CN117281080A - Application of food-borne bone soup nanoparticles in establishment of animal influence model of colonitis - Google Patents
Application of food-borne bone soup nanoparticles in establishment of animal influence model of colonitis Download PDFInfo
- Publication number
- CN117281080A CN117281080A CN202311074246.9A CN202311074246A CN117281080A CN 117281080 A CN117281080 A CN 117281080A CN 202311074246 A CN202311074246 A CN 202311074246A CN 117281080 A CN117281080 A CN 117281080A
- Authority
- CN
- China
- Prior art keywords
- bone soup
- food
- group
- borne
- colonitis
- 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
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 95
- 235000014347 soups Nutrition 0.000 title claims abstract description 90
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 60
- 241001465754 Metazoa Species 0.000 title claims abstract description 9
- 210000001072 colon Anatomy 0.000 claims abstract description 33
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 14
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 14
- 230000002550 fecal effect Effects 0.000 claims abstract description 13
- 241000699670 Mus sp. Species 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000012153 distilled water Substances 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims description 13
- 239000013641 positive control Substances 0.000 claims description 12
- 238000010171 animal model Methods 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 11
- 206010009887 colitis Diseases 0.000 claims description 9
- 230000003203 everyday effect Effects 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 210000002784 stomach Anatomy 0.000 claims description 6
- 230000006978 adaptation Effects 0.000 claims description 5
- 238000000465 moulding Methods 0.000 claims description 5
- 238000011725 BALB/c mouse Methods 0.000 claims description 4
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims description 4
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims description 4
- 229960001940 sulfasalazine Drugs 0.000 claims description 4
- 230000002262 irrigation Effects 0.000 claims description 3
- 238000003973 irrigation Methods 0.000 claims description 3
- 230000035622 drinking Effects 0.000 claims description 2
- 230000000968 intestinal effect Effects 0.000 abstract description 27
- 230000002757 inflammatory effect Effects 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 14
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 12
- 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 abstract description 7
- 108090001005 Interleukin-6 Proteins 0.000 abstract description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract description 7
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 abstract description 6
- 208000035861 hematochezia Diseases 0.000 abstract description 6
- 230000001575 pathological effect Effects 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 238000001641 gel filtration chromatography Methods 0.000 abstract description 3
- 208000035475 disorder Diseases 0.000 abstract description 2
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 abstract 1
- 239000002547 new drug Substances 0.000 abstract 1
- 241000282898 Sus scrofa Species 0.000 description 17
- 239000000243 solution Substances 0.000 description 12
- 235000013305 food Nutrition 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000000499 gel Substances 0.000 description 6
- 230000009266 disease activity Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 244000005709 gut microbiome Species 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 230000037396 body weight Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 3
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 3
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 3
- 102000003777 Interleukin-1 beta Human genes 0.000 description 3
- 108090000193 Interleukin-1 beta Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 102100033717 Retroviral-like aspartic protease 1 Human genes 0.000 description 3
- 101710188689 Small, acid-soluble spore protein 1 Proteins 0.000 description 3
- 101710188693 Small, acid-soluble spore protein 2 Proteins 0.000 description 3
- 101710166422 Small, acid-soluble spore protein A Proteins 0.000 description 3
- 101710166404 Small, acid-soluble spore protein C Proteins 0.000 description 3
- 101710174019 Small, acid-soluble spore protein C1 Proteins 0.000 description 3
- 101710174017 Small, acid-soluble spore protein C2 Proteins 0.000 description 3
- 101710174574 Small, acid-soluble spore protein gamma-type Proteins 0.000 description 3
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 3
- 235000005487 catechin Nutrition 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 229950001002 cianidanol Drugs 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- XFSBVAOIAHNAPC-XTHSEXKGSA-N 16-Ethyl-1alpha,6alpha,19beta-trimethoxy-4-(methoxymethyl)-aconitane-3alpha,8,10alpha,11,18alpha-pentol, 8-acetate 10-benzoate Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45C6[C@@H]([C@@]([C@H]31)(OC(C)=O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-XTHSEXKGSA-N 0.000 description 2
- XFSBVAOIAHNAPC-UHFFFAOYSA-N Aconitin Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(OC(C)=O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000019399 Colonic disease Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- 239000012506 Sephacryl® Substances 0.000 description 2
- 241000282894 Sus scrofa domesticus Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 229940039750 aconitine Drugs 0.000 description 2
