CN117462653B - Application of Oncoinhibin M in preparation of medicine for promoting cornea epithelial injury repair - Google Patents
Application of Oncoinhibin M in preparation of medicine for promoting cornea epithelial injury repair Download PDFInfo
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- CN117462653B CN117462653B CN202311599108.2A CN202311599108A CN117462653B CN 117462653 B CN117462653 B CN 117462653B CN 202311599108 A CN202311599108 A CN 202311599108A CN 117462653 B CN117462653 B CN 117462653B
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- 239000003814 drug Substances 0.000 title claims abstract description 25
- 230000008439 repair process Effects 0.000 title claims abstract description 24
- 230000006378 damage Effects 0.000 title claims abstract description 20
- 208000027418 Wounds and injury Diseases 0.000 title claims abstract description 15
- 208000014674 injury Diseases 0.000 title claims abstract description 14
- 230000001737 promoting effect Effects 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 210000004087 cornea Anatomy 0.000 title abstract description 19
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 16
- 235000010413 sodium alginate Nutrition 0.000 claims description 15
- 229940005550 sodium alginate Drugs 0.000 claims description 15
- 239000000661 sodium alginate Substances 0.000 claims description 15
- 239000000463 material Substances 0.000 claims description 10
- 230000007547 defect Effects 0.000 claims description 8
- 239000003889 eye drop Substances 0.000 claims description 7
- 229940012356 eye drops Drugs 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 abstract description 14
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 abstract description 14
- 238000011282 treatment Methods 0.000 abstract description 7
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 abstract description 6
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 210000002919 epithelial cell Anatomy 0.000 abstract description 2
- 210000001508 eye Anatomy 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 10
- 210000003560 epithelium corneal Anatomy 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 210000000981 epithelium Anatomy 0.000 description 4
- 239000012460 protein solution Substances 0.000 description 4
- 238000007790 scraping Methods 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 3
- 102000004140 Oncostatin M Human genes 0.000 description 3
- 108090000630 Oncostatin M Proteins 0.000 description 3
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000009841 epithelial lesion Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 229960004194 lidocaine Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229960002275 pentobarbital sodium Drugs 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NJDNXYGOVLYJHP-UHFFFAOYSA-L disodium;2-(3-oxido-6-oxoxanthen-9-yl)benzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=CC(=O)C=C2OC2=CC([O-])=CC=C21 NJDNXYGOVLYJHP-UHFFFAOYSA-L 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000008378 epithelial damage Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000003987 Oncostatin M Receptors Human genes 0.000 description 1
- 108010082522 Oncostatin M Receptors Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 210000001691 amnion Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 230000004453 corneal transparency Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940096984 ophthalmic cream Drugs 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/204—IL-6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of eye medicine preparation. Aiming at the problems that the treatment effect is insufficient by adopting a simple external medicament, the operation difficulty of the operation treatment is high and the cost is high, the invention provides the application of the Oncoinhibin M in preparing the medicament for promoting the repair of the corneal epithelial injury. The Oncoinhibin M is an OSM recombinant protein, and the concentration of the Oncoinhibin M in the medicine is 0.05-5 mug/mL. The invention can obviously promote the repair of the mouse cornea epithelial cells through the drug loaded with the tumor suppressor M, has lower cost and has no complications.
Description
Technical Field
The invention belongs to the technical field of eye medicine preparation, and particularly relates to application of Oncoinhibin M in preparation of a medicine for promoting cornea epithelial injury repair.
Background
Oncostatin M (OSM) is a cytokine belonging to interleukin-6 family and plays an important role in inflammatory reaction, tissue injury and regeneration, organ development, immune regulation and the like. The immune cells are taken as an indispensable part of the microenvironment of the limbal stem cells, and play a non-negligible role in regulating the functions of the limbal stem cells and participating in the repair of corneal epithelial damage. Oncostatin M is secreted by immune cells in a microenvironment, such as mononuclear cells/macrophages, neutrophils, dendritic cells and the like, and is combined with an Oncostatin M receptor (OMSR) to activate a JAK/STAT signal pathway, a Mitogen Activated Protein Kinase (MAPK) and other signal pathways, and the two pathways have important regulation effects on cell proliferation, growth, differentiation and the like.
