CN115282119A - High drug-loading rate liposome and preparation method thereof - Google Patents
High drug-loading rate liposome and preparation method thereof Download PDFInfo
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- CN115282119A CN115282119A CN202210921909.5A CN202210921909A CN115282119A CN 115282119 A CN115282119 A CN 115282119A CN 202210921909 A CN202210921909 A CN 202210921909A CN 115282119 A CN115282119 A CN 115282119A
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- 239000002502 liposome Substances 0.000 title claims abstract description 67
- 238000011068 loading method Methods 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 46
- 229940079593 drug Drugs 0.000 claims abstract description 43
- 239000002253 acid Substances 0.000 claims abstract description 26
- 239000002245 particle Substances 0.000 claims abstract description 24
- 239000011259 mixed solution Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000004005 microsphere Substances 0.000 claims abstract description 17
- 238000001125 extrusion Methods 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000001704 evaporation Methods 0.000 claims abstract description 10
- 239000007788 liquid Substances 0.000 claims abstract description 9
- 230000008719 thickening Effects 0.000 claims abstract description 8
- 230000008020 evaporation Effects 0.000 claims abstract description 4
- 238000005469 granulation Methods 0.000 claims abstract description 4
- 230000003179 granulation Effects 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 238000000935 solvent evaporation Methods 0.000 claims abstract 2
- 239000012071 phase Substances 0.000 claims description 29
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 16
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- 150000003904 phospholipids Chemical class 0.000 claims description 11
- 235000012000 cholesterol Nutrition 0.000 claims description 8
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 239000004310 lactic acid Substances 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 4
- 239000008346 aqueous phase Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 238000002390 rotary evaporation Methods 0.000 description 19
- 239000012528 membrane Substances 0.000 description 10
- 238000005538 encapsulation Methods 0.000 description 8
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 5
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 5
- 229960002930 sirolimus Drugs 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 229920000515 polycarbonate Polymers 0.000 description 4
- 239000004417 polycarbonate Substances 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010528 free radical solution polymerization reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920006289 polycarbonate film Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 239000012209 synthetic fiber Substances 0.000 description 1
Classifications
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- 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
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
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- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
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- A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2400/00—Materials characterised by their function or physical properties
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Abstract
The invention discloses a high drug-loading liposome and a preparation method thereof, wherein the preparation method of the high drug-loading liposome comprises the following steps: preparation of mixed solution: dissolving amphipathic molecules and a drug in an organic solvent to obtain an oil phase, and adding the water phase into the oil phase to be uniformly mixed to obtain a mixed solution; organic solvent evaporation: evaporating to remove the organic solvent in the mixed solution; preparing microspheres by extrusion: carrying out extrusion granulation on the mixed solution without the organic solvent, and controlling the particle size of the prepared microspheres at a nanometer level; evaporation and thickening: evaporating until no liquid volatilizes; adding of the oligolactic acid: adding oligolactic acid, and mixing to obtain liposome, wherein the addition amount of the oligolactic acid is more than 0.01% of the total weight of the liposome. The liposome prepared by the method of the invention has the effects of extremely high entrapment efficiency and stability under higher drug concentration.
Description
Technical Field
The invention relates to the field of liposome, in particular to a liposome with high drug loading capacity and a preparation method thereof.
Background
The liposome is a micro-vesicular body formed by encapsulating a medicament in a bilayer by using amphiphilic substances such as phospholipid and the like, and can effectively improve the administration effect of the water-insoluble medicament.
Generally, the liposome is administrated by an oral or injection mode, if the concentration is lower, the total dosage can be increased by increasing the dosage to achieve the treatment effect, but in the medical balloon or medical stent fixed-point administration mode which is just widely applied, the surface area of the designated administration position of the medical balloon or medical stent is limited, and the total drug loading capacity of the medical stent can be increased only by increasing the drug concentration in the liposome.
However, the drug loading of the liposome suspension disclosed in the prior art can only reach dozens of mug/mL, if the concentration of the drug in the liposome is simply increased, the encapsulation efficiency of the liposome is rapidly reduced, and if the drug loading concentration is only increased, the drug concentration is significantly reduced after the liposome is placed for 24 hours at normal temperature, so that the stability of the liposome is also significantly affected.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the problem that the stability of the existing liposome is sharply reduced under the condition of increasing the drug concentration, so that the high drug-loading liposome and the preparation method thereof, which can obtain extremely high entrapment rate and stability under higher drug concentration, are provided.
A preparation method of a high drug-loading capacity liposome comprises the following steps:
a preparation method of a high drug-loading rate liposome is characterized by comprising the following steps:
preparation of mixed solution: dissolving amphipathic molecules and a drug in an organic solvent to obtain an oil phase, and adding the water phase into the oil phase to be uniformly mixed to obtain a mixed solution;
evaporation of organic solvent: evaporating to remove the organic solvent in the mixed solution;
preparing microspheres by extrusion: carrying out extrusion granulation on the mixed solution without the organic solvent, and controlling the particle size of the prepared microspheres at a nanometer level;
evaporation and thickening: evaporating the solution to increase the concentration of the drug in the mixed solution;
adding of the oligolactic acid: adding oligolactic acid, and mixing to obtain liposome, wherein the addition amount of the oligolactic acid is more than 0.01% of the total weight of the liposome.
The number average relative molecular mass Mn of the oligolactic acid is less than 5000.
The addition amount of the oligolactic acid is 0.01-0.05% of the total weight of the liposome.
The amphiphilic molecule is phospholipid, and the mass ratio of the phospholipid to the medicine is (6-80): 1.
the mixed solution also comprises cholesterol, and the addition amount of the cholesterol in the oil phase is 2mg/mL.
The volume ratio of the oil phase to the water phase is (4-7): 1.
the water phase is PBS buffer solution with the mass concentration of 0.02M.
In the step of preparing the microspheres by extrusion, the particle size of the prepared microspheres is 100-1000nm.
The liposome with high drug loading capacity is prepared by the preparation method of the liposome with high drug loading capacity.
The high drug-loading liposome is applied to a medical balloon or a medical bracket.
The technical scheme of the invention has the following advantages:
according to the preparation method of the liposome with high drug loading capacity, provided by the invention, the liposome passes through the nano-scale microporous membrane under high pressure by adopting an extrusion method so that the particle size is reduced to a nano level, and meanwhile, the stability of the liposome microsphere can be effectively improved by combining with the finally added low-molecular-weight polylactic acid. Namely, the liposome prepared by the method has the drug loading concentration of more than 900 mug/mL, even more than 9000 mug/mL, and under the condition of extremely high drug loading concentration, the entrapment rate of more than 99 percent and excellent stability, so that the application requirement of a medical balloon or a medical stent can be effectively met.
Detailed Description
Example 1
A preparation method of a high drug-loading capacity liposome comprises the following steps:
preparing a mixed solution:
1.6g of phospholipid, 40mg of cholesterol and 200mg of sirolimus are dissolved in 20mL of ethanol to serve as an oil phase, the oil phase is added into 80mL of water phase, and the mixture is uniformly mixed, and the water phase is PBS buffer solution with the concentration of 0.02M.
(II) rotary evaporation:
the ethanol solvent is removed by rotation at the constant temperature of 42 ℃, and the pressure in the step is not specially required, and bumping is preferably avoided.
(III) controlling the particle size of the microspheres by an extruder:
the smaller the pore size of the membrane in the extruder, the smaller the extruded particle size, and the better the liposome stability. Theoretically, the average particle size of the extruded microspheres is 1.2 times of the pore diameter of the membrane, and in the invention, the extrusion granulation can be directly carried out on the membrane with the target pore diameter, and the pressure of an extruder can be reduced by adopting an extrusion mode of reducing the pore diameter from large to small. In this example, the liposomes with different particle sizes were prepared by extruding polycarbonate films of 50nm, 100nm and 200nm, respectively.
(IV) rotary evaporation thickening:
under the constant temperature condition of 42 ℃, the rotary evaporation can be carried out to the maximum extent that no liquid is evaporated, and the rotary evaporation process is verified not to cause the damage of the liposome, wherein the rotary evaporation is carried out to the extent that no liquid is evaporated in the embodiment.
(V) adding oligolactic acid to improve stability
And (3) adding the oligolactic acid into the product prepared in the step (IV), wherein the adding amount of the oligolactic acid is 0.03 percent of the total weight of the liposome. The preparation process of the oligolactic acid comprises the following steps: adding lactic acid into diphenyl ether for polymerization, wherein the volume ratio of lactic acid to diphenyl ether is 2: 3, the polymerization temperature is 160 ℃, and the polymerization time is 10h. The polymerization process of the present invention for the preparation of oligomeric lactic acid is described in the following references: wu Jingmei, wu Refeng solution polymerization process for the synthesis of polylactic acid [ J ]. Synthetic fiber industry, 2006, 29 (01): 14-15.
The liposomes having different particle sizes prepared in this example were measured to determine the particle size (nm), initial drug concentration (μ g/mL), drug concentration after 24 hours at room temperature (μ g/mL) and encapsulation ratio (%), and the results are shown in table 1 below.
TABLE 1
As can be seen from the table 1, the drug loading concentration of the liposome prepared by the method of the invention can even reach more than 9000 mug/mL, and the encapsulation efficiency can also reach more than 99% under the condition of extremely high drug loading concentration, and compared with the initial drug concentration (mug/mL), the drug concentration (mug/mL) result after 24 hours passes through is not obviously reduced, so that the stability of the liposome is proved to be excellent.
Example 2
A preparation method of a high drug-loading capacity liposome comprises the following steps:
preparing a mixed solution:
dissolving phospholipid, 40mg cholesterol and 200mg sirolimus in different amounts in 20mL ethanol as oil phase, adding the oil phase into 80mL water phase, and mixing uniformly, wherein the water phase is PBS buffer solution with the concentration of 0.02M. The dosages of phospholipid are respectively 16g, 4g, 1.6g and 1.2g.
(II) rotary evaporation:
the ethanol solvent is removed by rotation at the constant temperature of 42 ℃, and the pressure in the step is not specially required, and bumping is preferably avoided.
(III) controlling the particle size of the microspheres by an extruder:
the extruder is used for extruding a polycarbonate membrane with the membrane aperture of 100nm to prepare the liposome with the particle size of about 120 nm.
(IV) rotary evaporation thickening:
and (3) performing rotary evaporation at a constant temperature of 42 ℃ until no liquid is evaporated.
(V) adding oligolactic acid to improve stability
The oligolactic acid prepared in the method of example 1 was added to the product prepared in step (iv), and the amount of the oligolactic acid added in this example was 0.03% of the total weight of the liposome.
The liposome prepared in this example was examined to determine the particle size (nm), initial drug concentration (μ g/mL), drug concentration after 24 hours at room temperature (μ g/mL) and encapsulation efficiency (%), and the examination results are shown in table 2 below.
TABLE 2
As can be seen from the table 2, the liposome prepared by the method of the invention has stable drug-loading concentration even reaching 9000 mug/mL or more and excellent stability.
Example 3
A preparation method of a high drug-loading capacity liposome comprises the following steps:
preparing a mixed solution:
1.6g of phospholipid, 40mg of cholesterol and 200mg of sirolimus were dissolved in 20mL, 16mL and 11mL of ethanol, respectively, to obtain oil phases, and the oil phases were added to 80mL of aqueous phase, which was 0.02M PBS buffer, and mixed uniformly.
(II) rotary evaporation:
the ethanol solvent is removed by rotation at the constant temperature of 42 ℃, and no special pressure is required in the step, and bumping is preferably avoided.
(III) controlling the particle size of the microspheres by an extruder:
the extruder is used for extruding a polycarbonate membrane with the membrane aperture of 100nm to prepare the liposome with the particle size of about 120 nm.
(IV) rotary evaporation thickening:
and (3) carrying out rotary evaporation at a constant temperature of 42 ℃ until no liquid is evaporated.
(V) adding oligolactic acid to improve stability
The oligolactic acid prepared in example 1 was added to the product prepared in step (iv), and the amount of the oligolactic acid added in this example was 0.03% of the total weight of the liposome.
The liposome prepared in this example was examined to determine the particle size (nm), initial drug concentration (μ g/mL), drug concentration after 24 hours at room temperature (μ g/mL) and encapsulation efficiency (%), and the examination results are shown in table 3 below.
TABLE 3
As can be seen from the above Table 3, the liposome prepared by the method of the present invention can increase the drug-loading concentration by increasing the proportion of the oil phase properly, the drug-loading concentration can reach about 9000 μ g/mL, and excellent stability can be achieved at the high drug-loading concentration.
Example 4
A preparation method of a high drug-loading capacity liposome comprises the following steps:
preparing a mixed solution:
1.6g of phospholipid, 40mg of cholesterol and 200mg of sirolimus were dissolved in 20mL of ethanol as an oil phase, and the oil phase was added to 80mL of a water phase, which was 0.02M PBS buffer, and mixed uniformly.
(II) rotary evaporation:
the ethanol solvent is removed by rotation at the constant temperature of 42 ℃, and the pressure in the step is not specially required, and bumping is preferably avoided.
(III) controlling the particle size of the microspheres by an extruder:
the extruder adopts a polycarbonate membrane with the membrane aperture of 100nm for extrusion to prepare the liposome with the particle diameter of about 120 nm.
(IV) rotary evaporation thickening:
and (3) carrying out rotary evaporation at a constant temperature of 42 ℃ until no liquid is evaporated.
(V) adding oligolactic acid to improve stability
The oligolactic acid prepared by the method in example 1 is added to the product prepared by the step (IV), and the addition amount of the oligolactic acid is 0.0-0.05% of the total weight of the liposome in this example.
The liposome prepared in this example was examined to determine the particle size (nm), initial drug concentration (μ g/mL), drug concentration after 24 hours at room temperature (μ g/mL) and encapsulation efficiency (%), and the examination results are shown in table 4 below.
TABLE 4
As can be seen from the above Table 4, the stability at high drug loading concentration can be significantly improved by adding the lactic acid oligomer in the method of the present invention, and the effect is significant.
Example 5
A preparation method of a high drug-loading capacity liposome comprises the following steps:
preparing a mixed solution:
1.6g of phospholipid and 200mg of sirolimus were dissolved in 20mL of ethanol as an oil phase, and the oil phase was added to 80mL of a water phase, which was 0.02M PBS buffer and mixed uniformly.
(II) rotary evaporation:
the ethanol solvent is removed by rotation at the constant temperature of 42 ℃, and no special pressure is required in the step, and bumping is preferably avoided.
(III) controlling the particle size of the microspheres by an extruder:
in this example, a 100nm polycarbonate membrane was used for extrusion to prepare liposomes having a particle size of about 120 nm.
(IV) rotary evaporation thickening:
under the constant temperature condition of 42 ℃, the rotary evaporation can be carried out to the maximum extent that no liquid is evaporated, and the rotary evaporation process is verified not to cause the damage of the liposome, wherein the rotary evaporation is carried out to the extent that no liquid is evaporated in the embodiment.
(V) adding oligolactic acid to improve stability
The oligolactic acid prepared in the method of example 1 was added to the product prepared in step (iv), and the amount of the oligolactic acid added in this example was 0.03% of the total weight of the liposome.
The liposomes prepared in this example were examined to determine the particle size (nm), initial drug concentration (. Mu.g/mL), drug concentration (. Mu.g/mL) after 24 hours at room temperature, and encapsulation efficiency (%), and the examination results are shown in Table 5 below.
