CN1217662C - Cancer treating medicine - Google Patents
Cancer treating medicine Download PDFInfo
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- CN1217662C CN1217662C CN 03140103 CN03140103A CN1217662C CN 1217662 C CN1217662 C CN 1217662C CN 03140103 CN03140103 CN 03140103 CN 03140103 A CN03140103 A CN 03140103A CN 1217662 C CN1217662 C CN 1217662C
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- Prior art keywords
- total alkali
- herba macleayae
- macleayae cordatae
- ethanol
- medicine
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- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses a drug for treating cancers. The drug adopts bocconia cordata total alkali as a raw material added with pharmaceutic adjuvant frequently used pharmaceutically and prepared according to a preparation conventional technique. The weight content of the bocconia cordata total alkaloids from macleaya cordata exceeds 25%, and the weight content of sanguinarine chloride exceeds 30%. The present invention also discloses a preparation method of the bocconia cordata total alkali, which comprises three steps of acidic ethanol extraction, acid and alkali treatment and impurity removal and ethanol recrystallization and purification. The drug has the advantages of high effective component content, outstanding curative effect, obvious effect, various preparation formulation, convenient medication and transportation, nearly no toxic or side effect and wide popularization and use value.
Description
Affiliated technical field
The present invention relates to a kind of medicine for the treatment of cancer, being specifically related to a kind of is the Chinese patent medicine of feedstock production with the Chinese herbal medicine Herba Macleayae Cordatae.
Background technology
Herba Macleayae Cordatae Macleaya cordata (Willd) R.B[Bocconiacordata] be Papaveraceae Macleaya perennial plant, widely distributed in China, its homology plant Herba Macleayae Microcapae Macleaya microcarpa (Maxim) Fedde also does uncle and falls back to being used as medicine, medicinal its whole herb with root comprises fruit.Have parasite killing, the function of dispel the wind detoxifcation, dissipating blood stasis for subsidence of swelling, the clinical treatment of diseases such as trichomonas vaginitis, furuncle carbuncle midship, traumatic injury, rheumatic arthritis, tinea pedis, eczema, ulcer of the lower limb that are used for.Studies show that both at home and abroad Herba Macleayae Cordatae contains Sanguinarine (Sarguinarine), chelerythrine (Chelerythine), protopine (Protopine), α-allocryptopine (α-Allacryptine), bocconine multiple alkaloids such as (bocconoline).These alkaloids are the isoquinilone derivatives Alkaloid, have antibiotic, parasite killing, improve multiple pharmacological effect such as liver function, enhancing immunity, antitumor, relieving cough and asthma, analgesia.Still being difficult at present Herba Macleayae Cordatae is the Chinese medicine preparation that raw material is made the treatment cancer.
Summary of the invention
The object of the present invention is to provide a kind of is the medicine of the treatment cancer of feedstock production with the Herba Macleayae Cordatae, this effective ingredient content height, good effect, rapid-action, almost non-toxic side effect.
A kind of medicine for the treatment of cancer provided by the invention, be to be raw material with the Herba Macleayae Cordatae total alkali, add pharmaceutic adjuvant commonly used on the pharmaceutics, the medicament for preparing by the preparation common process, wherein the weight content of chelerythrine hydrochlorate is higher than 25% in the Herba Macleayae Cordatae total alkali, the weight content of Sanguinarine hydrochloride is higher than 30%.
Herba Macleayae Cordatae total alkali of the present invention prepares by following three steps:
(1) extract to concentrate: get the Chinese herbal medicine Herba Macleayae Cordatae, add the acidic ethanol reflux, extract, 1～4 time, merge extractive liquid, filters, with decompression filtrate recycling ethanol and through concentrate, leave standstill, centrifugal, it is standby to get supernatant;
(2) separate remove impurity: getting above-mentioned supernatant, is 8～10 with 20～40% sodium carbonate liquor adjust pHs, stirs evenly, leave standstill 24～48 hours, centrifugal, the collecting precipitation thing, with the methanol or the dissolve with ethanol of 6～10 times of weight of precipitate, centrifugal, branch is got supernatant, and residue is again with method dissolving 1～3 time, merge supernatant, be 3～4 with the hydrochloric acid adjust pH after, reclaim under reduced pressure is also concentrated, concentrated solution is put cold, and cold preservation was left standstill more than 18 hours, filters, the collecting precipitation thing in dry below 40 ℃, gets the total alkali crude product;
(3) crystallization purifying: get above-mentioned total alkali crude product, the ethanol that adds 10～20 times of total alkali crude product weight, 50 ℃ of heating for dissolving, filtered while hot, with decompression filtrate recycling ethanol to 1/3rd of filtrate volume, putting cold, cold preservation leaves standstill, separate out crystallization, decompress filter, leaching crystallization, in dry below 40 ℃, promptly make Herba Macleayae Cordatae total alkali of the present invention.
