CN111388423A - Preparation method of moxifloxacin hydrochloride liposome - Google Patents
Preparation method of moxifloxacin hydrochloride liposome Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a preparation method of moxifloxacin hydrochloride liposome, which is used for preparing moxifloxacin hydrochloride liposome with high entrapment rate, large drug-loading rate and good stability, wherein an improved ammonium sulfate gradient method is adopted, xanthan gum and carboxymethyl chitosan are added on the basis of the conventional liposome preparation to prepare the moxifloxacin hydrochloride liposome, and the entrapment rate and the drug-loading rate measurement experiments show that the moxifloxacin hydrochloride liposome prepared by the method has the entrapment rate of more than 90% and the drug-loading rate of more than 30%; stability investigation experiments show that the moxifloxacin hydrochloride liposome prepared by the method has the advantages that the 30d entrapment rate and the internal particle size are not obviously changed, and the stability is good. Therefore, the moxifloxacin hydrochloride liposome prepared by the method disclosed by the invention is high in entrapment rate, large in drug loading rate, good in stability and not easy to leak due to external influence.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a preparation method of moxifloxacin hydrochloride liposome.
Background
Moxifloxacin hydrochloride has the chemical name of 1-cyclopropyl-6-fluoro-8-methoxy-7- ([ S, S ] -2, 8-diazabicyclo [4.3.0] non-8-yl) -4-oxo-1, 4-dihydro-3-quinoline carboxylic acid hydrochloride. The moxifloxacin hydrochloride has spectral antibacterial activity, has activity on gram-positive bacteria, gram-negative bacteria, anaerobic bacteria, acid-fast bacteria and atypical microorganisms such as mycoplasma, chlamydia, legionella and the like, and simultaneously has better safety than other quinolone drugs.
The liposome (liposome) is an ultramicro spherical drug carrier preparation prepared by encapsulating drugs in the middle of a film formed by lipid bilayer layers, and can encapsulate water-soluble and fat-soluble drugs due to the structure of the liposome is similar to a biological film, thereby reducing the drug dosage, lowering the toxicity, delaying the release, changing the in-vivo distribution of the drugs, having the targeted therapeutic effect and improving the drug efficacy.
Common liposome preparation techniques include ethanol injection, membrane dispersion, reverse evaporation, and pH gradient. Wherein the pH gradient method is that different H passing through inner and outer water phases+Gradient medicine carrying, and improved encapsulation efficiency of amphiphilic medicine (especially weak acid and weak base medicine) in liposome. The ammonium sulfate gradient method is the most mature and widely applied in the pH gradient method. The ammonium sulfate gradient method is characterized in that an ammonium sulfate aqueous solution is used as an inner water phase of a liposome, a buffer solution is used as an outer water phase, concentration gradients of ammonium sulfate are generated on two sides of a phospholipid bilayer, and the ammonium sulfate gradients are used as motive power for generating pH value gradients. After weakly alkaline drug molecules in the external water phase enter the internal water phase through the phospholipid bilayer, the weakly alkaline drug molecules and SO are mixed4 2–Sulfate is formed, and phosphate is difficult to span the bilayer and can not return to the external water phase and is retained in the internal water phase of the liposome, so that the effect of encapsulating the drug is achieved.
The moxifloxacin hydrochloride is a water-soluble small-molecule drug, and the encapsulation rate and the drug-loading rate of the liposome to the water-soluble small-molecule drug are always low, and the stability is poor. As moxifloxacin hydrochloride shows a certain alkalescence, the active transfer method of the ammonium sulfate gradient method is adopted to prepare the moxifloxacin hydrochloride liposome, so that the entrapment rate and the drug-loading rate of the liposome can be expected to be improved, and the stability of the liposome is also expected to be improved.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to solve the technical problem of providing a preparation method of moxifloxacin hydrochloride liposome, which adopts an improved ammonium sulfate gradient method to prepare the moxifloxacin hydrochloride liposome so as to improve the entrapment rate and drug loading capacity of the liposome and improve the stability of the liposome.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the invention provides a preparation method of moxifloxacin hydrochloride liposome, which comprises the following steps:
s1, dissolving phospholipid and cholesterol in trichloromethane, adding an ammonium sulfate aqueous solution for short-time ultrasonic treatment (the power is 500-600W, the time is 20-30S), then adding xanthan gum and carboxymethyl chitosan, carrying out high-pressure homogenization treatment to obtain a liposome primary body, and carrying out size stabilization and dialysis on the liposome primary body by a microporous filter membrane to obtain a blank liposome;
s2, dissolving moxifloxacin hydrochloride in water to prepare a moxifloxacin hydrochloride solution;
s3, adding the moxifloxacin hydrochloride solution obtained in the step S2 into the blank liposome obtained in the step S1, uniformly mixing, and incubating in a water bath to obtain the moxifloxacin hydrochloride liposome.
The moxifloxacin hydrochloride liposome is prepared by an improved ammonium sulfate gradient method, xanthan gum and carboxymethyl chitosan are added in the preparation process of the liposome, more hydrophilic groups exist in the xanthan gum and the carboxymethyl chitosan, and the hydrophobic property between liposome bilayer structures can be reduced by doping the xanthan gum and the carboxymethyl chitosan into the liposome, so that retention of water-soluble drug molecules on a hydrophobic interface is facilitated, the water-soluble drug molecules are effectively encapsulated in reticular gaps embedded in the bilayer membranes, and the encapsulation rate and the drug loading rate are improved. Xanthan gum is also called xanthan gum, is an extracellular acidic heteropolysaccharide produced by fermentation of xanthomonas campestris, and is also a biological gum integrating thickening, suspension, emulsification and stabilization, carboxymethyl chitosan is a water-soluble chitosan derivative, and is also an amphoteric high-molecular polyelectrolyte, amino on the molecule of the xanthan gum is easy to protonate in solution and has positive charge, and the amino and the negatively charged anionic polysaccharide xanthan gum form a hydrophilic mixed viscous colloid through the complexation of the polyelectrolyte, and a layer of protective film structure can be formed on the surface of liposome, so that the stability of the liposome is greatly improved.
Preferably, the mass concentration of the phospholipid is 40-60mg/m L, the mass ratio of the phospholipid to cholesterol is 4-6:1, too low mass concentration of the phospholipid is not beneficial to encapsulation of drug molecules, and too high mass concentration of the phospholipid causes viscosity increase, so that more adhesion residues are left in a machine in a high-pressure homogenizing process, and the phospholipid utilization rate is reduced.
Preferably, the molar concentration of the ammonium sulfate aqueous solution is 500-600 mmol/L, and the addition amount of the ammonium sulfate aqueous solution is 1-3m L/50 mg phospholipid.
Preferably, the mass ratio of the xanthan gum to the phospholipid is 1:3-5 for optimal modification effect.
Preferably, the mass ratio of the carboxymethyl chitosan to the phospholipid is 1:5-7 for obtaining the optimal modification effect.
Preferably, the mass concentration of the moxifloxacin hydrochloride solution is 30-50mg/m L, the volume ratio of the moxifloxacin hydrochloride solution to blank liposomes is 1:1-2, and under the medicine-lipid ratio, the liposomes can achieve the optimal encapsulation efficiency and drug loading capacity.
Preferably, the dialysis is performed by taking 150-200 mmol/L NaCl as a dialysis medium and dialyzing at room temperature for 3-6h, when the dialysis time is too short, the ammonium sulfate gradient is small, which is not beneficial to improving the encapsulation efficiency, and the presence of ammonium sulfate in the aqueous phase outside the liposome affects the loading of moxifloxacin hydrochloride, and when the dialysis time is too long, the leakage of the aqueous phase ammonium sulfate in the liposome can be caused, and the encapsulation efficiency can not be improved.
Preferably, the temperature of the water bath incubation is 38-45 ℃ and the time is 20-30 min. The incubation temperature of the water bath is too low to provide enough energy for the drug to pass through the membrane, and the temperature is too high to increase the mobile phase of the membrane to cause drug leakage.
Preferably, the pressure of the high-pressure homogenization treatment is 700-900bar, the temperature is 60-70 ℃, and the cycle time is 3-5 times. The high-pressure homogenization treatment is beneficial to the formation of blank liposome and can also effectively remove the trichloromethane in the blank liposome.
Preferably, the pore diameter of the microporous filter membrane is 140nm to 150 nm. Within this particle size range, liposomes can be optimally encapsulated and loaded.
Preferably, the phospholipid is derived from natural phospholipid in soybean, egg yolk, animal brain or viscera, specifically one or more of natural lecithin, soybean lecithin, egg yolk lecithin and cephalin.
Compared with the prior art, the invention has the beneficial effects that:
the moxifloxacin hydrochloride liposome is prepared by an improved ammonium sulfate gradient method, the xanthan gum and the carboxymethyl chitosan are added on the basis of the preparation of the conventional liposome, and the xanthan gum and the carboxymethyl chitosan have a synergistic modification and improvement effect on the liposome, so that the prepared moxifloxacin hydrochloride liposome not only improves the entrapment rate and the drug-loading rate of the liposome, but also improves the stability of the liposome. The test for determining the entrapment rate and the drug-loading rate shows that the encapsulation rate of the moxifloxacin hydrochloride liposome prepared by the method can reach more than 90 percent, and the drug-loading rate can reach more than 30 percent; stability investigation experiments show that the moxifloxacin hydrochloride liposome prepared by the method has the advantages that the 30d entrapment rate and the internal particle size are not obviously changed, and the stability is good. Therefore, the moxifloxacin hydrochloride liposome prepared by the method disclosed by the invention is high in entrapment rate, large in drug loading rate, good in stability and not easy to leak due to external influence. The moxifloxacin hydrochloride liposome disclosed by the invention can be fused with a biological membrane, the retention time of a medicament is prolonged, the slow release and long-acting effects are exerted, the administration frequency can be reduced, the applicability is improved, and the moxifloxacin hydrochloride liposome can be used for administration of parts such as eyes and ears.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The test methods used in the following experimental examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
Example 1
A preparation method of moxifloxacin hydrochloride liposome comprises the following steps:
s1, dissolving phospholipid and cholesterol in trichloromethane, wherein the mass concentration of the phospholipid is 50mg/m L, the mass ratio of the phospholipid to the cholesterol is 5:1, adding an ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 550 mmol/L, and the addition amount of the ammonium sulfate aqueous solution is 2m L/50 mg of the phospholipid), carrying out short-time ultrasonic treatment (the power is 550W and the time is 25S), then adding xanthan gum and carboxymethyl chitosan, the mass ratio of the xanthan gum to the phospholipid is 1:4, and the mass ratio of the carboxymethyl chitosan to the phospholipid is 1:6, carrying out high-pressure homogenization treatment at the temperature of 65 ℃ under the pressure of 800bar, carrying out high-pressure homogenization circulation for 4 times to obtain a liposome primary body, placing the liposome primary body in an extruder, extruding and finishing granules by using a microporous filter membrane with the thickness of 145nm, and then dialyzing for 4.5 hours at room temperature by using NaCl with the thickness of 175 mmol/L as a dialysis medium to obtain blank liposome;
s2, dissolving moxifloxacin hydrochloride in water to prepare a moxifloxacin hydrochloride solution with the mass concentration of 40mg/m L;
s3, adding the moxifloxacin hydrochloride solution obtained in the step S2 into the blank liposome obtained in the step S1, wherein the volume ratio of the moxifloxacin hydrochloride solution to the blank liposome is 1:1.5, uniformly mixing, and then placing the mixture in a water bath at 41.5 ℃ for incubation for 25min to obtain the moxifloxacin hydrochloride liposome.
Example 2
A preparation method of moxifloxacin hydrochloride liposome comprises the following steps:
s1, dissolving phospholipid and cholesterol in trichloromethane, wherein the mass concentration of the phospholipid is 40mg/m L, the mass ratio of the phospholipid to the cholesterol is 4:1, adding an ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 500 mmol/L, and the addition amount of the ammonium sulfate aqueous solution is 1m L/50 mg of the phospholipid), carrying out short-time ultrasonic treatment (the power is 500W and the time is 20S), then adding xanthan gum and carboxymethyl chitosan, the mass ratio of the xanthan gum to the phospholipid is 1:3, and the mass ratio of the carboxymethyl chitosan to the phospholipid is 1:5, carrying out high-pressure homogenization treatment at the temperature of 60 ℃ under the pressure of 700bar, carrying out high-pressure homogenization circulation for 3 times to obtain a liposome primary body, placing the liposome primary body in an extruder, extruding and finishing granules by using a microporous filter membrane of 140nm, and then dialyzing for 3 hours at room temperature by using NaCl of 150 mmol/L as a dialysis medium to obtain a blank liposome;
s2, dissolving moxifloxacin hydrochloride in water to prepare a moxifloxacin hydrochloride solution with the mass concentration of 30mg/m L;
s3, adding the moxifloxacin hydrochloride solution obtained in the step S2 into the blank liposome obtained in the step S1, wherein the volume ratio of the moxifloxacin hydrochloride solution to the blank liposome is 1:1, uniformly mixing, and then placing the mixture in water bath at 38 ℃ for incubation for 20min to obtain the moxifloxacin hydrochloride liposome.
Example 3
A preparation method of moxifloxacin hydrochloride liposome comprises the following steps:
s1, dissolving phospholipid and cholesterol in trichloromethane, wherein the mass concentration of the phospholipid is 60mg/m L, the mass ratio of the phospholipid to the cholesterol is 6:1, adding an ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 600 mmol/L, and the addition amount of the ammonium sulfate aqueous solution is 3m L/50 mg of the phospholipid), carrying out short-time ultrasonic treatment (the power is 600W and the time is 30S), then adding xanthan gum and carboxymethyl chitosan, the mass ratio of the xanthan gum to the phospholipid is 1:5, and the mass ratio of the carboxymethyl chitosan to the phospholipid is 1:7, carrying out high-pressure homogenization treatment at the temperature of 70 ℃ under the pressure of 900bar, carrying out high-pressure homogenization circulation for 5 times to obtain a liposome primary body, placing the liposome primary body in an extruder, extruding and finishing granules by using a microporous filter membrane of 150nm, and then dialyzing for 6 hours at room temperature by using NaCl of 200 mmol/L as a dialysis medium to obtain a blank liposome;
s2, dissolving moxifloxacin hydrochloride in water to prepare a moxifloxacin hydrochloride solution with the mass concentration of 50mg/m L;
s3, adding the moxifloxacin hydrochloride solution obtained in the step S2 into the blank liposome obtained in the step S1, wherein the volume ratio of the moxifloxacin hydrochloride solution to the blank liposome is 1:2, uniformly mixing, and then placing the mixture in water bath at 45 ℃ for incubation for 30min to obtain the moxifloxacin hydrochloride liposome.
Comparative example 1
Compared with the embodiment 1, the difference is that the step S1 of the comparative example 1 is different, no xanthan gum and carboxymethyl chitosan are added in the step S1 of the comparative example 1. the step S1 of the comparative example 1 is to dissolve phospholipid and cholesterol in chloroform, the mass concentration of the phospholipid is 50mg/m L, the mass ratio of phospholipid and cholesterol is 5:1, add ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 550 mmol/L, the addition amount of the ammonium sulfate aqueous solution is 2m L/50 mg phospholipid), perform short-time ultrasonic treatment (the power is 550W and the time is 25S), then perform high-pressure homogenization treatment at the pressure of 800bar and the temperature of 65 ℃, perform high-pressure homogenization circulation for 4 times to obtain liposome primary particles, place the liposome primary particles in an extruder, extrude a microporous membrane with 145nm, then dialyze for 4.5 hours at room temperature by using 175 mmol/L Nacl as a dialysis medium to obtain blank liposome.
Comparative example 2
Compared with the embodiment 1, the difference is that the step S1 of the comparative example 2 is different, no xanthan gum is added in the step S1 of the comparative example 2. the step S1 of the comparative example 2 is specifically that phospholipid and cholesterol are dissolved in chloroform, the mass concentration of the phospholipid is 50mg/m L, the mass ratio of the phospholipid and the cholesterol is 5:1, an ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 550 mmol/L, and the addition amount of the ammonium sulfate aqueous solution is 2m L/50 mg of the phospholipid) is added for short-time ultrasonic treatment (the power is 550W and the time is 25S), then carboxymethyl chitosan, the mass ratio of the carboxymethyl chitosan and the phospholipid is 1:6, the mixture is placed in an extruder under the pressure of 800bar and the temperature of 65 ℃ for high-pressure homogenization treatment, high-pressure homogenization circulation is carried out for 4 times to obtain a liposome primary body, the liposome primary body is placed in the extruder, a microporous membrane extrusion filter membrane with 145nm, then Nacl with 175 mmol/L as a dialysis medium, and blank liposome is obtained after dialysis at room temperature for 4.5.
Comparative example 3
Compared with the embodiment 1, the difference is that the step S1 of the comparative example 3 is different, the mass ratio of the xanthan gum and the phospholipid in the step S1 of the comparative example 3 is different, the step S1 of the comparative example 3 is concretely that the phospholipid and the cholesterol are dissolved in chloroform, the mass concentration of the phospholipid is 50mg/m L, the mass ratio of the phospholipid and the cholesterol is 5:1, an ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 550 mmol/L, the adding amount of the ammonium sulfate aqueous solution is 2m L/50 mg of the phospholipid) is added for short-time ultrasonic treatment (the power is 550W, the time is 25S), then xanthan gum and carboxymethyl chitosan are added, the mass ratio of the xanthan gum and the phospholipid is 1:6, the mass ratio of the carboxymethyl chitosan and the phospholipid is 1:6, the mixture is placed at the pressure of 800bar, the temperature of 65 ℃ for high-pressure homogenization, a high-pressure blank cycle is carried out for 4 times, the liposome primary body is obtained, and the liposome primary body is placed in an extruder, whole particles are extruded by a microporous filter membrane of 145nm, then the Nacl is dialyzed at the room temperature of 175/L, and the.
Comparative example 4
Compared with the embodiment 1, the difference is that the step S1 of the comparative example 4 is different, the step S1 of the comparative example 4 is different in the mass ratio of carboxymethyl chitosan to phospholipid, the step S1 of the comparative example 4 is specifically that phospholipid and cholesterol are dissolved in chloroform, the mass concentration of phospholipid is 50mg/m L, the mass ratio of phospholipid to cholesterol is 5:1, an ammonium sulfate aqueous solution (the molar concentration of the ammonium sulfate aqueous solution is 550 mmol/L, the addition amount of the ammonium sulfate aqueous solution is 2m L/50 mg phospholipid) is added, short-time ultrasonic treatment (power is 550W and time is 25S) is carried out, then xanthan gum and carboxymethyl chitosan are added, the mass ratio of the xanthan gum to the phospholipid is 1:4, the mass ratio of the carboxymethyl chitosan to the phospholipid is 1:8, the mixture is placed at a pressure of 800bar, the temperature is 65 ℃ for high-pressure homogenization, high-pressure homogenization circulation is carried out for 4 times, the liposome primary body is obtained, the liposome primary body is placed in an extruder, the microporous filter membrane with 145nm is extruded, then the whole particles with 175/L, and the liposome is dialyzed at room temperature for 5.5 hours to obtain the liposome dialysis.
Experimental example 1 encapsulation efficiency and drug-loading rate measurement of moxifloxacin hydrochloride liposome
Moxifloxacin hydrochloride liposomes were prepared according to the methods of examples 1 to 3 and comparative examples 1 to 4, respectively, and then the encapsulation efficiency and the drug loading were measured according to the following methods.
Weighing 0.2m L moxifloxacin hydrochloride liposome, loading the moxifloxacin hydrochloride liposome onto a sephadex column, eluting with 160mmo L NaCl solution, collecting 40m L of free drug part, freeze-drying, dissolving the residue with a mobile phase to a constant volume of 5m L, performing sample injection measurement after filtering by a microporous filter membrane, calculating the amount of the free drug, taking 0.2m L moxifloxacin hydrochloride liposome solution, adding a proper amount of ethanol for complete destruction, measuring the mass concentration of total moxifloxacin hydrochloride by HP L C, and calculating the entrapment rate and drug loading rate of the liposome, wherein the result is shown in table 1.
Encapsulation efficiency is (1-m)1/m2)×100％
(m) drug loading rate2－m1)/(m3－m1)×100％
m1Is the drug mass of free moxifloxacin hydrochloride, m2To separate the total amount of moxifloxacin hydrochloride in the proliposome, m3Is the total mass of the nanoparticles.
As shown in the results of Table 1, the moxifloxacin hydrochloride liposome prepared by the method disclosed by the invention is high in entrapment rate and large in drug loading rate, the entrapment rate can reach more than 90%, and the drug loading rate can reach more than 30%; the comparative examples 1-2 show that the joint use of xanthan gum and carboxymethyl chitosan can synergistically enhance the entrapment rate and drug-loading capacity of the liposome, and because the xanthan gum and carboxymethyl chitosan have the synergistic modification and improvement effect on the liposome, the hydrophobicity between liposome bilayer structures can be effectively reduced, and drug molecules can be more favorably encapsulated in reticular gaps in the bilayer membrane, so that the entrapment rate and the drug-loading capacity are improved; as can be seen from comparative examples 3-4, the addition amounts of xanthan gum and carboxymethyl chitosan have relatively significant influence on the entrapment rate and drug-loading capacity of the liposome, and the excessively low addition amount cannot effectively reduce the hydrophobicity between liposome bilayer structures, so that the entrapment rate and the drug-loading capacity are excessively low.
TABLE 1 encapsulation efficiency and drug-loading rate of moxifloxacin hydrochloride liposome prepared by each experimental group
| Group of | Encapsulation efficiency/% | Loading capacity/% |
| Example 1 | 93.57±2.65 | 32.68±1.76 |
| Example 2 | 90.36±2.34 | 30.41±1.64 |
| Example 3 | 92.13±2.54 | 31.97±1.46 |
| Comparative example 1 | 77.58±2.21 | 23.45±1.57 |
| Comparative example 2 | 81.72±2.23 | 24.67±1.54 |
| Comparative example 3 | 85.53±2.45 | 25.59±1.65 |
| Comparative example 4 | 86.33±2.56 | 25.74±1.66 |
Experimental example 2 stability study of moxifloxacin hydrochloride liposome
The moxifloxacin hydrochloride liposome was prepared according to the methods of example 1 and comparative examples 1 to 4, respectively, and then the prepared moxifloxacin hydrochloride liposome was placed at room temperature, samples were taken on the 1 st day, the 7 th day, the 15 th day and the 30 th day to determine the encapsulation efficiency and the particle size, and the stability of the moxifloxacin hydrochloride liposome prepared in each experimental group was examined. The results are shown in Table 2.
As shown in the results of Table 2, the moxifloxacin hydrochloride liposome prepared by the method disclosed by the invention is good in stability at room temperature, and the encapsulation rate and the particle size are not obviously changed within 30 d; as can be seen from the comparative examples 1-2, the combined use of xanthan gum and carboxymethyl chitosan can synergistically improve the stability of the liposome, because the xanthan gum and the carboxymethyl chitosan can be complexed to form a hydrophilic mixed viscous colloid and form a layer of protective film structure on the surface of the liposome, the effect of improving the stability of the liposome is achieved; as can be seen from comparative examples 3-4, the addition amounts of xanthan gum and carboxymethyl chitosan also have a significant effect on the stability of the liposome, and excessively low addition amounts are not beneficial to the formation of a protective film structure on the surface of the liposome or cause the non-uniform protective film structure, thereby affecting the stability of the liposome.
TABLE 2 stability of moxifloxacin hydrochloride liposomes prepared in each experimental group
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (10)
1. The preparation method of the moxifloxacin hydrochloride liposome is characterized by comprising the following steps:
s1, dissolving phospholipid and cholesterol in chloroform, adding an ammonium sulfate aqueous solution for ultrasonic treatment, then adding xanthan gum and carboxymethyl chitosan, carrying out high-pressure homogenization treatment to obtain a liposome primary body, and carrying out granulation and dialysis on the liposome primary body by a microporous filter membrane to obtain a blank liposome;
s2, dissolving moxifloxacin hydrochloride in water to prepare a moxifloxacin hydrochloride solution;
s3, adding the moxifloxacin hydrochloride solution obtained in the step S2 into the blank liposome obtained in the step S1, uniformly mixing, and incubating in a water bath to obtain the moxifloxacin hydrochloride liposome.
2. The method for preparing moxifloxacin hydrochloride liposome according to claim 1, wherein the mass concentration of the phospholipid is 40-60mg/m L, and the mass ratio of the phospholipid to cholesterol is 4-6: 1.
3. The method for preparing moxifloxacin hydrochloride liposome as claimed in claim 1, wherein the molar concentration of the ammonium sulfate aqueous solution is 500-600 mmol/L, and the addition amount of the ammonium sulfate aqueous solution is 1-3m L/50 mg phospholipid.
4. The method for preparing moxifloxacin hydrochloride liposome according to claim 1, wherein the mass ratio of xanthan gum to phospholipid is 1: 3-5.
5. The method for preparing moxifloxacin hydrochloride liposome according to claim 1, wherein the mass ratio of carboxymethyl chitosan to phospholipid is 1: 5-7.
6. The method for preparing moxifloxacin hydrochloride liposome according to claim 1, wherein the mass concentration of the moxifloxacin hydrochloride solution is 30-50mg/m L, and the volume ratio of the moxifloxacin hydrochloride solution to the blank liposome is 1: 1-2.
7. The method for preparing moxifloxacin hydrochloride liposome as claimed in claim 1, wherein the dialysis is performed with 150-200 mmol/L Nacl as dialysis medium at room temperature for 3-6 h.
8. The method for preparing moxifloxacin hydrochloride liposome according to claim 1, wherein the temperature of water bath incubation is 38-45 ℃ and the time is 20-30 min.
9. The method for preparing moxifloxacin hydrochloride liposome as claimed in claim 1, wherein the pressure of the high pressure homogenization treatment is 700-900bar, the temperature is 60-70 ℃, and the cycle time is 3-5 times.
10. The method for preparing moxifloxacin hydrochloride liposome according to claim 1, wherein the pore size of the microporous filter membrane is 0.1-0.4 μm.
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Citations (4)
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| CN101766570A (en) * | 2010-01-18 | 2010-07-07 | 武汉大学 | PH-sensitive precursor cation nanometer liposome of target tumour cell and preparation method thereof |
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| US20140017298A1 (en) * | 2012-03-30 | 2014-01-16 | The Administrators Of The Tulane Educational Fund | Biopolymer hooks to create coatings on liposomes |
| CN103768021A (en) * | 2013-12-13 | 2014-05-07 | 中国医学科学院药用植物研究所 | Method for preparing sustained-release moxifloxacin nano-particle with high drug-loading capacity |
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| US20120100207A1 (en) * | 2009-07-02 | 2012-04-26 | Konica Minolta Holdings, Inc. | Process for producing liposomes by two-step emulsification method utilizing outer aqueous phase containing specific dispersing agent, process for producing liposome dispersion or dry powder thereof using the process for producing liposomes, and liposome dispersion or dry powder thereof produced thereby |
| CN101766570A (en) * | 2010-01-18 | 2010-07-07 | 武汉大学 | PH-sensitive precursor cation nanometer liposome of target tumour cell and preparation method thereof |
| US20140017298A1 (en) * | 2012-03-30 | 2014-01-16 | The Administrators Of The Tulane Educational Fund | Biopolymer hooks to create coatings on liposomes |
| CN103768021A (en) * | 2013-12-13 | 2014-05-07 | 中国医学科学院药用植物研究所 | Method for preparing sustained-release moxifloxacin nano-particle with high drug-loading capacity |
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Application publication date: 20200710 |