CN103230427A - Traditional Chinese medicine extract and preparation method thereof - Google Patents

Traditional Chinese medicine extract and preparation method thereof Download PDF

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CN103230427A
CN103230427A CN201310132447XA CN201310132447A CN103230427A CN 103230427 A CN103230427 A CN 103230427A CN 201310132447X A CN201310132447X A CN 201310132447XA CN 201310132447 A CN201310132447 A CN 201310132447A CN 103230427 A CN103230427 A CN 103230427A
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preparation
semen raphani
drug composition
natural drug
herba andrographis
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张宗升
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Abstract

The present invention relates to a nature drug composition, a preparation method and uses of the nature drug composition in preparation of attenuation synergism drugs in cancer chemotherapy. The nature drug composition comprises an extract, common andrographis herb lactone and raphanin according to a ratio of 5-9:3-8:2-3, wherein common andrographis herb and garden radish seed are subjected to water decoction concentration to obtain the extract. The composition provides good treatment effects for diarrhea related to cancer chemotherapy, and provides synergism effects for cancer chemotherapy.

Description

A kind of Chinese medicine extract and preparation method thereof
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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide 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.
Herba Andrographis is herb or the leaf of acanthaceous plant Herba Andrographis, and the nature and flavor bitter cold cures mainly damp-heat 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, Herba Andrographis 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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide and raphanin by weight in 5-9: the ratio of 3-8: 2-3 is formed.
Above-mentioned natural drug composition, wherein the usage ratio of Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide and raphanin is 9: 8: 3.
Wherein, Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide, can be by well known to a person skilled in the art the conventional method acquisition of purifying, 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, Herba Andrographis Semen Raphani water boiling concentration preparation method of extract is in the above-mentioned natural drug composition:
Be 1-4 according to proportion compatibility: 1 gets Herba Andrographis, Semen Raphani, distilled water immersion 1h, and heating decocts 1h, and silk filters, preserve filtrate, the medicinal residues adding distil water soaks, decocts, filters with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, and 70 ℃ of drying under reduced pressure, namely.
The preparation method of andrographolide is in the above-mentioned natural drug composition:
It is an amount of to take by weighing Common Andrographis Herd, the enzymolysis pre-treatment, and 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.
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, organic solvent is removed in decompression, residue volume fraction 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 Herba Andrographis Semen Raphani water boiling concentration extract
Be 1: 1 or 1-4 according to proportion compatibility: 1 other ratios are got Herba Andrographis, 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, is Herba Andrographis Semen Raphani water boiling concentration extract.
(2) preparation of andrographolide
It is an amount of to take by weighing Common Andrographis Herd, the enzymolysis pre-treatment, and 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) 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, organic solvent is removed in decompression, residue volume fraction 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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide 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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide 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.Through experimentation repeatedly, ratio between each component of natural drug composition of the present invention is at 5-9: 3-8: produce synergism during 2-3, potentiation is obvious, extraordinary effect is played in side effect, especially the usage ratio of each component be 9: 8: 3 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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide and each component of raphanin all can obtain by conventional means, wherein component also can be buied by commerce as wearing raphanin, 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 Herba Andrographis Semen Raphani water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Herba Andrographis, Semen Raphani, distilled water immersion 1h, and heating decocts 1h, and silk filters, preserve filtrate, the medicinal residues adding distil water soaks, decocts, filters with method, and twice filtrate is mixed, heating is concentrated into small size, ultrafiltration membrance filter, and 70 ℃ of drying under reduced pressure, namely.
(2) preparation of andrographolide
It is an amount of to take by weighing 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, get Ling Jingti and be andrographolide.
(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, organic solvent is removed in decompression, residue volume fraction 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 Herba Andrographis Semen Raphani water boiling concentration extract 45mg, andrographolide 40mg and the raphanin 15mg 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 Herba Andrographis Semen Raphani water boiling concentration extract 45mg, andrographolide 40mg and the raphanin 15mg 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 Semen Raphani water boiling concentration extract, andrographolide and raphanin is 9: 8: 3.The inventor to above-mentioned each composition usage ratio at 5-9: 3-8: the compositions that the multiple proportioning combination in the time of between the 2-3 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) Herba Andrographis, 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 Herba Andrographis Semen Raphani 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 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 Herba Andrographis 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
Figure BSA00000880062900041
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 BSA00000880062900051

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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide and raphanin by weight in 5-9: the ratio of 3-8: 2-3 is formed
Wherein Herba Andrographis Semen Raphani water boiling concentration preparation method of extract is:
Be 1-4 according to proportion compatibility: 1 gets Herba Andrographis, Semen Raphani, distilled water immersion, and heating decocts 1h, and silk filters, preserve filtrate, the medicinal residues adding distil water soaks, decocts, filters with method, and twice filtrate is mixed, heating concentrates, ultrafiltration membrance filter, and 70 ℃ of drying under reduced pressure, namely;
Wherein the preparation method of andrographolide is:
It is an amount of to take by weighing Common Andrographis Herd, the enzymolysis pre-treatment, and 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 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, organic solvent is removed in decompression, residue volume fraction 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 Herba Andrographis Semen Raphani water boiling concentration extract, andrographolide and raphanin is 9: 8: 3.
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 Herba Andrographis Semen Raphani water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Herba Andrographis, Semen Raphani, distilled water immersion, and heating decocts 1h, and silk filters, preserve filtrate, the medicinal residues adding distil water soaks, decocts, filters with method, and twice filtrate is mixed, heating concentrates, ultrafiltration membrance filter, and 70 ℃ of drying under reduced pressure, namely;
(2) preparation of andrographolide
It is an amount of to take by weighing Common Andrographis Herd, the enzymolysis pre-treatment, and 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 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, organic solvent is removed in decompression, residue volume fraction 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 Herba Andrographis Semen Raphani water boiling concentration extract in proportion, andrographolide evenly mixes with raphanin, 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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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103655807A (en) * 2013-12-14 2014-03-26 张宗升 Traditional Chinese medicine composition

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CN103655807A (en) * 2013-12-14 2014-03-26 张宗升 Traditional Chinese medicine composition

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Application publication date: 20130807