CN114539092B - Oat bran phenolic amide alkaloid, preparation method thereof and application thereof in preparation of antipruritic products - Google Patents
Oat bran phenolic amide alkaloid, preparation method thereof and application thereof in preparation of antipruritic products Download PDFInfo
- Publication number
- CN114539092B CN114539092B CN202210248498.8A CN202210248498A CN114539092B CN 114539092 B CN114539092 B CN 114539092B CN 202210248498 A CN202210248498 A CN 202210248498A CN 114539092 B CN114539092 B CN 114539092B
- Authority
- CN
- China
- Prior art keywords
- oat bran
- amide alkaloid
- phenolic
- alkaloid
- phenol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229940038580 oat bran Drugs 0.000 title claims abstract description 99
- -1 phenolic amide alkaloid Chemical class 0.000 title claims abstract description 93
- 230000001139 anti-pruritic effect Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000003908 antipruritic agent Substances 0.000 title claims abstract description 8
- 229930013930 alkaloid Natural products 0.000 title abstract description 70
- 239000000203 mixture Substances 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims description 13
- 239000002537 cosmetic Substances 0.000 claims description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract description 30
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 abstract description 18
- 238000003756 stirring Methods 0.000 abstract description 16
- 238000006243 chemical reaction Methods 0.000 abstract description 13
- 239000007821 HATU Substances 0.000 abstract description 9
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical class OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 abstract description 9
- 230000008034 disappearance Effects 0.000 abstract description 8
- 238000001704 evaporation Methods 0.000 abstract description 8
- 238000010898 silica gel chromatography Methods 0.000 abstract description 8
- 239000002904 solvent Substances 0.000 abstract description 8
- 150000001408 amides Chemical class 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000012544 monitoring process Methods 0.000 abstract description 2
- 208000003251 Pruritus Diseases 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 210000003491 skin Anatomy 0.000 description 17
- 229940126214 compound 3 Drugs 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 13
- 235000007319 Avena orientalis Nutrition 0.000 description 11
- 244000075850 Avena orientalis Species 0.000 description 10
- NTQVODZUQIATFS-WAUHAFJUSA-N (2s)-2-[[(2s)-6-amino-2-[[2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-methylbutanoic acid Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NTQVODZUQIATFS-WAUHAFJUSA-N 0.000 description 9
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 9
- 101710121435 Proteinase-activated receptor 2 Proteins 0.000 description 9
- 150000003797 alkaloid derivatives Chemical class 0.000 description 9
- 230000007803 itching Effects 0.000 description 9
- 108090000978 Interleukin-4 Proteins 0.000 description 8
- 102000004388 Interleukin-4 Human genes 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000002757 inflammatory effect Effects 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 7
- IDUUXROOZBOOPH-QHHAFSJGSA-N 2-{[(2E)-3-(3,4-dihydroxyphenyl)-1-hydroxyprop-2-en-1-ylidene]amino}-5-hydroxybenzoic acid Chemical group OC(=O)C1=CC(O)=CC=C1NC(=O)\C=C\C1=CC=C(O)C(O)=C1 IDUUXROOZBOOPH-QHHAFSJGSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 229960000520 diphenhydramine Drugs 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 229930190481 Avenanthramide Natural products 0.000 description 5
- 229940125898 compound 5 Drugs 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- 108090000193 Interleukin-1 beta Proteins 0.000 description 4
- 102000003777 Interleukin-1 beta Human genes 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
- 210000003630 histaminocyte Anatomy 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102100024304 Protachykinin-1 Human genes 0.000 description 3
- 101800003906 Substance P Proteins 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 210000000447 Th1 cell Anatomy 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- VTNULXUEOJMRKZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2H-tetrazol-5-ylmethyl)benzamide Chemical compound N=1NN=NC=1CNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O VTNULXUEOJMRKZ-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 241000209761 Avena Species 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101001033286 Mus musculus Interleukin-1 beta Proteins 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 101150033824 PAA1 gene Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010048222 Xerosis Diseases 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940119744 dextran 40 Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002366 mineral element Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- PCMORTLOPMLEFB-ONEGZZNKSA-N sinapic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-ONEGZZNKSA-N 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- NGSWKAQJJWESNS-ZZXKWVIFSA-N trans-4-coumaric acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/42—Amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/10—General cosmetic use
