CN108815131B - Ganglioside sustained release tablet and preparation method thereof - Google Patents
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Abstract
The invention discloses a ganglioside sustained-release tablet and a preparation method thereof, wherein the ganglioside sustained-release tablet is prepared from monosialoganglioside and a special pharmaceutic adjuvant by a special method of the invention. Simple process and low cost, and can effectively reduce the price of the medicine and reduce the burden of patients. Meanwhile, the prepared sustained-release tablet has good sustained-release effect, can be carried by a patient to supplement the medicine at any time, and is convenient to use.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to ganglioside sustained-release tablets.
Background
Gangliosides are a class of glycosphingolipids containing sialic acid, which are constituents of mammalian cell membranes and are particularly abundant in the nervous system. Its common name is monosialotetrahexosylganglioside sodium. The compound is mainly used for treating traumatic or vascular diseases of the central nervous system, such as brain injury, spinal cord injury, ischemic and hemorrhagic cerebrovascular accidents and Parkinson's disease, and has the following chemical structure:
along with the acceleration of the development process of the global aging society, the attention of governments of various countries to related diseases of the nervous system is greatly improved. Japanese and America successively release 'guide principles for treating cerebral apoplexy' and 'guidelines for treating adult ischemic cerebral apoplexy' in early stage. The department of health, China, and the department of health, and the department of Chinese medicine, the neurologic society of China, issued the guidelines for the prevention and treatment of brain disease, China. The formulation of the guideline provides more treatment methods for the clinical treatment of the nervous system, and improves the understanding of anticoagulation, thrombolysis, antiplatelet and brain protective agents to a certain extent. Although affected by regional differences, ethnic differences and prognosis evaluation, the development direction of stroke treatment drugs is still continuously explored, and the release of guidelines further guides clinical treatment drugs and objectively promotes the development of the nervous system drug market. The first discovery by the American S-BASSL neurologist was that the sodium ganglioside preparation (GM1) defines its function in promoting the regeneration of dendrites from damaged nerve cells. In 1984, China has participated in the clinical study of 'compound ganglioside for treating peripheral neuropathy' promoted by the world health organization; in 1995, the ganglioside preparation was successfully extracted from Chinese academy of China, and the drug of Brazilian TRB Pharma Ind Quimica EFarmaceuticala Ltd was approved and imported by the national drug administration for registration-the Monosialotetrahexosyl ganglioside sodium injection "remolde" (SYGEN) extracted from bovine brain; subsequently, the ganglioside sodium salt injection 'shijiein' (GM-1) extracted from the pig brain of Argentina TRB Pharma company is registered and imported, thereby avoiding the danger that the mad cow disease is possibly caused by extracting from the cow brain and being widely applied to treating the central nervous lesion.
The clinic shows that the monosialotetrahexosyl ganglioside sodium is a glycolipid compound substance with small molecular weight, can penetrate through a blood barrier and be directly embedded on a damaged nerve cell membrane, stabilizes and improves the material exchange function of the nerve cell membrane, and promotes the vitality recovery of apoptotic nerve cells by promoting the improvement of various morphological, biochemical, histochemical, neurophysiological and behavioral parameters. Has effects in promoting normal development of nerve cells, and repairing damaged nerve tissue. Is used for thrombolysis, anticoagulation or hemostasis and neonatal hypoxic ischemic encephalopathy, and has certain improvement effect on senile dementia and Parkinson's disease. At present, monosialotetrahexosyl ganglioside sodium enters part of provincial and municipal medical insurance, thereby having a larger boosting effect on the market. With the development of the aging society, the global nervous medicine market shows a rapidly growing situation, and neuroprotection has become one of the hot spots of the neurology treatment research.
In 6 months of 2017, the national food and drug administration carries out the on-the-fly inspection of the 'remodeling Jie' of the monosialotetrahexosyl ganglioside sodium injection produced by the Brazilian TRB factory, and because the production is not standardized and the import of the product is determined to be stopped, the ganglioside sodium nervous system drug has the trend of single supply and tension at present.
At present, only the monosialotetrahexosyl ganglioside sodium injection is sold in markets at home and abroad, the injection can be carried out in hospitals, the use is inconvenient, the price is high, and the limitation is large, so if a ganglioside medicine which is convenient for patients to supplement at any time and any place can be developed, the ganglioside injection has important social significance and national strategic significance.
Disclosure of Invention
The invention mainly solves the technical problem of providing the ganglioside sustained-release tablet and the preparation method thereof, has simple process, and can meet the requirement of supplementing medicaments for patients at any time and any place.
In order to solve the technical problems, the invention adopts a technical scheme that:
the ganglioside sustained release tablet consists of a tablet core and a sustained release coating film, wherein the weight ratio of the tablet core is 80-95%, and the weight ratio of the sustained release coating film is 5-20%.
Wherein the tablet core is composed of the following raw materials in parts by weight: 15 to 45 percent of monosialotetrahexosylganglioside sodium, 40 to 60 percent of framework material, 2 to 8 percent of adhesive, 2 to 10 percent of filler, 1 to 6 percent of pH regulator, 8 to 30 percent of enteric material and 0.5 to 1.5 percent of lubricant I; the slow release coating film is composed of the following raw materials in parts by weight: 70 to 90 percent of film forming agent, 5 to 10 percent of plasticizer, 4 to 10 percent of lubricant II and 1 to 10 percent of colorant.
Furthermore, the weight proportion of the tablet core is 90-95%, and the weight proportion of the sustained-release coating film is 5-10%.
Wherein the tablet core is composed of the following raw materials in parts by weight: 15 to 18 percent of monosialotetrahexosylganglioside sodium, 45 to 55 percent of framework material, 3 to 5 percent of adhesive, 6 to 8 percent of filler, 3 to 4 percent of pH regulator, 13 to 20 percent of enteric material and 0.8 to 1 percent of lubricant I; the slow release coating film is composed of the following raw materials in parts by weight: 77-85% of film forming agent, 6-9% of plasticizer, 6-9% of lubricant II and 3-5% of colorant.
Further, the framework material is ethyl cellulose; the adhesive is povidone and/or hypromellose, and is further selected from povidone; the filler is selected from one or more of lactose, microcrystalline cellulose and pregelatinized starch, and is further selected from lactose; the pH regulator is arginine; the enteric material is hydroxypropyl methylcellulose phthalate; the lubricant I is magnesium stearate and/or calcium stearate, and is further selected from magnesium stearate.
Further, the film forming agent is hydroxypropyl methyl cellulose, the plasticizer is polyethylene glycol 6000, the colorant is iron oxide red, and the lubricant II is talcum powder.
The ganglioside sustained-release tablet has reasonable prescription, can be easily purchased from various auxiliary materials in the market, has low price, and can effectively reduce the price of the medicine.
Further, the hardness of the ganglioside sustained-release tablet is 5-6 kg/mm2。
The invention also provides a preparation method of the ganglioside sustained-release tablet, which comprises the following steps:
(1) preparation of the tablet core: mixing the monosialotetrahexosyl ganglioside sodium, the filler, the framework material and the pH regulator, spraying the solution of the binder for granulation, coating the granules with the solution of the enteric material, drying, adding the lubricant I, granulating and tabletting.
(2) Coating preparation: dispersing the lubricant II in water, adding film-forming agent, plasticizer and colorant, stirring for coating, and drying.
The preparation process is simple and easy to operate, can be used for large-scale production, and can be popularized and applied.
Further, in the step (1), the mass concentration of the binder solution is 3-6%, and the mass concentration of the enteric material solution is 6-10%.
Further, in the step (1), the drying temperature is 55-60 ℃, and the particles are dried until the moisture content is not more than 2.0% by weight.
Further, in the step (1), the solvent is purified water and/or ethanol.
Further, in the step (2), the drying mode is oven drying or fluidized bed drying; the drying is that the mixture is firstly dried for 2 hours by cold air and then dried for 10 to 15 hours at the temperature of 50 to 70 ℃. .
The invention has the beneficial effects that:
(1) the ganglioside sustained-release tablet has reasonable prescription, good stability and high safety, can be carried about, and is convenient for patients to use at any time.
