PHARMACEUTICAL COMPOSITION FOR TREATING LEUKEMIA AND METHOD FOR PREPARING THE SAME

Abstract

A pharmaceutical composition for treating leukemia, including by weight 2 to 8% of realgar, 25 to 42% of indigo naturalis, 50 to 60% of salvia miltiorrhiza, and 6 to 10% of heterophylla.

Claims

1. A pharmaceutical composition for treating leukemia, the composition comprising by weight 2 to 8% of realgar, 25 to 42% of indigo naturalis, 50 to 60% of salvia miltiorrhiza, and 6 to 10% of heterophylla.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises by weight 3 to 5% of realgar, 27 to 35% of indigo naturalis, 52 to 57% of salvia miltiorrhiza, and 7 to 9% of heterophylla.

3. The pharmaceutical composition of claim 1, wherein the indigo naturalis is excellent grade indigo naturalis or special grade indigo naturalis.

4. A method for preparing the pharmaceutical composition of claim 1, the method comprising: mixing a realgar powder, a heterophylla powder, and an indigo naturalis powder to obtain a first mixture; adding water to the salvia miltiorrhiza at a ratio of 8-9 mL of water per 1 g of the salvia miltiorrhiza to obtain a second mixture, decocting the second mixture 1-2 times, for 50-55 min each time, then filtering to obtain a filtrate, and concentrating the filtrate at a temperature of 48-54 C. to yield a concentrate; and mixing the first mixture and the concentrate to form a pharmaceutical composition.

5. The method of claim 4, wherein the pharmaceutical composition is in a dosage form of a tablet, a pill, a capsule, or a granule.

6. The method of claim 5, wherein the pharmaceutical composition is in the dosage form of a tablet; the concentrate is a clear paste with a relative density of 1.15 to 1.20 measured at a temperature of 50 C.; and the clear paste is mixed with the first mixture, granulated, dried, sized, compressed, and coated to obtain the tablet.

7. The method of claim 5, wherein the pharmaceutical composition is in the dosage form of a pill; the concentrate is concentrated to a thick paste, then the thick paste is dried under reduced pressure into a dry paste, the dry paste is crushed into a fine powder to obtain a dry fine powder; and the dry fine powder is mixed with the mixture, and placed in a pill making machine with water and then dried to obtain the pill.

8. The method of claim 5, wherein the pharmaceutical composition is in the dosage form of a capsule; the concentrate is a clear paste with a relative density of 1.15 to 1.20 measured at a temperature of 50 C.; and the clear paste is mixed with the mixture, granulated, dried, sized, compressed, and filled into capsule.

9. The pharmaceutical composition of claim 2, wherein the indigo naturalis is excellent grade indigo naturalis or special grade indigo naturalis.

10. A method for preparing the pharmaceutical composition of claim 2, the method comprising: mixing a realgar powder, a heterophylla powder, and an indigo naturalis powder to obtain a first mixture; adding 8-9 times amount by weight of water to salvia miltiorrhiza to obtain a second mixture, decocting the second mixture 1-2 times, for 50-55 min each time, then filtering to obtain a filtrate, concentrating the filtrate at a temperature of 48-54 C. to yield a concentrate; and mixing the first mixture and the concentrate to form a pharmaceutical composition in a dosage form.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0031] The implementations of the present disclosure will be described in detail with the following embodiments, but it will be understood by those skilled in the art that the following embodiments are only illustrative of the present disclosure and should not be construed as limiting the scope of the present disclosure. If no specific conditions are indicated in the examples, it shall be performed according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used which are not specified by the manufacturer are all commercially available conventional products.

[0032] In this disclosure, the active components of the pharmaceutical composition are prepared as follows:

[0033] Realgar was extracted as follows: the realgar without impurities was taken and mixed with water (a mixed ratio of water to material was 0.5 mL/per gram). The mixture was ground for 5-10 min to be pasty, stirred with water (a mixed ratio of water to material was 40 mL/per gram) for 2 min, allowed to stand for 5 min. The supernatant was discarded, and the precipitate was collected and ground. Repeat the above operations. The suspension was combined, allowed to stand for 12 h or more. The supernatant was discarded. A solid was collected, filtered, and dried at 60 C. for 10 h or less, to yield realgar.

