Tablet containing mecobalamin and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to mecobalamin-containing tablets and a preparation method thereof. The mecobalamine tablet is prepared from the following components in parts by weight: 500 parts of mecobalamine, 160 to 400 parts of beta-cyclodextrin, 80 to 200 parts of trollflower polysaccharide, 80 to 200 parts of cinnamyl alcohol, 4350 to 12000 parts of a filling agent, 90 to 200 parts of a disintegrating agent, 120 to 360 parts of a stabilizing agent, 60 to 140 parts of a lubricating agent and a proper amount of an adhesive. Dry granulation is adopted, the preparation process is simple and feasible, and pharmacodynamic experiments find that the pharmaceutical composition disclosed by the invention is obvious in effect and suitable for clinical use, and can be further expanded in production.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a tablet containing methylcobalamin and a preparation method thereof. Background Art

[0002] Methylcobalamin is a drug for the treatment of peripheral neuropathy and is a vitamin B 12 Methyl vitamin B 12 , the structural formula is as follows:

[0003]

[0004] Mecobalamin Tablets (trade name: Methycobal) is an endogenous coenzyme B developed by Eisai Co., Ltd. 12 Preparation. Clinically used for peripheral neuropathy. First marketed in Japan, China imported methylcobalamin injection and tablets in 1998. Currently, there are two dosage forms on the market in China: tablets and capsules.

[0005] As a Chinese medicinal material used for both medicine and food, Nasturtium is the dried flower of the Ranunculaceae plant Nasturtium. Wild resources are very abundant, mainly produced in Hebei, Shanxi and Inner Mongolia in my country. The main chemical components are flavonoids, alkaloids, organic acids, volatile oils, etc. At present, the research on Nasturtium mainly focuses on antibacterial activity, anti-inflammatory, antioxidant, anti-cancer and tea beverages. Nasturtium polysaccharide is one of the main active substances of Nasturtium. There are not many literature reports on the extraction of Nasturtium polysaccharide. At present, the literature reports that the water boiling method is used to extract polysaccharides, but the water boiling method has the defects of long operation time, high temperature and low yield, and the extracted crude polysaccharide also contains protein.

[0006] In the current prior art, methylcobalamin tablets do not contain a combination of nasturtium polysaccharide and methylcobalamin, and there is no related report. Summary of the invention

[0007] In order to overcome the deficiencies of the prior art, the present invention provides a tablet containing methylcobalamin and a preparation method thereof. The methylcobalamin tablet contains nasturtium polysaccharide and methylcobalamin, as well as other auxiliary materials, thereby solving the defects of the current methylcobalamin tablets having high content of related substances and unobvious therapeutic effect.

[0008] Specifically, the technical solution of the present invention is achieved as follows:

[0009] The invention discloses a methylcobalamin tablet, which is composed of the following components by weight: 500 parts of methylcobalamin, 160-400 parts of beta-cyclodextrin, 80-200 parts of nasturtium polysaccharide, 80-200 parts of cinnamyl alcohol, 4350-12000 parts of filler, 90-200 parts of disintegrant, 90-270 parts of benzyl benzoate, 30-90 parts of vitamin C palmitate, 60-140 parts of lubricant and a proper amount of adhesive.

[0010] Furthermore, the preparation process of the methylcobalamin tablets of the present invention comprises the following steps:

[0011] 1) adding truncatum polysaccharide to a saturated aqueous solution of β-cyclodextrin, and drying to obtain a truncatum polysaccharide inclusion compound;

[0012] 2) mixing methylcobalamin, cinnamyl alcohol, benzyl benzoate and 1 / 4 of the filler evenly, and granulating to obtain drug-containing granules;

[0013] 3) dissolving the nasturtium polysaccharide inclusion compound and palmitic acid vitamin C ester in 60% ethanol water obtained in step A, spraying the solution on the surface of the drug-containing granules obtained in step B, drying, adding a disintegrant and 3 / 4 of a filler and mixing evenly, adding a binder to make a soft material, sieving, making granules, drying, adding a lubricant and mixing evenly, and tableting to obtain the product.

[0014] Further, in a preferred embodiment of the present invention, the methylcobalamin tablets are composed of the following components by weight: 500 parts of methylcobalamin, 20 parts of β-cyclodextrin, 15 parts of nasturtium polysaccharide, 3 parts of cinnamyl alcohol, 200 parts of microcrystalline cellulose, 17 parts of low-substituted hydroxypropyl cellulose, 8 parts of colloidal silicon dioxide and 5 parts of magnesium stearate.

[0015] Furthermore, in a preferred embodiment of the present invention, the filler is selected from one or two of microcrystalline cellulose, lactose, mannitol, and sorbitol; preferably microcrystalline cellulose and lactose.

[0016] Furthermore, in a preferred embodiment of the present invention, the disintegrant is selected from one or more of sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; preferably low-substituted hydroxypropyl cellulose.

[0017] Furthermore, in a preferred embodiment of the present invention, the adhesive is selected from a 10% aqueous solution of povidone K30 or a 30% starch slurry; preferably a 10% aqueous solution of povidone K30.

[0018] Further, in a preferred embodiment of the present invention, the methylcobalamin tablets are composed of the following components by weight: 500 parts of methylcobalamin, 160-400 parts of β-cyclodextrin, 80-200 parts of nasturtium polysaccharide, 80-200 parts of cinnamyl alcohol, 2900-8000 parts of microcrystalline cellulose and 1450-4000 parts of lactose, 90-200 parts of low-substituted hydroxypropyl cellulose, 90-270 parts of benzyl benzoate, 30-90 parts of vitamin C palmitate, 60-140 parts of magnesium stearate and an appropriate amount of 10% aqueous solution of povidone K30.

[0019] Furthermore, in a preferred embodiment of the present invention, the usage ratio of benzyl benzoate and vitamin C palmitate is 3:1.

[0020] Furthermore, the extraction method of the trollius polysaccharide of the present invention is:

[0021] 1) Soak the nasturtium in 50-80°C hot water for 1-3 hours, cool to room temperature, add β-glucosidase and brown algae pectinase, perform enzymolysis for 1-2 hours, adjust the temperature and pH, centrifuge, and reserve the supernatant for later use;

[0022] 2) adding 1-3 times the volume of 100% ethanol to the supernatant, letting it stand and filtering, and the filter residue is the crude polysaccharide of nasturtium;

[0023] 3) Dissolve the crude nasturtium polysaccharide in distilled water, adsorb it with a macroporous resin, elute it with an ethanol solution, collect the 65% ethanol eluate, dry it, and the filter residue is the nasturtium polysaccharide.

[0024] The dosage ratio of β-glucosidase and brown alginic pectinase in step 1) is 6-10:1; the temperature is 45-55° C., and the pH value is 4.5-5.5.

[0025] Further, in a preferred embodiment of the present invention, a methylcobalamin tablet is composed of the following components by weight: 500 parts of methylcobalamin, 300 parts of β-cyclodextrin, 140 parts of nasturtium polysaccharide, 140 parts of cinnamyl alcohol, 5000 parts of microcrystalline cellulose, 2500 parts of lactose, 120 parts of low-substituted hydroxypropyl cellulose, 150 parts of benzyl benzoate, 50 parts of vitamin C palmitate, 100 parts of magnesium stearate and an appropriate amount of 10% aqueous solution of povidone K30, and the preparation process of the methylcobalamin tablet comprises the following steps:

[0026] 1) adding truncatum polysaccharide to a saturated aqueous solution of β-cyclodextrin, and drying to obtain a truncatum polysaccharide inclusion compound;

[0027] 2) uniformly mixing methylcobalamin, cinnamyl alcohol, benzyl benzoate, 1 / 4 of microcrystalline cellulose and lactose, and granulating to obtain drug-containing granules;

[0028] 3) dissolving the nasturtium polysaccharide inclusion compound and palmitic acid vitamin C ester in 60% ethanol water obtained in step A, spraying the solution on the surface of the drug-containing granules obtained in step B, drying, adding a disintegrant and 3 / 4 of 4 microcrystalline cellulose and lactose, mixing evenly, adding a binder to make a soft material, sieving, making granules, drying, adding a lubricant to mix evenly, and tableting to obtain the product.

[0029] The 1 / 4 of microcrystalline cellulose and lactose described in the present invention should be specifically understood as 1 / 4 of the total weight of the microcrystalline cellulose and lactose after mixing. Taking Example 2 as an example, 1 / 4 of microcrystalline cellulose is 2000 parts; 1 / 4 of lactose is 1000 parts.