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to the technical field of pharmaceutical chemistry, and particularly discloses an oat bran phenol amide alkaloid, a preparation method thereof and application thereof in preparing antipruritic products. The oat bran phenolic amide alkaloid has a structure shown in a formula I or a formula II. The preparation method of the oat bran phenolic amide alkaloid specifically comprises the following steps: taking a reaction substrate caffeic acid analogue, adding an organic solvent, adding 4- (2-aminoethyl) phenol and triethylamine under stirring, and adding HATU after 3-6 minutes; after the addition is finished, continuing to react for 3 to 6 hours at room temperature, and monitoring the disappearance of the reaction raw materials by TLC; stopping stirring, evaporating the solvent under reduced pressure, and purifying the residue by silica gel column chromatography to obtain the oat bran phenolic amide alkaloid. Researches show that the oat bran phenolic amide alkaloid or the composition thereof has excellent antipruritic effect; thus, the oat bran amide alkaloids or compositions thereof may be used for developing antipruritic products.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemistry, in particular to oat bran phenol amide alkaloid, a preparation method thereof and application thereof in preparing antipruritic products.
Background
Cutaneous pruritus is the most common skin disorder of the elderly, and antihistamines are common drugs for clinically treating cutaneous pruritus. The balance of Th1/Th2 cells is closely related to abnormal expression of inflammatory factors of patients with cutaneous pruritus, and abnormal expression of Th1 cell factors with obviously increased inflammatory factors is found to play an important role in the etiology of cutaneous pruritus in a rat model of atopic dermatitis, so that the anti-inflammatory therapeutic agent has a good effect on clinical curative effects of cutaneous pruritus.
The traditional Chinese medicine has long history of treating skin diseases, has rich experience, can control recurrent skin diseases or prolong the recurrence time of the recurrent skin diseases, lightens or avoids the side effect of chemical medicines, delays the lesion progress and prolongs the survival time, so the trend of pursuing the traditional Chinese medicine with stable curative effect, safety and reliability is more obvious.
Oats are one of the major cereals worldwide and are recognized by the U.S. FDA as functional foods as an important source of proteins, vitamins and various mineral elements. Studies have shown that oat is rich in a variety of active ingredients, wherein avenanthramides are the main functional ingredients in oat, and have the functions of reducing blood fat, reducing blood sugar, reducing blood pressure and the like, which are all related to the antioxidation effect. In addition, avenanthramides can mediate inflammatory cell responses through interactions with cytokines and signaling pathways, have anti-inflammatory and antibacterial effects, and colloidal extracts containing avenanthramides have demonstrated antihistaminic and anti-inflammatory activity. Oat alkaloids have a variety of biological activities and are very beneficial to human and animal health. And the oat alkaloid has a single structure, and the application is greatly limited by factors such as low content of oat. Therefore, the improvement and optimization are carried out based on the avenanthramide structure, the synthesis of the analogues with the avenanthramide structure or the avenanthramide compounds with better activity is carried out, and the development of the avenanthramide analogues with anti-skin itch has important application value.
Disclosure of Invention
In view of the above, the invention firstly provides an oat bran phenolic amide alkaloid with a brand new structure, and researches show that the oat bran phenolic amide alkaloid has an antipruritic effect.
The detailed technical scheme of the invention is as follows:
an oat bran phenolic amide alkaloid having a structure of formula I or formula ii:
wherein R in formula I or I 1 、R 2 And R is 3 Are respectively and independently selected from H, OH or OCH 3 。
Preferably, the oat bran phenolic amide alkaloid is selected from any one of oat bran phenolic amide alkaloids-1-6; the structural formula of the oat bran phenolic amide alkaloid-1-6 is as follows:
the inventors have found in the study that R in the compound of the formula I or the structure of the formula II 1 、R 2 And R is 3 Oat bran phenolic amide alkaloids obtained after substitution by different groups, the antipruritic effect of which is greatly different; the inventor surprisingly found in the research that the itching relieving effect of the oat bran amide alkaloid-3 is far greater than that of other compounds, and has very remarkable itching relieving effect; its antipruritic effect is also remarkably highMixing the known avenanthramide with diphenhydramine as positive control drug; significant technical advances are made.
