Liquid formulations of pyridostigmine bromide

Abstract

The application relates to the technical field of pharmaceutical preparations, in particular to a liquid preparation of bromide pyridostigmine, which comprises, in terms of weight percentage, 10-20% of bromide pyridostigmine, 0.5-5% of a stabilizer, a pH value regulator and a solvent; the stabilizer is selected from non-ionic cellulose ether compounds; and the pH value of the liquid preparation of bromide pyridostigmine is 3-6. The liquid preparation of bromide pyridostigmine has the advantages of good stability, high safety, simple preparation, good patient compliance and important application value.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical formulation technology, specifically to a pyridostigmine bromide liquid formulation. Background Technology

[0002] Pyridostigmine bromide was first marketed in the 1950s and used as a first-line treatment for myasthenia gravis. Myasthenia gravis is a disease caused by autoantibodies damaging the postsynaptic membrane at the neuromuscular junction, leading to impaired neuromuscular transmission. Clinical manifestations include fluctuating skeletal weakness, fatigue intolerance, worsening with activity and relief with rest. Symptoms are mostly distributed in the muscles of the eyes, eyeballs, and limbs; in severe cases, respiratory muscles are affected, leading to respiratory failure. The "Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2020 Edition)" clearly states that the cholinesterase inhibitor pyridostigmine bromide is a first-line drug for treating all types of myasthenia gravis, relieving and improving clinical symptoms in patients, and is an essential medication for symptom relief in myasthenia gravis patients.

[0003] Pyridostigmine bromide is currently available in three main dosage forms: tablets, solutions, and syrups. Clinically, only tablets (pyridostigmine bromide tablets) are commonly used. However, patients with myasthenia gravis often experience difficulty swallowing, leading to poor adherence to pyridostigmine bromide tablets. Furthermore, the clinical dosage of pyridostigmine bromide needs to be adjusted according to individual circumstances. Dosage differences between adults and children are significant, ranging from a minimum of 30 mg to a maximum of 1500 mg. Adjusting the dosage of pyridostigmine bromide tablets is difficult, often resulting in inaccurate dosages due to factors like "breaking the tablet and guessing the dosage," which can easily lead to insufficient dosage (no therapeutic effect) or overdose (resulting in muscarinic reactions such as increased salivation, sweating, lacrimation, abdominal pain, diarrhea, and bradycardia) and cholinergic crisis (worsening muscle weakness and fasciculations). Therefore, to meet the clinical medication needs of patients with myasthenia gravis and improve patient adherence, it is necessary to provide an oral solution of pyridostigmine bromide.

[0004] Pyridostigmine bromide has the chemical formula 1-methyl-3-hydroxypyridinium bromide dimethylcarbamate; it has a bitter taste; it is very soluble in water, ethanol, or chloroform, and very slightly soluble in petroleum ether or diethyl ether. Stability studies of pyridostigmine bromide have shown that it has poor stability in solution and is easily degraded. Therefore, to ensure the safety, efficacy, and quality control of the drug, and to achieve effective risk control, related impurities must be kept below safe limits throughout the product's shelf life.

[0005] A prescription pyridostigmine oral solution containing 5% ethanol to improve solution stability poses risks of acute and chronic toxicity during use, and is generally not suitable for pediatric patients.

[0006] Therefore, there is an urgent need to develop a liquid formulation of pyridostigmine bromide with better stability and higher safety. Summary of the Invention

[0007] Based on this, the purpose of this application includes providing a pyridostigmine bromide liquid formulation with good stability and high safety. This liquid formulation can be accurately measured and administered according to actual needs, and the dosage adjustment is convenient, ensuring accurate dosage. This liquid formulation is suitable for adjunctive administration and has high compliance.

[0008] To achieve the above objectives, the following technical solution was adopted:

[0009] A pyridostigmine liquid formulation, by weight percentage, comprises 10% to 20% pyridostigmine, 0.5% to 5% stabilizer, pH adjuster and solvent;

[0010] The stabilizer is selected from nonionic cellulose ether compounds;

[0011] The pH value of the pyridostigmine liquid formulation is 3 to 6.

[0012] Furthermore, the nonionic cellulose ether compound includes at least one of hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; and / or

[0013] The pH adjuster includes a citrate-sodium citrate buffer system; and / or

[0014] The solvent is water.

[0015] Furthermore, the molecular weight of the nonionic cellulose ether compound is 500,000 to 1,000,000;

[0016] The pH buffer pair is citric acid and sodium citrate.

[0017] In one embodiment, the stabilizer is a mixture of hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose in a mass ratio of 1:(0.2-1):(0.2-1).

[0018] In one embodiment, the pyridostigmine liquid formulation further includes at least one of a sweetener, an antibacterial agent, and a flavoring.

[0019] A pyridostigmine liquid formulation, wherein each 1 mL of the pyridostigmine liquid formulation comprises 10 mg to 20 mg of pyridostigmine, 0.5 mg to 5 mg of stabilizer, pH adjuster and solvent;

[0020] The stabilizer is selected from nonionic cellulose ether compounds;

[0021] The pH value of the pyridostigmine bromide liquid formulation is 3.5 to 4.5.

[0022] In one embodiment, the nonionic cellulose ether compound includes at least one of hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; and / or

[0023] The pH adjuster includes citric acid and sodium citrate; and / or

[0024] The solvent is water.

[0025] Furthermore, the molecular weight of the nonionic cellulose ether compound is 500,000 to 1,000,000;

[0026] The pH buffer pair is citric acid and sodium citrate.

[0027] In one embodiment, each 1 mL of the pyridostigmine liquid formulation comprises 5 mg to 30 mg of methylcellulose, 5 mg to 30 mg of hydroxyethylcellulose, and 5 mg to 30 mg of hydroxypropyl methylcellulose.

[0028] In one embodiment, each 1 mL of the pyridostigmine bromide liquid formulation further includes:

[0029] Sweeteners of 100mg to 200mg; and / or

[0030] 0.5 mg to 2 mg of antibacterial agent; and / or

[0031] Food flavorings of 0.5mg to 10mg.

[0032] The pyridostigmine bromide liquid formulation provided in this application does not require the use of organic solvents, has excellent stability, improves safety, is suitable for clinical use in patients with myasthenia gravis, and helps improve patient compliance. Detailed Implementation

[0033] The present application is further described below with reference to embodiments and examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the protection scope of the appended claims.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0035] the term:

[0036] Unless otherwise stated or in case of contradiction, the terms or phrases used herein shall have the following meanings:

[0037] The terms "and / or," "or / and," and "and / or" as used herein include any one of two or more related listed items, as well as any and all combinations of the related listed items. These arbitrary and all combinations encompass any two related listed items, any more related listed items, or a combination of all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or," "or / and," and "and / or," it should be understood that, in this application, the technical solution undoubtedly includes solutions connected by "logical AND," and also undoubtedly includes solutions connected by "logical OR." For example, "A and / or B" includes three parallel solutions: A, B, and A+B. For example, the technical solution of "A, and / or, B, and / or, C, and / or, D" includes any one of A, B, C, and D (that is, a technical solution that is connected by "logical OR"), as well as any and all combinations of A, B, C, and D, that is, combinations of any two or three of A, B, C, and D, and also combinations of all four of A, B, C, and D (that is, a technical solution that is connected by "logical AND").

[0038] In this document, "preferred" is only used to describe a better implementation method or embodiment, and should be understood as not constituting a limitation on the scope of protection of this application.

[0039] In this application, "further" is used to describe the purpose and indicate differences in content, but should not be construed as a limitation on the scope of protection of this application.

[0040] In this application, the technical features described in an open-ended manner include both closed technical solutions consisting of the listed features and open technical solutions that include the listed features.

[0041] In this application, numerical intervals (i.e., numerical ranges) are involved. Unless otherwise specified, optional numerical distributions within the aforementioned numerical intervals are considered continuous and include the two endpoints (i.e., the minimum and maximum values) of the numerical range, as well as every value between these two endpoints. Unless otherwise specified, when a numerical interval refers only to integers within that interval, it includes the two endpoint integers of the numerical range, as well as every integer between the two endpoints. Furthermore, when multiple ranges are provided to describe features or characteristics, these ranges can be merged. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges to which they are included.

[0042] In this application, weight can be a well-known unit of mass in the chemical industry, such as μg, mg, g, or kg.

[0043] In this application, the molecular weight of the polymer compounds refers to their average value, in g / mol; for example, the molecular weight of nonionic cellulose ether compounds of 500,000 to 1,000,000 means that the average molecular weight of such compounds contained in the formulation is 500,000 g / mol to 1,000,000 g / mol.

[0044] This application provides a pyridostigmine bromide liquid formulation that does not require the addition of organic solvents, has excellent stability, high safety, and good patient compliance.

[0045] The oral solution of pyridostigmine bromide of this application inhibits the hydrolysis of pyridostigmine bromide by adding an appropriate amount of nonionic cellulose ether compound to the pyridostigmine bromide solution, thereby improving the stability of pyridostigmine bromide in aqueous solution and ensuring safety and efficacy.

[0046] In one embodiment, the pyridostigmine bromide liquid formulation comprises, by weight percentage, 10% to 20% pyridostigmine bromide, 0.5% to 5% stabilizer, pH adjuster and solvent;

[0047] The stabilizer is selected from nonionic cellulose ether compounds;

[0048] The pH value of pyridostigmine liquid formulations is 3–6.

[0049] In one embodiment, each 1 mL of the pyridostigmine bromide liquid formulation comprises 10 mg to 20 mg of pyridostigmine bromide, 1 mg to 5 mg of stabilizer, pH adjuster and solvent;

[0050] The stabilizer is selected from nonionic cellulose ether compounds;

[0051] The pH value of pyridostigmine liquid formulation is 3.5–4.5.

[0052] In one embodiment, the nonionic cellulose ether compound includes at least one of methylcellulose, hydroxyethylcellulose, and hydroxypropyl methylcellulose; and / or

[0053] pH adjusters include citric acid-sodium citrate buffer systems; and / or

[0054] The solvent is water.

[0055] Adding approximately 0.5% to 5% of a specific type of stabilizer (a nonionic cellulose ether compound) to an aqueous solution of pyridostigmine bromide inhibits the hydrolysis of pyridostigmine bromide and greatly improves its stability in aqueous solution.

[0056] In one embodiment, the pyridostigmine liquid formulation comprises 0.5% to 5% of a nonionic cellulose ether compound.

[0057] Using specific ratios of nonionic cellulose ether compounds and amines can further improve the stability of the pharmaceutical formulation described in this application.

[0058] In one embodiment, the stabilizer is a mixture of hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose in a mass ratio of 1:(0.2-1):(0.2-1).

[0059] In one embodiment, the stabilizer includes 5 mg to 30 mg of hydroxyethyl cellulose, 5 mg to 30 mg of hydroxypropyl cellulose, and 5 mg to 30 mg of hydroxypropyl methyl cellulose.

[0060] The pH of the aqueous solution of pyridostigmine bromide (10-100 mg / mL) is in the range of 3 to 6. The pH of the solution can be controlled in the range of 3.5 to 4.5 by using a pH adjusting agent (citric acid + sodium citrate) buffer salt system, thereby further improving the stability of the solution.

[0061] In one embodiment, the pH value of the pyridostigmine liquid formulation is 3.5 to 4.5.

[0062] Pyridostigmine bromide has a bitter taste, which severely affects patient compliance and limits its clinical use. Appropriate and effective taste masking methods can improve patient compliance, especially in children, increase efficacy, and enhance the clinical value of the drug. How to effectively mask the taste without affecting the effective release of the drug in the body is a major challenge in drug development. There are three main principles of drug taste masking: first, physical masking, which forms a physical barrier to prevent or slow down the release of the drug in the oral cavity and reduce contact between the bitter drug and taste buds; second, chemical masking, which prevents the bitter drug from binding to bitter taste receptors in the oral cavity, thus blocking signal transmission; and third, sensory masking, which interferes with central signal integration and confuses the brain's taste perception.

[0063] To improve the taste, in one embodiment, the pyridostigmine bromide liquid formulation further includes at least one of a sweetener and a flavoring. The combination of the sweetener and flavoring masks taste, interferes with central signal integration, and confuses the brain's taste perception. Studies have found that this combination is very effective in improving the taste of pyridostigmine bromide oral solution, thus improving patient adherence.

[0064] In one embodiment, the sweetener is at least one selected from sorbitol, mannitol, xylitol, acesulfame potassium, sucralose, and aspartame. The flavoring is generally selected from pharmaceutically acceptable flavorings that can mask the bitterness of the raw materials in the formulation, preferably fruit flavorings such as cherry, sweet orange, strawberry, and grape.

[0065] Optionally, the pyridostigmine bromide liquid formulation of one embodiment of this application further includes an antibacterial agent.

[0066] In one embodiment, the antibacterial agent includes at least one of sodium benzoate, methylparaben, ethylparaben, and potassium sorbate.

[0067] In one embodiment, each 1 mL of pyridostigmine bromide liquid formulation further includes:

[0068] Sweeteners of 100mg to 200mg; and / or

[0069] 0.5 mg to 2 mg of antibacterial agent; and / or

[0070] Food flavorings of 0.5mg to 10mg.

[0071] Furthermore, since the pH range of pyridostigmine liquid formulation is required to be between 3 and 6, it is preferable to select a bacteriostatic agent that has antibacterial effect under this pH range. Generally, a pharmaceutically acceptable bacteriostatic agent is selected, such as at least one selected from sodium benzoate, methylparaben, sodium methylparaben, ethylparaben, and potassium sorbate.

[0072] In another aspect of this application, a method for preparing a pyridostigmine bromide liquid formulation is also disclosed. This method is simple to operate and can be used to prepare the pyridostigmine bromide liquid formulation with excellent stability and good safety as described above.

[0073] In one embodiment, the method for preparing a pyridostigmine bromide liquid formulation includes the following steps:

[0074] Provide each raw material according to the formulation of the pyridostigmine liquid preparation described in any of the above technical solutions;

[0075] Preferably, the solvent is water;

[0076] Take approximately 80% of the total weight of water, add pH adjuster, pyridostigmine bromide and stabilizer, and optionally add antibacterial agent, sweetener and flavoring, stir to dissolve and clarify, then add the remaining water.

[0077] As a further example, in one embodiment, the preparation method of pyridostigmine bromide liquid formulation is as follows: Take 120 mL of water, add 200 mg of sodium benzoate, and stir to dissolve; add 1.8 g of sodium citrate and 1.7 g of citric acid, and stir to dissolve; add 1.8 g of pyridostigmine bromide, and stir to dissolve; add 15 g of sorbitol and 100 mg of acesulfame potassium, and stir to dissolve; add 400 mg of peach flavoring, and stir evenly; adjust the pH value to 3.5-4.5 with sodium citrate or citric acid; add water to make up to 100%; filter with a polyethersulfone filter membrane with a pore size of 10 microns; fill and bottle to obtain pyridostigmine bromide oral solution.

[0078] The components of the pyridostigmine bromide liquid formulation of this application work together to greatly inhibit the degradation of pyridostigmine bromide, improve the stability of the liquid formulation, and ensure the efficacy and safety of the liquid formulation. By further adding sweeteners and flavorings, the bitter taste of pyridostigmine bromide can be solved, thereby improving patient compliance.

[0079] The following are some specific examples.

[0080] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this application document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0081] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0082] Example 1

[0083] This embodiment focuses on the pH stability study of pyridostigmine bromide solutions. A 1.2% solution of pyridostigmine bromide was prepared with water, and the pH of the solution was adjusted to 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0 using 1 mol / L hydrochloric acid or sodium hydroxide to obtain pyridostigmine bromide solutions with different pH values. The stability of these solutions was evaluated after 30 days of exposure to high-temperature (60℃) conditions. The experimental results are shown in Table 1.

[0084] Table 1. Stability test results of pyridostigmine bromide solution under different pH conditions.

