KR101093720B1 - Composition for Injection Comprising Anticancer Drug - Google Patents

Abstract

The present invention relates to an anticancer composition for injection containing docetaxel, wherein the solubilizing agent of docetaxel is tetrahydroperpril alcohol polyethylene glycol ether and polyethylene glycol 660 12-hydroxystearate; An anticancer composition for injection comprising at least one selected from di-alpha-tocopherol, sodium bisulfite, and idieti (sodium salt), and a method for producing the anticancer composition for injection.

Docetaxel, Injection, Composition, Anticancer

Description

Composition for Injection Comprising Anticancer Drug

The present invention relates to an anticancer composition for injection containing docetaxel, wherein the solubilizing agent of docetaxel is tetrahydroperpril alcohol polyethylene glycol ether and polyethylene glycol 660 12-hydroxystearate; An anticancer composition for injection comprising at least one selected from di-alpha-tocopherol, sodium bisulfite, and idieti (sodium salt), and a method for producing the anticancer composition for injection.

Docetaxel (docetaxel) is a cancer chemotherapy agent having a wide range of anti-tumor and anti-leukemic activity, and particularly has an excellent anticancer effect against non-small cell lung cancer, breast cancer, ovarian cancer and head and neck cancer.

There are three types of docetaxel crystalline forms known to date: docetaxel trihydrate, docetaxel hemihydrate, and docetaxel anhydride, of which docetaxel trihydrate is most commonly used.

Docetaxel has strong lipophylic properties, very low solubility in water, physical instability, and difficulty in making it into injections due to poor solubility, and docetaxel injections also have problems with drug stability and toxicity due to solubilizers. In order to solve this problem, research is being actively conducted.

Conventionally, as a prior art for improving the stability of docetaxel drug, Korean Patent No. 310839 prepares a mixed matrix in which polyvinylpyrrolidone is mixed, and this is anhydrous ethanol and polyoxyethylene glycerol licinolate, polysorbate 80, anhydrous A method of preparing an injection solution by mixing with a solvent such as ethanol or polyethylene glycol is disclosed. However, the prior art has a problem that it contains a substance that can cause alcoholism by ethanol and hypersensitivity side effects by polysorbate 80.

International Patent WO 99/24073 also discloses docetaxel in a small amount of ethanol, which is dissolved in a 5% dextrose solution of acetyl gamma cyclodextrin (Ac-gamma-CD) or hydroxypropylmethyl beta cyclodextrin (HP-beta-CD). Ethanol was removed as much as possible by evaporation or any suitable method and then lyophilized to obtain a lyophilized composition. The lyophilized composition thus obtained is said to have a physical stability of 72 hours or more at a concentration of 0.3 to 1.2 mg / ml of the perfusate diluted again in a 5% dextrose solution. However, the above prior art also has a high possibility of remaining ethanol used in the process of dissolving docetaxel, the dilution of the prepared liquid composition has a disadvantage that a precipitate is formed when the concentration of docetaxel is low.

The present invention has been made to solve the problems of the prior art, an object of the present invention to improve the solubility of poorly soluble anti-cancer substances in water, as well as to provide an anticancer composition for injections and a method for preparing the same that greatly alleviate toxicity.

Another object of the present invention is to minimize the degradation of the active ingredient and loss of titer and to provide a stable anti-cancer composition for injection, it is possible to prevent the formation of precipitates when diluting for formulation, which is very useful as an intravenous injection for human It is to provide a composition and a method for producing the same.

The present invention relates to an anticancer composition for injection containing docetaxel, wherein the solubilizing agent of docetaxel is tetrahydroperpril alcohol polyethylene glycol ether and polyethylene glycol 660 12-hydroxystearate; An anticancer composition for injection comprising at least one selected from di-alpha-tocopherol, sodium bisulfite, and idieti (sodium salt), and a method for preparing the anticancer composition for injection.

