Application of sinomenine in the preparation of drugs for preventing / inhibiting the progression of filtration tract scarring after glaucoma filtration surgery

Abstract

The present invention belongs to the field of medicine, and discloses an application of sinomenine in the preparation of a drug for preventing / inhibiting the progression of scarring of the filtration tract after glaucoma filtration surgery, wherein the drug is a local ocular administration type drug. The present invention firstly discovers that sinomenine has a certain therapeutic effect on scarring of the filtration tract after glaucoma filtration surgery, and inhibits excessive fibrosis of the subconjunctiva and sclera surface after glaucoma filtration surgery through the anti-fibrosis effect of sinomenine, which can effectively delay and inhibit postoperative filtration tract fibrosis, prolong the survival of the filtration tract, and provide a new treatment idea for the disease.

Description

Technical Field

[0001] The invention belongs to the technical field of glaucoma filtering surgery medicine, and in particular relates to the use of sinomenine in the preparation of a drug for preventing and inhibiting the progression of filtration tract scarring after glaucoma filtering surgery. Background Art

[0002] Glaucoma is a group of diseases characterized by characteristic optic nerve atrophy and visual field loss. It is the world's leading irreversible cause of blindness. The prevention and treatment of glaucoma has long become a global public health issue.

[0003] Pathologically elevated intraocular pressure is the main independent risk factor for glaucoma. Currently, the only effective way to slow the progression of glaucoma is to reduce intraocular pressure. When antihypertensive drugs and laser treatment cannot control intraocular pressure, glaucoma filtering surgery (GFS) is the first choice. This procedure uses the method of creating a subconjunctival filtration channel to effectively control intraocular pressure. However, excessive fibrosis in the filtration area after surgery often leads to rapid wound healing and scarring, which often leads to surgical failure. Although the techniques and skills of minimally invasive surgery have been improved in recent years, surgical failure caused by excessive scarring in the surgical area is still the main reason for the inability to reduce intraocular pressure after surgery. Many scholars have never stopped studying anti-scarring treatment during and after GFS surgery, but the long-term success rate of filtering surgery, which is highly expected by using these drugs and techniques, is not satisfactory. Superficial corneal vascularization, bleb leakage, hypotony maculopathy, bleb infection and even endophthalmitis are common complications of these drugs. Therefore, it is an important topic in the current glaucoma research field to conduct in-depth research on the mechanism of filtration tract scarring after GFS surgery and actively explore drugs or methods with better effects, fewer side effects and more specificity, so as to inhibit scar formation after glaucoma surgery and improve the success rate of filtration surgery.

[0004] After filtration surgery, the healing and repair of the filtration channel follows general rules, namely hemostasis, inflammation, cell proliferation and cell remodeling. In the early postoperative period, wound hemostasis forms a fibrin clot, and neutrophils, macrophages and lymphocytes are attracted to the wound site, causing an inflammatory response. Subsequently, fibroblasts are activated to release extracellular matrix, leading to epithelialization, angiogenesis and granulation tissue formation, and ultimately causing tissue remodeling and scar formation. Among them, transforming growth factor-β (TGF-β) regulates the synthesis and secretion of extracellular matrix of trabecular meshwork cells and the contraction of trabecular meshwork cells, increases the resistance to aqueous humor outflow, and participates in the induction of fibrosis.

[0005] At present, glucocorticoids and some anti-metabolites, such as anti-mitotic mitomycin C (MMC) and 5-fluorouracil (5-Fluorouracil, 5-FU), are often used to relieve subconjunctival scarring, but the drug action time is short and there are many adverse reactions, such as hypotony, thin-walled filtration blebs, late filtration tract leakage, encapsulated cystic filtration tract, endophthalmitis, chronic hypotony maculopathy and corneal epithelial toxicity. Complications have been reported repeatedly. Clinically, there is still a need to seek efficient, safe and stable ways to prevent and inhibit filtration tract scarring after glaucoma filtration surgery. In recent years, a large number of scholars have devoted themselves to the study of new drugs to regulate scarring after GFS surgery, targeting different targets of the filtration tract scarring process. For example, Rho-associated kinase (ROCK) inhibitors and matrix metalloproteinase inhibitors related to biomechanical regulation have been used by more and more researchers in animal models. Various anti-cytokine drugs have also flourished in animal experiments and in vitro cell experiments, such as inhibitors of vascular endothelial growth factor, placental growth factor, anti-tumor necrosis factor, cytokine inhibitors, VEGF inhibitors, etc. Of course, the research on the use of traditional Chinese medicine to fight against scarring of the filtration tract after GFS surgery has also gradually increased, such as Qingguangan Granules reported by Peng Qinghua's team and homoharringtonine reported by Yu Dan and others. Of course, it is undeniable that these studies have indeed made breakthroughs in exploring new strategies for anti-scarring after filtration surgery; however, in-depth mechanism research and related issues that are truly applied in clinical practice still require more experiments and clinical data to answer. For example, the best route of administration, optimal dose, and optimal number of repetitions for such new drugs are still unknown.

