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CN-117205155-B - Tofenamic acid liposome and preparation method and application thereof

CN117205155BCN 117205155 BCN117205155 BCN 117205155BCN-117205155-B

Abstract

The invention relates to a tolfenamic acid liposome, a preparation method and application thereof, wherein the preparation raw materials of the tolfenamic acid liposome comprise phospholipid, cholesterol and tolfenamic acid, the tolfenamic acid is encapsulated in a lipid bilayer, and the tolfenamic acid liposome improves the solubility of the tolfenamic acid and has higher encapsulation rate and drug loading capacity.

Inventors

  • SHEN JIANZHONG
  • MA XIAOMEI
  • CHEN YINGXIAN

Assignees

  • 中国农业大学

Dates

Publication Date
20260505
Application Date
20231017

Claims (11)

  1. 1. The tolfenamic acid liposome is characterized by comprising, by mass, 10-12 parts of phospholipids, 2-6 parts of cholesterol and 1-1.5 parts of tolfenamic acid, wherein the tolfenamic acid is encapsulated in a phospholipid bilayer; the preparation raw materials of the liposome also comprise a solubilizer, wherein the solubilizer is DSPE-PEG2000; The phospholipid is hydrogenated phosphatidylcholine; The tolfenamic acid liposome is prepared by a method comprising the following steps: (1) Mixing phospholipid, cholesterol and tolfenamic acid with an organic solvent, and rotationally evaporating until a film is formed on the container wall; (2) Adding deionized water into the container in the step (1) and then performing ultrasonic treatment to obtain a dispersion liquid; (3) Homogenizing the dispersion liquid obtained in the step (2) under high pressure to obtain the final product; the times of high-pressure homogenization are 3-4 times.
  2. 2. The tolfenamic acid liposome according to claim 1, wherein the pH of the liposome is 6-7.
  3. 3. A method of preparing tolfenamic acid liposomes according to claim 1 or 2, comprising: (1) Mixing phospholipid, cholesterol and tolfenamic acid with an organic solvent, and rotationally evaporating until a film is formed on the container wall; (2) Adding deionized water into the container in the step (1) and then performing ultrasonic treatment to obtain a dispersion liquid; (3) Homogenizing the dispersion liquid obtained in the step (2) under high pressure to obtain the final product; the times of high-pressure homogenization are 3-4 times.
  4. 4. A method of preparing tolfenamic acid liposomes according to claim 3, further comprising mixing the dispersion with a pH adjusting agent after step (2).
  5. 5. The method for preparing tolfenamic acid liposome according to claim 4, characterized in that the pH adjuster comprises disodium succinate hexahydrate.
  6. 6. A method of preparing tolfenamic acid liposomes according to claim 3, wherein the organic solvent comprises methanol and/or chloroform.
  7. 7. A method for preparing tolfenamic acid liposome according to claim 3, wherein the rotary evaporation temperature is 36-38 ℃ and the rotation speed is 90-110 rpm.
  8. 8. A method of preparing tolfenamic acid liposomes according to claim 3, further comprising a water bath at 60-65 ℃ for 15-25min after adding deionized water.
  9. 9. A method for preparing a tolfenamic acid liposome according to claim 3, wherein the ultrasonic power is 400-600W for 10-15 min.
  10. 10. A method for preparing a tolfenamic acid liposome according to claim 3, wherein the high pressure homogenization is performed at a pressure of 15000-20000 psi for a time of 3-5 s.
  11. 11. Use of tolfenamic acid liposomes according to claim 1 or 2 for the preparation of anti-inflammatory, antipyretic or analgesic drugs.

Description

Tofenamic acid liposome and preparation method and application thereof Technical Field The invention belongs to the technical field of pharmaceutical chemistry, and relates to a tolfenamic acid liposome and a preparation method and application thereof. Background Tolfenamic acid is a member of the class of NSAID drug anthranilic acid derivatives found by the scientist of medical corporation in finland, and mainly exerts anti-inflammatory, rapid antipyretic and analgesic effects clinically. Tolfenamic acid has been approved for use in both the human and veterinary markets. A large number of research data show that tolfenamic acid is rapidly absorbed in animals, peaks within 1-2 hours after injection administration, and has no serious specific toxic reaction, and is determined to be a safer veterinary analgesic. However, tolfenamic acid has extremely low solubility in water, can not be used as a water injection, brings inconvenience when in administration, and affects the treatment effect. It is therefore highly desirable to provide a drug that can increase the solubility of tolfenamic acid while ensuring safety. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a tolfenamic acid liposome and a preparation method and application thereof. In order to achieve the aim of the invention, the invention adopts the following technical scheme: In a first aspect, the present invention provides a tolfenamic acid liposome, wherein the liposome is prepared from a phospholipid, cholesterol and tolfenamic acid, and the tolfenamic acid is encapsulated in a phospholipid bilayer. The tolfenamic acid liposome improves the solubility of tolfenamic acid, and has higher encapsulation efficiency and drug loading capacity. Preferably, the liposome comprises, by mass, 10-12 parts of phospholipids, 2-6 parts of cholesterol and 1-1.5 parts of tolfenamic acid. The mass parts of the phospholipids can be selected from 10 parts, 10.1 parts, 10.2 parts, 10.3 parts, 10.4 parts, 10.5 parts, 10.6 parts, 10.7 parts, 10.8 parts, 10.9 parts, 11 parts, 11.1 parts, 11.2 parts, 11.3 parts, 11.4 parts, 11.5 parts, 11.6 parts, 11.7 parts, 11.8 parts, 11.9 parts, 12 parts and the like, the mass parts of the cholesterol can be selected from 2 parts, 2.2 parts, 2.4 parts, 2.6 parts, 2.8 parts, 3 parts, 3.2 parts, 3.4 parts, 3.6 parts, 3.8 parts, 4 parts, 4.2 parts, 4.4 parts, 4.6 parts, 4.8 parts, 5 parts, 5.2 parts, 5.4 parts, 5.8 parts, 6 parts and the like, and the mass parts of the tolfenamic acid can be selected from 1 part, 1.2 parts, 1.6 parts, 1.8 parts, 3.8 parts, 3.2 parts, 3.4 parts, and the like, and the specific values can be selected from the other values within the range of 1.1. When the liposome is added in the mass parts, the entrapment rate and the drug loading rate of the liposome are better, and the effect is better. Preferably, the preparation raw material of the liposome further comprises a solubilizer. The addition of the solubilizer helps the lipid to disperse stably and increases the stability of the liposome. Preferably, the solubilizing agent comprises DSPE-PEG2000. Preferably, the phospholipid comprises any one or a combination of at least two of hydrogenated phosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, dioleoyl phosphatidylcholine, 1, 2-tetradecanoyl phosphatidylethanolamine, dioleoyl phosphatidylethanolamine or lecithin. Preferably, the phospholipid is hydrogenated phosphatidylcholine. The present invention creatively finds that the effect of hydrogenated phosphatidylcholine is superior to the effect of other phospholipids. Preferably, the pH of the liposome is 6-7, for example, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, etc., and other specific values in the above numerical ranges may be selected, which will not be described in detail herein. In a second aspect, the present invention provides a method for preparing a tolfenamic acid liposome according to the first aspect, the method comprising: (1) Mixing phospholipid, cholesterol and tolfenamic acid with an organic solvent, and rotationally evaporating until a film is formed on the container wall; (2) Adding deionized water into the container in the step (1) and then performing ultrasonic treatment to obtain a dispersion liquid; (3) Homogenizing the dispersion liquid obtained in the step (2) under high pressure to obtain the final product. Preferably, step (2) is followed by mixing the dispersion with a pH adjuster. Preferably, the pH adjuster comprises disodium succinate hexahydrate. Preferably, the organic solvent comprises methanol and/or chloroform. Preferably, the temperature of the rotary evaporation is 36-38 ℃ and the rotating speed is 90-110rpm. The temperature may be selected from 36 ℃, 36.2 ℃, 36.4 ℃, 36.6 ℃, 36.8 ℃, 37 ℃, 37.2 ℃, 37.4 ℃, 37.6 ℃, 37.8 ℃, 38 ℃ and the like, and the rotation speed may be selected from 90rpm, 92rpm, 94rpm, 96