According to the present invention, by appropriately mixing a poorly soluble anticancer substance with water, a pharmaceutically acceptable solubilizing agent can improve the solubility and greatly reduce the toxicity. In addition, the acid and buffer is added to adjust the pH to an appropriate range, or when the stabilizer is added to minimize the degradation of the active ingredient and the loss of titer, and when the anticancer composition for injection is stabilized to dilute the formulation. It is very useful as a human intravenous injection because it can prevent the formation of precipitates.

The present invention provides an anticancer composition for injection containing docetaxel, a poorly soluble anticancer substance, comprising: tetrahydroperpryl alcohol polyethylene glycol ether and polyethylene glycol 660 12-hydroxystearate as a solubilizing agent of docetaxel; Provided is an anticancer composition for injection comprising any one or more selected from di-alpha-tocopherol, sodium bisulfite, and idieti (sodium salt) as stabilizers.

Docetaxel as an anticancer substance in the above provides an anticancer composition for injection that is any one selected from the group of docetaxel anhydride, docetaxel trihydrate.

The anticancer composition for injection of the present invention provides an anticancer composition for injection that is adjusted to pH 4-6.

The anticancer drug composition for injection of the present invention may be used as a solubilizing agent in the range of 3000 to 5000 parts by weight, preferably 4000 parts by weight based on 100 parts by weight of dodetaxel.

The anticancer composition for injection of the present invention may be used as a solubilizer for polyethylene glycol 660 12-hydroxystearate 2500-4500 parts by weight, preferably 3400 parts by weight based on 100 parts by weight of dodetaxel.

The anticancer composition for injection of the present invention provides an anticancer composition for injection when the content of the stabilizer di-alpha tocopherol is 50 to 150 parts by weight based on 100 parts by weight of docetaxel when the di-alpha tocopherol is used as a stabilizer.

When the anticancer composition for injection of the present invention uses any one or more selected from the group of sodium bisulfite or idieti (sodium salt) as a stabilizer, the content of the sodium bisulfite or idieti (sodium salt) as the stabilizer is docetaxel 100 An anticancer composition for injection is added, which is added alone or in combination, based on 5 parts by weight.

The anticancer composition for injection of the present invention provides an anticancer composition for injection comprising a predetermined acid or / and buffer to adjust the pH of the anticancer composition.

The anticancer composition for injection of the present invention preferably provides an anticancer composition for injection, wherein the buffer is an acetate buffer having a pH of 4 to 6.

Hereinafter, the content of the anticancer composition for injection of the present invention will be described in more detail.

In the present invention, the anti-cancer substance which is poorly soluble in water is a concept that collectively refers to an anti-cancer substance that is difficult to use as an injection formulation in the state of low solubility in water, and usually has a very low solubility, preferably It includes an anticancer substance known to have a very low solubility of 30 µg / ml or less or any anticancer substance to be developed in the future. As a specific example of such an anticancer substance, docetaxel is shown.

Injectable compositions of the present invention, a specific solubilizer is introduced to improve the solubility of the anticancer substance in water. As the solubilizer, tetrahydroperpryl alcohol polyethylene glycol ether (glycoprolol) is used as a dissolution aid, and solutol polyethylene glycol 660 12-hydroxystearate (solutol) is used as a surfactant.

Glycofurol is a hydrophilic organic solvent that is harmless because it is nontoxic and is a very suitable solvent for solubilizing poorly soluble anticancer substances in water. Glycoprolol is a commercially available formulation and is well known as Glycoprolol 75 from Sigma as a representative product.

Solutol is a surfactant manufactured by BASF (aka Solutol HS-15) and contains approximately 30% polyethylene glycol and 70% polyethylene glycol ester, and is nontoxic and glycoprolol When used together, it effectively solubilizes a poorly soluble anticancer substance in water.

