CN103263475A - Traditional chinese medicine composition - Google Patents

Traditional chinese medicine composition Download PDF

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CN103263475A
CN103263475A CN2013101737792A CN201310173779A CN103263475A CN 103263475 A CN103263475 A CN 103263475A CN 2013101737792 A CN2013101737792 A CN 2013101737792A CN 201310173779 A CN201310173779 A CN 201310173779A CN 103263475 A CN103263475 A CN 103263475A
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flos caryophylli
galla chinensis
extract
preparation
ethanol
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阚兆云
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Abstract

The invention relates to a natural pharmaceutical composition and a preparation method thereof, and application of the natural pharmaceutical composition in preparation of attenuated synergistic medicines in cancer chemotherapy. The natural pharmaceutical composition is composed of nutgall/clove water-decocted concentrated extract, nutgall acetone extract, clove ethanol extract and eugenol in a ratio of (4-6):(3-6):(2-5):(4-8). The composition has excellent curative effects on diarrhoea related to cancer chemotherapy, and meanwhile, has a synergistic action on cancer chemotherapy.

Description

Chinese medicine composition
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 Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol, the preparation method of this natural drug composition and this natural drug composition 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.The chemotherapy prescription 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 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, electrolyte disturbance, 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.
Galla Chinensis can be astringed the lung, and astringing intestine to stop diarrhea cures mainly the chronic dysentery chronic diarrhea.Flos Caryophylli is alabastrum and the fruit of Myrtaceae syzygium species plant Flos Caryophylli, is used for the treatment of singultus, vomiting and diarrhoea, cures mainly dysentery.In recent years, Galla Chinensis 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, 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, by Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol by weight in 4-6: the ratio of 3-6: 2-5: 4-8 is formed.
Above-mentioned natural drug composition, wherein the usage ratio of Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol is 6: 6: 5: 8.
Wherein, Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction can be by well known to a person skilled in the art the method acquisition of purifying, and the natural drug of the present invention that these compositions that conventional method obtains or the commercial one-tenth of buying are grouped into all can obtain identical curative effect.
Preferably, Galla Chinensis Flos Caryophylli water boiling concentration preparation method of extract is in the above-mentioned natural drug composition:
Be 1-4 according to proportion compatibility: 1 gets Galla Chinensis, Flos Caryophylli, 10 times of amount distilled water immersion 1h, heating decocts 1h, and silk filters, preserve filtrate, medicinal residues add 6 times of distilled water again, soak, decoct, filter with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure of vacuum drying oven, namely.
The preparation method of Galla Chinensis acetone extract is in the above-mentioned natural drug composition:
Galla Chinensis is pulverized, and adds acetone, the water-bath lixiviate, and crude extract filters, and slowly drips 1% CaCl behind the activated carbon decolorizing 2Till no longer producing precipitation, the centrifugal 15min of 10000r/min gets precipitation, drips 0.01mol/L HCl until precipitation dissolving fully, the bag filter of packing into, and dialysis 48h, the rotary evaporation postlyophilization, namely.
Flos Caryophylli ethanol extraction preparation method is in the above-mentioned natural drug composition:
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol 12h filters, and residue continues to soak 12h, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, adds ethyl acetate extraction, and drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely.
The eugenol preparation method is in the above-mentioned natural drug composition:
Flos Caryophylli is pulverized, with the little backflow 30min down that boils of 95% ethanol, filter, filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol, uses the 25mL extracted with diethyl ether 3 times at every turn; The water layer hcl acidifying is transferred pH value of solution=5, uses extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, gets the pale yellow oily liquid body, is eugenol.
The present invention also provides the preferred manufacturing procedure of this natural drug composition, comprising:
(1) preparation of Galla Chinensis Flos Caryophylli water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Galla Chinensis, Flos Caryophylli, 10 times of amount distilled water immersion 1h, heating decocts 1h, and silk filters, preserve filtrate, medicinal residues add 6 times of distilled water again, soak, decoct, filter with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure of vacuum drying oven, namely.
(2) preparation of Galla Chinensis acetone extract
Galla Chinensis is pulverized, and adds acetone, the water-bath lixiviate, and crude extract filters, and slowly drips 1% CaCl behind the activated carbon decolorizing 2Till no longer producing precipitation, the centrifugal 15min of 10000r/min gets precipitation, drips 0.01mol/L HCl until precipitation dissolving fully, the bag filter of packing into, and dialysis 48h, the rotary evaporation postlyophilization, namely.
(3) Flos Caryophylli ethanol extraction preparation
