CN1416816A - Antineoplastic effect and medicine prepn of dioscin - Google Patents
Antineoplastic effect and medicine prepn of dioscin Download PDFInfo
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- CN1416816A CN1416816A CN 02146797 CN02146797A CN1416816A CN 1416816 A CN1416816 A CN 1416816A CN 02146797 CN02146797 CN 02146797 CN 02146797 A CN02146797 A CN 02146797A CN 1416816 A CN1416816 A CN 1416816A
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Abstract
The present invention discloses new application of dioscin obtained from yan plant in antineoplastic medicine and the tablet, capsule, dripping pill, injection and other medicine preparation with dioscin as medicine material.
Description
Technical field
The present invention in application aspect the antitumor drug and pharmaceutical preparation thereof, belongs to the field of Chinese medicines about dioscin (Dioscin).
Background technology
Dioscin (Dioscin) is a kind of extraction separation purification from Dioscoreaceae plant Dioscorea nipponica Mak. Ningpo Yam Rhizome plant rhizome such as (Dioscorea nipponicaMakino) and obtaining.Be a kind of known compound, 3 of dioscins are gone up the glucoses that connect and two rhamnose can obtain diosgenin (Diosgenin) after with acid degradation.The application that dioscin is used for the antitumor drug aspect does not appear in the newspapers.With Rhizoma Dioscoreae Nipponicae or Rhizoma Dioscoreae Zingiberensis, Dioscorea panthaica Prain et Burkill etc. is that the diosgenin (Diosgenin) of feedstock production has obvious antineoplastic, wherein to the most obvious report such as Ke Hu of S-180, hepatoma ascitic type, mouse cervical cancer and ehrlich ascites tumor effect, also there is very strong cytotoxicity (plata.medica.2002.68.4.289-384) in protodioscin unit (protodroscin) to 60 kinds of human cancer cells.From above report result, Rhizoma Dioscoreae soap former times unit or the glucosides that contains diosgenin (diosgenin) to a certain degree antitumor action is all arranged.The yam resource is very abundant, and wherein contained steroidal saponin amount is also higher, and toxic and side effects is very low, is a kind of antitumor drug that the exploitation future is arranged.
The chemical structural formula of dioscin (its English name is Dioscin)
Summary of the invention
One of purpose of the present invention has provided the pharmaceutical preparation of dioscin; Two of purpose of the present invention has provided the antineoplastic new usage of dioscin.
The present invention seeks to be achieved through the following technical solutions:
Pharmaceutical preparation of the present invention contains the dioscin of 1%-99% and the excipient of 99%-1% (medicine that comprises other adapted), preferably contain the dioscin of 30%-80% and the pharmaceutical excipient of 70%-20% (comprising the medicine that other compatibility is used), preferably contain the dioscin of 60%-70% and the excipient of 40%-30% (comprising the medicine that other compatibility is used).
Press practice of pharmacy, dioscin of the present invention can be prepared into the various clinical pharmaceutical dosage form as antitumor drug, comprise the dosage form of oral formulations or parenterai administration.Said oral formulations is selected from any in tablet, capsule, pill, granule, suspensoid, drop pill, the oral liquid; Said non-intestinal is selected from a kind of in the middle of injection, aerosol, suppository or the subcutaneous administration dosage form to dosage form.
Adjuvant in the antitumor drug of the present invention is meant conventional excipient, as solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent etc.The medicine that other compatibility in the antitumor drug of the present invention is used, the dioscin that refers to effective dose is certain medicine material, again compatibility other allowed the Chinese medicine or the chemical drugs that share.
Dioscin pharmaceutical preparation of the present invention has antitumor action, is to be confirmed by following effect experiment.
