CN115581664A - Abiraterone acetate nanocrystalline injection and preparation method thereof - Google Patents
Abiraterone acetate nanocrystalline injection and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of preparation of abiraterone acetate preparations, and provides an abiraterone acetate nanocrystal injection and a preparation method thereof. The abiraterone acetate nanocrystal injection per 1000mL provided by the invention comprises the following components: 25g of abiraterone acetate bulk drug, 1-2 g of stabilizer, 5-10 g of freeze-drying protective agent, 3-7 g of suspending agent, 0.01g of bacteriostatic agent, 3-5 g of osmotic pressure regulator and water for injection. The abiraterone acetate nanocrystal injection provided by the invention changes the administration route of the abiraterone acetate, and the abiraterone acetate is used in the form of the injection, so that the abiraterone acetate directly enters blood circulation, the administration is rapid and reliable, and the bioavailability is improved; and can reduce the administration dosage of the abiraterone acetate. In addition, the abiraterone acetate nanocrystal injection does not contain a large amount of surfactants and carrier materials, does not generate metabolites of materials, and is high in safety.
Description
Technical Field
The invention relates to the technical field of preparation of abiraterone acetate preparations, and in particular relates to an abiraterone acetate nanocrystal injection and a preparation method thereof.
Background
Prostate cancer is a common malignancy in the male reproductive system, and the incidence of prostate cancer is 2 nd and 6 th in all male malignancies worldwide. Lung cancer has been surpassed in the united states, with the prevalence of cancer in men at position 1 and mortality at position 2. The incidence of prostate cancer in China is far lower than that in European and American countries, but the incidence of prostate cancer is obviously increased along with the aging of population, the change of life style and the improvement of the detection rate of prostate cancer in recent years. The threat of prostate cancer to human health is becoming more and more serious and, as a result, prostate cancer is becoming of increasing concern.
Prostate cancer is usually diagnosed followed by surgery or Androgen Deprivation Therapy (ADT). Patients diagnosed with prostate cancer within the T2 stage can be completely cured of prostate cancer by radical prostate cancer surgery. Patients with metastatic prostate cancer or prostate cancer who can not be treated radically, or patients who can not be treated locally but can not be treated locally after curative treatment can be treated by endocrine. However, metastatic prostate cancer gradually develops into castration-resistant prostate cancer (CRPC) independent of hormone production after a median time of 18 to 24 months in endocrine therapy. In the past, CRPC treatment effect is poor, and prognosis is poor.
Abiraterone acetate is a 3-acetyl analogue of abiraterone, is a prodrug of abiraterone, is a CPY17 inhibitor, can completely block the synthesis of androgen in testis, adrenal gland and prostate cancer cells, and can cut off the fuel supply of androgen of tumors, thereby playing the aim of killing the prostate cancer cells. The medicine is firstly approved by FDA on the market in 2011 at 28/4, and is used for treating castration-resistant metastatic prostate cancer (mCRPC) by combining with prednisone or prednisolone.
At present, the common dosage form of the abiraterone acetate is a tablet, but the abiraterone acetate is a lipophilic compound, so that the solubility and the permeability of the abiraterone acetate tablet are low, the absorption of the abiraterone acetate in a body is influenced, and the bioavailability of the abiraterone acetate is reduced.
Disclosure of Invention
In view of the above, the present invention aims to provide an abiraterone acetate nanocrystal injection and a preparation method thereof. The injection provided by the invention enables the abiraterone acetate to be administered in an injection form, and improves the bioavailability of the abiraterone acetate.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an abiraterone acetate nanocrystal injection, wherein each 1000mL of the abiraterone acetate nanocrystal injection comprises the following components:
25g of abiraterone acetate raw material medicine, 1-2 g of stabilizing agent, 5-10 g of freeze-drying protective agent, 3-7 g of suspending agent, 0.01g of bacteriostatic agent, 3-5 g of osmotic pressure regulator and water for injection.
Preferably, the stabilizer comprises one or more of polysorbate 80 (II), polysorbate 20, polyoxyethylene (40) monostearate and bezoar-78.
