CN110893233A - Application of irisin in preparation of anti-inflammatory drugs - Google Patents
Application of irisin in preparation of anti-inflammatory drugs Download PDFInfo
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- CN110893233A CN110893233A CN201911315917.XA CN201911315917A CN110893233A CN 110893233 A CN110893233 A CN 110893233A CN 201911315917 A CN201911315917 A CN 201911315917A CN 110893233 A CN110893233 A CN 110893233A
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- 101800001026 Irisin Proteins 0.000 title claims abstract description 67
- LNQCUTNLHUQZLR-OZJWLQQPSA-N iridin Chemical compound OC1=C(OC)C(OC)=CC(C=2C(C3=C(O)C(OC)=C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C=C3OC=2)=O)=C1 LNQCUTNLHUQZLR-OZJWLQQPSA-N 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 229940124599 anti-inflammatory drug Drugs 0.000 title claims abstract description 28
- 102100026535 Fibronectin type III domain-containing protein 5 Human genes 0.000 title abstract 6
- 239000003814 drug Substances 0.000 claims abstract description 71
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 46
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims abstract description 45
- 229940079593 drug Drugs 0.000 claims abstract description 40
- 230000004054 inflammatory process Effects 0.000 claims abstract description 27
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 26
- 206010061218 Inflammation Diseases 0.000 claims abstract description 25
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 18
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims abstract description 13
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229960001138 acetylsalicylic acid Drugs 0.000 claims abstract description 13
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 13
- 229960002009 naproxen Drugs 0.000 claims abstract description 13
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims abstract description 13
- 229960005489 paracetamol Drugs 0.000 claims abstract description 13
- 229960000905 indomethacin Drugs 0.000 claims abstract description 12
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 11
- 230000003637 steroidlike Effects 0.000 claims abstract description 9
- 102400001216 Irisin Human genes 0.000 claims description 61
- 239000002202 Polyethylene glycol Substances 0.000 claims description 56
- 229920001223 polyethylene glycol Polymers 0.000 claims description 56
- 239000007962 solid dispersion Substances 0.000 claims description 33
- 239000000843 powder Substances 0.000 claims description 30
- 238000001035 drying Methods 0.000 claims description 16
- 238000002156 mixing Methods 0.000 claims description 16
- 239000004599 antimicrobial Substances 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 12
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 11
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 239000000853 adhesive Substances 0.000 claims description 6
- 230000001070 adhesive effect Effects 0.000 claims description 6
- 239000002158 endotoxin Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 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 claims description 5
- 102000005862 Angiotensin II Human genes 0.000 claims description 5
- 101800000733 Angiotensin-2 Proteins 0.000 claims description 5
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims description 5
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 5
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 5
- 108090001005 Interleukin-6 Proteins 0.000 claims description 5
- 108090001007 Interleukin-8 Proteins 0.000 claims description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 229950006323 angiotensin ii Drugs 0.000 claims description 5
- 230000000843 anti-fungal effect Effects 0.000 claims description 5
- 230000002558 anti-leprotic effect Effects 0.000 claims description 5
- 229940121375 antifungal agent Drugs 0.000 claims description 5
- 239000003443 antiviral agent Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 150000002240 furans Chemical class 0.000 claims description 5
- 238000000227 grinding Methods 0.000 claims description 5
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 5
- 150000007660 quinolones Chemical class 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 229940072185 drug for treatment of tuberculosis Drugs 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 230000000379 polymerizing effect Effects 0.000 claims description 2
- 229940003898 combination of sulfonamides Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
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- 238000006243 chemical reaction Methods 0.000 description 4
- 229940124530 sulfonamide Drugs 0.000 description 4
- 150000003456 sulfonamides Chemical class 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 3
- 101150100944 Nos2 gene Proteins 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 229940124976 antitubercular drug Drugs 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
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- 239000000814 tuberculostatic agent Substances 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010017553 Furuncle Diseases 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 241000779819 Syncarpia glomulifera Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000001739 pinus spp. Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
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- 208000037816 tissue injury Diseases 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229940036248 turpentine Drugs 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- 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]
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- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Marine Sciences & Fisheries (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of irisin in preparing anti-inflammatory drugs, and the preparation method of the irisin anti-inflammatory drugs specifically comprises the following steps: s1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 20-30 parts of aspirin, 10-20 parts of acetaminophen, 5-10 parts of indometacin, 5-10 parts of naproxen and 5-10 parts of naproxen according to the total weight parts of the medicaments, and selecting 20-30 parts of aspirin and 10-20 parts of acetaminophen, relating to the technical field of medicines. The application of the irisin in preparing the anti-inflammatory drug can realize that the anti-inflammatory effect of the anti-inflammatory drug is improved by adding the irisin into the non-steroidal drug, the irisin can achieve the aim of resisting inflammation by inhibiting the expression of inflammatory factors and the activation of key signal molecules NF-kB-p 65 and p38 of an inflammatory signal channel, is suitable for infectious and non-infectious inflammations, and can achieve the required curative effect without needing a patient to take a large amount of anti-inflammatory drugs for a long time, thereby ensuring the healthy life of the patient.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of irisin in preparation of anti-inflammatory drugs.
