 헤리세논(Hericenon C,D,E,F,G,H)과 에리나신 C(Erinacin C )를 함유하고 있다.Hersidium erynasus contained in the composition of the present invention is low in fat content and rich in fiber and other minerals, vitamin B group and D group. In particular, the content of beta glucan ( ß- D-glucan) is very high, and helisenone (Hericenon C, D, E, F, G, H) and erysin C that activate the synthesis of nerve growth factor (nerve growth factor) Contains (Erinacin C).
본 발명의 조성물이 함유하는 배지 성분 중 보리와 밀의 특성은 다음과 같다.Characteristics of barley and wheat among the media components contained in the composition of the present invention are as follows.
보리는 대표적인 알카리성 식품이며 단백질 10%, 지방 0.5%, 전분 75%로 이루어져 쌀보다 단백질 함량이 높고 섬유질이 풍부하며, 비타민, 미네랄, 회분, 펜톤산, 무기염류를 다량 함유하므로 성인병 예방에 효과가 있다. 보리에는 특히 비타민 B군이 많이 함유되어 있는데, 보리 100g 당 비타민 B1(thiamine)은 0.23㎎, 비타민 B2는 0.08㎎, 비타민 B3는 16㎎이 들어있다. 또한 보리는 콜레스테롤을 낮추고 면역기능을 활성화하는 베타 글루칸을 쌀의 50배 이상으로 함유하며, 섬유질도 쌀의 5배 이상 함유한다.Barley is a representative alkaline food, consisting of 10% protein, 0.5% fat, and 75% starch, which is higher in protein than fiber and rich in fiber, and contains a large amount of vitamins, minerals, ash, fentonic acid, and inorganic salts. have. Barley is particularly rich in vitamin B group, which contains 0.23 mg of vitamin B 1 (thiamine), 0.08 mg of vitamin B 2 and 16 mg of vitamin B 3 per 100 g of barley. In addition, barley contains more than 50 times the amount of beta glucan that lowers cholesterol and activates immune function, and contains 5 times more fiber than rice.
밀의 경우 통밀에는 비타민 B1(thiamine)과 뇌의 노화를 방지하는 셀레늄이 많이있고, 밀 배아에는 비타민 E가 다량 함유되어 있다.Wheat has a lot of vitamin B 1 (thiamine) and selenium to prevent brain aging, wheat wheat contains a lot of vitamin E.
특히 비타민 B1의 경우 우리 체내에서 비타민과 미네랄의 흡수를 돕는 하이드로킬로릭산(hydrochloic acid)을 만드는데 필수적이다. 40대 이후에는 하이드로킬로릭산의 기능이 감소하여 비타민과 미네랄의 흡수가 저하되므로 비타민 B1의 섭취가 필요하다. 1990년 신경학회(Annals of Neurobiology)에서 알츠하이머성 치매에 걸린 환자에게 과량의 티아민(thiamine)을 투여한 결과 효과가 있다고 알려진 바 있다.In particular, vitamin B 1 is essential for making hydrochloic acid, which helps the body absorb vitamins and minerals. After 40, hydrochloric acid function is reduced, so absorption of vitamins and minerals is reduced, so vitamin B 1 needs to be consumed. In the 1990s, the Neuros of Neurobiology was known to be effective in administering excess thiamine to patients with Alzheimer's dementia.
본 발명의 배양물 내에 포함된 이들 곡물배지는 균사체가 생장과정 중 만들어 분비한 유용한 성분들을 상당량 함유하게 된다. 이처럼 곡물배지에 함유되는 성분들은 균사체에 함유된 성분들과 마찬가지로, 뇌기능 활성화 및 뇌기능 보호 효과에 있어 중요한 생리활성을 나타낸다. 또한 곡물 성분은 부수적인 건강 증진 작용을 나타내며, 맛을 향상시켜 음용을 용이하게 한다.These grain mediums contained in the culture of the present invention will contain a significant amount of useful components produced and secreted by the mycelia during the growth process. As such, the components contained in the grain medium, like those contained in the mycelium, exhibit important physiological activities in brain function activation and brain function protection effect. In addition, the grain component exhibits ancillary health-promoting action, and enhances the taste to facilitate drinking.
본 발명의 조성물이 함유하는 옥수수는 그 세포벽에 다량의 항산화제와 페룰릭산(ferulic acid)을 함유한다.Corn contained in the composition of the present invention contains a large amount of antioxidants and ferulic acid in its cell walls.
항산화제는 체내 산화를 증가시켜 암, 심장질환, 치매를 유발할 수 있는 라다칼(free radical)을 제거시켜 준다. 항산화제의 양은 옥수수를 115℃ 정도의 고온에서 10, 25, 50분간 가열함에 따라 각각 22, 44, 53 %로 증가한다. Antioxidants increase the body's oxidation and remove free radicals that can cause cancer, heart disease and dementia. The amount of antioxidants increases to 22, 44 and 53% as corn is heated for 10, 25 and 50 minutes at temperatures as high as 115 ° C.
페룰릭산은 항암효과를 나타내는 페놀 중합체(phenolic compound)이다. 페룰릭산은 세포벽과 불용성 섬유에 연결되어 있어, 그 양은 옥수수를 115℃ 정도의 고온에서 10, 25, 50분간 가열함에 따라 각각 240, 550, 900% 까지 증가한다.Ferulic acid is a phenolic compound that exhibits anticancer effects. Ferulic acid is linked to cell walls and insoluble fibers, the amount of which increases by 240, 550 and 900% as corn is heated for 10, 25 and 50 minutes at temperatures as high as 115 ° C.
본 발명의 조성물은 밀에 배양한 펠리누스 바우미, 보리에 배양한 헤리시움 에리나세우스 및 옥수수 분말을 함께 함유함으로써, 상기 성분들을 단순히 혼합하였을 때 기대할 수 있는 수준보다 훨씬 높은 상승효과(synergy effect)를 나타낸다. 이는 상기 성분들이 체내로 섭취되면 각 성분들의 단독 효과가 나타나는 것 뿐 아니라, 복합적으로 상호 작용한 결과 추가의 생리활성효과까지 나타나기 때문인 것으로 보인다.The composition of the present invention contains Felinus Baumi cultured in wheat, Hersidium erynasus and corn powder cultured in barley together, so that the synergy effect is much higher than expected when simply mixing the above ingredients. effect). This may be due to the fact that when the components are ingested into the body, not only the single effect of each component is shown, but also the additional interaction effect as a result of the complex interaction.
본 발명의 조성물은 대뇌의 아세틸콜린 에스테라제의 활성을 효과적으로 억제하여, 대뇌의 주요 신경전달물질인 아세틸콜린의 농도를 높은 수준으로 유지할 수 있다.The composition of the present invention effectively inhibits the activity of acetylcholine esterase in the cerebrum, thereby maintaining a high level of acetylcholine, which is a major neurotransmitter of the cerebrum.
