CN103340929A - Natural drug extract - Google Patents
Natural drug extract Download PDFInfo
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- CN103340929A CN103340929A CN2013102909372A CN201310290937A CN103340929A CN 103340929 A CN103340929 A CN 103340929A CN 2013102909372 A CN2013102909372 A CN 2013102909372A CN 201310290937 A CN201310290937 A CN 201310290937A CN 103340929 A CN103340929 A CN 103340929A
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Abstract
The invention relates to a natural drug extract. The natural drug extract consists of an extract prepared by decocting and concentrating common andrographis herb and clove in water, common andrographis herb lactone extract, clove ethanol extract and eugenol by a ratio of (4-6):(3-6):(2-4):(6-9). The composition has an extremely good treatment effect on diarrhea related with cancer chemotherapy and also has a synergism effect on cancer chemotherapy.
Description
Technical field
The present invention relates to a kind of natural drug extract, relate more specifically to a kind of natural drug extract of being made up of Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol, this natural drug preparation method of extract and this natural drug extract are for the preparation of reducing cancer chemotherapy dependency diarrhoea and treatment of cancer 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.Chemotherapeutic no matter singly with or unite with toxicity such as all can cause that the patient suffers from 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.
Herba Andrographis is acanthaceous plant Herba Andrographis (Andrographis paniculata(Burm.f.) Nees) herb or leaf, the nature and flavor bitter cold cures mainly damp-heat dysentery.Flos Caryophylli is alabastrum and the fruit of Myrtaceae syzygium species plant Flos Caryophylli Eugenia caryophyllata Thunb.The energy warming the stomach, the kidney warming.Be used for the treatment of singultus, vomiting and diarrhoea, cure mainly dysentery.In recent years, Herba Andrographis and Flos Caryophylli 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 extract provided by the invention is made of in the ratio of 4-6:3-6:2-4:6-9 by weight Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol.
Above-mentioned natural drug extract, wherein the usage ratio of Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol is 6:6:4:9.
Wherein, Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction can be by well known to a person skilled in the art the conventional method acquisition of purifying, and adopt these compositions that conventional method obtains or the natural drug of the present invention that adopts the commercial one-tenth of buying to be grouped into all can obtain identical curative effect.
Preferably, Herba Andrographis Flos Caryophylli water boiling concentration preparation method of extract is in the above-mentioned natural drug extract:
Be to get Herba Andrographis, Flos Caryophylli at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and silk 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 andrographolide is in the above-mentioned natural drug extract:
Get Common Andrographis Herd, the enzymolysis pre-treatment, the ethanol hot dipping is filtered, recovery ethanol, get extractum, wash with petroleum ether, remove chlorophyll, water layer is spent the night with chloroform extraction, be divided into water layer, chloroform layer and intermediate layer, with intermediate layer precipitate ethyl alcohol recrystallization, namely.
Flos Caryophylli ethanol extraction preparation method is in the above-mentioned natural drug extract:
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol is filtered, and residue continues to soak, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely.
The eugenol preparation method is in the above-mentioned natural drug extract:
Flos Caryophylli is pulverized, and the little backflow 30min down that boils of 95% ethanol filters, and filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol extracted with diethyl ether 3 times; The water layer hcl acidifying is transferred pH value of solution=5, extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, namely.
The present invention also provides the preferred manufacturing procedure of this natural drug extract, comprising:
(1) preparation of Herba Andrographis Flos Caryophylli water boiling concentration extract
Be to get Herba Andrographis, Flos Caryophylli at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and silk 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 andrographolide
Get Common Andrographis Herd, the enzymolysis pre-treatment, the ethanol hot dipping is filtered, recovery ethanol, get extractum, wash with petroleum ether, remove chlorophyll, water layer is spent the night with chloroform extraction, be divided into water layer, chloroform layer and intermediate layer, with intermediate layer precipitate ethyl alcohol recrystallization, namely.