Background
Inflammation is a very common and important basic pathological process, trauma infection on the body surface and most common diseases and frequently encountered diseases (such as furuncle, carbuncle, pneumonia, hepatitis, nephritis and the like) of each organ belong to inflammatory diseases, defensive reaction of living tissues with vascular systems to injury factors is called inflammation, defensive reaction of living tissues with vascular systems to the injury factors is inflammation, vascular reaction is a central link of the inflammatory process, on one hand, the injury factors directly or indirectly cause damage to tissues and cells in the inflammatory process, on the other hand, the injury factors are diluted, killed and enclosed through inflammatory hyperemia and exudation reaction, and simultaneously, the damaged tissues are repaired and healed through regeneration of parenchyma and interstitial cells, so that the inflammation is a unified process of injury and damage resistance, and any factor capable of causing tissue injury can become a cause of inflammation, i.e., inflammatory factors, can be summarized in the following categories: biological factors, bacteria, viruses, rickettsia, mycoplasma, fungi, spirochetes, parasites and the like are the most common causes of inflammation, inflammation caused by biological pathogens is also called infection, exotoxin and endotoxin generated by bacteria can directly damage tissues, and viruses are replicated in infected cells to cause cell necrosis; second, physical factors, high temperature, low temperature, radioactive substances, ultraviolet rays and the like, and mechanical damage; and thirdly, chemical factors, exogenous chemical substances such as strong acid, strong base, turpentine, mustard gas and the like, and endogenous toxic substances such as decomposition products of necrotic tissues and metabolic products such as urea and the like accumulated in the body under certain pathological conditions.
At present, antibiotics are generally used for treating inflammation, but the antibiotics are only effective to infectious inflammation and are not effective to non-infectious inflammation, and in addition, although the existing glucocorticoid medicaments and non-steroidal anti-inflammatory medicaments can be used for anti-inflammatory treatment, the expected anti-inflammatory curative effect is achieved, the anti-inflammatory medicaments need to be taken for a long time in large quantities, and the anti-inflammatory medicaments are taken for a long time in large quantities, so that adverse reactions are generated, side effects are large, and great pain is brought to patients.
Disclosure of Invention
Technical problem to be solved
Aiming at the defects of the prior art, the invention provides the application of irisin in preparing anti-inflammatory drugs, and solves the problems that the existing antibiotics are only effective to infectious inflammation but are ineffective to non-infectious inflammation, the existing glucocorticoid drugs and non-steroidal anti-inflammatory drugs achieve the expected anti-inflammatory curative effect, the anti-inflammatory drugs need to be taken for a long time in large quantities, and the anti-inflammatory drugs can generate adverse reactions and have great side effects after being taken for a long time in large quantities.
