A method for preparing lidocaine-containing polycaprolactone microsphere injection

Abstract

The application provides a preparation method of lidocaine-containing polycaprolactone microsphere injection, and belongs to the technical field of facial filler preparation; the preparation process comprises the following steps: preparing modified gelatin hydrogel; preparing sustained-release antibacterial gel; preparing polycaprolactone microspheres; and preparing polycaprolactone microsphere injection. According to the application, lidocaine is added into the polycaprolactone microspheres, so that the lidocaine plays a role of anesthesia after people inject the polycaprolactone microsphere injection; the lidocaine can inhibit the generation and conduction of nerve impulses, leads to loss of sensation or numbness, and realizes the effect of local anesthesia, so that the pain of the patient can be relieved without additional use of anesthetics.

Description

Technical Field

[0001] The present invention relates to the technical field of facial filler preparation, and in particular to a method for preparing a lidocaine-containing polycaprolactone microsphere injection. Background Art

[0002] As people's living standards improve, they pay more and more attention to the pursuit of external beauty. Various cosmetic surgeries are widely adopted by people. The skin will naturally relax and form wrinkles, especially the aging of facial contours will become increasingly serious, including visible skin wrinkles, deep nasolabial folds, frown lines, marionette lines, cheek junction lines, wrinkles around the mouth, temporal collapse, etc. Similarly, the collapse of the nose bridge caused by congenital or traumatic factors and the misalignment of the brow bone and mandible have brought troubles and pain to people. Beauty is an eternal topic and goal pursued by mankind. How to effectively delay skin aging and beautify the face is still a problem that people continue to explore and solve.

[0003] Currently, injectable cosmetic products are still primarily imported. Additionally, filler injection materials are primarily categorized as degradable and non-degradable. Degradable materials are typically polymers such as hyaluronic acid, collagen, poly(L-lactic acid), and hydroxyapatite. Currently, dermal fillers have evolved to the third generation of synthetic polymer fillers, such as polylactic acid (PLA) or polycaprolactone (PCL). Because they decompose very slowly in the human body, third-generation fillers have a longer duration than first-generation collagen and second-generation hyaluronic acid fillers.

[0004] After the injection, some patients may experience a certain degree of pain or discomfort due to different physical conditions. This is because the needle piercing the skin during the injection process causes local trauma, and the injected substance may cause a certain degree of inflammation and swelling in the early stage.

[0005] Therefore, we propose a method for preparing a polycaprolactone microsphere injection containing lidocaine that can relieve pain and discomfort during filling injection. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the object of the present invention is to provide a method for preparing polycaprolactone microsphere injection containing lidocaine.

[0007] A method for preparing a lidocaine-containing polycaprolactone microsphere injection comprises the following steps:

[0008] S1: Preparation of modified gelatin hydrogel;

[0009] S2: Preparation of sustained-release antibacterial gel;

[0010] S3: Preparation of polycaprolactone microspheres;

[0011] S4: Preparation of polycaprolactone microsphere injection.

[0012] Furthermore, step S1 of preparing the modified gelatin hydrogel specifically comprises the following steps:

[0013] S1.1: Dissolve 5-6 parts by weight of type A gelatin in 50-60 parts by weight of phosphate buffer and stir magnetically at 45-50°C for 5-8 hours to obtain a clear solution.

[0014] S1.2: Add 3-4 parts by weight of methacrylic anhydride dropwise to the above clear solution. After 3-4 hours, dilute the solution to obtain a diluted solution.

[0015] S1.3: The diluted solution was placed in a dialysis bag to retain the modified molecule with a weight-average molecular weight Mw = 12,000, and dialyzed in an oven at 60-65°C for 6-7 days. After the dialysis, the solution was freeze-dried to obtain a modified gelatin hydrogel.

[0016] Furthermore, step S2 is to prepare a sustained-release antibacterial gel, which specifically comprises the following steps:

[0017] S2.1: Dissolve 40-50 parts by weight of glucose powder in water for injection to a 50 wt% solution, add 30-40 parts by weight of activated carbon, boil for 10-15 minutes, and cool to obtain a glucose solution.

[0018] S2.2: Add 2-3 parts by weight of tinidazole to the glucose solution, stir until the tinidazole is completely dissolved, let stand for 10-15 minutes, remove carbon, adjust the pH, fine filter, and sterilize with wet heat at 115-120°C for 20-30 minutes to obtain a tinidazole antibacterial solution;

[0019] S2.3: Place 10-20 parts by weight of modified gelatin hydrogel in 20-30 parts by weight of tinidazole antibacterial solution, soak at room temperature for 2-3 hours for drug loading, and obtain a sustained-release antibacterial gel.

[0020] Furthermore, step S3 of preparing polycaprolactone microspheres specifically comprises the following steps:

[0021] S3.1: Dissolve 1-2 parts by weight of polycaprolactone in dichloromethane to prepare a first solution with a concentration of 10-12 w / w%. Add the prescribed amount of lidocaine hydrochloride to 25-45% of the total volume of purified water and stir to completely dissolve it to obtain a second solution.

[0022] S3.2: The first solution and the second solution are then mixed to form a dispersed phase, and a 1-2 w / v% aqueous surfactant solution is prepared as the aqueous phase;

[0023] S3.3: Pre-saturate the aqueous phase with dichloromethane, then pour the dispersed phase into the aqueous phase and homogenize at high speed to obtain a microsphere suspension.

[0024] S3.4: Stir the above microsphere suspension at 25-30°C to remove the organic solvent, then repeatedly wash with water 2-3 times, and then dry to obtain polycaprolactone microspheres.

[0025] Furthermore, step S4 prepares polycaprolactone microsphere injection, which specifically includes the following steps:

[0026] S4.1: Gradually add sodium carboxymethyl cellulose powder to 50-55°C hot water with stirring. Once dissolved, sterilize with moist heat steam at 120-121°C for 25-30 minutes. Cool to produce a 9-10% carboxymethyl cellulose hydrogel.

[0027] S4.2: Mixing 3-4 parts by weight of polycaprolactone microspheres, 2-3 parts by weight of sustained-release antibacterial gel, and 6-7 parts by weight of carboxymethyl cellulose hydrogel to obtain a mixture;

[0028] S4.3: Add glycerol to the above mixture and mix well to evenly disperse the polycaprolactone microspheres. After sterilization, obtain the polycaprolactone microsphere injection.

[0029] Furthermore, in step S2.2, the pH value is adjusted to 4.5-4.6.

[0030] Furthermore, the surfactant in step S3.2 consists of polyvinyl alcohol and povidone K30 in a mass ratio of 8-9:2.

[0031] Furthermore, in step S3.3, the amount of dichloromethane added is 2-3% of the volume fraction of the aqueous phase.

[0032] Furthermore, in step S3.4, the stirring speed is 150-160 rpm, and the stirring time is 12-14 h.

[0033] Furthermore, in step S4.3, the weight content of glycerol in the mixture is 0.8-1%.

[0034] Compared with the prior art, the present invention has at least the following beneficial effects:

[0035] 1. The present invention adds lidocaine to polycaprolactone microspheres. When people inject the polycaprolactone microsphere injection, lidocaine has an anesthetic effect. Lidocaine can inhibit the generation and conduction of nerve impulses, causing loss of sensation or numbness, achieving the effect of local anesthesia, thereby alleviating the patient's pain without the need for additional anesthetics.

[0036] 2. The present invention achieves a sustained-release effect of lidocaine by encapsulating lidocaine in polycaprolactone microspheres, thereby prolonging the anesthesia time. At the same time, it can avoid serious adverse reactions caused by high-dose or rapid administration of lidocaine, such as toxicity to the central nervous system and cardiovascular system, which manifests as symptoms such as dizziness, tinnitus, nausea, hypotension, bradycardia, and even coma, thereby ensuring the safety of the polycaprolactone microsphere injection.

[0037] 3. The sustained-release antibacterial gel prepared by the modified gelatin hydrogel as a carrier in the present invention can make the polycaprolactone microsphere injection have a certain antibacterial effect, which can avoid people from causing inflammatory reactions in the early stage of filling the injection material. At the same time, the modified gelatin hydrogel is loaded with tinidazole, which can make tinidazole achieve a sustained-release effect, thereby realizing a longer-term antibacterial effect and avoiding people from getting infected after injecting the filling material.

[0038] 4. The present invention prepares a modified gelatin hydrogel by modifying gelatin, so that the modified gelatin hydrogel has a network-like porous structure, has properties similar to the extracellular matrix, is similar to the structure of the cell survival microenvironment, has good biocompatibility, can promote cell growth and tissue regeneration, and the network-like porous structure is convenient for loading tinidazole, thereby preparing a sustained-release antibacterial gel. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The accompanying drawings, which are incorporated herein and constitute a part of the specification, illustrate embodiments of the present disclosure and, together with the description, further serve to explain the principles of the present disclosure and to enable one skilled in the relevant art to make and use the present disclosure.

[0040] Figure 1 This is a flow chart of a method for preparing a lidocaine-containing polycaprolactone microsphere injection used in an embodiment of the present invention. DETAILED DESCRIPTION

[0041] The following describes in detail a method for preparing a lidocaine-containing polycaprolactone microsphere injection provided by the present invention, with reference to the accompanying drawings and specific examples. It is also noted that, for the sake of completeness, the following examples are best and preferred embodiments, and those skilled in the art may employ alternative methods for implementing known techniques. Furthermore, the accompanying drawings are provided solely for the purpose of describing the embodiments in greater detail and are not intended to limit the present invention.

[0042] Example 1

[0043] A method for preparing a polycaprolactone microsphere injection containing lidocaine, such as Figure 1 As shown, the following steps are included:

[0044] S1: Preparation of modified gelatin hydrogels

[0045] S1.1: Dissolve 5 parts by weight of type A gelatin in 50 parts by weight of phosphate buffer at 45°C with magnetic stirring for 5 h to obtain a clear solution.

[0046] S1.2: Add 3 parts by weight of methacrylic anhydride dropwise to the above clear solution. After 3 hours, dilute the solution to obtain a diluted solution.

[0047] S1.3: The diluted solution was placed in a dialysis bag to retain the modified molecule with a weight-average molecular weight (Mw) of 12,000. The solution was dialyzed in an oven at 60°C for 6 days. After dialysis, the solution was freeze-dried to obtain a modified gelatin hydrogel.

[0048] S2: Preparation of sustained-release antibacterial gel

[0049] S2.1: Dissolve 40 parts by weight of glucose powder in water for injection to a 50 wt% solution, add 30 parts by weight of activated carbon, boil for 10 minutes, and cool to obtain a glucose solution.

[0050] S2.2: Add 2 parts by weight of tinidazole to the glucose solution, stir until the tinidazole is completely dissolved, let stand for 10 minutes, remove carbon, adjust the pH to 4.5, fine filter, and sterilize with wet heat at 115°C for 20 minutes to obtain a tinidazole antibacterial solution;

[0051] S2.3: 10 parts by weight of the modified gelatin hydrogel was placed in 20 parts by weight of a tinidazole antibacterial solution and soaked at room temperature for 2 hours for drug loading to obtain a sustained-release antibacterial gel;

[0052] S3: Preparation of polycaprolactone microspheres

[0053] S3.1: Dissolve 1 part by weight of polycaprolactone in dichloromethane to prepare a first solution with a concentration of 10 w / w%. Add the prescribed amount of lidocaine hydrochloride to 25% of the total volume of purified water and stir until completely dissolved to obtain a second solution.

[0054] S3.2: The first solution and the second solution are then mixed to form a dispersed phase, and a 1 w / v% aqueous surfactant solution is prepared as the aqueous phase, wherein the surfactant is composed of polyvinyl alcohol and povidone K30 in a mass ratio of 4:1;

[0055] S3.3: Pre-saturate the aqueous phase with 2% by volume of dichloromethane, then pour the dispersed phase into the aqueous phase and homogenize at high speed to produce a microsphere suspension.

[0056] S3.4: Stir the microsphere suspension at 150 rpm at 25°C for 12 h to remove the organic solvent, then wash the suspension with water twice and dry it to obtain polycaprolactone microspheres.

[0057] S4: Preparation of polycaprolactone microsphere injection

[0058] S4.1: Gradually add sodium carboxymethyl cellulose powder to 50°C hot water with stirring. Once dissolved, sterilize with moist heat steam at 120°C for 25 minutes. Cool to produce a 9% carboxymethyl cellulose hydrogel.

[0059] S4.2: Mix 3 parts by weight of polycaprolactone microspheres, 2 parts by weight of sustained-release antibacterial gel, and 6 parts by weight of carboxymethyl cellulose hydrogel to obtain a mixture;

[0060] S4.3: Add glycerol to the above mixture, the weight content of glycerol in the mixture is 0.8%, mix evenly to evenly disperse the polycaprolactone microspheres, and obtain polycaprolactone microsphere injection after sterilization.

[0061] Example 2

[0062] A method for preparing a polycaprolactone microsphere injection containing lidocaine, such as Figure 1 As shown, the following steps are included:

[0063] S1: Preparation of modified gelatin hydrogels

[0064] S1.1: Dissolve 6 parts by weight of type A gelatin in 60 parts by weight of phosphate buffer solution at 45°C with magnetic stirring for 5 h to obtain a clear solution;

[0065] S1.2: Add 4 parts by weight of methacrylic anhydride dropwise to the above clear solution. After 3 hours, dilute the solution to obtain a diluted solution.

[0066] S1.3: The diluted solution was placed in a dialysis bag to retain the modified molecule with a weight-average molecular weight (Mw) of 12,000. The solution was dialyzed in an oven at 60°C for 6 days. After dialysis, the solution was freeze-dried to obtain a modified gelatin hydrogel.

[0067] S2: Preparation of sustained-release antibacterial gel

[0068] S2.1: Dissolve 50 parts by weight of glucose powder in water for injection to a 50 wt% solution, add 40 parts by weight of activated carbon, boil for 10 minutes, and cool to obtain a glucose solution.

[0069] S2.2: Add 3 parts by weight of tinidazole to the glucose solution, stir until the tinidazole is completely dissolved, let stand for 10 minutes, remove carbon, adjust the pH to 4.5, fine filter, and sterilize with wet heat at 115°C for 20 minutes to obtain a tinidazole antibacterial solution;

[0070] S2.3: 20 parts by weight of the modified gelatin hydrogel was placed in 30 parts by weight of a tinidazole antibacterial solution and soaked at room temperature for 2 hours for drug loading to obtain a sustained-release antibacterial gel;

[0071] S3: Preparation of polycaprolactone microspheres

[0072] S3.1: Dissolve 2 parts by weight of polycaprolactone in dichloromethane to prepare a first solution with a concentration of 12 w / w%. Add the prescribed amount of lidocaine hydrochloride to 45% of the total volume of purified water and stir until completely dissolved to obtain a second solution.

[0073] S3.2: The first solution and the second solution are then mixed to form a dispersed phase, and a 2 w / v% aqueous surfactant solution is prepared as the aqueous phase, wherein the surfactant is composed of polyvinyl alcohol and povidone K30 in a mass ratio of 9:2;

[0074] S3.3: Pre-saturate the aqueous phase with 3% by volume of dichloromethane, then pour the dispersed phase into the aqueous phase and homogenize at high speed to produce a microsphere suspension.

[0075] S3.4: Stir the microsphere suspension at 150 rpm at 25°C for 12 h to remove the organic solvent, then wash the suspension with water twice and dry it to obtain polycaprolactone microspheres.

[0076] S4: Preparation of polycaprolactone microsphere injection

[0077] S4.1: Gradually add sodium carboxymethyl cellulose powder to 50°C hot water with stirring. Once dissolved, sterilize with moist heat steam at 120°C for 25 minutes. Cool to produce a 10% carboxymethyl cellulose hydrogel.

[0078] S4.2: Mix 4 parts by weight of polycaprolactone microspheres, 3 parts by weight of sustained-release antibacterial gel, and 7 parts by weight of carboxymethyl cellulose hydrogel to obtain a mixture;

[0079] S4.3: Add glycerol to the above mixture, the weight content of glycerol in the mixture is 1%, mix evenly to evenly disperse the polycaprolactone microspheres, and obtain polycaprolactone microsphere injection after sterilization.

[0080] Example 3

[0081] A method for preparing a polycaprolactone microsphere injection containing lidocaine, such as Figure 1 As shown, the following steps are included:

[0082] S1: Preparation of modified gelatin hydrogels

[0083] S1.1: Dissolve 5 parts by weight of type A gelatin in 50 parts by weight of phosphate buffer solution at 50°C with magnetic stirring for 8 h to obtain a clear solution;

[0084] S1.2: Add 3 parts by weight of methacrylic anhydride dropwise to the above clear solution. After 4 hours, dilute the solution to obtain a diluted solution.

[0085] S1.3: The diluted solution was placed in a dialysis bag to retain the modified molecule with a weight-average molecular weight (Mw) of 12,000. The solution was dialyzed in an oven at 65°C for 7 days. After dialysis, the solution was freeze-dried to obtain a modified gelatin hydrogel.

[0086] S2: Preparation of sustained-release antibacterial gel

[0087] S2.1: Dissolve 40 parts by weight of glucose powder in water for injection to a 50 wt% solution, add 30 parts by weight of activated carbon, boil for 15 minutes, and cool to obtain a glucose solution.

[0088] S2.2: Add 2 parts by weight of tinidazole to the glucose solution, stir until the tinidazole is completely dissolved, let stand for 15 minutes, remove carbon, adjust the pH to 4.5, fine filter, and sterilize with wet heat at 120°C for 30 minutes to obtain a tinidazole antibacterial solution;

[0089] S2.3: 10 parts by weight of the modified gelatin hydrogel was placed in 20 parts by weight of a tinidazole antibacterial solution and soaked at room temperature for 3 hours for drug loading to obtain a sustained-release antibacterial gel;

[0090] S3: Preparation of polycaprolactone microspheres

[0091] S3.1: Dissolve 1 part by weight of polycaprolactone in dichloromethane to prepare a first solution with a concentration of 10 w / w%. Add the prescribed amount of lidocaine hydrochloride to 25% of the total volume of purified water and stir until completely dissolved to obtain a second solution.

[0092] S3.2: The first solution and the second solution are then mixed to form a dispersed phase, and a 1 w / v% aqueous surfactant solution is prepared as the aqueous phase, wherein the surfactant is composed of polyvinyl alcohol and povidone K30 in a mass ratio of 4:1;

[0093] S3.3: Pre-saturate the aqueous phase with 2% by volume of dichloromethane, then pour the dispersed phase into the aqueous phase and homogenize at high speed to produce a microsphere suspension.

[0094] S3.4: Stir the microsphere suspension at 160 rpm at 30°C for 14 h to remove the organic solvent, then repeatedly wash with water three times and dry to obtain polycaprolactone microspheres.

[0095] S4: Preparation of polycaprolactone microsphere injection

[0096] S4.1: Gradually add sodium carboxymethyl cellulose powder to 55°C hot water with stirring. Once dissolved, sterilize with moist heat steam at 121°C for 30 minutes. Cool to produce a 9% carboxymethyl cellulose hydrogel.

[0097] S4.2: Mix 3 parts by weight of polycaprolactone microspheres, 2 parts by weight of sustained-release antibacterial gel, and 6 parts by weight of carboxymethyl cellulose hydrogel to obtain a mixture;

[0098] S4.3: Add glycerol to the above mixture, the weight content of glycerol in the mixture is 0.8%, mix evenly to evenly disperse the polycaprolactone microspheres, and obtain polycaprolactone microsphere injection after sterilization.

[0099] Comparative Example 1

[0100] Compared with Example 1, Comparative Example 1 is different in that Comparative Example 1 is a polycaprolactone microsphere injection without adding lidocaine, and is recorded as Comparative Example 1.

[0101] Comparative Example 2

[0102] Compared with Example 1, the difference of Comparative Example 2 is that Comparative Example 2 is a commercially available lidocaine injection, which is recorded as Comparative Example 2.

[0103] The polycaprolactone microsphere injections prepared in Examples 1-3 and Comparative Example 1 were subcutaneously injected in 100 μL increments into 6-week-old SKH1-Hrhr hairless mice. The lidocaine injection of Comparative Example 2 was subcutaneously injected in the prescribed amount into 6-week-old SKH1-Hrhr hairless mice. After 5 minutes, the degree of muscle relaxation, mobility, and recovery time of the mice's limbs were observed. If anesthesia took effect, the mice's limbs would become weak. Normal mice were active and lively, while the activity of anesthetized mice was significantly reduced, generally manifested as an inability to stand, walk, or crawl independently. The observation results are shown in Table 1.

[0104] Table 1. Comparison of observation results of Examples 1-3 and Comparative Examples 1-2

[0105] Degree of relaxation of limbs Mobility Recovery time Example 1 Weakness in the limbs Unable to stand independently 8.2 hours Example 2 Weakness in the limbs Unable to stand independently 8.2 hours Example 3 Weakness in the limbs Unable to stand independently 8 hours Comparative Example 1 Limbs strong and normal Lively and active / Comparative Example 2 Weakness in the limbs Unable to stand independently 2.9 hours

[0106] As can be seen from Table 1, the degree of relaxation and activity of the limb muscles of the mice in Example 1 are the same as those in Comparative Example 2. Comparative Example 1 has no symptoms, indicating that the added lidocaine can play an anesthetic role. The recovery time of Example 1 is longer than that of Comparative Example 2, indicating that lidocaine has a sustained-release effect and can prolong the anesthesia time.

[0107] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Anyone skilled in the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by one of ordinary skill in the art without departing from the spirit and technical principles disclosed herein are intended to be covered by the claims of the present invention.

Claims

1. A method for preparing a polycaprolactone microsphere injection containing lidocaine, characterized in that: The steps include: S1: Preparation of modified gelatin hydrogel; S1.1: Dissolve 5-6 parts by weight of type A gelatin in 50-60 parts by weight of phosphate buffer and stir magnetically at 45-50°C for 5-8 hours to obtain a clear solution. S1.2: Add 3-4 parts by weight of methacrylic anhydride dropwise to the above clear solution. After 3-4 hours, dilute the solution to obtain a diluted solution. S1.3: The diluted solution was placed in a dialysis bag to retain the modified molecule with a weight-average molecular weight (Mw) of 12,000. The solution was dialyzed in an oven at 60-65°C for 6-7 days. After dialysis, the solution was freeze-dried to obtain a modified gelatin hydrogel. S2: Preparation of sustained-release antibacterial gel; S2.1: Dissolve 40-50 parts by weight of glucose powder in water for injection to a 50 wt% solution, add 30-40 parts by weight of activated carbon, boil for 10-15 minutes, and cool to obtain a glucose solution. S2.2: Add 2-3 parts by weight of tinidazole to the glucose solution, stir until the tinidazole is completely dissolved, and allow to stand for 10-15 minutes. Decarbonize, adjust the pH, filter, and sterilize with wet heat at 115-120°C for 20-30 minutes to obtain a tinidazole antibacterial solution. S2.3: placing 10-20 parts by weight of the modified gelatin hydrogel in 20-30 parts by weight of a tinidazole antibacterial solution and soaking at room temperature for 2-3 hours for drug loading to obtain a sustained-release antibacterial gel; S3: Preparation of polycaprolactone microspheres; S3.1: Dissolve 1-2 parts by weight of polycaprolactone in dichloromethane to prepare a first solution with a concentration of 10-12 w / w%. Add the prescribed amount of lidocaine hydrochloride to 25-45% of the total volume of purified water and stir to completely dissolve it to obtain a second solution. S3.2: The first solution and the second solution are then mixed to form a dispersed phase, and a 1-2 w / v% aqueous solution of a surfactant is prepared as the aqueous phase; S3.3: Pre-saturate the aqueous phase with dichloromethane, then pour the dispersed phase into the aqueous phase and homogenize at high speed to obtain a microsphere suspension. S3.4: Stirring the microsphere suspension at 25-30°C to remove the organic solvent, then repeatedly washing with water 2-3 times, and drying to obtain polycaprolactone microspheres; S4: Preparation of polycaprolactone microsphere injection; S4.1: Gradually add sodium carboxymethyl cellulose powder to 50-55°C hot water with stirring. Once dissolved, sterilize with moist heat steam at 120-121°C for 25-30 minutes. Cool to produce a 9-10% carboxymethyl cellulose hydrogel. S4.2: Mixing 3-4 parts by weight of polycaprolactone microspheres, 2-3 parts by weight of sustained-release antibacterial gel, and 6-7 parts by weight of carboxymethyl cellulose hydrogel to obtain a mixture; S4.3: Add glycerol to the above mixture and mix well to evenly disperse the polycaprolactone microspheres. After sterilization, obtain the polycaprolactone microsphere injection.

2. The method for preparing a lidocaine-containing polycaprolactone microsphere injection according to claim 1, characterized in that: In step S2.2, the pH value is adjusted to 4.5-4.

6.

3. The method for preparing a lidocaine-containing polycaprolactone microsphere injection according to claim 1, characterized in that: The surfactant in step S3.2 is composed of polyvinyl alcohol and povidone K30 in a mass ratio of 8-9:

2.

4. The method for preparing a lidocaine-containing polycaprolactone microsphere injection according to claim 1, characterized in that: In step S3.3, the amount of dichloromethane added is 2-3% of the volume fraction of the aqueous phase.

5. The method for preparing a lidocaine-containing polycaprolactone microsphere injection according to claim 1, characterized in that: In step S3.4, the stirring speed is 150-160 rpm and the stirring time is 12-14 h.

6. The method for preparing a lidocaine-containing polycaprolactone microsphere injection according to claim 1, characterized in that: In step S4.3, the weight content of glycerol in the mixture is 0.8-1%.

Images