Preparation method of colon-targeted plant empty capsule

Abstract

The invention discloses a preparation method of a colon-targeted plant empty capsule, which comprises the following steps: (1) slowly adding low-acyl gellan gum, guar gum, hydroxypropyl methyl cellulose and potassium citrate into a sol tank, uniformly mixing, adding purified water, stirring for 30 minutes, finally adding glycerol, continuously stirring to fully absorb water and swell, and standing for 30 minutes to obtain a gel solution; raising the temperature of the glue dissolving tank, stirring until uniform glue liquid is formed, slowly cooling, stirring at a constant temperature, maintaining the glue, and dipping the glue; (2) drying the material dipped with glue with hot air, then putting the dried material into a stabilizing box for balanced cooling, then taking down the capsule from the mold, and cutting the capsule as required to obtain a capsule body and a capsule cap; and (3) sleeving the capsule body and the capsule cap together. The prepared colon-targeted plant empty capsule has chemical inertness, cannot be subjected to cross-linking, condensation and other reactions with a filling medicine, and can effectively ensure the disintegration, dissolution and bioavailability of the capsule.

Description

Technical Field

[0001] The invention belongs to the technical field of plant capsule preparation, and particularly relates to a method for preparing colon-targeted plant hollow capsules. Background Art

[0002] The targeted drug delivery system (DDS) is an advanced drug delivery technology that can selectively transport and release drugs to specific target tissues, target organs or target cells. This system reduces toxic side effects by increasing drug concentration in the target area while reducing drug concentration in non-target areas, representing the fourth generation of drug dosage forms. As a potential target for drug delivery, the colon has lower levels of metabolic enzymes and transporters, which helps to improve the bioavailability of drugs. Peptide drugs show good absorption at the end of the small intestine, and their slow release in the colon helps to achieve long-term effects, especially in the treatment of nocturnal diseases. In addition, the lesion area in the proximal colon provides effectiveness for the direct release of drugs, making colon-targeted drug delivery a hot topic in DDS research.

[0003] However, there are some problems with the colon-targeted hollow capsules currently on the market. The positioning accuracy of pH-dependent or time-dependent colon-targeted capsules is insufficient. Flora / enzyme-triggered intestinal-targeted hollow capsules are usually coated with gelatin capsules, and the coating material is mainly azo compounds, which may cause toxic side effects, and its safety needs to be further improved. Summary of the invention

[0004] The present invention aims to overcome the defects of the prior art and provide a method for preparing colon-targeted plant hollow capsules.

[0005] The technical solution of the present invention is as follows:

[0006] A method for preparing colon-targeted plant hollow capsules comprises the following steps:

[0007] (1) Slowly add low acyl gellan gum, guar gum, hydroxypropyl methylcellulose and potassium citrate into a sol tank, mix well, add purified water, stir and soak for 30 minutes, finally add glycerin, stir continuously to make it fully absorb water and swell, heat the sol tank to 58-62° C., stir until a uniform glue solution is formed, slowly cool to 48-52° C., stir at a constant temperature for 0.8-1.2 hours, cure the glue for 1-24 hours, and then dip in glue;

[0008] (2) drying the material after dipping in the glue in step (1) at 30-40° C. with hot air for 1-3 hours, and then placing it in a stabilization box at 24-26° C. and a relative humidity of 50-60% for equilibrium cooling for 25-35 minutes, and then removing the capsule from the mold and cutting it as required to obtain a capsule body and a capsule cap;

[0009] (3) Put the capsule body and the capsule cap together, and use a light inspection table to remove the hard capsules that do not meet the quality requirements, such as those with bubbles, deformities, leakage, and bulges.

[0010] In a preferred embodiment of the present invention, the mass ratio of the low acyl gellan gum to the guar gum is 1.5:0.5.

[0011] Further preferably, the mass ratio of the low acyl gellan gum, guar gum and hydroxypropyl methylcellulose is 1.5:0.5:5.

[0012] In a preferred embodiment of the present invention, the potassium citrate accounts for 0.4-1.0% of the total mass of the glue.

[0013] Further preferably, the potassium citrate accounts for 0.8% of the total mass of the glue.

[0014] In a preferred embodiment of the present invention, the gum solution is composed of low acyl gellan gum, guar gum, hydroxypropyl methylcellulose, potassium citrate, glycerin and purified water in a mass percentage of 1.5%:0.5%:5%:0.8%:1%:91.2%.

[0015] In a preferred embodiment of the present invention, in step (1), the temperature of the sol tank is raised to 60°C, stirred to form a uniform glue solution, slowly cooled to 50°C, stirred at a constant temperature for 1 hour, cured for 1-24 hours, and then dipped in glue.

[0016] Further preferably, in the step (2), the material after dipping in the glue in the step (1) is dried in hot air at 30-40°C for 1-3h, then placed in a stabilization box at 25°C and a relative humidity of 55% for equilibrium cooling for 30min, and then the capsule is removed from the mold and cut as required to obtain the capsule body and the capsule cap.

[0017] The beneficial effects of the present invention are:

[0018] 1. The colon-targeted plant hollow capsules prepared by using low-acyl gellan gum and guar gum in the present invention do not contain animal ingredients, and there is no potential threat of animal epidemic diseases such as mad cow disease and foot-and-mouth disease, and there is no problem of residual antibiotics, feed additives, etc. in animals; in terms of heavy metal content, because gelatin raw materials are not used, the possibility of external chromium source pollution is completely eliminated, and the capsules prepared by the present invention do not contain nitrogen sources necessary for the growth and reproduction of microorganisms, so the product does not need to add preservatives.

[0019] 2. The colon-targeted plant hollow capsules prepared by the present invention are chemically inert and will not undergo cross-linking, condensation and other reactions with the filled drugs, thereby effectively ensuring the disintegration, dissolution and bioavailability of the capsules.

[0020] 3. The present invention is simple and only requires one time dipping, is low in cost, has universal applicability, and is easy to mass produce. DETAILED DESCRIPTION

[0021] The technical solution of the present invention is further illustrated and described below through specific implementation methods.

[0022] Examples 1 to 4

[0023] The group distribution ratios of Examples 1 to 4 are shown in Table 1:

[0024] Table 1 Distribution ratio of Examples 1-4

[0025]

[0026]

[0027] The preparation method of Examples 1-4 comprises the following steps:

[0028] (1) Slowly add low acyl gellan gum, guar gum, hydroxypropyl methylcellulose and potassium citrate into a sol tank, mix well, add purified water, stir and soak for 30 minutes, finally add glycerin, stir continuously to make it fully absorb water and swell, heat the sol tank to 60°C, stir until a uniform glue solution is formed, slowly cool to 50°C, stir at constant temperature for 1 hour, and cure the glue for 1 hour, then dip in glue;

[0029] (2) drying the material after dipping in the glue in step (1) at 40° C. hot air for 1 hour, then placing it in a stabilization box at 25° C. and a relative humidity of 55% for equilibrium cooling for 30 minutes, then removing the capsule from the mold and cutting it as required to obtain a capsule body and a capsule cap;

[0030] (3) Put the capsule body and the capsule cap together, remove the hard capsules that do not meet the quality requirements such as bubbles, deformities, leakage, and bulging using a light inspection table, and collect qualified colon-targeted plant hollow capsules for sealed storage.

[0031] (4) The disintegration performance of the colon-targeted plant hollow capsules obtained in step (3) was measured. The results are shown in Table 2.

[0032] Table 2 Effect of low acyl gellan gum / guar gum ratio on capsule disintegration performance

[0033]

[0034] (5) The capsule thickness, capsule formation rate, water content, friability and other indicators of the colon-targeted plant hollow capsules obtained in step (3) were measured, and the results are shown in Table 3:

[0035] Table 3 Effect of low acyl gellan gum / guar gum ratio on capsule quality

[0036]

[0037] The above results show that when the ratio of low acyl gellan gum to guar gum is 1:1, 1.5:0.5, and 2:0, the prepared capsules do not disintegrate in simulated gastric fluid (pH=1.2) for 2 hours, do not disintegrate in simulated intestinal fluid (pH=6.8) for 3 hours, and disintegrate in simulated colon fluid (pH=7.8) within half an hour, which meets the requirements of colon-targeted capsules in the Chinese Pharmacopoeia. Combined with the capsule thickness, capsule formation rate, water content, friability and other indicators of the colon-targeted plant hollow capsule samples, the quality of the prepared capsules is the best when the ratio of low acyl gellan gum to guar gum is 1.5:0.5.

