CN116036031A - Pharmaceutical composition containing adefovir - Google Patents
Pharmaceutical composition containing adefovir Download PDFInfo
- Publication number
- CN116036031A CN116036031A CN202310043868.9A CN202310043868A CN116036031A CN 116036031 A CN116036031 A CN 116036031A CN 202310043868 A CN202310043868 A CN 202310043868A CN 116036031 A CN116036031 A CN 116036031A
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- CN
- China
- Prior art keywords
- pharmaceutical composition
- adefovir
- filler
- cellulose
- starch
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 52
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229960001997 adefovir Drugs 0.000 title claims abstract description 39
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
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- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention discloses a pharmaceutical composition containing adefovir. In particular to a pharmaceutical composition taking a compound Ruidexivir with antiviral activity as an active ingredient, belonging to the technical field of pharmaceutical preparations. The prepared adefovir dipivoxil pharmaceutical composition is convenient for patients with light and medium dose, increases the compliance of the patients for medication, and has larger clinical application value; in addition, the prepared adefovir dipivoxil pharmaceutical composition has stable and controllable quality and is convenient for industrial production.
Description
The application is a divisional application of patent application number 202110364871.1 filed on the year 2021, month 04 and 06.
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a pharmaceutical composition taking a compound Ruidexivir with antiviral activity as an active ingredient.
Background
Novel coronavirus (COVID-19) has close relationship with Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV). It is proposed in the "antiviral therapist consensus of new coronavirus infected persons that inhibiting viral replication is critical for controlling the progress of new coronavirus infection, antiviral therapy is one of the main therapeutic measures of new coronavirus infection, and new coronavirus infection antiviral drugs should be selected reasonably in combination with the disease course of patients. The U.S. Food and Drug Administration (FDA) approved adefovir for injection in gide science for the treatment of new coronary hospitalized patients on day 22 of 10 2020, becoming the first formally approved new coronary treatment in the united states. . However, no specific oral drug has been used to treat the novel coronavirus infection so far. Thus, there is an urgent need for an effective oral antiviral drug to combat this disease.
Remdesivir, a broad-spectrum antiviral drug developed by Jide corporation of the United states pharmaceutical industry, was originally designed to treat Ebola virus, and early cell and animal experiments have shown that it can produce good antiviral activity against SARS coronavirus and MERS coronavirus by inhibiting RNA polymerase. In 11 months 2018, in order to cope with Ebola epidemic situation, congo (gold) starts a clinical control test under the initiative of the world and health organization, and the curative effects of 4 new drugs such as Remdesivir, MAb, REGN-EB3, zmapp and the like are tested. The race takes only 9 months to win or lose. Because the leading advantages of REGN-EB3 and mAb-114 are quite obvious, the committee decides to end the test in advance in month 8 of 2019, and the two medicines are promoted in a large scale. Adefovir thus exits the campaign against ebola early. However, during this time, gilid did not stop studying the role of adefovir in other areas, including coronaviruses, to "duplicate" the buried vopen.
It is worth mentioning that the prototype drug of adefovir GS-5734 is GS-441524, an FDA approved veterinary drug, which has been proposed for the treatment of infectious peritonitis in cats, which is rarely but deadly caused by feline coronavirus. Rad Wei Muqian is considered to be one of the most potential drugs most likely to achieve inhibition of new coronaviruses, among the most potential drugs for the treatment of new coronavirus pneumonia (covd-19). 5.7.2020, jilidean science announced that the Japanese Ministry of thick raw labor (MHLW) has been approved by a special approval route
(adefovir for injection) as a therapeutic agent for SARS-CoV-2 infection; the 10 month 8 day Jiled science published the three-phase clinical data of Ruidexivir for injection from a biorandomized, double-blind, placebo-controlled, phase 3 study conducted by the National Institute for Allergy and Infectious Disease (NIAID), covering about 1060 hospitalized patients worldwide. The data show that average recovery time for hospitalized patients receiving injection of adefovir is five days faster, while patients with severe disease are seven days faster, and these severe patients account for 85% of the total study.
Ruidexivir is a nucleoside analogue with broad-spectrum antiviral activity, which can inhibit RNA-dependent RNA polymerase (RdRp), and the active ingredient GS-5734 is a phosphoramidate precursor of 1' -cyano adenosine analogue, and is metabolized in cells to form active triphosphate form-NTP. Adefovir as a monophosphate prodrug can significantly increase the potency of the parent nucleoside by delivering monophosphate into the cell and effectively bypassing the rate limiting first phosphorylation step. The phenol and amino acid ester in the structure mask the negative charge of the monophosphate group, so that the monophosphate group can conveniently and passively permeate into cells. The cytolactonase (such as carboxylesterase-1 and cathepsin A) breaks down the ester into a carboxyl structure, then continues to break down into nucleoside monophosphates, and finally is phosphorylated to nucleoside triphosphates to exert antiviral effects.
Chemical name of adefovir: (2S) -2- ((S) - (((2R, 3S,4R, 5R) -5- (4-aminopyrrolo [2, 1-f)][1,2,4]Triazin-7-yl) -5-cyano-3, 4-dihydroxytetrahydrofuran-2-yl) methoxyphenoxyphosphoryl) amino) propanoic acid 2-ethylbutyl ester, formula C 27 H 35 N 6 O 8 P, molecular weight 602.58. The structural formula of the Ruidexivir compound is shown in formula I:
adefovir LogP is 2.2 and pka is 3.1. The solubility of adefovir is pH dependent: the solubility drops sharply at a pH value of 1 to 3; the solubility is basically unchanged at the pH value of 4-10, and the water solubility is poor (< 0.1 mg/ml). The dosage form of the Rede-Siwei which is clinically used at present is freeze-dried powder injection or injection with the specification of 100mg, and the Rede-Siwei is required to be infused and administrated by vein, has quick response and is suitable for critical patients with serious illness. Side effects that FDA suggests that adefovir may exist include: elevated levels of liver enzymes and allergic reactions include changes in blood pressure and heart rate, hypoxia, fever, shortness of breath, asthma, swelling (e.g. lips, periocular, subcutaneous), rash, nausea, sweating or trembling. For patients with mild or moderate disease, development of an oral administration dosage form with convenient administration and good medication compliance is urgently needed.
The presently clinically used rituximab for injection has the following disadvantages: 1. improper treatment is prone to systemic or localized infection; 2. excessive medicine or too fast instillation, adverse reaction is easy to generate, and even life is endangered; 3. continuous overdose, which is prone to overload in circulation, or electrolyte imbalance; 4. the number of iatrogenic diseases increases.
Therefore, there is an urgent need to develop an oral preparation of adefovir with strong operability of prescription process, simple preparation process and high dissolution rate.
Disclosure of Invention
The invention provides an oral pharmaceutical composition containing Rede-Siwei, which is convenient for light and medium patients to take, increases the medication compliance of the patients and has larger clinical application value; in addition, the prepared adefovir dipivoxil pharmaceutical composition has stable and controllable quality and is convenient for industrial production.
The invention provides a pharmaceutical composition containing adefovir, which comprises an active ingredient adefovir and pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials at least comprise a filling agent, a disintegrating agent and a lubricant; wherein the weight percentage of active ingredient adefovir in the pharmaceutical composition is 15-65%, preferably 20-50%, most preferably 25-45%.
In some embodiments of the pharmaceutical composition of the present invention, the filler is selected from one or more of sugar alcohols, celluloses, starches, inorganic salts. The filler is present in the pharmaceutical composition in an amount of 10-90% by weight, preferably 30-70% by weight. The sugar alcohol filler is selected from mannitol, maltitol, erythritol, lactitol, sorbitol or xylitol, preferably spray-dried mannitol. The cellulose filler is selected from microcrystalline cellulose, powdered cellulose or silicified microcrystalline cellulose. The inorganic salt filler is selected from anhydrous calcium hydrogen phosphate, dihydrate calcium hydrogen phosphate or calcium carbonate. The starch filler is selected from corn starch, potato starch or pregelatinized starch, preferably pregelatinized starch.
In some preferred embodiments of the pharmaceutical composition of the invention, the filler is selected from mannitol, or a mixture of mannitol and microcrystalline cellulose in a ratio of 1:1 to 4:1, the weight percentage of filler in the pharmaceutical composition being 10-90%, preferably 30-70%.
In some embodiments, the pharmaceutical composition of the present invention, the disintegrant is selected from one or more of crospovidone, croscarmellose sodium, low substituted hydroxypropylcellulose, sodium carboxymethyl starch, corn starch, or potato starch. Preferably, the disintegrant is selected from crospovidone, croscarmellose sodium or sodium carboxymethyl starch. The weight percentage of the disintegrating agent in the pharmaceutical composition is 1-10%.
In some embodiments, the pharmaceutical composition of the present invention, the lubricant is selected from one or more of magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oil, glyceryl behenate, stearic acid, sodium stearyl fumarate. Preferably, the lubricant is selected from magnesium stearate, glyceryl behenate or sodium stearyl fumarate. The weight percentage of the lubricant in the pharmaceutical composition is 0.5-5%.
The pharmaceutical composition of the invention, wherein the pharmaceutically acceptable auxiliary materials further comprise a binder, and the binder is selected from one or more of hypromellose, methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose and polyvinylpyrrolidone, preferably hypromellose or hypromellose. The weight percentage of the adhesive in the medicine composition is 0-10%.
The pharmaceutical composition of the invention, wherein the pharmaceutically acceptable auxiliary materials also comprise a solubilizer, which is selected from one or more of sodium dodecyl sulfate, polysorbate 80, polyoxyethylene hydrogenated castor oil and poloxamer, preferably sodium dodecyl sulfate. The weight percentage of the solubilizer in the pharmaceutical composition is 0-5%.
The pharmaceutical composition of the invention, wherein the pharmaceutically acceptable excipients further comprise glidants selected from colloidal silicon dioxide or talc. The glidant accounts for 0-2% of the pharmaceutical composition by weight.
The pharmaceutical composition of the present invention contains 100mg-400mg of active ingredient adefovir per unit dose. Preferably, the pharmaceutical composition of the present invention comprises 100mg, 200mg, 300mg or 400mg of the active ingredient adefovir per unit dose.
The pharmaceutical composition of the present invention is preferably prepared in a dosage form for oral administration, and may be a tablet, granule or capsule; when the dosage form is a tablet or granule, a coating is optionally applied. The coating is carried out with the addition of conventional coating media and film forming agents familiar to those skilled in the art (generally collectively referred to as coating materials), which may be selected from one or more of the following: hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethylcellulose, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers (e.g. VA64, BASF), shellac, copolymers of acrylic and/or methacrylic acid esters and trimethylammonium methacrylate, copolymers of dimethylaminomethacrylic acid and neutral methacrylic acid esters, polymers of methacrylic acid or methacrylic acid esters, ethyl acrylate-methyl methacrylate copolymers, methacrylic acid-methyl acrylate copolymers, propylene glycol, polyethylene glycol, triacetin, triethyl citrate and/or dye additives/pigments such as titanium dioxide, iron oxide, indigo or suitable lakes.
The pharmaceutical composition of the invention preferably comprises the following components in percentage by weight:
more preferably, the weight percentages of the components are as follows:
the medicine composition of the invention, a preferable technical scheme, comprises the following components by weight percent:
another preferred technical scheme comprises the following components in percentage by weight:
the pharmaceutical composition of the invention can be prepared by adopting the common granulation and tabletting technology of oral solid preparations, such as wet granulation, fluid bed granulation, dry compression granulation or direct mixed tabletting; in the embodiment of the invention, the preparation process of direct mixed tabletting is adopted, the operation is simple, and the industrial production is convenient.
The pharmaceutical composition of the present invention is preferably prepared by the following steps when preparing tablets:
(1) Mixing the formula amount of the adefovir and the filler uniformly, wherein the uniform mixing mode can be mixed by a mixer or one-step granulating and mixing by a wet granulator or a fluidized bed;
(2) Adding disintegrating agent, binder and/or solubilizer, mixing with the mixture obtained in step (1) uniformly or granulating;
(3) Sieving the lubricant with a 40-mesh sieve, and uniformly mixing the lubricant with the mixture obtained in the step (2);
(4) Tabletting the mixture obtained in the step (3) to obtain tablets.
Compared with the prior art, the invention has the following advantages:
(1) The pharmaceutical composition containing the adefovir provided by the invention is an oral dosage form, and is convenient for patients to take.
(2) The pharmaceutical composition containing the adefovir provided by the invention is convenient for patients with light and medium degree, increases the medication compliance of the patients, and can avoid the risk possibly caused by overdose of the injection medicine.
(3) The pharmaceutical composition containing the adefovir of the invention has the oral bioavailability of 66.1+/-47.8% proved by animal experiments.
(4) The pharmaceutical composition containing the adefovir provided by the invention has the advantages of simple preparation process and strong operability, and the prepared adefovir pharmaceutical composition has high dissolution rate and good stability.
Drawings
FIG. 1 is a dissolution profile of examples 1-2 in a hydrochloric acid dissolution medium at pH 1.0;
FIG. 2 is a graph of the dissolution of examples 1-2 in acetate buffer+0.1% SDS dissolution medium at pH 4.5;
FIG. 3 is a graph of the dissolution of examples 1-2 in phosphate buffer at pH 6.8+0.2% SDS dissolution medium;
FIG. 4 is a graph of the dissolution of examples 1-2 in purified water+0.3% SDS dissolution medium.
Detailed Description
The invention is further illustrated by the following examples. It should be understood that: the embodiments of the present invention are only given for illustrating the present invention, but not for limiting the present invention, and the simple modification of the present invention on the premise of the technical solution of the present invention is all within the protection scope of the present invention.
Example 1
| Names of raw and auxiliary materials | Action | Each tablet (mg) | Content (%) |
| Rede Sivir | Active ingredient | 100.00 | 29.85 |
| Mannitol (mannitol) | Filler (B) | 211.55 | 63.15 |
| Crosslinked povidone | Disintegrating agent | 16.75 | 5.00 |
| Magnesium stearate | Lubricant | 6.70 | 2.00 |
| Plain tablet weight | - | 335.00 | 100.00 |
The preparation method comprises the following steps:
(1) Uniformly mixing the adefovir and mannitol according to the weight percentage;
(2) Adding crospovidone and uniformly mixing the mixture obtained in the step (1);
(3) Sieving magnesium stearate with a 40-mesh sieve, and uniformly mixing the magnesium stearate with the mixture obtained in the step (2);
(4) Tabletting the mixture obtained in the step (3), and controlling the average weight difference to +/-3% by adopting a 10mm round punch, wherein the tabletting hardness is 4kg-12kg.
Example 2
The preparation method comprises the following steps:
(1) Uniformly mixing the adefovir, mannitol, microcrystalline cellulose and hypromellose according to weight percentage;
(2) Adding croscarmellose sodium, and uniformly mixing with the mixture obtained in the step (1);
(3) Sieving magnesium stearate with a 40-mesh sieve, and uniformly mixing with the mixture obtained in the step (2);
(4) Tabletting the mixture obtained in the step (3), and controlling the average weight difference to +/-3% by adopting a 10mm round punch, wherein the tabletting hardness is 4kg-12kg.
Quality evaluation experiments of examples 1-2
1. Determination of in vitro dissolution curve of oral solid preparation of Redewei
The in vitro dissolution test method is as follows: the paddle method was carried out at a speed of 50 revolutions per minute and 900ml of dissolution medium. Respectively measuring dissolution curves of a hydrochloric acid solution with the pH value of 1.0, an acetate buffer solution with the pH value of 4.5, SDS with the pH value of 0.1 percent, a phosphate buffer solution with the pH value of 6.8, SDS with the pH value of 0.2 percent and SDS with the pH value of 0.3 percent of purified water, respectively taking a proper amount of solution at 5min, 10min, 20min, 30min, 45min and 60min, filtering, and taking the subsequent filtrate as a sample solution; and precisely weighing a proper amount of the Ruidexivir reference substance, adding methanol for dissolution, and diluting with a dissolution medium to obtain a solution with the concentration of about 0.1mg/ml serving as a reference substance solution. According to high performance liquid chromatography (China pharmacopoeia 2015 edition four general rules 0512 high performance liquid chromatography), octadecyl silica gel bonding silica gel is used as filler, 20mmol/L ammonium acetate (glacial acetic acid is used for regulating pH value to 4.6) -methanol (42:58) is used as mobile phase, detection wavelength is 245nm, column temperature is 50 ℃, and flow rate is 1.0ml/min. Precisely measuring 5 μl of each of the control solution and the sample solution, respectively injecting into a liquid chromatograph, recording the chromatograms, and calculating the dissolution according to the external standard method with peak area, and the results are shown in tables 1-4.
The dissolution profiles of the adefovir dipivoxil tablets of examples 1-2 in different dissolution media are shown in figures 1-4.
TABLE 1 cumulative in vitro dissolution (%)
TABLE 2 cumulative in vitro dissolution (%)
TABLE 3 cumulative dissolution in vitro (%)
TABLE 4 cumulative dissolution in vitro (%)
Conclusion: from the above data, it is clear that examples 1 and 2 rapidly dissolve in hydrochloric acid at pH1.0, and the dissolution tendencies are substantially uniform in the other three media.
2. Stability investigation
In the study, the Redewei tablets of the examples 1-2 are respectively packaged by adopting an oral high-density polyethylene bottle (with the specification of 60 ml) and 1 bag of solid medical paper bag silica gel desiccant (with the specification of 2.0 g) is added, and then the influence factor test is carried out, the influence on the content, the dissolution rate and related substances is examined after the tablets are placed for 5 days at the high temperature of 40 ℃ and 60 ℃, and the results are shown in the table 5:
TABLE 5 Redox well plate influence factor investigation test results of examples 1-2
Conclusion: the content, related substances and dissolution rate of the Ruidexiwei tablet of the example 1 and the example 2 are not obviously changed under the condition of the influence factor test at the high temperature of 40 ℃ and 60 ℃, and the tablet meets the expected standard, and is proved to be stable under the high temperature condition.
3. Bioavailability of the active ingredients
To study the bioavailability of oral pharmaceutical compositions of adefovir, adefovir for injection (prepared in reference to patent WO 2019/014247) and adefovir dipivoxil tablet of example 1 were administered to 6 Beagle dogs (6 Beagle dogs tested were numbered P11, P12, P13, P14, P15, P16, respectively) at 2mg/kg, 100 mg/dose, respectively, using a single dose, dual cycle, parallel dosing design, plasma samples were collected and assayed for adefovir thereinAnd the main metabolite rad Wei Hegan (DHG) concentration, the pharmaceutical time curves were plotted and pharmacokinetic parameters were calculated. The Ruidexivir is used as a prodrug and is quickly converted into DHG after being absorbed into blood, so that the drug generation parameter calculation of the test is calculated according to the concentration of the DHG; AUC obtained after administration of adefovir for injection and adefovir dipivoxil tablet of example 1 last After dose normalization of the parameters, absolute bioavailability was calculated. The pharmacokinetic parameters of Beagle dogs after administration of adefovir for injection and adefovir dipivoxil tablet of example 1 are listed in table 6 below:
TABLE 6 pharmacokinetic parameters of the major metabolite of Rede Sivir, rede Si Wei Hegan (DHG)
Conclusion: after 100 mg/dose of the ryposivir tablets are administered to Beagle dogs (example 1), the dosage of the administration is 8.61-15.34mg/kg, the concentration point of the proto-drug which can be measured after the administration is less, DHG is the main component measured, and the absolute bioavailability of the ryposivir tablets is 66.1+/-47.8% based on the exposure amount of the DHG.
Claims (10)
1. A pharmaceutical composition containing adefovir, which comprises adefovir as an active ingredient and pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials at least comprise a filling agent, a disintegrating agent and a lubricant; wherein the weight percentage of the active ingredient of the Ruidexivir in the pharmaceutical composition is 15-65%, preferably 20-50%, and most preferably 25-45%.
2. The pharmaceutical composition according to claim 1, wherein the filler is selected from one or more of sugar alcohols, celluloses, starches, and the weight percentage of the filler in the pharmaceutical composition is 10-90%, preferably 30-70%; wherein,,
the sugar alcohol filler is selected from mannitol, maltitol, erythritol, lactitol, sorbitol or xylitol, preferably spray-dried mannitol;
the cellulose filler is selected from microcrystalline cellulose, powdered cellulose or silicified microcrystalline cellulose;
the starch filler is selected from corn starch, potato starch or pregelatinized starch, preferably pregelatinized starch.
3. Pharmaceutical composition according to claim 1, wherein the filler is selected from mannitol, or a mixture of mannitol and microcrystalline cellulose in a ratio of 1:1-4:1, the weight percentage of filler in the pharmaceutical composition being 10-90%, preferably 30-70%.
4. The pharmaceutical composition according to claim 1, wherein the disintegrant is one or more selected from crospovidone, croscarmellose sodium, low substituted hydroxypropyl cellulose, sodium carboxymethyl starch, corn starch or potato starch; preferably, the disintegrant is selected from crospovidone, croscarmellose sodium or sodium carboxymethyl starch; the weight percentage of the disintegrating agent in the pharmaceutical composition is 1-10%,
the lubricant is one or more selected from magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oil, glyceryl behenate, stearic acid and sodium stearyl fumarate; preferably, the lubricant is selected from magnesium stearate, glyceryl behenate or sodium stearyl fumarate; the weight percentage of the lubricant in the pharmaceutical composition is 0.5-5%.
5. The pharmaceutical composition according to claim 1, the pharmaceutically acceptable excipients further comprising a binder selected from one or more of hypromellose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, preferably hypromellose or hydroxypropyl cellulose; the weight percentage of the adhesive in the medicine composition is 0-10%.
6. The pharmaceutical composition according to claim 1, the pharmaceutically acceptable excipients further comprising a solubilising agent selected from one or more of sodium dodecyl sulphate, polysorbate 80, polyoxyethylene hydrogenated castor oil, poloxamer, preferably sodium dodecyl sulphate; the weight percentage of the solubilizer in the pharmaceutical composition is 0-5%.
7. The pharmaceutical composition according to claim 1, comprising 100mg-400mg of the active ingredient adefovir per unit dose of the pharmaceutical composition; preferably, the pharmaceutical composition comprises 100mg, 200mg, 300mg or 400mg of the active ingredient adefovir per unit dose.
8. The pharmaceutical composition of claim 1, which is prepared in a dosage form for oral administration; preferably, the dosage form is a tablet, granule or capsule; more preferably, the tablet or granule comprises a coating.
9. The pharmaceutical composition containing the adefovir comprises the following components in percentage by weight:
preferably, the weight percentages of the components are as follows:
10. the pharmaceutical composition containing the adefovir comprises the following components in percentage by weight:
or alternatively
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010264001 | 2020-04-07 | ||
| CN2020102640012 | 2020-04-07 | ||
| CN202110364871.1A CN113491673A (en) | 2020-04-07 | 2021-04-06 | Pharmaceutical composition containing Redexilvir |
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| CN202110364871.1A Division CN113491673A (en) | 2020-04-07 | 2021-04-06 | Pharmaceutical composition containing Redexilvir |
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| CN202110364871.1A Pending CN113491673A (en) | 2020-04-07 | 2021-04-06 | Pharmaceutical composition containing Redexilvir |
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