- STDXGNLCJACLFY-UHFFFAOYSA-N aconitine Natural products CCN1CC2(COC)C(O)CC(O)C34C5CC6(O)C(OC)C(O)C(OC(=O)C)(C5C6OC(=O)c7ccccc7)C(C(OC)C23)C14 STDXGNLCJACLFY-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000010835 comparative analysis Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 238000002270 exclusion chromatography Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000701474 Alistipes Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000007621 cluster analysis Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 229920003045 dextran sodium sulfate Polymers 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960003720 enoxolone Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000008971 epithelial apoptosis Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000007358 intestinal barrier function Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/02—Breeding vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Environmental Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Developmental Biology & Embryology (AREA)
- Biomedical Technology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Virology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Pain & Pain Management (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of biological medicine, in particular to application of food-borne bone soup nano particles in establishing a colonitis animal influence model, and the food-borne bone soup nano particles are separated and purified from pig bone soup through gel filtration chromatography, can protect mouse ulcerative colitis induced by DSS and regulate intestinal flora disorder caused by colonitis by reducing the generation of inflammatory factors IL1 beta, IL-6 and TNF-alpha and inhibit inflammatory expression, and can be used for increasing the weight and colon length of the colonitis mice, improving the hematochezia condition and fecal morphology of the colonitis mice, improving the colon pathological structure of the colonitis mice, and providing a new drug selection for clinic in the process of establishing the ulcerative colitis mice influence model.
Description
The application is named as: an application of food-borne bone soup nanoparticles, the application number of which is: the patent of 202210046761.5 is filed separately, and the application date of the parent application is 2022, 1 month and 17 days.
Technical Field
The invention relates to the field of biological medicine, in particular to application of food-borne bone soup nanoparticles in establishing a colonitis animal influence model.
Background
Ulcerative colitis (Ulcerative Colitis, UC) is a chronic nonspecific disease of colorectal mucosa with unknown etiology, which has the characteristics of chronic progression, long course, repeated attack and the like, and is characterized by abnormal production of cytokines to inflammation, increase expression of adhesion molecules and infiltration of cells, and finally cause epithelial apoptosis and mucosal injury. Currently, there is a lack of effective treatments, which are classified by WHO as one of the refractory diseases. The incidence and prevalence in china has increased continuously over the last 20 years and is closely related to the occurrence of colon cancer, and the treatment of UC has become a clinical troublesome problem. Although some glucocorticoids and immunosuppressants can relieve symptoms, the effect is not satisfactory, and serious adverse reactions can be caused by long-term application. Therefore, there is an urgent need for drugs with high safety and for the treatment of UC.
In recent years, naturally occurring nanoparticles (naturally occurring nanoparticles), which are widely present in some foods, have attracted widespread attention. The food-derived naturally occurring nanoparticles have been eaten by people for a long time along with foods, have good safety, bioavailability and biocompatibility, and are more suitable for application in the food and pharmaceutical industries.
For example, the advantages of green tea extract assembly to form nanocarriers of anticancer chemotherapeutic agents in terms of safety and biocompatibility show good prospects as drugs.
Milk protein nanoparticles can improve the absorption efficiency of oral folic acid and omega-3 polyunsaturated fatty acids in vivo.
The nano particles formed by gelatin self-assembly can carry catechin EGCG and retain the bioactivity of the catechin EGCG, and the catechin EGCG is a future functional food additive.
The nano-particles of the self-assembly of the glycyrrhetin can embed aconitine and can effectively reduce toxicity of aconitine to organisms.
Even some plant-derived edible naturally occurring nanoparticles have been shown to have therapeutic effects on intestinal inflammation.
The pig bone contains bone marrow, is rich in collagen, protein, lipid, polysaccharide, nucleic acid and mineral components, and is boiled at high temperature and stewed with slow fire to prepare the pig bone soup which is delicious in taste and rich in nutrition and is more and more favored by people around the world. The pig bone soup is found to contain a large amount of naturally occurring nano particles, and has been shown to have the functions of regulating immune function and repairing intestinal barrier damage. However, no report on food-borne bone soup nano-particles in preventing and treating intestinal inflammatory diseases exists so far.
Disclosure of Invention
The first aim of the invention is to provide an application of food-borne bone soup nanoparticles in establishing a colonitis animal influence model.
In order to achieve the aim of the invention, the invention is realized by the following technical scheme:
application of food-borne bone soup nanoparticles in preparing medicines for treating ulcerative colitis is provided.
