A carbidopa-levodopa gastric-retention sustained-release tablet, a preparation method and use thereof

Abstract

The present application relates to a kind of carbidopa and levodopa gastric retention sustained-release preparation and its preparation method and purposes, belong to medical field.The sustained-release preparation includes levodopa or its pharmaceutically acceptable salt, complex or hydrate, carbidopa or its pharmaceutically acceptable salt, complex or hydrate, also includes auxiliary material, at least one selected from swelling material, delayed release agent and / or gelation material.The carbidopa and levodopa gastric retention sustained-release preparation can achieve long time gastric floating without adding gas generator, and has good sustained-release effect.

Description

Technical Field

[0001] This invention relates to the pharmaceutical field, specifically to a carbapenem / levodopa gastric retention sustained-release formulation, its preparation method, and its uses. Background Technology

[0002] Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease, affecting a large population. It is characterized by resting tremor, bradykinesia, rigidity, and other symptoms that reduce quality of life. Ultimately, it leads to severe disability due to the inability to control motor function. It is mainly caused by the degeneration and loss of dopaminergic neurons in the substantia nigra and a significant reduction in dopamine levels in the striatum.

[0003] Levodopa is currently the first-line drug for treating Parkinson's disease. Levodopa is a prodrug of dopamine, which is metabolized into dopamine in the body by decarboxylases, thus replenishing dopamine in the brain. Because this decarboxylase exists in both the peripheral and central nervous systems, levodopa may be metabolized into water-soluble dopamine in the periphery and unable to cross the blood-brain barrier to reach the brain and exert its effects. Therefore, levodopa is often used in combination with peripheral decarboxylase inhibitors. Commercially available peripheral decarboxylase inhibitors are mainly benserazide and carbidopa. Their function is to inhibit the activity of peripheral dopa decarboxylase, allowing levodopa to cross the blood-brain barrier intact before being metabolized into dopamine to exert its therapeutic effect.

[0004] Since Parkinson's disease is currently incurable, symptoms can only be alleviated by supplementing the brain with dopamine, requiring long-term use of levodopa. As the disease progresses and the duration of medication is prolonged, patients often exhibit several motor complications. These motor complications include the end-of-dose phrenomenon (symptoms relapse before the next dose), drug-induced dyskinesia (drug-induced abnormal movements), and the on-off phrenomenon (unpredictable fluctuations in motor ability).

[0005] The mechanisms underlying these motor complications are not fully understood, but it is generally believed that controlling stable plasma levodopa concentrations can mitigate their occurrence. For patients experiencing a "shutdown" state, rapid onset of medication is required to restore mobility; however, to avoid end-of-dose effects and drug-induced motor dysfunction, medications with a long-lasting, stable release profile are desirable.

[0006] In China, the main Parkinson's disease treatment drugs available are levodopa / carbidopa tablets (Madopar), levodopa / carbidopa capsules, and carbapenem / levodopa extended-release tablets (Sinemet). In the United States, a carbapenem / levodopa extended-release capsule combination is available (RYTARY). Both levodopa / carbidopa tablets and capsules are conventional-release formulations, requiring patients to take the medication four times daily to ensure effective blood drug concentrations, significantly impacting their quality of life. Carbapenem / levodopa extended-release tablets reduce the dosing frequency to 2-3 times daily, but long-term use can lead to end-of-dose and "shutdown" effects, limiting patient mobility and requiring rapid attainment of therapeutic blood drug concentrations after administration. RYTARY combines immediate-release and extended-release components in a capsule, simultaneously meeting the requirements for rapid onset of action and relatively long-term stable blood drug concentrations. However, due to the short half-life of the drug and the intestinal release characteristics of the formulation, patients still need to take it three times daily.

[0007] Gastric retention is a possible solution to this problem and prolong the effective time of the drug. Currently disclosed gastric retention methods for levodopa / carbazide / dopa formulations include: 1) CN110996922A: Matrix gas generation reduces tablet density, allowing the drug to float in gastric juice. Simultaneously, the matrix material rapidly expands upon contact with gastric juice, preventing the tablet from passing through the pylorus. This method has a short gas-generating floating time and poor sustained release effect; it only achieves gastric retention, and the amount of drug absorbed in the intestine may be insufficient due to permeability issues; claims 41-42 describe adding an immediate-release layer to the membrane, resulting in low drug loading and complex manufacturing processes. 2) CN102149369B: A special drug delivery device uses a soft, folded inner layer of drug and swelling material, ultrasonically welded to an outer special material. After entering the stomach, the inner layer swells to achieve gastric retention. This method is difficult to apply to industrial production and has high costs, increasing the economic burden on patients. Summary of the Invention

[0008] To address the aforementioned issues, this invention provides a carbapenem / levodopa gastric retention sustained-release formulation that can be taken twice daily and still exert its effect, possessing sustained-release and / or dual-release properties.

[0009] In a first aspect, the present invention provides a carbapenem / levodopa gastric retention sustained-release formulation, comprising: an active ingredient, a delayed-release agent and other pharmaceutically acceptable excipients.

[0010] The active ingredients include levodopa or a pharmaceutically acceptable salt, complex or hydrate and carbidopa or a pharmaceutically acceptable salt, complex or hydrate;

[0011] The levodopa and carbidopa are present in the formulation in a ratio of about 2:1 to about 5:1.

[0012] In some embodiments, the ratio of levodopa to carbidopa is 4:1;

[0013] The content of the sustained-release agent is 0.2-5 parts by weight of 1 part by weight of active ingredient;

[0014] In some embodiments, the delayed-release agent is 0.6 parts by weight of 1 part by weight of the active ingredient; in some embodiments, the delayed-release agent is 0.8 parts by weight of 1 part by weight of the active ingredient; in some embodiments, the delayed-release agent is 1 part by weight of 1 part by weight of the active ingredient; in some embodiments, the delayed-release agent is 1.2 parts by weight of 1 part by weight of the active ingredient; in some embodiments, the delayed-release agent is 1.6 parts by weight of 1 part by weight of the active ingredient; in some embodiments, the delayed-release agent is 2 parts by weight of 1 part by weight of the active ingredient.

[0015] The delayed-release agent includes at least one of the following: methylcellulose, ethylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose, polyethylene, polyamide, polyvinyl alcohol, polyvinyl acetate, a polyvinyl acetate-povidone mixture, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, and acrylic resin. In some embodiments, the delayed-release agent is a polyvinyl acetate-povidone mixture.

[0016] When the delayed-release agent content in the sustained-release layer is less than or equal to 25 wt%, the tablet can maintain its shape after being placed in the disintegrator for 4 hours, but the tablet becomes soft; when the delayed-release agent content in the sustained-release layer is greater than 25 wt%, the tablet can maintain its shape after being placed in the disintegrator for 4 hours, but the tablet is harder.

[0017] The carbapenem / levodopa gastric retention sustained-release formulation also includes a pharmaceutically acceptable excipient package, which includes, but is not limited to, swelling materials, gelling materials, and lubricants.

[0018] The swelling material includes at least one selected from dried starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, croscarmellose sodium, and croscarmellose. In some embodiments, the swelling material is croscarmellose.

[0019] When a swelling material is used, the problem of tablet sticking during compression is effectively solved. Furthermore, by employing a water-absorbing and rapidly swelling material, the composition allows the tablets to swell to a diameter exceeding the pyloric diameter, preventing them from being smoothly emptied from the stomach. Simultaneously, the expanded tablet volume results in a density less than gastric juice, allowing it to float in the stomach. This combination of swelling and floating principles helps prolong the residence time in the upper digestive tract, avoiding drug waste and increasing drug bioavailability, while also reducing the frequency of administration.

[0020] This invention utilizes a gelling material to induce intestinal adhesion of the active ingredient, resulting in sustained drug release. After sufficient time for drug action, the tablet gradually shrinks due to dissolution and is expelled from the body, avoiding the risk of pyloric obstruction and impaired gastric function.

[0021] The gelling material includes at least one selected from hydroxypropyl methylcellulose, povidone, carbomer, alginate, chitosan, and polyethylene oxide. In some embodiments, the gelling material is a combination of polyethylene oxide and carbomer.

[0022] The lubricant includes at least one selected from magnesium stearate, stearic acid, talc, silica micronized silica powder, and colloidal silica. In some embodiments, the lubricant is magnesium stearate.

[0023] The tablet can be the aforementioned single-layer sustained-release tablet; or it can be a bilayer tablet containing a sustained-release layer and an immediate-release layer, producing dual release characteristics.

[0024] The sustained-release layer in the bilayer sheet includes one or more of the following: active ingredient, swelling material, delayed-release agent, gelling material, adhesive, and lubricant.

[0025] The adhesive includes one or more selected from hydroxypropyl methylcellulose and polyvinylpyrrolidone.

[0026] The active ingredients, swelling materials, delayed-release agents, gelling materials, and lubricants are required to be the same as those for the aforementioned single-layer sustained-release tablets.

[0027] The immediate-release layer of the bilayer tablet includes an active ingredient and other excipients, which include one or more of diluents, disintegrants, binders, and lubricants.

[0028] The adhesive includes one or more selected from hydroxypropyl methylcellulose and polyvinylpyrrolidone.

[0029] The diluent includes one or more of lactose, microcrystalline cellulose, pregelatinized starch, and mannitol. In some embodiments, the diluent is a combination of microcrystalline cellulose and pregelatinized starch.

[0030] The disintegrant includes one or more of croscarmellose sodium, sodium carboxymethyl starch, croscarmellose polyvinylpyrrolidone, and croscarmellose. In some embodiments, the disintegrant is croscarmellose.

[0031] The lubricant includes one or more of magnesium stearate, stearic acid, talc, and micronized silica gel. In some embodiments, the lubricant is magnesium stearate.

[0032] In a second aspect, the present invention provides a method for preparing the carbapenem / levodopa gastric retention sustained-release formulation described in the first aspect.

[0033] A method for preparing the carbapenem / levodopa gastric retention sustained-release formulation described in the first aspect may be wet granulation followed by tableting, dry granulation followed by tableting, or direct compression of powder into tablets.

[0034] The wet granulation followed by tableting includes the following steps:

[0035] (1) Premixing: The active ingredients, delayed release agents, swelling materials and gelling materials are mixed evenly to form a premix;

[0036] (2) Granulation: The binder is mixed with an appropriate amount of purified water to prepare a liquid binder. The premix is ​​mixed with the liquid binder and granulated, dried, and sized to obtain dry granules;

[0037] (3) Mixing: Mix the dry particles with the lubricant evenly to obtain the mixture;

[0038] (4) Tableting: The total mixture is filled into a tablet press and tableted to obtain the sustained-release tablet.

[0039] The dry granulation followed by tableting includes the following steps:

[0040] (1) Premixing: The active ingredients, delayed release agents, swelling materials and gelling materials are mixed evenly to form a premix;

[0041] (2) Granulation: The premix is ​​mixed with the binder and granulated using a dry granulator;

[0042] (3) Mixing: Mix the particles and lubricant evenly to obtain a mixture;

[0043] (4) Tableting: The total mixture is filled into a tableting machine and tableted to obtain the sustained-release tablet.

[0044] The direct compression of the powder into tablets includes the following steps:

[0045] (1) Premixing: The active ingredients, delayed release agents, swelling materials and gelling materials are mixed evenly to form a premix;

[0046] (2) Mixing: Mix the premix with the lubricant until homogeneous to obtain the final mixture;

[0047] (3) Tableting: The total mixture is filled into a tablet press and tableted to obtain the sustained-release tablet.

[0048] The method for preparing the bilayer tablet includes the following steps (taking direct powder compression as an example):

[0049] (1) Mixing of immediate-release layer materials: The active ingredients, fillers and disintegrants are mixed evenly to form a premix; the premix is ​​mixed evenly with the lubricant to obtain the total mixture of immediate-release layer materials;

[0050] (2) Mixing of sustained-release layer materials: Mix the active ingredients, delayed-release agents, swelling materials and gelling materials evenly to form a premix; mix the premix with the lubricant evenly to obtain the total mixture of sustained-release layer materials;

[0051] (3) Tableting: The mixture of immediate-release layer material is filled into the tablet press for pre-compression; the mixture of sustained-release layer material is filled above the pre-compressed layer for main compression; thus, the double-layer tablet is obtained.

