阅读说明：本技术 含硝羟喹啉的药物组合物、硝羟喹啉口服固体片剂及其制备方法和用途 (Pharmaceutical composition containing nitroxoline, nitroxoline oral solid tablet, and preparation method and application thereof ) 是由 刘江华 郭玉申 申帅 朱伟 于 2020-08-05 设计创作，主要内容包括：一种用于治疗膀胱癌的含硝羟喹啉的药物组合物、硝羟喹啉口服固体片剂及其制备方法和用途。所述药物组合物包含硝羟喹啉、填充剂、崩解剂、粘合剂和润滑剂；所述润滑剂选自十二烷基硫酸钠和硬脂富马酸钠中的一种或两种。所述的药物组合物,溶出速度适中,能够避免突释现象,防潮防渗透,稳定性好,安全有效,服用方便,患者顺应性强,满足了作为口服固体片剂的要求。所述的制备方法,生产工艺稳定,重现性好,易于大生产,具有较好的临床使用价值和社会效益。(A pharmaceutical composition containing nitroxoline for treating bladder cancer, oral solid tablet containing nitroxoline, and its preparation method and application are provided. The pharmaceutical composition comprises nitroxoline, a filler, a disintegrant, a binder and a lubricant; the lubricant is selected from one or two of sodium lauryl sulfate and sodium stearyl fumarate. The pharmaceutical composition has moderate dissolution speed, can avoid burst release phenomenon, is dampproof and impermeable, has good stability, safety and effectiveness, convenient administration and strong patient compliance, and meets the requirements of being taken as an oral solid tablet. The preparation method has the advantages of stable production process, good reproducibility, easy mass production, and good clinical use value and social benefit.)

A pharmaceutical composition containing nitroxoline, wherein the pharmaceutical composition comprises nitroxoline, a filler, a disintegrant, a binder, and a lubricant; the lubricant is selected from one or two of sodium lauryl sulfate and sodium stearyl fumarate.

A nitroxoline containing pharmaceutical composition as claimed in claim 1,

the weight percentage of the nitroxoline in the pharmaceutical composition is 30-65%, preferably 40-60%;

and/or the filler is one or more of lactose, starch, pregelatinized starch, microcrystalline cellulose, dextrin, mannitol, calcium hydrogen phosphate, mannitol and sorbitol; preferably one or more of lactose, starch and microcrystalline cellulose; more preferably lactose and/or starch; more preferably lactose and starch, wherein the mass percent of the lactose in the pharmaceutical composition is 10-25%, and the mass percent of the starch in the pharmaceutical composition is 23-30%; wherein, the lactose is preferably lactose monohydrate, and the starch is preferably corn starch;

and/or the filling agent accounts for 25-65% of the pharmaceutical composition by mass, and preferably accounts for 33-55% of the pharmaceutical composition by mass;

and/or the disintegrating agent is one or more of hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch and cross-linked sodium carboxymethyl cellulose, preferably hydroxypropyl cellulose, and more preferably low-substituted hydroxypropyl cellulose;

and/or the mass percentage of the disintegrant in the pharmaceutical composition is 1% -5%, preferably 2% -4%, more preferably 2% -3%;

and/or the adhesive is one or more of starch, povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose, preferably starch and/or hydroxypropyl methylcellulose, and more preferably starch; wherein the starch is preferably corn starch, and the hydroxypropyl methylcellulose is preferably E3 hydroxypropyl methylcellulose;

and/or the mass percentage of the adhesive in the pharmaceutical composition is 1-4%, preferably 1-3%;

and/or, the lubricant is sodium lauryl sulfate;

and/or the mass percentage of the lubricant in the pharmaceutical composition is 0.5% -4%, preferably 1% -2%.

A pharmaceutical composition comprising nitroxoline according to claim 1 or 2, wherein the pharmaceutical composition comprises a coating agent selected from one or more of opadry, polyvinyl alcohol, ewt and gastric soluble film coating premix, preferably gastric soluble film coating premix;

the gastric-soluble film coating premix preferably comprises titanium dioxide, talcum powder, polyethylene glycol, hydroxypropyl methylcellulose and lake, and more preferably a mixture consisting of titanium dioxide, talcum powder, polyethylene glycol 6000, hydroxypropyl methylcellulose and lemon yellow aluminum lake;

wherein, the weight increment of the coating agent is preferably 7 to 15 percent, and more preferably 10 to 12 percent.

A nitroxoline containing pharmaceutical composition according to any of the claims 1 to 3,

the pharmaceutical composition comprises the following components in parts by mass: 30 to 65 percent of nitroxoline, 25 to 65 percent of filling agent, 1 to 5 percent of disintegrating agent, 1 to 4 percent of adhesive and 0.5 to 4 percent of lubricant;

preferably, the pharmaceutical composition comprises the following components in parts by mass: 40% -60% of nitroxoline, 33% -55% of a filler, 2% -3% of a disintegrant, preferably 2% -2.5%, 1% -3% of a binder and 1% -2% of a lubricant;

more preferably, in the pharmaceutical composition, the filler is lactose and starch, the mass percent of the lactose in the pharmaceutical composition is 10% -25%, and the mass percent of the starch in the pharmaceutical composition is 23% -30%; the disintegrating agent is hydroxypropyl cellulose, the adhesive is starch, and the lubricant is sodium dodecyl sulfate.

