A method for producing gelatin for hard capsules using cowhide

Abstract

The present invention belongs to the technical field of gelatin extraction, and specifically relates to a method for producing gelatin for hard capsules using cowhide. The method is achieved through the following steps: pretreating the cowhide that has been cleaned; adding the pretreated cowhide to a phosphate buffer solution, sodium deoxycholate, and lipase for primary enzymatic hydrolysis; after the primary enzymatic hydrolysis ends, continuing to add a mixed enzyme for secondary enzymatic hydrolysis, and inactivating the enzyme after the enzymatic hydrolysis ends; adding distilled water to the enzymatic hydrolysis system and oscillating to form a sol for 4 h, then filtering to obtain a glue solution, centrifuging the glue solution, collecting the supernatant, and then freeze-drying. The special gelatin for hard capsules prepared by the present invention can reduce the moisture content of the prepared hollow capsules, while maintaining normal gelatin elasticity and toughness, enhancing water retention, having a high forming rate, and not easily causing the capsule shell to rupture; the special gelatin for hard capsules prepared by the present invention reduces temperature dependence and extends the storage period of the capsule shell.

Description

Technical Field

[0001] The present invention belongs to the technical field of gelatin extraction, and particularly relates to a method for producing gelatin for hard capsules using cowhide. Background Art

[0002] Hard capsules refer to capsule preparations that use appropriate preparation techniques to fill uniform powders made from raw materials or with appropriate dressings into hollow capsules. Hard capsules are favored by consumers at home and abroad more and more because of their smooth and beautiful appearance, which can cover up the inappropriate bitterness and odor of raw materials, making them easy to accept; no binder or pressure is required during the preparation process, so they disintegrate quickly in the gastrointestinal tract, and generally release functional substances within 3 - 10 minutes after taking. Compared with pills and tablets, hard capsules have a faster onset of action and better absorption; they have good stability. For example, vitamins are suitable to be filled into opaque hard capsules for easy storage; they can prolong the release of health care functional substances. First, the raw materials are made into granules, then coated with materials with different release rates, mixed in proportion, and filled into empty capsules to achieve the purpose of extended effect and many other advantages.

[0003] The water content of gelatin hollow capsules is approximately between 13 - 16%. The presence of moisture can maintain the elasticity and toughness of gelatin. If the moisture is too low, the capsules will become brittle and prone to capsule rupture; due to the strong hydrophilicity of the capsules, the capsule shells are prone to softening when the humidity is high. Summary of the Invention

[0004] Aiming at the problems existing in the prior art, the present invention provides a method for producing gelatin for hard capsules using cowhide. The gelatin extracted by this method has excellent properties such as elasticity and toughness. After being prepared into hard capsules, the surface is smooth, the formability is good, and the addition amount of plasticizer can be reduced, reducing the dependence on the surrounding environment.

[0005] The technical solution adopted by the present invention to achieve the above purpose is as follows:

[0006] The present invention provides a method for producing gelatin for hard capsules using cowhide, comprising the following steps:

[0007] (1) Cut the cleaned cowhide into pieces, soak it in an aqueous solution of fatty alcohol polyoxyethylene ether - sodium chloride, and obtain pretreated cowhide after filtration and water washing;

[0008] (2) Add the pretreated cowhide to a phosphate buffer solution, sodium deoxycholate, and lipase for primary enzymatic hydrolysis; (3) After the primary enzymatic hydrolysis is completed, continue to add a mixed enzyme for secondary enzymatic hydrolysis, and inactivate the enzyme after the enzymatic hydrolysis is completed; (4) Oscillate and solubilize the enzymatic hydrolysis system with distilled water for 4 h, then filter to obtain a glue solution, centrifuge the glue solution, collect the supernatant, and then freeze - dry it.

[0009] Further, in step (1), the concentration of the sodium chloride aqueous solution is 5%; the concentration of the fatty alcohol polyoxyethylene ether in the sodium chloride aqueous solution is 1.5%; the soaking time is 60 - 90 min.

[0010] Further, in step (2), the material ratio of the cowhide to the phosphate buffer solution is 1 g:10 mL; the pH value of the phosphate buffer solution is 6.5 - 6.8; the addition amount of the lipase accounts for 800 - 1000 U / g of the mass of the cowhide; the addition amount of sodium deoxycholate accounts for 0.5% of the mass of the cowhide.

[0011] Further, in step (3), the addition amount of the mixed enzyme accounts for 2000 - 2500 U / g of the mass of the cowhide.

[0012] Further, in step (3), the mixed enzyme is composed of acid protease and black yeast in a mass ratio of 5:1.

[0013] Further, the first enzymatic hydrolysis is carried out at 38 - 40 °C for 3 - 5 h; the second enzymatic hydrolysis is first carried out at 28 - 32 °C for 8 - 10 h, and then the temperature is raised to 35 - 38 °C for 15 - 20 h.

[0014] Further, in step (4), the mass ratio of the cowhide to the distilled water is 1:30.

[0015] The enzymatic hydrolysis method provided by the present invention first performs the first enzymatic hydrolysis with lipase for degreasing treatment. At the same time, after pre - treating the cowhide, it can improve the rate of subsequent enzymatic hydrolysis and the yield of gelatin. At the same time, in the second enzymatic hydrolysis process of the present invention, through the mixed enzymatic hydrolysis of acid protease and black yeast, the toughness and stability of the prepared gelatin are significantly improved, the dependence on the surrounding environment is reduced, and the hydrophilic property is weakened, and the formability is good. The enzyme - inactivating method used in the present invention is carried out in a boiling water bath, and the enzyme - inactivating time is 10 - 15 min.

[0016] The beneficial effects of the present invention are as follows:

[0017] (1) The special gelatin for hard capsules prepared by the present invention can reduce the moisture content of the prepared hollow capsules, while maintaining normal gelatin elasticity and toughness, enhancing water retention, having a high forming rate, and not easily occurring capsule shell rupture; (2) The special gelatin for hard capsules prepared by the present invention reduces the temperature dependence and extends the storage period of the capsule shell. Detailed implementation manners

[0018] The technical solutions of the present invention will be further explained and illustrated through specific examples below.

[0019] Example 1

[0020] (1) Cut the cleaned cowhide into pieces, soak it in an aqueous solution of fatty alcohol polyoxyethylene ether (1.5%) - sodium chloride (5 wt%) for 90 min, and obtain pretreated cowhide after filtration and water washing;

[0021] (2) Add 10 mL of phosphate buffer (pH 6.5), 5 mg of sodium deoxycholate and 1000 U / g of lipase to 1 g of the pretreated cowhide, and enzymatically hydrolyze at 38 °C for 4 h;

[0022] (3) After the first enzymatic hydrolysis is completed, continue to add 2500 U / g of a mixed enzyme (m acidic protease: m black yeast = 5:1). First, enzymatically hydrolyze at 28 - 32 °C for 10 h, then raise the temperature to 35 - 38 °C and enzymatically hydrolyze for 18 h. After the enzymatic hydrolysis is completed, inactivate the enzyme;

[0023] (4) Add 30 times the amount of 60 °C distilled water to the enzymatic hydrolysis system, oscillate and solubilize for 4 h, then filter to obtain a colloidal solution. Centrifuge the colloidal solution, collect the supernatant and freeze-dry it.

[0024] Example 2

[0025] (1) Cut the cleaned cowhide into pieces, soak it in an aqueous solution of fatty alcohol polyoxyethylene ether (1.5%) - sodium chloride (5 wt%) for 90 min, and obtain pretreated cowhide after filtration and water washing;

[0026] (2) Add 10 mL of phosphate buffer (pH 6.5), 5 mg of sodium deoxycholate and 1000 U / g of lipase to 1 g of the pretreated cowhide, and enzymatically hydrolyze at 38 °C for 4 h;

[0027] (3) After the first enzymatic hydrolysis is completed, continue to add 2000 U / g of a mixed enzyme (m acidic protease: m black yeast = 5:1). First, enzymatically hydrolyze at 28 - 32 °C for 8 h, then raise the temperature to 35 - 38 °C and enzymatically hydrolyze for 20 h. After the enzymatic hydrolysis is completed, inactivate the enzyme;

[0028] (4) Add 30 times the amount of 60 °C distilled water to the enzymatic hydrolysis system, oscillate and solubilize for 4 h, then filter to obtain a colloidal solution. Centrifuge the colloidal solution, collect the supernatant and freeze-dry it.

[0029] Example 3

[0030] (1) Cut the cleaned cowhide into pieces, soak it in an aqueous solution of fatty alcohol polyoxyethylene ether (1.5%) - sodium chloride (5 wt%) for 90 min, and obtain pretreated cowhide after filtration and water washing;

[0031] (2) Add 10 mL of phosphate buffer (pH 6.5), 5 mg of sodium deoxycholate and 1000 U / g of lipase to 1 g of the pretreated cowhide, and enzymatically hydrolyze at 38 °C for 4 h;

[0032] (3) After the first enzymatic hydrolysis, continue to add a mixed enzyme of 2300 U / g (m acidic protease: m black yeast = 5:1). First, perform enzymatic hydrolysis at 28 - 32 °C for 10 h, then raise the temperature to 35 - 38 °C and perform enzymatic hydrolysis for 15 h. After the enzymatic hydrolysis is completed, inactivate the enzyme.

[0033] (4) Add 30 times the amount of 60 °C distilled water to the enzymatic hydrolysis system, oscillate and solubilize for 4 h, then filter to obtain a colloidal solution. Centrifuge the colloidal solution, collect the supernatant, and then freeze-dry it.

[0034] Comparative Example 1

[0035] (1) Cut the cleaned cowhide into pieces, add an aqueous solution of fatty alcohol polyoxyethylene ether (1.5%) - sodium chloride (5 wt%) and soak for 90 min. After filtration and washing with water, obtain pretreated cowhide.

[0036] (2) Add 10 mL of phosphate buffer solution (pH value 6.5) and 1000 U / g lipase to 1 g of the pretreated cowhide, and perform enzymatic hydrolysis at 38 °C for 4 h.

[0037] (3) After the first enzymatic hydrolysis, continue to add a mixed enzyme of 2500 U / g (m acidic protease: m black yeast = 5:1). First, perform enzymatic hydrolysis at 28 - 32 °C for 10 h, then raise the temperature to 35 - 38 °C and perform enzymatic hydrolysis for 18 h. After the enzymatic hydrolysis is completed, inactivate the enzyme.

[0038] (4) Add 30 times the amount of 60 °C distilled water to the enzymatic hydrolysis system, oscillate and solubilize for 4 h, then filter to obtain a colloidal solution. Centrifuge the colloidal solution, collect the supernatant, and then freeze-dry it.

[0039] Comparative Example 2

[0040] (1) Cut the cleaned cowhide into pieces, add an aqueous solution of fatty alcohol polyoxyethylene ether (1.5%) - sodium chloride (5 wt%) and soak for 90 min. After filtration and washing with water, obtain pretreated cowhide.

[0041] (2) Add 10 mL of phosphate buffer solution (pH value 6.5), 5 mg of sodium deoxycholate and 1000 U / g lipase to 1 g of the pretreated cowhide, and perform enzymatic hydrolysis at 38 °C for 4 h.

[0042] (3) After the first enzymatic hydrolysis, continue to add 2500 U / g of acidic protease, then raise the temperature to 35 - 38 °C and perform enzymatic hydrolysis for 28 h. After the enzymatic hydrolysis is completed, inactivate the enzyme.

[0043] (4) Add 30 times the amount of 60 °C distilled water to the enzymatic hydrolysis system, oscillate and solubilize for 4 h, then filter to obtain a colloidal solution. Centrifuge the colloidal solution, collect the supernatant, and then freeze-dry it.

[0044] Comparative Example 3

[0045] (1) Cut the cleaned cowhide into pieces, soak it in an aqueous solution of fatty alcohol polyoxyethylene ether (1.5%) - sodium chloride (5 wt%) for 90 min, and obtain pretreated cowhide after filtration and washing with water.

[0046] (2) Add 10 mL of phosphate buffer (pH 6.5), 5 mg of sodium deoxycholate, and 1000 U / g of lipase to 1 g of the pretreated cowhide, and enzymatically hydrolyze at 38 °C for 4 h.

[0047] (3) After the first enzymatic hydrolysis is completed, continue to add 2500 U / g of a mixed enzyme (m acidic protease: m black yeast = 5:1), raise the temperature to 35 - 38 °C and enzymatically hydrolyze for 28 h, and inactivate the enzyme after the enzymatic hydrolysis is completed.

[0048] (4) Add 30 times the amount of 60 °C distilled water to the enzymatic hydrolysis system, oscillate and solubilize for 4 h, then filter to obtain a colloidal solution, centrifuge the colloidal solution, collect the supernatant and freeze-dry it.