The present invention also provides a composition comprising oat bran phenolic amide alkaloid-3 and oat bran phenolic amide alkaloid-4; wherein, the weight ratio of the oat bran phenolic amide alkaloid-3 to the oat bran phenolic amide alkaloid-4 is 1-5:1;
further preferably, the weight ratio of oat bran phenolic amide alkaloid-3 to oat bran phenolic amide alkaloid-4 is 2-4:1;
most preferably, the weight ratio of oat bran phenolic amide alkaloid-3 to oat bran phenolic amide alkaloid-4 is 3:1.
The inventors have surprisingly found in further studies that: a synergistic antipruritic effect may be produced without any combination of the compounds; however, when oat bran phenol amide alkaloid-3 and oat bran phenol amide alkaloid-4 are combined, the oat bran phenol amide alkaloid-3 and oat bran phenol amide alkaloid-4 can generate synergistic itching relieving effect, and the itching relieving effect is obviously higher than that of the oat bran phenol amide alkaloid-3 or the oat bran phenol amide alkaloid-4.
The invention also provides a preparation method of the oat bran phenolic amide alkaloid, which is prepared from caffeic acid analogues and 4- (2-amino ethyl) phenol as raw materials;
the caffeic acid analogues have the following structures:
wherein R is 1 、R 2 、R 3 Independently selected from H, OH or OCH 3 。
Preferably, the molar ratio of caffeic acid analog to 4- (2-aminoethyl) phenol is 1:1-3.
Preferably, the reaction substrate caffeic acid analogue is taken, an organic solvent is added, 4- (2-amino ethyl) phenol and triethylamine are added under stirring, and HATU is added after 3-6 minutes; after the addition is finished, continuing to react for 3 to 6 hours at room temperature, and monitoring the disappearance of the reaction raw materials by TLC; stopping stirring, evaporating the solvent under reduced pressure, and purifying the residue by silica gel column chromatography to obtain the oat bran phenolic amide alkaloid.
Preferably, the organic solvent, triethylamine and the reaction substrate caffeic acid analogue are used in a ratio of 30-60 mL:5-6 mL:4.5-5.0 g:1g.
Most preferably, the organic solvent, triethylamine and HATU are used in a ratio of 40ml to 5.5ml to 4.85g to 1g reaction substrate caffeic acid analog.
The invention also provides application of the compound or the composition in preparing antipruritic products; the product comprises a medicine, a skin care product or a cosmetic.
Preferably, the itch is one caused by dermatitis, burns, eczema, urticaria, xerosis cutis, superficial fungal infections or psoriasis.
Preferably, the itch is itch caused by diabetes, cholestasis, chronic kidney disease, tumor or AIDS.
The beneficial effects are that: (1) The oat bran phenolic amide alkaloid compound can obviously inhibit excessive secretion of inflammatory cytokines of skin itch mice; (2) The oat bran phenolic amide alkaloid compound can obviously reduce the scratching times of skin itching mice; (3) In particular to oat bran phenol amide alkaloid-3 and a composition formed by combining oat bran phenol amide alkaloid-3 and oat bran phenol amide alkaloid-4, wherein the anti-inflammatory and antipruritic activity of the composition is stronger than that of diphenhydramine and a known compound oat alkaloid; the oat bran amide alkaloids or compositions thereof may therefore be used for developing antipruritic products; (4) The method has the characteristics of rapid reaction, simple steps, high yield, high product purity, economy and applicability.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are only drawings of some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph of oat bran phenolic amide alkaloid compound-1 1 H-NMR spectrum.
FIG. 2 is a graph of oat bran phenolic amide alkaloid compound-1 13 C-NMR spectrum.