Used acidic ethanol is 65～85% ethanol with any adjusting pH to 3～4 in hydrochloric acid, sulphuric acid or the phosphoric acid in the above-mentioned preparation process (1).
The method for preparing the Herba Macleayae Cordatae total alkali among the present invention has method characteristics easy, with low cost, with short production cycle, is suitable for industrialized great production.The Herba Macleayae Cordatae total alkali that obtains thus can be made into the product of the acceptable any dosage form of pharmaceutics, as capsule, powder, granule, tablet, drop pill, oral liquid, freeze-dried powder or injection.Can according to circumstances add suitable adjuvant when making product, used pharmaceutic adjuvant is a kind of of acceptable any one adjuvant of pharmaceutics or several combinations.Effective ingredient content height of the present invention, determined curative effect, instant effect, dosage form be various, make things convenient for medication and transportation, almost non-toxic side effect, has bigger popularizing value.
The present invention is further illustrated below in conjunction with the specific embodiment.
The preparation of embodiment 1 Herba Macleayae Cordatae total alkali
Get 20Kg Herba Macleayae Cordatae fruit, grind, put into extraction pot, add 10 times of amounts and transfer 75% ethanol of pH to 3～4, reflux, extract, 2 times, each 1 hour with hydrochloric acid.Merge extractive liquid, filters.Filtrate is put in the concentration tank, and decompression recycling ethanol also is concentrated into relative density 1.08, leaves standstill, puts cold, centrifugal.Getting supernatant, to transfer the pH value of solution with 40% sodium carbonate liquor be 10, stirs evenly, and leaves standstill 48 hours, and centrifugal, the collecting precipitation thing is with the dissolve with ethanol of 8 times of weight of precipitate.Centrifugal, branch is got supernatant, and residue dissolves secondary with method, merges solution, and transferring the pH value of solution with hydrochloric acid is 3～4, decompression recycling ethanol, and concentrated solution leaves standstill, cold preservation 48 hours.Filter, the collecting precipitation thing in dry below 40 ℃, gets the total alkali crude product.
Above-mentioned total alkali crude product is added 15 times of amount ethanol, 50 ℃ of heating for dissolving, filtered while hot.Filtrate in 50 ℃ of decompression recycling ethanols to cumulative volume 1/3rd, placement, cold preservation 40 hours, separate out coarse-grain, decompress filter, the leaching coarse-grain, in dry below 40 ℃, macleaya cordata total alkali salt hydrochlorate 120g.Wherein contain chelerythrine hydrochloric acid 25.8%, Sanguinarine hydrochloride 31.3%.
The preparation of embodiment 2 Herba Macleayae Cordatae total alkali capsules
Get Herba Macleayae Cordatae total alkali 20g and mix with starch 200g, pulverize the back and cross 120 mesh sieves, mix homogeneously incapsulates, promptly.
The preparation of embodiment 3 Herba Macleayae Cordatae total alkali granules
Get Herba Macleayae Cordatae total alkali fine powder 10g, add dextrin 150g, mannitol 150g and soluble starch 40g, stevioside 2g, mix homogeneously is used 80% alcohol granulation, drying, and packing, promptly.
The preparation of embodiment 4 Herba Macleayae Cordatae total alkali oral liquids
Get Herba Macleayae Cordatae total alkali 10g, add 700ml distilled water and 10% hydrochloric acid solution 6ml, stirring and dissolving is filtered, and filtrate adds stevioside 1.2g and adding distil water again to 1000ml, mixing, filtration, and fill, sterilization, promptly.
The preparation of embodiment 5 Herba Macleayae Cordatae total alkali tablets
Get Herba Macleayae Cordatae total alkali fine powder 20g,, use 85% alcohol granulation with 200g starch mix homogeneously, drying, tabletting, the bag film-coat, promptly.
The preparation of embodiment 6 Herba Macleayae Cordatae total alkali injection
Get Herba Macleayae Cordatae total alkali 2.5g, polyoxyethylene sorbitan monoleate 6g, sodium chloride 9g adds injection water 800ml and 10% hydrochloric acid solution 4.5ml, and stirring and dissolving filters, and filtrate adds the injection water to 1000ml, and mixing filters with microporous filter membrane, embedding, and sterilization, promptly.
The preparation of embodiment 7 Herba Macleayae Cordatae total alkali freeze-dried powders
Get Herba Macleayae Cordatae total alkali 2g, mannitol 30g and sodium chloride 8g, add injection water 800ml and 10% hydrochloric acid solution 4ml, stirring and dissolving filters, filtrate adds the injection water to 1000ml, and mixing filters with microporous filter membrane, and filtrate is sub-packed in the sterilized cillin bottle, lyophilization, tamponade, gland, promptly.
