An oral superoxide dismutase-containing instant film and a preparation process thereof

Abstract

The application discloses an oral superoxide dismutase-containing instant film and a preparation process thereof, and belongs to the technical field of oral products. The application is prepared from dry bases, water and a superoxide dismutase solution; the dry bases are a composition of film-forming materials, glycerol, active ingredients, erythritol, citric acid, blueberry essence and sodium citrate, or a composition of film-forming materials, glycerol, active ingredients, citric acid, blueberry essence, sodium citrate and trehalose, or a composition of film-forming materials, glycerol, active ingredients, erythritol, citric acid, blueberry essence, sodium citrate and trehalose; and the preparation process of the application comprises material stirring, defoaming and coating film preparation. The application breaks through the application limitation of traditional drug forms and applies the technology to the field of new health functional foods.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of oral products, more particularly to a superoxide dismutase-containing oral fast-dissolving film and a preparation process thereof. BACKGROUND

[0002] The oral fast-dissolving film is a dosage form that dissolves and releases drugs through the oral mucosa rapidly and is suitable for local or systemic administration. The existing technology mainly focuses on the drug dosage form, including the formula composition, film-forming process, active ingredient protection technology and the like. The oral fast-dissolving film prepared by the existing technology has a difficult balance between mechanical strength and flexibility (too brittle or too sticky) and an uncontrollable dissolution rate. SUMMARY

[0003] The present application aims to overcome the deficiencies of the existing technology and provide a superoxide dismutase-containing oral fast-dissolving film and a preparation process thereof, which break through the application limitations of traditional drug dosage forms and apply the technology to the field of new health functional foods.

[0004] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0005] A superoxide dismutase-containing oral fast-dissolving film is prepared from a dry base, water and a superoxide dismutase solution.

[0006] The dry base is a combination of a film-forming material, glycerol, an active ingredient, erythritol, citric acid, blueberry flavor and sodium citrate or a combination of a film-forming material, glycerol, an active ingredient, citric acid, blueberry flavor, sodium citrate and trehalose or a combination of a film-forming material, glycerol, an active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate and trehalose; the film-forming material is a combination of hydroxypropyl methylcellulose and pullulan; and the active ingredient is one or both of silkworm chrysalis protein peptide and blueberry anthocyanin.

[0007] Further, the mass ratio of the dry base to water is (14.6-20.2) g:30 mL; the volume ratio of water to the superoxide dismutase solution is 1:1; and the concentration of superoxide dismutase in the superoxide dismutase solution is 10000 U / mL-100000 U / mL.

[0008] Further, when the dry base is a combination of a film-forming material, glycerol, an active ingredient, erythritol, citric acid, blueberry flavor and sodium citrate, the mass ratio of the film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor and sodium citrate is (8.3-9):(2-2.5):(0.1-1.3):(2.9-3.1):(0.4-0.6):(0.7-0.9):(0.2-0.4).

[0009] Further, when the dry base is a combination of the film forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose, the mass ratio of the film forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose is (8.3~9):(2~2.5):(0.1~1.3):(2.9~3.1):(0.4~0.6):(0.7~0.9):(0.2~0.4):(1.8~2.4).

[0010] Further, when the dry base is a combination of the film forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose, the mass ratio of the film forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose is (8.3~9):(2~2.5):(0.1~1.3):(2.9~3.1):(0.4~0.6):(0.7~0.9):(0.2~0.4):(1.8~2.4).

[0011] Further, the solvent used by the superoxide dismutase solution is a phosphate buffer solution, and the phosphate concentration in the phosphate buffer solution is 20mmol / L; the phosphate is disodium hydrogen phosphate dodecahydrate.

[0012] A preparation process of an oral superoxide dismutase-containing instant film, comprising the following steps:

[0013] (1) The film forming material, water and glycerol are stirred and dissolved to obtain a first glue solution;

[0014] (2) The citric acid, blueberry flavor and sodium citrate are added to the first glue solution, and the erythritol is added or not added, and then stirred and dissolved to obtain a second glue solution;

[0015] (3) When the erythritol is added in step (2), the superoxide dismutase solution and the active ingredient are added to the second glue solution, and the trehalose is added or not added, and then stirred and dissolved to obtain a slurry; when the erythritol is not added in step (2), the superoxide dismutase solution, the active ingredient and the trehalose are added to the second glue solution, and then stirred and dissolved to obtain a slurry;

[0016] (4) The slurry is subjected to a defoaming treatment, and then is coated and formed into a film to obtain the oral superoxide dismutase-containing instant film.