[0052] Thirdly, the present invention provides the use of the carbapenem / levodopa gastric retention sustained-release formulation described in the first aspect.

[0053] Use of the aforementioned carbolev-levodopa gastric retention sustained-release formulation in the preparation of a product for the treatment of Parkinson's disease.

[0054] Use of the aforementioned carbolev-levodopa gastric retention sustained-release formulation in the treatment of Parkinson's disease.

[0055] The present invention has the following beneficial effects:

[0056] (1) In the carbapenem-levodopa gastric retention sustained-release formulation provided by the present invention, when the content of the delayed-release agent in the sustained-release layer is less than or equal to 25 wt%, the tablet can maintain its tablet shape after being placed in the disintegrator for 4 hours, but the tablet becomes soft, thus achieving the effect of slow disintegration.

[0057] (2) The carboledopa gastric retention sustained-release formulation provided by the present invention can expand to a size greater than the size of the pyloric sphincter (>12mm) within about 1 hour or less after entering the gastric juice, and the expansion lasts for 6 hours or more; thus achieving the effect of slow release.

[0058] (3) The carbapenem-levodopa gastric retention bilayer sustained-release formulation provided by the present invention has good immediate and sustained release effects. After dissolution for 30 minutes, the cumulative release rate of active ingredients is greater than 40%, and the remaining active ingredients are continuously and slowly released within 8 hours. It can be administered twice a day, reducing the frequency of administration, improving the quality of life of patients, and reducing the burden on patients.

[0059] Terminology definition:

[0060] In the foregoing description of this invention, all figures disclosed herein, whether or not the words “approximately” or “about” are used, are approximate values. Based on the disclosed figures, the value of each figure may vary by less than ±10% or by a difference that is considered reasonable by those skilled in the art, such as ±1%, ±2%, ±3%, ±4%, or ±5%.

[0061] The term “including” and its variations, such as “including” and “contains”, should be understood as open-ended, meaning “including but not limited to”.

[0062] The terms “optional,” “optional,” or “optionally” mean that the event or situation described below may, but is not necessarily, occur. For example, “optional surfactant” means that the surfactant may or may not be present.

[0063] The term “weight percentage” or “percentage by weight” or “wt%” is defined as the weight of a single component in a composition divided by the total weight of all components in the composition and then multiplied by 100.

[0064] The term “and / or” should be understood to mean any one of the options or any combination of two or more of the options.

[0065] In this article, the term "treatment" refers to a clinical intervention intended to alter the natural course of a disease in an individual receiving treatment. Desired therapeutic effects include, but are not limited to, preventing the onset or recurrence of disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, slowing the rate of disease progression, improving or mitigating the disease state, and alleviating or improving prognosis.

[0066] The term "pharmaceutically acceptable" means: a substance or compound that, to the extent of adequate medical judgment, is suitable for contact with human and lower animal tissues without undesirable toxicity, irritation, allergic reactions or similar reactions, and has a reasonably reasonable benefit / risk ratio.

[0067] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0068] In this application, the "composition" can be conveniently presented in unit dose form and can be prepared by any method well known in the pharmaceutical industry. All methods involve the step of combining the active ingredient with a carrier constituting one or more adjunct components. Typically, the composition is prepared by uniformly and sufficiently combining the active compound with a liquid carrier, a finely pulverized solid carrier, or both. Attached Figure Description

[0069] Figure 1This is a comparison graph of the carbidopa blood concentration-time changes between the carbidopa gastric retention sustained-release bilayer tablets prepared in Example 1 and the control formulation.

[0070] Figure 2 This is a comparison graph of the blood concentration-time changes of levodopa in the carbodopa / levodopa gastric retention sustained-release bilayer tablets prepared in Example 1 and the control formulation.

[0071] Figure 3 This is a comparison graph of the carbidopa blood concentration-time changes between the carbidopa gastric retention sustained-release monolayer tablets prepared in Example 7 and the control formulation.

[0072] Figure 4 This is a graph comparing the blood concentration-time changes of levodopa in the carbapenem / levodopa gastric retention sustained-release monolayer tablets prepared in Example 7 with the control formulation. Detailed Implementation

[0073] To enable those skilled in the art to better understand the technical solutions of the present invention, some non-limiting embodiments are further disclosed below to provide a more detailed description of the present invention.

[0074] All reagents used in this invention can be purchased commercially or prepared by the methods described in this invention.

[0075] Example

[0076] Examples 1-5: Preparation of Carbohydrate-Levodopa Gastric Retention Sustained-Release Bilayer Tablets

[0077] Table 1. Dosage of Levodopa / Carbazoline Dual-Dopa Gastric Retention Sustained-Release Bilayer Tablets in Examples 1-5 (by weight, unit / mg)

[0078]

[0079]

[0080] The immediate-release layer consists of a uniform mixture of levodopa, carbidopa, pregelatinized starch, microcrystalline cellulose, and crospovidone, and a total amount of magnesium stearate is added. The mixture is then pre-compressed using a tablet press. The sustained-release layer consists of a uniform mixture of levodopa, carbidopa, polyvinyl acetate-povidone mixture, crospovidone, polyoxyethylene, and carbomer, and a total amount of magnesium stearate is added. The mixture is then filled onto the pre-compressed layer, and the main compression is performed simultaneously to obtain the gastric retention sustained-release bilayer tablet.

[0081] Examples 6-8: Preparation of Levodopa Gastric Retention Sustained-Release Tablets

[0082] Table 2. Prescription dosage of 6-8 kcal / mg Levodopa gastric retention sustained-release tablets (by weight, unit / mg)

[0083]

[0084] The prescribed amounts of levodopa, carbidopa, polyvinyl acetate-povidone mixture, crospovidone, polyoxyethylene and carbomer are mixed evenly, and the prescribed amount of magnesium stearate is added and mixed. The mixture is then filled into a tablet press and compressed to obtain the gastric retention sustained-release tablet.

[0085] Swelling test

[0086] The tablets prepared in Examples 1 and 7 were placed in hydrochloric acid medium at pH 1.2, and the swelling of the tablets at different times was investigated. The results are shown in Tables 3 and 4. This indicates that the tablets of Examples 1 and 7 have good swelling properties and can swell in the stomach to achieve a retention effect. During sample loading, the tablets floated on the surface of the medium within 5 seconds.

[0087] Table 3

[0088] time Average length / mm Average width / mm Average thickness / mm Expansion rate / % Before sampling 22.31 10.90 8.39 N / A Sampling for 1 hour 23.24 12.67 8.47 122 4 hours of sampling 24.21 13.13 9.79 152 8 hours of sampling 25.81 13.32 10.32 173

[0089] Table 4

[0090] time Average length / mm Average width / mm Average thickness / mm Expansion rate / % Before sampling 22.28 10.93 6.81 N / A Sampling for 1 hour 23.39 12.09 8.33 142 4 hours of sampling 24.10 12.65 9.60 176 8 hours of sampling 25.79 13.40 10.15 212

[0091] Comparative study of human pharmacokinetics

[0092] This study aimed to evaluate two test formulations, A1 (a carbapenem / levodopa gastric retention sustained-release bilayer tablet prepared in Example 1) and A2 (a carbapenem / levodopa gastric retention sustained-release bilayer tablet prepared in Example 7), and a control formulation (trade name: Specifications: Carbidopa 50mg, Levodopa 200mg; Batch No.: T035302; Content: Levodopa 99.5%, Carbidopa 99.1%; Production Date: July 14, 2021) The difference in the rate and extent of absorption of the test formulation and the control formulation in healthy subjects.

[0093] To be selected as a participant, all of the following criteria must be met:

[0094] 1) Gender: No gender restriction (appropriate male-female ratio), agree to refrain from unprotected sexual intercourse during the study period and for 6 months after the study, and must use physical contraception during the study period;

[0095] 2) Age: 18–45 years old, including boundary values;

[0096] 3) Weight: Men weighing ≥ 50 kg, women weighing ≥ 45 kg, with a body mass index (BMI) between 18-28 kg / m². 2 Between (BMI = weight (kg) / height) 2 (m 2 (including boundary values);

[0097] 4) Voluntarily sign a written informed consent form;

[0098] Exclusion criteria:

[0099] 1) Individuals with known hypersensitivity to this product or any of its excipients, or those with an allergic constitution; (medical history taking)

[0100] 2) Individuals with a history of serious illnesses affecting the cardiovascular, endocrine, nervous, respiratory, hematological, immunological, psychiatric, or metabolic systems; (medical history taking)

[0101] Based on the inclusion and exclusion criteria, 10 healthy subjects were enrolled in the fasting study.

[0102] This study employed a parallel design, with subjects taking the test formulation (A1), test formulation (A2), and control formulation (B) in the first, second, and third cycles, respectively.

[0103] First cycle: Subjects were admitted to the ward one day before administration and fasted for more than 10 hours. On the morning of administration, they took one tablet of the test preparation (A1) carbidopa extended-release tablet (specification: carbidopa 50mg, levodopa 200mg) with 240mL of water on an empty stomach.

[0104] Cleaning period: 7 days.

[0105] Second and third cycles: Subjects took the test formulation (A2) and control formulation (B) in the second and third cycles respectively, with other procedures the same as in the first cycle.

[0106] Blood sample collection:

[0107] After medication administration, 3 mL of venous blood was collected from subjects at 0 h before administration and at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, and 24 h after administration. The blood samples were placed in pre-chilled EDTA-K2 anticoagulant tubes and stored on ice after collection. A total of 170 (17*10) tubes of venous blood (3 mL / tube) were collected per cycle. Under ice-water bath conditions, the upper plasma layer was divided into two portions and transferred to labeled cryovials containing 100 μL of 500 g / L sodium metabisulfite. Each cryovial contained 700 μL of plasma, and the mixture was vortexed for 5 seconds. One portion was used for analysis, and the other was used as a backup. Both were immediately stored at approximately -20°C and transferred to an ultra-low temperature freezer at -80°C after each blood collection cycle, or directly placed in an ultra-low temperature freezer at -80°C. Samples must be kept under cryogenic conditions for at least 2 hours before being transferred to the analytical testing unit.

[0108] Safety assessment:

[0109] Physical examinations, vital signs (blood pressure, pulse, temperature), ECG, and laboratory tests were performed during study screening and follow-up after the study. Throughout the study and follow-up period, if any adverse events occurred in the subjects or if clinically significant abnormal laboratory test values ​​were found, the abnormalities were followed up until they returned to normal or the condition stabilized.

[0110] The concentrations of levodopa and carbidopa in plasma should be determined using validated analytical methods. The evaluation of the detection methods should comply with the requirements of the Chinese Pharmacopoeia 2020 edition "9012 Validation Guidelines for Quantitative Analysis Methods for Biological Samples" and GCP.

[0111] Based on each subject's individual blood drug concentration-time data, a comparison graph of blood drug concentration-time changes for carbidopa and levodopa was plotted.

[0112] Depend on Figures 1-4 It can be seen that the self-developed group (carbohydrate, levonorgestrel, and dopamine in gastric retention sustained-release bilayer tablets and monolayer tablets) showed a slower rate of decrease in blood drug concentration compared to the control group (control formulation), thus achieving a better sustained-release effect. Furthermore, the bilayer tablets, due to the addition of an immediate-release layer, rapidly increased blood drug concentration after administration. Compared to the control group's three-times-a-day dosing frequency, the self-developed group achieved a dosing frequency of twice a day while maintaining the therapeutic effect of the drug.

Claims

1. A gastro-retentive, sustained-release formulation of carbidopa-levodopa characterized in that, The gastric retention sustained-release preparation is a tablet, which can be a single-layer tablet or a double-layer tablet comprising a fast-release layer and a slow-release layer, and the double-layer tablet comprises the following components: The single-layer tablet comprises the following components: 。 2. A preparation method of the gastric retention sustained-release preparation of carbidopa-levodopa according to claim 1, characterized in that, The tablet can be prepared by wet granulation, dry granulation or direct compression of powder.

3. Use of the gastric retention sustained-release preparation of carbidopa-levodopa according to claim 1 or the gastric retention sustained-release preparation of carbidopa-levodopa obtained by the method of claim 2 in the preparation of a product for treating Parkinson's disease.

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