Application of 3-O-methyl chrysotoxin in preparation of medicine for treating xerophthalmia

Abstract

The invention belongs to the technical field of biomedicine, and relates to a novel application of 3-O-methyl chrysotoxin, in particular to an application of 3-O-methyl chrysotoxin in preparation of a medicine for treating xerophthalmia. The core of the 3-O-methyl chrysotoxin disclosed by the invention is that the 3-O-methyl chrysotoxin effectively relieves corneal epithelial cell injury induced by hyperosmosis and inhibits oxidative stress and proinflammatory factor release by activating an EGFR (Epidermal Growth Factor Receptor) signal channel. In-vitro and in-vivo experiments prove that the composition can remarkably enhance cell activity, reduce apoptosis and active oxygen accumulation and repair the steady state of a tear film. The compound is applied to preparation of xerophthalmia drugs and has important clinical value.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to a new use of 3-O-methyldendrobium nobile, particularly its use in the preparation of drugs for dry eye syndrome. Background Technology

[0002] Dry eye syndrome is a multifactorial ocular surface disease clinically characterized by loss of tear film homeostasis, accompanied by symptoms such as dryness, burning sensation, foreign body sensation, fluctuating vision, and photophobia. In severe cases, it can lead to vision loss. Dry eye syndrome not only affects patients' quality of life but can also cause visual impairment or even blindness in severe cases. Therefore, dry eye syndrome has become a significant public health issue worldwide. With changes in modern lifestyles, especially the prolonged use of video terminals and smartphones, the incidence of dry eye syndrome has been rising year by year, becoming a global public health problem. Currently, tear film hyperosmolarity and ocular surface inflammation are recognized as the core pathological mechanisms of the occurrence and development of dry eye syndrome.

[0003] Currently, the treatment of dry eye mainly focuses on relieving symptoms and restoring ocular surface homeostasis. Artificial tears can temporarily relieve dryness, but their bioavailability is low, and they usually only provide temporary symptom relief, with limited efficacy for moderate to severe dry eye. Anti-inflammatory drugs can effectively reduce inflammation, but long-term use has the potential to damage ocular surface tissues and cannot effectively repair epithelial cell damage and tear film homeostasis disruption caused by a hypertonic environment. Physical therapy can help improve lacrimal gland function, but its efficacy depends on patient cooperation and is relatively slow to take effect. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a new use of 3-O-methyldendrobium nobile, specifically involving the use of 3-O-methyldendrobium nobile in the preparation of dry eye drugs, which has the advantages of high safety, clear target, and tear film homeostasis regulation function, and has important clinical value.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] In a first aspect, the present invention provides the use of 3-O-methyldendrobine in the preparation of drugs for dry eye syndrome.

[0007] Preferably, the drug inhibits dry eye by binding to EGFR target proteins and activating the EGFR signaling pathway.

[0008] Preferably, the concentration of 3-O-methyldendrobine in the drug is 1-10 μM.

[0009] More preferably, the concentration of 3-O-methyldendrobine in the drug is 5 μM.

[0010] Preferably, the drug is an ophthalmic preparation.

[0011] More preferably, the dosage form of the ophthalmic preparation is eye drops, eye ointment, eye spray, ophthalmic gel, eye patch, intraocular injection, ophthalmic microsphere, ophthalmic implant, periocular injection, or ophthalmic sustained-release preparation.

[0012] Secondly, the present invention also provides a method for preparing a drug for dry eye syndrome, comprising the following steps:

[0013] S1. Mix polyethylene glycol 400 with physiological saline to obtain a premixed solution;

[0014] S2. Add 3-O-methyldendrobium nobile to the premixed solution. After thorough stirring and ultrasonic treatment, adjust the pH of the solution to 7.2-7.4, the osmotic pressure to 280-320 mOsm / L, and the concentration of 3-O-methyldendrobium nobile to 1-10 μM to obtain a 3-O-methyldendrobium nobile ophthalmic preparation.

[0015] Preferably, in step S1, the mass-to-volume ratio of polyethylene glycol 400 to physiological saline is 1 g: (18~20) mL.

[0016] More preferably, in step S1, the mass-to-volume ratio of polyethylene glycol 400 to physiological saline is 1 g: 19 mL.

[0017] Preferably, in step S2: the pH value of the adjusted solution is 7.3; the osmotic pressure of the adjusted solution is 300 mOsm / L; and the concentration of 3-O-methyldendrobine is 5 μM.

