CN103356814A - Chinese medicinal composition, its preparation method and application - Google Patents
Chinese medicinal composition, its preparation method and application Download PDFInfo
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- CN103356814A CN103356814A CN2013103051208A CN201310305120A CN103356814A CN 103356814 A CN103356814 A CN 103356814A CN 2013103051208 A CN2013103051208 A CN 2013103051208A CN 201310305120 A CN201310305120 A CN 201310305120A CN 103356814 A CN103356814 A CN 103356814A
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Abstract
The invention relates to a Chinese medicinal composition, its preparation method and application. The Chinese medicinal composition consists of an Aquilaria sinensis pomegranate peel decocted concentrated extract, an Aquilaria sinensis chloroform extract, a pomegranate peel ethanol extract and pomegranate peel tannin in a ratio of 4-8:3-7:1-2:5-8. The composition provided in the invention has excellent efficacy on cancer chemotherapy related diarrhea and simultaneously has a synergistic effect on cancer chemotherapy.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, relate more specifically to a kind of Chinese medicine composition that is comprised of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L, the preparation method of this Chinese medicine composition and this Chinese medicine composition are for the preparation of reducing the cancer chemotherapy induced diarrhea 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 is alone or unite with the toxicity such as all can cause that the patient suffers from diarrhoea, and diarrhoea is again Chemotherapy-induced Diarrhea behind the chemotherapy of tumors.In recent years emerging and applying along with chemotherapeutics such as 5-fluorouracil, taxanes, hydroxy camptothecin, irinotecan, xeloda etc., the incidence rate of Chemotherapy-induced Diarrhea improves year by year, 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-induced Diarrhea has been become the important component part of tumor patient wholistic therapy.
Chemotherapy-induced Diarrhea is with regard to its clinical manifestation, surely belongs to the Chinese medicine category of " having loose bowels ", and its etiology and pathogenesis mainly is the deficient of body negative and positive of qi and blood due to the spleen injury.Chinese medicine attracts people's attention for the research of having loose bowels, and there is no at present the Chinese patent medicine that the antagonism cancer chemotherapy has 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 the cancer chemotherapy induced diarrhea and playing the chemotherapeutic sensitivity effect that is easy to promote becomes clinical problem demanding prompt solution.
Lignum Aquilariae Resinatum is the Isolated From Thymelaeaceae Species Lignum Aquilariae Resinatum
Aquilaria sinensis(Lour.) the dry stem of Spreng, the property of medicine: bitter, sour, puckery, flat, return lung, large intestine channel; The relieving diarrhea with astringents effect is arranged, and is to control chronic diarrhea; Chronic dysentery; The common medicine of proctoptosis.Pericarpium Granati is the dry peel of Punicaceae plant Punica granatum L. Punica granatum L, the energy relieving diarrhea with astringents; Hemostasis; Anthelmintic; Dysentery.Cure mainly: chronic diarrhea; Chronic dysentery.In recent years, Lignum Aquilariae Resinatum and Pericarpium Granati antitumaous effect are confirmed, the inventor is through research and the experiment of each a large amount of formula proportion, obtained at last optimal drug ratio compositions of the present invention, it is the compositions of novelty, and proved that it has fabulous curative effect and can simultaneously to chemotherapeutic sensitivity, finish thus the present invention the cancer chemotherapy induced diarrhea.
Summary of the invention
A kind of Chinese medicine composition provided by the invention is made of in the ratio of 4-8:3-7:1-2:5-8 by weight Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L.
Above-mentioned Chinese medicine composition, wherein the usage ratio of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L is 8:7:2:8.
Wherein, Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati 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, the preparation method of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract is in the above-mentioned Chinese medicine composition:
Be 1-4 according to proportion compatibility: 1 gets Lignum Aquilariae Resinatum, Pericarpium Granati, distilled water immersion, and heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product.
