CN111557934A - Pharmaceutical composition containing docetaxel, preparation method and application thereof - Google Patents

Pharmaceutical composition containing docetaxel, preparation method and application thereof Download PDF

Info

Publication number
CN111557934A
CN111557934A CN202010520742.2A CN202010520742A CN111557934A CN 111557934 A CN111557934 A CN 111557934A CN 202010520742 A CN202010520742 A CN 202010520742A CN 111557934 A CN111557934 A CN 111557934A
Authority
CN
China
Prior art keywords
docetaxel
pharmaceutical composition
value
surfactant
polysorbate
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.)
Pending
Application number
CN202010520742.2A
Other languages
Chinese (zh)
Inventor
张吉旺
丁兆
胡和平
王爱丽
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SICHUAN HUIYU PHARMACEUTICAL CO Ltd
Original Assignee
SICHUAN HUIYU PHARMACEUTICAL CO Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by SICHUAN HUIYU PHARMACEUTICAL CO Ltd filed Critical SICHUAN HUIYU PHARMACEUTICAL CO Ltd
Priority to CN202010520742.2A priority Critical patent/CN111557934A/en
Publication of CN111557934A publication Critical patent/CN111557934A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The invention relates to a pharmaceutical composition containing docetaxel, a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. A pharmaceutical composition containing docetaxel, comprising docetaxel, a surfactant, a pH regulator and a solvent, wherein the docetaxel pharmaceutical composition is prepared by the following method: taking a prescription amount of surfactant, and adjusting the pH value of the surfactant to 3.0-4.5; adding docetaxel in the amount of the prescription and mixing evenly; adding solvent, mixing, and adjusting pH of the final mixture solution to 3.0-4.5. The pharmaceutical composition containing docetaxel of the invention can obtain a docetaxel pharmaceutical composition product with better quality by changing the charging sequence and controlling the pH of a solvent system before docetaxel is added to be 3.0-4.5.