[0017] Further, in step (4), the defoaming treatment is divided into three stages, the defoaming time of the first stage is 60s, the defoaming rotation speed is 1000r / min, and the vacuum degree is 101.7kPa; the defoaming time of the second stage is 100s, the defoaming rotation speed is 1600r / min, and the vacuum degree is 0.5kPa; the defoaming time of the third stage is 80s, the defoaming rotation speed is 1800r / min, and the vacuum degree is 0.5kPa.

[0018] Further, in step (4), the coating temperature is 55-65 DEG C, the coating speed is 5-15 mm / s, and the coating thickness is 0.6 mm+ / -0.1.

[0019] In summary, the present application has the following advantages:

[0020] The present application realizes efficient delivery of SOD by using food-grade carriers, opens up a new application of the oral dissolving film technology in the field of functional foods, and the obtained oral dissolving film has the following advantages:

[0021] (1) independently packaged, can be carried around;

[0022] (2) dissolving in the mouth, no need for water to send service;

[0023] (3) providing antioxidant health function;

[0024] (4) using food-grade film-forming material, ensuring safety;

[0025] (5) SOD activity is stable;

[0026] (6) formula palatability is strong, improving the eating experience;

[0027] (7) has mechanical strength and flexibility. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 The linear relationship diagram of the concentration of the superoxide dismutase solution added when preparing the oral dissolving film 3 in Example 2 and the oral dissolving film 4 to the oral dissolving film 5 in Example 3 and the detected amount of superoxide dismutase in the finally prepared oral dissolving film;

[0029] In the figure: the linear equation is y=0.0208x+142.05, R 2 =0.988. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0031] A preparation process of an oral dissolving film containing superoxide dismutase, comprising the following steps:

[0032] (1) stirring and dissolving the film-forming material (a combination of hydroxypropyl methylcellulose and pullulan), water and glycerol to obtain a first glue solution;

[0033] (2) adding citric acid, blueberry essence, sodium citrate, adding or not adding erythritol to the first glue solution, stirring and dissolving to obtain a second glue solution;

[0034] (3) when erythritol is added in step (2), adding superoxide dismutase solution and active ingredients to the second glue solution, adding or not adding trehalose, stirring and dissolving to obtain a slurry; when erythritol is not added in step (2), adding superoxide dismutase solution, active ingredients and trehalose to the second glue solution, stirring and dissolving to obtain a slurry;

[0035] The concentration of superoxide dismutase in the superoxide dismutase solution is 10000 U / mL-100000 U / mL, and the solvent used is a phosphate buffer solution with a phosphate concentration of 20 mmol / L (prepared by mixing phosphate and water), and the phosphate is preferably disodium hydrogen phosphate dodecahydrate; the active ingredient is one or both of silkworm chrysalis protein peptide and blueberry anthocyanin;

[0036] (4) carrying out defoaming treatment on the slurry (the defoaming treatment is divided into three stages, the defoaming time of the first stage is 60 s, the defoaming rotation speed is 1000 r / min, and the vacuum degree is 101.7 kPa; the defoaming time of the second stage is 100 s, the defoaming rotation speed is 1600 r / min, and the vacuum degree is 0.5 kPa; the defoaming time of the third stage is 80 s, the defoaming rotation speed is 1800 r / min, and the vacuum degree is 0.5 kPa), and then carrying out coating and film forming (the coating temperature is 55-65℃, the coating speed is 5-15 mm / s, and the coating thickness is 0.6 mm±0.1) to obtain the oral dissolving film containing superoxide dismutase;

[0037] The dry base is a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry essence and sodium citrate, or a combination of film-forming material, glycerol, active ingredient, citric acid, blueberry essence, sodium citrate and trehalose, or a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry essence, sodium citrate and trehalose;

[0038] When the dry base is a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry essence and sodium citrate, the mass ratio of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry essence and sodium citrate is (8.3-9):(2-2.5):(0.1-1.3):(2.9-3.1):(0.4-0.6):(0.7-0.9):(0.2-0.4);

[0039] When the dry base is a combination of the film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose, the mass ratio of the film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose is (8.3~9):(2~2.5):(0.1~1.3):(2.9~3.1):(0.4~0.6):(0.7~0.9):(0.2~0.4):(1.8~2.4).

[0040] When the dry base is a combination of the film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose, the mass ratio of the film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose is (8.3~9):(2~2.5):(0.1~1.3):(2.9~3.1):(0.4~0.6):(0.7~0.9):(0.2~0.4):(1.8~2.4).

[0041] The amount ratio of the dry base and water is (14.6~20.2)g:30mL; the volume ratio of water and superoxide dismutase solution is 1:1.

[0042] Example 1

[0043] a. 7.5g of hydroxypropyl methyl cellulose (purchased from Taian Ruite Cellulose Co., Ltd., model 60RT5, batch number 250220-12), 0.84g of pullulan (purchased from Shandong Mi Mei Biological Technology Co., Ltd., batch number P2025050704), 30ml of water and 2.5g of glycerol (purchased from Fengyi International Group, batch number SE2411-009) were stirred and dissolved at room temperature to form a hydroxypropyl methyl cellulose-pullulan first glue solution;

[0044] b. 3g of erythritol (purchased from Henan Hengrui Starch Technology Co., Ltd., model HS-OC-504, batch number 20250604), 0.5g of citric acid (purchased from Weifang Yingxuan Industry Co., Ltd., batch number 1AX2201018), 0.33g of sodium citrate (purchased from Shandong Yingxuan Industry Co., Ltd., batch number 20250306), 0.84g of blueberry flavor (purchased from Guangzhou Yanwei Jiang Biological Technology Co., Ltd., batch number ZVJ3005) were added to the hydroxypropyl methyl cellulose-pullulan first glue solution, and stirred and dissolved at room temperature to obtain a hydroxypropyl methyl cellulose-pullulan second glue solution;

[0045] c. Add 30 mL of superoxide dismutase solution with a concentration of 10,000 U / mL of superoxide dismutase [the superoxide dismutase solution is prepared by mixing SOD liquid with a 20 mmol / L sodium phosphate buffer; the SOD liquid is prepared according to the examples 1-5 of the patent "A high-temperature-resistant recombinant mutant SOD, its coding gene and application" (CN114277004A), and the sodium phosphate buffer is prepared by mixing twelve water sodium phosphate dibasic (purchased from Jiangsu Kelun Food Ingredients Co., Ltd.; batch number 23102501) and water] to the second hydroxypropyl methylcellulose-pullulan glue solution, 1 g of silkworm chrysalis protein peptide (purchased from Hainan Huapei Biological Technology Co., Ltd., batch number CY0250319), 0.16 g of blueberry anthocyanin (purchased from Shanxi Xinnuo Biological Technology Co., Ltd., batch number XN-2025030601), 2.4 g of trehalose (purchased from Hayashibara Co., Ltd., now renamed Nagase Microbiological Systems Co., Ltd., batch number 21169), and stirred and dissolved at room temperature to obtain a hydroxypropyl methylcellulose-pullulan slurry;

[0046] d. Put the hydroxypropyl methylcellulose-pullulan slurry into a vacuum defoaming container machine for defoaming treatment (the defoaming treatment is divided into three stages: the first stage of defoaming time is 60 s, the defoaming rotation speed is 1000 r / min, and the vacuum degree is 101.7 kPa; the second stage of defoaming time is 100 s, the defoaming rotation speed is 1600 r / min, and the vacuum degree is 0.5 kPa; the third stage of defoaming time is 80 s, the defoaming rotation speed is 1800 r / min, and the vacuum degree is 0.5 kPa);

[0047] e. The defoamed hydroxypropyl methylcellulose-pullulan slurry is transported to a mouth dissolving film coating machine and coated and formed at 60°C (coating speed is 15 mm / s, coating thickness is 0.6 mm±0.1) to obtain a mouth dissolving film 1.

[0048] The mouth dissolving film containing superoxide dismutase prepared in example 1 is detected, and the detection results are shown in table 1.