[0038] Examples 5 to 9

[0039] The group distribution ratios of Examples 5 to 9 are shown in Table 4:

[0040] Table 4: Allocation ratio of groups in Examples 5-9

[0041]

[0042] The preparation method of Examples 5-9 comprises the following steps:

[0043] (1) Slowly add low acyl gellan gum, guar gum, hydroxypropyl methylcellulose and potassium citrate into a sol tank, mix well, add purified water, stir and soak for 30 minutes, finally add glycerin, stir continuously to make it fully absorb water and swell, heat the sol tank to 60°C, stir until a uniform glue solution is formed, slowly cool to 50°C, stir at constant temperature for 1 hour, the viscosity of the glue solution is in the range of 1500-4000 mPa.s, cure the glue for 12 hours, and then dip in glue;

[0044] (2) drying the material after dipping in the glue in step (1) at 35° C. hot air for 2 h, then placing it in a stabilization box at 25° C. and a relative humidity of 55% for equilibrium cooling for 30 min, then removing the capsule from the mold and cutting it as required to obtain a capsule body and a capsule cap;

[0045] (3) Put the capsule body and the capsule cap together, remove the hard capsules that do not meet the quality requirements such as bubbles, deformities, leakage, and bulging using a light inspection table, and collect qualified colon-targeted plant hollow capsules for sealed storage.

[0046] (4) The disintegration performance of the colon-targeted plant hollow capsules obtained in step (3) was measured. The results are shown in Table 5.

[0047] Table 5 Effect of potassium ion concentration on capsule disintegration performance

[0048]

[0049] (5) The capsule thickness, capsule formation rate, water content, friability and other indicators of the colon-targeted plant hollow capsules obtained in step (3) were measured, and the results are shown in Table 6:

[0050] Table 6 Effect of potassium ion concentration on capsule quality

[0051]

[0052] The above results show that the capsules prepared with potassium citrate concentrations in the range of 0.4%-1.0% do not disintegrate in simulated gastric fluid (pH=1.2) for 2 hours, do not disintegrate in simulated intestinal fluid (pH=6.8) for 3 hours, and disintegrate in simulated colon fluid (pH=7.8) within half an hour, meeting the requirements of the Chinese Pharmacopoeia for colon-targeted capsules. Combined with the capsule thickness, capsule formation rate, water content, friability and other indicators of the colon-targeted plant hollow capsule samples, the quality of the capsules prepared when the potassium citrate concentration was 0.8% was the best.

[0053] Examples 10 to 13

[0054] The group distribution ratios of Examples 10 to 13 are shown in Table 7:

[0055] Table 7: Allocation ratio of components in Examples 10-13

[0056]

[0057] The preparation method of Examples 10-13 comprises the following steps:

[0058] (1) Slowly add low acyl gellan gum, guar gum, hydroxypropyl methylcellulose and potassium citrate into a sol tank, mix well, add purified water, stir and soak for 30 minutes, finally add glycerin, stir continuously to make it fully absorb water and swell, heat the sol tank to 60°C, stir until a uniform glue solution is formed, slowly cool to 50°C, stir at a constant temperature for 1 hour, and cure the glue for 24 hours, then dip in glue;

[0059] (2) drying the material after dipping in the glue in step (1) at 30° C. hot air for 3 h, then placing it in a stabilization box at 25° C. and a relative humidity of 55% for equilibrium cooling for 30 min, then removing the capsule from the mold and cutting it as required to obtain a capsule body and a capsule cap;

[0060] (3) Put the capsule body and the capsule cap together, remove the hard capsules that do not meet the quality requirements such as bubbles, deformities, leakage, and bulging using a light inspection table, and collect qualified colon-targeted plant hollow capsules for sealed storage.

[0061] (4) The disintegration performance of the colon-targeted plant hollow capsules obtained in step (3) was measured. The results are shown in Table 8.

