TW202300155A - Tofacitinib sustained-release preparation and preparation method thereof - Google Patents

Abstract

The invention discloses a tofacitinib sustained-release preparation and a preparation method thereof. The tofacitinib sustained-release preparation according to the present invention comprises a drug-containing tablet core and a sustained-release coating, wherein the drug-containing tablet core comprises tofacitinib bulk drug, filler, excipient, disintegrant, binder, and lubricant. The sustained-release coating comprises a coating -forming material and a pore-forming agent. The disintegrant comprises sodium carboxymethyl starch. The tofacitinib sustained-release preparation according to the present invention can reduce the food effect, achieving the sustained-release effect. Meanwhile, the treatment effect can be achieved by taking the medicine once a day, being biologically equivalent to the commercially available preparation.

Description

Tofacitinib sustained-release preparation and preparation method thereof

The invention relates to tofacitinib sustained-release preparation and a preparation method thereof.

Tofacitinib citrate is a new oral Janus kinase inhibitor developed by Pfizer, which can effectively inhibit the activity of JAK1 and JAK3 and block the signal transduction of many inflammatory cytokines. Indicated for adults with moderately to severely active rheumatoid arthritis (RA) who are insufficiently cured or intolerant of methotrexate, in combination with methotrexate or other non-biologic disease-modifying antirheumatic drugs (DMARDs) use. Its chemical name is 3-((3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1 -base)-3-oxo-propionitrile, the chemical formula is C16H20N6O, and the structural formula is as follows:

Patent CN202010347827.5 discloses an oral sustained-release formulation of tofacitinib, trade name Xeljanz XR, which is a once-daily dosage form, and its efficacy is consistent with that of the immediate-release dosage form Xeljanz. The tofacitinib sustained-release formulation has a certain problem of incomplete absorption, and the specification is adjusted to 11 mg in order to be equivalent to the 10 mg immediate-release formulation. In addition, the preparation uses osmotic pump drilling technology, the process is complicated, and toxic and harmful organic solvents are used in the preparation process, which is prone to the problem of organic solvent residues, which brings certain challenges to the industrial production process of the product.

Patent CN202010119445.7 discloses a tofacitinib citrate sustained-release tablet and a preparation method thereof, which only uses a skeleton. Patent CN201811365133.3 discloses a tofacitinib controlled-release tablet, its preparation method and its application, which only uses membrane control. These two patents respectively use matrix technology and membrane-controlled technology to prepare tofacitinib sustained-release preparations, but a single matrix or membrane-controlled technology is prone to strong food effects, which may cause sudden release in vivo and affect safety.

Patent CN202011512873.2 discloses a tofacitinib citrate sustained-release tablet with double membrane control and matrix sustained release. Patent CN201911300186.1 discloses tofacitinib citrate tablets and its preparation method. Both of these two patents use the dual slow-release technology of matrix and membrane control to achieve the stable release of drugs in vitro, but neither involves the issue of food effects.

The technical problem to be solved by the present invention is to provide a tofacitinib sustained-release preparation and a preparation method thereof in order to overcome the defect that the food effect of the tofacitinib sustained-release preparation needs to be improved in the prior art. The sustained-release preparation of the present invention has better sustained-release effect, can reduce the food effect, realizes that the therapeutic effect can be achieved by taking the medicine once a day, and is biologically equivalent to the commercially available preparation. In addition, the oral sustained-release dosage form of the present invention has a simple preparation process, low cost, and is easy to produce and scale up.

The invention provides a sustained-release preparation of tofacitinib, which comprises a drug-containing tablet core and a sustained-release coating film, wherein the drug-containing tablet core comprises a drug-containing tofacitinib bulk drug, a filler, a skeleton material, a disintegrant, an adhesive agent and lubricant; the slow-release coating film contains film-forming material and pore-forming agent; the disintegrating agent includes sodium carboxymethyl starch.

In the present invention, the disintegrant is preferably sodium carboxymethyl starch. The mass of the disintegrant is preferably 4-12% of the mass of the drug-containing tablet core, such as 4%, 8% or 12%.

In the present invention, the mass ratio of the sustained-release coating to the drug-containing tablet core may be a conventional mass ratio in the art, preferably (2-5):50, such as 3:50, 1:25 or 1 :10.

In the present invention, the tofacitinib bulk drug is tofacitinib or its pharmaceutical derivatives, such as tofacitinib (preferably tofacitinib crystal) and/or tofacitinib pharmaceutical salts. The pharmaceutical salt of tofacitinib is preferably tofacitinib citrate. The amount of the tofacitinib bulk drug is a therapeutically effective amount, generally 5%-20% of the mass of the drug-containing tablet core, such as 9%.

In the present invention, the filler can be a conventional filler in the art, preferably selected from lactose, microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, pregelatinized starch, sucrose, calcium hydrogen phosphate, starch and One or more of dextrins, preferably lactose. The amount of the filler can be selected according to the conventional amount of the filler in the art, preferably 40-70% of the mass of the drug-containing tablet core, such as 48%, 51%, 54%, 58%, 60% or 63%. %.

In the present invention, the skeleton material can be a conventional skeleton material in the field, preferably selected from hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, polyoxyethylene and carboxymethylcellulose One or more of sodium, more preferably hydroxypropyl methylcellulose. The amount of the skeleton material can be selected according to the conventional amount of the skeleton material in the art, preferably 10-30% of the mass of the drug-containing tablet core, such as 17.5%, 20%, 22.5%, 24%, 25% or 26%. %.

In the present invention, the binder can be a conventional binder in the art, preferably one or more selected from copovidone, hydroxypropyl cellulose, starch and pregelatinized starch, more preferably copolyvidone ketone. The amount of the binder can be selected according to the conventional amount of the binder in this field, preferably 1-10% of the mass of the drug-containing tablet core, for example 6%.

In the present invention, the lubricant can be a conventional lubricant in the art, preferably one or more selected from magnesium stearate, talcum powder, colloidal silicon dioxide and calcium stearate, more preferably Magnesium stearate. The amount of the lubricant can be selected according to the conventional amount of lubricants in this field, preferably 0.1-5%, such as 1%, of the mass of the drug-containing tablet core.

In the present invention, the film-forming material can be a conventional film-forming material in the art, preferably selected from ethyl cellulose aqueous dispersion, 30wt% polyvinyl acetate aqueous dispersion, polyvinyl acetate, methyl acrylate One or more of ester copolymer, polyamide and polyethylene, more preferably an aqueous dispersion of ethyl cellulose. The amount of the film-forming material can be selected from the usual amount of film-forming materials in the field, preferably 40-60% of the mass of the sustained-release coating film, such as 45%, 50% or 53%.

In the present invention, the porogen can be a conventional porogen in the field, preferably a polymer and/or a water-soluble excipient. The polymer is preferably selected from hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, povidone, crospovidone, copovidone, polyethylene glycol-polyethylene One or more of alcohol, polyvinyl alcohol, low-substituted hydroxypropyl cellulose, starch and pregelatinized starch, more preferably hydroxypropyl methylcellulose. The water-soluble excipient is preferably selected from one or more of mannitol, lactose, sorbitol, xylitol and maltitol, more preferably lactose. The amount of the porogen used can be selected according to the usual amount of porogen used in the art. The dosage of the polymer is preferably 20-50% of the mass of the sustained-release film, such as 30%, 35% or 45%. The amount of the water-soluble excipient is preferably less than or equal to 10% of the mass of the sustained-release coating, such as 3%, 5% or 8%.

In the present invention, the sustained-release coating film may also include other conventional excipients in the art except film-forming materials and porogens, preferably lubricants, plasticizers, colorants and surfactants one or more of.

Wherein, the lubricant can be a conventional lubricant in the art, preferably one or more selected from talcum powder, magnesium stearate, calcium stearate, micronized silica gel, kaolin, silicon dioxide and stearic acid, More preferably talcum powder. The amount of the lubricant can be selected according to the conventional amount of the lubricant in this field, preferably 1-10% of the mass of the slow-release coating, more preferably 6%.

