Anti-schizophrenia lyotropic liquid crystal long-acting injection as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly discloses an anti-schizophrenia lyotropic liquid crystal long-acting injection and a preparation method and application thereof, and the anti-schizophrenia lyotropic liquid crystal long-acting injection is composed of an anti-schizophrenia drug, an amphiphilic compound and an organic solvent; the anti-schizophrenia medicine is selected from any one of brexpiprazole, cariprazine and aripiprazole; the amphiphilic compound is selected from any one or more of soybean phosphatidylcholine, egg yolk phosphatidylcholine, glyceryl monooleate, glyceryl monopalmitate, glyceryl dioleate, glyceryl trioleate, vitamin E acetate and phytantriol; the organic solvent is selected from one or more of ethanol, N-methyl pyrrolidone, dimethyl sulfoxide and 1, 2-propylene glycol. The anti-schizophrenia lyotropic liquid crystal in-situ gel long-acting injection forms a stable semi-solid drug reservoir through solvent exchange after administration so as to play a therapeutic effect in long-acting treatment of positive schizophrenia and negative schizophrenia and prevention of schizophrenia relapse.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, specifically to a long-acting lyotropic liquid crystal injection for treating schizophrenia, its preparation method, and its application. Background Technology

[0002] Schizophrenia is a common neurological disorder characterized by thought disturbances, mood swings, and behavioral abnormalities. It has a high relapse and mortality rate in adults; however, its etiology is not fully understood. Research suggests that its pathogenesis involves the interaction of genetic factors, neurodevelopmental abnormalities, neurotransmitter imbalances (such as dopamine, glutamate, and the GABA system), and environmental factors (such as prenatal infection and social stress). While traditional antipsychotic drugs can effectively improve symptoms, they generally have significant safety risks, such as extrapyramidal reactions, tardive dyskinesia, metabolic syndrome (weight gain, dyslipidemia), cardiovascular toxicity, and hyperprolactinemia, severely limiting long-term medication adherence and quality of life for patients. Cariporazine, as a novel partial agonist of the dopamine D3 / D2 receptor, possesses a unique pharmacological mechanism that endows it with excellent clinical safety and tolerability. Clinical studies have shown that cariprazine, while effectively treating negative / positive symptoms, can significantly reduce the incidence of extrapyramidal syndrome (EPS), avoid abnormal fluctuations in metabolic parameters, and reduce the risk of sedation and orthostatic hypotension, making it particularly suitable for long-term maintenance therapy in patients with chronic disease. However, a core challenge in the treatment of schizophrenia lies in poor patient medication adherence.

[0003] To prolong the duration of drug efficacy and improve patient adherence, sustained-release systems offer an effective dosing strategy for the antipsychotic drug calcipoprazole. Among current sustained-release systems, long-acting injectable formulations based on lyotropic liquid crystals have attracted particular attention. The advantages of lyotropic liquid crystal systems lie primarily in their simplicity of manufacture, structural stability, and low risk of initial burst release, especially compared to other long-acting formulations such as microspheres (requiring complex preparation processes), polylactic-co-glycolic acid (PLGA) implants (exhibiting uncontrollable degradation rates), and oil suspensions (typically exhibiting significant initial burst release). Lyotropic liquid crystals are formed by a simple mixture of amphiphilic compounds and a solvent, existing in liquid form before injection. Upon solvent exchange with an aqueous solution, a phase transition occurs, forming a stable semi-solid drug reservoir with high mechanical strength. Simultaneously, different amphiphilic compounds can assemble into liquid crystal phases with various microstructures, such as inverted cubic or inverted hexagonal phases. In these microstructures, hydrophilic molecules are embedded within internal water channels, while hydrophobic molecules are incorporated into the lipid layers of the liquid crystal structure. This compartmentalized structure facilitates the slow release of the drug through diffusion via water channels and intermolecular interactions. The rapid assembly of the structure, combined with this sustained-release mechanism, can effectively achieve sustained drug release.

[0004] Therefore, a long-acting lyotropic liquid crystal injection for treating schizophrenia, its preparation method, and its application are provided. Summary of the Invention

[0005] The purpose of this invention is to address the deficiencies of the prior art by providing a long-acting lyotropic liquid crystal injection for treating schizophrenia, its preparation method, and its application, thereby resolving the problems raised in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a long-acting lyotropic liquid crystal injection for treating schizophrenia, comprising an antipsychotic drug, an amphiphilic compound, and an organic solvent; The antipsychotic drug has a mass-volume percentage of 1% to 7% (w / v), the amphiphilic compound has a mass percentage of 20% to 80% (w / v), and the organic solvent has a mass percentage of 15% to 30% (w / v). The antipsychotic drug is selected from any one of ibupropiazole, cariprazine, and aripiprazole; The amphiphilic compound is selected from any one or more of soybean phosphatidylcholine, egg yolk phosphatidylcholine, monooleate, monopalmitate, dioleate, trioleate, vitamin E acetate, and phytanetriol. The organic solvent is selected from one or more of ethanol, N-methylpyrrolidone, dimethyl sulfoxide, and 1,2-propanediol.

[0007] As a preferred embodiment of the present invention, the antipsychotic drug is cariprazine, the amphiphilic compounds are egg yolk phosphatidylcholine and dioleoylglycerol, and the organic solvent is 1,2-propanediol.

[0008] As a preferred embodiment of the present invention, the carilarazine has a mass-volume percentage of 4% (w / v).

[0009] As a preferred embodiment of the present invention, the mass ratio of egg yolk phosphatidylcholine to dioleoylglycerol is 1:0.5-2.

[0010] As a preferred embodiment of the present invention, the mass-to-volume ratio of the 1,2-propanediol is 25% (w / v).

[0011] A method for preparing a long-acting lyotropic liquid crystal injection for treating schizophrenia as described above includes the following steps: The antipsychotic drug cariprazine is mixed with ethyl acetate and hydrochloric acid gas to form a hydrochloride salt. The hydrochloride salt of the antipsychotic drug is then ground into nanoparticles using a wet milling method. Subsequently, the nanoparticles are mixed with an amphiphilic compound and an organic solvent in a water bath using a rotor stirring mechanism.

[0012] As a preferred embodiment of the present invention, the solvent for the wet milling method is 1,2-propanediol, the grinding speed is 400 rpm, and the grinding time is 6 h.

[0013] As a preferred embodiment of the present invention, the water bath temperature is 35 °C, the stirring speed is 60 rpm, and the stirring time is 2 h.

[0014] The use of a long-acting lyotropic liquid crystal injection for treating or preventing schizophrenia, as described above, in the preparation of a medicament for treating or preventing schizophrenia, wherein the schizophrenia is one or more of positive schizophrenia, negative schizophrenia, or relapse of schizophrenia.

[0015] Compared with the prior art, the present invention has the following significant advantages: This invention utilizes a lyotropic liquid crystal delivery system prepared by mixing an amphiphilic compound with an organic solvent to deliver the antipsychotic drug cariprazine. After administration, the organic solvent exchanges with body fluids, causing the amphiphilic compound to assemble into a gel reservoir, thereby encapsulating the antipsychotic drug to produce a sustained-release effect. This formulation is simple to prepare and has a good sustained-release effect, providing a novel long-acting formulation for the treatment of schizophrenia.

[0016] The lyotropic liquid crystal long-acting injectable agent for schizophrenia of the present invention is in an injectable liquid state before administration. After injection, it undergoes solvent exchange with body fluids and phase change to form a semi-solid drug reservoir. Furthermore, the reservoir can be naturally degraded in the body, avoiding the cumbersome steps of implantation and removal, as well as trauma to the body.

[0017] The lyotropic liquid crystal long-acting injectable formulation for treating schizophrenia of the present invention delivers cariprazine in the form of hydrochloride, ensuring that a portion of the cariprazine is encapsulated in the water channels within the gel liquid crystal structure to achieve sustained release.

[0018] The lyotropic liquid crystal long-acting injection for schizophrenia of the present invention, after gel formation, not only contains cariprazine in molecular form within the liquid crystal structure, but its nanoparticles are also encapsulated by the gel matrix. Therefore, the drug release rate is affected by gel degradation, which is beneficial for regulating release by controlling degradation.

[0019] The lyotropic liquid crystal long-acting injection for treating schizophrenia of the present invention can continuously deliver cariprazine for several weeks, and has the potential effect of a single dose with a long-acting effect lasting for several weeks in the treatment of schizophrenia, which can reduce the number of doses and improve patient medication adherence.

