Enteric-coated tablet for treating neuritis and preparation method thereof

Abstract

The invention provides an enteric-coated tablet for treating neuritis and a preparation method of the enteric-coated tablet. The enteric-coated tablet is prepared from the following components in percentage by weight: 0.01%-1% of mecobalamin, 60%-80% of butanedisulfonic acid adenosyl methionine, 10%-30% of a diluent, 4%-9% of an adhesive, 1%-5% of a disintegrating agent, 0.1%-1% of a lubricant and 8%-16% of an enteric-coated material. The enteric-coated tablet disclosed by the invention is simple in production process, universal in production equipment and low in cost, mainly overcomes the defect of large in-vivo absorption difference, and has a remarkable curative effect on treating neuritis.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to an enteric-coated tablet for treating neuritis and its preparation method. Background Technology

[0002] Neuritis, also known as peripheral neuritis, is a general term for peripheral neuritis and degenerative diseases caused by various pathological conditions. It is mainly divided into mononeuritis and polyneuritis. Mononeuritis involves damage to a single peripheral nerve, mostly caused by local trauma or compression resulting in sensory and motor disturbances in the nerve's innervation area. Polyneuritis is a general term for damage to multiple peripheral nerves caused by various factors, such as poisoning, nutritional and metabolic disorders, and infections.

[0003] Methylcobalamin, also known as methyl vitamin B12, is an active metabolite of vitamin B12 in the body. Its main functions are to promote the synthesis of DNA, nucleic acids, and phospholipids, maintain the integrity of nerve myelin sheath structure, and repair damaged nerve fibers. Therefore, it is widely used in the clinical treatment of peripheral neuropathy and other diseases. Methylcobalamin is a water-soluble vitamin; even if slightly excessive, it will be excreted in urine, generally posing no risk of accumulation. Therefore, long-term use is very safe. Furthermore, methylcobalamin is mostly taken orally. After entering the body, its concentration in the blood reaches peak levels in about three hours, and it is then distributed to various organs and tissues, including the blood, kidneys, pancreas, adrenal glands, liver, and gastrointestinal tract, providing effective therapeutic effects.

[0004] Mecobalamin is generally effective in treating the following four diseases: 1. Diabetic Peripheral Neuropathy: A significant portion of diabetic peripheral neuropathy is caused by persistently high blood sugar levels. Therefore, the first consideration is adjusting the dosage and type of hypoglycemic agents to lower fasting and postprandial blood glucose levels. For diabetic patients who have already experienced lower limb numbness, oral mecobalamin can be chosen to promote regeneration in damaged areas of the nerve axon. Simultaneously, mecobalamin can significantly improve nerve conduction velocity, and when used in combination with hypoglycemic agents, it has a positive therapeutic effect on microvascular and nerve damage.

[0005] 2. Shingles-related neuralgia: Shingles is mainly caused by the varicella-zoster virus, so antiviral medications are highly recommended for these patients. In addition, neurotrophic drugs, such as mecobalamin, should be used in conjunction. Mecobalamin can penetrate well into neuronal cell bodies, repairing nerves damaged by the varicella-zoster virus, effectively relieving or reducing neuralgia, and reducing the risk of postherpetic neuralgia.

[0006] 3. Megaloblastic anemia occurs when the levels of folic acid and vitamin B12 in the body are low, leading to a deficiency of coenzymes. This results in increased RNA synthesis, ultimately causing an imbalance in nucleocytoplasmic development. The cell nucleus remains in a reticular structure and cannot retract in time, resulting in gigantic cells. Timely supplementation with methylcobalamin can help normal DNA synthesis, promote red blood cell growth, and alleviate anemia symptoms caused by vitamin deficiency.

[0007] 4. Acute facial neuritis, commonly known as facial paralysis, is mainly caused by viral infection. Famciclovir is the primary antiviral drug with good antiviral effects. Clinically, in addition to hormones and antiviral drugs, oral mecobalamin is often preferred for treating facial neuritis to nourish the nerves, and its effect is often better than that of ordinary vitamin B12.

