Colchicine film

Abstract

Disclosed in the present application is a colchicine film, which comprises, in percentage by mass, 0.6-6% of an active ingredient part, with the balance being an excipient part. The active ingredient part comprises colchicine. The excipient part comprises 45-90% of a first high-molecular polymer, 0-45% of a second high-molecular polymer, and 1-10% of a plasticizer, the first high-molecular polymer comprising polyoxyethylene having a molecular weight of 0.1-0.5 million. Compared with the prior art, the present application has the effects of facilitating the use and reducing intestinal irritation, and / or, the colchicine film obtained in the present application also has the beneficial effects of good flexibility, and / or good film-forming performance, and / or excellent peelability, thereby facilitating patients to rapidly and accurately peel off and take out required doses of the film during use, and achieving the effects of accurately controlling the drug doses and rapidly exerting the effects.

Description

A colchicine film agent

[0001] Cross-references to related applications

[0002] This application claims priority to Chinese Patent Application No. 202410799980.X, filed on June 20, 2024, entitled “A Colchicine Film Agent”, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This application relates to the technical field of orally dissolving films, and more specifically, to a colchicine film agent. Background Technology

[0004] Oral thin film (OTF) is a novel oral drug delivery system, also known as oral dissolving film, oral dispersible film, oral fast-dissolving film, oral fast-dissolving film, and tongue film, etc. It is a film-like preparation made by processing raw drug and suitable film-forming materials.

[0005] When used, the orally dissolving film is placed on the tongue. The film is moistened by saliva and dissolves rapidly, releasing the medication, which can be absorbed through the mucous membrane or gastrointestinal tract. As a novel oral dosage form, orally dissolving films have the following advantages compared to existing tablets, capsules, or oral solutions: ① The orally dissolving film dissolves rapidly in the oral cavity, allowing the medication to quickly enter the bloodstream through the oral mucosa, resulting in rapid onset of action; ② The release rate of the drug can be controlled, ensuring stable drug release; ③ The dosage of the drug in the orally dissolving film can be precisely controlled, reducing drug waste and improving therapeutic efficacy; ④ It does not require water to take, and its small size and light weight make it convenient for patients to use in any situation. Therefore, orally dissolving films have the advantages of rapid absorption, efficient release, accurate dosage, and ease of use.

[0006] Currently, the oral dissolving film formulations approved for marketing in my country include memantine hydrochloride oral dissolving film, aripiprazole oral dissolving film, ondansetron oral dissolving film, tadalafil oral dissolving film, montelukast sodium oral dissolving film, and olanzapine oral dissolving film. Therefore, the variety of oral dissolving film formulations researched in my country is relatively limited. Furthermore, the research on oral dissolving film formulations is not yet fully developed, and different products exhibit varying film-forming properties and tear-off characteristics.

[0007] Gout is a disease caused by excessive uric acid deposition. During an acute gout attack, early anti-inflammatory and analgesic treatment is recommended (generally within 24 hours). Colchicine is effective in reducing inflammation and pain, improving patients' quality of life. However, excessive use of colchicine can cause toxic side effects. Common adverse reactions include nausea, vomiting, diarrhea, abdominal pain, and gastrointestinal reactions; in severe cases, it can prevent patients from adhering to medication regimens. Currently, colchicine is generally available in tablet or oral liquid form, which is highly irritating to the intestines. There is little record of colchicine film formulation preparation.

[0008] Given the significant differences in the required dosage of colchicine for treating familial Mediterranean fever (FMF) and gout, and the relatively low dosage required for FMF treatment, current tablet formulations are limited by the difficulty in accurately dispensing whole tablets, making it difficult to meet the needs of low-dose individualized treatment. Furthermore, colchicine, as a highly active drug, has an extremely narrow therapeutic window, with the therapeutic dose being very close to the toxic dose, requiring extremely high accuracy in dosage dispensing. Traditional oral tablets have significant shortcomings in dosage adjustment, easily leading to dosage errors and increasing medication risks. Therefore, developing a colchicine oral instant-dissolving film with rapid dissolution characteristics and good dispensing operability has significant clinical application prospects and is urgently needed. However, there are no reports in this field regarding the film-forming properties, flexibility, and tearability of colchicine films. Summary of the Invention

[0009] This application aims to overcome at least one of the defects of the prior art and provide a colchicine film that is easy to take, has a rapid onset of action, and is less irritating to the intestines; and / or the colchicine film provided by this application can achieve good flexibility, and / or film-forming properties and / or easy tearing, meeting the needs for good dispensing operability and precise drug delivery.

[0010] Based on this, the technical solution adopted in this application is:

[0011] On the one hand, this application provides a colchicine film-forming agent, which, by mass percentage, comprises 0.6-6% of the active ingredient portion, with the remainder being the excipient portion;

[0012] The active ingredient includes colchicine;

[0013] The auxiliary materials include 45-90% of a first polymer, 0-45% of a second polymer, and 1-10% of a plasticizer;

[0014] The first polymer comprises polyethylene oxide with a molecular weight of 100,000 to 500,000.

[0015] Furthermore, the first polymer is a combination of polyethylene oxide with a molecular weight of 100,000 and polyethylene oxide with a molecular weight of 200,000 to 500,000.

[0016] Further, the polyoxyethylene with a molecular weight of 100,000 includes PEO N-10; the polyoxyethylene with a molecular weight of 200,000 to 500,000 includes one or more of PEO N-80, PEO N-750 and PEO N-301.

[0017] Furthermore, the ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is 1:1 to 9 or 1 to 9:1.

[0018] In some embodiments, the first polymer is PEO N-10 and PEO N-80.

[0019] Furthermore, in some embodiments, the ratio of PEO N-10 to PEO N-80 is 1:1.

[0020] In some embodiments, the product comprises 40–50% PEO N-10 and 40–50% PEO N-80 by weight percentage.

[0021] Furthermore, the plasticizer includes one or two of glycerol and propylene glycol; the second polymer includes one or more of polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol and polyvinylpyrrolidone with a molecular weight of 200 to 6000.

[0022] Further, by mass percentage, the second polymer comprises 1 to 15% polyvinylpyrrolidone.

[0023] Furthermore, the second polymer comprises 0.5 to 10% hydroxypropyl methylcellulose by mass percentage.

[0024] Further, by mass percentage, the second polymer comprises polyvinylpyrrolidone and 0.5–10% hydroxypropyl methylcellulose.

[0025] Furthermore, the ratio of the plasticizer to polyvinylpyrrolidone is 1:0.25 to 4.

[0026] Furthermore, the excipient portion also includes 0.1% to 5% surfactant by weight percentage.

[0027] Furthermore, the excipients also include one or more of the following: buffers, sweeteners, flavorings, colorings, antibacterial agents, and saliva stimulants.

[0028] Furthermore, by weight percentage, the excipient portion also includes 0.5-5% buffer, 0.1-2% sweetener, 0.1-1% flavoring, 0.01-0.1% coloring, 0.05-0.5% antibacterial agent, and 0.1-2% salivary stimulant.