In order to prepare the injection, first, the solution was prepared by heating and stirring the solvent and dissolving it in the aqueous phase as the first solution, and then dissolving the poorly soluble anticancer substance in the glycoprole as the second solution. It is good to add the stabilizer selected according to the dissolution characteristics to the first solution or the second solution, respectively or together. For example, a stabilizer that may be added to the first solution, which is an aqueous phase, may be used as one or more selected from the group of sodium bisulfite or EDTA (EDTA, sodium salt). As a stabilizer which may be added to the second solution which is an oil phase, di-alpha tocopherol of oil phase may be used. Sodium bisulfite is a hydrophilic reducible antioxidant, and EDTA (EDTA) is a stabilizer that fixes metal ions and forms chelate compounds with trace metals such as iron and copper to prevent auto-oxidation of injections. Stabilization of the material prevents the loss of potency due to decomposition. In addition, di-alpha tocopherol in oil can stabilize the anticancer substance by a lipophilic reducing antioxidant mechanism, thereby preventing the loss of titer due to decomposition.

The stabilizer is different in content added according to its type. When any one or more selected from the group of sodium bisulfite or editiei (EDTA, sodium salt) is used, it is sufficient to add 5 to 10 parts by weight based on 100 parts by weight of dodetaxel, and when di-alpha tocopherol is used. It is good to add in the range of 50-150 weight part with respect to 100 weight part of dodetaxel.

In addition, the aqueous phase constituting the first solution may include a buffer solution for stabilization of the drug. Especially docetaxel is stable between pH 4-6, but when formulated using tertiary distilled water as the aqueous phase, the final pH of the formulation is usually in the range of 6-7. Therefore, a buffer may be used to adjust the pH range to pH 4-6, more preferably pH 5-5.5, and examples of such buffers include acetic acid buffer solutions having a pH of 4-6.

The amount of glycoprolol and solutol mixed varies depending on the type and content of the anticancer substance used, and does not require any particular limitation. Preferably, the weight ratio of glycoprolol: solutol is 3.0 to 5.0: 2.5 to 4.5, preferably Is added in a weight ratio of 4: 3.4. Within the above composition range, it is possible to efficiently solubilize the majority of the anticancer substances that are poorly soluble in water.

The second solution is slowly added dropwise to the first solution prepared as described above and mixed according to specific anticancer substances. Preferably, the pH of the final solution is in a weakly acidic region, more preferably pH 4-6, and more preferably. Preferably adjusted to a pH of 5 to 5.5. The reason for adjusting the pH to the above range is to solve the problem of lowering stability due to decomposition of the anticancer substances, that is, commonly used anticancer substances over time. As such, the pH adjusting agent for adjusting the acidity of the final liquid is not particularly limited, and various acids such as acetic acid, citric acid, phosphoric acid, ascorbic acid, gluconic acid, succinic acid, tartaric acid and lactic acid, and salts thereof may be used. Acetic acid may be used.

The anticancer composition for injection of the above composition is diluted in about 5 to 100 times, preferably 5 to 20 times, in physiological saline solution or 5% glucose solution during actual clinical administration. In addition to the stability at the time of storage, the anticancer substance is required to be physically and stably dispersed even after a certain period of time due to the small change in the particle size distribution even when diluting the composition for actual clinical administration.

After the dilution of the anticancer composition for the main detergent for 10 hours and 100 times with a 5% glucose solution, and after 24 hours before and after dilution with 10 times and 100 times with physiological saline, it was left for 24 hours after dilution. When the particle size distribution does not change much, it can be confirmed that it is physically stable after a certain time. These results suggest that the anticancer composition according to the present invention will be very effective even in actual clinical administration.

The present invention includes a method for producing an anticancer composition for injection containing docetaxel.

The present invention provides a method for preparing an anticancer composition for injection containing docetaxel, comprising the steps of: (1) adding di-alpha tocopherol as a docetaxel and a stabilizer to tetrahydroperpril alcohol polyethylene glycol ether; (2) mixing and dissolving acetic acid buffer solution in polyethylene glycol 660 12-hydroxystearate; (3) dropping and mixing the solution containing docetaxel of step (1) into the solution of step (2); (4) adjusting the pH by adding a pH adjusting agent to the solution obtained in step (3); (5) shows a method for producing an anticancer composition for injection containing docetaxel comprising the step of mixing the solution obtained in step (4).

