Prepn process and medicinal composition of amorphous Adefovir dipivoxil

Abstract

The present invention relates to preparation process and medicinal composition of amorphous Adeforvir dipivolxil. The amorphous Adeforvir dipivolxil preparing process includes the following steps: adding pure crystalline or oily Adeforvir dipivolxil into organic solvent with the weight ratio between Adeforvir dipivolxil and organic solvent being 1 to 1-20, dissolving at 20-80 deg.c, decompression evaporating at 20-80 deg.c to obtain foamed solid, and final vacuum drying at 20-40 deg.c. The amorphous Adeforvir dipivolxil as effective component in 2-50 wt% is further mixed with excipient(s) in 50-98 wt% to produce medicinal composition of Adeforvir dipivolxil.

Description

technical field

[0001] The present invention relates to the preparation method of amorphous 9-[2[[bis(pivaloyloxy)methoxy]phosphinyl]methoxyethyladenine, whose common name is adefovir dipivoxil (AD), and its containing Pharmaceutical composition of amorphous adefovir dipivoxil. Background technique

[0002] Adefovir dipivoxil is a broad-spectrum antiviral drug. It is a polymerase inhibitor and a reverse transcriptase inhibitor. It has antagonism activity against many viruses, including HIV (AIDS virus), HBV (hepatitis B virus), HCMV (human Cytomegalovirus), HSV-I, II (herpes virus type I, II), MSV (Moloney murine sarcoma virus), FLV (hemophilia leukemia virus).

[0003] Clinical trials have shown that adefovir dipivoxil has high anti-chronic hepatitis B virus (HBV) DNA activity, and can reduce the hepatitis B e antigen in blood and seroconversion, and is resistant to lamivudine and famciclovir. Serial HBV still has anti-activity, and its own drug resistance is small. In S...

Examples

Embodiment 1

[0023] Embodiment 1: Preparation of amorphous adefovir dipivoxil

[0024] Add 10 g of oily adefovir dipivoxil, add 10 g of dichloromethane to dissolve at 20°C, evaporate to dryness under reduced pressure at 20°C to obtain an amorphous powder, put it in a vacuum oven and dry it under vacuum at 20°C to obtain a white amorphous powder.

Embodiment 2

[0025] Embodiment 2: Preparation of amorphous adefovir dipivoxil

[0026] Add 20 g of chloroform to dissolve 10 g of crystalline adefovir dipivoxil at 35°C, evaporate to dryness under reduced pressure at 35°C to obtain an amorphous powder, and dry it in a vacuum oven at 30°C to obtain a white amorphous powder.

Embodiment 3

[0027] Embodiment 3: Preparation of amorphous adefovir dipivoxil

[0028] Add 10 g of oily adefovir dipivoxil, add 30 g of methanol to dissolve at 40°C, evaporate to dryness under reduced pressure at 40°C to obtain an amorphous powder, put it in a vacuum oven and dry it under vacuum at 40°C to obtain a white amorphous powder.

technical field

[0001] The present invention relates to the preparation method of amorphous 9-[2[[bis(pivaloyloxy)methoxy]phosphinyl]methoxyethyladenine, whose common name is adefovir dipivoxil (AD), and its containing Pharmaceutical composition of amorphous adefovir dipivoxil. Background technique

[0002] Adefovir dipivoxil is a broad-spectrum antiviral drug. It is a polymerase inhibitor and a reverse transcriptase inhibitor. It has antagonism activity against many viruses, including HIV (AIDS virus), HBV (hepatitis B virus), HCMV (human Cytomegalovirus), HSV-I, II (herpes virus type I, II), MSV (Moloney murine sarcoma virus), FLV (hemophilia leukemia virus).

[0003] Clinical trials have shown that adefovir dipivoxil has high anti-chronic hepatitis B virus (HBV) DNA activity, and can reduce the hepatitis B e antigen in blood and seroconversion, and is resistant to lamivudine and famciclovir. Serial HBV still has anti-activity, and its own drug resistance is small. In S...

Examples

Embodiment 1

[0023] Embodiment 1: Preparation of amorphous adefovir dipivoxil

[0024] Add 10 g of oily adefovir dipivoxil, add 10 g of dichloromethane to dissolve at 20°C, evaporate to dryness under reduced pressure at 20°C to obtain an amorphous powder, put it in a vacuum oven and dry it under vacuum at 20°C to obtain a white amorphous powder.

Embodiment 2

[0025] Embodiment 2: Preparation of amorphous adefovir dipivoxil

[0026] Add 20 g of chloroform to dissolve 10 g of crystalline adefovir dipivoxil at 35°C, evaporate to dryness under reduced pressure at 35°C to obtain an amorphous powder, and dry it in a vacuum oven at 30°C to obtain a white amorphous powder.

Embodiment 3

[0027] Embodiment 3: Preparation of amorphous adefovir dipivoxil

[0028] Add 10 g of oily adefovir dipivoxil, add 30 g of methanol to dissolve at 40°C, evaporate to dryness under reduced pressure at 40°C to obtain an amorphous powder, put it in a vacuum oven and dry it under vacuum at 40°C to obtain a white amorphous powder.