CN117653713A - Application of epidermal growth factor in preparing medicine for treating interstitial cystitis - Google Patents
Application of epidermal growth factor in preparing medicine for treating interstitial cystitis Download PDFInfo
- Publication number
- CN117653713A CN117653713A CN202211288480.7A CN202211288480A CN117653713A CN 117653713 A CN117653713 A CN 117653713A CN 202211288480 A CN202211288480 A CN 202211288480A CN 117653713 A CN117653713 A CN 117653713A
- Authority
- CN
- China
- Prior art keywords
- interstitial cystitis
- growth factor
- epidermal growth
- bladder
- medicament
- 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
- 102000009024 Epidermal Growth Factor Human genes 0.000 title claims abstract description 50
- 208000005615 Interstitial Cystitis Diseases 0.000 title claims abstract description 49
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 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 21
- 101800003838 Epidermal growth factor Proteins 0.000 title claims abstract description 20
- 229940116977 epidermal growth factor Drugs 0.000 title claims abstract description 20
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 14
- 210000005068 bladder tissue Anatomy 0.000 claims abstract description 14
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 13
- 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
- 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
- 230000027939 micturition Effects 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000080 wetting agent Substances 0.000 claims abstract description 4
- 206010063057 Cystitis noninfective Diseases 0.000 claims abstract description 3
- 238000011282 treatment Methods 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 7
- 210000004877 mucosa Anatomy 0.000 abstract description 5
- 239000012752 auxiliary agent Substances 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract 1
- 210000003932 urinary bladder Anatomy 0.000 description 26
- 239000002158 endotoxin Substances 0.000 description 18
- 229920006008 lipopolysaccharide Polymers 0.000 description 18
- 210000002700 urine Anatomy 0.000 description 12
- 208000000283 familial pityriasis rubra pilaris Diseases 0.000 description 11
- 230000002757 inflammatory effect Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 102400001368 Epidermal growth factor Human genes 0.000 description 8
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 8
- 210000000981 epithelium Anatomy 0.000 description 8
- 229940118019 malondialdehyde Drugs 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 102000019197 Superoxide Dismutase Human genes 0.000 description 7
- 108010012715 Superoxide dismutase Proteins 0.000 description 7
- 230000001575 pathological effect Effects 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000002485 urinary effect Effects 0.000 description 7
- 206010016654 Fibrosis Diseases 0.000 description 6
- 230000004761 fibrosis Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 239000000090 biomarker Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 210000004969 inflammatory cell Anatomy 0.000 description 4
- 230000008439 repair process Effects 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000010562 histological examination Methods 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- -1 polyethylene Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- QAXBVGVYDCAVLV-UHFFFAOYSA-N tiletamine Chemical compound C=1C=CSC=1C1(NCC)CCCCC1=O QAXBVGVYDCAVLV-UHFFFAOYSA-N 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010033372 Pain and discomfort Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- GDSCFOSHSOWNDL-UHFFFAOYSA-N Zolasepam Chemical compound N=1CC(=O)N(C)C(N(N=C2C)C)=C2C=1C1=CC=CC=C1F GDSCFOSHSOWNDL-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000003443 bladder cell Anatomy 0.000 description 1
- 208000029162 bladder disease Diseases 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229960002580 cefprozil Drugs 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
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000007360 epithelial dysfunction Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000001913 submandibular gland Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229960004523 tiletamine Drugs 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 208000026533 urinary bladder disease Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 229960001366 zolazepam Drugs 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides an application of an Epidermal Growth Factor (EGF) in preparing a medicament for treating interstitial cystitis, and the EGF can establish an excellent interstitial cystitis therapeutic agent. 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 used for reducing frequent urination, recovering bladder elasticity, reducing bladder inflammation, and improving antioxidant capacity in bladder tissue. The invention provides a new effect of an epidermal growth factor, which can be used for treating interstitial cystitis and repairing bladder mucosa and has excellent effect.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of an epidermal growth factor in preparing a medicine for treating interstitial cystitis.