FIG. 3 is a oat bran phenolic amide alkaloid compound-2 1 H-NMR spectrum.
FIG. 4 is a graph of oat bran phenolic amide alkaloid compound-2 13 C-NMR spectrum.
FIG. 5 is a graph of oat bran phenolic amide alkaloid compound-3 1 H-NMR spectrum.
FIG. 6 is a graph of oat bran phenolic amide alkaloid compound-3 13 C-NMR spectrum.
FIG. 7 is a oat bran phenolic amide alkaloid compound-4 1 H-NMR spectrum.
FIG. 8 is a graph of oat bran phenolic amide alkaloid compound-5 13 C-NMR spectrum.
FIG. 9 is a graph of oat bran phenolic amide alkaloid compound-5 1 H-NMR spectrum.
FIG. 10 is a graph of oat bran phenolic amide alkaloid compound-5 13 C-NMR spectrum.
FIG. 11 is a graph of oat bran phenolic amide alkaloid compound-6 1 H-NMR spectrum.
FIG. 12 is a graph of oat bran phenolic amide alkaloid compound-6 13 C-NMR spectrum.
Detailed Description
The technical scheme of the present invention will be clearly and completely described in the following examples. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1:
preparation of oat bran phenol amide alkaloid compound-1 (abbreviated as PAA-1) compound
(E) -3- (4-hydroxy-3-methoxyphenyl) acrylic acid (1.0 g) was weighed into a 100mL clean round bottom flask, magneton was placed, 40mL anhydrous dichloromethane was added, 4- (2-aminoethyl) phenol (1.84 g) and triethylamine (5.5 mL) were added with stirring, and HATU (4.85 g) was added after 5 minutes. After the addition was completed, the reaction was continued at room temperature for 5 hours, and TLC monitored the disappearance of the starting material. Stopping stirring, evaporating solvent under reduced pressure, subjecting the residue to silica gel column chromatography (200-300 mesh), and purifying to obtain oat bran phenolic amide alkaloid compound-1. The structure is as follows:
example 2:
preparation of oat bran phenol amide alkaloid compound-2 (abbreviated as PAA-2) compound
(E) -3- (4-hydroxyphenyl) acrylic acid (1.0 g) was weighed into a 100mL clean round bottom flask, the magneton was placed in 40mL dry dichloromethane, 4- (2-aminoethyl) phenol (1.84 g) and triethylamine (5.5 mL) were added with stirring, and after 5 minutes HATU (4.85 g) was added. After the addition was completed, the reaction was continued at room temperature for 5 hours, and TLC monitored the disappearance of the starting material. Stopping stirring, evaporating solvent under reduced pressure, subjecting the residue to silica gel column chromatography (200-300 mesh), and purifying to obtain oat bran phenolic amide alkaloid compound-2. The structure is as follows:
example 3:
preparation of oat bran phenol amide alkaloid compound-3 (abbreviated as PAA-3) compound
(E) -3- (3, 4-dihydroxyphenyl) acrylic acid (1.0 g) was weighed into a 100mL clean round bottom flask, magneton was placed, 40mL anhydrous dichloromethane was added, 4- (2-aminoethyl) phenol (1.84 g) was added with stirring, triethylamine (5.5 mL) was added, and HATU (4.85 g) was added after 5 minutes. After the addition was completed, the reaction was continued at room temperature for 5 hours, and TLC monitored the disappearance of the starting material. Stopping stirring, evaporating solvent under reduced pressure, subjecting the residue to silica gel column chromatography (200-300 mesh), and purifying to obtain oat bran phenolic amide alkaloid compound-3. The structure is as follows:
example 4:
preparation of oat bran phenol amide alkaloid compound-4 (abbreviated as PAA-4) compound
