CN112851774A - 一种多肽片段b及其应用 - Google Patents
一种多肽片段b及其应用 Download PDFInfo
- Publication number
- CN112851774A CN112851774A CN202110145124.9A CN202110145124A CN112851774A CN 112851774 A CN112851774 A CN 112851774A CN 202110145124 A CN202110145124 A CN 202110145124A CN 112851774 A CN112851774 A CN 112851774A
- Authority
- CN
- China
- Prior art keywords
- amino acid
- polypeptide fragment
- inflammatory bowel
- bowel disease
- colon
- 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.)
- Granted
Links
- 239000012634 fragment Substances 0.000 title claims abstract description 34
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 29
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 29
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 29
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 47
- 210000001072 colon Anatomy 0.000 claims abstract description 32
- 150000001413 amino acids Chemical class 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 3
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000001575 pathological effect Effects 0.000 claims description 6
- 238000004904 shortening Methods 0.000 claims description 6
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 241000792859 Enema Species 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000007920 enema Substances 0.000 claims description 2
- 229940095399 enema Drugs 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 235000013373 food additive Nutrition 0.000 claims description 2
- 239000002778 food additive Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 27
- 238000010172 mouse model Methods 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000011161 development Methods 0.000 abstract description 2
- 102000008070 Interferon-gamma Human genes 0.000 abstract 1
- 108010074328 Interferon-gamma Proteins 0.000 abstract 1
- 229960003130 interferon gamma Drugs 0.000 abstract 1
- NSFBOCKFBVQQKB-CQWNSWRRSA-N mastoparan-B Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(C)C)[C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)=CNC2=C1 NSFBOCKFBVQQKB-CQWNSWRRSA-N 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 16
- 229920003045 dextran sodium sulfate Polymers 0.000 description 11
- 239000013641 positive control Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 240000006024 Lactobacillus plantarum Species 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 229940072205 lactobacillus plantarum Drugs 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- HRGGPWBIMIQANI-GUBZILKMSA-N Asp-Gln-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HRGGPWBIMIQANI-GUBZILKMSA-N 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- PYFNONMJYNJENN-AVGNSLFASA-N Lys-Lys-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PYFNONMJYNJENN-AVGNSLFASA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000000258 photobiological effect Effects 0.000 description 2