Background
Interstitial Cystitis (IC) is a chronic bladder disease characterized by inflammation in the pelvic area with recurrent pain and discomfort. Chronic inflammation and epithelial dysfunction are recognized as major causative factors for interstitial cystitis. The urinary epithelium of a normal bladder is static, but can be repaired rapidly when damaged or is affected by poisons. However, when cellular proliferation is not functioning, the damaged urinary epithelium cannot be repaired, eventually leading to increased permeability of the urinary epithelium and an impaired barrier function, followed by a reduced ability to regenerate the urinary epithelium. In the case of interstitial cystitis, increased apoptosis of the urinary epithelium is found, with reduced proliferation of cells, implying a change in the dynamic balance of the urinary bladder epithelium. The treatment regimen for interstitial cystitis has not been standardized. In the guidelines for interstitial cystitis treatment of the American urology and surgery Association (AUA), a six-line algorithm for treating interstitial cystitis is proposed (refer to the guide line of AUA). However, this proposed therapy is directed mainly to symptomatically controlling and removing dysfunctional tissue, and not actively repairing damaged tissue and aiding healthy urinary epithelial regeneration. There is no effective therapy with long-term benefit demonstrated.
In many clinical settings, "high concentration platelet plasma" (PRP) has been widely used in regenerative medicine, including sports medicine, dermatology, orthopedics, and oral surgery. The principle of action is that various growth factors and cytokines involved in the inflammatory response during wound healing and tissue regeneration are released from platelets. A study of the efficacy of intravesical PRP injection for four months in "interstitial cystitis patients without improvement of the condition with conventional therapy" using GRA scale (Global Response Assessment) to evaluate improvement of the overall symptoms of interstitial cystitis therapy indicated that positive results persisted from the first dose injected to three months after the fourth dose of PRP injection; various urinary functional proteins, growth factors, cytokines, and tissue regeneration were evaluated in vivo after PRP injection to evaluate objective evidence (objective evidence). The specific cytokine and protein expression levels are indeed consistent with subjective symptom improvement assessment of the patient.
However, PRP therapy is considered to be controversial at many levels in clinical guidelines and recommendations for the treatment of interstitial cystitis. First, the PRP preparation procedure and dosage used, never been standardized, are dependent on the skill and experience of the practitioner, as well as the equipment. Secondly, there is no way to examine whether PRP injection contains growth factor species known to promote repair and regeneration at every site of application. PRP therapy is therefore not an ideal and effective therapy, and furthermore, the detailed mechanism by which PRP acts on interstitial cystitis is still unclear, based on the characteristics of platelet polypeptides. The standards of the contents of platelets, growth factors and cytokines in PRP never agree, and the content of EGF in the PRP prepared in general is extremely low, so that the economic benefit is low in terms of the practical operation level, and the curative effect cannot be ensured.
Disclosure of Invention
In view of the above problems, the present invention proposes the application of epidermal growth factor in preparing medicine for treating interstitial cystitis, and the "epidermal growth factor" (EGF) of the present invention can establish excellent therapeutic agent for interstitial cystitis.
Further, the medicament is a pharmaceutical composition comprising an active agent, an auxiliary agent, 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 medicament is used for reducing the degree of frequent urination.
Further, the medicament is used for restoring bladder elasticity.
Further, the medicament is for reducing bladder inflammation.
Further, the medicament is used for improving the antioxidant capacity in bladder tissue.
The invention provides a new effect of an epidermal growth factor, which can be used for treating interstitial cystitis and repairing bladder mucosa and has excellent 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 RBC and urine content results between different experimental groups in an example;
FIG. 2 is a graphical representation of tissue section staining results between different experimental groups in one embodiment;
FIG. 3 is a graph showing the results of inflammatory cytokine levels between different experimental groups according to one embodiment;
FIG. 4 is a graphical representation of antioxidant biomarker levels in bladder tissue homogenates between different experimental groups according to an example.
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.
The invention provides application of EGF (epidermal growth factor) in treating interstitial cystitis and repairing bladder mucosa. Interstitial cystitis has chronic inflammatory signs, and indeed the pathogenesis is not completely understood. Early research observations have confirmed that: compared with the control group without IC or other patients with bacterial cystitis, the concentration of EGF in urine is obviously improved, and the EGF concentration of the patients who successfully finish treatment is obviously reduced, so that EGF and interstitial cystitis are positively correlated. However, the inventors have found that interstitial cystitis can be treated with EGF. The inventor deduces that the damaged bladder tissue cells of the IC patient have urgent repair requirements, so that the EGF concentration is greatly increased, and therefore, the inflamed damaged bladder cells are reasonably deduced, repair and regeneration are required, the EGF high requirement is caused, and the interstitial cystitis can be effectively treated by directly using the EGF.
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, while being detectable in almost whole body fluids. EGF acts 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.