본 발명의 조성물은 글루타메이트에 의한 신경독성을 억제하여, 신경세포의 퇴행을 현저히 감소시킬 수 있다.The composition of the present invention can inhibit neurotoxicity by glutamate, which can significantly reduce neuronal degeneration.
본 발명의 조성물은 베타 아밀로이드에 의한 뇌세포손상을 억제하여, 알츠하이머성 치매를 예방 및 치료할 수 있다.The composition of the present invention can inhibit brain cell damage caused by beta amyloid, thereby preventing and treating Alzheimer's dementia.
본 발명의 조성물은 신경전구세포가 신경세포로 분화되는 것을 촉진하여, 신경세포의 재생 및 분화를 촉진할 수 있다.The composition of the present invention may promote the differentiation of neural progenitor cells into neurons, thereby promoting the regeneration and differentiation of neurons.
본 발명의 조성물은 상기 성분들 뿐 아니라 이와 동일 또는 유사한 기능을 지닌 다른 유효성분을 추가로 함유할 수 있다.The composition of the present invention may further contain the above ingredients as well as other active ingredients having the same or similar functions.
본 발명의 조성물은 상기 버섯 추출물과 상이한 기능을 지닌 다른 유효성분을 추가로 함유할 수 있다.The composition of the present invention may further contain another active ingredient having a different function from the mushroom extract.
본 발명의 조성물은 상기 기재한 유효성분 이외에 추가로 약제학적 또는 식품에서 허용 가능한 보조성분을 1종 이상 포함함으로써, 뇌기능 활성화 및 뇌기능 보호용 약제학적 조성물 또는 뇌기능 활성화 및 뇌기능 보호용 식품 조성물로서 제공될 수 있다.The composition of the present invention comprises at least one auxiliary ingredient which is acceptable in pharmaceutical or food, in addition to the above-described active ingredient, as a pharmaceutical composition for brain function activation and brain function protection or food composition for brain function activation and brain function protection Can be provided.
본 발명의 조성물 제조시 약학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당분야의 적정한 방법으로, 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라, 또는 성분에 따라 바람직하게 제제화할 수 있다.Pharmaceutically acceptable carrier in the preparation of the composition of the present invention may be used in combination with saline, sterile water, Ringer's solution, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, antioxidant Other conventional additives such as agents, buffers, bacteriostatic agents and the like can be added. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.
본 발명의 조성물의 제제 형태는 과립제, 산제, 과립제, 피복정, 정제, 캡슐제, 탕제, 엑기스제, 좌제, 시럽, 즙, 현탁제, 유제 및 활성 화합물의 서방출형 제제 등이 될 수 있다.Formulation forms of the compositions of the present invention may be granules, powders, granules, coated tablets, tablets, capsules, milk preparations, extracts, suppositories, syrups, juices, suspensions, emulsions and sustained release formulations of the active compounds, and the like. .
본 발명의 조성물의 투여량 또는 섭취량은 경구투여시 1.5mg/kg/day인 것이 바람직하며, 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. The dosage or intake of the composition of the present invention is preferably 1.5 mg / kg / day upon oral administration, and the type of formulation and the age, weight, general health condition, sex and diet, time of administration, route of administration and composition of the patient. It can be adjusted according to various factors including the rate of secretion, the duration of treatment, and the drug used concurrently.
본 발명의 식품 조성물에는 필요에 따라 다양한 보조성분을 추가할 수 있으며, 예를 들면 비타민 A, 비타민 B1, 비타민 B2, 비타민 B3, 비타민 B6 , 비타민 B12, 엽산(folic acid), 비타민 C, 비타민 D3, 비타민 E 등의 비타민(Vitamin) 류와, 구리, 칼슘, 철, 마그네슘, 칼륨, 아연 등의 미네랄 또는 유산균 등이 있다.Various auxiliary ingredients may be added to the food composition of the present invention as needed, for example, vitamin A, vitamin B 1 , vitamin B 2 , vitamin B 3 , vitamin B 6 , vitamin B 12 , folic acid, Vitamins such as vitamin C, vitamin D 3 and vitamin E, minerals such as copper, calcium, iron, magnesium, potassium, zinc, and lactic acid bacteria, and the like.
본 발명의 식품 조성물 중, 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 향미제로는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 들 수 있다. 천연 탄수화물로는 포도당, 과당 등의 단당류, 말토스, 수크로오스 등의 이당류, 덱스트린, 사이클로덱스트린 등의 다당류, 자일리톨, 소르비톨, 에리트리톨 등의 당알코올류 등이 들 수 있다. In the food composition of the present invention, the health beverage composition may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. Flavoring agents include natural sweeteners such as taumartin and stevia extract, and synthetic sweeteners such as saccharin and aspartame. Natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol.
본 발명의 조성물은 인체에 투약하는 경우 천연 추출물인 관계로 다른 합성 의약품에 비하여 부작용의 우려가 없다. 실제로 본 발명의 조성물을 마우스에 적정투여농도의 3배 이상인 5g/kg/day 이상을 투여하여도 체중의 감소 또는 사망 등 어떠한 부작용도 나타나지 않았으므로, 본 발명의 조성물은 섭취량에 관계없이 체내에 아주 안전한 상태에서 흡수되는 것으로 보인다.Since the composition of the present invention is a natural extract when administered to a human body, there is no fear of side effects compared to other synthetic pharmaceuticals. Indeed, even when the composition of the present invention was administered to mice over 5 g / kg / day, which is three times higher than the proper dose, no side effects such as weight loss or death were observed. It appears to be absorbed in a safe state.
이하 본 발명의 조성물의 제조방법에 대해 설명한다.Hereinafter, a method for preparing the composition of the present invention will be described.
본 발명의 조성물 제조시 버섯 추출물은, 버섯 배양용 배지에 선택된 종의 버섯 종균을 접종하고, 적절한 온도 및 습도가 유지되는 항온조건에서 일정기간 동안 배양한 후 균사체를 수확하여 멸균 건조하고 열수추출하여 얻는다.Mushroom preparation during the preparation of the composition of the present invention, inoculated mushroom seed of the selected species in the culture medium for culture, incubated for a certain period of time at constant temperature and humidity is maintained, the mycelium is harvested by sterilization drying and hot water extraction Get
버섯을 배양할 배지는 밀에 배양한 펠리누스 바우미의 경우 삶은 밀, 헤리시움 에리나세우스의 경우 삶은 보리를 사용하는 것이 바람직하다.The medium for cultivating mushrooms is boiled wheat in the case of Felinus Baumi cultured in wheat, and boiled barley in the case of Hersidium erynasus.