(2) The preparation method of the ganglioside sustained-release tablet has simple process and low raw material cost, can effectively reduce the medicine cost, remarkably reduce the medicine burden of patients, can be produced in large scale and has industrial application value.
Drawings
FIG. 1 is a graph showing the release profile of the sustained release tablet of the present invention in 0.1N hydrochloric acid;
fig. 2 is a graph showing the release profile of the sustained-release tablet of the present invention in a buffer solution having a pH of 4.0;
fig. 3 is a graph showing the release profile of the sustained-release tablet of the present invention in a buffer solution having a pH of 6.8;
fig. 4 is a graph showing the release profile of the sustained-release tablet of the present invention in water.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. In the present invention, all amounts, parts and percentages are by weight and all raw materials are commercially available, unless otherwise specified.
Example 1 preparation of ganglioside sustained release tablets (300 mg/tablet, 1000 tablets total):
tablet core prescription:
| composition (I) | Dosage of | Content (wt.) |
| Monosialotetrahexosyl ganglioside sodium | 55g | 16.77％ |
| Ethyl cellulose | 180g | 54.88％ |
| Hydroxypropyl methylcellulose phthalate | 45g | 13.72％ |
| Arginine | 12g | 3.66％ |
| Povidone | 13g | 3.96％ |
| Lactose | 20g | 6.10％ |
| Magnesium stearate | 3g | 0.91％ |
| Total weight of | |
100％ |
The prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) | |
| | 20g | 80％ | |
| Polyethylene glycol 6000 | 2g | 8％ | |
| Talcum powder | 2g | 8％ | |
| Iron oxide red | 1g | 4％ | |
| Total amount of | |
100％ |
The preparation process of the sustained-release tablet comprises the following steps:
(1) preparation of the tablet core: crushing monosialotetrahexosyl ganglioside sodium, lactose, ethyl cellulose and arginine, sieving with a 100-mesh sieve, mechanically mixing uniformly, spraying povidone aqueous solution containing 5% into the mixture for 40-mesh granulation, spraying hydroxypropyl methylcellulose phthalate ethanol solution containing 8% into the granules for coating after the granulation is finished, drying at 55 ℃ until the moisture content is within 2.0%, adding magnesium stearate into the dried granules, sieving with a 20-mesh sieve for size stabilization, placing the granules into a mixer for uniform mixing, flushing and reducing the height to 14.8mm for tabletting, wherein each tablet is about 300mg and contains 50mg of main drug GM1, and the hardness of the tablet is controlled to be 5-6 kg/mm2。
(2) Coating preparation: uniformly dispersing talcum powder in water, adding hydroxypropyl methyl cellulose, polyethylene glycol 6000 and a coloring agent after stirring, continuously stirring uniformly for coating, wherein the rotating speed of a coating pot is 36 r/min, the hot air temperature is 50 ℃, the compressed air pressure is 0.2MPa, the weight gain is about 5%, coating is finished, cold air drying is carried out for 2 hours, and coated tablets are placed in an oven and dried for 12 hours at the temperature of 60 ℃ to obtain the finished product.
EXAMPLE 2 preparation of ganglioside sustained-release tablets
Tablet core prescription:
the prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) |
| Hydroxypropyl methylcellulose | 20g | 80％ |
| Polyethylene glycol 6000 | 2g | 8％ |
| Talcum powder | 2g | 8％ |
| Iron oxide red | 1g | 4％ |
| Total amount of | |
100％ |
The preparation process comprises the following steps:
(1) preparation of the tablet core: pulverizing monosialotetrahexosylganglioside sodium, lactose, ethyl cellulose and arginine, and sieving with a sieve of 10%0 mesh sieve, uniformly mechanically mixing, spraying 5% povidone water solution into the mixture for 40 mesh granulation, spraying 8% hydroxypropyl methylcellulose phthalate ethanol solution for coating the granules after the granulation is finished, drying at 60 ℃ until the water content is 1.8%, adding magnesium stearate into the dried granules, sieving with a 20 mesh sieve for granulation, uniformly mixing in a mixer, upward flushing to reduce the height to 14.8mm for tabletting, wherein each tablet is about 300mg, the main drug containing GM1 is 50mg, and the hardness of the tablet is controlled to be 5-6 kg/mm2。
(2) Coating preparation: uniformly dispersing talcum powder in water, adding hydroxypropyl methyl cellulose, polyethylene glycol 6000 and a coloring agent after stirring, continuously stirring uniformly for coating, wherein the rotating speed of a coating pot is 36 r/min, the hot air temperature is 60 ℃, the compressed air pressure is 0.3MPa, the weight gain is about 5%, coating is finished, cold air drying is carried out for 2 hours, and a coated tablet is placed in an oven and dried for 12 hours at the temperature of 60 ℃ to obtain the finished product.
EXAMPLE 3 preparation of ganglioside sustained-release tablets
Tablet core prescription:
| composition (I) | Dosage of | Content (wt.) |
| Monosialotetrahexosyl ganglioside sodium | 55g | 16.67％ |
| Ethyl cellulose | 170g | 51.52％ |
| Hydroxypropyl radicalMethyl cellulose phthalate | 55g | 16.67％ |
| Arginine | 10g | 3.03％ |
| Povidone | 15g | 4.55％ |
| Lactose | 22g | 6.67％ |
| Magnesium stearate | 3g | 0.91％ |
| Total weight of | |
100％ |
The prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) |
| Hydroxypropyl methylcellulose | 20g | 80％ |
| Polyethylene glycol 6000 | 2g | 8％ |
| Talcum powder | 2g | 8％ |
| Iron oxide red | 1g | 4％ |
| Total amount of | |
100％ |
The preparation process comprises the following steps:
(1) preparation of the tablet core: crushing monosialotetrahexosyl ganglioside sodium, lactose, ethyl cellulose and arginine, sieving with a 100-mesh sieve, mechanically mixing uniformly, spraying povidone aqueous solution containing 5 percent into the mixture for 40-mesh sieve granulation, spraying hydroxypropyl methylcellulose phthalate ethanol solution containing 8 percent into the granules for coating after the granulation is finished, drying at 58 ℃ until the moisture content is 1.7 percent, adding magnesium stearate into the dried granules, sieving with a 20-mesh sieve for granulation, uniformly mixing in a mixer, upward flushing, reducing the height to 14.8mm for tabletting, wherein each tablet is about 300mg and contains 50mg of main drug GM1, and the hardness of the tablets is controlled to be 5-6 kg/mm2。
(2) Coating preparation: uniformly dispersing talcum powder in water, adding hydroxypropyl methyl cellulose, polyethylene glycol 6000 and a coloring agent after stirring, continuously stirring uniformly for coating, wherein the rotating speed of a coating pot is 36 r/min, the hot air temperature is 50 ℃, the compressed air pressure is 0.3MPa, the weight gain is about 5%, coating is finished, cold air drying is carried out for 2 hours, and coated tablets are placed in an oven and dried for 12 hours at the temperature of 60 ℃ to obtain the finished product.
EXAMPLE 4 preparation of ganglioside sustained-release tablets
Tablet core prescription:
| composition (I) | Dosage of | Content (wt.) | |
| Monosialotetrahexosyl ganglioside sodium | 148.5g | 45％ | |
| | 132g | 40％ | |
| Hydroxypropyl methylcellulose phthalate | 26.4g | 8％ | |
| Arginine | 3.3g | 1％ | |
| Povidone | 6.6g | 2％ | |
| Lactose | 8.25g | 2.5％ | |
| Magnesium stearate | 1.65g | 0.5％ | |
| Total weight of | |
100％ |
The prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) |
| Hydroxypropyl methylcellulose | 17.5g | 70％ |
| Polyethylene glycol 6000 | 2.5 |
10％ |
| Talcum powder | 2.5 |
10％ |
| Iron oxide red | 2.5 |
10％ |
| Total amount of | |
100％ |
The procedure was as in example 2.
Example 5 preparation of ganglioside sustained release tablets the tablet core formulation:
| composition (I) | Dosage of | Content (wt.) | |
| Monosialotetrahexosyl ganglioside sodium | 48.5 |
15％ | |
| | 198g | 60％ | |
| Hydroxypropyl methylcellulose phthalate | 33g | 10％ | |
| Arginine | 4.95g | 1.5％ | |
| Povidone | 6.6g | 2 | |
| Lactose | 33g | ||
| 10％ | |||
| Magnesium stearate | 4.95g | 1.5％ | |
| Total weight of | |
100％ |
The prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) |
| Hydroxypropyl methylcellulose | 22.5g | 90％ |
| Polyethylene glycol 6000 | 1.25 |
5％ |
| Talcum powder | 1g | 4％ |
| Iron oxide red | 0.25g | 1％ |
| Total amount of | |
100％ |
The procedure was as in example 1.
EXAMPLE 6 preparation of ganglioside sustained-release tablets
Tablet core prescription:
the prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) |
| Hydroxypropyl methylcellulose | 21.25g | 85％ |
| Polyethylene glycol 6000 | 1.25 |
5％ |
| Talcum powder | 1.75g | 7％ |
| Iron oxide red | 0.75g | 3％ |
| Total amount of | |
100％ |
The procedure was as in example 2.
EXAMPLE 7 preparation of ganglioside sustained-release tablets
Tablet core prescription:
| composition (I) | Dosage of | Content (wt.) |
| Monosialotetrahexosyl ganglioside sodium | 69.96g | 21.2％ |
| Ethyl cellulose | 148.5g | 45％ |
| Hydroxypropyl methylcellulose phthalate | 42.9g | 13％ |
| Arginine | 13.2g | 4％ |
| Povidone | 26.4g | 8％ |
| Lactose | 26.4g | 8％ |
| Magnesium stearate | 2.64g | 0.8％ |
| Total weight of | |
100％ |
The prescription of the coating liquid is as follows:
the procedure was as in example 3.
EXAMPLE 8 preparation of ganglioside sustained-release tablets
Tablet core prescription:
| composition (I) | Dosage of | Content (wt.) |
| Monosialotetrahexosyl ganglioside sodium | 59.4g | 18％ |
| Ethyl cellulose | 171.6g | 52％ |
| Hydroxypropyl methylcellulose phthalate | 33g | 10％ |
| Arginine | 19.8g | 6％ |
| Povidone | 9.9g | 3 |
| Lactose | 33g | |
| 10％ | ||
| Magnesium stearate | 3.3g | 1％ |
| Total weight of | |
100％ |
The prescription of the coating liquid is as follows:
| composition (I) | Dosage of | Content (wt.) |
| Hydroxypropyl methylcellulose | 20g | 80％ |
| Polyethylene glycol 6000 | 2g | 8％ |
| Talcum powder | 2g | 8％ |
| Iron oxide red | 1g | 4％ |
| Total amount of | |
100％ |
The procedure was as in example 3.
The above examples show that the ganglioside sustained release tablet of the present invention has reasonable formulation, and various excipients used in the sustained release tablet of the present invention can be easily purchased in the market, and have low price, and can significantly reduce the medication burden of patients. The invention prepares the ganglioside medicament into the sustained release tablet, which is convenient for carrying and is convenient for patients to take at any time. The preparation method of the ganglioside sustained-release tablet is simple, easy to operate and capable of being directly produced in large scale.
EXAMPLE 9 measurement of Release degree
The determination method comprises the following steps: adopting a general rule of 0931 dissolution and release determination of 2015 edition of Chinese pharmacopoeia general rule, rotating speed of 50rpm, dissolution medium: a. 0.1N hydrochloric acid; b. PH 4.0 acetate buffer solution; c. phosphate buffer solution with pH 6.8; d. and (3) water. The medium volume is 900ml, the temperature is 37.0 ℃. + -. 0.5 ℃, and four curves are determined (see FIGS. 1-4).
Taking 10 tablets of the coated tablets prepared in examples 1-3, respectively taking 5mL of the tablets at 0.5h, 2h, 4h, 6h, 8h, 10h, 12h, 16h, 20h and 24h according to the release degree conditions, filtering, taking the filtrate as a test solution, supplementing 5mL of blank dissolution medium in time, and measuring the concentration of the sample by ultraviolet, wherein the data are as follows:
TABLE 1 Release in 0.1N hydrochloric acid (%)
| Time (h) | 0.5 | 2 | 4 | 6 | 8 |
| Example 1 | 2.81 | 8.43 | 15.57 | 23.12 | 33.21 |
| Example 2 | 1.95 | 7.58 | 15.19 | 24.33 | 35.63 |
| Example 3 | 1.22 | 8.76 | 17.43 | 27.56 | 36.89 |
| Time (h) | 10 | 12 | 16 | 20 | 24 |
| Example 1 | 43.32 | 51.67 | 68.33 | 83.22 | 92.55 |
| Example 2 | 46.89 | 56.22 | 71.33 | 87.12 | 95.22 |
| Example 3 | 47.99 | 59.56 | 79.12 | 90.32 | 98.08 |
Table 2 Release (%), in buffer solution at pH 4.0
Table 3 Release (%), in buffer solution at pH 6.8
| Time (h) | 0.5 | 2 | 4 | 6 | 8 |
| Example 1 | 1.97 | 7.33 | 14.32 | 21.45 | 31.43 |
| Example 2 | 2.03 | 7.96 | 14.89 | 23.67 | 33.44 |
| Example 3 | 1.22 | 7.88 | 15.36 | 27.16 | 35.52 |
| Time (h) | 10 | 12 | 16 | 20 | 24 |
| Example 1 | 41.99 | 49.35 | 64.42 | 79.46 | 91.34 |
| Example 2 | 44.26 | 51.09 | 67.88 | 82.27 | 93.95 |
| Example 3 | 44.42 | 53.25 | 72.67 | 84.64 | 95.51 |
Table 4 release in water (%)
| Time (h) | 0.5 | 2 | 4 | 6 | 8 |
| Example 1 | 1.88 | 7.25 | 13.22 | 21.42 | 29.89 |
| Example 2 | 1.63 | 7.18 | 14.32 | 22.56 | 32.76 |
| Example 3 | 1.83 | 8.I2 | 15.05 | 26.19 | 34.77 |
| Time (h) | 10 | 12 | 16 | 20 | 24 |
| Example 1 | 40.56 | 48.33 | 63.56 | 78.33 | 90.59 |
| Example 2 | 43.73 | 50.45 | 66.99 | 81.04 | 92.16 |
| Example 3 | 45.53 | 52.87 | 71.93 | 83.99 | 94.76 |
From the data, the ganglioside sustained-release tablet prepared by the method shows good sustained-release preparation main characteristics of sustained and sustained release of the drug in four different dissolution media of 0.1N hydrochloric acid, PH 4.0 acetate buffer solution, PH 6.8 phosphate buffer solution and water, has uniform drug release speed and stable quality, does not have burst release phenomenon, and basically achieves complete release after 24 hours.
In conclusion, the ganglioside sustained-release tablet has stable product quality and good sustained-release effect, can effectively control the blood drug concentration and increase the safety of medication, and has convenient administration, convenient carrying and low price. The preparation method has the advantages of simple preparation process, convenience, rapidness, low cost, suitability for mass production and higher application value.
The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes performed by the present specification and drawings, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.
Claims (8)
1. The ganglioside sustained-release tablet is characterized by comprising a tablet core and a sustained-release coating film, wherein the weight ratio of the tablet core is 80-95%, and the weight ratio of the sustained-release coating film is 5-20%;
wherein the tablet core is composed of the following raw materials in parts by weight: 15 to 45 percent of monosialotetrahexosylganglioside sodium, 40 to 60 percent of framework material, 2 to 8 percent of adhesive, 2 to 10 percent of filler, 1 to 6 percent of pH regulator, 8 to 30 percent of enteric material and 0.5 to 1.5 percent of lubricant I;
the slow release coating film is composed of the following raw materials in parts by weight: 70-90% of film-forming agent, 5-10% of plasticizer, 4-10% of lubricant II and 1-10% of colorant;
the framework material is ethyl cellulose; the binder is povidone; the filler is selected from lactose; the pH regulator is arginine; the pH regulator is arginine; the enteric material is hydroxypropyl methylcellulose phthalate; the lubricant one is selected from magnesium stearate;
the film forming agent is hydroxypropyl methyl cellulose, the plasticizer is polyethylene glycol 6000, the colorant is iron oxide red, and the lubricant II is talcum powder.
2. The ganglioside sustained-release tablet of claim 1, wherein the weight ratio of the tablet core is 90-95%, and the weight ratio of the sustained-release coating is 5-10%;
wherein the tablet core is composed of the following raw materials in parts by weight: 15 to 18 percent of monosialotetrahexosylganglioside sodium, 45 to 55 percent of framework material, 3 to 5 percent of adhesive, 6 to 8 percent of filler, 3 to 4 percent of pH regulator, 13 to 20 percent of enteric material and 0.8 to 1 percent of lubricant I;
the slow release coating film is composed of the following raw materials in parts by weight: 77-85% of film forming agent, 6-9% of plasticizer, 6-9% of lubricant II and 3-5% of colorant.
3. The ganglioside sustained-release tablet according to claim 1 or 2, wherein the hardness of the ganglioside sustained-release tablet is 5-6 kg/mm2。
4. A process for preparing a ganglioside sustained release tablet as claimed in any one of claims 1 to 3, which comprises the steps of:
(1) preparation of the tablet core: mixing monosialotetrahexosyl ganglioside sodium, a filler, a framework material and a pH regulator, spraying a solution of a binder for granulation, coating the granules with a solution of an enteric material, drying, adding a lubricant I, granulating and tabletting;
(2) coating preparation: dispersing the lubricant II in water, adding film-forming agent, plasticizer and colorant, stirring for coating, and drying.
5. The preparation method of the ganglioside sustained release tablet according to claim 4, wherein in step (1), the mass concentration of the binder solution is 3-6%, and the mass concentration of the enteric material solution is 6-10%.
6. The process for preparing a ganglioside sustained-release tablet according to claim 4, wherein in step (1), the drying temperature is 55 to 60 ℃, and the granules are dried until the moisture content is not more than 2.0% by weight.
7. The process for preparing ganglioside sustained release tablets according to claim 4, wherein in step (1), the solvent is purified water and/or ethanol.
8. The process for preparing ganglioside sustained-release tablets according to claim 4, wherein in step (2), said drying mode is oven drying or fluidized bed drying; the drying is that the mixture is firstly dried for 2 hours by cold air and then dried for 10 to 15 hours at the temperature of 50 to 70 ℃.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6620792B1 (en) * | 1992-03-13 | 2003-09-16 | Fidia S.P.A. | Pharmaceutical compositions containing monosialoganglioside GM1 or derivative thereof suitable for the treatment of parkinson's disease |
| CN104490837A (en) * | 2014-12-30 | 2015-04-08 | 哈尔滨医科大学科技开发总公司 | Oral preparation of monosialotetrahexosyl ganglioside sodium |
| CN106309410A (en) * | 2016-10-14 | 2017-01-11 | 珠海赛隆药业股份有限公司 | Monosialotetrahexosylganglioside sodium slow-release capsule and preparation method thereof |
| CN106361718A (en) * | 2016-10-14 | 2017-02-01 | 珠海赛隆药业股份有限公司 | Colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium |
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2018
- 2018-09-11 CN CN201811059641.9A patent/CN108815131B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6620792B1 (en) * | 1992-03-13 | 2003-09-16 | Fidia S.P.A. | Pharmaceutical compositions containing monosialoganglioside GM1 or derivative thereof suitable for the treatment of parkinson's disease |
| CN104490837A (en) * | 2014-12-30 | 2015-04-08 | 哈尔滨医科大学科技开发总公司 | Oral preparation of monosialotetrahexosyl ganglioside sodium |
| CN106309410A (en) * | 2016-10-14 | 2017-01-11 | 珠海赛隆药业股份有限公司 | Monosialotetrahexosylganglioside sodium slow-release capsule and preparation method thereof |
| CN106361718A (en) * | 2016-10-14 | 2017-02-01 | 珠海赛隆药业股份有限公司 | Colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium |
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Denomination of invention: Ganglioside sustained release tablet and its preparation method Effective date of registration: 20230705 Granted publication date: 20210101 Pledgee: Luxian County Agriculture and Small and Medium sized Enterprise Financing Guarantee Co.,Ltd. Pledgor: SICHUAN QIGEMAN PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980047484 |