Description

Pharmaceutical composition containing docetaxel, preparation method and application thereof
Technical Field
The invention relates to a pharmaceutical composition containing docetaxel, a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations.
Background
Docetaxel is a taxoid antineoplastic agent that prevents the rapid division of cancer cells by promoting microtubule aggregation and preventing normal physiological depolymerization of microtubules, stopping them in G2 and M phases until death. The composition has good curative effect in treating various solid tumors (breast cancer, non-small cell lung cancer, prostatic cancer and the like) no matter single medicine or combined use with other medicines. Docetaxel injection is firstly marketed in Mexico in 4 months in 1995, marketed in European Union in 11 months, approved by FDA in 1996, approved to be imported in China in 1997, approved to be sold in nearly hundreds of countries or regions such as China, Europe, America, Japan and the like at present, and various simulated drugs are also marketed in China.
Because docetaxel is easy to degrade when contacting water, docetaxel products are mostly stored in an anhydrous state. In clinical use, the docetaxel is dissolved and diluted by a 5% glucose solution or a 0.9% sodium chloride solution and then is directly used. Meanwhile, because docetaxel is difficult to dissolve in water, in order to ensure convenience of clinical use and quality consistency of medicines used clinically, docetaxel products leaving factories of pharmaceutical factories are mostly anhydrous mixed solutions containing surfactants, solvents and pH regulators. The surfactant and the solvent are mainly used for increasing the solubility of the docetaxel in the mixed liquid so as to meet the quality requirement of clinical use of the injection on an insoluble substance, and the pH regulator is mainly used for ensuring that the pH value of the injection meets the final clinical use requirement and ensuring the chemical stability of the medicine during storage.
The applicant's prior chinese patent application CN107157926A discloses a method for preparing docetaxel injection. The preparation method mainly comprises the following three steps: 1) adding a proper amount of citric acid into polysorbate 80, and stirring until the citric acid is completely dissolved; 2) adding the docetaxel with the prescription amount into the solution obtained in the step (1), and starting stirring while adding; 3) and (3) after the step 2 is finished, adding a proper amount of absolute ethyl alcohol solution and uniformly mixing. The process steps are mainly used for improving the quality of the final injection by controlling the addition speed of the docetaxel. Based on the research results of the process, the inventor further researches and discovers that the pH value of the solution added with the docetaxel in the preparation method also has great influence on the quality of the final docetaxel injection.
Disclosure of Invention
The present invention aims to provide a docetaxel pharmaceutical composition having higher quality based on the prior research efforts of the applicant. The invention further aims to provide a preparation method capable of preparing a docetaxel pharmaceutical composition with higher quality and application of the docetaxel pharmaceutical composition in preparation of a medicine for treating tumors.
In order to achieve the above purpose, the invention provides the following technical scheme:
a pharmaceutical composition containing docetaxel, comprising docetaxel, a surfactant, a pH regulator and a solvent, wherein the docetaxel pharmaceutical composition is prepared by the following method:
1) taking a prescription amount of surfactant, adding a proper amount of pH regulator into the surfactant, uniformly mixing, and regulating the pH value of the mixed liquid to 3.0-4.5;
2) adding docetaxel in a prescription amount into the mixed solution obtained in the step 1, and uniformly mixing;
3) and (3) adding a solvent into the mixed solution obtained in the step (2), uniformly mixing, and adjusting the pH value of the final mixture solution to be 4.5.
The above surfactants are: can increase the compatible effect between the docetaxel and the solvent, and simultaneously increase the dissolving capacity of the docetaxel in water, and can dissolve the docetaxel which is difficult to dissolve in 5 percent glucose injection or 0.9 percent sodium chloride injection which is clinically used, such as polysorbate, cyclodextrin, polyoxyethylene castor oil and the like.
The above solvents are: can dissolve docetaxel, increase the dissolving capacity of docetaxel in water, and can be used for clinical injection, such as ethanol, isobutanol, polyethylene glycol 300, polyethylene glycol 400, acetonitrile, etc.
The pH regulator can regulate the pH value of the mixed solution, can increase the stability of docetaxel, and can be used for clinical injection, and mainly comprises some acids for injection, such as citric acid, Lewis acid, lactic acid, malic acid, citric acid, and the like.
Preferably, the surfactant is polysorbate, such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80. More preferably, the surfactant is polysorbate 80.
Preferably, the pH adjusting agent is a lewis acid. More preferably, the pH regulator is citric acid anhydrous.