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol 12h filters, and residue continues to soak 12h, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, adds ethyl acetate extraction, and drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely.
(4) eugenol preparation
Flos Caryophylli is pulverized, with the little backflow 30min down that boils of 95% ethanol, filter, filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol, uses the 25mL extracted with diethyl ether 3 times at every turn; The water layer hcl acidifying is transferred pH value of solution=5, uses extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, gets the pale yellow oily liquid body, is eugenol.
(5) choose Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol in proportion, evenly mix, namely.
The preparation method of above-mentioned natural drug composition also comprises: the product that step (5) 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 is originally with Galla Chinensis Flos Caryophylli water boiling concentration extract, the Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol make up, and by definite these amounts of components proportionings of a large amount of experiments, make said composition performance synergism, through experimentation repeatedly, ratio between each component of natural drug composition of the present invention is at 4-6: 3-6: 2-5: produce synergism during 4-8, potentiation is obvious, extraordinary effect is played in side effect, especially the usage ratio in each component is 6: 6: 5: 8 o'clock especially obvious, this is that the inventor pays a large amount of creative works and obtains, and those of ordinary skills only can't obtain this ratio range and optimum amount ratio by disclosed content.
4, this natural drug composition Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and each component of eugenol all can obtain by conventional means, wherein component such as eugenol 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 Galla Chinensis Flos Caryophylli water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Galla Chinensis, Flos Caryophylli, 10 times of amount distilled water immersion 1h, heating decocts 1h, and silk filters, preserve filtrate, medicinal residues add 6 times of distilled water again, soak, decoct, filter with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure of vacuum drying oven, namely.
(2) preparation of Galla Chinensis acetone extract
Galla Chinensis is pulverized, and adds acetone, the water-bath lixiviate, and crude extract filters, and slowly drips 1% CaCl behind the activated carbon decolorizing 2Till no longer producing precipitation, the centrifugal 15min of 10000r/min gets precipitation, drips 0.01mol/L HCl until precipitation dissolving fully, the bag filter of packing into, and dialysis 48h, the rotary evaporation postlyophilization, namely.
(3) Flos Caryophylli ethanol extraction preparation
Get Flos Caryophylli, drying is pulverized, and sieves, and soak with ethanol 12h filters, and residue continues to soak 12h, and twice filtrate is merged, and 3000rpm is centrifugal, separation of supernatant, and ethanol is removed in distillation, adds ethyl acetate extraction, and drying under reduced pressure becomes dry extract again, pulverizes, and sieves, namely.
(4) eugenol preparation
Flos Caryophylli is pulverized, with the little backflow 30min down that boils of 95% ethanol, filter, filtrate is fixed (pH=9~10) with 5% sodium hydroxide, filters, and steams except ethanol, uses the 25mL extracted with diethyl ether 3 times at every turn; The water layer hcl acidifying is transferred pH value of solution=5, uses extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, gets the pale yellow oily liquid body, is eugenol.
Second step: the preparation of preparation
(1) preparation of natural drug composition capsule preparations of the present invention
Take by weighing Galla Chinensis Flos Caryophylli water boiling concentration extract 24mg, Galla Chinensis acetone extract 24mg, Flos Caryophylli ethanol extraction 20mg and the eugenol 32mg of above-mentioned steps preparation respectively, take by weighing starch 395mg, magnesium stearate 5mg, evenly mix, be filled to capsule.
(2) preparation of natural drug composition tablet of the present invention
Take by weighing Galla Chinensis Flos Caryophylli water boiling concentration extract 24mg, Galla Chinensis acetone extract 24mg, Flos Caryophylli ethanol extraction 20mg and the eugenol 32mg of above-mentioned steps preparation respectively, take by weighing starch 295mg, lactose 100mg, evenly mix, 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 Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol is 6: 6: 5: 8.The inventor to above-mentioned each component ratio at 4-6: 3-6: 2-5: the compositions that the multiple proportioning combination between 4-8 obtains has been carried out and last 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) Galla Chinensis, 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 Galla Chinensis Flos Caryophylli water boiling concentration extract 10g.kg -1(being equivalent to contain the crude drug amount), the C group is Galla Chinensis acetone extract 10g.kg -1(being equivalent to contain the crude drug amount), D group Flos Caryophylli ethanol extraction and eugenol were by 5: 8 mixed 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, the degree of Galla Chinensis Flos Caryophylli water boiling concentration extract group chemotherapy dependency diarrhoea is lower than model group, and natural drug composition group of the present invention diarrhoea incidence rate 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 0.5ml, gives cyclophosphamide 10gkg simultaneously -1D -1Negative control group gives 0.5mL 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
Figure BSA00000895227000052