The application of the food-borne bone soup nano-particles in medicines for regulating and controlling dysbacteriosis and repairing intestinal mucosa injury.
The application of the food-borne bone soup nano-particles in the medicines for reducing the production of inflammatory factors and inhibiting the expression of inflammatory diseases.
Preferably, the inflammatory factor comprises any one or more of IL1 beta, IL-6 and TNF-alpha.
The preparation method of the food-borne bone soup nano-particles comprises the following steps:
(1) Performing hot processing on the pig bones to prepare pig bone soup;
(2) Centrifuging the pig bone soup obtained in the step (1) to obtain a supernatant;
(3) And (3) separating the supernatant obtained in the step (2) by combining gel exclusion chromatography with a dynamic light scattering instrument to obtain the pig bone soup functional nano-particles.
Preferably, the pig bone thermal processing process in step (1) is as follows: soaking Os Sus Domestica in sodium citrate solution, washing with distilled water to remove blood water, boiling with distilled water, and filtering to obtain Os Sus Domestica soup.
Preferably, the concentration of the sodium citrate solution is 0.5-3%.
Preferably, the feed liquid ratio of pig bones to distilled water in the boiling process is 1 (1-3) kg/L.
Preferably, the boiling time is 0.5-3 hours.
Preferably, the centrifugation speed in step (2) is 5000-10000r.min -1 The centrifugation time is 10-20min.
Preferably, the separation step in step (3) is as follows: introducing the supernatant into a gel exclusion chromatographic column to combine the functional nano particles on the gel exclusion chromatographic column, eluting with a buffer solution, simultaneously monitoring the eluent by combining 280nm ultraviolet bands with online dynamic light scattering, collecting the eluent with a light scattering peak, and drying the eluent to obtain the functional nano particles in the pig bone soup.
Preferably, the gel exclusion chromatographic column is agarose or a cross-linked derivative thereof;
the separation range is 60kDa-20000 kDa, and the pore diameter is 45-165 μm.
Preferably, the gel exclusion chromatographic column is of the type Sephacryl S-1000 SF.
Preferably, the buffer eluent is a phosphate buffer with a concentration of 0.01-0.1M and a pH of 6.5-7.5.
Preferably, the particle size of the functional nanoparticle is 100-300nm.
Application of food-borne bone soup nanoparticles in establishing a colitis animal influence model.
The method for establishing the animal influence model of the colonitis comprises the following steps:
(S.1) randomly dividing experimental animals into a normal group, a model group, a food-borne bone soup particle group, a bone soup group and a positive control group, and adapting to the environment;
(S.2) preparing a solution of DSS (direct sequence) by distilled water, and respectively feeding the solution to a model group, a food-source bone soup particle group, a bone soup group and a positive control group for free drinking to mold;
wherein, in the molding process:
the normal group and the model group irrigate the stomach with distilled water every day;
respectively carrying out stomach irrigation on the food-source bone soup granule solution and the bone soup by the food-source bone soup granule group and the bone soup group;
the positive control group is irrigated with sulfasalazine solution every day;
(S.3) starting from the first day of administration, recording the weight, the fecal form and the fecal blood-carrying condition of the experimental animal at fixed point and time every day, and scoring the fecal form and the fecal blood-carrying condition according to reference standards;
(S.4) after the end of the administration, the experimental animal is killed by neck removal, the colon is taken out, the excrement in the colon is collected, and the effect of the food-borne bone soup nano-particles on the colonitis of the experimental animal is evaluated.
Preferably, the colitis is ulcerative colitis.
Preferably, the experimental animal in the step (S.1) is SPF grade female BALB/c mice (20+ -2 g) of five weeks old;
the adaptation environment conditions are as follows: the temperature was 23.+ -. 2 ℃ and the humidity was 50.+ -. 5% and the mice adaptation time was 7 days.
Preferably, in the step (s.2), the concentration of the food-derived bone soup particle solution is identical to that of the bone soup.
Preferably, the concentration of DSS solution is 5%.
Preferably, the food-derived bone soup granule group and the bone soup group are respectively subjected to stomach irrigation at a dose of 50 mL (food-derived bone soup granule group solution or bone soup)/kg/day.
Preferably, the positive control group is gavaged at a dose of 250 mg/kg/day with sulfasalazine solution.
