Triamcinolone acetonide nanoemulsion as well as preparation method and application thereof

Abstract

The invention discloses a triamcinolone acetonide nanoemulsion as well as a preparation method and application thereof, and belongs to the technical field of medicines, the triamcinolone acetonide nanoemulsion is prepared from the following components in percentage by mass: 0.001%-10% of triamcinolone acetonide, 1%-20% of an organic solvent, 4%-50% of an oily medium, 1%-10% of a surfactant, 0.1%-5% of an osmotic pressure regulator and the balance of water for injection, totaling 100%; the preparation method comprises the following steps: dissolving triamcinolone acetonide in an organic solution, and adding an oily medium to form an oil phase; dissolving the surfactant and the osmotic pressure regulator in water to form a water phase; mixing and homogenizing at high pressure; and removing the organic solvent, and then adjusting the pH value to 7.0-7.4. The triamcinolone acetonide nanoemulsion can also be prepared into freeze-dried powder; according to the triamcinolone acetonide nanoemulsion disclosed by the invention, the drug loading capacity is improved; the particle size is small, so that the stability is improved, the problems of medicine deposition and non-uniform distribution can be solved, and the occurrence of thrombus is reduced; and after freeze-drying, the drug delivery volume can be adjusted by redissolving, so that the problem that large-volume drug delivery is needed in the prior art is solved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a triamcinolone acetonide nanoemulsion, a preparation method thereof and applications thereof. Background Art

[0002] Thyroid-associated orbitopathy (TAO), also known as Graves' ophthalmopathy, is an autoimmune orbital disease closely related to thyroid dysfunction (particularly Graves' disease). Common clinical symptoms include upper eyelid retraction, tarsus (noticeable during gaze), eyelid edema, proptosis, diplopia, restricted eye movements, conjunctival congestion / edema, and optic neuropathy. Currently, triamcinolone acetonide suspension is commonly used to treat these eye symptoms.

[0003] The standard formula of triamcinolone acetonide suspension currently used clinically is shown in Table 1:

[0004] Different manufacturers may adjust the ratio of excipients, but the concentration of the active ingredient (triamcinolone acetonide) is fixed at 40 mg / mL.

[0005] The above-mentioned triamcinolone acetonide suspension, which is currently commonly used in clinical practice, has at least the following limitations when injected into the orbit in the clinical treatment of thyroid-related eye diseases: (1) Poor dosing regimen: 1) Large volumes of medication are required, with an intraorbital volume of 1mL-5mL. Large-volume injection may cause eye displacement or proptosis; a sharp increase in intraorbital pressure may compromise optic nerve blood supply (compression of the central retinal artery or ciliary artery), leading to decreased vision or even ischemic optic neuropathy; increased intraocular pressure; the drug is prone to leakage into non-target areas, thereby reducing efficacy; and the drug is prone to reflux into blood vessels, increasing the risk of systemic absorption.

[0006] 2) Frequent injections, repeated every 4 weeks. Multiple high-dose injections may cause chronic elevated intraorbital pressure, affecting optic nerve blood supply, increasing mechanical damage, and reducing patient compliance with treatment. (2) Pharmaceutical defects: The particle size is large, generally 10-100 μm, which leads to: 1). Drug deposition at the injection site; 2) Uneven distribution within the orbit and poor targeting; 3). Diffusion is restricted and bioavailability is reduced; (3) Security risks: 1) It may induce local thrombosis, i.e. there is a risk of particle embolism; 2). Repeated and frequent injections increase the probability of tissue damage.

[0007] While those skilled in the art have made improvements to triamcinolone acetonide preparations, for example, a master's thesis titled "Study of Triamcinolone Acetonide Injectable Fat Emulsion Preparations Based on the QbD Concept" discloses formulating triamcinolone acetonide into an oil-in-water (O / W) submicron emulsion with medium-chain triglycerides as the dispersed phase, the inventors discovered through experiments that increasing the drug loading significantly reduces the stability of the triamcinolone acetonide fat emulsion using this method. Another example is formulating the drug into a latex for topical skin administration, which is unsuitable for orbital injection for thyroid-related eye diseases. Summary of the Invention

[0008] One of the purposes of the present invention is to provide a triamcinolone acetonide nanoemulsion to solve the above problems.