[0062] Table 8 Effect of the ratio of gellan gum-guar gum to hydroxypropyl cellulose on the disintegration properties of colon enteric capsules

[0063]

[0064]

[0065] (5) The capsule thickness, capsule formation rate, water content, friability and other indicators of the colon-targeted plant hollow capsules obtained in step (3) were measured, and the results are shown in Table 9:

[0066] Table 9 Effect of the ratio of gellan gum-guar gum to hydroxypropyl cellulose on capsule quality

[0067]

[0068] The above results show that the capsules prepared with the ratio of low acyl gellan gum: guar gum: hydroxypropyl methylcellulose of 1.5:0.5:5 and 1.35:0.45:7 did not disintegrate in simulated gastric fluid (pH=1.2) for 2 hours, did not disintegrate in simulated intestinal fluid (pH=6.8) for 3 hours, and disintegrated within half an hour in simulated colon fluid (pH=7.8), which meets the requirements of colon-targeted capsules in the Chinese Pharmacopoeia. However, the capsule thickness and friability of the capsules prepared with the ratio of low acyl gellan gum, guar gum and hydroxypropyl methylcellulose of 1.35:0.45:7 did not meet the requirements of the Chinese Pharmacopoeia. Therefore, combined with the capsule thickness, capsule formation rate, moisture content, friability and other indicators of the colon-targeted plant hollow capsule samples, the capsule quality was best when the ratio of low acyl gellan gum, guar gum and hydroxypropyl methylcellulose was 1.5:0.5:5.

[0069] The above description is only a preferred embodiment of the present invention, and therefore cannot be used to limit the scope of the present invention. That is, equivalent changes and modifications made according to the patent scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A method for preparing colon-targeted plant hollow capsules, characterized in that: The steps include: (1) Slowly add low acyl gellan gum, guar gum, hydroxypropyl methylcellulose and potassium citrate into a sol tank, mix well, add purified water, stir and soak for 30 minutes, finally add glycerin, stir continuously to make it fully absorb water and swell, heat the sol tank to 58-62° C., stir until a uniform glue solution is formed, slowly cool to 48-52° C., stir at a constant temperature for 0.8-1.2 hours, cure the glue for 1-24 hours, and then dip in glue; (2) drying the material after dipping in the glue in step (1) at 30-40° C. with hot air for 1-3 hours, and then placing it in a stabilization box at 24-26° C. and a relative humidity of 50-60% for equilibrium cooling for 25-35 minutes, and then removing the capsule from the mold and cutting it as required to obtain a capsule body and a capsule cap; (3) Put the capsule body and the capsule cap together, and use a light inspection table to remove the hard capsules that do not meet the quality requirements, such as those with bubbles, deformities, leakage, and bulges.

2. The preparation method according to claim 1, characterized in that: The mass ratio of the low acyl gellan gum to the guar gum is 1.5:0.

5.

3. The preparation method according to claim 2, characterized in that: The mass ratio of the low acyl gellan gum, guar gum and hydroxypropyl methylcellulose is 1.5:0.5:

5.

4. The preparation method according to claim 1, characterized in that: The potassium citrate accounts for 0.4-1.0% of the total mass of the glue.

5. The preparation method according to claim 4, characterized in that: The potassium citrate accounts for 0.8% of the total mass of the glue.

6. The preparation method according to claim 1, characterized in that: The glue solution is composed of low acyl gellan gum, guar gum, hydroxypropyl methylcellulose, potassium citrate, glycerin and purified water in the mass percentages of 1.5%: 0.5%: 5%: 0.8%: 1%: 91.2%.

7. The preparation method according to any one of claims 1 to 6, characterized in that: In the step (1), the temperature of the sol tank is raised to 60° C., stirred to form a uniform glue solution, slowly cooled to 50° C., stirred at a constant temperature for 1 hour, cured for 1-24 hours, and then dipped in glue.

8. The preparation method according to claim 7, characterized in that: In the step (2), the material after dipping in the glue in the step (1) is dried in hot air at 30-40° C. for 1-3 hours, and then placed in a stabilization box at 25° C. and a relative humidity of 55% for equilibrium cooling for 30 minutes. The capsule is then removed from the mold and cut as required to obtain a capsule body and a capsule cap.

Images