Preparation process of a small molecule bird's nest peptide and its compound tablets

Abstract

The present invention provides a preparation process of a small molecule bird's nest peptide and its compound tablets, belonging to the technical field of proteins and peptides; the preparation process of the small molecule bird's nest peptide includes the following steps: freeze-crushing the bird's nest; enzymatic hydrolysis with a compound enzyme. The present invention first repeatedly freeze-crushes the bird's nest to make bird's nest powder, then adds it to deionized water, heats and stews it, and then adds a compound enzyme composed of neutral protease and flavor protease for ultrasonic-assisted enzymatic hydrolysis to obtain a small molecule bird's nest peptide. Among them, when the neutral protease and flavor protease are mixed in a mass ratio of 1:(2.8 - 3.4) for enzymatic hydrolysis of the bird's nest, hydrolysis can be carried out from multiple positions to form smaller peptide segments, effectively improving the degree of hydrolysis. With the hydrolysis of proteins, sialic acid originally bound to the proteins is also released, thereby effectively increasing the content of sialic acid in the prepared small molecule bird's nest peptide.

Description

Technical Field

[0001] The present invention relates to the technical field of proteins and peptides, and particularly to a preparation process of a small molecule bird's nest peptide and its compound tablets. Background Art

[0002] As a traditional nourishing treasure, bird's nest has a long history of consumption in Asian regions, especially in China. It is considered to have many health care effects such as beauty care, nourishing yin and moistening the lungs, and enhancing immunity. Its nutritional value stems from components such as rich proteins, carbohydrates, minerals, and sialic acid. The traditional way of consuming bird's nest is mostly by stewing, which is a time-consuming process. Moreover, the digestion and absorption efficiency of macromolecular proteins and other components in the bird's nest in the gastrointestinal tract is relatively low. The human digestive system needs to consume a large amount of energy and time to break down these macromolecules into absorbable small molecule fragments, resulting in some nutritional components being excreted from the body before being fully utilized.

[0003] With the continuous development of biotechnology, the enzymatic hydrolysis technology has emerged, providing a new way for the deep processing of bird's nest. By treating the bird's nest with specific enzymes, the macromolecular proteins in it can be directionally hydrolyzed into small molecule bird's nest peptides. These small molecule bird's nest peptides are easier to penetrate the gastrointestinal mucosa and be rapidly absorbed by the human body compared to macromolecular bird's nest proteins, greatly improving the bioavailability.

[0004] Currently, formulating bird's nest peptides into oral preparations is one of the popular nutritional supplement forms. However, ordinary oral preparations of bird's nest peptides, such as conventional capsules or tablets, have the problem of rapid drug release, resulting in a sharp increase in blood drug concentration in a short time, followed by a rapid decline, showing a peak-valley effect. On the one hand, this peak-valley effect cannot continuously and stably provide the required bird's nest peptides for the body, making it difficult to fully exert its health care function; on the other hand, the excessively high peak blood drug concentration may cause some potential adverse reactions, such as gastrointestinal discomfort, etc., and the low blood drug concentration period also greatly reduces the drug efficacy.

[0005] Therefore, it is necessary to propose a preparation process of a small molecule bird's nest peptide and its compound tablets with a sustained release effect to improve its bioavailability. Summary of the Invention

[0006] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a preparation process of a small molecule bird's nest peptide and its compound tablets.

[0007] A small molecule bird's nest peptide, its preparation process includes the following steps:

[0008] (1) Freeze-crush the bird's nest:

[0009] Place the bird's nest in a freezer at -15 to -5 °C and freeze it for 20 to 30 minutes. Then place it in a crusher and crush it for 20 to 30 minutes. Repeat this process 2 to 3 times. After passing through a 60 to 100 mesh sieve, bird's nest powder is obtained;

[0010] (2)Complex enzyme hydrolysis:

[0011] Add the above-mentioned bird's nest powder to deionized water according to the solid-liquid ratio of 1 g : (40 - 50) mL, heat and stir at 90 to 100 °C for 1 to 2 hours. When it cools to 45 to 50 °C, add complex enzyme and carry out ultrasonic-assisted heat preservation enzyme hydrolysis for 3 to 4 hours. Then use a boiling water bath to inactivate the enzyme for 10 to 20 minutes. After centrifugal separation, collecting the supernatant and vacuum freeze-drying, small molecule bird's nest peptides are obtained;

[0012] Among them, the complex enzyme is composed of neutral protease and flavor protease mixed in a mass ratio of 1 : (2.8 - 3.4), and the addition amount of the complex enzyme is 4000 - 5000 U / g of bird's nest powder.

