CN115607505A - A kind of oral preparation of azvudine and its preparation method and application - Google Patents

Abstract

The invention discloses an oral preparation of azlodine, a preparation method and application thereof, relating to the technical field of medicine and solving the problem that the prior art lacks oral medicines for treating patients with novel coronavirus pneumonia. The oral administration of the Alzheimer's disease comprises 0.3-8% of Alzheimer's disease and 92-99.7% of auxiliary materials, wherein the auxiliary materials comprise one or more of fillers, binders, disintegrating agents and lubricants; when the auxiliary materials comprise a filler, a binder, a disintegrating agent and a lubricant, the mass ratio of the filler, the binder, the disintegrating agent and the lubricant is (60-95): (0 to 8): (1-20): (0.1-5). The preparation method is used for preparing the oral preparation of the Alzheimer's disease. The oral preparation of the Alzheimer's disease and the preparation method and the application thereof provided by the invention are used for treating patients with the novel coronavirus pneumonia or AIDS without hospitalization.

Description

A kind of oral preparation of azvudine and its preparation method and application

technical field

The invention relates to the technical field of medicine, in particular to an oral preparation of azvudine, a preparation method and application thereof.

Background technique

AIDS (Acquired Immune Deficiency Syndrome, AIDS) is caused by infection with HIV (Human Immunodeficiency Virus, HIV), a virus that can attack the human immune system. It takes the most important CD4 T lymphocytes in the human immune system as the main attack target, destroys the cells in large quantities, and makes the human body lose its immune function. Therefore, the human body infected with AIDS is prone to various diseases and malignant tumors, with a high mortality rate. In July 2021, the State Drug Administration approved Azvudine for use in combination with nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors to treat adult HIV-1 infected patients with high viral load.

The new coronavirus is also a virus that can attack the human immune system. People infected with the new coronavirus pneumonia often need to be hospitalized for anti-infection treatment, which requires a lot of medical resources and economic costs for treatment.

Contents of the invention

The object of the present invention is to provide an oral preparation of azvudine and its preparation method and application, which are used to treat patients infected with novel coronavirus pneumonia or patients infected with AIDS, without hospitalization for anti-infection treatment, reducing medical expenses , saving medical resources.

In order to achieve the above object, the present invention provides the following technical solutions:

In the first aspect, the present invention provides an oral preparation of azvudine, including azvudine and auxiliary materials, the mass percentage of said azvudine is 0.3%-8%, and the mass percentage of said auxiliary materials is 92%- 99.7%, the auxiliary material includes one or more of fillers, binders, disintegrants, and lubricants; when the auxiliary materials include fillers, adhesives, disintegrants, and lubricants, the filler The mass ratio of the agent, the binder, the disintegrant and the lubricant (60-95): (0-8): (1-20): (0.1-5).

Compared with the prior art, the oral preparation of azvudine provided in the embodiment of the present invention includes azvudine and auxiliary materials. Among them, Azvudine is a synthetic nucleoside analogue whose target is the viral RNA polymerase (RdRp), which can block the synthesis and replication of RNA chains in host cells by inhibiting the activity of RdRp . In addition, as a nucleoside analogue, Azvudine can also be incorporated as a substrate by "simulating" natural nucleosides during viral replication, thereby terminating the synthesis of viral RNA chains or causing loss of viral viability, preventing RNA replication. Since the new coronavirus, like HIV, is an RNA virus, azvudine can specifically inhibit the activity of viral RNA-dependent RNA polymerase (RdRp) during the viral replication process, thereby inhibiting the viral replication process. The purpose of using oral preparations to treat new coronavirus pneumonia and AIDS is achieved, so that patients do not need to be hospitalized for anti-infection treatment, reducing medical expenses and saving medical resources. At the same time, since the mass percentage of azvudine in the embodiment of the present invention is 0.3% to 8%, and the mass percentage of the auxiliary material is 92% to 99.7%, within the range of this mass percentage, azvudine can be uniformly dispersed in the auxiliary material Inside. The auxiliary materials include fillers, binders, disintegrants and lubricants, the mass ratio of fillers, binders, disintegrators and lubricants (60-95): (0-8): (1-20): (0.1~5). Therefore, within this mass ratio range, the excipients, while acting as a carrier, are also conducive to the formation of the form of the oral preparation of azvudine, and also have important functions such as solubilization, dissolution aid, and sustained and controlled release. Because azvudine is wrapped by excipients, it can also improve the stability of the drug, reduce the adverse reactions caused by direct contact between azvudine and the human digestive system, increase the compliance of patients with medication, and make the process of taking drugs easier for patients. easy.

It can be seen from the above that the oral preparation of azvudine in the embodiment of the present invention is used to treat patients infected with novel coronavirus pneumonia or patients infected with AIDS. It does not require hospitalization for anti-infection treatment, which reduces medical expenses and saves medical resource.

In the second aspect, the present invention also provides a method for preparing an oral preparation of azvudine, comprising:

Azvudine is mixed with auxiliary materials to obtain a premix;

The premix is made into an oral preparation of azvudine.

Compared with the prior art, the beneficial effect of the preparation method of the oral azvudine preparation provided by the present invention is the same as that of the first aspect of the oral azvudine preparation, and will not be repeated here.

In the third aspect, the application of an oral preparation of azvudine in the preparation of medicines for treating human immunodeficiency diseases.

Compared with the prior art, the beneficial effect of the application of the azvudine oral preparation provided by the present invention in the treatment of human immunodeficiency diseases is the same as that of the first aspect of the azvudine oral preparation, and will not be repeated here.

Description of drawings

The accompanying drawings described here are used to provide a further understanding of the present invention, and constitute a part of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention, and do not constitute improper limitations to the present invention. In the attached picture:

Fig. 1 shows the flowchart of the preparation method of the oral preparation of azvudine in this embodiment.

detailed description

In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention.

In addition, the terms "first" and "second" are used for descriptive purposes only, and cannot be interpreted as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features. Thus, a feature defined as "first" and "second" may explicitly or implicitly include one or more of these features. In the description of the present invention, "plurality" means two or more, unless otherwise specifically defined. "Several" means one or more than one, unless otherwise clearly and specifically defined.

The early symptoms of the new coronavirus infection in the human body are similar to those of common cold symptoms caused by viral infections. The main manifestations are fatigue, fatigue, and muscle soreness. A small number of patients also have gastrointestinal reactions, such as abdominal pain and diarrhea. As the symptoms worsen, the patient will experience dyspnea, chest tightness, shortness of breath, and even severe symptoms such as respiratory distress. Imaging examinations will reveal ground-glass interstitial changes in the lungs, and sepsis, septic shock, coagulation disorders, and renal failure may also occur in severe cases. Therefore, it is necessary to develop an oral specific drug for the treatment of novel coronavirus pneumonia.

在临床上，阿兹夫定作为一种人工合成的核苷类似物，可在细胞内磷酸化，成为有活性的5’-三磷酸盐代谢物(即阿兹夫定三磷酸盐)，阿兹夫定三磷酸盐能抑制重组HIV逆转录酶的活性，导致病毒的DNA 链合成中止。下面结合实施例从阿兹夫定口服制剂和制备方法两个角度详细描述。In view of the above problems, the embodiment of the present invention provides an application of azvudine oral preparations in the preparation of medicines for the treatment of human immunodeficiency diseases, so that when treating patients with novel coronavirus pneumonia, it is not necessary to be hospitalized for anti-infection treatment, reducing the Medical expenses save medical resources. Among them, the human immunodeficiency disease can be novel coronavirus pneumonia, AIDS or other human immunodeficiency diseases, which will not be described here. The chemical name of Azvudine is 1-(4-azido-2-deoxy-2-fluoro-β-D-ribofuranosyl)cytosine, and its structural formula is:

Clinically, Azvudine, as a synthetic nucleoside analogue, can be phosphorylated in cells to become an active 5'-triphosphate metabolite (ie, Azvudine triphosphate). Zivudine triphosphate can inhibit the activity of recombinant HIV reverse transcriptase, leading to the suspension of DNA chain synthesis of the virus. The following is a detailed description from two aspects of the oral formulation of azvudine and the preparation method in conjunction with the examples.