The preparation method of Lignum Aquilariae Resinatum chloroform extract is in the above-mentioned Chinese medicine composition:
Get the Lignum Aquilariae Resinatum coarse powder, 95% alcohol reflux 3 times, merge extractive liquid, and concentrating under reduced pressure, with the gained crude extract, the suitable quantity of water suspendible is used equal-volume chloroform extraction 3 times, and decompression and solvent recovery namely gets the Lignum Aquilariae Resinatum chloroform extract.
Pericarpium Granati ethanol extraction preparation method is in the above-mentioned Chinese medicine composition:
Dry Pericarpium Granati is pulverized, sieve, 60% alcohol steep 30min, concentrating under reduced pressure after filtering, after the extractum lyophilization light yellow to the yellowish-brown powder, be the Pericarpium Granati ethanol extraction.
The Tannin in Punica granatum L preparation method is in the above-mentioned Chinese medicine composition:
Dry Pericarpium Granati is pulverized, and sieves, and 50% acetone reflux, extract, 2h filters, and filtering residue 50% acetone again reflux, extract, once merges twice extracting solution, rotary evaporation desolventizing, the thick liquid that obtains, pre-freeze 48h in the placement refrigerator, lyophilization and get final product.
The present invention also provides the preferred preparation method of this Chinese medicine composition, comprising:
(1) preparation of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Lignum Aquilariae Resinatum, Pericarpium Granati, distilled water immersion, and heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product.
(2) preparation of Lignum Aquilariae Resinatum chloroform extract
Get the Lignum Aquilariae Resinatum coarse powder, 95% alcohol reflux 3 times, merge extractive liquid, and concentrating under reduced pressure, with the gained crude extract, the suitable quantity of water suspendible is used equal-volume chloroform extraction 3 times, and decompression and solvent recovery namely gets the Lignum Aquilariae Resinatum chloroform extract.
(3) Pericarpium Granati ethanol extraction preparation
Dry Pericarpium Granati is pulverized, sieve, 60% alcohol steep 30min, concentrating under reduced pressure after filtering, after the extractum lyophilization light yellow to the yellowish-brown powder, be the Pericarpium Granati ethanol extraction.
(4) Tannin in Punica granatum L preparation
Dry Pericarpium Granati is pulverized, and sieves, and 50% acetone reflux, extract, 2h filters, and filtering residue 50% acetone again reflux, extract, once merges twice extracting solution, rotary evaporation desolventizing, the thick liquid that obtains, pre-freeze 48h in the placement refrigerator, lyophilization and get final product.
(5) choose in proportion Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L, evenly mix, and get final product.
The preparation method of above-mentioned Chinese medicine composition also comprises: the product that step (5) makes is further made capsule or the tablet that contains Chinese medicine composition 100mg or 200mg specification by the pharmacy means of routine.
The beneficial effect of Chinese medicine composition of the present invention aspect anti-Chemotherapy-induced Diarrhea and inhibition tumor is as follows:
1, Chinese medicine composition of the present invention causes studies show that of diarrhea of mouse model at irinotecan: the diarrhoea reaction for the irinotecan induced mice has obvious antagonism.
2, proved that this Chinese medicine composition can strengthen chemotherapeutics to the inhibitory action of tumor, adopted mouse tumor model, observed this Chinese medicine composition and cyclophosphamide combined to the inhibitory action of mouse interior tumor.Studies show that: this Chinese medicine composition can obviously increase cyclophosphamide for the inhibitory action of tumor.
3, the inventor makes up Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L originally, and determine consumption proportion between these components by great many of experiments, make said composition bring into play good synergism, obtain unexpected effect.Pass through our repeatedly experimentation, ratio between each component of Chinese medicine composition of the present invention has produced unexpected synergism when 4-8:3-7:1-2:5-8, potentiation is obvious, extraordinary effect is played in side effect, especially especially obvious when the usage ratio of each component is 8:7:2:8, 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 Chinese medicine composition Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and each component of Tannin in Punica granatum L all can obtain by conventional means, wherein component such as Tannin in Punica granatum L 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 Chinese medicine 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 Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Lignum Aquilariae Resinatum, Pericarpium Granati, distilled water immersion, and heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product.