(II) technical scheme
In order to achieve the purpose, the invention is realized by the following technical scheme: the application of irisin in preparing anti-inflammatory drugs specifically comprises the following steps:
s1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 20-30 parts of aspirin, 10-20 parts of acetaminophen, 5-10 parts of indometacin, 5-10 parts of naproxen and 5-10 parts of naproxone according to the total weight ratio of the medicaments, and sequentially adding 20-30 parts of aspirin, 10-20 parts of acetaminophen, 5-10 parts of indometacin, 5-10 parts of naproxen and 5-10 parts of naproxone into a grinder for fully grinding and mixing until the particle size of the medicaments is 100 meshes and 150 meshes, thus obtaining the combined non-steroidal anti-inflammatory medicament;
s2, preparation of solid dispersion: sequentially adding the combined non-steroidal anti-inflammatory drug prepared by S1 and polyethylene glycol PEG into a mixed reagent bottle for mixing, heating the mixed drug in the reagent bottle until the polyethylene glycol PEG is completely melted, then adding 30-40 parts of irisin and 5-10 parts of solvent by total weight of the drug, stirring until the liquid is transparent, cooling under stirring until the liquid is completely solidified, naturally drying or drying under reduced pressure, and removing the solvent to obtain a solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in a weight ratio of 1: 0.5: 2;
s3, preparation of combined medicine tablets: adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol (PEG) and the irisin in the weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, adding a polyvinylpyrrolidone adhesive into the prepared combined drug micro powder to be bonded, pouring the mixed drug into a tabletting machine to be extruded and molded, and drying to obtain a combined tablet;
s4, preparation of the combined pharmaceutical preparation: and (3) adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in the weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, mixing the micro powder and the antimicrobial drug according to a certain ratio, and subpackaging according to the amount of 1-30g per bottle to obtain the compound powder injection containing the non-steroidal anti-inflammatory drug, the irisin anti-inflammatory drug and the antimicrobial drug.
Preferably, the inflammation is caused by angiotensin II and lipopolysaccharide, and the inflammatory factors include IL-1 β, TNF- α, IL-6, IL-8 and Nos 2.
Preferably, the polyvinylpyrrolidone in step S3 is a polymer compound obtained by polymerizing N-vinyl-2-pyrrolidone.
Preferably, the antimicrobial drug in step S4 is one or more of sulfonamides, quinolones, furans, antituberculosis drugs, anti-leprosy drugs, antifungal drugs, and antiviral drugs.
Preferably, the irisin is used as an active ingredient for preparing anti-inflammatory drugs in a pharmaceutical composition which receives additives in pharmacy.
Preferably, the anti-inflammatory drug is prepared into a powder preparation or a solid preparation, the powder preparation is a compound powder injection, and the solid preparation is a tablet.
(III) advantageous effects
The invention provides application of irisin in preparing an anti-inflammatory drug. Compared with the prior art, the method has the following beneficial effects: the application of the irisin in preparing the anti-inflammatory drug comprises the following steps: s1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 20-30 parts of aspirin, 10-20 parts of acetaminophen, 5-10 parts of indometacin, 5-10 parts of naproxen and 5-10 parts of naproxone according to the total weight parts of the medicaments, and preparing a solid dispersion: sequentially adding the combined non-steroidal anti-inflammatory drug prepared by the step S1 and polyethylene glycol PEG into a mixed reagent bottle for mixing, heating the mixed drug in the reagent bottle until the polyethylene glycol PEG is completely melted, then adding 30-40 parts of irisin and 5-10 parts of solvent by weight, and S3, preparing the combined drug tablet: adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol (PEG) and the irisin in a weight ratio of 1: 0.5: 2 obtained in the step S2 into a small pulverizer for pulverization to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, then adding a polyvinylpyrrolidone adhesive into the prepared combined drug micro powder for bonding, then pouring the mixed drug into a tabletting machine for extrusion forming, and drying to obtain a combined tablet, wherein the preparation method comprises the following steps of S4: the micro powder and the antimicrobial drug are mixed according to a certain proportion, and are subpackaged according to the loading of 1-30g per bottle to obtain the compound powder injection containing the non-steroidal drug, the irisin anti-inflammatory drug and the antimicrobial drug, the anti-inflammatory effect of the anti-inflammatory drug can be improved by adding the irisin into the non-steroidal drug, the irisin can achieve the aim of resisting inflammation by inhibiting the expression of inflammatory factors and the activation of key signal molecules NF-kB-p 65 and p38 of an inflammation signal channel, the compound powder injection is suitable for infectious and non-infectious inflammations, a patient does not need to take a large amount of anti-inflammatory drugs for a long time to achieve the required curative effect, adverse reactions and great pain brought to the patient by taking a large amount of the anti-inflammatory drugs for a long time are well avoided, and the healthy life of the patient is guaranteed.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of the invention provides three technical schemes: the application of irisin in preparing anti-inflammatory drugs specifically comprises the following embodiments:
example 1
S1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 25 parts of aspirin, 15 parts of acetaminophen, 8 parts of indometacin, 8 parts of naproxen and 8 parts of naproxone according to the total weight ratio of the medicaments, and sequentially adding the selected 25 parts of aspirin, 15 parts of acetaminophen, 8 parts of indometacin, 8 parts of naproxen and 8 parts of naproxone into a grinder for fully grinding and mixing until the granularity of the medicaments is 130 meshes, so as to obtain the combined non-steroidal anti-inflammatory medicament;
s2, preparation of solid dispersion: sequentially adding the combined non-steroidal anti-inflammatory drug prepared in the step S1 and polyethylene glycol PEG into a mixed reagent bottle for mixing, heating the mixed drug in the reagent bottle until the polyethylene glycol PEG is completely melted, then adding 35 parts of irisin and 8 parts of solvent in parts by weight of the total weight of the drugs, stirring until the liquid is transparent, cooling under stirring until the liquid is completely solidified, naturally drying or drying under reduced pressure, and removing the solvent to obtain a solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in a weight ratio of 1: 0.5: 2;
s3, preparation of combined medicine tablets: adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol (PEG) and the irisin in a weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, then adding a polyvinylpyrrolidone adhesive into the prepared combined drug micro powder to be bonded, wherein the polyvinylpyrrolidone is a high molecular compound generated by polymerization of N-vinyl-2-pyrrolidone, then pouring the mixed drug into a tabletting machine to be extruded and molded, and drying to obtain a combined tablet;
s4, preparing a combined medicinal preparation, namely adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin obtained in the step S2 into a small-sized pulverizer to pulverize, so as to obtain solid dispersion micropowder containing the non-steroidal anti-inflammatory drug and the irisin, then mixing the micropowder with the antimicrobial drug according to a certain proportion, and subpackaging according to the amount of 15g per bottle, so as to obtain the compound powder injection containing the non-steroidal anti-inflammatory drug and the irisin, wherein the inflammation is caused by angiotensin II and lipopolysaccharide, and the inflammatory factors comprise IL-1 β, TNF- α, IL-6, IL-8 and Nos2, the antimicrobial drug is one or a combination of more of sulfonamides, quinolones, furans, antitubercular drugs, antileprosy drugs, antifungal drugs and antiviral drugs, and the irisin reduces the inflammatory factor expression and inflammatory cell infiltration in the adipose tissue inflammation caused by obesity.
Example 2
S1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 20 parts of aspirin, 10 parts of acetaminophen, 5 parts of indometacin, 5 parts of naproxen and 5 parts of naproxone according to the total weight ratio of the medicaments, and sequentially adding the selected 20 parts of aspirin, 10 parts of acetaminophen, 5 parts of indometacin, 5 parts of naproxen and 5 parts of naproxone into a grinder for fully grinding and mixing until the granularity of the medicaments is 100 meshes, so as to obtain the combined non-steroidal anti-inflammatory medicament;
s2, preparation of solid dispersion: sequentially adding the combined non-steroidal anti-inflammatory drug prepared in the step S1 and polyethylene glycol PEG into a mixed reagent bottle for mixing, heating the mixed drug in the reagent bottle until the polyethylene glycol PEG is completely melted, then adding 30 parts of irisin and 5 parts of solvent in parts by weight of the total weight of the drugs, stirring until the liquid is transparent, cooling under stirring until the liquid is completely solidified, naturally drying or drying under reduced pressure, and removing the solvent to obtain a solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in a weight ratio of 1: 0.5: 2;
s3, preparation of combined medicine tablets: adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol (PEG) and the irisin in a weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, then adding a polyvinylpyrrolidone adhesive into the prepared combined drug micro powder to be bonded, wherein the polyvinylpyrrolidone is a high molecular compound generated by polymerization of N-vinyl-2-pyrrolidone, then pouring the mixed drug into a tabletting machine to be extruded and molded, and drying to obtain a combined tablet;
s4, preparing a combined medicinal preparation, namely adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin obtained in the step S2 into a small-sized pulverizer to pulverize, so as to obtain solid dispersion micropowder containing the non-steroidal anti-inflammatory drug and the irisin, then mixing the micropowder with the antimicrobial drug according to a certain proportion, and subpackaging according to the amount of 20g per bottle, so as to obtain the compound powder injection containing the non-steroidal anti-inflammatory drug and the irisin, wherein the inflammation is caused by angiotensin II and lipopolysaccharide, and the inflammatory factors comprise IL-1 β, TNF- α, IL-6, IL-8 and Nos2, the antimicrobial drug is one or a combination of more of sulfonamides, quinolones, furans, antitubercular drugs, antileprosy drugs, antifungal drugs and antiviral drugs, and the irisin reduces the inflammatory factor expression and inflammatory cell infiltration in the adipose tissue inflammation caused by obesity.
Example 3
S1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 30 parts of aspirin, 20 parts of acetaminophen, 10 parts of indometacin, 10 parts of naproxen and 10 parts of naproxone according to the total weight ratio of the medicaments, and sequentially adding the selected 30 parts of aspirin, 20 parts of acetaminophen, 10 parts of indometacin, 10 parts of naproxen and 10 parts of naproxone into a grinder for fully grinding and mixing until the granularity of the medicaments is 150 meshes, so as to obtain the combined non-steroidal anti-inflammatory medicament;
s2, preparation of solid dispersion: sequentially adding the combined non-steroidal anti-inflammatory drug prepared in the step S1 and polyethylene glycol PEG into a mixed reagent bottle for mixing, heating the mixed drug in the reagent bottle until the polyethylene glycol PEG is completely melted, then adding 40 parts of irisin and 10 parts of solvent by weight of the total weight of the drugs, stirring until the liquid is transparent, cooling under stirring until the liquid is completely solidified, naturally drying or drying under reduced pressure, and removing the solvent to obtain a solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in a weight ratio of 1: 0.5: 2;
s3, preparation of combined medicine tablets: adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol (PEG) and the irisin in a weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, then adding a polyvinylpyrrolidone adhesive into the prepared combined drug micro powder to be bonded, wherein the polyvinylpyrrolidone is a high molecular compound generated by polymerization of N-vinyl-2-pyrrolidone, then pouring the mixed drug into a tabletting machine to be extruded and molded, and drying to obtain a combined tablet;
s4, preparing a combined medicinal preparation, namely adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin obtained in the step S2 into a small-sized pulverizer to pulverize, so as to obtain solid dispersion micropowder containing the non-steroidal anti-inflammatory drug and the irisin, then mixing the micropowder with the antimicrobial drug according to a certain proportion, and subpackaging according to the amount of 25g per bottle, so as to obtain the compound powder injection containing the non-steroidal anti-inflammatory drug and the irisin, wherein the inflammation is caused by angiotensin II and lipopolysaccharide, and the inflammatory factors comprise IL-1 β, TNF- α, IL-6, IL-8 and Nos2, the antimicrobial drug is one or a combination of more of sulfonamides, quinolones, furans, antitubercular drugs, antileprosy drugs, antifungal drugs and antiviral drugs, and the irisin reduces the inflammatory factor expression and inflammatory cell infiltration in the adipose tissue inflammation caused by obesity.
Effects of the embodiment
100 patients treated with irisin-containing anti-inflammatory drugs according to examples 1 to 3 of the present invention were collected and investigated, and 86 patients were cured in one treatment course, accounting for 86% of the investigated population.
