High-strength organic pullulan hollow capsule as well as preparation method and application thereof

Abstract

The invention discloses a high-strength organic pullulan hollow capsule and a preparation method and application thereof, and belongs to the field of pharmaceutical preparations, and the preparation method comprises the following steps: adding a gelling agent and a coagulant aid into high-purity water, stirring until the gelling agent and the coagulant aid are completely dissolved to obtain a mixed solution, and heating to prepare an auxiliary material solution; adding organic pullulan into high-purity water, uniformly mixing, adding the auxiliary material liquid, uniformly mixing, incubating, adding a plasticizer, continuously stirring until the auxiliary material liquid is completely dissolved, and stably preserving heat at 45-60 DEG C to obtain a glue solution; the preparation method comprises the following steps: preparing a pulullan gel solution, dipping the gel solution in a mold for molding, then drying in a drying oven to obtain a capsule cap body gel blank, demolding by using a demolding device, cutting and sleeving to obtain the high-strength organic pulullan hollow capsule with the tensile strength of 26.08-42.5 Mpa, the elongation at break of 1.97-3.80%, the single section strength of the hollow capsule body of 17.52-39.39 N and the single section strength of the hollow capsule cap of 15.22-35.46 N.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical preparations, in particular to a high-strength organic pullulan hollow capsule and its preparation method and application. BACKGROUND

[0002] Pullulan, as a natural microbial polysaccharide, has good film-forming property, biocompatibility and biodegradability, and is an ideal raw material for preparing hollow capsules. Organic pullulan is a "purer and more natural" pullulan designed specifically for organic products with strict requirements on raw material sources and production processes. Due to its natural and safe properties, organic pullulan has a wide range of applications in the fields of food, medicine and cosmetics, especially in high-end and organic products.

[0003] However, the main problem of the existing organic pullulan hollow capsule in strength is that its gelation ability is poor, which leads to the capsule shell being easily broken or deformed under stress. This problem not only affects the overall performance of the product, but also may adversely affect the stability and effectiveness of the drug.

[0004] At the same time, NOP requires strict standards for the safety, environmental protection and traceability of capsule materials, which poses new challenges to the research and production of organic pullulan hollow capsules. For example, NOP stipulates that the capsule material must not contain chemical synthetic additives or harmful substances, and must have clear records of source and production process. However, existing research still has a large gap in meeting these requirements, especially in how to improve the overall strength of the capsule through multi-factor synergistic improvement while taking into account the NOP standards. There is still a lack of systematic exploration.

[0005] Therefore, it is a technical problem to be solved in the industry to develop an organic pullulan hollow capsule that not only meets the NOP organic certification standards, but also significantly improves the strength. SUMMARY

[0006] The technical problem to be solved is that the existing organic pullulan hollow capsule has poor gelation ability, which leads to the capsule shell being easily broken or deformed under stress, affecting the overall performance of the product, and may adversely affect the stability and effectiveness of the drug.

[0007] The purpose of the present application is to provide a high-strength organic pullulan hollow capsule and its preparation method and application. By synergistically optimizing organic pullulan, gelling agent, coagulant and plasticizer, and changing the dissolution method of organic pullulan, the tensile strength, elongation at break and impact resistance of the capsule are significantly improved while ensuring the organic properties.

[0008] Technical solution: The preparation method of the high-strength organic pullulan hollow capsule comprises the following steps: S1, material preparation: take 100 parts of organic pullulan with a molecular weight of 10,000-600,000 Da, 1-5 parts of gelatin, 0.5-4 parts of coagulant, and 0.3-2 parts of plasticizer according to the mass fraction ratio; S2, preparation of auxiliary liquid: add 1-5 parts of gelatin and 0.5-4 parts of coagulant to 25-30 parts of high-purity water, stir until dissolved to obtain a mixed liquid, and incubate the mixed liquid at 90-100 DEG C for 1h to obtain an auxiliary liquid; S3, add 100 parts of organic pullulan to 350-450 parts of high-purity water at 60-70 DEG C, mix uniformly using a high-speed stirring device, then add the auxiliary liquid and continue stirring until the mixture is uniform, incubate at 60-70 DEG C for 4-5 hours, stir every hour, add 0.3-2 parts of plasticizer, continue stirring until completely dissolved, and obtain a glue liquid at 45-60 DEG C stable incubation; S4, dip the glue liquid into the mold to form, then dry in an oven at 25-35 DEG C, RH=40-60% for 30-90 minutes to obtain a capsule cap blank, and then use a demolding device for demolding, cutting and fitting to obtain a high-strength organic pullulan hollow capsule.

[0009] Preferably, the average molecular weight of the organic pullulan in step S1 is 50-300,000 Da, and the viscosity at 30 DEG C is 40-60 mm 2 / s.

[0010] Preferably, the gelatin in step S1 is one or a mixture of several of gellan gum, carrageenan, locust bean gum, high-fat pectin, tragacanth gum, organic gum arabic, organic guar gum, agar, xanthan gum, and pullulan.

[0011] Preferably, the coagulant in step S1 is one or a mixture of several of calcium carbonate, potassium carbonate, calcium chloride, potassium chloride, calcium citrate, potassium citrate, and organic calcium gluconate.

[0012] Preferably, the plasticizer in step S1 is one or a mixture of several of organic glycerol, organic konjac glucomannan, sorbitol, and organic inulin.

[0013] Preferably, the stirring speed of the high-speed stirring device in step S3 is 1000-2000 r / min, and the stirring time is 5-10 min.

[0014] Preferably, the stirring speed is 200-300 r / min and the stirring time is 5-10 min every hour in step S3.

[0015] Preferably, the stable incubation time in step S3 is 25-35 min.

[0016] The application also discloses a high-strength organic pullulan hollow capsule prepared by any of the above methods.

[0017] The application also discloses a high-strength organic pullulan hollow capsule in the preparation of hard capsules.

[0018] Compared with the prior art, the application has at least the following beneficial effects: 1. The preparation method of the high-strength organic pullulan hollow capsule is simple, meets NOP organic certification standards, and is low in cost. 2. The high-strength organic pullulan hollow capsule prepared by the application realizes significant improvement in the strength of the organic pullulan hollow capsule through formula optimization. 3. The application significantly improves the tensile strength, elongation at break and impact resistance of the capsule by synergistically optimizing the organic pullulan, the gelling agent, the coagulant and the plasticizer, and changing the dissolution mode of the organic pullulan, while ensuring the organic property. 4. The high-strength organic pullulan hollow capsule prepared by the application has a tensile strength of 26.08-42.5 Mpa, an elongation at break of 1.97-3.80%, a single joint strength of the hollow capsule body of 17.52-39.39 N, and a single joint strength of the hollow capsule cap of 15.22-35.46 N. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 The performance test chart of the high-strength organic pullulan hollow capsule prepared by the application is shown in the figure. DETAILED DESCRIPTION

[0020] To make the purpose, technical scheme and advantages of the application clearer, specific embodiments of the application will be described below with reference to the accompanying drawings. Figure 1 The technical scheme of the application is described clearly and completely. Obviously, the described embodiments are part of the embodiments of the application, rather than all the embodiments. Based on the described embodiments of the application, all other embodiments obtained by those skilled in the art belong to the scope of protection of the application.