Cornea, which is a unique transparent tissue of the surface of the eyeball, is an important component of the visual system, accounting for about 70% of the refraction of light. Among them, the corneal epithelium is located in the outermost layer of the cornea and plays a key role in keeping the ocular surface moist, resisting infection, maintaining corneal transparency and optical function. The integrity of the corneal epithelium and barrier function is critical to maintaining clear and stable vision, but is most likely to be compromised by various stimuli due to its exposure to the external environment.
At present, clinical medicines and surgical treatment means mainly adopt the modes of taking the eye by using medicines containing amino acid, low molecular peptide, oligosaccharide and other substances for resisting bacteria and diminishing inflammation or promoting wound healing, using therapeutic cornea contact lenses, amniotic membrane covering, eyelid cleavage suturing, autologous serum, limbal stem cell transplantation and the like according to different damage degrees of cornea epithelium. However, these treatments still have a certain limitation, and the treatment effect of the pure external drugs is insufficient, and the operation difficulty of the surgical treatment is high and the cost is high. Therefore, based on the specificity of the macromolecular target, the effective and convenient macromolecular medicament is developed to accelerate and improve the healing of the corneal epithelial wound, and has urgent practical significance.
Disclosure of Invention
Aiming at the problems that the treatment effect of the pure external medicine is insufficient, the operation difficulty of the operation treatment is high and the cost is high, the invention provides the application of the tumor suppressor M in preparing the medicine for promoting the repair of the corneal epithelial injury, the repair of the mouse corneal epithelial cells can be obviously promoted by the medicine loaded with the tumor suppressor M, the cost is low, and no complications are found.
The invention is realized by the following technical scheme:
Application of Oncostatin M in preparing medicine for promoting cornea epithelial injury repair is provided.
Further, the Oncoinhibin M is an OSM recombinant protein.
Further, the corneal epithelial damage is a corneal epithelial defect caused by mechanical damage.
Further, the concentration of the Oncoinhibin M in the medicine is 0.05-5 mug/mL, preferably the concentration of the Oncoinhibin M in the medicine is 0.1-3 mug/mL, more preferably 0.1-1 mug/mL.
Furthermore, the medicament for promoting the repair of the corneal epithelial injury is an eye injection or an eye external medicament.
Further, the dosage form of the external use medicine for eyes is eye liquid or eye semisolid preparation.
Further, the ophthalmic liquid is an eye drop or an eye rinse, and the ophthalmic semisolid preparation is an ophthalmic ointment, an ophthalmic cream or an ophthalmic gel.
Further, the eye drops are oxidized sodium alginate eye drops.
Further, the preparation method of the oxidized sodium alginate eye drops comprises the following steps: uniformly mixing oxidized sodium alginate and Oncoinhibin M to prepare an aqueous solution, and oscillating for 3-8 hours at the temperature of 28-40 ℃ to obtain an Oncoinhibin M-loaded slow-release material;
Further, the vibration is carried out within the range of 30-38 ℃, preferably at a constant temperature of 37 ℃.
Further, a shaker is used for shaking.
Further, the shaking is carried out for 4 to 7 hours, preferably 6 hours.
Further, in the aqueous solution prepared by uniformly mixing the oxidized sodium alginate and the Oncoinhibin M, the concentration of the oxidized sodium alginate is 15-40mg/mL, and the concentration of the Oncoinhibin M is 0.05-5 mug/mL.
Further, the concentration of the oxidized sodium alginate is 20-30mg/mL, preferably 25mg/mL.
The invention has the beneficial effects that:
Oncoinhibin M receptor expression enrichment in human and mouse limbal stem cells. Therefore, OSM can exert a regulatory effect on limbal stem cells to promote repair of corneal epithelial lesions. The invention can effectively promote the repair of corneal epithelial injury, shorten the treatment time and avoid complications; the invention uses the tumor suppressor M to prepare the medicine for promoting the repair of the corneal epithelial injury, has simple operation and has wide development and application prospects.