The EGF of the present invention is not limited in source, and may be extracted from artificial or natural sources, including but not limited to EGF (oligo-1), HEGF (hEGF, human Oligopeptide-1), recombinant HEEGF (rhEGF, sh-EGF, rh-oligo-1, sh-oligo-1).
Example one
The present invention can improve Lipopolysaccharide (LPS) induced interstitial cystitis (Interstitial Cystitis) through EGF treatment.
Experimental animals:
female Sprague-Dawley rats (Japan SLC, hamamatsu, japan) weighing 200-300 grams were used for this experiment. The raising environment is maintained at 22-24 deg.c and 50-60% relative humidity, and the light is changed day and night for 12 hr to make the feed and drinking water sufficient at any time. All procedures of this experiment followed the national institutes of health animal care guidelines for use (NIH, bethesda, MD, USA).
Rat experimental model:
a total of 15 rats were assigned to three groups, normal control, pathological control and experimental. First, 16mg/kg of xylazine and 0.04mg/kg of Zoletil are intramuscularly injected TM (zolazepam plus tiletamine). The bladder is exposed by making an operation incision in the lower abdomen, cutting the top of the bladder, placing one end of a medical grade polyethylene tube (PE-50 tube) into the bladder, and truly suturing and sealing the bladder, wherein the other end of the tube passes through the subcutaneous layer of the left abdomen and passes out of the body from the rear neck. Confirm that the drainage of the pipeline is unobstructed and has no liquidAfter leakage at the incision, the tube was sutured fixed, the abdominal wound was closed by suturing, and finally 15mg/kg of cefprozil was given for intramuscular injection to prevent infection. All animals were placed in an incubator until fully awake.
Four days after LPS-induced interstitial cystitis (LPS-induced IC, described in the following paragraph) was performed, and 24-hour urine specimens were collected using metabolic cages before sacrifice, and observed for color and blood content.
Lipopolysaccharide (LPS) -induced Interstitial Cystitis (IC) uses LPS to induce interstitial cystitis pattern and EGF treatment:
a line was connected from the top of the bladder, and the external end was fixed to the rat posterior cervical portion for LPS (150. Mu.l) induction of interstitial cystitis. 150 μl LPS was purified by extraction from phenol (1 μg/. Mu.l) (E.coli O55: B5; sigma-Aldrich, st.Louis, MO, USA). LPS was infused twice a week through the line for six times over three weeks, resulting in chronic inflammation of the bladder epithelium, with normal control groups substituting saline for LPS. The experimental group was given 400. Mu.L of a solution containing 2. Mu.g EGF on the day of IC induction (day 0), then on the seventh day (day 7), and on the 14 th day (day 14). Finally the animals were sacrificed on day 21 for further histological examination.
Histological examination:
on day 21 after the first LPS injection, the bladder was fixed with 4% para-formaldehyde after animal sacrifice. The bladder of the normal control group was removed on the seventh day after the first saline infusion. The tissues were cut to a thickness of 5 μm with a cryo-processor and stained with hematoxylin and eosin (H & E). In addition, various corresponding histological examinations were performed with the following staining method, epithelial desquamation (cytokeratin immunostaining), mast cell infiltration (toluidine blue staining), tissue fibrosis (Masson trichromatic staining), apoptosis (in situ end marker staining).
Inflammatory cytokines and oxidative labeling concentration:
bladder tissue was homogenized at day 21 with 100 μl of the rapid cell lysate, incubated at 4deg.C for 30 min, centrifuged at 12,000g for 20 min, total protein was obtained from the supernatant, and protein concentration was measured by BCA protein quantification. TNF-alpha, IL-6, IL-8, and IL-1β were also detected in the bladder tissue homogenates by enzyme-linked immunosorbent assay (ELISA). The nuclear extract in the supernatant was obtained using NE-PER Nuclear and Cytoplasmic Extraction system.
Statistical analysis:
the data obtained from the experiments were counted and presented as mean.+ -. Standard deviation, and the group differences were further compared by Tukey's HDS test after performing One-Way ANOVA. Statistical software was used with GraphPad Prism eighth edition (GraphPad Software, la Jolla, CA, USA). The statistically significant difference assay p-value was set to 0.05.
Based on the above experimental results, at least the following therapeutic effects can be obtained:
(1) EGF improves the haematuria symptoms and pathological tissue changes of LPS-induced interstitial cystitis
Fig. 1 shows RBC and urine contents between different experimental groups according to the embodiment of the invention, as shown in fig. 1, compared with the case of no EGF (black Bar), the case of the patient's blood urine is less and the urine volume is also reduced by the case of the EGF (gray Bar), so that EGF can reduce red blood cells, improve the blood urine appearance, add treatment effect and reduce the patient's frequent urine level (remark: blood urine detection value p <0.05 p <0.01 p < 0.001).