Preferably, the lyoprotectant includes one or more of mannitol, polyvinylpyrrolidone, gelatin, sodium thiosulfate, and sorbitol.
Preferably, the suspending agent comprises one or more of sodium carboxymethyl cellulose, methyl cellulose and hydroxypropyl cellulose.
Preferably, the bacteriostatic agent comprises one or more of thimerosal sodium, benzyl alcohol, benzoic acid and chlorobutanol.
Preferably, the osmolality adjusting agent comprises sodium chloride and/or glucose.
The invention also provides a preparation method of the abiraterone acetate nanocrystal injection, which comprises the following steps:
dispersing the abiraterone acetate raw material drug and the stabilizer in water, and sequentially mixing and homogenizing to obtain an abiraterone acetate nanocrystal suspension;
after subpackaging the abiraterone acetate nanocrystal suspension, adding a freeze-drying protective agent into the obtained subpackaged abiraterone acetate nanocrystal suspension, and freeze-drying to obtain abiraterone acetate nanocrystal freeze-dried powder;
dispersing the abiraterone acetate nanocrystal freeze-dried powder in water for injection, adding a suspending agent, a bacteriostatic agent and an osmotic pressure regulator, and supplementing the water for injection to a full dose to obtain the abiraterone acetate nanocrystal injection;
the homogenizing comprises sequentially performing high shear homogenizing and high pressure homogenizing.
Preferably, the rotation speed of the high-shear homogenizing is 1000-3000 rpm, and the time is 10-20 min; the pressure of the high-pressure homogenization is 700-1400 bar, and the times of the high-pressure homogenization are 3-6 times.
Preferably, before subpackaging the abiraterone acetate nanocrystal suspension, sterilizing is further performed.
Preferably, the parameters of freeze-drying include: the precooling temperature is-35 to-45 ℃, and the time is 3 to 5 hours; the pressure of vacuum drying is 15-25 Pa, and the time is 20-26 h.
The invention provides an abiraterone acetate nanocrystal injection, wherein each 1000mL of the abiraterone acetate nanocrystal injection comprises the following components: 25g of abiraterone acetate raw material medicine, 1-2 g of stabilizing agent, 5-10 g of freeze-drying protective agent, 3-7 g of suspending agent, 0.01g of bacteriostatic agent, 3-5 g of osmotic pressure regulator and water for injection. The abiraterone acetate nanocrystal injection provided by the invention changes the administration route of the abiraterone acetate, and the abiraterone acetate is used in the form of the injection, so that the abiraterone acetate directly enters blood circulation, the administration is rapid and reliable, and the bioavailability is improved; and can reduce the administration dosage of the abiraterone acetate. In addition, the abiraterone acetate nanocrystal injection does not contain a large amount of surfactants and carrier materials, does not generate metabolites of materials, and is high in safety.
The invention also provides a preparation method of the abiraterone acetate nanocrystal injection in the technical scheme, which comprises the following steps: dispersing the abiraterone acetate raw material drug and the stabilizer in water, and sequentially mixing and homogenizing to obtain an abiraterone acetate nanocrystal suspension; after subpackaging the abiraterone acetate nanocrystal suspension, adding a freeze-drying protective agent into the obtained subpackaged abiraterone acetate nanocrystal suspension, and freeze-drying to obtain abiraterone acetate nanocrystal freeze-dried powder; dispersing the abiraterone acetate nanocrystal freeze-dried powder in water for injection, adding a suspending agent, a bacteriostatic agent and an osmotic pressure regulator, and supplementing the water for injection to the full amount to obtain the abiraterone acetate nanocrystal injection; the homogenizing comprises sequentially performing high shear homogenizing and high pressure homogenizing. The preparation method provided by the invention reduces the particle size of the abiraterone acetate raw material drug to a nanometer level through high-shear homogenization and high-pressure homogenization, and increases the specific surface area of the indissolvable abiraterone acetate raw material drug; meanwhile, the abiraterone acetate freeze-dried powder achieves the nanometer level by combining freeze drying, has uniform particle size, is suitable for being used as an injection raw material, and is beneficial to improving the dissolution of the abiraterone acetate. In addition, the injection is used for administration, so that the abiraterone acetate is directly released in blood, and the bioavailability of the abiraterone acetate is obviously improved.
