M-crystal system of adefovir dipivoxil ester and preparation method and medicine application

Abstract

The present invention provides a novel adefovir dipivoxil crystal model which is of easy preparation method, convenient operation, high efficiency and high purity. Adefovir dipivoxil is dissolved in a certain amount of dichloromethane at certain temperature, and then is crystallized to get M crystal model. The M crystal model of the present invention then experiences X-radial diffraction, infrared absorption spectrum detection through KBr swuash method to measure the thermal dereference analysis (DSC) as well as other examinations. The M crystal model is determined to be a crystal shape of adefovir dipivoxil. The present invention also relates to the application of the novel crystal model in the drugs.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and relates to a new crystal form of adefovir dipivoxil, a preparation method of the new crystal and its application in medicine. Background technique

[0002] Adefovir dipivoxil is a new type of oral broad-spectrum antiviral drug, originally synthesized by Gillid Sciences of the United States. Adefovir dipivoxil inhibits viral transcription and replication by inhibiting viral DNA polymerase and transcriptase. It has a strong inhibitory effect on hepatitis B virus and HIV, and also has a strong inhibitory effect on hepatitis B virus resistant to lamivudine and famciclovir. It is a ring-opening nucleoside reverse transcriptase inhibitor. The prodrug of defovir (PMEA) has a higher bioavailability than adefovir. Adefovir dipivoxil was developed by Gilead Sciences in the United States. It was approved by the FDA for the first time on September 20, 2002. The English name is Adefovir. Dipivoxil, trad...

Examples

Embodiment 1

[0032] Embodiment 1. M crystal form adefovir dipivoxil and its preparation

[0033] Take 5g of adefovir dipivoxil, dissolve it in 25ml of dichloromethane, put it in an ice-water bath at 10°C, concentrate it in a rotary evaporator for 20min under reduced pressure, spin dry the dichloromethane to obtain a solidified product, scrape out the solid, and wash it with 5ml of petroleum ether , at P 2 o 5 In an existing vacuum desiccator, vacuum-dry at room temperature for more than 8 hours to obtain the M crystal form of adefovir dipivoxil of the present invention. Its X-ray diffraction diagram, infrared absorption spectrum diagram and thermal difference analysis diagram are consistent with the accompanying drawings.

Embodiment 2

[0034] Embodiment 2. Tablet containing M crystal form adefovir dipivoxil and its preparation

[0035] Prescription: M crystal form adefovir dipivoxil 10g, hydroxypropyl cellulose 100g, sodium carboxymethyl starch 30g.

[0036] Preparation method: the above two materials were crushed through 100 mesh respectively, dried under reduced pressure at 100°C for more than 10 hours, cooled to room temperature, mixed evenly with M crystal form adefovir dipivoxil, granulated by dry granulator, and pressed into 1000 Tablets, that is, tablets of M crystal form adefovir dipivoxil, each containing 10 mg of M crystal form adefovir dipivoxil.

Embodiment 3

[0037] Example 3. Capsules containing M crystal form adefovir dipivoxil and its preparation

[0038] Prescription: M crystal form adefovir dipivoxil 5g, lactose 50g, microcrystalline cellulose 65g, sodium carboxymethyl starch 20g, magnesium stearate 1g.

[0039] Preparation method: the above-mentioned lactose, microcrystalline cellulose, and sodium carboxymethyl starch were respectively crushed through 100 meshes, dried under reduced pressure at 100°C for more than 10 hours, cooled to room temperature, and mixed evenly with M crystal form adefovir dipivoxil. Granulate by dry granulation machine, add magnesium stearate, mix well, and fill into 1000 empty capsules to obtain the capsules of M crystal form adefovir dipivoxil, each capsule contains M crystal form adefovir dipivoxil 5 mg.

technical field

[0001] The invention belongs to the technical field of medicine, and relates to a new crystal form of adefovir dipivoxil, a preparation method of the new crystal and its application in medicine. Background technique

[0002] Adefovir dipivoxil is a new type of oral broad-spectrum antiviral drug, originally synthesized by Gillid Sciences of the United States. Adefovir dipivoxil inhibits viral transcription and replication by inhibiting viral DNA polymerase and transcriptase. It has a strong inhibitory effect on hepatitis B virus and HIV, and also has a strong inhibitory effect on hepatitis B virus resistant to lamivudine and famciclovir. It is a ring-opening nucleoside reverse transcriptase inhibitor. The prodrug of defovir (PMEA) has a higher bioavailability than adefovir. Adefovir dipivoxil was developed by Gilead Sciences in the United States. It was approved by the FDA for the first time on September 20, 2002. The English name is Adefovir. Dipivoxil, trad...

Examples

Embodiment 1

[0032] Embodiment 1. M crystal form adefovir dipivoxil and its preparation

[0033] Take 5g of adefovir dipivoxil, dissolve it in 25ml of dichloromethane, put it in an ice-water bath at 10°C, concentrate it in a rotary evaporator for 20min under reduced pressure, spin dry the dichloromethane to obtain a solidified product, scrape out the solid, and wash it with 5ml of petroleum ether , at P 2 o 5 In an existing vacuum desiccator, vacuum-dry at room temperature for more than 8 hours to obtain the M crystal form of adefovir dipivoxil of the present invention. Its X-ray diffraction diagram, infrared absorption spectrum diagram and thermal difference analysis diagram are consistent with the accompanying drawings.

Embodiment 2

[0034] Embodiment 2. Tablet containing M crystal form adefovir dipivoxil and its preparation

[0035] Prescription: M crystal form adefovir dipivoxil 10g, hydroxypropyl cellulose 100g, sodium carboxymethyl starch 30g.

[0036] Preparation method: the above two materials were crushed through 100 mesh respectively, dried under reduced pressure at 100°C for more than 10 hours, cooled to room temperature, mixed evenly with M crystal form adefovir dipivoxil, granulated by dry granulator, and pressed into 1000 Tablets, that is, tablets of M crystal form adefovir dipivoxil, each containing 10 mg of M crystal form adefovir dipivoxil.

Embodiment 3

[0037] Example 3. Capsules containing M crystal form adefovir dipivoxil and its preparation

[0038] Prescription: M crystal form adefovir dipivoxil 5g, lactose 50g, microcrystalline cellulose 65g, sodium carboxymethyl starch 20g, magnesium stearate 1g.

[0039] Preparation method: the above-mentioned lactose, microcrystalline cellulose, and sodium carboxymethyl starch were respectively crushed through 100 meshes, dried under reduced pressure at 100°C for more than 10 hours, cooled to room temperature, and mixed evenly with M crystal form adefovir dipivoxil. Granulate by dry granulation machine, add magnesium stearate, mix well, and fill into 1000 empty capsules to obtain the capsules of M crystal form adefovir dipivoxil, each capsule contains M crystal form adefovir dipivoxil 5 mg.

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