Further, the food-borne bone soup nano-particles are applied to increasing the weight and colon length of a colonitis mouse, improving the hematochezia condition and the fecal morphology of the colonic disease mouse and improving the colon pathological structure of the colonic disease mouse.
Therefore, the invention has the following beneficial effects:
(1) The food-source pig bone soup nanoparticle component obtained by gel filtration chromatography separation and purification from pig bone soup is prepared by reducing the production of inflammatory factors IL1b, IL-6 and TNF-alpha, inhibiting inflammatory expression and recovering inflammatory intestinal flora imbalance, so that the potential application of the food-source pig bone soup nanoparticle in ulcerative colitis treatment is explored.
(2) The invention provides application of food-borne bone soup nano-particles in preventing and treating ulcerative colitis, the food-borne bone soup nano-particles can increase the weight and colon length of a colonitis mouse, improve the hematochezia condition and fecal morphology of the colonitis mouse, improve the colon pathological structure of the enteritis mouse, can be used as a potential medicament for preventing and treating ulcerative colitis, and provide a new medicament selection for clinic.
Drawings
Fig. 1 is a TEM electron microscope observation diagram of the food-borne bone soup nanoparticle prepared by the present invention.
FIG. 2 is a graph showing the effect of food-borne bone soup nanoparticles on body weight, disease Activity Index (DAI), colon length, colon weight to colon length ratio.
FIG. 3 is a graph showing the effect of food-borne bone soup nanoparticles on intestinal tissue pathological changes and intestinal tissue inflammatory factor secretion.
Fig. 4 is a graph showing the effect of food-borne bone soup nanoparticles on the richness and diversity of intestinal flora.
FIG. 5 is a graph showing the results of comparative analysis of the microbial community composition of different samples.
Fig. 6 is a graph showing the effect of food-borne bone soup nanoparticles on the structure of intestinal microbiota.
Detailed Description
The invention is further described below with reference to the drawings and specific examples. Those of ordinary skill in the art will be able to implement the invention based on these descriptions. In addition, the embodiments of the present invention referred to in the following description are typically only some, but not all, embodiments of the present invention. Therefore, all other embodiments, which can be made by one of ordinary skill in the art without undue burden, are intended to be within the scope of the present invention, based on the embodiments of the present invention.
The preparation method of the food-borne bone soup nano-particles comprises the following steps:
(1) Pig bones are soaked in a 1% sodium citrate solution for 30 minutes, and then washed with distilled water for 3 times to remove blood. Adding distilled water according to a feed liquid ratio of 1:2kg/L, boiling for 2 hours, cooling to normal temperature, and finally filtering with gauze to obtain pig bone soup;
(2) Taking the coarse filtrate in a centrifuge with a centrifugation speed of 8000r.min -1 Centrifuging at 40deg.C for 10min to obtain supernatant;
(3) The supernatant was rapidly separated using a gel exclusion chromatography column (10 mm ×120 mm) packed with Sephacryl S-1000 SF packed with 0.05M phosphate buffer (pH 7.0) and equilibrated at the flow rate: the sample loading was 1mL at 0.3mL/min, elution with the same phosphate buffer was continued and the eluted fractions were monitored simultaneously with UV 280nm and DLS. Collecting the peak with strong laser light scattering signal absorbed under 280nm, collecting the pig bone soup colloid particles as functional nanoparticles at peak time of 105-115 min, desalting in distilled water, lyophilizing for use, wherein the particle size distribution is 50-500nm, the average particle size is 220-nm, the surface is negatively charged, zeta potential is-15 mV, and TEM (electron microscope) observation diagram shows that the pig bone soup colloid particles are uniform spheres.
[ EXAMPLES ]
The experimental animals of the invention are SPF-class female BALB/c mice (20+ -2 g) 30, purchased from Zhejiang province experimental animal center. At a temperature of 23.+ -. 2 ℃ and humidity of 50.+ -. 5%, the mice will adapt to the new conditions for 7 days.
The molding medicine of the invention is DSS dextran sodium sulfate, which is purchased from MP company, and the molecular weight of the molding medicine is 36000-50000.
