A gelatin hollow capsule not easy to absorb moisture and a preparation process thereof

Abstract

The application discloses a gelatin hollow capsule not easy to absorb moisture and a preparation process thereof, and relates to the technical field of medical capsules. The application prepares a gelatin hollow capsule, adopts gelatin and acetylated tremella polysaccharide modified gelatin as capsule materials, so that the hollow capsule has good durability and the moisture absorption of the gelatin hollow capsule is reduced. The molecular weight of the gelatin used in the application is 10000-100000 Da, so that the flowability of the glue liquid is good, the glue liquid is easy to defoam and uniformly dip, and the coating capsule rate is improved. The acetylated tremella polysaccharide modified gelatin is used, the molecular weight of the acetylated tremella polysaccharide modified gelatin is large, the strength of the hollow capsule after film formation is improved, and the brittle phenomenon of the capsule is reduced. The tremella polysaccharide is also acetylated and modified in the application, the hydrophobic effect of the tremella polysaccharide is enhanced, and the moisture absorption of the gelatin hollow capsule is reduced.

Description

Technical Field

[0001] This invention relates to the field of medical capsule technology, specifically to a non-hygroscopic gelatin hollow capsule and its preparation process. Background Technology

[0002] Gelatin capsules, as a traditional drug carrier, are widely used in the pharmaceutical field due to their good biocompatibility and disintegration properties. However, existing gelatin capsules generally suffer from high hygroscopicity, easily absorbing water and softening / deforming in high humidity environments, leading to leakage of contents or capsule adhesion. Capsules prepared by conventional processes have a loose structure, allowing moisture to easily penetrate. Although existing technologies have attempted to improve moisture resistance by adding preservatives or surface coatings, problems such as limited dosage and impaired disintegration remain, failing to fundamentally solve the hydrophilicity problem of gelatin materials.

[0003] To address the aforementioned issues, this application provides a gelatin hollow capsule that is not easily hygroscopic and its preparation process. Summary of the Invention

[0004] The purpose of this invention is to provide a gelatin empty capsule that is not easily hygroscopic and its preparation process, so as to solve the problems raised in the prior art.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A process for preparing a non-hygroscopic gelatin empty capsule includes the following steps:

[0007] Step 1: Take gelatin, acetylated tremella polysaccharide-modified gelatin, and deionized water, pass steam through, and react at 25-30℃ for 30-40 minutes. Raise the temperature to 80-85℃, stir evenly, add sodium dodecyl sulfate, stir evenly, add oxalic acid-modified sodium alginate and calcium chloride, stir evenly, and let stand. Then dip the gelatin into the gelatin and shape it to obtain gelatin hollow capsule material.

[0008] Step 2: Coat the surface of the gelatin hollow capsule material with a mixture of polyacrylic acid resin and n-butyl acetate, stir, dry, cure, cool, and cut to obtain gelatin hollow capsules that are not easily hygroscopic.

[0009] In a more optimized form, the non-hygroscopic gelatin hollow capsule comprises the following components, by weight: 50-60 parts gelatin, 50-60 parts acetylated tremella polysaccharide-modified gelatin, 5-8 parts deionized water, 12-16 parts sodium dodecyl sulfate, 12-15 parts sarsaparilla acid-modified sodium alginate, 2-6 parts calcium chloride, 10-12 parts polyacrylic acid resin, and 30-40 parts n-butyl acetate.

[0010] Ideally, the mass ratio of the gelatin to the acetylated tremella polysaccharide-modified gelatin is 1:1-1.1.

[0011] A more optimized method for preparing the acetylated tremella polysaccharide-modified gelatin includes the following steps: taking gelatin and deionized water, stirring evenly to obtain a gelatin solution, adding acetylated tremella polysaccharide, stirring evenly to obtain a mixed solution; adjusting the pH of the mixed solution to 8, freeze-drying, and then placing it in a KBr saturated solution, reacting at 60-62℃ for 22-26 hours to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolving the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in deionized water to obtain a composite solution; adding lysozyme and deionized water to the composite solution, stirring evenly, adjusting the pH using sodium hydroxide solution, then heating the solution in a water bath for 30-40 minutes, cooling, to obtain the acetylated tremella polysaccharide-modified gelatin.

[0012] Ideally, the mass ratio of the gelatin to the acetylated tremella polysaccharide is 1:1.

[0013] In a more optimized manner, lysozyme and deionized water are added to the composite solution, stirred evenly, the pH value is adjusted to 10 using sodium hydroxide solution, and then the solution is heated in a water bath for 30-40 minutes and cooled to obtain acetylated tremella polysaccharide-modified gelatin.

[0014] A more optimized method for preparing the acetylated Tremella polysaccharide is as follows: Imidazole and ethyl acetate are mixed evenly, chloroacetic acid is added, and the mixture is heated to 90-95℃ for 7-9 hours. After standing, washing, and drying, an ionic liquid is obtained. Tremella polysaccharide is added to the ionic liquid, mixed evenly, acetic anhydride is added, and the mixture is reacted for 12-14 hours. Anhydrous ethanol is added, and the mixture is filtered, washed, and dried to obtain the acetylated Tremella polysaccharide.

[0015] In a more optimized manner, the preparation method of the oxaliplatin-modified sodium alginate is as follows: oxaliplatin is added to a sodium alginate solution, stirred evenly, and dried to obtain oxaliplatin-modified sodium alginate.

[0016] Compared with the prior art, the beneficial effects of the present invention are:

[0017] 1. This application prepares a gelatin hollow capsule, using gelatin and acetylated tremella polysaccharide-modified gelatin as the capsule material, which improves the durability of the hollow capsule and reduces its hygroscopicity. The gelatin used in this application has a molecular weight of 10,000-100,000 Da, which makes the gel solution flow well, facilitates defoaming and uniform coating, and improves the coating and encapsulation rate.

[0018] 2. Acetylated Tremella fuciformis polysaccharide is used to modify gelatin. The acetylated Tremella fuciformis polysaccharide-modified gelatin has a large molecular weight, which improves the film-forming strength of the empty capsules and reduces the brittleness of the capsules. This application also acetylates the Tremella fuciformis polysaccharide, enhancing its hydrophobic effect and thus reducing the hygroscopicity of the gelatin empty capsules.

[0019] 3. This application uses oxalic acid to modify sodium alginate. Oxalic acid can improve the antibacterial effect of the capsule. The phenolic hydroxyl groups on oxalic acid form hydrogen bonds with the carboxyl groups on sodium alginate, reducing the exposure of hydrophilic groups and thus improving the hydrophobicity and water resistance of the capsule. Detailed Implementation

[0020] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] The sources and types of substances involved in this application are not specifically limited. Exemplary examples include: gelatin: molecular weight 10,000-70,000 Da, CAS number: 9000-70-8, which can be purchased from Shanghai Ruichu Biotechnology Co., Ltd.; Tremella fuciformis polysaccharide: molecular weight > 100,0000 Da, type: V30287, which can be purchased from Shanghai Yuanye Biotechnology Co., Ltd.; and polyacrylic acid resin: pharmaceutical grade polyacrylic acid resin, which can be purchased from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0022] Example 1: A preparation process for a non-hygroscopic gelatin hollow capsule, comprising the following steps:

[0023] Step 1: Preparation of sodium alginate modified with sageric acid:

[0024] 0.22g of oxalic acid was added to 1L of sodium alginate solution with a concentration of 1.5% w / v, stirred evenly, and dried to obtain oxalic acid-modified sodium alginate.

[0025] Step 2: Preparation of acetylated Tremella polysaccharide:

[0026] Take 3.5g imidazole and 50mL ethyl acetate, stir well, add 5.8g chloroacetic acid, heat to 92℃ and react for 8h, let stand, wash and dry to obtain ionic liquid; take 4g of Tremella polysaccharide and add to 4.4g ionic liquid, stir well, add 6g acetic anhydride, react for 13h, add 100mL anhydrous ethanol, filter, wash and dry to obtain acetylated Tremella polysaccharide;

[0027] Step 3: Preparation of gelatin modified with acetylated tremella polysaccharide:

[0028] Take 4g of gelatin and 200mL of deionized water, stir well to obtain a gelatin solution, add acetylated tremella polysaccharide, control the mass ratio of gelatin to acetylated tremella polysaccharide to be 1:1, stir well to obtain a mixed solution, adjust the pH of the mixed solution to 8, freeze dry, and then place it in a sealed container of KBr saturated solution (relative humidity 79%), react at 61℃ for 24h to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolve 2g of the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in 100mL of deionized water to obtain a composite solution;

[0029] Add 2g of lysozyme and 100mL of deionized water to the composite solution, stir well, adjust the pH value to 10 with 0.1mol / L sodium hydroxide solution, heat the solution in an 80℃ water bath for 0.5h, cool, and obtain acetylated tremella polysaccharide modified gelatin.

[0030] Step 4: Preparation of non-hygroscopic gelatin capsules:

[0031] Take gelatin, acetylated tremella polysaccharide-modified gelatin, and deionized water, pass steam through them, react at 28°C for 35 minutes, raise the temperature to 82°C, stir evenly, add sodium dodecyl sulfate, continue stirring for 35 minutes, add oxalic acid-modified sodium alginate and calcium chloride, stir evenly, and let stand for 3.5 hours; then dip the gelatin and shape it to obtain gelatin hollow capsule material.

[0032] A mixture of polyacrylic acid resin and n-butyl acetate was used to coat the surface of gelatin hollow capsule material. The mixture was stirred, dried for 1.2 hours at 75°C, cured, cooled, and cut to obtain gelatin hollow capsules that do not easily absorb moisture.

[0033] The non-hygroscopic gelatin hollow capsules comprise the following components, by weight: 55 parts gelatin, 58 parts acetylated tremella polysaccharide-modified gelatin, 6 parts deionized water, 14 parts sodium lauryl sulfate, 13 parts sarsaparilla acid-modified sodium alginate, 4 parts calcium chloride, 11 parts polyacrylic acid resin, and 35 parts n-butyl acetate.

[0034] Example 2: A process for preparing a non-hygroscopic gelatin hollow capsule, comprising the following steps:

[0035] Step 1: Preparation of sodium alginate modified with sageric acid:

[0036] 0.22g of oxalic acid was added to 1L of sodium alginate solution with a concentration of 1.5% w / v, stirred evenly, and dried to obtain oxalic acid-modified sodium alginate.

[0037] Step 2: Preparation of acetylated Tremella polysaccharide:

[0038] Take 3.5g imidazole and 50mL ethyl acetate, stir well, add 5.8g chloroacetic acid, heat to 90℃ and react for 7h, let stand, wash and dry to obtain ionic liquid; take 4g of Tremella polysaccharide and add to 4.4g ionic liquid, stir well, add 6g acetic anhydride, react for 12h, add 100mL anhydrous ethanol, filter, wash and dry to obtain acetylated Tremella polysaccharide;

[0039] Step 3: Preparation of gelatin modified with acetylated tremella polysaccharide:

[0040] Take 4g of gelatin and 200mL of deionized water, stir well to obtain a gelatin solution, add acetylated tremella polysaccharide, control the mass ratio of gelatin to acetylated tremella polysaccharide to be 1:1, stir well to obtain a mixed solution, adjust the pH of the mixed solution to 8, freeze dry, and then place it in a sealed container of KBr saturated solution (relative humidity 79%), react at 60℃ for 22h to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolve 2g of the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in 100mL of deionized water to obtain a composite solution;

[0041] Add 2g of lysozyme and 100mL of deionized water to the composite solution, stir well, adjust the pH value to 10 with 0.1mol / L sodium hydroxide solution, heat the solution in an 80℃ water bath for 0.5h, cool, and obtain acetylated tremella polysaccharide modified gelatin.

[0042] Step 4: Preparation of non-hygroscopic gelatin capsules:

[0043] Take gelatin, acetylated tremella polysaccharide-modified gelatin, and deionized water, pass steam through them, react at 25°C for 30 minutes, raise the temperature to 80°C, stir evenly, add sodium dodecyl sulfate, continue stirring for 30 minutes, add oxalic acid-modified sodium alginate and calcium chloride, stir evenly, and let stand for 3 hours; then dip the gelatin and shape it to obtain gelatin hollow capsule material.