[0018] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0019] The use of 3-O-methyldendrobium nobile in the preparation of dry eye drugs provided by this invention: 3-O-methyldendrobium nobile effectively reduces corneal epithelial cell damage induced by high osmotic pressure and inhibits oxidative stress and the release of pro-inflammatory factors by activating the EGFR signaling pathway. This provides a novel candidate for dry eye drugs with high safety, clear target, and tear film homeostasis regulation function for clinical use. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 A flowchart of network pharmacological analysis for screening active ingredients of Dendrobium and identifying potential targets for treating dry eye syndrome;

[0022] Figure 2 Figure showing the docking results of 3-O-methyldendrobine with EGFR target protein molecules;

[0023] Figure 3 Figure 1 shows the results of molecular dynamics simulation analysis of 3-O-methyldendrobine and EGFR target proteins.

[0024] Figure 4 Figure showing the effect of different osmotic pressures on HCEC cell viability;

[0025] Figure 5 Figure 1 shows the effect of 3-O-methyldendrobium nobile treatment on the activity of HCEC cells under different conditions. Figure 2 shows the statistical analysis of the effect of different concentrations of 3-O-methyldendrobium nobile on the activity of HCEC cells under isotonic conditions. Figure 3 shows the statistical analysis of the effect of different concentrations of 3-O-methyldendrobium nobile on the activity of HCEC cells under hyperotonic conditions.

[0026] Figure 6 A statistical analysis graph of HCEC cell activity in the EGFR signaling pathway validation experiment;

[0027] Figure 7 Figure A shows the results of Calcein-AM / PI staining in the EGFR signaling pathway validation experiment; Figure B shows the statistical analysis of cell apoptosis rate.

[0028] Figure 8 The images show the results of DCFH-DA staining in the EGFR signaling pathway validation experiment; Figure A shows the DCFH-DA staining map; Figure B shows the statistical analysis of the relative ROS level.

[0029] Figure 9 The figures show the results of pro-inflammatory factor levels in the EGFR signaling pathway validation experiment; Figure A is the statistical analysis of the pro-inflammatory factor TNF-α; Figure B is the statistical analysis of the pro-inflammatory factor IL-1β; Figure C is the statistical analysis of the pro-inflammatory factor IL-6; and Figure D is the statistical analysis of the pro-inflammatory factor IL-8.

[0030] Figure 10 The images show the results of eye photography of mice in each group 7 days after drug intervention in Example 4. Detailed Implementation

[0031] The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0032] It should be noted that the order of description of the following embodiments is not intended to limit the preferred order of embodiments. Furthermore, in the description of this invention, the term "comprising" means "including but not limited to". Various embodiments of the invention may exist in the form of a range; it should be understood that the description in the form of a range is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the invention; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values ​​within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single digits within the range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. Additionally, whenever a numerical range is indicated herein, it means including any referenced number (fraction or integer) within the indicated range.

[0033] Dendrobium, a traditional medicinal plant of the Orchidaceae family, is widely used in clinical treatment based on traditional Chinese medicine principles due to its effects of nourishing yin and clearing heat, improving eyesight and promoting fluid production. Dendrobium contains a variety of highly complex chemical components, such as polysaccharides, alkaloids, bibenzyl groups, and phenanthrene compounds. In-depth analysis of the active ingredients in Dendrobium, and screening and identification of monomeric compounds with high affinity and clear targets for dry eye syndrome, are of great significance and promising application prospects for improving the precision of dry eye treatment, enhancing the repair capacity of corneal epithelial cells, and restoring tear film homeostasis.

[0034] The following specific embodiments further illustrate the use of 3-O-methyldendrobium nobile extract in the preparation of drugs for dry eye syndrome. This section further illustrates the content of the present invention with reference to specific embodiments, but should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art, such as the conditions described in *Molecular Cloning: A Laboratory Manual (Fourth Edition)* published by Cold Spring Harbor Laboratory or the conditions recommended by the manufacturer. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0035] In the following embodiments, the contents of the CytoNCA plugin are described in the reference ([1] Tang Y, Li M, Wang J, et al. CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks[J]. Biosystems, 2015, 127: 67-72.).