[0021] Embodiment 1: The application discloses a preparation method of a high-strength organic pullulan hollow capsule, which comprises the following steps: S1, preparation of auxiliary material liquid: 4 parts of carrageenan and 1.2 parts of potassium chloride are added into 25 parts of high-purity water according to the mass ratio, and stirred until completely dissolved to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min; the mixed liquid is incubated at 90-100 DEG C for 1 h to prepare an auxiliary material liquid; S2, 100 parts of organic pullulan with a molecular weight of 50-300 thousand Da are added to 400 parts of high-purity water at 65 DEG C and mixed uniformly using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary material liquid is added and continuously stirred until mixed uniformly, incubated at 65 DEG C for 4-5 hours, stirred once every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 0.8 parts of organic glycerol is added, continuously stirred until completely dissolved, and the glue liquid is obtained by stabilizing at 53 DEG C for 30 min; S3, the glue liquid is molded by mold dipping, then dried in an oven at 30 DEG C and RH=50% for 60 minutes to obtain a capsule cap glue blank, and the high-strength organic pullulan hollow capsule is obtained by demolding, cutting and fitting using a demolding device.

[0022] The application further discloses a high-strength organic pullulan hollow capsule prepared by the method.

[0023] The application further discloses a high-strength organic pullulan hollow capsule prepared by the method.

[0024] Embodiment 2 discloses a preparation method of a high-strength organic pullulan hollow capsule, and the preparation method comprises the following steps: S1, auxiliary material liquid preparation: 4 parts of carrageenan and 1.2 parts of potassium chloride are added to 25 parts of high-purity water and stirred until completely dissolved to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min; the mixed liquid is incubated at 90 DEG C-100 DEG C for 1 h to prepare an auxiliary material liquid; S2, 100 parts of organic pullulan with a molecular weight of 50-300 thousand Da are added to 400 parts of high-purity water at 65 DEG C and mixed uniformly using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary material liquid is added and continuously stirred until mixed uniformly, incubated at 65 DEG C for 4-5 hours, stirred once every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 0.8 parts of organic glycerol is added, continuously stirred until completely dissolved, and the glue liquid is obtained by stabilizing at 53 DEG C for 30 min; S3, the glue liquid is molded by mold dipping, then dried in an oven at 30 DEG C and RH=50% for 60 minutes to obtain a capsule cap glue blank, and the high-strength organic pullulan hollow capsule is obtained by demolding, cutting and fitting using a demolding device.

[0025] Embodiment 3 discloses a preparation method of a high-strength organic pullulan hollow capsule, and the preparation method comprises the following steps: S1, auxiliary material liquid preparation: 4 parts of carrageenan and 1.2 parts of potassium chloride are added into 25 parts of high-purity water according to the mass fraction ratio, and stirring is performed until complete dissolution to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min; the mixed liquid is incubated at 90-100 DEG C for 1 h to prepare an auxiliary material liquid; S2, 100 parts of organic pullulan with a molecular weight of 300-500 million Da are added into 400 parts of high-purity water at 65 DEG C, and then mixed uniformly by using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary material liquid is added and continuously stirred until uniform mixing, and then incubated at 65 DEG C for 4-5 hours, stirring is performed once every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 0.8 parts of organic glycerol is added, and then continuously stirred until complete dissolution, and then stable incubation is performed at 53 DEG C for 30 min to obtain a glue liquid; S3, the glue liquid is molded by mold dipping, and then dried in an oven at 30 DEG C and RH=50% for 60 min to obtain a capsule cap blank, and then demolding, cutting and fitting are performed by using a demolding device to obtain a high-strength organic pullulan hollow capsule.

[0026] Embodiment 4, a preparation method of a high-strength organic pullulan hollow capsule disclosed by the application, comprising the following steps: S1, material preparation: a gelatinizing agent is weighed according to a mass ratio of xanthan gum: gellan gum: carrageenan = 1:4:5, a coagulating agent is weighed according to a mass ratio of potassium citrate: organic calcium gluconate = 1:1, and a plasticizer is weighed according to a mass ratio of organic glycerol: sorbitol = 1:1; S2, auxiliary material liquid preparation: 2.5 parts of the gelatinizing agent and 1.2 parts of the coagulating agent are added into 30 parts of high-purity water according to the mass fraction ratio, and stirring is performed until complete dissolution to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min; the mixed liquid is incubated at 90-100 DEG C for 1 h to prepare an auxiliary material liquid; S3, 100 parts of organic pullulan with a molecular weight of 50-300 million Da are added into 350 parts of high-purity water at 70 DEG C, and then mixed uniformly by using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary material liquid is added and continuously stirred until uniform mixing, and then incubated at 70 DEG C for 4 hours, stirring is performed once every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 1.5 parts of the plasticizer is added, and then continuously stirred until complete dissolution, and then stable incubation is performed at 50 DEG C for 35 min to obtain a glue liquid; S4, the glue liquid is molded by mold dipping, and then dried in an oven at 35 DEG C and RH=60% for 60 min to obtain a capsule cap blank, and then demolding, cutting and fitting are performed by using a demolding device to obtain a high-strength organic pullulan hollow capsule.

[0027] Embodiment 5, the application discloses a preparation method of a high-strength organic pullulan hollow capsule, and comprises the following steps: S1, material preparation: the gelatin is weighed according to the mass ratio of yellow gum: carrageenan = 1:1; S2, preparation of auxiliary liquid: 4 parts of gelatin and 1.2 parts of potassium carbonate are added into 30 parts of high-purity water according to the mass fraction ratio, and stirring is performed until the mixture is completely dissolved to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min; the mixed liquid is incubated at 90-100 DEG C for 1 h to prepare an auxiliary liquid; S3, 100 parts of organic pullulan with a molecular weight of 50-300 million Da are added into 400 parts of high-purity water at 60 DEG C, and then mixed uniformly by using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary liquid is added and continuously stirred until the mixture is uniformly mixed, and then incubated at 60 DEG C for 5 hours, and the stirring is performed once every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 0.5 parts of organic konjak mannan is added, and then continuously stirred until completely dissolved, and then the mixed liquid is incubated at 55 DEG C for 30 min to obtain a glue liquid; S4, the glue liquid is molded by dipping into a mold, and then dried in an oven at 28 DEG C and RH=50% for 80 min to obtain a capsule cap blank, and then the capsule cap blank is demolded, cut and fitted by using a demolding device to obtain the high-strength organic pullulan hollow capsule.

[0028] Embodiment 6, the application discloses a preparation method of a high-strength organic pullulan hollow capsule, and comprises the following steps: S1, material preparation: the gelatin is weighed according to the mass ratio of yellow gum: carrageenan = 1:1; S2, preparation of auxiliary liquid: 4 parts of gelatin and 1.2 parts of potassium carbonate are added into 30 parts of high-purity water according to the mass fraction ratio, and stirring is performed until the mixture is completely dissolved to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min; the mixed liquid is incubated at 90-100 DEG C for 1 h to prepare an auxiliary liquid; S3, 100 parts of organic pullulan with a molecular weight of 50-300 million Da are added into 400 parts of high-purity water at 60 DEG C, and then mixed uniformly by using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary liquid is added and continuously stirred until the mixture is uniformly mixed, and then incubated at 60 DEG C for 5 hours, and the stirring is performed once every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 0.5 parts of organic konjak mannan is added, and then continuously stirred until completely dissolved, and then the mixed liquid is incubated at 55 DEG C for 30 min to obtain a glue liquid; S4, the glue liquid is molded by mold dipping glue, and then dried in an oven at 35 DEG C, RH = 45% for 50 minutes to obtain a capsule cap blank, and the high-strength organic pullulan hollow capsule is obtained after demolding, cutting and fitting by using a demolding device.