[0013] Furthermore, a process for preparing a composite tablet using the above-mentioned small molecule bird's nest peptides includes the following steps:

[0014] S1: Prepare the coating solution

[0015] Dissolve polymethacrylate copolymer and poly(lactic-co-glycolic acid) copolymer in ethyl acetate respectively, then mix and carry out homogenization and vacuum degassing to obtain the coating solution;

[0016] S2: Prepare the extracts

[0017] Ultrasonically assist in extracting white matsutake and fresh osmanthus flowers with ethanol solution respectively to obtain white matsutake extract and osmanthus flower extract;

[0018] S3: Prepare the composite tablet

[0019] Make small molecule bird's nest peptides, N-acetylneuraminic acid, xylitol, the above-mentioned white matsutake extract and the above-mentioned osmanthus flower extract into bird's nest peptide tablets, and then evenly spray the above-mentioned coating solution on the surface. After drying, the composite tablet is obtained.

[0020] Furthermore, S1 specifically includes the following steps:

[0021] S1.1: Add polymethacrylate copolymer to ethyl acetate according to the solid-liquid ratio of 1 g : (20 - 30) mL, stir well to dissolve, and obtain polymethacrylate copolymer solution;

[0022] S1.2: Add poly(lactic-co-glycolic acid) copolymer to ethyl acetate according to the solid-liquid ratio of 1 g : (20 - 30) mL, stir well to dissolve, and obtain poly(lactic-co-glycolic acid) copolymer solution;

[0023] S1.3: Stir and mix the above polymethacrylate copolymer solution and polylactic acid-glycolic acid copolymer solution evenly for 10 - 20 min. After vacuum degassing, a coating solution is obtained.

[0024] Further, S2 specifically includes the following steps:

[0025] S2.1: Wash, dry, crush, and sieve white matsutake mushrooms, then add them to a 50% ethanol solution at a material-liquid ratio of 1 g : (20 - 30) mL, and perform ultrasonic-assisted extraction for 1 - 2 h. Repeat this process 2 - 3 times. After filtration and evaporation concentration, a white matsutake mushroom extract is obtained.

[0026] S2.2: Wash, dry, and mash fresh osmanthus flowers, then add them to a 70% ethanol solution at a material-liquid ratio of 1 g : (30 - 40) mL, and perform ultrasonic-assisted extraction for 1 - 2 h. After repeating this process 2 times, filter, perform vacuum concentration, and dry to obtain an osmanthus flower extract.

[0027] Further, S3 specifically includes the following steps:

[0028] S3.1: Mix small molecule bird's nest peptide, N-acetylneuraminic acid, xylitol, the white matsutake mushroom extract prepared in step S2.1, the osmanthus flower extract prepared in step S2.2 with a filler, a disintegrant, and a binder solution, then perform tabletting and drying to obtain bird's nest peptide tablets.

[0029] S3.2: Place the above bird's nest peptide tablets into a rotary coater, and evenly spray the coating solution prepared in step S1.3 on their surfaces. After drying and curing, composite tablets are obtained.

[0030] Further, the polymethacrylate copolymer is any one of Eudragit L30D-55 and Eudragit L100-55.

[0031] Further, the volume ratio of the polymethacrylate copolymer solution to the polylactic acid-glycolic acid copolymer solution is (3 - 5) : 1.

[0032] Further, by mass, the bird's nest peptide tablets include: 20 - 30 parts of small molecule bird's nest peptide, 1 - 3 parts of N-acetylneuraminic acid, 6 - 8 parts of xylitol, 8 - 10 parts of white matsutake mushroom extract, 4 - 6 parts of osmanthus flower extract, 12 - 16 parts of filler, 0.1 - 0.5 parts of disintegrant, and 0.6 - 1 part of binder.

[0033] Further, the filler is any one of microcrystalline cellulose or starch.

[0034] Further, the disintegrant is any one of cross-linked carboxymethylcellulose sodium or cross-linked povidone, and the binder is any one of povidone or hydroxypropyl methylcellulose.

[0035] Compared with the prior art, the present invention has at least the following beneficial effects:

[0036] 1. In the present invention, the bird's nest is first repeatedly frozen and crushed to make bird's nest powder, then added to deionized water, heated and stewed, and then a complex enzyme composed of neutral protease and flavor protease mixed in a mass ratio of 1:(2.8 - 3.4) is added for ultrasonic-assisted enzymatic hydrolysis to obtain small molecule bird's nest peptides. Among them, when neutral protease and flavor protease are mixed in a mass ratio of 1:(2.8 - 3.4) to carry out enzymatic hydrolysis of the bird's nest, hydrolysis can be carried out from multiple positions, forming smaller peptide segments, effectively improving the degree of hydrolysis. With the hydrolysis of proteins, sialic acid originally bound to the proteins is also released, thus effectively increasing the content of sialic acid in the prepared small molecule bird's nest peptides.

[0037] 2. In the present invention, the Tricholoma matsutake and Osmanthus fragrans are first extracted with ethanol solution respectively to obtain Tricholoma matsutake extract and Osmanthus fragrans extract, and then the two are mixed with small molecule bird's nest peptides to make bird's nest peptide tablets. Since the active ingredients of Tricholoma matsutake extract can inhibit the activity of tyrosinase and reduce the production of melanin, and Osmanthus fragrans extract can interfere with the synthesis of melanin by regulating the signal transduction pathway in melanocytes, while small molecule bird's nest peptides can promote the metabolism of skin cells. When the three are combined, on the one hand, Tricholoma matsutake extract and Osmanthus fragrans extract play a role from the perspective of inhibiting the generation and transport of melanin, and on the other hand, small molecule bird's nest peptides accelerate the renewal of cells containing melanin, forming a synergistic whitening effect. In addition, small molecule bird's nest peptides contain amino acid residues with antioxidant activity, which can cooperate with the antioxidant components in Tricholoma matsutake extract and Osmanthus fragrans extract to play an antioxidant role at different redox potentials, forming a multi-level antioxidant network, thus achieving a synergistic antioxidant effect.

[0038] 3. In the present invention, first, polymethacrylate copolymer and poly(lactic-co-glycolic acid) copolymer are respectively dissolved in ethyl acetate, and then the two are mixed to make a coating solution. After the coating solution is evenly sprayed on the surface of the bird's nest peptide tablets and dried, a barrier can be formed on the surface of the bird's nest peptide tablets to prevent the rapid dissolution of the bird's nest peptides and extracts, slow down their release rate, and further reduce the gastrointestinal burden. In addition, since the structure of the polymethacrylate copolymer contains acidic groups and is relatively stable in an acidic environment and will not ionize, it can further reduce the dissolution amount of the bird's nest peptides and extracts in gastric juice and reduce the damage of gastric juice to them. When in a neutral or weakly alkaline environment, the acidic groups in the structure will ionize, increasing the repulsive force between polymer chains, resulting in the swelling of the composite coating material, which is beneficial to the release and exertion of the efficacy of the bird's nest peptides and extracts in the bird's nest peptide tablets, thus achieving the effect of improving the bioavailability of small molecule bird's nest peptides, Tricholoma matsutake extract and Osmanthus fragrans extract. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The accompanying drawings incorporated herein and constituting a part of the specification illustrate embodiments of the present disclosure, and together with the specification further serve to explain the principles of the present disclosure and enable those skilled in the relevant art to implement and use the present disclosure.

[0040] Figure 1 It is a process flow chart of the preparation of small molecule bird's nest peptide adopted in the embodiments of the present invention.

[0041] Figure 2 It is a cumulative release rate curve graph of the composite tablets prepared in Example 1 of the present invention.

[0042] Figure 3 It is a cumulative release rate curve graph of the bird's nest peptide tablets prepared in Comparative Example 6 of the present invention. Detailed Description of the Invention

[0043] The following describes in detail the preparation process of a small molecule bird's nest peptide and its composite tablets provided by the present invention in conjunction with the accompanying drawings and specific embodiments.

