Carprofen liposome and a preparation method thereof

Abstract

The application provides carprofen liposomes and a preparation method thereof, and the preparation method comprises the following steps: (1) dissolving phospholipid, cholesterol, carprofen and an antioxidant in a complex solvent, removing the complex solvent to obtain a mixture; and (2) dispersing and homogenizing the mixture in a sucrose aqueous solution to obtain the carprofen liposomes. The liposomes are used as the drug carrier of carprofen, the solubility of carprofen in water is effectively enhanced, the effective residence time of the drug at a lesion site is prolonged, the treatment effect of carprofen is improved, and the liposomes have high biocompatibility and biodegradability, and the safety of the drug is improved.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical chemistry technology, specifically relating to a carbofen liposome and its preparation method. Background Technology

[0002] Carbofen is a highly effective nonsteroidal anti-inflammatory drug (NSAID) for animals, developed by Pfizer in the 1970s. In veterinary clinical practice, it is mainly used to treat postoperative pain and inflammation in dogs and cats, and can effectively control pain caused by osteoarthritis in dogs. Extensive research data shows that carbofen is rapidly and completely absorbed, reaching peak plasma concentration in 0.5-1 hour, with a plasma half-life of approximately 12 hours. Most of it is metabolized into β-glucuronide and excreted in the urine. Its gastrointestinal effects and nephrotoxicity are far less than other NSAIDs, and it has been identified as a relatively safe veterinary anti-inflammatory and analgesic. However, carbofen has extremely low solubility in water, making it difficult to prepare aqueous injections, which causes inconvenience during administration and limits its therapeutic effect.

[0003] CN116270556A discloses a method for preparing a veterinary carbofen transdermal agent. The method involves heating a solvent to a certain temperature, adding a prescribed amount of carbofen to dissolve it, then adding a transdermal agent and mixing thoroughly. Purified water is added to bring the volume to near full, and after adjusting the pH with an acid-base adjuster, purified water is added to bring the volume to full, thus obtaining the carbofen transdermal agent. Using the solvent as a medium and combining it with a transdermal penetration enhancer gives carbofen high transdermal permeability, allowing it to be administered through the skin to achieve antipyretic, analgesic, anti-inflammatory, and antipyretic effects. Modification of the transdermal penetration enhancer laurocapram further improves its enhancing activity and reduces irritation, thus enhancing the therapeutic effect and mildness of the transdermal agent.

[0004] CN115919846A discloses a carbofen inclusion complex, its preparation method, and its application. The inclusion complex comprises an inclusion agent and carbofen encapsulated within the inclusion agent; the mass ratio of the inclusion agent to carbofen is (4-6):(1-3). The inclusion agent includes any one of α-cyclodextrin, β-cyclodextrin, or hydroxypropylcyclodextrin. Compared with existing technologies, this carbofen inclusion complex improves the water solubility of carbofen, facilitating animal administration. The inclusion agent and organic solvent synergistically enhance the efficacy of carbofen, achieving a high inclusion rate and effectively overcoming the technical bottleneck of carbofen's insolubility in water. Furthermore, the use of spray drying avoids heating and cooling processes, reducing drug efficacy loss and material loss, while simplifying the production process and facilitating industrial production applications.

[0005] In the existing technology, most of the processes for encapsulating carbofen have too high technical requirements, cannot effectively encapsulate carbofen, and are prone to adverse reactions.

[0006] Liposomes, as drug carriers, can encapsulate various types of drugs, including both hydrophobic and hydrophilic ones, through their hydrophobic layer and hydrophilic core, thereby improving drug solubility. Furthermore, the structure of liposomes is remarkably similar to that of cell membranes, giving them high biocompatibility and biodegradability. Therefore, liposomes can protect drugs from enzymatic degradation before reaching the lesion site. Simultaneously, the physical encapsulation of drugs within the liposome enhances drug stability, reduces toxicity, increases dosage, and achieves better therapeutic effects. In addition, the bilayer surface formed by amphiphilic phospholipids can be structurally modified with ligands or other functional groups through physical or chemical means, giving liposomes tissue targeting capabilities, prolonging their effective retention time at the lesion site, and even enabling highly efficient targeted drug delivery. Liposomes are an ideal drug carrier for enhancing drug solubility in water, improving efficacy, and increasing drug safety.

[0007] Therefore, developing a carbofen liposome with good encapsulation efficiency and drug loading capacity can effectively improve the water solubility of carbofen and thus enhance its efficacy, which is a key research focus in this field. Summary of the Invention

[0008] In view of the shortcomings of the prior art, the purpose of this invention is to provide a carbofen liposome and its preparation method, which has good encapsulation efficiency and drug loading, and effectively improves the water solubility of carbofen.

[0009] To achieve this objective, the present invention adopts the following technical solution:

[0010] In a first aspect, the present invention provides a method for preparing carbofen liposomes, the method comprising the following steps:

[0011] (1) Dissolve phospholipids, cholesterol, carbofenone and antioxidants in a composite solvent, remove the composite solvent, and obtain a mixture;

[0012] (2) The mixture is dissolved in a sucrose aqueous solution for dispersion and homogenization to obtain the carbofen liposome.

[0013] This invention utilizes liposomes as a drug carrier for carboprofen, which effectively enhances the solubility of carboprofen in water, prolongs the effective retention time of the drug at the lesion site, and improves the therapeutic effect of carboprofen. Furthermore, liposomes possess high biocompatibility and biodegradability, increasing drug safety. This invention incorporates antioxidants into the raw materials to effectively prevent oxidative deterioration of the raw material components within the liposomes. This invention uses sucrose solution as a lyophilization protectant to prevent damage to the morphology and stability of the liposomes during the lyophilization process.

[0014] Preferably, the phospholipid comprises any one or a combination of two of the following: hydrogenated phosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearate phosphatidylcholine, dioleoyl phosphatidylcholine, 1,2-tetradecanoyl phosphatidylethanolamine, dioleoyl phosphatidylethanolamine, or lecithin.

[0015] Preferably, the phospholipid is distearate phosphatidylcholine.

[0016] Preferably, the mass ratio of phospholipid to cholesterol is (1.5-2.5):1, for example, it can be 1.6:1, 1.8:1, 2:1, 2.2:1, 2.4:1, etc.

[0017] Preferably, the total amount of phospholipids and cholesterol is in a mass ratio of carbofen to (10-20):1, for example, 12:1, 14:1, 16:1, 18:1, etc.

[0018] Preferably, the antioxidant is vitamin E.

[0019] Preferably, the composite solvent includes methanol and chloroform.

[0020] Preferably, the volume ratio of methanol to chloroform is (0.8-1.2):1, for example, it can be 0.9:1, 1:1, 1.1:1, etc.

[0021] Preferably, the sucrose content in the sucrose aqueous solution is 10-20% by mass, for example, it can be 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, etc.

[0022] Preferably, the dispersion is performed using ultrasound.

[0023] Preferably, the power of the ultrasound is 200-400 W, for example, 250 W, 300 W, 350 W, etc., and the duration is 8-12 min, for example, 9 min, 10 min, 11 min, etc.

[0024] Preferably, the homogenization is performed using a microjet high-pressure homogenizer.

[0025] Preferably, the homogeneous pressure coefficient is 15,000-20,000 psi, for example, it can be 16,000 psi, 17,000 psi, 18,000 psi, 19,000 psi, etc.

[0026] Preferably, the homogenization process is repeated 2-3 times.

[0027] Preferably, the preparation method includes the following steps:

[0028] (1) Dissolve phospholipids, cholesterol, carbofenone and vitamin E in a composite solvent, which is a mixture of methanol and chloroform in a volume ratio of (0.8-1.2):1. Remove the composite solvent to obtain a mixture.

[0029] The phospholipids include any one or a combination of two of the following: hydrogenated phosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearyl phosphatidylcholine, dioleoyl phosphatidylcholine, 1,2-tetradecanoyl phosphatidylethanolamine, dioleoyl phosphatidylethanolamine, or lecithin, preferably distearyl phosphatidylcholine;

[0030] The mass ratio of phospholipids to cholesterol is (1.5-2.5):1;

[0031] The total amount of phospholipids and cholesterol is in a mass ratio of (10-20):1 to carbofen.

[0032] (2) Dissolve the mixture in a sucrose aqueous solution with a sucrose content of 12-16% by mass and disperse it by ultrasonication at 200-400 W for 8-12 min. Then homogenize it using a microfluidic high pressure homogenizer at a pressure coefficient of 15000-20000 psi. Repeat the homogenization 2-3 times to obtain the carbofen liposome.

[0033] In a second aspect, the present invention provides a carbofen liposome, which is prepared by the preparation method described in the first aspect;

[0034] Preferably, the encapsulation efficiency of the carbofen liposomes is 66.7-73.5%, for example, it can be 67%, 68%, 69%, 71%, 73%, etc.

[0035] Preferably, the drug loading of the carbofen liposome is 4.2-4.6%, for example, 4.3%, 4.4%, 4.5%, etc.

[0036] The numerical range described in this invention includes not only the point values ​​listed above, but also any point values ​​within the numerical ranges not listed above. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific point values ​​included in the range.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] This invention utilizes liposomes as a drug carrier for carboprofen, which effectively enhances the solubility of carboprofen in water, prolongs the effective retention time of the drug at the lesion site, and improves the therapeutic effect of carboprofen. Furthermore, liposomes possess high biocompatibility and biodegradability, increasing drug safety. This invention incorporates antioxidants into the raw materials to effectively prevent oxidative deterioration of the raw material components within the liposomes. This invention uses sucrose solution as a lyophilization protectant to prevent damage to the morphology and stability of the liposomes during the lyophilization process. Attached Figure Description

[0039] Figure 1 Transmission electron microscopy image of carbofen liposomes prepared in Example 1;

[0040] Figure 2 The particle size distribution diagram of carbofen liposomes prepared in Example 1;

[0041] Figure 3 The potential diagram is of the carbofen liposomes prepared in Example 1. Detailed Implementation

[0042] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0043] The terms “comprising,” “including,” “having,” “containing,” or any other variations thereof, as used herein, are intended to cover non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that includes the listed elements is not limited to those elements and may also include other elements not expressly listed or elements inherent to such composition, step, method, article, or apparatus.

[0044] "Optional" or "any one" means that the matter or event described thereafter may or may not occur, and the description includes both the possibility that the event will occur and the possibility that the event will not occur.

[0045] The indefinite articles “a” and “an” preceding an element or component of this invention do not impose any limitation on the quantity (i.e., number of occurrences) of the element or component. Therefore, “an” or “a” should be interpreted as including one or at least one, and the singular form of an element or component also includes the plural form, unless the quantity clearly refers only to the singular form.

[0046] The terms "one embodiment," "some embodiments," "exemplary," "specific example," or "some examples," etc., used in this invention refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the invention. In this document, the illustrative expressions of the above terms are not necessarily directed at the same embodiment or example.

[0047] The reagents or instruments used in the following examples are from the following sources:

[0048] Carbofen: McLean C830557;

[0049] Distearate phosphatidylcholine: Sigma 850365;

[0050] Cholesterol: Sigma C8667.

[0051] Example 1

[0052] This embodiment provides a carbofenoxate liposome, which is prepared by the following method:

[0053] (1) Weigh 10 mg distearate, 5 mg cholesterol, 1 mg carbofen and 0.25 mg vitamin E and dissolve them in 4 mL of methanol and chloroform composite solvent (1:1, v / v) to obtain a mixed solution. Transfer the solution to a 50 mL round bottom flask and evaporate the composite solvent by rotary evaporation at 37 °C and a rotation speed of 100 r / min to obtain a solid mixture.

[0054] (2) Dissolve 0.5 mg of sucrose in 3 mL of deionized water and add it to the round-bottom flask of step (1). Incubate the mixture with the solid mixture in a water bath at 60°C for 25 min, and then sonicate at room temperature at 300 W for 10 min to obtain a liposome dispersion.

[0055] (3) The liposome dispersion was homogenized three times at a pressure coefficient of 18000 psi using a micro-jet high-pressure homogenizer (NanoGenizer30K). The dispersion changed from turbid to clear, and carbofenoxan liposomes with uniform particle size were obtained.

[0056] Example 2

[0057] This embodiment provides a carbofenoxate liposome, which is prepared by the following method:

[0058] (1) Weigh 9 mg distearate, 6 mg cholesterol, 0.8 mg carbofen and 0.3 mg vitamin E and dissolve them in 5 mL of methanol and chloroform composite solvent (1:1.2, v / v) to obtain a mixed solution. Transfer the solution to a 50 mL round bottom flask and evaporate the composite solvent by rotary evaporation at 37 °C and a rotation speed of 100 r / min to obtain a solid mixture.

[0059] (2) Dissolve 0.4 mg of sucrose in 2.5 mL of deionized water and add it to the round-bottom flask of step (1). Incubate the mixture with the solid mixture in a water bath at 60°C for 25 min, and then sonicate at room temperature for 12 min at 200 W power to obtain a liposome dispersion.

[0060] (3) The liposome dispersion was homogenized four times at a pressure coefficient of 15000 psi using a microjet high-pressure homogenizer (NanoGenizer30K). The dispersion changed from turbid to clear, and carbofenoxan liposomes with uniform particle size were obtained.

[0061] Example 3

[0062] This embodiment provides a carbofenoxate liposome, which is prepared by the following method:

[0063] (1) Weigh 10 mg distearate, 4 mg cholesterol, 1.2 mg carbofen and 0.25 mg vitamin E and dissolve them in 6 mL of methanol and chloroform composite solvent (1.2:1, v / v) to obtain a mixed solution. Transfer the solution to a 50 mL round bottom flask and evaporate the composite solvent by rotary evaporation at 37 °C and a rotation speed of 100 r / min to obtain a solid mixture.

[0064] (2) Dissolve 0.7 mg of sucrose in 3 mL of deionized water and add it to the round-bottom flask of step (1). Incubate the mixture with the solid mixture in a water bath at 60°C for 25 min, and then sonicate at room temperature at 400 W for 8 min to obtain a liposome dispersion.

[0065] (3) The liposome dispersion was homogenized three times at a pressure coefficient of 20,000 psi using a microjet high-pressure homogenizer (NanoGenizer30K). The dispersion changed from turbid to clear, and carbofenoxan liposomes with uniform particle size were obtained.

[0066] Example 4

[0067] This embodiment provides a carbofen liposome, which differs from Example 1 only in that distearylphosphatidylcholine is replaced with an equal amount of hydrogenated phosphatidylcholine; other raw materials, dosages and preparation methods are the same as in Example 1.

[0068] Example 5

[0069] This embodiment provides a carbofen liposome, which differs from Example 1 only in that the distearate phosphatidylcholine is adjusted to 8 mg and the cholesterol is adjusted to 7 mg; the other raw materials, dosages and preparation methods are the same as in Example 1.

[0070] Example 6

[0071] This embodiment provides a carbofen liposome, which differs from Example 1 only in that the distearate phosphatidylcholine is adjusted to 11 mg and the cholesterol is adjusted to 4 mg; the other raw materials, dosages and preparation methods are the same as in Example 1.

[0072] Example 7

[0073] This embodiment provides a carbofen liposome, which differs from Example 1 only in that the methanol and chloroform composite solvent is replaced with an equal amount of methanol; the other raw materials, amounts and preparation methods are the same as in Example 1.

[0074] Example 8

[0075] This embodiment provides a carbofen liposome, which differs from Example 1 only in that the methanol and chloroform composite solvent is replaced with an equal amount of chloroform; the other raw materials, amounts and preparation methods are the same as in Example 1.

[0076] Example 9

[0077] This embodiment provides a carbofen liposome, which differs from Example 1 only in that the carbofen is adjusted to 1.8 mg; the other raw materials, dosages and preparation methods are the same as in Example 1.

[0078] Example 10

[0079] This embodiment provides a carbofen liposome, which differs from Example 1 only in that the carbofen is adjusted to 0.5 mg; the other raw materials, dosages and preparation methods are the same as in Example 1.

[0080] Comparative Example 1

[0081] This comparative example provides a carbofen liposome, which differs from Example 1 only in that vitamin E is not added; all other raw materials, amounts, and preparation methods are the same as in Example 1.

[0082] Comparative Example 2

[0083] This comparative example provides a carbofenoxan liposome, which differs from Example 1 only in that sucrose is replaced with an equal amount of glucose; all other raw materials, amounts, and preparation methods are the same as in Example 1.

[0084] Comparative Example 3

[0085] This comparative example provides a carbofen liposome, which differs from Example 1 only in step (2). Step (2) of this comparative example is as follows:

[0086] Dissolve 0.5 mg of sucrose in 3 mL of deionized water and add it to the round-bottom flask of step (1). Incubate the mixture with the solid mixture in a water bath at 60°C for 25 min to obtain a liposome dispersion. Other raw materials, dosages and preparation methods are the same as in Example 1.

[0087] Test Example 1

[0088] The carbofen liposomes prepared in the examples and comparative examples were tested using transmission electron microscopy. For example, the transmission electron microscopy image of the carbofen liposomes prepared in Example 1 is shown below. Figure 1 As shown, by Figure 1 It can be seen that carbofen liposomes are evenly distributed, uniform in size, and are all single-chambered liposomes, with carbofen encapsulated in a lipid bilayer.

[0089] The particle sizes in the obtained electron micrographs were statistically analyzed to obtain the average particle size of each carbofen liposome sample. The results are shown in Table 1. For example, the particle size distribution of the carbofen liposomes prepared in Example 1 is shown in Table 1. Figure 2 As shown.

[0090] The dispersibility of carbofen liposomes prepared in the examples and comparative examples was tested, and the dispersibility index (PDI) results are shown in Table 1.

[0091] Potentiometric tests were performed on the carbofenoxine liposomes prepared in the examples and comparative examples. For example, the potential diagram of the carbofenoxine liposomes prepared in Example 1 is shown below. Figure 3 As shown.

[0092] Table 1

[0093]

[0094] According to the table data, the carbofen liposomes prepared using the technical solution provided by this invention in Examples 1-3 are uniform in size, small in particle size, and have good dispersibility. As shown in Examples 1 and 4, when phospholipids are replaced with other common types, the dispersibility is poor. As shown in Examples 1 and 5-6, the best effect is achieved when the ratio of phospholipids to cholesterol is (8-12):(4-6). When the proportion of cholesterol is too high, it will increase the particle size of the liposomes and at the same time, the dispersibility will be poor. When the proportion of phospholipids is too high, it will cause the product to have a larger particle size and poor dispersibility. As shown in Examples 1 and 7-8, the best results were achieved when the composite solvent was methanol and chloroform. When methanol was used as the solvent alone, the particle size was not uniform and the average particle size increased significantly. When chloroform was used as the solvent alone, the dispersibility was poor. As shown in Examples 1 and Comparative Example 1, the absence of the antioxidant vitamin E slightly affected the particle size. As shown in Examples 1 and Comparative Example 2, replacing sucrose with glucose slightly affected the particle size. As shown in Examples 1 and Comparative Example 3, homogenization without prior dispersion resulted in larger particle sizes, agglomeration, and poor dispersibility.

[0095] Test Example 2

[0096] Carbofen liposome encapsulation efficiency and drug loading assay

[0097] Detection was performed using ultra-high performance liquid chromatography-tandem mass spectrometry:

[0098] (1) Analytical methods: A Waters ACQUITY UPLC® HSS T3 column (100 × 2.1 mm, 1.8 μm) was used; mobile phase A was formic acid:water (0.001:1, v / v), and mobile phase B was formic acid:acetonitrile (0.001:1, v / v). The flow rate was 0.3 ml·min. -1 The column temperature is set to 40℃.

[0099] Ultra-high performance liquid chromatography elution program:

[0100]

[0101] Mass spectrometry parameters: negative ion mode (ESI) was used. + The quantitative ion pair is 274 > 228 m / z, the qualitative ion pair is 274 > 88 m / z, and the collision energy is 30 V.

[0102] (2) Sample pretreatment: Take 1 mL of carbofen liposome solution, add 4 mL of acetonitrile, shake for 10 min, centrifuge at 8000 rpm for 15 min, take 1 mL of supernatant for detection by ultra-high performance liquid chromatography-tandem mass spectrometry, and calculate the mass of carbofen loaded into liposomes.

[0103] The encapsulation ratio formula is:

[0104] Encapsulation efficiency (%) = (mass of encapsulated carbofen / initial mass of carbofen) × 100%;

[0105] The formula for drug loading is:

[0106] Drug loading (%) = (mass of carbofenol encapsulated / total mass of initial input materials) × 100%; the test results are shown in Table 2.

[0107] Table 2

[0108]

[0109] According to the table data, the carbofen liposomes prepared using the technical solution provided by this invention in Examples 1-3 have higher encapsulation efficiency and higher drug loading. Examples 1 and 4 show that when phospholipids are replaced with other common types, the drug loading significantly decreases. Examples 1 and 5-6 show that the optimal effect is achieved when the ratio of phospholipids to cholesterol is (8-12):(4-6). Excessive cholesterol ratio reduces both encapsulation efficiency and drug loading, as does excessive phospholipid ratio. As shown in Examples 1 and 7-8, the best results are achieved when the composite solvent is methanol and chloroform. Using methanol as a single solvent reduces the encapsulation efficiency, while using chloroform as a single solvent results in less drug encapsulation. As shown in Examples 1 and 1, the encapsulation efficiency is reduced when the antioxidant vitamin E is not added. As shown in Examples 1 and 2, the encapsulation efficiency is reduced when sucrose is replaced with glucose. As shown in Examples 1 and 3, agglomeration occurs when homogenization is performed directly without dispersion, thereby reducing drug loading and encapsulation efficiency.

[0110] The applicant declares that the present invention is illustrated by the above embodiments, but the present invention is not limited to the above process steps, that is, it does not mean that the present invention must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials used in the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing carbofen liposomes, characterized in that, The preparation method includes the following steps: (1) Dissolve phospholipids, cholesterol, carbofenone and antioxidants in a composite solvent, remove the composite solvent, and obtain a mixture; (2) The mixture is dissolved in a sucrose aqueous solution for dispersion and homogenization to obtain the carbofen liposomes; The phospholipid is distearate phosphatidylcholine; The mass ratio of phospholipids to cholesterol is (1.5-2.5):1; The total amount of phospholipids and cholesterol is in a mass ratio of (10-20):1 to carbofen. The antioxidant is vitamin E; The composite solvent includes methanol and chloroform.

2. The preparation method according to claim 1, characterized in that, The volume ratio of methanol to chloroform is (0.8-1.2):

1.

3. The preparation method according to claim 1, characterized in that, The sucrose aqueous solution contains 10-20% sucrose by mass.

4. The preparation method according to claim 1, characterized in that, The dispersion is performed using ultrasound.

5. The preparation method according to claim 4, characterized in that, The ultrasound power is 200-400 W, and the duration is 8-12 min.

6. The preparation method according to claim 1, characterized in that, The homogenization was performed using a microjet high-pressure homogenizer.

7. The preparation method according to claim 6, characterized in that, The pressure coefficient of the homogeneous material is 15,000-20,000 psi.

8. The preparation method according to claim 1, characterized in that, The homogenization process was repeated 2-3 times.

9. The preparation method according to claim 1, characterized in that, The preparation method includes the following steps: (1) Dissolve phospholipids, cholesterol, carbofenone and vitamin E in a composite solvent, which is a mixture of methanol and chloroform in a volume ratio of (0.8-1.2):

1. Remove the composite solvent to obtain a mixture. The phospholipid is distearate phosphatidylcholine; The mass ratio of phospholipids to cholesterol is (1.5-2.5):1; The total amount of phospholipids and cholesterol is in a mass ratio of (10-20):1 to carbofen. (2) Dissolve the mixture in a sucrose aqueous solution with a sucrose content of 12-16% by mass and disperse it by ultrasonication at 200-400 W for 8-12 min. Then homogenize it using a microfluidic high pressure homogenizer at a pressure coefficient of 15000-20000 psi. Repeat the homogenization 2-3 times to obtain the carbofen liposome.

10. A carboprofen liposome, characterized in that, The carbofen liposomes were prepared using the preparation method described in any one of claims 1-9.

11. The carboprofen liposome according to claim 10, characterized in that, The encapsulation efficiency of the carbofen liposomes was 66.7-73.5%.

12. The carbofen liposome according to claim 10, characterized in that, The drug loading of the carbofen liposomes is 4.2-4.6%.

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