NAD microcapsule powder, and preparation method and application thereof

Abstract

The application provides NAD microcapsule powder and a preparation method and application thereof, and belongs to the technical field of biological medicine preparation. The NAD microcapsule powder comprises wall material and NAD core material; the mass ratio of the NAD core material and the raw material of the wall material is 20-30:70-80; the raw material of the wall material comprises octenyl succinate starch, gum arabic, sunflower lecithin and malt dextrin with a mass ratio of 20-25:1-2:10-20:30-50. The NAD microcapsule powder can resist gastric acid digestion, improve the bioavailability of NAD, solve the problem that NAD is easy to lose activity when taken orally, enrich the administration types of NAD, and has the advantages of simple preparation process, low cost, high yield, stable NAD content, good flowability of the prepared NAD microcapsule powder and good market promotion and application value.

Description

Technical Field

[0001] This invention belongs to the field of biopharmaceutical preparation technology, specifically relating to an NAD microcapsule powder, its preparation method, and its application. Background Technology

[0002] NAD (nicotinamide adenine dinucleotide), also known as coenzyme I, is composed of nicotinamide, adenine, and two ribose sugars linked by a phosphodiester bond. It exists in its oxidized form (NAD). + It exists in both its NADH and reduced form (NADH), and participates in various enzymatic reactions as an electron carrier, via hydride anions (H+). - ) and proton (H + The transfer of ) enables the redox function.

[0003] The disadvantages of NAD include low availability, instability, and easy degradation. Orally ingested NAD is inactivated upon contact with gastric acid, resulting in significantly reduced absorption and consumption before it can exert its full effect, thus limiting its application. Currently, only tablets and injections are available on the market, while various other formulations have been developed or are under development, such as sublingual tablets, sustained-release coated microspheres, and capsules. The main reason for the limitation of oral administration of NAD is its low bioavailability, which can be attributed to its easy degradation and loss of activity in gastric acid, and the inconvenience of injection formulations. Summary of the Invention

[0004] The purpose of this invention is to provide a NAD microencapsulated powder that effectively protects NAD from decomposition, improves its bioavailability, and expands the application prospects of NAD.

[0005] This invention provides an NAD microcapsule powder, comprising a wall material and an NAD core material; The mass ratio of the raw materials for the NAD core material and the wall material is 20~30:70~80; The raw materials for the wall material include octenyl succinate starch ester, gum arabic, sunflower lecithin, and maltodextrin; The mass ratio of octenyl succinate starch ester, gum arabic, sunflower lecithin and maltodextrin is 20~25:1~2:10~20:30~50.

[0006] Preferably, the mass ratio of the raw materials for the NAD core material and the wall material is 25:75.

[0007] Preferably, the mass ratio of octenyl succinate starch ester, gum arabic, sunflower lecithin and maltodextrin is 20:2:15:38.

[0008] This invention provides a method for preparing the NAD microcapsule powder, comprising the following steps: The raw materials for the wall material are dissolved in water to obtain a wall material solution; The wall material solution and NAD core material are mixed and then homogenized to obtain a mixed system. The mixture was spray-dried to obtain NAD microcapsule powder.

[0009] Preferably, the mass percentage of the raw materials in the wall material solution is 20% to 25%.

[0010] Preferably, the homogenization process includes shearing and homogenization.

[0011] Preferably, the shearing speed is 8000~12000 rpm, and the shearing time is 8~12 min.

[0012] Preferably, the homogenization is performed 2 to 4 times, and the pressure for each homogenization is 500 to 700 bar.

[0013] Preferably, the inlet air temperature of the spray dryer is 140~160℃, and the outlet air temperature is 65~75℃; After spray drying, the product is passed through an 80-mesh sieve, and the undersize material is collected to obtain NAD microcapsule powder.

[0014] This invention provides a drug for NAD intervention in related diseases, comprising the NAD microcapsule powder or NAD microcapsule powder prepared by the preparation method and pharmaceutically acceptable excipients.