(3) Flos Caryophylli ethanol extraction preparation
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol is filtered, and residue continues to soak, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely.
(4) eugenol preparation
Flos Caryophylli is pulverized, and the little backflow 30min down that boils of 95% ethanol filters, and filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol extracted with diethyl ether 3 times; The water layer hcl acidifying is transferred pH value of solution=5, extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, namely.
(5) choose Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol in proportion, evenly mix, namely.
Above-mentioned natural drug preparation method of extract, also comprise: the product that step (5) makes is further made the capsule that contains natural drug extract 100mg or 200mg specification by the pharmacy means of routine, maybe will make the tablet that contains natural drug extract 100mg or 200mg specification by wet granulation technology.
The beneficial effect of natural drug extract of the present invention aspect anti-chemotherapy dependency diarrhoea and inhibition tumor is as follows:
1, natural drug extract 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 extract can strengthen chemotherapeutics to the inhibitory action of tumor, adopted mouse tumor model, observed this natural drug extract and cyclophosphamide combined to the inhibitory action of mouse interior tumor.Studies show that: this natural drug extract can obviously increase cyclophosphamide for the inhibitory action of tumor.
3, the inventor makes up Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol 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 extract of the present invention has produced unexpected synergism when 4-6:3-6:2-4:6-9, potentiation is obvious, extraordinary effect is played in side effect, especially especially obvious when the usage ratio of each component is 6:6:4:9, 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 extract Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and each component of eugenol all can obtain by conventional means, some of them component for example andrographolide 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 extract 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 Herba Andrographis Flos Caryophylli water boiling concentration extract
Be to get Herba Andrographis, Flos Caryophylli at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and silk 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 andrographolide
Get Common Andrographis Herd, the enzymolysis pre-treatment, the ethanol hot dipping is filtered, recovery ethanol, get extractum, wash with petroleum ether, remove chlorophyll, water layer is spent the night with chloroform extraction, be divided into water layer, chloroform layer and intermediate layer, with intermediate layer precipitate ethyl alcohol recrystallization, namely.
(3) Flos Caryophylli ethanol extraction preparation
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol is filtered, and residue continues to soak, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely.
(4) eugenol preparation
Flos Caryophylli is pulverized, and the little backflow 30min down that boils of 95% ethanol filters, and filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol extracted with diethyl ether 3 times; The water layer hcl acidifying is transferred pH value of solution=5, extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, namely.
Second step: the preparation of preparation
(1) preparation of natural drug extract capsule preparation of the present invention
Take by weighing Herba Andrographis Flos Caryophylli water boiling concentration extract 24mg, andrographolide 24mg, Flos Caryophylli ethanol extraction 16mg and the eugenol 36mg 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 extract tablet of the present invention
Take by weighing Herba Andrographis Flos Caryophylli water boiling concentration extract 24mg, andrographolide 24mg, Flos Caryophylli ethanol extraction 16mg and the eugenol 36mg 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 Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol is 6:6:4:9.Inventor's compositions that the multiple proportioning combination between 4-6:3-6:2-4:6-9 the time obtains to above-mentioned each composition usage ratio carried out with on identical experiment, find that all the natural drug extract 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 extract for treating chemotherapy dependency diarrhoea effect
1, test material
(1) Herba Andrographis, Flos Caryophylli 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 Herba Andrographis Flos Caryophylli water boiling concentration extract 10g.kg
-1(being equivalent to contain the crude drug amount), the C group is andrographolide 10g.kg
-1(being equivalent to contain the crude drug amount), D group Flos Caryophylli ethanol extraction mixes 10g.kg with eugenol in the 4:9 ratio