[0008] Under normal circumstances, the therapeutic dose of methylcobalamin generally does not produce toxic side effects. However, a small number of people are allergic to the excipients in the drug, and may experience allergic symptoms such as rashes and hives while taking methylcobalamin. Some people may also experience gastrointestinal irritation symptoms such as abdominal discomfort, decreased appetite, nausea, and diarrhea after taking methylcobalamin.

[0009] Therefore, there is an urgent need for a drug to treat neuritis or peripheral neuritis with little or no side effects. Summary of the Invention

[0010] To address the aforementioned problems, this invention provides an enteric-coated tablet for treating neuritis and its preparation method. The production process is simple, the production equipment is universal, and the cost is low. Most importantly, it solves the problem of large differences in in vivo absorption, resulting in significant therapeutic effects for neuritis.

[0011] On one hand, the present invention discloses an enteric-coated tablet for treating neuritis, which is prepared from the following components and proportions: 0.01%-1% methylcobalamin, 60%-80% S-adenosylmethionine disulfate, 10%-30% diluent, 4%-9% binder, 1%-5% disintegrant, 0.1%-1% lubricant, and 8%-16% enteric material.

[0012] Preferably, the diluent is one or more of the following: microcrystalline cellulose colloidal silica copolymer, lactose, anhydrous calcium carbonate, and mannitol.

[0013] Preferably, the enteric material is one or more of hydroxypropyl methylcellulose acetate succinate, polymethyl methacrylate, and hydroxypropyl methylcellulose phthalate.

[0014] Preferably, the lubricant is one or more of magnesium stearate, stearic acid, and polyethylene glycol.

[0015] On the other hand, the present invention also discloses a method for preparing the above-mentioned enteric-coated tablets, the method comprising the following steps: S1. Preparation of adhesive: Dissolve the adhesive in a suitable solvent to prepare a solution with a solid content of 1%-8%, and then dissolve the enteric coating powder in a suitable solvent to prepare a solution with a solid content of 3%-9%. S2. First, place the raw material S-adenosylmethionine disulfonate and diluent in the equipment, start the equipment, and mix evenly. Control the equipment inlet air temperature at 30-60℃ and the absolute humidity of the inlet air at less than 5g / kg. Then, spray the binder solution into the equipment using a spray method for one-step granulation and drying. After granulation for a period of time, spray in polyethylene glycol solution, then add the active ingredient methylcobalamin again, mix evenly, and continue spraying in the binder to continue granulation. After granulation is completed, continue drying to control the particle moisture content to ≤1.2%. S3. Transfer the granules to a mixer, add disintegrant and lubricant, mix evenly, and compress into tablets to obtain unprocessed tablets; S4. Transfer the uncoated film to the coating equipment, turn on the equipment, control the absolute humidity of the incoming air to within 5g / kg, spray in the coating solution, stop coating when the coating weight increases to 9%-13%, dry for 10-30 minutes, control the moisture content to ≤1.6%, and the product is ready.

[0016] Compared with the prior art, the beneficial effects of the present invention are: The enteric-coated tablets prepared in this invention have achieved unexpected results in the treatment of neuritis or peripheral neuritis, showing better efficacy than methylcobalamin alone. Furthermore, this invention solves the problems of methylcobalamin's stability and low absorption after administration.

[0017] The enteric-coated tablets of this invention have a simple production process, low equipment requirements, are convenient to take, and have low production costs. Attached Figure Description

[0018] Figure 1 The dissolution curves of methylcobalamin in the enteric-coated tablets of Examples 1, 2, and 3 of this invention are shown. Figure 2 This is a dissolution curve of S-adenosylmethionine disulfate in the enteric-coated tablets of Examples 1, 2, and 3 of the present invention. Detailed Implementation

[0019] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments and accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0020] Example 1 The enteric-coated tablets provided in this embodiment have the following formulation per 1000 dosage units: Preparation method of enteric-coated tablets: S1. Preparation of the adhesive: Dissolve the HPC adhesive in a suitable solvent (ethanol) to prepare an HPC solution with a solid content of 3%. Prepare a mixed solvent using the prescribed amounts of ethanol, isopropanol, and acetone. Take 95% of this mixed solvent and slowly add hydroxypropyl methylcellulose acetate succinate while stirring. Continue stirring until completely dissolved. Then, take 5% of the mixed solvent and add ferric oxide and titanium dioxide while stirring for at least 20 minutes until uniformly dispersed. Add this to the completely dissolved hydroxypropyl methylcellulose acetate succinate solution and continue stirring for at least 2 hours until uniformly dispersed. Set aside for use. Maintain stirring during the coating process.