In the step (1), 3000-5000 parts by weight of tetrahydroperpryl alcohol polyethylene glycol ether and 50-150 parts by weight of di-alpha tocopherol are mixed with 100 parts by weight of docetaxel, and then heated at 50-60 ° C. and dissolved at 100-300 rpm. Docetaxel can be dissolved by stirring until In this case, the docetaxel may be any one selected from the group of docetaxel anhydride and docetaxel trihydrate.

In the step (2), the polyethylene glycol 660 12-hydroxystearate 2500-4500 parts by weight and the acetic acid buffer solution are mixed and then heated at 50-60 ° C. and stirred until dissolved at 100-300 rpm. At this time, the acetic acid buffer solution may be mixed with 3,400 mg of polyethylene glycol 660 12-hydroxystearate in a ratio of 1.8 ml of acetic acid buffer, and then heated and stirred until dissolved.

Step (3) is a mixture of docetaxel, tetrahydroperpryl alcohol polyethylene glycol ether and di-alpha tocopherol obtained in step (1) of polyethylene glycol 660 12-hydroxystearate and acetic acid buffer solution obtained in step (2). Mix by dropping (dropping) 1 to 10ml per minute into the mixture. At this time, the mixture may be mixed with stirring at 50 to 60 ° C. at 100 to 300 rpm.

In step (4), a pH adjuster is added to the solution obtained in step (3) to adjust the final pH to 4-6, acetic acid, citric acid, phosphoric acid, ascorbic acid, gluconic acid, succinic acid, tartaric acid and Lactic acid and the like and salts thereof, preferably an acetic acid buffer solution having a pH of 4 to 6 can be used.

In step (5), the solution obtained in step (4) may be stirred at 300 to 500 rpm for 2 to 4 hours at 50 to 60 ° C. to prepare an anticancer composition for injection containing docetaxel.

In the preparation of an anticancer composition for injection containing docetaxel, the present invention comprises the steps of: dissolving and adding docetaxel to (1 ′) tetrahydroperpryl alcohol polyethylene glycol ether; (2 ′) mixing and dissolving polyethylene glycol 660 12-hydroxystearate with at least one selected from sodium bisulfite and editiei (EDTA, sodium salt) as an acetate buffer and stabilizer; (3 ') dropping and mixing the solution containing docetaxel in step (1') into the solution in step (2 '); (4 ') adjusting the pH by adding a pH adjusting agent to the solution obtained in step (3'); (5 ') shows a method for producing an anticancer composition for injection containing docetaxel comprising the step of mixing the solution obtained in step (4').

Step (1 ') is a mixture of 3000 to 5000 parts by weight of tetrahydroperpryl alcohol polyethylene glycol ether with respect to 100 parts by weight of docetaxel, and then heated to 50 to 60 ℃ and stirred until dissolved at 100 to 300 rpm to dissolve the docetaxel have. In this case, the docetaxel may be any one selected from the group of docetaxel anhydride and docetaxel trihydrate.

Step (2 ') is 2500 to 4,500 parts by weight of polyethylene glycol 660 12-hydroxystearate, at least one selected from sodium bisulfite, idieti (sodium salt) as a stabilizer, and acetic acid buffer solution After mixing, the mixture may be heated at 50 to 60 ° C. and stirred until dissolved at 100 to 300 rpm. At this time, the acetic acid buffer solution may be mixed with 3,400 mg of polyethylene glycol 660 12-hydroxystearate in a ratio of 1.8 ml of acetic acid buffer, and then heated and stirred until dissolved.

Step (3 ') is a polyethylene glycol 660 12-hydroxystearate, stabilizer and acetic acid buffer solution obtained by mixing the docetaxel and tetrahydroperpryl alcohol polyethylene glycol ether obtained in step (1') in step (2 '). 1 drop to 1 ~ 10ml per minute into the mixed solution (mixing). At this time, the mixture may be mixed with stirring at 50 to 60 ° C. at 100 to 300 rpm.

