Vitamin C liposome coating composition and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a vitamin C lipidosome wrapping composition and a preparation method thereof.The vitamin C lipidosome wrapping composition comprises lipidosome, and the lipidosome comprises a main membrane material and auxiliary components; the HSPC and the DPPC synergistically improve the liposome membrane compactness and reduce drug leakage, the active loading of vitamin C is driven by a pH gradient method (the pH of an external water phase is 4.0-the pH of an internal water phase is 7.4), the encapsulation efficiency is improved to 92% or above, and the particle size of the liposome is controlled to be 100 + / -20 nm and PDI is controlled to be smaller than or equal to 0.15 through combination of high-pressure homogenization and ultrasound.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and specifically to a preparation method of a vitamin C liposome-encapsulated composition. By optimizing the liposome formulation and preparation process, the stability, encapsulation efficiency and bioavailability of vitamin C are improved. Background Art

[0002] Vitamin C (ascorbic acid) is easily oxidized and degraded, has poor stability under light, high temperature or the presence of metal ions, and has a low oral bioavailability (about 30%-50%). Traditional liposome preparation methods (such as thin film dispersion method, reverse evaporation method) have the following problems: low encapsulation efficiency of vitamin C (usually <60%); uneven liposome particle size distribution (polydispersity index PDI>0.3); drug leakage or liposome aggregation is likely to occur during long-term storage; the preparation process is complex and difficult to scale up industrially. In view of the above problems, a vitamin C liposome-encapsulated composition and its preparation method are proposed. Summary of the Invention

[0003] The purpose of the present invention is to provide a vitamin C liposome with a high encapsulation efficiency (≥90%), small particle size (50-150 nm) and uniform distribution (PDI≤0.2); by optimizing the lipid composition and preparation process, the chemical stability and long-term storage performance of vitamin C are improved; the process flow is simplified, the production cost is reduced, and it is suitable for industrial production.

[0004] The technical solution adopted by the present invention to solve its technical problems is: a vitamin C liposome-encapsulated composition described in the present invention includes liposomes, and the liposomes include main film materials and auxiliary components.

[0005] Preferably, the main film material is a mixture of hydrogenated soy phosphatidylcholine (HSPC) and dipalmitoyl phosphatidylcholine (DPPC) in a certain mass ratio to improve membrane rigidity and antioxidant properties.

[0006] Preferably, the main film material is a mixture of hydrogenated soy phosphatidylcholine (HSPC) and dipalmitoyl phosphatidylcholine (DPPC) in a mass ratio of 3:1.

[0007] Preferably, the main film material is a mixture of hydrogenated soy phosphatidylcholine (HSPC) and dipalmitoyl phosphatidylcholine (DPPC) in a mass ratio of 1:1.

[0008] Preferably, the auxiliary components include 10%-20% cholesterol based on the total mass of lipids, 1%-5% polyethylene glycol-2000-distearoyl phosphatidylethanolamine (PEG-DSPE) based on the total mass of lipids, and 0.05%-0.2% antioxidant based on the total mass of lipids.

[0009] Preferably, the antioxidant is α-tocopherol.

[0010] A preparation method of a liposome-encapsulated vitamin C composition, which is applicable to the liposome-encapsulated vitamin C composition described in any one of the above, and the method comprises the following steps: S1: Dissolve HSPC, DPPC, cholesterol, PEG-DSPE and α-tocopherol in a chloroform-methanol (volume ratio 2:1) mixed solvent, and perform rotary evaporation (temperature 40 °C, vacuum -0.09 MPa) to form a uniform lipid film, and dry it under nitrogen protection for 2 hours; S2: Dissolve vitamin C in a citric acid buffer solution with pH 4.0 (concentration 50 mg / mL), add it to the lipid film for hydration (temperature 55 °C, ultrasonic power 200 W, time 10 min) to form a crude liposome suspension; S3: Refine the liposomes by high-pressure homogenization method (pressure 800 - 1200 bar, cycle 5 times) to obtain a liposome dispersion with uniform particle size; S4: Remove free vitamin C by ultrafiltration centrifugation (cut-off molecular weight 10 kDa), add a freeze-drying protectant (trehalose:mannitol = 2:1), and perform freeze-drying to obtain liposome powder.

[0011] The advantages of the present invention are as follows: 1. The present invention synergistically improves the compactness of the liposome membrane by HSPC and DPPC, reducing drug leakage.

[0012] 2. The present invention drives the active loading of vitamin C by the pH gradient method (external aqueous phase pH 4.0 → internal aqueous phase pH 7.4), and the encapsulation efficiency is increased to more than 92%.

[0013] 3. The present invention controls the liposome particle size within 100 ± 20 nm and PDI ≤ 0.15 by combining high-pressure homogenization and ultrasonic treatment.

