Two-layer drug structure

Abstract

The present invention provides a two-layer drug structure that allows the drug-active ingredient to be released slowly after entering the intestinal tract. [Solution] The drug has a two-layer structure comprising a spherical core 11 containing a drug active ingredient, a coating polymer layer 12 having a certain thickness that covers the outer surface of the core and contracts inward in the gastric acid environment and expands outward in the intestinal environment, and a plurality of hydrophilic pologen microparticles 13 embedded in the coating polymer layer that are exposed and dissolved in intestinal fluid when the coating polymer layer expands outward, and that form channels.

Description

Technical Field

[0001] The present invention relates to a two-layer drug structure, and particularly to a two-layer drug structure that can enable a drug active ingredient to be slowly released after entering the intestinal tract.

Background Art

[0002] Currently, oral drugs are generally the main form of drug treatment. When a patient swallows a drug, the drug enters the stomach from the esophagus. Most drugs are decomposed by gastric acid after entering the stomach, mixed with gastric juice, and then transported to the small intestine. In order to avoid decomposition in the stomach, some drugs coat the drug active ingredient with an enteric coating or capsule (i.e., enteric tablets or capsules). After the drug enters the small intestine, the enteric coating or capsule is decomposed in the intestinal environment, and only at this time is the drug active ingredient released.

Summary of the Invention

Problems to be Solved by the Invention

[0003] However, after the enteric tablets or capsules enter the intestinal environment, all of the drug active ingredients therein are simultaneously released due to the rupture of the enteric coating or capsule, so the drug active ingredient cannot be continuously and slowly released. Therefore, it is desirable to propose a drug structure that can enable the drug active ingredient to be slowly released after entering the intestinal tract.

Means for Solving the Problems

[0004] An object of the present invention is, in view of the above problems, to provide a two-layer drug structure including a spherical core containing a drug active ingredient, a coating polymer layer having a certain thickness, covering the outer surface of the core, contracting inwardly in an acidic gastric environment, and expanding outwardly in an intestinal environment, and a plurality of hydrophilic porogen microparticles embedded in the coating polymer layer, which are exposed to intestinal fluid to form channels when the coating polymer layer expands outwardly.

Effects of the Invention

[0005] The two-layer drug structure described above provides a drug structure in which the drug active ingredient is released slowly after entering the intestinal tract. [Brief explanation of the drawing]

[0006] [Figure 1] This is a cross-sectional view of a two-layer drug structure according to an embodiment of the present invention. [Figure 2] This is a schematic diagram illustrating the changes in the gastrointestinal tract of a two-layer drug structure according to an embodiment of the present invention. [Modes for carrying out the invention]

[0007] In order to fully understand the purpose, features, and effects of this invention, the invention will be described in detail with reference to the following specific examples.

[0008] The two-layer drug structure 1 produced by this embodiment, as shown in Figure 1, comprises a core 11, a coating polymerization layer 12, and hydrophilic pologen microparticles 13 dispersed in the coating polymerization layer 12. The core 11 is spherical and contains a drug active ingredient, which may be a drug or a bioactive natural product such as quercetin, silibinin, puerarin, and curcumin. The coating polymerization layer 12 has a constant thickness, covers the outer surface of the core 11, contracts inward in the gastric acid environment (approximately gastric acid environment), and expands outward in the intestinal environment (approximately intestinal environment). The hydrophilic pologen microparticles 13 are embedded in the coating polymerization layer 12, and when the coating polymerization layer 12 expands outward, the hydrophilic pologen microparticles 13 are exposed to the intestinal fluid and dissolved by the intestinal fluid to form channels.

[0009] The method for producing the two-layer drug structure 1 according to this embodiment will be further described below.

[0010] First, a coating solution for preparing the coating polymerization layer 12 is prepared, and the components of the coating solution are shown in Table 1 below.

[0011] JPEG0003255426000002.jpg65166

[0012] In the components of the above coating solution, carrageenan is an anionic polysaccharide colloid that has gastric acid resistance and enteric coating properties. Due to the carrageenan, the coating polymer layer 12 contracts inward in the gastric acid environment of the stomach to resist gastric acid, and can be dissolved in the weakly acidic to neutral environment of the intestinal tract. In other embodiments, instead of carrageenan, other anionic polysaccharide colloids may be selected, including xanthangum, gellan gum, guar gum, carboxymethyl guar gum (CMG), curdlan, gum arabic, algin, pectin, sodium carboxymethylcellulose (CMC), sodium starch glycolate (CMS), cellulose acetate phthalate, levan, sorbitol, xylitol, erythritol, methylcellulose, ethylcellulose, maltodextrin, glucomannan, lignin, or combinations thereof.

[0013] In the components of the coating solution described above, whole milk powder is used as the protein component necessary for the coating solution, and since protein can be denatured and coagulated upon contact with acidic components, the decomposition of the coating polymerization layer 12 can be avoided. In other embodiments, instead of whole milk powder, other proteins including alkaline amino acid polymers, skim milk powder, whey protein powder, casein powder, soybean isolated protein powder, pea protein powder, corn protein powder, yeast protein powder, or combinations thereof may be selected. The alkaline amino acid polymer is a protein or polypeptide whose pH exceeds 7 under isoelectric point conditions and whose main components are lysine and arginine, and includes protamine, clevein, sturgeon protamine, lysozyme, polylysine, polyarginine, or alkaline soybean polypeptide.

[0014] In the components of the above coating solution, microcrystalline cellulose is used as a binder. In other embodiments, other binders including poly(acrylic acid), poly(acrylamide), poly(vinyl alcohol), poly(vinyl pyrrolidone), or combinations thereof may be selected.

[0015] In the components of the above coating solution, titanium dioxide is used as a solid dispersant, and in other embodiments, other solid dispersants may be selected. In some examples, the solid dispersant is selected from the group consisting of polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinylacetate copolymer (PVP-VA), polyvinylpyrrolidone crosslinked (PVP-CL), polyvinyl alcohol (PVA), polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose phthalate (HPMCP), hypromellose methylcellulose acetate succinate (HPMC-AS), corn starch, potato starch, silica, trehalose, sucrose, and inulin, or combinations thereof. In the components of the coating solution described above, hydroxypropylcellulose serves as an intestinal mucus adhesive, and in other embodiments, other intestinal mucus adhesives may be selected. In some examples, the mucosal adhesion auxiliary polymer is selected from the group consisting of natural polymer adhesive materials, semi-synthetic polymer adhesive materials, synthetic polymer adhesive materials, or combinations thereof.

[0016] In some examples, the natural polymer adhesive material is selected from the group consisting of gelatin, starch, hyaluronic acid, chitosan, chitosan oligosaccharides, phytoaglutinin, or combinations thereof.

[0017] In some examples, the semi-synthetic polymer adhesive material is selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), chitosan derivatives, chitosan cysteine, chitosan thiobutylamine, or combinations thereof.

[0018] In some examples, the synthetic polymer adhesive material is selected from the group consisting of carbomer, monoglyceride, polyvinyl alcohol, polyacrylic acid, polyglycol, or a combination thereof.

[0019] In the components of the above coating solution, starch is used as a coating agent, and in other embodiments, other types of coating agents such as lactose may be selected. In the components of the above coating solution, magnesium stearate is used as a smoothing agent, and in other embodiments, other smoothing agents may be selected as auxiliary excipients.

[0020] In the components of the coating solution described above, the polyglycol is a hydrophilic pologen, which is embedded in the coating layer in the form of powdery fine particles and forms a plurality of dispersed hydrophilic pologen fine particles 13. In other embodiments, instead of polyglycol, other proteins that are easily degraded by intestinal proteases or commonly used organic aqueous pologens may be used, and include polyvinyl alcohol, povidone, urea and hydroxypropyl methylcellulose or a combination thereof.