(2) preparation of Lignum Aquilariae Resinatum chloroform extract
Get the Lignum Aquilariae Resinatum coarse powder, 95% alcohol reflux 3 times, merge extractive liquid, and concentrating under reduced pressure, with the gained crude extract, the suitable quantity of water suspendible is used equal-volume chloroform extraction 3 times, and decompression and solvent recovery namely gets the Lignum Aquilariae Resinatum chloroform extract.
(3) Pericarpium Granati ethanol extraction preparation
Dry Pericarpium Granati is pulverized, sieve, 60% alcohol steep 30min, concentrating under reduced pressure after filtering, after the extractum lyophilization light yellow to the yellowish-brown powder, be the Pericarpium Granati ethanol extraction.
(4) Tannin in Punica granatum L preparation
Dry Pericarpium Granati is pulverized, and sieves, and 50% acetone reflux, extract, 2h filters, and filtering residue 50% acetone again reflux, extract, once merges twice extracting solution, rotary evaporation desolventizing, the thick liquid that obtains, pre-freeze 48h in the placement refrigerator, lyophilization and get final product.
Second step: the preparation of preparation
(1) preparation of Chinese medicinal composition capsules preparation of the present invention
Take by weighing respectively Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract 32mg, Lignum Aquilariae Resinatum chloroform extract 28mg, Pericarpium Granati ethanol extraction 8mg and the Tannin in Punica granatum L 32mg of above-mentioned steps preparation, take by weighing simultaneously starch 395mg, magnesium stearate 5mg, evenly mix, be filled to capsule.
(2) preparation of Chinese medicine composition tablet of the present invention
Take by weighing respectively Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract 32mg, Lignum Aquilariae Resinatum chloroform extract 28mg, Pericarpium Granati ethanol extraction 8mg and the Tannin in Punica granatum L 32mg of above-mentioned steps preparation, take by weighing simultaneously starch 295mg, lactose 100mg, 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 Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L is 8:7:2:8.Inventor's compositions that the multiple proportioning combination between 4-8:3-7:1-2:5-8 the time obtains to above-mentioned each composition usage ratio carried out with on identical experiment, find that all the Chinese medicine composition in this amount ranges can obtain good synergism, can play good effect and the treatment of cancer is had potentiation the cancer chemotherapy induced diarrhea.Below be the pharmacodynamics data that preferred embodiment obtains:
Test example 1: the pharmacodynamic study of traditional Chinese medicine composition for treating Chemotherapy-induced Diarrhea effect
1, test material
(1) Lignum Aquilariae Resinatum, Pericarpium Granati is purchased from 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 Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract 10g.kg
-1(being equivalent to contain the crude drug amount), the C group is Lignum Aquilariae Resinatum chloroform extract 10g.kg
-1(being equivalent to contain the crude drug amount), D group pomegranate skin ethanol extraction mixes 10g.kg with Tannin in Punica granatum L in the 2:8 ratio
-1(being equivalent to contain the crude drug amount), the E group is Chinese medicine 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 the Chemotherapy-induced Diarrhea model at every day 1 time.B, C, D, E group with corresponding extract gavage 8 days, places metabolic cage with mice continuously, spreads white filter paper at the bottom of the cage observing the stool situation, and observes mice crissum situation and Mus tail fecal pollution situation, and in conjunction with cotton swab stimulation anus defecation, 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: moderate diarrhoea, stool wet and not molding.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, Chinese medicine composition group Incidence of Diarrhea of the present invention obviously alleviates.The results are shown in Table 1.