- 239000006041 probiotic Substances 0.000 description 2
- 235000018291 probiotics Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- SVBXIUDNTRTKHE-CIUDSAMLSA-N Ala-Arg-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O SVBXIUDNTRTKHE-CIUDSAMLSA-N 0.000 description 1
- YCRAFFCYWOUEOF-DLOVCJGASA-N Ala-Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 YCRAFFCYWOUEOF-DLOVCJGASA-N 0.000 description 1
- ZPWMEWYQBWSGAO-ZJDVBMNYSA-N Arg-Thr-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZPWMEWYQBWSGAO-ZJDVBMNYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- YNCHFVRXEQFPBY-BQBZGAKWSA-N Asp-Gly-Arg Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N YNCHFVRXEQFPBY-BQBZGAKWSA-N 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 1
- HVKAAUOFFTUSAA-XDTLVQLUSA-N Glu-Tyr-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O HVKAAUOFFTUSAA-XDTLVQLUSA-N 0.000 description 1
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 1
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 1
- DUAWRXXTOQOECJ-JSGCOSHPSA-N Gly-Tyr-Val Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O DUAWRXXTOQOECJ-JSGCOSHPSA-N 0.000 description 1
- FNXSYBOHALPRHV-ONGXEEELSA-N Gly-Val-Lys Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN FNXSYBOHALPRHV-ONGXEEELSA-N 0.000 description 1
- 206010020565 Hyperaemia Diseases 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
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-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
- 241000880493 Leptailurus serval Species 0.000 description 1
- ULXYQAJWJGLCNR-YUMQZZPRSA-N Leu-Asp-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O ULXYQAJWJGLCNR-YUMQZZPRSA-N 0.000 description 1
- VGPCJSXPPOQPBK-YUMQZZPRSA-N Leu-Gly-Ser Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O VGPCJSXPPOQPBK-YUMQZZPRSA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- MIMXMVDLMDMOJD-BZSNNMDCSA-N Lys-Tyr-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O MIMXMVDLMDMOJD-BZSNNMDCSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- CAODKDAPYGUMLK-FXQIFTODSA-N Met-Asn-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CAODKDAPYGUMLK-FXQIFTODSA-N 0.000 description 1
- RMLWDZINJUDMEB-IHRRRGAJSA-N Met-Tyr-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N RMLWDZINJUDMEB-IHRRRGAJSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- SXAGUVRFGJSFKC-ZEILLAHLSA-N Thr-His-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SXAGUVRFGJSFKC-ZEILLAHLSA-N 0.000 description 1
