Preparation method of rare ginsenoside liposome

Abstract

The invention relates to the field of ginsenoside liposome extraction, in particular to a preparation method of rare ginsenoside liposome. According to the preparation method of the rare ginsenoside lipidosome, the problem that rare ginsenoside is not dispersed in water and insoluble in water is solved, the vacuum freezing heating drying machine is further provided, ice crystals are sequentially fed into the vacuum heating drying system in a low-flow-density state through the spray freezing system, and the rare ginsenoside lipidosome is obtained. According to the present invention, the particulate powder containing the ginsenoside liposome is rapidly dried, and the smaller the particle size of the particulate powder containing the ginsenoside liposome is, the easier the ginsenoside liposome is absorbed by the human body, such that the bioavailability of the conventional rare ginsenoside absorbed by the human body is improved, and the rare ginsenoside liposome with characteristics of high entrapment rate and high drug loading capacity can be continuously produced, finally, the technical defect that the human body absorption bioavailability of the ginsenoside liposome is relatively low due to the problems of low encapsulation efficiency and low drug loading capacity after the extracted ginsenoside liposome is processed into a drug product is overcome.

Description

Technical Field

[0001] The invention relates to the field of ginsenoside liposome extraction, and in particular to a method for preparing rare ginsenoside liposome. Background Art

[0002] Ginsenoside liposomes are a new type of drug delivery system designed to improve the bioavailability and therapeutic effects of ginsenosides. Ginsenoside liposomes are the main active ingredients extracted from ginseng, and have multiple biological activities such as anti-inflammatory, antioxidant, immunomodulatory and anti-tumor. In the extraction and processing technology of ginsenoside liposomes, there are technical difficulties that ginsenosides are not dispersed or soluble in water. After the extracted ginsenoside liposomes are processed into a powder state using a homogenizer and a freeze dryer, the extracted ginsenoside liposomes are processed into drug products and still have problems of low encapsulation rate and low drug loading, which ultimately leads to low bioavailability of ginsenoside liposomes absorbed by the human body. Summary of the invention

[0003] In order to overcome the problems of low encapsulation rate and low drug loading after the extracted ginsenoside liposomes are processed into drug products, resulting in low bioavailability of ginsenoside liposomes absorbed by the human body, the present invention provides a method for preparing rare ginsenoside liposomes.

[0004] The technical solution of the present invention is a method for preparing rare ginsenoside liposomes, which comprises the following steps: Step 1, using 50% rare ginsenoside extract as a raw material, dissolving it in 60% ethanol at a volume ratio of 20, adding phospholipids, rare ginsenoside: phospholipid = 1:0.5-1.5, and then adding phytosterols, rare ginsenoside: phytosterols = 1:0.2-0.6, stirring and reacting at 85° C. for 3 hours to obtain a first reactant; Step 2, adding polyvinylpyrrolidone K30 to the first reactant, rare ginsenoside: polyvinylpyrrolidone K30 = 1:0.05-0.3, and continuing to stir at 85° C. to react for 3 hours to obtain a second reactant; Step 3, adding sucrose fatty acid ester to the second reactant, rare ginsenoside: sucrose fatty acid ester = 1:0.2, stirring at 85° C. to react for 4 hours, to obtain a third reactant; Step 4, separating the precipitate and the clear liquid of the third reactant, dissolving the obtained precipitate with an ethanol solvent, and continuing to add ethanol dropwise at 85° C. with stirring, repeating 3-4 times, and then removing the ethanol through reduced pressure concentration to obtain a concentrated solution; Step 5, placing the concentrated liquid in a shearing machine, a homogenizer and a vacuum freeze-heating dryer for processing to obtain a micro-particle powder containing ginsenoside liposomes.

[0005] Furthermore, the phospholipid is one or more of soybean lecithin, sunflower lecithin and egg yolk lecithin.

[0006] Furthermore, the vacuum freeze-heating dryer is composed of a spray freezing system and a vacuum heating drying system.