[0021] Dissolve polyethylene glycol 6000 in ethanol to prepare a solution with a solid content of 8%, and set aside for later use.

[0022] S2. First, place the raw material S-adenosylmethionine disulfate and diluent in a fluidized bed, start the equipment, and mix evenly; The equipment inlet air temperature is controlled at 30-60℃, and the absolute humidity of the inlet air is controlled within 5g / kg. Then, the 3% HPC solution of the adhesive is sprayed in using a spray method for one-step granulation and drying. After granulation has been going on for 1-2 hours, stop adding HPC solution and replace it with polyethylene glycol solution by spraying until it is completely added. Then add the active ingredient methylcobalamin again, turn on the air inlet to fluidize the material, mix it evenly, and then continue to spray the binder HPC solution to continue granulation until spraying is complete. After granulation, continue drying at 30-60℃ for 1-2 hours, keeping the moisture content ≤1.2%. S3. After drying, transfer the granules to a mixer, add the disintegrant sodium croscarmellose and the lubricant magnesium stearate, mix evenly, compress into tablets, and obtain plain tablets. S4. Transfer the uncoated flakes to the coating equipment, turn on the equipment, and adjust the speed of the coating pan to make the flakes flow. Set the inlet air temperature to 25-40℃, the main unit speed to 2-3 rpm, and preheat for 10-20 minutes. Adjust the spray volume, spray angle, and distance between the nozzle and the material surface. Set the inlet air temperature to 25-40℃, inlet air humidity to less than 5g / kg, flake bed temperature to 20-30℃, main unit speed to 2-7 rpm, atomization pressure to 0.70-1.20 bar, liquid supply peristaltic pump speed to 30-60 rpm, and air volume to 1500-2500 m³ / h. 3At a negative pressure of -90 to 70 kPa, begin coating. During coating, adjust the airflow and peristaltic pump speed according to the tablet condition. Take samples every hour to check the appearance; the coated tablets should be dry, non-sticky, and fine. The target weight gain after coating is 9%-13%. After spraying, adjust the coating pan speed to 2-3 rpm, set the temperature to 40℃, and dry for 1-2 hours. Remove the tablets from the pan and package them using PA / AL / PVC rigid sheets and PTP aluminum foil.

[0023] Example 2 The enteric-coated tablets provided in this embodiment have the following formulation per 1000 dosage units: Preparation method of enteric-coated tablets: S1. Preparation of the adhesive: Dissolve the HPC adhesive in a suitable solvent (ethanol) to prepare an HPC solution with a solid content of 3%. Prepare a mixed solvent using the prescribed amounts of ethanol, isopropanol, and acetone. Take 95% of this mixed solvent and slowly add it to the polymethyl methacrylate solution while stirring. Continue stirring until completely dissolved. Then, take 5% of the mixed solvent and add ferric oxide and titanium dioxide while stirring for at least 20 minutes until uniformly dispersed. Add this mixture to the completely dissolved polymethyl methacrylate solution and continue stirring for at least 2 hours until uniformly dispersed. Set aside for use. Maintain stirring during the coating process.

[0024] Dissolve polyethylene glycol 6000 in ethanol to prepare a solution with a solid content of 8%, and set aside for later use.

