CN113925838A - Compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salt thereof and preparation method thereof - Google Patents
Compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salt thereof and preparation method thereof Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K9/2004—Excipients; Inactive ingredients
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- A61K9/2022—Organic macromolecular compounds
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- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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- A61K9/2806—Coating materials
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
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- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Abstract
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof and a preparation method thereof. The compound sustained-release tablet can be a single-layer tablet or a double-layer tablet, and is used for treating type 2 diabetes, particularly peripheral neuropathy caused by type 2 diabetes. The compound composition is prepared into the sustained-release tablet, so that the time of the synergistic interaction of the two active ingredients can be exerted and prolonged, the stimulation of the medicine to the gastrointestinal tract can be reduced, the compliance of a patient is improved, the peak valley phenomenon of a common preparation in blood after the medicine is taken is avoided, the occurrence of adverse reaction is reduced, and the safety of medication is improved.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof and a preparation method thereof.
Background
Epalrestat is an aldose reductase inhibitor, and is mainly used for treating diabetes and its complications. Epalrestat has absolute therapeutic effect on neuropathy induced by diabetes, and has therapeutic effect on diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic gastroparesis, cataract, foot ulcer, diabetic macroangiopathy, diabetic microangiopathy, hyperglycemia, hyperglycosemia hemoglobin level, and other complications.
Sitagliptin is a dipeptidyl peptidase 4(DPP-4) inhibitor that increases active incretin, C-peptide levels, lowers glucagon levels, and improves glycemic control by reducing glucose production and increasing tissue uptake of blood glucose.
Research shows that diabetic peripheral neuropathy patients are accompanied with deficiency of NO synthesis and release functions, and low concentration of NO causes poor vasodilation of neurointima, so that local blood flow is reduced. The clinical use of epalrestat and sitagliptin is helpful to improve the nerve function, the oxidative stress and the NO levelAnd the clinical curative effect is improved. And the combination of the two does not increase adverse reactions, and the clinical safety is higher. Although the epalrestat belongs to BCS II medicines, the solubility of the epalrestat is related to pH, and the epalrestat tablet shows the characteristics of quick release speed and easy uneven release in intestinal tracts, the blood concentration can reach the peak value within 1 hour, and T is1/2It was 2 hours. The plasma drug concentration of the sitagliptin tablet reaches a peak value after 1 to 4 hours of taking the tablet. The compound sustained-release tablet prepared from the two active ingredients can keep the synergistic effect of the two active ingredients for a long time. And no product or related report for preparing the epalrestat and the pharmaceutical composition of the sitagliptin or the pharmaceutically acceptable salt thereof into the compound sustained release tablet exists in the market at present.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof and a preparation method thereof.
The invention provides a compound sustained-release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof, which contains epalrestat, an active component of the sitagliptin, anhydrous calcium hydrophosphate, a skeleton sustained-release material and pharmaceutic adjuvants; the tablet core of the compound sustained-release tablet is a single-layer tablet, and a sustained-release coating film is wrapped outside the tablet core;
the sitagliptin active component is sitagliptin and/or a pharmaceutically acceptable salt thereof and/or a hydrate of the salt; wherein the mass ratio of the active components of the epalrestat to the sitagliptin is 0.2: 1-5: 1; the weight ratio of the total weight of the sitagliptin active components to the anhydrous calcium hydrophosphate is 0.6-1.2: 1; the total weight mass ratio of the framework slow-release material to the single-layer tablet core is 0.1-0.5: 1.
The invention further provides a preparation method of the compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof, which comprises the following steps:
1) sieving the active components of epalrestat and sitagliptin by a 100-mesh sieve, and sieving the auxiliary materials by a 60-mesh sieve;
2) preparing granules containing active substances from the raw materials and auxiliary materials in the prescription amount by wet granulation and/or dry granulation;
3) granulating the prepared granules containing active substances, and mixing; the mesh number of the used whole grain sieve is 1.0 mm;
4) the prepared granules containing the active substance are pressed into a single-layer tablet core;
5) preparing coating liquid and coating with film to obtain the final product.
The invention provides a compound sustained release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof, wherein a tablet core of the compound sustained release tablet is a double-layer tablet, and a sustained release coating film is wrapped outside the tablet core;
the double-layer tablet consists of an epalrestat layer and a sitagliptin active component layer; wherein the epalrestat layer comprises epalrestat, a skeleton slow-release material and a first pharmaceutical excipient, and the mass ratio of the epalrestat to the skeleton slow-release material is 1: 0.15-1: 0.65;
the sitagliptin active component layer comprises a sitagliptin active component, anhydrous calcium hydrogen phosphate and a second pharmaceutical adjuvant, wherein the weight ratio of the total weight of the sitagliptin active component to the anhydrous calcium hydrogen phosphate is 0.6-1.2: 1;
in the tablet core, the mass ratio of the active components of epalrestat to sitagliptin is 0.2: 1-5: 1;
the sitagliptin active component is sitagliptin and/or a pharmaceutically acceptable salt thereof and/or a hydrate of the salt.
Further, the preparation method of the compound sustained-release tablet of epalrestat and sitagliptin or the pharmaceutically acceptable salt thereof comprises the following steps:
1) pretreating raw materials and auxiliary materials: the epalrestat and sitagliptin active component raw materials are sieved by a 100-mesh sieve, and the auxiliary materials are sieved by a 60-mesh sieve.
2) Wet granulation of epalrestat layer: weighing epalrestat raw materials with the prescription amount, uniformly mixing the raw materials with auxiliary materials except the lubricant to prepare a soft material, and carrying out ventilation drying at the temperature of 60-80 ℃ for 1-2.5h to obtain granules after an epalrestat layer is dried;
3) drying the epalrestat layer, granulating the granules by using a 1.0mm screen, adding a lubricant, and mixing to obtain epalrestat layer total mixed granules;
4) and (3) carrying out layered dry granulation on the active component of sitagliptin: weighing the sitagliptin raw material in the formula amount, uniformly mixing the sitagliptin raw material with auxiliary materials except the lubricant, granulating by using a dry method granulator, and crushing and granulating the strip-shaped object obtained by granulation at a proper speed through a 1.0mm screen mesh to obtain sitagliptin layer particles;
4) adding a lubricant into the sitagliptin layer particles for total mixing to obtain sitagliptin layer total mixed particles;
5) pressing the epalrestat layer total mixed granules and the sitagliptin layer total mixed granules into a double-layer tablet core by using a tablet press;
6) preparing coating liquid for slow-release film coating.
In a preferred embodiment of the invention, the particle size range D (0.9) of the epalrestat and sitagliptin active components is 50-300 μm.
According to the preferable scheme, the mass ratio of the epalrestat to the sitagliptin active components is 0.4: 1-3: 1.
As a preferred embodiment of the present invention, the sitagliptin active ingredient is one or more of sitagliptin, sitagliptin phosphate or a hydrate thereof.
As a preferred embodiment of the present invention, the weight ratio of the total weight of the sitagliptin active components to the anhydrous calcium hydrogen phosphate is 0.8-1.2: 1.
as a preferable scheme of the invention, the skeleton slow-release material is a cellulose derivative or an ethylene-based and propylene-based polymer, and comprises one or a mixture of more of methyl cellulose, hydroxymethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone and acrylic resin.
The slow-release coating film consists of the following components: 30-60% of film forming material, 5-10% of plasticizer, 10-30% of speed regulator or pore-forming agent and 8-18% of opacifier; the weight gain of the slow-release coating film is 5-8%.
Because epalrestat is easy to decompose under light, the compound sustained-release tablet needs a film coating to achieve the purpose of avoiding light. The coating may also control drug release. The coating material comprises several of film-forming materials, plasticizers, speed regulators, pore-forming agents and opacifiers, wherein the film-forming materials are selected from cellulose acetate, polyacrylic resin, carboxymethyl cellulose, ethyl cellulose and hydroxypropyl cellulose; the plasticizer is selected from glycerol, propylene glycol, polyethylene glycol, castor oil, triacetin, and diethyl phthalate; the speed regulator is selected from sodium chloride, potassium oxide, lactose, sucrose, hydroxypropyl methylcellulose, and sodium carboxymethylcellulose; the pore-forming agent is selected from sucrose, mannitol, starch, and polyethylene glycol; the opacifier is selected from titanium dioxide. Different coating materials can be added according to the situation.
As a preferred scheme of the invention, when the tablet core of the compound sustained-release tablet is a single-layer tablet, the pharmaceutic adjuvant comprises 20-60% of filler, 0-10% of adhesive, 0-5% of disintegrant, 0-5% of glidant and 0-5% of lubricant which are equivalent to the total weight of the tablet core;
when the tablet core of the compound sustained-release tablet is a double-layer tablet, the first pharmaceutical auxiliary material comprises 20-45% of filler, 0-6% of adhesive, 0-5% of disintegrant, 0-2% of glidant and 0-2% of lubricant which are equivalent to the weight of the epalrestat layer;
the second pharmaceutic adjuvant comprises 40-60% of filler, 0-5% of adhesive, 0-5% of disintegrant, 0-2% of glidant and 0-2% of lubricant which are equivalent to the weight of the sitagliptin active component layer;
the filler is selected from one or more of microcrystalline cellulose except anhydrous calcium hydrogen phosphate, mannitol, lactose, and starch; the adhesive is one or more selected from starch slurry, polyvidone, hydroxypropyl methylcellulose, and hydroxypropyl cellulose; the disintegrant is one or more selected from sodium carboxymethyl starch, calcium carboxymethyl cellulose, crospovidone, and croscarmellose sodium; the glidant is selected from one or more of talcum powder and colloidal silicon dioxide; the lubricant is one or more selected from magnesium stearate, sodium stearyl fumarate, and pulvis Talci.
The invention aims to provide a compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof, which is used for treating type 2 diabetes, in particular peripheral neuropathy caused by type 2 diabetes. The two active components are prepared into the compound sustained-release tablet, so that the dissolution rates of the two active components are close to each other, thereby prolonging the synergistic interaction time of the two drugs on one hand, reducing the release of epalrestat, sitagliptin or the medicinal salt thereof in the stomach, reducing the local drug concentration and reducing the stimulation of the drugs on the gastrointestinal tract; the two active ingredients are prepared into the compound sustained-release tablet, so that the compound sustained-release tablet is convenient to take and can improve the compliance of patients; compared with the common preparation, the preparation avoids the peak-valley phenomenon in blood after the common preparation is taken, reduces the occurrence of adverse reaction, improves the medication safety and improves the clinical curative effect.
Detailed Description
The invention is further illustrated below by means of preferred examples, but the invention is not limited to the following examples.
Example 1: epalrestat and sitagliptin film-controlled framework sustained-release single-layer tablet (1000 tablets)
(1) Tablet core part
75g of epalrestat, 50g of sitagliptin phosphate, 45g of anhydrous calcium hydrogen phosphate, 80g of mannitol, 60g of hydroxypropyl methyl cellulose, 6g of hydroxypropyl cellulose, 5g of croscarmellose sodium, 2g of colloidal silicon dioxide, 5g of sodium stearyl fumarate and 2g of magnesium stearate;
(2) film-controlled slow-release coating part
18g of ethyl cellulose, 5g of hydroxypropyl methyl cellulose, 2g of diethyl phthalate and 5g of titanium dioxide
The preparation method comprises the following steps:
(1) pretreating raw materials and auxiliary materials: raw materials of epalrestat, sitagliptin or medicinal salt thereof are sieved by a 100-mesh sieve, and auxiliary materials such as a filling agent and the like are sieved by a 60-mesh sieve.
(2) And (3) wet granulation: weighing raw materials, uniformly mixing with adjuvants except hydroxypropyl cellulose, glidant and lubricant, adding hydroxypropyl cellulose water solution, mixing to obtain soft mass, and air drying at 60-80 deg.C for 1-2.5 hr.
(3) Mixing the above prepared granules containing active substance with glidant, grading with 1.0mm screen, adding lubricant, and mixing.
(4) The total blended granules are compressed into single-layer tablet cores by a tablet press.
(5) Preparing coating liquid for slow-release film coating.
Example 2: epalrestat and sitagliptin film-controlled framework sustained-release single-layer tablet (1000 tablets)
(1) Tablet core part
75g of epalrestat, 50g of sitagliptin, 50g of anhydrous calcium hydrogen phosphate, 52g of microcrystalline cellulose, 35g of mannitol, 60g of carboxymethyl cellulose, 5g of hydroxypropyl methyl cellulose, 6g of croscarmellose sodium, 2g of colloidal silicon dioxide, 4g of sodium stearyl fumarate and 2g of magnesium stearate;
(2) film-controlled slow-release coating material
14g of cellulose acetate, 9g of hydroxypropyl methylcellulose, 2g of polyoxyethylene polyoxypropylene glycol and 5g of titanium dioxide.
The preparation method comprises the following steps: in keeping with the method of example 1, the core portion was granulated using the aqueous solution of hydroxypropylcellulose of example 1 as the binder, but instead using purified water as the wetting agent.
Example 3: epalrestat and sitagliptin film-controlled matrix sustained-release double-layer tablet (1000 tablets)
(1) Tablet core part
Epalrestat slow release layer: 75g of epalrestat, 42g of mannitol, 12g of lactose, 35g of hydroxypropyl methyl cellulose, 4g of carboxymethyl cellulose calcium and 2g of magnesium stearate;
an immediate release layer of sitagliptin or a pharmaceutically acceptable salt thereof: 50g of sitagliptin phosphate, 50g of anhydrous calcium hydrogen phosphate, 40g of mannitol, 3g of croscarmellose sodium, 5g of sodium stearyl fumarate and 2g of magnesium stearate;
(2) film-controlled slow-release coating part
14g of Eudragit RS, 4g of Eudragit RL, 4g of polyethylene glycol, 3g of diethyl phthalate and 5g of titanium dioxide.
The preparation method comprises the following steps:
(1) pretreating raw materials and auxiliary materials: raw materials of epalrestat, sitagliptin or medicinal salt thereof are sieved by a 100-mesh sieve, and auxiliary materials such as a filling agent and the like are sieved by a 60-mesh sieve.
(2) And (3) wet granulation: weighing appropriate amount of epalrestat raw materials and adjuvants, mixing well, adding purified water as wetting agent, mixing to make soft material, and air drying at 60-80 deg.C for 1-2.5h to obtain epalrestat layer dried granule.
(3) And (3) drying the epalrestat layer, granulating the granules by using a 1.0mm screen, adding a lubricant, and mixing to obtain the epalrestat layer total mixed granules. (4) And (3) dry granulation: weighing a proper amount of sitagliptin raw materials and auxiliary materials, uniformly mixing, granulating by using a dry granulation machine, and crushing and granulating the strip-shaped object obtained by granulation through a 1.0mm screen mesh at a proper speed to obtain sitagliptin layer granules.
(4) The active substance-containing granules prepared above were individually sized with a 1.0mm sieve, and a lubricant was added thereto and mixed.
(5) And pressing the epalrestat layer total mixed granules and the sitagliptin layer total mixed granules into a double-layer tablet core by using a tablet press.
(6) Preparing coating liquid for slow-release film coating.
Example 4: epalrestat and sitagliptin film-controlled matrix sustained-release double-layer tablet (1000 tablets)
(1) Tablet core part
Epalrestat slow release layer: 75g of epalrestat, 60g of mannitol, 20g of carboxymethyl cellulose, 19g of hydroxypropyl methyl cellulose, 4g of carboxymethyl cellulose calcium and 2g of magnesium stearate;
an immediate release layer of sitagliptin or a pharmaceutically acceptable salt thereof: 50g of sitagliptin, 60g of anhydrous calcium hydrogen phosphate, 28g of microcrystalline cellulose, 3g of crospovidone, 5g of sodium stearyl fumarate and 2g of magnesium stearate;
(2) coating material
14g of Eudragit RS, 4g of Eudragit RL, 4g of polyethylene glycol, 3g of diethyl phthalate and 5g of titanium dioxide.
The preparation method comprises the following steps: in accordance with the preparation of example 3.
According to the first method of the determination method of the dissolution rate and the release rate of 0931 in the four general rules of the 2020 edition of Chinese pharmacopoeia, the compound sustained-release tablet is placed in a dissolution cup, and a proper amount of solution is absorbed in 1h, 2h, 4h, 6h, 8h, 12h and 24h respectively and is supplemented with dissolution media with the same volume and the temperature of 37 +/-0.5 ℃. The amount of elution was measured by a predetermined method and calculated for each tablet (granule).
The in vitro dissolution test data of the compound sustained release tablets of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof of examples 1-4 are shown in tables 1-2.
TABLE 1 Epalrestat and cilastatin or its medicinal salt compound sustained release tablet in vitro dissolution test data
TABLE 2 cilastatin in vitro dissolution test data for cilastatin and cilastatin or its pharmaceutical salt compound sustained release tablets
As can be seen from the data in the table, in the compound sustained-release tablet, the dissolution curves of the epalrestat and the sitagliptin or the medicinal salt thereof are relatively close, so that the two active ingredients can play a synergistic effect in a longer time, and the problems of gastrointestinal irritation and incapability of playing the synergistic effect caused by the excessively fast dissolution of the epalrestat are avoided. The two active components of the invention are both sustained-release, which can reduce the release of the active components in the stomach, reduce the local drug concentration and reduce the stimulation of the drug to the gastrointestinal tract.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.
Claims (10)
1. A compound sustained release tablet of epalrestat and sitagliptin or its pharmaceutical salt is characterized in that the tablet contains epalrestat, active component of sitagliptin, anhydrous calcium hydrogen phosphate, skeleton sustained release material and pharmaceutical excipients; the tablet core of the compound sustained-release tablet is a single-layer tablet, and a sustained-release coating film is wrapped outside the tablet core;
the sitagliptin active component is sitagliptin and/or a pharmaceutically acceptable salt thereof and/or a hydrate of the salt; wherein the mass ratio of the active components of the epalrestat to the sitagliptin is 0.2: 1-5: 1; the weight ratio of the total weight of the sitagliptin active components to the anhydrous calcium hydrophosphate is 0.6-1.2: 1; the total weight mass ratio of the framework slow-release material to the single-layer tablet core is 0.1-0.5: 1.
2. A compound sustained release tablet of epalrestat and sitagliptin or its pharmaceutical salt is characterized in that the tablet core of the compound sustained release tablet is a double-layer tablet, and a sustained release coating film is wrapped outside the tablet core;
the double-layer tablet consists of an epalrestat layer and a sitagliptin active component layer; wherein the epalrestat layer comprises epalrestat, a skeleton slow-release material and a first pharmaceutical excipient, and the mass ratio of the epalrestat to the skeleton slow-release material is 1: 0.15-1: 0.65;
the sitagliptin active component layer comprises a sitagliptin active component, anhydrous calcium hydrogen phosphate and a second pharmaceutical adjuvant, wherein the weight ratio of the total weight of the sitagliptin active component to the anhydrous calcium hydrogen phosphate is 0.6-1.2: 1;
in the tablet core, the mass ratio of the active components of epalrestat to sitagliptin is 0.2: 1-5: 1;
the sitagliptin active component is sitagliptin and/or a pharmaceutically acceptable salt thereof and/or a hydrate of the salt.
3. The compound sustained-release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that the particle size range D (0.9) of the epalrestat and sitagliptin active ingredients is 50-300 μm.
4. The compound sustained-release tablet of epalrestat and sitagliptin or pharmaceutically acceptable salts thereof according to claim 1 or 2, characterized in that the mass ratio of the active components of epalrestat and sitagliptin is 0.4: 1-3: 1.
5. The compound sustained-release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that the sitagliptin active component is one or more of sitagliptin, sitagliptin phosphate or a hydrate thereof.
6. The compound sustained-release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that the weight ratio of the total weight of the sitagliptin active ingredients to the anhydrous calcium hydrogen phosphate is 0.8-1.2: 1.
7. the compound sustained-release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that the skeleton sustained-release material is a cellulose derivative or a vinyl and propenyl polymer, and comprises one or a mixture of more of methylcellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, carboxyethyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone and acrylic resin;
the slow-release coating film consists of the following components: 30-60% of film forming material, 5-10% of plasticizer, 10-30% of speed regulator or pore-forming agent and 8-18% of opacifier; the weight gain of the slow-release coating film is 5-8%.
8. The compound sustained-release tablet of epalrestat and sitagliptin or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that when the tablet core of the compound sustained-release tablet is a single-layer tablet, the pharmaceutic adjuvant comprises 20-60% of filler, 0-10% of adhesive, 0-5% of disintegrant, 0-5% of glidant and 0-5% of lubricant, which are equivalent to the total weight of the tablet core;
when the tablet core of the compound sustained-release tablet is a double-layer tablet, the first pharmaceutical auxiliary material comprises 20-45% of filler, 0-6% of adhesive, 0-5% of disintegrant, 0-2% of glidant and 0-2% of lubricant which are equivalent to the weight of the epalrestat layer;
the second pharmaceutic adjuvant comprises 40-60% of filler, 0-5% of adhesive, 0-5% of disintegrant, 0-2% of glidant and 0-2% of lubricant which are equivalent to the weight of the sitagliptin active component layer;
the filler is selected from one or more of microcrystalline cellulose except anhydrous calcium hydrogen phosphate, mannitol, lactose, and starch; the adhesive is one or more selected from starch slurry, polyvidone, hydroxypropyl methylcellulose, and hydroxypropyl cellulose; the disintegrant is one or more selected from sodium carboxymethyl starch, calcium carboxymethyl cellulose, crospovidone, and croscarmellose sodium; the glidant is selected from one or more of talcum powder and colloidal silicon dioxide; the lubricant is one or more selected from magnesium stearate, sodium stearyl fumarate, and pulvis Talci.
9. A method for preparing the compound sustained release tablet of epalrestat and sitagliptin or the pharmaceutically acceptable salt thereof according to claim 1, wherein a tablet core of the compound sustained release tablet is a single-layer tablet, and the preparation method comprises the following steps:
1) sieving the active components of epalrestat and sitagliptin by a 100-mesh sieve, and sieving the auxiliary materials by a 60-mesh sieve;
2) preparing granules containing active substances from the raw materials and auxiliary materials in the prescription amount by wet granulation and/or dry granulation;
3) granulating the prepared granules containing active substances, and mixing; the mesh number of the used whole grain sieve is 1.0 mm;
4) the prepared granules containing the active substance are pressed into a single-layer tablet core;
5) preparing coating liquid and coating with film to obtain the final product.
10. A method for preparing the compound sustained-release tablet of epalrestat and sitagliptin or the pharmaceutically acceptable salt thereof according to claim 2, wherein a tablet core of the compound sustained-release tablet is a double-layer tablet, and the preparation method comprises the following steps:
1) pretreating raw materials and auxiliary materials: the epalrestat and sitagliptin active component raw materials are sieved by a 100-mesh sieve, and the auxiliary materials are sieved by a 60-mesh sieve.
2) Wet granulation of epalrestat layer: weighing epalrestat raw materials with the prescription amount, uniformly mixing the raw materials with auxiliary materials except the lubricant to prepare a soft material, and carrying out ventilation drying at the temperature of 60-80 ℃ for 1-2.5h to obtain granules after an epalrestat layer is dried;
3) drying the epalrestat layer, granulating the granules by using a 1.0mm screen, adding a lubricant, and mixing to obtain epalrestat layer total mixed granules;
4) and (3) carrying out layered dry granulation on the active component of sitagliptin: weighing the sitagliptin raw material in the formula amount, uniformly mixing the sitagliptin raw material with auxiliary materials except the lubricant, granulating by using a dry method granulator, and crushing and granulating the strip-shaped object obtained by granulation at a proper speed through a 1.0mm screen mesh to obtain sitagliptin layer particles;
5) adding a lubricant into the sitagliptin layer particles for total mixing to obtain sitagliptin layer total mixed particles;
6) pressing the epalrestat layer total mixed granules and the sitagliptin layer total mixed granules into a double-layer tablet core by using a tablet press;
7) preparing coating liquid for slow-release film coating.
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