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 by Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol by weight in 4-6: the ratio of 3-6: 2-5: 4-8 is formed
Wherein Galla Chinensis Flos Caryophylli water boiling concentration preparation method of extract is:
Be 1-4 according to proportion compatibility: 1 gets Galla Chinensis, Flos Caryophylli, 10 times of amount distilled water immersion 1h, heating decocts 1h, and silk filters, preserve filtrate, medicinal residues add 6 times of distilled water again, soak, decoct, filter with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure of vacuum drying oven, namely;
Wherein the preparation method of Galla Chinensis acetone extract is:
Galla Chinensis is pulverized, and adds acetone, the water-bath lixiviate, and crude extract filters, and slowly drips 1% CaCl behind the activated carbon decolorizing 2Till no longer producing precipitation, the centrifugal 15min of 10000r/min gets precipitation, drips 0.01mol/L HCl until precipitation dissolving fully, the bag filter of packing into, and dialysis 48h, the rotary evaporation postlyophilization, namely;
Wherein the preparation method of Flos Caryophylli ethanol extraction is:
Get Flos Caryophylli, drying is pulverized, sieve, with 7-10 times of soak with ethanol 12h, cross the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged centrifugal 15 minutes of 3000rpm, separation of supernatant, ethanol and impurity are removed in distillation, add ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverize, cross 100 mesh sieves, namely;
Wherein the preparation method of eugenol is:
Flos Caryophylli is pulverized, with the little backflow 30min down that boils of 95% ethanol, filter, filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol, uses the 25mL extracted with diethyl ether 3 times at every turn; The water layer hcl acidifying is transferred pH value of solution=5, uses extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, gets the pale yellow oily liquid body, is eugenol.
2. natural drug composition as claimed in claim 1 is characterized in that wherein the usage ratio of Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction and eugenol is 6: 6: 5: 8.
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 Galla Chinensis Flos Caryophylli water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Galla Chinensis, Flos Caryophylli, 10 times of amount distilled water immersion 1h, heating decocts 1h, and silk filters, preserve filtrate, medicinal residues add 6 times of distilled water again, soak, decoct, filter with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure of vacuum drying oven, namely;
(2) preparation of Galla Chinensis acetone extract
Galla Chinensis is pulverized, and adds acetone, the water-bath lixiviate, and crude extract filters, and slowly drips 1% CaCl behind the activated carbon decolorizing 2Till no longer producing precipitation, the centrifugal 15min of 10000r/min gets precipitation, drips 0.01mol/L HCl until precipitation dissolving fully, the bag filter of packing into, and dialysis 48h, the rotary evaporation postlyophilization, namely;
(3) preparation of Flos Caryophylli ethanol extraction
Get Flos Caryophylli, drying is pulverized, sieve, with 7-10 times of soak with ethanol 12h, cross the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged centrifugal 15 minutes of 3000rpm, separation of supernatant, ethanol and impurity are removed in distillation, add ethyl acetate extraction, drying under reduced pressure becomes dry extract again, pulverize, cross 100 mesh sieves, namely;
(4) preparation of eugenol
Flos Caryophylli is pulverized, with the little backflow 30min down that boils of 95% ethanol, filter, filtrate is fixed with 5% sodium hydroxide, filters, and steams except ethanol, uses the 25mL extracted with diethyl ether 3 times at every turn; The water layer hcl acidifying is transferred pH value of solution=5, uses extracted with diethyl ether 3 times, and combining extraction liquid is used anhydrous sodium sulfate drying, steams except ether, gets the pale yellow oily liquid body, is eugenol;
(5) choose Galla Chinensis Flos Caryophylli water boiling concentration extract, Galla Chinensis acetone extract, Flos Caryophylli ethanol extraction in proportion and evenly mix with eugenol, namely.
4. the preparation method of natural drug composition as claimed in claim 3, it is characterized in that also comprising: the product that step (5) makes is further made the capsule that contains natural drug composition 100mg or 200mg specification by the pharmacy means of routine, maybe will make the tablet that contains natural drug composition 100mg or 200mg specification by wet granulation technology.
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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CN103655713A (en) * 2013-12-14 2014-03-26 张宗升 Natural medicine composition

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CN103655862A (en) * 2013-12-14 2014-03-26 张宗升 Natural pharmaceutical composition as well as preparation method and application thereof
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Application publication date: 20130828