[0009] In order to achieve the above object, the technical solution adopted by the present invention is as follows: a triamcinolone acetonide nanoemulsion, whose formula is calculated by mass ratio and consists of the following components: Triamcinolone acetonide 0.001%-10%, Organic solvent 1%-20%, Oily medium 4%-50%, Surfactant 1%-10%, Osmotic pressure regulator 0.1%-5%, pH adjuster and water for injection; excluding the pH adjuster, the rest totaling 100% is adjusted to pH 7.0-7.4 with the pH adjuster.

[0010] Among the above components, triamcinolone acetonide is used as a pharmacologically active ingredient, an organic solvent is used to dissolve triamcinolone acetonide, an oily medium is used as a drug carrier, a surfactant is used as an emulsifier, an osmotic pressure regulator is used to regulate osmotic pressure, and a pH regulator is used to regulate pH value.

[0011] As a preferred technical solution, the organic solvent is selected from at least one of dimethyl sulfoxide, dichloromethane, ethanol, propylene glycol, polyethylene glycol 400, benzyl alcohol, and ethyl oleate.

[0012] As a preferred technical solution, the oily medium is selected from at least one of long-chain fatty acid triglycerides, medium-chain fatty acid triglycerides, fish oil, olive oil, and vitamin E oil.

[0013] As a further preferred technical solution, the long-chain fatty acid triglyceride is soybean oil or safflower oil.

[0014] As a preferred technical solution, the surfactant is selected from at least one of phospholipids, poloxamers, polysorbates, bile salts, vitamin E derivatives, and chitosan derivatives.

[0015] As a further preferred technical solution, the phospholipid is egg yolk lecithin or soybean lecithin; the poloxamer is P188 or P407; the polysorbate is Tween80 or Tween20; the bile salt is sodium deoxycholate; the vitamin E derivative is TPGS; and the chitosan derivative is carboxymethyl chitosan.

[0016] As a preferred technical solution, the osmotic pressure regulator is selected from at least one of glycerol, sorbitol, glucose, sucrose, xylitol, mannitol, sodium chloride, sodium acetate, and sodium citrate.

[0017] A second object of the present invention is to provide a method for preparing the above-mentioned triamcinolone acetonide nanoemulsion, which adopts the following technical scheme: first dissolving triamcinolone acetonide in an organic solution to obtain a triamcinolone acetonide solution, then adding the oily medium to the triamcinolone acetonide solution to obtain an oil phase; dissolving the surfactant and the osmotic pressure regulator in water for injection to obtain an aqueous phase; mixing the oil phase and the aqueous phase and then homogenizing under high pressure, then removing the organic solution, and finally adjusting the pH to 7.0-7.4 with a pH regulator to obtain the triamcinolone acetonide nanoemulsion.

[0018] As a preferred technical solution, the method for removing the organic solution is dialysis or rotary evaporation.

[0019] As a preferred technical solution, a freeze-drying protectant is further added to the triamcinolone acetonide nanoemulsion and then freeze-dried to obtain a freeze-dried triamcinolone acetonide nanoemulsion.

[0020] The freeze-drying protective agent is selected from at least one of mannitol, trehalose, sucrose, polyvinyl pyrrolidone, sorbitol, maltitol, dextran, and maltitol; and the added mass of the freeze-drying protective agent is 5%-20% of the triamcinolone acetonide nanoemulsion.

[0021] The third object of the present invention is to provide the use of the above-mentioned triamcinolone acetonide nanoemulsion in the preparation of an injection for treating thyroid-related eye diseases.

[0022] The present invention firstly adopts an organic solvent to dissolve triamcinolone acetonide to form a triamcinolone acetonide solution, thereby making the prepared triamcinolone acetonide nanoemulsion have a particle size of less than 500 nm, thereby improving stability and being stable for 7 days. Compared with the triamcinolone acetonide suspension, the triamcinolone acetonide nanoemulsion provided by the present invention can solve the problems of drug deposition and uneven distribution, thereby reducing the occurrence of thrombosis.