[0029] In this regard, unless otherwise specified, the mass percentage is a percentage relative to the total mass of the film agent.

[0030] On the other hand, this application provides a method for treating or preventing gout, which includes administering a preventatively effective amount of the aforementioned film to a patient who requires the method.

[0031] On the other hand, this application provides a colchicine film-forming agent, which includes an active ingredient portion and an excipient portion;

[0032] The active ingredient includes colchicine;

[0033] The auxiliary material includes a first polymer; the first polymer includes polyoxyethylene with a molecular weight of 100,000 to 500,000.

[0034] In some embodiments, the first polymer is a combination of polyethylene oxide with a molecular weight of 100,000 and polyethylene oxide with a molecular weight of 200,000 to 500,000.

[0035] In some embodiments, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to 9:1 and greater than 1:9.

[0036] Optionally, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than 2.3:1 and greater than or equal to 1:4.

[0037] Optionally, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to 1.5:1 and greater than or equal to 1:4.

[0038] Optionally, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to 1:1 and greater than or equal to 1:2.3.

[0039] In some embodiments, the polyethylene oxide with a molecular weight of 200,000 to 500,000 is polyethylene oxide with a molecular weight of 200,000, 300,000, or 400,000; optionally, the polyethylene oxide with a molecular weight of 100,000 includes PEO N-10; the polyethylene oxide with a molecular weight of 200,000 to 500,000 includes one or both of PEO N-80 and PEO N-750; optionally, the polyethylene oxide with a molecular weight of 100,000 is PEO N-10 and the polyethylene oxide with a molecular weight of 200,000 to 500,000 is PEO N-80.

[0040] In some embodiments, the colchicine film agent comprises 45-90% of a first polymer by weight; alternatively, the colchicine film agent comprises 80-90% of a first polymer by weight; alternatively, the colchicine film agent comprises 83-90% of a first polymer by weight.

[0041] In some embodiments, the excipient portion further includes a second polymer, which includes one or more of polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, and polyvinylpyrrolidone with a molecular weight of 200 to 6000.

[0042] Optionally, the second polymer comprises at least hydroxypropyl methylcellulose; alternatively, the second polymer comprises a composition of hydroxypropyl methylcellulose and other polymers, wherein the other polymers include one or more of polyethylene glycol, hydroxypropyl cellulose and polyvinylpyrrolidone with a molecular weight of 200 to 6000.

[0043] Optionally, the second polymer comprises a composition of hydroxypropyl methylcellulose and polyvinylpyrrolidone or a composition of hydroxypropyl methylcellulose and hydroxypropyl cellulose.

[0044] In some embodiments, the colchicine film agent comprises 0-45% by weight of a second polymer; alternatively, it comprises 1-10% by weight of a second polymer; alternatively, it comprises 1-8% by weight of a second polymer.

[0045] In some embodiments, the mass ratio of the hydroxypropyl methylcellulose to the other polymer is 1:1 to 1:5; optionally, the mass ratio of the hydroxypropyl methylcellulose to the other polymer is 1:1 to 1:4; optionally, the mass ratio of the hydroxypropyl methylcellulose to the other polymer is 1:1 to 1:3.

[0046] In some embodiments, the excipient portion further includes a plasticizer, said plasticizer comprising one or more of triethyl citrate, glycerin, and propylene glycol; optionally, the plasticizer is glycerin; optionally, the excipient portion contains 1-10% plasticizer by weight; optionally, the excipient portion contains 1-7.5% plasticizer by weight; optionally, the excipient portion contains 1-5% plasticizer by weight; optionally, it contains 1-3% plasticizer by weight.

[0047] In some embodiments, the excipient portion further includes a surfactant having an HLB value greater than or less than 10; optionally, the surfactant has an HLB value of not less than 20; optionally, the surfactant includes one or more of sodium dodecyl sulfate, Tween, or glyceryl monostearate polyoxyethylene stearate; optionally, the surfactant is sodium dodecyl sulfate; optionally, the excipient portion contains 0.1-5% surfactant by mass percentage; optionally, the excipient portion contains 0.1-3% surfactant by mass percentage; optionally, the excipient portion contains 0.6-3% surfactant.

[0048] In some embodiments, the colchicine film comprises, by weight percentage, an active ingredient portion and an excipient portion; wherein the active ingredient portion comprises 0.6–6% colchicine; and / or, the excipient portion comprises 45–90% a first polymer; optionally, by weight percentage, it comprises 80–90% a first polymer; optionally, by weight percentage, it comprises 83–90% a first polymer; and / or 0–45% a second polymer; and / or 1–10% a plasticizer; and / or 0.1–5% a surfactant; and / or the second polymer comprises 0–10% hydroxypropyl methylcellulose and 0.5–15% polyvinylpyrrolidone.

[0049] In some embodiments, the excipient portion further includes one or more of a buffer, sweetener, flavoring, coloring, antibacterial agent, and salivary stimulant.

[0050] In some embodiments, the excipient portion further includes, by weight percentage, 0.5-5% buffer; and / or 0.1-2% sweetener; and / or 0.1-1% flavoring; and / or 0.01-0.1% coloring; and / or 0.05-0.5% antibacterial agent; and / or 0.1-2% salivary stimulant.

[0051] In this regard, unless otherwise specified, the mass percentage is a percentage relative to the total mass of the film agent.

[0052] Furthermore, this application provides the use of the colchicine film agent in the preparation of a medicament for the treatment or prevention of gout, the treatment or prevention of thalassemia, or the reduction of the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients diagnosed with atherosclerotic disease or with multiple cardiovascular disease risk factors.

[0053] In another aspect, this application provides a method for treating or preventing gout, treating or preventing thalassemia, or reducing the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients diagnosed with atherosclerotic disease or with multiple cardiovascular disease risk factors, comprising administering an effective amount of colchicine film to a patient in need of the method.

[0054] Compared with the prior art, the beneficial effects of this application are as follows:

[0055] The colchicine film obtained in this application can be used as an oral dissolving agent, which has the effects of convenient use and reducing intestinal irritation, and / or the colchicine film obtained in this application has the beneficial effects of good film-forming properties, and / or good flexibility, and / or easy tearing, so that patients can quickly and accurately tear off the required dose of film when using it, thereby achieving the effect of precise control of drug dosage and rapid onset of action.

[0056] Specifically, in this application, colchicine, also known as colchicine alkaloid, is an alkaloid with the chemical formula C. 22 H 25 NO6 is primarily used as an active ingredient in the treatment of gout and Mediterranean fever, and to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients diagnosed with atherosclerotic disease or with multiple cardiovascular risk factors.

[0057] The excipients are mainly used as carriers for the active pharmaceutical ingredient, wherein the first polymer is primarily used as a film-forming material. In some embodiments, the first polymer of this application includes polyethylene oxide, and the molecular weight of the polyethylene oxide is 100,000 to 500,000; optionally, the molecular weight of the polyethylene oxide is 100,000 to 400,000.

[0058] In some embodiments, the molecular weight of the polyoxyethylene is about 100,000, about 150,000, about 200,000, about 250,000, about 300,000, about 350,000 and / or about 400,000.

[0059] Polyoxyethylene, also known as polyethylene oxide, is abbreviated as PEO. Among common types of polyoxyethylene, PEO N-10 has a molecular weight of 100,000, PEO N-80 has a molecular weight of 200,000, and PEO N-750 has a molecular weight of 300,000. In some embodiments, polyoxyethylene with a molecular weight of 200,000 to 500,000 can be one or more of PEO N-80, PEO N-750, and PEO N-301.

[0060] In this application, the first polymeric substance has a mass percentage of 45-90%. In some embodiments, the mass percentage of the first polymeric substance is approximately 46-90%, approximately 47-90%, approximately 48-90%, approximately 49-90%, approximately 50-90%, approximately 51-90%, approximately 52-90%, approximately 53-90%, approximately 54-90%, approximately 55-90%, approximately 56-90%, approximately 57-90%, approximately 58-90%, approximately 59-90%, approximately 60-90%, approximately 61-90%, approximately 62-90%, approximately 63-90%, approximately 64-90%, and approximately 65-90%. 66–90%, approximately 67–90%, approximately 68–90%, approximately 69–90%, approximately 70–90%, approximately 71–90%, approximately 72–90%, approximately 73–90%, approximately 74–90%, approximately 75–90%, approximately 76–90%, approximately 77–90%, approximately 78–90%, approximately 79–90%, approximately 80–90%, approximately 81–90%, approximately 82–90%, approximately 83–90%, approximately 84–90%, approximately 85–90%, approximately 86–90%, approximately 87–90%, approximately 88–90% %, approximately 89-90%, approximately 45-89%, approximately 45-88%, approximately 45-87%, approximately 45-86%, approximately 45-85%, approximately 45-84%, approximately 45-83%, approximately 45-82%, approximately 45-81%, approximately 45-80%, approximately 45-79%, approximately 45-78%, approximately 45-77%, approximately 45-76%, approximately 45-75%, approximately 45-74%, approximately 45-73%, approximately 45-72%, approximately 45-71%, approximately 45-70%, approximately 45-69%, approximately 4 5–68%, approximately 45–67%, approximately 45–66%, approximately 45–65%, approximately 45–64%, approximately 45–63%, approximately 45–62%, approximately 45–61%, approximately 45–60%, approximately 45–59%, approximately 45–58%, approximately 45–57%, approximately 45–56%, approximately 45–55%, approximately 45–54%, approximately 45–53%, approximately 45–52%, approximately 45–51%, approximately 45–50%, approximately 45–49%, approximately 45–48%, approximately 45–47%, or approximately 45–46%.

[0061] Specifically, in some technical solutions, the mass ratio of polyethylene oxide with a molecular weight of 100,000 to polyethylene oxide with a molecular weight of 200,000 to 500,000 is approximately 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, and so on. The ratios are approximately 1:3.6, 1:3.7, 1:3.8, 1:3.9, 1:4, 1:4.1, 1:4.2, 1:4.3, 1:4.4, 1:4.5, 1:4.6, 1:4.7, 1:4.8, 1:4.9, 1:5, 1:5.1, 1:5.2, 1:5.3, 1:5.4, 1:5.5, 1:5.6, 1:5.7, 1:5.8, 1:5.9, 1:6, 1:6.1, 1:6.2, 1:6.3, 1:6.4, 1:6.5, 1:6.6, 1:6.7, approximately... The ratios are approximately 1:6.8, 1:6.9, 1:7, 1:7.1, 1:7.2, 1:7.3, 1:7.4, 1:7.5, 1:7.6, 1:7.7, 1:7.8, 1:7.9, 1:8, 1:8.1, 1:8.2, 1:8.3, 1:8.4, 1:8.5, 1:8.6, 1:8.7, 1:8.8, 1:8.9, 1:9, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, and approximately 1. The ratios are approximately 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3:1, 3.1:1, 3.2:1, 3.3:1, 3.4:1, 3.5:1, 3.6:1, 3.7:1, 3.8:1, 3.9:1, 4:1, 4.1:1, 4.2:1, 4.3:1, 4.4:1, 4.5:1, 4.6:1, 4.7:1, 4.8:1, 4.9:1, 5:1, 5.1:1, and 5.2:1, approximately 5.3:1, approximately 5.4:1, approximately 5.5:1, approximately 5.6:1, approximately 5.7:1, approximately 5.8:1, approximately 5.9:1, approximately 6:1, approximately 6.1:1, approximately 6.2:1, approximately 6.3:1, approximately 6.4:1, approximately 6.5:1, approximately 6.6:1, approximately 6.7:1, approximately 6.8:1, approximately 6.9:1, approximately 7:1, approximately 7.1: 1. Approximately 7.2:1, approximately 7.3:1, approximately 7.4:1, approximately 7.5:1, approximately 7.6:1, approximately 7.7:1, approximately 7.8:1, approximately 7.9:1, approximately 8:1, approximately 8.1:1, approximately 8.2:1, approximately 8.3:1, approximately 8.4:1, approximately 8.5:1, approximately 8.6:1, approximately 8.7:1, approximately 8.8:1, approximately 8.9:1, or approximately 9:1.

[0062] Specifically, in some technical solutions, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to m and greater than n; optionally, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than m and greater than or equal to n; optionally, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to m and greater than or equal to n; wherein m is greater than n, and m and n are selected from any of the following values: approximately 1:1, approximately 1:1.1, approximately 1:1.2, approximately 1:1.3, approximately 1:1.4, approximately 1:1.5, approximately 1:1.6, approximately 1:1.7, approximately... 1:1.8, approximately 1:1.9, approximately 1:2, approximately 1:2.1, approximately 1:2.2, approximately 1:2.3, approximately 1:2.4, approximately 1:2.5, approximately 1:2.6, approximately 1:2.7, approximately 1:2.8, approximately 1:2.9, approximately 1:3, approximately 1:3.1, approximately 1:3.2, approximately 1:3.3, approximately 1:3.4, approximately 1:3.5, approximately 1:3.6, approximately 1:3.7, approximately 1:3.8, approximately 1:3.9, approximately 1:4, approximately 1:4.1, approximately 1:4.2, approximately 1:4.3, approximately 1:4.4, approximately 1:4.5, approximately 1:4.6, approximately 1:4.7, approximately 1:4.8, approximately 1:4.9, approximately 1:5, approximately 1:5.1, approximately 1:5.2, approximately 1:5.3, approximately 1:5.4, approximately 1:5.5, approximately 1:5.6, approximately 1:5.7, approximately 1:5.8, approximately 1:5.9, approximately 1:6, approximately 1:6.1, approximately 1:6.2, approximately 1:6.3, approximately 1:6.4, approximately 1:6.5, approximately 1:6.6, approximately 1:6.7, approximately 1:6.8, approximately 1:6.9, approximately 1:7, approximately 1:7.1, approximately 1:7.2, approximately 1:7.3, approximately 1:7.4, approximately 1:7.5, approximately 1:7.6, approximately 1:7.7, approximately 1:7.8, approximately 1:7.9, approximately 1:8, approximately 1:8.1, approximately 1: 8.2, approximately 1:8.3, approximately 1:8.4, approximately 1:8.5, approximately 1:8.6, approximately 1:8.7, approximately 1:8.8, approximately 1:8.9, approximately 1:9, approximately 1.1:1, approximately 1.2:1, approximately 1.3:1, approximately 1.4:1, approximately 1.5:1, approximately 1.6:1, approximately 1.7:1, approximately 1.8:1, approximately 1.9:1, approximately 2:1, approximately 2.1:1, approximately 2.2:1, approximately 2.3:1, approximately 2.4:1, approximately 2.5:1, approximately 2.6:1, approximately 2.7:1, approximately 2.8:1, approximately 2.9:1, approximately 3:1, approximately 3.1:1, approximately 3.2:1, approximately 3.3:1, approximately 3.4:1, approximately 3.5:1, approximately 3.6:1, approximately 3.7:1, approximately 3.8:1, approximately 3.9:1, approximately 4:1, approximately 4.1:1, approximately 4.2:1, approximately 4.3:1, approximately 4.4:1, approximately 4.5:1, approximately 4.6:1, approximately 4.7:1, approximately 4.8:1, approximately 4.9:1, approximately 5:1, approximately 5.1:1, approximately 5.2:1, approximately 5.3:1, approximately 5.4:1, approximately 5.5:1, approximately 5.6:1, approximately 5.7:1, approximately 5.8:1, approximately 5.9:1, approximately 6:1, approximately 6.1:1, approximately 6.2: 1. Approximately 6.3:1, approximately 6.4:1, approximately 6.5:1, approximately 6.6:1, approximately 6.7:1, approximately 6.8:1, approximately 6.9:1, approximately 7:1, approximately 7.1:1, approximately 7.2:1, approximately 7.3:1, approximately 7.4:1, approximately 7.5:1, approximately 7.6:1, approximately 7.7:1, approximately 7.8:1, approximately 7.9:1, approximately 8:1, approximately 8.1:1, approximately 8.2:1, approximately 8.3:1, approximately 8.4:1, approximately 8.5:1, approximately 8.6:1, approximately 8.7:1, approximately 8.8:1, approximately 8.9:1, or approximately 9:1.

[0063] Plasticizers are substances added to polymerizing agents that increase the plasticity of the polymer, primarily used to improve the mechanical properties of oral films, including tensile strength and elongation. In some embodiments, the plasticizer contains hydroxyl groups; more specifically, the plasticizer's molecular formula contains two or more hydroxyl groups. Further, in some embodiments, the plasticizer includes one or two of triethyl citrate, glycerol, and propylene glycol; optionally, the plasticizer in this application is glycerol.

[0064] In some embodiments, the plasticizer is present in a mass percentage of approximately 1–2%, approximately 1–2.5%, approximately 1–3%, approximately 1–4%, approximately 1–5%, approximately 1–6%, approximately 1–7%, approximately 1–7.5%, approximately 1–8%, approximately 1–9%, approximately 1–10%, approximately 2–10%, approximately 3–10%, approximately 4–10%, approximately 5–10%, approximately 6–10%, approximately 7–10%, approximately 8–10%, or approximately 9–10%.

[0065] In some embodiments, the second polymer mass percentage is about 0-45%, about 1-45%, about 2-45%, about 3-45%, about 4-45%, about 5-45%, about 6-45%, about 7-45%, about 8-45%, about 9-45%, about 10-45%, about 11-45%, about 12-45%, about 13-45%, about 14-45%, about 15-45%, about 16-45%, about 17-45%, about 18-45%, about 19-45%. 5%, approximately 20-45%, approximately 21-45%, approximately 22-45%, approximately 23-45%, approximately 24-45%, approximately 25-45%, approximately 26-45%, approximately 27-45%, approximately 28-45%, approximately 29-45%, approximately 30-45%, approximately 31-45%, approximately 32-45%, approximately 33-45%, approximately 34-45%, approximately 35-45%, approximately 36-45%, approximately 37-45%, approximately 38-45%, approximately 39-45%, approximately 40-45% Approximately 41-45%, approximately 42-45%, approximately 43-45%, approximately 44-45%, approximately 1-2%, approximately 1-3%, approximately 1-4%, approximately 1-5%, approximately 1-6%, approximately 1-7%, approximately 1-8%, approximately 1-9%, approximately 1-10%, approximately 0-10%, approximately 1-11%, approximately 1-12%, approximately 1-13%, approximately 1-14%, approximately 1-15%, approximately 1-16%, approximately 1-17%, approximately 1-18%, approximately 1-19%, approximately 1-20%, approximately The percentages are approximately 1–21%, 1–22%, 1–23%, 1–24%, 1–25%, 1–26%, 1–27%, 1–28%, 1–29%, 1–30%, 1–31%, 1–32%, 1–33%, 1–34%, 1–35%, 1–36%, 1–37%, 1–38%, 1–39%, 1–40%, 1–41%, 1–42%, 1–43%, or 1–44%.

[0066] In this application, the second polymer comprises polyethylene glycol with a molecular weight of 200 to 6000, and polyethylene glycol is abbreviated as PEG; in some embodiments, the second polymer comprises one or more of PEG-300, PEG-400, PEG-540, PEG-600, PEG-900, PEG-1000, PEG-1450, PEG-1540, PEG-2000, PEG-3000, PEG-3350, PEG-4000, PEG-4600, PEG-6000, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, and polyvinylpyrrolidone.

[0067] Optionally, the second polymer includes hydroxypropyl methylcellulose, also known as hydroxypropyl methylcellulose, abbreviated as HPMC. Optionally, in some embodiments, the second polymer is HPMC E5. In some embodiments, the second polymer includes at least HPMC E5.

[0068] In some embodiments, the mass percentage of hydroxypropyl methylcellulose is approximately 0.5–0.6%, approximately 0.5–0.7%, approximately 0.5–0.8%, approximately 0.5–0.9%, approximately 0.5–1%, approximately 0.5–1.1%, approximately 0.5–1.2%, approximately 0.5–1.3%, approximately 0.5–1.4%, approximately 0.5–1.5%, approximately 0.5–1.6%, approximately 0.5–1.7%, approximately 0.5–1.8%, approximately... Approximately 0.5–1.9%, approximately 0.5–2%, approximately 0.5–3%, approximately 0.5–4%, approximately 0.5–5%, approximately 0.5–6%, approximately 0.5–7%, approximately 0.5–8%, approximately 0.5–9%, approximately 0–10%, approximately 0.1–10%, approximately 0.2–10%, approximately 0.3–10%, approximately 0.4–10%, approximately 0.5–10%, approximately 0.6–10%, approximately 0.7–10%, approximately 0.8%. ~10%, approximately 0.9-10%, approximately 1-10%, approximately 1.1-10%, approximately 1.2-10%, approximately 1.3-10%, approximately 1.4-10%, approximately 1.5-10%, approximately 1.6-10%, approximately 1.7-10%, approximately 1.8-10%, approximately 1.9-10%, approximately 2-10%, approximately 3-10%, approximately 4-10%, approximately 5-10%, approximately 6-10%, approximately 7-10%, approximately 8- 10%, approximately 9-10%, approximately 0-9%, approximately 0-8%, approximately 0-7%, approximately 0-6%, approximately 0-5%, approximately 0-4%, approximately 0-3%, approximately 0-2%, approximately 0-1%, approximately 0.2-10%, approximately 0.2-9%, approximately 0.2-8%, approximately 0.2-7%, approximately 0.2-6%, approximately 0.2-5%, approximately 0.2-4%, approximately 0.2-3%, approximately 0.2-2%, or approximately 0.2-1%.

[0069] Optionally, the second polymer of this application further includes polyvinylpyrrolidone (PVP). Preferably, in some embodiments, the second polymer includes PVP-K30; alternatively, in some embodiments, the second polymer includes PVP-K90.

[0070] In some embodiments, the mass percentage of polyvinylpyrrolidone is about 1-2%, about 1-3%, about 1-4%, about 1-5%, about 1-6%, about 1-7%, about 1-8%, about 1-9%, about 1-10%, about 1-11%, about 1-12%, about 1-13%, about 1-14%, about 2-15%, about 3-15%, about 4-15%, about 5-15%, about 6-15%, about 7-15%, about 8-15%, about 9- 15%, approximately 10-15%, approximately 11-15%, approximately 12-15%, approximately 13-15%, approximately 14-15%, approximately 0-10%, approximately 0-9%, approximately 0-8%, approximately 0-7%, approximately 0-6%, approximately 0-5%, approximately 0-4%, approximately 0-3%, approximately 0.5-10%, approximately 0.5-9%, approximately 0.5-8%, approximately 0.5-7%, approximately 0.5-6%, approximately 0.5-5%, approximately 0.5-4%, or approximately 0.5-3%.

[0071] In some embodiments, the second polymer of this application comprises a composition of hydroxypropyl methylcellulose and polyvinylpyrrolidone or a composition of hydroxypropyl methylcellulose and hydroxypropyl cellulose; optionally, the mass ratio of hydroxypropyl methylcellulose to polyvinylpyrrolidone is about 1:1 to 1:5, about 1:1 to 1:4, or about 1:1 to 1:3. Alternatively, the mass ratio of hydroxypropyl methylcellulose to hydroxypropyl cellulose is about 1:1 to 1:5, about 1:1 to 1:4, or about 1:1 to 1:3.

[0072] In some embodiments, the mass ratio of the plasticizer to polyvinylpyrrolidone in this application is about 1:0.25, about 1:0.5, about 1:0.6, about 1:0.7, about 1:0.8, about 1:0.9, about 1:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, about 1:2, about 1:3, or about 1:4.

[0073] Surfactants, also known as surfactants, are compounds used to enhance the solubility and wettability of oral dissolving films, thereby enabling faster release of the active pharmaceutical ingredient. Optionally, the surfactant in this application is one or more of sodium lauryl sulfate, polysorbate, Tween 80, and Span 80. In some embodiments, the surfactant in this application includes one or more of sodium lauryl sulfate, Tween, or glyceryl monostearate polyoxyethylene stearate. In some embodiments, the surfactant in this application is sodium lauryl sulfate. In some embodiments, the surfactant in this application is glyceryl monostearate polyoxyethylene stearate.

[0074] In some embodiments, the surfactant of this application is present in a mass percentage of approximately 0.1–0.2%, approximately 0.1–0.3%, approximately 0.1–0.4%, approximately 0.1–0.5%, approximately 0.1–0.6%, approximately 0.1–0.7%, approximately 0.1–0.8%, approximately 0.1–0.9%, approximately 0.1–1%, approximately 0.1–2%, approximately 0.1–3%, approximately 0.1–4%, approximately 0.1–5%, approximately 0.2–5%, approximately 0.3–5%, approximately 0.4–5%, approximately 0.5–5%, approximately 0.6–5%, approximately 0.6–3%, approximately 0.7–5%, approximately 0.8–5%, approximately 0.9–5%, approximately 1–5%, approximately 2–5%, approximately 3–5%, or approximately 4–5%.

[0075] A buffer is a solid composition that can be used to control the fugacity of a gas or liquid under high temperature and high pressure conditions, or at normal temperature and pressure. In some embodiments, the buffer of this application has a mass percentage of approximately 0.5-5%, approximately 0.6-5%, approximately 0.7-5%, approximately 0.8-5%, approximately 0.9-5%, approximately 1-5%, approximately 1.1-5%, approximately 1.2-5%, approximately 1.3-5%, approximately 1.4-5%, approximately 1.5-5%, approximately 1.6-5%, approximately 1.7-5%, approximately 1.8-5%, approximately 1.9-5%, approximately 2-5%, approximately 3-5%, approximately 4-5%, and approximately... 0.5–0.6%, approximately 0.5–0.7%, approximately 0.5–0.8%, approximately 0.5–0.9%, approximately 0.5–1%, approximately 0.5–1.1%, approximately 0.5–1.2%, approximately 0.5–1.3%, approximately 0.5–1.4%, approximately 0.5–1.5%, approximately 0.5–1.6%, approximately 0.5–1.7%, approximately 0.5–1.8%, approximately 0.5–1.9%, approximately 0.5–2%, approximately 0.5–3%, or approximately 0.5–4%.

[0076] Furthermore, the buffer in this application is one or more of disodium hydrogen phosphate heptahydrate, citric acid, sodium citrate, and sodium bicarbonate; disodium hydrogen phosphate heptahydrate may be selected as the buffer.

[0077] Sweeteners are food additives used to mask the unpleasant odor and bitterness of active pharmaceutical ingredients. In some embodiments, the sweetener in this application is present in a mass percentage of approximately 0.1–0.2%, approximately 0.1–0.3%, approximately 0.1–0.4%, approximately 0.1–0.5%, approximately 0.1–0.6%, approximately 0.1–0.7%, approximately 0.1–0.8%, approximately 0.1–0.9%, approximately 0.1–1%, approximately 0.1–1.1%, approximately 0.1–1.2%, or approximately 0.1–1. 3%, approximately 0.1–1.4%, approximately 0.1–1.5%, approximately 0.1–1.6%, approximately 0.1–1.7%, approximately 0.1–1.8%, approximately 0.1–1.9%, approximately 0.2–2%, approximately 0.3–2%, approximately 0.4–2%, approximately 0.5–2%, approximately 0.6–2%, approximately 0.7–2%, approximately 0.8–2%, approximately 0.9–2%, or approximately 1–2%.

[0078] Furthermore, the sweetener of this application is one or more of sucrose, glucose, sodium saccharin, aspartame, maltose, and AK sugar; aspartame may be selected as the sweetener.

[0079] Flavorings, also known as flavor enhancers or umami agents, are primarily used to improve the unpleasant taste of drugs. In some embodiments, the flavorings in this application are present in a weight percentage of approximately 0.1–0.2%, 0.1–0.3%, 0.1–0.4%, 0.1–0.5%, 0.1–0.6%, 0.1–0.7%, 0.1–0.8%, 0.1–0.9%, 0.2–1%, 0.3–1%, 0.4–1%, 0.5–1%, 0.6–1%, 0.7–1%, 0.8–1%, or 0.9–1%.

[0080] Furthermore, the fragrance of this application is one or more of peppermint oil, cinnamon oil, spearmint oil, nutmeg oil, menthol, and fruit fragrance; wherein the fruit fragrance can be apple-type, cherry-type, etc. Optionally, the fragrance of this application is DL-menthol and cherry fragrance.

[0081] Pigments, also known as food colorings, are substances primarily used for coloring food, imparting color and improving the appearance of food. In some embodiments, the pigment content of this application is approximately 0.01–0.02%, 0.01–0.03%, 0.01–0.03%, 0.01–0.04%, 0.01–0.05%, 0.01–0.06%, 0.01–0.07%, 0.01–0.08%, 0.01–0.09%, 0.02–0.1%, 0.03–0.1%, 0.04–0.1%, 0.05–0.1%, 0.06–0.1%, 0.07–0.1%, 0.08–0.1%, or 0.09–0.1% by mass.

[0082] In this application, the pigment includes, but is not limited to, one or more of silicon dioxide, titanium dioxide, or FD&C. Optionally, the pigment in this application is FD&C Red #40 or FD&C Red #6.

[0083] Antimicrobial agents refer to a class of agents used to control plant diseases caused by various pathogenic microorganisms. In some embodiments, the antimicrobial agent of this application is present in a mass percentage of approximately 0.05–0.1%, approximately 0.05–0.2%, approximately 0.05–0.3%, approximately 0.05–0.4%, approximately 0.1–0.5%, approximately 0.2–0.5%, approximately 0.3–0.5%, or approximately 0.4–0.5%.

[0084] Furthermore, the antibacterial agent of this application is methylparaben and / or propylparaben, which may be selected as methylparaben and propylparaben.

[0085] In some embodiments, the mass ratio of methylparaben to propylparaben is about 1:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9, about 1:2, about 1.1:1, about 1.2:1, about 1.3:1, about 1.4:1, about 1.5:1, about 1.6:1, about 1.7:1, about 1.8:1, about 1.9:1, or about 2:1.

[0086] Saliva stimulants are substances used to stimulate the salivary glands to produce saliva, thereby aiding in the rapid breakdown of the oral coating. In some embodiments, the saliva stimulant of this application is present in a mass percentage of approximately 0.1–0.2%, approximately 0.1–0.3%, approximately 0.1–0.4%, approximately 0.1–0.5%, approximately 0.1–0.6%, approximately 0.1–0.7%, approximately 0.1–0.8%, approximately 0.1–0.9%, approximately 0.1–1%, approximately 0.1–1.1%, approximately 0.1–1.2%, approximately 0.1–1.3%, approximately 0.1–1.4%, approximately 0.1–1.5%, approximately 0.1–1.6%, or approximately 0%. 0.1–1.7%, approximately 0.1–1.8%, approximately 0.1–1.9%, approximately 0.2–2%, approximately 0.3–2%, approximately 0.4–2%, approximately 0.5–2%, approximately 0.6–2%, approximately 0.7–2%, approximately 0.8–2%, approximately 0.9–2%, approximately 1–2%, approximately 1.1–2%, approximately 1.2–2%, approximately 1.3–2%, approximately 1.4–2%, approximately 1.5–2%, approximately 1.6–2%, approximately 1.7–2%, approximately 1.8–2%, or approximately 1.9–2%.

[0087] Furthermore, the saliva stimulants of this application include, but are not limited to, one or more of citric acid, malic acid, lactic acid, ascorbic acid, and tartaric acid. Optionally, the saliva stimulant of this application is a sodium citrate dihydrate polymer or anhydrous citric acid.

[0088] In this application, the colchicine film agent can be prepared using traditional film preparation methods, such as coating, hot melt extrusion, semi-solid solvent casting, solid dispersion extrusion, and spheronization. Optionally, the colchicine film agent of this application is prepared using the coating method.

[0089] In this application, the preparation method of the colchicine film is as follows: weigh the active ingredient and excipients according to the proportion, add them to a stirrer and mix evenly, degas under vacuum, pour into a coating machine for coating, heat and dry to remove moisture, demold, cut into the required specifications, and package to obtain the required film.

[0090] Specifically, in some embodiments, a propeller agitator is used. The vacuum-degassed mixture is then coated onto a release liner using an HED coating machine. The release liner can be a 3M ScotchPak™ film.

[0091] Specifically, in some embodiments, the film agent of this application has the beneficial effects of good film-forming properties, good plasticity, controllable extensibility, easy tearing, and more precise drug dosage.

[0092] In some embodiments, the film-forming agent of this application has the beneficial effects of rapid dissolution, high release rate, low side effects, and good therapeutic effect.

[0093] In some embodiments, the film formulation of this application has the advantages of better taste, portability, and ease of use compared to traditional tablets or oral liquids, making it more suitable for people with poor compliance. Detailed Implementation

[0094] To more clearly illustrate the technical solution of this application, the implementation scheme of this application will be described in detail below with reference to specific embodiments. Those skilled in the art should understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of this application. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are followed. Where the manufacturers of the preparations or instruments used are not specified, they are all conventional products that can be purchased on the market.

[0095] The manufacturers of some of the drug components used in this technical solution are shown in Table 1 below.

[0096] Table 1

[0097] Example 1

[0098] Preparation of a colchicine film agent

[0099] In this embodiment, the colchicine film formulation is shown in Table 2. PEO N-10 is polyethylene oxide, model N-10; PEO N-80 is polyethylene oxide, model N-80; and FD&C Red #40 is a pigment. The preparation method of this formulation film is as follows:

[0100] Weigh the active ingredient and excipients according to the specified proportions. Add the weighed components to a mixer (manufacturer: Langley Holdings plc, model: LIUIO) and mix thoroughly to obtain a homogeneous mixture. Degas the mixture under vacuum and pour the degassed mixture into a coating machine (manufacturer: HED International Inc., model: TC-71LC). The film is coated using a laboratory tape casting / coating system. The mixture is evenly coated onto a release liner, then the film is heated and dried to remove moisture. It is then demolded, cut to the required specifications, and packaged to obtain the desired film formulation. The active ingredient is colchicine, and the excipients are other pharmaceutical excipients besides the active ingredient.

[0101] Examples 2-7

[0102] The preparation methods of Examples 2-7 are the same as those of Example 1, except that the mass ratio of PEO N-10 to PEO N-80 is different. The dosage of other excipients is the same as that of Example 1. For specific formulation details, please refer to Table 2.

[0103] Table 2 *Removed during the process, and its usage is not counted in intermediate or finished products.