Detailed Description
The invention provides an abiraterone acetate nanocrystal injection, wherein each 1000mL of the abiraterone acetate nanocrystal injection comprises the following components:
25g of abiraterone acetate raw material medicine, 1-2 g of stabilizing agent, 5-10 g of freeze-drying protective agent, 3-7 g of suspending agent, 0.01g of bacteriostatic agent, 3-5 g of osmotic pressure regulator and water for injection.
In the present invention, the starting materials used in the present invention are preferably commercially available products unless otherwise specified.
The abiraterone acetate nanocrystal injection provided by the invention contains 25g of abiraterone acetate raw material medicine per 1000 mL.
The abiraterone acetate nanocrystal injection provided by the invention contains 1-2 g of stabilizer per 1000mL, preferably 1.2-1.8 g, more preferably 1.4-1.6 g, and even more preferably 1.5g. In the present invention, the stabilizer preferably includes one or more of polysorbate 80 (II), polysorbate 20, polyoxyethylene (40) monostearate, and bezoar-78, and more preferably polysorbate 80 (II).
The abiraterone acetate nanocrystal injection provided by the invention contains 5-10 g of freeze-drying protective agent per 1000mL, preferably 6-9 g, and further preferably 7-8 g. In the present invention, the lyoprotectant preferably includes one or more of mannitol, polyvinylpyrrolidone, gelatin, sodium thiosulfate, and sorbitol, and is further preferably mannitol.
The abiraterone acetate nanocrystal injection per 1000mL provided by the invention comprises 3-7 g of a suspending agent, preferably 4-6 g, and further preferably 5g. In the present invention, the suspending agent preferably includes one or more of sodium carboxymethyl cellulose, methyl cellulose and hydroxypropyl cellulose, and more preferably sodium carboxymethyl cellulose.
The Abiraterone acetate nanocrystal injection provided by the invention contains 0.01g of bacteriostatic agent per 1000 mL. In the present invention, the bacteriostatic agent preferably comprises one or more of thimerosal sodium, benzyl alcohol, benzoic acid and chlorobutanol, and more preferably is thimerosal sodium.
The abiraterone acetate nanocrystal injection provided by the invention contains 3-5 g of osmotic pressure regulator per 1000mL, preferably 3.5-4.5 g, and more preferably 4g. In the present invention, the osmotic pressure regulator preferably includes sodium chloride and/or glucose, and more preferably sodium chloride.
The abiraterone acetate nanocrystal injection provided by the invention contains water for injection in each 1000 mL.
In the present invention, the pH of the abiraterone acetate nanocrystal injection is preferably 5 to 7, and more preferably 6.
The invention also provides a preparation method of the abiraterone acetate nanocrystal injection in the technical scheme, which comprises the following steps:
dispersing the abiraterone acetate raw material drug and the stabilizer in water, and sequentially mixing and homogenizing to obtain an abiraterone acetate nanocrystal suspension;
after subpackaging the abiraterone acetate nanocrystal suspension, adding a freeze-drying protective agent into the obtained subpackaged abiraterone acetate nanocrystal suspension, and freeze-drying to obtain abiraterone acetate nanocrystal freeze-dried powder;
dispersing the abiraterone acetate nanocrystal freeze-dried powder in water for injection, adding a suspending agent, a bacteriostatic agent and an osmotic pressure regulator, and supplementing the water for injection to the full amount to obtain the abiraterone acetate nanocrystal injection;
the homogenizing comprises sequentially performing high shear homogenizing and high pressure homogenizing.
The abiraterone acetate nano-crystal suspension is prepared by dispersing an abiraterone acetate raw material drug and a stabilizer in water, and sequentially mixing and homogenizing; the homogenizing comprises sequentially performing high shear homogenizing and high pressure homogenizing.
In the present invention, the water is preferably ultrapure water. In the present invention, the mixing is preferably ultrasonic mixing; the power of the ultrasonic mixing is preferably 30 to 50W, more preferably 35 to 45W, and even more preferably 40W; the time is preferably 5 to 10min. In the invention, the rotation speed of the high-shear homogenizing is preferably 1000-3000 rpm, and the time is preferably 10-20 min; the high shear homogenization is preferably carried out in a high shear homogenizer. In the invention, the high-pressure homogenization pressure is preferably 700bar to 1400bar, more preferably 1000bar to 1300bar, and even more preferably 1100bar to 1200bar; the frequency of the high-pressure homogenization is preferably 3-6 times; the high-pressure homogenization is preferably carried out in a high-pressure homogenizer.
In the invention, the particle size of the abiraterone acetate raw material drug is reduced to a nanometer level through high-shear homogenization and high-pressure homogenization, the specific surface area of the indissolvable abiraterone acetate raw material drug is increased, and the bioavailability of the abiraterone acetate is improved.
After obtaining the abiraterone acetate nanocrystal suspension, subpackaging the abiraterone acetate nanocrystal suspension, adding a freeze-drying protective agent into the obtained subpackaged abiraterone acetate nanocrystal suspension, and freeze-drying to obtain the abiraterone acetate nanocrystal freeze-dried powder.
In the invention, before subpackaging the abiraterone acetate nanocrystal suspension, preferably, degerming is further performed. In the present invention, the sterilization is preferably performed by filtration sterilization; the pore size of the filter sterilized by filtration is preferably 0.22. Mu.m.
The subpackaging parameters are not particularly limited, and the freeze-drying protective agent can be uniformly dispersed in the abiraterone acetate nanocrystal suspension.
In the present invention, the parameters of the freeze-drying include: the pre-cooling temperature is preferably-35 to-45 ℃, and is further preferably-40 ℃; the time is preferably 3 to 5 hours, and more preferably 4 hours; the pressure for vacuum drying is preferably 15 to 25Pa, and more preferably 20Pa; the time is preferably 20 to 26 hours, and more preferably 24 hours.
According to the invention, the abiraterone acetate raw material medicine is prepared into the abiraterone acetate nanocrystal freeze-dried powder with smaller particle size, so that the solubility and the permeability of the abiraterone acetate are improved, namely the solubility and the permeability of the abiraterone acetate are improved, and the bioavailability of the abiraterone acetate is further improved.
After obtaining the abiraterone acetate nanocrystal freeze-dried powder, dispersing the abiraterone acetate nanocrystal freeze-dried powder in water for injection, adding a suspending agent, a bacteriostatic agent and an osmotic pressure regulator, and supplementing the water for injection to the full amount to obtain the abiraterone acetate nanocrystal injection.
After said additional injection water is added to full volume, the present invention preferably further comprises stirring. In the present invention, the rotation speed of the stirring is preferably 400 to 700rpm, and more preferably 500 to 600rpm; the time is preferably 8 to 15min, and more preferably 10min.
The abiraterone acetate nanocrystal injection and the preparation method thereof provided by the present invention are described in detail below with reference to the following examples, which should not be construed as limiting the scope of the present invention.
Example 1
1. Weighing 25g of abiraterone acetate bulk drug and 1.5g of polysorbate 80 (II), adding 200mL of ultrapure water, ultrasonically mixing for 10min under 40W until the materials are uniform, homogenizing for 20min at 3000rpm by using a high-shear homogenizer, and adding the materials into a high-pressure homogenizer to homogenize for 3 times at 1200bar under high pressure to obtain abiraterone acetate nanocrystal suspension.
2. Filtering and sterilizing the abiraterone acetate nanocrystal suspension through a 0.22-micron filter membrane, subpackaging, filling 5mL of sterilized abiraterone acetate nanocrystal suspension into each 20mL of penicillin bottles, adding 0.2g of mannitol into each penicillin bottle, pre-freezing the penicillin bottles in a refrigerator at-45 ℃ for 4h, taking out the vials from a cold trap under 25Pa, and performing vacuum drying for 24h to obtain the abiraterone acetate nanocrystal freeze-dried powder.