[0049] Table 1

[0050]

[0051] Example 2

[0052] a. Stir and dissolve 7.5 g of hydroxypropyl methylcellulose, 0.84 g of pullulan, 30 ml of water and 2 g of glycerol at room temperature to prepare a first glue solution A; stir and dissolve 7.5 g of hydroxypropyl methylcellulose, 0.84 g of pullulan, 30 ml of water and 2.5 g of glycerol at room temperature to prepare a first glue solution B;

[0053] b. Add 3 g of erythritol, 0.5 g of citric acid, 0.33 g of sodium citrate, and 0.84 g of blueberry flavor to the first glue solution A and the first glue solution B respectively, and stir to dissolve at room temperature to obtain the second glue solution C and the second glue solution D;

[0054] c. Add 30 mL of superoxide dismutase solution with a concentration of 10000 U / mL of superoxide dismutase, 1 g of silkworm pupa protein peptide, and 0.16 g of blueberry anthocyanin to the second glue solution C and the second glue solution D respectively, and stir to dissolve at room temperature to obtain the slurry 1 and the slurry 2;

[0055] d. Put the slurry 1 and the slurry 2 into a vacuum defoaming container machine respectively, and perform defoaming treatment (the defoaming treatment is divided into three stages, the defoaming time of the first stage is 60 s, the defoaming rotation speed is 1000 r / min, and the vacuum degree is 101.7 kPa; the defoaming time of the second stage is 100 s, the defoaming rotation speed is 1600 r / min, and the vacuum degree is 0.5 kPa; the defoaming time of the third stage is 80 s, the defoaming rotation speed is 1800 r / min, and the vacuum degree is 0.5 kPa);

[0056] e. Deliver the defoamed slurry 1 and the defoamed slurry 2 to a mouth dissolving film coating machine respectively, and coat and form films at 60°C (the coating speed is 15 mm / s, and the film thickness is 0.6 mm±0.1) to obtain the oral dissolving film 2 (containing 2 g of glycerol) and the oral dissolving film 3 (containing 2.5 g of glycerol).

[0057] The oral dissolving film containing superoxide dismutase prepared is detected, and the detection results are shown in Table 2.

[0058] Table 2

[0059]

[0060] Example 3

[0061] a. Stir and dissolve 7.5 g of hydroxypropyl methyl cellulose, 0.84 g of pullulan, 30 ml of water, and 2.5 g of glycerol at room temperature to form a first glue solution A; and prepare a first glue solution B according to the parameters and steps of preparing the first glue solution A;

[0062] b. Add 3 g of erythritol, 0.5 g of citric acid, 0.33 g of sodium citrate, and 0.84 g of blueberry flavor to the first glue solution A and the first glue solution B respectively, and stir to dissolve at room temperature to obtain the second glue solution C and the second glue solution D;

[0063] c. Add 30 mL of superoxide dismutase solution with a concentration of 50000 U / mL of superoxide dismutase, 1 g of silkworm pupa protein peptide, and 0.16 g of blueberry anthocyanin to the second glue solution C, and stir to dissolve at room temperature to obtain the hydroxypropyl methyl cellulose-pullulan slurry 1;

[0064] To the second glue liquid D, 30 mL of 100000 U / mL superoxide dismutase solution, 1 g of silkworm chrysalis protein peptide, and 0.16 g of blueberry anthocyanin were added, and stirred and dissolved at room temperature to obtain hydroxypropyl methyl cellulose-pullulan slurry 2;

[0065] d, respectively, the hydroxypropyl methyl cellulose-pullulan slurry 1, the hydroxypropyl methyl cellulose-pullulan slurry 2 were put into the vacuum defoaming container machine, and defoaming treatment was carried out (the defoaming treatment was divided into three sections, the defoaming time of the first section was 60 s, the defoaming rotation speed was 1000 r / min, the vacuum degree was 101.7 kPa; the defoaming time of the second section was 100 s, the defoaming rotation speed was 1600 r / min, the vacuum degree was 0.5 kPa; the defoaming time of the third section was 80 s, the defoaming rotation speed was 1800 r / min, the vacuum degree was 0.5 kPa);

[0066] e, the defoamed hydroxypropyl methyl cellulose-pullulan slurry 1, the defoamed hydroxypropyl methyl cellulose-pullulan slurry 2 were respectively transported to the oral dissolving film coating machine, and film coating was carried out at 60°C (coating speed was 15 mm / s, coating thickness was 0.6 mm±0.1), to obtain oral dissolving film 4 (containing SOD 50000 U / mL), oral dissolving film 5 (containing SOD 100000 U / mL).