[0014] 4. The present invention makes the redispersibility of the freeze-dried liposomes good (particle size change rate < 5%) by compounding trehalose and mannitol. Description of the Drawings

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0016] Figure 1 It is a flow chart of the preparation method in the embodiment; Figure 2 It is a particle size distribution diagram of liposomes in the embodiment; Figure 3 TEM images for comparing the liposome morphology before and after lyophilization in the examples; Detailed implementation manners

[0017] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0018] Examples Please refer to Figures 1-3 As shown, a vitamin C liposome encapsulation composition includes liposomes. The liposomes include a main film material and auxiliary components. 60 mg of hydrogenated soy phosphatidylcholine (HSPC) and 20 mg of dipalmitoyl phosphatidylcholine (DPPC) are selected and mixed to improve membrane rigidity and antioxidant properties. The auxiliary material selects 15 mg of cholesterol, 5 mg of PEG-DSPE, and 0.1 mg of α-tocopherol.

[0019] The preparation process is carried out according to the following steps: S1: Dissolve HSPC, DPPC, cholesterol, PEG-DSPE and α-tocopherol in a chloroform-methanol (volume ratio 2:1) mixed solvent, and perform rotary evaporation (temperature 40 °C, vacuum degree -0.09 MPa) to form a uniform lipid film, and dry it under nitrogen protection for 2 hours; S2: Dissolve vitamin C in a citric acid buffer solution with pH 4.0 (concentration 50 mg / mL), add it to the lipid film for hydration (temperature 55 °C, ultrasonic power 200 W, time 10 min) to form a crude liposome suspension; S3: Refine the liposomes by high-pressure homogenization method (pressure 800 - 1200 bar, cycle 5 times) to obtain a liposome dispersion with uniform particle size; S4: Remove free vitamin C by ultrafiltration centrifugation (cut-off molecular weight 10 kDa), add a lyoprotectant (trehalose:mannitol = 2:1), and freeze-dry to obtain liposome powder.

[0020] HSPC and DPPC cooperate to improve the compactness of the liposome membrane, reduce drug leakage, drive the active loading of vitamin C by the pH gradient method (external aqueous phase pH 4.0 → internal aqueous phase pH 7.4), and the encapsulation efficiency is increased to over 92%. Through high-pressure homogenization combined with ultrasound, with a high-pressure homogenization pressure of 1000 bar and 5 cycles, the liposome particle size is controlled within 100 ± 20 nm, and PDI ≤ 0.15. In this invention, the reconstitution property of the freeze-dried liposome is good (particle size change rate < 5%) by the compounding of trehalose and mannitol. This process can make the overall encapsulation efficiency reach 93.5%, the average particle size 108 nm, and PDI 0.12. The encapsulation efficiency remains > 85% after storage at 4°C for 3 months.

[0021] In the description of this specification, the description with reference to terms such as "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0022] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art of this industry should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed.

Claims

1. A liposome-encapsulated vitamin C composition, characterized in that: It includes liposomes, and the liposomes include a main film material and auxiliary components. The main film material is a mixture of hydrogenated soy phosphatidylcholine (HSPC) and dipalmitoyl phosphatidylcholine (DPPC) in a certain mass ratio.

2. A vitamin C liposome-encapsulated composition according to claim 1, wherein: The main film material is a mixture of hydrogenated soy phosphatidylcholine (HSPC) and dipalmitoyl phosphatidylcholine (DPPC) in a mass ratio of 3:

1.

3. A liposome-encapsulated vitamin C composition according to claim 1, characterized in that: The main film material is a mixture of hydrogenated soy phosphatidylcholine (HSPC) and dipalmitoyl phosphatidylcholine (DPPC) in a mass ratio of 1:

1.

4. The lipidosome-encapsulated composition of vitamin C according to claim 1, wherein: The auxiliary components include 10%-20% cholesterol based on the total mass of lipids, 1%-5% polyethylene glycol-2000-distearoyl phosphatidylethanolamine (PEG-DSPE) based on the total mass of lipids, and 0.05%-0.2% antioxidant based on the total mass of lipids.

5. A vitamin C liposome-encapsulated composition according to claim 4, characterized in that: The antioxidant is α-tocopherol.

6. A preparation method of a liposome-encapsulated vitamin C composition, characterized in that, This method is applicable to a method for preparing a vitamin C liposome-encapsulated composition according to any one of claims 1-5. This method includes the following steps: S1: Dissolve HSPC, DPPC, cholesterol, PEG-DSPE and α-tocopherol in a chloroform-methanol (volume ratio 2:1) mixed solvent, and perform rotary evaporation (temperature 40 °C, vacuum degree -0.09 MPa) to form a uniform lipid film, and dry it under nitrogen protection for 2 hours; S2: Dissolve vitamin C in a citric acid buffer solution with a pH of 4.0 (concentration 50 mg / mL), add it to the lipid film for hydration (temperature 55 °C, ultrasonic power 200 W, time 10 min) to form a crude liposome suspension; S3: Refine the liposomes by high-pressure homogenization (pressure 800-1200 bar, cycle 5 times) to obtain a liposome dispersion with uniform particle size; S4: Remove free vitamin C by ultrafiltration centrifugation (cut-off molecular weight 10 kDa), add a freeze-drying protectant (trehalose:mannitol = 2:1), and freeze-dry to obtain liposome powder.

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