CN116036241A - Application of epidermal growth factor in preparing medicine for treating gastric ulcer - Google Patents
Application of epidermal growth factor in preparing medicine for treating gastric ulcer Download PDFInfo
- Publication number
- CN116036241A CN116036241A CN202310128348.8A CN202310128348A CN116036241A CN 116036241 A CN116036241 A CN 116036241A CN 202310128348 A CN202310128348 A CN 202310128348A CN 116036241 A CN116036241 A CN 116036241A
- Authority
- CN
- China
- Prior art keywords
- epidermal growth
- growth factor
- egf
- medicament
- gastric
- 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.)
- Pending
Links
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 title claims abstract description 77
- 101800003838 Epidermal growth factor Proteins 0.000 title claims abstract description 74
- 229940116977 epidermal growth factor Drugs 0.000 title claims abstract description 74
- 208000007107 Stomach Ulcer Diseases 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 102000009024 Epidermal Growth Factor Human genes 0.000 title claims abstract 17
- 201000005917 gastric ulcer Diseases 0.000 title abstract description 14
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 19
- 230000036541 health Effects 0.000 claims abstract description 9
- 230000001737 promoting effect Effects 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 4
- 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 claims abstract description 4
- 239000013543 active substance Substances 0.000 claims abstract description 4
- 239000002775 capsule Substances 0.000 claims abstract description 4
- 239000000084 colloidal system Substances 0.000 claims abstract description 4
- 239000002270 dispersing agent Substances 0.000 claims abstract description 4
- 239000008103 glucose Substances 0.000 claims abstract description 4
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 4
- 239000003921 oil Substances 0.000 claims abstract description 4
- 239000000375 suspending agent Substances 0.000 claims abstract description 4
- 239000000080 wetting agent Substances 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 229940116978 human epidermal growth factor Drugs 0.000 claims description 3
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 102000018386 EGF Family of Proteins Human genes 0.000 claims 1
- 108010066486 EGF Family of Proteins Proteins 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 208000025865 Ulcer Diseases 0.000 description 20
- 230000002496 gastric effect Effects 0.000 description 19
- 231100000397 ulcer Toxicity 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 14
- 230000003902 lesion Effects 0.000 description 14
- 210000004877 mucosa Anatomy 0.000 description 12
- 210000002784 stomach Anatomy 0.000 description 10
- 102000001301 EGF receptor Human genes 0.000 description 9
- 108060006698 EGF receptor Proteins 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 210000004400 mucous membrane Anatomy 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 210000002919 epithelial cell Anatomy 0.000 description 6
- 210000001156 gastric mucosa Anatomy 0.000 description 6
- 229960000381 omeprazole Drugs 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 210000003079 salivary gland Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 5
- 230000003628 erosive effect Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- 241000590002 Helicobacter pylori Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940037467 helicobacter pylori Drugs 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 102000000591 Tight Junction Proteins Human genes 0.000 description 2
- 108010002321 Tight Junction Proteins Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000000270 basal cell Anatomy 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 229960003151 mercaptamine Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000009854 mucosal lesion Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229940126409 proton pump inhibitor Drugs 0.000 description 2
- 239000000612 proton pump inhibitor Substances 0.000 description 2
- -1 respectively Chemical compound 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000001913 submandibular gland Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001578 tight junction Anatomy 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- DJAHKBBSJCDSOZ-AJLBTXRUSA-N (5z,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one;(5e,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C/CCC(C)=O.CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CCC(C)=O DJAHKBBSJCDSOZ-AJLBTXRUSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 102400000921 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- KMZQAVXSMUKBPD-DJWKRKHSSA-N Lafutidine Chemical compound C=1C=COC=1C[S+]([O-])CC(=O)NC\C=C/COC(N=CC=1)=CC=1CN1CCCCC1 KMZQAVXSMUKBPD-DJWKRKHSSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- SMTZFNFIKUPEJC-UHFFFAOYSA-N Roxane Chemical compound CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1 SMTZFNFIKUPEJC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 206010061577 Ulcer haemorrhage Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 210000004430 acanthocyte Anatomy 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- UJOHNXQDVUADCG-UHFFFAOYSA-L aluminum;magnesium;carbonate Chemical compound [Mg+2].[Al+3].[O-]C([O-])=O UJOHNXQDVUADCG-UHFFFAOYSA-L 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 229940124410 anti-helicobacter pylori agent Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- KZFDVWZZYOPBQZ-UHFFFAOYSA-K bismuth;potassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [K+].[Bi+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KZFDVWZZYOPBQZ-UHFFFAOYSA-K 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000002318 cardia Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- SULICOHAQXOMED-YDXPQRMKSA-H dibismuth;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Bi+3].[Bi+3].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O.[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O.[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O SULICOHAQXOMED-YDXPQRMKSA-H 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- 229960004770 esomeprazole Drugs 0.000 description 1