[0030] The 3 / 4 of microcrystalline cellulose and lactose described in the present invention should be specifically understood as 3 / 4 of the total weight of the microcrystalline cellulose and lactose after mixing. Taking Example 1 as an example, 3 / 4 of microcrystalline cellulose is 6000 parts; 3 / 4 of lactose is 2000 parts.

[0031] Compared with the prior art, the present invention has the following advantages:

[0032] In the pharmacodynamic experiment, the tablets prepared by the present invention significantly increased the percentage of blood flow, and increased the sensory nerve conduction velocity and the motor nerve conduction velocity, which were significantly different from those of the methylcobalamin tablets alone (P<0.05 or P<0.01), indicating that the tablets prepared by the present invention have a significant improvement effect on peripheral neuritis.

[0033] After the methylcobalamin is added into the nasturtium polysaccharide, the nasturtium polysaccharide can be slowly released to form a stable system with the methylcobalamin, thereby reducing the hygroscopicity of the methylcobalamin, significantly reducing the single impurity and total impurity contents of related substances, and adding a stabilizer to further reduce impurities. The finally prepared tablets save the coating step, thereby greatly reducing the cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 : The single impurity content of the relevant embodiments of the present invention, wherein the single impurity content of embodiments 1-6 is below 0.15%.

[0035] Figure 2 : The total impurity content of the relevant embodiments of the present invention, wherein the total impurity content of embodiments 1-6 is below 0.35%.

[0036] Figure 3 : Dissolution of the embodiments of the present invention in aqueous solution, dissolution comparison at 0, 1, 2, 5, 7, 10, 15, 20, and 30 min. It can be seen that the final dissolution of embodiments 1-3 is significantly higher than that of comparative examples 5-6.

[0037] Figure 4: The normal group had a significant difference compared with the model group (P<0.01), the Example 3 group had a significant difference compared with the model group (P<0.05), and there was no significant difference between the comparative example 3 combined positive control group and the model group.

[0038] Figure 5 : Comparative effect of motor nerve conduction velocity between the embodiments of the present invention and the model group.

[0039] Figure 6 : Comparative effect of sensory nerve conduction velocity between the embodiments of the present invention and the model group. DETAILED DESCRIPTION

[0040] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0041] 1. Research on the extraction of nasturtium polysaccharides

[0042] Detection method of trollius polysaccharides: HPGPC chromatographic conditions used Waters 2695 high performance liquid chromatograph, Agilent PL aquagel-OH 50 gel column (7.5mm×300mm, 8μm), ultrapure water as the mobile phase, a volume flow rate of 1.0mL / min, Waters2424 evaporative light scattering detector, gas (N2) pressure of 30psi, gain 100, drift tube temperature of 60°C, nebulizer mode of 60%, column temperature of 30°C, and injection volume of 20μL.

[0043] Method 1: Extraction and purification of nasturtium polysaccharide

[0044] 1) taking 3 kg of nasturtium powder, adding 50° C. hot water and soaking for 1 hour, cooling to room temperature, adding β-glucosidase and brown algae pectinase, enzymolysis for 1 hour, adjusting pH, centrifuging, and reserving the supernatant for later use; wherein, the ratio of β-glucosidase to brown algae pectinase is 6:1; adjusting the temperature and pH value (temperature 45° C., pH value 4.5) to promote the activity of the enzyme;

[0045] 2) adding 1 volume of 100% ethanol to the supernatant, letting it stand and filtering, and the filter residue is the crude polysaccharide of nasturtium;

[0046] 3) Dissolve the crude nasturtium polysaccharide in distilled water, adsorb it with a macroporous resin, elute it with an ethanol solution, collect the 65% ethanol eluate, dry it, and the filter residue is the nasturtium polysaccharide.

[0047] Method 2: Extraction and purification of nasturtium polysaccharides

[0048] 1) taking 3 kg of nasturtium powder, adding 80° C. hot water to soak for 2 hours, cooling to room temperature, adding β-glucosidase and brown algae pectinase, enzymolysis for 2 hours, adjusting pH, centrifuging, and reserving the supernatant for later use; wherein, the ratio of β-glucosidase to brown algae pectinase is 10:1; adjusting the temperature and pH value (temperature 55° C., pH value 4.5-5.5) to promote enzyme activity;

[0049] 2) adding 1-3 times the volume of 100% ethanol to the supernatant, standing and filtering, and the filter residue is the crude polysaccharide of nasturtium;

[0050] 3) Dissolve the crude polysaccharide from the truncatum var. nasturtium in distilled water, adsorb it with a macroporous resin, elute it with an ethanol solution, collect the 65% ethanol eluate, dry it, and the residue is the truncatum var. nasturtium var. nasturtium polysaccharide.

[0051] Method 3: Extraction and purification of nasturtium polysaccharide

[0052] 1) taking 3 kg of nasturtium powder, adding 70° C. hot water to soak for 3 hours, cooling to room temperature, adding β-glucosidase and brown algae pectinase, enzymolysis for 1.5 hours, adjusting pH, centrifuging, and reserving the supernatant for later use; wherein, the ratio of β-glucosidase to brown algae pectinase is 8:1; adjusting the temperature and pH value (temperature 50° C., pH value 5.0) to promote the activity of the enzyme;

[0053] 2) Add 2 times the volume of 100% ethanol to the supernatant, let it stand and filter, and the filter residue is the crude polysaccharide of nasturtium;

[0054] 3) Dissolve the crude polysaccharide from the truncatum var. nasturtium in distilled water, adsorb it with a macroporous resin, elute it with an ethanol solution, collect the 65% ethanol eluate, dry it, and the residue is the truncatum var. nasturtium var. nasturtium polysaccharide.

[0055] Method 4: Extraction and purification of nasturtium polysaccharide

[0056] 1) Wash and dry the nasturtium to constant weight, crush it, and pass it through a 40-mesh sieve. Heat the raw material with petroleum ether at 40°C twice to remove lipids; treat it with acetone at 50°C twice to remove pigments; treat it with 80% ethanol at 70°C twice, take 3kg of nasturtium powder and extract it in batches, add 20 times the amount of water each time, extract at 95°C, extract for 3 hours, and extract twice;

[0057] 2) Add 2 times the volume of 100% ethanol to the supernatant, let it stand and filter, and the filter residue is the crude polysaccharide of nasturtium;

[0058] 3) Dissolve the crude nasturtium polysaccharide in distilled water, adsorb it with a macroporous resin, elute it with an ethanol solution, collect the 65% ethanol eluate, dry it, and the filter residue is the nasturtium polysaccharide.

[0059] Method 5: Extraction and purification of nasturtium polysaccharide

[0060] The ratio of β-glucosidase to brown alginic pectinase in step 1) is 1:1, and the rest is the same as method 3.

[0061] Table 1 The yield of nasturtium polysaccharide

[0062] method Nasturtium raw material (kg) Nasturtium polysaccharide (g) Yield (%) 1 3 73.26 24.42 2 3 75.18 25.06 3 3 76.29 25.43 4 3 68.46 22.82 5 3 50.77 16.92

[0063] For the above method of preparing nasturtium polysaccharide, from the perspective of yield, the steps of selecting method 1 to method 3 of the present invention are more suitable for the present invention. The nasturtium polysaccharide in the above method is used for the preparation of methylcobalamin below.

[0064] Example 1: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0065]

[0066] Preparation process:

[0067] 1) adding truncatum polysaccharide to a saturated aqueous solution of β-cyclodextrin, and drying to obtain a truncatum polysaccharide inclusion compound;

[0068] 2) uniformly mixing methylcobalamin, cinnamyl alcohol, benzyl benzoate, 1 / 4 of microcrystalline cellulose and lactose, and granulating to obtain drug-containing granules;

[0069] 3) dissolving the nasturtium polysaccharide inclusion compound and palmitic acid vitamin C ester in 60% ethanol water obtained in step A, spraying the solution on the surface of the drug-containing granules obtained in step B, drying, adding a disintegrant and 3 / 4 of 4 microcrystalline cellulose and lactose, mixing evenly, adding a binder to make a soft material, sieving, making granules, drying, adding a lubricant to mix evenly, and tableting to obtain the product.

[0070] Example 2: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0071]

[0072]

[0073] The preparation process is the same as that of Example 1.

[0074] Example 3: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0075]

[0076] The preparation process is the same as that of Example 1.

[0077] Example 4: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0078]

[0079] The preparation process is the same as that of Example 1.

[0080] Example 5: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0081]

[0082] The preparation process is the same as that of Example 1.