In step (4 '), a pH adjuster is added to the solution obtained in step (3') to adjust the final pH to 4-6, acetic acid, citric acid, phosphoric acid, ascorbic acid, gluconic acid, succinic acid, Tartaric acid and lactic acid and the like and salts thereof, preferably an acetic acid buffer having a pH of 4 to 6 can be used.

In step (5 '), the solution obtained in step (4') may be stirred at 300 to 500 rpm for 2 to 4 hours at 50 to 60 ° C to prepare an anticancer composition for injection containing docetaxel.

The anticancer composition for injection of the present invention and a method for producing the same have been investigated under various conditions. In order to achieve the object of the present invention, it is preferable to provide the anticancer composition for injection and the method for preparing the same under the above-mentioned conditions. .

Hereinafter, the present invention will be described in detail with reference to Examples and Test Examples. However, these are intended to explain the present invention in more detail, and the scope of the present invention is not limited thereto.

Example 1 Preparation of Injectable Composition Containing Docetaxel Trihydrate (I)

(1) Tetrahydroperpril alcohol 4000 mg polyethylene glycol ether, 100 mg docetaxel trihydrate, 100 mg di-alpha tocopherol were added, followed by stirring until dissolved at 200 rpm at 55 ° C. to obtain a solution.

(2) 3400 mg of polyethylene glycol 660 12-hydroxystearate and 1.8 ml of acetic acid buffer (pH 4.1) were mixed and stirred at 55 ° C. until dissolved at 200 rpm to obtain a solution.

(3) The solution containing docetaxel of step (1) was dropped into the solution of step (2) at a rate of 1 ml per minute and mixed at 55 rpm to 200 rpm.

(4) The pH of the solution was adjusted to 5.5 by adding an acetic acid buffer of pH 4.1 to the solution obtained in step (3) as a pH adjusting agent.

(5) The solution obtained in step (4) was mixed at 400 rpm for 3 hours at 55 ° C. to prepare a composition for injection comprising docetaxel trihydrate.

Acetate buffer solution of pH 4.1 in the above was prepared 100ml of 0.2M sodium acetate (acetic acid) was used to adjust the pH to 4.1 using acetic acid (acetic acid).

Example 2 Preparation of Injectable Composition Containing Docetaxel Anhydride (I)

Injection including docetaxel anhydride using the same composition and method as in Example 1, except that docetaxel anhydrous is used instead of docetaxel trihydrate in step (1) of Example 1 A composition for preparation was prepared.

Example 3 Preparation of an Injectable Composition Containing Docetaxel Trihydrate (II)

4000 mg of (1 ′) tetrahydroperpril alcohol polyethylene glycol ether and 100 mg of docetaxel trihydrate were added thereto, followed by stirring until dissolved at 200 rpm at 55 ° C. to obtain a solution.

3400 mg of (2 ') polyethylene glycol 660 12-hydroxystearate, 10 mg of sodium bisulfite, and 1.8 ml of acetic acid buffer (pH 4.1) were mixed, followed by stirring until dissolved at 200 rpm at 55 ° C. to obtain a solution. .

(3 ') The solution containing the docetaxel of step (1') was dropped into the solution of step (2 ') at a rate of 1 ml per minute and mixed at 55 rpm to 200 rpm.

(4 ') The pH of the solution was adjusted to 5.5 by adding an acetic acid buffer of pH 4.1 to the solution obtained in step (3') as a pH adjusting agent.

(5 ') The solution obtained in step (4') was mixed at 400 rpm for 3 hours at 55 ° C to prepare a composition for injection containing docetaxel trihydrate.

Acetate buffer solution of pH 4.1 in the above was prepared 100ml of 0.2M sodium acetate (acetic acid) was used to adjust the pH to 4.1 using acetic acid (acetic acid).