(E) -3- (3, 4-dihydroxyphenyl) acrylic acid (1.0 g) was weighed into a 100mL clean round bottom flask, magneton was placed, 40mL anhydrous dichloromethane was added, 4- (2-aminoethyl) phenol (1.84 g) was added with stirring, triethylamine (5.5 mL) was added, and HATU (4.85 g) was added after 5 minutes. After the addition was completed, the reaction was continued at room temperature for 5 hours, and TLC monitored the disappearance of the starting material. Stopping stirring, evaporating solvent under reduced pressure, subjecting the residue to silica gel column chromatography (200-300 mesh), and purifying to obtain oat bran phenolic amide alkaloid compound-4. The structure is as follows:
example 5:
preparation of oat bran phenol amide alkaloid compound-5 (abbreviated as PAA-5) compound
(E) -3- (4-hydroxy-3-methoxyphenyl) acrylic acid (1.0 g) was weighed into a 100mL clean round bottom flask, magneton was placed, 40mL anhydrous dichloromethane was added, 4- (2-aminoethyl) -2-methoxyphenyl (1.84 g) was added with stirring, triethylamine (5.5 mL) was added after 5 minutes, HATU (4.85 g). After the addition was completed, the reaction was continued at room temperature for 5 hours, and TLC monitored the disappearance of the starting material. Stopping stirring, evaporating solvent under reduced pressure, subjecting the residue to silica gel column chromatography (200-300 mesh), and purifying to obtain oat bran phenolic amide alkaloid compound-5. The structure is as follows:
example 6:
preparation of oat bran phenol amide alkaloid compound-6 (abbreviated as PAA-6) compound
(E) -3- (4-hydroxy-3, 5-dimethoxyphenyl) acrylic acid (1.0 g) was weighed into a 100mL clean round bottom flask, magneton was placed, 40mL anhydrous dichloromethane was added, 4- (2-aminoethyl) phenol (1.84 g) and triethylamine (5.5 mL) was added with stirring, and HATU (4.85 g) was added after 5 minutes. After the addition was completed, the reaction was continued at room temperature for 5 hours, and TLC monitored the disappearance of the starting material. Stopping stirring, evaporating solvent under reduced pressure, subjecting the residue to silica gel column chromatography (200-300 mesh), and purifying to obtain oat bran phenolic amide alkaloid compound-6. The structure is as follows:
experimental example:
the invention uses a mouse skin itch model inhibition experiment to prove that the oat bran phenol amide alkaloid compound and the composition have itching relieving activity. The content of IL-1 beta, IL-4, PAR-2 and P substances in serum is detected by an ELISA method.
The oat bran phenol amide alkaloid compound and the antipruritic activity of the composition
Kunming mice, SPF grade, male, body weight (35+ -2) g, constant temperature (20+ -2) deg.C, humidity 40% -70%, feeding environment for 12h (7:00-19:00) of light rhythm, free feeding, and adaptive feeding for 1 week. The mice are randomly divided into a normal group, a skin itch model group, a diphenhydramine group, an oat alkaloid group, an oat bran phenol amide alkaloid compound-1-6 groups and an oat bran phenol amide alkaloid compound composition group (the mass ratio of the oat bran phenol amide alkaloid compound-3 to the oat bran phenol amide alkaloid compound-4 is 1:1), wherein each group comprises 10 mice. After the start of the experiment, the mice of each group except the normal group were subcutaneously injected with 125/mg.kg of D-galactose injection from the cervical back of each group for 6 weeks (normal group was given the same dose of physiological saline). Starting at week 7, mice in each drug group were dosed at 0.5mg/cm 2 Is applied by 1 time in evening every day for 7 days (normal group, skin aging pruritus model group dailyThe same dose of distilled water was administered). During the experiment, the scissors on the back of the neck of the mouse shave hair, and the hair on the back of the neck is kept free.
TABLE 1 influence of oat bran phenol amide alkaloid compounds on mouse pruritus latency and pruritus frequency
Note that compared with the skin itch model group * p<0.05, ** p<0.01.