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 229940077716 histamine h2 receptor antagonists for peptic ulcer and gord Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000007358 intestinal barrier function Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229960003303 lafutidine Drugs 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229960004872 nizatidine Drugs 0.000 description 1
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 229960005019 pantoprazole Drugs 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002062 proliferating 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
- 210000001187 pylorus Anatomy 0.000 description 1
- 229960004157 rabeprazole Drugs 0.000 description 1
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960003320 roxatidine Drugs 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229950006156 teprenone Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1808—Epidermal growth factor [EGF] urogastrone
-
- 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
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
-
- 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
- A23V2250/54—Proteins
- A23V2250/542—Animal Protein
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides application of an epidermal growth factor in preparing a medicament for treating gastric ulcer. The EGF is extracted from artificial or natural sources, including EGF, HEGF, rhEGF, sh-EGF, rh-oligopeptides-1, and sh-oligopeptides-1. The medicine is a medical composition comprising an active agent, an auxiliary agent, a dispersing agent, a wetting agent and/or a suspending agent. The carrier of the epidermal growth factor is water, colloid, hyaluronic acid, natural oil and/or glucose. The medicine is one of capsule, tablet or oral liquid. The invention also provides application of the epidermal growth factor in preparing food for promoting health of digestive tract. The invention provides an application of Epidermal Growth Factor (EGF) in gastric ulcer treatment and gastrointestinal tract health care.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of the medicine in preparation of medicines for treating gastric ulcer.
Background
Gastric ulcers are chronic ulcers that occur between the pylorus and the cardia of the stomach, a common, frequently occurring disease worldwide. Gastric ulcers are ulcers which are formed by gastric acid and pepsin erosion and defence by losing balance between their erosive and defensive actions, gastric acid self-digestion of mucous membrane, helicobacter Pylori (HP) infection, weakening of gastric mucous membrane self-protective barrier, and erosion.
Common medications for gastric ulcers include: antacid drugs such as aluminum hydroxide, aluminum magnesium carbonate, calcium carbonate, magnesium oxide, etc.; h2 receptor antagonists such as famotidine, roxatidine, lafutidine, nizatidine, and the like; proton Pump Inhibitors (PPI) such as lansoprazole, rabeprazole, omeprazole, pantoprazole, and esomeprazole, etc.; anti-helicobacter pylori agents such as clarithromycin, metronidazole, amoxicillin, and the like; gastric mucosa protectants such as bismuth potassium citrate, sucralfate, colloidal bismuth tartrate capsule, teprenone, etc.
However, most commonly used drugs have certain side effects, for example, omeprazole may cause digestive tract symptoms such as abdominal pain and diarrhea, influence calcium absorption, increase the risk of fracture caused by calcium and phosphorus metabolism, increase the risk of anemia caused by inhibition of gastric acid secretion, and the like.
Disclosure of Invention
In view of the above, the first aspect of the present invention proposes the use of an epidermal growth factor in the preparation of a medicament for treating gastric ulcers.
Furthermore, the EGF is extracted from artificial or natural sources, including EGF, HEGF and rhEGF, sh-EGF, rh-oligopeptides-1 and sh-oligopeptides-1.
Further, the molecular weight of the epidermal growth factor is 6.0-6.2kDa.
Further, the medicament is a pharmaceutical composition comprising an active agent, an adjuvant, a dispersing agent, a wetting agent and/or a suspending agent.
Further, the carrier of the epidermal growth factor is water, colloid, hyaluronic acid, natural oil and/or glucose.
Further, the medicine is one of a capsule, a tablet or an oral liquid.
In a second aspect, the invention provides the use of an epidermal growth factor in the manufacture of a food for promoting gut health.
The invention provides an application of Epidermal Growth Factor (EGF) in gastric ulcer treatment and gastrointestinal tract health care, and can achieve the effect of gastric ulcer treatment. EGF can be used as a natural growth promoting factor of gastrointestinal mucosa and has the advantage of small side effect.