[0067] The prepared oral dissolving film containing superoxide dismutase was detected, and the detection results are shown in Table 3.

[0068] Table 3

[0069]

[0070] From the detection results of oral dissolving film 3~oral dissolving film 5, it can be known that the higher the concentration of superoxide dismutase solution, the lower the folding resistance, but when the concentration is 10000 U / mL~100000 U / mL, it meets the requirements; the higher the concentration of superoxide dismutase solution, the longer the disintegration time; the enzyme activity loss rate of superoxide dismutase solution with a concentration of 10000 U / mL is 5.4%, the enzyme activity loss rate of superoxide dismutase solution with a concentration of 50000 U / mL is 13.4%, the enzyme activity loss rate of superoxide dismutase solution with a concentration of 100000 U / mL is 27.7%, the higher the concentration of superoxide dismutase solution, the higher the enzyme activity loss rate. The linear relationship between the concentration of superoxide dismutase solution added during the preparation of the oral dissolving film and the detection amount of superoxide dismutase in the finally prepared oral dissolving film is shown in Table 4. Figure 1

[0071] Example 4

[0072] The same as the operation steps of Example 1, 1.8 g of trehalose was added to obtain oral dissolving film 6. ​

[0073] The prepared oral instant film containing superoxide dismutase was detected, and the detection results are shown in Table 4.

[0074] Table 4

[0075]

[0076] Example 5

[0077] The same as the operation steps of Example 1, except that erythritol is not added, and the amount of trehalose added is 3 g, to obtain oral instant film 7.

[0078] The prepared oral instant film containing superoxide dismutase was detected, and the detection results are shown in Table 5.

[0079] Table 5

[0080]

[0081] Comparative Example 1

[0082] a. Stir and dissolve 8.34 g of hydroxypropyl methyl cellulose, 30 ml of water and 2.5 g of glycerol at room temperature to form a first hydroxypropyl methyl cellulose glue solution;

[0083] Stir and dissolve 8.34 g of pullulan, 30 ml of water and 2.5 g of glycerol at room temperature to form a first pullulan glue solution;

[0084] Stir and dissolve 8.34 g of gelatin (purchased from Shui County Fuyuan Gelatin Co., Ltd., batch number 20230219), 30 ml of water and 2.5 g of glycerol at 60°C to form a first gelatin glue solution;

[0085] Stir and dissolve 8.34 g of polyvinyl alcohol (purchased from Feicheng Linyuan High Polymer Material Co., Ltd., batch number 202412001), 30 ml of water and 2.5 g of glycerol at 80°C to form a first polyvinyl alcohol glue solution;

[0086] b. Add 3 g of erythritol, 0.5 g of citric acid, 0.33 g of sodium citrate and 0.84 g of blueberry essence to the first hydroxypropyl methyl cellulose glue solution, the first pullulan glue solution, the first gelatin glue solution and the first polyvinyl alcohol glue solution respectively, and stir and dissolve at room temperature to obtain a second hydroxypropyl methyl cellulose glue solution, a second pullulan glue solution, a second gelatin glue solution and a second polyvinyl alcohol glue solution;

[0087] c. 30 mL of 10,000 U / mL superoxide dismutase solution, 1 g of silkworm pupa protein peptide, 0.16 g of blueberry anthocyanin, and 2.4 g of trehalose were added into the second glue solution of hydroxypropyl methyl cellulose, the second glue solution of pullulan, the second glue solution of gelatin, and the second glue solution of polyvinyl alcohol respectively, and stirred and dissolved at room temperature to obtain hydroxypropyl methyl cellulose slurry, pullulan slurry, gelatin slurry, and polyvinyl alcohol slurry;

[0088] d. The hydroxypropyl methyl cellulose slurry, the pullulan slurry, the gelatin slurry, and the polyvinyl alcohol slurry were placed into a vacuum defoaming container machine for defoaming treatment (the defoaming treatment was divided into three stages, the defoaming time of the first stage was 60 s, the defoaming rotation speed was 1,000 r / min, and the vacuum degree was 101.7 kPa; the defoaming time of the second stage was 100 s, the defoaming rotation speed was 1,600 r / min, and the vacuum degree was 0.5 kPa; the defoaming time of the third stage was 80 s, the defoaming rotation speed was 1,800 r / min, and the vacuum degree was 0.5 kPa);

[0089] e. The defoamed hydroxypropyl methyl cellulose slurry, the pullulan slurry, the gelatin slurry, and the polyvinyl alcohol slurry were conveyed to a mouth dissolving film coating machine, and film coating was performed at 60°C (the coating speed was 15 mm / s, and the coating thickness was 0.6 mm±0.1) to obtain oral fast dissolving film 8 (the film forming material was hydroxypropyl methyl cellulose slurry), oral fast dissolving film 9 (the film forming material was pullulan), oral fast dissolving film 10 (the film forming material was gelatin), and oral fast dissolving film 11 (the film forming material was polyvinyl alcohol).