Wherein, the plasticizer can be a conventional plasticizer in the art, preferably glycerin, propylene glycol, polyethylene glycol, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, One or more of dibutyl sebacate, triethyl citrate and tributyl citrate, more preferably triethyl citrate. The amount of the plasticizer can be selected according to the conventional amount of the plasticizer in this field, preferably 1-10% of the mass of the slow-release coating, more preferably 6%.

Wherein, the colorant can be a conventional colorant in the art.

Wherein, the surfactant can be a conventional surfactant in the art.

The present invention also provides the preparation method of the tofacitinib sustained-release preparation as described above, which includes the following steps: performing tabletting and coating according to each component of the tofacitinib sustained-release preparation.

Wherein, the tableting is carried out according to the conventional tableting operation in this field, specifically: pre-preparing the ingredients (such as including tofacitinib bulk drug, filler, skeleton material, disintegrant and binder) except the lubricant. Mix, then add a lubricant for total mixing, and then compress into tablets to obtain the drug-containing tablet core. The premixing time is preferably 10-20 minutes, more preferably 15 minutes. The mixing time is preferably 4-6 minutes, more preferably 5 minutes. The tablet core hardness is preferably controlled at 8-12kg.

Wherein, the coating is carried out according to conventional coating operations in the art, specifically: coating the drug-containing tablet core with a coating solution comprising water, film-forming material and pore-forming agent. The water is preferably pure water. The consumption of described water is the consumption of conventional water in this field.

On the basis of not violating common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain preferred examples of the present invention. The reagents and raw materials used in the present invention are all commercially available.

The positive and progressive effect of the present invention is that the tofacitinib sustained-release preparation of the present invention can reduce the food effect and achieve the sustained-release effect, and at the same time achieve the therapeutic effect by taking the medicine once a day, which is bioequivalent to the commercially available preparations.

The present invention is further illustrated below by means of examples, but the present invention is not limited thereto within the scope of the examples. For the experimental methods that do not specify specific conditions in the following examples, select according to conventional methods and conditions, or according to the product instructions.

The percentages in the examples are percentages by mass.

Example 1-6

The present invention prepares the tablet core with the following composition by direct compression, and the weight of a single drug-containing tablet wafer is 200 mg.

Table 1 Composition of drug-containing tablet cores in Examples 1-3 (mg/tablet) Element Example 1 Example 2 Example 3 massmg Chip ratio massmg Chip ratio massmg Chip ratio Tofacitinib citrate 17.78 9% 17.78 9% 17.78 9% lactose 108.22 54% 102.22 51% 96.22 58% Hydroxypropylmethylcellulose 52.00 26% 50.00 25% 48.00 twenty four% Sodium carboxymethyl starch 8.00 4% 16.00 8% 24.00 12% Copovidone 12.00 6% 12.00 6% 12.00 6% Magnesium stearate 2.00 1% 2.00 1% 2.00 1%

Table 2 Composition of drug-containing tablet cores in Examples 4-6 (mg/tablet) Element Example 4 Example 5 Example 6 massmg Chip ratio massmg Chip ratio massmg Chip ratio Tofacitinib citrate 17.78 9% 17.78 9% 17.78 9% lactose 115.22 58% 120.22 60% 125.22 63% Hydroxypropylmethylcellulose 45.00 22.5% 40.00 20% 35.00 17.5% Sodium carboxymethyl starch 8.00 4% 8.00 4% 8.00 4% Copovidone 12.00 6% 12.00 6% 12.00 6% Magnesium stearate 2.00 1% 2.00 1% 2.00 1%

The coating liquid composition of table 3 embodiment 1-6 Element Mass percentage (%) Aqueous dispersion of ethyl cellulose (the main component is ethyl cellulose) 53* Hydroxypropylmethylcellulose 30 lactose 5 talcum powder 6 triethyl citrate 6 The mass ratio of purified water:sustained release film is 32:10

* is the solid content in the ethylcellulose aqueous dispersion. Ethyl cellulose aqueous dispersion is a commercially available auxiliary material, the manufacturer is Colorcon, and the trade name is Surelease.

Preparation Process:

(1) Pretreatment: pass the raw material medicine and each auxiliary material through a 30-mesh sieve;

(2) Premixing: Weigh other ingredients except magnesium stearate and mix for 15 minutes;

(3) Total blending: adding magnesium stearate and mixing for 5 minutes;

(4) Tablet compression: compress the mixed materials to control the hardness at 8-12kg;

(5) Coating: The slow-release film ingredients were formulated into a coating solution, and the coating was performed with a weight gain of 6%.

Example 7-9

The present invention prepares the tablet core with the following composition by direct compression, and the weight of a single drug-containing tablet wafer is 200 mg.

Table 4 Composition of drug-containing tablet cores in Examples 7-9 (mg/tablet) Element Example 7-9 massmg Chip ratio Tofacitinib citrate 17.78 9% lactose 110.22 55% Hydroxypropylmethylcellulose 50.00 25% Sodium carboxymethyl starch 8.00 4% Copovidone 12.00 6% Magnesium stearate 2.00 1%

The composition of the coating solution of Table 5 Example 7-9 (mass percentage (%)) Element Example 7 Example 8 Example 9 Aqueous dispersion of ethyl cellulose (the main component is ethyl cellulose) 50* 53* 45* Hydroxypropylmethylcellulose 30 35 40 lactose 8 0 3 talcum powder 6 6 6 triethyl citrate 6 6 6

* is the solid content in the ethylcellulose aqueous dispersion.

In Examples 7, 8 and 9, the mass ratios of purified water:sustained release film were 32:10, 31:10 and 3:1, respectively.

Preparation Process:

(1) Pretreatment: pass the raw material medicine and each auxiliary material through a 30-mesh sieve;

(2) Premixing: Weigh other ingredients except magnesium stearate and mix for 15 minutes;

(3) Total blending: adding magnesium stearate and mixing for 5 minutes;

(4) Tablet compression: compress the mixed materials to control the hardness at 8-12kg;

(5) Coating: The slow-release film ingredients were formulated into a coating solution, and the coating was performed with a weight gain of 6%.

Release assay:

According to the "Chinese Pharmacopoeia" 2020 edition four general rules 0931 dissolution and release test method (the second method, 75rpm, dissolution medium 900 ml), the release characteristics of the tablet were determined within a time interval of 10h, and the pH6. 8 Release in phosphate buffered saline (in %).

Table 6 The relationship between release (%) and time (h) of Examples 1-9 time (h) 1 2.5 4 10 Example 1 8 27 50 96 Example 2 12 34 60 97 Example 3 15 40 68 99 Example 4 10 31 59 98 Example 5 12 34 63 97 Example 6 12 39 70 98 Example 7 12 36 58 97 Example 8 10 33 57 96 Example 9 13 40 64 99

According to the release curves of Examples 1-9 in Table 6, it can be shown that the sustained-release preparation of tofacitinib in the present invention can effectively control drug release and achieve a sustained-release effect.

Example 10-12

The present invention prepares the tablet core with the following composition by direct compression, and the weight of a single drug-containing tablet wafer is 200 mg.

Table 7 Composition of drug-containing tablet cores in Examples 10-12 (mg/tablet) Element Examples 10-12 massmg Chip ratio Tofacitinib citrate 17.78 9% lactose 110.22 55% Hydroxypropylmethylcellulose 50.00 25% Sodium carboxymethyl starch 8.00 4% Copovidone 12.00 6% Magnesium stearate 2.00 1%

The coating liquid composition of table 8 embodiment 10-12 Element Mass percentage (%) Aqueous dispersion of ethyl cellulose (the main component is ethyl cellulose) 53* Hydroxypropylmethylcellulose 30 lactose 5 talcum powder 6 triethyl citrate 6 The mass ratio of purified water:sustained release film is 32:10

* is the solid content in the ethylcellulose aqueous dispersion.

Preparation Process:

(1) Pretreatment: pass the raw material medicine and each auxiliary material through a 30-mesh sieve;

(2) Premixing: Weigh other ingredients except magnesium stearate and mix for 15 minutes;

(3) Total blending: adding magnesium stearate and mixing for 5 minutes;

(4) Tablet compression: compress the mixed materials to control the hardness at 8-12kg;

(5) Coating: The slow-release film ingredients were formulated into a coating liquid, and the weight gain of coating was 4% (Example 10), 8% (Example 11), and 10% (Example 12).