열수추출시 건조된 균사체와 추출에 사용할 증류수의 사용비율은 완전 건조된 균사체 시료 80g에 대해 500㎖의 증류수를 사용하는 것이 바람직하며, 열수추출시간은 6∼10시간 정도인 것이 바람직하다. The use ratio of the dried mycelium and distilled water to be used for extracting hot water is preferably 500 ml of distilled water for 80 g of the completely dried mycelium sample, and the hot water extraction time is preferably about 6 to 10 hours.
각 버섯들의 열수추출시 온도는 일정하게 유지시키고 수분의 증발은 최대한 억제하여 가장 안정된 조건에서 추출이 이루어지도록 한다.When extracting the hot water of each mushroom, the temperature is kept constant and the evaporation of moisture is suppressed as much as possible, so that extraction is performed under the most stable conditions.
본 발명의 조성물 제조시 옥수수는 115℃ 정도의 고온에서 멸균한 후 건조하여 분말을 얻는다.Corn in the preparation of the composition of the present invention is sterilized at a high temperature of about 115 ℃ and dried to obtain a powder.
상기와 같이 준비한 펠리누스 바우미 배양물의 열수 추출물 50∼70 중량%, 헤리시움 에리나세우스 배양물의 열수 추출물 10∼30 중량%, 옥수수 분말 10∼30 중량%를 혼합하여, 그대로 사용하거나 또는 필요에 따라 적절한 용매에 녹여 사용한다.50 to 70% by weight of the hydrothermal extract of the Felinus Baumi culture prepared as described above, 10 to 30% by weight of the hydrothermal extract of Herridium erinaceus culture, 10 to 30% by weight of the corn powder are mixed or used as necessary. Dissolve in a suitable solvent and use.
이와 같이 제조된 본 발명의 조성물은 우수한 뇌기능 활성화 및 보호 효과를 나타내면서도 부작용을 나타내지 않기 때문에, 성장기 어린이나 수험생을 위한 건강보조식품을 비롯하여 치매 치료용 의약품 등의 다양한 목적으로 사용될 수 있다.The composition of the present invention prepared as described above can be used for a variety of purposes, such as pharmaceutical products for the treatment of dementia, including dietary supplements for growing children or examinees because they do not show side effects while showing excellent brain function activation and protective effect.
이하, 실시예에서 본 발명을 보다 상세히 설명하되, 하기 실시예에 의해 본 발명의 범위가 국한되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited by the following Examples.
[제조실시예] 본 발명의 조성물 제조Preparation Example Preparation of Composition of the Invention
본 발명의 조성물을 다음과 같이 제조하였다.The composition of the present invention was prepared as follows.
펠리누스 바우미를 통밀에 접종하고 21∼26 , 70∼80% 의 습도가 유지되는 항온조건에서 약 60일간 배양하였다. 배양된 균사체를 수확하고 건조한 후, 열수추출기를 이용하여 100℃에서 7∼9시간 동안 추출하였다. Felinus Baumi was inoculated into whole wheat and incubated for about 60 days under constant temperature conditions of 21-26, 70-80% humidity. The cultured mycelium was harvested and dried, and extracted for 7-9 hours at 100 ℃ using a hot water extractor.
헤리시움 에리나세우스를 쌀보리에 접종하고 21∼26 , 70∼80% 의 습도가 유지되는 항온조건에서 약 30일간 배양한다. 배양된 균사체는 수확하고 건조 후 열수추출기를 이용하여 100℃에서 7∼9시간 동안 추출하였다. Herein is inoculated with erythium erynasus and incubated for about 30 days at constant temperature maintaining humidity of 21-26, 70-80%. The cultured mycelium was harvested and dried for 7-9 hours at 100 ℃ using a hot water extractor.
각 버섯들의 열수추출시 온도는 일정하게 유지시켰으며 수분의 증발은 최대한 억제하여 가장 안정된 조건에서 추출이 이루어지도록 하였다.The temperature of each mushroom was maintained at a constant temperature and the evaporation of moisture was restrained as much as possible to ensure extraction under the most stable conditions.
옥수수는 115℃에서 50분 동안 멸균한 후 건조하여 분말을 얻었다.Corn was sterilized at 115 ° C. for 50 minutes and then dried to obtain a powder.
상기와 같이 준비한 펠리누스 바우미의 열수 추출물, 헤리시움 에리나세우스의 열수 추출물, 옥수수 분말을 6:2:2의 비율로 혼합하여 본 발명의 조성물을 제조하였다.A hydrothermal extract of Felinus Baumi, a hydrothermal extract of Hersidium erynasus, and corn powder prepared as described above were mixed in a ratio of 6: 2: 2 to prepare a composition of the present invention.
상기에서 제조한 본 발명의 조성물을 정상 원숭이세포, 인간 폐암세포, 인간 간암세포, 인간 위암세포에 20㎎/㎖의 농도로 첨가하여 배양한 후, MTT 분석을 통해 세포생존률을 측정하여 세포독성이 없음을 확인하였다.The composition of the present invention prepared above was cultured by adding 20 mg / ml to normal monkey cells, human lung cancer cells, human liver cancer cells, and human gastric cancer cells, and then cytotoxicity was determined by measuring cell viability through MTT analysis. It was confirmed that none.
[실시예 1] 본 발명의 조성물에 의한 아세틸콜린 에스테라제 활성 억제Example 1 Inhibition of Acetylcholine Esterase Activity by the Composition of the Present Invention
본 발명의 조성물에 의한 아세틸콜린 에스테라제 활성 억제효과를 다음과 같이 확인하였다.The inhibitory effect of acetylcholine esterase activity by the composition of the present invention was confirmed as follows.
몸무게 30∼35 g의 ICR 마우스를 각각 10 마리씩 대조군과 실험군의 두 군으로 분류하였다. 대조군에는 증류수를, 실험군군에는 상기에서 제조한 본 발명의 조성물을을 1.5/mg/day로 6주간 경구 투여하였다.ICR mice weighing 30-35 g each were divided into two groups, a control group and an experimental group. Distilled water was used as a control group, and the experimental group was orally administered to the experimental group at 1.5 / mg / day for 6 weeks.
대조군과 실험군 마우스의 대뇌(cerebrum)를 각각 적출하여, 다음과 같이 아세틸콜린 에스테라제의 활성을 측정하였다.The cerebrum of the control group and the experimental group mice were respectively extracted and the activity of acetylcholine esterase was measured as follows.
대뇌 30 ㎎을 0.3 ㎖의 완충액에 넣고 균질분쇄기(homogenizer)로 완전분쇄하여 10 ㎖의 균질분쇄액을 얻었다. 30 mg of cerebrum was added to 0.3 ml of buffer, and completely pulverized with a homogenizer to obtain 10 ml of homogeneous grinding solution.