FIG. 2 is a graph showing the staining results of tissue sections between different experimental groups in the example of the present invention, as shown by the staining results of hematoxylin and eosin (H & E) staining results of FIG. 2, LPS-induced interstitial cystitis tissue sections, normal epithelial tissue structures are not present any more, and EGF treatment helps to return to normal; as shown by Masson trichromatography on the right in fig. 2, bladder tissue was less fibrosed via EGF treatment.
The LPS-induced interstitial cystitis tissues were shown to have abnormal inflammatory cell infiltration and epithelial thickening, and these abnormalities were all observed in the experimental group to be reversed by EGF treatment and returned to normal.
EGF is administered in a group that is more intact and free of rupture of the mucosa against inflammatory cells, alleviating inflammation and avoiding spread. The large area of blue fibrosis induced by LPS results in severe fibrosis symptoms in patients, while EGF is administered to alleviate fibrosis symptoms.
(2) EGF reduces inflammatory cytokines
FIG. 3 is a graph showing the results of the content of inflammatory cytokines among different experimental groups according to the embodiment of the present invention, wherein the inflammatory hormone biomarkers include: expression of TNF- α, IL-6, IL-1β in bladder tissue. Fig. 3 shows, from left to right, EGF treatment to reduce inflammatory cytokine levels, TNF- α, IL-6, and IL-1β, and gene order associated with tissue fibrosis, p <0.05 p <0.01 p <0.001, respectively.
As shown in fig. 3, the normal control group (white Bar) was highest, and outperformed the pathological control group (black Bar) and the experimental group (gray Bar). Through the related inflammation indexes (related factors), the EGF group is given with fewer inflammatory cells and inflammatory biological hormones than the pathological control group, so that the inflammatory symptoms of patients can be obviously reduced and the EGF group can be effectively treated.
(3) EGF has antioxidant effect on LPS-induced interstitial cystitis
FIG. 4 is a graph showing the results of the content of antioxidant biomarkers in bladder tissue homogenates among different experimental groups according to an embodiment of the invention, wherein the detected antioxidant biomarkers in bladder tissue homogenates include: malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). As shown in fig. 4 oxidative stress biomarkers, EGF can inhibit Malondialdehyde (MDA) production while promoting antioxidant enzymes that are inhibited by interstitial cystitis pathological conditions: peroxidase (GSH-Px), and superoxide dismutase (SOD). In the pathological control group, MDA content is greatly increased in interstitial cystitis condition, while EGF can reduce MDA content in bladder tissue and repair antioxidant enzymes such as: GSH-Px, SOD, decreased activity due to LPS infusion, < p <0.05, < p <0.01, < p <0.001.
The EGF-administered group had less intravesical malondialdehyde (Bladder MDA Level) than the pathological control group and thus had antioxidant capacity. Meanwhile, the concentration of antioxidant substances such as glutathione (Bladder GSH Level) and serum superoxide dismutase (Bladder SOD Level) in the bladder can reach the same value as that in a normal bladder (Sham), so that the bladder tissue has antioxidant capacity and can be effectively treated.
Embodiment two
In the EGF pharmaceutical composition for treating wounds provided in this embodiment, the pharmaceutically acceptable carrier 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 them, including but not limited to water, colloids, hyaluronic acid, natural oils, glucose, and the like, can correspond to a variety of matrices.
The active protein containing EGF enters human body through any carrier to reach the application of repairing in the bladder. Specific functions include:
1) Reducing the blood urine and frequent urine degree of the patient;
2) Reducing symptoms of mucosa (H & E) and fibrosis (Masson's Trichrome) of a patient, reducing bladder loss of elasticity, and indirectly solving frequent urination;
3) Reducing the ratio of inflammatory cells to inflammatory biological hormone so as to obviously reduce the inflammatory symptoms of patients;
4) Reduce bladder malondialdehyde (Bladder MDA Level), and promote antioxidant substance concentration such as bladder glutathione (Bladder GSH Level) and serum superoxide dismutase (Bladder SOD Level) to reach the same value as normal bladder, so as to make bladder tissue have antioxidant capacity;
through the above functions, the EGF proposed in this embodiment can effectively treat interstitial cystitis.
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 application of epidermal growth factor in preparing medicine for treating interstitial cystitis.