Example 4 Preparation of an Injectable Composition Containing Docetaxel Anhydride (II)

Injectable agent containing docetaxel anhydride using the same composition and method as in Example 3 except that docetaxel anhydrous is used instead of docetaxel trihydrate in step (1) of Example 1 A composition for preparation was prepared.

<Test Example 1>

In the Examples 1 to 4, the respective compositions obtained without the addition of the pH adjuster in the step (4) of Examples 1 and 2 and (4 ') of the Examples 3 and 4 when the respective compositions for injection were prepared. Injectable compositions of Examples 1 "and 4" were diluted in McIlvaine buffer solution of pH 3-8, respectively, and left at 40 degreeC, and after 24 and 48 hours, the residual rate of docetaxel was measured using HPLC, and the The results are shown in Table 1 below.

HPLC operating conditions are as follows.

Column: C18, 4.6 × 250mm, 5㎛

Mobile Phase: ACN: Phosphoric acid (2mM) = 45: 55 (v / v)

Flow rate: 1ml / min

Oven Temperature: 40 ℃

UV wave length: 227nm

HPLC system: Shiseido Manospace

Integrator: Hitachi D-2000

Table 1. Measurement of Docetaxel Residual Rate of Injectable Compositions According to pH

* Injectable compositions of Examples 1 "to 4" of Table 1 are prepared according to Examples 1 and 2 (4) and Examples 3 and 4 (4) when preparing the injectable compositions of Examples 1 to 4. The composition for injection is obtained without adding a pH adjusting agent in step ').

As shown in Table 1, the residual rate of docetaxel in the composition for injection over time at pH 3 to 8 was confirmed, and the residual rate of docetaxel at pH 4 to 6, preferably pH 5 to 6, is high, and thus the range of injection It was found that docetaxel is stable in the composition.

Therefore, it can be seen that the composition for injection containing the docetaxel of the present invention is preferably maintained at pH 4-6, preferably pH 5-6.

Test Example 2 Measurement of Particle Size of an Injectable Composition Containing Docetaxel

Before dilution of each composition for injections prepared to evaluate the stability of the composition for injection comprising the docetaxel trihydrate prepared in Example 1 and the composition for injection containing the docetaxel trihydrate prepared in Example 2 (Initial); 24 hr before dilution with 10% dilution with 5% glucose; Before dilution with 100% glucose, 24 h after dilution; Before 10-fold dilution of saline, 24 hours after dilution; Particle size was measured using Zetasize Nano ZS of Malvern, UK, before and after dilution of 100-fold saline for 24 hours and the results are shown in Table 2 below.

Table 2. Particle Size of Injectable Compositions Containing Docetaxel Before and After Dilution

* The particle size measurement results in Table 2 are expressed as average values and deviations (S.D.) measured three times.

As shown in Table 2, the particle size of the injectable composition containing docetaxel is not significantly large even after 24 hours at 10-fold and 100-fold dilution with 5% glucose and / or physiological saline, respectively. The composition for injections containing docetaxel suggests stability.

<Test Example 3>

For the injectable composition comprising each of the docetaxel prepared in Examples 1 to 4 for 0 days, 5 days, 10 days and 20 days, 30 days at room temperature and 40 ℃ each using HPLC Docetaxel residual rate in the composition for injection was measured and the results are shown in Tables 3-1 and 3-2 below.

HPLC operating conditions are as follows.

Column: C18, 4.6 × 250mm, 5㎛

Mobile Phase: ACN: Phosphoric acid (2mM) = 45: 55 (v / v)

Flow rate: 1ml / min

Oven Temperature: 40 ℃

UV wave length: 227nm

HPLC system: Shiseido Manospace

Integrator: Hitachi D-2000

Table 3-1. Residual Docetaxel (%) measurement at room temperature

Table 3-2. Docetaxel Residual Rate (%) Determination at Different Temperatures at 40 ℃

As shown in Table 3-1 and Table 3-2, the docetaxel residual ratio in the injectable composition comprising the docetaxel of the present invention for 30 days at room temperature and 40 ° C. remains at least 80%, and thus the composition for injection comprising the docetaxel of the present invention. It was found that the stability is excellent.