[0090] The prepared oral fast dissolving film containing superoxide dismutase was detected, and the detection results are shown in Table 6.

[0091] Table 6

[0092]

[0093] As shown in Table 6, when the film forming material is hydroxypropyl methyl cellulose, the prepared oral fast dissolving film has poor folding endurance; when the film forming material is pullulan, gelatin, or polyvinyl alcohol, the prepared oral fast dissolving film has a slow dissolving speed.

[0094] Comparative Example 2

[0095] a. 0.84 g of gelatin and 30 mL of water were stirred and dissolved at 60°C, followed by the addition of 7.5 g of hydroxypropyl methyl cellulose and 2.5 g of glycerol, which were stirred and dissolved at room temperature to form a hydroxypropyl methyl cellulose-gelatin first glue solution;

[0096] 0.84g polyvinyl alcohol and 30ml water were stirred and dissolved at 80℃, then 7.5g hydroxypropyl methyl cellulose and 2.5g glycerol stirred and dissolved at room temperature to form a hydroxypropyl methyl cellulose-polyvinyl alcohol first glue solution;

[0097] b, 3g erythritol, 0.5g citric acid, 0.33g sodium citrate and 0.84g blueberry essence were added to the hydroxypropyl methyl cellulose-gelatin first glue solution and the hydroxypropyl methyl cellulose-polyvinyl alcohol first glue solution respectively, and stirred and dissolved at room temperature to obtain a hydroxypropyl methyl cellulose-gelatin second glue solution and a hydroxypropyl methyl cellulose-polyvinyl alcohol second glue solution;

[0098] c, 30ml 10000U / ml superoxide dismutase solution, 1g silkworm pupa protein peptide, 0.16g blueberry anthocyanin and 2.4g trehalose were added to the hydroxypropyl methyl cellulose-gelatin second glue solution and the hydroxypropyl methyl cellulose-polyvinyl alcohol second glue solution respectively, and stirred and dissolved at room temperature to obtain a hydroxypropyl methyl cellulose-gelatin slurry and a hydroxypropyl methyl cellulose-polyvinyl alcohol slurry;

[0099] d, the hydroxypropyl methyl cellulose-gelatin slurry and the hydroxypropyl methyl cellulose-polyvinyl alcohol slurry were respectively placed in a vacuum defoaming container machine for defoaming treatment (the defoaming treatment was divided into three stages, the defoaming time of the first stage was 60s, the defoaming rotation speed was 1000r / min, and the vacuum degree was 101.7kPa; the defoaming time of the second stage was 100s, the defoaming rotation speed was 1600r / min, and the vacuum degree was 0.5kPa; the defoaming time of the third stage was 80s, the defoaming rotation speed was 1800r / min, and the vacuum degree was 0.5kPa);

[0100] e, the defoamed hydroxypropyl methyl cellulose-gelatin slurry and the defoamed hydroxypropyl methyl cellulose-polyvinyl alcohol slurry were respectively transported to a mouth dissolving film coating machine and coated and formed into films at 60℃ (the coating speed was 15mm / s, and the coating thickness was 0.6mm±0.1) to obtain a mouth dissolving film 12 (the film forming material was hydroxypropyl methyl cellulose-gelatin) and a mouth dissolving film 13 (the film forming material was hydroxypropyl methyl cellulose-polyvinyl alcohol).

