Saccharide sustained release composition and method for preparing same

Abstract

A saccharide sustained-release composition and a method for preparing the same are provided, the composition comprising a saccharide substance and a sustained-release agent, the sustained-release agent being at least two selected from hydroxypropyl methylcellulose, sodium alginate, cellulose, methylcellulose, ethylcellulose, microcrystalline cellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyethylene oxide, carboxyvinyl polymer, polyethylene oxide, polyvinyl acetate aqueous dispersion, monoglyceryl oleate, monoglyceryl stearate, carbomer homopolymer, carbomer alternating copolymer, carrageenan, shellac, guar gum, xanthan gum, alginic acid, and starch.

Description

[Technical Field]

[0001] The present invention relates to the technical field of preparing sustained release products, and in particular to a saccharide sustained release composition and a method for preparing the same. [Background technology]

[0002] Diabetic hypoglycemia is a common diabetic complication. Statistics show that 24%-64% of diabetic patients suffer from hypoglycemia of varying degrees, with nocturnal episodes occurring frequently. Furthermore, numerous clinical studies have shown that more than 50% of diabetic hypoglycemia incidents occur between 10 PM and 6 AM. Nocturnal hypoglycemia is difficult to detect and often not alleviated promptly, potentially leading to high blood glucose levels the next morning. In this case, indiscriminately increasing the dosage of hypoglycemic medications can have serious consequences. Elderly diabetic patients, especially, require special attention because their central nervous system's ability to recognize blood glucose levels is impaired, leading to hypoglycemia episodes lasting too long and increasing the risk of fatal hypoglycemia.

[0003] Currently, a common method for preventing nocturnal hypoglycemia in diabetics is to eat carbohydrates such as biscuits and sweets before bed. However, due to individual differences, i.e., differences in the ability to digest and absorb different types and amounts of carbohydrates among different patients, it is difficult to stably control nocturnal blood glucose levels in each type of patient by directly consuming these foods. Furthermore, regular foods may contain other substances that adversely affect the condition of diabetic patients, making them inappropriate for some patients. Therefore, to improve the versatility and stability of diabetic hypoglycemia prevention and management and to avoid the adverse effects of eating regular foods before bed, the development of stable, sustained-release carbohydrate-containing foods is urgently needed.

[0004] From the above, it was found that there are two technical problems in the process of developing carbohydrate-containing foods with sustained release function: One is to achieve a sustained release effect of sugar substances in the body. Sugar substances such as glucose and maltose are highly soluble in water, and when these highly soluble substances are directly administered orally, they are quickly digested and absorbed. However, because the development of diabetic hypoglycemia is a slow and continuous process, products must achieve a gradual, slow release effect of sugar substances. Many researchers have added hydrophobic polymers to solid oral dosage forms to control their release, but these hydrophobic polymers are not only difficult to biodegrade in the body but also pH-dependent. The human gastrointestinal environment experiences a gradient of pH, and many internal and external factors, such as stress level, drugs that affect acid secretion, illness, race, age, and dietary habits, can cause changes in the pH of the human gastrointestinal tract. Therefore, the pH-dependent nature of hydrophobic polymers used to regulate the sustained release of sugar substances can lead to individual differences in the sustained release effect. The second is to ensure product stability, i.e., consistency of dissolution. Sugars (e.g., maltose) are highly hygroscopic and readily absorb water even under relatively low relative humidity conditions (e.g., 40% relative humidity), which increases their particle volume and ultimately changes their dissolution characteristics. Furthermore, different sugars have different compressibility, with some sugars (e.g., maltose) having poor compressibility and being difficult to compress into sheets. Therefore, it is necessary to select appropriate coating formulations and production technologies to compensate for the inferior physical properties of sugars (e.g., glucose and maltose) (e.g., high hygroscopicity and poor compressibility) and ensure product stability. Therefore, there is an urgent need in the art for a new saccharide sustained-release composition that has an appropriate sustained-release effect, high stability, and a simple manufacturing process. Summary of the Invention

[0005] The present invention provides a saccharide sustained-release composition, the composition comprising a saccharide substance and a sustained-release agent, the sustained-release agent being at least two selected from hydroxypropyl methylcellulose, sodium alginate, cellulose, methylcellulose, ethylcellulose, microcrystalline cellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyethylene oxide, carboxyvinyl polymer, polyethylene oxide, polyvinyl acetate aqueous dispersion, monoglyceryl oleate, monoglyceryl stearate, carbomer homopolymer, carbomer alternating copolymer, carrageenan, shellac, guar gum, xanthan gum, alginic acid and starch.

[0006] In one preferred embodiment, the saccharide sustained release composition further comprises a diluent and a flow agent. In another preferred embodiment, the saccharide sustained release composition further comprises a diluent, a flow agent and a binder. In a more preferred embodiment, the saccharide substance in the saccharide sustained-release composition is selected from glucose, maltose, lactose, galactose, fructose, mannose, xylose, sucrose, fucose, arabinose, rhamnose, ribose, sorbose, lactulose, lactitol, tagatose, maltulose, palatinose, isomaltose, trehalose, sophorose, rutinose, kojibiose, nigerose, laminaribiose, gentiobiose, turanose, gentiobiulose, mannobiose, melibiulose, xylobiose, sorbitol, mannitol, erythritol, or a combination thereof. In a more preferred embodiment, the mass percentage content of the saccharide substance in the entire sustained-release composition is 45%-85%, preferably 60%-80%. In one most preferred embodiment, the sugar substance is glucose or maltose, and its mass percentage content in the entire sustained-release composition is 50%-80%, preferably 70%-80%. In a more preferred embodiment, the mass percentage content of the sustained-release agent in the entire sustained-release composition is 5%-40%, preferably 12%-24%. In one most preferred embodiment, the sustained-release agent is a combination of hydroxypropyl methylcellulose and sodium alginate, and its mass percentage content relative to the total sustained-release composition is 5%-35%, preferably 10%-30%, more preferably 15%-25%. Preferably, the viscosity of the hydroxypropyl methylcellulose is 75,000-140,000 mPa·s, preferably 90,000-120,000 mPa·s, more preferably 100,000 mPa·s; alternatively, the viscosity of the hydroxypropyl methylcellulose is 11,250-21,000 mPa·s, preferably 13,000-18,000 mPa·s, more preferably 15,000 mPa·s.

[0007] In one preferred embodiment, the saccharide sustained-release composition is in the form of granules or tablets, and preferably the granules or tablets further comprise a coating. More preferably, the coating comprises a film-forming agent, a plasticizer, and an anti-adherent. In a more preferred embodiment, the film-forming agent in the coating of the saccharide sustained-release composition is selected from hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium methylcellulose, an acrylic acid ester-based polymer, or a combination thereof. In a further preferred embodiment, the mass percentage content of the film-forming agent in the coating portion is 55%-95%, preferably 65%-85%. In one most preferred embodiment, the film-forming agent is hydroxypropyl methylcellulose, and its mass percentage content in the coating portion is 65%-95%, preferably 75%-85%. Preferably, the viscosity of the hydroxypropyl methylcellulose is 1-20 mPa·s, preferably 2-15 mPa·s, more preferably 3-10 mPa·s, and most preferably 5 mPa·s. In a more preferred embodiment, the plasticizer in the coating is selected from castor oil, coconut oil, glycerin, propylene glycol, low molecular weight propylene glycol, polysorbate, sorbitan ester, triethyl citrate, diethyl phthalate, dibutyl phthalate, tributyl citrate, or a combination thereof. In a more preferred embodiment, the mass percentage content of the plasticizer in the coating portion is 5%-20%, preferably 5%-15%. In one most preferred embodiment, the plasticizer is triethyl citrate, and its content by weight percentage relative to the coating portion is 5%-18%, preferably 5%-10%.

[0008] In a more preferred embodiment, the anti-adherent agent in the coating of the saccharide sustained-release composition is selected from magnesium stearate, magnesium silicate, stearic acid, glyceryl stearate, monoglyceryl stearate, sodium stearate, talc, colloidal silica, magnesium oxide, magnesium trisilicate, or a combination thereof. In a more preferred embodiment, the mass percentage content of the anti-blocking agent in the coating portion is 2%-20%, preferably 5%-15%. In one most preferred embodiment, the anti-tack agent is a combination of monoglyceryl stearate and magnesium stearate, and its content by weight percentage in the coating portion is 2%-15%, preferably 2%-12%. In one preferred embodiment, the coating contains, by weight of the coating, about 80.33% hydroxypropyl methylcellulose, about 8.83% triethyl citrate, about 2.81% monoglyceryl stearate, and about 8.03% magnesium stearate. Preferably, the viscosity of the hydroxypropyl methylcellulose is 5 mPa·s. In one preferred embodiment, the saccharide sustained-release composition comprises a core and a coating. Based on the total weight of the core, the core contains about 79.24% maltose, about 16.64% hydroxypropyl methylcellulose, about 1.11% sodium alginate, about 1.9% microcrystalline cellulose, and about 1.11% magnesium stearate. Preferably, the viscosity of the hydroxypropyl methylcellulose is 15,000 mPa·s. In another preferred embodiment, the saccharide sustained-release composition comprises a core and a coating. Based on the total weight of the core, the core contains approximately 71.43% glucose, approximately 24% hydroxypropyl methylcellulose, approximately 1% sodium alginate, approximately 1.71% microcrystalline cellulose, approximately 1% magnesium stearate, and approximately 0.86% hydroxypropyl methylcellulose. Preferably, the viscosity of the approximately 24% hydroxypropyl methylcellulose is 100,000 mPa·s, and the viscosity of the approximately 0.86% hydroxypropyl methylcellulose is 15 mPa·s.

[0009] In one preferred embodiment, the saccharide sustained-release composition comprises a core and a coating, and the percentage of the weight of the coating to the weight of the core is 2%-8%, preferably 3%-6%. In another preferred embodiment, the saccharide sustained-release composition comprises a core and a coating, and the weight percentage of the coating to the weight of the core is 15%-25%, preferably 18%-22%. In a more preferred embodiment, the saccharide sustained-release composition releases less than 35%, preferably 25%, more preferably 15% of its original mass within 2 hours after administration; less than 50%, preferably 40%, more preferably 35% of its original mass within 4 hours after administration; more than 50%, preferably 55%, more preferably 60% of its original mass within 8 hours after administration; and more than 80%, preferably 90% of its original mass within 24 hours after administration. In one more preferred embodiment, the dosage form of the saccharide sustained release composition is a tablet, pill or capsule, preferably a tablet. In a more preferred embodiment, the method for preparing the core of the saccharide sustained-release composition includes direct granulation, dry granulation and wet granulation; where wet granulation includes high shear granulation, low shear granulation, extrusion / spheronization granulation, melt granulation and boiling granulation. In a further preferred embodiment, the method for preparing the cores is direct granulation or high shear granulation. For different saccharides of the present invention, the present invention provides different optimal core formulations to achieve optimal sustained-release effects, i.e., the saccharide sustained-release composition preferably releases less than 35%, preferably 25%, more preferably 15% of its original mass within 2 hours after administration; preferably releases less than 50%, preferably 40%, more preferably 35% of its original mass within 4 hours after administration; preferably releases more than 50%, preferably 55%, more preferably 60% of its original mass within 8 hours after administration; and preferably releases more than 80%, preferably 90% of its original mass within 24 hours after administration. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 shows the maltose sustained-release curves of the core of the maltose sustained-release composition containing hydroxypropylmethylcellulose of different viscosities. [Figure 2] FIG. 2 shows the maltose sustained release curves of the coated and uncoated maltose sustained release compositions. [Figure 3] FIG. 3 shows the maltose sustained-release curves of the maltose sustained-release composition under different pH conditions. [Figure 4] FIG. 4 shows the maltose sustained release curves of the maltose sustained release composition over different time periods. [Figure 5] FIG. 5 shows the glucose release curves of the glucose release compositions containing different types of sustained-release agents under different pH conditions. [Figure 6]FIG. 6 shows the sugar substance release curves of sustained release compositions containing different sugar substances. [Figure 7] FIG. 7 shows the glucose release curves containing different coated glucose release compositions. [Figure 8] FIG. 8 shows the glucose release curves of the glucose release composition under different pH conditions. [Figure 9] Figure 9 shows the glucose release curves of the glucose sustained-release composition over different time periods. In Figures 1 to 9, the horizontal axis represents the time for detecting the dissolution rate, and the vertical axis represents the mass percentage content of the released drug. DETAILED DESCRIPTION OF THE INVENTION

[0011] Unless otherwise specified herein, each such component or preferred components thereof can be combined with each other to form a new technical solution. In this specification, unless otherwise specified, all the embodiments and preferred embodiments mentioned can be combined with each other to form a new technical solution. In this specification, unless otherwise specified, all technical features and preferred features mentioned can be combined with each other to form a new technical solution. In this specification, unless otherwise specified, the term "one" as used herein means "at least one." Unless otherwise stated, all tests referred to herein are performed at room temperature. In this specification, all percentages, parts, etc. are by weight unless otherwise stated. "Ranges" disclosed herein are expressed in terms of lower and upper limits. Each range may have one or more lower limits and one or more upper limits. A specified range is specified by selecting a lower limit and an upper limit. The selected lower and upper limits define the boundaries of the particular range. All such definable ranges are inclusive and combinable, i.e., any lower limit can be combined with any upper limit to form a range. As used herein, ranges defined by "about" are typically within experimental error. For example, if the experimental error is 0.1, then "about 7" refers to 7±0.1.

[0012] Specifically, the present invention provides a saccharide sustained-release composition, characterized in that the composition comprises a saccharide substance and a sustained-release agent, and the sustained-release agent comprises at least two selected from hydroxypropylmethylcellulose, sodium alginate, cellulose, methylcellulose, ethylcellulose, microcrystalline cellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyethylene oxide, carboxyvinyl polymer, polyethylene oxide, polyvinyl acetate aqueous dispersion, monoglyceryl oleate, monoglyceryl stearate, carbomer homopolymer, carbomer alternating copolymer, carrageenan, shellac, guar gum, xanthan gum, alginic acid, and starch. Here, the term "comprises" means that the pharmaceutical composition may contain any other components, and these components may be present in any amount as long as the components present in this amount are acceptable to the human body and do not substantially affect the biological activity of the active ingredient in the pharmaceutical composition of the present invention.

[0013] In one preferred embodiment, the saccharide sustained release composition further comprises a diluent and a flow agent. In another preferred embodiment, the saccharide sustained release composition further comprises a diluent, a flow agent and a binder. In a more preferred embodiment, the saccharide substance in the saccharide sustained-release composition is selected from glucose, maltose, lactose, galactose, fructose, mannose, xylose, sucrose, fucose, arabinose, rhamnose, ribose, sorbose, lactulose, lactitol, tagatose, maltulose, palatinose, isomaltose, trehalose, sophorose, rutinose, kojibiose, nigerose, laminaribiose, gentiobiose, turanose, gentiobiulose, mannobiose, melibiulose, xylobiose, sorbitol, mannitol, erythritol, or a combination thereof. In a more preferred embodiment, the mass percentage content of the saccharide substance in the entire sustained-release composition is 45%-85%, preferably 60%-80%. In one most preferred embodiment, the sugar substance is glucose or maltose, and its mass percentage content in the entire sustained-release composition is 50%-80%, preferably 70%-80%.

[0014] The term "sustained-release agent" refers to a substance that delays the release of a particular substance in a formulation (e.g., the saccharide substance in this patent) from the formulation. The sustained-release agents in the saccharide sustained-release compositions described in this application are at least two, for example, two, three, or four, selected from hydroxypropyl methylcellulose, sodium alginate, cellulose, methylcellulose, ethylcellulose, microcrystalline cellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyethylene oxide, carboxyvinyl polymer, polyethylene oxide, polyvinyl acetate aqueous dispersion, monoglyceryl oleate, monoglyceryl stearate, carbomer homopolymer, carbomer alternating copolymer, carrageenan, shellac, guar gum, xanthan gum, alginic acid, and starch.

[0015] In a more preferred embodiment, the mass percentage content of the sustained-release agent relative to the total mass of the sustained-release composition is 5%-40%, preferably 12%-24%. In a more preferred embodiment, the sustained-release agent is a combination of hydroxypropyl methylcellulose and sodium alginate, and its mass percentage content relative to the total sustained-release composition is 5%-35%, preferably 10%-30%, more preferably 15%-25%. Preferably, the viscosity of the hydroxypropyl methylcellulose is 75,000-140,000 mPa·s, preferably 90,000-120,000 mPa·s, more preferably 100,000 mPa·s; or, the viscosity of the hydroxypropyl methylcellulose is 11,250-21,000 mPa·s, preferably 13,000-18,000 mPa·s, more preferably 15,000 mPa·s. In one preferred embodiment, the diluent is selected from microcrystalline cellulose.

[0016] The term "flow agent" refers to a substance that increases the flow rate of powder in a formulation and reduces powder aggregation and clumping. The flow agents in the saccharide sustained-release compositions described in the present application include magnesium stearate, stearic acid, calcium stearate, sodium stearate, zinc stearate, glyceryl stearate, diglyceryl stearate, glyceryl tristearate, myristic acid, palmitic acid, polyethylene glycol, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polyoxyethylene 10 oleyl ether, polyoxyethylene 15 hydroxystearate, polyoxyethylene 20 hexadecyl ether, polyoxyethylene 40 stearate, potassium benzoate, sodium benzoate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, talc, colloidal silica, and tribasic calcium. The additives are selected from phosphate, calcium silicate, cellulose, magnesium silicate, magnesium oxide, silica, magnesium trisilicate, sodium lauryl sulfate, sodium stearyl fumarate, magnesium lauryl sulfate, or combinations thereof. In one preferred embodiment, the fluidizing agent in the saccharide sustained release composition is selected from magnesium stearate.

[0017] The term "binder" refers to a solid powder or viscous liquid that binds non-viscous or less viscous materials into agglomerates and particles, or for compaction. The binder in the saccharide sustained-release composition described in the present application is selected from hydroxypropyl methylcellulose, ethyl cellulose, hydroxypropyl cellulose, vinyl cellulose, hydroxyethyl methylcellulose, polyethylene glycol, hydroxyethyl cellulose, calcium carboxymethylcellulose, calcium glycolate cellulose, carmellose calcium, chitosan hydrochloride, sodium carboxymethylcellulose, magnesium aluminum silicate, methylcellulose, polyethylene oxide, sodium alginate, starch, corn starch, pregelatinized starch, pregelatinized starch, hydroxypropyl starch, dextrin, maltodextrin, glucose, sucrose, compressible sugar, zein, gelatin, guar gum, polymethacrylate, sorbitol, gum arabic, carbomer, polyvinylpyrrolidone, copovidone, povidone, keratin powder, inulin, or a combination thereof.

[0018] In one preferred embodiment, the binder in the saccharide sustained-release composition is hydroxypropyl methylcellulose, which preferably has a viscosity of 1-100 mPa·s, preferably 5-50 mPa·s, more preferably 10-30 mPa·s, and most preferably 12-20 mPa·s, e.g., 15 mPa·s. In one preferred embodiment, the saccharide sustained-release composition is in the form of granules or tablets, and preferably, the granules or tablets further comprise a coating. More preferably, the coating comprises a film-forming agent, a plasticizer, and an anti-adherent. Here, the weight percentages of the saccharide substance, sustained-release agent, diluent, fluidizer, and binder are generally calculated based on the weight of the saccharide sustained-release composition excluding the coating.

[0019] The term "film-forming agent" refers to a polymer or material that forms a continuous thin film. In the present application, the film-forming agent in the coating is selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium methylcellulose, acrylic acid ester-based polymers, or a combination thereof. In a more preferred embodiment, the mass percentage content of the film-forming agent relative to the coating portion is 55%-95%, preferably 65%-85%. In a more preferred embodiment, the film-forming agent is hydroxypropyl methylcellulose, and its mass percentage content in the coating is 65%-95%, preferably 75%-85%. Preferably, the viscosity of the hydroxypropyl methylcellulose is 1-20 mPa·s, preferably 2-15 mPa·s, more preferably 3-10 mPa·s, and most preferably 5 mPa·s.

[0020] The term "plasticizer" refers to a substance that changes the flexibility, tensile strength, or adhesiveness of the film formed in the formulation. The plasticizer in the coating of the saccharide sustained-release composition described in the present application is selected from castor oil, coconut oil, glycerin, propylene glycol, low molecular weight propylene glycol, polysorbate, sorbitan ester, triethyl citrate, diethyl phthalate, dibutyl phthalate, tributyl citrate, or a combination thereof. In a more preferred embodiment, the mass percentage content of the plasticizer in the coating portion is 5%-20%, preferably 5%-15%. In a more preferred embodiment, the plasticizer is triethyl citrate, and its content by mass percentage relative to the coating portion is 5%-18%, preferably 5%-10%.

[0021] The term "anti-adherent" refers to a substance that reduces the adhesive strength of a solid dosage form during the coating process. The anti-adherent agent in the coating described in this application is selected from magnesium stearate, magnesium silicate, stearic acid, glyceryl stearate, monoglyceryl stearate, sodium stearate, talc, colloidal silica, magnesium oxide, magnesium trisilicate, or a combination thereof. In a more preferred embodiment, the mass percentage content of the anti-blocking agent in the coating portion is 2%-20%, preferably 5%-15%. In one most preferred embodiment, the anti-tack agent is a combination of monoglyceryl stearate and magnesium stearate, and its content by weight percentage in the coating portion is 2%-15%, preferably 2%-12%.

[0022] The term "diluent" refers to an ingredient used to increase the volume or weight of a formulation. The diluent in the coating described herein is selected from microcrystalline cellulose, ethyl cellulose, powdered cellulose, cellulose acetate, silicified microcrystalline cellulose, calcium cellulose, anhydrous lactose, lactose monohydrate, glucose, polyglucose, sucrose, isomaltose, compressible sugar, fructose, trehalose, corn syrup, lactitol, xylitol, erythritol, sorbitol, starch, pregelatinized starch, corn starch, wheat starch, starch hydrolysate, dextrin, maltodextrin, calcium phosphate anhydrous, calcium carbonate, calcium sulfate, calcium lactate, calcium phosphate dihydrate, tribasic calcium phosphate, ethyl acrylate, α-whey protein, magnesium carbonate, magnesium oxide, sodium chloride, dimethyl silicone, methacrylic acid, ethyl acrylate copolymer, methyl methacrylate copolymer, amino methacrylate copolymer, methyl methacrylate copolymer dispersion, or a combination thereof.

[0023] In one preferred embodiment, the saccharide sustained-release composition comprises a core and a coating, which contains, by weight of the coating, about 80.33% hydroxypropyl methylcellulose, about 8.83% triethyl citrate, about 2.81% monoglyceryl stearate, and about 8.03% magnesium stearate, wherein the viscosity of the hydroxypropyl methylcellulose is 5 mPa·s. In one preferred embodiment, the saccharide sustained-release composition comprises a core and a coating, and the core contains, by total weight of the core, about 79.24% maltose, about 16.64% hydroxypropyl methylcellulose, about 1.11% sodium alginate, about 1.9% microcrystalline cellulose, and about 1.11% magnesium stearate, where the viscosity of the hydroxypropyl methylcellulose is 15,000 mPa·s. In another preferred embodiment, the saccharide sustained-release composition comprises a core and a coating, and the core contains, by total weight of the core, about 71.43% glucose, about 24% hydroxypropyl methylcellulose, about 1% sodium alginate, about 1.71% microcrystalline cellulose, about 1% magnesium stearate, and about 0.86% hydroxypropyl methylcellulose, wherein the viscosity of the about 24% hydroxypropyl methylcellulose is 100,000 mPa·s and the viscosity of the about 0.86% hydroxypropyl methylcellulose is 5 mPa·s. In one preferred embodiment, the saccharide sustained-release composition comprises a core and a coating, and the weight percentage of the coating to the weight of the core is 2%-8%, preferably 3%-6%. In another preferred embodiment, the saccharide sustained-release composition comprises a core and a coating. The weight percentage of the coating of the saccharide sustained-release composition relative to the weight of the core is 15%-25%, preferably 18%-22%. Generally, drug release in tablet dosage forms follows a first-order release mechanism: drug release is rapid initially, and after 60%-80% of the original drug mass is released, the release slows down. Therefore, in experiments to detect dissolution rate, multiple detection time points are set at short intervals in the early stage; after most of the drug is released, the detection time intervals are extended. In the human body, drug absorption takes up to 6-8 hours. Therefore, in this application, to investigate the drug release status in saccharide sustained-release compositions, the dissolution rate detection time points are set at 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h.

[0024] The saccharide sustained-release composition described in the present invention has the property of stable sustained release, which is in line with the temporal characteristics of nocturnal hypoglycemic attacks in diabetes, and when taken before going to bed, it can effectively control blood sugar levels and prevent nocturnal hypoglycemia. In a more preferred embodiment, the saccharide sustained-release composition releases less than 35%, preferably 25%, more preferably 15% of its original mass within 2 hours after administration; less than 50%, preferably 40%, more preferably 35% of its original mass within 4 hours after administration; more than 50%, preferably 55%, more preferably 60% of its original mass within 8 hours after administration; and more than 80%, preferably 90% of its original mass within 24 hours after administration. In one more preferred embodiment, the dosage form of the saccharide sustained release composition is a tablet, pill or capsule, preferably a tablet. In a more preferred embodiment, the method for preparing the core of the saccharide sustained-release composition includes direct granulation, dry granulation and wet granulation; where wet granulation includes high shear granulation, low shear granulation, extrusion / spheronization granulation, melt granulation and boiling granulation. In a more preferred embodiment, the core is prepared by direct granulation or high shear granulation, which not only avoids temperature and moisture, two factors that are detrimental to drug stability, but also shortens the process time and reduces the equipment and space requirements.

[0025] The present invention will be described in more detail below with reference to examples. However, it should be understood that these examples are for illustrative purposes only and do not limit the scope of the present invention. The origins of the raw materials used in the examples are shown in Table 1 below. [Table 1] [Example]

[0026] (Formulation of maltose sustained release composition) Tablets were prepared with the maltose sustained-release formulation shown in Table 2 below. The sustained-release agent plays an important role in controlling the regular sustained release of the drug. The dissolution characteristics of maltose in the sustained-release formulation (formulation shown in Table 2) were investigated using a combination of two different viscosities of hydroxypropyl methylcellulose (viscosity: 15,000 mPa·s and 100,000 mPa·s) and sodium alginate as the sustained-release agent. [Table 2]

[0027] Using the "First Method (Basket Method)" recorded in the General Provisions of 0931 Dissolution and Release Measurement Methods in the "Chinese Pharmacopoeia" (2020 Edition, Part IV), the dissolution rates of tablets made with two different formulations were measured and sampled, and the dissolution rates were measured and analyzed using peroxide glucose oxidase (PGO) technology. The specific conditions were as follows: (1) First method (basket method): Use 500 mL of dissolution medium, basket speed 50 rpm, solution temperature 37.5°C; however, the dissolution medium for the first 2 hours is HCl solution at pH 1.2, and the dissolution medium for the next 22 hours is potassium dihydrogen phosphate-sodium hydroxide buffer solution at pH 6.8. (2) Peroxidative glucose oxidase (PGO) technique: Maltose was converted to glucose by treatment with α-glucoside; PGO reagent was added to this, and the resulting mixture was incubated with a glucose standard containing PGO reagent at 37°C for 10 minutes to develop color; the absorbance of both samples was scanned at 520 nm.

[0028] The sample concentration was determined from the absorbance measured as described above, the mass percentage of maltose elution was calculated (as in Table 3), and a time curve was created (as in Figure 1). [Table 3] As can be seen from Table 3 and Figure 1, both Formulations 1 and 2 achieve a sustained sugar release effect. Compared with Formulation 2, the composition of Formulation 1 releases slowly within 8 hours and dissolves a larger total amount within 24 hours: within 2 hours, the release amount is less than 35% of its original mass; within 4 hours, the release amount is less than 50% of its original mass; within 8 hours, the release amount is more than 60% of its original mass; and within 24 hours, the release amount is more than 80% of its original mass, which is more in line with the temporal characteristics of nocturnal attacks of diabetic hypoglycemia. [Example]

[0029] (Coated tablets of maltose sustained release composition) Based on the formulation in Table 4 below, one coating layer was added to the maltose sustained-release composition tablets of Formulation 1 in Example 1. The mass percentage of the coating in the total weight of the maltose sustained-release composition tablets (excluding the coating portion) was 4%±1%. To further investigate whether an increase in coating influences the release performance of the maltose sustained-release composition, the dissolution characteristics of maltose in the sustained-release composition with and without coating were examined. [Table 4]

[0030] The dissolution rate of maltose sustained-release compositions prepared with two different coating formulations was measured using the "First Method (Basket Method)" recorded in the General Provisions of 0931 Dissolution and Release Measurement Methods of the "Chinese Pharmacopoeia" (2020 Edition, Part IV) and samples were taken. The dissolution rate was measured and analyzed using peroxide glucose oxidase (PGO) technology. The specific conditions are as described in Example 1. By the above method, the mass percentage of maltose elution was calculated (as in Table 5) and a time curve was generated (as in Figure 2). [Table 5]

[0031] As can be seen from Table 5 and Figure 2, the maltose dissolution profiles of the coated and uncoated tablets are similar, i.e., the release characteristics of maltose in the coated maltose sustained-release composition are similar to those of the uncoated case, i.e., the amount released within 2 hours is less than 35% of its original mass; the amount released within 4 hours is less than 50% of its original mass; the amount released within 8 hours is more than 60% of its original mass; and the amount released within 24 hours is more than 80% of its original mass, which is consistent with the temporal characteristics of nocturnal attacks of diabetic hypoglycemia. [Example]

[0032] (Method for preparing a maltose sustained-release composition) The proportions of the raw materials for the core are shown in Formula 1 in Example 1, and the proportions of the coating are shown in Table 4 in Example 2. The detailed preparation steps are as follows: (1) Core 1) Total mixing: The blended amounts of maltose, microcrystalline cellulose, hydroxypropyl methylcellulose (viscosity: 15,000 mPa·s) and sodium alginate were passed through a mesh; after sieving, the raw materials were mixed in a mixer for 5 minutes; finally, the blended amount of magnesium stearate was passed through a mesh and added to the mixer, followed by stirring and lubrication for 5 minutes. 2) Tableting: Using a standard concave punch (specification: 20 mm x 10 mm), tablets were pressed in a high-speed tablet press to an average tablet weight of approximately 1200 mg and a hardness between 80 and 280 N. (2) Coating section a. Preparation of coating solution: The formulated amount of hydroxypropyl methylcellulose (viscosity: 5 mPa·s) and triethyl citrate were added to the ethanol solution, and then water was slowly added and stirred uniformly; at the same time, the formulated amount of magnesium stearate and monoglyceryl stearate were added to the ethanol solution and homogenized; finally, the two were mixed to obtain the coating solution. b. Coating: The cores were placed in a coating machine and preheated at a temperature of 40±1°C; then, the coating solution was sprayed onto the preheated cores to obtain a uniform coating until a weight gain of 3%-5% was achieved; finally, the coated tablets were dried at 40±1°C for 120 minutes. [Example]

[0033] (Consideration of dissolution characteristics of maltose sustained-release composition) Three different pH gradient dissolution media were set up and maltose sustained-release compositions were sampled to simulate three different pH environments of the stomach (acidic) and intestinal (basic) tracts. The "first method (basket method)" recorded in the General Provisions of 0931 Dissolution and Release Degree Measurement Method of the "Chinese Pharmacopoeia" (2020 edition, Part IV) was used to measure and sample the dissolution of maltose sustained-release compositions under three different pH environments, and the dissolution was measured and analyzed using peroxide glucose oxidase (PGO) technology. The specific measurement conditions are as described in Example 1. However, for condition 1 shown in Table 6, the dissolution medium is as follows: the dissolution medium for the first 2 hours is an HCl solution at pH 1.2, and the dissolution medium for the next 22 hours is a buffer solution of sodium acetate trihydrate and glacial acetic acid at pH 5.5; for condition 2 shown in Table 6, the dissolution medium for the first 2 hours is an HCl solution at pH 1.2, and the dissolution medium for the next 22 hours is a buffer solution of potassium dihydrogen phosphate and sodium hydroxide at pH 6.8; and for condition 3 shown in Table 6, the dissolution medium for the first 2 hours is an HCl solution at pH 1.2, and the dissolution medium for the next 22 hours is a buffer solution of potassium dihydrogen phosphate and sodium hydroxide at pH 7.4.

[0034] Using the above method, the amount of dissolution of the maltose sustained-release composition within 24 hours was measured (shown in Table 6), and the sustained-release curve of this maltose was created (shown in Figure 3). [Table 6] As can be seen from Table 6 and Figure 3, under any gastrointestinal pH environment, the amount of maltose sustained-release composition released within 2 hours was less than 25% of its original mass; within 4 hours, it was less than 40% of its original mass; within 8 hours, it was more than 55% of its original mass; and within 24 hours, it was more than 80% of its original mass. The above results indicate that, on the one hand, this maltose sustained-release composition is not affected by changes in pH environment and can adapt to the acid-base changes of the gastrointestinal environment; and, on the other hand, the release of maltose in the maltose sustained-release composition is consistent with the onset time characteristics of nocturnal hypoglycemia in diabetic patients, and after taking it before bed, it can effectively control blood glucose levels and prevent nocturnal hypoglycemia. [Example]

[0035] (Stability test of maltose sustained-release composition) The stability of the maltose sustained-release composition prepared in Example 3 was examined by a dissolution test and a dosage increase test. First, the dissolution rate of the prepared maltose sustained-release composition was measured using "Method 1 (basket method)" recorded in General Provisions 0931 Dissolution and Release Determination Method of the Chinese Pharmacopoeia (2020 Edition, Part 4), and samples were taken. The dissolution rate was measured and analyzed using glucose peroxide oxidase (PGO) technology. The specific conditions were as described in Example 1. The inventors obtained the release status of maltose from the maltose sustained-release composition at the beginning, 2 months, 4 months, and 6 months (shown in Table 7), and generated a sustained-release curve of maltose (shown in Figure 4). [Table 7]

[0036] As can be seen from Table 7 and Figure 4, after 6 months of storage, the dissolution status of maltose was almost consistent with that at the beginning, i.e., the amount released within 2 hours of the maltose sustained-release composition was less than 25% of its original mass; the amount released within 4 hours was less than 40% of its original mass; the amount released within 8 hours was more than 50% of its original mass; and the amount released within 24 hours was more than 80% of its original mass. Furthermore, the changes in appearance of the maltose sustained-release composition with and without coating were investigated under long-term test conditions (temperature: 25°C; humidity: 60%) and accelerated test conditions (temperature: 40°C; humidity: 75%), thereby determining the stability of the maltose sustained-release composition (shown in Table 8). [Table 8] As can be seen from Table 8, under the long-term test conditions, the sustained-release compositions did not deliquesce within 14 days, regardless of whether they were coated. However, in the accelerated test, the sustained-release composition without a coating and having only a core began to deliquesce from the next day; the coated sustained-release composition began to deliquesce from the 14th day. Therefore, coating can effectively enhance the stability of maltose sustained-release compositions. [Example]

[0037] (Formulation of sustained glucose release composition) According to the method of Example 1, tablets of the glucose sustained-release composition shown in Table 9 below were prepared. [Table 9]

[0038] The "First Method (Basket Method)" recorded in the General Provisions of 0931 Dissolution and Release Measurement Methods in the "Chinese Pharmacopoeia" (2020 Edition, Part IV) was used to measure the dissolution of tablets made with two different formulations. The dissolution was measured and analyzed using peroxide glucose oxidase (PGO) technology. The specific conditions were as follows: (1) First method (basket method): 500 mL of dissolution medium was used, the basket speed was 50 rpm, and the solution temperature was 37.5°C; however, in conditions 1 and 3 shown in Table 9, the dissolution medium was water and its pH was 6.5; in conditions 2 and 4 shown in Table 9, the dissolution medium was a pH 1.2 HCl solution for the first 2 hours, and a pH 6.8 potassium dihydrogen phosphate-sodium hydroxide buffer solution for the next 22 hours. (2) Peroxidative glucose oxidase (PGO) technique: The sample treated in (1) was taken, and PGO reagent was added to it. The sample was incubated with a glucose standard containing PGO reagent at 37°C for 10 minutes to allow color development; the absorbance of both samples was scanned at 520 nm.

[0039] The sample concentration was determined from the absorbance measured as described above, the mass percentage of glucose elution was calculated (as in Table 10), and a time curve was created (as in Figure 5). [Table 10] As can be seen from Table 10 and Figure 5, the glucose tablets prepared with Formula 1 showed significant differences in glucose dissolution under different pH conditions; whereas the glucose tablets prepared with Formula 2 showed essentially the same glucose dissolution under any pH conditions, i.e., the release amount within 2 hours was less than 35% of its original mass; the release amount within 4 hours was less than 50% of its original mass; the release amount within 8 hours was more than 60% of its original mass; and the release amount within 24 hours was more than 80% of its original mass. [Example]

[0040] (Comparison of formulations of different sugar sustained release compositions) The glucose in Formulation 2 of Example 6 was replaced with maltitol to study the dissolution characteristics of the sugar substances in the two types of sustained-release compositions. The formulations of the two types of tablets are shown in Table 11 below. [Table 11]

[0041] The "first method (basket method)" recorded in General Provisions 0931 Dissolution and Release Determination Methods of the Chinese Pharmacopoeia (2020 edition, Part IV) was used to measure the dissolution of two sustained-release compositions, and the dissolution was measured and analyzed using glucose peroxide oxidase (PGO) technology; however, the specific conditions for detecting glucose are described in Example 6, and the specific experimental conditions for detecting maltitol are described in Example 1. The dissolution medium for the first 2 hours was an HCl solution with a pH of 1.2, and the dissolution medium for the next 22 hours was a potassium dihydrogen phosphate-sodium hydroxide buffer solution with a pH of 6.8.

[0042] Using the above method, the mass percentage of sugar substances dissolved was calculated (as in Table 12) and a time curve was generated (as in Figure 6). [Table 12] As can be seen from Table 12 and Figure 6, both Formulations 1 and 2 have a sustained release effect. Compared to Formulation 1, Formulation 2 releases less and slower sugars, with less than 30% released within 8 hours. After 8 hours, the sugar release rate increased significantly, but even within 24 hours, the release rate was still less than 70%. [Example]

[0043] (Coated tablets of sustained glucose release composition) Coated glucose sustained-release tablets were prepared according to the method of Example 3, except that the core composition was Formulation 1 of Example 7, and the coating composition was as shown in Table 13 below. The mass percentage of the coating in the total weight of the core was 20%±1%. [Table 13]

[0044] The dissolution rates of glucose sustained-release compositions containing coatings prepared with three different formulations were measured and analyzed using the "First Method (Basket Method)" recorded in General Provisions 0931 Dissolution and Release Determination Methods of the Chinese Pharmacopoeia (2020 Edition, Part IV) and peroxide glucose oxidase (PGO) technology under the specific conditions described in Example 6. However, for formulations 1 to 3 in Table 12, the dissolution medium for the first 2 hours was an HCl solution with a pH of 1.2, and the dissolution medium for the next 22 hours was a potassium dihydrogen phosphate-sodium hydroxide buffer solution with a pH of 6.8.

[0045] By the above method, the mass percentage of glucose elution was calculated (as in Table 14) and the time curve was generated (as in Figure 7). [Table 14] As can be seen from Table 14 and Figure 7, each formulation achieves sustained sugar release. Compared to Formulation 1, Formulation 2 releases glucose at a slower rate, with less than 15% released within 24 hours; Formulation 3 releases glucose at a slower rate within the first 2 hours, not exceeding 15% of its original mass; and then gradually increases over the next 6 hours, with less than 35% released within 4 hours and more than 55% released within 8 hours; and more than 90% released within 24 hours. [Example]

[0046] (Method for preparing a sustained glucose release composition) The proportions of the raw materials for the core portion are shown in Formulation 2 of Example 6, and the proportions of the raw materials for the coating portion are shown in Formulation 3 of Example 7. The detailed preparation steps are as follows: (1) Core a. Pretreatment: The prescribed amount of hydroxypropyl methylcellulose (viscosity: 5 mPa·s) was slowly added to swirling hot water and dispersed evenly to avoid clumping; the above dispersion was cooled, stirred for about 1 hour, cooled to room temperature, and formed a solution. b. Granulation: The blended amounts of glucose and microcrystalline cellulose were passed through a mesh; after sieving, they were placed in a rapid mixer granulator and mixed to obtain a uniform dry mix; the dry mix was granulated using hydroxypropylmethylcellulose binder and kneaded in the mixer granulator for 1 to 3 minutes; the mixture was passed through a mesh mill to obtain wet granules. c. Drying: The wet granules were placed in a fluidized bed and dried at an inlet temperature of 60°C ± 5°C so that the weight loss rate was less than 5%; the granules were passed through a mesh mill to obtain uniform granules. d. Total mixing: The formulated amount of hydroxypropyl methylcellulose (viscosity: 100,000 mPa·s) and sodium alginate were passed through a mesh; after sieving, the raw materials were mixed in a mixer for 5 minutes; the formulated amount of magnesium stearate was passed through a mesh, added to the mixer, and stirred and lubricated for 5 minutes. e. Tableting: Using a standard concave punch (specification: 20 mm x 10 mm), tablets were pressed in a high-speed tablet press to an average tablet weight of approximately 1,400 mg and a hardness between 80 and 280 N. (2) Coating section a. Preparation of coating solution: The formulated amount of hydroxypropyl methylcellulose (viscosity: 5 mPa·s) and triethyl citrate were added to the ethanol solution, and then water was slowly added and stirred uniformly; at the same time, the formulated amount of magnesium stearate and monoglyceryl stearate were added to the ethanol solution and homogenized; finally, the two were mixed to obtain the coating solution. b. Coating: The cores were placed in a coating machine and preheated at a temperature of 40±1°C; then, the coating solution was sprayed onto the preheated cores to obtain a uniform coating until a weight gain of 19-21% was achieved; finally, the coated tablets were dried at 40±1°C for 120 minutes. [Example]

[0047] (Consideration of dissolution rate of sustained glucose release composition) Different pH environments of the gastrointestinal tract were simulated to examine the degree of dissolution of the glucose sustained-release composition. The dissolution rate of the prepared sustained-release glucose composition was measured using "Method 1 (basket method)" recorded in General Provisions 0931 Dissolution and Release Rate Measurement Method of the Chinese Pharmacopoeia (2020 Edition, Part IV) and sampled. The dissolution rate was measured and analyzed using peroxide glucose oxidase (PGO) technology. The specific measurement conditions are as shown in Example 6. For Condition 1 shown in Table 15, the dissolution medium was as follows: HCl solution at pH 1.2 for the first 2 hours, and sodium acetate trihydrate and glacial acetic acid buffer solution at pH 5.5 for the next 22 hours; for Condition 2 shown in Table 15, HCl solution at pH 1.2 for the first 2 hours, and potassium dihydrogen phosphate-sodium hydroxide buffer solution at pH 6.8 for the next 22 hours; and for Condition 3 shown in Table 15, HCl solution at pH 1.2 for the first 2 hours, and potassium dihydrogen phosphate-sodium hydroxide buffer solution at pH 7.4 for the next 22 hours.

[0048] Three different pH gradient dissolution media were set up and glucose sustained-release compositions were sampled to simulate the pH environments of the three types of stomach (acidic) and intestinal (basic) tracts. The amount of glucose sustained-release composition dissolved within 8 hours was measured (as shown in Table 15), and a sustained-release curve of this glucose was created (as shown in Figure 8). [Table 15] As can be seen from Table 15 and Figure 8, under any pH condition of the gastrointestinal tract, the glucose sustained-release composition released less than 15% of its original mass within 2 hours; less than 35% of its original mass within 4 hours; more than 50% of its original mass within 8 hours; and more than 90% of its original mass within 24 hours. This indicates that the glucose sustained-release composition prepared by the inventors is not affected by changes in pH and can adapt to the acid-base changes of the gastrointestinal tract. Furthermore, the glucose release from the glucose sustained-release composition is consistent with the onset time characteristics of nocturnal hypoglycemia in diabetic patients, demonstrating that taking the composition before bed can effectively control blood glucose levels and prevent nocturnal hypoglycemia. [Example]

[0049] (Stability test of glucose sustained-release composition) The stability of the sustained glucose release composition prepared in Example 9 was examined. First, the inventors measured the dissolution rate of the prepared sustained-release glucose composition using "Method 1 (basket method)" recorded in General Provisions 0931, Dissolution and Release Measurement Methods, of the Chinese Pharmacopoeia (2020 Edition, Part IV). They then measured and analyzed the dissolution rate using glucose peroxide oxidase (PGO) technology. The specific measurement conditions were as described in Example 6. For the four time periods shown in Table 16, the dissolution medium for the first two hours was a pH 1.2 HCl solution, and the dissolution medium for the next 22 hours was a pH 6.8 potassium dihydrogen phosphate-sodium hydroxide buffer solution. The inventors obtained the glucose release profiles of the sustained-release glucose composition at the beginning, two months, four months, and six months (shown in Table 16), and plotted the glucose release curves (shown in Figure 9). [Table 16] As can be seen from Table 16 and Figure 9, after 6 months of storage, the glucose dissolution profile was almost consistent with that at the beginning, i.e., the amount released within 2 hours was no more than 15% of its original mass; the amount released within 4 hours was less than 40% of its original mass; the amount released within 8 hours was more than 55% of its original mass; and the amount released within 24 hours was more than 90% of its original mass. This suggests that the glucose sustained-release composition prepared by the inventors based on Example 9 has good stability.