As described above, although described with reference to a preferred embodiment of the present invention, those skilled in the art will be variously modified and modified within the scope of the present invention without departing from the spirit and scope of the invention described in the claims below. It will be appreciated that it can be changed.

According to the present invention, an injectable composition comprising docetaxel which is very useful as a human intravenous injectable formulation can be provided.

Claims (7)

delete delete delete In the manufacturing method of the anticancer composition for injection containing docetaxel, (1) To the tetrahydroperpryl alcohol polyethylene glycol ether, docetaxel anhydride, docetaxel trihydrate, any one selected from the group of docetaxel, and di-alpha-tocopherol as a stabilizer are added and dissolved. Dissolving docetaxel by mixing 3000-5000 parts by weight of hydroperl alcohol polyethylene glycol ether and 50-150 parts by weight of di-alpha tocopherol and then warming at 50-60 ° C. until stirring at 100-300 rpm; (2) After mixing 2500-4500 parts by weight of polyethylene glycol 660 12-hydroxystearate and an acetic acid buffer solution with respect to 100 parts by weight of docetaxel in step (1), when heated at 50-60 ° C. and dissolved at 100-300 rpm. Stir until, but the acetic acid buffer is mixed in a ratio of 1.8ml of acetic acid buffer solution to 3400mg polyethylene glycol 660 12-hydroxystearate, and then stirred until it is dissolved at 100-300rpm warmed at 50-60 ℃; (3) dropping the solution containing docetaxel obtained in step (1) into the solution obtained in step (2) at 1 to 10 ml per minute, and mixing, stirring at 100 to 300 rpm at 50 to 60 ° C. And mixing; (4) adjusting the pH by adding an acetic acid buffer having a pH of 4 to 6 as a pH adjusting agent to adjust the final pH of the solution obtained in step (3) to 4 to 6; (5) a method of producing an anticancer composition for injection containing docetaxel comprising the step of mixing the solution obtained in step (4) at 50 to 60 ° C for 300 to 500 rpm for 2 to 4 hours. In the manufacture of an anticancer composition for injection containing docetaxel, (1 ') Tetrahydroperpryl alcohol polyethylene glycol ether is added to docetaxel, which is any one selected from the group of docetaxel anhydride and docetaxel trihydrate, and then dissolved. Dissolving docetaxel by mixing ˜5000 parts by weight and stirring at 50 to 60 ° C. and heating until dissolved at 100 to 300 rpm; (2 ') Polyethylene glycol 660 12-hydroxystearate 2500-4500 parts by weight based on 100 parts by weight of docetaxel of the step (1'), any one selected from sodium bisulfite, idieti (sodium salt) as a stabilizer After mixing 5-10 parts by weight and the acetic acid buffer solution, the mixture is stirred until it is heated at 50-60 ° C. and dissolved at 100-300 rpm. The acetic acid buffer solution is acetic acid buffer solution for 3400 mg of polyethylene glycol 660 12-hydroxystearate. Mixing in a ratio of 1.8 ml and then warming at 50-60 ° C. and stirring until dissolved at 100-300 rpm; (3 ') dropping the solution containing docetaxel obtained in step (1') to the solution obtained in step (2 ') at 1 to 10 ml per minute and mixing, but mixing at 50 to 60 ℃ 100 ~ Mixing with stirring at 300 rpm; (4 ') adjusting the pH by adding an acetic acid buffer having a pH of 4 to 6 as a pH adjusting agent to adjust the final pH of the solution obtained in step (3') to 4 to 6; (5 ') the preparation of an anticancer composition for injection containing docetaxel, comprising the step of mixing the solution obtained in step (4') at 300 to 500 rpm for 2 to 4 hours at 50 to 60 ° C. Way. delete delete