[0049] Effect Example (1) After extracting gelatin from cowhide in the examples and comparative examples, the gelatin extraction rate was statistically analyzed. At the same time, the gel strength of the extracted gelatin was detected, and the Bloom force was detected using a texture analyzer: Prepare an aqueous gelatin solution with a concentration of 6.67% (w / v), then place it in a 10 °C water bath for 16 h to form a sample with a diameter of 4.0 cm and a height of 5.0 cm. Then, use a probe with a diameter of 12.7 mm, a test distance of 4.0 mm, and a test speed of 0.5 mm / s, set five parallel tests, and the maximum pressure (g) that the prepared sample can withstand is the Bloom force; the gelatin extraction rate is calculated according to the following formula:

[0050] Cowhide gelatin extraction rate = (mass of freeze-dried gelatin finished product / dry weight of cowhide) * 100%;

[0051] The specific results are shown in Table 1.

[0052] Table 1

[0053]

[0054] (2) Prepare hard capsule shells from the examples and comparative examples: 1000 g of gelatin, 30 g of pigment, 200 g of nano-titanium dioxide, 8 g of mannitol, and 30 parts of water, prepare hard capsule shells, dry and harden them to make the water content 8 - 9% and the shell thickness 0.2 - 0.3 mm; (1) Take 50 samples, immediately place them into glass tubes one by one. The inner diameter of the glass tube is 24 mm and the length is 200 mm. Let a 20 g polytetrafluoroethylene material weight freely fall from the glass tube mouth, and observe whether the capsule breaks; (2) Immerse the hard capsule shells in artificial gastric juice and detect the disintegration time. The specific results are shown in Table 2.

[0055] Table 2

[0056] Friability Disintegration time Example 1 2 tablets 8 min Comparative Example 1 7 tablets 12 min Comparative Example 2 12 tablets 15 min

[0057] (3) Detect the drying loss rate of the prepared hollow capsules: Weigh 1.0 g of the hollow capsules precisely into a weighing bottle that has been dried to a constant weight. Then place it in an oven and treat it at 105 °C for 6 h. After cooling to room temperature in a desiccator, weigh it again and calculate the drying loss rate. At the same time, detect the ignition residue: Place the hollow capsules in a crucible for carbonization. After the carbonization is completed, add sulfuric acid dropwise, then heat until the sulfuric acid is completely removed, and then place it in a high-temperature furnace for ignition until it is completely ashed, and calculate the ignition residue rate. The specific results are shown in Table 3.

[0058] Table 3

[0059] Loss on drying (%) Residue on ignition (%) Example 1 10.115 1.25 Comparative Example 1 11.038 1.59 Comparative Example 2 12.517 1.73

Claims

1. A method for producing gelatin for hard capsules using cowhide, characterized in that, It includes the following steps: (1) Cut the cleaned cowhide into pieces, soak it in an aqueous solution of fatty alcohol polyoxyethylene ether - sodium chloride, and obtain pretreated cowhide after filtration and water washing; (2) Add the pretreated cowhide to a phosphate buffer solution, sodium deoxycholate and lipase for primary enzymatic hydrolysis; (3) After the primary enzymatic hydrolysis is completed, continue to add a mixed enzyme for secondary enzymatic hydrolysis, and inactivate the enzyme after the enzymatic hydrolysis is completed; (4) Oscillate and solubilize the enzymatic hydrolysis system with distilled water for 4 h, then filter to obtain a glue solution, centrifuge the glue solution, collect the supernatant and then freeze-dry it; In step (1), the concentration of the sodium chloride aqueous solution is 5%; the concentration of the fatty alcohol polyoxyethylene ether in the sodium chloride aqueous solution is 1.5%; the soaking time is 60 - 90 min; In step (2), the material-liquid ratio of the cowhide to the phosphate buffer solution is 1 g:10 mL; the pH value of the phosphate buffer solution is 6.5 - 6.8; the addition amount of the lipase accounts for 800 - 1000 U / g of the mass of the cowhide; the addition amount of the sodium deoxycholate accounts for 0.5% of the mass of the cowhide; In step (3), the addition amount of the mixed enzyme accounts for 2000 - 2500 U / g of the mass of the cowhide; In step (3), the mixed enzyme is composed of acid protease and Saccharomyces nigricans in a mass ratio of 5:1; The primary enzymatic hydrolysis is carried out at 38 - 40 °C for 3 - 5 h; the secondary enzymatic hydrolysis is first carried out at 28 - 32 °C for 8 - 10 h, and then the temperature is raised to 35 - 38 °C for 15 - 20 h.

2. The method according to claim 1, wherein In step (4), the mass ratio of the enzymatic hydrolysis system to distilled water is 1:30.

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