[0023] The present invention utilizes a method of pre-dissolving with an organic solvent before preparation, which increases the drug loading capacity of the triamcinolone acetonide nanoemulsion, achieving a drug loading capacity of up to 60 mg / mL. Existing technologies, including triamcinolone acetonide suspensions currently used clinically and triamcinolone acetonide fat emulsions reported in the literature, only achieve a maximum drug loading capacity of 40 mg / mL; other literature reports a drug loading capacity of only 19.17 mg / mL. The solubility of medium-chain triglycerides alone in triamcinolone acetonide in this literature is limited, reaching a maximum of 10 mg / mL. The solubility is increased by adding a cosolvent, resulting in a drug loading capacity of only 19.17 mg / mL. As those skilled in the art will appreciate, it is virtually impossible to increase the drug loading capacity to 60 mg / mL.

[0024] The triamcinolone acetonide nanoemulsion prepared by the present invention is freeze-dried by adding a freeze-drying protective agent, and is redissolved after freeze-drying, and the nanoemulsion is also very stable; The benefits of freeze-drying include: (1) significantly improved stability and extended shelf life, extremely low moisture content (<1%), reduced triamcinolone acetonide degradation, and long-term storage at room temperature. Tests have shown that it is stable at 25°C for at least 1 year; (2) easy to transport and store. Small size and light weight reduce transportation costs and do not require a cold chain; (3) flexible use and rapid reconstitution. Ready-to-use: freeze-dried powder for injection is reconstituted with sterile water before use, and the dosage is accurate: the solid form avoids liquid packaging errors; (4) fewer additives and preservatives, only freeze-dried protective agents are required, and no antibacterial agents, buffer salts, etc. used in liquid preparations are required.

[0025] The triamcinolone acetonide nanoemulsion provided by the present invention can be reconstituted after freeze-drying to adjust the administration volume, thereby solving the problem of large-volume administration required in the prior art.

[0026] Compared with the prior art, the advantages of the present invention are: (1) The triamcinolone acetonide nanoemulsion provided by the present invention can reduce the number of drug administrations by sustained release and increasing the drug loading; (2) The oily medium (oil phase) in the triamcinolone acetonide nanoemulsion of the present invention can effectively protect the drug, isolate oxygen, and reduce drug oxidation, while the drug in the triamcinolone acetonide suspension is directly exposed to the aqueous phase and is easily hydrolyzed and oxidized; (3) The triamcinolone acetonide nanoemulsion of the present invention can be freeze-dried after adding a freeze-drying protective agent, which is convenient for transportation and storage; the concentration of the drug can be controlled by adding an aqueous solution (using water for freeze-drying and reconstitution), which is convenient for adjusting the dosage of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The particle size stability of different triamcinolone acetonide dosage forms at 4°C; Figure 2 Comparison of particle sizes with different drug loadings; Figure 3 The release profiles of different triamcinolone acetonide dosage forms are shown; Figure 4 The weight changes of mice in different treatment groups during the drug administration process; Figure 5 Evaluation of the eyelid width of the right eye of mice after administration to different treatment groups; Figure 6 Evaluation of the left eyelid width of mice after administration in different treatment groups; Figure 7 The diagram shows the eye bulge of mice in different treatment groups; Figure 8 Figure 2 is the Trab test results of mice in different treatment groups after treatment; Figure 9 This is the D-dimer detection result after treatment in different treatment groups. DETAILED DESCRIPTION

[0028] The present invention will be further described below with reference to the embodiments.

[0029] Example 1

[0030] A triamcinolone acetonide nanoemulsion, comprising the following raw materials by mass: Triamcinolone acetonide 10% Dimethyl sulfoxide 10% Capric triglyceride 20% Soy lecithin 10% Sucrose 10% The rest is water for injection, totaling 100%; Finally, the pH was adjusted to 7.0 using 10 mM hydrochloric acid / sodium hydroxide solution; The preparation method comprises: dissolving the aforementioned amount of triamcinolone acetonide in dimethyl sulfoxide to obtain a triamcinolone acetonide solution, which is then added to a prescribed amount of capric triglyceride to obtain an oil phase; dissolving the prescribed amount of soy lecithin in water to obtain an aqueous phase; mixing the oil phase and aqueous phase, and homogenizing the mixture at a pressure of 650 bar for 5 minutes; dialyzing the mixture against water for injection for 2 days to obtain a triamcinolone acetonide nanoemulsion from which free drug and organic solvent have been removed; and adjusting the pH to 7.0 by adding a 10 mM hydrochloric acid / sodium hydroxide solution. Sucrose (20% by weight of the mass of the triamcinolone acetonide nanoemulsion) is then added to the triamcinolone acetonide nanoemulsion, dissolved, and then freeze-dried to obtain a freeze-dried triamcinolone acetonide emulsion.