An oral preparation of azvudine provided by an embodiment of the present invention includes azvudine and auxiliary materials, the mass percentage of azvudine is 0.3% to 8%, the mass percentage of auxiliary materials is 92% to 99.7%, and the auxiliary materials include: One or more of fillers, binders, disintegrants, lubricants. When the auxiliary materials include fillers, binders, disintegrants and lubricants, the mass ratio of fillers, binders, disintegrators and lubricants (60-95): (0-8): (1-20) : (0.1~5). It should be understood that the dosage form of the azvudine oral preparation may be a solid dosage form, and the solid dosage form may include tablets, dispersions, capsules or other solid preparations, which are not limited here. When the solid dosage form is a tablet, the oral formulation of azvudine in the embodiment of the present invention also includes a coating layer and/or indentation, the coating layer can be a film coating layer, and the film coating layer can be a gastric Soluble film coating material.

The oral preparations of azvudine provided in the embodiments of the present invention include azvudine and auxiliary materials. Among them, Azvudine is a synthetic nucleoside analogue whose target is the viral RNA polymerase (RdRp), which can block the synthesis and replication of RNA chains in host cells by inhibiting the activity of RdRp . In addition, as a nucleoside analogue, Azvudine can also be incorporated as a substrate by "simulating" natural nucleosides during viral replication, thereby terminating the synthesis of viral RNA chains or causing loss of viral viability, preventing RNA replication. Since the new coronavirus, like HIV, is an RNA virus, azvudine can specifically inhibit the activity of viral RNA-dependent RNA polymerase (RdRp) during the viral replication process, thereby inhibiting the viral replication process, The purpose of using oral preparations to treat new coronavirus pneumonia and AIDS is achieved, so that patients do not need to be hospitalized for anti-infection treatment, reducing medical expenses and saving medical resources. At the same time, since the mass percentage of azvudine in the embodiment of the present invention is 3% to 8%, and the mass percentage of the auxiliary material is 92% to 97%, within the range of this mass percentage, azvudine can be uniformly dispersed in the auxiliary material Inside. The auxiliary materials include fillers, binders, disintegrants and lubricants, the mass ratio of fillers, binders, disintegrators and lubricants (60-95): (0-8): (1-20): (0.1~5). Therefore, within this mass ratio range, the excipients, while acting as a carrier, are also conducive to the formation of the form of the oral preparation of azvudine, and also have important functions such as solubilization, dissolution aid, and sustained and controlled release. Because azvudine is wrapped by excipients, it can also improve the stability of the drug, reduce the adverse reactions caused by direct contact between azvudine and the human digestive system, increase the compliance of patients with medication, and make the process of taking drugs easier for patients. easy.

It can be seen from the above that the oral preparation of azvudine in the embodiment of the present invention is used to treat patients infected with novel coronavirus pneumonia or patients infected with AIDS. It does not require hospitalization for anti-infection treatment, which reduces medical expenses and saves medical resource.

Exemplarily, the mass ratio of filler, binder, disintegrant and lubricant in the embodiment of the present invention can also be (70-95): (0.5-5): (2-10): (0.3-3 ).

Exemplarily, in the oral formulation of azvudine according to the embodiment of the present invention, for fillers, fillers are introduced into azvudine, which may include microcrystalline cellulose, lactose, mannitol, silicified microcrystalline cellulose and one or more of calcium hydrogen phosphate, preferably one or both of microcrystalline cellulose and lactose, can ensure that the oral preparation of azvudine reaches the quality or volume standard for making solid dosage forms.

For the binder, the binder includes one or more of corn starch, hydroxypropyl cellulose, hypromellose, and povidone.

For the lubricant, the lubricant includes one or both of stearate, talc and glyceryl behenate, wherein the stearate includes magnesium stearate, sodium stearyl fumarate, hard One or more of calcium fatty acid.

For the disintegrant, the disintegrator includes one or more of crospovidone, croscarmellose sodium and carboxymethyl starch sodium, preferably croscarmellose sodium, One or two of sodium carboxymethyl starch.