Release assay:

According to the "Chinese Pharmacopoeia" 2020 edition four general rules 0931 dissolution and release test method (the second method, 75rpm, dissolution medium 900 ml), the release characteristics of the tablet were determined within a time interval of 10h, and the pH6. 8 Release in phosphate buffered saline (in %).

Table 9 The relationship between the release (%) and time (h) of Examples 10-12 time (h) 1 2.5 4 10 Example 10 10 29 51 98 Example 11 8 twenty four 48 98 Example 12 7 twenty one 45 97

According to the release curves of Examples 10-12 in Table 9 and Example 2 in Table 6, it can be shown that the sustained-release coating film weight gain is between 4%-10%, and the tofacitinib sustained-release preparation in the present invention releases in vitro There is no significant difference, that is, the present invention is easy to produce and scale up, has good reproducibility and is controllable in release.

comparative example 1

The present invention prepares the drug-containing tablet core of the following composition through direct compression, and the weight of a single drug-containing tablet wafer is 200 mg.

Table 10 Composition of drug-containing tablet core in Comparative Example 1 (mg/tablet) Element Comparative example 1 massmg Chip ratio Tofacitinib citrate 17.78 9% lactose 108.22 54% Hydroxypropylmethylcellulose 52.00 26% Crospovidone 8.00 4% Sodium carboxymethyl starch 0 0 Copovidone 12.00 6% Magnesium stearate 2.00 1%

Table 11 The composition of the coating solution of Comparative Example 1 (mass percentage (%)) Element Mass percentage (%) Aqueous dispersion of ethyl cellulose (the main component is ethyl cellulose) 53* Hydroxypropylmethylcellulose 30 lactose 5 talcum powder 6 triethyl citrate 6 The mass ratio of purified water:sustained release film is 32:10

* is the solid content in the ethylcellulose aqueous dispersion.

Preparation Process:

(1) Pretreatment: pass the raw material medicine and each auxiliary material through a 30-mesh sieve;

(2) Premixing: Weigh other ingredients except magnesium stearate and mix for 15 minutes;

(3) Total blending: adding magnesium stearate and mixing for 5 minutes;

(4) Tablet compression: compress the mixed materials to control the hardness at 8-12kg;

(5) Coating: The slow-release film ingredients were formulated into a coating solution, and the coating was performed with a weight gain of 6%.

Release assay:

According to the "Chinese Pharmacopoeia" 2020 edition four general rules 0931 dissolution and release test method (the second method, 75rpm, dissolution medium 900 ml), the release characteristics of the tablet were determined within a time interval of 10h, and the pH6. 8 Release in phosphate buffered saline (in %).

Table 12 The relationship between the release (%) and time (h) of Comparative Example 1 time (h) 1 2.5 4 10 Release of Comparative Example 1 (%) 9 26 53 98

Combining the release curves of Comparative Example 1 in Table 12 and Example 1 in Table 6, it can be seen that there is no significant difference between Comparative Example 1 and Example 1 in the in vitro release process.

Example 13 Pharmacokinetic experiment in Beagle dogs

Take healthy adult Beagle dogs, and divide them into 3 groups randomly (Example Group, Comparative Example Group 1, administering one tablet at a time), and crossover experiment. The administration of a single administration example group is Example 1, and the administration of Comparative Example Group 1 is Comparative Example 1. The in vivo pharmacokinetic experiments were studied on an empty stomach and after eating respectively. Fasting for 12 hours before the experiment, the eating group was given lipid (semi-fat and lean minced pork), 150 g each, and then administered; the fasting group was given 100 ml of water, Dosing followed. 8 hours after administration, arrange to eat at the same time. The dogs in each group collected 3 ml of blood via the great saphenous vein at the scheduled time, anticoagulated with heparin, and centrifuged at low temperature to collect plasma samples for testing. Take the example group as the test preparation T ₁ , and the comparative example group 1 as the test preparation T ₂ .

Table 13 In vivo pharmacokinetic data of two groups of preparations Example 1 (T1) Comparative example 1 (T2) fasting to eat eating/fasting fasting to eat eating/fasting AUC (ng/ml*h) 373.0 390.8 1.05 359.0 395.5 1.10 C _max (ng/ml) 62.5 70.2 1.12 59.3 81.5 1.37

According to the pharmacokinetic experiment result in the beagle dog body in table 13, it can be seen that:

In the example group (T ₁ ), there was no significant difference in Cmax and AUC between the fasted and fed states, and the Cmax and AUC in the fed state were 1.12 and 1.05 times of those in the fasted state, respectively.

In the control group 1 (T ₂ ), there was no significant difference in AUC between the fasting state and the fed state. The AUC in the fed state was 1.10 times that of the fasted state, but the Cmax in the fed state was significantly higher than that in the fasted state. 1.37 times.

Table 14 and Fig. 1-2 show the drug content test results in the blood at various time periods under the fasting and fed states of T1 and T2.

Table 14 In vivo release data of two groups of preparations time (h) Fasting (ng/ml) Food intake (ng/ml) T1 T2 T1 T2 0 0.9 0.6 0.1 0.4 0.5 14.5 9.7 0.3 4.8 1 29.2 25.1 0.8 15.2 1.5 35.8 40.2 5.2 43.1 2 43.4 51.8 13.4 61.7 2.5 51.7 59.3 23.1 74.6 3 55.9 52.1 30.8 81.5 3.5 62.5 46.9 41.4 64.9 4 55.4 41.8 62.6 59.2 4.5 49.8 36.3 70.2 50.3 5 41.7 31.8 61.2 41.7 6 34.2 27.9 51.6 30.6 7 28.6 19.6 40.5 24.7 8 16.7 14.7 25.4 19.5 10 10.2 11.3 15.4 11.1 12 4.1 7.2 7.8 3.9 twenty four 0.9 1.8 0.9 0.4

It can be seen from Table 13-14, Figure 1 and Figure 2 that when the disintegrant is sodium carboxymethyl starch and its content is 4% (T1), its food effect is obviously controlled. The T1 release preparation is sufficient to resist the extrusion of the gastrointestinal tract and food in the body, can reduce the food effect, and at the same time can achieve the therapeutic effect by taking the medicine once a day.

Show by above-mentioned result, embodiment group shows less food effect under the state of taking food, and safety is high in vivo; Burst release in vivo, food effect is obvious.

none

Figure 1 is the pharmacokinetic curves of the two formulations in Example 13 after fasting administration. Figure 2 is the pharmacokinetic curves of the two formulations administered after eating in Example 13.

Claims (10)

A tofacitinib sustained-release preparation, characterized in that it includes a drug-containing tablet core and a sustained-release coating, wherein the drug-containing tablet core comprises a tofacitinib bulk drug, a filler, a skeleton material, a disintegrating agent, and a binder and a lubricant; the slow-release coating film contains film-forming material and a pore-forming agent; the disintegrating agent includes sodium carboxymethyl starch. Tofacitinib sustained-release preparation as described in Claim 1, is characterized in that the disintegrant is sodium carboxymethyl starch. Tofacitinib sustained-release preparation as described in Claim 1 or 2, is characterized in that the content of the disintegrant is 4-12% of the mass of the drug-containing tablet core, such as 4%, 8% or 12%. The tofacitinib sustained-release preparation as described in Claim 1, is characterized in that the mass ratio of the sustained-release coating to the drug-containing tablet core is (2-5):50, such as 3:50, 1:25 or 1 :10. Tofacitinib sustained-release preparation as described in claim item 1, is characterized in that, the tofacitinib crude drug is tofacitinib and/or tofacitinib medicinal salt; the tofacitinib is preferably tofacitinib Cloth crystals, the pharmaceutical salt of tofacitinib is preferably tofacitinib citrate; and/or, the dosage of the tofacitinib raw material is 5%-20% of the mass of the drug-containing tablet core, such as 9%. Tofacitinib sustained-release preparation as described in claim 1, characterized in that the tofacitinib sustained-release preparation meets one or more of the following conditions: The filler is selected from one or more of lactose, microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, pregelatinized starch, sucrose, calcium hydrogen phosphate, starch and dextrin, more preferably lactose; The dosage of the filler is 40-70% of the mass of the drug-containing tablet core, such as 48%, 51%, 54%, 58%, 60% or 63%; The skeleton material is selected from one or more of hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, polyoxyethylene and sodium carboxymethylcellulose, more preferably hydroxypropylmethylcellulose cellulose; The amount of the skeleton material is 10-30% of the mass of the drug-containing tablet core, such as 17.5%, 20%, 22.5%, 24%, 25% or 26%; The binder is selected from one or more of copovidone, hydroxypropyl cellulose, starch and pregelatinized starch, preferably copovidone; The amount of the binder is generally 1-10% of the mass of the drug-containing tablet core, such as 6%; The lubricant is selected from one or more of magnesium stearate, talcum powder, colloidal silicon dioxide and calcium stearate, more preferably magnesium stearate; The dosage of the lubricant is 0.1-5%, for example 1%, of the mass of the drug-containing tablet core. Tofacitinib sustained-release preparation as described in claim 1, characterized in that the tofacitinib sustained-release preparation meets one or more of the following conditions: The film-forming material is selected from one or more of ethyl cellulose aqueous dispersion, 30wt% polyvinyl acetate aqueous dispersion, polyvinyl acetate, methyl acrylate copolymer, polyamide and polyethylene, more preferably Ground is ethyl cellulose aqueous dispersion; The amount of the film-forming material is 40-60% of the quality of the sustained-release film, such as 45%, 50% or 53%; The porogen is a polymer and/or a water-soluble excipient; the polymer is preferably selected from hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, povidone, cross-linked One or more of povidone, copovidone, polyethylene glycol-polyvinyl alcohol, polyvinyl alcohol, low-substituted hydroxypropyl cellulose, starch and pregelatinized starch is more preferably hydroxypropyl methylcellulose element; the water-soluble excipient is preferably selected from one or more of mannitol, lactose, sorbitol, xylitol and maltitol, more preferably lactose; The sustained-release coating also includes one or more of a lubricant, a plasticizer, a colorant and a surfactant; the lubricant is preferably selected from talcum powder, magnesium stearate, calcium stearate, micropowdered silica gel, One or more of kaolin, silicon dioxide and stearic acid, more preferably talcum powder; the plasticizer is preferably glycerin, propylene glycol, polyethylene glycol, dimethyl phthalate, diphthalate One or more of ethyl ester, dibutyl phthalate, dibutyl sebacate, triethyl citrate and tributyl citrate, more preferably triethyl citrate. Tofacitinib sustained-release preparation as described in claim item 7, characterized in that the tofacitinib sustained-release preparation meets one or more of the following conditions: The polymer is used in an amount of 20-50% of the slow-release film quality, such as 30%, 35% or 45%; The amount of the water-soluble excipient is less than or equal to 10% of the mass of the slow-release coating film, such as 3%, 5% or 8%; The consumption of this lubricant is 1-10% of this sustained-release film quality, is more preferably 6%; The dosage of the plasticizer is 1-10% of the mass of the slow-release coating film, more preferably 6%. The preparation method of tofacitinib sustained-release preparation as described in any one of claim items 1-8, is characterized in that, it comprises the following steps: according to each component of this tofacitinib sustained-release preparation, carry out tabletting, coating , you can. The preparation method of tofacitinib sustained-release preparation as described in claim item 9, is characterized in that, the operation of the tabletting is specifically: premixing the ingredients except the lubricant, then adding the lubricant for total mixing, and then tableting Obtain the drug-containing tablet core; the premixed time is preferably 10-20min, more preferably 15min; the total mixing time is preferably 4-6min, more preferably 5min; the compressed tablet is preferably Control the hardness of the tablet core at 8-12kg; and/or, the coating operation is specifically: coating the drug-containing tablet core with a coating solution comprising water, film-forming material and pore-forming agent; the water is preferably The ground is pure water.

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