CN114224878B - Compound medicine for treating Parkinson's disease - Google Patents
Compound medicine for treating Parkinson's disease Download PDFInfo
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- CN114224878B CN114224878B CN202210056368.4A CN202210056368A CN114224878B CN 114224878 B CN114224878 B CN 114224878B CN 202210056368 A CN202210056368 A CN 202210056368A CN 114224878 B CN114224878 B CN 114224878B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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Abstract
The invention discloses a compound medicine for treating Parkinson's disease, and belongs to the technical field of medicine preparation. The compound medicine comprises the following components in parts by weight: 250 parts of levodopa, 56 parts of benserazide hydrochloride, 4-7 parts of microcrystalline cellulose, 40-60 parts of mannitol, 40-60 parts of calcium hydrophosphate, 15-20 parts of pregelatinized starch, 10-15 parts of crospovidone, 10-15 parts of povidone, 3-7 parts of ethyl cellulose and 3-7 parts of magnesium stearate. The compound medicine tablet of the invention has small tablet shape and is easy to swallow. And a layer of hydrophobic protective film is formed outside the granules, so that the tablets have high performance, the requirements of packaging materials needing high-barrier materials can be met by using conventional aluminum-plastic packaging, and the tablet has important medical value. In addition, the preparation method is simple to operate, omits the process steps of separately drying the levodopa and the benserazide, and has great economic value.
Description
Related patent
The invention relates to a divisional application of Chinese patent application with the application number of 202110425424.2, the application date of 20/04 in 2021, which is named as ' a compound medicine for treating Parkinson's disease and a preparation method thereof '.
Technical Field
The invention belongs to the technical field of medicine preparation, and particularly relates to a compound medicine for treating Parkinson's disease.
Background
Parkinson's disease, like Alzheimer's disease, is a common degenerative disease of the nervous system, and there is no effective treatment at present. Studies have shown that dopamine is deficient in the basal ganglia of patients with parkinson's disease or parkinson's syndrome, and therefore the current treatments are mainly based on drugs that control dopamine secretion, deep brain electrical stimulation using electric current, and the like.
Unlike dopamine, which does not naturally enter the brain itself (through the blood-brain barrier), levodopa can cross the blood-brain barrier into the center, acting as a direct metabolic precursor of dopamine, which makes dopamine replacement therapy feasible. However, levodopa is rapidly decarboxylated outside the brain to convert to dopamine, which results in a great waste of levodopa and frequent adverse reactions. It would therefore be beneficial to inhibit the decarboxylation of levodopa outside the brain, which can be achieved by the simultaneous administration of levodopa and an extracerebral decarboxylase inhibitor, such as benserazide. Clinical practice shows that the compound preparation (poly-barusine) with the ratio of 4:1, namely the commercial medicine medobab, can obtain good curative effect, has the same effect as large dose of levodopa, and has much better tolerance. After long-term use of the poly-barusine, the symptoms of the Parkinson's disease are obviously improved, and the poly-barusine compound preparation is a first-line medicament for treating the Parkinson's disease or the Parkinson's disease.
The Chinese invention patent CN101797244B discloses a bazedoary oral disintegrating tablet, however, at present, only bazedoary tablet common preparations are available in domestic market, the oral disintegrating tablet is not on the market, and only Meiduo has clinical availability in domestic market.
The US4424235 discloses a hydrodynamics balance controlled release composition containing levodopa and a decarboxylase inhibitor, the method provides a preparation method of a poly-baryonazine sustained and controlled release preparation, the weight of the poly-baryonazine preparation prepared by the method reaches 550mg, levodopa and benserazide are required to be separately granulated and are scored, the preparation process is complicated, the tablets are large, and certain risk is caused to patients suffering from Parkinson swallowing.
Disclosure of Invention
In order to solve at least one of the above technical problems, the technical solution provided by the present invention is as follows:
the invention provides a compound medicine for treating Parkinson's disease, which comprises the following components in parts by weight: 250 parts of levodopa, 56 parts of benserazide hydrochloride, 4-7 parts of microcrystalline cellulose, 40-60 parts of mannitol, 40-60 parts of calcium hydrophosphate, 15-20 parts of pregelatinized starch, 10-15 parts of crospovidone, 10-15 parts of povidone, 3-7 parts of ethyl cellulose and 3-7 parts of magnesium stearate.
