A delayed-release plant hollow capsule and its production process

Abstract

The present invention belongs to the technical field of capsule preparation, and discloses a delayed-release plant hollow capsule and a production process thereof. The present invention uses hydroxypropyl methylcellulose, high-acyl gellan gum and low-acyl gellan gum as raw materials, optimizes the gellan gum sol process and capsule making process, solves the problems of uneven gel solution and difficulty in gelling when different types of gellan gum are mixed, and prepares delayed-release plant hollow capsules with good formability, high qualified rate, no brittleness and dissolution that meets the use requirements.

Description

Technical Field

[0001] The invention belongs to the technical field of capsule preparation, and in particular relates to a delayed-release plant hollow capsule and a production process thereof. Background Art

[0002] Capsules are one of the most commonly used dosage forms of medicines because they are moisture-proof, anti-oxidation, have high bioavailability, are easy to take, and have good compliance. The quality of capsules (excluding the contents) often depends on the quality of the capsule shell, and the quality of the capsule shell directly affects the effect and safety of the clinical use of capsules. Plant capsules refer to capsules made from terrestrial or marine plants that have been processed, refined, and chemically modified. Compared with the currently widely used animal gelatin hollow capsules, the significant advantages of plant hollow capsules are stable chemical properties, no cross-linking reaction, and wide adaptability; they are highly safe because plant hollow capsules do not contain the protein toxins of animal gelatin, do not add any preservatives, and do not require ethylene oxide sterilization. Acid resistance is an important indicator for measuring the quality of capsules.

[0003] There are usually three methods in the prior art for preparing capsules with enteric or acid-resistant properties: ① Wrap the drug with a layer of enteric coating and fill it into an ordinary capsule shell; ② After the drug is filled into the capsule shell, wrap the capsule shell with a layer of enteric coating; ③ Use the secondary dipping method to produce an enteric capsule shell, and then fill the drug into the capsule. The above three methods all involve enteric materials, which are made into enteric coatings and wrapped around the outside of the drug or capsule shell. The entire drug production process involves coating technology, capsule production technology, and capsule filling technology. Not only is the process complicated, but it also requires effective and accurate docking between the pharmaceutical factory and the capsule factory. Due to the complexity of the production process, the raw material cost and labor cost required are also very high, and professional personnel are required to operate. In addition, since a large amount of toxic organic solvents are used in the production process, there is a risk of residual. In particular, the secondary dipping method involved in the third method has high requirements for capsule production equipment, and capsule production equipment needs to be customized, which has the problem of high equipment cost.

[0004] Compared with the above three methods, the production of enteric or acid-resistant capsules by one-time dipping and molding can greatly simplify the production process and save production costs. Patent (CN102665697A) has developed an acid-resistant capsule that is formed by one-time dipping and molding. The patent uses aqueous solvents, gellan gum and water-soluble film-forming polymers to prepare acid-resistant capsules without adding gelling aids, and focuses on the effect of the ratio of gellan gum and water-soluble film-forming polymers on capsule performance. However, the patent does not clearly point out the type of gellan gum, and does not clearly propose the specific parameters of the production process, nor does it study the effects of the type or parameters of gellan gum and process parameters on capsule performance. The properties of different types of gellan gum are very different, and the requirements for the production process will also be different.

[0005] Therefore, in the research in this field, there is still a need to develop a production process for delayed-release plant hollow capsules that can be formed by one-time dipping and molding. The production process should have the characteristics of simple process, easy operation, good product molding effect, and no use of toxic organic solvents. The final product should be insoluble in the stomach and soluble in the intestine. Summary of the invention

[0006] The present invention aims at the problems existing in the prior art and provides a delayed-release plant hollow capsule and a production process thereof. The present invention adopts hydroxypropyl methylcellulose, high-acyl gellan gum and low-acyl gellan gum as raw materials, optimizes the gellan gum sol process and capsule making process, solves the problems of uneven gel solution and difficulty in gelling when different types of gellan gum are mixed, and prepares delayed-release plant hollow capsules with good formability, high qualified rate, no brittleness and solubility meeting the use requirements.

[0007] In order to achieve the above-mentioned object, in a first aspect, the present invention provides a production process of delayed-release plant hollow capsules, comprising the following steps:

[0008] S1: Adding materials: adding water to the sol kettle, heating to the first temperature, adding hydroxypropyl methylcellulose and low acyl gellan gum to the sol kettle, stirring until the glue liquid is in a uniform state; cooling to the second temperature, adding high acyl gellan gum, stirring until the glue liquid is in a uniform state; adding gelling agent, stirring until the glue liquid is in a uniform state;

[0009] S2: emulsifying the glue;

[0010] S3: Vacuuming: stop emulsification, cool down, and vacuumize;

[0011] S4: Filtration: filtering the glue solution to obtain the glue solution after filtration, and keeping it warm;

[0012] S5: capsule making: after the temperature of the glue tank reaches the third temperature, glue is released, and at the same time, the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After glue dipping, capsule conveying, drying, demolding, length setting, cutting, and fitting are sequentially performed to obtain delayed-release plant hollow capsules.

[0013] The inventors found in the long-term capsule production research process that the capsules containing gellan gum have certain acid resistance, but when gellan gum with different parameters is added, the acid resistance varies greatly. Therefore, it is considered that the properties of gellan gum itself directly affect the acid resistance of the capsule.

[0014] Gellan gum is divided into high acyl gellan gum and low acyl gellan gum. The main difference between high acyl gellan gum and low acyl gellan gum in structure is that each repeating unit of high acyl gellan gum has an acyl group connected to the glucose molecule, and its acyl groups are divided into two categories: one is the acetyl group connected to the 6th carbon atom of the glucose molecule with a β-1,3 bond; the other is the glyceryl group connected to the 2nd carbon atom of the glucose molecule with a β-1,3 bond, in which the average proportion of glyceryl group is twice that of acetyl group. It is precisely because of the presence of acetyl and glyceryl groups in the molecule that high acyl gellan gum presents different properties from low acyl gellan gum. By subjecting high acyl gellan gum to high temperature and alkali treatment, part of the acetyl and glyceryl acyl groups in its structure can be removed, thereby controlling the acyl content on the gellan gum and obtaining deacylated gellan gum. When the content of acetyl and glyceryl groups is different, the properties of gellan gum are greatly different, and its dissolution conditions and gelation conditions are not the same. Therefore, different types of gellan gum cannot be mixed in actual production, which will lead to problems such as uneven gel solution and difficulty in gelation. The inventors optimized the sol and capsule production process and determined the sol and capsule production process containing different types of gellan gum compositions, which can be applied to the production of delayed-release capsules, and the product has excellent acid resistance.

[0015] In a preferred embodiment, in step S1, each repeating unit of the low acyl gellan gum contains 1%-30% acetyl and 15%-40% glycerol acyl, and each repeating unit of the high acyl gellan gum contains 20%-45% acetyl and 30%-55% glycerol acyl; preferably, each repeating unit of the low acyl gellan gum contains 18% acetyl and 26% glycerol acyl; each repeating unit of the high acyl gellan gum contains 30% acetyl and 45% glycerol acyl.

[0016] In a preferred embodiment, in step S1, the mass ratio of hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum is 50-100:0.5-5:0.1-5.

[0017] In a preferred embodiment, in step S1, the water is purified water, and the mass ratio of the total amount of hypromellose, low acyl gellan gum and high acyl gellan gum to purified water is 1:3-1:5.

[0018] In a preferred embodiment, in step S1, the gelling agent includes one or more of sodium chloride, potassium chloride, sodium citrate, and potassium acetate.

[0019] In a preferred embodiment, in step S1, the first temperature is 85-95°C, and the second temperature is 80-85°C.

[0020] In a preferred embodiment, in step S2, the emulsification time is 30-50 minutes.

[0021] In a preferred embodiment, the temperature is lowered to 60-75°C in step S3.

[0022] In a preferred embodiment, in step S4, the insulation time is 4-6 hours and the insulation temperature is 60-65°C.