- FDQXPJCLVPFKJW-KJEVXHAQSA-N Thr-Met-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N)O FDQXPJCLVPFKJW-KJEVXHAQSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- WDGDKHLSDIOXQC-ACRUOGEOSA-N Tyr-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 WDGDKHLSDIOXQC-ACRUOGEOSA-N 0.000 description 1
- NVZVJIUDICCMHZ-BZSNNMDCSA-N Tyr-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O NVZVJIUDICCMHZ-BZSNNMDCSA-N 0.000 description 1
- OUUBKKIJQIAPRI-LAEOZQHASA-N Val-Gln-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O OUUBKKIJQIAPRI-LAEOZQHASA-N 0.000 description 1
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000010832 independent-sample T-test Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008946 inflammatory intestinal reaction Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 230000003870 intestinal permeability Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003870 salicylic acids Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/335—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Lactobacillus (G)
-
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
- C12R2001/25—Lactobacillus plantarum
Abstract
本发明属于生物医药技术领域,具体涉及一种多肽片段B及其应用,所述多肽片段B具有SEQ ID No.1所示的氨基酸序列,其中,第10位氨基酸Xaa为Arg、Phe、Glu、Thr或不存在,第16位氨基酸Xaa为Asn、Val、Leu、Gly或不存在,第25位氨基酸Xaa为Ser、Glu、Met、Arg或不存在。MP‑B显著改善了IBD小鼠模型的结肠病理性形态,降低了结肠组织病理学评分和结肠干扰素‑γ表达含量,具有干预小鼠炎症性肠病发生的能力。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种多肽片段B及其应用。
背景技术
炎症性肠病(inflammatory bowel disease,IBD)是一种特发性慢性肠道炎症性疾病,其病变主要位于结直肠段,并累及黏膜及黏膜肌层,严重的还有肝胆、肌肉皮肤及凝血方面的并发症,病情反复发作者20-30%可能转化为结直肠癌,是一种非常严重的肠道炎症性疾病,可分为溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD)两大类。目前认为,IBD是在环境、遗传、感染和免疫等多因素相互作用下,肠道黏膜固有免疫及获得免疫出现异常而导致的肠道炎性反应,肠黏膜固有层内炎症反应被认为是IBD发病机制的基石。近几十年来,IBD的发病率呈现逐年上升趋势,而传统的IBD治疗药物,如水杨酸类、类固醇激素类及免疫抑制剂等主要是减轻炎症和调节免疫紊乱,以有效控制疾病发作,但这些传统方法无法使其彻底根治,并常伴随一些严重不良反应的发生,对患者的生存质量造成严重的危害,因此,急切需要新的IBD治疗方法。
近年来,微生态制剂正逐渐成为IBD治疗的新思路,经研究发现此类制剂可改善IBD患者肠道中不同程度的菌群失调。乳酸杆菌L.plantarum是一类较为常见的益生菌,研究发现其可在肠道内通过黏附和定植作用抑制致病菌的损伤,调节免疫缺陷小鼠的肠道通透性,进而干预结肠炎的发展,而微小膜蛋白(micro integral membrane protein,MIMP)则是L.plantarum CGMCC 1258菌株分离出的能与侵袭性致病大肠埃希菌竞争性粘附于肠上皮细胞的活性多肽片段,序列为SEQ ID No.2所示:THTVGSYFSVQNGYVGAFSQALGNSEYAMNSPLGSLDGRTTMYNLLGVKYLFAREDQLKKQ,此片段能显著改善肠道的炎症状态,预防IBD小鼠肠道菌群失调。然而,因MIMP是由61个氨基酸组成的生物大分子,较大的分子量易产生免疫原性,不易成药,使其临床应用受到了限制;另外,较大分子量也不利于药物的工业化生产。从药用价值及经济利益出发,为此对MIMP进行了进一步结构修饰与改造,以提高MIMP片段的药理活性或/和成药性,进而有利于该活性片段的临床应用与经济效益。
发明内容
为了解决现有技术中对炎症性肠病具有改善作用的MIMP存在的易产生免疫原性和不易成药的缺陷,本发明的目的在于提供一种多肽片段B、药物制剂及其应用,本发明的多肽片段B能够显著改善IBD小鼠模型的病理性结肠缩短和其结肠组织病理学评分。
本发明是通过如下技术方案实现的:
