Medicinal plant empty capsule and preparation method thereof

Abstract

The invention provides a medicinal plant empty capsule and a preparation method thereof. The medicinal plant empty capsule is prepared from the following raw materials in percentage by mass: 13 percent to 19 percent of hydroxypropyl methyl cellulose, 0.2 percent to 0.5 percent of low-acyl gellan gum, 0.45 percent to 0.7 percent of iota-carrageenan, 0.08 percent to 0.135 percent of potassium salt and / or sodium salt, 0.4 percent to 0.6 percent of glycerol and 79.065 percent to 85.87 percent of water. The medicinal plant empty capsule provided by the invention has wide pH responsiveness, can have excellent disintegration performance and dissolution performance in various pH media, has excellent encapsulation rate, stability, safety and the like, solves the technical bottlenecks of animal-derived empty capsules and plant empty capsules, and provides a new thought for a drug delivery system.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical preparations and drug delivery, and in particular to a medicinal plant hollow capsule and a preparation method thereof. BACKGROUND

[0002] Under the background of high-speed iteration of modern medicine and biotechnology, the drug delivery system (DDS) as the core hub connecting drug research and development and clinical application, its precision and controllability become the key breakthrough point to improve drug efficacy. For oral solid preparations, rapid disintegration and high-efficiency dissolution are the core requirements to ensure the rapid onset of drugs, especially in the scene of emergency drugs, children's drugs, etc., the disintegration rate of capsules directly affects the treatment effect. However, the traditional gelatin capsule mainly uses animal-derived materials, which is not safe, and the production process often introduces chemical reagents such as formaldehyde for bleaching or preservation, which is easy to cause heavy metal pollution. More importantly, the amino group (-NH2) in the gelatin molecule is easy to react with aldehyde-containing drugs to form irreversible cross-linked structures, causing the capsule shell to harden and disintegrate to delay, which greatly reduces the in-vitro dissolution of the drug and affects the drug efficacy. Although natural plant-based materials such as starch and cellulose can solve the problems brought by animal-derived materials and significantly improve safety, they still face new challenges, such as lack of full-pH responsive disintegration ability, inability to achieve precise drug targeted delivery, premature drug release or drug delayed release, and inability to meet the rapid drug release requirements, which significantly reduces drug efficacy. At the same time, natural plant-based materials have poor stability and insufficient mechanical properties, which are prone to damage and moisture absorption during storage and transportation, seriously affecting the quality of the preparation. SUMMARY

[0003] Therefore, it is necessary to provide a medicinal plant hollow capsule with high safety, full-pH responsive disintegration ability, precise drug targeted release, and high stability.

[0004] In a first aspect, the present application provides a medicinal plant hollow capsule, the raw material composition of the medicinal plant hollow capsule comprises, by mass percentage:

[0005] hydroxypropyl methyl cellulose 13%-19%,

[0006] low acyl gellan gum 0.2%-0.5%,

[0007] ι-carrageenan 0.45%-0.7%,

[0008] potassium salt and / or sodium salt 0.08%-0.135%,

[0009] glycerol 0.4%-0.6%, and

[0010] water 79.065%-85.87%.

[0011] In some embodiments, the medicinal plant hollow capsule also satisfies at least one of the following characteristics (1)-(6):

[0012] (1) the mass ratio of the low acyl gellan gum to iota carrageenan is (3-4):(5-7);

[0013] (2) the mass content of acyl groups in the low acyl gellan gum is 0.8%-1.2%;

[0014] (3) the molecular weight of the hydroxypropyl methyl cellulose is 70,000 Da-800,000 Da;

[0015] (4) the viscosity of a 2% hydroxypropyl methyl cellulose aqueous solution measured at 20°C is 500 mPa·s-2000 mPa·s;

[0016] (5) the gel strength of a 1% iota carrageenan aqueous solution measured at 20°C after heating to 78-90°C and cooling is 50 g / cm²-150 g / cm²;

[0017] (6) the water is deionized water.

[0018] In some embodiments, the medicinal plant hollow capsule has a water content of <7%; and / or, the medicinal plant hollow capsule has a wall thickness of 0.085 mm-0.115 mm.

[0019] In a second aspect, the present application also provides a preparation method of the medicinal plant hollow capsule of the first aspect, comprising the following steps:

[0020] adding a potassium salt and / or a sodium salt and a low acyl gellan gum to 35°C-45°C water to prepare a first mixture;

[0021] heating the first mixture to 78°C-85°C, and sequentially adding hydroxypropyl methyl cellulose, iota carrageenan, and glycerol, and stirring until dissolved to prepare a second mixture;

[0022] performing sol-gel and gel retention on the second mixture to prepare a glue solution;

[0023] dipping the preheated mold in the glue solution to cover the surface of the mold with the glue solution, and drying the mold in an environment with a temperature of 30°C-42°C and a relative humidity of 50%-65%, and then cooling and demolding to prepare the medicinal plant hollow capsule.

[0024] In some embodiments, the preparation method of the medicinal plant hollow capsule also satisfies at least one of the following (1)-(8):

[0025] (1) the temperature for sol-gel is 78°C-85°C;

[0026] (2) the time for the sol is 2.5h-3.5h;

[0027] (3) the time for the dipping is 1s-2s;

[0028] (4) the pulling speed for the dipping is 45mm / s-55mm / s;

[0029] (5) the temperature for the keeping is 55℃-60℃;

[0030] (6) the time for the keeping is 0.5h-1.5h;

[0031] (7) the temperature for the preheated mold is 30℃-35℃;

[0032] (8) the temperature for the cooling is 22℃-28℃;

[0033] (9) the time for the cooling is 15 min-20 min;

[0034] (10) the time for the drying treatment is 60 min-100min.

[0035] In some embodiments, the drying comprises at least two stages of convection drying;

[0036] Optionally, the medium flow rate for the convection drying is 1 m / s-2 m / s.

[0037] In some embodiments, the two-stage drying further satisfies at least one of (1)-(7) below:

[0038] (1) the temperature for the first-stage convection drying is 40℃±1℃;

[0039] (2) the relative humidity for the first-stage convection drying is 58%-62%;

[0040] (3) the time for the first-stage convection drying is 35min-40min;

[0041] (4) the temperature for the second-stage convection drying is 35℃±1℃;

[0042] (5) the relative humidity for the second-stage convection drying is 50%-54%;

[0043] (6) the time for the second-stage convection drying is 50 min-60 min;

[0044] (7) the first-stage convection drying and the second-stage convection drying are performed in sequence.

[0045] In a third aspect, the present application also provides a drug delivery system, comprising a drug and a medicinal plant hollow capsule encapsulating the drug, wherein the medicinal plant hollow capsule comprises the medicinal plant hollow capsule provided in the first aspect or the medicinal plant hollow capsule prepared by the preparation method provided in the second aspect.

[0046] In some embodiments, the drug delivery system further satisfies the features shown in (1) and / or (2) as follows:

[0047] (1) the drug comprises a natural drug and / or a chemical drug;

[0048] Optionally, the natural drug comprises a Chinese medicinal material or an extract thereof.

[0049] Optionally, the chemical drug comprises an antibiotic drug and / or an acid-inhibiting drug.

[0050] Further optionally, the antibiotic drug comprises one or more of cefradine, amoxicillin, azithromycin, and levofloxacin.

[0051] Further optionally, the acid-inhibiting drug comprises one or more of ranitidine, omeprazole, lansoprazole, and famotidine.

[0052] (2) the drug delivery system comprises delivering the drug to the stomach and / or the intestinal tract.

[0053] In some embodiments, the drug delivery system further comprises a pharmaceutically acceptable excipient.

[0054] Optionally, the excipient comprises one or more of a filler, a binder, a disintegrant, a plasticizer, a lubricant, and a diluent.

[0055] Compared with the conventional technology, the technical solution of the present application has the following beneficial effects:

[0056] The present application uses low acyl gellan gum and iota carrageenan to construct a gel network with wide pH responsiveness, which can have excellent disintegration performance and dissolution performance in various pH media. Further, the present application further compounding with hydroxypropyl methyl cellulose to synergistically promote the disintegration performance of the material, which meets the release requirements of the medicinal plant hollow capsule in the stomach and intestinal environment, significantly promotes the release of the drug, and improves the targeting accuracy of the drug and the drug efficacy. At the same time, the present application also has the advantages of improving the capsule forming rate, mechanical properties, stability, and safety of the material, etc., which solves the technical bottlenecks of traditional animal-derived hollow capsules and traditional plant hollow capsules. The present application can be widely applied in oral solid preparations, health products, functional foods, or special population preparations, especially in drug delivery systems requiring rapid disintegration and high dissolution efficiency. The special population preparations need to match the rapid disintegration characteristics to improve the medication compliance, including pediatric medication, geriatric medication, etc. Attached Figure Description

[0057] Figure 1 The images show the SEM images of the membrane disintegration process of the medicinal plant hollow capsules provided in this application in simulated gastric juice (pH=1.2); (a) and (d) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration for 2 min in simulated gastric juice (pH=1.2) at different magnifications; (b) and (e) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration for 6 min in simulated gastric juice (pH=1.2) at different magnifications; and (c) and (f) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration for 9 min in simulated gastric juice (pH=1.2) at different magnifications.

[0058] Figure 2 The images show the SEM images of the membrane disintegration process of the medicinal plant hollow capsules provided in this application in acetate-sodium acetate buffer (pH=4.5); (a) and (d) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration in acetate-sodium acetate buffer (pH=4.5) for 2 min at different magnifications; (b) and (e) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration in acetate-sodium acetate buffer (pH=4.5) for 6 min at different magnifications; and (c) and (f) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration in acetate-sodium acetate buffer (pH=4.5) for 9 min at different magnifications.

[0059] Figure 3 The images show the SEM images of the membrane disintegration process of the medicinal plant hollow capsules provided in this application in simulated intestinal fluid (pH=6.8); (a) and (d) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration for 2 min in simulated intestinal fluid (pH=6.8) at different magnifications; (b) and (e) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration for 6 min in simulated intestinal fluid (pH=6.8) at different magnifications; and (c) and (f) in the images show the microstructure of the capsule shells of the medicinal plant hollow capsules after disintegration for 9 min in simulated intestinal fluid (pH=6.8) at different magnifications.

[0060] Figure 4The SEM images of the film disintegration process of the medicinal plant hollow capsule provided in the present application in distilled water (pH=7.0); in the figure, (a), (d) are the microstructure of the capsule shell of the medicinal plant hollow capsule disintegrated in distilled water (pH=7.0) for 2 min under different magnifications; (b), (e) are the microstructure of the capsule shell of the medicinal plant hollow capsule disintegrated in distilled water (pH=7.0) for 6 min under different magnifications; (c), (f) are the microstructure of the capsule shell of the medicinal plant hollow capsule disintegrated in distilled water (pH=7.0) for 9 min under different magnifications.

[0061] Figure 5 The dissolution curves of the medicinal plant hollow capsule and the gelatin hollow capsule provided in the present application respectively loaded with cefradine in four different dissolution media.

[0062] Figure 6 The dissolution curves of the medicinal plant hollow capsule and the gelatin hollow capsule provided in the present application respectively loaded with ranitidine hydrochloride in four different dissolution media. DETAILED DESCRIPTION

[0063] In order to facilitate the understanding of the present application, the present application will be described more fully below with reference to the accompanying drawings. The preferred embodiments of the present application are shown in the accompanying drawings. However, the present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thorough and comprehensive.

[0064] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. The terminology used in the description of the present application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application.

[0065] As used herein, "optionally", "optional", "alternatively" mean being selected from the group consisting of "yes" or "no"; if there are multiple "options" in a technical solution, each "option" is independent of each other unless otherwise specified, and there is no contradictory relationship or mutual restriction. The term "and / or" used herein includes any and all combinations of one or more related listed items. The terms "a plurality of", "multiple", and the like, as used herein, mean greater than 2 or equal to 2 unless otherwise specified. For example, "one or more" means one, two, or more than two. The open technical features or technical solutions described herein with the terms "contain", "include", "comprise" and the like, unless otherwise specified, do not exclude additional members outside the listed members, which can be regarded as providing both closed features or solutions composed of listed members and open features or solutions including additional members outside the listed members.

[0066] In the present application, the terms "first", "second", "third", "fourth" and the like in the "first aspect", "second aspect", "third aspect", "fourth aspect" and the like are only for the purpose of description and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the technical features indicated. Moreover, "first", "second", "third", "fourth" and the like only serve the purpose of non-exhaustive enumeration description and should be understood as not constituting a closed limitation on the quantity.

[0067] Unless otherwise specified, all embodiments and optional embodiments of the present application can be combined with each other to form new technical solutions.

[0068] Drug delivery system (DDS) refers to a technical system that comprehensively controls the distribution of drugs in the body in space, time and dose. Its goal is to deliver the right amount of drug to the right place at the right time, including drug controlled release, drug targeting, enhancing drug stability, adjusting drug metabolism time, and promoting drug absorption and passing through biological barriers, thereby increasing the utilization efficiency of drugs, improving efficacy, reducing cost, and reducing toxicity and side effects.

[0069] Traditional drug delivery systems include oral tablets, capsules, intravenous injections, inhalation preparations and transdermal patches, etc. Compared with other drug delivery systems, capsules can mask the unpleasant smell of drugs, improve drug stability, and have higher drug efficacy and bioavailability. At the same time, compared with other drug delivery systems, it can more accurately control drug release. However, the shell material of the traditional capsule has problems of safety, stability and controlled release effect, and the present application aims to develop a plant-based medicinal hollow capsule with full pH-responsive disintegration performance, high stability and safety, providing a new idea for the field of drug delivery systems.

[0070] In a first aspect, the present application provides a medicinal plant hollow capsule, the raw material composition of the medicinal plant hollow capsule comprises, by mass percentage:

[0071] Hydroxypropyl methylcellulose 13%-19%,

[0072] Low acyl gellan gum 0.2%-0.5%,

[0073] Iota carrageenan 0.45%-0.7%,

[0074] Potassium salt and / or sodium salt 0.08%-0.135%,

[0075] Glycerol 0.4%-0.6%, and

[0076] Water 79.065% - 85.87%.

[0077] The application adopts a compound system of low acyl gellan gum (GG) and iota carrageenan (i-C), optimizes the synergistic mechanism of the three, constructs a network system with pH responsiveness, further compounds hydroxypropyl methyl cellulose (HPMC) to form a continuous film skeleton, and prepares a medicinal plant hollow capsule with excellent drug controlled release effect, which can improve drug targeting and improve the accuracy of the target site of drug action. At the same time, it has excellent stability and mechanical properties, which is beneficial to transportation and storage. The medicinal plant hollow capsule provided by the application significantly improves the drug delivery efficiency and the stability of the preparation, and has important practical significance.

[0078] In some embodiments, the raw material composition of the medicinal plant hollow capsule includes, by mass percentage:

[0079] Hydroxypropyl methyl cellulose 13% - 17%,

[0080] Low acyl gellan gum 0.2% - 0.4%,

[0081] Iota carrageenan 0.5% - 0.7%,

[0082] Potassium salt and / or sodium salt 0.09% - 0.13%,

[0083] Glycerol 0.4% - 0.6%, and

[0084] Water 81.17% - 85.81%.

[0085] In some embodiments, the mass ratio of the low acyl gellan gum to the iota carrageenan is (3-4):(5-7), which can form a gel network with excellent pH responsiveness in the above ratio range, and the pH response range includes 1-7, which is beneficial to more targeted drug delivery. As a non-limiting example, including but not limited to 3:5, 3:6, 3:7, 4:5, 4:6, 4:7 or the range formed by any two of the foregoing and the values within the range.

[0086] In some embodiments, the mass content of acyl groups in the low acyl gellan gum is 0.8% - 1.2%. As a non-limiting example, including but not limited to 0.8%, 0.9%, 1%, 1.1%, 1.2% or the range formed by any two of the foregoing and the values within the range.

[0087] In some embodiments, the hydroxypropyl methylcellulose has a molecular weight of 70,000 Da to 800,000 Da. By way of non-limiting example, including but not limited to 70,000 Da, 100,000 Da, 200,000 Da, 500,000 Da, 800,000 Da, or a range formed by any two of the foregoing, and values within the range.

[0088] In some embodiments, the aqueous solution of hydroxypropyl methylcellulose having a mass concentration of 2% has a viscosity of 500 mPa-s to 2000 mPa-s measured at 20°C. By way of non-limiting example, including but not limited to 500 mPa-s, 800 mPa-s, 1000 mPa-s, 1500 mPa-s, 2000 mPa-s, or a range formed by any two of the foregoing, and values within the range.

[0089] In some embodiments, the aqueous solution of i-carrageenan having a mass concentration of 1%, heated to 78-90°C, cooled, has a gel strength of 50 g / cm² to 150 g / cm² measured at 20°C. By way of non-limiting example, including but not limited to 50 g / cm², 60 g / cm², 70 g / cm², 80 g / cm², 90 g / cm², 100 g / cm², 110 g / cm², 120 g / cm², 130 g / cm², 140 g / cm², 150 g / cm², or a range formed by any two of the foregoing, and values within the range.

[0090] In some embodiments, the medicinal plant hollow capsule has a water content of < 7%, and in the present application, the medicinal plant hollow capsule has a water content of ≥ 6% and < 7%, and within the range of the water content, the medicinal plant hollow capsule is beneficial to balance the friability and storage stability of the medicinal plant hollow capsule.

[0091] In some embodiments, the medicinal plant hollow capsule has a mass content of bound water that accounts for ≥ 88% of the total water mass content of the medicinal plant hollow capsule. Further, the medicinal plant hollow capsule has a mass content of bound water that accounts for 88% to 92% of the total water mass content of the medicinal plant hollow capsule.

[0092] In some embodiments, the medicinal plant hollow capsule has a wall thickness of 0.085 mm to 0.115 mm. By way of non-limiting example, including but not limited to 0.085 mm, 0.09 mm, 0.095 mm, 0.1 mm, 0.105 mm, 0.11 mm, 0.115 mm, or a range formed by any two of the foregoing, and values within the range.

[0093] In some embodiments, the content of potassium salt and / or sodium salt in the raw material composition of the medicinal plant hollow capsule is 0.09%-0.11% by mass percentage, and further, the content of potassium salt and / or sodium salt in the raw material composition of the medicinal plant hollow capsule is 0.096% to better achieve the technical effects of the present application.

[0094] In some embodiments, the potassium salt includes potassium citrate.

[0095] In some embodiments, the sodium salt includes sodium carbonate.

[0096] In some embodiments, the water is deionized water.

[0097] In some embodiments, the raw material composition of the medicinal plant hollow capsule includes, by mass percentage:

[0098] hydroxypropyl methyl cellulose 15%,

[0099] low acyl gellan gum 0.26%,

[0100] i-kappa carrageenan 0.54%,

[0101] potassium citrate 0.051%,

[0102] sodium carbonate 0.045%,

[0103] glycerol 0.49%, and

[0104] water 83.614%.

[0105] The medicinal plant hollow capsule provided by the present application does not contain animal-derived materials and ingredients, has high safety, and is produced without using formaldehyde, with a heavy metal content <10 ppm, meeting the standards of the Chinese Pharmacopoeia (heavy metal content ≤20 ppm); does not contain nitrogen sources and does not require preservatives, meeting the requirements of halal, vegetarian, and GMP, and is suitable for sensitive groups of people.

[0106] In a second aspect, the present application further provides a preparation method of the medicinal plant hollow capsule provided in the first aspect, including the following steps:

[0107] S10, adding potassium salt and / or sodium salt and low acyl gellan gum to 35-45°C water to prepare a first mixture.

[0108] S20, heating the first mixture to 78-85°C, and sequentially adding hydroxypropyl methyl cellulose, i-kappa carrageenan, and glycerol, stirring to dissolve, to prepare a second mixture.

[0109] S30, performing sol and gel retention on the second mixture to prepare a glue solution.

[0110] S40, dipping the preheated mold in the glue solution to cover the mold surface with the glue solution, drying treatment in an environment with a temperature of 30-42°C and a relative humidity of 50-65%, cooling, demolding, and preparing the hollow medicinal plant capsule.

[0111] In some embodiments, the dipping time is 1-2s. As non-limiting examples, including but not limited to 1s, 1.2s, 1.4s, 1.5s, 1.8s, 2s, or a range formed by any two of the foregoing and numerical values within the range. Within this time range, the glue solution content and thickness of the mold surface, and the uniformity of the glue solution can be controlled, thereby controlling the finished product thickness and surface uniformity of the hollow medicinal plant capsule.

[0112] In some embodiments, the pulling speed of the dipping process is 45-55mm / s, as non-limiting examples, including but not limited to 45mm / s, 48mm / s, 50mm / s, 52mm / s, 55mm / s, or a range formed by any two of the foregoing and numerical values within the range. Further, the 50mm / s pulling speed used in the present application can better form a glue solution with uniform thickness on the mold surface, thereby better achieving the technical effects of the present application.

[0113] In some embodiments, the temperature of the sol is 78-85°C.

[0114] In some embodiments, the time of the sol is 2.5-3.5h.

[0115] In some embodiments, the temperature of the glue preservation is 55-60°C.

[0116] In some embodiments, the time of the glue preservation is 0.5-1.5h.

[0117] In some embodiments, the temperature of the preheated mold is 30-35°C.

[0118] In some embodiments, the temperature of the cooling is 22-28°C.

[0119] In some embodiments, the time of the cooling is 15-20min.

[0120] In some embodiments, the drying treatment includes at least two stages of convection drying.

[0121] In some embodiments, the medium flow rate of the convection drying is 1-2m / s. As non-limiting examples, including but not limited to 1m / s, 1.2m / s, 1.5m / s, 1.8m / s, 2m / s, or a range formed by any two of the foregoing and numerical values within the range. Further, the hot air speed of 1.5m / s±0.2m / s used in the present application can better achieve the technical effects of the present application.

[0122] In some embodiments, the temperature of the first-stage convection drying is 40℃±1℃.

[0123] In some embodiments, the relative humidity of the first-stage convection drying is 58%-62%.

[0124] In some embodiments, the time of the first-stage convection drying is 35min-40min.

[0125] In some embodiments, the temperature of the second-stage convection drying is 35℃±1℃.

[0126] In some embodiments, the relative humidity of the second-stage convection drying is 50%-54%.

[0127] In some embodiments, the time of the second-stage convection drying is 50min-60min.

[0128] In some embodiments, the first-stage convection drying and the second-stage convection drying are performed in sequence.

[0129] In some embodiments, the drying process is a 3-stage, 4-stage, or 5-stage convection drying, and the drying process is performed by alternately performing the first-stage convection drying and the second-stage convection drying.

[0130] The present application can improve the stability and mechanical properties of the medicinal plant hollow capsules by removing free water from the material in stages and controlling the proportion of bound water in the material through segmented drying.

[0131] In some embodiments, in step S40, the mold containing the glue solution is placed in a cooling room at 22℃-28℃ for 15min-20min, which can allow the hollow capsules to be fully shaped, further stabilize the performance of the hollow capsules, and better facilitate the release of the hollow capsules from the mold.

[0132] In some embodiments, in step S40, the mold is removed using a mechanical demolding device and / or a small amount of lubricant to assist in demolding, and the capsules are peeled off from the mold to obtain intact and undamaged medicinal plant hollow capsules.

[0133] In some embodiments, the mechanical demolding device uses pneumatic demolding.

[0134] In some embodiments, the pressure of the pneumatic demolding is 0.2MPa-0.3MPa. Within this pressure range, the deformation and surface defects of the capsule shell can be significantly reduced, the damage to the capsule shell caused by the demolding process can be reduced, and the yield can be significantly improved.

[0135] The medicinal plant hollow capsule provided by the present application adopts a low-temperature drying process, greatly reducing the production energy consumption. Defective products are removed through machine vision lamp inspection, and the finished product rate is high. Moreover, the medicinal plant hollow capsule provided by the present application is fully biodegradable, with a 6-month decomposition rate of ≥90% in soil, meeting the European Union environmental regulations, and having both industrial feasibility and environmental friendliness.

[0136] In a third aspect, the present application also provides a drug delivery system, comprising a drug and a medicinal plant hollow capsule encapsulating the drug, wherein the medicinal plant hollow capsule comprises the medicinal plant hollow capsule provided in the first aspect or the medicinal plant hollow capsule prepared by the preparation method provided in the second aspect.

[0137] In some embodiments, the drug comprises a natural drug and / or a chemical drug.

[0138] In some embodiments, the natural drug comprises a Chinese medicinal material or an extract thereof.

[0139] In some embodiments, the chemical drug comprises an antibiotic drug and / or an acid-inhibiting drug.

[0140] As non-limiting examples, the antibiotic drug comprises one or more of cefradine, amoxicillin, azithromycin, and levofloxacin.

[0141] As non-limiting examples, the acid-inhibiting drug comprises one or more of ranitidine, omeprazole, lansoprazole, and famotidine.

[0142] The medicinal plant hollow capsule provided by the present application has excellent drug dissolution efficiency, and the drug delivery system composed of the medicinal plant hollow capsule can quickly and fully release drugs such as cefradine and ranitidine hydrochloride when delivering the drugs, and has a similar dissolution curve to the traditional gelatin capsule (the similarity factor f2 of the drug dissolution curve to the reference preparation (such as a gelatin capsule) is >50). Moreover, the medicinal plant hollow capsule in the drug delivery system of the present application has no cross-linking reaction with the drug, and the degradation rate is <3% under the condition of 60°C / RH75% for 6 months, which is significantly better than that of the gelatin capsule (>15%), solving the problem of delayed dissolution of aldehyde-containing drugs.

[0143] In some embodiments, the drug delivery system comprises delivering the drug to the stomach and / or the intestinal tract.

[0144] In some embodiments, the drug delivery system further comprises a pharmaceutically acceptable excipient.

[0145] In some embodiments, the excipient comprises one or more of a filler, a binder, a disintegrant, a plasticizer, a lubricant, and a diluent.

[0146] It should be noted that the experimental methods in the following examples of the present application without specific conditions are generally according to the conventional conditions, or according to the conditions suggested by the manufacturers. The various common chemical reagents used in the examples are commercially available products, or can be prepared by those skilled in the art according to known means.

[0147] The model numbers and sources of some raw materials and reagents involved in the specific embodiments of the present application are as follows:

[0148] Hydroxypropyl methyl cellulose was purchased from Huzhou Zhanwang Pharmaceutical Co., Ltd., with a molecular weight of 70,000 Da-800,000 Da, and was prepared into a 2wt% hydroxypropyl methyl cellulose aqueous solution, and the viscosity measured at 20℃ was 500 mPa·s-2000 mPa·s.

[0149] Low acyl gellan gum was purchased from Fufeng Biological Technology Co., Ltd., with a mass content of acyl group of 0.8%-1.2%.

[0150] I-kappa carrageenan was purchased from Lvxin (Fujian) Food Co., Ltd., with a mass concentration of 1% i-kappa carrageenan aqueous solution, heated to 78-90℃, cooled, and the gel strength measured at 20℃ was 50 g / cm²-150 g / cm².

[0151] Example 1

[0152] The present embodiment provides a medicinal plant hollow capsule and a preparation method thereof, which are as follows:

[0153] The raw material composition of the medicinal plant hollow capsule includes, by mass percentage:

[0154] Hydroxypropyl methyl cellulose 15%,

[0155] Low acyl gellan gum 0.2%,

[0156] I-kappa carrageenan 0.6%,

[0157] Potassium citrate 0.051%,

[0158] Sodium carbonate 0.045%,

[0159] Glycerol 0.49%, and

[0160] Water 83.614%.

[0161] The preparation method of the medicinal plant hollow capsule includes:

[0162] Potassium citrate, sodium carbonate and low acyl gellan gum were added to 40℃ water to prepare a first mixture.

[0163] The first mixture is heated to 80℃± 2℃, and hydroxypropyl methyl cellulose, iota carrageenan and glycerol are added in sequence, and stirred until completely dissolved to prepare a second mixture.

[0164] The second mixture is dissolved at 80℃± 2℃ for 3h, and then cooled to 55-60℃ for 1h to prepare a glue solution.

[0165] The mold preheated to 30-35℃ is dipped in the glue solution, the dipping speed is 45mm / s, and the dipping time is 2s.

[0166] The mold surface is covered with glue solution, and then subjected to convection drying, as follows:

[0167] The first-stage convection drying is performed at a drying temperature of 40℃, a relative humidity of 60%, a hot air flow rate of 2m / s, and a drying time of 40min.

[0168] The second-stage convection drying is performed at a drying temperature of 35℃, a relative humidity of 52%, a hot air flow rate of 1.5m / s, and a drying time of 60min.

[0169] Then, it is placed in a 25℃ cooling room for 20min, and the dried hollow capsules are separated from the mold, and then cut and fitted according to the hollow capsule standard, and the hollow capsules that do not meet the quality requirements (《Chinese Pharmacopoeia》2020 edition four general rules 0921 (hollow capsule quality standard)) such as bubbles, deformities, leaks and bulges are removed using a lamp inspection table, and the qualified medicinal plant hollow capsules are sealed and stored.

[0170] Example 2

[0171] The present embodiment provides a medicinal plant hollow capsule and a preparation method thereof, as follows:

[0172] The raw material composition of the medicinal plant hollow capsule includes, by mass percentage:

[0173] hydroxypropyl methyl cellulose 15%,

[0174] low acyl gellan gum 0.3%,

[0175] iota carrageenan 0.6%,

[0176] potassium citrate 0.051%,

[0177] sodium carbonate 0.045%,

[0178] glycerol 0.49%, and

[0179] water 83.514%.

[0180] The preparation method of the medicinal plant hollow capsule comprises the following steps:

[0181] Potassium citrate, sodium carbonate and low acyl gellan gum are added into 40℃ water to prepare a first mixture.

[0182] The first mixture is heated to 82℃± 2℃, and then hydroxypropyl methyl cellulose, iota carrageenan and glycerol are added in sequence, and stirred until completely dissolved to prepare a second mixture.

[0183] The second mixture is sol-gel at 80℃± 2℃ for 1h, and then cooled to 55-60℃ for 1h to prepare a glue solution.

[0184] A mold preheated to 30-35℃ is dipped in the glue solution, the dipping speed is 55mm / s, the dipping time is 1s, the surface of the mold is covered with the glue solution, and then convection drying is performed, specifically as follows:

[0185] The first-stage convection drying is performed at a drying temperature of 40℃, a relative humidity of 60%, a hot air flow rate of 2m / s and a drying time of 30min.

[0186] The second-stage convection drying is performed at a drying temperature of 35℃, a relative humidity of 52%, a hot air flow rate of 1.5m / s and a drying time of 50min.

[0187] Then, the dried hollow capsule is separated from the mold, and then cut and embedded according to the hollow capsule standard, and the hollow capsules that do not meet the quality requirements (Chinese Pharmacopoeia 2020 edition four general rules 0921 (hollow capsule quality standard)) such as bubbles, deformities, leaks and bulges are removed by using a lamp inspection table, and the qualified medicinal plant hollow capsules are sealed and stored.

[0188] Example 3

[0189] The present embodiment provides a medicinal plant hollow capsule and a preparation method thereof, specifically as follows:

[0190] The raw material composition of the medicinal plant hollow capsule comprises, by mass percentage:

[0191] hydroxypropyl methyl cellulose 15%,

[0192] low acyl gellan gum 0.26%,

[0193] iota carrageenan 0.54%,

[0194] potassium citrate 0.051%,

[0195] sodium carbonate 0.045%,

[0196] Glycerol 0.49%, and

[0197] Water 83.614%.

[0198] The preparation method of the medicinal plant hollow capsule comprises the following steps:

[0199] Potassium citrate, sodium carbonate and low acyl gellan gum are added into water at 40℃ to prepare a first mixture.

[0200] The first mixture is heated to 80℃± 2℃, and hydroxypropyl methylcellulose and i-kappa carrageenan are sequentially added and stirred until completely dissolved to prepare a second mixture.

[0201] The second mixture is sol-gel at 84℃± 1℃ for 2h, and then cooled to 55-60℃ for 1h to prepare a glue solution.

[0202] A mold preheated to 30-35℃ is dipped in the glue solution at a dipping speed of 50mm / s for 1.5s to cover the surface of the mold with the glue solution, and then subjected to convection drying, specifically as follows:

[0203] First-stage convection drying is performed at a drying temperature of 40℃, a relative humidity of 60%, a hot air flow rate of 2m / s and a drying time of 40min.

[0204] Second-stage convection drying is performed at a drying temperature of 35℃, a relative humidity of 52%, a hot air flow rate of 1.5m / s and a drying time of 60min.

[0205] Then, the dried hollow capsule is separated from the mold, and then cut and fitted according to the standard of the hollow capsule, and the hollow capsules that do not meet the quality requirements (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0921 (Hollow Capsule Quality Standard)) such as bubbles, deformities, leaks and bulges are removed by using a lamp inspection table, and the qualified medicinal plant hollow capsules are sealed and stored.

[0206] Example 4

[0207] The present embodiment provides a medicinal plant hollow capsule and a preparation method thereof, specifically as follows:

[0208] The raw material composition of the medicinal plant hollow capsule comprises, by mass percentage:

[0209] Hydroxypropyl methylcellulose 15%,

[0210] Low acyl gellan gum 0.4%,

[0211] I-kappa carrageenan 0.6%,

[0212] Potassium citrate 0.051%,

[0213] Sodium carbonate 0.045%,

[0214] Glycerol 0.49%, and

[0215] Water 83.414%.

[0216] The preparation method of the medicinal plant empty capsule comprises the following steps:

[0217] Potassium citrate, sodium carbonate and low acyl gellan gum are added into water at 40℃ to prepare a first mixture.

[0218] The first mixture is heated to 80℃±2℃, and then hydroxypropyl methylcellulose and ι-carrageenan are added in sequence, and stirred until completely dissolved to prepare a second mixture.

[0219] The second mixture is sol-gel at 82℃±2℃ for 2 hours, and then cooled to 55-60℃ for 1 hour to prepare a glue solution.

[0220] A mold preheated to 30-35℃ is dipped in the glue solution, the dipping speed is 50mm / s, the dipping time is 2s, the surface of the mold is covered with glue solution, and then convection drying is performed, specifically as follows:

[0221] First-stage convection drying, drying temperature is 40℃, relative humidity is 60%, hot air flow rate is 2m / s, and drying time is 35min.

[0222] Second-stage convection drying, drying temperature is 35℃, relative humidity is 52%, hot air flow rate is 1.5m / s, and drying time is 45min.

[0223] Then, it is placed in a 25℃ cooling room for 20min, the dried empty capsule is separated from the mold, and then cutting and fitting are performed according to the empty capsule standard, and the empty capsules that do not meet the quality requirements (《Chinese Pharmacopoeia》2020 edition four general rules 0921 (empty capsule quality standard)) such as bubbles, deformities, leaks, and bulges are removed by using a lamp inspection table, and the qualified medicinal plant empty capsules are sealed and stored.

[0224] Examples 5-15

[0225] The present embodiment provides a medicinal plant empty capsule and a preparation method thereof, specifically as follows:

[0226] The raw material composition of the medicinal plant empty capsule comprises, by mass percentage:

[0227] Table 1: Formulation of medicinal plant empty capsules of examples 5-15

[0228]

[0229] The preparation method of the medicinal plant hollow capsule is the same as that of Example 3 according to the formulation in Table 1.

[0230] Test Example 1: Disintegration performance test

[0231] The disintegration performance of the medicinal plant hollow capsules prepared in Examples 1-15 and the commercially available HPMC plant hollow capsules was tested in different media. The medicinal plant hollow capsules prepared in Examples 1-15 and the commercially available HPMC plant hollow capsules were all 1# hollow capsules that met the standard of Hydroxypropyl Methylcellulose Hollow Capsules in the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules. The media were artificial simulated liquids with different pH values, specifically pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0. The pH = 1.2 was prepared according to the preparation in the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules 0921, the pH = 4.5 was prepared according to the preparation in the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules 0921, the pH = 6.8 was prepared according to the preparation in the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules 0921, and the pH = 7.0 was prepared according to the preparation in the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules 0921.

[0232] The disintegration performance test was performed according to the disintegration time limit test method in the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules, and the test results are shown in Table 2.

[0233] Table 2: Disintegration performance test results of medicinal plant hollow capsules

[0234]

[0235] As shown by the results in Table 2, the medicinal plant hollow capsules prepared in the present application can all completely disintegrate within 15 minutes in pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0, all meeting the requirements of the Chinese Pharmacopoeia 2020 Edition Volume IV General Rules 0921 (hollow capsule disintegration time limit standard), and the disintegration performance is better than that of the commercially available HPMC plant hollow capsules.

[0236] The microstructure of the capsule shell during the disintegration of the medicinal plant hollow capsules provided in the present application in pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0 is specifically shown in FIGS. Figure 1 , FIGS. Figure 2 , FIGS. Figure 3 , and FIGS. Figure 4 .

[0237] Test Example 2: Physical performance test

[0238] The shell thickness, capsule forming rate, water content and tensile strength of the medicinal plant hollow capsules prepared in Examples 1-15 and the commercially available HPMC plant hollow capsules were tested, and the test methods were as follows:

[0239] The medicinal plant hollow capsules prepared in Examples 1-15 and the commercially available HPMC plant hollow capsules were all 1# hollow capsules in line with the standard of hydroxypropyl methylcellulose hollow capsules in the fourth part of Chinese Pharmacopoeia 2020.

