CN103340994A - Natural medicine composition, preparation method and application thereof - Google Patents
Natural medicine composition, preparation method and application thereof Download PDFInfo
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- CN103340994A CN103340994A CN2013102931751A CN201310293175A CN103340994A CN 103340994 A CN103340994 A CN 103340994A CN 2013102931751 A CN2013102931751 A CN 2013102931751A CN 201310293175 A CN201310293175 A CN 201310293175A CN 103340994 A CN103340994 A CN 103340994A
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Abstract
The invention relates to a natural medicine composition, and a preparation method and application of the natural medicine composition. The natural medicine composition is prepared from the concentrated extract of the decoction of rhizoma alismatis and hawthorn, alisol B acetate, and crataegin in a proportion of 3-8:2-5:3-7. The composition is extremely good in treatment effect on the diarrhea relevant to cancer chemotherapy and simultaneously has synergistic effect on the cancer chemotherapy.
Description
Technical field
The present invention relates to a kind of natural drug composition, relate more specifically to a kind of natural drug composition of being made up of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones, the preparation method of this natural drug composition and this natural drug composition are being suffered from diarrhoea for the preparation of minimizing cancer chemotherapy dependency and treatment of cancer are being played purposes in the medicine of potentiation.
Background technology
Malignant tumor is current harm humans existence, one of healthy principal disease, and its treatment means comprises operation, chemotherapy, radiotherapy, Chinese medicine, and the effect of chemotherapeutic treatment tumor is particularly outstanding.The chemotherapy prescription with or unite with all can causing toxicities such as patient, diarrhoea, diarrhoea makes the chemotherapy dependency suffer from diarrhoea again behind the chemotherapy of tumors.Emerging and applying along with chemotherapeutics such as 5-fluorouracil, taxanes, hydroxy camptothecin, irinotecan, xeloda etc. in recent years, the incidence rate of chemotherapy dependency diarrhoea improves year by year, and if do not carry out active treatment, easily cause patient's dehydration, malnutrition, serum electrolyte disorder, acid base imbalance etc., it is unfavorable greatly not only the rehabilitation of body to be brought, also bring certain difficulty to CC, therefore effective treatment of chemotherapy dependency diarrhoea has been become the important component part of tumor patient wholistic therapy.
Chemotherapy dependency diarrhoea is with regard to its clinical manifestation, surely belongs to the Chinese medicine category of " having loose bowels ", and Chinese medicine attracts people's attention for the research of having loose bowels, but at present still unmatchful anticancer disease chemotherapy have the Chinese patent medicine of alleviating diarrhoea and potentiation.Therefore, research and develop a kind of high-efficiency low-toxicity, cheap, the natural Chinese medicine that can be used for alleviating cancer chemotherapy dependency diarrhoea and playing the chemotherapeutic sensitivity effect that is easy to promote becomes clinical problem demanding prompt solution.
Rhizoma Alismatis beginning is stated from Shennong's Herbal, classify as top grade, call its " sweet in the mouth, temperature, tonify deficiency win, except cold and heat pathogen, invigorating the spleen and replenishing QI power, longue meat, obey normal hearing and eyesight for a long time.Cure mainly diarrhea due to hypofunction of the spleen; Fructus Crataegi another name Fructus Pyri Pashiae fruit, Rhododendron simsii Planch. fruit, it is long-pending to help digestion; Change the stasis of blood that stagnates.Cure mainly eating accumulation, dysentery.In recent years, Rhizoma Alismatis and Fructus Crataegi antitumaous effect are confirmed, the inventor is through research and the experiment of each a large amount of formula proportion, obtained optimal drug ratio compositions of the present invention at last, it is the compositions of novelty, and proved that it has fabulous curative effect and can finish the present invention thus simultaneously to chemotherapeutic sensitivity cancer chemotherapy dependency diarrhoea.
Summary of the invention
A kind of natural drug composition provided by the invention is made of in the ratio of 3-8:2-5:3-7 by weight Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones.
Above-mentioned natural drug composition, wherein the usage ratio of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones is 8:5:7.
Wherein, Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas can be by well known to a person skilled in the art conventional method acquisitions of purifying, and the natural drug of the present invention that adopts these compositions that conventional method obtains or the one-tenth that adopts commerce to buy to be grouped into all can obtain identical curative effect.
Preferably, Rhizoma Alismatis Fructus Crataegi water boiling concentration preparation method of extract is in the above-mentioned natural drug composition:
Be to get Rhizoma Alismatis, Fructus Crataegi at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating concentrates, ultrafiltration membrance filter, drying under reduced pressure, namely.
The preparation method of Rhizoma Alismatis terpene alcohol B acetas is in the above-mentioned natural drug composition:
With Rhizoma Alismatis coarse powder 80% ethanol percolation, reclaim ethanol to 10%, silicagel column on the oil-like extracts that obtains, after being 10:1 petroleum ether-ethyl acetate eluting with the volumetric ratio, be 10:3 petroleum ether-ethyl acetate eluting again with the ratio of solvent, thin layer chromatography detects, collect fraction, get crystallization, use the petroleum ether-ethyl acetate recrystallization again, namely get Rhizoma Alismatis terpene alcohol B acetas.
The Fructus Crataegi total flavones preparation method is in the above-mentioned natural drug composition:
Get haw pulp, with 60% alcohol reflux 2 times, h l.5 at every turn, merge extractive liquid, reclaims ethanol, gets extractum, and extractum adds an amount of distilled water respectively, stirs evenly, and adds CaCl
21g, standing over night, centrifugal, collect supernatant, transfer pH to 7～8 with ammonia, add in the macroporous adsorptive resins, regulate flow velocity 5 mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
The present invention also provides the preferred manufacturing procedure of this natural drug composition, comprising:
(1) preparation of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract
Be to get Rhizoma Alismatis, Fructus Crataegi at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating concentrates, ultrafiltration membrance filter, drying under reduced pressure, namely.
(2) preparation of Rhizoma Alismatis terpene alcohol B acetas
With Rhizoma Alismatis coarse powder 80% ethanol percolation, reclaim ethanol to 10%, silicagel column on the oil-like extracts that obtains, after being 10:1 petroleum ether-ethyl acetate eluting with the volumetric ratio, be 10:3 petroleum ether-ethyl acetate eluting again with the ratio of solvent, thin layer chromatography detects, collect fraction, get crystallization, use the petroleum ether-ethyl acetate recrystallization again, namely get Rhizoma Alismatis terpene alcohol B acetas.
(3) Fructus Crataegi total flavones preparation
Get haw pulp, with 60% alcohol reflux 2 times, h l.5 at every turn, merge extractive liquid, reclaims ethanol, gets extractum, and extractum adds an amount of distilled water respectively, stirs evenly, and adds CaCl
21g, standing over night, centrifugal, collect supernatant, transfer pH to 7～8 with ammonia, add in the macroporous adsorptive resins, regulate flow velocity 5 mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
(4) choose Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones in proportion, evenly mix, namely.
The preparation method of above-mentioned natural drug composition also comprises: the product that step (4) makes is further made capsule or the tablet that contains natural drug composition 100mg or 200mg specification by the pharmacy means of routine.
The beneficial effect of natural drug composition of the present invention aspect anti-chemotherapy dependency diarrhoea and inhibition tumor is as follows:
1, natural drug composition of the present invention causes the diarrhea of mouse Study of model to show at irinotecan: the diarrhoea reaction for the irinotecan induced mice has tangible antagonism.
2, proved that this natural drug composition can strengthen chemotherapeutics to the inhibitory action of tumor, adopted mouse tumor model, observed this natural drug composition and cyclophosphamide combined to the inhibitory action of mouse interior tumor.Studies show that: this natural drug composition can obviously increase cyclophosphamide for the inhibitory action of tumor.
3, the inventor makes up Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones originally, and by the consumption proportion between definite these components of a large amount of experiments, make said composition bring into play good synergism, obtain unexpected effect.Pass through our experimentation repeatedly, ratio between each component of natural drug composition of the present invention has produced unexpected synergism when 3-8:2-5:3-7, potentiation is obvious, extraordinary effect is played in side effect, especially especially obvious when the usage ratio of each component is 8:5:7, this is that the inventor pays a large amount of creative works and obtains, and those of ordinary skills only can't simply obtain this ratio range and optimum amount ratio by disclosed content.
4, this natural drug composition Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and each component of Fructus Crataegi total flavones all can obtain by conventional means, some of them component for example Fructus Crataegi total flavones also can be buied by commerce, and such compositions itself has the convenience of acquisition, lower-cost effect.This also is the product that has splendid curative effect and higher industrial practicality concurrently that the inventor obtains by a large amount of creative work sides.
The specific embodiment
Further set forth the preparation of natural drug composition of the present invention below by embodiment and test example, with and the beneficial effect in diarrhea and antitumor, used.
Embodiment
The first step: the preparation of various extracts
(1) preparation of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract
Be to get Rhizoma Alismatis, Fructus Crataegi at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating concentrates, ultrafiltration membrance filter, drying under reduced pressure, namely.
(2) preparation of Rhizoma Alismatis terpene alcohol B acetas
With Rhizoma Alismatis coarse powder 80% ethanol percolation, reclaim ethanol to 10%, silicagel column on the oil-like extracts that obtains, after being 10:1 petroleum ether-ethyl acetate eluting with the volumetric ratio, be 10:3 petroleum ether-ethyl acetate eluting again with the ratio of solvent, thin layer chromatography detects, collect fraction, get crystallization, use the petroleum ether-ethyl acetate recrystallization again, namely get Rhizoma Alismatis terpene alcohol B acetas.
(3) Fructus Crataegi total flavones preparation
Get haw pulp, with 60% alcohol reflux 2 times, h l.5 at every turn, merge extractive liquid, reclaims ethanol, gets extractum, and extractum adds an amount of distilled water respectively, stirs evenly, and adds CaCl
21g, standing over night, centrifugal, collect supernatant, transfer pH to 7～8 with ammonia, add in the macroporous adsorptive resins, regulate flow velocity 5 mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
Second step: the preparation of preparation
(1) preparation of natural drug composition capsule preparations of the present invention
Take by weighing Rhizoma Alismatis Fructus Crataegi water boiling concentration extract 40mg, Rhizoma Alismatis terpene alcohol B acetas 25mg and the Fructus Crataegi total flavones 35mg of above-mentioned steps preparation respectively, take by weighing starch 395mg, magnesium stearate 5mg simultaneously, evenly mix, be filled to capsule.
(2) preparation of natural drug composition tablet of the present invention
Take by weighing Rhizoma Alismatis Fructus Crataegi water boiling concentration extract 40mg, Rhizoma Alismatis terpene alcohol B acetas 25mg and the Fructus Crataegi total flavones 35mg of above-mentioned steps preparation respectively, take by weighing starch 295mg, lactose 100mg simultaneously, evenly mix, with wet granulation, drying, mix with the 5mg magnesium stearate behind the granulate, be pressed into tablet.
Drug effect and pharmacology's data:
Compositions is in following test example: the usage ratio of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones is 8:5:7.Inventor's compositions that the multiple proportioning combination between 3-8:2-5:3-7 the time obtains to above-mentioned each composition usage ratio carried out with on identical experiment, find that all the natural drug composition in this amount ranges can obtain good synergism, can play good effect and treatment for cancer is had potentiation cancer chemotherapy dependency diarrhoea.Below be the pharmacodynamics data that preferred embodiment obtains:
Test example 1: the pharmacodynamic study of natural drug composition treatment chemotherapy dependency diarrhoea effect
1, test material
(1) Rhizoma Alismatis, Fructus Crataegi is purchased in medical material market.
(2) mice, male, ad lib drinking-water before the experiment.
2, test method:
Mice is divided into 5 groups at random, and 5 every group, the A group is model group, and the B group is Rhizoma Alismatis Fructus Crataegi water boiling concentration extract 10g.kg
-1(being equivalent to contain the crude drug amount), the C group is Rhizoma Alismatis terpene alcohol B acetas 10g.kg
-1(being equivalent to contain the crude drug amount), D group Fructus Crataegi total flavones 10g.kg
-1(being equivalent to contain the crude drug amount), the E group is natural drug composition 10g.kg of the present invention
-1(being equivalent to contain the crude drug amount), irinotecan intraperitoneal injection (75mg/kg), continuous 4 days, copies chemotherapy dependency diarrhoea model at every day 1 time.B, C, D, E group were irritated stomach 8 days with corresponding extract continuously, and mice is placed metabolic cage, spread white filter paper at the bottom of the cage with observation stool situation, and observed mice crissum situation and Mus tail fecal pollution situation, stimulated the anus defecation in conjunction with cotton swab, and every day, observed and recorded was 2 times.Diarrhoea degree standard scoring is as follows: 0 minute: stool is normal or do not have; 1 minute: laxativeness, stool is visible slight wet soft; 2 minutes: the wet and not molding of moderate diarrhoea, stool.And there is slight crissum painted; 3 minutes, severe diarrhoea, watery stool is also painted with the severe crissum.
3, experimental result
Compare with model group, natural drug composition group diarrhoea incidence rate of the present invention obviously alleviates.The results are shown in Table 1.
Table 1 present composition is to mice chemotherapy dependency diarrhoea incidence rate and scoring influence
Annotate: a is equivalent to contain the crude drug amount
Test example 2: the pharmacodynamic study of natural drug composition antitumor action of the present invention
1, experiment material
(1) Kunming mouse, body weight 20 ± 2g, ad lib drinking-water before the experiment, 24h natural light irradiation.
(2) cyclophosphamide, the permanent auspicious medical Pharmacy stock Co., Ltd in Jiangsu product.
2, test method:
To mice S
180The inhibition test of sarcoma growth
Employing was gone down to posterity 5-7 days, and well-grown milky ascites is diluted to tumor cell suspension with an amount of physiological saline solution, and cell number is 10
7/ mL, 5 every group, the right axillary fossa subcutaneous vaccination of every Mus 0.2mL(contains oncocyte 2 * 10
6Individual).Inoculation random packet next day, experimental group natural drug composition of the present invention is divided into (200,100mg/mL) two dosage groups, every Mus is irritated stomach 0.5 ml, gives cyclophosphamide 10gkg simultaneously
-1D
-1Negative control group gives 0.5 mL distilled water; The positive drug group gives cyclophosphamide 10gkg
-1D
-1, successive administration 10 days.The conventional raising, drinking-water, food is not limit.Drug withdrawal next day, mice all takes off cervical vertebra puts to death, and strips subcutaneous solid tumor tumor piece, weighs, and calculates tumor control rate (%) by following formula:
Tumor control rate=(the average tumor of the matched group average tumor of heavy (C)-experimental group heavy (T))/average tumor of matched group heavy (C)
3, result of the test
Natural drug composition of the present invention is low, high dose group all can strengthen the cyclophosphamide agent with to S
180The effect of inhibition degree, especially the strongest with the high dose group effect.(as table 2)
Table 2 natural drug composition of the present invention is to S
180The tumor inhibition effect of mice
| Group | Suppression ratio (%) |
| Cyclophosphamide | 32.5 |
| Compositions is low+cyclophosphamide | 36.9 |
| Height+cyclophosphamide | 47.8 |
Claims (5)
1. natural drug composition that reduces cancer chemotherapy dependency diarrhoea and the treatment cancer is played potentiation, it is characterized in that said composition is made of in the ratio of 3-8:2-5:3-7 by weight Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones
Wherein Rhizoma Alismatis Fructus Crataegi water boiling concentration preparation method of extract is:
Be to get Rhizoma Alismatis, Fructus Crataegi at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating concentrates, ultrafiltration membrance filter, drying under reduced pressure, namely;
Wherein the preparation method of Rhizoma Alismatis terpene alcohol B acetas is:
With Rhizoma Alismatis coarse powder 80% ethanol percolation, reclaim ethanol to 10%, silicagel column on the oil-like extracts that obtains, after being 10:1 petroleum ether-ethyl acetate eluting with the volumetric ratio, be 10:3 petroleum ether-ethyl acetate eluting again with the ratio of solvent, thin layer chromatography detects, collect fraction, get crystallization, use the petroleum ether-ethyl acetate recrystallization again, namely get Rhizoma Alismatis terpene alcohol B acetas;
Wherein the preparation method of Fructus Crataegi total flavones is:
Get haw pulp, with 60% alcohol reflux 2 times, h l.5 at every turn, merge extractive liquid, reclaims ethanol, gets extractum, and extractum adds an amount of distilled water respectively, stirs evenly, and adds CaCl
21g, standing over night, centrifugal, collect supernatant, transfer pH to 7～8 with ammonia, add in the macroporous adsorptive resins, regulate flow velocity 5 mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
2. natural drug composition as claimed in claim 1 is characterized in that wherein the usage ratio of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas and Fructus Crataegi total flavones is 8:5:7.
3. as the preparation method of the natural drug composition of claim 1 or 2, it is characterized in that this method comprises:
(1) preparation of Rhizoma Alismatis Fructus Crataegi water boiling concentration extract
Be to get Rhizoma Alismatis, Fructus Crataegi at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating concentrates, ultrafiltration membrance filter, drying under reduced pressure, namely;
(2) preparation of Rhizoma Alismatis terpene alcohol B acetas
With Rhizoma Alismatis coarse powder 80% ethanol percolation, reclaim ethanol to 10%, silicagel column on the oil-like extracts that obtains, after being 10:1 petroleum ether-ethyl acetate eluting with the volumetric ratio, be 10:3 petroleum ether-ethyl acetate eluting again with the ratio of solvent, thin layer chromatography detects, collect fraction, get crystallization, use the petroleum ether-ethyl acetate recrystallization again, namely get Rhizoma Alismatis terpene alcohol B acetas;
(3) preparation of Fructus Crataegi total flavones
Get haw pulp, with 60% alcohol reflux 2 times, h l.5 at every turn, merge extractive liquid, reclaims ethanol, gets extractum, and extractum adds an amount of distilled water respectively, stirs evenly, and adds CaCl
21g, standing over night, centrifugal, collect supernatant, transfer pH to 7～8 with ammonia, add in the macroporous adsorptive resins, regulate flow velocity 5 mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely;
(4) choose Rhizoma Alismatis Fructus Crataegi water boiling concentration extract, Rhizoma Alismatis terpene alcohol B acetas in proportion and evenly mix with Fructus Crataegi total flavones, namely.
4. the preparation method of natural drug composition as claimed in claim 3 is characterized in that also comprising: the product that step (4) makes is further made capsule or the tablet that contains natural drug composition 100mg or 200mg specification by the pharmacy means of routine.
5. as the purposes of each described natural drug composition of claim 1-2 in preparing the medicine that reduces the reaction of cancer chemotherapy dependency diarrhoea and the treatment cancer is played potentiation.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103181959A (en) * | 2013-03-27 | 2013-07-03 | 张宗升 | Traditional chinese medicine composition and preparation method thereof |
| CN103191265A (en) * | 2013-03-27 | 2013-07-10 | 张宗升 | Traditional chinese medicine extract and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103181959A (en) * | 2013-03-27 | 2013-07-03 | 张宗升 | Traditional chinese medicine composition and preparation method thereof |
| CN103191265A (en) * | 2013-03-27 | 2013-07-10 | 张宗升 | Traditional chinese medicine extract and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 房玉祥: "中西医结合治疗小儿腹泻86例疗效观察", 《河北中医药学报》 * |
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Application publication date: 20131009 |