Drawings
The accompanying drawings assist in a further understanding of the present application. For convenience of description, only parts related to the related invention are shown in the drawings.
FIG. 1 is a graph showing the change of the surface of gastric mucosal tissue of an experimental mouse according to an embodiment of the present invention;
FIG. 2 is a view showing pathological sections of gastric mucosal tissue of an experimental mouse according to an embodiment of the present invention.
Detailed Description
The present application is described in further detail below with reference to the drawings and examples. The specific embodiments described herein are offered by way of illustration only, and not by way of limitation. Embodiments and features of embodiments in this application may be combined with each other without conflict.
Epidermal growth factor (hereinafter, EGF), a small molecule polypeptide consisting of 53 amino acids, was originally found in the submandibular glands of mice and urine of humans, has been intensively studied for decades. EGF is capable of promoting mitosis during cell culture, i.e., inducing DNA synthesis and cell division, and is detectable in body fluids and in many organs throughout the body. EGF can act on the "neural precursor cell line" at very low nanomolar concentrations, demonstrating its proprietary receptor system. Meanwhile, EGF has been shown to promote cell growth and development. And plays an important role in preventing oxidative stress and apoptosis due to blood flow restriction.
In the early 1980 s, an animal experiment found that, after destroying the major salivary glands of rats, a large area of ulcer wounds appeared in the stomach, meaning that "EGF secreted by the submandibular gland" had a protective effect on the gastric mucosa. Particularly, after the rat is subjected to salivary gland resection, the protection function of EGF is more prominent; compared to the control group, the salivary gland resected rats had reduced DNA and RNA synthesis in the "oxygenic mucosa". In aqueous extracts of salivary gland tissue, it was observed that cell growth of rat acid-secreting mucosa was significantly affected. In another rat experiment, which studied the role of EGF secreted by the mandibular gland, it was shown that saliva containing EGF at physiological concentration significantly reduced the area of gastric ulcer wounds, while saliva without EGF had no effect on gastric ulcer wounds. In rats where salivary glands are resected and ulcers are induced by "cysteamine" (cysteamine) agents, the use of exogenous EGF inhibits "gastrin" and lowers gastric pH, also reversing the decrease in blood flow in the mucosa.
Not only salivary glands, endogenous EGF is produced via the mucosa of the digestive tract, and its receptor is widely present in the epithelial cells of the digestive tract. In previous rat experiments, it was demonstrated that the expression level of EGFR receptor (EGFR) varies at the tissue level during gastroesophageal reflux wound healing. On day 14 after countercurrent treatment with strong acid, both mRNA and protein expression levels of EGF receptor were significantly increased, and the presence of EGF receptor was observed after labeling of most esophageal epithelial basal cells with "immunohistochemical staining" (immunohistochemically staining). Damage caused by reverse flow of strong acid results in an increase in basal cell number, i.e., promotion of cell proliferation and an increase in expression of EGF receptor, meaning that an increased response of EGF receptor to EGF is urgent and critical in the healing process of esophageal mucosa.
EGF receptor is expressed throughout the digestive tract. In normal intact esophageal mucosa, most of the EGF receptor is present in the basal and acanthocyte layers, gradually decreasing toward the "shallow epithelial layer". To cope with the "EGF reduction in damaged gastroesophageal mucosa", the site on the digestive tract that receives EGF (binding sites) can be used as a functional site (functional site) of the luminal EGF. Exogenous EGF, due to its low molecular weight, is accessible to receptors deep in the basal layer by absorption and diffusion, and furthermore, ulcers may lead to the exposure of proliferating cells to the basal layer. Previous experimental and clinical studies have shown that EGF is beneficial in maintaining digestive tract health.
Expression of EGF receptor in patients with "inflammatory digestive tract diseases", such as: patients with inflammatory bowel disease, crohn's disease, ulcerative colitis are under a great degree of negative regulation. The expression level of EGF receptor is inhibited in digestive tract lesions, indicating that EGF-related response is weakened in those diseases. In murine models of colitis, EGF significantly improved the "apical tight junction channel" (apical tight junction) between epithelial cells, reducing mucosal inflammatory responses, and thus alleviating ulcerative lesions. The use of EGF does not cause the deterioration of 'colonitis-related colorectal cancer', but rather inhibits neutrophil infiltration in the mucosa, promoting the mucosa of the lesion area to remain intact. More importantly, EGF was used to significantly reduce a variety of inflammatory cytokines in serum, including interleukin-6 (IL-6) and serum tumor necrosis factor-alpha (TNF-alpha). Endogenous EGF can maintain the homeostasis of the digestive tract, strengthen the integrity of the intestinal barrier, prevent injury, and play an important role in promoting ulcer wound healing.
In the case of highly recurrent gastrointestinal ulcer, helicobacter pylori infection is often combined, and according to the result of histoimmune examination, EGF and EGFR receptor expression of the antrum (antrum) of the disease are found to be significantly increased, but EGF secretion in saliva is not particularly increased, and EGFR receptor expression returns to normal value after successful elimination of helicobacter pylori by antibiotics, and EGF continues to maintain similar concentration as in healthy subjects after infection. The local high demands of EGF at the problem occurrence are shown for gastrointestinal mucosal lesions, whereas according to previous cancer experimental models, there is no known risk of carcinogenesis with exogenous EGF.
Thus, several studies have demonstrated the potential of Epidermal Growth Factor (EGF) in the treatment of gastric ulcers.
Example one
This example demonstrates the effect of EGF in the treatment of gastric ulcers by the animal model of alcohol-induced gastric ulcers. To analyze the gastric protective effect of EGF in mice, the inventors designed animal experiments to induce acute gastric injury in Balb/c mice by oral administration of 75% ethanol and pre-administer EGF (10. Mu.g/400 ul) three days prior to induction. Omeprazole is a proton pump inhibitor and is widely used clinically in diseases caused by gastric hyperacidity, such as gastric ulcer lesions. Therefore, omphalzole was used as the positive control group for the test of this example. After induction with ethanol, mice were sacrificed. And taking down the gastric mucosa tissue of the mouse, and observing the surface change and histopathological section of the gastric mucosa tissue. The specific experimental method is as follows:
step1: animal disease pattern and sample treatment procedure
All animal protocols were performed according to approved methods and according to laboratory animal ethics and recommendations. Purchased from national laboratory animal center. Male Balb/c mice (6-7 weeks old;20-25 g) were divided into four groups:
group one: normal mice group;
group two-ETOH group (ulcer mode group): three consecutive days of water consumption followed by 400ml of 75% ethanol 12 hours after the third day of feeding;
group three-EGF group (sample experimental group): three consecutive days of EGF (400 ul/day, 10. Mu.g EGF) followed by 400ml of 75% ethanol 12 hours after the third day of feeding;
group four-ome group (drug positive control group): three days of omeprazole (20 mg/kg) was orally administered in succession, followed by 400ml of 75% ethanol at 12 hours after the third day of feeding.
Step2: ulcer index study
Mice were sacrificed 4 hours after 75% ethanol administration, stomach tissue was removed, and then the mice' stomach was opened longitudinally, expanded, fixed, and washed with saline. Lesions in the mucosa were examined at 10 x magnification to assess the status of ulcers, as well as the number and severity of each gastric ulcer. The stomach of each animal was recorded with photographs. The ulcer index per animal was calculated using the following scoring system as a record of mucosal lesions from congestion, bleeding to complete erosion:
0, no disease; 1-2, small lesions; 3-4, small ulcers; 5-6, large ulcers; 7. full is an ulcer.
Step3: histological analysis
Rats were sacrificed 4 hours after 75% ethanol administration, stomach tissue was removed, samples of the mice' stomach were fixed in 10% formalin, and wax blocks were made. Serial sections with a thickness of 5 μm were prepared and subjected to conventional hematoxylin and eosin (H & E) staining. Hemorrhagic lesions, epithelial cell lesions and oedema of the gastric mucosa and concomitant leukocyte infiltration were scored, with lesion levels ranging from grade 1 to grade 5 depending on severity:
1 = minimum (< 1%); 2 = slight (1-25%); 3 = medium (26-50%); 4 = moderate/severe (51-75%); 5 = severe/high (76-100%).
Step4: statistical analysis
The ulcer index and the histologically observed lesion index were obtained from individual animals, and the average value of each group was calculated. Data are expressed as mean ± SEM. One-way anova with post hoc Tukey's test was performed on multiple experimental groups using GraphPad Prism v5.0 software (GraphPad Software, inc., san Diego, calif., USA). The statistically significant difference assay p-value was set to 0.05.