[0240] (1) Shell thickness: measured by digital thickness gauge (SD-201 type), referring to the inspection method of capsules in Chinese Pharmacopoeia (2020 edition) 0982, randomly selecting 3 points in the middle of the capsule body for measurement, and taking the average value.

[0241] (2) Capsule forming rate: according to the general rule of capsules in Chinese Pharmacopoeia (2020 edition), capsules were prepared by dipping-gluing-drying-mold removal process, and after removing defects such as bubbles and deformities on the lamp inspection table, the proportion of qualified capsules to the total number of preparations was calculated.

[0242] (3) Water content: according to GB 5009.3-2016 "National food safety standard Determination of moisture in food" direct drying method, the capsule shell was dried at 105°C to constant weight, and the weight loss percentage was calculated.

[0243] (4) Tensile strength: referring to GB / T 1040.1-2018 "Determination of tensile properties of plastics Part 1: General", the capsule film was cut into 10mm×80mm samples, and tested by universal material testing machine (CMT4204 type) with a tensile rate of 5mm / min.

[0244] The results measured according to the above test methods are shown in Table 3:

[0245] Table 3: Physical property test results of medicinal plant hollow capsules

[0246]

[0247] As shown in Table 3, the medicinal plant hollow capsules prepared in the present application have better capsule thickness, capsule forming rate, water content and tensile strength than the commercially available HPMC plant hollow capsules, which shows that the medicinal plant hollow capsules prepared in the present application have significant progress compared with the prior art.

[0248] Test Example 3: Dissolution test of medicinal plant hollow capsules

[0249] The medicine plant hollow capsules prepared in examples 3, 12-15, the commercially available gelatin hollow capsules were loaded with antibiotic drug (cefradine), the medicine plant hollow capsules prepared in examples 1-15 and the commercially available HPMC plant hollow capsules were all 1# hollow capsules meeting the standard of hydroxypropyl methylcellulose hollow capsules in the fourth part of Chinese Pharmacopoeia 2020, and the loading amount of the drug was 0.25 g, and the dissolution test was carried out in different media, which were artificial simulated solutions with different pH values, specifically pH = 1.2, pH = 4.5, pH = 6.8, pH = 7.0, the pH = 1.2 was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020, the pH = 4.5 was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020, the pH = 6.8 was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020, and the pH = 7.0 was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020.

[0250] The dissolution test was carried out according to 0931 (dissolution test method) in the fourth part of Chinese Pharmacopoeia 2020, and the test results are shown in Table 4:

[0251] Table 4: Dissolution test results of medicine plant hollow capsules loaded with cefradine

[0252]

[0253] As shown by the results in Table 4, the dissolution rate of the medicine plant hollow capsules of the present application is greater than 85%, so it can be seen that the medicine plant hollow capsules prepared in the present application have significant progress compared with the prior art. At the same time, it can also be seen from the results that the proportion of low acyl gellan gum, iota carrageenan and hydroxypropyl methylcellulose has a significant effect on the dissolution of the hollow capsules, so it can be seen that low acyl gellan gum, iota carrageenan and hydroxypropyl methylcellulose have a synergistic effect, and the three can improve the dissolution of the hollow capsules within a specific proportion range.

[0254] The dissolution test results of the medicine plant hollow capsules (example 13) of the present application loaded with cefradine in pH = 1.2, pH = 4.5, pH = 6.8, pH = 7.0 are specifically shown in the following table 5: Figure 5 .

[0255] Test example 4: Test of antibiotic drug targeted delivery system

[0256] The plant medicine empty capsules prepared in Example 3, the commercial HPMC plant empty capsules, and the commercial gelatin empty capsules were loaded with antibiotic drugs (cefradine), the plant medicine empty capsules prepared in Examples 1-15 and the commercial HPMC plant empty capsules were all 1# empty capsules meeting the standard of hydroxypropyl methylcellulose empty capsules in the fourth part of Chinese Pharmacopoeia 2020, and the loading amount of the drugs was 0.25 g. The dissolution was tested in different media, which were artificial simulated solutions with different pH values, specifically pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0. The pH = 1.2 solution was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020, the pH = 4.5 solution was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020, the pH = 6.8 solution was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020, and the pH = 7.0 solution was prepared according to 0921 in the fourth part of Chinese Pharmacopoeia 2020.

[0257] The dissolution was tested according to 0931 (dissolution test method) in the fourth part of Chinese Pharmacopoeia 2020, and the test results were as follows:

[0258] The plant medicine empty capsules of the present application all showed excellent dissolution performance in pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0, and the dissolution rate was higher than 85% at 30 minutes. The results showed that the capsules of the present application realized efficient drug release across a wide pH range through the synergistic effect of low acyl gellan gum and iota carrageenan, solved the problems of slow disintegration of HPMC capsules in acidic medium and easy crosslinking of gelatin capsules in alkaline environment, and were especially suitable for rapid delivery of antibiotic drugs.

[0259] Test Example 5: Test of acid-inhibiting drug targeted delivery system

[0260] The medicine plant hollow capsule prepared in Example 3, the commercially available HPMC plant hollow capsule, and the commercially available gelatin hollow capsule were loaded with an acid-inhibiting drug (ranitidine hydrochloride), the medicine plant hollow capsules prepared in Examples 1-15 and the commercially available HPMC plant hollow capsule were all 1# hollow capsules meeting the standard of hydroxypropyl methylcellulose hollow capsules in the Pharmacopoeia of the People's Republic of China 2020 Edition Volume IV General Rules, the loading amount of the drug was 0.25 g, and the dissolution was tested in different media, i.e., artificial simulated solutions with different pH values, specifically, pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0. The pH = 1.2 solution was prepared according to the Pharmacopoeia of the People's Republic of China 2020 Edition Volume IV General Rules 0921, the pH = 4.5 solution was prepared according to the Pharmacopoeia of the People's Republic of China 2020 Edition Volume IV General Rules 0921, the pH = 6.8 solution was prepared according to the Pharmacopoeia of the People's Republic of China 2020 Edition Volume IV General Rules 0921, and the pH = 7.0 solution was prepared according to the Pharmacopoeia of the People's Republic of China 2020 Edition Volume IV General Rules 0921.