[0007] Furthermore, a spray freezing system includes a refrigerator, a freezing chamber, a two-way feed valve, a low-temperature pumping machine, an electric rotating frame, a lower grinding disc, an upper grinding disc, an atomizing nozzle and an annular spray pipe; a freezing chamber is installed in the refrigerator; a two-way feed valve is connected to the freezing chamber; a low-temperature pumping machine is connected to the freezing chamber; the two-way feed valve is connected to the electric rotating frame; an annular spray pipe is fixedly connected to the electric rotating frame; the outlet end of the two-way feed valve is rotatably connected to the atomizing nozzle, and the atomizing nozzle is connected to the outlet end of the two-way feed valve; the atomizing nozzle is connected to the annular spray pipe; a plurality of impact bulge structures are provided on the inner wall of the freezing chamber; all nozzle ends of the annular spray pipe are facing the impact bulge structure of the freezing chamber; a lower grinding disc is fixedly connected in the freezing chamber; an upper grinding disc close to the lower grinding disc is fixedly connected to the electric rotating frame.

[0008] Furthermore, an inner container is fixedly connected in the freezing chamber; the lower grinding disc and the upper grinding disc are both configured as an annular structure surrounding the outer side of the inner container.

[0009] Furthermore, the freezing chamber and the inner tank are both configured as an inverted cone structure that contracts downward.

[0010] Furthermore, the freezing chamber is provided with a plurality of spiral guide strip structures which are in close contact with the surface of the inner tank; the spiral guide strip structures of the freezing chamber are in close contact with the outer surface of the inner tank.

[0011] Furthermore, a plurality of impact nets are fixedly connected between the freezing chamber and the inner liner.

[0012] Furthermore, the inner liner is made of solid material, and the upper surface of the inner liner is set to a hemispherical structure; a plurality of through-hole structures are opened on the inner liner, and the lower outlet end of the through-hole structure is located on the side annular surface of the inner liner, and the lower outlet end of the through-hole structure is located on the side of the inner liner close to the impact net; a screen is fixedly connected to the inlet end of the through-hole structure of the inner liner.

[0013] Furthermore, a brush strip close to the surface of the inner container is fixedly connected to the electric rotating frame.

[0014] Beneficial effects of the present invention: The preparation method of the rare ginsenoside liposome of the present invention solves the problem that the rare ginsenoside is not dispersed or soluble in water, and also provides a vacuum freeze-heating dryer composed of a spray freezing system and a vacuum heating drying system. The spray freezing system first spray-freezes the extracted ginsenoside liposome solution and then continuously impacts and breaks it into dispersed micro-particle ice crystals. The ice crystals are sequentially sent into a vacuum heating drying system in a low flow density state to quickly dry the micro-particle powder containing the ginsenoside liposome. The smaller the particle size of the micro-particle powder containing the ginsenoside liposome, the easier it is to be absorbed by the human body, thereby improving the human body absorption bioavailability of conventional rare ginsenosides, and can continuously produce rare ginsenoside liposomes with high encapsulation rate and high drug loading, finally overcoming the technical disadvantage that the extracted ginsenoside liposome has low encapsulation rate and low drug loading after being processed into a pharmaceutical product, resulting in low human body absorption bioavailability of the ginsenoside liposome. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 It is a schematic diagram of the structure of a spray freezing system of the present invention; Figure 2 It is a schematic diagram of the structure of a freezing chamber of a spray freezing system of the present invention; Figure 3 It is a schematic diagram of the cross-sectional structure of a refrigeration chamber of a spray refrigeration system of the present invention; Figure 4 It is a schematic diagram of the cross-sectional structure of an upper grinding disc of a spray freezing system of the present invention; Figure 5 This is a schematic diagram of the structure of an upper grinding disc of a spray freezing system of the present invention; Figure 6 The figure is a schematic diagram of the inner tank structure of a spray freezing system of the present invention.