Through the experiment, the effect result of EGF on ethanol induced acute gastric injury can be obtained:
first, EGF can significantly slow down the ulceration of gastric mucosal tissue. FIG. 1 is a graph showing the change of the surface of gastric mucosal tissue of the experimental mice in this example, and the gastric mucosal tissue of the ulcer pattern group (ETOH group) shows the symptoms of a large area hemorrhagic ulcer in terms of anatomical observation (FIG. 1-A). The gastric mucosal ulcer index, the extent of lesions, was significantly reduced in mice pretreated with EGF and Omeprazole for three days compared to the ulcer model group (ETOH) lacking any treatment (FIG. 1-B).
Secondly, EGF provides protection effect for stomach wall structure. FIG. 2 is a view of pathological sections of gastric mucosal tissue of the experimental mice in this example, and the ethanol resulted in significant pathological changes in the gastric epithelial tissue of the mice, including hemorrhagic lesions, epithelial cell loss, swelling, and leukocyte infiltration (edema with leucocytes) (FIG. 2-A). However, in the groups pretreated with EGF and Omeprazole, respectively, ethanol-induced gastric epithelial tissue damage was significantly slowed, significantly protecting the stomach wall structure compared to the group of ulcers without any treatment (ETOH), and tissue section staining showed that the stomach wall was nearly intact, with little difference compared to the normal group of mice (FIG. 2-A). The bleeding lesions of the gastric mucosa, as well as the index of epithelial cell lesions, also reached a degree of improvement of the significant statistical difference (fig. 2-B).
The experimental results intuitively show that EGF can effectively improve gastric mucosal injury induced by ethanol, so that the gastric ulcer treatment effect can be achieved through the epidermal growth factor.
Embodiment two
In this embodiment, the epidermal growth factor is not limited in source, and may be extracted from artificial or natural sources, including but not limited to epidermal growth factor (EGF, oligo-1), human epidermal growth factor (hEGF, human Oligopeptide-1), recombinant human epidermal growth factor (rhEGF, sh-EGF, rh-Oligopeptide-1, sh-Oligopeptide-1), etc.
Embodiment three
In this embodiment, the acceptable carrier for the EGF is not particularly limited, and includes but is not limited to active agents, adjuvants, dispersants, wetting agents, suspending agents, and the like, and the group consisting of water, colloids, hyaluronic acid, natural oils, glucose, and the like, to complete the correspondence of the diversified substrates.
Embodiment IV
In this example, the epidermal growth factor enters the human body through any of the carriers described in the second example, and the treatment of gastric ulcer is completed.
Embodiment five
EGF is an important gastrointestinal mucosa protective factor. In the experiment of the first murine model, EGF binding to EGF receptor was demonstrated to promote gut health by promoting gut maturation and maintaining gut epithelial cells in a constant fashion. In this example, the EGF is used to promote health of the digestive tract.
The invention provides the efficacy of EGF in maintaining the health of the digestive tract, especially in treating gastric ulcer, and opens up a new direction of EGF application.
While the present application has been particularly shown and described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the application as defined by the appended claims.
Claims (7)
1. The use of epidermal growth factor in the preparation of a medicament for treating gastric ulcers.
2. The use of an epidermal growth factor according to claim 1, wherein said epidermal growth factor has a molecular weight of 6.0-6.2kDa in the manufacture of a medicament for treating gastric ulcers.
3. The use of an epidermal growth factor according to claim 1, wherein said epidermal growth factor is extracted from synthetic or natural sources, including epidermal growth factor EGF, human epidermal growth factor hEGF and recombinant human epidermal growth factors rhEGF, sh-EGF, rh-oligopeptides-1, sh-oligopeptides-1.
4. The use of epidermal growth factor according to claim 1, in the manufacture of a medicament for the treatment of gastric ulcers, wherein said medicament is a pharmaceutical composition comprising an active agent, an adjuvant, a dispersing agent, a wetting agent and/or a suspending agent.
5. The use of an epidermal growth factor according to claim 1, wherein the carrier of said epidermal growth factor is water, colloid, hyaluronic acid, natural oils and/or glucose for the preparation of a medicament for the treatment of gastric ulcers.
6. The use of an epidermal growth factor according to claim 1, in the manufacture of a medicament for treating gastric ulcers, wherein said medicament is one of a capsule, a tablet or an oral liquid.