本发明提供一种多肽片段B,具有SEQ ID No.1所示的氨基酸序列。
优选地,所述SEQ ID No.1所示的氨基酸序列的第10位氨基酸Xaa为Arg、Phe、Glu、Thr或不存在,第16位氨基酸Xaa为Asn、Val、Leu、Gly或不存在,第25位氨基酸Xaa为Ser、Glu、Met、Arg或不存在。
本发明还在于提供一种所述的多肽片段B在制备抗炎症性肠病药物中的应用。
本发明还在于提供一种所述的多肽片段B在制备抗炎症性肠病食品或食品添加剂中的应用。
本发明还在于提供一种所述的多肽片段B在制备抗炎症性肠病保健品中的应用。
优选地,所述多肽片段B在制备改善炎症性肠病的病理性结肠缩短的药物中的应用。
优选地,所述多肽片段B在制备降低炎症性肠病的结肠组织病理学评分的药物中的应用。
本发明还在于提供一种药物制剂,包括权利要求1所述的多肽片段B以及药学上可接受的载体、赋形剂或稀释剂。
优选地,所述药物制剂的剂型为注射剂、胶囊剂、片剂、颗粒剂、混悬剂、灌肠剂、乳剂或散剂。
相对于现有技术,本发明的有益效果为:
本发明通过葡聚糖硫酸钠(Dextran sulfate sodium,DSS)化学诱导法建立急性炎症性肠病(IBD)小鼠模型,以结肠形态学以及组织病理学的分析手段,探索多肽片段B(简称MP-B)是否对IBD小鼠模型有改善作用。研究结果表明,在与MIMP同等剂量下,多肽片段B的干预显著改善了IBD小鼠模型的结肠病理性形态,并降低了IBD小鼠模型的结肠组织病理学评分,具有可改善及干预小鼠炎症性肠病发生的能力。且MP-B片段相比于MIMP具有更小的分子量,也有利于MP-B片段的成药与应用,揭示了多肽片段B在制备预防、干预及治疗炎症性肠病活性产品中的应用潜力。
本发明所用缩写具体含义如下:
Thr为苏氨酸;His为组氨酸;Val为缬氨酸;Gly为甘氨酸;Ser为丝氨酸;Phe为苯丙氨酸;Asn为天冬酰胺;Tyr为酪氨酸;Ala为丙氨酸;Leu为亮氨酸;Glu为谷氨酸;Met为甲硫氨酸;Pro为脯氨酸;Asp为天冬氨酸;Arg为精氨酸;Lys为赖氨酸;Gln为谷氨酰胺。
附图说明
图1为模型组小鼠与空白对照组小鼠的体重变化趋势图,#P<0.05,##P<0.01,###P<0.001,与空白对照组比较,两独立样本t检验进行显著性检验;
图2为空白对照组、模型组、MIMP阳性对照组和MP-B实验组的小鼠结肠长度对比图,*P<0.05,**P<0.01,***P<0.001,与模型组比较;##P<0.01,与空白对照组比较,单因素方差分析进行显著性检验;
图3为空白对照组、模型组、MIMP阳性对照组和MP-B实验组小鼠结肠组织病理学显微图(HE染色20×镜检;A.空白对照组;B.模型组;C.MIMP阳性对照组;D.MP-B实验组);
以及E.组织病理学评分对比图(*P<0.05,**P<0.01,***P<0.001,与模型组比较;###P<0.001,与空白对照组比较,单因素方差分析进行显著性检验)。
具体实施方式
下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。以下对至少一个示例性实施例的描述实际上仅仅是说明性的,决不作为对本发明及其应用或使用的任何限制。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例中所使用的试剂、材料与设备如表1所示:
表1
名称 | 制造商 |
雄性C57BL6小鼠,清洁级 | 上海斯莱克公司(Shanghai,China) |
葡聚糖硫酸钠(DSS) | MP Biomedicals(CA,United States) |
磷酸缓冲溶液(PBS) | 上海博光生物科技有限公司(Shanghai,China) |
MIMP | 苏州强耀生物公司(Suzhou,China) |
4%多聚甲醛 | 上海博光生物科技有限公司(Shanghai,China) |
实施例1:MP-B的干预对DSS诱导小鼠炎症性肠病作用的实验
本实施例所用多肽片段B(MP-B)的序列为SEQ ID No.1所示的氨基酸序列的第10位氨基酸Xaa为Glu,第16位氨基酸Xaa为Gly,第25位氨基酸Xaa为Met时的序列,即SPLGSLDGRETMYNLGGVKYLFARMDQLKKQ。
1.实验方法
1.1急性炎症性肠病小鼠模型的建立
当给予小鼠一定浓度的DSS溶液即可诱导以腹泻、便血、溃疡、粒细胞浸润为特征的急性炎症性肠病模型。实验分组遵循随机性原则,依据小鼠的体重进行分层随机分组。将40只健康雄性C57BL6小鼠,按每组10只分成四组:
空白对照组:每天以水灌胃,灌胃体积为0.4mL/20g;
模型组:以质量分数为2.5wt%的DSS水溶液灌胃,连续饮用7天,且DSS水溶液为新鲜配制的,每隔1天更换1次;
MIMP阳性对照组:先给予小鼠一周的预给药进程,即前7天用质量分数为50μg/kg的MIMP溶液灌胃小鼠,第8天开始,每天给小鼠灌胃2.5wt%的DSS水溶液(灌胃体积为0.4mL/20g),并以质量分数为50μg/kg的MIMP溶液灌胃小鼠(灌胃体积为0.4mL/20g);
MP-B实验组:先给予小鼠一周的预给药进程,即前7天用质量分数为50μg/kg的MP-B溶液灌胃小鼠,第8天开始,每天给小鼠灌胃2.5wt%的DSS水溶液(灌胃体积为0.4mL/20g),并以质量分数为50μg/kg的MP-B溶液灌胃小鼠(灌胃体积为0.4mL/20g);
每日记录各组小鼠体重变化以确定急性炎症性肠病小鼠模型是否成功建立。
1.2样本采集
颈椎脱臼处死小鼠,将其置于手术台上,暴露腹腔,观察肠道情况,有无充血、溃疡及粘连情况出现。同时从肛门端至回盲端完整取出小鼠结肠,测量结肠长度后,将肠道沿纵轴剖开,冲洗肠道粪便,保存于4%多聚甲醇中。
1.3组织病理学评价
对步骤1.2中保存于4%多聚甲醇的结肠样本进行组织病理切片,苏木精-伊红染色、脱水后将切片密封并在光学显微镜下检查,由两名盲检人员进行组织病理学评分:
评定标准:0分,无明显炎症;1分,基底层中度炎症浸润;2分,粘膜中度增生或重度炎症浸润;3分,粘膜重度增生,杯状细胞不存在;4分,隐窝不存在或溃疡。
1.4统计学分析