As can be seen from the experimental data in table 1, oat bran phenolic amide alkaloid compound-3 (PAA-3), which has significantly longer incubation time for pruritus in mice than other oat bran phenolic amide alkaloid compounds, as well as the known oat alkaloid and positive control drug diphenhydramine; the pruritus frequency of the oat bran phenol amide alkaloid compound is obviously less than that of other oat bran phenol amide alkaloid compounds, and the oat alkaloid and a positive control drug diphenhydramine are known. This illustrates: r in the compound of the formula I or the structure shown in the formula II 1 、R 2 And R is 3 Oat bran phenolic amide alkaloids obtained after substitution by different groups, the antipruritic effect of which is greatly different; the itching relieving effect of the oat bran phenolic amide alkaloid-3 is far greater than that of other compounds, and has very remarkable itching relieving effect; the antipruritic effect is obviously higher than that of the known oat alkaloid and the positive control drug diphenhydramine; significant technical advances are made.
As can also be seen from the experimental data in table 1, when oat bran phenol amide alkaloid-3 and oat bran phenol amide alkaloid-4 are combined, the antipruritic effect is significantly higher than that of either oat bran phenol amide alkaloid-3 or oat bran phenol amide alkaloid-4 alone; is also obviously higher than the known avenanthramide and the positive control drug diphenhydramine; this demonstrates that oat bran phenolic amide alkaloid-3 and oat bran phenolic amide alkaloid-4, when combined, produce synergistic antipruritic effects.
Furthermore, we tested the effect of oat bran phenolic amide alkaloid compound-3 (PAA-3) of the present invention on IL-1β, IL-4, PAR-2, substance P: the occurrence of cutaneous pruritus is related to immune cells (eosinophils, mast cells, etc.) and inflammatory factors (interleukins, histamine, etc.). Mast cells are widely present around the blood vessels of skin and tissues and contain inflammatory factors such as histamine, heparin, 5-hydroxytryptamine, etc., and mast cells and the above-mentioned inflammatory factors play an important role in the induction of allergies. In addition, IL-1β and IL-4 are common inflammatory factors in diseases, and PAR is a member of the G protein-coupled receptor family. PAR-2 can promote vascular endothelial leukocyte adhesion migration, promote expression and release of IL-1 and the like, and has important pro-inflammatory effect and tissue injury mediating effect. Meanwhile, PAR-2 may stimulate mast cells to secrete IL-4. Thus, after 1h of application on day 7, 0.025% low molecular dextran-40 injection was intravenously injected and after 30min, the camera recorded the mouse scratch performance. Blood is collected from eyeballs, and the mixture is centrifuged for 10min at 3000r/min, so that serum is collected, and the content of IL-1 beta, IL-4, PAR-2 and P substances in the serum is detected by an enzyme-linked immunosorbent assay.
TABLE 2 Effect of oat bran phenol amide alkaloid compound-3 on mouse IL-1 beta, IL-4
Note comparison with the normal group # p<0.05, ## p is less than 0.01; comparison with the skin itch model group * p<0.05, ** p<0.01.
TABLE 3 Effect of oat bran phenolic amide alkaloid compound-3 on mouse serum PAR-2
Note comparison with the normal group # p<0.05, ## p is less than 0.01; comparison with the skin itch model group * p<0.05, ** p<0.01.
TABLE 4 influence of oat bran phenol amide alkaloid compound-3 on mouse serum substance P
Note comparison with the normal group # p<0.05, ## p is less than 0.01; comparison with the skin itch model group * p<0.05, ** p<0.01.
As can be seen from the data in table 2, the skin itch model group showed an increased IL-1 beta significance and a decreased IL-4 significance compared to the normal group. Compared with the skin itch model group, the oat bran phenol amide alkaloid compound-3 group has obviously reduced IL-1 beta and obviously increased IL-4 after administration, which indicates that the oat bran phenol amide alkaloid compound-3 has the effect of relieving skin itch. As can be seen from the data in table 3, the skin itch model group had a significantly increased PAR-2 content compared to the normal group. After administration, compared with the skin itch model group, the content of PAR-2 in the oat bran phenolic amide alkaloid compound-3 group is obviously reduced. As can be seen from the data in table 4, the skin itch model group P was significantly elevated compared to the normal group. After administration, the oat bran phenolic amide alkaloid compound-3 group P substance was significantly reduced compared to the skin itch model group.