[0104] Examples 8-14

[0105] The preparation methods of Examples 8-14 are the same as those of Example 1. The difference between Examples 8-11 and Example 1 is that the second polymer used is different, while the amounts of other excipients are the same as those of Example 1. The difference between Example 12 and Example 1 is that the ratio of hydroxypropyl methylcellulose to polyvinylpyrrolidone (PVP-K30) is different, while the amounts of other excipients are the same as those of Example 1. The difference between Example 13 and Example 11 is that the ratio of hydroxypropyl methylcellulose to hydroxypropyl cellulose (HPC EXF) is different, while the amounts of other excipients are the same as those of Example 11. The difference between Example 14 and Example 9 is that the ratio of hydroxypropyl methylcellulose to polyvinylpyrrolidone (PVP-K90) is different, while the amounts of other excipients are the same as those of Example 9. For specific formulation details, please refer to Table 3.

[0106] Table 3 *Removed during the process and not counted in the intermediate or finished product. "-" indicates that the component is not in the formulation.

[0107] Examples 15-17 and Examples 24-25

[0108] The preparation methods of Examples 15-17 and Examples 24-25 are the same as those of Example 1. The only difference between Examples 15-16 and Example 1 is the plasticizer used; the amounts of other excipients are the same as those of Example 1. The only difference between Examples 17 and Examples 24-25 and Example 1 is the mass percentage of the plasticizer used and the mass percentage of the first polymer; the amounts of other excipients are the same as those of Example 1. For specific formulation details, please refer to Table 4.

[0109] Table 4 *Removed during the process and not counted in the intermediate or finished product. "-" indicates that the component is not in the formulation.

[0110] Examples 18-20 and Example 26

[0111] The preparation methods of Examples 18-20 and Example 26 are the same as those of Example 1. The only difference between Example 18 and Example 1 is the different surfactants used, while the amounts of other excipients are the same as those of Example 1. The difference between Examples 19-20 and Example 26 and Example 1 is the different mass percentages of surfactants and the first polymer used, while the amounts of other excipients are the same as those of Example 1. The formulation details are shown in Table 5.

[0112] Table 5 *Removed during the process and not counted in the intermediate or finished product. "-" indicates that the component is not in the formulation.

[0113] Examples 21-23

[0114] The preparation methods for Examples 21-23 are the same as those for Example 1. The difference between Examples 21-23 and Example 1 lies in the type and amount of the first polymer used, while the amounts of other excipients are the same as in Example 1. See Table 6 for specific formulation details.

[0115] Table 6 *Removed during the process and not counted in the intermediate or finished product. "-" indicates that the component is not in the formulation.

[0116] Examples 27-30

[0117] The preparation methods of Examples 27-30 are the same as those of Example 1. The difference between Examples 27-30 and Example 1 is that the amount of the first polymer and the second polymer and the amount of plasticizer are different. The amounts of other excipients are the same as those of Example 1. For specific formulation details, please refer to Table 7.

[0118] Table 7 *Removed during the process and not counted in the intermediate or finished product. "-" indicates that the component is not in the formulation.

[0119] The effects of the colchicine film obtained in Examples 1-30 were tested, and the film-forming properties, flexibility and tearability were examined.

[0120] Experimental Example 1: Content Uniformity

[0121] Content uniformity refers to the degree of uniformity of the active ingredient contained in each dosage unit of a pharmaceutical preparation. Colchicine film formulations are low-dose preparations with high requirements for formulation composition, and their content uniformity reflects film-forming performance.

[0122] Experimental methods and instruments

[0123] 1) Instrument: High Performance Liquid Chromatograph (Manufacturer: Shimadzu, Model: LC2010)

[0124] 2) Experimental methods:

[0125] For the film preparations of Examples 1-29, 10 films were randomly selected from each example, each approximately 60 mg. The weight of each film was accurately recorded, and the films were transferred to 25 mL volumetric flasks. A methanol-water solution (methanol:water = 20:80) was added to approximately half the volumetric flask. The flasks were then sonicated for 10 minutes under ice pack cooling, with manual shaking performed periodically. After sonication, the solution temperature was allowed to equilibrate to room temperature, and then diluted to the mark with diluent and mixed thoroughly. The solution was then filtered through a 0.45 μm nylon membrane. The first 3 mL of filtrate was discarded, and the subsequent filtrate was collected. After centrifugation, the clear supernatant was collected and used for HPLC detection to determine the content. The RSD of the content was calculated and recorded. The results are shown in Table 8.

[0126] Table 8

[0127] Experimental Example 2: Flexural Strength Test

[0128] A mechanical stress test method based on repeated folding to fracture was used to evaluate the flexibility of colchicine film, reflecting its ductility and fatigue resistance.

[0129] Experimental methods:

[0130] The membrane formulations prepared in Examples 1-30 were each cut into standard test samples with a size of 1 inch × 1 inch. Each sample was folded longitudinally along one side of the center line, and then continuously folded in the opposite direction until the membrane broke mechanically. Six independent samples (n=6) were tested for each membrane formulation, and the number of folds that each membrane could withstand before breaking was recorded, and the average number of folds was recorded. The results are shown in Table 9.

[0131] Table 9

[0132] Actual test data shows that the number of folds for different formulations of the film varies from more than 2 to 150 times.

[0133] Experiment Example 3 Tearability Test

[0134] Experimental methods and instruments

[0135] 1) Instrument: Intelligent electronic tensile testing machine (Manufacturer: Jinan Langguang Electromechanical Technology Co., Ltd., Model: C610M)

[0136] 2) Experimental methods:

[0137] The membrane formulations prepared in Examples 1-29 were each cut into standard test samples with a size of 1 inch × 1 inch. A centerline tear line was rolled onto each sample, corresponding to the center of one side and the center of the parallel side. The two ends of the sample were clamped in the upper and lower jigs of a tensile testing machine. The test type was set to tensile strength and deformation rate test, and the jig separation speed was 10 mm / min. The testing machine was started, and the test ended when the sample was completely torn in half. Three independent samples (n=3) were measured in parallel for each membrane formulation, and the average value of the maximum tear force and the average value of the displacement were recorded. The results are shown in Table 10.

[0138] Table 10

[0139] Obviously, the above embodiments of this application are merely examples for clearly illustrating the technical solution of this application, and are not intended to limit the specific implementation of this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the claims of this application should be included within the protection scope of the claims of this application.

Claims

1. A colchicine film-forming agent, characterized in that, By weight percentage, it includes 0.6-6% active ingredient portion, with the remainder being excipient portion; The active ingredient includes colchicine; The auxiliary materials include 45-90% of a first polymer, 0-45% of a second polymer, and 1-10% of a plasticizer; The first polymer comprises polyethylene oxide with a molecular weight of 100,000 to 500,000.

2. The colchicine film-forming agent according to claim 1, characterized in that, The first polymer is a combination of polyethylene oxide with a molecular weight of 100,000 and polyethylene oxide with a molecular weight of 200,000 to 500,000.

3. The colchicine film-forming agent according to claim 2, characterized in that, The polyoxyethylene with a molecular weight of 100,000 includes PEO N-10; the polyoxyethylene with a molecular weight of 200,000 to 500,000 includes one or more of PEO N-80, PEO N-750 and PEO N-301.

4. A colchicine film-forming agent according to claim 2 or 3, characterized in that, The ratio of the polyoxyethylene with a molecular weight of 100,000 to the polyoxyethylene with a molecular weight of 200,000 to 500,000 is 1:1 to 9 or 1 to 9:

1.

