CN115607505A

CN115607505A - Oral preparation of azfudin, preparation method and application

Info

Publication number: CN115607505A
Application number: CN202211356895.3A
Authority: CN
Inventors: 沈广青; 彭俊清; 张家艾
Original assignee: China Pharmaceutical University
Current assignee: China Pharmaceutical University
Priority date: 2022-11-01
Filing date: 2022-11-01
Publication date: 2023-01-17

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

Oral preparation of azfudin, preparation method and application

Technical Field

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

Background

Acquired Immune Deficiency Syndrome (AIDS) is caused by infection with the Human Immunodeficiency Virus (HIV), a Virus that attacks the immune system of the Human body. It takes the most important CD4T lymphocyte in human immune system as main target to destroy the cell greatly and make human body lose immune function. Therefore, the human body infected with AIDS is easy to be infected with various diseases and generate malignant tumor with high fatality rate. 2021. In 7 months of the year, the national drug administration approved azfudine for use in combination with nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors in the treatment of high viral load adult HIV-1 infected patients.

The novel coronavirus is also a virus capable of attacking the immune system of a human body, and people infected with the novel coronavirus pneumonia are often required to be hospitalized for anti-infection treatment, so that a large amount of medical resources and economic cost are required to be spent for treatment.

Disclosure of Invention

The invention aims to provide an oral preparation of azlodine, a preparation method and application thereof, which is used for treating patients infected with novel coronavirus pneumonia or patients infected with AIDS, and can be used for anti-infection treatment without hospitalization, thereby reducing medical expenditure and saving medical resources.

In order to achieve the above purpose, the invention provides the following technical scheme:

in a first aspect, the invention provides an oral preparation of azlodine, which comprises 0.3-8% of azlodine and 92-99.7% of auxiliary materials, wherein the auxiliary materials comprise one or more of a filler, a binder, a disintegrant and a lubricant; when the auxiliary materials comprise a filler, a binder, a disintegrating agent and a lubricant, the mass ratio of the filler to the binder to the disintegrating agent to the lubricant is (60-95): (0 to 8): (1-20): (0.1-5).

Compared with the prior art, the oral preparation of the azvudine provided by the embodiment of the invention comprises the azvudine and auxiliary materials. Wherein, the azlodine is an artificially synthesized nucleoside analog, the target point of the azlodine is RNA polymerase (RdRp) of a virus, and the azlodine can block the synthesis and the replication of an RNA chain in a host cell by inhibiting the activity of the RdRp. In addition, as a nucleoside analog, azxidine can also be incorporated as a substrate during viral replication by "mimicking" the natural nucleoside, thereby stopping viral RNA strand synthesis or causing loss of viral viability, preventing RNA replication. As the novel coronavirus is an RNA virus like an HIV virus, in the virus replication process, the Alzheimer's disease can specifically inhibit the activity of RNA polymerase (RdRp) of virus RNA dependence, so as to inhibit the virus replication process, and further achieve the purpose of treating the novel coronavirus pneumonia and AIDS by using an oral preparation, so that a patient does not need to be hospitalized for anti-infection treatment, the medical expense is reduced, and the medical resource is saved. Meanwhile, in the embodiment of the invention, the mass percent of the azlodine is 0.3-8%, and the mass percent of the auxiliary material is 92-99.7%, so that the azlodine can be uniformly dispersed in the auxiliary material within the mass percent range. The auxiliary materials comprise a filler, an adhesive, a disintegrating agent and a lubricant, wherein the mass ratio of the filler to the adhesive to the disintegrating agent to the lubricant is (60-95): (0 to 8): (1-20): (0.1-5). Therefore, in the mass ratio range, the auxiliary materials serve as carriers and are beneficial to the formation of the form of the oral preparation of the azlodine, and the auxiliary materials also have important functions of solubilization, dissolution assistance, sustained and controlled release and the like. Because the azxifudin is wrapped by the auxiliary materials, the stability of the medicine can be improved, the adverse reaction caused by direct contact of the azxifudin and the digestive system of a human body is reduced, the medication compliance of a patient is improved, and the process of taking the medicine by the patient is easier.

Therefore, the oral preparation of the azfudin provided by the embodiment of the invention is used for treating patients infected with the novel coronavirus pneumonia or patients infected with AIDS, and anti-infection treatment is not required to be performed in hospital, so that medical expenditure is reduced, and medical resources are saved.