[0016] Figure numbers: 1-refrigeration machine, 2-freezing chamber, 201-impact convex block structure, 202-spiral guide strip structure, 21-two-way feeding valve, 22-low-temperature pumping machine, 23-electric rotating frame, 24-lower grinding disc, 25-upper grinding disc, 26-brush bar, 31-atomizing nozzle, 32-annular spray pipe, 4-inner tank, 401-through hole structure, 41-screen, 5-impact net. DETAILED DESCRIPTION

[0017] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0018] Example 1 A method for preparing rare ginsenoside liposomes, the method comprising the following steps: Step 1, using 50% rare ginsenoside extract as a raw material, dissolving it in 60% ethanol at a volume ratio of 20, adding phospholipids, rare ginsenoside: phospholipid = 1:0.5-1.5, the phospholipids are a mixture of soybean lecithin, sunflower lecithin and egg yolk lecithin, and then adding phytosterols, rare ginsenoside: phytosterols = 1:0.2-0.6, stirring and reacting at 85°C for 3h to obtain a first reactant; Step 2, adding polyvinylpyrrolidone K30 to the first reactant, rare ginsenoside: polyvinylpyrrolidone K30 = 1:0.05-0.3, and continuing to stir at 85° C. to react for 3 hours to obtain a second reactant; Step 3, adding sucrose fatty acid ester to the second reactant, rare ginsenoside: sucrose fatty acid ester = 1:0.2, stirring at 85° C. to react for 4 hours, to obtain a third reactant; Step 4, separating the precipitate and the clear liquid of the third reactant, dissolving the obtained precipitate with an ethanol solvent, and continuing to add ethanol dropwise at 85° C. with stirring, repeating 3-4 times, and then removing the ethanol through reduced pressure concentration to obtain a concentrated solution; Step 5, placing the concentrated liquid in a shearing machine, a homogenizer and a vacuum freeze-heating dryer for processing to obtain a particulate powder containing ginsenoside liposomes, wherein the vacuum freeze-heating dryer is composed of a spray freezing system and a vacuum heating drying system.

[0019] A spray freezing system, such as Figure 1-Figure 6 As shown, it includes a refrigerator 1, a freezing chamber 2, a two-way material delivery valve 21, a low-temperature material pumping machine 22, an electric rotating frame 23, a lower grinding disc 24, an upper grinding disc 25, an atomizing nozzle 31 and an annular material spraying pipe 32; the freezing chamber 2 is installed in the refrigerator 1; the upper part of the freezing chamber 2 is connected to the two-way material delivery valve 21; the lower part of the freezing chamber 2 is connected to the low-temperature material pumping machine 22; the two-way material delivery valve 21 is connected to the electric rotating frame 23, and the electric rotating frame 23 consists of an annular rotating frame and a DD motor that drives the annular rotating frame to rotate; the electric An annular spray pipe 32 is fixedly connected to the rotating frame 23; the outlet end of the two-way material delivery valve 21 is rotatably connected to the atomizing nozzle 31, and the atomizing nozzle 31 is connected to the outlet end of the two-way material delivery valve 21; the atomizing nozzle 31 is connected to the annular spray pipe 32; a plurality of impact convex block structures 201 are provided on the inner wall of the freezing chamber 2; all nozzle ends of the annular spray pipe 32 are facing the impact convex block structure 201 of the freezing chamber 2; a lower grinding disc 24 is fixedly connected in the freezing chamber 2; an upper grinding disc 25 close to the lower grinding disc 24 is fixedly connected to the electric rotating frame 23.

[0020] like Figure 3As shown, an inner liner 4 is fixedly connected to the freezing chamber 2; the lower grinding disc 24 and the upper grinding disc 25 are both arranged as annular structures surrounding the outer side of the inner liner 4; the freezing chamber 2 and the inner liner 4 are both arranged as inverted cone structures that contract downward; a plurality of spiral guide strip structures 202 are arranged on the freezing chamber 2; all the spiral guide strip structures 202 of the freezing chamber 2 are closely attached to the outer surface of the inner liner 4, and the spiral guide strip structures 202 passing between the inner wall of the freezing chamber 2 and the outer surface of the inner liner 4 together form a spiral flow channel.