[0031] Example 2

[0032] A triamcinolone acetonide nanoemulsion, comprising the following raw materials, calculated by mass percentage: Triamcinolone acetonide 10% Dichloromethane 15% Soybean oil 20% Tween80 1% Glycerin 5% Trehalose 15% The rest is water for injection, totaling 100%; The pH was adjusted to 7.2 using 10 mM hydrochloric acid / sodium hydroxide solution; The preparation method comprises the following steps: dissolving the triamcinolone acetonide in dichloromethane to obtain a triamcinolone acetonide solution, and then adding the solution to a prescribed amount of soybean oil to obtain an oil phase; dissolving a prescribed amount of Tween 80 and glycerol in water to obtain an aqueous phase; uniformly mixing the oil phase and the aqueous phase, and homogenizing the mixture under a high-pressure homogenizer at a pressure of 700 bar for 5 minutes; rotary evaporating the triamcinolone acetonide nanoemulsion to remove dichloromethane, adding a 10mM hydrochloric acid / sodium hydroxide solution to adjust the pH to 7.0, and obtaining a triamcinolone acetonide nanoemulsion; and adding trehalose in an amount of 10% by weight of the triamcinolone acetonide nanoemulsion to the triamcinolone acetonide nanoemulsion, dissolving the mixture, and then freeze-drying the mixture to obtain a freeze-dried triamcinolone acetonide emulsion.

[0033] Example 3

[0034] A triamcinolone acetonide nanoemulsion, comprising the following raw materials, calculated by mass percentage: Triamcinolone acetonide 10% Polyethylene glycol 400 18% Vitamin E oil 20% Poloxamer P188 0.8% Sorbitol 0.5% The rest is water for injection, totaling 100%; The pH was adjusted to 7.3 using 10 mM hydrochloric acid / sodium hydroxide solution; The preparation method is the same as that in Example 1.

[0035] Example 4

[0036] A triamcinolone acetonide nanoemulsion, comprising the following raw materials, calculated by mass percentage: Triamcinolone acetonide 8% Propylene glycol 20% Fish oil 15% Sodium chloride 1% Glucan 10% The rest is water for injection, totaling 100%; The pH was adjusted to 7.4 using 10 mM hydrochloric acid / sodium hydroxide solution; The preparation method is the same as that in Example 1.

[0037] Example 5

[0038] Triamcinolone acetonide 10% Polyethylene glycol 400 15% Olive oil 20% Tween80 2% Sodium acetate 0.8% The rest is water for injection, totaling 100%; 10 mM hydrochloric acid / sodium hydroxide solution to adjust pH to 7.1; The preparation method is the same as that in Example 1.

[0039] Performance Test Example 1 Stability test (1) Experimental drugs: 1) The triamcinolone acetonide nanoemulsion prepared according to Example 1 above, referred to as "triamcinolone acetonide nanoemulsion"; the prescription is: Triamcinolone acetonide 60mg Dimethyl sulfoxide 1mL Capric triglyceride 100mg Soy lecithin 18mg Sucrose 100mg The rest is water for injection, totaling 1 mL; The pH was adjusted to 7.0 using 10 mM hydrochloric acid / sodium hydroxide solution; 2) The triamcinolone acetonide fat emulsion prepared in the paper "Study on the Preparation of Triamcinolone Acetonide Injectable Fat Emulsion Based on the QbD Concept" was prepared in the laboratory of the aforementioned paper and is referred to as "triamcinolone acetonide fat emulsion." The specific preparation method is as follows: Weigh the prescribed amount of medium-chain triglycerides, egg yolk lecithin (PC-98T), polysorbate 80, and triamcinolone acetonide in sequence and dissolve them all into the oil phase. Weigh the prescribed amount of glycerol and add 80% of the total amount of water to dissolve it into the aqueous phase, which is then kept warm and set aside. The two phases are mixed in a shearing machine at a shear rate of 20,000 rpm for 5 minutes to form a colostrum, and the mixture is mixed until a uniform emulsion is formed. Add water to the required amount and stir until uniform. The emulsion was placed in a high-pressure microfluidizer for recirculation and redispersion. The first homogenization pressure was 12,000 psi, the second homogenization pressure was 15,000 psi, and the third homogenization pressure was 18,000 psi. The pH value was adjusted to between 5.0 and 6.5, stirred evenly, and the emulsion was collected.