The preparation of embodiment 8 Herba Macleayae Cordatae total alkali drop pill
Taking polyethylene glycol 4000 280g, heating and melting adds Herba Macleayae Cordatae total alkali fine powder 10g under constantly stirring, pour into behind the mixing in the drop pill machine of preheating, splashes in the refrigerative liquid paraffin with the speed of 60～80/min, takes out, and removes liquid paraffin, drying, promptly.
Pharmacodynamic test of active extract
1, Herba Macleayae Cordatae total alkali freeze-dried powder extracorporeal anti-tumor function
Adopt cultured tumor cells in vitro to measure the anti tumor activity in vitro of Herba Macleayae Cordatae total alkali lyophilized powder by the direct observation of mtt assay and cellular morphology.The experiment before with 0.9% normal saline doubling dilution in Herba Macleayae Cordatae total alkali lyophilized powder is mixed with 120.0,60.0,30.0,15.0,7.5 μ g/ml in total alkali, the medicinal liquid of drawing the above-mentioned various concentration of 10 μ L in the test adds in the 190 μ L culture medium, observe the human large intestine cancer lovo cell of Herba Macleayae Cordatae total alkali lyophilized powder to In vitro culture, people's hepatocarcinoma Hep3D cell, human bladder cancer T24 cell, the influence of mice SRS82 lymphoma cell growth, and with 5-Fu as positive control.The result shows the half-inhibition concentration (IC of Herba Macleayae Cordatae total alkali lyophilized powder to animal and human's tumor cell line
50) all below 10 μ g/ml, show that Herba Macleayae Cordatae total alkali lyophilized powder has a very strong antitumor action external; Morphology is the result show, what give Herba Macleayae Cordatae total alkali lyophilized powder respectively organizes tumor cell, and cell number descends after the administration, occurs becoming big, becomes the circle phenomenon than many cells, float in the culture medium, the prompting cell is dead, under observation finds, with the raising of dosage, cell number descends, when concentration reached certain value, large tracts of land was dead or all dead, and cell quantity has tangible dose-dependence.IC
50See the following form.
The external inhibitory action of table 1 Herba Macleayae Cordatae total alkali lyophilized powder to each group growth of cancer cells
| The tumor strain | IC50 (μ g/ml) and 95% fiducial limit |
| Human large intestine cancer Lovo cell | 1.96(1.73-2.06) |
| People's hepatocarcinoma Hep3D cell | 2.46(2.13-2.76) |
| Human bladder cancer T24 cell | 3.21(2.98-3.63) |
| Mice SRS82 sarcoma cell | 3.65(3.19-4.21) |
2, Herba Macleayae Cordatae total alkali lyophilized powder anti-tumor in vivo effect
Test is adopted in the body and is moved the anti-tumor in vivo effect that tumor has been studied the Herba Macleayae Cordatae total alkali.Drug administration by injection and two kinds of route of administration of gastric infusion are adopted in test, and test dose designs as following table:
Table 2 Herba Macleayae Cordatae total alkali freeze dried powder amount design table (in total alkali)
| Route of administration | The dosage group | Dosage (mg/kg) |
| Drug administration by injection | High dose group | 12.0 |
| Middle dosage group | 6.0 | |
| Low dose group | 3.0 | |
| Oral administration | High dose group | 160 |
| Middle dosage group | 80 | |
| Low dose group | 40 |
(1) In vitro culture mice S180 ascites tumor cell behind the inoculation kunming mice, extracts the ascites tumor cell, every mouse peritoneal injection 2.0 * 10
6Cell; Beginning in the 2nd day mouse vein administration of inoculation back or oral administration, successive administration 10 days, the life span of observing mice is calculated increase in life span.Experiment repeats twice.The results are shown in Table 3.
