L-menthol freeze-dried nanoemulsion and preparation method thereof
By preparing L-menthol nanoemulsion lyophilized formulations, the problems of poor solubility and unstable content of L-menthol solutions in water were solved, achieving the stability and sustained effect of transparent solutions, which are suitable for clinical use.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NANJING CORE TECH CO LTD
- Filing Date
- 2024-11-18
- Publication Date
- 2026-05-19
AI Technical Summary
The existing L-menthol solution is poorly soluble in water and its content is unstable, resulting in inconsistent clinical efficacy.
L-menthol was prepared into a nanoemulsion and then lyophilized to form a lyophilized formulation. After reconstitution, a transparent solution was formed, which was then reconstituted using physiological saline.
This achieves stability and consistent concentration of L-menthol solution, facilitating clinical use.
Smart Images
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Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, and more specifically, to a lyophilized nanoemulsion formulation containing L-menthol and its preparation method. Background Technology
[0002] L-Menthol is a compound extracted from peppermint oil. It has a cool aroma and can give people a refreshing and cool feeling. Pharmacologically, L-menthol mainly produces a cooling sensation by stimulating cold receptors. This effect can affect a variety of tissues in the body, including smooth muscle.
[0003] In clinical practice, solutions containing L-menthol are used during gastroscopy and colonoscopy to inhibit gastrointestinal motility and ensure a clear view. However, because L-menthol is poorly soluble in water, solutions prepared using conventional methods have low and unstable concentrations, making it difficult to achieve a consistently effective result for clinical use.
[0004] The purpose of this invention is to prepare L-menthol into a nanoemulsion and then freeze-dry it to obtain a freeze-dried formulation, which is then reconstituted with physiological saline before use. Summary of the Invention
[0005] This invention provides a novel formulation and preparation process for a lyophilized L-menthol nanoemulsion, characterized by its ability to form an almost transparent L-menthol solution upon reconstitution, facilitating clinical use.
[0006] The first objective of this invention is achieved through the following technical solution:
[0007] An L-menthol nanoemulsion solution comprises an active ingredient, L-menthol, excipients, and purified water. The pH value of the L-menthol nanoemulsion solution is 5.5–6.5. The excipients include: (1) castor oil as an oil phase solvent, (2) glycerin as a humectant, (3) lecithin as an emulsifier, (4) hydrochloric acid or sodium hydroxide as a pH adjuster, and (5) mannitol as a lyophilization protectant.
[0008] In one embodiment of the present invention, the active ingredient is L-menthol, and the types and percentages of other components are as follows:
[0009]
[0010]
[0011] The second objective of this invention is to provide a method for preparing L-menthol nanoemulsion lyophilized agent.
[0012] (1) Preparation of oil phase: Add the prescribed amount of L-menthol and lecithin to castor oil, stir and dissolve to form a light yellow transparent solution.
[0013] (2) Preparation of aqueous phase: Take a small amount of purified water, add glycerol and mannitol, and stir to dissolve.
[0014] (3) Preparation of nanoemulsion: Keep the temperature of both the oil phase and the water phase at about 40°C. Slowly add the oil phase to the water phase. After all the oil phase is added, turn on the high shear homogenizer head. The shearing speed is not less than 5000 rpm and the shearing time is not less than 1 hour. At the same time, keep the temperature of the emulsion below 60°C. Visually, the emulsion should be a fine and uniform light yellow emulsion.
[0015] (4) Adjust pH: Adjust the pH of the nanoemulsion solution prepared in step (3) to 5.5-6.5 with sodium hydroxide or hydrochloric acid, add water to make up the volume, and dispense into 10ml vials.
[0016] (5) Place the vial into a freeze dryer, pre-freeze at -45℃ for 4 hours, raise the temperature to -10~-25℃ and maintain for 10-14 hours, raise the temperature to 15℃ and maintain for 1-3 hours, control the moisture content to <3.5%, and freeze drying is complete. Detailed Implementation
[0017] The beneficial effects of the present invention can be demonstrated through the following series of tests.
[0018] Example 1:
[0019]
[0020] Preparation process:
[0021] (1) Preparation of oil phase: Add the prescribed amount of L-menthol and lecithin to castor oil, stir and dissolve to form a light yellow transparent solution.
[0022] (2) Preparation of aqueous phase: Take a small amount of purified water, add glycerol and mannitol, and stir to dissolve.
[0023] (3) Preparation of nanoemulsion: Keep the temperature of both the oil phase and the water phase at about 40°C. Slowly add the oil phase to the water phase. After all the oil phase is added, turn on the high shear homogenizer head. The shearing speed is 6500 rpm and the shearing time is 100 minutes. At the same time, keep the temperature of the emulsion below 60°C. Visually, the emulsion should be a fine and uniform light yellow emulsion.
[0024] (4) Adjust pH: Adjust the pH of the nanoemulsion solution prepared in step (3) to 5.5-6.5 with sodium hydroxide or hydrochloric acid, add water to make up the volume, and dispense into 10ml vials.
[0025] (5) Place the vial into the freeze dryer, pre-freeze at -45℃ for 4 hours, raise the temperature to -15℃ and maintain for 12 hours, raise the temperature to 15℃ and maintain for 2 hours, and the freeze drying is complete.
[0026] (6) The sample was removed, and the moisture content determined by the Karl Fischer method was 2.83%.
[0027] Result determination:
[0028] The lyophilized formulation was mixed with 10 ml of 0.9% sodium chloride solution and shaken for 1 min to obtain a transparent, opalescent, homogeneous liquid. The particle size of the solution was measured and compared with the monitoring data before lyophilization. The results are as follows:
[0029]
[0030] The results above show that the L-menthol nanoemulsion freeze-dried formulation prepared according to the method of this patent has no significant difference in transmittance and particle size before freeze-drying and after freeze-drying and reconstitution.
Claims
1. A lyophilized nanoemulsion formulation of L-menthol, characterized in that, Its ingredients are formulated with active ingredient L-menthol, excipients and purified water.
2. The lyophilized nanoemulsion formulation of L-menthol as described in claim 1, characterized in that, The pH value of the L-menthol nanoemulsion solution is 5.5 to 6.5, and the excipients include: (1) castor oil as an oil phase solvent, (2) glycerin as a humectant, (3) lecithin as an emulsifier, (4) hydrochloric acid or sodium hydroxide as a pH adjuster, and (5) mannitol as a freeze-drying protectant.
3. The lyophilized nanoemulsion formulation of L-menthol as described in claim 2, characterized in that, The types and percentages of its components are as follows:
4. The lyophilized nanoemulsion formulation of L-menthol as described in claim 2, characterized in that: The preparation method is as follows: (1) Preparation of oil phase: Add the prescribed amount of L-menthol and lecithin to castor oil, stir and dissolve to form a light yellow transparent solution. (2) Preparation of aqueous phase: Take a small amount of purified water, add glycerol and mannitol, and stir to dissolve. (3) Preparation of nanoemulsion: Keep the temperature of both the oil phase and the water phase at about 40°C. Slowly add the oil phase to the water phase. After all the oil phase is added, turn on the high shear homogenizer head. The shearing speed is not less than 5000 rpm and the shearing time is not less than 1 hour. At the same time, keep the temperature of the emulsion below 60°C. Visually, the emulsion should be a fine and uniform light yellow emulsion. (4) Adjust pH: Adjust the pH of the nanoemulsion solution prepared in step (3) to 5.5-6.5 with sodium hydroxide or hydrochloric acid, add water to make up the volume, and dispense into 10ml vials. (5) Place the vial into a freeze dryer, pre-freeze at -45℃ for 4 hours, raise the temperature to -10~-25℃ and maintain for 10-14 hours, raise the temperature to 15℃ and maintain for 1-3 hours, control the moisture content to <3.5%, and freeze drying is complete.