[0020] The lyotropic liquid crystal long-acting injectable formulation for treating schizophrenia of the present invention delivers cariprazine via subcutaneous injection, which can avoid the first-pass effect and gastrointestinal absorption instability of oral formulations, and is especially suitable for special patient groups with swallowing disorders or metabolic abnormalities. Attached Figure Description

[0021] Figure 1 This is the precursor solution of the lyotropic liquid crystal long-acting injectable anti-schizophrenia preparation obtained in Example 1; Figure 2 The image shows the inverted state of the preform solutions of the lyotropic liquid crystal long-acting injection for schizophrenia prepared in Example 1 after they have formed a gel. Figure 3 The images show different textures of the long-acting lyotropic liquid crystal injection formulations D3, D4, and D5 prepared in Example 1 after forming gels under a polarizing microscope. Figure 4 Rheological information of the formulations D3, D4, and D5 of the anti-schizophrenic lyotropic liquid crystal long-acting injection obtained in Example 1; A is viscosity measurement; B is frequency scanning; Figure 5 The cumulative release percentage curves of cariprazine in vitro for formulations D3, D4, and D5 of the anti-schizophrenic lyotropic liquid crystal long-acting injection prepared in Example 1 are shown. Figure 6 Melt phase transition analysis of the D3 formulation of the anti-schizophrenic lyotropic liquid crystal long-acting injection prepared in Example 1; Figure 7 The changes in in vivo fluorescence intensity of the D3 formulation of the anti-schizophrenic lyotropic liquid crystal long-acting injection prepared in Example 1 after subcutaneous injection in mice were labeled with indocyanine green. Detailed Implementation

[0022] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0023] Example 1: A method for preparing a long-acting lyotropic liquid crystal injection for treating schizophrenia, the injection comprising the following components: an antipsychotic drug, an amphiphilic compound, and an organic solvent; The antipsychotic drug is cariprazine, and the mass-volume percentage of the antipsychotic drug is 1% to 7% (w / v). The amphiphilic compounds are egg yolk phosphatidylcholine and dioleoyl glycerol, with a mass ratio of 1:0.5 to 2. The organic solvent is 1,2-propanediol, and the mass-volume ratio of the organic solvent is 25% (w / v); The steps include the following: 40 mg of caliprazine was mixed with 400 ml of ethyl acetate, and then excess ethyl acetate hydrochloric acid gas was added while stirring. Stirring was continued for 1 h to ensure complete reaction. The mixture was then filtered through a 0.45 μm nylon organic filter membrane, and the resulting filter cake was dried in a drying oven at 60 °C for 2 h to obtain caliprazine hydrochloride. The obtained caliprazine hydrochloride was mixed with 1,2-propanediol at a mass ratio and milled using a ball mill at 400 rpm for 6 h to form nanoparticles. Finally, it was mixed with egg yolk phosphatidylcholine and dioleoylglycerol in the proportions shown in Table 1, and stirred in a 35 °C water bath for 2 h to form a prodrug solution for a long-acting lyotropic liquid crystal injection for antipsychotic purposes.

[0024] Table 1: Mass ratio of egg yolk phosphatidylcholine to dioleoylglycerol in lyotropic liquid crystal formulations

[0025] The results showed that all formulations with a mass ratio of egg yolk phosphatidylcholine to dioleoyl glyceride of 1:0.5–2 could form [the desired effect]. Figure 1 The precursor solution morphology is shown. Example 2

[0026] The in vitro gel formation of the lyotropic liquid crystal long-acting injectable precursor solution for anti-schizophrenia prepared in Example 1 was evaluated.

[0027] The method is as follows: Take 0.5 ml of the precursor solution prepared in Example 1 and place it in a vial. Add 30% (w / w) pH 7.4 phosphate buffer solution (PBS). After vortexing, evaluate the gel formation using the inverted vial method. The results are as follows: Figure 2 As shown.

[0028] The results of bottle inversion showed that formulations D1 and D2 remained fluid after mixing with PBS and could not exist in a semi-solid gel state, therefore they were not suitable for long-term drug delivery. However, formulations D3, D5, and D5, with a mass ratio of egg yolk phosphatidylcholine to dioleoylglycerol in the range of 1:1 to 2, could all form gels through solvent exchange, thus serving as semi-solid reservoirs for encapsulating drugs. Example 3

[0029] The anti-schizophrenic lyotropic liquid crystal long-acting injectable gel prepared in Example 2 was observed under a polarized light microscope. To verify the self-assembled liquid crystal structure formed by egg yolk phosphatidylcholine and dioleoyl glycerol after solvent exchange, the gel obtained in Example 2 was uniformly spread on a glass slide and then observed under a polarized light microscope in polarized light mode. Simultaneously, micrographs were taken for structural analysis. Figure 3 ).

[0030] The results showed that D3 appeared as a black background under a polarizing microscope. Figure 3 A) indicates that the composition is isotropic and exhibits no birefringence. In contrast, fan-shaped textures were observed in sample D4. Figure 3 B) indicates the presence of an inverse hexagonal phase liquid crystal structure; while the Maltese cross and myelin sheath texture in sample D5 are typical characteristics of lamellar phase liquid crystals. Figure 3 (C) confirmed the formation of liquid crystals in the layered phase of the sample.

[0031] The variation in liquid crystal structure is primarily due to changes in the proportion of amphiphilic compounds. Dioleoglycerate has a structure with two hydrophobic chains, and the larger space occupied by the hydrophobic tail makes it easier to assemble into an inverse cubic or inverse hexagonal phase structure with a large negative curvature. Therefore, in D3, the content of dioleoglycerate is relatively high, forming an isotropic Fd3m cubic phase. Subsequently, the content of dioleoglycerate decreases, and it is replaced by egg yolk phosphatidylcholine, whose hydrophilic head and hydrophobic tail occupy roughly the same space. This leads to a decrease in the negative curvature of the structure assembled by the amphiphilic materials, resulting in the observed transformation of the liquid crystal structure from the inverse hexagonal phase of D4 to the layered phase of D5.

[0032] Example 4: Rheological analysis was performed on the lyotropic liquid crystal long-acting injection precursor solution for anti-schizophrenia prepared in Example 1 and the lyotropic liquid crystal long-acting injection gel for anti-schizophrenia prepared in Example 2. The method is as follows: The sample was evenly spread on the test platform of the rheometer, filling the gaps in the parallel plate clamps and eliminating air bubbles. Temperature equilibration was then performed before measurement. To assess the injectability of the precursor solution sample, the shear rate of the precursor solution was measured within the range of 0.1–100 s⁻¹ to collect viscosity data under different shear conditions. Simultaneously, the mechanical properties of the gel were analyzed using modulus measurement. In short, frequency sweeps were performed on both gels within the angular frequency range of 0.1–100 rad / s, and their storage modulus (G′) and loss modulus (G′′) were recorded to evaluate viscoelastic behavior. The results are as follows: Figure 4 As shown.

[0033] The results showed that during viscosity testing, the precursor solutions of formulations D3, D4, and D5 all exhibited shear-thinning behavior. Figure 4A). This indicates that as the shear rate increases, the interaction forces between the amphiphilic compounds are disrupted, leading to a decrease in viscosity. This shear-thinning behavior ensures a lower viscosity during injection, facilitating a smooth injection process, and the viscosity rapidly recovers in the post-injection resting state to ensure the formation of a stable drug reservoir. Furthermore, after the shear rate exceeds 3 s⁻¹, the viscosities of all three formulations are below 0.3 Pa, meeting the viscosity requirements for injectable formulations.

[0034] The modulus curves of the gels formed from the three formulations D3, D4, and D5 after frequency scanning are shown below. Figure 4 As shown in Figure B. During the testing process, their storage modulus was consistently greater than their loss modulus, indicating that they are all solid-like structures dominated by viscous characteristics. Furthermore, their modulus remained relatively stable throughout the entire range of angular frequency variations, confirming that the internal structure of the gel can remain stable to resist external forces under angular frequency strain.

[0035] Example 5: Evaluation of the in vitro sustained-release effect of the lyotropic liquid crystal long-acting injection for treating schizophrenia prepared in Example 1; The method is as follows: PBS (pH 7.4) containing 20% ​​(v / v) ethanol was used as the in vitro release medium to simulate the subcutaneous pH environment of the human body. One ml of the antipsychotic lyotropic liquid crystal long-acting injectable gel was placed in 80 ml of the release medium, and the experiment was conducted using a horizontal shaker at 100 rpm and 37 ± 1 °C. 20 ml of the release medium was collected at predetermined time points, and an equal volume of medium preheated to 37 ± 1 °C was added at each time point. The collected samples were filtered through a 0.45 μm microporous membrane filter and then quantitatively analyzed by high-performance liquid chromatography (HPLC) to plot the release curve; the results are shown below. Figure 5 As shown.