The experimental procedure is as follows:
the food-borne nanoparticles were dissolved with distilled water until the light scattering value was consistent with that of bone Shang Yuanshang. 30 BALB/c mice were randomly assigned to a normal group (designated Control), a model group (designated DSS), a food-borne bone soup particle group (designated BSNPs), a bone soup group (designated BS), and a positive Control group (sulfasalazine, SASP, designated SASP). After one week of environmental adaptation, DSS was formulated as a 5% solution in distilled water and was given free-drinking to DSS, BSNPs, BS, SASP groups for modeling for 7 consecutive days. During the molding period, the Control group and the DSS group irrigate the stomach with distilled water every day; the BSNPs and BS groups were intragastrically dosed at 50 mL (BSNPs or BS)/kg/day. The SASP group was gavaged at a dose of 250 mg/kg/day.
Starting from the first day of dosing, mice body weight, stool morphology, stool blood status were recorded at fixed point daily and scored for stool morphology, stool blood status according to reference standards. Fecal morphology: normally, score 0; soft and shaped, 1 minute; very soft, 2 minutes; diarrhea, 3 minutes. Hematochezia condition: blood is not present in the stool, and the score is 0; occult blood in the stool, 1 minute; blood is obviously in the stool, and 2 minutes; diarrhea-like hematochezia with staining of the anus, 3 minutes. 7 days after administration, mice were sacrificed from cervical removal, the colon was removed, and stool feces were collected in the colon for 16s rRNA measurement. The length of the colon was measured with a ruler, the colon was washed with normal saline, divided into two parts, one part was fixed with paraformaldehyde, paraffin-embedded, cut into 4 μm sections, HE stained, and the pathological changes of intestinal tissues were observed with an optical microscope. After another liquid nitrogen freeze, -80 degrees celsius was reserved for inflammatory factor mRNA expression analysis.
The degree of colitis in mice can be reflected by clinical indicators. Mice with severe colitis will lose weight, have increased disease activity index and a shorter colon length. In addition, the ratio of the weight of the colon to the length of the colon can be used as an index for measuring the degree of colonitis, and the more inflammatory the colon is, the greater the ratio is.
FIG. 2 is the effect of food-borne bone soup nanoparticles on body weight, disease Activity Index (DAI), colon length, colon weight to colon length ratio. As can be seen from fig. 1, compared with the Control group, the model DSS group body weight is reduced, the disease activity index is increased, the colon length is obviously shortened, the ratio of the colon weight to the colon length is obviously increased, and the model is established; compared with a model DSS group, the food-borne bone soup nano-particle BSNPs group and the bone soup source Shang Zu BS group obviously improve the weight and the colon length of mice, reduce the ratio of disease activity index to the colon weight and the colon length, and have the effect equivalent to or even slightly better than that of a positive control medicine SASP, and have statistical significance.
FIG. 3 is the effect of food-borne bone soup nanoparticles on intestinal tissue pathology and intestinal tissue inflammatory factor secretion. The intestinal tissue condition is evaluated by HE staining, and the result shows that the intestinal mucosa epithelial cells of the normal group are complete, the intestinal lines are normal, the intestinal cells are not inflammatory infiltrated or damaged, and the intestinal tissue is good. The model group has obvious intestinal wall thickening, large-area neutrophil infiltration exists in an intrinsic layer, intestinal villus is irregular, local villus and intestinal lines disappear, necrotic tissues and inflammatory cells infiltrate, and inflammatory states are obvious. In the food-borne bone soup nanoparticle group and the positive control group, the intestinal wall edema is changed into mild, intestinal villus epithelium is complete, neutrophil infiltration is obviously relieved, and the inflammatory degree is reduced. Histological scores also show that the food-borne bone soup nanoparticles reduce histological scores, indicating that the food-borne bone soup nanoparticles play a protective role on the intestinal tract. TNF-alpha, IL-6 and IL-1 beta are important inflammation related factors of intestinal inflammation, and through the analysis of the expression of the inflammation factors TNF-alpha, IL-6 and IL-1 beta in colon tissues, the model DSS group obviously increases the expression of the TNF-alpha, IL-6 and IL-1 beta compared with the Control group, and the food-borne bone soup nano-particle BSNPs group and the bone soup Shang Zu BS group obviously reduce the expression of the inflammation factors, which indicates that the food-borne bone soup nano-particles inhibit the generation of the inflammation factors.