In an achievable manner, in the oral formulation of azvudine according to the embodiment of the present invention, the particle size distribution (Particle Size Distribution, PSD) D50 of azvudine is 1 μm-90 μm. The particle size distribution reflects the percentage of particles with different particle size distributions in the total particles in the powder sample. Among them, D50 means: the corresponding particle size when the cumulative particle size distribution percentage of a sample reaches 50%. Its physical meaning is that the particles with a particle size larger than it account for 50%, and the particles smaller than it also account for 50%. D50 is also called the median diameter or median particle diameter. D50 is often used to indicate the average particle size of powder. When the particle size distribution of azvudine in the embodiment of the present invention is within this range, the adhesion on the surface of azvudine is reduced, the electrostatic adsorption is weakened, and it is not easy to aggregate. Therefore, when azvudine and auxiliary materials are mixed , can carry out mixing and sieving relatively smoothly, thereby reducing the difficulty of sieving, reducing the sieving time, and avoiding the situation that the mixed material in sieving will block the sieve hole or get stuck in the sieve hole.

In one example, the particle size distribution D50 of azvudine in the embodiment of the present invention may also be 1 μm˜70 μm. In another example, the particle size distribution D50 of azvudine in the embodiment of the present invention may also be 1 μm˜50 μm.

In an optional manner, the existence forms of azvudine in the embodiment of the present invention include free base form and/or pharmaceutically acceptable salt form.

Fig. 1 shows the flowchart of the preparation method of the oral preparation of azvudine in this embodiment.

As shown in Figure 1, the present invention also provides a preparation method for oral preparations of azvudine, including:

Step 101: Mix and granulate azvudine and auxiliary materials to obtain a premix.

In one example, Azvudine can be mixed with fillers, binders, and disintegrants, and put into a wet granulator to make soft materials to obtain wet granules, which are then dried in a fluidized bed. Obtain dry whole grains. The sieved lubricant is then added for mixing to obtain a premix.

In another example, the azvudine can be mixed with a filler, a binder, a disintegrant and a lubricant, and then put into a dry granulator for granulation to obtain a premix.

In yet another example, Azvudine can be mixed with fillers, binders, and part of the disintegrant, and then granulated with a top spray granulator to obtain granules, and then the lubricating powder obtained after sieving can be added. Agents are mixed to obtain a premix.

It should be understood that in the embodiment of the present invention, any one of the above three methods can be used to obtain the premixture, and the preparation can also be prepared by using a direct pressure process and a fluidized bed process. No matter which granulation method is adopted, the oral azvudine formulation of the embodiment of the present invention can be obtained.

Step 102: Prepare the premixture into an oral preparation of azvudine.

For example: the premix is compressed into tablets or dispersible tablets using a rotary tablet machine, the premix is encapsulated into capsules, or the tablet is compressed into a powder or granule dispersion. It should be understood that a dispersant refers to a dosage form that can be dispersed in water before administration, and the dispersant of the embodiments of the present invention can be dispersed in an aqueous medium such as purified water within 5 minutes or less, preferably 3 minutes or less, so Ease of administration, eg, to children, the elderly, or patients who have difficulty swallowing. At the same time, since the dissolution becomes slow and incomplete when the content of microcrystalline cellulose is high, the solubility of the dispersed dosage form can be improved by reducing the amount of microcrystalline cellulose. When it is made into tablets, it can be made into plain tablets of the target specifications, or it can be film-coated to make coated tablets. Among them, the azvudine oral preparation prepared according to the technical solution of the present invention has good particle flow properties, a wide granulation process window, smooth sieving process, no sieve blocking or stuck sieve phenomenon, and no shrapnel appears in the tablet. And the phenomenon of unstable tablet weight, it is easier to realize the challenge of higher-speed tablet compression in industrialized mass production, and achieve the purpose of saving time and energy.

In order to verify the effect of the oral formulation of azvudine provided in the examples of the present invention, the examples of the present invention take solid dosage forms as tablets and dispersions for illustration.

Embodiment one

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 1 μm. The quantity of the azvudine oral preparation of the embodiment of the present invention is 1000 tablets, and Table 1 shows the composition ratio table of the azvudine oral preparation of the embodiment 1 of the present invention.

The composition ratio table of the azvudine oral preparation of table 1 embodiment one

The preparation method of the oral preparation of azvudine provided in Embodiment 1 of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine, lactose, microcrystalline cellulose, corn starch, and croscarmellose sodium, and put it into a wet granulator to make soft materials to obtain wet-finished Granules are then dried in a fluidized bed to obtain dry granules. Then add the sieved magnesium stearate for mixing to obtain a premix.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablet is film-coated in a coating machine with a gastric-soluble film coating material to obtain the oral preparation of azvudine. The target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment two

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 30 μm. The quantity of the oral preparation of azvudine in the embodiment of the present invention is 1000 tablets, and Table 2 shows the composition ratio table of the oral preparation of azvudine in the second embodiment of the present invention.

The component distribution table of the azvudine oral preparation of table 2 embodiment two

The preparation method of the oral preparation of azvudine provided in the second embodiment of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine, lactose, microcrystalline cellulose, hydroxypropyl cellulose, and cross-linked povidone, and put it into a wet granulator to make soft materials to obtain wet-finished Granules are then dried in a fluidized bed to obtain dry granules. Then add the sieved calcium stearate for mixing to obtain a premix.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablet is film-coated in a coating machine with a gastric-soluble film coating material to obtain the oral preparation of azvudine. The target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment three

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 50 μm. The quantity of the oral preparation of azvudine in the embodiment of the present invention is 1000 tablets, and Table 3 shows the composition ratio table of the oral preparation of azvudine in the third embodiment of the present invention.

Table 3 The component distribution table of the azvudine oral preparation of embodiment three

The preparation method of the oral preparation of azvudine provided in Example 3 of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine with silicified microcrystalline cellulose, hypromellose, povidone, and sodium carboxymethyl starch, and put it into a wet granulator to make soft materials. Wet granules are obtained, and then dried in a fluidized bed to obtain dry granules. Then add the sieved magnesium stearate for mixing to obtain a premix.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablets are film-coated and indented in a coating machine with a gastric-soluble film-coating material to obtain azvudine For oral preparations, the target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment Four

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 90 μm. The quantity of the oral preparation of azvudine in the embodiment of the present invention is 1000 tablets, and Table 4 shows the composition ratio table of the oral preparation of azvudine in the fourth embodiment of the present invention.

The component distribution table of the azvudine oral preparation of table 4 embodiment four

The preparation method of the oral preparation of azvudine provided in the fourth embodiment of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine with calcium hydrogen phosphate, microcrystalline cellulose, hydroxypropyl cellulose, and cross-linked povidone, and put it into a wet granulator to make soft materials to obtain wet Granules are sized, and then dried in a fluidized bed to obtain dry granules. Then add the sieved magnesium stearate for mixing to obtain a premix.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablet is film-coated in a coating machine with a gastric-soluble film coating material to obtain the oral preparation of azvudine. The target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment five

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is 70 μm. The quantity of the oral preparation of azvudine in the embodiment of the present invention is 1000 tablets, and Table 5 shows the composition ratio table of the oral preparation of azvudine in the fifth embodiment of the present invention.

The component distribution table of the azvudine oral preparation of table 5 embodiment five

The preparation method of the oral preparation of azvudine provided in the fifth embodiment of the present invention comprises the following steps:

The first step is to prepare the premix: Azivudine is mixed with lactose, microcrystalline cellulose, povidone, and croscarmellose sodium, and put into a wet granulator to make soft materials to obtain wet Granules are sized, and then dried in a fluidized bed to obtain dry granules. Then add the sieved glyceryl behenate for mixing to obtain a premix.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablet is film-coated in a coating machine with a gastric-soluble film coating material to obtain the oral preparation of azvudine. The target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment six

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 20 μm. The quantity of the oral preparation of azvudine in the embodiment of the present invention is 1000 tablets, and Table 6 shows the composition ratio table of the oral preparation of azvudine in the sixth embodiment of the present invention.

The component distribution table of the azvudine oral preparation of table 6 embodiment six

The preparation method of the oral preparation of azvudine provided in Example 6 of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine with mannitol, microcrystalline cellulose, corn starch, and crospovidone evenly, then add sieved magnesium stearate for mixing to obtain the premix things.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablet is film-coated in a coating machine with a gastric-soluble film coating material to obtain the oral preparation of azvudine. The target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment seven

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 20 μm. The quantity of the oral preparation of azvudine in the embodiment of the present invention is 1000 tablets, and Table 7 shows the composition ratio table of the oral preparation of azvudine in the seventh embodiment of the present invention.

Table 7 The composition ratio table of the azivudine oral preparation of Example 7

The preparation method of the oral preparation of azvudine provided by Embodiment 7 of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine with silicified microcrystalline cellulose, corn starch, and partially cross-linked carmellose sodium, and then granulate it with a top-spray granulator to obtain whole granules. Then add the sodium stearyl fumarate obtained after sieving and mix to obtain a premix.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then the plain tablet is film-coated in a coating machine with a gastric-soluble film coating material to obtain the oral preparation of azvudine. The target coating weight gain is 2% to 4% of the tablet core weight.

Embodiment Eight

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine, and the particle size distribution D50 of azvudine is: 50 μm. The oral formulation of azvudine in the embodiment of the present invention is a dispersant, and Table 8 shows the composition ratio of the oral formulation of azvudine in the eighth embodiment of the present invention.

The component distribution table of the azvudine oral preparation of table 8 embodiment eight

The preparation method of the oral preparation of azvudine provided in the eighth embodiment of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine with lactose, microcrystalline cellulose, and croscarmellose sodium evenly, then add sieved magnesium stearate and mix to obtain the premix .

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then pressurized into granules to obtain the oral preparation of azvudine, that is, the dispersion.

Embodiment nine

The embodiment of the present invention provides an oral preparation of azvudine, and the selected active ingredient is azvudine. The particle size distribution D50 of azvudine is: 30 μm. The oral azvudine preparation of the embodiment of the present invention is a dispersant, and Table 9 shows the composition ratio table of the oral azvudine preparation of the ninth embodiment of the present invention.

The composition ratio table of the azvudine oral preparation of table 9 embodiment nine

Embodiment ten

The embodiment of the present invention provides an oral preparation of azvudine, the selected active ingredient is azvudine particle size distribution D50: 80 μm. The azvudine oral preparation of the embodiment of the present invention is a dispersant, and Table 10 shows the composition ratio of the azvudine oral preparation of the tenth embodiment of the present invention.

The composition ratio table of the azvudine oral preparation of table 10 embodiment nine

Material name components mass (g) active ingredient 1 Azvudine 3 filler Silicified microcrystalline cellulose 109 disintegrant Croscarmellose Sodium 5 lubricant Sodium stearyl fumarate 3

The preparation method of the oral preparation of azvudine provided in the tenth embodiment of the present invention comprises the following steps:

The first step is to prepare the premix: mix Azvudine with silicified microcrystalline cellulose and croscarmellose sodium evenly, then add the sodium stearyl fumarate obtained after sieving and mix to obtain the premix mixture.

The second step is to prepare the oral preparation of azvudine: the premix is compressed into tablets, and then pressurized into granules to obtain the oral preparation of azvudine, that is, the dispersion.

The embodiment of the present invention also carries out the content test, dissolution test, disintegration test and friability test of the azvudine oral preparation prepared in the embodiment to obtain the content, dissolution rate, disintegration time limit, friability Fragmentation. Among them, the dissolution rate refers to the speed and degree of dissolution of a drug from a solid preparation such as a tablet in a specified solvent.