[0044] A mixture of polyacrylic acid resin and n-butyl acetate was used to coat the surface of gelatin hollow capsule material. The mixture was stirred, dried for 1 hour at 70°C, cured, cooled, and cut to obtain gelatin hollow capsules that do not easily absorb moisture.

[0045] The non-hygroscopic gelatin hollow capsules comprise the following components, by weight: 50 parts gelatin, 50 parts acetylated tremella polysaccharide-modified gelatin, 5 parts deionized water, 12 parts sodium dodecyl sulfate, 12 parts sarsaparilla acid-modified sodium alginate, 2 parts calcium chloride, 10 parts polyacrylic acid resin, and 30 parts n-butyl acetate.

[0046] Example 3: A process for preparing a non-hygroscopic gelatin hollow capsule, comprising the following steps:

[0047] Step 1: Preparation of sodium alginate modified with sageric acid:

[0048] 0.22g of oxalic acid was added to 1L of sodium alginate solution with a concentration of 1.5% w / v, stirred evenly, and dried to obtain oxalic acid-modified sodium alginate.

[0049] Step 2: Preparation of acetylated Tremella polysaccharide:

[0050] Take 3.5g imidazole and 50mL ethyl acetate, stir well, add 5.8g chloroacetic acid, heat to 95℃ and react for 9h, let stand, wash and dry to obtain ionic liquid; take 4g of Tremella polysaccharide and add to 4.4g ionic liquid, stir well, add 6g acetic anhydride, react for 14h, add 100mL anhydrous ethanol, filter, wash and dry to obtain acetylated Tremella polysaccharide;

[0051] Step 3: Preparation of gelatin modified with acetylated tremella polysaccharide:

[0052] Take 4g of gelatin and 200mL of deionized water, stir well to obtain a gelatin solution, add acetylated tremella polysaccharide, control the mass ratio of gelatin to acetylated tremella polysaccharide to be 1:1, stir well to obtain a mixed solution, adjust the pH of the mixed solution to 8, freeze dry, and then place it in a sealed container of KBr saturated solution (relative humidity 79%), react at 62℃ for 26h to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolve 2g of the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in 100mL of deionized water to obtain a composite solution;

[0053] Add 2g of lysozyme and 100mL of deionized water to the composite solution, stir well, adjust the pH value to 10 with 0.1mol / L sodium hydroxide solution, heat the solution in an 80℃ water bath for 0.5h, cool, and obtain acetylated tremella polysaccharide modified gelatin.

[0054] Step 4: Preparation of non-hygroscopic gelatin capsules:

[0055] Take gelatin, acetylated tremella polysaccharide-modified gelatin, and deionized water, pass steam through them, react at 30°C for 40 minutes, raise the temperature to 85°C, stir evenly, add sodium dodecyl sulfate, continue stirring for 40 minutes, add oxalic acid-modified sodium alginate and calcium chloride, stir evenly, and let stand for 4 hours; then dip the gelatin and shape it to obtain gelatin hollow capsule material.

[0056] A mixture of polyacrylic acid resin and n-butyl acetate was used to coat the surface of gelatin hollow capsule material. The mixture was stirred, dried for 2 hours at 80°C, cured, cooled, and cut to obtain gelatin hollow capsules that do not easily absorb moisture.

[0057] The non-hygroscopic gelatin empty capsules comprise the following components, by weight: 55 parts gelatin, 60 parts acetylated tremella polysaccharide-modified gelatin, 8 parts deionized water, 16 parts sodium dodecyl sulfate, 15 parts sarsaparilla acid-modified sodium alginate, 6 parts calcium chloride, 12 parts polyacrylic acid resin, and 40 parts n-butyl acetate.

[0058] Comparative Example 1: Gelatin without acetylated tremella polysaccharide modification, otherwise the same as in Example 1:

[0059] Step 1: Preparation of sodium alginate modified with sageric acid:

[0060] 0.22g of oxalic acid was added to 1L of sodium alginate solution with a concentration of 1.5% w / v, stirred evenly, and dried to obtain oxalic acid-modified sodium alginate.