완충액(pH 7.3) 790㎕에 기질로 ATCh(아세틸티오콜린 아이오다이드) 5mM 용액 60㎕를 첨가하고, 커플링제(coupling agent)로 DTNB(디티오니트로벤조산) 5mM 용액 120㎕를 첨가하여 약 3분간 반응(incubation)시켰다. 상기 반응액에 대조군과 투여군으로부터 얻은 뇌 추출물 10㎕를 각각 첨가하고, 415㎚에서 흡광도를 측정하였다. 정확도를 높이기 위해 5회 반복실험을 하였으며, 흡광도에 따라 아세틸콜린 에스테라제의 활성을 환산하여 그 결과를 도 1에 나타내었다.To 790 µl of buffer (pH 7.3), 60 µl of ATCh (acetylthiocholine iodide) 5 mM solution was added as a substrate, and 120 µl of DTNB (dithionitrobenzoic acid) 5 mM solution was added as a coupling agent. The reaction was incubated for a minute. 10 μl of the brain extract obtained from the control group and the administration group was added to the reaction solution, and the absorbance was measured at 415 nm. Five experiments were performed to increase the accuracy, and the results of the conversion of acetylcholine esterase activity according to absorbance are shown in FIG. 1.
그 결과, 본 발명의 조성물을 투여한 실험군은 대조군에 비해 50∼57% 아세틸콜린 에스테라제의 활성이 억제됨을 관찰할 수 있었다.As a result, the experimental group administered the composition of the present invention was observed that the activity of 50-57% acetylcholine esterase is inhibited compared to the control group.
이와 같이 본 발명의 조성물은 대뇌의 아세틸콜린 에스테라제의 활성을 효과적으로 억제하므로, 결과적으로 아세틸콜린의 유효농도를 증가시켜 대뇌의 기능을 활성화시킬 수 있다.As such, the composition of the present invention effectively inhibits the activity of acetylcholine esterase in cerebrum, and consequently increases the effective concentration of acetylcholine, thereby activating cerebral function.
[실시예 2] 본 발명의 조성물에 의한 글루타메이트 흥분성 신경독성 억제 및 그에 의한 신경세포 보호효과Example 2 Inhibition of Glutamate Excitatory Neurotoxicity by the Composition of the Present Invention and Its Neuronal Protective Effect
본 발명의 조성물에 의한 글루타메이트 흥분성 신경독성 억제 및 그에 의한 신경세포 보호효과를 다음과 같이 확인하였다.Glutamate excitatory neurotoxicity inhibition by the composition of the present invention and the neuronal protective effect thereof was confirmed as follows.
1) 대뇌피질 신경세포에서의 확인1) Confirmation in cortical neurons
태어난지 1∼2일령 ICR 마우스를 무균상태에서 대뇌를 적출한 후 멸균된 완충용액(pH 7.3)에서 세척하였다. 세척된 대뇌를 5㎖ 트립신-DMEM에 넣고 37℃에서 20분간 방치한 후, 다시 5㎖ 트립신-DMEM에 넣고 37℃에서 20분 반응시켰다. DMEM을 제거하고 5㎖의 완충용액으로 2회 조심스럽게 세척한 후, 5㎖의 10% FBS가 함유된 DMEM을 넣고 조심스럽게 10∼20번 피펫팅(pipetting)하였다.ICR mice from 1 to 2 days of age were harvested from sterile cerebrum and washed in sterile buffer (pH 7.3). The washed cerebrum was placed in 5 ml trypsin-DMEM and left at 37 ° C. for 20 minutes, and then placed in 5 ml trypsin-DMEM and reacted at 37 ° C. for 20 minutes. After removing DMEM and carefully washing twice with 5 ml of buffer, DMEM containing 5 ml of 10% FBS was added and carefully pipetting 10-20 times.
피펫팅 후 해마토사이토미터(hematocytometer)로 세포 수를 측정하고, 배지에 다이디옥시뉴클레오타이드(dideoxynucleotide)를 첨가하여 신경세포 외의 세포 증식을 억제하였다. 젤라틴 코팅된 96웰(well) 플레이트에 각 웰마다 1×104의 마우스 대뇌피질 신경세포를 넣어 배양하였다.After pipetting, the number of cells was measured by a hematocytometer, and a didioxynucleotide was added to the medium to inhibit the proliferation of extracellular neurons. 1 x 10 4 mouse cortical neurons were cultured in each well in a gelatin coated 96 well plate.
배양 5일부터 본 발명의 조성물을 3.75, 1.25, 0.42 ㎎/㎖로 24시간 동안 전처리한 후, 흥분성 신경독소인 글루타메이트를 1mM의 농도로 24시간 동안 처리하였다. 이때 생리식염수만을 처리한 대조군과, 본 발명의 조성물을 전처리하지 않고 글루타메이트만을 처리한 비교군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 2에 나타내었다.After 5 days of culture, the composition of the present invention was pretreated with 3.75, 1.25, 0.42 mg / ml for 24 hours, and then the excitatory neurotoxin glutamate was treated at a concentration of 1 mM for 24 hours. At this time, a control group treated with physiological saline only and a comparison group treated with glutamate only without pretreatment of the composition of the present invention were also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 2 the results.
그 결과, 예상된 바와 같이 글루타메이트만 투여한 비교군은 글루타메이트의 신경독성에 의해 세포사(apoptosis)가 증가하여 대조군보다 낮은 세포생존률을 나타내었다.As a result, as expected, the comparison group administered with glutamate only showed apoptosis due to neurotoxicity of glutamate, resulting in lower cell viability than the control group.
반면 본 발명의 조성물을 0.42 ㎎/㎖의 농도로 투여한 실험군은 비교군에 비해 세포생존률이 28% 정도 증가하는 것으로 나타났다. In contrast, the experimental group administered with the composition of the present invention at a concentration of 0.42 mg / ml showed a 28% increase in cell viability compared to the comparison group.
따라서 본 발명의 조성물은 글루타메이트에 의한 신경독성을 억제하여 대뇌피질 신경세포의 퇴행을 현저히 감소시킴을 알 수 있다.Therefore, the composition of the present invention can be seen to significantly reduce the degeneration of cortical neurons by inhibiting neurotoxicity by glutamate.
2) PC12 신경세포에서의 확인2) Identification in PC12 Neurons
본 발명의 조성물에 의한 글루타메이트 흥분성 신경독성 억제 및 그에 따른 PC12 신경세포 보호효과를 다음과 같이 확인하였다.Glutamate excitatory neurotoxicity inhibition by the composition of the present invention and the resulting PC12 neurons protective effect was confirmed as follows.
PC12 신경세포는 신경세포의 분화 및 보호의 연구에 사용되는 랫 아드레날 피오크로모사이토마(Rat adrenal pheochromocytoma) 세포이다.PC12 neurons are Rat adrenal pheochromocytoma cells used in the study of differentiation and protection of neurons.
젤라틴 코팅된 96 웰플레이트에 각 웰마다 1 ×104 개의 PC12 세포를 넣고 배양하였다. 배양 후 24시간부터 본 발명의 조성물을 3.75, 1.25, 0.42 ㎎/㎖로 24시간 동안 전처리한 후, 흥분성 신경독소인 글루타메이트를 1mM의 농도로 24시간 동안 처리하였다. 이때 생리식염수만을 처리한 대조군과, 본 발명의 조성물을 전처리하지 않고 글루타메이트만을 처리한 비교군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 3에 나타내었다.1 x 10 4 PC12 cells were incubated in each well in a gelatin-coated 96 well plate. After 24 hours of incubation, the composition of the present invention was pretreated with 3.75, 1.25, 0.42 mg / ml for 24 hours, and then the excitatory neurotoxin glutamate was treated at a concentration of 1 mM for 24 hours. At this time, a control group treated with physiological saline only and a comparison group treated with glutamate only without pretreatment of the composition of the present invention were also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 3 the results.
그 결과, 예상된 바와 같이 글루타메이트만 투여한 비교군은 글루타메이트의 신경독성에 의해 세포사가 증가하여 대조군보다 낮은 세포생존률을 나타내었다.As a result, as expected, the comparison group administered only glutamate showed lower cell viability than the control group due to increased cell death due to neurotoxicity of glutamate.
반면 본 발명의 조성물을 0.42 ㎎/㎖의 농도로 투여한 실험군은 비교군에 비해 세포생존률이 8% 정도 증가하는 것으로 나타났다. On the other hand, the experimental group administered with the composition of the present invention at a concentration of 0.42 mg / ㎖ appeared to increase the cell survival rate by about 8% compared to the comparison group.
따라서 본 발명의 조성물은 글루타메이트에 의한 신경독성을 억제하여 PC12 신경세포의 퇴행을 현저히 감소시킴을 알 수 있다.Therefore, it can be seen that the composition of the present invention significantly reduces the degeneration of PC12 neurons by inhibiting neurotoxicity by glutamate.
[실시예 3] 본 발명의 조성물에 의한 베타 아밀로이드 독성 억제 및 그에 의한 대뇌피질 신경세포 보호효과Example 3 Inhibition of Beta Amyloid Toxicity by the Composition of the Present Invention and Protective Effect of Cortical Neurons
본 발명의 조성물에 의한 베타 아밀로이드 독성 억제 및 그에 의한 신경세포 보호효과를 다음과 같이 확인하였다.Inhibition of beta amyloid toxicity by the composition of the present invention and thereby the neuronal protective effect was confirmed as follows.
1) 대뇌피질 신경세포에서의 확인1) Confirmation in cortical neurons
태어난지 1∼2일령된 ICR 마우스를 무균상태에서 대뇌를 적출한 후 멸균된 완충용액(pH 7.3)에서 세척하였다. 세척된 대뇌를 5㎖ 트립신 DMEM 에 넣고 37℃ 에서 20분간 방치 후, 다시 5㎖ 트립신 DMEM 에 넣고 37℃에서 20분 반응시켰다. DMEM을 제거한 후 5㎖ 완충용액으로 2회 조심스럽게 세척한 후,5㎖의 10% FBS가 함유된 DMEM을 넣고 조심스럽게 10∼20번 피펫팅하였다.ICR mice 1 to 2 days of age were harvested from the cerebrum under aseptic conditions and washed in sterile buffer (pH 7.3). The washed cerebrum was placed in 5 ml trypsin DMEM and left at 37 ° C. for 20 minutes, and then placed in 5 ml trypsin DMEM and reacted at 37 ° C. for 20 minutes. After the DMEM was removed, the solution was carefully washed twice with 5 ml of buffer solution, and then 5 ml of DMEM containing 10% FBS was added and carefully pipetted 10-20 times.
피펫팅 후 해마토사이토미터로 세포 수를 측정하고, 배지에 다이디옥시뉴클레오타이드를 첨가하여 신경세포 외의 세포 증식을 억제하였다. 젤라틴 코팅된 96웰 플레이트에 각 웰마다 1×104의 마우스 대뇌피질 신경세포를 넣어 배양하였다.After pipetting, the cell number was measured by a haematocytometer, and didioxynucleotide was added to the medium to inhibit cell proliferation outside of neurons. Each well was incubated with 1 × 10 4 mouse cortical neurons in a gelatin coated 96 well plate.
배양 5일부터 본 발명의 조성물을 3.75, 1.25, 0.42 ㎎/㎖로 24시간 동안 전처리한 후, 알츠하이머성 치매를 유발하는 베타 아밀로이드를 25mM의 농도로 24시간 동안 처리하였다. 이때 생리식염수만을 처리한 대조군과, 본 발명의 조성물을 전처리하지 않고 베타 아밀로이드만을 처리한 비교군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 4에 나타내었다.After 5 days of culture, the composition of the present invention was pretreated at 3.75, 1.25, 0.42 mg / ml for 24 hours, and then beta amyloid causing Alzheimer's dementia was treated at a concentration of 25 mM for 24 hours. At this time, a control group treated only with saline and a comparison group treated with only beta amyloid without pretreatment of the composition of the present invention were also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 4 the results.
그 결과, 예상된 바와 같이 베타 아밀로이드만 투여한 비교군은 베타 아밀로이드에 의해 세포사가 증가하여 대조군보다 낮은 세포생존률을 나타내었다.As a result, as compared with the beta amyloid-treated group as expected, the cell death was increased by beta amyloid showed a lower cell survival rate than the control group.
반면 본 발명의 조성물을 0.42 ㎎/㎖의 농도로 투여한 실험군은 비교군에 비해 세포생존률이 10% 정도 증가하는 것으로 나타났다.On the other hand, the experimental group administered with the composition of the present invention at a concentration of 0.42 mg / ㎖ showed a 10% increase in cell viability compared to the comparison group.
따라서 본 발명의 조성물은 베타 아밀로이드에 의한 세포손상을 억제하여 알츠하이머성 치매를 예방 및 치료할 수 있음을 알 수 있다.Therefore, it can be seen that the composition of the present invention can prevent and treat Alzheimer's dementia by inhibiting cell damage caused by beta amyloid.