[0044] Example 1

[0045] A preparation process of a small molecule bird's nest peptide composite tablet, as Figure 1 shown, includes the following steps:

[0046] (1) Freeze-crush the bird's nest:

[0047] Place the bird's nest in a freezer at -15°C for 20 minutes, then place it in a crusher and crush for 20 minutes. Repeat 2 times. After passing through a 60-mesh sieve, bird's nest powder is obtained;

[0048] (2) Hydrolyze with a composite enzyme:

[0049] Add the above-mentioned bird's nest powder to deionized water according to a solid-liquid ratio of 1 g:40 mL, heat and stir at 90°C for 1 h. When it cools to 45°C, add a composite enzyme, and perform ultrasonic-assisted incubation hydrolysis for 3 h. Then, inactivate the enzyme in a boiling water bath for 10 minutes. After centrifugal separation, collect the supernatant and vacuum freeze-dry to obtain small molecule bird's nest peptide;

[0050] Among them, the composite enzyme is composed of neutral protease and flavor protease mixed in a mass ratio of 1:2.8, and the addition amount of the composite enzyme is 4000 U / g of bird's nest powder;

[0051] S1: Prepare the coating solution

[0052] S1.1: Add polymethacrylate copolymer to ethyl acetate according to a solid-liquid ratio of 1 g:20 mL, stir well to dissolve, and obtain a polymethacrylate copolymer solution;

[0053] S1.2: Add the poly (lactic-co-glycolic acid) copolymer to ethyl acetate at a solid-liquid ratio of 1 g: 20 mL, and stir well to dissolve it to obtain a poly (lactic-co-glycolic acid) copolymer solution;

[0054] S1.3: Stir and mix the above poly (methyl methacrylate) copolymer solution and poly (lactic-co-glycolic acid) copolymer solution evenly for 10 min. After vacuum degassing, a coating solution is obtained;

[0055] S2: Prepare the extract

[0056] S2.1: After cleaning, drying, crushing and sieving the white matsutake, add it to a 50% ethanol solution at a solid-liquid ratio of 1 g: 20 mL, and perform ultrasonic-assisted extraction for 1 h. Repeat 2 times. After filtration and evaporation concentration, a white matsutake extract is obtained;

[0057] S2.2: After cleaning, drying and mashing the fresh osmanthus flowers, add them to a 70% ethanol solution at a solid-liquid ratio of 1 g: 30 mL, and perform ultrasonic-assisted extraction for 1 h. After repeating 2 times, filter and concentrate under reduced pressure, then add it to petroleum ether, continue to concentrate under reduced pressure and dry to obtain an osmanthus flower extract;

[0058] S3: Prepare the composite tablets

[0059] S3.1: By mass, mix 20 parts of small molecule bird's nest peptide, 1 part of N-acetylneuraminic acid, 6 parts of xylitol, 8 parts of the white matsutake extract prepared in step S2.1, 4 parts of the osmanthus flower extract prepared in step S2.2 with 12 parts of microcrystalline cellulose, 0.1 part of cross-linked carboxymethyl cellulose sodium, 0.6 part of polyvinylpyrrolidone and water, and then perform tabletting and drying to obtain bird's nest peptide tablets;

[0060] S3.2: Put the above bird's nest peptide tablets into a rotary coater, and evenly spray the coating solution prepared in step S1.3 on its surface. After drying and curing, composite tablets are obtained.

[0061] Example 2

[0062] A preparation process of small molecule bird's nest peptide composite tablets, as Figure 1 shown, includes the following steps:

[0063] (1) Freeze and crush the bird's nest:

[0064] Place the bird's nest in a -10 °C freezer for 25 min, then place it in a crusher and crush for 25 min. Repeat 2 times. After passing through an 80-mesh sieve, bird's nest powder is obtained;

[0065] (2) Composite enzyme hydrolysis:

[0066] Add the above-mentioned bird's nest powder to deionized water at a solid-liquid ratio of 1 g: 45 mL, heat and stir at 95 °C for 1.5 h. When cooled to 47 °C, add a composite enzyme and carry out ultrasonic-assisted heat preservation and enzymolysis for 3.5 h. Then, inactivate the enzyme in a boiling water bath for 15 min. After centrifugal separation, collect the supernatant and carry out vacuum freeze-drying to obtain small molecule bird's nest peptides;

[0067] Among them, the composite enzyme is composed of neutral protease and flavor protease mixed at a mass ratio of 1: 3.1, and the addition amount of the composite enzyme is 4500 U / g of bird's nest powder;

[0068] S1: Prepare a coating solution

[0069] S1.1: Add polymethacrylate copolymer to ethyl acetate at a solid-liquid ratio of 1 g: 25 mL, stir well to dissolve, and obtain a polymethacrylate copolymer solution;

[0070] S1.2: Add poly (lactic-co-glycolic acid) copolymer to ethyl acetate at a solid-liquid ratio of 1 g: 25 mL, stir well to dissolve, and obtain a poly (lactic-co-glycolic acid) copolymer solution;

[0071] S1.3: Stir and mix the above-mentioned polymethacrylate copolymer solution and poly (lactic-co-glycolic acid) copolymer solution evenly for 15 min. After vacuum degassing, obtain a coating solution;

[0072] S2: Prepare an extract

[0073] S2.1: After cleaning, drying, pulverizing and sieving the white matsutake, add it to a 50% ethanol solution at a solid-liquid ratio of 1 g: 25 mL, carry out ultrasonic-assisted extraction for 1.5 h, repeat 2 times, filter and evaporate and concentrate to obtain a white matsutake extract;

[0074] S2.2: After cleaning, drying and mashing the fresh osmanthus flowers, add them to a 70% ethanol solution at a solid-liquid ratio of 1 g: 35 mL, carry out ultrasonic-assisted extraction for 1.5 h, repeat 2 times, filter and carry out vacuum concentration, then add to petroleum ether, continue vacuum concentration and drying to obtain an osmanthus flower extract;

[0075] S3: Prepare a composite tablet

[0076] S3.1: By mass, mix 25 parts of small molecule bird's nest peptides, 2 parts of N-acetylneuraminic acid, 7 parts of xylitol, 9 parts of the white matsutake extract prepared in step S2.1, 5 parts of the osmanthus flower extract prepared in step S2.2 with 14 parts of starch, 0.3 part of crospovidone, 0.8 part of hypromellose and water, then carry out tabletting and drying to obtain bird's nest peptide tablets;

[0077] S3.2: Place the above-mentioned bird's nest peptide tablets into a rotary coater, spray the coating liquid prepared in step S1.3 evenly on the surface thereof, and after drying and solidification, obtain a composite tablet.

[0078] Example 3

[0079] A preparation process of a small molecule bird's nest peptide composite tablet, such as Figure 1 As shown, the following steps are included:

[0080] (1) Frozen crushed bird’s nest:

[0081] Place the bird's nest in a -5℃ freezer for 30 minutes, then place it in a crusher and crush it for 30 minutes, repeat 3 times, and pass it through a 100-mesh sieve to obtain bird's nest powder;

[0082] (2) Compound enzyme hydrolysis:

[0083] The bird's nest powder was added to deionized water at a solid-liquid ratio of 1g:50mL, heated and stirred at 100°C for 2h, and when cooled to 50°C, a composite enzyme was added, and ultrasonic-assisted enzymolysis was performed for 4h, and then the enzyme was inactivated in a boiling water bath for 20min. After centrifugation, the supernatant was collected and vacuum freeze-dried to obtain a small molecule bird's nest peptide;

[0084] The compound enzyme is prepared by mixing neutral protease and flavor protease in a mass ratio of 1:3.4, and the amount of the compound enzyme added is 5000U / g bird's nest powder;

[0085] S1: Preparation of coating solution

[0086] S1.1: Add polymethacrylate copolymer into ethyl acetate at a solid-liquid ratio of 1 g:30 mL, stir thoroughly to dissolve, and obtain a polymethacrylate copolymer solution;

[0087] S1.2: Add polylactic acid-glycolic acid copolymer into ethyl acetate at a solid-liquid ratio of 1 g:30 mL, stir thoroughly to dissolve, and obtain a polylactic acid-glycolic acid copolymer solution;

[0088] S1.3: The polymethacrylate copolymer solution and the polylactic acid-glycolic acid copolymer solution are stirred and mixed uniformly for 20 minutes, and after vacuum degassing, a coating solution is obtained;

[0089] S2: Preparation of extracts

[0090] S2.1: After washing, drying, crushing and sieving the white pine mushroom, add it into 50% ethanol solution at a solid-liquid ratio of 1 g:30 mL, perform ultrasonic-assisted extraction for 2 h, repeat 3 times, filter, evaporate and concentrate to obtain the white pine mushroom extract;

[0091] S2.2: After cleaning, drying, and mashing fresh osmanthus flowers, add them to a 70% ethanol solution at a material-liquid ratio of 1 g: 40 mL, perform ultrasonic-assisted extraction for 2 h, repeat twice, then filter and concentrate under reduced pressure. Next, add it to petroleum ether, continue to concentrate under reduced pressure and dry to obtain osmanthus flower extract;

[0092] S3: Prepare compound tablets

[0093] S3.1: By mass, mix 30 parts of small molecule bird's nest peptide, 3 parts of N-acetylneuraminic acid, 8 parts of xylitol, 10 parts of the white matsutake extract prepared in step S2.1, 6 parts of the osmanthus flower extract prepared in step S2.2 with 16 parts of starch, 0.5 part of cross-linked carboxymethylcellulose sodium, 1 part of polyvinylpyrrolidone and water, then perform tabletting and drying to obtain bird's nest peptide tablets;

[0094] S3.2: Put the above-mentioned bird's nest peptide tablets into a rotary coater, evenly spray the coating solution prepared in step S1.3 on its surface, and after drying and curing, obtain compound tablets.

[0095] Comparative Example 1

[0096] The difference between this Comparative Example 1 and Example 1 is that the mass ratio of neutral protease to flavor protease in step (2) is adjusted to 1:2.7.

[0097] Comparative Example 2

[0098] The difference between this Comparative Example 2 and Example 1 is that the mass ratio of neutral protease to flavor protease in step (2) is adjusted to 1:3.5.

[0099] Comparative Example 3

[0100] The difference between this Comparative Example 3 and Example 1 is that the white matsutake extract and osmanthus flower extract in step S3.1 are replaced with an equal amount of small molecule bird's nest peptide.

[0101] Comparative Example 4

[0102] The difference between this Comparative Example 4 and Example 1 is that the small molecule bird's nest peptide and osmanthus flower extract in step S3.1 are replaced with an equal amount of white matsutake extract.

[0103] Comparative Example 5

[0104] The difference between this Comparative Example 5 and Example 1 is that the white matsutake extract and small molecule bird's nest peptide in step S3.1 are replaced with an equal amount of osmanthus flower extract.

[0105] Comparative Example 6

[0106] The difference between this Comparative Example 6 and Example 1 is that step S3.2 is removed.

[0107] Test Example

[0108] Test 1: The content of sialic acid in the small molecule bird's nest peptides prepared in Examples 1-3 and Comparative Examples 1-2 was determined by high performance liquid chromatography, and the results are shown in Table 1.

[0109] Table 1: Comparison table of test results of the content of sialic acid in small molecule bird's nest peptides

[0110]

[0111] As can be seen from Table 1, after adjusting the mass ratio of neutral protease to flavor protease to 1:2.7 and 1:3.5 in Comparative Example 1 and Comparative Example 2, the content of sialic acid in the small molecule bird's nest peptides prepared was significantly lower than that in Examples 1-3. It can be seen that when neutral protease and flavor protease are mixed at a mass ratio of 1:(2.8-3.4) for enzymatic hydrolysis of bird's nest, the hydrolysis degree can be effectively improved, thereby effectively increasing the content of sialic acid in the prepared small molecule bird's nest peptides.

[0112] Test 2: The bird's nest peptide tablets prepared in Examples 1-3 and Comparative Examples 3-5 were respectively dissolved in deionized water to prepare bird's nest peptide solutions with a mass fraction of 0.05%. Then, 1 mL was taken and placed in a test tube respectively, and then 1 mL of phosphate buffer (pH 6.8) and 1 mL of 0.03% tyrosine solution were added to each test tube. Then, after being placed in a water bath at 37 °C for 10 min, 1 mL of tyrosinase solution was added. After mixing evenly, it was left standing for 25 min, and the absorbance value (A) at a wavelength of 475 nm was measured with a spectrophotometer. The absorbance value (B) at a wavelength of 475 nm was measured with an equal volume of phosphate buffer instead of tyrosinase; the absorbance value (C) at a wavelength of 475 nm was measured with an equal volume of distilled water instead of the bird's nest peptide solutions prepared in Examples 1-3 and Comparative Examples 3-5, and the absorbance value (D) at a wavelength of 475 nm was measured with an equal volume of phosphate buffer instead of tyrosinase solution. Calculate the inhibition rate of the sample on tyrosinase, and its calculation formula is as follows:

[0113] Inhibition rate (%) = [(C - D) - (A - B)] / (C - D) × 100%, and the results are shown in Table 2.

[0114] Table 2: Comparison table of test results of the inhibition rate of tyrosinase

[0115]

[0116] As can be seen from Table 2, the inhibition rates of the tablets prepared with single small molecule bird's nest peptide, single white matsutake extract and single osmanthus extract in Comparative Example 3, Comparative Example 4 and Comparative Example 5 on tyrosinase were all lower than those in Examples 1-3. It can be seen that the three have a synergistic effect on inhibiting the activity of tyrosinase, that is to say, small molecule bird's nest peptide, white matsutake extract and osmanthus extract have a synergistic whitening effect.

[0117] Test 3: The bird's nest peptide tablets prepared in Examples 1-3 and Comparative Examples 3-5 were separately dissolved in deionized water to prepare a sample solution with a mass fraction of 0.05%. Then, 1 mL of the sample solution was taken into a test tube, 5 mL of 0.06 mmol / L DPPH ethanol solution was added, and after mixing, the reaction was carried out for 30 min. The absorbance A1 was measured at a wavelength of 517 nm; pure water was used to replace the sample solution, and the absorbance A0 was measured; absolute ethanol was used to replace the DPPH ethanol solution, and the absorbance A2 was measured. The DPPH scavenging rate was calculated, and the formula was scavenging rate = [A0 - (A1 - A2)] × 100%. The results are shown in Table 3.

[0118] Table 3: Comparison table of DPPH scavenging rate test results

[0119]

[0120] As can be seen from Table 3, the scavenging rates of the tablets prepared in Comparative Examples 3, 4, and 5 for DPPH are all lower than those in Examples 1-3. It can be seen that small molecule bird's nest peptide, white matsutake extract, and osmanthus extract have a synergistic effect on scavenging free radicals, that is to say, the three have a synergistic antioxidant effect.

[0121] Test 4: The composite tablets prepared in Example 1 and Comparative Example 6 were separately placed in the original release solution (10 mL of PBS buffer solution with pH 7.4 and 10 mL of hydrochloric acid solution with pH 1.5), and in a constant temperature water bath shaker, shaken at a low speed at 37 °C. 1 mL of the release solution was taken at 2, 4, 6, 8, 10, 12, 14, 16, and 18 h, and at the same time, an equal amount of the original release solution was replenished, and the cumulative release rate curve was measured and plotted. The results are as Figure 2 and Figure 3 shown.

[0122] From Figure 2 it can be seen that the composite tablets prepared in Example 1 have a sustained release property, while Figure 3 the bird's nest peptide tablets prepared in Comparative Example 6 do not have a sustained release property, and they are almost completely released within 2 h. In addition, the cumulative release rate of the composite tablets prepared in Example 1 under the condition of pH = 7.4 is significantly higher than that at pH = 1.5. It can be seen that after the composite coating material is coated on the surface of the bird's nest peptide tablets, it can reduce the release of the bird's nest peptide tablets in the acidic environment of gastric juice, improve its stability, and thus improve the bioavailability of the bird's nest peptide tablets.