2. The use of epidermal growth factor according to claim 1, in the manufacture of a medicament for the treatment of interstitial cystitis, wherein the medicament is a pharmaceutical composition comprising an active agent, an adjuvant, a dispersing agent, a wetting agent and/or a suspending agent.
3. The use of epidermal growth factor according to claim 1, wherein the carrier of the epidermal growth factor is water, colloid, hyaluronic acid, natural oils and/or glucose.
4. The use of epidermal growth factor according to claim 1, in the manufacture of a medicament for the treatment of interstitial cystitis, wherein said medicament is for reducing the degree of frequent urination.
5. The use of epidermal growth factor according to claim 1, in the manufacture of a medicament for the treatment of interstitial cystitis, wherein said medicament is for restoring bladder elasticity.
6. The use of epidermal growth factor according to claim 1, in the manufacture of a medicament for the treatment of interstitial cystitis, wherein said medicament is for reducing bladder inflammation.
7. The use of epidermal growth factor according to claim 1, in the manufacture of a medicament for the treatment of interstitial cystitis, wherein the medicament is for increasing the antioxidant capacity in bladder tissue.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW111132952 | 2022-08-31 | ||
| TW111132952A TW202410915A (en) | 2022-08-31 | Application of epidermal growth factor in the treatment of interstitial cystitis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117653713A true CN117653713A (en) | 2024-03-08 |
Family
ID=90068810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211288480.7A Pending CN117653713A (en) | 2022-08-31 | 2022-10-20 | Application of epidermal growth factor in preparing medicine for treating interstitial cystitis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117653713A (en) |
-
2022
- 2022-10-20 CN CN202211288480.7A patent/CN117653713A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Schultz et al. | Neovascular growth factors | |
| KR101800040B1 (en) | Modulating aquaporins with relaxin | |
| Li et al. | Leucine-rich α-2-glycoprotein-1 promotes diabetic corneal epithelial wound healing and nerve regeneration via regulation of matrix metalloproteinases | |
| Hsu et al. | The effects of isoliquiritigenin on endometriosis in vivo and in vitro study | |
| CN111298104A (en) | Application of exenatide injection in medicine for treating and preventing intrauterine adhesion | |
| Izumi et al. | Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing | |
| Park et al. | Effects of nuclear factor-κB small interfering RNA on posterior capsule opacification | |
| Vitar et al. | Substance P/neurokinin-1 receptor pathway blockade ameliorates limbal stem cell deficiency by modulating mTOR pathway and preventing cell senescence | |
| WO2016090892A1 (en) | Water-soluble gel for treating diabetic foot | |
| CN117653713A (en) | Application of epidermal growth factor in preparing medicine for treating interstitial cystitis | |
| KR102128003B1 (en) | Pharmaceutical composition for preventing or treating tendinopathy comprising isolated mitochondria | |
| WO2024045071A1 (en) | Use of epidermal growth factor in preparing medicament for treating interstitial cystitis | |
| CN105188731B (en) | For treating the protein s LURP-1 of eye disease | |
| US20210046161A1 (en) | Skin ointment for treating labia minora skin | |
| CN116440059A (en) | Cell-free fat extract loaded soluble microneedle and preparation method and application thereof | |
| Yan et al. | Cell-free matrix derived from adipose mesenchymal stromal cells enhances corneal rehabilitation via delivery of nerve regenerative PGRN | |
| EP2656853A1 (en) | Method for treating acute cerebral and spinal blood flow disorders of an ischaemic or haemorrhagic nature | |
| KR20190014454A (en) | Composition for Inhibition or Treatment of Keloids and Hypertrophic Scar Comprising CRIF1 Antagonist | |
| CN114225011A (en) | Compound preparation for preventing and treating GSM and application thereof | |
| TW202410915A (en) | Application of epidermal growth factor in the treatment of interstitial cystitis | |
| US20240016893A1 (en) | Compositions and methods for treating wounds | |
| Zhao et al. | Decreased autophagic activity of detrusor cells is involved in the inflammatory response of interstitial cystitis/bladder pain syndrome | |
| Yang et al. | Intrauterine infusion of platelet‐rich plasma improves fibrosis by transforming growth factor beta 1/Smad pathway in a rat intrauterine adhesion model | |
| TW202220678A (en) | Use of stem cell preparation by administering to kidney locus for treating kidney disease | |
| Li et al. | Sanchi-mediated inactivation of IL1B accelerates wound healing through the NFκB pathway deficit |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication |