Preparation method of liposome entrapping water-soluble medicines

Abstract

The invention relates to a preparation method of a liposome entrapping water-soluble medicines. According to the invention, a water-soluble medicine is dissolved in amino-acid-structure-containing high-molecular hydrophilic colloids such as gelatin, collagen or albumin; poloxamer is added and the mixture is well mixed, such that a W / W type colloidal solution is formed; the solution is lyophilized; the formed lyophilized powder is transferred into a tert-butanol solution containing a liposome material, and the mixture is well dispersed; and the mixture is subjected to lyophilization, such that high-entrapment-efficiency liposome entrapping the water-soluble medicine is formed. According to the liposome preparation method, W / W type colloid is combined with a two-step lyophilization preparation technology, such that problems such as low water-soluble medicine load, low entrapment efficiency and poor stability of existing preparation methods of liposome entrapping water-soluble medicines are solved. The method provided by the invention is used for preparing liposome used for entrapping water-soluble medicines, and is especially suitable for preparing liposome used for entrapping poor-thermal-stability or macromolecular medicines. The method can also be used for covering medicine bitterness or odor, and for separating medicines from other components.

Description

Technical field

[0001] The invention belongs to the field of pharmaceutical preparations, more specifically, the invention relates to a liposome and a preparation method thereof.

Background technique

[0002] Liposomes are monolayer or multilayer microcapsules composed of ordered lipid bilayers. Liposome belongs to the colloidal system, has a cell-like structure, has a strong affinity with the cell membrane, and can increase the ability of the encapsulated drug to penetrate the cell membrane. Liposomes have good biocompatibility, can realize targeted delivery of drugs in vivo, and have many advantages such as prolonging drug action time, increasing drug stability in vivo and in vitro, reducing drug toxicity, and enhancing pharmacological effects.

[0003] An ideal liposome needs to meet the following requirements: (1) The shape of the liposome is round and non-aggregated, and the particle size range can be effectively controlled by the preparation method to achieve the ...

Examples

Embodiment 1

[0049] Embodiment 1: insulin liposome

[0050] Insulin liposomes were prepared in this example, and the composition of insulin liposomes is shown in Table 1.

[0051] Table 1 Insulin liposome composition ratio

[0052]

[0053] Insulin liposome lyophilized powder preparation method: as figure 2 As shown in the process flow, according to the mass ratio of the above components, weigh the components respectively, add the polymer hydrophilic colloid material into water to form a solution, add insulin, Poloxamer (Poloxamer), and additive I to dissolve, A hydrocolloid solution containing the drug is formed and freeze-dried to form freeze-dried powder I. Dissolve the lipid material, polyoxyethylene hydrogenated castor oil, and additive II in tert-butanol at 60°C, and mix well to form tert-butanol solution I. Add the lyophilized powder I to the tert-butanol solution I, ultrasonicate at 20KHz for 2 minutes to form the tert-butanol solution II, quickly freeze in liquid nitrogen t...

Embodiment 2

[0056] Embodiment 2: growth hormone liposome

[0057] This embodiment prepares growth hormone liposomes, and the composition of growth hormone liposomes is shown in Table 2.

[0058] Table 2 Somatotropin liposome composition ratio

[0059]

[0060] Preparation method of growth hormone liposome freeze-dried powder: according to the mass ratio of the above components, weigh the components respectively, add the polymer hydrophilic colloid material into water to form a solution, add growth hormone, poloxamer, and additives I is dissolved to form a hydrocolloid solution containing growth hormone, and freeze-dried to form a freeze-dried powder I. Dissolve lipid material, polyoxyethylene hydrogenated castor oil, and additive II in tert-butanol, and heat in a water bath at 55°C to form tert-butanol solution I. Add lyophilized powder I to tert-butanol solution I, ultrasonic (60KHz) for 1 min to form tert-butanol solution II, quick-freeze in liquid nitrogen to form a solid, and lyo...

Embodiment 3

[0061] Embodiment 3: the quality evaluation of growth hormone liposome

[0062] In this example, the growth hormone liposome prepared in Example 2 was used for quality evaluation.

[0063] Microscopic morphology and particle size analysis: Take 100mg of liposome freeze-dried powder and add 2ml of water to form a liposome solution, absorb a certain amount of liposome suspension and stain with 1% phosphotungstic acid, and observe the liposome under a scanning electron microscope. For the morphological characteristics of the plastids, the particle size of the liposomes was measured using a Coulter particle size analyzer.

[0064] Determination of encapsulation efficiency: take 1ml liposome solution, load it on a Sephadex G-50 gel column, use distilled water as the eluent, take different volumes of the eluted part, separate and receive the free growth hormone eluted part, use The content was analyzed by HPLC, and the encapsulation efficiency of the somatotropin liposome was calcu...

Technical field

[0001] The invention belongs to the field of pharmaceutical preparations, more specifically, the invention relates to a liposome and a preparation method thereof.

Background technique

[0002] Liposomes are monolayer or multilayer microcapsules composed of ordered lipid bilayers. Liposome belongs to the colloidal system, has a cell-like structure, has a strong affinity with the cell membrane, and can increase the ability of the encapsulated drug to penetrate the cell membrane. Liposomes have good biocompatibility, can realize targeted delivery of drugs in vivo, and have many advantages such as prolonging drug action time, increasing drug stability in vivo and in vitro, reducing drug toxicity, and enhancing pharmacological effects.

[0003] An ideal liposome needs to meet the following requirements: (1) The shape of the liposome is round and non-aggregated, and the particle size range can be effectively controlled by the preparation method to achieve the ...

Examples

Embodiment 1

[0049] Embodiment 1: insulin liposome

[0050] Insulin liposomes were prepared in this example, and the composition of insulin liposomes is shown in Table 1.

[0051] Table 1 Insulin liposome composition ratio

[0052]

[0053] Insulin liposome lyophilized powder preparation method: as figure 2 As shown in the process flow, according to the mass ratio of the above components, weigh the components respectively, add the polymer hydrophilic colloid material into water to form a solution, add insulin, Poloxamer (Poloxamer), and additive I to dissolve, A hydrocolloid solution containing the drug is formed and freeze-dried to form freeze-dried powder I. Dissolve the lipid material, polyoxyethylene hydrogenated castor oil, and additive II in tert-butanol at 60°C, and mix well to form tert-butanol solution I. Add the lyophilized powder I to the tert-butanol solution I, ultrasonicate at 20KHz for 2 minutes to form the tert-butanol solution II, quickly freeze in liquid nitrogen t...

Embodiment 2

[0056] Embodiment 2: growth hormone liposome

[0057] This embodiment prepares growth hormone liposomes, and the composition of growth hormone liposomes is shown in Table 2.

[0058] Table 2 Somatotropin liposome composition ratio

[0059]

[0060] Preparation method of growth hormone liposome freeze-dried powder: according to the mass ratio of the above components, weigh the components respectively, add the polymer hydrophilic colloid material into water to form a solution, add growth hormone, poloxamer, and additives I is dissolved to form a hydrocolloid solution containing growth hormone, and freeze-dried to form a freeze-dried powder I. Dissolve lipid material, polyoxyethylene hydrogenated castor oil, and additive II in tert-butanol, and heat in a water bath at 55°C to form tert-butanol solution I. Add lyophilized powder I to tert-butanol solution I, ultrasonic (60KHz) for 1 min to form tert-butanol solution II, quick-freeze in liquid nitrogen to form a solid, and lyo...

Embodiment 3

[0061] Embodiment 3: the quality evaluation of growth hormone liposome

[0062] In this example, the growth hormone liposome prepared in Example 2 was used for quality evaluation.

[0063] Microscopic morphology and particle size analysis: Take 100mg of liposome freeze-dried powder and add 2ml of water to form a liposome solution, absorb a certain amount of liposome suspension and stain with 1% phosphotungstic acid, and observe the liposome under a scanning electron microscope. For the morphological characteristics of the plastids, the particle size of the liposomes was measured using a Coulter particle size analyzer.

[0064] Determination of encapsulation efficiency: take 1ml liposome solution, load it on a Sephadex G-50 gel column, use distilled water as the eluent, take different volumes of the eluted part, separate and receive the free growth hormone eluted part, use The content was analyzed by HPLC, and the encapsulation efficiency of the somatotropin liposome was calcu...

Images