The deep mechanism research is explained; the oat bran phenolic amide alkaloid compound or composition may be used for relieving itching by regulating PAR-2 and substance P expression to reduce, inflammatory cytokine secretion to reduce.
The foregoing disclosure is illustrative of the preferred embodiments of the present invention, and is not to be construed as limiting the scope of the invention, as it is understood by those skilled in the art that all or part of the above-described embodiments may be practiced with equivalents thereof, which fall within the scope of the invention as defined by the appended claims.
Claims (2)
1. A composition comprising oat bran phenolic amide alkaloid-3 and oat bran phenolic amide alkaloid-4; wherein, the weight ratio of the oat bran phenolic amide alkaloid-3 to the oat bran phenolic amide alkaloid-4 is 1:1;
the structural formulas of oat bran phenol amide alkaloid-3 and oat bran phenol amide alkaloid-4 are as follows:
oat bran phenolic amide alkaloid-3;
oat bran phenolic amide alkaloid-4.
2. Use of the composition of claim 1 for the preparation of an antipruritic product; the product comprises a medicament or a cosmetic.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210248498.8A CN114539092B (en) | 2022-03-14 | 2022-03-14 | Oat bran phenolic amide alkaloid, preparation method thereof and application thereof in preparation of antipruritic products |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210248498.8A CN114539092B (en) | 2022-03-14 | 2022-03-14 | Oat bran phenolic amide alkaloid, preparation method thereof and application thereof in preparation of antipruritic products |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114539092A CN114539092A (en) | 2022-05-27 |
CN114539092B true CN114539092B (en) | 2023-11-17 |
Family
ID=81663491
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210248498.8A Active CN114539092B (en) | 2022-03-14 | 2022-03-14 | Oat bran phenolic amide alkaloid, preparation method thereof and application thereof in preparation of antipruritic products |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114539092B (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101401850A (en) * | 2008-11-11 | 2009-04-08 | 江西本草天工科技有限责任公司 | Piper hancei total alkaloid extract and uses thereof |
KR101310980B1 (en) * | 2013-02-18 | 2013-09-25 | 주식회사 내추럴솔루션 | The cosmetics and functional food composition for improving anti-oxidant, anti-inflammatory and anti-wrinkling containing lycium chinense mill stem extracts |
CN103508919A (en) * | 2012-06-25 | 2014-01-15 | 复旦大学 | Alkaloid compound and use of the same in preparation of anti-complement drugs |
CN107805257A (en) * | 2017-09-12 | 2018-03-16 | 烟台大学 | A kind of capsule of weeping forsythia alkaloid extract and its preparation method and application |
CN115417788A (en) * | 2022-08-31 | 2022-12-02 | 中国人民解放军空军军医大学 | Anti-inflammatory compound and preparation method and application thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2892923B1 (en) * | 2005-11-08 | 2009-01-16 | Engelhard Lyon Sa | USE OF PARA-COUMARIC OR PARA-HYDROXYCINNAMIC ACID DERIVATIVES IN COSMETIC OR DERMATOLOGICAL COMPOSITIONS. |
US20200289458A1 (en) * | 2017-09-22 | 2020-09-17 | Inmed Pharmaceuticals Inc. | Topical formulations of cannabinoids and use thereof in the treatment of pain |
-
2022
- 2022-03-14 CN CN202210248498.8A patent/CN114539092B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101401850A (en) * | 2008-11-11 | 2009-04-08 | 江西本草天工科技有限责任公司 | Piper hancei total alkaloid extract and uses thereof |
CN103508919A (en) * | 2012-06-25 | 2014-01-15 | 复旦大学 | Alkaloid compound and use of the same in preparation of anti-complement drugs |
KR101310980B1 (en) * | 2013-02-18 | 2013-09-25 | 주식회사 내추럴솔루션 | The cosmetics and functional food composition for improving anti-oxidant, anti-inflammatory and anti-wrinkling containing lycium chinense mill stem extracts |
CN107805257A (en) * | 2017-09-12 | 2018-03-16 | 烟台大学 | A kind of capsule of weeping forsythia alkaloid extract and its preparation method and application |