In the compound medicine, the levodopa and the benserazide hydrochloride are main medicine components. Wherein 56 parts of benserazide hydrochloride is equivalent to 49.12 parts of benserazide, and the weight ratio of levodopa to benserazide is more than 5:1. the compound medicine of the invention breaks through the situation that the weight ratio of levodopa to benserazide in the traditional poly-barfilament hydrazine is 4: the proportion of 1 is restricted, and unexpected technical effect is achieved.
In the invention, in the compound medicine, the microcrystalline cellulose is a disintegrant; the mannitol is a filling agent; the calcium hydrophosphate is a filler and a retarder; the pregelatinized starch is an adhesive; the crospovidone is a disintegrant; the povidone is an adhesive; the ethyl cellulose is a protective coating; the magnesium stearate is a lubricant.
In some embodiments of the invention, the following components are included in parts by weight: 250 parts of levodopa, 56 parts of benserazide hydrochloride, 4.95 parts of microcrystalline cellulose, 50 parts of mannitol, 50 parts of calcium hydrophosphate, 18.7 parts of pregelatinized starch, 12 parts of crospovidone, 11 parts of povidone, 5 parts of ethyl cellulose and 5.5 parts of magnesium stearate.
A second aspect of the present invention provides a method for preparing the compound medicament of the first aspect of the present invention, comprising the steps of:
s1, sieving the total amount of levodopa, the total amount of calcium hydrophosphate, the total amount of pregelatinized starch, the total amount of microcrystalline cellulose and the total amount of crospovidone, stirring and mixing to obtain a first mixture, and adding a part of povidone aqueous solution to prepare first wet granules;
s2, sieving the total amount of benserazide hydrochloride and the total amount of mannitol, stirring and mixing to obtain a second mixture, and adding the rest of ethanol solution of povidone to prepare second wet granules;
s3, mixing the first wet particles obtained in the step S1 and the second wet particles obtained in the step S2 into a third mixture, adding an ethanol solution of the total amount of the ethyl cellulose, and drying;
and S4, adding the total amount of magnesium stearate into the dried material obtained in the step S3, and mixing.
In some embodiments of the invention, step S1 specifically comprises:
s11, sieving the total amount of levodopa, the total amount of calcium hydrophosphate, the total amount of pregelatinized starch, the total amount of microcrystalline cellulose and the total amount of crospovidone, adding the sieved materials into a wet granulator, and stirring for 5 minutes to obtain a first mixture;
s12, dissolving a part of povidone in purified water, and stirring until the povidone is completely dissolved to obtain povidone aqueous solution;
s13, slowly adding the povidone aqueous solution obtained in the step S12 into the first mixture obtained in the step S11 by using a peristaltic pump, stirring while adding, and starting a cutter of a granulator for 2 minutes after adding is completed within 3 minutes to obtain first wet granules;
s14, placing the first wet particle discharging material in the step S13 into a sealed container.
In some embodiments of the invention, step S2 specifically comprises:
s21, sieving the total amount of benserazide hydrochloride and the total amount of mannitol, adding into a wet granulator, and stirring for 5 minutes to obtain a second mixture;
s22, dissolving the rest of povidone in ethanol, and stirring until the povidone is completely dissolved to obtain povidone ethanol solution;
s23, slowly adding the povidone ethanol solution obtained in the step S22 into the second mixture obtained in the step S21 through a peristaltic pump, stirring while adding, and starting a cutter of a granulator for 1 minute after adding is completed within 2 minutes to obtain second wet granules;
s23, placing the second wet particle discharge obtained in the step S23 in a sealed container.
In some embodiments of the invention, step S3 specifically comprises:
s31, transferring the first wet granules in the step S1 and the second wet granules in the step S2 to a fluidized bed;
s32, dissolving ethyl cellulose in ethanol, and stirring until the ethyl cellulose is completely dissolved to obtain an ethyl cellulose ethanol solution;
s33, starting a granulation function of the fluidized bed, slowly spraying the ethyl cellulose ethanol solution in the step S32 onto the first wet granules and the second wet granules in the fluidized bed through a peristaltic pump, and finishing spraying within 5 minutes;
and S34, drying until the moisture of the material is lower than 1.2%.
In some embodiments of the invention, in step S34, the drying is carried out to a moisture content of the material of less than 1.0%.
In some embodiments of the invention, step S4 specifically comprises:
s41, transferring the material dried in the step S3 to a mixer;
and S42, sieving the total amount of magnesium stearate, adding the sieved magnesium stearate into the mixer in the step S41, and starting total mixing for 8 minutes to obtain the compound medicine.
In some embodiments of the invention, step S4 further comprises:
s43, tabletting the compound medicine.
In some embodiments of the invention, in step S1, the partial amount of povidone means 2/3 to 3/4 of the total amount. In some embodiments of the invention, the total amount of povidone is 11 parts by weight and the partially polymerized portion amount of povidone is 8 parts by weight of povidone.
The invention has the advantages of
Compared with the prior art, the invention has the following beneficial effects:
the prior art of the polysilzide tablet has complex preparation process, large tablet size and certain risk for swallowing of Parkinson patients, and the benserazide is very easy to hydrolyze, and the degradation of impurities is not well controlled. The compound medicine of the invention weighs about 465mg per tablet, and the tablet shape is smaller than that of the marketed MEIDOUBA product, and the weight of the tablet is 553mg per tablet.
The existing product has poor stability, and can reach a qualified product only by using a glass bottle or an aluminum-aluminum package. The compound medicine tablet prepared by the invention forms a layer of hydrophobic protective film outside the granules, and unexpectedly, the requirements of packaging materials needing high-barrier materials can be met by using conventional aluminum-plastic packaging.
The preparation method provided by the invention is simple to operate, omits the process steps of single drying of levodopa and benserazide, saves resources, and has great economic value.
The compound medicine prepared by the invention is a first-line basic treatment medicine in the Parkinson medicine treatment guideline, only an imported medicine 'Meiduoba' is sold in the market at present, the compound medicine prepared by the invention has one more choice for guaranteeing the medication of Parkinson patients, the medicine treatment cost of the patients can be reduced, and the compound medicine has high social value.
Drawings
Figure 1 shows the dissolution profile of a combination drug prepared according to example 1 of the present invention and medoba.
Detailed Description
Unless otherwise indicated, implicit from the context, or customary in the art, all parts and percentages herein are based on weight and the testing and characterization methods used are in step with the filing date of the present application. Where applicable, the contents of any patent, patent application, or publication referred to in this application are incorporated herein by reference in their entirety, and the equivalent family of patents is also incorporated by reference, in particular for the definitions set forth in these documents regarding synthetic techniques, product and process designs, polymers, comonomers, initiators or catalysts, and the like, in the art. To the extent that a definition of a particular term disclosed in the prior art is inconsistent with any definitions provided herein, the definition of the term provided herein controls.
The numerical ranges in this application are approximations that can include values outside of the ranges unless otherwise specified. A numerical range includes all numbers from a lower value to an upper value, in increments of 1 unit, provided that there is a separation of at least 2 units between any lower value and any higher value. For example, if a compositional, physical, or other property (e.g., molecular weight, melt index, etc.) is recited as 100 to 1000, it is intended that all individual values, e.g., 100, 101, 102, etc., and all subranges, e.g., 100 to 166, 155 to 170, 198 to 200, etc., are explicitly recited. For ranges containing a numerical value less than 1 or containing a fraction greater than 1 (e.g., 1.1,1.5, etc.), then 1 unit is considered to be 0.0001,0.001,0.01, or 0.1, as appropriate. For ranges containing single digit numbers less than 10 (e.g., 1 to 5), 1 unit is typically considered 0.1. These are merely specific examples of what is intended to be expressed and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application.
In addition, unless explicitly stated otherwise, the use of the terms "a", "an" or "the" are intended to include the plural forms as well. The terms "comprising," "including," "having," and derivatives thereof do not exclude the presence of any other component, step or procedure, and are not intended to exclude the presence of other elements, steps or procedures not expressly disclosed herein. To the extent that any doubt is eliminated, all compositions herein containing, including, or having the term "comprise" may contain any additional additive, adjuvant, or compound, unless expressly stated otherwise. Conversely, the term "consisting essentially of 8230%, \8230composition" excludes any other components, steps or processes from the scope of any of the terms hereinafter recited, insofar as those terms are necessary for operational performance. The term "consisting of 8230%" \8230comprises "does not include any components, steps or processes not specifically described or listed. Unless explicitly stated otherwise, the term "or" refers to the listed individual members or any combination thereof.
In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more clear, the present invention is further described in detail below with reference to the embodiments.
Examples
The following examples are used herein to demonstrate preferred embodiments of the invention. It will be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function in the invention, and thus can be considered to constitute preferred modes for its practice. Those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit or scope of the invention.
Unless defined otherwise, 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 invention belongs and the disclosures and references cited herein and the materials to which they refer are incorporated by reference.
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
The experimental methods not specifically described in the following examples are all conventional methods unless otherwise specified. The instruments used in the following examples are, unless otherwise specified, laboratory-standard instruments; the test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified.
Example 1 Compound medicine for treating Parkinson's disease and preparation method thereof
The embodiment provides a compound medicine for treating Parkinson's disease, which is a tablet, and the content of each 1000 tablets is as follows:
| composition (I) | Content (g) | Function(s) |
| Levodopa (L-dopa) | 250 | Principal Components |
| Benserazide hydrochloride | 56 | Principal component |
| Microcrystalline cellulose | 4.95 | Disintegrating |
| Mannitol | ||
| 50 | Filler | |
| |
50 | Fillers and retarders |
| Pregelatinized starch | 18.7 | Adhesive agent |
| Cross-linked polyvidone | 12 | Disintegrating agent |
| Povidone | 11 | Adhesive agent |
| Ethyl cellulose | 5 | Protective coating |
| Magnesium stearate | 5.5 | Lubricant agent |
The preparation method of the compound medicine comprises the following steps:
pulverizing levodopa, benserazide hydrochloride and adjuvants respectively, sieving, and storing.
The preparation method comprises four main steps of A, B, C and D:
a: preparation of wet granules comprising levodopa
Step one, adding the total amount of levodopa, the total amount of calcium hydrophosphate, the total amount of pregelatinized starch, the total amount of microcrystalline cellulose and the total amount of crospovidone into a wet granulator, and stirring for 5 minutes;
step two, dissolving 8g of povidone in 20g of purified water, and stirring until the povidone is completely dissolved;
step three, slowly adding the solution in the step two into the mixture in the step one in the wet granulator through a peristaltic pump, stirring while adding, and starting a cutter of the granulator for 2 minutes after adding is finished within 3 minutes;
step four, discharging the wet particles in the step three and placing the discharged wet particles in a sealed container;
b: preparation of Wet granules containing benserazide
Step one, sieving the total amount of benserazide hydrochloride and the total amount of mannitol, adding into a wet granulator, and stirring for 5 minutes;
step two, dissolving the rest 3g of povidone in 15g of ethanol, and stirring until the povidone is completely dissolved;
step three, slowly adding the solution in the step two into the mixture in the step one in the wet granulator through a peristaltic pump, stirring while adding, and starting a cutter of the granulator for 1 minute after adding within 2 minutes;
step four, discharging the wet particles in the step three and placing the discharged wet particles in a sealed container;
c: preparation of a Dry Material comprising Levodopa and benserazide
Transferring the wet granules in the step four of the part A and the step four of the part B into a fluidized bed;
step two, dissolving ethyl cellulose in 50g of ethanol, and stirring until the ethyl cellulose is completely dissolved;
step three, starting a granulation function of a fluidized bed, slowly spraying the solution in the step two onto the wet granules in the step one in the fluidized bed through a peristaltic pump, and finishing spraying within 5 minutes;
and step four, continuously drying until the moisture content is lower than 1.0%.
D: preparation of compound medicine finished product
Step one, transferring the dried material in the step C to a mixer;
step two, adding the sieved magnesium stearate into the mixer in the step one; starting total mixing for 8 minutes; and the content uniformity is measured to be qualified;
step three, tabletting;
step four, aluminum-plastic packaging, wherein the aluminum foil is 28 microns and the PVC/PCTFE 2000 type is adopted.
The compound medicine prepared by the preparation method has the weight of about 465mg per tablet, and the tablet shape is smaller than that of the marketed MEIDOUBA product, and the weight of the tablet is 553mg per tablet. In addition, the preparation method omits the process step of separately drying levodopa and benserazide, a layer of hydrophobic protective film is formed outside the particles, and unexpectedly, the requirement of the packaging material needing the high-barrier material can be met by using the conventional aluminum-plastic packaging.
Example 2 comparison of the Performance of the combination of the drug for the treatment of Parkinson's disease prepared in example 1 with that of Meloba-
The compound medicine for treating parkinson's disease prepared in example 1 was compared in performance with medoba (roche).
First, the dissolution curves of the compound medicine for treating parkinson's disease prepared in example 1 and medoba were measured by high performance liquid chromatography, respectively, and the results are shown in fig. 1. The result shows that the degree of matching f2 of the dissolution curve of the compound medicine prepared in the example 1 and the meduoba reaches 74.3.
The stability of the compound medicine prepared in example 1 and related substances of medoba was measured by high performance liquid chromatography (8230), and the results are shown in table 1.
TABLE 1 comparative table of stability data of substances
As can be seen from table 1, the compound drug prepared in example 1 has significantly lower impurity content than medoba. Before storage, meduoba contained 0.03%, 1.40%, 0.17%, 0.13% and 2.2% of impurity a, impurity B, impurity C, impurity D and total impurities, respectively, whereas the compound drug prepared in example 1 contained no impurity a and contained 0.39%, 0.05%, 0.14% and 0.85% of impurity B, impurity C, impurity D and total impurities, respectively. After 10 days of storage, meduoba contained 0.09%, 1.97%, 0.17%, 0.22% and 2.9% of impurity a, impurity B, impurity C, impurity D and total impurities, respectively, while the compound drug prepared in example 1 contained 0.04%, 0.51%, 0.05%, 0.18% and 1.2% of impurity a, impurity B, impurity C, impurity D and total impurities, respectively. Therefore, the impurities of the compound medicine prepared in the example 1 are low, and the total impurity content is obviously lower than that of meduoba.
All documents mentioned in this application are incorporated by reference in this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.
Claims (9)
1. The compound medicine for treating Parkinson's disease is characterized by comprising the following components in parts by weight: 250 parts of levodopa, 56 parts of benserazide hydrochloride, 4 to 7 parts of microcrystalline cellulose, 40 to 60 parts of mannitol, 40 to 60 parts of calcium hydrophosphate, 15 to 20 parts of pregelatinized starch, 10 to 15 parts of crospovidone, 10 to 15 parts of povidone, 3 to 7 parts of ethyl cellulose and 3 to 7 parts of magnesium stearate, wherein the preparation method of the compound medicine comprises the following steps:
s1, sieving the total amount of levodopa, the total amount of calcium hydrophosphate, the total amount of pregelatinized starch, the total amount of microcrystalline cellulose and the total amount of crospovidone, stirring and mixing to obtain a first mixture, and adding a part of povidone aqueous solution to prepare first wet granules;
s2, sieving the total amount of benserazide hydrochloride and the total amount of mannitol, stirring and mixing to obtain a second mixture, and adding the rest of ethanol solution of povidone to prepare second wet granules;
s3, mixing the first wet particles obtained in the step S1 and the second wet particles obtained in the step S2 into a third mixture, adding an ethanol solution of the total amount of the ethyl cellulose, and drying;
and S4, adding the total amount of magnesium stearate into the dried material obtained in the step S3, and mixing.
2. The compound medicine according to claim 1, characterized by comprising the following components in parts by weight: 250 parts of levodopa, 56 parts of benserazide hydrochloride, 4.95 parts of microcrystalline cellulose, 50 parts of mannitol, 50 parts of calcium hydrophosphate, 18.7 parts of pregelatinized starch, 12 parts of crospovidone, 11 parts of povidone, 5 parts of ethyl cellulose and 5.5 parts of magnesium stearate.
3. The compound medicine according to claim 1, wherein the preparation method comprises the following step S1:
s11, sieving the total amount of levodopa, the total amount of calcium hydrophosphate, the total amount of pregelatinized starch, the total amount of microcrystalline cellulose and the total amount of crospovidone, adding the sieved materials into a wet granulator, and stirring for 5 minutes to obtain a first mixture;
s12, dissolving a part of povidone into purified water, and stirring until povidone is completely dissolved to obtain povidone aqueous solution;
s13, slowly adding the povidone aqueous solution obtained in the step S12 into the first mixture obtained in the step S11 by using a peristaltic pump, stirring while adding, and starting a cutter of a granulator for 2 minutes after the addition is finished within 3 minutes to obtain first wet granules;
s14, placing the first wet particle discharging material in the step S13 into a sealed container.
4. The compound medicine according to claim 1, wherein the preparation method comprises the following step S2:
s21, sieving the total amount of benserazide hydrochloride and the total amount of mannitol, adding into a wet granulator, and stirring for 5 minutes to obtain a second mixture;
s22, dissolving the rest of povidone in ethanol, and stirring until the povidone is completely dissolved to obtain povidone ethanol solution;
s23, slowly adding the povidone ethanol solution obtained in the step S22 into the second mixture obtained in the step S21 by using a peristaltic pump, stirring while adding, and starting a cutter of a granulator for 1 minute after adding is completed within 2 minutes to obtain second wet granules;
s23, placing the second wet particle discharging material in the step S23 in a sealed container.
5. The compound medicine according to claim 1, wherein the preparation method comprises the following step S3:
s31, transferring the first wet granules in the step S1 and the second wet granules in the step S2 to a fluidized bed;
s32, dissolving ethyl cellulose in ethanol, and stirring until the ethyl cellulose is completely dissolved to obtain an ethyl cellulose ethanol solution;
s33, starting a granulation function of the fluidized bed, slowly spraying the ethyl cellulose ethanol solution in the step S32 onto the first wet granules and the second wet granules in the fluidized bed through a peristaltic pump, and finishing spraying within 5 minutes;
and S34, drying until the moisture of the material is lower than 1.2%.
6. The combination drug of claim 5, wherein in step S34, the mixture is dried to a moisture content of less than 1.0%.
7. The compound medicine according to claim 1, wherein the step S4 in the preparation method specifically comprises:
s41, transferring the dried material in the step S3 to a mixer;
and S42, sieving the total amount of magnesium stearate, adding the sieved magnesium stearate into the mixer in the step S41, and starting total mixing for 8 minutes to obtain the compound medicine.
8. The compound medicine of claim 7, wherein the preparation method of step S4 further comprises:
s43, tabletting the compound medicine.
9. The compound medicine according to any one of claims 1 to 8, wherein in the preparation method, in step S1, the partial amount of povidone is 2/3 to 3/4 of the total amount.
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| WO2006035414A2 (en) * | 2004-09-30 | 2006-04-06 | Ranbaxy Laboratories Limited | Carbidopa and levodopa dispersible tablets |
| CN101623278B (en) * | 2008-07-09 | 2013-02-27 | 北京德众万全药物技术开发有限公司 | Medicinal composition containing levodopa and benserazide hydrochloride |
| CN101926785A (en) * | 2009-06-18 | 2010-12-29 | 北京科信必成医药科技发展有限公司 | Medicinal controlled release preparation for treating parkinsonism and preparation method thereof |
| CN101797244B (en) * | 2010-04-01 | 2012-07-04 | 青岛科技大学 | Levodopa/benserazide orally disintegrating tablet |
| CN102885804B (en) * | 2011-07-20 | 2015-09-02 | 上海信谊药厂有限公司 | Dopamine prodrug composition and preparation method thereof |
| CN103127117A (en) * | 2011-12-02 | 2013-06-05 | 苏州法莫生物技术有限公司 | Pharmaceutical composition of levodopa/benserazide/folic acid compounds and purpose thereof |
| CN105078952A (en) * | 2015-08-10 | 2015-11-25 | 中国康复研究中心 | Levodopa preparation and application thereof |
| ES2895054T3 (en) * | 2016-08-18 | 2022-02-17 | Ilko Ilac Sanayi Ve Ticaret Anonim Sirketi | Antiparkinson tablet formula with improved dissolution profile |
| JP7066351B2 (en) * | 2017-08-18 | 2022-05-13 | 大原薬品工業株式会社 | Levodopa-containing miniaturized tablets with good sustained release |
| CN107951875A (en) * | 2017-12-05 | 2018-04-24 | 王增强 | A kind of composite preparation containing levodopa |
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