[0040] The prescription is: Triamcinolone acetonide 40mg Medium chain triglycerides 100mg Egg yolk lecithin 18mg Tween80 1mg Glycerol 22.1mg The rest is water for injection, totaling 1 mL; Sodium hydroxide was used to adjust the pH to 7.0-7.4; 3) Triamcinolone acetonide suspension, Tongxitong, 40 mg / mL, purchased from Kunming Jida Pharmaceutical Co., Ltd.; referred to as “triamcinolone acetonide suspension”.

[0041] (2) Experimental method: The drug loading of the three experimental drugs was 40 mg / mL. The samples were placed at 4°C for 7 days. The particle sizes were measured using a laser particle size analyzer Zetasizer (Nano ZS90, UK) on the 1st, 2nd, 3rd, 4th, and 7th day, respectively. (3) Experimental results: Figure 1 As shown, from Figure 1 It can be seen that the particle size of triamcinolone acetonide nanoemulsion is stable at about 200 nm at 4°C for 7 days; although the initial particle size of triamcinolone acetonide fat emulsion is also small, the particle size increases on the 5th day; the original particle size of triamcinolone acetonide suspension is large, and the particle size further increases with time.

[0042] Performance Test Example 2 Comparison of drug loading of triamcinolone acetonide in different dosage forms The maximum drug loading of triamcinolone acetonide fat emulsion reported in the literature is 40 mg / mL, while the maximum drug loading of triamcinolone acetonide nanoemulsion prepared in Examples 1-5 of the present application can reach 60 mg / mL. When the drug loading of the triamcinolone acetonide nanoemulsion of the present application is greater than 60 mg / mL, the drug will precipitate, and when the drug loading is greater than 60 mg / mL, the particle size of the nanoemulsion will increase, such as Figure 2 In addition, the drug loading of triamcinolone acetonide nanoemulsion can be adjusted by adding water for injection after freeze-drying.

[0043] (1) Experimental drug: Same as the performance test example 1 above; (2) Experimental method: Triamcinolone acetonide nanoemulsions with different drug loadings (20, 40, 60, and 80 mg / mL) were prepared, and their particle sizes were measured using a laser particle size analyzer Zetasizer (Nano ZS90, UK). (3) Experimental results: The results are as follows Figure 2 As shown in the figure, when the drug loading of triamcinolone acetonide nanoemulsion is less than or equal to 60 mg / mL, the particle size of the nanoemulsion is stable at about 200 nm, while when the drug loading is greater than 60 mg / mL, the particle size of the nanoemulsion increases to about 500 nm.

[0044] Performance Test Example 3 Sustained release effect of triamcinolone acetonide nanoemulsion (1) Experimental drug: Same as the performance test example 1 above; (2) Experimental method: 1 mL of each experimental object was placed in a 5000MW dialysis bag, and then placed in a PBS solution containing Tween 80. 1 mL of the solution was taken every 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours to detect the content of triamcinolone acetonide under HPLC; Among them, the HPLC detection conditions were: methanol: water (525:475) as the mobile phase, the detection wavelength was 240 nm, and the injection volume was 20 μL.

[0045] (3) Experimental results: Figure 3 As shown, from Figure 3 It can be seen that triamcinolone acetonide nanoemulsion delays drug release through lipid carriers and has significant sustained-release properties compared with suspensions and fat emulsions, thereby reducing the frequency of clinical administration.

[0046] Performance Test Example 4 In vivo animal experiments (1) Animal modeling: SKG mice were injected intraperitoneally with 3 mg of zymosan A (yeast O-glycan A) at 8 weeks of age, and the model was successfully established after 12 weeks. After the successful establishment of the model, the drug was administered once every 4 days around the eye fundus, for a total of 4 doses, with 50 mg / kg given to each eye. During the administration period, the eyelid width and eyeball protrusion of the mice were measured every two days, and the weight of the mice was measured. After the administration, the blood of the mice was collected for the detection of anti-thyroid hormone receptor antibodies (TRAb) and D-dimer; (2) Mouse grouping: Normal healthy mice served as controls (referred to as the "healthy group"), and model mice were randomly divided into the "modeling group," the "triamcinolone acetonide suspension" group (Tongxitong, 40 mg / mL, Kunming Jida Pharmaceutical Co., Ltd.), and the "triamcinolone acetonide nanoemulsion" group (prepared according to Example 1), with 3 mice in each group. Drugs were administered by orbital injection.