2) PC12 신경세포에서의 확인2) Identification in PC12 Neurons
본 발명의 조성물에 의한 베타 아밀로이드 독성 억제 및 그에 의한 PC12 신경세포 보호효과를 다음과 같이 확인하였다.Inhibition of beta amyloid toxicity by the composition of the present invention and thereby the PC12 neurons protective effect was confirmed as follows.
젤라틴 코팅된 96 웰플레이트에 각 웰마다 1 ×104 개의 PC12 세포를 넣고 배양하였다. 배양 5일부터 알츠하이머성 치매를 유발하는 베타 아밀로이드를 25mM의 농도로 24시간 동안 전처리한 후, 본 발명의 조성물을 3.75, 1.25, 0.42 ㎎/㎖로 24시간 동안 처리하였다. 이때 생리식염수만을 처리한 대조군과, 본 발명의 조성물을 전처리하지 않고 베타 아밀로이드만을 처리한 비교군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 5에 나타내었다.1 x 10 4 PC12 cells were incubated in each well in a gelatin-coated 96 well plate. After beta amyloid causing Alzheimer's dementia from 24 days of culture for 24 hours at a concentration of 25mM, the composition of the present invention was treated with 3.75, 1.25, 0.42 mg / ml for 24 hours. At this time, a control group treated only with saline and a comparison group treated with only beta amyloid without pretreatment of the composition of the present invention were also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 5 the results.
그 결과, 예상된 바와 같이 베타 아밀로이드만 투여한 비교군은 베타 아밀로이드에 의해 세포사가 증가하여 대조군보다 낮은 세포생존률을 나타내었다.As a result, as compared with the beta amyloid-treated group as expected, the cell death was increased by beta amyloid showed a lower cell survival rate than the control group.
반면 본 발명의 조성물을 0.42 ㎎/㎖의 농도로 투여한 실험군은 비교군에 비해 세포생존률이 25% 정도 증가하는 것으로 나타났다.On the other hand, the experimental group administered with the composition of the present invention at a concentration of 0.42 mg / ㎖ showed a 25% increase in cell viability compared to the comparison group.
따라서 본 발명의 조성물은 베타 아밀로이드에 의한 세포손상을 억제하여 알츠하이머성 치매를 예방 및 치료할 수 있음을 알 수 있다.Therefore, it can be seen that the composition of the present invention can prevent and treat Alzheimer's dementia by inhibiting cell damage caused by beta amyloid.
[실시예 4] 본 발명의 조성물에 의한 뇌세포 분화Example 4 Brain Cell Differentiation by Compositions of the Invention
본 발명의 조성물에 의한 뇌세포 분화촉진 효과를 다음과 같이 확인하였다.The brain cell differentiation promoting effect of the composition of the present invention was confirmed as follows.
PC12 세포에 본 발명의 조성물을 0.42 ㎎/㎖의 농도로 3일동안 처리한 후, 세포 모양을 현미경으로 관찰하여 신경세포로 분화된 세포 수를 측정하였다.After PC12 cells were treated with the composition of the present invention at a concentration of 0.42 mg / ml for 3 days, the cell morphology was observed under a microscope to determine the number of cells differentiated into neurons.
도 6에 나타난 바와 같이, 본 발명의 조성물을 처리한 군에서는 PC12 세포로부터 뉴라이트(neurite)가 성장하여 뇌세포로 분화되는 것을 관찰할 수 있었다.As shown in FIG. 6, in the group treated with the composition of the present invention, it was observed that neurite grew from PC12 cells and differentiated into brain cells.
따라서 본 발명의 조성물은 뇌세포 분화를 촉진함을 알 수 있다.Therefore, it can be seen that the composition of the present invention promotes brain cell differentiation.
[실시예 5] 본 발명의 조성물과 기존의 뇌세포 보호물질 간의 효과 비교Example 5 Comparison of Effects Between the Compositions of the Present Invention and Existing Brain Cell Protective Materials
본 발명의 조성물과 기존에 뇌세포 보호물질로 알려진 상황버섯인 펠리누스 린테우스의 효과를 다음과 같이 비교하였다.The composition of the present invention was compared with the effects of Felinus linteus, a situation mushroom known as a brain cell protection substance as follows.
1) 베타 아밀로이드로부터 대뇌피질 신경세포의 보호효과 비교1) Comparison of protective effects of cortical neurons from beta amyloid
태어난지 1∼2일령 ICR 마우스를 무균상태에서 대뇌를 적출한 후 멸균된 완충용액(pH 7.3)에서 세척하였다. 세척된 대뇌를 5㎖ 트립신-DMEM에 넣고 37℃에서 20분간 방치한 후, 다시 5㎖ 트립신-DMEM에 넣고 37℃에서 20분 반응시켰다. DMEM을 제거하고 5㎖의 완충용액으로 2회 조심스럽게 세척한 후, 5㎖의 10% FBS가 함유된 DMEM을 넣고 조심스럽게 10∼20번 피펫팅(pipetting)하였다.ICR mice from 1 to 2 days of age were harvested from sterile cerebrum and washed in sterile buffer (pH 7.3). The washed cerebrum was placed in 5 ml trypsin-DMEM and left at 37 ° C. for 20 minutes, and then placed in 5 ml trypsin-DMEM and reacted at 37 ° C. for 20 minutes. After removing DMEM and carefully washing twice with 5 ml of buffer, DMEM containing 5 ml of 10% FBS was added and carefully pipetting 10-20 times.
피펫팅 후 해마토사이토미터(hematocytometer)로 세포 수를 측정하고, 배지에 다이디옥시뉴클레오타이드(dideoxynucleotide)를 첨가하여 신경세포 외의 세포 증식을 억제하였다. 젤라틴 코팅된 96웰(well) 플레이트에 각 웰마다 1×104의 마우스 대뇌피질 신경세포를 넣어 배양하였다.After pipetting, the number of cells was measured by a hematocytometer, and a didioxynucleotide was added to the medium to inhibit the proliferation of extracellular neurons. 1 x 10 4 mouse cortical neurons were cultured in each well in a gelatin coated 96 well plate.
배양 5일부터 베타 아밀로이드25-35를 25mM의 농도로 24시간 동안 전처리한 후, 각 조성물을 0.42 ㎎/㎖로 24시간 동안 처리하였다. 이때 아밀로이드만을 처리한 대조군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 7에 나타내었다.From day 5 of culture, beta amyloid 25-35 was pretreated at 25 mM for 24 hours, and then each composition was treated with 0.42 mg / ml for 24 hours. At this time, the control treated with amyloid alone was also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 7 the results.
그 결과, 본 발명의 조성물을 투여한 군은 아밀로이드 투여 대조군에 비해 세포생존률이 10% 높은 반면, 펠리누스 린테우스 투여군의 경우 아밀로이드 투여 대조군보다 세포생존률이 오히려 2% 감소하였다. As a result, the group to which the composition of the present invention was administered had a 10% higher cell survival rate than the amyloid control group, whereas the group containing Felinus linteus reduced the cell survival rate by 2% rather than the amyloid control group.