[0261] The dissolution was tested according to the Pharmacopoeia of the People's Republic of China 2020 Edition Volume IV General Rules 0931 (dissolution test method), and the test results were as follows:

[0262] Table 4: Dissolution test results of the medicine plant hollow capsule loaded with ranitidine hydrochloride

[0263]

[0264] After the medicine plant hollow capsule (Example 13) of the present application was loaded with ranitidine hydrochloride, the dissolution in pH = 1.2 for 30 minutes reached 89.4 ± 1.0, which was not significantly different from that of the commercially available gelatin capsule (89.8 ± 1%), and there was no delayed release caused by the Schiff base reaction of the gelatin capsule. In pH = 6.8 and pH = 7.0, the dissolution for 30 minutes was greater than 85%, which indicated that the capsule of the present application could avoid the cross-linking reaction of gelatin with aldehyde-containing drugs, and could overcome the delayed disintegration problem of HPMC material at low pH, and was suitable for the targeted delivery of acid-inhibiting drugs.

[0265] The dissolution test results of the medicine plant hollow capsule (Example 13) of the present application loaded with ranitidine hydrochloride in pH = 1.2, pH = 4.5, pH = 6.8, and pH = 7.0 are shown in Table 4 and FIG. 1. Figure 6 .

[0266] The technical features of the above-described examples can be combined in any manner. To make the description concise, not all possible combinations of the technical features in the above-described examples are described, however, as long as the combinations of the technical features do not contradict each other, they should be considered as within the scope of the present disclosure.

[0267] The above-described embodiments are merely illustrative of several embodiments of the present application, which are described in more detail and in a specific and detailed manner, but should not be construed as limiting the scope of the patent. It should be noted that for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present application, and these are all within the scope of the present application. Therefore, the scope of protection of the patent of the present application should be subject to the appended claims.

Claims

1. A medicinal plant empty capsule, characterized in that, The raw material composition of the medicinal plant empty capsules, by weight percentage, includes: Hydroxypropyl methylcellulose 13%-19%, Low-acyl gellan gum 0.2%-0.5%, ι-carrageenan 0.45%-0.7%, Potassium and / or sodium salts 0.08%-0.135%, Glycerol 0.4%-0.6%, and Water content: 79.065% - 85.87%.

2. The medicinal plant empty capsule according to claim 1, characterized in that, The medicinal plant hollow capsules also satisfy at least one of the following features (1) to (6): (1) The mass ratio of the low-acyl gellan gum to 1-carrageenan is (3-4):(5-7); (2) The mass content of acyl groups in the low-acyl gellan gum is 0.8%-1.2%; (3) The molecular weight of the hydroxypropyl methylcellulose is 70,000 Da-800,000 Da; (4) The viscosity of the 2% hydroxypropyl methylcellulose aqueous solution measured at 20°C is 500 mPa·s-2000 mPa·s; (5) A 1% aqueous solution of ι-carrageenan was heated to 78-90℃, cooled, and the gel strength was measured at 20℃ to be 50 g / cm²-150 g / cm². (6) The water is deionized water.

3. The medicinal plant empty capsule according to claim 1, characterized in that, The water content of the medicinal plant hollow capsule is <7%; and / or the wall thickness of the medicinal plant hollow capsule is 0.085 mm-0.115 mm.

4. The method for preparing the medicinal plant empty capsules according to any one of claims 1 to 3, characterized in that, Includes the following steps: Potassium salts and / or sodium salts, and low-acyl gellan gum are added to water at 35℃-45℃ to prepare the first mixture; The first mixture is heated to 78℃-85℃, and hydroxypropyl methylcellulose, 1-carrageenan and glycerol are added sequentially and stirred until dissolved to prepare the second mixture. The second mixture is sol-gelled and retained to prepare an adhesive solution; The preheated mold is dipped in the adhesive solution to cover the surface of the mold. It is then placed in an environment of 30℃-42℃ and 50%-65% relative humidity for drying, cooling, and demolding to prepare medicinal plant hollow capsules.

5. The method for preparing medicinal plant empty capsules according to claim 4, characterized in that, The preparation method of medicinal plant empty capsules also satisfies at least one of the following (1) to (10): (1) The temperature of the sol is 78℃-85℃; (2) The sol time is 2.5h-3.5h; (3) The time for applying the adhesive is 1s-2s; (4) The lifting speed for applying the adhesive is 45mm / s-55mm / s; (5) The temperature for maintaining the adhesive is 55℃-60℃; (6) The retention time is 0.5h-1.5h; (7) The temperature of the preheated mold is 30℃-35℃; (8) The cooling temperature is 22℃-28℃; (9) The cooling time is 15 min-20 min; (10) The drying time is 60 min-100 min.

6. The method for preparing medicinal plant empty capsules according to claim 4, characterized in that, The drying process includes at least two stages of convection drying; Optionally, the flow rate of the medium used for convection drying is 1 m / s to 2 m / s.

7. The method for preparing medicinal plant empty capsules according to claim 6, characterized in that, Two-stage airflow convection drying also satisfies at least one of the following (1) to (7): (1) The temperature of the first stage of convective drying is 40℃±1℃; (2) The relative humidity for the first stage of convective drying is 58%-62%; (3) The first stage of convection drying takes 35-40 minutes; (4) The temperature for the second stage of convective drying is 35℃±1℃; (5) The relative humidity for the second stage of convective drying is 50%-54%; (6) The second stage of convective drying takes 50 min-60 min; (7) The first stage of convection drying and the second stage of convection drying are carried out in sequence.

8. A drug delivery system, characterized in that, The drug delivery system includes a drug and a medicinal plant hollow capsule encapsulating the drug, wherein the medicinal plant hollow capsule includes the medicinal plant hollow capsule according to any one of claims 1 to 3 or the medicinal plant hollow capsule prepared by the preparation method according to any one of claims 4 to 7.

9. The drug delivery system according to claim 8, characterized in that, The drug delivery system also satisfies the following features as shown in (1) and / or (2): (1) The medicines include natural medicines and / or chemical medicines; Optionally, the natural medicine includes Chinese medicinal herbs or their extracts; Optionally, the chemical drug includes antibiotics and / or acid-suppressing drugs; Further optionally, the antibiotic includes one or more of cefadroxil, amoxicillin, azithromycin, and levofloxacin; Further, optionally, the acid-suppressing drugs include one or more of ranitidine, omeprazole, lansoprazole, and famotidine; (2) The drug delivery system includes delivering drugs to the stomach and / or intestines.

10. The drug delivery system according to claim 8 or 9, characterized in that, The drug delivery system also includes pharmaceutically acceptable excipients; Optionally, the excipients include one or more of fillers, binders, disintegrants, plasticizers, lubricants, and diluents.

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