[0015] This invention provides an NAD microencapsulated powder, comprising a wall material and an NAD core material; the mass ratio of the raw materials of the NAD core material and the wall material is 20-30:70-80; the raw materials of the wall material include octenyl succinate starch ester, gum arabic, sunflower lecithin, and maltodextrin in a mass ratio of 20-25:1-2:10-20:30-50. The NAD microencapsulated powder encapsulates the NAD core material within the wall material, which not only improves storage stability but also resists gastric digestion, enhances NAD bioavailability, and solves the problem of easy loss of activity after oral administration, thus enriching the types of NAD delivery.

[0016] The present invention also provides a method for preparing the NAD microcapsule powder, which is simple to operate, has low preparation cost, high yield, stable NAD content, and produces NAD microcapsule powder with good flowability, and has good market promotion and application value. Attached Figure Description

[0017] Figure 1 This is a flowchart illustrating the preparation of NAD microcapsule powder according to the present invention; Figure 2 Electron microscopy observation results of NAD raw materials; Figure 3 Electron microscopy observation results of NAD microcapsule powder prepared in Example 1; Figure 4 Electron microscopy observation results of NAD microcapsule powder prepared in Example 2; Figure 5 Electron microscopy observation results of NAD microcapsule powder prepared in Example 3; Figure 6 The results are from the storage stability test of NAD raw materials; Figure 7 The results are for the storage stability determination of NAD microcapsule powder; Figure 8 The results are based on the gastric digestion assay of NAD raw material and NAD microcapsule powder. Detailed Implementation

[0018] This invention provides an NAD microcapsule powder, comprising a wall material and an NAD core material; The mass ratio of the raw materials for the NAD core material and the wall material is 20~30:70~80; The raw materials for the wall material include octenyl succinate starch ester, gum arabic, sunflower lecithin, and maltodextrin; The mass ratio of octenyl succinate starch ester, gum arabic, sunflower lecithin and maltodextrin is 20~25:1~2:10~20:30~50.

[0019] In this invention, the NAD microcapsule powder has a core-shell structure, consisting of microparticles encapsulating an NAD core material with a particle size of 130-145 nm. The wall material serves as the shell layer, encapsulating the NAD core material. The NAD core material is purchased from Huihai (Suzhou) Biotechnology Co., Ltd. The preferred mass ratio of the raw materials for the NAD core material to the wall material is 25:75.

[0020] In this invention, the mass ratio of octenyl succinate starch ester, gum arabic, sunflower lecithin, and maltodextrin can be 20:2:15:38, 20:1.5:15:38.5, or 20:1:12:42. Octenyl succinate starch ester, as the main emulsifier and main wall material component, has the functions of emulsification, encapsulation, and improved stability and strength. Gum arabic, as a natural emulsifier and film-forming component, plays a stabilizing, protective, slow-release, and easy-drying role. Sunflower lecithin, as an auxiliary emulsifier, has interfacial stability and makes the mixed system more stable, with higher encapsulation and better rehydration. Maltodextrin, as a filler and carrier, has the functions of increasing yield, reducing cost, preventing sticking, and aiding solubility. This invention does not impose special restrictions on the source of the octenyl succinate starch ester, gum arabic, sunflower lecithin, and maltodextrin; any source of the above-mentioned components known in the art may be used.

[0021] This invention provides a method for preparing the NAD microcapsule powder, comprising the following steps: The raw materials for the wall material are dissolved in water to obtain a wall material solution; The wall material solution and NAD core material are mixed and then homogenized to obtain a mixed system. The mixture was spray-dried to obtain NAD microcapsule powder.

[0022] This invention dissolves the raw materials of the wall material in water to obtain a wall material solution.

[0023] In this invention, the mass percentage of the raw materials in the wall material solution is preferably 20% to 25%, and can be 23%. This invention does not have any particular limitation on the type of water used; pharmaceutical water well-known in the art can be used, such as distilled water or purified water. The dissolution is preferably carried out under heating conditions to ensure rapid and complete dissolution of the raw materials. The heating temperature is preferably 55 to 65°C, and can be 58 to 62°C, or 60°C.

[0024] In this invention, when the wall material solution and the NAD core material are mixed, it is preferable to add the NAD core material to the wall material solution. The homogenization treatment preferably includes shearing and homogenization. The homogenization treatment serves to: 1) refine particle size: using high-pressure shearing and impact to pulverize material particles / droplets to the micron or nanometer scale, achieving ultrafine dispersion; 2) uniform mixing: breaking up agglomerates, making the component distribution of the multiphase system highly uniform, and improving the stability of the system; 3) emulsification homogenization: preparing a stable emulsion to prevent oil-water separation. The shearing speed is preferably 8000~12000 rpm, or 9000~11000 rpm, or 10000 rpm. The shearing time is preferably 8~12 min, or 9~11 min, or 10 min. The number of homogenizations is preferably 2~4 times, or 3 times. The pressure of each homogenization is preferably 500~700 bar, or 550~650 bar, or 600 bar.

[0025] In this invention, the inlet air temperature for spray drying is preferably 140~160℃, and can be 150℃. The outlet air temperature for spray drying is preferably 65~75℃, and can be 70℃. After spray drying, the product is preferably passed through an 80-mesh sieve, and the undersize material is collected to obtain NAD microcapsule powder.

[0026] In this invention, the NAD microcapsule powder exhibits excellent storage stability. When stored at 4°C for 30 days, the NAD content retention rate remains above 98%. When stored at room temperature (25°C) for 30 days, the NAD content retention rate remains above 80%. When stored at 40°C for 30 days, the NAD content retention rate remains around 50%. When stored at 60°C for 30 days, the NAD content retention rate remains above 40%, which is a significant improvement compared to NAD raw materials (40-45% retention rate at 25°C and 10% retention rate at 60°C).

[0027] In this invention, the NAD microcapsule powder also exhibits good resistance to gastric digestion. After digestion in simulated gastric juice for 120 minutes, the NAD content retention rate of the NAD microcapsule powder is over 60%, while the NAD content retention rate of the NAD raw material is around 20%, indicating that the NAD microcapsule powder provides three times the NAD utilization rate compared to the NAD raw material when administered orally.

[0028] The following detailed description, in conjunction with embodiments, illustrates an NAD microcapsule powder, its preparation method, and its applications provided by the present invention. However, these descriptions should not be construed as limiting the scope of protection of the present invention.

[0029] Example 1 A method for preparing NAD microcapsule powder 1. Raw material composition: Core material: NAD 25g; Ingredients: 15g sunflower lecithin, 20g octenyl succinate starch ester, 2g gum arabic, 38g maltodextrin, and 300g purified water.

[0030] 2. Preparation process Step 1: Place the auxiliary materials in 60℃ pure water and stir until completely dissolved to obtain the wall material solution; Step 2: Lower the temperature of the wall material solution to 40°C, add the NAD core material, and after it dissolves, shear it at 10,000 rpm for 10 minutes to obtain a mixed system; Step 3: The sheared mixture is subjected to high-pressure homogenization at 600 bar for a total of 3 times to obtain a homogeneous system; Step 4: Spray dry the homogenized system at an inlet air temperature of 150℃ and an outlet air temperature of 70℃. Pass the powder through an 80-mesh sieve to obtain the finished NAD microcapsule powder.

[0031] Example 2 A method for preparing NAD microcapsule powder 1. Raw material composition: Core material: NAD 25g; Ingredients: 10g sunflower lecithin, 25g octenyl succinate starch ester, 1.5g gum arabic, 38.5g maltodextrin, and 300g purified water.

[0032] 2. Preparation process Same preparation method as in Example 1.

[0033] Example 3 A method for preparing NAD microcapsule powder 1. Raw material composition: Core material: NAD 25g; Ingredients: 12g sunflower lecithin, 20g octenyl succinate starch ester, 1g gum arabic, 42g maltodextrin, and 300g purified water.

[0034] 2. Preparation process Same preparation method as in Example 1.

[0035] Example 4 Characterization of NAD microcapsule powder The particle size and zeta potential of the NAD microcapsule powder prepared in Examples 1-3 were measured. At the same time, the spherical structure of the NAD microcapsule powder and the NAD core structure were observed by electron microscopy.

[0036] Particle size and zeta potential: The NAD raw material and the NAD microcapsule powder of Examples 1-3 were dispersed in water at a concentration of 0.02 g / mL, filtered with a 0.45 μm filter, and the particle size and zeta potential of the composite particles were measured using a Malvern nanoparticle size potentiometer.

[0037] The results are shown in Table 1. As can be seen from Table 1, the particle size of the NAD microcapsule powder is significantly reduced compared to the NAD raw material, dispersing between 133.5 and 143.6 nm. Simultaneously, the zeta potential of the NAD microcapsule powder shows a significant change compared to the NAD raw material, ranging from -17.9 to 18.47 mV.

[0038] Table 1. Particle size and zeta potential results of NAD microcapsules

[0039] Electron microscopy results are shown in Figures 2-5 The NAD raw material was observed to be rod-shaped, while the NAD microcapsule powder all exhibited a spherical structure. This indicates that the NAD microcapsule powder formed nanospheres.

[0040] Example 5 Storage stability of NAD microcapsule powder The method for detecting the storage stability of NAD microcapsules involves determining the effect of different temperatures on the retention rate of the microcapsules. The NAD microcapsules prepared in Examples 1-3 and the NAD raw material were stored at different temperatures of 4℃, 25℃, 40℃, and 60℃ for 30 days, respectively. The NAD content was measured every 5 days using HPLC. The specific steps are as follows: 1. Preparation of external standard solution: Weigh 25 mg of NAD standard, place it in a 25 mL volumetric flask, add pure water to dissolve and dilute to the mark, shake well, filter through a 0.45 μm aqueous filter membrane, and take the filtrate as the test solution.

[0041] 2. Sample preparation: Weigh an appropriate amount (calculate the mass of sample containing 25mg of NAD according to the NAD content conversion, for example, if the sample content is 10%, then weigh 250mg of sample) and mix it evenly. Place it in a 25mL volumetric flask, add pure water to dissolve and dilute to the mark, shake well, filter through a 0.45μm aqueous filter membrane, and take the filtrate as the test solution.

[0042] 3. Reference chromatographic conditions: Column: C18 column (5μm×250mm×4.6mm); Mobile phase: methanol / 10mmol / L potassium dihydrogen phosphate aqueous solution (pH=5.5)=10:90; Flow rate: 1.0mL / min; Column oven temperature: 30℃; Injection volume: 5μL; UV detection wavelength: 260nm; Analysis time: 15min.

[0043] 4. Determination: Take the solution to be tested, analyze it with high performance liquid chromatography, and quantify it using the external standard method.

[0044] 5. Presentation of Analysis Results Formula I; W—NAD content in the sample, %; A1—NAD peak area in the external standard solution; A2—NAD peak area in the sample; m1—Mass of NAD standard weighed, mg; m2—mass of the sample taken, mg; V1—volume of external standard solution diluted to volume, mL; V2 — The final volume of the sample, in mL.

[0045] The retention rate was calculated using Formula II. The result for the NAD microcapsules was calculated as the average value of the products from Examples 1-3.

[0046] Retention rate (%) = NAD content in the product after storage / NAD content in the initial product × 100% Formula II.

[0047] See results Figure 6 and Figure 7The retention rates of both NAD microcapsules and NAD raw materials decreased with increasing temperature and prolonged storage time. The retention rate of NAD raw materials decreased more significantly between 25 and 60°C, while the retention rate of NAD microcapsules decreased with prolonged storage time, but the decrease was not as significant as that of NAD raw materials. This indicates that the preparation of NAD microcapsules is beneficial to improving the retention rate of NAD and has good storage stability.