2) 글루타메이트로부터 PC12 신경세포의 보호효과2) Protective effect of PC12 neurons from glutamate
젤라틴 코팅된 96 웰플레이트에 각 웰마다 1 ×104 개의 PC12 신경세포를 넣고 배양하였다. 배양 후 24시간부터 각 조성물을 0.42 ㎎/㎖로 24시간 동안 전처리한 후, 흥분성 신경독소인 글루타메이트를 1mM의 농도로 24시간 동안 처리하였다. 이때 글루타메이트만을 처리한 대조군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 8에 나타내었다.1 x 10 4 PC12 neurons were cultured in each well in a gelatin-coated 96 well plate. After 24 hours of incubation, each composition was pretreated at 0.42 mg / ml for 24 hours, and then the excitatory neurotoxin glutamate was treated at a concentration of 1 mM for 24 hours. At this time, a control group treated with glutamate only was also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 8 the results.
그 결과, 본 발명의 조성물을 투여한 군은 글루타메이트 투여 대조군에 비해 세포생존률이 6% 높은 반면, 펠리누스 린테우스 투여군의 경우 글루타메이트 투여 대조군보다 세포생존률이 오히려 2% 감소하였다. As a result, the group to which the composition of the present invention was administered was 6% higher in cell survival than the glutamate-administered control group, but the cell survival rate was decreased by 2% compared to the glutamate-administered group in the Felinus linteus administration group.
3) 베타 아밀로이드로부터 PC12 신경세포의 보호효과3) Protective effect of PC12 neurons from beta amyloid
젤라틴 코팅된 96 웰플레이트에 각 웰마다 1 ×104 개의 PC12 신경세포를 넣고 10% FBS가 함유된 RPMI 배지에서 배양하였다. 배양 5일부터 베타 아밀로이드25-35를 25mM의 농도로 24시간 동안 전처리한 후, 각 조성물을 0.42 ㎎/㎖로 24시간 동안 처리하였다. 이때 생리식염수만을 처리한 대조군과, 본 발명의 조성물을 전처리하지 않고 베타 아밀로이드만을 처리한 비교군도 함께 준비하였다. 각 군에 대해 MTT 법으로 세포생존률을 측정한 후 그 결과를 도 9에 나타내었다.1 x 10 4 PC12 neurons were added to each well in a gelatin-coated 96 well plate and cultured in RPMI medium containing 10% FBS. From day 5 of culture, beta amyloid 25-35 was pretreated at 25 mM for 24 hours, and then each composition was treated with 0.42 mg / ml for 24 hours. At this time, a control group treated only with saline and a comparison group treated with only beta amyloid without pretreatment of the composition of the present invention were also prepared. After measuring the cell viability by the MTT method for each group is shown in Figure 9 the results.
그 결과, 본 발명의 조성물을 투여한 군은 글루타메이트 투여 대조군에 비해 세포생존률이 31% 높은 반면, 펠리누스 린테우스 투여군의 경우 글루타메이트 투여 대조군에 비해 세포생존률이 4% 높은 것으로 나타났다.As a result, the group to which the composition of the present invention was administered was 31% higher in cell survival than the glutamate-administered control group, whereas the group of Felinus linteus-administered group was 4% higher in cell survival than the glutamate-administered control group.
4) 결론4) Conclusion
본 발명의 조성물은 기존에 뇌세포 보호물질로 알려진 펠리누스 린테우스에 비해 훨씬 효과적으로 글루타메이트에 의한 흥분성 신경독성 및 베타 아밀로이드에 의한 알츠하이머성 치매를 억제할 수 있다.The composition of the present invention can more effectively suppress excitatory neurotoxicity by glutamate and Alzheimer's dementia by beta amyloid compared to Felinus linteus, which is known as a brain cell protecting substance.
이러한 효과는 본 발명의 조성물이 포함하는 펠리누스 바우미가 기존에 사용된 다른 종의 버섯인 펠리누스 린테우스에 비해 우수한 뇌세포 보호효과를 나타내기 때문일 수도 있으나, 본 발명의 조성물은 펠리누스 바우미 외에도 헤리시움 에리나세우스 및 옥수수를 함께 함유하여 상기 성분들이 복합적으로 상승작용을 일으킴으로써, 어느 한 성분만을 사용하는 경우보다 더 우수한 효과를 나타내기 때문으로 생각된다.This effect may be because the pellinus Baumi included in the composition of the present invention exhibits superior brain cell protection effect compared to the other species of mushrooms, pellinus linteus, but the composition of the present invention is in addition to the pellinus Baumi It is thought that the combination of Hersidium erythanus and corn together produces a synergistic effect of the above components, resulting in a better effect than the use of only one component.
본 발명의 조성물은 대뇌의 아세틸콜린 에스테라제의 활성을 효과적으로 억제하고, 글루타메이트에 의한 신경독성을 억제하며, 베타 아밀로이드에 의한 뇌세포손상을 억제하고, 신경세포의 재생 및 분화를 촉진하는 효과가 기존의 뇌기능 활성화 및 뇌기능 보호용 조성물에 비해 현저하게 뛰어나다.The composition of the present invention effectively inhibits the activity of acetylcholine esterase in the cerebrum, inhibits neurotoxicity by glutamate, inhibits brain cell damage by beta amyloid, and promotes regeneration and differentiation of nerve cells. It is remarkably superior to existing brain function activation and brain function protection composition.
본 발명의 조성물은 천연물들을 함유하므로 기존의 뇌기능 활성화 및 뇌기능 보호용 조성물에 비해 부작용을 나타내지 않는다. Since the composition of the present invention contains natural products, there is no side effect compared to the conventional brain function activation and brain function protection composition.
따라서 본 발명의 조성물은 성장기 어린이나 수험생을 위한 건강보조식품을 비롯하여 치매 치료용 의약품 등의 다양한 목적으로 사용될 수 있다.Therefore, the composition of the present invention can be used for a variety of purposes, such as health care foods for growing children or examinees, as well as drugs for treating dementia.
도 1은 본 발명의 조성물이 아세틸콜린 에스테라제의 활성을 억제함을 나타낸 도이다.1 is a diagram showing that the composition of the present invention inhibits the activity of acetylcholine esterase.
도 2는 본 발명의 조성물이 글루타메이트에 의한 흥분성 신경독성으로부터 대뇌피질 신경세포를 보호함을 나타낸 도이다.2 is a diagram showing that the composition of the present invention protects cerebral cortical neurons from excitatory neurotoxicity by glutamate.