[0061] Step 2: Preparation of non-hygroscopic gelatin capsules:

[0062] Take gelatin and deionized water, pass steam through them, react at 28°C for 35 minutes, raise the temperature to 82°C, stir evenly, add sodium dodecyl sulfate, continue stirring for 35 minutes, add oxalic acid-modified sodium alginate and calcium chloride, stir evenly, and let stand for 3.5 hours; then dip the gelatin and shape it to obtain gelatin hollow capsule material.

[0063] A mixture of polyacrylic acid resin and n-butyl acetate was used to coat the surface of gelatin hollow capsule material. The mixture was stirred, dried for 1.2 hours at 75°C, cured, cooled, and cut to obtain gelatin hollow capsules that do not easily absorb moisture.

[0064] The non-hygroscopic gelatin empty capsules comprise the following components, by weight: 113 parts gelatin, 6 parts deionized water, 14 parts sodium dodecyl sulfate, 13 parts oxalic acid-modified sodium alginate, 4 parts calcium chloride, 11 parts polyacrylic acid resin, and 35 parts n-butyl acetate.

[0065] Comparative Example 2: No gelatin added, otherwise the same as Example 1:

[0066] Step 1: Preparation of sodium alginate modified with sageric acid:

[0067] 0.22g of oxalic acid was added to 1L of sodium alginate solution with a concentration of 1.5% w / v, stirred evenly, and dried to obtain oxalic acid-modified sodium alginate.

[0068] Step 2: Preparation of acetylated Tremella polysaccharide:

[0069] Take 3.5g imidazole and 50mL ethyl acetate, stir well, add 5.8g chloroacetic acid, heat to 92℃ and react for 8h, let stand, wash and dry to obtain ionic liquid; take 4g of Tremella polysaccharide and add to 4.4g ionic liquid, stir well, add 6g acetic anhydride, react for 13h, add 100mL anhydrous ethanol, filter, wash and dry to obtain acetylated Tremella polysaccharide;

[0070] Step 3: Preparation of gelatin modified with acetylated tremella polysaccharide:

[0071] Take 4g of gelatin and 200mL of deionized water, stir well to obtain a gelatin solution, add acetylated tremella polysaccharide, control the mass ratio of gelatin to acetylated tremella polysaccharide to be 1:1, stir well to obtain a mixed solution, adjust the pH of the mixed solution to 8, freeze dry, and then place it in a sealed container of KBr saturated solution (relative humidity 79%), react at 61℃ for 24h to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolve 2g of the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in 100mL of deionized water to obtain a composite solution;

[0072] Add 2g of lysozyme and 100mL of deionized water to the composite solution, stir well, adjust the pH value to 10 with 0.1mol / L sodium hydroxide solution, heat the solution in an 80℃ water bath for 0.5h, cool, and obtain acetylated tremella polysaccharide modified gelatin.

[0073] Step 4: Preparation of non-hygroscopic gelatin capsules:

[0074] Acetylated tremella polysaccharide-modified gelatin and deionized water were introduced and steam was introduced. The mixture was reacted at 28°C for 35 minutes, then heated to 82°C and stirred until homogeneous. Sodium dodecyl sulfate was added and stirring was continued for 35 minutes. Sodium alginate modified with oxalic acid and calcium chloride were added and stirred until homogeneous. The mixture was then allowed to stand for 3.5 hours. The mixture was then dipped in the gelatin and shaped to obtain gelatin hollow capsule material.

[0075] A mixture of polyacrylic acid resin and n-butyl acetate was used to coat the surface of gelatin hollow capsule material. The mixture was stirred, dried for 1.2 hours at 75°C, cured, cooled, and cut to obtain gelatin hollow capsules that do not easily absorb moisture.

[0076] The non-hygroscopic gelatin hollow capsules comprise the following components, by weight: 113 parts acetylated tremella polysaccharide-modified gelatin, 6 parts deionized water, 14 parts sodium dodecyl sulfate, 13 parts sarsaparilla acid-modified sodium alginate, 4 parts calcium chloride, 11 parts polyacrylic acid resin, and 35 parts n-butyl acetate.

[0077] Comparative Example 3: Sodium alginate modified with sage-like acid was not used; all other aspects were the same as in Example 1.

[0078] Step 1: Preparation of acetylated Tremella polysaccharide:

[0079] Take 3.5g imidazole and 50mL ethyl acetate, stir well, add 5.8g chloroacetic acid, heat to 92℃ and react for 8h, let stand, wash and dry to obtain ionic liquid; take 4g of Tremella polysaccharide and add to 4.4g ionic liquid, stir well, add 6g acetic anhydride, react for 13h, add 100mL anhydrous ethanol, filter, wash and dry to obtain acetylated Tremella polysaccharide;

[0080] Step 2: Preparation of gelatin modified with acetylated tremella polysaccharide:

[0081] Take 4g of gelatin and 200mL of deionized water, stir well to obtain a gelatin solution, add acetylated tremella polysaccharide, control the mass ratio of gelatin to acetylated tremella polysaccharide to be 1:1, stir well to obtain a mixed solution, adjust the pH of the mixed solution to 8, freeze dry, and then place it in a sealed container of KBr saturated solution (relative humidity 79%), react at 61℃ for 24h to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolve 2g of the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in 100mL of deionized water to obtain a composite solution;

[0082] Add 2g of lysozyme and 100mL of deionized water to the composite solution, stir well, adjust the pH value to 10 with 0.1mol / L sodium hydroxide solution, heat the solution in an 80℃ water bath for 0.5h, cool, and obtain acetylated tremella polysaccharide modified gelatin.

[0083] Step 3: Preparation of non-hygroscopic gelatin capsules:

[0084] Take gelatin, acetylated tremella polysaccharide-modified gelatin, and deionized water, pass steam through them, react at 28°C for 35 minutes, raise the temperature to 82°C, stir evenly, add sodium dodecyl sulfate, continue stirring for 35 minutes, add sodium alginate and calcium chloride, stir evenly, and let stand for 3.5 hours; then dip the gelatin and shape it to obtain gelatin hollow capsule material.

[0085] A mixture of polyacrylic acid resin and n-butyl acetate was used to coat the surface of gelatin hollow capsule material. The mixture was stirred, dried for 1.2 hours at 75°C, cured, cooled, and cut to obtain gelatin hollow capsules that do not easily absorb moisture.

[0086] The non-hygroscopic gelatin empty capsules comprise the following components, by weight: 55 parts gelatin, 58 parts acetylated tremella polysaccharide-modified gelatin, 6 parts deionized water, 14 parts sodium lauryl sulfate, 13 parts sodium alginate, 4 parts calcium chloride, 11 parts polyacrylic acid resin, and 35 parts n-butyl acetate.

[0087] experiment:

[0088] The non-hygroscopic gelatin empty capsules prepared in Examples 1-3 and Comparative Examples 1-3 were subjected to performance testing. One hundred non-hygroscopic gelatin empty capsules were randomly selected, and capsules with defects such as breakage, air bubbles, and wrinkles were removed. The percentage of good-quality empty capsules with good morphology was used to calculate the coating encapsulation rate. Moisture absorption rate: One hundred non-hygroscopic gelatin empty capsules were randomly selected, weighed and recorded as W0, and placed at 25℃ and 75% relative humidity for 24 hours. The empty capsules were then removed, weighed, and recorded as W1. The moisture absorption rate of the empty capsules was calculated as: Moisture absorption rate % = (W1 - W0) / W0 × 100%. One hundred and ten thousand non-hygroscopic gelatin empty capsules were selected, and their friability was tested according to the friability test method in the 2020 edition of the Chinese Pharmacopoeia. The unbroken pass rate was calculated as the friability pass rate. The data obtained are shown in Table 1 below.

[0089] Table 1:

[0090]

[0091] Conclusions: In Comparative Example 1, without the addition of acetylated Tremella polysaccharide-modified gelatin, the hygroscopicity of the gelatin capsules decreased, the strength of the capsule film after formation decreased, the brittleness of the capsules increased, and the brittleness qualification rate decreased. In Comparative Example 2, without the addition of gelatin, the coating encapsulation rate decreased. In Comparative Example 3, without the use of oxalic acid-modified sodium alginate, the hygroscopicity of the gelatin capsules decreased. Examples 1-3 of this application use gelatin and acetylated Tremella polysaccharide-modified gelatin as capsule materials, resulting in good capsule durability and reduced hygroscopicity. The gelatin used in this application has a molecular weight of 10,000-100,000 Da, which makes the gel solution flow well, easy to defoam and evenly coat, and improves the coating encapsulation rate. The use of acetylated Tremella polysaccharide-modified gelatin enhances the hydrophobic effect of Tremella polysaccharide, thereby reducing the hygroscopicity of the gelatin capsules. Modifying sodium alginate with oxalic acid enhances the antibacterial effect of the capsules. The phenolic hydroxyl groups on oxalic acid form hydrogen bonds with the carboxyl groups on sodium alginate, reducing the exposure of hydrophilic groups and improving the hygroscopicity of the gelatin capsules.

[0092] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

Claims

1. A process for the production of a gelatin hollow capsule which is not susceptible to moisture absorption, characterized in that: Includes the following steps: Step 1: Take gelatin, acetylated tremella polysaccharide-modified gelatin, and deionized water, pass steam through, and react at 25-30℃ for 30-40 minutes. Raise the temperature to 80-85℃, stir evenly, add sodium dodecyl sulfate, stir evenly, add oxalic acid-modified sodium alginate and calcium chloride, stir evenly, and let stand. Then dip the gelatin into the gelatin and shape it to obtain gelatin hollow capsule material. Step 2: Take a mixture of polyacrylic acid resin and n-butyl acetate to coat the surface of the gelatin hollow capsule material, stir, dry, cure, cool, and cut to obtain gelatin hollow capsules that are not easily hygroscopic. The preparation method of the acetylated Tremella polysaccharide-modified gelatin includes the following steps: Take gelatin and deionized water, stir evenly to obtain a gelatin solution, add acetylated tremella polysaccharide, stir evenly to obtain a mixed solution; adjust the pH of the mixed solution to 8, freeze-dry, and then place it in a saturated KBr solution and react at 60-62℃ for 22-26 h to obtain a pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin; then dissolve the pre-crosslinked composite material of acetylated tremella polysaccharide and gelatin in deionized water to obtain a composite solution; add lysozyme and deionized water to the composite solution, stir evenly, adjust the pH to 10 using sodium hydroxide solution, then heat the solution in a water bath for 30-40 min, cool, and obtain acetylated tremella polysaccharide modified gelatin; The preparation method of the rat oxalic acid modified sodium alginate is as follows: rat oxalic acid is added to sodium alginate solution, stirred evenly, and dried to obtain rat oxalic acid modified sodium alginate.

2. A process for the production of a moisture resistant gelatin hollow capsule according to claim 1, characterized in that: The non-hygroscopic gelatin hollow capsules comprise the following components, by weight: 50-60 parts gelatin, 50-60 parts acetylated tremella polysaccharide-modified gelatin, 5-8 parts deionized water, 12-16 parts sodium dodecyl sulfate, 12-15 parts sarsaparilla acid-modified sodium alginate, 2-6 parts calcium chloride, 10-12 parts polyacrylic acid resin, and 30-40 parts n-butyl acetate.

3. The preparation process of a non-hygroscopic gelatin hollow capsule according to claim 1, characterized in that: In step one, the mass ratio of gelatin to acetylated tremella polysaccharide-modified gelatin is 1:1-1.

1.

4. The process for the preparation of a moisture resistant gelatin hollow capsule as claimed in claim 1 wherein: In the preparation method of gelatin modified with acetylated tremella polysaccharide, the mass ratio of gelatin to acetylated tremella polysaccharide is 1:

1.

5. A process for the preparation of a moisture resistant gelatin hollow capsule as claimed in claim 1, wherein: The preparation method of the acetylated Tremella polysaccharide is as follows: take imidazole and ethyl acetate, stir evenly, add chloroacetic acid, heat to 90-95℃ and react for 7-9 hours, let stand, wash and dry to obtain ionic liquid; take Tremella polysaccharide and add it to the ionic liquid, stir evenly, add acetic anhydride, react for 12-14 hours, add anhydrous ethanol, filter, wash and dry to obtain acetylated Tremella polysaccharide.

6. A gelatin hollow capsule that is not easily absorbing moisture, prepared according to any one of claims 1-5.

Images