[0006] A large number of alternative anti-scar strategies, such as microRNA29b silencing collagen genes and photodynamic therapy, have shown satisfactory results in improving the long-term efficacy of standard animal GFS models. However, to date, almost no drug has been found to be effective in large-scale prospective clinical comparative trials. Therefore, in clinical treatment, no drug has been found to replace MMC or 5-Fu.

[0007] In summary, the known common drugs currently used in clinical practice to treat filtration tract scarring after glaucoma filtration surgery all cause varying degrees of organ or tissue damage, and these adverse reactions are the main obstacle to their long-term clinical application. Summary of the invention

[0008] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the above background technology and provide a use of sinomenine and its derivatives or pharmaceutically acceptable salts thereof in the preparation of a drug for preventing and inhibiting the progression of filtration tract scarring after glaucoma filtration surgery.

[0009] In order to solve the above technical problems, the technical solution proposed by the present invention is:

[0010] A use of sinomenine in the preparation of a drug for preventing / inhibiting the progression of filtration tract scarring after glaucoma filtration surgery.

[0011] In the above application, preferably, the glaucoma filtering surgery includes trabeculectomy, various types of aqueous humor drainage nails or drainage disc implantation.

[0012] Preferably, the scarring of the filtration tract after glaucoma filtration surgery progresses to filtration bleb encapsulation or filtration tract scarring caused by excessive fibrosis of the filtration area after glaucoma filtration surgery.

[0013] Preferably, the drug is a drug for topical ocular administration.

[0014] Preferably, the topical ocular administration type drug is a subconjunctival injection drug or an eye drop drug.

[0015] Preferably, in the subconjunctival injection drug, the concentration of sinomenine is 0.5-25 mg / mL, more preferably 1.56-3.13 mg / mL; in the eye drop drug, the concentration of sinomenine is 1-10 mg / mL, more preferably 5-10 mg / mL.

[0016] Preferably, the dosage form of the drug is an injection, a sustained-release preparation or an ophthalmic preparation.

[0017] Preferably, the injection is a solution or powder type; the sustained-release agent is a sustained-release preparation with a water-soluble carrier or a poorly soluble carrier as a controlled-release system, a sustained-release injection suspension, a microsome ophthalmic sustained-release drug delivery, a biodegradable nanoparticle, a hydrogel sustained-release drug delivery system or a biodegradable polymer sustained-release film; the ophthalmic preparation is an eye drop, an eye ointment or an ophthalmic gel.

[0018] Preferably, the drug further comprises a pharmaceutically acceptable excipient.

[0019] Preferably, the auxiliary materials include any one or more of a pH regulator, an isotonicity regulator, an antibacterial agent, a thickener, a solubilizer, a cosolvent, and the like.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The present invention discovers for the first time that sinomenine has a certain therapeutic effect on scarring of the filtration tract after glaucoma filtration surgery. Through the anti-fibrotic effect of sinomenine, the excessive fibrosis of the subconjunctival and scleral surface after glaucoma filtration surgery is inhibited, which can effectively delay and inhibit postoperative filtration tract fibrosis and prolong the survival of the filtration tract, providing a new treatment idea for the disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 It is the blank control group of the HE staining test in the embodiment of the present invention;

[0024] Figure 2 This is the simple surgery group of the HE staining test in the embodiment of the present invention;

[0025] Figure 3 It is the positive control group of the HE staining test in the embodiment of the present invention;

[0026] Figure 4 It is the negative control group of the HE staining test in the embodiment of the present invention;

[0027] Figure 5 The sinomenine group in the HE staining test in the embodiment of the present invention;

[0028] Figure 6 It is the blank control group of the VG staining test in the embodiment of the present invention;

[0029] Figure 7 This is the simple surgery group of the VG staining test in the embodiment of the present invention;

[0030] Figure 8 It is the positive control group of the VG staining test in the embodiment of the present invention;

[0031] Fig. 9 It is the negative control group of the VG staining test in the embodiment of the present invention;

[0032] Fig.10 This is the sinomenine group of the VG staining test in the embodiment of the present invention. DETAILED DESCRIPTION

[0033] In order to facilitate the understanding of the present invention, the present invention will be described more comprehensively and meticulously below in conjunction with the accompanying drawings and preferred embodiments of the present invention, but the protection scope of the present invention is not limited to the following specific embodiments.