5. The colchicine film-forming agent according to claim 1, characterized in that, The plasticizer includes one or two of glycerol and propylene glycol; the second polymer includes one or more of polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol and polyvinylpyrrolidone with a molecular weight of 200 to 6000.

6. The colchicine film-forming agent according to claim 5, characterized in that, The second polymer comprises 1 to 15% polyvinylpyrrolidone by mass percentage.

7. The colchicine film-forming agent according to claim 5, characterized in that, The second polymer comprises 0.5 to 10% hydroxypropyl methylcellulose by weight percentage.

8. The colchicine film-forming agent according to claim 1, characterized in that, The auxiliary materials also include 0.1% to 5% surfactant.

9. The colchicine film-forming agent according to claim 1, characterized in that, The excipients also include one or more of the following: buffers, sweeteners, flavorings, colorings, antibacterial agents, and saliva stimulants.

10. A colchicine film-forming agent according to claim 1 or 9, characterized in that, The excipients, by weight percentage, also include 0.5-5% buffer, 0.1-2% sweetener, 0.1-1% flavoring, 0.01-0.1% coloring, 0.05-0.5% antibacterial agent, and 0.1-2% saliva stimulant.

11. A method for treating or preventing gout, comprising administering to a patient in need of the method a preventatively effective amount of the film agent according to any one of claims 1 to 10.

12. A colchicine film-forming agent, characterized in that, Includes the active ingredient portion and the excipient portion; The active ingredient includes colchicine; The auxiliary material includes a first polymer; the first polymer includes polyoxyethylene with a molecular weight of 100,000 to 500,000.

13. The colchicine film-forming agent according to claim 12, characterized in that, The first polymer is a combination of polyethylene oxide with a molecular weight of 100,000 and polyethylene oxide with a molecular weight of 200,000 to 500,000.

14. The colchicine film-forming agent according to claim 13, characterized in that, The mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to 9:1 and greater than 1:

9. Preferably, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than 2.3:1 and greater than or equal to 1:

4. Preferably, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to 1.5:1 and greater than or equal to 1:

4. More preferably, the mass ratio of the polyethylene oxide with a molecular weight of 100,000 to the polyethylene oxide with a molecular weight of 200,000 to 500,000 is less than or equal to 1:1 and greater than or equal to 1:2.

3.

15. The colchicine film-forming agent according to claim 13 or 14, characterized in that, The polyoxyethylene with a molecular weight of 200,000 to 500,000 is polyoxyethylene with a molecular weight of 200,000, 300,000, or 400,000; preferably, the polyoxyethylene with a molecular weight of 100,000 includes PEO N-10, and the polyoxyethylene with a molecular weight of 200,000 to 500,000 includes one or two of PEO N-80 and PEO N-750; more preferably, the polyoxyethylene with a molecular weight of 100,000 is PEO N-10 and the polyoxyethylene with a molecular weight of 200,000 to 500,000 is PEO N-80.

16. The colchicine film-forming agent according to any one of claims 12-15, characterized in that, The excipients also include a second polymer, which includes one or more of polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol and polyvinylpyrrolidone with a molecular weight of 200 to 6000. Preferably, the second polymer comprises at least hydroxypropyl methylcellulose; more preferably, the second polymer comprises a composition of hydroxypropyl methylcellulose and other polymers, wherein the other polymers include one or more of polyethylene glycol, hydroxypropyl cellulose and polyvinylpyrrolidone with a molecular weight of 200 to 6000. More preferably, the second polymer comprises a composition of hydroxypropyl methylcellulose and polyvinylpyrrolidone or a composition of hydroxypropyl methylcellulose and hydroxypropyl cellulose.

17. The colchicine film-forming agent according to claim 16, characterized in that, It contains 0 to 45% of a second polymer by weight; preferably, it contains 1 to 10% of a second polymer by weight; more preferably, it contains 1 to 8% of a second polymer by weight.

18. The colchicine film-forming agent according to claim 16, characterized in that, The mass ratio of the hydroxypropyl methylcellulose to the other polymer is 1:1 to 1:5; preferably, the mass ratio of the hydroxypropyl methylcellulose to the other polymer is 1:1 to 1:

3.

19. The colchicine film-forming agent according to any one of claims 12-18, characterized in that, The excipients also include plasticizers, which include one or more of triethyl citrate, glycerin, and propylene glycol; preferably, the plasticizer is glycerin; preferably, the excipients contain 1-10% plasticizer by mass percentage; preferably, the excipients contain 1-7.5% plasticizer by mass percentage; more preferably, the excipients contain 1-5% plasticizer by mass percentage; and even more preferably, the excipients contain 1-3% plasticizer by mass percentage.

20. The colchicine film-forming agent according to any one of claims 12-19, characterized in that, The excipient portion further includes a surfactant, wherein the surfactant has an HLB value of not less than 10; preferably, the surfactant has an HLB value of not less than 20; preferably, the surfactant includes one or more of sodium dodecyl sulfate, Tween, or glyceryl monostearate polyoxyethylene stearate; more preferably, the surfactant is sodium dodecyl sulfate; even more preferably, the excipient portion contains 0.1-5% surfactant by mass percentage; preferably, the excipient portion contains 0.1-3% surfactant by mass percentage; more preferably, the excipient portion contains 0.6-3% surfactant.

21. The colchicine film-forming agent according to any one of claims 12-20, characterized in that, The product comprises, by weight percentage, an active ingredient portion and an excipient portion; wherein the active ingredient portion comprises 0.6–6% colchicine; and / or, The excipient portion comprises 45-90% of a first polymer; preferably, by mass percentage, it comprises 80-90% of a first polymer; preferably, by mass percentage, it comprises 83-90% of a first polymer; and / or 0-45% of a second polymer; and / or 1-10% of a plasticizer; and / or 0.1-5% of a surfactant; And / or the second polymer comprises 0-10% hydroxypropyl methylcellulose and 0.5-15% polyvinylpyrrolidone.

22. The colchicine film-forming agent according to any one of claims 12-21, characterized in that, The excipients portion further includes one or more of the following: buffers, sweeteners, flavorings, colorings, antibacterial agents, and saliva stimulants; preferably, by weight percentage, the excipients portion further includes 0.5-5% buffers; and / or 0.1-2% sweeteners; and / or 0.1-1% flavorings; and / or 0.01-0.1% colorings; and / or 0.05-0.5% antibacterial agents; and / or 0.1-2% saliva stimulants.

23. Use of the colchicine film according to any one of claims 12-22 in the preparation of a medicament for the treatment or prevention of gout, the treatment or prevention of thalassemia syndrome, or the reduction of the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients diagnosed with atherosclerotic disease or with multiple cardiovascular disease risk factors.

24. A method for treating or preventing gout, treating or preventing thalassemia syndrome, or reducing the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in an adult patient with a confirmed atherosclerotic disease or multiple cardiovascular disease risk factors, comprising administering to a patient requiring the method an effective amount of the colchicine film of any one of claims 12-22.

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