[0036] In the following examples, all data are expressed as mean ± standard deviation (Mean ± SD); "Indicates a significant difference (P < 0.05)," "Indicates a highly significant difference (P < 0.01)" "" indicates an extremely significant difference (P < 0.001).

[0037] In the following embodiments, mOsm or mOsm / L represents a unit of solution osmotic pressure, which means the osmotic pressure generated by 1 mmol of molecules per liter of solution. For details, please refer to the literature ([2] Pharmaceutical Terminology Approval Committee [ed.]. 2014. Pharmaceutical Terminology. 2014 | 2nd Edition [M]. Beijing: Science Press).

[0038] Example 1: Screening of active ingredients from Dendrobium and network pharmacological analysis of potential targets for treating dry eye syndrome

[0039] This embodiment uses network pharmacology analysis to screen for potential active compounds and targets in Dendrobium for treating dry eye syndrome. Figure 1 Specifically:

[0040] (1) Chemical components related to the genus Dendrobium spp. were collected from the ETCM database (http: / / www.tcmip.cn / ETCM / ) and the HERB database (http: / / herb.ac.cn / ), and a total of 92 monomeric compounds were identified.

[0041] (2) The drug-likeness evaluation analysis of the 92 monomeric compounds obtained in step (1) was performed using the SwissADME database (https: / / www.swissadme.ch / ). Compounds with high gastrointestinal absorption and at least two "Yes" responses in the drug-likeness evaluation were selected, and finally 43 monomeric compounds with potential pharmacological activity were obtained.

[0042] (3) Using the SwissTargetPrediction database (https: / / www.swisstargetprediction.ch / ), the TargetNet database (http: / / targetnet.scbdd.com / ), and the Super-PRED database (https: / / prediction.charite.de / ), target prediction analysis was performed on the 43 monomer compounds obtained in step (2), and a total of 909 candidate targets were obtained.

[0043] (4) Search the GeneCards database (https: / / www.genecards.org / ) using “Dry Eye” as the keyword, and select genes with a relevance score greater than 10 as therapeutic targets for dry eye, obtaining a total of 601 disease targets; map the 909 candidate targets obtained in step (3) with the 601 disease targets to identify 76 potential targets for Dendrobium to treat dry eye.

[0044] (5) A PPI network was constructed using Cytoscape 3.10.3 software (https: / / cytoscape.org / , NHGRI & NRNB, America), and topology analysis was performed using the CytoNCA plugin. Among them, 3-O-methyldendrobine plays a core role in the network topology.

[0045] 3-O-methyldendrobin is derived from a monomeric compound of Dendrobium species, possessing a bibenzyl chemical structure, and its molecular formula is C0. 17 H 20 O4, with a molecular weight of 288.34, has the following chemical structural formula: This monomer has good lipid solubility and is readily soluble in organic solvents such as dimethyl sulfoxide, ethanol, and methanol.

[0046] Example 2: Validation of the binding of 3-O-methyldendrobine to EGFR target protein

[0047] 2.1 Molecular docking analysis

[0048] Molecular docking analysis was performed using Discovery Studio 2019 (Dassault Systèmes, France) software to analyze the interactions between 3-O-methyldendrobine and the 76 potential targets obtained in Example 1.

[0049] Figure 2 The docking results of 3-O-methyldendrobium nobile with the EGFR target protein are shown. The results indicate that 3-O-methyldendrobium nobile exhibits a low docking free energy of -32.27 kcal / mol with the EGFR target protein. Generally, a binding free energy less than -5 kcal / mol indicates a strong interaction between the monomer and the target protein; this result demonstrates that 3-O-methyldendrobium nobile has excellent binding affinity to the EGFR target protein.

[0050] 2.2 Molecular Dynamics Simulation Analysis

[0051] To further evaluate the stability of 3-O-methyldendrobine binding to EGFR target proteins in a dynamic system, this section presents a 100 ns molecular dynamics simulation. Specifically, three independent simulations were performed using GROMACS 2022 software (https: / / www.gromacs.org / , GROMACS development team) with CHARMM36 and GAFF2 force fields in an explicit water molecule environment.