[0034] Unless otherwise defined, all the professional terms used below have the same meanings as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0035] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0036] The administration method adopted by the present invention includes subconjunctival injection and eye drop administration. Subconjunctival injection is to inject the drug into the loose space between the conjunctiva and the sclera, so that the drug can obtain a higher concentration in the aqueous humor, the anterior uveal tract, the lens and the front part of the vitreous body, thereby improving and prolonging the efficacy. The method is relatively simple to operate, and can not only quickly and accurately apply the drug to the eye, improve the efficacy, but also avoid the disadvantages of systemic medication. Eye drop administration has the advantages of being easy to use and reducing systemic side effects.

[0037] The specific operation of local injection is as follows (taking sinomenine concentration of 3.13 mg / mL as an example):

[0038] S1: Take an appropriate position and apply topical anesthetic (0.5% dicaine solution) to the affected eye once every 3-5 minutes for a total of 3 times.

[0039] S2: Take a 5mL disposable sterile syringe and draw out 1mL: 0.6mL (15mg) of 25mg sinomenine hydrochloride injection + 1mL of 2% lidocaine + 3.2mL of sterile water for injection. Take another 1mL disposable sterile syringe and draw out 1mL of the mixture for subconjunctival injection.

[0040] S3: The operator holds the syringe in the right hand and pulls the lower eyelid with the left thumb. The patient is asked to look inward and upward to fully expose the bulbar conjunctiva. The syringe is placed horizontally at an angle of 10-15° to the eyeball. The needle is inserted into the bulbar conjunctiva 5-6mm away from the corneal margin on the temporal side near the dome. The bulbar conjunctiva is gently lifted and the needle is inserted about 3-4mm. The drug solution is slowly injected. The bulbar conjunctiva at this location is bulging like a fish bubble. The injection volume is generally 0.3-1mL.

[0041] S4: After the injection is completed, remove the needle and apply antibiotic eye drops. Ask the patient to close their eyes and rest for 3-5 minutes. Leave the patient if there is no reaction.

[0042] Example:

[0043] Application of sinomenine in the preparation of drugs for preventing / inhibiting the progression of filtration tract scarring after glaucoma filtration surgery.

[0044] The animal modeling method adopted by the present invention is a classic modeling method for studying scarring of the filtration tract after glaucoma filtering surgery. This method can represent the pathological process and pathophysiological manifestations of scarring of the filtration tract after clinical filtering surgery. The control group uses mitomycin intervention, which is currently recognized as a representative drug with anti-scarring. Studies have shown that collagen fibers, myofibroblasts characterized by a-smooth muscle actin (a-smooth muscle actin, a-SMA) and fibronectin (fibronectin, FN) are key factors in scar formation after filtering surgery. The present invention applies sinomenine and mitomycin to the filtering surgery model of high intraocular pressure rabbits, and evaluates the effect of sinomenine on scarring of the filtration tract after high intraocular pressure rabbit filtering surgery by observing the expression of collagen fibers, a-SMA, and FN in the filtration area tissue, aiming to provide new ideas for the clinical treatment of pulmonary fibrosis.

[0045] 1. Materials

[0046] 1. Experimental Animals

[0047] Hunan Taiping Biotechnology Co., Ltd. provided 50 New Zealand rabbits of ordinary grade (License: SYXK (Xiang) 2019-0009), male, weighing 2.0-2.5 kg. The laboratory was selected in the Animal Experiment Center of Hunan University of Chinese Medicine. The 50 New Zealand rabbits were randomly divided into 5 groups (10 in the blank control group and 40 in the experimental group) using random numbers. All New Zealand rabbits had no eye damage or skin ulcers. New Zealand rabbits were raised in the laboratory of the Animal Experiment Center of Hunan University of Chinese Medicine.

[0048] The animal husbandry, management and related operations of this experiment were in compliance with the relevant requirements of the Hunan Provincial Regulations on the Administration of Laboratory Animals.

[0049] 2. Experimental drugs and reagents

[0050] Sodium carboxymethyl cellulose, methyl cellulose, mitomycin C, DAB colorimetric kit, paraformaldehyde, 10% chloral hydrate, sodium pentobarbital, phosphorylated protease inhibitors, and BCA protein quantitative detection kit were purchased from Changshaville Biotechnology Co., Ltd.; tobramycin dexamethasone eye ointment was produced by Alcon, USA; and levofloxacin eye drops were produced by Santen Pharmaceutical China Co., Ltd.

[0051] 2. Methods

[0052] 1. Establishment of glaucoma filtration surgery model

[0053] 1.1 Establishment of chronic intraocular hypertension model

[0054] After one week of adaptive feeding, 50 healthy New Zealand rabbits were selected. According to the method in the literature, 10% chloral hydrate was injected into the ear vein to anesthetize the experimental animals (0.6mL / kg), and 2% methylcellulose M813699 (400mPa.s) 0.2mL was injected into the anterior chamber of the right eye once a week for two consecutive weeks. The intraocular pressure of the operated eye (right eye) was measured before modeling and 1d, 3d, and 7d after modeling. The modeling was considered successful when the intraocular pressure increased by 8mmHg from the baseline intraocular pressure level 7d after surgery, and it was generally stable above 25mmHg (1mmHg=0.133kPa); if the intraocular pressure did not increase after modeling, or the intraocular pressure fell after the increase, a secondary modeling was performed; if the secondary modeling still failed, the experimental rabbit was eliminated from this study.

[0055] 1.2 Establishment of glaucoma filtering surgery model

[0056] Fifty rabbits with chronic ocular hypertension were selected, and 10 were randomly selected as group A (blank control group). The remaining 40 rabbits were used to establish a glaucoma filtering surgery model according to the method in the references, as follows: Before surgery, the operated eye (right eye) was instilled with pilocarpine eye drops for 4 times (15 min / time). 2.0% sodium pentobarbital (30 mg / kg) was injected into the ear vein for general anesthesia. The eyelid margin of the experimental rabbit was disinfected with complex iodine, the operated eye was exposed with an eyelid opener, and the conjunctival sac was flushed with levofloxacin eye drops. The operation was performed under an ophthalmic surgical microscope, the bulbar conjunctiva above the nose was cut, and a conjunctival flap with the fornix as the base was made, and the scleral surface was cauterized to stop bleeding. A rectangular scleral flap with a base of about 1 / 2 scleral thickness and a size of about 5×4 mm was made with the corneal limbus as the base. The tissue of 2×2 mm in size, including the inner sclera, trabeculae and surrounding iris, was routinely removed. The scleral flap was sutured with 2 stitches of 10-0 nylon suture, and the conjunctiva was sutured continuously.

[0057] 2. Animal Grouping and Dosing

[0058] (1) Group A (blank control group): rabbits with chronic ocular hypertension received no special treatment;

[0059] (2) Group B (simple surgery group): routine trabeculectomy was performed without the use of special drugs during or after the operation;

[0060] (3) Group C (positive control group): After the scleral flap was made during the operation, a 0.4 mg / mL mitomycin C (MMC) pad was placed under the scleral flap and between the scleral flap and conjunctival flap for 3 minutes, then rinsed with normal saline, and then the corneal and scleral tissue including the trabeculae were removed;

[0061] (4) Group D (negative control group) underwent conventional trabeculectomy, and on the 1st and 3rd days after surgery, PBS was injected subconjunctivally, with about 1 mL injected (a 1 mL mixture of 0.8 mL PBS and 0.2 mL 2% lidocaine was drawn out with a 1 mL disposable sterile syringe and injected subconjunctivally).

[0062] (5) Group E (Sinomenine group): Conventional trabeculectomy was performed, and about 1 mL of Sinomenine solution was injected subconjunctivally on the 1st and 3rd days after surgery (specific method: take 1 mL of the following: 0.6 mL of 25 mg Sinomenine hydrochloride injection (15 mg) + 1 mL of 2% lidocaine + 3.2 mL of sterile water for injection, and take another 1 mL of the mixture with a 1 mL disposable sterile syringe for subconjunctival injection).

[0063] 3. Get materials

[0064] After the experimental rabbits in each group completed the surgical modeling and drug intervention, the rabbit eye models in each group were sampled 28 days after surgery: the experimental rabbits were anesthetized and killed, the eyeballs of the operated eyes (right eyes) of the experimental rabbits were taken and fixed in 4% paraformaldehyde fixative and stored in a constant temperature 4°C refrigerator; the surrounding tissues were carefully removed under a microscope and fixed for 1 hour. After the tissue hardened, a 30G needle was used to puncture the anterior chamber to allow the fixative to enter the interior of the eyeball and then fixed for another 24 hours. The filtering bleb tissue (including the connected sclera, Tenon's capsule and conjunctival tissue) was cut out and made into paraffin sections for HE staining, VG staining and immunohistochemistry.

[0065] 4.Indicator detection

[0066] 4.1 Measurement of intraocular pressure

[0067] The right eye of the experimental rabbit was anesthetized with oxybuprocaine hydrochloride eye drops. The cornea was touched 10 times within 15 seconds with a Tonopen pen tonometer. The intraocular pressure displayed by the tonometer was recorded. The average value was taken after more than 3 measurements. Each intraocular pressure measurement was performed by the same person. The baseline intraocular pressure of the experimental rabbit was measured before modeling, and then the intraocular pressure was measured 1d, 7d, and 14d after the chronic high intraocular pressure model was established. The baseline intraocular pressure of the high intraocular pressure model rabbits in each group was measured, and then the intraocular pressure of each group of glaucoma filtering surgery models was measured 1d, 7d, 14d, 21d, and 28d after surgery.

[0068] 4.2 Expression of collagen fibers, a-SMA, and FN in filtration zone tissues

[0069] After HE staining, routine histological observation was performed on some paraffin sections; after VanGieson staining, the collagen deposition and fibrosis levels were evaluated, and 5 high-power fields were randomly selected under the 400-fold field of view of the light microscope to observe the ratio of collagen fibers to the field area, and the average value was taken for statistical analysis. After immunohistochemistry was performed on some paraffin sections, 5 high-power fields were randomly selected under the 400-fold field of view of the light microscope to determine the average optical density of a-SMA and FN, and the average value was calculated as the expression level of a-SMA and FN in the sample.

[0070] 5. Statistical Analysis

[0071] SPSS 23.0 was used for data analysis, and all experimental data were expressed as mean ± standard deviation. Indicates. Repeated measures ANOVA was used to compare intraocular pressure values ​​before and after each group. One-way ANOVA was used if the data between groups were normally distributed, otherwise non-parametric tests were used. LSD-t test was used for pairwise comparisons between groups if the variance was homogeneous, and Tamhane method was used if the variance was not homogeneous. P<0.05 was considered statistically significant.

[0072] 3. Results

[0073] 1. Postoperative intraocular pressure in each group

[0074] 1.1 Successful establishment of high intraocular pressure model

[0075] As shown in Table 1, the intraocular pressure of each group was within the normal range before modeling, and there was no statistically significant difference in intraocular pressure among the groups; after high intraocular pressure modeling, the intraocular pressure of the rabbit eyes selected into the group was significantly higher than that before modeling, and the difference was statistically significant, indicating that the rabbit eyes maintained a high intraocular pressure state and the chronic high intraocular pressure model was successfully established.

[0076] Table 1 Comparison of intraocular pressure values ​​before and after high intraocular pressure modeling in each group (n=10, )

[0077]

[0078] Note: A: blank control group; B: simple surgery group; C: positive control group; D: negative control group; E: sinomenine group;

[0079] The intraocular pressure of each group was compared with that before modeling, *P<0.05, **P<0.01, ***P<0.001.

[0080] 1.2 Postoperative intraocular pressure of rabbit eyes in each group after GFS

[0081] Before surgery, the intraocular pressure of each group was in a state of high intraocular pressure, and the difference was not statistically significant (P>0.05); the intraocular pressure values ​​of each group were significantly lower than those before surgery 1d and 7d after surgery, and the difference was statistically significant (P<0.05); from 14d after surgery, the intraocular pressure of the simple surgery group and the negative control group began to rise, and although the difference with the blank control group (chronic high intraocular pressure model group) was still statistically significant, it was close to the critical value of high intraocular pressure; 21d after surgery, the intraocular pressure of the simple surgery group and the negative control group exceeded the normal range and remained high since then, but there was still a difference from the high intraocular pressure state before surgery, and it was statistically significant (P<0.05).

[0082] The intraocular pressure of the sinomenine group and the positive control group (MMC group) decreased significantly at 1d, 7d, 14d, 21d and 28d after surgery compared with that before surgery (P<0.05), and remained stable within the normal range. There was no significant statistical difference in intraocular pressure between the two groups (P>0.05). 7d after surgery, the difference in intraocular pressure between the sinomenine group and the simple surgery group began to show statistical significance (P<0.05).

[0083] Comprehensive statistical results, as shown in Table 2, showed that the sinomenine group and the positive control group had a good effect in lowering intraocular pressure. Subconjunctival injection of sinomenine after surgery could effectively maintain the target intraocular pressure for a period of time, and the effect was not significantly different from that of intraoperative application of MMC. The intraocular pressure of the simple surgery group and the negative control group decreased and then rebounded after surgery. Although it was still lower than the preoperative high intraocular pressure model state, the filtering bleb function was significantly worse than that of the sinomenine group and the positive control group.

[0084] Table 2 Comparison of intraocular pressure values ​​before and after GFS surgery in each group (n=10, )

[0085]

[0086]

[0087] Note: A: blank control group; B: simple surgery group; C: positive control group; D: negative control group; E: sinomenine group;

[0088] The intraocular pressure of each group was compared with that before modeling, *P<0.05, **P<0.01, ***P<0.001.

[0089] 2. HE staining

[0090] The staining results showed that the blank control group had a clear structure, regular and orderly arrangement of cells, and a small number of fibroblasts, while the other four groups all had an increase in fibroblasts after GFS surgery. The simple surgery group and the negative control group had severe structural abnormalities, some cells were degenerated and necrotic, the nucleolus disappeared, and the fibroblasts increased significantly; the positive control group and the sinomenine group had relatively few fibroblasts; compared with the sinomenine group, the negative control group had more and denser fibroblasts and rich blood vessels, and some blood vessels were filled with red blood cells, and light staining was seen around the blood vessels, with mild fibrosis. It can be seen that the filtration bleb tissue that was intervened with sinomenine after surgery had significantly less fibroblast proliferation and a significantly lower degree of fibrosis than the tissue that was only intervened with placebo PBS (see Figure 1-5 ).

[0091] 3. VG staining

[0092] VG staining can dye collagen fibers red. The staining results showed that compared with the blank control group, the collagen fibers in the filtration area tissue of the simple surgery group and the negative control group increased significantly, and the collagen fiber content in the filtration tract tissue of the positive control group and the sinomenine group was relatively small, indicating that the filtration bleb tissue intervened by sinomenine and the filtration bleb tissue infiltrated with MMC cotton pads during surgery had a low degree of postoperative fibrosis, relatively few filtration tract scars, and good function maintenance. This result is consistent with the HE staining results (see Figure 6-10 ).

[0093] In summary, sinomenine is an alkaloid extracted from the herbal medicine Sinomenine, and the main effects of Sinomenine are to dispel rheumatism and dredge the meridians. The present invention first discovered that sinomenine intervention in high intraocular pressure rabbit eyes after GFS surgery can better control the intraocular pressure of rabbit eyes after GFS surgery to an ideal state and maintain it for a longer time; at the same time, significantly lighter fibrosis and less collagen fiber deposition can be observed in the tissue of rabbit eyes after GFS surgery intervened by sinomenine.

Claims

1. A use of sinomenine hydrochloride in the preparation of a drug for preventing / inhibiting the progression of filtration tract scarring after glaucoma filtration surgery, characterized in that: The glaucoma filtration surgery includes trabeculectomy, aqueous humor drainage nail or drainage disc implantation, the filtration tract scarring after glaucoma filtration surgery progresses to filtration bleb encapsulation or filtration tract scarring caused by excessive fibrosis of the filtration area after glaucoma filtration surgery, and the drug is a drug for subconjunctival injection or eye drop administration.

2. The use according to claim 1, characterized in that: In the subconjunctival injection drug, the concentration of sinomenine hydrochloride is 0.5-25 mg / mL; in the eye drop drug, the concentration of sinomenine hydrochloride is 1-10 mg / mL.

3. The use according to claim 1 or 2, characterized in that: The drug also includes pharmaceutically acceptable excipients.

4. The use according to claim 3, characterized in that: The auxiliary materials include any one or more of a pH regulator, an isotonicity regulator, an antibacterial agent, a thickener, a solubilizer, and a cosolvent.

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