[0021] The working steps of a spray freezing system of the present invention are as follows: first, the staff connects the two inlet ends of the two-way feeding valve 21 to the conveying equipment containing the extracted ginsenoside liposome solution and the compressed cold air conveying equipment respectively, and connects the outlet end of the low-temperature pumping machine 22 to the gas-solid separation device, wherein the gas outlet end of the external gas-solid separation device is connected to the circulating gas inlet end of the external compressed cold air conveying equipment, and the material outlet end of the external gas-solid separation device is connected to the material feed end of an external vacuum heating drying system. After the refrigerator 1 cools the interior of the freezing chamber 2 to a low-temperature environment, the external The compressed cold air conveying equipment continuously conveys a low-temperature cold air flow to the inside of the freezing chamber 2 through the two-way delivery valve 21, the atomizing nozzle 31 and the annular spray pipe 32. At the same time, the low-temperature pumping machine 22 continuously sucks the inside of the freezing chamber 2. The cold air flow successively flows through the spiral flow channel of the freezing chamber 2 and the low-temperature pumping machine 22. Finally, the cold air flow returns to the external compressed cold air conveying equipment through the air outlet end of the external gas-solid separation device, thereby realizing the circulation of the cold air flow between the freezing chamber 2 and the external compressed cold air conveying equipment, so that the inside of the freezing chamber 2 is kept in a low-temperature environment.

[0022] During this period, the electric rotating frame 23 drives the annular spray pipe 32, the atomizing nozzle 31 and the upper grinding disc 25 to rotate, and the externally connected ginsenoside liposome solution conveying equipment continuously conveys the extracted ginsenoside liposome solution to the atomizing nozzle 31 through the two-way conveying valve 21, and the atomizing nozzle 31 sprays the extracted ginsenoside liposome solution into the annular spray pipe 32 in the form of water mist, and the water mist is then sprayed outward from each nozzle end of the annular spray pipe 32, and at the same time, the water mist is quickly affected by the low temperature of the cold air flow to form ice crystals, and the ice crystals sprayed outward from each nozzle end of the annular spray pipe 32 will continuously hit the impact convex structure 201 in various areas of the inner wall of the freezing chamber 2, so that the ice crystals are broken after colliding with the impact convex structure 201, and the broken ice crystals fall downward between the lower grinding disc 24 and the upper grinding disc 25, and the rotating upper grinding disc 25 cooperates with the stationary lower grinding disc 24 to crush the broken ice crystals. The ice crystals are ground into microparticles of uniform coarseness and fineness. The ice crystals that have been ground between the upper grinding disc 25 and the lower grinding disc 24 flow downward along the spiral flow channel between the freezing chamber 2 and the inner tank 4 along with the cold air flow. The microparticles of ice crystals are continuously pumped into an external gas-solid separation device by a low-temperature pump 22, and the microparticles of ice crystals pass through the discharge end of the external gas-solid separation device and enter an external vacuum heating and drying system. The external vacuum heating and drying system quickly dries the microparticles of ice crystals to obtain microparticles of ginsenoside liposomes. The smaller the particle size of the microparticles of ginsenoside liposomes, the easier it is to be absorbed by the human body, thereby improving the human body absorption bioavailability of conventional rare ginsenosides. At the same time, the spray freezing system and the vacuum heating and drying system provided by the present invention can realize continuous production of rare ginsenoside liposomes with high encapsulation rate and high drug loading without stopping the machine.