[0036] The chromatographic conditions for the high performance liquid chromatography method are as follows: the mobile phase is a mixture of 47.5% water (containing 1% trifluoroacetic acid) and 52.5% methanol; the flow rate is 1 ml / min; the detection wavelength is 248 nm; and the elution time is 15 min.

[0037] The results showed that the release rates of the three antipsychotic lyotropic liquid crystal in situ gels exhibited a pattern of D5 > D4 > D3 over 32 days. Formulation D5 showed severe burst release behavior, with over 85% cumulative release on the first day, followed by complete drug release on the second day, failing to achieve long-acting drug delivery. In contrast, both D3 and D4 maintained sustained drug delivery for up to 32 days. Specifically, the cumulative release rates of D3 and D4 within 12 hours were 32.6 ± 6.7% and 33.3 ± 2.2%, respectively, showing significantly lower initial burst release behavior than D5. Subsequently, the release rate of D4 gradually showed a faster trend than D3, and at day 32, the cumulative release rate of 83.7 ± 4.7% was higher than that of D3 (72.3 ± 2.6%). This difference in release rate is mainly attributed to the differences in the liquid crystal structure of the gels.

[0038] Formulation D3 has an inverted cubic phase structure. Due to the greater negative curvature of its amphiphilic compound assembly, it possesses a smaller "water channel" liquid crystal structure. In contrast, the inverted hexagonal phase liquid crystal structure of D4 results in even smaller negative curvature and larger water channels. Consequently, drug molecules are released more rapidly from these larger "water channels," leading to a greater release rate for D4 than D3. Formulation D5, with its lamellar liquid crystal structure, lacks similar channel-like structures to encapsulate the drug, thus exhibiting a rapid release process. Furthermore, the gel degradation rate also contributes to the differences in drug release. Since egg yolk phosphatidylcholine is soluble in ethanol, it slowly decomposes in the release medium after gel formation, leading to the release of cariprazine. The content of egg yolk phosphatidylcholine gradually increases from D3 to D5, so D3 is least affected by degradation, thus exhibiting the longest-lasting release trend.

[0039] Therefore, D3 formulations, which aim to delay drug release rates, are the optimal formulations for long-acting delivery of antipsychotic drugs due to their relatively low initial release and the slowest cumulative release trend over 32 days.

[0040] Example 6: Melt phase transition analysis of the lyotropic liquid crystal long-acting injection for treating schizophrenia prepared in Example 1; The method is as follows: Five mg of the D3 formulation lyotropic liquid crystal precursor solution and gel were placed in aluminum crucibles and immediately capped and sealed. The samples were stabilized at 30 °C for 30 min using a differential calorimeter, and then heated from 30 °C to 200 °C at a heating rate of 10 °C / min. An empty crucible was used as a control during the experiment. This procedure allows for the determination of the melting temperature of the solid components and the total heat transferred during the observed heating process; the results are as follows: Figure 6 As shown.

[0041] The results showed that no endothermic peak was observed in the lyotropic liquid crystal precursor solution within the temperature range of 30-200 °C, indicating that no melting phase transition occurred within this temperature range. This suggests that the precursor solution of the gel was homogeneous and stable, and its melting phase transition was independent of temperature. However, a sharp endothermic peak appeared in the lyotropic liquid crystal gel at 174.8 °C, which was caused by the liquid crystal structure formed inside the gel. Specifically, the inverted cubic liquid crystal structure formed by D3 has the characteristic of maintaining structural stability within a certain temperature range. However, as the temperature rises, the molecular thermal motion becomes more intense, and the structure tends to be destroyed. Therefore, when the test temperature is 174.8 °C, the liquid crystal cannot maintain the integrity of the structure, resulting in a sharp endothermic peak. This phenomenon of an endothermic peak appearing after the phase transition of the lyotropic liquid crystal gel not only proves the formation of a microscopically ordered structure but also indicates that this structure has sufficient thermal stability and can maintain its structural integrity at physiological temperatures after injection.

[0042] Example 7: In order to visualize the in vivo localization and release of cariprasine in lyotropic liquid crystals, the in vivo imaging of mice after fluorescent labeling of the anti-schizophrenic lyotropic liquid crystal long-acting injection prepared in Example 1 was analyzed. The method is as follows: In vivo imaging was performed using 6-week-old female ICR mice. Prior to the experiment, the mice's abdomens were shaved to facilitate injection and observation. Indocyanine green (ICR) at a mass-to-volume ratio of 0.02% (w / v) was added to the D3 lyotropic liquid crystal precursor solution prepared in Example 1 using a physical labeling method. Mice were divided into an injection group (using ICR-labeled carilazine lyotropic liquid crystal precursor solution) and a control group (n = 3 in each group). Subsequently, 200 μL of ICR-labeled ICR precursor solution was subcutaneously injected into the abdomen of the injection group mice. At specified time points, both groups of mice were anesthetized with isoflurane, and fluorescence images were acquired using a small animal in vivo imaging system. The results are as follows: Figure 7 As shown.