上述实验方法中的实验数据以表示,使用GraphPad Prism(ver.8.0,GraphPad Software Inc.,San Diego,CA,USA)绘制图表,SPSS Program(ver.25.0,SPSSInc.,Chicago,IL,USA)进行统计学检验,符合正态性和方差齐性时采用单因素方差分析或两独立样本t检验进行显著性检验。设α=0.05,P<0.05为差异有统计学显著性。
2.实验结果分析
2.1MP-B的干预显著改善炎症性肠病小鼠的病理性结肠缩短
图1为模型组小鼠与空白对照组小鼠的体重变化趋势图,可以看出,在给予DSS诱导一周后,模型组小鼠的体重显著下降(与空白对照组比较,###P<0.001,有显著性差异),说明急性炎症性肠病小鼠模型建立成功。
图2为空白对照组、模型组、MIMP阳性对照组和MP-B实验组的小鼠结肠长度对比图,可以看出,模型组小鼠的结肠长度(5.3±0.6)与空白对照组(结肠长度9.2±0.8)相比显著缩短(###P<0.001),而MP-B实验组小鼠(结肠长度8.0±0.5)相对于模型组小鼠(结肠长度5.3±0.6)的结肠缩短有明显差异(与模型组比较,***P<0.001,有显著性差异),说明MP-B的干预可以显著逆转这种缩短,与MIMP阳性对照组(结肠长度7.6±0.5)的效果相当,改善了炎症性肠病小鼠的病理性结肠形态。
2.2MP-B的干预显著降低炎症性肠病小鼠结肠组织病理学评分
图3为空白对照组、模型组、MIMP阳性对照组和MP-B实验组小鼠结肠组织病理学显微图(HE染色20×镜检;A.空白对照组;B.模型组;C.MIMP阳性对照组;D.MP-B实验组);以及E.组织病理学评分对比图(*P<0.05,**P<0.01,***P<0.001,与模型组比较;###P<0.001,与空白对照组比较,单因素方差分析进行显著性检验)。
病理学评分:A空白对照组0.0±0.0;B.模型组7.6±0.6;MIMP阳性对照组3.1±0.2;MP-B实验组1.4±0.6。
可以看出,在结肠组织病理学评分中,MIMP和MP-B的干预均能使炎症性肠病小鼠的结肠组织学评分显著降低(***P<0.001,具有显著性差异)。病理学状况也有相应程度的改善,粘膜层上皮结构较为完整,上皮细胞形态结构正常、未见明显炎症的发生,说明MP-B的干预可改善DSS诱导所致的结肠组织粘膜层的大面积溃疡,减少了淋巴细胞与中性粒细胞的浸润,并进一步干预肠道炎症的发生。
实施例2
本实施例中所使用的试剂、材料与设备,以及实验方法均同实施例1,区别仅仅在于:本实施例所用多肽片段B(MP-B)的序列为SEQ ID No.1所示的氨基酸序列的第10位氨基酸Xaa为Arg,第16位氨基酸Xaa为Asn,第25位氨基酸Xaa为Glu时的序列,即SPLGSLDGRRTMYNLNGVKYLFAREDQLKKQ。
实施例3
本实施例中所使用的试剂、材料与设备,以及实验方法均同实施例1,区别仅仅在于:本实施例所用多肽片段B(MP-B)的序列为SEQ ID No.1所示的氨基酸序列的第10位氨基酸Xaa为Thr,第16位氨基酸Xaa为Val,第25位氨基酸Xaa为Ser时的序列,即SPLGSLDGRTTMYNLVGVKYLFARSDQLKKQ。
实施例4
本实施例中所使用的试剂、材料与设备,以及实验方法均同实施例1,区别仅仅在于:本实施例所用多肽片段B(MP-B)的序列为SEQ ID No.1所示的氨基酸序列的第10位氨基酸Xaa、第16位氨基酸Xaa和第25位氨基酸Xaa均不存在时的序列,即SPLGSLDGRTMYNLGVKYLFARDQLKKQ。
将实施例2~实施例4按照实施例1的实验方法测试后,其分析结果与实施例1的结果差异不大,说明本发明的多肽片段B的干预能够显著改善IBD小鼠模型的结肠病理性形态、降低IBD小鼠模型的结肠组织病理学评分,具有可改善及干预小鼠炎症性肠病发生的能力。
以上所述的具体实施例,对本发明的目的、技术方案和有益效果进行了进一步详细说明,所应理解的是,以上所述仅为本发明的具体实施例而已,并不用于限制本发明,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
序列表
<110> 上海珑欣生物医学科技有限公司
<120> 一种多肽片段B及其应用
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 31
<212> PRT
<213> 植物乳杆菌(Lactobacillus plantarum)
<400> 1
Ser Pro Leu Gly Ser Leu Asp Gly Arg Xaa Thr Met Tyr Asn Leu Xaa
1 5 10 15
Gly Val Lys Tyr Leu Phe Ala Arg Xaa Asp Gln Leu Lys Lys Gln
20 25 30
<210> 2
<211> 61
<212> PRT
<213> 植物乳杆菌(Lactobacillus plantarum)
<400> 2
Thr His Thr Val Gly Ser Tyr Phe Ser Val Gln Asn Gly Tyr Val Gly
1 5 10 15
Ala Phe Ser Gln Ala Leu Gly Asn Ser Glu Tyr Ala Met Asn Ser Pro
20 25 30
Leu Gly Ser Leu Asp Gly Arg Thr Thr Met Tyr Asn Leu Leu Gly Val
35 40 45
Lys Tyr Leu Phe Ala Arg Glu Asp Gln Leu Lys Lys Gln
50 55 60
Claims (9)
1.一种多肽片段B,其特征在于,具有SEQ ID No.1所示的氨基酸序列。
2.根据权利要求1所述的多肽片段B,其特征在于,所述SEQ ID No.1所示的氨基酸序列的第10位氨基酸Xaa为Arg、Phe、Glu、Thr或不存在,第16位氨基酸Xaa为Asn、Val、Leu、Gly或不存在,第25位氨基酸Xaa为Ser、Glu、Met、Arg或不存在。
3.一种权利要求1所述的多肽片段B的应用,其特征在于,在制备抗炎症性肠病药物中的应用。