Preferably, the solvent is ethanol.
Preferably, the docetaxel, the polysorbate 80 and the ethanol are combined according to the following weight ratio: 20:540-550:390-410. More preferably, the weight ratio of the docetaxel to the polysorbate 80 to the ethanol is as follows: 20:540:395.
Preferably, the pharmaceutical composition is an injection.
Preferably, in the step 2, the adding time of the docetaxel is not less than 20 min.
Preferably, in the step 2, the adding time of the docetaxel is 15min to 30 min.
Preferably, in step 2, docetaxel is added to the solution obtained in step 1 at a constant speed.
Preferably, in the step 2, the adding speed of the docetaxel is 0.13 g/min-0.53 g/min.
Preferably, in the step 2, when the amount of the docetaxel is 8g, the adding speed of the docetaxel is not more than 0.53 g/min; when the dosage of the docetaxel is 4g, the adding speed of the docetaxel is not more than 0.265 g/min.
Preferably, in the step 2, when the amount of the docetaxel is 8g, the adding speed of the docetaxel is not more than 0.27 g/min; when the dosage of the docetaxel is 4g, the adding speed of the docetaxel is not more than 0.13 g/min.
A preparation method of the pharmaceutical composition containing docetaxel.
The application of the pharmaceutical composition containing docetaxel in preparing a medicine for treating tumors.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the pharmaceutical composition containing docetaxel, the order of charging a surfactant, a pH regulator, docetaxel and a solvent is changed in the preparation process, the pH value (3.0-4.5) of the docetaxel in a solvent system is controlled in a matching manner, the degradation damage of docetaxel in the preparation process and the stable placement process is reduced, and the product quality of the docetaxel pharmaceutical composition is improved.
2. According to the pharmaceutical composition containing docetaxel, the surfactant is polysorbate 80, the pH regulator is anhydrous citric acid, the citric acid and the polysorbate 80 are mixed before ethanol is added, then docetaxel serving as an active component is added, and an environment system with the compatibility of polysorbate 80 and docetaxel and the pH value of 3.0-4.5 can be formed firstly under the environment system with the pH value of 3.0-4.5; then adding ethanol and mixing uniformly, wherein the ethanol forms a coating layer on the outer layer of the environment system, which not only can protect the environment system of polysorbate 80-docetaxel from being oxidized and degraded, but also can realize faster fusion with injection diluent (such as 5% glucose solution or 0.9% sodium chloride solution) during clinical use, and form a uniform and stable solution system.
Description of the drawings:
FIG. 1 is a graph showing the state of precipitate precipitated after the product obtained in example 1 and the original preparation were diluted with 0.9% sodium chloride injection to give a solution containing 0.74mg/ml docetaxel, and stored for 15 days.
FIG. 2 is a substance profile of HPLC assay of the product obtained in example 1 stored in a sealed state at 60 ℃ for 0 day.
FIG. 3 is a substance profile of HPLC assay of the product obtained in example 1 stored in a sealed state at 60 ℃ for 5 days.
FIG. 4 is a substance profile of HPLC assay of the product obtained in example 1 stored in a sealed state at 60 ℃ for 10 days.
FIG. 5 is a substance profile of HPLC assay of the product obtained in example 1 stored in a sealed state at 60 ℃ for 30 days.
FIG. 6 is the related substance profile of HPLC detection of original preparation stored at 60 deg.C for 0 days in a sealed manner.
FIG. 7 is the related substance profile of HPLC detection of original preparation stored in a sealed state at 60 deg.C for 5 days.
FIG. 8 is the related substance profile of HPLC detection of original preparation stored in a sealed condition at 60 deg.C for 10 days.
FIG. 9 is the related substance profile of HPLC detection of original preparation stored in a sealed state at 60 deg.C for 30 days.
Detailed Description
The present invention will be described in further detail with reference to test examples and specific embodiments. It should be understood that the scope of the above-described subject matter is not limited to the following examples, and any techniques implemented based on the disclosure of the present invention are within the scope of the present invention.
In each embodiment and comparative example of the invention, the polysorbate 80, the ethanol and the citric acid are in anhydrous states, and the anhydrous limit is that the water content of each raw material is less than 0.5 wt.%.
Example 1:
prescription
Figure BDA0002531946560000061
The docetaxel pharmaceutical composition of example 1 was obtained by the following method:
1) adding citric acid into polysorbate 80 in a prescription amount, uniformly stirring, and stopping adding the citric acid when the pH value of a mixed liquid of the polysorbate and the citric acid is 3.6;
2) adding docetaxel in a prescribed amount into the mixed liquid obtained in the step 1, and stirring until the liquid is uniformly mixed; wherein, docetaxel is added into the mixed liquid obtained in the step 1 at a constant speed, the adding time is 30min, and the adding speed is about 0.13 g/min;