CN115417788A (en) * | 2022-08-31 | 2022-12-02 | 中国人民解放军空军军医大学 | Anti-inflammatory compound and preparation method and application thereof |
Non-Patent Citations (3)
Title |
---|
Characterization and profiling of phenolic amides from Cortex Lycii by ultra-high performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry;Jingxian Zhang等;《Analytical and bioanalytical chemistry》;第407卷;第581-595页 * |
Cinnamoylphenethylamine 1H-NMR chemical shifts: a concise reference for ubiquitous compounds;Pedersen, Hans A等;《Natural Product Communications》;第05卷(第08期);第1259-1262页 * |
Effect of cinnamamides on atopic dermatitis through regulation of IL-4 in CD4+ cells;Choi, E. J等;《Journal of Enzyme Inhibition and Medicinal Chemistry》;第34卷(第01期);第613-619页 * |
Also Published As
Publication number | Publication date |
---|---|
CN114539092A (en) | 2022-05-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3114895B2 (en) | Pharmaceutical preparations for the treatment of inflammatory diseases | |
EP2878305A1 (en) | Pharmaceutical composition for preventing or treating stat3-mediated disease, comprising salvia plebeia r. br. extract or fraction thereof as active ingredientcomposition pharmaceutique pour la prévention ou le traitement de maladies médiées par stat-3, contenant un extrait ou une fraction de salvia plebeia r. br. en tant que principe actif | |
Chen et al. | The protective effects of 18β-Glycyrrhetinic acid on Imiquimod-Induced psoriasis in mice via suppression of mTOR/STAT3 signaling | |
KR101510936B1 (en) | Composition comprising extract of Martensia bibarii for prevention and treatment of autoimmune disease or inflammatory disease | |
CN114539092B (en) | Oat bran phenolic amide alkaloid, preparation method thereof and application thereof in preparation of antipruritic products | |
WO2018175334A1 (en) | Compositions and methods for skin treatments | |
KR101514257B1 (en) | Pharmaceutical Composition and Quasi-Drug Cosmetic Using Same | |
JP5923375B2 (en) | CGRP response promoter | |
ES2941463T3 (en) | Compositions for the treatment of atopic dermatitis | |
JP2007031302A (en) | Adiponectin production accelerator and metabolic syndrome preventive | |
US9540378B2 (en) | Composition comprising purine derivatives or salt thereof for preventing or treating atopic dermatitis | |
JP4381495B2 (en) | MCP-1 receptor antagonist comprising organic germanium compound as active ingredient, and preventive or therapeutic agent for inflammatory disease and organ disorder involving MCP-1 | |
AU2017346183B2 (en) | Composition for preventing or treating psoriasis containing monoacetyl diacylglycerol compound | |
JP2010202569A (en) | Antiallergic and anti-inflammatory composition | |
JP2020117488A (en) | Method for treating inflammatory disorder | |
JP7396585B2 (en) | Composition for suppressing TSLP gene expression, suppressing IL-33 gene expression, or promoting filaggrin production | |
KR101606885B1 (en) | Pharmaceutical composition for preventing and treating allergic disease comprising adenine or pharmaceutically acceptable salt thereof as an active ingredient | |
KR20010086473A (en) | Composition of essential oil having an inhibitary activity on the formation of leucotriens | |
KR102532055B1 (en) | Composition comprising dihydrofuran-2-one derivative for treating inflammatory disease | |
WO2024050434A1 (en) | ISOQUINOLINE COMPOUNDS AND THEIR USE IN TREATING AhR MEDIATED DISEASES | |
TW202408482A (en) | Plectranthus amboinicus extract for use in inhibiting immune responses | |
CN115381818A (en) | Method for promoting autophagy degradation function of cells and application | |
WO2013085346A1 (en) | Novel phytosphingosine derivatives, and composition comprising same for preventing and treating inflammatory skin diseases, autoimmune diseases, and hyperkeratosis diseases | |
CN117482104A (en) | Application of astragalus polysaccharide as programmed necrosis inhibitor | |
JP2015054832A (en) | Filaggrin production promoter |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |