Pharmaceutical composition for treating Parkinson's disease and preparation method thereof

Abstract

The invention provides a pharmaceutical composition for treating Parkinson's disease and a preparation method of the pharmaceutical composition. Carbidopa-levodopa sustained-release tablets prepared from the pharmaceutical composition have an in-vitro drug release curve similar to that of a reference preparation 'Ninine', bioequivalence and better stability. In the preparation process, each batch has better content uniformity; raw materials and auxiliary materials are easy to obtain, the production process is simple, and commercialized production is facilitated.

Description

A pharmaceutical composition for treating Parkinson's disease and a preparation method thereof

[0001] This application claims priority to Chinese patent application CN202211257606.4, filed on October 14, 2022. This application incorporates the entire text of the aforementioned Chinese patent application. Technical Field

[0002] The present invention belongs to the field of medical technology, and in particular relates to a carbendazim-levodopa composition and a preparation method thereof. Background Art

[0003] Parkinson's disease (PD), also known as "parkinsonism," is one of the most common neurological disorders, and its symptoms are related to dopamine depletion in the striatum. Dopamine administration is clearly ineffective in treating Parkinson's disease because it cannot cross the blood-brain barrier. However, levodopa can cross the blood-brain barrier and is converted to dopamine in the brain. When levodopa is administered orally, it is rapidly decarboxylated to dopamine in tissues outside the brain, resulting in only a small portion of the administered dose being transported to the central nervous system to exert its effects. When carbidopa is taken in combination with levodopa, it reduces the amount of levodopa required to produce a specific response by approximately 75% and increases levodopa's plasma levels and half-life.

[0004] Sinemet CR (Sinemet CR) is a sustained-release tablet containing carbidopa and levodopa as its active ingredients. It is indicated for the following: idiopathic Parkinson's disease; post-encephalitic parkinsonism; symptomatic parkinsonism (caused by carbon monoxide or manganese poisoning); and for reducing "off" time in patients who have previously experienced end-of-dose worsening ("fading" phenomenon) with levodopa / dehydroxylase inhibitor combination therapy or levodopa alone, peak-dose dyskinesia, akinesia, or other symptoms similar to short-term dyskinesia.

[0005] Sinemet CR uses a polyvinylacetate-crotonic acid copolymer as a pharmaceutical carrier. This excipient is difficult to obtain in China, limiting the commercial production of carbofuran-levodopa sustained-release tablets. Carbofuran-levodopa sustained-release tablets have been available in China since 1995, but there are still no domestically available generic versions.

[0006] Summary of the Invention

[0007] The present invention provides a carbidopa-levodopa composition, comprising levodopa, carbidopa and a pharmaceutical carrier, wherein the pharmaceutical carrier is an acrylic resin.

[0008] In some embodiments, the acrylic resin is selected from the group consisting of methacrylic acid and methyl methacrylate copolymers, and methacrylic acid and ethyl acrylate copolymers.

[0009] In some embodiments, the weight ratio of carbidopa to levodopa is 1:(4-10), preferably 1:4.

[0010] In some embodiments, the methacrylic acid and methyl methacrylate copolymer is a methacrylic acid and methyl methacrylate (1:1) copolymer, for example, the methacrylic acid and methyl methacrylate copolymer is Eudragit® L 100.

[0011] In some embodiments, the methacrylic acid and ethyl acrylate copolymer is a methacrylic acid and ethyl acrylate (1:1) copolymer, for example, the methacrylic acid and ethyl acrylate copolymer is Eudragit L 100-55 or Eudragit L30D-55.

[0012] In some embodiments, the carbendazim composition further comprises one or more of a cellulose derivative, a lubricant, and a colorant.

[0013] In some embodiments, the carbidopa-levodopa composition comprises, by weight, 10.0-20.0% carbidopa; 70.0-95.0% levodopa; and 0.5-15.0% methacrylic acid and methyl methacrylate copolymer or methacrylic acid and ethyl acrylate copolymer.

[0014] In some embodiments, the carbendazim composition further comprises 1.0-15.0% of a cellulose derivative.

[0015] In some embodiments, the carbendazim composition further comprises 0.5-2.0% of a lubricant.

[0016] In some embodiments, the carbendazim composition further comprises 0-2.00% of a colorant.

[0017] In some embodiments, the carbidopa content is 17.0-19.0%.