[0021] After preparing the coating solution for preparing the coating polymerization layer 12, the coating solution is sprayed onto the surface of the core 11 (preparation amount 250g) using a fluidized bed reactor (fluidized bed reactor spraying conditions: sterile environment, air pressure 2.5~5kg / cm²). 2 The hot air temperature is 40-50°C, and the air flow rate to the fluidized bed is 0.8-1.5 m³. 3 The rate is / min, and the nozzle has a flow rate of 0.1~0.25m 3The flow rate of the coating solution was 50-100 ml / h, and the coating spraying time was approximately 1.5-3 hours. Finally, a two-layer drug structure 1 with a particle size of 40-80 mesh was produced.

[0022] The morphological changes of the two-layer drug structure 1 when it enters the gastrointestinal tract are as shown in states (a) to (c) of FIG. 2. The size of the original structure of the two-layer drug structure 1 is as shown in state (a). When the two-layer drug structure 1 enters the stomach, the size of its structure becomes as shown in state (b). Since the coating polymer layer 12 contracts inward, the overall structural dimension of the two-layer drug structure 1 becomes smaller. Also, because the coating polymer layer 12 can resist erosion by gastric acid, the hydrophilic halogen microparticles 13 are embedded inside the coating polymer layer 12. When the two-layer drug structure 1 enters the environment of weak acid to neutral in the intestinal tract, the size of the structure of the two-layer drug structure 1 becomes as shown in state (c). Since the coating polymer layer 12 expands slowly, the overall structural dimension of the two-layer drug structure 1 becomes larger. Also, the intestinal fluid in the intestinal tract penetrates into the coating polymer layer 12, so that the hydrophilic halogen microparticles 13 come into contact with the intestinal fluid and gradually dissolve. When the hydrophilic halogen microparticles 13 dissolve, pores are formed in the space originally occupied by the hydrophilic halogen microparticles 13 in the coating polymer layer 12, so that the coating polymer layer 12 becomes a porous structure, and the intestinal fluid can enter the two-layer drug structure 1 and contact and react with the core 11 (containing the drug active ingredient) to dissolve the drug active ingredient. This dissolution reaction proceeds slowly inside the two-layer drug structure 1. The intestinal fluid forms an intestinal fluid-drug active ingredient complex with the drug active ingredient in the core 11, and this intestinal fluid-drug active ingredient complex is released from the pores formed in the coating polymer layer 12. As the dissolution amount of the hydrophilic halogen microparticles 13 increases, the pores formed in the coating polymer layer 12 also increase, thereby increasing the rate at which the intestinal fluid-drug active ingredient complex is released from the pores of the coating polymer layer 12. The two-layer drug structure 1 is maintained in the intestinal tract for 2 to 3 hours and then slowly decomposes and disintegrates. That is, in the process of the slow decomposition and disintegration of the two-layer drug structure 1, the intestinal fluid-drug active ingredient complex is slowly released and absorbed by the surface of the intestinal tract, thereby achieving the purpose of slow release of the drug active ingredient in the intestinal tract.

[0023] The above two-layer drug structure contracts inward in the gastric environment and expands in the intestinal environment. Through the design of the hydrophilic porogen microparticles in the coating polymer layer, it enables the sustained release of the drug active ingredient in the intestinal tract.

[0024] As described above, the present invention has been disclosed by way of preferred embodiments. However, as can be understood by those skilled in the art, the above embodiments are merely for explaining the present invention and should not be construed as limiting the scope of the present invention. It should be noted that all equivalent changes and substitutions to the above embodiments should be regarded as being included within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to that defined by the scope of claims for utility model registration.

Explanation of Reference Signs

[0025] 1 Two-layer drug structure 11 Core 12 Coating polymer layer 13 Hydrophilic porogen microparticles

Claims

[Claim 1] A spherical core containing a drug-active ingredient, A coating polymer layer having a certain thickness, covering the outer surface of the core, which contracts inward in the gastric acid environment and expands outward in the intestinal environment, Multiple hydrophilic pologen microparticles are embedded in the coating polymerization layer, and when the coating polymerization layer expands outward, they are exposed to and dissolved in the intestinal fluid, and also form channels. A two-layer drug structure containing this.

Images