Table 3 Herba Macleayae Cordatae total alkali lyophilized powder is to the influence of S180 ascites tumor mice increase in life span
| Route of administration | The dosage group | Dosage (mg/kg) | Tumour inhibiting rate (%) |
| Drug administration by injection | High dose group | 12.0 | 78.6±6.85 |
| Middle dosage group | 6.0 | 50.9±4.17 | |
| Low dose group | 3.0 | 37.7±3.41 | |
| Oral administration | High dose group | 160 | 66.2±5.81 |
| Middle dosage group | 80 | 42.2±5.19 | |
| Low dose group | 40 | 32.6±2.18 | |
| Positive drug | 5-Fu | 20 | 53.7±3.58 |
(2) H22 hepatoma carcinoma cell, inoculate kunming mice respectively after, extract the ascites tumor cell, every right axil subcutaneous injection 2.0 * 10 of mice
5Cell; Inoculation back administration in the 2nd day, successive administration 10 days was put to death mice on the 11st day, peeled off tumor, weighed, and calculated tumour inhibiting rate.Experiment repeats twice.The result shows and sees Table 3:
Table 4 Herba Macleayae Cordatae total alkali lyophilized powder is to the inhibitory action of H22 hepatocarcinoma
| Route of administration | The dosage group | Dosage (mg/kg) | Tumour inhibiting rate (%) |
| Drug administration by injection | High dose group | 12.0 | 63.2±4.36 |
| Middle dosage group | 6.0 | 51.2±4.65 | |
| Low dose group | 3.0 | 32.7±2.68 | |
| Oral administration | High dose group | 160 | 50.8±4.18 |
| Middle dosage group | 80 | 39.7±2.85 | |
| Low dose group | 40 | 25.4±3.17 | |
| Positive drug | 5-Fu | 20 | 46.2±4.01 |
3, acute toxicity test
Give the macleaya cordata total aqueous slkali to mice by 0.2ml/10g body weight filling stomach or tail vein injection, observe general performance and the death condition of mice.The result shows, irritates the LD of stomach and drug administration by injection
50Be respectively 925.4mg/kg (886.3-968.6mg/kg) and 39.1mg/kg (34.6-43.8mg/kg).
Claims (4)
1, a kind of medicine for the treatment of cancer, it is characterized in that being is raw material with the Herba Macleayae Cordatae total alkali, add pharmaceutic adjuvant commonly used on the pharmaceutics, the medicament for preparing by the preparation common process, wherein the weight content of chelerythrine hydrochlorate is higher than 25% in the Herba Macleayae Cordatae total alkali, the weight content of Sanguinarine hydrochloride is higher than 30%.
2, the medicine of treatment cancer according to claim 1 is characterized in that described Herba Macleayae Cordatae total alkali prepares by following three steps:
(1) extract to concentrate: get the Chinese herbal medicine Herba Macleayae Cordatae, add the acidic ethanol reflux, extract, 1～4 time, merge extractive liquid, filters, with decompression filtrate recycling ethanol and through concentrate, leave standstill, centrifugal, it is standby to get supernatant;
(2) separate remove impurity: getting above-mentioned supernatant, is 8～10 with 20～40% sodium carbonate liquor adjust pHs, stirs evenly, leave standstill 24～48 hours, centrifugal, the collecting precipitation thing, with the methanol or the dissolve with ethanol of 6～10 times of weight of precipitate, centrifugal, branch is got supernatant, and residue is again with method dissolving 1～3 time, merge supernatant, be 3～4 with the hydrochloric acid adjust pH after, reclaim under reduced pressure is also concentrated, concentrated solution is put cold, and cold preservation was left standstill more than 18 hours, filters, the collecting precipitation thing in dry below 40 ℃, gets the total alkali crude product;
(3) crystallization purifying: get above-mentioned total alkali crude product, the ethanol that adds 10～20 times of total alkali crude product weight, 50 ℃ of heating for dissolving, filtered while hot, with decompression filtrate recycling ethanol to 1/3rd of filtrate volume, putting cold, cold preservation leaves standstill, separate out crystallization, decompress filter, leaching crystallization, in dry below 40 ℃, promptly get the Herba Macleayae Cordatae total alkali.
3, the medicine of treatment cancer according to claim 2 is characterized in that described acidic ethanol is with any regulates 65～85% ethanol of pH to 3～4 in hydrochloric acid, sulphuric acid or the phosphoric acid.
4, the medicine of treatment cancer according to claim 1 and 2 is characterized in that described medicament is capsule, powder, granule, tablet, drop pill, oral liquid, freeze-dried powder or injection.
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| CN101088551B (en) * | 2006-06-13 | 2010-09-08 | 黄家曦 | Medicine for treating liver fibrosis |
| EP2014651A1 (en) * | 2007-07-12 | 2009-01-14 | Exonhit Therapeutics SA | Compounds and methods for modulating Rho GTPases |
| CN101904849A (en) * | 2010-08-19 | 2010-12-08 | 苏州大学 | Application of Sanguinarine in Preparation of Tumor Radiation Therapy Sensitizer |
| CN103429235A (en) * | 2010-12-15 | 2013-12-04 | 赖鸿政 | Compounds and uses thereof for the treatment of cancer |
| CN104248635B (en) * | 2013-06-27 | 2016-12-28 | 天津中医药大学 | Protopine Alkaloid is used for the application suppressed in the medicine of P gp in preparation |
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