[0025] S2. First, place the raw material S-adenosylmethionine disulfate and diluent in a fluidized bed, start the equipment, and mix evenly; The equipment inlet air temperature is controlled at 30-60℃, and the absolute humidity of the inlet air is controlled within 5g / kg. Then, the 3% HPC solution of the adhesive is sprayed in using a spray method for one-step granulation and drying. After granulation has been going on for 1-2 hours, stop adding HPC solution and replace it with polyethylene glycol solution by spraying until it is completely added. Then add the active ingredient methylcobalamin again, turn on the air inlet to fluidize the material, mix it evenly, and then continue to spray the binder HPC solution to continue granulation until spraying is complete. After granulation, continue drying at 30-60℃ for 1-2 hours, keeping the moisture content ≤1.2%. S3. After drying, transfer the granules to a mixer, add the disintegrant sodium croscarmellose and the lubricant magnesium stearate, mix evenly, compress into tablets, and obtain plain tablets. S4. Transfer the uncoated flakes to the coating equipment, turn on the equipment, and adjust the speed of the coating pan to make the flakes flow. Set the inlet air temperature to 25-40℃, the main unit speed to 2-3 rpm, and preheat for 10-20 minutes. Adjust the spray volume, spray angle, and distance between the nozzle and the material surface. Set the inlet air temperature to 25-40℃, inlet air humidity to less than 5g / kg, flake bed temperature to 20-30℃, main unit speed to 2-7 rpm, atomization pressure to 0.70-1.20 bar, liquid supply peristaltic pump speed to 30-60 rpm, and air volume to 1500-2500 m³ / h. 3 At a negative pressure of -90 to 70 kPa, begin coating. During coating, adjust the airflow and peristaltic pump speed according to the tablet condition. Take samples every hour to check the appearance; the coated tablets should be dry, non-sticky, and fine. The target weight gain after coating is 9%-13%. After spraying, adjust the coating pan speed to 2-3 rpm, set the temperature to 40℃, and dry for 1-2 hours. Remove the tablets from the pan and package them using PA / AL / PVC rigid sheets and PTP aluminum foil.

[0026] Example 3 The enteric-coated tablets provided in this embodiment have the following formulation per 1000 dosage units: Preparation method of enteric-coated tablets: S1. Preparation of the adhesive: Dissolve the HPC adhesive in a suitable solvent (ethanol) to prepare an HPC solution with a solid content of 3%. Prepare a mixed solvent using the prescribed amounts of ethanol, isopropanol, and acetone. Take 95% of this mixed solvent and slowly add hydroxypropyl methylcellulose phthalate while stirring. Continue stirring until completely dissolved. Then, take 5% of the mixed solvent and add yellow iron oxide and titanium dioxide while stirring for at least 20 minutes until uniformly dispersed. Add this to the completely dissolved hydroxypropyl methylcellulose phthalate solution and continue stirring for at least 2 hours until uniformly dispersed. Set aside for use. Maintain stirring during the coating process.

[0027] Dissolve polyethylene glycol 6000 in ethanol to prepare a solution with a solid content of 8%, and set aside for later use.

[0028] S2. First, place the raw material S-adenosylmethionine disulfate and diluent in a fluidized bed, start the equipment, and mix evenly; The equipment inlet air temperature is controlled at 30-60℃, and the absolute humidity of the inlet air is controlled within 5g / kg. Then, the 3% HPC solution of the adhesive is sprayed in using a spray method for one-step granulation and drying. After granulation has been going on for 1-2 hours, stop adding HPC solution and replace it with polyethylene glycol solution by spraying until it is completely added. Then add the active ingredient methylcobalamin again, turn on the air inlet to fluidize the material, mix it evenly, and then continue to spray the binder HPC solution to continue granulation until spraying is complete. After granulation, control the inlet air temperature at 30-60℃ and continue drying for 1-2 hours, controlling the moisture content to ≤1.2%.

[0029] S3. After drying, transfer the granules to a mixer, add the disintegrant sodium croscarmellose and the lubricant magnesium stearate, mix evenly, compress into tablets, and obtain plain tablets. S4. Transfer the uncoated flakes to the coating equipment, turn on the equipment, and adjust the speed of the coating pan to make the flakes flow. Set the inlet air temperature to 25-40℃, the main unit speed to 2-3 rpm, and preheat for 10-20 minutes. Adjust the spray volume, spray angle, and distance between the nozzle and the material surface. Set the inlet air temperature to 25-40℃, inlet air humidity to less than 5g / kg, flake bed temperature to 20-30℃, main unit speed to 2-7 rpm, atomization pressure to 0.70-1.20 bar, liquid supply peristaltic pump speed to 30-60 rpm, and air volume to 1500-2500 m³ / h. 3 At a negative pressure of -90 to 70 kPa, begin coating. During coating, adjust the airflow and peristaltic pump speed according to the tablet condition. Take samples every hour to check the appearance; the coated tablets should be dry, non-sticky, and fine. The target weight gain after coating is 9%-13%. After spraying, adjust the coating pan speed to 2-3 rpm, set the temperature to 40℃, and dry for 1-2 hours. Remove the tablets from the pan and package them using PA / AL / PVC rigid sheets and PTP aluminum foil.

[0030] The dissolution data of methylcobalamin in the enteric-coated tablets prepared in Examples 1, 2 and 3 are shown in Table 1.

[0031] Table 1: Dissolution data of methylcobalamin in enteric-coated tablets Figure 1 The dissolution curves of methylcobalamin in the enteric-coated tablets prepared in Examples 1, 2 and 3 are shown.

[0032] The dissolution data of S-adenosylmethionine disulfate in the enteric-coated tablets prepared in Examples 1, 2 and 3 are shown in Table 2.

[0033] Table 2: Dissolution data of S-adenosylmethionine disulfate in enteric-coated tablets Figure 2 The dissolution curves of S-adenosylmethionine disulfate in the enteric-coated tablets prepared in Examples 1, 2 and 3 are shown.

[0034] The enteric-coated tablets prepared by this invention are effective in treating neuritis or peripheral neuritis compared to using methylcobalamin alone. This invention also solves the problems of methylcobalamin's stability and low absorption after administration.

[0035] The enteric-coated tablets of this invention have a simple production process, low equipment requirements, are convenient to take, and have low production costs.

[0036] The detailed descriptions listed above are merely specific descriptions of feasible embodiments of the present invention, and are not intended to limit the scope of protection of the present invention. All equivalent embodiments or modifications made without departing from the spirit of the present invention should be included within the scope of protection of the present invention.

[0037] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0038] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style of the specification is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. An enteric-coated tablet for treating neuritis, characterized in that, The enteric-coated tablets are prepared from the following components and proportions: 0.01%-1% methylcobalamin, 60%-80% S-adenosylmethionine disulfate, 10%-30% diluent, 4%-9% binder, 1%-5% disintegrant, 0.1%-1% lubricant, and 8%-16% enteric material.

2. The enteric-coated tablet according to claim 1, characterized in that, The diluent is one or more of the following: microcrystalline cellulose colloidal silica copolymer, lactose, anhydrous calcium carbonate, and mannitol.

3. The enteric-coated tablet according to claim 2, characterized in that, The enteric material is one or more of hydroxypropyl methylcellulose acetate succinate, polymethyl methacrylate, and hydroxypropyl methylcellulose phthalate.

4. The enteric-coated tablet according to claim 3, characterized in that, The lubricant is one or more of magnesium stearate, stearic acid, and polyethylene glycol.

5. The method for preparing enteric-coated tablets according to any one of claims 1-4, characterized in that, The method includes the following steps: S1. Preparation of adhesive: Dissolve the adhesive in a suitable solvent to prepare a solution with a solid content of 1%-8%, and then dissolve the enteric coating powder in a suitable solvent to prepare a solution with a solid content of 3%-9%. S2. First, place the raw material S-adenosylmethionine disulfonate and diluent in the equipment, start the equipment, and mix evenly. Control the equipment inlet air temperature at 30-60℃ and the absolute humidity of the inlet air at less than 5g / kg. Then, spray the binder solution into the equipment using a spray method for one-step granulation and drying. After granulation for a period of time, spray in polyethylene glycol solution, then add the active ingredient methylcobalamin again, mix evenly, and continue spraying in the binder to continue granulation. After granulation is completed, continue drying to control the particle moisture content to ≤1.2%. S3. Transfer the granules to a mixer, add disintegrant and lubricant, mix evenly, and compress into tablets to obtain unprocessed tablets; S4. Transfer the uncoated film to the coating equipment, turn on the equipment, control the absolute humidity of the incoming air to within 5g / kg, spray in the coating solution, stop coating when the coating weight increases to 9%-13%, dry for 10-30 minutes, control the moisture content to ≤1.6%, and the product is ready.

Images