Drawings
FIG. 1 is a graph showing the cornea repair status and the cornea epithelial defect area percentage of the animal experiment 1 mouse;
FIG. 2 is a graph showing the cornea repair status and the cornea epithelial defect area percentage of the animal experiment 2 mouse;
FIG. 3 is a graph showing the cornea repair status and the cornea epithelial defect area percentage of the animal experiment 3 mouse.
Detailed Description
The invention will be described in further detail with reference to specific embodiments and drawings.
The specific techniques or conditions are not identified in the examples and are described in the literature in this field or are carried out in accordance with the product specifications. The reagents or apparatus used were conventional products commercially available through regular channels, with no manufacturer noted. The sources of the tumor suppressor M (OSM) recombinant protein are as follows: RPA110Mu01 of the Wuhan cloud clone technology Co., ltd, purchased commercially, was in the form of powder.
Example 1
The OsM recombinant protein powder is dissolved by normal saline to prepare OSM recombinant protein solutions with the concentration of 0.05 mug/mL, 0.1 mug/mL, 1 mug/mL, 3 mug/mL and 5 mug/mL respectively, and the OSM recombinant protein solution is used as an eye injection for promoting the repair of corneal epithelial injury.
Animal experiment 1
(1) Cornea epithelial defect animal model establishment: 8 week old C57bl/6 male mice (50 mg/kg) were anesthetized with intraperitoneal injection of pentobarbital sodium, and lidocaine was topically applied to the ocular surface. The central corneal epithelium of the mice was marked using a 2.5mm diameter trephine and scraped with an epithelial spatula.
(2) Drug administration group: the lesion area was observed 24 hours, 0 hours, and 24 hours after scraping the corneal epithelium in mice by subconjunctival injection of 5 μl of 0.1 μg/mL OSM recombinant protein solution per eye, 0 hours, 24 hours after scraping the epithelium, and 36 hours.
Control group: the damaged area was observed 24 hours, 0 hours, and 24 hours after scraping the corneal epithelium by the mice, by injecting 5 μl of physiological saline per eye under conjunctiva, and after scraping the epithelium, at 0 hours, 24 hours, and 36 hours.
The results are shown in FIG. 1. The damage repair rate of the administration group (0.1 mug/mL OSM) is faster, and the damage area of the corneal epithelium is reduced to 0 after 36 hours.
Example 2
(1) 25Mg of oxidized sodium alginate and 1mL of physiological saline are added into a centrifuge tube;
(2) Adding 10 mu L of OSM recombinant protein solution prepared in advance by using physiological saline and having the concentration of 100 mu g/mL into the centrifuge tube in the step (1);
(3) Placing the centrifuge tube containing the mixed solution for 6 hours at a temperature of 37 ℃ in a shaking table, and obtaining the slow-release material loaded with 1 mug/mL of OSM recombinant protein. The obtained slow release material is transparent and non-viscous liquid with good fluidity at normal temperature.
Example 3
Referring to the method of example 2, a sustained release material loaded with 0.1. Mu.g/mL OSM recombinant protein was prepared.
Animal experiment 2
(1) Cornea epithelial defect animal model establishment: 8 week old C57bl/6 male mice (50 mg/kg) were anesthetized with intraperitoneal injection of pentobarbital sodium, and lidocaine was topically applied to the ocular surface. The central corneal epithelium of the mice was marked using a 2.5mm diameter trephine and scraped with an epithelial spatula.
(2) Dosing group 1: eye-dropping is carried out at intervals of 6 hours by using a slow-release material loaded with 1 mug/mL OSM recombinant protein, and the eye-dropping is carried out continuously for 6 times; dosing group 2: eye-dropping is carried out continuously for 6 times every 6 hours by using a slow-release material loaded with 0.1 mug/mL OSM recombinant protein; control group: the eyes were spotted using 25mg/mL oxidized sodium alginate, 6 times in succession. The repair of epithelial lesions was observed in each group of mice using sodium fluorescein staining at modeling 0h, 12h, 24h, respectively.
As shown in FIG. 2, the slow release material loaded with OSM recombinant protein at the concentration of 0.1 mug/mL and 1 mug/mL can effectively promote the damage repair of the cornea epithelium.
Animal experiment 3
(1) Cornea epithelial defect animal model establishment: 8 week old C57bl/6 male mice (50 mg/kg) were anesthetized with intraperitoneal injection of pentobarbital sodium, and lidocaine was topically applied to the ocular surface. The central corneal epithelium of the mice was marked using a 2.5mm diameter trephine and scraped with an epithelial spatula.
(2) Drug administration group: eye-spotting was performed 6 times continuously every 6 hours using a 1. Mu.g/mL slow release material loaded with OSM recombinant protein. Sodium alginate group: eyes were spotted every 6h using 25mg/mL oxidized sodium alginate, and the eyes were spotted 6 times consecutively. Control group: normal saline was used to spot eyes, and eyes were continuously spotted 6 times. The repair of epithelial lesions was observed in each group of mice using sodium fluorescein staining at modeling 0h, 12h, 24h and 36h, respectively.
As shown in figure 3, the slow-release material loaded with the tumor suppressor M can effectively promote the damage repair of the corneal epithelium.
The above examples are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solution of the present invention should fall within the scope of protection defined by the claims of the present invention without departing from the spirit of the present invention.
Claims (2)
1. The application of the Oncoinhibin M in preparing a medicament for promoting the repair of corneal epithelial injury is characterized in that the corneal epithelial injury is corneal epithelial defect caused by mechanical injury, the medicament for promoting the repair of the corneal epithelial injury is oxidized sodium alginate eye drops, and the concentration of the Oncoinhibin M in the oxidized sodium alginate eye drops is 0.1-1 mug/mL; the preparation method of the oxidized sodium alginate eye drops comprises the following steps: uniformly mixing oxidized sodium alginate and Oncoinhibin M to prepare an aqueous solution, and oscillating for 3-8 hours at the temperature of 28-40 ℃ to obtain the Oncoinhibin M-loaded slow-release material.
2. The use according to claim 1, wherein the concentration of the oxidized sodium alginate in the aqueous solution prepared by uniformly mixing the oxidized sodium alginate and the Oncoinhibin M is 15-40mg/mL.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311599108.2A CN117462653B (en) | 2023-11-28 | 2023-11-28 | Application of Oncoinhibin M in preparation of medicine for promoting cornea epithelial injury repair |
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| CN202311599108.2A CN117462653B (en) | 2023-11-28 | 2023-11-28 | Application of Oncoinhibin M in preparation of medicine for promoting cornea epithelial injury repair |
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| CN117462653B true CN117462653B (en) | 2024-08-30 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0290948A2 (en) * | 1987-05-04 | 1988-11-17 | Oncogen | Oncostatin M and novel compositions having anti-neoplastic activity |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5451506A (en) * | 1985-12-20 | 1995-09-19 | Oncogen Limited Partnership | Oncostatin M and novel compositions having anti-neoplastic activity |
| PL1904056T3 (en) * | 2005-07-18 | 2009-09-30 | Minu Llc | Use of a macrolide to restore corneal sensation |
| CN108379558A (en) * | 2018-05-28 | 2018-08-10 | 暨南大学 | Application of the interleukin 22 in the drug for preparing treatment persistent corneal epithelial defects |
| CN111848832B (en) * | 2019-04-30 | 2024-02-20 | 苏州大学 | Application of fluorine-containing compound modified cationic polymer as drug carrier and preparation method thereof |
| CN113081956A (en) * | 2021-04-12 | 2021-07-09 | 青岛大学附属医院 | Natamycin eye drops modified by oxidized sodium alginate and preparation method thereof |
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- 2023-11-28 CN CN202311599108.2A patent/CN117462653B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0290948A2 (en) * | 1987-05-04 | 1988-11-17 | Oncogen | Oncostatin M and novel compositions having anti-neoplastic activity |
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