4.一种权利要求1所述的多肽片段B的应用,其特征在于,在制备抗炎症性肠病食品或食品添加剂中的应用。
5.一种权利要求1所述的多肽片段B的应用,其特征在于,在制备抗炎症性肠病保健品中的应用。
6.根据权利要求3所述的应用,其特征在于,在制备改善炎症性肠病的病理性结肠缩短的药物中的应用。
7.根据权利要求3所述的应用,其特征在于,在制备降低炎症性肠病的结肠组织病理学评分的药物中的应用。
8.一种药物制剂,其特征在于,包括权利要求1所述的多肽片段B以及药学上可接受的载体、赋形剂或稀释剂。
9.根据权利要求8所述的药物制剂,其特征在于,所述药物制剂的剂型为注射剂、胶囊剂、片剂、颗粒剂、混悬剂、灌肠剂、乳剂或散剂。
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110145124.9A CN112851774B (zh) | 2021-02-02 | 2021-02-02 | 一种多肽片段b及其应用 |
PCT/CN2022/080880 WO2022166999A1 (zh) | 2021-02-02 | 2022-03-15 | 一种多肽片段b及其应用 |
US17/737,058 US20230051694A1 (en) | 2021-02-02 | 2022-05-05 | Polypeptide fragment b (mp-b) and use thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110145124.9A CN112851774B (zh) | 2021-02-02 | 2021-02-02 | 一种多肽片段b及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112851774A true CN112851774A (zh) | 2021-05-28 |
CN112851774B CN112851774B (zh) | 2022-07-26 |
Family
ID=75986356
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110145124.9A Active CN112851774B (zh) | 2021-02-02 | 2021-02-02 | 一种多肽片段b及其应用 |
Country Status (3)
Country | Link |
---|---|
US (1) | US20230051694A1 (zh) |
CN (1) | CN112851774B (zh) |
WO (1) | WO2022166999A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022166999A1 (zh) * | 2021-02-02 | 2022-08-11 | 上海珑欣生物医学科技有限公司 | 一种多肽片段b及其应用 |
WO2023138644A1 (zh) * | 2022-01-21 | 2023-07-27 | 四川好医生攀西药业有限责任公司 | 多肽化合物及其治疗肠炎的用途 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1644681A (zh) * | 2004-12-17 | 2005-07-27 | 上海交大昂立股份有限公司 | 一种植物乳杆菌及其应用 |
US20050202437A1 (en) * | 2002-08-28 | 2005-09-15 | Genesis Research And Development Corporation Limited | Polynucleotides and polypeptides, materials incorporating them and methods for using them |
CN103044532A (zh) * | 2012-08-09 | 2013-04-17 | 刘志华 | 一种具有肠上皮细胞保护功能的蛋白序列及其应用 |
CN104093733A (zh) * | 2011-09-07 | 2014-10-08 | 皇家创新有限公司 | 植物乳杆菌所分泌的具有免疫调节功能的肽 |
CN109206482A (zh) * | 2018-09-30 | 2019-01-15 | 福建蓝昊生物科技有限公司 | 一种抑制消化道炎症的海藻源短肽及其应用 |
US20200369729A1 (en) * | 2017-12-11 | 2020-11-26 | Institut Pasteur | Peptidomimetics, method of synthesis and uses thereof |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112851774B (zh) * | 2021-02-02 | 2022-07-26 | 上海珑欣生物医学科技有限公司 | 一种多肽片段b及其应用 |
-
2021
- 2021-02-02 CN CN202110145124.9A patent/CN112851774B/zh active Active
-
2022
- 2022-03-15 WO PCT/CN2022/080880 patent/WO2022166999A1/zh active Application Filing
- 2022-05-05 US US17/737,058 patent/US20230051694A1/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050202437A1 (en) * | 2002-08-28 | 2005-09-15 | Genesis Research And Development Corporation Limited | Polynucleotides and polypeptides, materials incorporating them and methods for using them |