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

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

preparing the premix into an oral preparation of the Alzheimer's disease.

Compared with the prior art, the preparation method of the oral preparation of the alzheimer's disease provided by the invention has the same beneficial effect as the first aspect of the oral preparation of the alzheimer's disease, and the details are not repeated herein.

In a third aspect, the use of an oral formulation of azvudine for the manufacture of a medicament for the treatment of human immunodeficiency disorders.

Compared with the prior art, the beneficial effect of the application of the oral preparation of the alzheimer's disease in the treatment of the human immunodeficiency diseases is the same as that of the first aspect of the alzheimer's disease, and the details are not repeated herein.

Drawings

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention and not to limit the invention. In the drawings:

fig. 1 shows a flow chart of a method for preparing an oral formulation of alzheimer's disease in this example.

Detailed Description

In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not limit the invention.

Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or to implicitly indicate the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise. The meaning of "a number" is one or more unless specifically limited otherwise.

The early symptoms of the human body after the novel coronavirus infection are similar to the symptoms of the cold caused by the general virus infection, and are mainly manifested by fatigue, hypodynamia and muscular soreness, and a few patients can also show gastrointestinal reactions such as abdominal pain and diarrhea. With the symptoms aggravated, patients may have severe symptoms of dyspnea, chest distress, shortness of breath, and even respiratory distress. The imaging examination shows that the lung has the pulmonary interstitial changes like the vitreous grinding, and the serious manifestations also can show sepsis, septic shock, coagulation dysfunction, renal failure and the like. Therefore, there is a need to develop an oral specific drug for treating the novel coronavirus pneumonia.

In view of the above problems, the embodiment of the present invention provides an application of an oral azvudine formulation in preparing a medicament for treating human immunodeficiency diseases, so that when treating a novel coronavirus pneumonia patient, hospitalization is not required for anti-infection treatment, medical expenses are reduced, and medical resources are saved. The human immunodeficiency disease may be a novel coronavirus pneumonia, AIDS or other human immunodeficiency diseases, which are not described herein. The chemical name of the azfudine is 1- (4-azide-2-deoxy-2-fluoro-beta-D-ribofuranosyl) cytosine, and the structural formula is as follows:

clinically, alzheimer's is an artificially synthesized nucleoside analog that is phosphorylated in cells to become an active 5' -triphosphate metabolite (i.e., alzheimer's triphosphate), which inhibits the activity of recombinant HIV reverse transcriptase, resulting in the cessation of viral DNA strand synthesis. The oral preparation of alzheimer's disease and the preparation method are described in detail below with reference to the examples.

The oral preparation of the azlodine provided by the embodiment of the invention comprises 0.3-8% of the azlodine and 92-99.7% of the auxiliary material by mass, wherein the auxiliary material comprises one or more of a filling agent, a bonding agent, a disintegrating agent and a lubricating agent. 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). It is understood that the dosage form of the oral preparation of alzheimer's disease can be a solid dosage form, and the solid dosage form can include tablets, dispersions, capsules or other solid preparations, and is not limited herein. When the solid dosage form is a tablet, the oral preparation of alzheimer's disease according to the embodiment of the present invention further comprises a coating layer, which may be a film coating layer, which may be a gastric-soluble film coating material, and/or indentations.

The oral preparation of the Alzheimer's disease provided by the embodiment of the invention comprises the Alzheimer's disease and auxiliary materials. Wherein, the azlodine is an artificially synthesized nucleoside analog, the target point of the azlodine is RNA polymerase (RdRp) of a virus, and the azlodine can block the synthesis and the replication of an RNA chain in a host cell by inhibiting the activity of the RdRp. In addition, as a nucleoside analog, azxidine can also be incorporated as a substrate during viral replication by "mimicking" the natural nucleoside, thereby stopping viral RNA strand synthesis or causing loss of viral viability, preventing RNA replication. As the novel coronavirus is an RNA virus like an HIV virus, in the virus replication process, the Alzheimer's disease can specifically inhibit the activity of RNA polymerase (RdRp) of virus RNA dependence, so as to inhibit the virus replication process, and further achieve the purpose of treating the novel coronavirus pneumonia and AIDS by using an oral preparation, so that a patient does not need to be hospitalized for anti-infection treatment, the medical expense is reduced, and the medical resource is saved. Meanwhile, in the embodiment of the invention, the mass percent of the azvudine is 3-8%, and the mass percent of the auxiliary material is 92-97%, so that the azvudine can be uniformly dispersed in the auxiliary material within the mass percent range. The auxiliary materials comprise a filler, a binder, a disintegrating agent and a lubricant, wherein the mass ratio of the filler to the binder to the disintegrating agent to the lubricant is (60-95): (0 to 8): (1-20): (0.1-5). Therefore, in the mass ratio range, the auxiliary materials serve as carriers and are beneficial to the formation of the form of the oral preparation of the azlodine, and the auxiliary materials also have important functions of solubilization, dissolution assistance, sustained and controlled release and the like. Because the azxifudin is wrapped by the auxiliary materials, the stability of the medicine can be improved, the adverse reaction caused by direct contact of the azxifudin and the digestive system of a human body is reduced, the medication compliance of a patient is improved, and the process of taking the medicine by the patient is easier.

