Ultrafine fibre preparation of taxol and method and apparatus for preparing the same

Abstract

The invention relates to a superfine fiber formulation of Paclitaxel, its preparation process and apparatus, wherein the preparing process comprises dissolving the Paclitaxel into biologically degradable macromolecular solution, carrying out electrical spinning, forming superfine fiber nonwoven fabrics or fabric felt coated by Paclitaxel. The formulation is specially adapted for the localized treatment after tumor operation.

Description

technical field

[0001] The invention relates to a biodegradable microfiber dosage form of paclitaxel.

[0002] The present invention also relates to a preparation method of the above-mentioned ultrafine fiber dosage form.

[0003] The invention also relates to a device for carrying out the above-mentioned preparation method. technical background

[0004] Paclitaxel, whose trade name is Taxol, is the drug of choice for ovarian cancer and breast cancer, and it also has a good effect on other cancers. But like many other anticancer drugs, the solubility of paclitaxel in water is very poor. The paclitaxel injection currently used clinically is to dissolve paclitaxel in 1:1 polyoxyethylene modified castor oil (trade name Cremophor EL) and In the mixed solution of ethanol, it is diluted 5-20 times with normal saline before injection. However, Cremophor EL often causes strong side effects, such as hypersensitivity, nephrotoxicity, and neurotoxicity, which may lead to death in se...

Examples

Embodiment 1

[0025] Embodiment 1. 0.28g polylactic acid PLA (containing D-configuration 2.8%, viscosity-average molecular weight is 91,000) is dissolved in the mixed solvent of 1.5ml chloroform and 1.5ml acetone, then adds 0.014g paclitaxel, ultrasonic vibration makes it Fully dissolve. The solution was then added to a 5 ml syringe, using a right angled flat spinneret made with an 8 gauge needle. The flow rate of the solution at the spinneret is 0.08ml / min, the applied voltage is 26,000 volts, and the distance between the two poles is 20cm.

[0026] The average diameter of the resulting drug-loaded fiber is 800nm, see figure 2 .

Embodiment 2

[0027] Example 2. Dissolve 0.15 g of L-polylactic acid PLLA (viscosity average molecular weight: 153,000) in a mixed solvent of 2 ml of chloroform and 1 ml of acetone, then add 0.015 g of paclitaxel, and ultrasonically oscillate to fully dissolve it. The solution was then added to a 5 ml syringe, using a right angled flat spinneret made with an 8 gauge needle. The flow rate of the solution at the spinneret is 0.07ml / min, the applied voltage is 25,000 volts, and the distance between the two poles is 20cm.

[0028] The average diameter of the resulting drug-loaded fibers is 1.0 μm, see image 3; For its release behavior in Tris-HCl buffer, see Figure 4.

Embodiment 3

[0029]Example 3. Dissolve 0.15 g of polylactic acid PLA (containing D-configuration 2.8%, viscosity-average molecular weight of 91,000) in a mixed solvent of 2 ml of chloroform and 1 ml of acetone, then add 0.075 g of paclitaxel, and ultrasonically vibrate to fully dissolve it . The solution was then added to a 5 ml syringe, using a right angled flat spinneret made with an 8 gauge needle. The flow rate of the solution at the spinneret is 0.1ml / min, the applied voltage is 28,000 volts, and the distance between the two poles is 20cm.

[0030] The average diameter of the obtained drug-loaded fibers was 1.3 μm.

technical field

[0001] The invention relates to a biodegradable microfiber dosage form of paclitaxel.

[0002] The present invention also relates to a preparation method of the above-mentioned ultrafine fiber dosage form.

[0003] The invention also relates to a device for carrying out the above-mentioned preparation method. technical background

[0004] Paclitaxel, whose trade name is Taxol, is the drug of choice for ovarian cancer and breast cancer, and it also has a good effect on other cancers. But like many other anticancer drugs, the solubility of paclitaxel in water is very poor. The paclitaxel injection currently used clinically is to dissolve paclitaxel in 1:1 polyoxyethylene modified castor oil (trade name Cremophor EL) and In the mixed solution of ethanol, it is diluted 5-20 times with normal saline before injection. However, Cremophor EL often causes strong side effects, such as hypersensitivity, nephrotoxicity, and neurotoxicity, which may lead to death in se...

Examples

Embodiment 1

[0025] Embodiment 1. 0.28g polylactic acid PLA (containing D-configuration 2.8%, viscosity-average molecular weight is 91,000) is dissolved in the mixed solvent of 1.5ml chloroform and 1.5ml acetone, then adds 0.014g paclitaxel, ultrasonic vibration makes it Fully dissolve. The solution was then added to a 5 ml syringe, using a right angled flat spinneret made with an 8 gauge needle. The flow rate of the solution at the spinneret is 0.08ml / min, the applied voltage is 26,000 volts, and the distance between the two poles is 20cm.

[0026] The average diameter of the resulting drug-loaded fiber is 800nm, see figure 2 .

Embodiment 2

[0027] Example 2. Dissolve 0.15 g of L-polylactic acid PLLA (viscosity average molecular weight: 153,000) in a mixed solvent of 2 ml of chloroform and 1 ml of acetone, then add 0.015 g of paclitaxel, and ultrasonically oscillate to fully dissolve it. The solution was then added to a 5 ml syringe, using a right angled flat spinneret made with an 8 gauge needle. The flow rate of the solution at the spinneret is 0.07ml / min, the applied voltage is 25,000 volts, and the distance between the two poles is 20cm.

[0028] The average diameter of the resulting drug-loaded fibers is 1.0 μm, see image 3; For its release behavior in Tris-HCl buffer, see Figure 4.

Embodiment 3

[0029]Example 3. Dissolve 0.15 g of polylactic acid PLA (containing D-configuration 2.8%, viscosity-average molecular weight of 91,000) in a mixed solvent of 2 ml of chloroform and 1 ml of acetone, then add 0.075 g of paclitaxel, and ultrasonically vibrate to fully dissolve it . The solution was then added to a 5 ml syringe, using a right angled flat spinneret made with an 8 gauge needle. The flow rate of the solution at the spinneret is 0.1ml / min, the applied voltage is 28,000 volts, and the distance between the two poles is 20cm.

[0030] The average diameter of the obtained drug-loaded fibers was 1.3 μm.

Images