[0083] Example 6: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0084]

[0085] The preparation process is the same as that of Example 1.

[0086] Comparative Example 1: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0087]

[0088]

[0089] The preparation process is the same as that of Example 1.

[0090] Comparative Example 2: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0091]

[0092] The preparation process is the same as that of Example 1.

[0093] Comparative Example 3: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0094]

[0095]

[0096] The preparation process is the same as that of Example 1.

[0097] Comparative Example 4: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0098]

[0099] The preparation process is the same as that of Example 1.

[0100] Comparative Example 5: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0101]

[0102]

[0103] The preparation process is the same as that of Example 1.

[0104] Comparative Example 6: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0105]

[0106] The preparation process is the same as that of Example 1.

[0107] Comparative Example 7: A tablet containing methylcobalamin, the content and preparation process of which are as follows

[0108]

[0109]

[0110] The preparation process is the same as that of Example 1.

[0111] 1. Physical performance testing

[0112] 1.1 Accelerated test conditions: The impurity content and dissolution effect data of the 0th, 1st, 2nd, 3rd and 6th months were tested under accelerated conditions (temperature: 40±2°C, humidity 75±5%).

[0113] 1.2 Detection of related substances

[0114] Chromatographic conditions: octadecylsilane bonded silica gel as filler (Luna C18 column, 4.6mm×250mm, 5μm or equivalent column); 0.03mol / L potassium dihydrogen phosphate solution (adjust pH to 4.5 with 0.2mol / L sodium hydroxide solution or phosphoric acid)-acetonitrile (84:16) as mobile phase; detection wavelength 342nm, detection column temperature 35-45℃; detection flow rate 0.8-1.2ml / min.

[0115] Reference substance: Take about 10 mg of methylcobalamin reference substance, place it in a 20 ml volumetric flask, add water to dissolve and dilute to the scale, shake well, place under natural light for 5 to 10 minutes, take 20 μl and inject it into the liquid chromatograph, adjust the flow rate so that the retention time of the methylcobalamin peak is about 12 minutes, and record the chromatogram.

[0116] Test sample: Crush the tablets of this product, accurately weigh (equivalent to 5 mg of methylcobalamin), accurately add 10 ml of mobile phase, dissolve the methylcobalamin by ultrasound, filter, and take the filtrate as the test solution; accurately measure 1 ml, place in a 100 ml volumetric flask, dilute to the scale with mobile phase, shake well, and use as the control solution.

[0117] According to the chromatographic conditions under the content determination item, accurately measure 20μl of the test solution and the control solution, inject them into the liquid chromatograph respectively, and record the chromatogram.

[0118] 1.3 Dissolution testing

[0119] The dissolution test was conducted using the second method of General Rules 0931 of the 2020 edition of the Chinese Pharmacopoeia, with water as the dissolution medium and a rotation speed of 50 r / min. Test object: the dissolution of the relevant embodiments of the present invention, specifically including Examples 1-6 and Comparative Examples 5-6.

[0120] 1.4 Test results

[0121] 1.4.1 Content of related substances

[0122] Figure 1 :from Figure 1 It can be seen that the single impurity content of Examples 1-6 is below 0.15%, and the single impurity content of Example 3 is below 0.1%. Even after the accelerated test, the impurity content is only 0.06%. The comparative example does not contain the stabilizer component, and the impurity content of methylcobalamin is significantly increased. In the first month, the impurity content exceeds 0.2%. The use of different dosages or preparation processes also has a greater impact on the content of related substances, resulting in a final impurity content that is significantly higher than that of Examples 1-6.

[0123] Figure 2 :from Figure 2 It can be seen that the impurity content of Examples 1-6 is below 0.35%, which is basically consistent with the detection of the single impurity content, indicating that the stabilizer and nasturtium polysaccharide play an important role in the stabilization of methylcobalamin.

[0124] Figure 3 : Dissolution of the embodiments of the present invention in aqueous solution, dissolution comparison at 0, 1, 2, 5, 7, 10, 15, 20, and 30 min. It can be seen that the final dissolution of embodiments 1-3 is significantly higher than that of comparative examples 5-6.

[0125] 2. Pharmacodynamics Experiment

[0126] 2.1 Animals and groups

[0127] 32 male SPF mice aged 6-8 weeks, weighing 40±5g, license number: SYXK (Lu)

[0128] 20230031 Production unit: Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The mice were divided into: normal group (n=10), model group (n=10), positive control group (n=10), Example 3 group (n=10) and Comparative Example 3 group (n=10).