An oral solid tablet of nitroxoline, comprising nitroxoline as an active ingredient and a filler, a disintegrant, a binder, a lubricant; wherein the lubricant is selected from one or two of sodium lauryl sulfate and sodium stearyl fumarate.

Nitroxoline oral solid tablet according to claim 5, characterized in that the tablet comprises 30-65% preferably 45-55% nitroxoline, 25-65% preferably 30-55% filler, 1-5% preferably 2-4% disintegrant, 1-4% preferably 1.5-3% binder and 0.5-4% preferably 1-3% lubricant by mass based on the total weight of the tablet.

An oral solid tablet of nitroxoline comprising nitroxoline as an active ingredient together with fillers, disintegrants, binders, lubricants, said tablet being further coated with one or more coating agents; wherein the lubricant is selected from one or two of sodium lauryl sulfate and sodium stearyl fumarate.

Nitroxoline oral solid tablet according to claim 7, characterized in that the tablet comprises 30-65% preferably 45-55% nitroxoline, 25-65% preferably 30-55% filler, 1-5% preferably 2-4% disintegrant, 1-4% preferably 1.5-3% binder and 0.5-4% preferably 1-3% lubricant, by mass based on the total weight of the tablet; and the weight gain percentage of the coating agent is 7-15% by weight, preferably 9-12%.

Nitroxoline oral solid tablet according to any one of claims 5 to 8, wherein the filler is selected from one or more of lactose, starch, pregelatinized starch, microcrystalline cellulose, dextrin, mannitol, dibasic calcium phosphate, mannitol and sorbitol, preferably lactose and/or starch; wherein, the lactose is preferably lactose monohydrate, and the starch is preferably corn starch.

Nitroxoline oral solid tablet according to claim 9, wherein the fillers are lactose and starch, wherein lactose is present in an amount of 10-30%, preferably 15-25% and starch is present in an amount of 15-35%, preferably 20-30% by weight, based on the total weight of the tablet.

A nitroxoline oral solid tablet according to any one of claims 5 to 10, wherein the disintegrant is selected from one or more of hydroxypropylcellulose, crospovidone, sodium carboxymethyl starch and croscarmellose sodium, preferably hydroxypropylcellulose, more preferably low substituted hydroxypropylcellulose.

A nitsholoquinoline oral solid tablet according to any one of claims 5 to 11, wherein the binder is selected from one or more of starch, povidone, hypromellose, hyprolose and sodium carboxymethylcellulose, preferably starch and/or hypromellose; wherein the starch is preferably corn starch, and the hydroxypropyl methylcellulose is preferably E3 hydroxypropyl methylcellulose.

A nitroxoline oral solid tablet according to any one of claims 7 to 12, wherein the coating agent is selected from one or more of opadry, polyvinyl alcohol, ewing and gastric-soluble film coating premixes; preferably, the coating agent is a gastric-soluble film coating premix; more preferably, the coating agent is a gastric-soluble film coating premix, and the weight gain of the coating agent is 7-15%, preferably 10-12%.

A nitroxoline oral solid tablet of claim 13, wherein the gastric-soluble film coating premix comprises titanium dioxide, talc, polyethylene glycol, hypromellose, and a lake.

Nitroxoline oral solid tablet according to any one of claims 7 to 14, the tablet comprises 30-65% preferably 45-55% of nitroxoline as active ingredient, 10-30% preferably 15-25% of lactose and/or 15-35% preferably 20-30% of starch as filler, 1-5% preferably 2-4% of hydroxypropyl cellulose as disintegrant, 1-4% preferably 1.5-3% of starch or hydroxypropyl methylcellulose as binder, and 0.5 to 4%, preferably 1 to 3%, of sodium lauryl sulfate or sodium stearyl fumarate as lubricant, and the tablets are further coated with a gastric-soluble film coating premix in a weight percentage of 7-15%, preferably 9-12% by weight.

Method for the preparation of a pharmaceutical composition containing nitroxoline according to any of the claims 1 to 4, characterized in that it comprises the following steps:

s1, mixing the nitroxoline, the filler and the disintegrating agent, mixing with a solution containing a binder, performing wet granulation, drying, and finishing to obtain granules after finishing;

s2, mixing the granules with a lubricant, and tabletting to obtain the finished product;

when the pharmaceutical composition contains a coating agent, the tableting of step S2 is followed by coating.

Use of the pharmaceutical composition of any one of claims 1 to 4 or the oral solid tablet of nitroxoline of any one of claims 5 to 15 in the preparation of a medicament for the treatment of bladder cancer.