[0023] Example 2 On the basis of Example 1, Figure 1-Figure 6 As shown, in the present embodiment, a plurality of impact nets 5 are fixedly connected in the spiral flow channel between the freezing chamber 2 and the inner liner 4; when ice crystals flow downward along the spiral guide strip structure 202 of the freezing chamber 2 with the cold air flow, the ice crystals will continuously impact on the impact net 5, so that the ice crystals in the cold air flow are further broken, and the ice crystals can be further dispersed in the cold air flow while being continuously impacted by the impact net 5; the inner liner 4 is made of solid material, and the upper surface of the inner liner 4 is set as a hemispherical structure; the inner liner 4 is provided with a plurality of through hole structures 401 obliquely penetrated in the up and down directions, and the lower outlet end of the through hole structure 401 is located on the side ring surface of the inner liner 4, and the lower outlet end of the through hole structure 401 is located on the side of the inner liner 4 close to the impact net 5; a screen 41 for intercepting ice crystals is fixedly connected to the inlet end of each through hole structure 401 of the inner liner 4; three brush strips 26 close to the surface of the inner liner 4 are fixedly connected to the electric rotating frame 23.

[0024] After the compressed air is sprayed into the freezing chamber 2, it flows in the form of a cold air flow, wherein part of the cold air flow carries ice crystals and flows downward along the spiral guide strip structure 202 of the freezing chamber 2. During this process, another part of the cold air flow will pass through the screen 41 from top to bottom and through each through-hole structure 401 of the inner tank 4, and flow downward into the spiral flow channel between the freezing chamber 2 and the inner tank 4, so that the ice crystals carried by the cold air flow originally flowing downward along the spiral flow channel are further dispersed by the cold air flow flowing out of the through-hole structure 401, thereby further reducing the proportion of ice crystals in the cold air flow, and the through-hole structure 401 is arranged on the side of the inner tank 4 close to the impact net 5, and the cold air flow flowing out of the through-hole structure 401 can increase the ice crystal content along the spiral flow channel. The cold air flow and the overall flow rate of ice crystals flowing downward in the flow channel increase the impact force of ice crystals hitting the impact net 5 and the fluidity of passing through the impact net 5, thereby preventing a small amount of ice crystals gathered into a group from being stuck in the impact net 5 and causing blockage. The lower the proportion of ice crystals in the cold air flow, the lower the wear of the cold air flow by the ice crystals in the cold air flow on the interior of the low-temperature pumping machine 22 when the cold air flow flows through the interior of the low-temperature pumping machine 22, thereby providing anti-wear protection for the interior of the low-temperature pumping machine 22 and increasing the service life of the low-temperature pumping machine 22. The electric rotating frame 23 drives the three brush strips 26 to rotate closely against the surface of the inner tank 4. The brush strips 26 can promptly brush the ice crystals attached to the screen 41 downward along the surface of the hemispherical structure of the inner tank 4.

[0025] Although the present disclosure has been shown and described with reference to specific exemplary embodiments of the present disclosure, it should be understood by those skilled in the art that various changes in form and details may be made to the present disclosure without departing from the spirit and scope of the present disclosure as defined by the appended claims and their equivalents. Therefore, the scope of the present disclosure should not be limited to the above-mentioned embodiments, but should be determined not only by the appended claims, but also by the equivalents of the appended claims.

Claims

1. A method for preparing rare ginsenoside liposomes, the method comprising the following steps: Step 1, using 50% rare ginsenoside extract as a raw material, dissolving it in 60% ethanol at a volume ratio of 20, adding phospholipids, rare ginsenoside: phospholipid = 1:0.5-1.5, and then adding phytosterols, rare ginsenoside: phytosterols = 1:0.2-0.6, stirring and reacting at 85° C. for 3 hours to obtain a first reactant; Step 2, adding polyvinylpyrrolidone K30 to the first reactant, rare ginsenoside: polyvinylpyrrolidone K30 = 1:0.05-0.3, and continuing to stir at 85° C. to react for 3 hours to obtain a second reactant; Step 3, adding sucrose fatty acid ester to the second reactant, rare ginsenoside: sucrose fatty acid ester = 1:0.2, stirring at 85° C. to react for 4 hours, to obtain a third reactant; Step 4, separating the precipitate and the clear liquid of the third reactant, dissolving the obtained precipitate with an ethanol solvent, and continuing to add ethanol dropwise at 85° C. with stirring, repeating 3-4 times, and then removing the ethanol through reduced pressure concentration to obtain a concentrated solution; Step 5, placing the concentrated liquid in a shearing machine, a homogenizer and a vacuum freeze-heating dryer for processing to obtain a micro-particle powder containing ginsenoside liposomes.

2. The method for preparing rare ginsenoside liposomes according to claim 1, characterized in that: The lecithin is one or more of soybean lecithin, sunflower lecithin and egg yolk lecithin.

3. The method for preparing a rare ginsenoside liposome according to claim 1, characterized in that: The vacuum freeze-heating dryer consists of a spray freezing system and a vacuum heating drying system.

4. A method for preparing a rare ginsenoside liposome according to claim 3, wherein the spray freezing system comprises a refrigerator (1), a freezing chamber (2), a two-way material delivery valve (21), a low-temperature material pumping machine (22), an electric rotating frame (23), a lower grinding disc (24), an upper grinding disc (25), an atomizing nozzle (31) and an annular material spraying pipe (32); a freezing chamber (2) is installed in the refrigerator (1); a two-way material delivery valve (21) is connected to the freezing chamber (2); a low-temperature material pumping machine (22) is connected to the freezing chamber (2); the two-way material delivery valve (21) is connected to the electric rotating frame (23); An annular material spraying pipe (32) is fixedly connected to the movable rotating frame (23); the outlet end of the two-way material delivery valve (21) is rotatably connected to an atomizing nozzle (31), and the atomizing nozzle (31) is connected to the outlet end of the two-way material delivery valve (21); the atomizing nozzle (31) is connected to the annular material spraying pipe (32); a plurality of impact convex block structures (201) are provided on the inner wall of the freezing chamber (2); all the nozzle ends of the annular material spraying pipe (32) face the impact convex block structure (201) of the freezing chamber (2); a lower grinding disc (24) is fixedly connected in the freezing chamber (2); and an upper grinding disc (25) close to the lower grinding disc (24) is fixedly connected to the electric rotating frame (23).

5. The method for preparing rare ginsenoside liposomes according to claim 4, characterized in that: An inner liner (4) is fixedly connected to the freezing chamber (2); the lower grinding disc (24) and the upper grinding disc (25) are both arranged as an annular structure surrounding the outer side of the inner liner (4).

6. The method for preparing rare ginsenoside liposomes according to claim 5, characterized in that: The freezing chamber (2) and the inner container (4) are both configured as an inverted cone structure that contracts downward.

7. According to the method for preparing rare ginsenoside liposomes as claimed in claim 5, a plurality of spiral guide strip structures (202) are provided on the freezing chamber (2) and are in close contact with the surface of the inner liner (4); the spiral guide strip structures (202) of the freezing chamber (2) are in close contact with the outer surface of the inner liner (4).

8. The method for preparing rare ginsenoside liposomes according to claim 5, characterized in that: A plurality of impact nets (5) are fixedly connected between the freezing chamber (2) and the inner container (4).

9. The method for preparing rare ginsenoside liposomes according to any one of claims 5 to 8, characterized in that: The inner liner (4) is made of solid material, and the upper surface of the inner liner (4) is set to a hemispherical structure; a plurality of through hole structures (401) are opened on the inner liner (4), and the lower outlet ends of the through hole structures (401) are located on the side annular surface of the inner liner (4), and the lower outlet ends of the through hole structures (401) are all located on the side of the inner liner (4) close to the impact net (5); and the screen (41) is fixedly connected to the upper inlet end of the through hole structure (401) of the inner liner (4).

10. The method for preparing rare ginsenoside liposomes according to claim 9, characterized in that: A brush strip (26) is fixedly connected to the electric rotating frame (23) and is in close contact with the surface of the inner container (4).

Images