Freeze drying preparation of amifostine, and preparation method

Abstract

A freeze-dried amifostine is prepared from amifostine, acetone and the solution of pharmacologically acceptable excipient through prefreezing, sublimated drying, and drying again.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a freeze-dried amifostine preparation and a preparation method thereof. Background technique

[0002] Amifostine is an alkyl phosphorothioate compound (dihydrogen phosphorothioate S-2-(3-aminopropylamino) ethyl ester), it is a broad-spectrum selective cell protector, the main function is to protect Hematopoietic stem cells have obvious protective effects on red and white blood cells and platelets, and can reduce the toxic and side effects of radiotherapy and chemotherapy on the liver, kidney, heart, and nervous system. It is mainly suitable for the adjuvant treatment of tumor radiotherapy or cytotoxic chemotherapy. On the other hand, the combination of amifostine and radiotherapy or cytotoxic antineoplastic drugs can enhance the patient's tolerance to antitumor treatment, which is conducive to increasing the treatment dose and shortening the treatment period...

Examples

Embodiment 1

[0032] Take 250.0 g of commercially available amifostine (trihydrate), add 1150 ml of water for injection, and stir to completely dissolve. Slowly add 200.0ml of acetone dropwise to the solution under stirring, the solution is clear at this time, add water for injection to 2000.0ml. Add 0.1% activated carbon for needles under stirring, keep at 25°C for 30 minutes, decarbonize and filter, and then filter the filtrate through a 0.22 μm microporous membrane until it becomes clear. Fill in aseptically treated vials, 2.0ml per bottle, freeze-dry according to the method of Example 7 in a freeze dryer, and aseptically seal to obtain the preparation A of the present invention.

Embodiment 2

[0034] Preparation B of the present invention was prepared according to the method of Example 1, except that 100.0 g of mannitol (Shandong Jiejing Group) was added to the amifostine-containing solution, and freeze-dried according to the method of Example 7.

Embodiment 3-5

[0036] Preparations C, D, and E of the present invention were prepared according to the method of Example 2, except that each milliliter of solution contained 60 mg, 150 mg, and 280 mg of amifostine, 0.075 ml, 0.1 ml, and 0.15 ml of acetone, and contained no excipients and lactose. 100mg, containing 180mg of glycine, and adding activated carbon according to the dosage of 0.06%, 0.5%, 2.5% (g / ml) respectively, stirring at 20, 25, and 30°C for 30, 20, and 10 minutes, decarbonizing and filtering, according to the implementation Freeze drying by the method of Example 7.

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a freeze-dried amifostine preparation and a preparation method thereof. Background technique

[0002] Amifostine is an alkyl phosphorothioate compound (dihydrogen phosphorothioate S-2-(3-aminopropylamino) ethyl ester), it is a broad-spectrum selective cell protector, the main function is to protect Hematopoietic stem cells have obvious protective effects on red and white blood cells and platelets, and can reduce the toxic and side effects of radiotherapy and chemotherapy on the liver, kidney, heart, and nervous system. It is mainly suitable for the adjuvant treatment of tumor radiotherapy or cytotoxic chemotherapy. On the other hand, the combination of amifostine and radiotherapy or cytotoxic antineoplastic drugs can enhance the patient's tolerance to antitumor treatment, which is conducive to increasing the treatment dose and shortening the treatment period...

Examples

Embodiment 1

[0032] Take 250.0 g of commercially available amifostine (trihydrate), add 1150 ml of water for injection, and stir to completely dissolve. Slowly add 200.0ml of acetone dropwise to the solution under stirring, the solution is clear at this time, add water for injection to 2000.0ml. Add 0.1% activated carbon for needles under stirring, keep at 25°C for 30 minutes, decarbonize and filter, and then filter the filtrate through a 0.22 μm microporous membrane until it becomes clear. Fill in aseptically treated vials, 2.0ml per bottle, freeze-dry according to the method of Example 7 in a freeze dryer, and aseptically seal to obtain the preparation A of the present invention.

Embodiment 2

[0034] Preparation B of the present invention was prepared according to the method of Example 1, except that 100.0 g of mannitol (Shandong Jiejing Group) was added to the amifostine-containing solution, and freeze-dried according to the method of Example 7.

Embodiment 3-5

[0036] Preparations C, D, and E of the present invention were prepared according to the method of Example 2, except that each milliliter of solution contained 60 mg, 150 mg, and 280 mg of amifostine, 0.075 ml, 0.1 ml, and 0.15 ml of acetone, and contained no excipients and lactose. 100mg, containing 180mg of glycine, and adding activated carbon according to the dosage of 0.06%, 0.5%, 2.5% (g / ml) respectively, stirring at 20, 25, and 30°C for 30, 20, and 10 minutes, decarbonizing and filtering, according to the implementation Freeze drying by the method of Example 7.