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

Illustratively, the oral formulation of the alzheimer's disease treatment agent of the embodiments of the present invention, for the filler, the filler is introduced into the alzheimer's disease treatment agent, which may include one or more of microcrystalline cellulose, lactose, mannitol, silicified microcrystalline cellulose and calcium hydrogen phosphate, preferably one or both of microcrystalline cellulose and lactose, and thus, the oral formulation of the alzheimer's disease treatment agent can meet the quality or volume standard for preparing solid dosage forms.

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

For the lubricant, the lubricant comprises one or two of stearate, talcum powder and glyceryl behenate, wherein the stearate comprises one or more of magnesium stearate, sodium stearyl fumarate and calcium stearate.

For the disintegrant, the disintegrant comprises one or more of crospovidone, croscarmellose sodium, and sodium carboxymethyl starch, preferably one or both of croscarmellose sodium and sodium carboxymethyl starch.

In a realisable form, the Particle Size Distribution (PSD) D50 of the oral formulations of Alzheimer's disease according to embodiments of the invention is in the range 1 μm to 90 μm. The particle size distribution reflects the percentage of particles with different particle size distributions in the total amount of particles in the powder sample. Wherein D50 represents: the cumulative percent particle size distribution for a sample at 50% corresponds to the particle size. Its physical meaning is that the particle size is greater than 50% of its particles and less than 50% of its particles, D50 also being referred to as median or median particle size. D50 is often used to denote the average particle size of the powder. When the particle size distribution of the azvudine is in the range, the adhesion of the surface of the azvudine is reduced, the electrostatic adsorption is weakened, and the azvudine is not easy to gather, so that when the azvudine and auxiliary materials are mixed, the materials can be mixed and sieved more smoothly, the sieving difficulty is reduced, the sieving time is shortened, and the situation that the mixed materials are blocked in sieve holes or clamped in the sieve holes during sieving is avoided.

In one example, the D50 particle size distribution of the azlodine of the embodiments of the present invention may also be between 1 μm and 70 μm. In another example, the particle size distribution D50 of the azlodine of an embodiment of the present invention may also be from 1 μm to 50 μm.

In an alternative form, the present forms of azlactone of the embodiments of the present invention include the free base form and/or the pharmaceutically acceptable salt form.

As shown in fig. 1, the present invention also provides a method for preparing an oral formulation of alzheimer's disease, comprising:

step 101: and mixing the azvudine and the auxiliary materials, and granulating to obtain the premix.

In one example, the azlodine may be mixed with a filler, binder, and disintegrant, then placed in a wet granulator to make a soft mass, resulting in wet granules, which are then dried by a fluidized bed, resulting in dry granules. And adding the sieved lubricant and mixing to obtain the premix.

In another example, the azlodine may be blended with a filler, a binder, a disintegrant, and a lubricant and then placed in a dry granulator for granulation to provide a premix.

In yet another example, the azlodine may be mixed with a filler, a binder, and a portion of a disintegrant, and then granulated using a top-spray granulator to obtain whole granules, which are then mixed with a sieved lubricant to obtain a premix.

It is to be understood that embodiments of the present invention may obtain the premix in any of the three ways described above, and that the formulation may also be prepared using a direct pressure process and a fluidized bed process. Regardless of the granulation method, the oral preparation of the alzheimer's disease according to the present invention can be obtained.

Step 102: preparing the premix into an oral preparation of the Alzheimer's disease.