3) adding the ethanol into the mixed liquid obtained in the step 2, uniformly mixing, and adjusting the pH value of the final mixture solution to 3.0-4.5 (the final pH value is 3.6 in the embodiment);
4) and (4) filtering the mixed liquid obtained in the step (3) through a filter membrane of 0.22 mu m for sterilization and filtration, and then filling and capping to obtain the docetaxel injection.
Wherein, the pH value detection method in the step 1) and the step 3) comprises the following steps: after 0.5g of the solution was dissolved in 10ml of water, the pH value was measured by the method (notification 0631 in the fourth 2015 edition of Chinese pharmacopoeia), and the read pH value was recorded.
Example 2
Prescription
Figure BDA0002531946560000062
Figure BDA0002531946560000071
The docetaxel pharmaceutical composition of example 2 was obtained by the following method:
1) adding citric acid into polysorbate 80 according to the prescription amount, uniformly stirring, and stopping adding the citric acid when the pH value of a mixed liquid of the polysorbate and the citric acid is 3.0;
2) adding docetaxel in a prescribed amount into the mixed liquid obtained in the step 1, and stirring until the liquid is uniformly mixed; wherein, docetaxel is added into the mixed liquid obtained in the step 1 at a constant speed, the adding time is 15min, and the adding speed is about 0.53 g/min;
3) adding the ethanol into the mixed liquid obtained in the step 2, uniformly mixing, and adjusting the pH value of the final mixture solution to 3.0-4.5 (the pH value is 3.0 according to the final measurement result in the embodiment);
4) and (4) filtering the mixed liquid obtained in the step (3) through a filter membrane of 0.22 mu m for sterilization and filtration, and then filling and capping to obtain the docetaxel injection.
The pH detection methods in step 1) and step 3) are the same as those in step 1) and step 3) of example 1.
Example 3
Prescription
Figure BDA0002531946560000072
The docetaxel pharmaceutical composition of example 3 was obtained by the following method:
1) adding citric acid into polysorbate 80 in a prescription amount, uniformly stirring, and stopping adding the citric acid when the pH value of a mixed liquid of the polysorbate and the citric acid is 4.5;
2) adding docetaxel in a prescribed amount into the mixed liquid obtained in the step 1, and stirring until the liquid is uniformly mixed; wherein, docetaxel is added into the mixed liquid obtained in the step 1 at a constant speed, the adding time is 30min, and the adding speed is about 0.27 g/min;
3) adding the ethanol into the mixed liquid obtained in the step 2, uniformly mixing, and adjusting the pH value of the final mixture solution to 3.0-4.5 (the final pH value is 4.5 according to the measurement result in the embodiment);
4) and (4) filtering the mixed liquid obtained in the step (3) through a filter membrane of 0.22 mu m for sterilization and filtration, and then filling and capping to obtain the docetaxel injection.
The pH detection methods in step 1) and step 3) are the same as those in step 1) and step 3) of example 1.
Comparative example 1:
the prescription information of comparative example 1 is the same as that of example 1. Comparative example 1 differs from example 1 in that: in step 1 of comparative example 1, the addition of citric acid was stopped when the pH of the mixed liquid of polysorbate and citric acid was 2.8.
Except for the above differences, example 1 and comparative example 1 were handled in exactly the same manner (final pH 2.8).
Comparative example 2:
the prescription information of comparative example 2 is the same as that of example 1. Comparative example 1 differs from example 1 in that: in step 1 of comparative example 2, the addition of citric acid was stopped when the pH of the mixed liquid of polysorbate and citric acid was 6.4.
Except for the above differences, example 1 and comparative example 2 were handled in exactly the same manner (final pH 3.6).
Comparative example 3:
the prescription information of comparative example 3 is the same as that of example 1. Comparative example 3 differs from example 1 in that the pharmaceutical composition of comparative example 3 is obtained by the following method:
1) taking ethanol with the prescription amount, adding docetaxel with the prescription amount into the ethanol, and uniformly stirring; wherein, the docetaxel is added with ethanol at constant speed for 15min, and the adding speed is about 0.53 g/min.
2) Adding anhydrous citric acid into the mixed liquid obtained in the step (1) until the liquid is uniformly mixed;
3) adding polysorbate 80 into the mixed liquid obtained in the step 2, stirring and uniformly mixing, and adjusting the pH value of the final mixture solution to 3.0-4.5 (the pH value is 3.6 according to the final measurement result in the embodiment);
4) and (4) filtering the mixed liquid obtained in the step (3) through a filter membrane of 0.22 mu m for sterilization and filtration, and then filling and capping to obtain the docetaxel injection.
Wherein, the method for detecting the pH value in the step 3) is the same as the method for detecting the pH value in the step 3) in the example 1.
Comparative example 4:
the prescription information of comparative example 4 is the same as that of example 1. Comparative example 4 differs from example 1 in that the pharmaceutical composition of comparative example 3 is obtained by the following method:
1) taking ethanol with the prescription amount, adding polysorbate 80 with the prescription amount into the ethanol, and stirring until the liquid is uniformly mixed;
2) adding citric acid into the mixed liquid obtained in the step (1) and stirring until the liquid is uniformly mixed;
3) adding docetaxel into the mixed liquid obtained in the step 2 and stirring until the liquid is uniformly mixed; wherein, the docetaxel is added with ethanol at constant speed for 15min, and the adding speed is about 0.53 g/min; and adjusting the pH of the final mixture solution to between 3.0 and 4.5 (the final pH of the mixture is 3.6);
4) and (4) filtering the mixed liquid obtained in the step (3) through a filter membrane of 0.22 mu m for sterilization and filtration, and then filling and capping to obtain the docetaxel injection.
Wherein, the method for detecting the pH value in the step 3) is the same as the method for detecting the pH value in the step 3) in the example 1.
Test and analysis of the results
The original preparation products, the preparation products obtained in examples 1 to 3 and the preparation products obtained in comparative examples 1 to 4 were stored in a sealed manner at 60 ℃ for 30 days under the same volume and the same condition, and the product stability test data of each example, comparative example and original preparation were recorded on days 0, 5, 10 and 30, respectively, and the results are shown in table 1.
TABLE stability data at 160 deg.C
Figure BDA0002531946560000101
Figure BDA0002531946560000111
And (3) analyzing an experimental result:
as is clear from the results shown in Table 1, the stability index of the pharmaceutical compositions prepared in the original research, examples 1 to 3 and comparative examples 1 to 4 was substantially unchanged in pH within 30 days. As can be seen by comparing the related substance detection data of each product, the stability of the products obtained in examples 1-3 is significantly higher than that of the original developer and the products obtained in comparative examples 1-4. (the total impurities of the products obtained in examples 1-3 are basically about 1.5% and the maximum simple substance is basically about 0.7% -0.8% after the products are stored in a sealing way at 60 ℃ for 30 days; the total impurities of the products obtained in the original research and comparative examples 1-4 are basically more than 2.6% and the maximum single impurity is basically more than 1.28%) after the products are stored in a sealing way at 60 ℃ for 30 days)
The original research preparation product, the preparation products obtained in examples 1 to 3 and the preparation products obtained in comparative examples 1 to 4 were diluted with 0.9% sodium chloride injection to obtain a compatible solution with a docetaxel content of 0.74mg/ml, and then the solution was left at 25 ± 2 ℃ for 120 days under the same conditions, and the precipitation of the products obtained in each example, comparative example and the original research preparation was recorded at 0 th, 2 th, 15 th, 30 th, 90 th and 120 th days, respectively, and the recorded results are shown in table 2.
TABLE 225. + -. 2 ℃ precipitation
Day 0 2 days 15 days 30 days 90 days 120 days
Original preparation Precipitate is not separated out Precipitate is not separated out Precipitate is separated out --- --- ---
Example 1 Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out
Example 2 Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out
Example 3 Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out
Comparative example 1 Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out
Comparative example 2 Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out Precipitate is not separated out
Comparative example 3 Precipitate is not separated out Precipitate is separated out --- --- --- ---
Comparative example 4 Precipitate is not separated out Precipitate is not separated out Precipitate is separated out --- --- ---
And (3) analyzing an experimental result:
as is clear from the results shown in Table 2, the pharmaceutical compositions prepared in examples 1 to 3 were diluted and left standing at room temperature (25. + -. 2 ℃ C.) for 120 days, and no precipitation occurred. The original preparation precipitates on day 15, while the pharmaceutical compositions prepared in comparative examples 3 and 4 precipitate on day 2 and day 15, respectively, at room temperature (25. + -. 2 ℃) after dilution.
As shown in fig. 1, the product obtained in example 1 was not precipitated on the left side, and after being diluted with 0.9% sodium chloride injection to form a compatible solution with docetaxel content of 0.74mg/ml, a photograph of precipitated state of the precipitate was stored for 15 days; the right side is a photograph of precipitate separated state after the original preparation is diluted into a compatible solution with the docetaxel content of 0.74mg/ml by 0.9 percent sodium chloride injection and stored for 15 days.
In conclusion, the pharmaceutical composition containing docetaxel obtained in embodiments 1 to 3 of the present invention has higher stability.

Claims (10)

1. A pharmaceutical composition containing docetaxel, comprising docetaxel, a surfactant, a pH regulator and a solvent, characterized in that the docetaxel pharmaceutical composition is prepared by the following method:
1) taking a prescription amount of surfactant, adding a proper amount of pH regulator into the surfactant, uniformly mixing, and regulating the pH value of the mixed liquid to 3.0-4.5;
2) adding docetaxel in a prescription amount into the mixed solution obtained in the step 1, and uniformly mixing;
3) adding a solvent into the mixed solution obtained in the step 2, uniformly mixing, and adjusting the pH value of the final mixed solution to 3.0-4.5;
wherein the pH value in the step 1) is a value determined by the following method: taking 0.5g of surfactant to-be-detected substance, adding 10ml of water to dissolve, measuring according to a method, and reading the pH value; the pH value in the step 3) is a value determined by the following method: dissolving 1g of the medicinal liquid in 5ml of water, measuring according to the method, and reading the pH value; the in-law measurement is performed according to the method of the general rule 0631 of the fourth 2015 edition of the Chinese pharmacopoeia.
2. Docetaxel-containing pharmaceutical composition as claimed in claim 1, characterized in that: the surfactant is polysorbate.
3. Docetaxel-containing pharmaceutical composition as claimed in claim 2, characterized in that: the surfactant is polysorbate 80.
4. Docetaxel-containing pharmaceutical composition as claimed in claim 1, characterized in that: the pH regulator is Lewis acid.
5. Docetaxel-containing pharmaceutical composition according to claim 4, characterized in that: the pH regulator is anhydrous citric acid.
6. Docetaxel-containing pharmaceutical composition as claimed in claim 1, characterized in that: the solvent is absolute ethyl alcohol.
7. The docetaxel-containing pharmaceutical composition as set forth in any one of claims 1 to 6, wherein: the docetaxel, the polysorbate 80 and the ethanol are combined according to the following weight ratio: 20:540-550:390-410.
8. The docetaxel-containing pharmaceutical composition as set forth in any one of claims 1 to 6, wherein: the pharmaceutical composition is an injection.
9. A process for the preparation of a docetaxel-containing pharmaceutical composition in accordance with any one of claims 1 to 6.
10. Use of a docetaxel-containing pharmaceutical composition in accordance with any one of claims 1 to 6 for the preparation of a medicament for the treatment of tumors.
CN202010520742.2A 2020-06-10 2020-06-10 Pharmaceutical composition containing docetaxel, preparation method and application thereof Pending CN111557934A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010520742.2A CN111557934A (en) 2020-06-10 2020-06-10 Pharmaceutical composition containing docetaxel, preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010520742.2A CN111557934A (en) 2020-06-10 2020-06-10 Pharmaceutical composition containing docetaxel, preparation method and application thereof

Publications (1)

Publication Number Publication Date
CN111557934A true CN111557934A (en) 2020-08-21

Family

ID=72073821

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010520742.2A Pending CN111557934A (en) 2020-06-10 2020-06-10 Pharmaceutical composition containing docetaxel, preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN111557934A (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008026048A2 (en) * 2006-08-31 2008-03-06 Wockhardt Research Centre Stable injectable pharmaceutical compositions of docetaxel
CN101415416A (en) * 2006-01-30 2009-04-22 基拉尔化学巴西私人控股公司 Pharmaceutical compositions containing docetaxel and a degradation inhibitor and a process for obtaining the same
CN101708177A (en) * 2009-11-23 2010-05-19 浙江万马药业有限公司 Medicine composition containing docetaxel and preparation method thereof
CN102988285A (en) * 2012-12-13 2013-03-27 哈药集团技术中心 Docetaxel injection composition and preparation method thereof
CN107157926A (en) * 2017-07-20 2017-09-15 四川汇宇制药有限公司 A kind of preparation method of injection docetaxel

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101415416A (en) * 2006-01-30 2009-04-22 基拉尔化学巴西私人控股公司 Pharmaceutical compositions containing docetaxel and a degradation inhibitor and a process for obtaining the same
WO2008026048A2 (en) * 2006-08-31 2008-03-06 Wockhardt Research Centre Stable injectable pharmaceutical compositions of docetaxel
CN101708177A (en) * 2009-11-23 2010-05-19 浙江万马药业有限公司 Medicine composition containing docetaxel and preparation method thereof
CN102988285A (en) * 2012-12-13 2013-03-27 哈药集团技术中心 Docetaxel injection composition and preparation method thereof
CN107157926A (en) * 2017-07-20 2017-09-15 四川汇宇制药有限公司 A kind of preparation method of injection docetaxel

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
刘芳，等: "多西他赛纳米乳注射液的制备与质量控制", 《沈阳药科大学学报》 *
朱雷，等: "多西他赛注射液的制备及质量控制", 《西北药学杂志》 *

Similar Documents

Publication Publication Date Title
CN104042567A (en) Ampelopsin nano-micelle and application thereof
CN108430460A (en) Include the pharmaceutical composition and preparation method thereof of dutasteride and propylene glycol monolaurate
CN107661294B (en) Anti-hypertension drug fat emulsion injection and preparation method thereof
CN102988285A (en) Docetaxel injection composition and preparation method thereof
CN112402371B (en) Rudesiwei injection and preparation method thereof
CN108066774A (en) A kind of injection Cabazitaxel composition and preparation method thereof
CN111557934A (en) Pharmaceutical composition containing docetaxel, preparation method and application thereof
CN106880589B (en) Paclitaxel injection and preparation method thereof
CN114432242B (en) Apremilast nanocrystalline composition and preparation method thereof
CN104800172A (en) Carbazochrome sodium sulfonate powder injection for injection and preparation method thereof
CN104490902B (en) A kind of composite vitamin for injection freeze drying powder injection composition and preparation method thereof
CN105476954B (en) A kind of lomefloxacin hydrochloride injection and preparation method
CN103497225A (en) Tartaric acid mikamycin for injection and preparations and preparation method thereof
CN110856746B (en) Freeze-dried micelle preparation containing carfilzomib and preparation method thereof
CN109044969B (en) Preparation method of paclitaxel injection
CN107157926B (en) Preparation method of docetaxel injection
CN102210686A (en) Pharmaceutical composition containing ganciclovir compound, and preparation method thereof
CN105997873A (en) Oil-in-water type terazosin nanoemulsion antihypertensive drug
CN111603439A (en) Long-acting in-situ phase change gel injection of brexpiprazole and preparation method thereof
CN110327284A (en) A kind of cefodizime sodium for injection and preparation method thereof
CN102697741B (en) Oxaliplatin vesicular phospholipid gel injection
CN106937944A (en) A kind of injection metronidazole freeze-dried powder and preparation method thereof
CN105232476B (en) The preparation method of nolatrexed dihydrochloride freeze drying powder injection
CN113425677B (en) Carbazochrome sodium sulfonate water injection and preparation method and application thereof
CN107362144A (en) A kind of Lurasidone brain targeted liposome injection and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20200821