CN1644681A (zh) * | 2004-12-17 | 2005-07-27 | 上海交大昂立股份有限公司 | 一种植物乳杆菌及其应用 |
CN104093733A (zh) * | 2011-09-07 | 2014-10-08 | 皇家创新有限公司 | 植物乳杆菌所分泌的具有免疫调节功能的肽 |
CN103044532A (zh) * | 2012-08-09 | 2013-04-17 | 刘志华 | 一种具有肠上皮细胞保护功能的蛋白序列及其应用 |
US20200369729A1 (en) * | 2017-12-11 | 2020-11-26 | Institut Pasteur | Peptidomimetics, method of synthesis and uses thereof |
CN109206482A (zh) * | 2018-09-30 | 2019-01-15 | 福建蓝昊生物科技有限公司 | 一种抑制消化道炎症的海藻源短肽及其应用 |
Non-Patent Citations (2)
Title |
---|
MINGMING YIN 等: ""Micro Integral Membrane Protein (MIMP),a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum,Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines"", 《CELLULAR PHYSIOLOGY AND BIOCHEMISTRY》 * |
屈潇 等: ""乳杆菌微小膜蛋白对肠上皮细胞Caco-2的细胞毒性研究"", 《中国微生态学杂志》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022166999A1 (zh) * | 2021-02-02 | 2022-08-11 | 上海珑欣生物医学科技有限公司 | 一种多肽片段b及其应用 |
WO2023138644A1 (zh) * | 2022-01-21 | 2023-07-27 | 四川好医生攀西药业有限责任公司 | 多肽化合物及其治疗肠炎的用途 |
Also Published As
Publication number | Publication date |
---|---|
CN112851774B (zh) | 2022-07-26 |
US20230051694A1 (en) | 2023-02-16 |
WO2022166999A1 (zh) | 2022-08-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10654895B2 (en) | Polypeptide, DNA molecule encoding the polypeptide, vector, preparation method and use | |
CN112851774B (zh) | 一种多肽片段b及其应用 | |
CN112679589B (zh) | 一种多肽片段d及其应用 | |
CN112812158B (zh) | 一种多肽片段c及其应用 | |
CN108434165B (zh) | 曲札茋苷在制备治疗和/或预防炎性肠病的药物中的应用 | |
CN114644683A (zh) | 促进肝细胞增殖和/或抑制肝细胞凋亡的多肽及其用途 | |
EP4177259A1 (en) | Polypeptide for repairing mucosal damage or skin wound and use thereof | |
CN114209808A (zh) | 一种多肽rk12用于制备治疗痤疮药物的应用 | |
CN113499426A (zh) | 一种乳源多肽在制备防治酒精性脂肪肝药物、保健品或食品添加物中的应用 | |
CN113493491A (zh) | 一种用于预防或治疗溃疡性结肠炎的多肽 | |
CN103641889A (zh) | 一种降糖肽及其药物用途 | |
CN114668775B (zh) | 纤维素衍生物在制备治疗溃疡性结肠炎药物中的应用 | |
JP6789339B2 (ja) | 急性肺傷害の予防及び改善のうち少なくともいずれかのためのコルジセプス・シケイダエ(Cordyceps cicadae)菌糸体活性物質の製造方法及び使用 | |
WO2004033484A2 (en) | Use of stable glutamine derivatives to improve drug absorption | |
CN113583098B (zh) | 一种来源于真菌的环状拟肽及其制备方法和应用 | |
CN112656794B (zh) | 吡咯喹啉醌或其盐在制备用于防治前列腺增生药物中的用途及药物组合物 | |
US11666617B2 (en) | Treatment of warts | |
CN114129705B (zh) | 一种多肽在预防和治疗肺炎的药物中的应用 | |
CN115068492B (zh) | 蒙花苷在制备预防或治疗肺纤维化的药物中的应用 | |
WO2022042590A1 (zh) | 用于修复皮肤创伤或黏膜损伤的多肽及其应用 | |
CN113198004A (zh) | 一种修复肠粘膜的凝结芽孢杆菌制剂 | |
CN116425836A (zh) | A+多肽/蛋白质及其应用 | |
CN110551705A (zh) | 肺炎链球菌蛋白PepN在抗过敏性哮喘中的应用 | |
JP2015039317A (ja) | エラスターゼに対する阻害活性を有する新規ポリペプチド、そのdna、及びそれらの利用 | |
CN102716462A (zh) | 一种以氨溴索与匹多莫德为活性成分的药用组合物 |
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 |