[0052] Figure 3 The results of molecular dynamics simulation analysis of 3-O-methyldendrobium nobile with EGFR target protein are shown. The vertical axis "RMSD" represents the root mean square deviation, an indicator used to assess the conformational stability of the protein-ligand complex and the deviation of atomic positions from their initial positions. A lower RMSD value indicates limited main chain fluctuation and higher overall stability. The results show that the complex system reaches equilibrium after 80 ns, with an average fluctuation of approximately 2 Å across three repetitions, indicating that 3-O-methyldendrobium nobile exhibits high stability when binding to the EGFR target protein. The binding free energy of the complex was quantified using the MM / PBSA method. The average binding free energies of the three repetitions were -50.435 kJ / mol, -51.211 kJ / mol, and -49.876 kJ / mol, with a standard deviation of only 0.547 kJ / mol. These experimental results demonstrate that 3-O-methyldendrobium nobile can bind to the EGFR target protein with extremely high affinity and stability.

[0053] Example 3: Protective effect and mechanism of 3-O-methyldendrobine on human corneal epithelial cells

[0054] 3.1 Hyperosmolar Stress Experiment

[0055] 3.1.1 Cell Seeding

[0056] Human corneal epithelial cells (HCEC cells, American Center for Type Culture Collection, catalog number: CRL-3582) were used as experimental subjects and cultured in basal medium (Thermo Fisher Scientific, catalog number: 17005-042, osmotic pressure approximately 290 mOsm). HCEC cells were then cultured at a rate of 5 × 10⁻⁶ cells / year. 3 One sample per well was inoculated into a 96-well plate and incubated overnight at 37°C in a 5% CO2 incubator for adhesion, digestion, and resuspension.

[0057] 3.1.2 Preparation and Treatment of High-Permeability Model

[0058] The osmotic pressure of the basal medium was adjusted using hypertonic sodium chloride solution (sodium chloride solution with a mass concentration higher than 0.9%), and osmotic pressure gradients were set at 312 mOsm, 400 mOsm, 450 mOsm, 500 mOsm, and 550 mOsm. The basal medium with different osmotic pressures was added to 96-well plates, 100 μL per well, and incubated at 37°C in a 5% CO2 incubator for 24 h. The viability of HCEC cells in each osmotic pressure gradient group was quantitatively determined using a CCK-8 assay kit (Shanghai Beyotime Biotechnology Co., Ltd., catalog number: C0038).

[0059] Figure 4 The results show the effect of different osmotic pressures on HCEC cell viability. The results show that as the osmotic pressure increases from 312 mOsm to 550 mOsm, HCEC cell viability decreases in a dose-dependent manner; among them, when the osmotic pressure reaches 550 mOsm, cell viability decreases by about 50%, therefore 550 mOsm was selected as the osmotic pressure in the hyperosmotic environment for subsequent experiments.

[0060] 3.1.3 Effects of 3-O-methyldendrobine treatment on the viability of HCEC cells under different conditions

[0061] In isotonic (312 mOsm) and hypertonic (550 mOsm) environments, the concentrations of 3-O-methyldendrobium nobile were set at 0, 0.5 μM, 1 μM, 5 μM and 10 μM, respectively. In addition, a separate group of HCEC cells in isotonic environment without 3-O-methyldendrobium nobile treatment was set up as the isotonic control group in the hypertonic environment experiment. The activity of HCEC cells in each group was quantitatively measured, and the remaining procedures were performed according to the steps in 3.1.1 and 3.1.2.

[0062] Figure 5 The results show the effects of 3-O-methyldendrobium nobile treatment on the activity of HCEC cells under different conditions. Figure A shows the statistical analysis of the effects of different 3-O-methyldendrobium nobile concentrations on HCEC cell activity under isotonic conditions; Figure B shows the statistical analysis of the effects of different 3-O-methyldendrobium nobile concentrations on HCEC cell activity under hypertonic conditions. The leftmost gray bar on the horizontal axis represents the isotonic control group. The results show that HCEC cell activity increased in a dose-dependent manner; when the concentration of 3-O-methyldendrobium nobile was 5 μM, the activity of HCEC cells under isotonic conditions was significantly enhanced (…). Figure 5 Figure A in the figure shows that it significantly reduced the decrease in HCEC cell activity under hyperosmolar conditions. Figure 5 (Figure B in the diagram).

[0063] 3.2 EGFR signaling pathway verification experiment

[0064] Erlotinib, a common EGFR protein inhibitor, binds to ATP, thereby blocking the transfer of phosphate groups from EGFR protein to its substrate. This embodiment utilizes this principle to design experiments to verify the relationship between the EGFR signaling pathway and the protective effect of 3-O-methyldendrobium nobile on corneal epithelial cells.