[0129] Growth conditions: Raise in a quiet space with a room temperature of 25-27°C and a humidity of 45%, drink sterilized water, and ensure that the mice are healthy and free from malnutrition and other diseases.

[0130] 2.2 Model group establishment

[0131] Animal grouping: Spontaneous type 2 diabetic db / db mice were divided into a model group, a positive control group, Example 3 group and Comparative Example 3 group.

[0132] Dosage: Oral administration. Calculated based on methylcobalamin, the dosage for mice with a human weight of 70 kg is 13.65 mg / kg, twice a day, at 8 am and 8 pm, for 12 consecutive weeks.

[0133] Another 10 BALB / c mice were set as the normal group. The mice in the normal group and the model group were gavaged with equal doses of 0.9% saline twice a day, at 8 am and 8 pm, for 12 consecutive weeks.

[0134] 2.3 Detection indicators

[0135] 2.3.1 The biological signal acquisition system detected the motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (ScV) of mice. After anesthesia, the mice were fixed in prone position and the body temperature was maintained at 37°C. The biological signal acquisition system measured the MCV and SCV on the right side of the mice.

[0136] 2.4.2 Laser Doppler flowmeter to detect changes in blood flow in the sciatic nerve tissue of mice Anesthetized mice were fixed in a supine position, and animal laser Doppler blood flowmeter was used to detect changes in blood flow in the sciatic nerve tissue of mice.

[0137] 2.4 Statistical analysis

[0138] Graphad Prism 9.0 was used for statistical analysis, and the data were expressed as mean ± standard deviation. The data of each group were tested for normal distribution and homogeneity of variance, which met the requirements of Pearson's test, and one-way analysis of variance was used for comparison between groups. P < 0.05 was considered statistically significant.

[0139] 2.5 Results Analysis

[0140] Figure 4 : As for the percentage change of blood flow, it can be seen that the normal group has a significant difference compared with the model group (P<0.01), the Example 3 group has a significant difference compared with the model group (P<0.05), and there is no significant difference between the comparative example 3 combined positive control group and the model group.

[0141] Figure 5 : It can be seen that the motor nerve conduction velocity has significant differences between each embodiment group and the model group, indicating that methylcobalamin alone has significant therapeutic effects, and embodiment 3 group has significant differences compared with methylcobalamin alone and comparative example 3 of the present invention (P<0.01), suggesting that vegetable polysaccharide and methylcobalamin have a synergistic effect and can improve the motor nerve conduction velocity.

[0142] Figure 6 :The conduction velocity of sensory nerves is similar to that of motor nerves, which further proves the effectiveness of the embodiments of the present invention. The embodiment 3 group has significant differences (P<0.01) compared with the single use of methylcobalamin and the comparative example 3 group of the present invention, suggesting that vegetable polysaccharide and methylcobalamin have a synergistic effect and can increase the conduction velocity of sensory nerves.

Claims

1. A methylcobalamin tablet, characterized in that The methylcobalamin tablets are composed of the following components by weight: 500 parts of methylcobalamin, 160-400 parts of β-cyclodextrin, 80-200 parts of nasturtium polysaccharide, 80-200 parts of cinnamyl alcohol, 4350-12000 parts of filler, 90-200 parts of disintegrant, 90-270 parts of benzyl benzoate, 30-90 parts of vitamin C palmitate, 60-140 parts of lubricant and an appropriate amount of binder. The preparation process of the methylcobalamin tablets comprises the following steps: 1) adding truncatum polysaccharide to a saturated aqueous solution of β-cyclodextrin and drying to obtain a truncatum polysaccharide inclusion compound; 2) mixing methylcobalamin, cinnamyl alcohol, benzyl benzoate and 1 / 4 of the filler evenly, and granulating to obtain drug-containing granules; 3) dissolving the nasturtium polysaccharide inclusion compound and palmitic acid vitamin C ester in 60% ethanol water obtained in step A, spraying the solution on the surface of the drug-containing granules obtained in step B, drying, adding a disintegrant and 3 / 4 of a filler and mixing evenly, adding a binder to make a soft material, sieving, making granules, drying, adding a lubricant and mixing evenly, and tableting to obtain the product.