도 3은 본 발명의 조성물이 글루타메이트에 의한 흥분성 신경독성으로부터 PC12 세포를 보호함을 나타낸 도이다.3 is a diagram showing that the composition of the present invention protects PC12 cells from excitatory neurotoxicity by glutamate.
도 4는 본 발명의 조성물이 베타 아밀로이드에 의한 대뇌피질 신경세포 퇴행을 억제함을 나타낸 도이다.4 is a diagram showing that the composition of the present invention inhibits cortical neuronal degeneration by beta amyloid.
도 5는 본 발명의 조성물이 베타 아밀로이드에 의한 PC12 세포 퇴행을 억제함을 나타낸 도이다.5 is a diagram showing that the composition of the present invention inhibits PC12 cell degeneration by beta amyloid.
도 6은 본 발명의 조성물이 PC12 세포의 뇌세포 분화를 유도함을 나타낸 도이다.6 is a diagram showing that the composition of the present invention induces brain cell differentiation of PC12 cells.
도 7은 본 발명의 조성물과 공지의 뇌기능 활성화 및 뇌기능 보호용 조성물의 알츠하이머성 치매 억제효과를 대뇌피질 신경세포에서 확인하고 비교하여 나타낸 도이다. Figure 7 is a diagram showing the comparison of the Alzheimer's dementia inhibitory effect of the composition of the present invention and known brain function activation and brain function protection in cerebral cortical neurons.
도 8은 본 발명의 조성물과 공지의 뇌기능 활성화 및 뇌기능 보호용 조성물의 신경세포 보호효과를 PC12 신경세포에서 확인하고 비교하여 나타낸 도이다. Figure 8 is a diagram showing the comparison of the neurons protective effect of the composition of the present invention and known brain function activation and brain function protection in the PC12 neurons.
도 9는 본 발명의 조성물과 공지의 뇌기능 활성화 및 뇌기능 보호용 조성물의 알츠하이머성 치매 억제효과를 PC12 신경세포에서 확인하고 비교하여 나타낸 도이다. Figure 9 is a diagram showing the comparison of the Alzheimer's dementia inhibitory effect of the composition of the present invention and known brain function activation and brain function protection in PC12 neurons.
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2003-0066803A KR100537954B1 (en) | 2003-09-26 | 2003-09-26 | Composition activating and protecting brain fuctions |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2003-0066803A KR100537954B1 (en) | 2003-09-26 | 2003-09-26 | Composition activating and protecting brain fuctions |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20050030738A KR20050030738A (en) | 2005-03-31 |
KR100537954B1 true KR100537954B1 (en) | 2005-12-20 |
Family
ID=37386923
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR10-2003-0066803A KR100537954B1 (en) | 2003-09-26 | 2003-09-26 | Composition activating and protecting brain fuctions |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR100537954B1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101349113B1 (en) | 2012-04-19 | 2014-01-20 | 대한민국 | Pharmacological composition for dementia prevention or treatment comprising specific substance extracted from Hericium erinacium and preparation method thereof |
TWI770390B (en) * | 2019-06-13 | 2022-07-11 | 鼎赫生物科技股份有限公司 | Use of a Hericium erinaceus solid-state culture extract for preparing a composition for delaying aging |
-
2003
- 2003-09-26 KR KR10-2003-0066803A patent/KR100537954B1/en not_active IP Right Cessation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101349113B1 (en) | 2012-04-19 | 2014-01-20 | 대한민국 | Pharmacological composition for dementia prevention or treatment comprising specific substance extracted from Hericium erinacium and preparation method thereof |
TWI770390B (en) * | 2019-06-13 | 2022-07-11 | 鼎赫生物科技股份有限公司 | Use of a Hericium erinaceus solid-state culture extract for preparing a composition for delaying aging |
Also Published As
Publication number | Publication date |
---|---|
KR20050030738A (en) | 2005-03-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Marques et al. | Paullinia cupana: a multipurpose plant–a review | |
US20010006983A1 (en) | Multicomponent biological vehicle | |
KR101687982B1 (en) | Composition for improving sexual functionality having effects of increasing of the number of sperm and protection of environmental hormone and manufacturing method thereof | |
KR101576887B1 (en) | Composition comprising extract of Dendropanax morbifera Lev. for the treatment and prevention of diseases caused by heavy metal poisoning | |
US7514104B2 (en) | Composition containing an extract of pericarpium zanthoxyli for protecting brain cells and improving memory | |
US20110160136A1 (en) | Polyphenols for the treatment of cartilage disorders | |
KR101093998B1 (en) | Functional composition for the prevention of hangover and improving liver function | |
KR20210064915A (en) | Composition for improving muscle function, comprising grub extract | |
KR101447760B1 (en) | Dietary and pharmaceutical compositions comprising a sage extract containing a mixture of tricyclic diterpenes and their derivatives and their uses | |
KR101045279B1 (en) | Composition of functional food with weight loss effect | |
KR20180117251A (en) | Fermentative product of Sagunjatang having brain neuron cell-protective activity and uses thereof | |
KR100537954B1 (en) | Composition activating and protecting brain fuctions | |
JP5403320B2 (en) | Degreasing inhibitor, β-hexosaminidase release inhibitor, antiallergic agent and anti-inflammatory agent obtained from natural extract | |
KR20180137971A (en) | Composition of the hot water extract of Dendropanax morbiferus Lev. having anti-apoptotic activity for preventing and treating of neurodegenerative diseases | |
KR102634302B1 (en) | Composition for preventing or treating cognitive impairment comprising extract of iris lactea | |
KR100690071B1 (en) | Functional composition for the prevention and improvement of hangover | |
US8128969B2 (en) | Hypoglycemic composition containing acacia bark derivative | |
KR102517948B1 (en) | Pharmaceutical composition and health functional food for prevention or treatment of obesity containing complex medicinal herb extracts | |
KR102641021B1 (en) | A composition for prevention and treatment of osteoporosis comprising extract from wheat bran | |
KR102323577B1 (en) | Composition for preventing or treating depression comprising mixed extract of Dioscorea nipponica Makino and Prickly Pear | |
EP2052730B1 (en) | Composition for preventing and/or treating tumor containing component originating in the bark of tree belonging to the genus acacia | |
KR20090042839A (en) | Composition for preventing and/or treating itching containing component originating in the bark of tree belonging to the genus acacia | |
KR20100030403A (en) | A composition for reducing sleep induction time and prolonging sleeping time, and a method for preparing the same | |
KR20220168782A (en) | A composition for prevention and treatment of osteoporosis comprising extract from Finger1ho | |
KR20220170316A (en) | Health supplement that induces brain cell protective effect to prevent and treat degenerative diseases and enhance memory |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20111213 Year of fee payment: 7 |
|
LAPS | Lapse due to unpaid annual fee |