[0029] Comparative Example 1, a conventional organic pullulan hollow capsule preparation method disclosed by the present application, comprising the following steps: S1, preparation of auxiliary liquid: 4 parts of carrageenan and 1.2 parts of potassium chloride are added to 30 parts of high-purity water and stirred until completely dissolved to obtain a mixed liquid, the stirring speed is 250 r / min, and the stirring time is 5 min, the mixed liquid is incubated at 90 DEG C ~ 100 DEG C for 1 h to prepare an auxiliary liquid; S2, 100 parts of organic pullulan with a molecular weight of 20-200 million Da are added to 350 parts of high-purity water at 90-100 DEG C and mixed uniformly using a high-speed stirring device, the stirring speed is 2000 r / min, the stirring time is 5 min, the auxiliary liquid is added and continuously stirred until mixed uniformly, incubated at 55 DEG C for 4 hours, stirred every hour, the stirring speed is 250 r / min, the stirring time is 5 min, 0.8 parts of organic glycerol is added and continuously stirred until completely dissolved, and the glue liquid is obtained by incubating at 53 DEG C for 30 min; S3, the glue liquid is molded by mold dipping glue, and then dried in an oven at 30 DEG C, RH = 50% for 60 minutes to obtain a capsule cap blank, and the high-strength organic pullulan hollow capsule is obtained after demolding, cutting and fitting by using a demolding device.

[0030] The above is the preferred embodiment of the present application, it should be noted that for those skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A method for preparing a high-strength organic pullulan hollow capsule, characterized by, It comprises the following steps: S1, preparation: according to the mass fraction of the proportion of 100 parts of organic pullulan with molecular weight of 100,000 Da to 600,000 Da, 1-5 parts of gelling agent, 0.5-4 parts of coagulant, 0.3-2 parts of plasticizer; S2, preparation of auxiliary liquid: 1-5 parts of gelling agent, 0.5-4 parts of coagulant are added into 25-30 parts of high-purity water and stirred until dissolved to obtain a mixed solution, and the mixed solution is incubated at 90-100 DEG C for 1h to prepare an auxiliary liquid; S3, 100 parts of organic pullulan is added into 350-450 parts of high-purity water at 60-70 DEG C, and mixed uniformly by using a high-speed stirring device, then the auxiliary liquid is added and stirred until mixed uniformly, and incubated at 60-70 DEG C for 4-5 hours, stirred once an hour, 0.3-2 parts of plasticizer is added, and continue to stir until completely dissolved, and obtain a glue liquid at 45-60 DEG C stable incubation; S4, the glue liquid is molded by mold dipping, then dried in an oven at 25-35 DEG C, RH=40-60% for 30-90 minutes to obtain a capsule cap blank, and the high-strength organic pullulan hollow capsule is obtained by using a demolding device for demolding, cutting and fitting.

2. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The organic pullulan polysaccharide in step S1 has an average molecular weight of 50,000-300,000 Da and a viscosity of 40-60 mmHg at 30°C. 2 / s.

3. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The gelling agent in step S1 is one or a mixture of several of gellan gum, carrageenan, locust bean gum, high-fat pectin, tragacanth gum, organic gum arabic, organic guar gum, agar, xanthan gum, and gum arabic.

4. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The coagulant in step S1 is one or several of calcium carbonate, potassium carbonate, calcium chloride, potassium chloride, calcium citrate, potassium citrate, and organic calcium gluconate.

5. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The plasticizer in step S1 is one or several of organic glycerol, organic konjac glucomannan, sorbitol, and organic inulin.

6. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The stirring speed of the high-speed stirring device in step S3 is 1000-2000 r / min, and the stirring time is 5-10 min.

7. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The stirring speed of the high-speed stirring device in step S3 is 1000-2000 r / min, and the stirring time is 5-10 min.

8. The method for preparing high-strength organic pullulan polysaccharide empty capsules according to claim 1, characterized in that, The stable incubation time in step S3 is 25-35 min.

9. A high-strength organic pullulan hollow capsule, characterized by, Prepared by the method of any one of claims 1-8.

10. The high-strength organic pullulan hollow capsule of claim 9 is used in the preparation of hard capsules.

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