[0085]

[0086] In Table 1, "NA" means that pyridostigmine bromide was not detected, indicating that pyridostigmine bromide has been completely degraded under these conditions.

[0087] Table 1 shows that pyridostigmine bromide degrades quite rapidly under alkaline conditions. Even during the initial analysis, at pH 9.0, the sample had already degraded by more than half. At pH 7.0 and 8.0, the sample showed significant degradation after 10 days of storage at 60°C. The degradation of pyridostigmine bromide under acidic conditions is affected by pH. At pH 1, the degradation rate exceeded 50% after 30 days of storage at 60°C. It exhibits good stability at pH 4.0, with a degradation rate not exceeding 8% after 10 days at 60°C.

[0088] Example 2

[0089] This embodiment is a validation of the pyridostigmine bromide liquid formulation provided in this application, including the preparation of different formulations and their performance comparison studies.

[0090] 1. Sample Preparation for Examples

[0091] Prepare the raw materials for the liquid formulations of each embodiment according to Tables 2 and 3, and prepare the corresponding solutions. The preparation method is as follows: Take water accounting for about 80% of the total weight, add pH adjuster, pyridostigmine bromide, stabilizer, and other pharmaceutical excipients in sequence, stir to dissolve and clarify, add water to make up to 100%, and filter.

[0092] Each 1 mL of the pyridostigmine bromide liquid formulation comprises 5 mg to 30 mg of methylcellulose, 5 mg to 30 mg of hydroxyethylcellulose, and 5 mg to 30 mg of hydroxypropyl methylcellulose.

[0093] Table 2. Formulations of different formulations of pyridostigmine bromide liquid preparations (Formulations 1–6)

[0094]

[0095] In Table 2, “—” indicates that the ingredient was not added to the corresponding formulation. The molecular weights of hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose are 500,000 to 1,000,000.

[0096] Table 3. Formulations of different formulations of pyridostigmine bromide liquid preparations (Formulations 7–12)

[0097]

[0098] In Table 3, “—” indicates that the ingredient was not added to the corresponding formulation. The molecular weights of hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose are 500,000 to 1,000,000.

[0099] (2) Preparation of comparative samples

[0100] Prepare the raw materials for each comparative liquid formulation according to Table 4, and prepare the corresponding solutions. The preparation method is as follows: Take water accounting for about 80% of the total weight, add pH adjuster, pyridostigmine bromide, stabilizer, and other pharmaceutical excipients in sequence, stir to dissolve and clarify, add water to make up to 100%, and filter.

[0101] Table 4. Formulations of different formulations for comparative formulations (Formulations 1–6)

[0102]

[0103] In Table 4, “—” indicates that the ingredient was not added to the corresponding formulation. The stabilizers in Comparative Formulations 1 to 3 all have a molecular weight of 500,000 to 1,000,000. The stabilizers in Comparative Formulations 4 to 6 have a molecular weight of 400,000 for hydroxyethyl cellulose, 370,000 for hydroxypropyl cellulose, and 400,000 for hydroxypropyl methyl cellulose.

[0104] 3. Performance evaluation of liquid formulations with different formulations in the examples and comparative examples

[0105] (1) Stability evaluation

[0106] In accordance with the requirements of the General Chapter 9001 of the Chinese Pharmacopoeia 2020 (Part IV) and the Technical Guidelines for Stability Testing of Active Pharmaceutical Ingredients and Preparations and Stability Studies of Chemical Drugs (Active Pharmaceutical Ingredients and Preparations), accelerated stability studies (40±2℃, 75%±5%RH) and long-term stability studies (25±2℃, 60%±5%RH) were conducted on the oral solutions of pyridostigmine bromide in the above examples and comparative formulations.

[0107] The properties, pH value, related substances, and content of the pyridoxine liquid formulations in each example and comparative example were tested under accelerated and long-term stability conditions.

[0108] The content of pyridostigmine bromide was detected by high performance liquid chromatography (HPLC), and the specific detection conditions were as follows:

[0109] Chromatographic column: octylsilane-bonded silica gel (C8, 250 mm × 4.6 mm, 5 μm) was used as the packing material;

[0110] Mobile phase: 4 g / L sodium dodecyl sulfate solution (pH adjusted to 3.0 with phosphoric acid) - acetonitrile (1000:400);

[0111] Flow rate: 1 mL / min;

[0112] Column temperature: 30℃;

[0113] Detection wavelength: 220nm.