[0101] Comparative Example 3

[0102] a, 7.5g hydroxypropyl methyl cellulose, 0.84g pullulan, 30ml water and 1.667g glycerol were stirred and dissolved at room temperature to prepare a glue solution 1;

[0103] 7.5g hydroxypropyl methyl cellulose, 0.84g pullulan, 30ml water and 3g glycerol were stirred and dissolved at room temperature to prepare a glue solution 2;

[0104] The 7.5 g hydroxypropyl methyl cellulose, 0.84 g pullulan, 30 ml water and 3.334 g glycerol are stirred and dissolved at room temperature to prepare glue liquid 3;

[0105] b, 3 g erythritol, 0.5 g citric acid, 0.33 g sodium citrate and 0.84 g blueberry flavor are added to glue liquid 1-glue liquid 3 respectively, and stirred and dissolved at room temperature to obtain glue liquid 4, glue liquid 5 and glue liquid 6;

[0106] c, 30 mL of 10000 U / mL superoxide dismutase solution, 1 g silkworm pupa protein peptide, 0.16 g blueberry anthocyanin and 2.4 g trehalose are added to glue liquid 4-glue liquid 6 respectively, and stirred and dissolved at room temperature to obtain slurry 1, slurry 2 and slurry 3;

[0107] d, the slurry 1-slurry 3 is respectively put into a vacuum defoaming container machine for defoaming treatment (the defoaming treatment is divided into three stages, the defoaming time of the first stage is 60 s, the defoaming rotation speed is 1000 r / min, and the vacuum degree is 101.7 kPa; the defoaming time of the second stage is 100 s, the defoaming rotation speed is 1600 r / min, and the vacuum degree is 0.5 kPa; the defoaming time of the third stage is 80 s, the defoaming rotation speed is 1800 r / min, and the vacuum degree is 0.5 kPa);

[0108] e, the defoamed slurry 1-slurry 3 is respectively transported to a mouth dissolving film coating machine, and coated and formed at 60°C (coating speed is 15 mm / s, coating thickness is 0.6 mm±0.1) to obtain the oral dissolving film 14 (1.667 g glycerol), the oral dissolving film 15 (3 g glycerol) and the oral dissolving film 16 (3.334 g glycerol).

[0109] The oral dissolving film containing superoxide dismutase prepared by the preparation of the comparative example 2 and the comparative example 3 is detected, and the detection results are shown in table 7.

[0110] Table 7

[0111]

[0112] As shown in table 7, when the film forming material is hydroxypropyl methyl cellulose-gelatin, the SOD enzyme activity is very low, and the addition of gelatin will interfere with the enzyme activity detection; when the film forming material is hydroxypropyl methyl cellulose-polyvinyl alcohol, the oral dissolving film dissolves slowly. When 1.667 g glycerol is added, the oral dissolving film has low folding resistance and is easy to break during transportation; when 3 g or 3.334 g glycerol is added, the surface of the oral dissolving film is too sticky, which affects the sub-packaging and the taking experience.

[0113] Comparative example 4

[0114] The same operation steps as in the preparation of oral fast dissolving film 4 in Example 3, except that the equal volume of superoxide dismutase solution in step c is replaced by water to obtain oral fast dissolving film 17.

[0115] Comparative Example 5

[0116] The same operation steps as in Example 1, except that the amount of trehalose added is changed to 0.6 g to obtain oral fast dissolving film 18; the amount of trehalose added is changed to 1.2 g to obtain oral fast dissolving film 19; and the amount of trehalose added is changed to 3 g to obtain oral fast dissolving film 20.

[0117] The oral fast dissolving films prepared in Comparative Example 4 and Comparative Example 5 are detected, and the detection results are shown in Table 8.

[0118] Table 8

[0119]

[0120] In the present application, the performance detection method of the oral fast dissolving film is:

[0121] (1) The folding resistance detection method: 5 pieces of 2x2 cm 2 size oral fast dissolving films are taken, and the middle position of the oral dissolving film is repeatedly folded by 180° until it is broken, and the average folding number is recorded;

[0122] (2) The disintegration time detection method:

[0123] In vivo test: 50 volunteers aged 25 years old (25 men and 25 women) use clean water to gargle, and then place 2x2 cm 2 size oral fast dissolving films on the tongue surface, and at the same time, the time is counted. The volunteers pause the timing when they cannot feel the foreign body without chewing and actively swallowing, and the time is recorded and averaged;

[0124] In vitro test: 5 pieces of 2x2 cm 2 oral fast dissolving films are taken and placed in beakers containing 50 mL of 37℃ water, vortexed, and the time for the oral fast dissolving film to completely dissolve in water is observed and recorded by naked eye, and the average value is taken;

[0125] (3) The SOD enzyme activity detection method: 5 pieces of 3x3 cm 2 size oral dissolving films are taken, and 1 mL of water is used to dissolve them, and then the SOD enzyme activity is detected according to GB / T5009.171-2003 "Determination of superoxide dismutase (SOD) activity in health food", and the average SOD enzyme activity is calculated.