For example: tabletting the premix by a rotary tablet machine to prepare tablets or dispersible tablets, encapsulating the premix into capsules or pressurizing the tablets into powder or granular dispersing agents. It is to be understood that the dispersant means a dosage form which can be dispersed in water before administration, and the dispersant of the embodiment of the present invention can be dispersed in an aqueous medium such as purified water within 5 minutes or less, preferably within 3 minutes or less, thereby facilitating administration, for example, administration to children, the elderly, or patients with dysphagia. Meanwhile, since the dissolution becomes slow and incomplete when the content of microcrystalline cellulose is high, the solubility of the dispersion formulation can be improved by reducing the amount of microcrystalline cellulose. When the composition is prepared into tablets, plain tablets with target specifications can be prepared, and the plain tablets can also be subjected to film coating to prepare coated tablets. The granule flow property of the oral preparation of the azvudine prepared according to the technical scheme of the invention is good, the granulation process window is wide, the sieving process is smooth, the phenomena of sieve blockage or sieve blockage and unstable tablet weight do not occur in tabletting, the challenge of high-speed tabletting in industrial mass production is realized more easily, and the purposes of saving time and energy are achieved.

In order to verify the effect of the oral preparation of azvudine provided by the embodiments of the present invention, the embodiments of the present invention exemplify the solid dosage form as a tablet and a dispersing agent.

Example one

The embodiment of the invention provides an oral preparation of Alzheimer's disease, the active ingredient selected by the preparation is Alzheimer's disease, and the particle size distribution D50 of Alzheimer's disease is as follows: 1 μm. The number of the oral preparation of alzheimer's disease in the present example was 1000 tablets, and table 1 shows the component ratio table of the oral preparation of alzheimer's disease in the first example of the present invention.

TABLE 1 ingredient ratio table of the oral formulation of azxifudin of example one

The preparation method of the oral preparation of the azlodine provided by the embodiment of the invention comprises the following steps:

first, a premix is prepared: mixing azfudine, lactose, microcrystalline cellulose, corn starch and croscarmellose sodium, placing into a wet granulator, making into soft mass to obtain wet granules, and drying with a fluidized bed to obtain dry granules. And adding the sieved magnesium stearate and mixing to obtain the premix.

Secondly, preparing an oral preparation of the azvudine: tabletting the premix, and then carrying out film coating on the plain tablets in a coating machine by using a gastric-soluble film coating material to obtain the oral preparation of the azvudine, wherein the weight of the target coating is increased by 2-4% of the weight of the tablet core.

Example two

The embodiment of the invention provides an oral preparation of Alzheimer's disease, the active ingredient selected by the preparation is Alzheimer's disease, and the particle size distribution D50 of Alzheimer's disease is as follows: and 30 μm. The number of the oral preparation of alzheimer's disease in the present example was 1000 tablets, and table 2 shows the component ratio table of the oral preparation of alzheimer's disease in the second example of the present invention.

TABLE 2 ingredient ratio Table of the oral formulation of azxifudin of example two

first, a premix is prepared: mixing the azlodine, the lactose, the microcrystalline cellulose, the hydroxypropyl cellulose and the crospovidone, putting the mixture into a wet granulator to prepare a soft material to obtain wet granules, and then drying the wet granules by a fluidized bed to obtain dry granules. And adding the sieved calcium stearate and mixing to obtain the premix.

EXAMPLE III

The embodiment of the invention provides an oral preparation of Alzheimer's disease, the active ingredient selected by the preparation is Alzheimer's disease, and the particle size distribution D50 of Alzheimer's disease is as follows: 50 μm. The number of the oral formulations of alzheimer's disease in the present example was 1000 tablets, and table 3 shows the component ratio table of the oral formulations of alzheimer's disease in the third example of the present invention.

TABLE 3 ingredient ratio Table of oral formulations of azfudin according to example III

The preparation method of the oral preparation of the azlodine provided by the third embodiment of the invention comprises the following steps:

first, a premix is prepared: mixing the azvudine with silicified microcrystalline cellulose, hydroxypropyl methylcellulose, polyvidone and sodium carboxymethyl starch, putting into a wet granulator to prepare soft materials to obtain wet granules, and drying by a fluidized bed to obtain dry granules. And adding the sieved magnesium stearate and mixing to obtain the premix.

Secondly, preparing an oral preparation of the azvudine: tabletting the premix, and then carrying out film coating and indentation on the plain tablets in a coating machine by using a gastric-soluble film coating material to obtain the oral preparation of the azvudine, wherein the weight of the target coating is increased by 2-4% of the weight of the tablet core.