2. The methylcobalamin tablet according to claim 1, characterized in that The methylcobalamin tablets are composed of the following components by weight: 500 parts of methylcobalamin, 20 parts of beta-cyclodextrin, 15 parts of nasturtium polysaccharide, 3 parts of cinnamyl alcohol, 200 parts of microcrystalline cellulose, 17 parts of low-substituted hydroxypropyl cellulose, 8 parts of colloidal silicon dioxide and 5 parts of magnesium stearate.

3. The methylcobalamin tablet according to claim 1, characterized in that The filler is selected from one or two of microcrystalline cellulose, lactose, mannitol, and sorbitol; preferably microcrystalline cellulose and lactose.

4. The methylcobalamin tablet according to claim 1, characterized in that The disintegrant is selected from one or more of sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; preferably low-substituted hydroxypropyl cellulose.

5. The methylcobalamin tablet according to claim 1, characterized in that The adhesive is selected from a 10% aqueous solution of povidone K30 or a 30% starch slurry; preferably a 10% aqueous solution of povidone K30.

6. The methylcobalamin tablet according to claim 1, characterized in that The methylcobalamin tablets are composed of the following components by weight: 500 parts of methylcobalamin, 160-400 parts of beta-cyclodextrin, 80-200 parts of nasturtium polysaccharide, 80-200 parts of cinnamyl alcohol, 2900-8000 parts of microcrystalline cellulose and 1450-4000 parts of lactose, 90-200 parts of low-substituted hydroxypropyl cellulose, 90-270 parts of benzyl benzoate, 30-90 parts of vitamin C palmitate, 60-140 parts of magnesium stearate and an appropriate amount of 10% aqueous solution of povidone K30.

7. The methylcobalamin tablet according to claim 6, characterized in that The dosage ratio of benzyl benzoate and vitamin C palmitate is 3:

1.

8. The methylcobalamin tablet according to claim 1, characterized in that The extraction method of the trollius polysaccharide is: 1) Soak the nasturtium in 50-80°C hot water for 1-3 hours, cool to room temperature, add β-glucosidase and brown algae pectinase, perform enzymolysis for 1-2 hours, adjust the temperature and pH, centrifuge, and reserve the supernatant; 2) adding 1-3 times the volume of 100% ethanol to the supernatant, standing and filtering, and the filter residue is the crude polysaccharide of nasturtium; 3) Dissolve the crude polysaccharide from the truncatum var. nasturtium in distilled water, adsorb it with a macroporous resin, elute it with an ethanol solution, collect the 65% ethanol eluate, dry it, and the residue is the truncatum var. nasturtium var. nasturtium polysaccharide.

9. The methylcobalamin tablet according to claim 8, characterized in that The dosage ratio of β-glucosidase and brown alginic pectinase in step 1) is 6-10:1; the temperature is 45-55° C., and the pH value is 4.5-5.

5.

10. A methylcobalamin tablet, characterized in that: The methylcobalamin tablets are composed of the following components by weight: 500 parts of methylcobalamin, 300 parts of β-cyclodextrin, 140 parts of nasturtium polysaccharide, 140 parts of cinnamyl alcohol, 5000 parts of microcrystalline cellulose, 2500 parts of lactose, 120 parts of low-substituted hydroxypropyl cellulose, 150 parts of benzyl benzoate, 50 parts of vitamin C palmitate, 100 parts of magnesium stearate and an appropriate amount of 10% aqueous solution of povidone K30. The preparation process of the methylcobalamin tablets comprises the following steps: 1) adding truncatum polysaccharide to a saturated aqueous solution of β-cyclodextrin and drying to obtain a truncatum polysaccharide inclusion compound; 2) uniformly mixing methylcobalamin, cinnamyl alcohol, benzyl benzoate, 1 / 4 of microcrystalline cellulose and lactose, and granulating to obtain drug-containing granules; 3) dissolving the nasturtium polysaccharide inclusion compound and palmitic acid vitamin C ester in 60% ethanol water obtained in step A, spraying the solution on the surface of the drug-containing granules obtained in step B, drying, adding a disintegrant and 3 / 4 of 4 microcrystalline cellulose and lactose, mixing evenly, adding a binder to make a soft material, sieving, making granules, drying, adding a lubricant to mix evenly, and tableting to obtain the product.

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