CN103263500A - Traditional Chinese medicine extract and preparation method thereof - Google Patents
Traditional Chinese medicine extract and preparation method thereof Download PDFInfo
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- CN103263500A CN103263500A CN2013101737519A CN201310173751A CN103263500A CN 103263500 A CN103263500 A CN 103263500A CN 2013101737519 A CN2013101737519 A CN 2013101737519A CN 201310173751 A CN201310173751 A CN 201310173751A CN 103263500 A CN103263500 A CN 103263500A
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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 hawthorn/radish seed water-decocted concentrated extract, hawthorn total flavone and raphanin in a ratio of (2-5):(3-7):(4-8). The composition has excellent curative effects on diarrhoea related to cancer chemotherapy, and meanwhile, has a synergistic action on 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 Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin, 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, 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.
Fructus Crataegi cures mainly eating accumulation, dysentery.Semen Raphani is the dry mature seed of crucifer Radix Raphani, is used for the treatment of retention of food and drink, abdominal distention, stagnant dysentery.In recent years, Fructus Crataegi and Semen Raphani 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 Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin by weight in 2-5: the ratio of 3-7: 4-8 is formed.
Above-mentioned natural drug composition, wherein the usage ratio of Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin is 5: 7: 8.
Wherein, Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones, can be by well known to a person skilled in the art the conventional method acquisition of purifying, 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, Fructus Crataegi Semen Raphani water boiling concentration preparation method of extract is in the above-mentioned natural drug composition:
Be 1: 1 or 1-4 according to proportion compatibility: 1 other ratios are got Fructus Crataegi, Semen Raphani, 10 times of amount distilled water immersion 1h, heating decocts 1h on the electric furnace that adds asbestos gauge, 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 adopts 70 ℃ of drying under reduced pressure 36h of vacuum drying oven to get pale brown toner end, namely.
The preparation method of Fructus Crataegi total flavones is in the above-mentioned natural drug composition:
Get haw pulp, with 60% alcohol reflux 2 times, each 1.5h, 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 5mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
The raphanin preparation method is in the above-mentioned natural drug composition:
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH7.0, add dichloromethane extraction respectively 3 times, merge solvent, removal of solvent under reduced pressure, residue 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane namely.
The present invention also provides the preferred manufacturing procedure of this natural drug composition, comprising:
(1) preparation of Fructus Crataegi Semen Raphani water boiling concentration extract
Be 1: 1 or 1-4 according to proportion compatibility: 1 other ratios are got Fructus Crataegi, Semen Raphani, 10 times of amount distilled water immersion 1h, heating decocts 1h on the electric furnace that adds asbestos gauge, 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 adopts 70 ℃ of drying under reduced pressure 36h of vacuum drying oven to get pale brown toner end, namely.
(2) preparation of Fructus Crataegi total flavones
Get haw pulp, with 60% alcohol reflux 2 times, each 1.5h, 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 5mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
(3) raphanin preparation
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH7.0, add dichloromethane extraction respectively 3 times, merge solvent, removal of solvent under reduced pressure, residue 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane namely.
(4) choose Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin in proportion, evenly mix, namely.
The preparation method of above-mentioned natural drug composition, also comprise: the product that step (4) 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.
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 Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin originally, and by the consumption proportion between definite these components of a large amount of experiments, makes said composition performance synergism, obtains unexpected effect.Pass through our experimentation repeatedly, ratio between each component of natural drug composition of the present invention is at 2-5: 3-7: produced unexpected synergism during 4-8, potentiation is obvious, extraordinary effect is played in side effect, especially the usage ratio of each component be 5: 7: 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 simply obtain this ratio range and optimum amount ratio by disclosed content.
4, this natural drug composition Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and each component of raphanin 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 Fructus Crataegi Semen Raphani water boiling concentration extract
Be 1: 1 or 1-4 according to proportion compatibility: 1 other ratios are got Fructus Crataegi, Semen Raphani, 10 times of amount distilled water immersion 1h, heating decocts 1h on the electric furnace that adds asbestos gauge, 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 adopts 70 ℃ of drying under reduced pressure 36h of vacuum drying oven to get pale brown toner end, namely.
(2) preparation of Fructus Crataegi total flavones
Get haw pulp, with 60% alcohol reflux 2 times, each 1.5h, 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 5mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely.
(3) raphanin preparation
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH7.0, add dichloromethane extraction respectively 3 times, merge solvent, removal of solvent under reduced pressure, residue 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane namely.
Second step: the preparation of preparation
(1) preparation of natural drug composition capsule preparations of the present invention
Take by weighing Fructus Crataegi Semen Raphani water boiling concentration extract 25mg, Fructus Crataegi total flavones 35mg and the raphanin 40mg 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 Fructus Crataegi Semen Raphani water boiling concentration extract 25mg, Fructus Crataegi total flavones 35mg and the raphanin 40mg 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 Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin is 5: 7: 8.The inventor to above-mentioned each composition usage ratio at 2-5: 3-7: the compositions that the multiple proportioning combination in the time of between the 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) Fructus Crataegi, Semen Raphani
(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 Fructus Crataegi Semen Raphani water boiling concentration extract 10g.kg
-1(being equivalent to contain the crude drug amount), the C group is Fructus Crataegi total flavones 10g.kg
-1(being equivalent to contain the crude drug amount), D group raphanin 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 Fructus Crataegi Semen Raphani 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
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 Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin by weight in 2-5: the ratio of 3-7: 4-8 is formed
Wherein Fructus Crataegi Semen Raphani water boiling concentration preparation method of extract is:
Be 1-4 according to proportion compatibility: 1 gets Fructus Crataegi, Semen Raphani, distilled water immersion, and heating decocts 1h, and silk filters, medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure, namely;
Wherein the preparation method of Fructus Crataegi total flavones is:
Get haw pulp, with 60% alcohol reflux 2 times, each 1.5h, 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 5mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely;
Wherein the preparation method of raphanin is:
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH7.0, add dichloromethane extraction respectively 3 times, merge solvent, removal of solvent under reduced pressure, residue 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane namely.
2. natural drug composition as claimed in claim 1 is characterized in that wherein the usage ratio of Fructus Crataegi Semen Raphani water boiling concentration extract, Fructus Crataegi total flavones and raphanin is 5: 7: 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 Fructus Crataegi Semen Raphani water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Fructus Crataegi, Semen Raphani, distilled water immersion, and heating decocts 1h, and silk filters, medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated into small size, ultrafiltration membrance filter, 70 ℃ of drying under reduced pressure, namely;
(2) preparation of Fructus Crataegi total flavones
Get haw pulp, with 60% alcohol reflux 2 times, each 1.5h, 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 5mL/min, with distilled water flush away impurity, be the mobile phase desorption with ethanol, reclaim ethanol, namely;
(3) preparation of raphanin
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH7.0, add dichloromethane extraction respectively 3 times, merge solvent, removal of solvent under reduced pressure, residue 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane namely;
(4) choose Fructus Crataegi Semen Raphani water boiling concentration extract in proportion, Fructus Crataegi total flavones evenly mixes with raphanin, 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 (4) 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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2013
- 2013-04-16 CN CN2013101737519A patent/CN103263500A/en active Pending
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| CN1367016A (en) * | 2002-02-04 | 2002-09-04 | 苏双喜 | Compound preparation for curing diarrhea |
| CN1698875A (en) * | 2005-06-06 | 2005-11-23 | 姚力 | Medicinal wine for treatment of cancer |
| CN102091315A (en) * | 2011-03-02 | 2011-06-15 | 青岛大学 | Ginger and dark plum fruit composition and preparation method thereof, and application of ginger and dark plum fruit composition in preparation of attenuation and synergy medicaments for radiotherapy and chemotherapy of cancers |
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Application publication date: 20130828 |