[0065] 3.2.1 Experimental Grouping

[0066] This experiment was divided into a normal control group, a hyperosmolar model group, a drug protection group, an erlotinib group, and a combination group. Table 1 shows the specific intervention methods for each group. The remaining procedures were carried out according to the steps in 3.1.

[0067] Table 1: Experimental Grouping for EGFR Signaling Pathway Validation

[0068]

[0069] 3.2.2 HCEC cell viability

[0070] Figure 6 The statistical analysis of HCEC cell viability in the EGFR signaling pathway validation experiment is shown. The results indicate that the HCEC cell viability in the erlotinib group and the combination group was significantly lower than that in other groups, while there was no significant difference between the two groups. Figure 6 This indicates that erlotinib exacerbated the decline in HCEC cell activity caused by hyperosmolar stress and blocked the protective effect of 3-O-methyldendrobine.

[0071] 3.2.3 Calcein-AM / PI staining

[0072] Each group was stained using the Calcein-AM / PI double staining kit (Shanghai Beyotime Biotechnology Co., Ltd., catalog number: C2015S). Images were collected and observed under a fluorescence microscope (Leica Microsystems, Germany, model: Mateo FL). The apoptosis rate was calculated by counting the number of cells in both fluorescent colors.

[0073] Figure 7 The results of Calcein-AM / PI staining in the EGFR signaling pathway validation experiment are shown. Figure A shows the Calcein-AM / PI staining, with green representing live cells and red representing apoptotic cells. Figure B shows the statistical analysis of the apoptosis rate. The results indicate that 3-O-methyldendrobine alleviated apoptosis induced in HCEC cells under hyperosmolar conditions, while erlotinib, as an EGFR protein inhibitor, blocked this effect.

[0074] 3.2.4 DCFH-DA staining

[0075] DCFH-DA reactive oxygen species (ROS) detection kit (Shanghai Beyotime Biotechnology Co., Ltd., catalog number: S0033S) was used to stain each group with DCFH-DA, and images were collected and observed under a fluorescence microscope. The relative fluorescence intensity of each group was calculated based on the fluorescence intensity of the normal control group to measure the relative level of intracellular ROS.

[0076] Figure 8 The results of DCFH-DA staining in the EGFR signaling pathway validation experiment are shown; Figure A is the DCFH-DA staining image; Figure B is the statistical analysis of relative ROS levels. The results indicate that 3-O-methyldendrobium nobile reduced the accumulation of reactive oxygen species induced in HCEC cells under hyperosmolar conditions, and erlotinib, as an EGFR protein inhibitor, played a role in suppressing this effect.

[0077] 3.2.5 Pro-inflammatory factor levels

[0078] The levels of pro-inflammatory factors TNF-α, IL-1β, IL-6, and IL-8 in each group of samples were measured using the Human TNF-α Quantikine ELISA Kit (R&D Systems, Inc., catalog number: DTA00D), Human IL-1β / IL-1F2 Quantikine ELISA Kit (R&D Systems, Inc., catalog number: DLB50), Human IL-6 Quantikine ELISA Kit (R&D Systems, Inc., catalog number: D6050), and Human IL-8 / CXCL8 Quantikine ELISA Kit (R&D Systems, Inc., catalog number: D8000C).

[0079] Figure 9 The results of the EGFR signaling pathway validation experiment show the levels of pro-inflammatory factors; Figure A shows the statistical analysis of the pro-inflammatory factor TNF-α; Figure B shows the statistical analysis of the pro-inflammatory factor IL-1β; Figure C shows the statistical analysis of the pro-inflammatory factor IL-6; and Figure D shows the statistical analysis of the pro-inflammatory factor IL-8. The results show that the levels of all pro-inflammatory factors were elevated in HCEC cells under hyperosmolar conditions, and treatment with 3-O-methyldendrobine reduced the increase in pro-inflammatory factor levels induced by hyperosmolar stress. Erlotinib, as an EGFR protein inhibitor, was able to block this effect.

[0080] The above experimental results indicate that 3-O-methyldendrobine exerts its effects through the EGFR signaling pathway, significantly reducing apoptosis, oxidative stress, and inflammation in HCEC cells under hyperosmolar conditions.

[0081] Example 4: Protective effect of 3-O-methyldendrobium nobile ophthalmic preparation on a mouse model of dry eye.