Table 1 present composition is on mice Chemotherapy-induced Diarrhea incidence rate and scoring impact
Annotate: a is equivalent to contain the crude drug amount
Test example 2: the pharmacodynamic study of Chinese medicine 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).The inoculation next day random packet, experimental group Chinese medicine composition of the present invention is divided into (200,100mg/mL) two dosage groups, every Mus gavage 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
Chinese medicine 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.(such as table 2)
Table 2 Chinese medicine composition of the present invention is to S
180The tumor inhibition effect of mice
Group | Suppression ratio (%) |
Cyclophosphamide | 32.5 |
Compositions is low+cyclophosphamide | 39.6 |
Height+cyclophosphamide | 47.3 |
Claims (5)
1. one kind is reduced the cancer chemotherapy induced diarrhea and the treatment cancer is played the Chinese medicine composition of potentiation, it is characterized in that said composition is made of in the ratio of 4-8:3-7:1-2:5-8 by weight Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L
Wherein the preparation method of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract is:
Be 1-4 according to proportion compatibility: 1 gets Lignum Aquilariae Resinatum, Pericarpium Granati, distilled water immersion, and heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product;
Wherein the preparation method of Lignum Aquilariae Resinatum chloroform extract is:
Get the Lignum Aquilariae Resinatum coarse powder, 95% alcohol reflux 3 times, merge extractive liquid, and concentrating under reduced pressure, with the gained crude extract, the suitable quantity of water suspendible is used equal-volume chloroform extraction 3 times, and decompression and solvent recovery namely gets the Lignum Aquilariae Resinatum chloroform extract;
Wherein the preparation method of Pericarpium Granati ethanol extraction is:
Dry Pericarpium Granati is pulverized, sieve, 60% alcohol steep 30min, concentrating under reduced pressure after filtering, after the extractum lyophilization light yellow to the yellowish-brown powder, be the Pericarpium Granati ethanol extraction;
Wherein the preparation method of Tannin in Punica granatum L is:
Dry Pericarpium Granati is pulverized, and sieves, and 50% acetone reflux, extract, 2h filters, and filtering residue 50% acetone again reflux, extract, once merges twice extracting solution, rotary evaporation desolventizing, the thick liquid that obtains, pre-freeze 48h in the placement refrigerator, lyophilization and get final product.
2. Chinese medicine composition as claimed in claim 1 is characterized in that wherein the usage ratio of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction and Tannin in Punica granatum L is 8:7:2:8.
3. such as the preparation method of the Chinese medicine composition of claim 1 or 2, it is characterized in that the method comprises:
(1) preparation of Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract
Be 1-4 according to proportion compatibility: 1 gets Lignum Aquilariae Resinatum, Pericarpium Granati, distilled water immersion, and heating decocts, and filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product;
(2) preparation of Lignum Aquilariae Resinatum chloroform extract
Get the Lignum Aquilariae Resinatum coarse powder, 95% alcohol reflux 3 times, merge extractive liquid, and concentrating under reduced pressure, with the gained crude extract, the suitable quantity of water suspendible is used equal-volume chloroform extraction 3 times, and decompression and solvent recovery namely gets the Lignum Aquilariae Resinatum chloroform extract;
(3) preparation of Pericarpium Granati ethanol extraction
Dry Pericarpium Granati is pulverized, sieve, 60% alcohol steep 30min, concentrating under reduced pressure after filtering, after the extractum lyophilization light yellow to the yellowish-brown powder, be the Pericarpium Granati ethanol extraction;
(4) preparation of Tannin in Punica granatum L
Dry Pericarpium Granati is pulverized, and sieves, and 50% acetone reflux, extract, 2h filters, and filtering residue 50% acetone again reflux, extract, once merges twice extracting solution, rotary evaporation desolventizing, the thick liquid that obtains, pre-freeze 48h in the placement refrigerator, lyophilization and get final product;
(5) choosing in proportion Lignum Aquilariae Resinatum Pericarpium Granati water boiling concentration extract, Lignum Aquilariae Resinatum chloroform extract, Pericarpium Granati ethanol extraction evenly mixes with Tannin in Punica granatum L, and get final product.
4. the preparation method of Chinese medicine composition as claimed in claim 3 characterized by further comprising: the product that step (5) makes is further made capsule or the tablet that contains Chinese medicine composition 100mg or 200mg specification by the pharmacy means of routine.
5. such as the purposes of each described Chinese medicine composition of claim 1-2 in preparing the medicine that reduces the reaction of cancer chemotherapy induced diarrhea and the treatment cancer is played potentiation.
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