Table 11 shows the content, dissolution rate, disintegration time limit, and friability of Examples 1 to 10. Among them, the dissolution conditions: 0.01mol/L hydrochloric acid solution, 900ml, 37°C, paddle method 50rpm, 30min, the results as follows:

The test result of table 11 embodiment one to embodiment ten

As can be seen from the above table: the dissolution rate of the azvudine oral preparations prepared in embodiments 1 to 10 is 0.01mol/L hydrochloric acid solution, 900ml, and the dissolution rate of azvudine in 37 ℃ is greater than 80%. The contents of the azvudine oral preparations prepared in Examples 1 to 10 are all greater than 99.9%, and the disintegration time of the azvudine oral preparations prepared in Examples 1 to 10 are all less than or equal to 5 min. The friability of the prepared azvudine oral preparation is less than 1%. It can be seen from the above that the oral formulation of azvudine in the embodiment of the present invention disintegrates faster in the body, so that the human body absorbs faster, and the content of azvudine is high. Therefore, the oral preparation of azvudine in the embodiment of the present invention does not require hospitalization for anti-infection treatment when treating patients infected with novel coronavirus pneumonia or AIDS, which reduces medical expenses and saves medical resources.

Under accelerated conditions (40°C ± 2°C; 75%RH ± 5%RH), store for 6 months, sample and detect the dissolution and impurity situation in 0 month, January, March and June respectively, and record the results of Example 1 The dissolution of ~10 samples has no obvious change, and its dissolution is less affected by temperature and humidity, and the product quality is stable. And the largest single impurity does not exceed 0.1%, the total impurity does not exceed 0.5%, the impurity hardly grows, and has good safety.

The above descriptions are only specific implementations of the present invention, and it is obvious that various modifications and combinations can be made thereto without departing from the spirit and scope of the present invention. Accordingly, the specification and drawings are merely illustrative of the invention as defined by the appended claims and are deemed to cover any and all modifications, variations, combinations or equivalents within the scope of the invention. Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and equivalent technologies thereof, the present invention intends to include these modifications and variations. Any person familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present invention, and all should be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be determined by the protection scope of the claims.

Claims (10)

1. An oral preparation of Alzheimer's disease is characterized by comprising 0.3-8% of Alzheimer's disease and 92-99.7% of auxiliary materials by mass, wherein the auxiliary materials comprise one or more of fillers, binders, disintegrants and lubricants;

when the auxiliary materials comprise a filler, a binder, a disintegrating agent and a lubricant, the mass ratio of the filler, the binder, the disintegrating agent and the lubricant is (60-95): (0 to 8): (1-20): (0.1-5).

2. The oral formulation of alzheimer's disease as claimed in claim 1 wherein said oral formulation of alzheimer's disease comprises a tablet, a capsule and a dispersion.

3. The oral formulation of azvudine according to claim 1, wherein when the excipient comprises a filler, the filler comprises one or more of microcrystalline cellulose, lactose, mannitol, silicified microcrystalline cellulose and dibasic calcium phosphate.

4. The oral formulation of azvudine according to claim 1, wherein when the excipient comprises a binder, the binder comprises one or more of corn starch, hydroxypropyl cellulose, hypromellose and povidone.

5. The oral formulation of azvudine according to claim 1, wherein when the excipient comprises a disintegrant, the disintegrant comprises one or more of crospovidone, croscarmellose sodium and sodium carboxymethyl starch.

6. The oral formulation of azfudine according to claim 1, wherein when said excipient comprises a lubricant, said lubricant comprises one or more of stearate, talc and glyceryl behenate.

7. The oral formulation of alzheimer's disease as claimed in any of claims 1 to 6 wherein said alzheimer's disease has a particle size distribution D50 of 1 μm to 90 μm and said alzheimer's disease is present in a form comprising the free base form and/or the pharmaceutically acceptable salt form.

8. A method for producing an oral preparation of azlodine according to any one of claims 1 to 7, comprising:

mixing and granulating the azvudine and auxiliary materials to obtain a premix;

preparing the premix into an oral preparation of the azvudine.

9. The method for preparing an oral formulation of azxivudine according to claim 8, wherein the granulation is one or more of dry granulation, wet granulation or top-spray granulation.

10. An application of the oral preparation of Alzheimer's disease in preparing the medicines for treating human immunodeficiency diseases is disclosed.

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