[0123] The above embodiments are only illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical idea disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A process for preparing a compound tablet using small molecule bird's nest peptides, characterized in that, It includes the following steps: S1: Prepare the coating solution S1.1: Add the polymethacrylate copolymer to ethyl acetate at a solid-liquid ratio of 1 g:(20 - 30) mL, and stir well to dissolve to obtain a polymethacrylate copolymer solution; S1.2: Add the poly(lactic-co-glycolic acid) copolymer to ethyl acetate at a solid-liquid ratio of 1 g:(20 - 30) mL, and stir well to dissolve to obtain a poly(lactic-co-glycolic acid) copolymer solution; S1.3: Stir and mix the above polymethacrylate copolymer solution and poly(lactic-co-glycolic acid) copolymer solution evenly for 10 - 20 min, and after vacuum degassing, obtain the coating solution; S2: Prepare the extract Ultrasonically assist the extraction of white matsutake and fresh osmanthus flowers with an ethanol solution respectively to obtain white matsutake extract and osmanthus flower extract; S3: Prepare the composite tablets S3.1: Mix the small molecule bird's nest peptide, N-acetylneuraminic acid, xylitol, the white matsutake extract and osmanthus flower extract prepared in step S2 with a filler, a disintegrant and an adhesive solution, and then carry out tabletting and drying to obtain the bird's nest peptide tablets; S3.2: Put the above bird's nest peptide tablets into a rotary coater, and evenly spray the coating solution prepared in step S1.3 on its surface. After drying and curing, obtain the composite tablets; The polymethacrylate copolymer is any one of Eudragit L30D-55 and Eudragit L100-55; The volume ratio of the polymethacrylate copolymer solution to the poly(lactic-co-glycolic acid) copolymer solution is (3 - 5):1; The bird's nest peptide tablets, by mass, are composed of: 20 - 30 parts of small molecule bird's nest peptide, 1 - 3 parts of N-acetylneuraminic acid, 6 - 8 parts of xylitol, 8 - 10 parts of white matsutake extract, 4 - 6 parts of osmanthus flower extract, 12 - 16 parts of filler, 0.1 - 0.5 parts of disintegrant and 0.6 - 1 part of adhesive; The preparation process of the small molecule bird's nest peptide includes the following steps: (1) Freeze and crush the bird's nest: Place the bird's nest in a freezer at -15~-5°C for 20 - 30 min, then place it in a crusher and crush for 20 - 30 min. Repeat 2 - 3 times. After passing through a 60 - 100 mesh sieve, obtain the bird's nest powder; (2) Composite enzyme hydrolysis: Add the above bird's nest powder to deionized water at a solid-liquid ratio of 1 g:(40 - 50) mL, heat and stir at 90 - 100°C for 1 - 2 h. When cooled to 45 - 50°C, add the composite enzyme, and ultrasonically assist the incubation and hydrolysis for 3 - 4 h. Then use a boiling water bath to inactivate the enzyme for 10 - 20 min. After centrifugal separation, collect the supernatant and vacuum freeze-dry to obtain the small molecule bird's nest peptide; Among them, the composite enzyme is composed of neutral protease and flavor protease mixed in a mass ratio of 1:(2.8 - 3.4), and the addition amount of the composite enzyme is 4000 - 5000 U / g of bird's nest powder.

2. The process for preparing the composite tablet according to claim 1, characterized in that, S2 specifically includes the following steps: S2.1: After washing, drying, pulverizing and sieving the white matsutake, add it to a 50% ethanol solution at a material-liquid ratio of 1 g:(20 - 30) mL, ultrasonically assist the extraction for 1 - 2 h, repeat 2 - 3 times, and after filtration and evaporation concentration, obtain the white matsutake extract; S2.2: After cleaning, drying, and mashing fresh osmanthus flowers, add them to a 70% ethanol solution at a material-liquid ratio of 1 g : (30 - 40) mL, perform ultrasonic-assisted extraction for 1 - 2 h, repeat twice, then filter, concentrate under reduced pressure, and dry to obtain osmanthus flower extract.

3. The process for preparing the composite tablet according to claim 1, characterized in that, The filler is any one of microcrystalline cellulose or starch.

4. The process for preparing a composite tablet according to claim 1, characterized in that, The disintegrant is any one of croscarmellose sodium or crospovidone, and the binder is any one of povidone or hypromellose.

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