[0043] The fluorescence image acquisition conditions of the small animal live imaging instrument are as follows: excitation wavelength 780 nm; emission wavelength 845 nm; exposure time 1 s.

[0044] The results showed that no fluorescence signal was detected in the uninjected control group mice throughout the test period, while the fluorescence intensity at the injection site in the lyotropic liquid crystal injection group mice showed a gradual decreasing trend over 28 days, indicating that the lyotropic liquid crystal in situ gel has sustained-release capability as a drug reservoir. However, compared with the sustained release of cariprasine in vitro for more than 32 days, the formulation was released more quickly in mice, which is due to the difference in gel degradation rate. In the in vitro release experiment, although the addition of 20% ethanol (v / v) to the release medium could promote gel decomposition, the gel underwent a faster decomposition process in vivo under the action of phospholipase and lipase, ultimately leading to the difference in the duration of release in vitro and in vivo. Therefore, as a carrier for delivering antipsychotic drugs, this lyotropic liquid crystal in situ gel has the potential to achieve a therapeutic effect of more than 21 days.

[0045] The above embodiments merely illustrate implementation methods of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A long-acting lyotropic liquid crystal injection for treating schizophrenia, characterized in that: It consists of antipsychotic drugs, amphiphilic compounds, and organic solvents; The antipsychotic drug has a mass-volume percentage of 1% to 7% (w / v), the amphiphilic compound has a mass percentage of 20% to 80% (w / v), and the organic solvent has a mass percentage of 15% to 30% (w / v). The antipsychotic drug is selected from any one of ibupropiazole, cariprazine, and aripiprazole; The amphiphilic compound is selected from any one or more of soybean phosphatidylcholine, egg yolk phosphatidylcholine, monooleate, monopalmitate, dioleate, trioleate, vitamin E acetate, and phytanetriol. The organic solvent is selected from one or more of ethanol, N-methylpyrrolidone, dimethyl sulfoxide, and 1,2-propanediol.

2. The lyotropic liquid crystal long-acting injection for treating schizophrenia according to claim 1, characterized in that: The antipsychotic drug is cariprazine, the amphiphilic compounds are egg yolk phosphatidylcholine and dioleoylglycerol, and the organic solvent is 1,2-propanediol.

3. The lyotropic liquid crystal long-acting injection for treating schizophrenia according to claim 2, characterized in that: The carilarazine has a mass-volume percentage of 4% (w / v).

4. The lyotropic liquid crystal long-acting injection for treating schizophrenia according to claim 3, characterized in that: The mass ratio of egg yolk phosphatidylcholine to dioleoyl glycerol is 1:0.5-2.

5. The lyotropic liquid crystal long-acting injection for treating schizophrenia according to claim 4, characterized in that: The mass-to-volume ratio of the 1,2-propanediol is 25% (w / v).

6. A method for preparing a long-acting lyotropic liquid crystal injection for treating schizophrenia as described in any one of claims 1-5, characterized in that: The specific steps are as follows: The antipsychotic drug cariprazine is mixed with ethyl acetate and hydrochloric acid gas to form hydrochloride. The hydrochloride of the antipsychotic drug is ground into nanoparticles by wet milling. Then, it is mixed with an amphiphilic compound and an organic solvent in a water bath using a rotor stirring to obtain the final product.

7. The preparation method according to claim 6, characterized in that: The solvent used in the wet milling process is 1,2-propanediol, the milling speed is 400 rpm, and the milling time is 6 h.

8. The preparation method according to claim 6, characterized in that: The water bath temperature was 35 °C, the stirring speed was 60 rpm, and the stirring time was 2 h.

9. The use of a lyotropic liquid crystal long-acting injection for treating or preventing schizophrenia as described in any one of claims 1-5 in the preparation of a medicament for treating or preventing schizophrenia, characterized in that: The schizophrenia mentioned refers to one or more of the following: positive schizophrenia, negative schizophrenia, and relapsed schizophrenia.

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