CN1397279A

CN1397279A - Hydroxycamptothecin tablet and its preparing process

Info

Publication number: CN1397279A
Application number: CN 02138929
Authority: CN
Inventors: 陈秀珍; 刘德芳; 刘海英
Original assignee: Huangshi Lishizhen Medicine Group Wuhan Xisu Pharmaceutical Co Ltd
Current assignee: Huangshi Lishizhen Medicine Group Wuhan Xisu Pharmaceutical Co Ltd
Priority date: 2002-08-15
Filing date: 2002-08-15
Publication date: 2003-02-19

Abstract

A hydroxycamptothecin table is prepared from hydroxycamptothecin, diluent chosen from microcrystal cellulose, starch, hydroxymethyl starch sodium and glycine, adhesive chosen from starch paste, PVP and gelatin, disintegrant, and lubricant chosen from talc powder and magnesium stearate.

Description

Hydroxycamptothecin tablet and preparation method

Technical field

The invention belongs to medicine preparation, be specifically related to hydroxycamptothecin tablet and preparation method.

Background technology

Hydroxy camptothecin has anticancer wide spectrum, characteristics evident in efficacy.At present domestic have only its injection formulation using, and the injection formulation patent application of compound alkyl camptothecine, 96112301 are arranged.The injection of hydroxy camptothecin is because of there is the shortcoming of poor stability in alkaline aqueous solution, and is easy to change, and said preparation is after seeing light, heat and air, color and luster is deepened two days later, produces trickle precipitation after 3 months, and main content descends, catabolite increases, and its curative effect descends, and toxic and side effects increases.When using, must under doctor or nurse's operation, just can finish injection.

Summary of the invention

The objective of the invention is to propose a kind of new oral formulations of hydroxy camptothecin, tablet, and preparation method thereof.

Hydroxycamptothecin tablet, its main medicinal raw material comprises: active substance hydroxy camptothecin, the diluent of medicinal tablets, tablet binder and disintegrating agent, lubricant.Diluent can be selected one or more in microcrystalline Cellulose, starch, Sodium Hydroxymethyl Stalcs, the glycosides propylhomoserin; Binding agent can be selected a kind of in starch slurry, PVP rubber cement, the gelatine size; A kind of in the selectable Pulvis Talci of lubricant, the magnesium stearate.

The preferred medicinal raw material of hydroxycamptothecin tablet comprises: the active substance hydroxy camptothecin, and the diluent of medicinal tablets and disintegrating agent are selected starch, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs and glycine, and tablet binder is selected starch slurry, and lubricant is selected magnesium stearate.

Its method is: get hydroxy camptothecin, starch, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, glycine porphyrize respectively filter, and the addition mix homogeneously of equivalent is made soft material with starch slurry, sieving is granulated, put under 70 ℃ of conditions dryly, add magnesium stearate, mix homogeneously after rescreening the filter granulate, tabletting, packing.

Specific implementation method

The screening of medicinal raw material:

1, the selection of diluent:

This tablet hydroxycamptothecin containing 5mg is a bonding agent with the starch slurry, and Sodium Hydroxymethyl Stalcs is that disintegrating agent, magnesium stearate are lubricant, selects diluent, sees Table 1:

Numbering	Hydroxy camptothecin g	Microcrystalline Cellulose g	Starch g	Sodium Hydroxymethyl Stalcs g	Glycosides propylhomoserin g	Dissolution (%)	Other
Numbering	Hydroxy camptothecin g	Microcrystalline Cellulose g	Starch g	Sodium Hydroxymethyl Stalcs g	Glycosides propylhomoserin g	Dissolution (%)	Other	??1	??0.3	??5.7				??57.5	Satisfied
??2	??0.3	??2.85	??2.85			??62.5	Satisfied	??1	??0.3	??5.7				??57.5	Satisfied
??2	??0.3	??2.85	??2.85			??62.5	Satisfied	??3	??0.3	??1.35	??4.35			??67.0	Satisfied
??4	??0.3	??2.85	??2.55	??0.3		??67.2	Satisfied	??3	??0.3	??1.35	??4.35			??67.0	Satisfied
??4	??0.3	??2.85	??2.55	??0.3		??67.2	Satisfied	??5	??0.3	??2.85	??1.95	??0.9		??63.6	Satisfied
??6	??0.3	??2.85	??1.35	??1.5		??60.8	Satisfied	??5	??0.3	??2.85	??1.95	??0.9		??63.6	Satisfied
??6	??0.3	??2.85	??1.35	??1.5		??60.8	Satisfied	??7	??0.3	??2.85	??0.3	??2.55		??58.3	Satisfied
??8	??0.3	??2.85		??2.85		??53.4	Satisfied	??7	??0.3	??2.85	??0.3	??2.55		??58.3	Satisfied
??8	??0.3	??2.85		??2.85		??53.4	Satisfied	??9	??0.3	??2.25	??0.6	??2.85		??62.7	Satisfied
??10	??0.3	??2.25	??1.2	??2.25		??67.6	Satisfied	??9	??0.3	??2.25	??0.6	??2.85		??62.7	Satisfied
??10	??0.3	??2.25	??1.2	??2.25		??67.6	Satisfied	??11	??0.3	??2.25		??2.25	??0.342	??76.6	Satisfied
??12	??0.3	??2.25	??2.25		??0.342	??84.3	Satisfied	??11	??0.3	??2.25		??2.25	??0.342	??76.6	Satisfied
??12	??0.3	??2.25	??2.25		??0.342	??84.3	Satisfied	??13	??0.3	??1.05	??2.25		??0.342	??83.9	Satisfied

As seen from the above table, 13 prescriptions are all satisfied, and our preferred starch and microcrystalline Cellulose are diluent, and Sodium Hydroxymethyl Stalcs is a disintegrating agent.

