CN1939311B - Ginseng sapogenin aglycone derivative biological preparation and its usage - Google Patents
Ginseng sapogenin aglycone derivative biological preparation and its usage Download PDFInfo
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- CN1939311B CN1939311B CN2006101417633A CN200610141763A CN1939311B CN 1939311 B CN1939311 B CN 1939311B CN 2006101417633 A CN2006101417633 A CN 2006101417633A CN 200610141763 A CN200610141763 A CN 200610141763A CN 1939311 B CN1939311 B CN 1939311B
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Abstract
An antineoplastic compound 25mdt, that is, 20(s)-25-methoxyl-dammarane-3 beta, 12 beta, 20-triol, is a protopanoxadiol derivative, its antineoplastic medicine and its antineoplastic application is suppressing the growth and reproduction of tumor cells, inducing the differentiation and wither of tumor cells, preventing the transfer of tumor cells, improving immunity, and treating cancers are disclosed.
Description
Technical field:
The present invention relates to a kind of anticancer usage of new protopanoxadiol saponin aglycone derivative and the new antitumoral preparation that contains this chemical compound.The name of this chemical compound is called 20 (S)-25-methoxyl group-dammarane-3 β, 12 β, 20-triol [20-triol is called for short 25mdt for 20 (S)-25-methoxyl-dammarane-3 β, 12 β].
Background technology:
Cancer is the second-biggest-in-the-world disease of torturing the human life, and mortality rate is only second to cardiovascular and cerebrovascular disease, is one of human dead main factor.In the whole world 6,000,000,000 populations, all kinds of cancer patients 3,500 ten thousand are arranged approximately at present.The annual whole world of the death toll that cancer causes has 6,300,000 people approximately, according to internal authority organ of survey statistics, will double to the year two thousand twenty cancer mortality number, reaches more than 1,000 ten thousand people.In recent years, the big production of industry causes environment for human survival constantly to worsen.Various carcinogenic factors such as chemistry, virus, physics radiation increase gradually, and the cancer morbidity of China also rises year by year.According to health ministry health statistics information centre, National urban malignant tumor prevalence male in 1999 is that 169.58 people/ten thousand people, women are that prevalence is that 148.90 people/ten thousand people, small and medium-sized cities are 110.70 people/ten thousand people in 110.05 people/ten thousand people, the big city.If calculate by China's 1,300,000,000 populations, the new cases of annual malignant tumor reach 2,000,000 people.
At present, the common method of treatment cancer has operation, radiotherapy and Drug therapy etc.The professional person points out, from 50, mainly rely on surgical intervention and radiocurable progressive the raising in so far 40 years of cancer patient relative survival rate the sixties, surgical operation and radiocurable progress be the peak closely, is difficult to expect to have again bigger breakthrough.And Drug therapy can become the healing of merit ground or obviously prolong patient's life, occupies more and more main status in treatment for cancer.The chemotherapy of tumor is conceived to the direct killing tumor cell basically, and often there is following problem in this treatment pattern: to the solid tumor weak effect that increasess slowly or almost there is not influence; Drug selectivity is very little, and toxicity is many and serious, and wherein bone marrow depression is topmost dose limitation factor.The tumor cell dynamics research has been obtained remarkable progress but imperfection; Lacking simple and practical method, to predict tumor outer in what phase, and some therapeutic regimens commonly used are almost many from clinical experience.The Biotherapeutics of tumor is the four-mode of the tumor after operation, radiation and chemotherapy, mainly passes through the biologically of the work of tumor host defense mechanism or biological preparation in order to adjusting body self, thereby suppresses or the elimination tumor.Though there is not too big toxic and side effects, because specification requirement is tight, complex process, so the price height, numerous cancer patients and family members are difficult to bear, and influence its popularizing in field of cancer.
In view of above-mentioned various reasons, people turn to sight in the research and development of natural antitumor medicine.No matter be inhibition or killing tumor cell, adjustment body's immunity, improve symptom and feature, alleviate toxic and side effects of chemoradiotherapy, or the conditioning after being ill of tumor, natural anti-cancer drugs has important function.Thus, the natural plants new therapy will become the fifth-largest Therapeutic Method of the operation that continues, radiotherapy, chemotherapy, biotherapy.
Many scholars' the ginsenoside that studies show that has tangible antitumor and immunoregulation effect, microcirculation improvement effect, improves multiple biological activity such as quality of life.But absorb because the natural ginseng saponin is difficult, and be the prototype that the natural ginseng saponin is brought into play its drug effect by low polarity saponin, aglycon or the derivant of the two that natural saponin is transformed.Therefore, very active about the research of the preparation of low polarity saponin, aglycon or the derivant of the two and anti-tumor activity, found that they when having multiple anti-tumor activity, have no side effect substantially.Find that from the present low polarity saponin, aglycon or the derivant of the two with anti-tumor activity have: ginsenoside-Rg
3, Rh
2, C-K, Mc, PPD and 3 β, 12 β-dihydroxy-20 (22), 24 (25)-diene dammarane [dammar-3 β, 12 β-dihydroxyl-20 (22), 24 (25)-diene] and 3 β, 6 α, 12 β-three hydroxyl-20 (22), 24 (25)-diene dammarane [dammar-3 β, 6 α, 12 β-trihydroxyl-20 (22), 24 (25)-diene] etc.The antitumor drug that has gone on the market is joined a capsule (ginsenoside-Rg
3), the antitumor drug that is being used for clinical and experimental study has ginsenoside-Rh
2And ginsenoside-C-K.
In anticancer experimentation to external various human tumor cell, we find and have invented a kind of new protopanoxadiol derivative with anti-tumor activity, its chemical constitution is 20 (S)-25-methoxyl group-dammarane-3 β, 12 β, 20-triol [20 (S)-25-methoxyl-dammarane-3 β, 12 β, 20-triol is called for short 25mdt].25mdt is the derivant of PPD, but studies have shown that, 25mdt all is better than PPD and ginsenoside-Rg to the inhibitory action of inside and outside tumor cell
3
Summary of the invention:
The invention provides protopanoxadiol saponin aglycone derivative-20 (S)-25-methoxyl group-dammarane-3 β with following structural formula, 12 β, 20-triol [20 (S)-25-methoxyl-dammarane-3 β, 12 β, 20-triol, be called for short 25mdt], anticancer usage and contain the new antitumoral preparation of 25mdt as active component.
A kind of ginsenoside's aglycone derivative 25mdt has inducing tumor cell differentiation, apoptosis, suppresses anti-tumor activities such as growth of tumour cell, and market development and application prospect are huge.
The structural formula of 25mdt
In the new antitumoral preparation provided by the present invention, be effective ingredient with 25mdt, its total effective dose is 1-50mg/kg/d.
In the new antitumoral preparation provided by the present invention, 25mdt can make the preparation of various pharmaceutical dosage forms with any officinal with compounding ingredient and excipient.
In the new antitumoral preparation provided by the present invention, 25mdt can with any chemotherapeutic biological preparation in the market, comprise hormones, alkylating agent class, platinum class, anti-metabolism, topoisomerase enzyme inhibitor class, anti-microfilament microtubule class, induce differentiation class, neoplasm growth class, human body immunity improving class and other medicines, be prepared into compound preparation.
In the new antitumoral preparation provided by the present invention, preparation formulation is oral, injection or local application's dosage form.
In the new antitumoral preparation provided by the present invention, peroral dosage form comprises tablet, powder, suspension, emulsion, capsule, granule, coated tablet, pill, liquid, syrup and limonada etc.
In the new antitumoral preparation provided by the present invention, injection type comprises water preparation, freeze-dried powder, vein emulsion, heterogeneous plasmalogen preparation, venous microemulsion, suspension etc.
In the new antitumoral preparation provided by the present invention, local application's dosage form comprises ointment, solid, suspension, water preparation, powder, paste, suppository, aerosol, paste, liniment, enema and Emulsion etc.
25mdt has inhibition human tumor cells (sarcoma S-180, Louise-lung carcinoma cell, ehrlich carcinoma etc.) growth and propagation, inducing tumor cell differentiation, apoptosis suppress tumor neogenetic blood vessels and generate, suppress invading profit and transfer, enhancing human body immunity power and reducing anti-tumor activities such as toxic and side of tumor.25mdt can be made into to be used for any medicinal and health product dosage form of various cancers treatment, is mainly used in the treatment of malignant tumor, has broad application prospects.
The specific embodiment:
Embodiment 1:25mdt suppresses the experiment of S-180 growth of tumour cell
Laboratory animal, 50 of healthy Kunming kind white mice, body weight 19-24 gram, male, provide by Chinese Medical Sciences University's animal center.All animals all drink water, ingest, keep natural lighting under same environment.25 ℃ of temperature, humidity 60-70%.The animal full-valence pellet feed is provided by Shenyang City's laboratory animal feed factory.
Experiment is divided into 5 groups: A: lotus tumor matched group (ig distilled water 10mL.kg-1); B:25mdt organizes (ig 10mg/Kg/d); C: ginsenoside-Rg3 organizes (ig 10mg/kg/d); D: protopanoxadiol group (ig PPD 10mg/kg/d); E: Western medicine group D (ip paclitaxel 10mg/kg/d).
Chose transplantation tumor 7 days, tumor growth is good, the tangible mice of abdominal tympanites, and inoculation cancerous cell suspension 0.2mL/ is only.Inoculation back mice is divided into into 5 groups at random by body weight, 10 every group, is respectively in the inoculation back and begins administration, every day 1 time, successive administration 12 days next day.Administration finishes next day, and dislocation was put to death after animal was weighed, and separated subcutaneous lump and weighed, and carried out statistical disposition, calculated tumour inhibiting rate.
25mdt sees Table 1 to the influence of S-180 tumor-bearing mice." t " check between statistical procedures method employing group.
Tumour inhibiting rate (%)=[(lotus tumor matched group tumor weight-experimental group tumor is heavy)/lotus tumor matched group tumor is heavy] * 100%
Experimental result shows: with lotus tumor matched group relatively, Western medicine group (ip 20mg.kg-1), 25mdt group (ig50mg.kg-1) all with its there were significant differences P＜0.01.And more also there are significant difference P＜0.05 in ginsenoside-Rg3 group (ig 50mg.kg-1) and protopanoxadiol group (ig 20mg.kg-1) with lotus tumor matched group.
Table 1 25mdt is to the result of S-180 tumor-bearing mice tumor-inhibiting action
Remarks: 1, dosage is 0.1mg/10g; 2, compare * P＜0.01 with lotus tumor matched group.
Embodiment 2:25mdt is to ehrlich carcinoma mice existence influence experiment
Experiment mice was raised 3 days, and it is good to choose growth conditions, and abdominal tympanites is significantly inoculated the mice of 2 all ehrlich carcinomas, and the skin of abdomen sterilization is only given every experiment mice lumbar injection cancerous cell suspension 0.2mL/ under aseptic condition.Inoculation back mice is subleased at random by body weight, is divided into into 5 groups, 10 every group, is respectively in the inoculation back and begins gastric infusion, every day 1 time, successive administration 12 days next day.Observe dead mouse situation and record, 25mdt sees Table 2 to the existence influence of ehrlich carcinoma mice.
Experimental result shows: compare with the ehrlich carcinoma matched group, 25mdt has obvious prolongation effect to the ehrlich carcinoma survival time of mice; PPD has apparent in view prolongation effect to the ehrlich carcinoma survival time of mice; The effect of other groups is not obvious.Illustrate that 25mdt is bigger to the effect that suppresses ehrlich carcinoma.
Table 2 25mdt is to the influence of ehrlich carcinoma survival time of mice
Embodiment 3:25mdt suppresses the Mice Bearing Lewis Lung Cancer growth experiment
Experiment is divided into 5 groups: A: lotus tumor matched group (ig distilled water 10mL.kg-1); B:25md organizes (ig 10mg/Kg/d); C: ginsenoside-kg3 organizes (ig 10mg/kg/d); D: protopanoxadiol group (ig PPD 10mg/kg/d); E: Western medicine group D (ip paclitaxel 10mg/kg/d).
Get the 15th day well-grown Lewis tumor-bearing mice ascites in inoculation back, after Sterile Saline dilution in 1: 3, the right oxter sc inoculation of Kunming mouse forelimb 0.2ml/ only, mice is divided into into 5 groups at random by body weight in the inoculation back, every group 10, be respectively in inoculating back next day and begin administration, every day 1 time, successive administration 12 days.Administration finishes next day, and dislocation was put to death after animal was weighed, and separated subcutaneous lump and weighed, and carried out statistical disposition, calculated tumour inhibiting rate.
25mdt sees Table 3 to the influence of Mice Bearing Lewis Lung Cancer." t " check between statistical procedures method employing group.
Table 3 25mdt is to the result of Mice Bearing Lewis Lung Cancer tumor-inhibiting action
| Group | Dosage (mg/kg) | Number of animals (n) | Tumor heavy (g) | Tumour inhibiting rate (%) |
| A | - | 10 | 2.31± 2.80 | |
| B | 10 | 10 | 1.00± 0.92 | 56.7 |
| C | 10 | 10 | 1.30± 1.73 | 44.8 |
| D | 10 | 10 | 1.33± 2.19 | 41.6 |
| E | 10 | 10 | 1.07± 1.44 | 53.7 |
The preparation of embodiment 4:25mdt tablet
25mdt 40g and lactose 24g, microcrystalline Cellulose 30g, common mistake 80 mesh sieves of carboxymethyl starch sodium 5g of crossing 100 mesh sieves are mixed, with 80% ethanol system soft material, granulate with 18 mesh sieves, 60 ℃ of aeration-dryings, with behind the 18 mesh sieve granulate with 1g magnesium stearate mix homogeneously, charge and attack sheet with Φ 6mm scrobicula, every contains 25mdt 40mg.
Embodiment 5: the preparation of granule
25mdt, mannitol, lactose, stevioside, dextrin pulverize separately are crossed 120 mesh sieves, and divide and to get 300g, 1250g, 100g, 5g, 125g to put stirrer for mixing even, add binding agent, mix and make soft material; Make granule with 14 mesh sieves, drying, granulate, packing.Every bag contains 25mdt 300mg.
Claims (1)
1.20 (S)-and 25-methoxyl group-dammarane-3 β, 12 β, the application of 20-triol in preparation treatment breast carcinoma and lung cancer drugs preparation and health product.
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| CN2006101417633A CN1939311B (en) | 2006-10-01 | 2006-10-01 | Ginseng sapogenin aglycone derivative biological preparation and its usage |
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| CN1939311B true CN1939311B (en) | 2011-07-20 |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101234117B (en) * | 2008-02-20 | 2012-11-07 | 江苏正大天晴药业股份有限公司 | Medical use of a pair of ginseng saponin aglycones and their mixture |
| CN102008493A (en) * | 2010-10-27 | 2011-04-13 | 吉林大学 | Application of panaxadiol saponin in preparing medicines combined with glucocorticoid receptor |
| CN110237080A (en) * | 2018-03-08 | 2019-09-17 | 深圳以诺生物制药有限公司 | Low polarity rare ginsenoside mixture and application thereof |
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2006
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Non-Patent Citations (2)
| Title |
|---|
| M.M.Anisimov etc..A COMPARATIVE STUDY OF THE CYTOTOXIC EFFECT OF DAMMARAN ROW TRITERPENOIDS AND BETULIN ON EARLY EMBRYOGENESIS OF THE SEA URCHIN.《Toxican》.1978, * |
| 封颖璐.人参皂苷与肿瘤.《 国外医学肿瘤学分册》.2005, * |
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