TABLE 5
As can be seen from the above Table 5, the drug loading concentration of the liposome prepared by the method of the present invention can reach more than 9000 μ g/mL, and the encapsulation efficiency can also reach more than 99% under the extremely high drug loading concentration condition, and the drug concentration (μ g/mL) after 24 hours is not significantly reduced compared with the initial drug concentration (μ g/mL), which proves that the stability of the liposome is excellent.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (10)
1. A preparation method of a liposome with high drug loading capacity is characterized by comprising the following steps:
preparation of mixed solution: dissolving amphipathic molecules and a drug in an organic solvent to obtain an oil phase, and adding the water phase into the oil phase to be uniformly mixed to obtain a mixed solution;
organic solvent evaporation: evaporating to remove the organic solvent in the mixed solution;
preparing microspheres by extrusion: carrying out extrusion granulation on the mixed solution without the organic solvent, and controlling the particle size of the prepared microspheres at a nanometer level;
evaporation and thickening: evaporating until no liquid volatilizes;
adding of the oligolactic acid: adding lactic acid oligomer in the amount of over 0.01 wt% of the liposome and mixing to obtain liposome.
2. The process according to claim 1, wherein the oligolactic acid has a number average relative molecular mass Mn of less than 5000.
3. The method according to claim 1 or 2, wherein the amount of the lactic acid oligomer added is 0.01 to 0.05% by weight based on the total weight of the liposome.
4. The method according to any one of claims 1 to 3, wherein the amphiphilic molecule is a phospholipid, and the mass ratio of the phospholipid to the drug is (6-80): 1.
5. the method according to claim 4, wherein the mixed solution further comprises cholesterol, and the amount of cholesterol added in the oil phase is 0 to 2mg/mL.
6. The production method according to any one of claims 1 to 5, wherein the volume ratio of the oil phase to the aqueous phase is (4 to 7): 1.
7. the method according to any one of claims 1 to 6, wherein the aqueous phase is PBS buffer at a mass concentration of 0.02M.
8. The method according to any one of claims 1 to 7, wherein in the step of preparing the microspheres by extrusion, the microspheres are prepared to have a particle size of 100 to 1000nm.
9. A liposome with high drug loading capacity, which is prepared by the preparation method of the liposome with high drug loading capacity of any one of claims 1 to 8.
10. Use of a high drug loading liposome according to claim 9 in a medical balloon or medical stent.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102949343A (en) * | 2011-08-26 | 2013-03-06 | 石药集团中奇制药技术（石家庄）有限公司 | Method for increasing fat-soluble drug loading capacity in liposome |
| US20140328899A1 (en) * | 2011-07-13 | 2014-11-06 | Shaare Zedek Medical Center | Liposomes co-encapsulating a bisphosphonate and an amphipathic agent |
| CN105267147A (en) * | 2014-07-08 | 2016-01-27 | 广州瑞济生物技术有限公司 | Preparation method for oxaliplatin precursor liposome used for injection |
| CN109381429A (en) * | 2018-09-18 | 2019-02-26 | 湖北大学 | A kind of taxol target slow-release liposome and preparation method thereof that leucocyte is film modified |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140328899A1 (en) * | 2011-07-13 | 2014-11-06 | Shaare Zedek Medical Center | Liposomes co-encapsulating a bisphosphonate and an amphipathic agent |
| CN102949343A (en) * | 2011-08-26 | 2013-03-06 | 石药集团中奇制药技术（石家庄）有限公司 | Method for increasing fat-soluble drug loading capacity in liposome |
| CN105267147A (en) * | 2014-07-08 | 2016-01-27 | 广州瑞济生物技术有限公司 | Preparation method for oxaliplatin precursor liposome used for injection |
| CN109381429A (en) * | 2018-09-18 | 2019-02-26 | 湖北大学 | A kind of taxol target slow-release liposome and preparation method thereof that leucocyte is film modified |
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