[0050] While the present invention has been described with reference to specific examples, it will be apparent to those skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope of the invention. It is therefore intended by the appended claims to cover all such variations within the scope of the invention.

Claims

1. The composition comprises a saccharide substance and a sustained-release agent, wherein the sustained-release agent is at least two selected from hydroxypropyl methylcellulose, sodium alginate, cellulose, methylcellulose, ethylcellulose, microcrystalline cellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyethylene oxide, carboxyvinyl polymer, polyethylene oxide, polyvinyl acetate aqueous dispersion, monoglyceryl oleate, monoglyceryl stearate, carbomer homopolymer, carbomer alternating copolymer, carrageenan, shellac, guar gum, xanthan gum, alginic acid, and starch.

2. The saccharide sustained-release composition according to claim 1, characterized in that the saccharide sustained-release composition further comprises a diluent and a fluidizing agent; preferably, the saccharide sustained-release composition further comprises a diluent, a fluidizing agent and a binder.

3. The sugar substance is selected from glucose, maltose, lactose, galactose, fructose, mannose, xylose, sucrose, fucose, arabinose, rhamnose, ribose, sorbose, lactulose, tagatose, maltulose, palatinose, isomaltose, trehalose, sophorose, rutinose, kojibiose, nigerose, laminaribiose, gentiobiose, turanose, gentiobiulose, mannobiose, melibiulose, xylobiose, sorbitol, lactitol, mannitol, erythritol, or a combination thereof; Preferably, the mass percentage content of the saccharide substance in the entire sustained-release composition is 45%-85%, preferably 60%-80%; The sugar substance is glucose or maltose, and its mass percentage content in the entire sustained-release composition is 50%-80%, preferably 70%-80%. The saccharide sustained-release composition according to claim 1 .

4. The mass percentage content of the sustained-release agent relative to the total mass of the sustained-release composition is 5%-40%, preferably 12%-24%; More preferably, the sustained-release agent is a combination of hydroxypropylmethylcellulose and sodium alginate, and the mass percentage content of the sustained-release agent in the entire sustained-release composition is 5%-35%, preferably 10%-30%, more preferably 15%-25%; Preferably, the viscosity of the hydroxypropyl methylcellulose is 75,000-140,000 mPa-sec, preferably 90,000-120,000 mPa-sec, more preferably 100,000 mPa-sec; Preferably, the viscosity of the hydroxypropyl methylcellulose is 11,250-21,000 mPa-sec, preferably 13,000-18,000 mPa-sec, more preferably 15,000 mPa-sec. The saccharide sustained-release composition according to claim 1 .

5. The saccharide sustained-release composition is in the form of granules or tablets, and preferably, the granules or tablets further comprise a coating; more preferably, the coating comprises a film-forming agent, a plasticizer, and an anti-adhesive agent; preferably, the film-forming agent of the coating is selected from hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium methylcellulose, and acrylic ester-based polymers; Preferably, the mass percentage content of the film-forming agent relative to the coating portion is 55%-95%, preferably 65%-85%; More preferably, the film-forming agent is hydroxypropyl methylcellulose, and its mass percentage content in the coating portion is 65%-95%, preferably 75%-85%; However, the viscosity of the hydroxypropyl methylcellulose is 1-20 mPa·s, preferably 2-15 mPa·s, more preferably 3-10 mPa·s, and most preferably 5 mPa·s. The saccharide sustained-release composition according to claim 1 .

6. The plasticizer of the coating is selected from castor oil, coconut oil, glycerin, propylene glycol, low molecular weight propylene glycol, polysorbate, sorbitan ester, triethyl citrate, diethyl phthalate, dibutyl phthalate, tributyl citrate, or a combination thereof; Preferably, the mass percentage content of the plasticizer relative to the coating portion is 5%-20%, preferably 5%-15%; More preferably, the plasticizer is triethyl citrate, and its mass percentage content in the coating portion is 5%-18%, preferably 5%-10%; Preferably, the anti-blocking agent of the coating is selected from magnesium stearate, magnesium silicate, stearic acid, glyceryl stearate, monoglyceryl stearate, sodium stearate, talc, colloidal silica, magnesium oxide, magnesium trisilicate, or a combination thereof; Preferably, the mass percentage content of the anti-blocking agent relative to the coating portion is 2%-20%, preferably 5%-15%; More preferably, the anti-tack agent is a combination of monoglyceryl stearate and magnesium stearate, and its content by mass percentage relative to the coating portion is 2% to 15%, preferably 2% to 12%; Preferably, the coating of the saccharide sustained-release composition contains, by total weight of the coating, about 80.33% hydroxypropyl methylcellulose, about 8.83% triethyl citrate, about 2.81% monoglyceryl stearate, and about 8.03% magnesium stearate; provided that the viscosity of the hydroxypropyl methylcellulose is 5 mPascal-seconds; Preferably, the core of the saccharide sustained-release composition contains, by total weight of the core, about 79.24% maltose, about 16.64% hydroxypropyl methylcellulose, about 1.11% sodium alginate, about 1.9% microcrystalline cellulose, and about 1.11% magnesium stearate; and the viscosity of the hydroxypropyl methylcellulose is 15,000 mPascal-seconds. The saccharide sustained-release composition according to claim 5 .

7. The saccharide sustained-release composition according to claim 5, characterized in that the percentage of the mass of the coating portion relative to the mass of the core portion is 2%-8%, preferably 3%-6%.

8. 6. The saccharide sustained-release composition according to claim 5, wherein the core of the saccharide sustained-release composition contains, by total weight of the core, about 71.43% glucose, about 24% hydroxypropyl methylcellulose, about 1% sodium alginate, about 1.71% microcrystalline cellulose, about 1% magnesium stearate, and about 0.86% hydroxypropyl methylcellulose; wherein the viscosity of the about 24% hydroxypropyl methylcellulose is 100,000 mPa-second, and the viscosity of the about 0.86% hydroxypropyl methylcellulose is 15 mPa-second; and preferably, the percentage of the mass of the coating portion to the mass of the core is 15%-25%, preferably 18%-22%.

9. A method for preparing the saccharide sustained-release composition of claim 1, characterized in that it comprises mixing the saccharide substance and the sustained-release agent in the saccharide sustained-release composition of claim 1 by direct granulation, dry granulation or wet granulation to obtain granules.

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