Experimental example 1Dioscin is to the inhibitory action of tumor cell in vitro
Cell MCF-7 (human breast cancer cell), NCI-H446 (human small cell lung carcinoma), MGC-803 (gastric carcinoma cells), Swillc (human colon cancer cell), U251 (human glioma cell), SGC-7901 (gastric carcinoma cells), K562 (human erythroleukemia cell), A375-S
2(human melanoma cell), Hela (human cervical carcinoma cell), BEL-7204 (human liver cancer cell), HL-60 (leukaemia) are all available from Jilin Province tumour hospital
Reagent dioscin (Dioscin) is because Tianyao Science and Technology Co Ltd, Jilin natural drug institute Chemistry for Chinese Traditional Medicine chamber provides white, needle-shaped crystals; Tetramethyl azo azoles salt (MTT), potassium penicillin G, streptomycin sulfate, HEPES and DMSO are Sigma company product; Pancreatin is the Difco product; New-born calf serum (FBS) is Beijing Heng Shengma of unit biotechnology research institute product; The RPMI-1640 culture medium is the Hyclone product;
Instrument CK2TRC-3 fluorescence inverted microscope, the OLYMPUS-japanese product; D-63450-CO
2Incubator, Hera-Germany product; The FCANF129004 microplate reader is a TECAN-Australia product.The method mtt assay is with the exponential phase cell dissociation, and is centrifugal, and numeration is with 1 * 10
5Individual/mL density is inoculated in 96 well culture plates, every hole 100 μ L cultivated after 24 hours, added the Concentraton gradient medicine, establish solvent control and blank simultaneously, cultivate after 44 hours, every hole adds 20 μ LMTT (5mg/mL), cultivates 4 hours again, abandon supernatant, every hole adds 150 μ L dimethyl sulfoxide, vibrates 10 minutes, uses microplate reader and surveys the OD value in the 492nm place.
Table 1 mtt assay is measured the suppression ratio (%) of 11 kinds of tumor cells
The result as can be seen from Table 1, dioscin all has very strong inhibition growth effect and has tangible dose-effect relationship above-mentioned 11 kinds of tumor cells, wherein to human melanoma cell (A375-S
2), early young leukaemia (HL-60), human cervical carcinoma cell (Hela) effect are the most remarkable for the people.Dioscin when concentration reaches 8 μ g/mL to human melanoma cell (A375-S
2) wait eight cell inhibiting rates almost to reach 100% (more than 98%).
Experimental example 2The whole antitumor action of dioscin
Animal S
180Deng 4 kinds of tumor ascites mice of going down to posterity, all available from the institute of oncology, Jilin Province.Kunming mice, body weight 18-22g is available from the high and new technology industrial development zone Experimental Animal Center.
The medicine dioscin is provided by Tianyao Science and Technology Co Ltd, Jilin natural drug institute Chemistry for Chinese Traditional Medicine chamber, and white, needle-shaped crystals, purity are more than 98%.Cyclophosphamide for injection, specification are that 200mg/ props up, and lot number is 20010102, Hualian Pharmaceutical Co., Ltd., Shanghai's product.
Instrument electronic balance, model are enzyme Teller-Tuo benefit AB204-N
The method laboratory mice is divided into matched group (ig distilled water 200mlkg-1) at random, cyclophosphamide (ip20mgkg-1), dioscin (ig200mg, 100mg and 50mgkg-1), chose transplantation tumor 7 days, tumor growth is good, abdominal part swells tangible mice, the skin of abdomen sterilization, thrust the abdominal cavity with disposable nontoxic hemostix through stomach wall, extract ascites, put into aseptic beaker is diluted to 1: 3 with normal saline cancerous cell suspension, in the right oxter inoculation of every mice 0.2ml, each treated animal begins administration next day in inoculated tumour, once a day, successive administration is 10 days.After administration finishes, the animal back of weighing is put to death, peel off lump and weigh, respectively organize tumor growth situation (each treated animal initial number is 10, and listed number of animals is and removes remaining number behind the dead animal in the table).Test shows that dioscin 200,100,50mg are to S
180, HepA, U
14All has the obvious suppression effect with the EAC tumor cell, to S
180Tumour inhibiting rate be 39-62%, be 36-66% to the HepA tumour inhibiting rate, to U
14Tumour inhibiting rate is 37-54%, is 38-56% to the EAC tumour inhibiting rate, and concrete result of the test sees Table 2-5.