[0114] (2) Impurity Detection

[0115] Impurities generated from the degradation of pyridostigmine bromide include impurity compounds produced by the hydrolysis reaction, including impurity A, impurity B, and impurity C. See Table 5 for details.

[0116] Table 5

[0117]

[0118] Impurities A and B can be detected by liquid chromatography, and the detection conditions are described in (1). Impurity C (N,N-dimethylformamide) is difficult to detect under liquid conditions, so gas chromatography is used to detect the content of impurity C. The detection conditions include:

[0119] Chromatographic conditions (gas phase conditions): A capillary column with PEG-20M as the stationary phase was used;

[0120] The initial column temperature was 40℃, held for 1 minute, then increased to 180℃ at a rate of 15℃ per minute, and then increased to 230℃ at a rate of 20℃ per minute, held for 1 minute.

[0121] Inlet temperature 200℃;

[0122] The carrier gas is helium, and the flow rate is 1 mL per minute.

[0123] Inject 1 μL of sample.

[0124] (3) Test results

[0125] The stability and impurity test results of different prescription liquid formulations are shown in Table 6.

[0126] Table 6. Stability and impurity detection results of different prescription liquid formulations.

[0127]

[0128]

[0129]

[0130] According to Table 6, it was found that the pyridostigmine bromide liquid formulations of the examples all had good clarity and stability in the early stage of preparation. However, after being stored for 6 to 24 months, the formulations of the comparative examples showed varying degrees of degradation. In comparison, the liquid formulations of this application have stronger stability, better impurity control, and higher safety.

[0131] All references to this application are incorporated herein by reference as if each document were individually incorporated herein by reference. Unless they conflict with the purpose and / or technical solution of this application, all cited references are incorporated herein by reference in their entirety and for all purposes. When references are cited in this application, the definitions of relevant technical features, terms, nouns, phrases, etc., are also incorporated herein by reference. Examples and preferred embodiments of the cited technical features may also be incorporated herein by reference, but only to the extent that they enable the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, this application shall prevail or modifications shall be made adaptably to the description in this application.

[0132] The technical features of the above-described embodiments and examples can be combined in any suitable manner. For the sake of brevity, not all possible combinations of the technical features in the above-described embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0133] The embodiments described above merely illustrate several implementation methods of this application and should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Furthermore, it should be understood that after reading the above teachings, those skilled in the art can make various alterations or modifications to this application, and the equivalent forms obtained also fall within the protection scope of this application. It should also be understood that technical solutions obtained by those skilled in the art based on the technical solutions provided in this application through logical analysis, reasoning, or limited experimentation are all within the protection scope of the appended claims. Therefore, the protection scope of this patent application should be determined by the appended claims, and the specification can be used to interpret the content of the claims.

Claims

1. A liquid formulation of pyridostigmine bromide, characterized by, The bromine pyridostigmine liquid preparation includes 12 mg of bromine pyridostigmine, 5 mg of stabilizer, pH regulator and solvent per 1 mL; The stabilizer is selected from hydroxyethyl cellulose, hydroxypropyl cellulose or hydroxypropyl methyl cellulose, and the molecular weight is 500000-1000000; The pH of the bromine pyridostigmine liquid preparation is 3.5-4.5; The solvent is water.

2. The liquid formulation of pyridostigmine bromide according to claim 1, wherein The pH regulator is selected from pH buffer pair.

3. The liquid formulation of pyridostigmine bromide according to claim 2, wherein The pH buffer pair is citric acid and sodium citrate.

4. The liquid formulation of bromoprisamine according to any one of claims 1 to 3, wherein The bromine pyridostigmine liquid preparation further includes, per 1 mL: 100 mg-200 mg of sweetener; and / or 0.5 mg-2 mg of bacteriostatic agent; and / or 0.5 mg-10 mg of food flavor.

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