[0126] The above merely describes the preferred embodiments of the present application, and the protection scope of the present application is not limited to the above-described embodiments. Any technical solution falling within the concept of the present application shall fall within the protection scope of the present application. It should be noted that, for ordinary skilled persons in the art, some improvements and refinements without departing from the principles of the present application shall also be considered as falling within the protection scope of the present application.

Claims

1. An oral superoxide dismutase-containing fast dissolving film, characterized by, The dry base, water and superoxide dismutase solution are prepared; The dry base is a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate or a combination of film-forming material, glycerol, active ingredient, citric acid, blueberry flavor, sodium citrate, trehalose or a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose; the film-forming material is a combination of hydroxypropyl methyl cellulose and pullulan at a mass ratio of 7.5:0.84; the active ingredient is one or both of silkworm chrysalis protein peptide and blueberry anthocyanin; The dry base and water are used in a ratio of (14.6-20.2) g:30 mL; the water and superoxide dismutase solution are used in a volume ratio of 1:1; the concentration of superoxide dismutase in the superoxide dismutase solution is 10000 U / mL-100000 U / mL; When the dry base is a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, the mass ratio of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate is (8.3-9):(2-2.5):(0.1-1.3):(2.9-3.1):(0.4-0.6):(0.7-0.9):(0.2-0.4); When the dry base is a combination of film-forming material, glycerol, active ingredient, citric acid, blueberry flavor, sodium citrate, trehalose, the mass ratio of film-forming material, glycerol, active ingredient, citric acid, blueberry flavor, sodium citrate, trehalose is (8.3-9):(2-2.5):(0.1-1.3):(0.4-0.6):(0.7-0.9):(0.2-0.4):(2.9-3.1); When the dry base is a combination of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose, the mass ratio of film-forming material, glycerol, active ingredient, erythritol, citric acid, blueberry flavor, sodium citrate, trehalose is (8.3-9):(2-2.5):(0.1-1.3):(2.9-3.1):(0.4-0.6):(0.7-0.9):(0.2-0.4):(1.8-2.4); The preparation of the oral fast-dissolving film includes the following steps: (1) The film-forming material, water and glycerol are stirred and dissolved to obtain a first glue solution; (2) Citric acid, blueberry flavor and sodium citrate are added to the first glue solution, and erythritol is added or not added, and then stirred and dissolved to obtain a second glue solution; (3) When erythritol is added in step (2), superoxide dismutase solution and active ingredient are added to the second glue solution, and trehalose is added or not added, and then stirred and dissolved to obtain a slurry; when erythritol is not added in step (2), superoxide dismutase solution, active ingredient and trehalose are added to the second glue solution, and then stirred and dissolved to obtain a slurry; (4) The slurry is subjected to defoaming treatment, and then coated and film-formed to obtain an oral fast-dissolving film containing superoxide dismutase; the coating thickness is 0.6 mm±0.

1.

2. The superoxide dismutase-containing oral fast dissolving film according to claim 1, wherein The solvent of the superoxide dismutase solution is a phosphate buffer solution, and the concentration of the phosphate in the phosphate buffer solution is 20 mmol / L; the phosphate is sodium phosphate dibasic dodecahydrate.

3. The superoxide dismutase-containing oral fast dissolving film according to claim 1, wherein, In the step (4), the defoaming treatment is divided into three stages, the defoaming time of the first stage is 60 s, the defoaming rotation speed is 1000 r / min, and the vacuum degree is 101.7 kPa; the defoaming time of the second stage is 100 s, the defoaming rotation speed is 1600 r / min, and the vacuum degree is 0.5 kPa; the defoaming time of the third stage is 80 s, the defoaming rotation speed is 1800 r / min, and the vacuum degree is 0.5 kPa.

4. The superoxide dismutase-containing oral fast dissolving film according to claim 1, wherein, In the step (4), the coating temperature is 55-65 ℃, and the coating speed is 5-15 mm / s.

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