Table 2 dioscin is to mice S
180The influence that tumor is heavy
The heavy tumour inhibiting rate group of dosage number of animals the weight of animals (g) tumor
Mg.kg
-1(n) (g) (%) matched group-10 20.6 ± 1.68 28.3 ± 1.83 2.08 ± 0.86 cyclophosphamide 20 10 20.9 ± 1.72 26.1 ± 2.37 0.78 ± 0.31 after the administration before the administration
* *62.5 dioscin 200 9 20.4 ± 1.10 27.2 ± 3.39 0.93 ± 0.35
*55.3 dioscin 100 10 20.8 ± 1.47 27.8 ± 2.89 0.98 ± 0.37
*52.3 dioscin 50 9 20.5 ± 1.43 28.0 ± 3.18 1.25 ± 0.18
*39.9
Annotate: compare with matched group,
* *P＜0.001
*P＜0.01
*P＜0.05
The influence that table 3 dioscin is heavy to mice HepA tumor
The heavy tumour inhibiting rate group of dosage number of animals the weight of animals (g) tumor
Mg.kg
-1(n) (g) (%) matched group-10 19.7 ± 1.76 28.2 ± 1.93 2.13 ± 0.67 cyclophosphamide 20 9 19.9 ± 1.60 25.1 ± 2.38 0.71 ± 0.29 after the administration before the administration
* *66.7 dioscin 200 10 19.4 ± 1.08 26.2 ± 3.46 0.88 ± 0.28
* *58.7 dioscin 100 10 19.7 ± 1.57 26.8 ± 2.90 1.05 ± 0.39
* *50.6 dioscin 50 9 19.7 ± 1.42 28.2 ± 3.20 1.36 ± 0.19
*36.1
Annotate: compare with matched group,
* *P＜0.001
*P＜0.01
Table 4 dioscin is to mice U
14The influence that tumor is heavy
The heavy tumour inhibiting rate group of dosage number of animals the weight of animals (g) tumor
Mg.kg
-1(n) (g) (%) matched group-10 19.7 ± 1.76 27.4 ± 1.93 1.97 ± 0.76 cyclophosphamide 20 10 20.9 ± 1.60 25.1 ± 2.38 0.89 ± 0.24 after the administration before the administration
* *54.8 dioscin 200 10 20.4 ± 1.08 25.8 ± 3.46 0.94 ± 0.37
* *52.3 dioscin 100 8 20.7 ± 1.57 25.7 ± 2.90 1.02 ± 0.25
*48.2 dioscin 50 9 20.6 ± 1.42 28.0 ± 3.20 1.23 ± 0.16
*37.6
Annotate: compare with matched group,
* *P＜0.001
*P＜0.01
*P＜0.05
The influence that table 5 dioscin is heavy to mice EAC tumor
The heavy tumour inhibiting rate group of dosage number of animals the weight of animals (g) tumor
Mg.kg
-1(n) (g) (%) matched group-9 20.8 ± 2.03 29.2 ± 1.87 1.97 ± 0.77 cyclophosphamide 20 9 20.9 ± 1.60 27.1 ± 2.12 0.85 ± 0.29 after the administration before the administration
* *56.9 dioscin 200 10 20.4 ± 1.08 26.5 ± 3.35 0.93 ± 0.25
*52.8 dioscin 100 10 20.7 ± 1.57 27.8 ± 2.47 1.05 ± 0.26
*46.7 dioscin 50 9 20.3 ± 1.42 27.3 ± 3.29 1.22 ± 0.39
*38.1
Annotate: compare with matched group,
* *P＜0.001
*P＜0.01
*P＜0.05
Above-mentioned isolated experiment and integral experiment show that dioscin all has the obvious suppression effect to stripped and whole tumor cell.Isolated experiment shows, when concentration is 8 μ g/mL to human melanoma cell (A375-S
2) wait eight cell inhibiting rates almost to reach 100% (more than 98%); Integral experiment shows that dioscin 200,100,50mg are to S
180, HepA, U
14All have the obvious suppression effect with the EAC tumor cell, tumour inhibiting rate can reach 36-67%.
The specific embodiment Embodiment 1The preparation of drop pill
Take by weighing the 300g Macrogol 4000, in water-bath, melt, add dioscin raw material 100g, stir, in the impouring insulating tube, regulate thermostat, make medicinal liquid under 80-90C, splash in the liquid paraffin that cooled off (temperature ± 4 ℃), after dripping off, to blot paraffin oil on the pill impouring filter paper, add a small amount of Pulvis Talci again, mixing gets 1000 of dioscin drop pill.Oral, a 2-3 grain, three times on the one, one after each meal.
Embodiment 2The preparation of microencapsule tablet
Take by weighing stearic acid 15g and 21mL respectively as compound recipe capsule material, take by weighing dioscin 100g as capsule core material, by the spray congealing encystation, capsule directly is 8-100um with compressed air.Then with microcapsule and microcrystalline Cellulose mixing, add the mixed encystation material of 10% ethyl cellulose alcoholic solution, make granule by 18 order nylon mesh,, placed exsiccator interior 24 hours in oven dry below 35 ℃, add 1%-2% magnesium stearate tabletting, get the dioscin microencapsule tablet, sheet heavily is 0.3g, and is oral, a 1-2 sheet, a twice-daily.
Embodiment 3The preparation of capsule
Dioscin raw material 1000g, medical starch 1000g, mix homogeneously, the 0# capsule of packing into, every 0.35g, each oral 1-2 grain, twice of every day.
Embodiment 4The preparation of tablet
Dioscin raw material 1000g, medical starch 500g, mix homogeneously is used an amount of alcohol granulation, through the pelletizing machine granulate, tabletting, every 0.25g, oral, each 1-2 sheet, twice of every day.
Embodiment 5The preparation of granule
Dioscin raw material 100g, starch 1000g, Icing Sugar 400g, mix homogeneously is used an amount of alcohol granulation, and drying, granulate, packing are promptly.Oral, a 5g, twice on the one.
Embodiment 6The preparation of injection
Dioscin raw material 10g, propylene glycol 20ml, Polyethylene Glycol-400 50ml, water for injection 300ml mixes heating in water bath 30 minutes, add benzyl alcohol 50ml, reuse water for injection adds to 1000ml, handles 10 minutes in ultrasound wave, heats 30 minutes in the water-bath again, transfer pH value 5.5-6.5, filter clear and bright, embedding, the sterilization promptly.Every 2ml, intramuscular injection, a 2ml, 1-2 time on the one.
Claims (10)
1, a kind of pharmaceutical preparation is characterized in that containing dioscin and one or more pharmaceutically acceptable pharmaceutical excipients of dose therapeutically effective, or can with the other medicines of dioscin prescription.
2, pharmaceutical preparation according to claim 1, but it is characterized in that containing dioscin and the pharmaceutical excipient of 99%-1% or the medicine of other prescription of 1%-99%.
3, pharmaceutical preparation according to claim 2, but it is characterized in that containing dioscin and the pharmaceutical excipient of 70%-20% or the medicine of other prescription of 30%-80%.
4, pharmaceutical preparation according to claim 3, but it is characterized in that containing dioscin and the pharmaceutical excipient of 40%-30% or the medicine of other prescription of 60%-70%.
5, pharmaceutical preparation according to claim 1 is characterized in that said medicine is the dosage form of oral formulations or parenterai administration.
6, pharmaceutical preparation according to claim 5 is characterized in that said oral formulations is selected from any in the middle of the tablet, pill, capsule, granule, suspensoid, drop pill, oral liquid.
7, pharmaceutical preparation according to claim 5 is characterized in that said parenterai administration dosage form is selected from any in the middle of injection, aerosol, suppository or the subcutaneous administration dosage form.
8, the application of dioscin in the preparation antitumor drug.
9, purposes according to Claim 8 is characterized in that said antitumor is meant the inhibition to tumor cell.
10,, it is characterized in that said tumor cell is human breast cancer cell, human small cell lung carcinoma, gastric carcinoma cells, human colon cancer cell, human glioma cell, gastric carcinoma cells, human erythroleukemia cell, human melanoma cell, human cervical carcinoma cell, human liver cancer cell, promyelocytic leukemia cell, sarcoma 180, liver ascites, mouse cervical cancer-14 or ehrlich carcinoma according to the purposes of claim 9.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101333241B (en) * | 2008-06-06 | 2011-07-27 | 江苏黄河药业股份有限公司 | Process for extracting dioscin, preparation thereof and use |
| CN101296703B (en) * | 2005-10-28 | 2011-07-27 | 金善砺 | Extract of the family dioscoreaceae and composition for preventing or treating peripheral neuropathy comprising the same |
| CN105641698A (en) * | 2014-09-30 | 2016-06-08 | 复旦大学 | Composite medicine containing autophagy inhibitor and diosgenin and application of composite medicine |
-
2002
- 2002-11-08 CN CN 02146797 patent/CN1416816A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101296703B (en) * | 2005-10-28 | 2011-07-27 | 金善砺 | Extract of the family dioscoreaceae and composition for preventing or treating peripheral neuropathy comprising the same |
| US8202554B2 (en) | 2005-10-28 | 2012-06-19 | Sun-Yeou Kim | Extract of the family dioscoreaceae and composition for preventing or treating peripheral neuropathy comprising the same |
| CN101333241B (en) * | 2008-06-06 | 2011-07-27 | 江苏黄河药业股份有限公司 | Process for extracting dioscin, preparation thereof and use |
| CN105641698A (en) * | 2014-09-30 | 2016-06-08 | 复旦大学 | Composite medicine containing autophagy inhibitor and diosgenin and application of composite medicine |
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