[0082] 4.1 Preparation of 3-O-methyldendrobium nobile ophthalmic formulation

[0083] Polyethylene glycol 400 (g) and physiological saline (mL) were mixed at a mass-to-volume ratio of 1:19 to obtain a premixed solution. 3-O-methyldendrobium nobile was slowly added to the premixed solution. After thorough stirring and sonication, the pH of the solution was adjusted to 7.2-7.4, the osmotic pressure was adjusted to 280-320 mOsm / L, and the concentration of 3-O-methyldendrobium nobile was adjusted to 5 μM to obtain a 3-O-methyldendrobium nobile ophthalmic preparation.

[0084] 4.2 Establishment of a mouse model of dry eye syndrome

[0085] Eight-week-old healthy C57BL / 6 mice (Beijing Beiyou Biotechnology Co., Ltd., strain number: C57BL / 6J) were selected, and 0.5% scopolamine hydrobromide solution was applied topically to both eyes. By blocking the parasympathetic nerve innervation of the lacrimal gland, tear film homeostasis loss and ocular surface dryness damage were induced, thus obtaining a mouse model of dry eye syndrome.

[0086] 4.3 Drug administration intervention

[0087] This experiment was divided into a normal group, a dry eye control group, and a dry eye treatment group. Mice in the dry eye treatment group received topical instillation of 3-O-methyldendrobium nobile ophthalmic preparation in both eyes daily, once every 12 hours (twice daily), for 7 consecutive days. The dry eye control group received an equal volume of ophthalmic preparation base solution without 3-O-methyldendrobium nobile. On the 7th day after administration, 1 μL of 1% sodium fluorescein solution was instilled into the ocular surface of each group of mice. After the mice blinked naturally, the cornea was observed and photographed under a cobalt blue filter using a slit-lamp microscope (Suzhou Kangjie Medical Co., Ltd., model: KJ900A-2).

[0088] Figure 10 The images show the results of eye photographs taken in mice in each group 7 days after drug intervention. The results showed that the corneas of mice in the dry eye control group exhibited widespread green fluorescence staining, while the corneas of mice in the dry eye treatment group showed less green fluorescence staining. These results indicate that the 3-O-methyldendrobium nobile ophthalmic preparation can effectively repair corneal epithelial barrier damage caused by insufficient tear production.

[0089] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

Use of 1,3-O-methyldendrobium nobile in the preparation of drugs for dry eye syndrome.

2. The use as described in claim 1, characterized in that, The drug inhibits dry eye by binding to EGFR target proteins and activating the EGFR signaling pathway.

3. The use as described in claim 1 or 2, characterized in that, The concentration of 3-O-methyldendrobine in the drug is 1-10 μM.

4. The use as described in claim 3, characterized in that, The concentration of 3-O-methyldendrobine in the drug is 5 μM.

5. The use as described in any one of claims 1-4, characterized in that, The drug is an ophthalmic preparation.

6. The use as described in claim 5, characterized in that, The dosage forms of the ophthalmic preparations are eye drops, eye ointments, eye sprays, ophthalmic gels, eye patches, intraocular injections, ophthalmic microspheres, ophthalmic implants, periocular injections, or ophthalmic sustained-release preparations.

7. A method for preparing a drug for dry eye syndrome, characterized in that, Includes the following steps: S1. Mix polyethylene glycol 400 with physiological saline to obtain a premixed solution; S2. Add 3-O-methyldendrobium nobile to the premixed solution. After thorough stirring and ultrasonic treatment, adjust the pH of the solution to 7.2-7.4, the osmotic pressure to 280-320 mOsm / L, and the concentration of 3-O-methyldendrobium nobile to 1-10 μM to obtain a 3-O-methyldendrobium nobile ophthalmic preparation.

8. The preparation method according to claim 7, characterized in that, In step S1: the mass-to-volume ratio of polyethylene glycol 400 to physiological saline is 1 g: (18~20) mL.

9. The preparation method according to claim 8, characterized in that, In step S1: the mass-to-volume ratio of polyethylene glycol 400 to physiological saline is 1 g: 19 mL.

10. The preparation method according to claim 7, characterized in that, In step S2: the pH of the adjusted solution is 7.3; The osmotic pressure of the adjusted solution is 300 mOsm / L; The concentration of 3-O-methyldendrobine was adjusted to 5 μM.

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