[0018] In some embodiments, the levodopa content is 70.0-75.0%.

[0019] In some embodiments, the content of the copolymer of methacrylic acid and methyl methacrylate or the copolymer of methacrylic acid and ethyl acrylate is 1.0-8.0%.

[0020] In some embodiments, the content of the copolymer of methacrylic acid and methyl methacrylate or the copolymer of methacrylic acid and ethyl acrylate is 1.5-4.0%.

[0021] In some embodiments, the cellulose derivative content is 3.0-8.0%.

[0022] In some embodiments, the lubricant content is 0.5-1.5%.

[0023] In some embodiments, the colorant content is 0.05-0.50%.

[0024] In some embodiments, the colorant content is 0.05-0.20%.

[0025] In some embodiments, the cellulose derivative is selected from one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose. In some preferred embodiments, the cellulose derivative is selected from hydroxypropyl cellulose.

[0026] In some embodiments, the lubricant is selected from one or more of magnesium stearate, talc, stearic acid, silicon dioxide, and sodium stearyl fumarate. In some preferred embodiments, the lubricant is selected from magnesium stearate.

[0027] In some embodiments, the colorant is selected from one or more of caramel, red iron oxide, aluminum hydroxide, grape skin extract, beet red powder, β-carotene, annato, carmine, turmeric, and bell pepper red.

[0028] In some preferred embodiments, the colorant is selected from red iron oxide.

[0029] In some preferred embodiments, the colorant is selected from a mixture of red iron oxide and aluminum hydroxide.

[0030] The present invention also provides a carbidopa-levodopa composition, which comprises, by weight percentage: 17.0-19.0% carbidopa, 70.0-75.0% levodopa, 1.5-4.0% acrylic resin, 3.0-8.0% hydroxypropyl cellulose, 0.5-1.5% magnesium stearate, and 0-2.0% colorant.

[0031] in,

[0032] The acrylic resin is selected from a copolymer of methacrylic acid and methyl methacrylate (1:1) and a copolymer of methacrylic acid and ethyl acrylate (1:1).

[0033] The present invention also provides a carbidopa-levodopa composition, which comprises, by weight percentage: 17.0-19.0% carbidopa, 70.0-75.0% levodopa, 1.5-4.0% acrylic resin, 3.0-8.0% hydroxypropyl cellulose, 0.5-1.5% magnesium stearate, and 0.05-0.50% colorant.

[0034] in,

[0035] The acrylic resin is selected from a copolymer of methacrylic acid and methyl methacrylate (1:1) and a copolymer of methacrylic acid and ethyl acrylate (1:1).

[0036] The present invention also provides a carbidopa-levodopa composition, which comprises, by weight percentage: 17.0-19.0% carbidopa, 70.0-75.0% levodopa, 1.5-4.0% acrylic resin, 3.0-8.0% hydroxypropyl cellulose, 0.5-1.5% magnesium stearate, and 0.05-0.20% colorant.

[0037] in,

[0038] The acrylic resin is selected from a copolymer of methacrylic acid and methyl methacrylate (1:1) and a copolymer of methacrylic acid and ethyl acrylate (1:1).

[0039] The present invention also provides use of the carbocycline-levodopa combination in preparing a medicament for treating Parkinson's disease or movement disorder-related diseases.

[0040] The Parkinson's or movement disorder-related diseases described in the present invention can be primary Parkinson's disease; post-encephalitic Parkinson's syndrome; symptomatic Parkinson's syndrome (carbon monoxide or manganese poisoning); Parkinson's syndrome (including Parkinson's plus syndrome, secondary Parkinson's syndrome, hereditary / familial Parkinson's syndrome); movement disorders characterized by end-of-dose deterioration ("fading away" phenomenon) in patients who have previously been treated with a combination of levodopa / decarboxylase inhibitors or levodopa alone, peak-dose dyskinesia, akinesia, or similar short-term movement disorder phenomena.

[0041] The present invention also provides a carbendazim and levodopa oral solid preparation, comprising the carbendazim and levodopa composition described above.

[0042] In some preferred embodiments, the oral solid dosage form is a tablet. In some preferred embodiments, the oral solid dosage form is a sustained-release tablet.