3. And (3) uniformly dispersing all the abiraterone acetate nanocrystal freeze-dried powder obtained in the step (2) in 800mL of water for injection, then respectively adding 5g of sodium carboxymethylcellulose, 0.01g of thiomersal sodium and 3g of sodium chloride, supplementing the water for injection to 1000mL, and stirring at 600rpm for 10min till uniformity to obtain the abiraterone acetate nanocrystal injection.
Example 2
1. Weighing 25g of abiraterone acetate bulk drug and 1.5g of polysorbate 80 (II), adding 200mL of ultrapure water, ultrasonically mixing for 8min under 50W until the mixture is uniform, homogenizing for 20min at 3000rpm by using a high-shear homogenizer, and adding the mixture into a high-pressure homogenizer to homogenize for 3 times at 1200bar under high pressure to obtain an abiraterone acetate nanocrystal suspension.
2. Filtering and sterilizing the abiraterone acetate nanocrystal suspension through a 0.22-micron filter membrane, subpackaging, filling 5mL of sterilized abiraterone acetate nanocrystal suspension into each 20mL of penicillin bottles, adding 0.2g of mannitol into each penicillin bottle, pre-freezing the penicillin bottles in a refrigerator at-40 ℃ for 4h, taking out the vials from a cold trap under 20Pa, and performing vacuum drying for 24h to obtain the abiraterone acetate nanocrystal freeze-dried powder.
3. And (3) uniformly dispersing all the abiraterone acetate nanocrystal freeze-dried powder obtained in the step (2) in 800mL of water for injection, then respectively adding 3g of sodium carboxymethylcellulose, 0.01g of thiomersal sodium and 5g of sodium chloride, supplementing the water for injection to 1000mL, and stirring at 500rpm for 10min till uniformity to obtain the abiraterone acetate nanocrystal injection.
Example 3
1. Weighing 25g of abiraterone acetate bulk drug and 1.5g of polysorbate 80 (II), adding 200mL of ultrapure water, ultrasonically mixing for 8min under 40W until the materials are uniform, homogenizing for 20min at 3000rpm by using a high-shear homogenizer, and adding the materials into a high-pressure homogenizer to homogenize for 3 times at 1300bar under high pressure to obtain an abiraterone acetate nanocrystal suspension.
2. Filtering and sterilizing the abiraterone acetate nanocrystal suspension through a 0.22-micron filter membrane, subpackaging, filling 5mL of sterilized abiraterone acetate nanocrystal suspension into each 20mL of penicillin bottles, adding 0.2g of mannitol into each penicillin bottle, pre-freezing the penicillin bottles in a refrigerator at-45 ℃ for 4h, taking out the vials from a cold trap under 25Pa, and performing vacuum drying for 24h to obtain the abiraterone acetate nanocrystal freeze-dried powder.
3. And (3) uniformly dispersing all the abiraterone acetate nanocrystal freeze-dried powder obtained in the step (2) in 800mL of water for injection, respectively adding 7g of sodium carboxymethylcellulose, 0.01g of sodium thimerosal and 3g of sodium chloride, adding the water for injection to 1000mL, and stirring at 500rpm for 10min until the mixture is uniform to obtain the abiraterone acetate nanocrystal injection.
Example 4
1. Weighing 25g of abiraterone acetate bulk drug and 2g of polysorbate 80 (II), adding 200mL of ultrapure water, ultrasonically mixing for 10min under 45W until the materials are uniform, homogenizing for 20min at 3000rpm by using a high-shear homogenizer, adding into a high-pressure homogenizer, and homogenizing for 3 times at 1100bar under high pressure to obtain abiraterone acetate nanocrystal suspension.
2. Filtering and sterilizing the abiraterone acetate nanocrystal suspension through a 0.22-micron filter membrane, subpackaging, filling 5mL of sterilized abiraterone acetate nanocrystal suspension into each 20mL of penicillin bottles, adding 0.2g of mannitol into each penicillin bottle, pre-freezing the penicillin bottles in a refrigerator at-40 ℃ for 4h, taking out the vials from a cold trap under 20Pa, and performing vacuum drying for 24h to obtain the abiraterone acetate nanocrystal freeze-dried powder.