[0023] In a preferred embodiment, in step S4, the viscosity of the filtered glue solution is 20-100 mPa.s (tested at 25°C).

[0024] In a preferred embodiment, in step S5, the third temperature is 58-72°C.

[0025] In a preferred embodiment, in step S5, the drying is stage drying, including four stages, the temperature of stage one is set at 18-23°C, the temperature of stage two is set at 20-30°C, the temperature of stage three is set at 25-38°C, the temperature of stage four is set at 25-35°C, and the drying time of each stage is 10-30 minutes.

[0026] In a second aspect, the present invention provides delayed-release plant hollow capsules prepared by the above production process.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] 1. The present invention conducts research on gellan gum with different acyl contents, optimizes the sol and capsule making processes, determines a production process suitable for producing delayed-release capsules, and determines the addition amounts of two types of gellan gum and the sol temperature. The capsules produced by this process have the advantages of smooth appearance and uniform thickness, and the production conditions are mild.

[0029] 2. The production process of the present invention does not involve toxic organic solvents, and no toxic organic solvent residues are left, thereby avoiding the risks of personnel poisoning and flammable and explosive raw materials during the production process.

[0030] 3. The process of the present invention does not require secondary dipping, which reduces the difficulty of production technology, is conducive to large-scale production in terms of process parameters and actual operation, and does not require professional personnel to operate.

[0031] 4. The delayed-release hollow capsule of the present invention has no obvious leakage in a pH 1.2 simulated gastric fluid medium within 1 hour, and releases rapidly in a pH 6.8 simulated intestinal fluid medium, and has a good delayed-release function. DETAILED DESCRIPTION

[0032] In order to make the technical means, creative features, purpose and efficacy of the present invention easy to understand, the present invention is further explained in conjunction with specific embodiments below, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without creative work all belong to the protection scope of the present invention. In the following embodiments, unless otherwise specified, the operating methods used are conventional operating methods, the equipment used are conventional equipment, and the equipment materials used in each embodiment are the same.

[0033] The following sources of raw materials are provided for illustrative purposes:

[0034] Hydroxypropyl methylcellulose: model 60HD5, purchased from Shandong Heda Group Co., Ltd.;

[0035] Low acyl gellan gum: purchased from Zhejiang Tianwei Biotechnology Co., Ltd., 3 types, parameters are: each repeating unit contains 18% acetyl and 26% glyceryl, each repeating unit contains 28% acetyl and 35% glyceryl, and each repeating unit contains 5% acetyl and 17% glyceryl;

[0036] High acyl gellan gum: purchased from Zhejiang Tianwei Biotechnology Co., Ltd., 3 types, with parameters as follows: 30% acetyl and 45% glyceryl acyl per repeating unit, 43% acetyl and 52% glyceryl acyl per repeating unit, and 25% acetyl and 32% glyceryl acyl per repeating unit.

[0037] Gelling agent: Sodium chloride, purchased from Yantai Shuangshuang Chemical Co., Ltd.

[0038] Example 1-2 and Comparative Example 1-2

[0039] The production process steps of delayed-release vegetable empty capsules are as follows:

[0040] S1: Feeding: Add 200 kg of purified water into the sol kettle, turn on the stirring motor, and start heating at the same time; after the temperature in the sol kettle reaches the first temperature, slowly add 50 kg of hydroxypropyl methylcellulose and 1 kg of low acyl gellan gum into the sol kettle, stir for 20 minutes until the glue liquid is uniform, start cooling, and after cooling to the second temperature, slowly add 0.5 kg of high acyl gellan gum, stir for 20 minutes until the glue liquid is uniform, and finally add the gelling agent, stir for 15 minutes until the glue liquid is uniform;

[0041] S2: Emulsification: Stop stirring and use an emulsification pump to emulsify the glue for 30 minutes;

[0042] S3: Vacuuming: stop emulsification, cool down to 68; turn on the vacuum pump, and close the exhaust valve when the glue liquid level rises to 20cm close to the vacuum suction port. Open it again after the liquid level drops. After 3-6 times of operation, stop vacuuming;

[0043] S4: Filtration: Filter the glue solution, test the viscosity at 25°C, and then introduce it into a glue barrel. Keep it warm for 5 hours. The insulation temperature is set to 63°C.