[0043] The present invention also provides a method for preparing a carbendazim-levodopa composition, characterized in that:

[0044] (1) Carbidopa, levodopa, cellulose derivatives, and optionally colorants are added and mixed uniformly;

[0045] (2) Then, a wetting agent is added to the mixture obtained in step (1) for wet granulation and drying;

[0046] (3) The dried particles in step (2) are evenly mixed with acrylic resin and lubricant;

[0047] Wherein, the acrylic resin is selected from methacrylic acid and methyl methacrylate copolymer, methacrylic acid and ethyl acrylate copolymer.

[0048] The optional addition of a colorant means that a colorant may be added or not.

[0049] In some embodiments, the acrylic resin is selected from a methacrylic acid and methyl methacrylate (1:1) copolymer and a methacrylic acid and ethyl acrylate (1:1) copolymer.

[0050] In some embodiments, the wetting agent is selected from water, ethanol, acetic acid, acetone, ethyl acetate, methyl isobutyl ketone, anisole, ethyl ether, 2-methyl-1-propanol, 1-butanol, ethyl formate, 2-butanol, formic acid, n-propanol, butyl acetate, n-heptane, n-pentanol, tert-butyl methyl ether, isopropyl acetate, isobutyl acetate, methyl acetate, 2-propanol, isopropylbenzene, 3-methyl-1-butanol, propyl acetate, dimethyl sulfoxide, tetrahydrofuran, or a mixed solvent. In some embodiments, the wetting agent is selected from water and ethanol, or a mixed solvent.

[0051] In some embodiments, the carbendazim and levodopa composition can be further compressed into tablets after being uniformly mixed in step (3). DETAILED DESCRIPTION

[0052] The present invention may be better understood by reference to the following definitions provided herein.

[0053] As used herein, % is weight / weight (w / w) percentage unless otherwise specified.

[0054] As used herein, unless otherwise specified, carbidopa is carbidopa monohydrate, and the percentage, weight or weight ratio in the composition and preparation are all calculated based on carbidopa anhydrate.

[0055] In the present invention, carbidopa and levodopa in the carbidopa-levodopa composition may be present in any suitable form, for example, in the form of granules, powder or crystals.

[0056] For the purposes of this invention, the term "cellulose derivative" refers to the product of an esterification or etherification reaction between the hydroxyl groups in a cellulose polymer and a chemical reagent. Cellulose derivatives can be categorized into three main groups: cellulose ethers, cellulose esters, and cellulose ether esters, based on the structural characteristics of the reaction products. These compounds include, but are not limited to, cellulose nitrate, cellulose acetate, cellulose acetate butyrate, cellulose xanthate, hydroxyethyl cellulose, cyanoethyl cellulose, hydroxypropyl cellulose, hypromellose, sodium carboxymethyl cellulose, methyl cellulose, ethyl cellulose, and others known to those skilled in the art.

[0057] In some embodiments, the cellulose derivative is selected from hydroxypropyl cellulose, hypromellose, sodium carboxymethyl cellulose, methyl cellulose, ethyl cellulose, preferably hydroxypropyl cellulose.

[0058] In some embodiments, the cellulose derivative is selected from hydroxypropyl cellulose, and the content is 1-15%, preferably 3-8%.

[0059] In some embodiments, the weight ratio of the cellulose derivative to the methacrylic acid and methyl methacrylate (1:1) copolymer or the methacrylic acid and ethyl acrylate (1:1) copolymer is 1.0-5.0:1, preferably 1.2-3.5:1.

[0060] As used herein, the term "lubricant" refers to a substance used in the formulation to reduce friction during tableting or other processes. Such compounds include, for example, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, talc, silicon dioxide, sodium stearyl fumarate, and zinc stearate, as well as other substances known to those of ordinary skill in the art.

[0061] In some embodiments, the lubricant is magnesium stearate, and the content is 0.5-2%, preferably 0.5-1.5%.

[0062] In the present invention, the term "colorant" refers to a compound used to impart color to a solid (e.g., tablet) pharmaceutical preparation. These compounds include, for example, but are not limited to, FD&C Red No. 3, FD&C Red No. 20, FD&C Yellow No. 6, FD&C Blue No. 2, D&C Green No. 5, D&C Orange No. 5, D&C Red No. 8, caramel, red iron oxide, aluminum hydroxide, and other FD&C. dyes and natural colorants such as grape skin extract, beet red powder, beta-carotene, annato, carmine, turmeric, bell pepper red, and other substances known to those of ordinary skill in the art. The amount of colorant used varies as needed.

[0063] In some embodiments, the colorant is selected from one or both of aluminum hydroxide and red iron oxide.

[0064] In some embodiments, the colorant is selected from red iron oxide, and the content is 0-2%, preferably 0.05-0.20%.

[0065] In some embodiments, the colorant is selected from a mixture of aluminum hydroxide and red iron oxide. In some embodiments, the red iron oxide is 0.05-0.20% and the aluminum hydroxide content is 0-0.4%.

[0066] In some embodiments, the carbendazim composition may further include other pharmaceutically acceptable excipients.

[0067] In embodiments of the present invention, the amounts of carbidopa and levodopa in the carbidopa-levodopa composition will generally be determined by the therapeutically effective amount.

[0068] As used herein, a "therapeutically effective amount" is an amount or quantity of a drug sufficient to elicit the required or desired therapeutic response, in other words, an amount sufficient to elicit a significant biological response when administered to a patient.

[0069] In an embodiment of the present invention, the therapeutic amount of carbidopa / levodopa in the carbidopa-levodopa composition can be: 12.5 mg / 50 mg, 23.75 mg / 95 mg, 25 mg / 100 mg, 36.25 mg / 145 mg, 48.75 mg / 195 mg, 50 mg / 200 mg, 61.25 mg / 245 mg, 10 mg / 100 mg, 25 mg / 250 mg.

[0070] In some preferred embodiments of the present invention, the therapeutic amount of carbidopa / levodopa in the carbidopa-levodopa composition can be: 23.75 mg / 95 mg, 36.25 mg / 145 mg, 48.75 mg / 195 mg, 61.25 mg / 245 mg, 25 mg / 100 mg, 50 mg / 200 mg.

[0071] In some preferred embodiments of the present invention, the therapeutic amount of carbidopa / levodopa in the carbidopa-levodopa composition may be: 25 mg / 100 mg, 50 mg / 200 mg.

[0072] The carbocycline-levodopa composition of the present invention can be prepared into various dosage forms in any shape or form known in the art of pharmaceutical science. The dosage form of the present invention can be a tablet or other dosage form. The dosage form can also include surface markings, cuts, grooves, letters, and / or numbers for decorative, identification, and / or other purposes.

[0073] As is commonly done in the art, the dosage form may include a finishing coating to provide desired gloss, color, flavor, or other aesthetic characteristics.

[0074] In some preferred embodiments, the carbendazim composition can be further prepared into a sustained-release tablet.

[0075] As a preferred embodiment of the present invention, the carbendazim sustained-release tablet comprises the following components:

[0076] As a preferred embodiment of the present invention, the carbendazim sustained-release tablet comprises the following components:

[0077] As a preferred embodiment of the present invention, the carbendazim sustained-release tablet comprises the following components:

[0078] As a preferred embodiment of the present invention, the carbendazim sustained-release tablet comprises the following components:

[0079] In some embodiments, the carbendazim sustained-release tablets may further include other pharmaceutically acceptable excipients.

[0080] The sustained-release carboplatin tablets prepared using the present invention exhibit similar in vitro drug release profiles, bioequivalence, and improved stability to the reference preparation, Sinime. During the preparation process, each batch exhibits improved content uniformity. Furthermore, the raw materials are readily available, the production process is simple, and commercial production is facilitated.

[0081] The present invention will be further described below with reference to the following examples, but they are not intended to limit the present invention. The following examples should not be construed as exhaustive, but rather as merely illustrative of a few of the many embodiments encompassed by the present invention. All raw and auxiliary materials used are commercially available.

[0082] Preparation of Carbopol-Levodopa Sustained-Release Tablets

[0083] The preparation method of the sustained-release tablets of Examples 1 to 6 comprises the following steps:

[0084] Weigh the prescribed amount of red iron oxide and hydroxypropyl cellulose, optionally add the prescribed amount of aluminum hydroxide, mix, and sieve. Place the mixture in a granulation pot along with the prescribed amount of carbidopa and levodopa, mix thoroughly, and add water and / or ethanol as a wetting agent for wet granulation. The above materials are granulated using a rotary granulator and then fluidized bed dried. The dried granules are granulated and then mixed thoroughly with the prescribed amount of a 1:1 copolymer of methacrylic acid and methyl methacrylate or a 1:1 copolymer of methacrylic acid and ethyl acrylate. Magnesium stearate is then added, mixed, and tableted. The formulation contents of Examples 1-6 are shown in Table 1.

[0085] Table 1 Content of each component of Examples 1 to 6 Carbohydrate-L-Dopa sustained-release tablets (mg / tablet)

[0086] In vitro dissolution test:

[0087] Method: The preparation prepared in the present invention was subjected to a dissolution test according to the 2020 Chinese Pharmacopoeia dissolution test. The measurement conditions are as follows:

[0088] Experimental solution: 0.1N HCl and pH 4.5 buffer solution

[0089] Speed: Paddle method 50rpm

[0090] Solution volume: 900ml

[0091] Dissolution Similarity:

[0092] The similarity factor f2, used in Scale-Up and Past-Approval Changes for Intermediate Release Products (SUPAC-IR), is used here to assess the similarity of dissolution profiles. A formulation prepared in accordance with the present invention has similar dissolution profiles to a reference formulation if the f2 value calculated by SUPAC-IR for the formulation's dissolution rate is at least 50. The f2 value is calculated from the start of the test until at least one line has been dissolved to 85%.

[0093] data:

[0094] Table 2 Dissolution data of levodopa from carbocycline sustained-release tablets in 0.1N HCl

[0095] Table 3 Dissolution data of levodopa in carbocycline-levodopa sustained-release tablets at pH 4.5

[0096] According to Table 2 and Table 3, the dissolution curves of Examples 1 to 6 of the carbohydidine sustained-release tablets prepared by the present invention can well match those of the original reference preparation (Xinning) at both pH 1.0 and pH 4.5.

[0097] Stability test:

[0098] Analytical method: High performance liquid chromatography (HPLC) was used to calculate the percentage of levodopa and carbidopa-related substances by peak area normalization method.

[0099] Chromatographic conditions:

[0100] Chromatographic column: Waters X-Bridge C18 5um 4.6mm*250mm detection

[0101] Mobile phase: buffer solution plus appropriate amount of anhydrous ethanol

[0102] Flow rate: 1.0 mL / min

[0103] Column temperature: 25°C

[0104] Injection volume: 50 μL

[0105] Detection wavelength: 280nm;

[0106] Buffer solution: Weigh 6.9 g of sodium dihydrogen phosphate monohydrate, dissolve it in 900 mL of purified water, adjust the pH to 2.0 with phosphoric acid, and dilute to 1000 mL with purified water.

[0107] Comparative Example: The preparation method is the same as that for the carbendazim sustained-release tablets in Examples 1 to 6, except that the methacrylic acid and methyl methacrylate (1:1) copolymer or the methacrylic acid and ethyl acrylate (1:1) copolymer is replaced with a polyvinyl acetate-crotonic acid copolymer, and the tablets are packaged in aluminum-plastic blister packaging. The prescription information is as follows:

[0108] Comparative example prescription (mg / tablet):

[0109] Test 1:

[0110] The samples of Examples 1 to 6 were packaged in aluminum-plastic blisters and compared with a reference preparation (Xinning) and a comparative example. The samples were tested at 60°C and RH 75% for 10 days. The results are shown in Table 4. The largest single impurity of levodopa-related substances was levodopa-related substance A, and the largest single impurity of carbidopa-related substances was 3,4-dihydroxypropiophenone. Related substances of levodopa or carbidopa are as described in the United States Pharmacopoeia (USP-NF2021) monograph on carbidopa-levodopa sustained-release tablets.

[0111] Table 4 10-day stability test data at 60°C and RH75%

[0112] Test 2:

[0113] The samples of Examples 1 to 6 were packaged in aluminum-plastic blisters and compared with the reference preparation (Xinning) and the comparative example. The samples were observed at 40°C and RH75% for 6 months to observe the changes in 3,4-dihydroxypropiophenone in the preparations. The results are shown in Table 5.

[0114] Table 5 6-month stability test data at 40°C and RH75%

[0115] As shown in Tables 4 and 5, the carbidopa sustained-release tablets prepared by the present invention significantly improved the stability of carbidopa in the carbidopa sustained-release tablets compared with the reference preparation, and especially reduced the formation of 3,4-dihydroxypropiophenone, a carbidopa-related substance.

[0116] The above embodiments are merely illustrative of the present invention, and the present invention may also be implemented in other specific ways or in other specific forms without departing from the gist or essential characteristics of the present invention. Therefore, the described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention is to be determined by the appended claims, and any variations equivalent to the intent and scope of the claims are intended to be within the scope of the present invention.

Claims

1. A carbidopa-levodopa composition comprising levodopa, carbidopa and a pharmaceutical carrier, wherein: The pharmaceutical carrier is acrylic resin.

2. The composition according to claim 1, characterized in that The acrylic resin is selected from methacrylic acid and methyl methacrylate copolymer, methacrylic acid and ethyl acrylate copolymer; preferably, the methacrylic acid and methyl methacrylate copolymer is a methacrylic acid and methyl methacrylate (1:1) copolymer, and the methacrylic acid and ethyl acrylate copolymer is a methacrylic acid and ethyl acrylate (1:1) copolymer.

3. The composition according to claim 1, characterized in that The weight ratio of carbidopa to levodopa is 1:4 to 10, preferably 1:

4.

4. The composition according to claim 2, characterized in that Calculated by weight, it comprises: 10.0-20.0%, preferably 17.0-19.0%, of carbidopa; 70.0-95.0%, preferably 70.0-75.0%, of levodopa; and 0.5-15.0%, preferably 1.0-8.0%, and more preferably 1.5-4.0%, of a copolymer of methacrylic acid and methyl methacrylate or a copolymer of methacrylic acid and ethyl acrylate.

5. The composition according to claim 1, characterized in that It also contains one or more of a cellulose derivative, a lubricant, and a colorant.

6. The composition according to claim 5, characterized in that The invention comprises, by weight percentage, 10.0-20.0% carbidopa, preferably 17.0-19.0%; 70.0-95.0% levodopa, preferably 70.0-75.0%; 0.5-15.0% acrylic resin, preferably 1.0-8.0%, more preferably 1.5-4.0%; 1.0-15.0% cellulose derivative, preferably 3.0-8.0%; 0.5-2.0% lubricant, preferably 0.5-1.5%; and 0-2.00% colorant.

7. The composition according to claim 5, characterized in that The cellulose derivative is selected from one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, methyl cellulose, and ethyl cellulose, preferably hydroxypropyl cellulose; the lubricant is selected from one or more of magnesium stearate, talc, stearic acid, silicon dioxide, and sodium stearyl fumarate, preferably magnesium stearate; the colorant is selected from one or more of caramel, red iron oxide, aluminum hydroxide, grape skin extract, beet red powder, β-carotene, annatto, carmine, turmeric, and bell pepper red, preferably one or both of red iron oxide and aluminum hydroxide.

8. The composition according to any one of claims 1 to 7, wherein The composition is further formulated into tablets; preferably sustained-release tablets.

9. The composition according to claim 8, characterized in that The tablets contain the following components: The acrylic resin is a copolymer of methacrylic acid and methyl methacrylate (1:1) or a copolymer of methacrylic acid and ethyl acrylate (1:1).

10. The composition according to claim 9, characterized in that The tablet may further include other pharmaceutically acceptable excipients.

11. The method for preparing the cardiolipin-levodopa composition according to any one of claims 1 to 10, characterized in that: The following steps are involved: (1) Carbidopa, levodopa and cellulose derivatives, optionally with a colorant, are mixed uniformly; (2) Then, a wetting agent is added to the mixture obtained in step (1) for wet granulation and drying; (3) The dried particles in step (2) are evenly mixed with acrylic resin and lubricant; (4). Optionally, the mixture of step (3) is mixed evenly and then compressed into tablets.

12. The preparation method according to claim 11, characterized in that The wetting agent is selected from a single or mixed solvent of water, ethanol, acetic acid, acetone, ethyl acetate, methyl isobutyl ketone, anisole, ethyl ether, 2-methyl-1-propanol, 1-butanol, ethyl formate, 2-butanol, formic acid, n-propanol, butyl acetate, n-heptane, n-pentanol, tert-butyl methyl ether, isopropyl acetate, isobutyl acetate, methyl acetate, 2-propanol, isopropylbenzene, 3-methyl-1-butanol, propyl acetate, dimethyl sulfoxide, and tetrahydrofuran; preferably, the wetting agent is selected from a single or mixed solvent of water and ethanol.

13. Use of the carbendazim-levodopa composition according to any one of claims 1 to 10 in the preparation of a medicament for treating Parkinson's disease or movement disorder-related diseases.