3. And (3) uniformly dispersing all the abiraterone acetate nanocrystal freeze-dried powder obtained in the step (2) in 800mL of water for injection, then respectively adding 5g of sodium carboxymethylcellulose, 0.01g of thiomersal sodium and 3g of sodium chloride, supplementing the water for injection to 1000mL, and stirring at 500rpm for 12min till uniformity to obtain the abiraterone acetate nanocrystal injection.
Examples 1-4 the average particle size of the abiraterone acetate nanocrystal lyophilized powder obtained in step 2 is shown in table 1.
Table 1 average particle size of abiraterone acetate nanocrystal lyophilized powder obtained in examples 1 to 4
As can be seen from table 1: the abiraterone acetate freeze-dried powder prepared by the high-pressure homogenization-freeze drying method achieves the nano level, is uniform in particle size, and is suitable for serving as an injection raw material.
Adopts the second method of 0931, the four-part general rule of the 2020 edition of Chinese pharmacopoeia. 10mg of abiraterone acetate crude drug, and abiraterone acetate nanocrystal injections (each example corresponds to 10mg of abiraterone acetate) obtained in examples 1, 2, 3 and 4 were dispersed in a dissolution cup containing 500mL of dissolution medium with physiological saline, and dissolution test was performed at 37. + -. 0.5 ℃ and 50 rpm. The dissolution test satisfies the conditions of a leak tank. After 0.083, 0.25, 0.5, 1, 2, 4, 6 and 8 hours, 1mL of sample is taken, and 1mL of fresh dissolution medium is supplemented. After passing the removed sample through a 0.22 μm microporous filter, the subsequent filtrate was analyzed by HPLC and the cumulative release was calculated. The formula for calculating the release degree is as follows: the release rate (%) = released drug amount/total drug amount 100%, and the results are shown in tables 2 and 3.
TABLE 2 in vitro dissolution test results for abiraterone acetate crude drug
Table 3 in vitro dissolution test results of abiraterone acetate nanocrystal injection obtained in examples 1 to 4
As can be seen from tables 2 and 3: the abiraterone acetate nanocrystal injection has quite fast dissolution rate under physiological conditions, which shows that the abiraterone acetate nanocrystal injection can remarkably improve the dissolution rate of the abiraterone acetate, promotes the absorption of the abiraterone acetate in blood, improves the bioavailability of the abiraterone acetate, and can exert curative effect more quickly and better.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. The abiraterone acetate nanocrystal injection is characterized in that each 1000mL of the abiraterone acetate nanocrystal injection comprises the following components:
25g of abiraterone acetate raw material medicine, 1-2 g of stabilizing agent, 5-10 g of freeze-drying protective agent, 3-7 g of suspending agent, 0.01g of bacteriostatic agent, 3-5 g of osmotic pressure regulator and water for injection.
2. The abiraterone acetate nanocrystal injection of claim 1, wherein the stabilizer comprises one or more of polysorbate 80 (II), polysorbate 20, polyoxyethylene (40) monostearate, and brij-78.
3. The abiraterone acetate nanocrystal injection according to claim 1, wherein the lyoprotectant comprises one or more of mannitol, polyvinylpyrrolidone, gelatin, sodium thiosulfate, and sorbitol.
4. The abiraterone acetate nanocrystal injection of claim 1, wherein the suspending agent comprises one or more of sodium carboxymethylcellulose, methylcellulose, and hydroxypropylcellulose.
5. The abiraterone acetate nanocrystal injection of claim 1, wherein the bacteriostatic agent comprises one or more of thimerosal, benzyl alcohol, benzoic acid and chlorobutanol.
6. The abiraterone acetate nanocrystal injection according to claim 1, wherein the osmotic pressure regulator comprises sodium chloride and/or glucose.
7. The preparation method of the abiraterone acetate nanocrystal injection as described in any one of claims 1 to 6, comprising the following steps:
dispersing the abiraterone acetate raw material drug and the stabilizer in water, and sequentially mixing and homogenizing to obtain an abiraterone acetate nanocrystal suspension;
after subpackaging the abiraterone acetate nanocrystal suspension, adding a freeze-drying protective agent into the obtained subpackaged abiraterone acetate nanocrystal suspension, and freeze-drying to obtain abiraterone acetate nanocrystal freeze-dried powder;
dispersing the abiraterone acetate nanocrystal freeze-dried powder in water for injection, adding a suspending agent, a bacteriostatic agent and an osmotic pressure regulator, and supplementing the water for injection to the full amount to obtain the abiraterone acetate nanocrystal injection;
the homogenizing comprises sequentially carrying out high-shear homogenizing and high-pressure homogenizing.
8. The method of claim 7, wherein the high shear homogenization is carried out at a rotation speed of 1000-3000 rpm for a period of 10-20 min; the pressure of the high-pressure homogenization is 700-1400 bar, and the times of the high-pressure homogenization are 3-6 times.
9. The preparation method of claim 7, wherein the abiraterone acetate nanocrystal suspension is sterilized before being dispensed.
10. The method of claim 7, wherein the freeze-drying parameters include: the precooling temperature is-35 to-45 ℃, and the time is 3 to 5 hours; the pressure of vacuum drying is 15-25 Pa, and the time is 20-26 h.
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| WO2014009436A1 (en) * | 2012-07-11 | 2014-01-16 | Sandoz Ag | Nanosuspension of abiraterone acetate |
| CN109223722A (en) * | 2018-10-30 | 2019-01-18 | 广州中医药大学(广州中医药研究院) | Nanocrystalline injection of progesterone and preparation method thereof |
| CN109568266A (en) * | 2017-09-28 | 2019-04-05 | 神威药业集团有限公司 | A kind of andrographolide nano suspension |
| CN109718198A (en) * | 2017-10-30 | 2019-05-07 | 浙江京新药业股份有限公司 | A kind of injection and preparation method thereof for treating prostate cancer |
| CN112933053A (en) * | 2021-01-29 | 2021-06-11 | 中国药科大学 | Abiraterone acetate nanocrystal and preparation method thereof |
| CN113061154A (en) * | 2021-03-25 | 2021-07-02 | 中国医学科学院生物医学工程研究所 | Preparation method and application of novel abiraterone derivative for injection |
| CN113546037A (en) * | 2020-04-20 | 2021-10-26 | 鲁南制药集团股份有限公司 | Abiraterone acetate suppository and preparation method thereof |
| CN114948885A (en) * | 2022-05-20 | 2022-08-30 | 广东西捷药业有限公司 | Improved abiraterone acetate nanocrystal oral preparation and preparation method thereof |
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2022
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014009436A1 (en) * | 2012-07-11 | 2014-01-16 | Sandoz Ag | Nanosuspension of abiraterone acetate |
| CN109568266A (en) * | 2017-09-28 | 2019-04-05 | 神威药业集团有限公司 | A kind of andrographolide nano suspension |
| CN109718198A (en) * | 2017-10-30 | 2019-05-07 | 浙江京新药业股份有限公司 | A kind of injection and preparation method thereof for treating prostate cancer |
| CN109223722A (en) * | 2018-10-30 | 2019-01-18 | 广州中医药大学(广州中医药研究院) | Nanocrystalline injection of progesterone and preparation method thereof |
| CN113546037A (en) * | 2020-04-20 | 2021-10-26 | 鲁南制药集团股份有限公司 | Abiraterone acetate suppository and preparation method thereof |
| CN112933053A (en) * | 2021-01-29 | 2021-06-11 | 中国药科大学 | Abiraterone acetate nanocrystal and preparation method thereof |
| CN113061154A (en) * | 2021-03-25 | 2021-07-02 | 中国医学科学院生物医学工程研究所 | Preparation method and application of novel abiraterone derivative for injection |
| CN114948885A (en) * | 2022-05-20 | 2022-08-30 | 广东西捷药业有限公司 | Improved abiraterone acetate nanocrystal oral preparation and preparation method thereof |
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