It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (6)
1. The application of irisin in preparing anti-inflammatory drugs is characterized in that: the preparation method of the irisin anti-inflammatory drug specifically comprises the following steps:
s1, preparation of the combined non-steroidal anti-inflammatory drug: firstly, respectively selecting 20-30 parts of aspirin, 10-20 parts of acetaminophen, 5-10 parts of indometacin, 5-10 parts of naproxen and 5-10 parts of naproxone according to the total weight ratio of the medicaments, and sequentially adding 20-30 parts of aspirin, 10-20 parts of acetaminophen, 5-10 parts of indometacin, 5-10 parts of naproxen and 5-10 parts of naproxone into a grinder for fully grinding and mixing until the particle size of the medicaments is 100 meshes and 150 meshes, thus obtaining the combined non-steroidal anti-inflammatory medicament;
s2, preparation of solid dispersion: sequentially adding the combined non-steroidal anti-inflammatory drug prepared by S1 and polyethylene glycol PEG into a mixed reagent bottle for mixing, heating the mixed drug in the reagent bottle until the polyethylene glycol PEG is completely melted, then adding 30-40 parts of irisin and 5-10 parts of solvent by total weight of the drug, stirring until the liquid is transparent, cooling under stirring until the liquid is completely solidified, naturally drying or drying under reduced pressure, and removing the solvent to obtain a solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in a weight ratio of 1: 0.5: 2;
s3, preparation of combined medicine tablets: adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol (PEG) and the irisin in the weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, adding a polyvinylpyrrolidone adhesive into the prepared combined drug micro powder to be bonded, pouring the mixed drug into a tabletting machine to be extruded and molded, and drying to obtain a combined tablet;
s4, preparation of the combined pharmaceutical preparation: and (3) adding the solid dispersion containing the non-steroidal anti-inflammatory drug, the polyethylene glycol PEG and the irisin in the weight ratio of 1: 0.5: 2 obtained in the step (S2) into a small pulverizer to be pulverized to obtain solid dispersion micro powder containing the non-steroidal anti-inflammatory drug and the irisin, mixing the micro powder and the antimicrobial drug according to a certain ratio, and subpackaging according to the amount of 1-30g per bottle to obtain the compound powder injection containing the non-steroidal anti-inflammatory drug, the irisin anti-inflammatory drug and the antimicrobial drug.
2. The use of irisin in the manufacture of an anti-inflammatory medicament according to claim 1, wherein said inflammation is caused by angiotensin II and lipopolysaccharide and inflammatory factors include IL-1 β, TNF- α, IL-6, IL-8, and Nos 2.
3. The use of an irisin according to claim 1 in the preparation of an anti-inflammatory medicament, wherein: the polyvinylpyrrolidone in step S3 is a polymer compound formed by polymerizing N-vinyl-2-pyrrolidone.
4. The use of an irisin according to claim 1 in the preparation of an anti-inflammatory medicament, wherein: the antimicrobial drug in step S4 is one or a combination of sulfonamides, quinolones, furans, antituberculosis drugs, anti-leprosy drugs, antifungal drugs, and antiviral drugs.
5. The use of an irisin according to claim 1 in the preparation of an anti-inflammatory medicament, wherein: the irisin is used as an active ingredient in the application of a pharmaceutical composition which receives additives in pharmacy in preparing anti-inflammatory drugs.
6. The use of an irisin according to claim 1 in the preparation of an anti-inflammatory medicament, wherein: the anti-inflammatory drug is prepared into a powder preparation or a solid preparation, the powder preparation is a compound powder injection, and the solid preparation is a tablet.
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| US5466436A (en) * | 1991-12-06 | 1995-11-14 | Glaxo Group Limited | Medicaments for treating inflammatory conditions or for analgesia |
| CN1530096A (en) * | 2003-03-17 | 2004-09-22 | 王玉万 | Powder injection containing nonsteroidal anti-infecting chemical |
| US20090264530A1 (en) * | 2008-04-16 | 2009-10-22 | Nickell Robert P | Combined nsaid and acetaminophen formulation and method |
| CN107496908A (en) * | 2017-09-04 | 2017-12-22 | 南京医科大学 | Application of the irisin in anti-inflammatory drug is prepared |
| CN107951896A (en) * | 2016-10-21 | 2018-04-24 | 中山大学 | Application of the class I non-steroid anti-inflammatory drugs in anti-zika virus |
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| US5466436A (en) * | 1991-12-06 | 1995-11-14 | Glaxo Group Limited | Medicaments for treating inflammatory conditions or for analgesia |
| CN1530096A (en) * | 2003-03-17 | 2004-09-22 | 王玉万 | Powder injection containing nonsteroidal anti-infecting chemical |
| US20090264530A1 (en) * | 2008-04-16 | 2009-10-22 | Nickell Robert P | Combined nsaid and acetaminophen formulation and method |
| CN107951896A (en) * | 2016-10-21 | 2018-04-24 | 中山大学 | Application of the class I non-steroid anti-inflammatory drugs in anti-zika virus |
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