[0044] S5: Capsule making: After the temperature reaches the third temperature, glue is released, and the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After dipping, the capsule is transported, dried, demolded, fixed in length, cut, and fitted in sequence to obtain a delayed-release plant hollow capsule.

[0045] In S1, each repeating unit of the low acyl gellan gum contains 18% of acetyl groups and 26% of glyceryl groups, and each repeating unit of the high acyl gellan gum contains 30% of acetyl groups and 45% of glyceryl groups.

[0046] The mass ratio of hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum is 100:2:1.

[0047] In S5, drying is divided into four stages, and the drying time for each stage is 25 minutes.

[0048] The process parameters of Example 1-2 and Comparative Example 1-2 are shown in Table 1:

[0049] Table 1

[0050]

[0051] Example 3

[0052] The production process steps of delayed-release vegetable empty capsules are as follows:

[0053] S1: Feeding: Add 200 kg of purified water into the sol kettle, turn on the stirring motor, and start heating at the same time; after the temperature in the sol kettle reaches the first temperature, slowly add 50 kg of hydroxypropyl methylcellulose and 5 kg of low acyl gellan gum into the sol kettle, stir for 20 minutes until the glue liquid is uniform, start cooling, and after cooling to the second temperature, slowly add 1 kg of high acyl gellan gum, stir for 20 minutes until the glue liquid is uniform, and finally add the gelling agent, stir for 15 minutes until the glue liquid is uniform;

[0054] S2: Emulsification: Stop stirring and use an emulsification pump to emulsify the glue for 40 minutes;

[0055] S3: Vacuuming: stop emulsification, cool down to 72°C; turn on the vacuum pump, and close the exhaust valve when the glue liquid level rises to 20cm close to the vacuum suction port. Wait until the liquid level drops and then open it again. After 3-6 times of operation, stop vacuuming;

[0056] S4: Filtration: Filter the glue solution, test the viscosity and then introduce it into the glue barrel, keep it warm for 5 hours, and set the insulation temperature to 60.

[0057] S5: capsule making: after the temperature reaches the third temperature, glue is released, and the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After dipping, capsule conveying, drying, demolding, length setting, cutting, and sleeve-fitting are sequentially performed to obtain delayed-release plant hollow capsules.

[0058] In S1, each repeating unit of the low acyl gellan gum contains 28% of acetyl groups and 35% of glyceryl groups, and each repeating unit of the high acyl gellan gum contains 43% of acetyl groups and 52% of glyceryl groups.

[0059] The mass ratio of hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum is 50:5:1.

[0060] In S5, drying is divided into four stages, and the drying time for each stage is 25 minutes.

[0061] Example 4

[0062] The raw material feeding amount and the specific operation steps are the same as those in Example 3, except that the acetyl and glyceryl contents of the gellan gum are different. Each repeating unit of the low acyl gellan gum contains 5% acetyl and 17% glyceryl, and each repeating unit of the high acyl gellan gum contains 25% acetyl and 32% glyceryl.

[0063] Comparative Example 3

[0064] S1: Adding materials: Add purified water into the sol kettle, turn on the stirring motor, and start heating at the same time; after the temperature in the sol kettle reaches 83, add hydroxypropyl methylcellulose, low acyl gellan gum, high acyl gellan gum and gelling agent into the sol kettle together, and stir for 40 minutes until the gel liquid is uniform;

[0065] S2: Emulsification: Stop stirring and use an emulsification pump to emulsify the glue for 30 minutes;

[0066] S3: Vacuuming: stop emulsification, cool down to 68; turn on the vacuum pump, and close the exhaust valve when the glue liquid level rises to 20cm close to the vacuum suction port. Open it again after the liquid level drops. After 3-6 times of operation, stop vacuuming;

[0067] S4: Filtration: Filter the glue solution, test the viscosity and then introduce it into the glue barrel, keep it warm for 5 hours, and set the insulation temperature to 63.

[0068] S5: Capsule making: When the temperature reaches 65, glue is added. At the same time, the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After dipping, the capsules are transported, dried, demolded, fixed in length, cut, and fitted in sequence. The temperature of the first stage of drying is 23, the second stage is 30, the third stage is 35, and the fourth stage is 28. The drying time of each stage is 25 minutes.

[0069] The amount and structure of the hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum used in Comparative Example 3 are the same as those in Example 2, and the viscosity of the gel solution detected in step S4 is 122 mPa.s.

[0070] Comparative Example 4

[0071] S1: Adding materials: Add purified water into the sol kettle, turn on the stirring motor, and start heating at the same time; after the temperature in the sol kettle reaches 90, add hydroxypropyl methylcellulose, low acyl gellan gum, high acyl gellan gum and gelling agent into the sol kettle together, and stir for 40 minutes until the gel liquid is uniform;

[0072] S2: Emulsification: Stop stirring and use an emulsification pump to emulsify the glue for 30 minutes;

[0073] S3: Vacuuming: stop emulsification, cool down to 68; turn on the vacuum pump, and close the exhaust valve when the glue liquid level rises to 20cm close to the vacuum suction port. Open it again after the liquid level drops. After 3-6 times of operation, stop vacuuming;

[0074] S4: Filtration: Filter the glue solution, test the viscosity at 25°C, and then introduce it into a glue barrel. Keep it warm for 5 hours. The insulation temperature is set to 63°C.

[0075] S5: Capsule making: When the temperature reaches 65, glue is added. At the same time, the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After dipping, the capsules are transported, dried, demolded, fixed in length, cut, and fitted in sequence. The temperature of the first stage of drying is 23, the second stage is 30, the third stage is 35, and the fourth stage is 28. The drying time of each stage is 25 minutes.

[0076] The amount and structure of the hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum used in Comparative Example 4 are the same as those in Example 2, and the viscosity of the gel solution detected in step S4 is 5 mPa.s.

[0077] Comparative Example 5

[0078] S1: Adding materials: Add purified water to the sol kettle, turn on the stirring motor, and start heating at the same time; when the temperature in the sol kettle reaches 90°C, add hydroxypropyl methylcellulose, low acyl gellan gum, high acyl gellan gum and gelling agent into the sol kettle, stir for 20 minutes, cool down to 83°C, and stir for another 20 minutes until the gel liquid is uniform;

[0079] S2: Emulsification: Stop stirring and use an emulsification pump to emulsify the glue for 30 minutes;

[0080] S3: Vacuuming: stop emulsification, cool down to 68; turn on the vacuum pump, and close the exhaust valve when the glue liquid level rises to 20cm close to the vacuum suction port. Open it again after the liquid level drops. After 3-6 times of operation, stop vacuuming;

[0081] S4: Filtration: Filter the glue solution, test the viscosity at 25°C, and then introduce it into a glue barrel. Keep it warm for 5 hours. The insulation temperature is set to 63°C.

[0082] S5: Capsule making: When the temperature reaches 65, glue is added. At the same time, the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After dipping, the capsules are transported, dried, demolded, fixed in length, cut, and fitted in sequence. The temperature of the first stage of drying is 23, the second stage is 30, the third stage is 35, and the fourth stage is 28. The drying time of each stage is 25 minutes.

[0083] The amount and structure of the hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum used in Comparative Example 5 are the same as those in Example 2, and the viscosity of the gel solution detected in step S4 is 15 mPa.s.

[0084] Test Case

[0085] 1. Friability: The friability is tested according to the requirements of Hydroxypropyl Methylcellulose Empty Capsules in the Chinese Pharmacopoeia 2020 edition.

[0086] 2. Dissolution: The dissolution performance of the test samples was measured in a medium simulated by gastric fluid (pH 1.2) and a medium simulated by intestinal fluid (pH 6.8) using the method in the Japanese Pharmacopoeia.

[0087] The capsule forming and dissolution conditions of Examples 1-4 and Comparative Examples 1-5 are shown in Table 2:

[0088] Table 2

[0089] sample Pass rate (%) Appearance friability Dissolution (%) Example 1 85 No obvious defects No brittleness 10.2 Example 2 88 No obvious defects No brittleness 10.8 Example 3 83 No obvious defects No brittleness 11.0 Example 4 87 No obvious defects No brittleness 10.5 Comparative Example 1 55 Thin wall, obvious defects such as shredding 4 capsules / 10 capsules 32.4 Comparative Example 2 62 Uneven wall thickness, thick top, obvious defects 3 capsules / 10 capsules 40.2 Comparative Example 3 24 Difficult to shape / / Comparative Example 4 15 Difficult to shape / / Comparative Example 5 20 Difficult to shape / /

[0090] In the mass production process, the capsules obtained by the method of the present invention have good molding effect, high qualified rate, stable mass production, and acid resistance. However, the capsules of comparative examples 1-2 have problems such as thick top, uneven wall thickness, severe incision and shredding because the sol temperature and the viscosity of the glue solution are not within the preferred range. Comparative examples 3-5 do not dissolve the gellan gum in steps, resulting in uneven glue state, and the viscosity of the glue solution cannot be controlled within the scope of the claims. There are serious problems of glue flow and uncontrollable excessive thickness of the capsule wall when dipping the glue. Therefore, the capsules cannot be formed, and the formed capsules are difficult to be peeled off from the mold pin, which has problems in practical applications.

[0091] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A production process for delayed-release plant hollow capsules, characterized in that: The steps include: S1: Adding materials: adding water to the sol kettle, heating to the first temperature, adding hydroxypropyl methylcellulose and low acyl gellan gum to the sol kettle, stirring until the glue liquid is in a uniform state; cooling to the second temperature, adding high acyl gellan gum, stirring until the glue liquid is in a uniform state; adding gelling agent, stirring until the glue liquid is in a uniform state; S2: emulsifying the glue; S3: Vacuuming: stop emulsification, cool down, and vacuumize; S4: Filtration: filtering the glue solution to obtain the glue solution after filtration, and keeping it warm; S5: capsule making: after the temperature of the glue tank reaches the third temperature, glue is released, and the viscometer is turned on to measure the viscosity of the glue in the glue tank. When the viscosity reaches a stable state, glue dipping is started. After glue dipping, capsule conveying, drying, demolding, length setting, cutting, and sleeve-fitting are sequentially performed to obtain delayed-release plant hollow capsules; In step S1, each repeating unit of the low acyl gellan gum contains 1%-30% of acetyl and 15%-40% of glyceryl acyl, and each repeating unit of the high acyl gellan gum contains 20%-45% of acetyl and 30%-55% of glyceryl acyl; In step S1, the first temperature is 85-95°C, and the second temperature is 80-85°C; In step S5, the third temperature is 58-72°C.

2. The production process according to claim 1, characterized in that: In step S1, the mass ratio of hydroxypropyl methylcellulose, low acyl gellan gum and high acyl gellan gum is 50-100:0.5-5:0.1-5.

3. The production process according to claim 1, characterized in that: In step S2, the emulsification time is 30-50 minutes.

4. The production process according to claim 1, characterized in that: In step S4, the insulation time is 4-6 hours and the insulation temperature is 60-65°C.

5. The production process according to claim 1, characterized in that: In step S4, the viscosity of the glue solution at 25°C after filtration is 20-100 mPa.s.

6. The production process according to claim 1, characterized in that: In step S5, the drying is stage drying, including four stages. The temperature of stage one is set at 18-23°C, the temperature of stage two is set at 20-30°C, the temperature of stage three is set at 25-38°C, and the temperature of stage four is set at 25-35°C. The drying time of each stage is 10-30 minutes.

7. The delayed-release plant hollow capsules prepared by the production process of delayed-release plant hollow capsules according to any one of claims 1 to 6.

Images