2, the selection of binding agent:

We are with the composition of 12 in the table 1, and magnesium stearate is a lubricant, investigate several bonding agents: see Table 2:

Numbering	Binding agent	Dissolution (%)	Other
Numbering	Binding agent	Dissolution (%)	Other	1	Starch slurry (5%)	84.3	Satisfied
2	Starch slurry (10%)	82.0	Satisfied	1	Starch slurry (5%)	84.3	Satisfied
2	Starch slurry (10%)	82.0	Satisfied	3	PVP rubber cement (3%)	85.3	Satisfied
4	PVP rubber cement (7.5%)	82.1	Satisfied	3	PVP rubber cement (3%)	85.3	Satisfied
4	PVP rubber cement (7.5%)	82.1	Satisfied	5	Gelatine size (5%)	83.7	Satisfied

As seen from the above table, several bonding agents do not have tangible influence to dissolution.We are from cost consideration, and we will select starch slurry (5%) is bonding agent.

3, selection of lubricants

We are with the composition of the prescription in the table 1 12, and starch slurry (5%) is a bonding agent, investigates several lubricants, sees Table 3:

Numbering	Lubricant	Dissolution (%)	Other
Numbering	Lubricant	Dissolution (%)	Other	1	Pulvis Talci (0.5%)	84.2	Satisfied

2	Magnesium stearate (0.3%)	?84.3	Satisfied
2	Magnesium stearate (0.3%)	?84.3	Satisfied	3	Magnesium stearate (0.5%)	?82.7	Satisfied

As seen from the above table, several lubricants do not have tangible influence to dissolution, and our preferred magnesium stearate (0.3%) is the lubricant of hydroxycamptothecin tablet.

According to above-mentioned selection, we have selected following ratio is the raw material composition of hydroxy camptothecin: hydroxy camptothecin, starch, microcrystalline Cellulose, glycine and Sodium Hydroxymethyl Stalcs, starch slurry, magnesium stearate: 5: 34.5: 34.5: 20: 5.7: 50: 0.3.

Its method is: get hydroxy camptothecin 5g, starch 34.5g, microcrystalline Cellulose 34.5g, Sodium Hydroxymethyl Stalcs 5.71g, glycine 20g is porphyrize respectively, cross 80 mesh sieves, the addition mix homogeneously of equivalent is made soft material with starch slurry (5%), granulate with the filter of 30 mesh sieves, put drying under 70 ℃ of conditions, add magnesium stearate 0.3g, mix homogeneously behind the reuse 40 mesh sieves filter granulate, tabletting, packing.

Hydroxycamptothecin tablet according to above method preparation is all up to specification through the check of institute for drug control, Hubei Province;

Oral through animal experiment: as mice S180 sarcoma dosage to be respectively 4mg, 6mg, the administration of 12mg/ kilogram, the mouse tumor growth inhibition ratio is respectively 31.6%, 33.7%, 47.7%.

Mouse junction cancer C-26 dosage is respectively 6mg, the administration of 12mg/ kilogram, and tumor control rate is respectively 36%, 37.9%.

Claims

1, hydroxycamptothecin tablet, its main medicinal raw material comprises: active substance hydroxy camptothecin, the diluent of medicinal tablets, tablet binder, lubricant.

2, hydroxycamptothecin tablet according to claim 1 is characterized in that diluent can select one or more in microcrystalline Cellulose, starch, lactose, the glycosides propylhomoserin.

3, hydroxycamptothecin tablet according to claim 1 is characterized in that binding agent can select a kind of in starch slurry, PVP rubber cement, the gelatine size.

4, hydroxycamptothecin tablet according to claim 1, it is characterized in that the selectable Pulvis Talci of lubricant, magnesium stearate in a kind of.

5, hydroxycamptothecin tablet according to claim 1, it is characterized in that its main medicinal raw material comprises: the active substance hydroxy camptothecin, the diluent of medicinal tablets is selected starch, microcrystalline Cellulose and glycine, and tablet binder is selected starch slurry, and lubricant is selected magnesium stearate.

6, as hydroxycamptothecin tablet as described in the claim 5, the weight ratio that it is characterized in that each raw material is: hydroxy camptothecin, starch, microcrystalline Cellulose, glycine and Sodium Hydroxymethyl Stalcs, starch slurry, magnesium stearate: 5: 34.5: 34.5: 20: 5.7: 50: 0.3.

7, the preparation method of hydroxycamptothecin tablet: its method is: get hydroxy camptothecin, starch, microcrystalline Cellulose, glycine porphyrize respectively filter, and the addition mix homogeneously of equivalent is made soft material with starch slurry, sieving is granulated, put under 70 ℃ of conditions dryly, add magnesium stearate, mix homogeneously after rescreening the filter granulate, tabletting, packing.