[0047] (3) Experimental results: The results are as follows Figure 4-9 As shown, from Figure 4 It can be seen that after the modeling, the weight of the mice decreased and remained relatively stable during the treatment period; from Figure 7 As can be seen in the figure, after the modeling, the mice developed exophthalmos, conjunctival congestion, and upper eyelid retraction; After the treatment, it was clearly observed that the eyelids of the mice in the triamcinolone acetonide suspension group and the triamcinolone acetonide nanoemulsion group returned to normal width. Figure 5 、 Figure 6 As shown, and the eyeball bulge has improved, as shown Figure 7 As shown; Trab is an important indicator of thyroid disease. After the treatment, the Trab levels of both the triamcinolone acetonide suspension group and the triamcinolone acetonide nanoemulsion group returned to the healthy range. Figure 8 As shown; After the treatment, it can be seen that the amount of D-dimer in the mice in the triamcinolone acetonide nanoemulsion group was no different from that in the healthy mice. Figure 9 As shown in the results, triamcinolone acetonide nanoemulsion effectively alleviated the symptoms of thyroid-related eye disease, and no thrombosis-related complications were observed in the triamcinolone acetonide suspension group. above Figure 8 and Figure 9 *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

[0048] 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 and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A triamcinolone acetonide nanoemulsion, characterized in that Its formula is composed of the following components by mass ratio: Triamcinolone acetonide 0.001%-10%, Organic solvent 1%-20%, Oily medium 4%-50%, Surfactant 1%-10%, Osmotic pressure regulator 0.1%-5%, pH adjusters and water for injection; The total amount of the mixture except the pH adjuster is 100%. The pH is adjusted to 7.0-7.4 with the pH adjuster.

2. The triamcinolone acetonide nanoemulsion according to claim 1, wherein The organic solvent is selected from at least one of dimethyl sulfoxide, dichloromethane, ethanol, propylene glycol, polyethylene glycol 400, benzyl alcohol, and ethyl oleate.

3. The triamcinolone acetonide nanoemulsion according to claim 1, wherein The oily medium is selected from at least one of long-chain fatty acid triglycerides, medium-chain fatty acid triglycerides, fish oil, olive oil, and vitamin E oil.

4. The triamcinolone acetonide nanoemulsion according to claim 3, wherein The long-chain fatty acid triglyceride is soybean oil or safflower oil.

5. The triamcinolone acetonide nanoemulsion according to claim 1, wherein The surfactant is selected from at least one of phospholipids, poloxamers, polysorbates, bile salts, vitamin E derivatives, and chitosan derivatives.

6. The triamcinolone acetonide nanoemulsion according to claim 1, wherein The osmotic pressure regulator is selected from at least one of glycerol, sorbitol, glucose, sucrose, xylitol, mannitol, sodium chloride, sodium acetate, and sodium citrate; and the pH regulator is selected from one of hydrochloric acid and sodium hydroxide.

7. The method for preparing the triamcinolone acetonide nanoemulsion according to any one of claims 1 to 6, wherein: The method comprises the following steps: firstly dissolving triamcinolone acetonide in an organic solution to obtain a triamcinolone acetonide solution, then adding the oily medium to the triamcinolone acetonide solution to form an oil phase; dissolving the surfactant and the osmotic pressure regulator in water for injection to obtain an aqueous phase; mixing the oil phase and the aqueous phase, homogenizing under high pressure, removing the organic solution, and finally adjusting the pH to 7.0-7.4 with a pH regulator to obtain the triamcinolone acetonide nanoemulsion.

8. The preparation method according to claim 7, characterized in that The pressure of the high-pressure homogenization is 500-800 bar, and the homogenization time is 5 min-20 min; the method for removing the organic solution is dialysis or rotary evaporation.

9. The preparation method according to claim 7, characterized in that A freeze-drying protective agent is further added to the triamcinolone acetonide nanoemulsion and then freeze-dried to obtain a freeze-dried triamcinolone acetonide nanoemulsion.

10. Use of the triamcinolone acetonide nanoemulsion according to any one of claims 1 to 6 in the preparation of an injection for treating thyroid-related eye diseases.

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