7. The use of epidermal growth factor in the preparation of a food for promoting digestive tract health.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310128348.8A CN116036241A (en) | 2023-02-17 | 2023-02-17 | Application of epidermal growth factor in preparing medicine for treating gastric ulcer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310128348.8A CN116036241A (en) | 2023-02-17 | 2023-02-17 | Application of epidermal growth factor in preparing medicine for treating gastric ulcer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116036241A true CN116036241A (en) | 2023-05-02 |
Family
ID=86113610
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310128348.8A Pending CN116036241A (en) | 2023-02-17 | 2023-02-17 | Application of epidermal growth factor in preparing medicine for treating gastric ulcer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116036241A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118001378A (en) * | 2024-04-08 | 2024-05-10 | 山东第二医科大学 | Use of substances overexpressing MOCS a in the preparation of a product for the treatment of diseases induced by helicobacter pylori infection |
-
2023
- 2023-02-17 CN CN202310128348.8A patent/CN116036241A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118001378A (en) * | 2024-04-08 | 2024-05-10 | 山东第二医科大学 | Use of substances overexpressing MOCS a in the preparation of a product for the treatment of diseases induced by helicobacter pylori infection |
| CN118001378B (en) * | 2024-04-08 | 2024-06-11 | 山东第二医科大学 | Use of substances overexpressing MOCS a in the preparation of a product for the treatment of diseases induced by helicobacter pylori infection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mullin et al. | Proton pump inhibitors: actions and reactions | |
| TWI241192B (en) | Topical formulations for delivery of interleukin-11 | |
| Lee et al. | Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole | |
| Maruoka et al. | Vonoprazan is superior to proton pump inhibitors in healing artificial ulcers of the stomach post‐endoscopic submucosal dissection: A propensity score‐matching analysis | |
| CN116036241A (en) | Application of epidermal growth factor in preparing medicine for treating gastric ulcer | |
| Adewoye et al. | Anti-ulcerogenic mechanism of magnesium in indomethacin induced gastric ulcer in rats | |
| Guo et al. | Antiangiogenic effect of a highly selective cyclooxygenase-2 inhibitor on gastric ulcer healing in rats | |
| Périco et al. | Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats | |
| Utkir | PREVENTION OF ACUTE EROSIVE AND ULCERATIVE LESIONS OF THE UPPER GASTROINTESTINAL TRACT IN PATIENTS WITH EXTENSIVE THERMAL BURNS | |
| Armbrecht et al. | Treatment of reflux oesophagitis of moderate and severe grade with ranitidine or pantoprazole—comparison of 24‐hour intragastric and oesophageal pH | |
| WO2024168796A1 (en) | Use of epidermal growth factor in preparation of drug for treating gastric ulcer | |
| EP0584286B1 (en) | Use of platelet derived growth factor in the preparation of a medicament for the treatment of gastrointestinal ulcers | |
| Strader et al. | Esophageal function and occurrence of Barrett’s esophagus in Zollinger-Ellison syndrome | |
| Hatlebakk et al. | Gastro-oesophageal reflux during 3 months of therapy with ranitidine in reflux oesophagitis | |
| WO1982000762A1 (en) | Agent for alimentary canal | |
| IE59739B1 (en) | The use of nitrofurantoin for the treatment and prophylaxi of gastrointestinal disorders | |
| Orlando et al. | Gastroesophageal reflux disease | |
| El Zahaby et al. | Role of rebamipide and or pantoprazole in preventing dexamethasone induced gastritis in senile male albino rats | |
| TW201429479A (en) | Use of fucoidan for treating cachexia and cancer | |
| RU2646450C1 (en) | Method of treatment of precancerous and early stages of cancerous diseases of gaster | |
| CN111184712A (en) | Application of composition in preparing medicine for treating diseases caused by atopic eczema | |
| RU2798721C1 (en) | Method of prevention of postoperative pancreatic fistula during resection interventions on the pancreas | |
| RU2236228C2 (en) | Method for preventing relapses of hemorrhages out of ulcers and erosions at helicobacter pylori-associated ulcerous gastric and duodenal disease | |
| Osato | Chemotherapy of human carcinoma with citronellal and citral and their action on carcinoma tissue in its histological aspects up to healing | |
| RU2520599C1 (en) | Method for endoscopic bioplasty of gastroduodenal ulcers with complex bioplastic material |
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 |