Example four

The embodiment of the invention provides an oral preparation of Alzheimer's disease, the active ingredient selected by the preparation is Alzheimer's disease, and the particle size distribution D50 of Alzheimer's disease is as follows: and 90 μm. The number of the oral formulation of azvudine in the example of the present invention is 1000 tablets, and table 4 shows the component ratio table of the oral formulation of azvudine in the example four of the present invention.

TABLE 4 ingredient ratio Table of oral formulation of azxifudin of example four

The preparation method of the oral preparation of azfudin provided by the fourth embodiment of the invention comprises the following steps:

first, a premix is prepared: mixing the azlodine with calcium hydrogen phosphate, microcrystalline cellulose, hydroxypropyl cellulose and crospovidone, putting into a wet granulator to prepare a soft material to obtain wet granules, and then drying by a fluidized bed to obtain dry granules. And adding the sieved magnesium stearate and mixing to obtain the premix.

EXAMPLE five

The embodiment of the invention provides an oral preparation of the Alzheimer's disease, the selected active ingredient is the Alzheimer's disease, and the particle size distribution D50 of the Alzheimer's disease is 70 mu m. The number of the oral formulations of alzheimer's disease in the present example was 1000 tablets, and table 5 shows the component ratio table of the oral formulations of alzheimer's disease in the fifth example.

TABLE 5 ingredient ratio Table of oral formulations of azvudine according to example five

The preparation method of the oral preparation of azfudin provided by the fifth embodiment of the invention comprises the following steps:

first, a premix is prepared: mixing the azlodine with lactose, microcrystalline cellulose, polyvidone and croscarmellose sodium, placing into a wet granulator to make soft mass to obtain wet granules, and drying with a fluidized bed to obtain dry granules. Adding sieved glyceryl behenate, and mixing to obtain a premix.

EXAMPLE six

The embodiment of the invention provides an oral preparation of azvudine, which adopts the active ingredient of the azvudine, wherein the particle size distribution D50 of the azvudine is as follows: 20 μm. The number of the oral formulations of alzheimer's disease in the present example was 1000 tablets, and table 6 shows the component ratio table of the oral formulations of alzheimer's disease in the sixth example.

TABLE 6 ingredient ratio table for oral preparation of azvudine according to example six

The preparation method of the oral preparation of the azlodine provided by the sixth embodiment of the invention comprises the following steps:

first, a premix is prepared: uniformly mixing the azvudine, mannitol, microcrystalline cellulose, corn starch and crospovidone, adding the sieved magnesium stearate, and mixing to obtain the premix.

EXAMPLE seven

The embodiment of the invention provides an oral preparation of Alzheimer's disease, the active ingredient selected by the preparation is Alzheimer's disease, and the particle size distribution D50 of Alzheimer's disease is as follows: 20 μm. The number of the oral formulations of alzheimer's disease in the present example was 1000 tablets, and table 7 shows the component ratio table of the oral formulations of alzheimer's disease in the seventh example of the present invention.

TABLE 7 ingredient ratio Table of the oral formulation of azfuding of EXAMPLE seven

The preparation method of the oral preparation of the azlodine provided by the seventh embodiment of the invention comprises the following steps:

first, a premix is prepared: mixing the azlodine, silicified microcrystalline cellulose, corn starch and partially cross-linked sodium carboxymethyl cellulose, granulating by a top-spraying granulator to obtain whole granules, and adding the sieved sodium stearyl fumarate to mix to obtain a premix.

Example eight

The embodiment of the invention provides an oral preparation of Alzheimer's disease, the active ingredient selected by the preparation is Alzheimer's disease, and the particle size distribution D50 of Alzheimer's disease is as follows: 50 μm. The oral preparation of alzheimer's disease according to the present invention is a dispersant, and table 8 shows the component ratio table of the oral preparation of alzheimer's disease according to the eighth embodiment of the present invention.

TABLE 8 ingredient ratio Table of oral formulations of azvudine according to example eight

The preparation method of the oral preparation of the azlodine provided by the eighth embodiment of the invention comprises the following steps:

first, a premix is prepared: uniformly mixing the azvudine, lactose, microcrystalline cellulose and croscarmellose sodium, adding the sieved magnesium stearate, and mixing to obtain the premix.

Secondly, preparing an oral preparation of the azvudine: the premix is tabletted and then pressurized to be granular to obtain the oral preparation of the azfudine, namely the dispersing agent.

Example nine

The embodiment of the invention provides an oral preparation of azvudine, which adopts the active ingredients of the azvudine and has the particle size distribution D50 that: and 30 μm. The oral alzheimer's disease preparation of the present invention is a dispersant, and table 9 shows a component ratio table of the oral alzheimer's disease preparation of the ninth embodiment of the present invention.

TABLE 9 ingredient ratio Table of oral formulations of azvudine according to example nine

EXAMPLE ten

The embodiment of the invention provides an oral preparation of Alzheimer's disease, which adopts the active ingredients of Alzheimer's disease with the particle size distribution D50 as follows: 80 μm. The oral alzheimer's disease preparation of the present invention is a dispersant, and table 10 shows a component ratio table of the oral alzheimer's disease preparation of the present invention.

TABLE 10 ingredient ratio Table of the oral formulation of azvudine of EXAMPLE nine

Name of material	Components	Quality (g)
			Active ingredient 1	Azfudine	3
Filler	Silicified microcrystalline cellulose	109
			Disintegrating agent	Croscarmellose sodium	5
Lubricant agent	Stearic acid sodium fumarate	3

first, a premix is prepared: uniformly mixing the azvudine, silicified microcrystalline cellulose and croscarmellose sodium, adding the sieved sodium stearyl fumarate, and mixing to obtain a premix.

Secondly, preparing an oral preparation of the azvudine: tabletting the premix, and then pressurizing to granules to obtain the oral preparation of the azlodine, namely the dispersing agent.

The embodiment of the invention also performs content test, dissolution test, disintegration test and friability test on the oral preparation of the alzheimer's disease prepared in the embodiment to obtain the content, dissolution rate, disintegration time and friability of the oral preparation of the alzheimer's disease. The dissolution rate refers to the rate and extent of dissolution of a drug from a solid preparation such as a tablet in a predetermined solvent.

Table 11 shows the contents, dissolution rates, disintegration time periods, and friability of examples one to ten, wherein the dissolution conditions were: 0.01mol/L hydrochloric acid solution, 900ml,37 ℃, paddle method 50rpm,30min, the results are as follows:

table 11 test results of examples one to ten

As can be seen from the above table: in the oral preparation of the alzheimer's disease prepared in the first to the tenth examples, the dissolution rate of the alzheimer's disease is more than 80% in 900ml of hydrochloric acid solution at 37 ℃ under the dissolution condition, the content of the alzheimer's disease prepared in the first to the tenth examples is more than 99.9%, the disintegration time of the alzheimer's disease prepared in the first to the tenth examples is less than or equal to 5min, and the friability of the alzheimer's disease prepared in the first to the tenth examples is less than 1%. Therefore, the oral preparation of the azlodine provided by the embodiment of the invention has higher disintegration speed in vivo, so that the human body can absorb the azlodine at a higher speed, and the content of the azlodine is high. Therefore, when the oral preparation of the azfuding provided by the embodiment of the invention is used for treating a patient infected with the novel coronavirus pneumonia or a patient infected with AIDS, hospitalization is not needed for anti-infection treatment, the medical expense is reduced, and the medical resource is saved.

The samples of examples 1 to 10 were stored for 6 months under accelerated conditions (40 ℃ C. + -2 ℃ C.; 75% RH. + -.5% RH), and sampled at 0 month, 1 month, 3 months and 6 months, respectively, to detect the dissolution and impurity conditions, and it was found that there was no significant change in the dissolution of the samples of examples 1 to 10, the effects of the dissolution thereof on temperature and humidity were small, and the product quality was stable. And the maximum single impurity is not more than 0.1 percent, the total impurity is not more than 0.5 percent, the impurity hardly grows, and the safety is good.

While the foregoing is directed to embodiments of the present invention, it will be apparent that various modifications and combinations can be made without departing from the spirit and scope of the invention. Accordingly, the specification and figures are merely exemplary of the invention as defined in the appended claims and are intended to cover any and all modifications, variations, combinations, or equivalents within the scope of the invention. It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents. Any person skilled in the art can easily conceive of changes or substitutions within the technical scope of the present disclosure, and all such changes or substitutions are included in the scope of the present disclosure. Therefore, the protection scope of the present invention shall be subject to the protection scope of the appended claims.

Claims

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.