-1(being equivalent to contain the crude drug amount), the E group is natural drug extract 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 extract 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 extract 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 extract 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 extract 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 extract of the present invention is to S
180The tumor inhibition effect of mice
| Group | Suppression ratio (%) |
| Cyclophosphamide | 32.5 |
| Compositions is low+cyclophosphamide | 42.8 |
| Height+cyclophosphamide | 51.3 |
Claims (5)
1. natural drug extract 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 4-6:3-6:2-4:6-9 by weight Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol
Wherein Herba Andrographis Flos Caryophylli water boiling concentration preparation method of extract is:
Be to get Herba Andrographis, Flos Caryophylli at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and silk 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 andrographolide is:
Get Common Andrographis Herd, the enzymolysis pre-treatment, the ethanol hot dipping is filtered, recovery ethanol, get extractum, wash with petroleum ether, remove chlorophyll, water layer is spent the night with chloroform extraction, be divided into water layer, chloroform layer and intermediate layer, with intermediate layer precipitate ethyl alcohol recrystallization, namely;
Wherein the preparation method of Flos Caryophylli ethanol extraction is:
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol is filtered, and residue continues to soak, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely;
Wherein the preparation method of eugenol is:
Flos Caryophylli is pulverized, and the little backflow 30min down that boils of 95% ethanol filters, and filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol extracted with diethyl ether 3 times; The water layer hcl acidifying is transferred pH value of solution=5, extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, namely.
2. natural drug extract as claimed in claim 1 is characterized in that wherein the usage ratio of Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction and eugenol is 6:6:4:9.
3. as the natural drug preparation method of extract of claim 1 or 2, it is characterized in that this method comprises:
(1) preparation of Herba Andrographis Flos Caryophylli water boiling concentration extract
Be to get Herba Andrographis, Flos Caryophylli at 1: 1 according to proportion compatibility, distilled water immersion, heating decocts, and silk 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 andrographolide
Get Common Andrographis Herd, the enzymolysis pre-treatment, the ethanol hot dipping is filtered, recovery ethanol, get extractum, wash with petroleum ether, remove chlorophyll, water layer is spent the night with chloroform extraction, be divided into water layer, chloroform layer and intermediate layer, with intermediate layer precipitate ethyl alcohol recrystallization, namely;
(3) preparation of Flos Caryophylli ethanol extraction
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol is filtered, and residue continues to soak, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely;
(4) preparation of eugenol
Flos Caryophylli is pulverized, and the little backflow 30min down that boils of 95% ethanol filters, and filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol extracted with diethyl ether 3 times; The water layer hcl acidifying is transferred pH value of solution=5, extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, namely;
(5) choose Herba Andrographis Flos Caryophylli water boiling concentration extract, andrographolide, Flos Caryophylli ethanol extraction in proportion and evenly mix with eugenol, namely.
4. natural drug preparation method of extract as claimed in claim 3 is characterized in that also comprising: the product that step (5) makes is further made capsule or the tablet that contains natural drug extract 100mg or 200mg specification by the pharmacy means of routine.
5. as the purposes of each described natural drug extract 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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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103655720A (en) * | 2013-12-14 | 2014-03-26 | 张宗升 | Natural medicine composition and preparation method thereof |
| CN103655933A (en) * | 2013-12-14 | 2014-03-26 | 张宗升 | Traditional Chinese medicine composition as well as preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103191201A (en) * | 2013-03-27 | 2013-07-10 | 张宗升 | Traditional chinese medicine composition and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103191201A (en) * | 2013-03-27 | 2013-07-10 | 张宗升 | Traditional chinese medicine composition and preparation method thereof |
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| 张明发等: "丁香温经止痛和温中止泻药理研究", 《中药材》 * |
| 杜毅等: "荜茇化学成分与药理作用研究概况", 《中国中医药科技》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103655720A (en) * | 2013-12-14 | 2014-03-26 | 张宗升 | Natural medicine composition and preparation method thereof |
| CN103655933A (en) * | 2013-12-14 | 2014-03-26 | 张宗升 | Traditional Chinese medicine composition as well as preparation method and application thereof |
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Application publication date: 20131009 |