Fig. 4 is the effect of food-borne bone soup nanoparticles on the richness and diversity of intestinal flora. The Chao1 and the observed specs index reflect the richness of the flora, and the higher the index of the two indexes is, the higher the richness is; shannon index reflects flora diversity with Simpson index, and as such, the higher the two indices, the higher the diversity. Intestinal inflammation reduces the richness and diversity of the intestinal microbiota. The DSS model group has significantly reduced intestinal flora richness and diversity compared to the Control normal group. And the food source bone soup nano-particle BSNPs group and the bone soup source Shang Zu BS group obviously improve the richness and diversity of intestinal flora, and have biological significance. The food-borne bone soup nano-particles have the function of regulating and controlling intestinal microflora.
FIG. 5 is a comparative analysis of the microbial community composition of different samples. PCoA and NMDS analysis results show that the food-borne bone soup nano-particle BSNPs group, the bone soup source Shang Zu BS group, the positive Control SASP group are closer to the Control group, and the four groups are far away from the model DSS group. The same results are shown for the non-weighted group average cluster analysis (UPGMA, unweightedPair-groupMethod with Arithmetic Means). These results indicate that the food-derived bone soup nanoparticles can restore the imbalance of intestinal inflammatory microflora.
Fig. 6 shows the effect of food-borne bone soup nanoparticles on intestinal microbiota structure. The results indicate that DSS causes significant changes in the intestinal microflora structure. DSS is up-regulated at the gate level compared to the normal Control groupCampilobacterotaAnd (3) withFirmicutesBut reduce the relative abundance ofThe relative abundance of bacteroidota.In addition, DSS also increases significantlyFirmicute/BacteroidotaAt the genus level, DSS is significantly reducedMuribaculaceae(Figure 5D), Alistipes(Figure 5H), andAlloprevotellathe relative abundance of (Figure 5G) increasesThe helicobacter and Lachnospiraceae_N4A136_group.And the food-borne bone soup nano-particle BSNPs group, the bone soup source Shang Zu BS group and the positive control group recover the bacterial groups to be normal. These results indicate that the food-derived bone soup nano-particles have the effect of regulating intestinal flora of enteritisDisorder function.
Therefore, the data show that the food-source bone soup nanoparticle component obtained by gel filtration chromatography separation and purification from the bone soup of the invention can protect the mouse ulcerative colitis induced by DSS and regulate intestinal flora disorder caused by colitis by reducing the production of inflammatory factors IL1b, IL-6 and TNF-alpha and inhibiting inflammatory expression, thereby seeking the potential application of the bone soup nanoparticle in ulcerative colitis treatment.
In addition, in the process of establishing an ulcerative colitis mouse influence model, the food-borne bone soup nano-particles can be used for increasing the weight and colon length of the colitis mouse, improving the hematochezia condition and the fecal morphology of the colitis mouse and improving the colon pathological structure of the enteritis mouse, can be used as a potential medicament for preventing and treating the ulcerative colitis, and can provide a new medicament selection for clinic.
Claims (5)
1. Application of food-borne bone soup nanoparticles in establishing a colitis animal influence model.
2. The use according to claim 1, wherein,
the method for establishing the animal influence model of the colonitis comprises the following steps:
(S.1) randomly dividing experimental animals into a normal group, a model group, a food-borne bone soup particle group, a bone soup group and a positive control group, and adapting to the environment;
(S.2) preparing a solution of DSS (direct sequence) by distilled water, and respectively feeding the solution to a model group, a food-source bone soup particle group, a bone soup group and a positive control group for free drinking to mold;
wherein, in the molding process:
the normal group and the model group irrigate the stomach with distilled water every day;
respectively carrying out stomach irrigation on the food-source bone soup granule solution and the bone soup by the food-source bone soup granule group and the bone soup group;
the positive control group is irrigated with sulfasalazine solution every day;
(S.3) starting from the first day of administration, recording the weight, the fecal form and the fecal blood-carrying condition of the experimental animal at fixed point and time every day, and scoring the fecal form and the fecal blood-carrying condition according to reference standards;
(S.4) after the end of the administration, the experimental animal is killed by neck removal, the colon is taken out, the excrement in the colon is collected, and the effect of the food-borne bone soup nano-particles on the colonitis of the experimental animal is evaluated.
3. The use according to claim 1 or 2, characterized in that,
the colitis is ulcerative colitis.
4. The use according to claim 2, wherein,
the experimental animal in the step (S.1) is SPF grade female BALB/c mice with five weeks of age;
the adaptation environment conditions are as follows: the temperature was 23.+ -. 2 ℃ and the humidity was 50.+ -. 5% and the mice adaptation time was 7 days.
5. The use according to claim 2, wherein,
and (2) the concentration of the food-source bone soup granule solution in the step (S.2) is consistent with that of the bone soup.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311074246.9A CN117281080A (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles in establishment of animal influence model of colonitis |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311074246.9A CN117281080A (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles in establishment of animal influence model of colonitis |
| CN202210046761.5A CN114344337B (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210046761.5A Division CN114344337B (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117281080A true CN117281080A (en) | 2023-12-26 |
Family
ID=81091697
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311074246.9A Pending CN117281080A (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles in establishment of animal influence model of colonitis |
| CN202210046761.5A Active CN114344337B (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210046761.5A Active CN114344337B (en) | 2022-01-17 | 2022-01-17 | Application of food-borne bone soup nanoparticles |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN117281080A (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109953305B (en) * | 2017-12-14 | 2024-01-26 | 浙江工商大学 | Method for maintaining and optimizing flavor of pig bone soup by utilizing microporous filtration |
-
2022
- 2022-01-17 CN CN202311074246.9A patent/CN117281080A/en active Pending
- 2022-01-17 CN CN202210046761.5A patent/CN114344337B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN114344337A (en) | 2022-04-15 |
| CN114344337B (en) | 2024-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5325109B2 (en) | Composition for the treatment of atopic dermatitis containing bamboo extract and Koganebana extract | |
| Xu et al. | Protective effects of astragalus polysaccharide nanoparticles on septic cardiac dysfunction through inhibition of TLR4/NF-κB signaling pathway | |
| CN111265662A (en) | Use of intervention 14-3-3 in the treatment of sepsis | |
| Mao et al. | GelNB molecular coating as a biophysical barrier to isolate intestinal irritating metabolites and regulate intestinal microbial homeostasis in the treatment of inflammatory bowel disease | |
| CN115068629B (en) | Drug-loaded nanoparticle based on curcumin and cerium oxide as well as preparation method and application thereof | |
| CN113398073A (en) | Salvianic acid A sodium self-assembled liposome for treating ulcerative colitis and preparation method thereof | |
| Ge et al. | Physicochemical characteristics and anti-hyperlipidemic effect of polysaccharide from BaChu mushroom (Helvella leucopus) | |
| Lin et al. | Efficient fucoidan extraction and purification from Sargassum cristaefolium and preclinical dermal biological activity assessments of the purified fucoidans | |
| CN114344337B (en) | Application of food-borne bone soup nanoparticles | |
| Feng et al. | Pectin–zein based stigmasterol nanodispersions ameliorate dextran sulfate sodium-induced colitis in mice | |
| CN112691115A (en) | Arabinoxylan and compound for preventing/treating gastrointestinal mucosa and liver injury | |
| CN108079001B (en) | Application of xylan esterification product in preparing medicine for preventing or treating inflammatory diseases and cancers | |
| CN110101731A (en) | Chrysanthemum cauline leaf activity extract and the preparation method and application thereof with prevention and treatment eye disease | |
| CN112691114A (en) | Application of momordica polysaccharide in preparation of medicine for treating ulcerative colitis and pharmaceutical preparation of momordica polysaccharide | |
| TWI726184B (en) | Polysaccharides of brown algae, method of producing the same and application thereof | |
| JP3638967B2 (en) | Remedies for nephrotic syndrome and liver damage symptoms | |
| FU et al. | Biochanin A, as the Lrg1/TGF-β/Smad2 pathway blockade, attenuates blood-brain barrier damage after cerebral ischemiare-perfusion by modulating leukocyte migration patterns. | |
| JP4786911B2 (en) | Allergic disease treatment | |
| Wang et al. | Neuroprotective Effects of Microglial Membrane‐Derived Biomimetic Particles for Spinal Cord Injury | |
| JP6997839B2 (en) | External pharmaceutical composition for the prevention and treatment of rheumatoid arthritis | |
| CN116270634B (en) | Application of Zhongwuning in preparing medicine for preventing and treating liver diseases | |
| CN116236513B (en) | Application of artemisia sphaerocephala root extract in preparation of anti-rheumatoid arthritis drugs | |
| CN113995751B (en) | Application of epalrestat in preparing medicine for preventing and treating cerebral arterial thrombosis | |
| CN108186675A (en) | Heparin iron complexes are to the treatment use of chronic inflam matory anemia | |
| CN117018073A (en) | Application of green plum-derived nano-particles in preparation of medicines for preventing and treating ulcerative colitis |
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 |