[0048] Example 6 In vitro gastric juice digestion stability of NAD microcapsule powder Preparation of simulated gastric juice: Adjust the pH of NaCl solution (0.2% w / v) to 1.2 with concentrated hydrochloric acid, weigh out an appropriate amount of pepsin and add it to make the final concentration 3.2 g / L.

[0049] Appropriate amounts of NAD raw material and NAD microcapsule powder prepared in Examples 1-3 were weighed and placed in 10 mL of different simulated digestion solutions. The mixtures were then placed in a water bath at a constant temperature of 37°C and stirred at 100 r / min. The reaction solutions were placed in different test tubes, and the reactions were stopped at 10 min, 20 min, 30 min, 60 min, 90 min, and 120 min, respectively. The retention rates of the raw material and microcapsule powder at different times were measured. The retention rate was calculated using Formula III.

[0050] Retention rate (%) = NAD content in the digested product / NAD content in the initial product × 100% Formula III.

[0051] See results Figure 8 As digestion time increased, the retention rates of both NAD microcapsule powder and NAD raw materials showed a decreasing trend. However, the retention rate of NAD microcapsule powder was over 60% after 120 minutes of digestion, while the retention rate of NAD raw materials was only 30%. This indicates that NAD microcapsule powder can effectively resist gastric juice digestion compared to NAD raw materials, greatly improving the NAD retention rate.

[0052] Based on the results of the above embodiments, the prepared NAD microcapsule powder not only has good storage stability, but also resists gastric digestion, ensuring the bioavailability of oral NAD administration.

[0053] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A NAD microcapsule powder, characterized in that, Including wall materials and NAD core materials; The mass ratio of the raw materials for the NAD core material and the wall material is 20~30:70~80; The raw materials for the wall material include octenyl succinate starch ester, gum arabic, flower lecithin and maltodextrin; The mass ratio of octenyl succinate starch ester, gum arabic, sunflower lecithin and maltodextrin is 20~25:1~2:10~20:30~50.

2. The NAD microcapsule powder according to claim 1, characterized in that, The mass ratio of the raw materials for the NAD core material and the wall material is 25:

75.

3. The NAD microcapsule powder according to claim 1, characterized in that, The mass ratio of octenyl succinate starch ester, gum arabic, sunflower lecithin, and maltodextrin is 20:2:15:

38.

4. A method for preparing NAD microcapsule powder according to any one of claims 1 to 3, characterized in that, Includes the following steps: The raw materials for the wall material are dissolved in water to obtain a wall material solution; The wall material solution and NAD core material are mixed and then homogenized. A mixed system is obtained; The mixture was spray-dried to obtain NAD microcapsule powder.

5. The preparation method according to claim 4, characterized in that, The mass percentage of the raw materials in the wall material solution is 20% to 25%.

6. The preparation method according to claim 4, characterized in that, The homogenization process includes shearing and homogenization.

7. The preparation method according to claim 6, characterized in that, The shearing speed ranges from 8000 to 12000 rpm, and the shearing time ranges from 8 to 12 minutes.

8. The preparation method according to claim 6, characterized in that, The homogenization is performed 2 to 4 times, with each homogenization performed at a pressure of 500 to 700 bar.

9. The preparation method according to any one of claims 4 to 8, characterized in that, The inlet air temperature of the spray dryer is 140~160℃, and the outlet air temperature is 65~75℃. After spray drying, the product is passed through an 80-mesh sieve, and the undersize material is collected to obtain NAD microcapsule powder.

10. A drug for NAD intervention in related diseases, characterized in that, It includes the NAD microcapsule powder according to any one of claims 1 to 3 or the NAD microcapsule powder prepared by the preparation method according to any one of claims 4 to 8 and pharmaceutically acceptable excipients.

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