[0034] Indigo naturalis was extracted as follows: the leaves and the stems of Baphicacanthus cusia (Nees) Bremek. were cut into small pieces, and water (a mixed ratio of water to material was 30 mL/per gram) was added and soaked for 3-5 days until the stems were peeled and the leaves were rotted. When the extract was dark green, the stems and leaves were removed. The obtained extract was screened using a 40-mesh sieve, and 5 kg of lime (CaO) per 50 kg of the medicinal material was mixed with the extract. The mixture was stirred and allowed to stand. When the extract was changed from blackish green to purple, the supernatant was discarded, and water and the medicinal material was mixed (a mixed ratio of water to material was 10 mL/per gram), stirred, and a foam on the liquid surface was collected, dried, pulverized, and screened using a 100-mesh sieve, to yield indigo naturalis.

[0035] Salvia miltiorrhiza was extracted as follows: the impurities of the pure root of red-rooted salvia was removed. The pure root was cut, and dried to obtain the pure medicinal material. The medicinal material was mixed with water (a mixed ratio of water to material was 8-9 mL/per gram), boiled and extracted for 1-2 times, each for 50-55 min. The filtrate was combined and concentrated to obtain a clear paste with a relative density of 1.15-1.24 (50 C.).

[0036] Heterophylla was extracted as follows: the medicinal herbs of Radix Pseudostellariae without fibrous roots was boiled in boiling water, dried, pulverized into fine powders in a pulverizer, and further pulverized into ultrafine powders in an ultrafine pulverizer.

Example 1

[0037] Realgar, indigo naturalis, salvia miltiorrhiza, and heterophylla were prepared with a weight percentage of 2%, 42%, 50% and 6%, respectively.

[0038] Water was added to the salvia miltiorrhiza at a ratio of 8 mL of water per 1 g of the salvia miltiorrhiza, decocted 2 times, for 50 min each time, then filtered to obtain a filtrate, the filtrate was then combined and concentrated at a temperature of 48-54 C. to yield a clear paste with a relative density of 1.15 to 1.20 (50 C.).

[0039] The homogenized fine powders of realgar, indigo naturalis, and heterophylla were added to the clear paste, granulated, dried, sized, and compressed (weight 0.25 g), and coated to obtain the pharmaceutical composition for treating leukemia.

Example 2

[0040] Realgar, indigo naturalis, salvia miltiorrhiza, and heterophylla were prepared with a weight percentage of 8%, 25%, 60% and 7%, respectively.

[0041] Water was added to the salvia miltiorrhiza at a ratio of 9 mL of water per 1 g of the salvia miltiorrhiza, decocted 2 times, for 55 min each time, then filtered to obtain a filtrate, the filtrate was then combined and concentrated at a temperature of 48-54 C. to yield a clear paste with a relative density of 1.15 to 1.20 (50 C.).

[0042] The homogenized fine powders of realgar, indigo naturalis, and heterophylla were added to the clear paste, granulated, dried, sized, and compressed (weight 0.25 g), and coated to obtain the pharmaceutical composition for treating leukemia.

Example 3

[0043] Realgar, indigo naturalis, salvia miltiorrhiza, and heterophylla were prepared with a weight percentage of 5%, 27%, 58% and 10%, respectively.

[0044] Water was added to the salvia miltiorrhiza at a ratio of 8 mL of water per 1 g of the salvia miltiorrhiza, decocted 2 times, for 55 min. each time, then filtered to obtain a filtrate, the filtrate was then combined and concentrated to yield a thick paste, then the thick paste is dried and crushed into a fine powder.

[0045] The fine powder of salvia miltiorrhiza were added into the homogenized fine powders of realgar, indigo naturalis, and heterophylla, mixed uniformly, placed in a pill making machine, panned with water and dried to obtain pills with a weight of 0.25 g.

Example 4

[0046] Realgar, indigo naturalis, salvia miltiorrhiza, and heterophylla were prepared with a weight percentage of 4%, 35%, 52% and 9%, respectively.

[0047] Water was added to the salvia miltiorrhiza at a ratio of 9 mL of water per 1 g of the salvia miltiorrhiza, decocted 2 times, for 50 min each time, then filtered to obtain a filtrate, the filtrate was then combined and concentrated at a temperature of 48-54 C. to yield a clear paste with a relative density of 1.15 to 1.20 (50 C.).

[0048] The homogenized fine powders of realgar, indigo naturalis, and heterophylla were added to the clear paste, granulated, dried, sized, and filled into a capsule (the weight is 0.25 g) to obtain the pharmaceutical composition for treating leukemia in a capsule form.

Example 5

[0049] Realgar, indigo naturalis, salvia miltiorrhiza, and heterophylla were prepared with a weight percentage of 3%, 32%, 57% and 8%, respectively.

[0050] Water was added to the salvia miltiorrhiza at a ratio of 9 mL of water per 1 g of the salvia miltiorrhiza, decocted 2 times, for 55 min each time, then filtered to obtain a filtrate, the filtrate was then combined and concentrated at a temperature of 48-54 C. to yield a clear paste with a relative density of 1.15 to 1.20 (50 C.).

[0051] The homogenized fine powders of realgar, indigo naturalis, and heterophylla were added to the clear paste, granulated, dried, sized, and filled into a capsule (weight 0.25 g) to obtain the pharmaceutical composition for treating leukemia in a capsule form.

Example 6

[0052] Different dosage forms of the pharmaceutical compositions prepared in Examples 1-5 were used in clinical validation for treating leukemia. The compound realgar natural indigo tablet prepared by the example of Chinese Patent Application No. 200410050453.1 was used as the control group. A total of 600 patients were selected and randomly divided into six groups, that is, 100 patients in each group. On the first day of treatment, 3 to 5 tablets or pills or capsules were taken each time, 3 times a day, and on and after the 10th days, 30 tablets or pills or capsules were taken per day, and 10 for each time. The control group was taken according to the administration method taught in Chinese Patent Application No. 200410050453.1.

[0053] Efficacy criteria (cf. Suzhou National Leukemia Chemotherapy Symposium, 1987):

[0054] Complete Remission (CR): No clinical symptoms or signs due to leukemia cell infiltration, normal or nearly normal life, hemogram: Hb100 g/L (male) or 90 g/L (female), neutrophil absolute value 1.510.sup.9/L, platelet 10010.sup.9/L, peripheral blood classification without leukemia cells, myelogram: the myeloblast+promyelocyte 5%, red blood cells and megakaryocytes are normal.

[0055] Partial remission (PR): myeloblasts of bone marrow+promyelocytes of bone marrow >5% and myeloblasts of bone marrow+promyelocytes of bone marrow 20%, or one of the clinical and hemogram did not reach the standard of complete remission.

[0056] Complete remission rate=numbers of complete remission per group/total numbers of patient per group; partial remission rate=1complete remission rate. The specific results are shown in Table 1.

TABLE-US-00001 TABLE 1 Comparison of efficacy of pharmaceutical compositions of the disclosure and control group Groups Complete remission rate (%) Partial remission rate (%) Example 1 92.9% 7.1% Example 2 93.0% .sup.7% Example 3 93.8% 6.2% Example 4 94.1% 5.9% Example 5 93.6% 6.4% Control Group 82.1% 17.9%

[0057] As shown in Table 1, the therapeutic effect of the pharmaceutical compositions for treating leukemia provided by the present disclosure is higher than that of the control group.

[0058] Unless otherwise indicated the numerical ranges involved in the invention include the end values. While particular embodiments of the invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects, and therefore, the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention.