CN101322825A - Medicament composition for treating malignant tumour - Google Patents
Medicament composition for treating malignant tumour Download PDFInfo
- Publication number
- CN101322825A CN101322825A CNA2007101111533A CN200710111153A CN101322825A CN 101322825 A CN101322825 A CN 101322825A CN A2007101111533 A CNA2007101111533 A CN A2007101111533A CN 200710111153 A CN200710111153 A CN 200710111153A CN 101322825 A CN101322825 A CN 101322825A
- Authority
- CN
- China
- Prior art keywords
- rhizoma
- extract
- pharmaceutical composition
- tablet
- pill
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a drug combination used for curing and/or preventing malignant tumor, in particular to an oral drug combination used for curing and/or preventing the malignant tumor. The drug combination comprises Chinese rhubarb, the rhizome of Chinese goldthread, turmeric, loosestrife, oriental waterplantain rhizome and zedoray rhizome. The best drug effect can be realized by effectively reducing the serum copper level and increasing the proportions of zinc and copper of sufferers who suffers from the malignant tumor and restraining the generation of the blood vessels of the malignant tumor. The invention also relates to the application of the drug combination which takes the Chinese rhubarb, the rhizome of Chinese goldthread, the turmeric, the loosestrife, the oriental waterplantain rhizome and the zedoray rhizome as main ingredients in curing and/or preventing the malignant tumor.
Description
Technical field:
The present invention relates to prepare a kind of pharmaceutical composition that is used for the treatment of malignant tumor.This pharmaceutical composition comprises Radix Et Rhizoma Rhei, Rhizoma Coptidis, Rhizoma Curcumae Longae, Herba Lysimachiae, Rhizoma Alismatis, Rhizoma Curcumae.This pharmaceutical composition can be tablet, pill, capsule, powder, granule, injection and/or oral liquid.
Background of invention:
Malignant tumor is the disease of common but severe harm humans health.20 th century later, academia confirm: the generation of malignant tumor, evolution are unusual with copper zinc content in the body.Case control study shows: compare with normal person and non-malignant patient, copper level significantly increases in the malignant tumor patient body, and zinc level significantly reduces, and copper zinc ratio increases.In clinical practice, mensuration serum copper zinc content has certain value to the diagnosis of malignant tumor.But since do not have clear and definite copper zinc content unusually in malignant tumor effect in development and the transfer process takes place, before 2000, the medicinal application that this area academia also will not influence copper zinc content is in the treating and/or preventing of malignant tumor.
In clinical practice, anti-copper medicine is used for the treatment of a kind of non-malignant tumors disease---hepatolenticular degeneration of copper Developmental and Metabolic Disorder, and is not applied to the report of the treatment and the prevention of malignant tumor.2000, American scholar found that by animal model the anti-copper medicine Tetrathiomolybdate (TM) of treatment hepatolenticular degeneration can suppress the new vessels generative process, and the research has caused the concern of this area academia.The research prompting, anti-copper medicine may generate by the new vessels that suppresses malignant tumor and reach the generation evolution that suppresses malignant tumor.
The research of this area is verified, and malignant tumor self must possess and starts and promote the ability that new vessels generates, with the metabolism that satisfies self and the needs of nutrient substance supply.If there is not angiogenesis, the growth of primary tumo(u)r can not surpass 1～2mm, can not occur soaking into and shifting yet.Suppress tumor-blood-vessel growth, closely related with generation, development, infiltration and the transfer of blocking-up tumor.Suppress tumor-blood-vessel growth, also the generation of tumor capable of blocking and prevention precancerous lesion are to the pernicious transformation of cancer.The not only growth of entity tumor, infiltration and transfer rely on new vessels and generate, and the growth of blood system malignant tumor (as malignant lymphoma, Lymphocytic leukemia etc.) and transfer are also closely related with angiogenesis.Growth of tumor, transfer, recurrence, prognosis and angiogenesis are closely related, are target spot with the angiogenesis of tumor, and the exploitation angiogenesis inhibitor is the research focus in oncotherapy field over nearly 20 years.Angiogenesis inhibitor not only can be used for the treatment of most of entity tumors, also can be used for the prevention of cancer and the treatment of blood system malignant tumor.The malignant tumor angiogenesis promotes that with multiple angiogenesis the factor is relevant, and the many targeting of angiogenesis inhibitor promote the factor and receptor, perhaps its cofactor in angiogenesis.
From a series of up-to-date studies show that of beginning in 2000, copper is that most of angiogenesis promote the factor, concretely, the synthetic trace elements necessary that comprises VEGF (VEGF), epidermal growth factor (EGF), fiber mother cell growth factor (FGF), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin 8 (IL-8).Therefore, anti-copper medicine can suppress the synthetic of the angiogenesis promotion factor, thereby suppresses the angiogenesis of malignant tumor, and then suppresses the generation development and the transfer of malignant tumor.
The inventor has finished the present invention according to above-mentioned theory.The inventor confirms that at cellular level pharmaceutical composition involved in the present invention can reduce malignant cell copper content effectively by embodiment 2, increases zinc level, reduces copper/zinc ratio; Confirm that by embodiment 3 pharmaceutical composition involved in the present invention can suppress vascular endothelial cell in-vitro multiplication, migration and pipe effectively and form ability; By embodiment 4 in animal body level confirm that pharmaceutical composition involved in the present invention can suppress the growth and the angiogenesis of malignant tumor effectively; Confirm that by embodiment 5 pharmaceutical composition involved in the present invention can increase the drainage of malignant tumor patient copper effectively, reduce the malignant tumor patient SCL, increase the serum zinc level, reduce serum copper zinc ratio, suppress the malignant tumor angiogenesis effectively, reach the purpose of treatment malignant tumor.
Summary of the invention:
The invention provides a kind of pharmaceutical composition that treats and/or prevents malignant tumor, described compositions main component comprises Radix Et Rhizoma Rhei, Rhizoma Coptidis, Rhizoma Curcumae Longae, Herba Lysimachiae, Rhizoma Alismatis, Rhizoma Curcumae.
The application of pharmaceutical composition in treating and/or preventing malignant tumor that the present invention also provides main component to comprise Radix Et Rhizoma Rhei, Rhizoma Coptidis, Rhizoma Curcumae Longae, Herba Lysimachiae, Rhizoma Alismatis, Rhizoma Curcumae.
The medicine of the present invention's preparation can be made into multiple dosage forms such as tablet, pill, capsule powder, granule, oral liquid, unguentum, cream, injection.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.Preferably tablet, pill, capsule, powder, granule are more preferably tablet, pill, capsule.
Also can add one or more pharmaceutically acceptable carriers in the described pharmaceutical composition.Described carrier comprise the pharmaceutical field routine diluent, filler, excipient, binding agent, wetting agent, collapse and release agent, absorption enhancer, surfactant, absorption carrier, lubricant, antiseptic etc., add flavouring agent, sweeting agent etc. in case of necessity.
The route of administration of described compositions can be oral administration, intramuscular administration, intravenous administration, percutaneous dosing.Oral administration preferably.
Described Radix Et Rhizoma Rhei is meant any type of material medicines such as the Radix Et Rhizoma Rhei crude drug, fecula, decoction pieces, Radix Et Rhizoma Rhei crude extract, emodin extract, chrysophanic acid extract of the dry root and rhizome of polygonum rheum palmatum, Rheum tanguticum or Rheum officinale and preparation thereof.Be preferably Radix Et Rhizoma Rhei crude extract, emodin extract, chrysophanic acid extract, more preferably the emodin extract.
Described Rhizoma Coptidis is meant Ranunculaceae herbaceos perennial Rhizoma Coptidis (flavor connect), Coptis deltoidea C.Y.Cheng et Hsiao (refined company). or any type of material medicines such as the Rhizoma Coptidis crude drug of the dry root and rhizome of Coptis Teeta Wall C and preparation thereof, fecula, decoction pieces, Rhizoma Coptidis extract, berberine extract.Be preferably Rhizoma Coptidis extract, berberine extract, more preferably the berberine extract.
Described Rhizoma Curcumae Longae is meant any type of material medicines such as the Rhizoma Curcumae Longae crude drug, fecula, decoction pieces, Rhizoma Curcumae Longae extract, curcumin extraction of zingiberaceous plant Rhizoma Curcumae Longae rhizome and preparation thereof.Be preferably Rhizoma Curcumae Longae extract, curcumin extraction, more preferably curcumin extraction.
Described Herba Lysimachiae is meant any type of material medicines such as the Herba Lysimachiae crude drug, fecula, decoction pieces, Herba Lysimachiae extract of the herb of Primulaceae perennial herb prey Lysimachia christinae Hance (Lysimachia christinae Hance) and preparation thereof.Be preferably Herba Lysimachiae extract.
Described Rhizoma Alismatis is meant any type of material medicines such as the Rhizoma Alismatis crude drug, fecula, decoction pieces, Rhizoma Alismatis extract, Rhizoma Alismatis steroidal extract, Rhizoma Alismatis total triterpenes extract of the dry tuber of Alismataceae plant Rhizoma Alismatis and preparation thereof.Be preferably Rhizoma Alismatis extract, Rhizoma Alismatis steroidal extract, Rhizoma Alismatis total triterpenes extract, more preferably the Rhizoma Alismatis total triterpenes extract.
Described Rhizoma Curcumae is meant any type of material medicines such as the Rhizoma Curcumae crude drug, fecula, decoction pieces, Rhizoma Curcumae extract of the dry rhizome of zingiberaceous plant Rhizoma Curcumae, Radix Curcumae or Guangxi zedoary and preparation thereof.Be preferably Rhizoma Curcumae extract.
It is being used for the treatment of of effective ingredient and/or the tablet that prevents malignant tumor, pill, capsular preparation method that the present invention also provides with above described Radix Et Rhizoma Rhei, Rhizoma Coptidis, Rhizoma Curcumae Longae, Herba Lysimachiae, Rhizoma Alismatis, Rhizoma Curcumae.
The component of described compositions and parts by weight are: Radix Et Rhizoma Rhei 5-10 Rhizoma Coptidis 5-10 Rhizoma Curcumae Longae 5-10 Herba Lysimachiae 10-20 Rhizoma Alismatis 5-10 Rhizoma Curcumae 5-10.Be preferably: Radix Et Rhizoma Rhei 6 Rhizoma Coptidis 6 Rhizoma Curcumae Longaes 9 Herba Lysimachiaes 15 Rhizoma Alismatis 5 Rhizoma Curcumae 9.
Described tablet, pill, capsule are to be prepared from by the following method: get Radix Et Rhizoma Rhei 6g Rhizoma Coptidis 6g Rhizoma Curcumae Longae 9g Herba Lysimachiae 15g Rhizoma Alismatis 5g Rhizoma Curcumae 9g, Rhizoma Alismatis, Herba Lysimachiae, Rhizoma Curcumae Longae, Rhizoma Curcumae and Radix Et Rhizoma Rhei (3g) water is decocted twice, filter the rear filtrate standing over night, be condensed into thick extractum, again Rhizoma Coptidis 6g and residue Radix Et Rhizoma Rhei (3g) are pulverized and above-mentioned extractum mixing, add appropriate amount of auxiliary materials and granulate.Formulation method prepares tablet, pill and capsule routinely.
Described tablet, pill, capsule can also be prepared from by the following method: with emodin extract 0.25g berberine extract 0.25g curcumin extraction 0.25g Herba Lysimachiae extract 0.625g Rhizoma Alismatis total triterpenes extract 0.625g Rhizoma Curcumae extract 0.625g mixing, add appropriate amount of auxiliary materials and granulate.Formulation method prepares tablet, pill and capsule routinely.
Described tablet, pill and capsular specification are every 0.3 gram-1.0 grams, are preferably 0.5 gram.
Described tablet, pill and capsular every day dosage be the 3-5 gram.
The accompanying drawing summary:
Fig. 1: pastille serum is handled the optical microscope photograph that the human vascular endothelial cell pipe in back forms.
Fig. 2: pastille serum is handled the human migration of vascular endothelial cells result's in back optical microscope photograph.
Fig. 3: the inhibition curve of 1 pair of transplanted tumor in nude mice growth of Chinese medicinal tablet provided by the present invention
Fig. 4: 2 pairs of nude mices of Chinese medicinal tablet provided by the present invention are transplanted the inhibition curve of growth of colorectal carcinoma
Fig. 5: Chinese medicinal tablet provided by the present invention is transplanted the colorectal cancer therapeutic effect to nude mice and to the influence of microvessel density
Detailed Description Of The Invention:
The invention provides a kind of pharmaceutical composition that treats and/or prevents malignant tumour, described composition main component comprises rheum officinale, the coptis, turmeric, desmodium, rhizoma alismatis, curcuma zedoary and relative medicine carrier.
Described composition further comprises carrier, excipient etc., further can also comprise at present existing be used for the treatment of malignant tumour etc.
The method of administration of described composition can be administration in topical, oral administration, the muscle, intravenous administration, percutaneous dosing. Oral administration preferably.
According to used method of administration, above-mentioned composition can be carried out administration with various pharmaceutically useful forms. For example, pharmaceutical composition of the present invention can be used with the form of solid, solution, emulsion, dispersion, protomere, liposome etc., wherein, contain the rheum officinale, the coptis, the turmeric that are useful on the present invention's practice in the composition that obtains, desmodium, rhizoma alismatis, curcuma zedoary is as its active component, other form that active component and for example conventional nontoxic pharmaceutically suitable carrier can be mixed and made into tablet, micropill, capsule, suppository, solution, emulsion, suspension and be suitable for using. Spendable carrier comprises that the triglycerides, glucan of glucose, lactose, Arabic gum, gelatin, mannitol, gelatinized corn starch, magnesium trisilicate, talcum, cornstarch, keratin, colloidal silica, potato starch, urea, medium chain and other are applicable to the carrier of solid, semisolid or liquid form that preparation produces. In addition, also can use auxiliary material, stabilizing agent, thickener, colouring agent, anticorrisive agent and spices. Proof carrier used in the invention process is. The content of active component is the amount that is enough to produce required effect in disease to be treated in the pharmaceutical composition.
Described rheum officinale refers to any type of material medicines such as the rheum officinale crude drug, fecula, medicine materical crude slice, rheum officinale CE, archen extract, Rhein extract of the dry root and rhizome of the ancient especially big Huang of polygonum rheum palmatum, Tang or Rheum officinale and preparation thereof. Be preferably rheum officinale CE, archen extract, Rhein extract, more preferably the archen extract. Used proof rheum officinale is rheum officinale crude drug and archen extract in the invention process.
The described coptis refers to the Ranunculaceae herbaceos perennial coptis (flavor connect), the triangle leaf coptis (refined company). or cloud connects any type of material medicines such as the coptis crude drug, fecula, medicine materical crude slice, coptis extract, berberine extract of the dry root and rhizome of C and preparation thereof. Be preferably coptis extract, berberine extract, more preferably the berberine extract. The used proof coptis is coptis crude drug and berberine extract in the invention process.
Described turmeric refers to any type of material medicines such as the turmeric crude drug, fecula, medicine materical crude slice, Turmeric P.E, curcumin extraction of the rhizome of zingiberaceous plant turmeric and preparation thereof. Be preferably Turmeric P.E, curcumin extraction, more preferably curcumin extraction. Proof turmeric used in the invention process is turmeric crude drug and curcumin extraction.
Described desmodium refers to any type of material medicines such as the desmodium crude drug, fecula, medicine materical crude slice, Herba Lysimachiae extract of the herb of Primulaceae perennial herb prey Lysimachia christinae (Lysimachia christinae Hance) and preparation thereof. Be preferably Herba Lysimachiae extract. Proof desmodium used in the invention process is desmodium crude drug and Herba Lysimachiae extract.
Described rhizoma alismatis refers to any type of material medicines such as the rhizoma alismatis crude drug, fecula, medicine materical crude slice, Alisma extract, rhizoma alismatis steroidal extract, Rhizoma alismatis total triterpene alcohol extract of the dry tuber of Notes On Alism At Aceae rhizoma alismatis and preparation thereof. Be preferably Alisma extract, rhizoma alismatis steroidal extract, Rhizoma alismatis total triterpene alcohol extract, more preferably Rhizoma alismatis total triterpene alcohol extract. Proof rhizoma alismatis used in the invention process is rhizoma alismatis crude drug and Rhizoma alismatis total triterpene alcohol extract.
Described curcuma zedoary refers to any type of material medicines such as the curcuma zedoary crude drug, fecula, medicine materical crude slice, Rhizoma Curcumae extract of the dry rhizome of zingiberaceous plant curcuma zedoary, root tuber of aromatic turmeric or Guangxi zedoary and preparation thereof. Be preferably Rhizoma Curcumae extract. Used proof curcuma zedoary is curcuma zedoary crude drug and Rhizoma Curcumae extract in the proof property the invention process.
Described pharmaceutical composition can be made into lozenge, tablet, pill, capsule, pulvis, granula, injection, oral liquor and other types of formulations. The medicine of above-mentioned various formulations all can be according to the conventional method preparation of pharmaceutical field. Preferably tablet, pill, capsule.
Also can add one or more pharmaceutically acceptable carriers in the described pharmaceutical composition. Described carrier comprise the pharmaceutical field routine diluent, filler, excipient, adhesive, wetting agent, collapse and release agent, sorbefacient, surfactant, absorption carrier, lubricant etc., add in case of necessity flavouring agent, sweetener etc. Be limited to these but have more than.
The component of described composition and parts by weight are: rheum officinale 5-10 coptis 5-10 turmeric 5-10 desmodium 10-20 rhizoma alismatis 5-10 curcuma zedoary 5-10. Be preferably: rheum officinale 6 coptiss 6 turmerics 9 desmodiums 15 rhizoma alismatis 5 curcuma zedoarys 9.
The present invention also provides the preparation method of two kinds of described tablets, pill, capsule, uses respectively described rheum officinale, the coptis, turmeric, desmodium, rhizoma alismatis, curcuma zedoary crude drug and extract preparation.
Described tablet, pill, capsule are to be prepared from by the following method: get rheum officinale crude drug 6g coptis crude drug 6g turmeric crude drug 9g desmodium crude drug 15g rhizoma alismatis crude drug 5g curcuma zedoary crude drug 9g, rhizoma alismatis, desmodium, turmeric, curcuma zedoary and rheum officinale (3g) water is decocted twice, filter the rear filtrate hold over night, be condensed into thick medicinal extract, again coptis 6g and residue rheum officinale (3g) are pulverized and above-mentioned medicinal extract mixing, add appropriate amount of auxiliary materials and granulate. Formulation method prepares tablet, pill and capsule routinely. The specific embodiment is seen embodiment 1.
In order to improve active ingredient purity and bioavilability, reach better curative effect, described tablet, pill, capsule can also be prepared from by the following method: with archen extract 0.25g berberine extract 0.25g curcumin extraction 0.25g Herba Lysimachiae extract 0.625g Rhizoma alismatis total triterpene alcohol extract 0.625g Rhizoma Curcumae extract 0.625g mixing, add appropriate amount of auxiliary materials and granulate. Formulation method prepares tablet, pill and capsule routinely. The specific embodiment is seen embodiment 2. This kind preparation method's curative effect is stable, and bioavilability is high, but cost is higher.
The specification of described tablet, pill and capsule is every 0.3 gram-1.0 grams, is preferably 0.5 gram.
Described tablet, pill and capsular usage and dosage are every day 2-3 time, each 3-6 grain.
" malignant tumor " comprises whole cancers and sarcoma and whole blood system malignant tumor to term as used in this specification.Proof malignant tumor used in the invention process is a colorectal cancer.
As used in this specification described embodiment is used to describe the present invention below in conjunction with the present invention of drawings and Examples detailed description, rather than restriction the present invention.
Embodiment
Embodiment 1: Chinese medicine compound tablet provided by the invention, pill and capsular preparation
Get Radix Et Rhizoma Rhei 6g Rhizoma Coptidis 6g Rhizoma Curcumae Longae 9g Herba Lysimachiae 15g Rhizoma Alismatis 5g Rhizoma Curcumae 9g, Rhizoma Alismatis, Herba Lysimachiae, Rhizoma Curcumae Longae, Rhizoma Curcumae and Radix Et Rhizoma Rhei (3g) water is decocted twice, filter the rear filtrate standing over night, be condensed into thick extractum, again Rhizoma Coptidis 6g and residue Radix Et Rhizoma Rhei (3g) are pulverized and above-mentioned extractum mixing, add appropriate amount of auxiliary materials and granulate.Promptly, make 30, every 0.375g for every dose after the tabletting drying.
Embodiment 2: Chinese medicine compound tablet provided by the invention, pill and capsular preparation
With emodin extract 0.25g berberine extract 0.25g curcumin extraction 0.25g Herba Lysimachiae extract 0.625g Rhizoma Alismatis total triterpenes extract 0.625g Rhizoma Curcumae extract 0.625g mixing, add appropriate amount of auxiliary materials and granulate.Formulation method prepares tablet, pill and capsule routinely.
The Chinese medicine compound tablet that embodiment 3 the present invention relates to is to the metabolic influence of colorectal cancer cells copper zinc
1. the preparation of pastille serum
The tablet that Application Example 1 and embodiment 2 are provided.15 New Zealand white rabbit of picked at random, 5 is one group, is designated as medication group 1, medication group 2 and matched group respectively, fasting is 1 day before the experiment.Medication group subsequently 1 is 5 slices/time of oral tablets day by day, and 2 times/day, 12 hours at interval, administration was 10 days altogether.Medication group 2 is 3 slices/time of oral tablets day by day, and 2 times/day, 12 hours at interval, administration was 10 days altogether.Matched group gives not contain the adjuvant of effective composition.After the administration 10 days, each is organized rabbit and all directly gets blood through the heart inserting needle without anesthesia under routine disinfection, getting the blood bottle tiltedly put 2 hours, after treating that serum is separated out, put in the cold closet and spend the night, draw that upper serum is centrifugal next day, behind the sucking filtration, degerming, it is standby to put-20 times preservations, is designated as pastille serum 1, pastille serum 2 and blank serum respectively.
2. pastille serum is to the influence of colorectal cancer cells copper zinc content
Conventional method is cultivated colorectal carcinoma cell line LOVO, HT29.When cell fusion occupies about 80% of whole visual field in flakes, during cell quantity absolute value 〉=105, can detect copper, zinc content in the cell, constitute a cell model.Be divided into 4 groups, every group by 3 identical cell models formations, one group adds serum-free medium, one group adds the blank serum of 0.5ml, two groups add 0.5ml pastille serum 1 and pastille serum 2 respectively in addition, be numbered 2 groups of culture fluid group, blank serum group, 1 group of pastille serum and pastille serum respectively, it is standby to cultivate after 24 hours results.Adopt improvement Loway method to calculate the content of Cu2+, Zn2+ and total protein in the cell model, with the ratio (ng/mg) of Cu2+, Zn2+ content and total protein content in the cell model as cell model Cu2+, Zn2+ assay value.Each organizes data all so that (x ± s) expression, the t check is adopted in the paired data analysis.
3. result
The variation of Cu2+, Zn2+ content and Cu2+/Zn2+ ratio sees Table 1 in culture fluid group, blank serum group and the two pastille serum group cells.
Cu2+ content significantly is lower than culture fluid group and blank serum group (p＜0.01) in the two pastille serum group cells, and Zn2+ content is significantly higher than culture fluid group and blank serum group (p＜0.01), and Cu2+/Zn2+ ratio significantly is lower than culture fluid group and blank serum group.2 groups of pastille serum to fall the copper effect more obvious.
Table 1: the variation of Cu2+, Zn2+ content and Cu2+/Zn2+ ratio in culture fluid group, blank serum group and the two pastille serum group cells (x ± s)
| Group | Cu2+(ng/mg) | Zn2+(ng/mg) | Cu2+/Zn2+ |
| The culture fluid group | 98.83±5.26 | 76.56±4.38 | 1.29±0.23 |
| Blank serum group | 99.24±3.12 | 72.65±2.38 | 1.11±0.31 |
| 1 group of pastille serum | 74.64±3.87 | 86.25±2.62 | 0.86±0.16 |
| 2 groups of pastille serum | 62.94±4.23 | 85.67±2.83 | 0.73±0.22 |
Embodiment 4: the Chinese medicine compound tablet that the present invention relates to forms the influence of ability to vascular endothelial cell proliferation, migration and pipe
1: pastille serum is to the inhibitory action of human vascular endothelial cell proliferation.
With human umbilical vein endothelial cell (HUVEC, available from Cascade Biologics company, Cot:C-003-5C) place the Medium 200 (available from Cascade Biologics company) that contains 10% hyclone (FBS) to cultivate (37 ℃, 5%CO2,95% humidity), get the 4th generation cell be inoculated in 96 well culture plates by density 4000/250ul, set 2 groups of culture fluid group, blank serum group, 1 group of pastille serum and pastille serum, all do 3 multiple holes for every group.The preparation of blank serum, pastille serum 1 and pastille serum 2 is with embodiment 3.Treat that the cell stand density reaches 80%, add the culture fluid of 10ul, blank serum, pastille serum 1 and pastille serum 2 respectively, continue to cultivate (M200 culture medium, 2%FBS) after 48 hours, Thiazolyl blue tetrazolium bromide salt (MTT) 20ul that adds 5mg/ml, 37 ℃ were continued to hatch 4 hours, stop cultivating, abandon supernatant, every hole adds 150ulDMSO, vibration was measured each hole light absorption value at 490nm wavelength place with BIO-RAD Model 3500 microplate reader after 1 hour gently, represented the quantity of living cells in each hole with light absorption value.Above-mentioned experiment repeats 3 times.The result as shown in Table 2, the quantity of 1 group of pastille serum and 2 groups of living cells of pastille serum significantly is lower than culture fluid group and blank serum group (p＜0.01).
Table 2: culture fluid group, blank serum group and two pastille serum group light absorption values (x ± s)
| Group | Light absorption value |
| The culture fluid group | 0.61±0.11 |
| Blank serum group | 0.62±0.09 |
| 1 group of pastille serum | 0.47±0.12 |
| 2 groups of pastille serum | 0.44±0.08 |
2: pastille serum forms the inhibitory action of ability to human vascular endothelial cell pipe.
The every hole of 24 well culture plates adds BD Matrigel
TMMatrix virgin rubber 200ul, make it to aggregate into glue, the 4th generation human umbilical vein endothelial cell (HUVEC) suspension is seeded in 24 orifice plates that scribble Matrigel glue by 30000cell/500ul density, set 2 groups of culture fluid group, blank serum group, 1 group of pastille serum and pastille serum, all do 3 multiple holes for every group.The preparation of blank serum, pastille serum 1 and pastille serum 2 is with embodiment 3.Add the culture fluid of 10ul, blank serum, pastille serum 1 and pastille serum 2 respectively, all do 3 multiple holes for every group.37 ℃, 5%CO2,95% humidity were cultivated 24 hours, the formation of OLYMPUS CK40-RFL observation by light microscope vascular endothelial cell pipe, and 4 low power fields countings are got in every hole, with OLYMPUS CK40 digital camera take pictures (Fig. 1).The result is as shown in table 3, and 2 groups of vascular endothelial cell pipes of 1 group of pastille serum and pastille serum form and significantly are lower than culture fluid group and blank serum group (p＜0.01).
Table 3: culture fluid group, blank serum group and two pastille serum group vascular endothelial cell pipes formation quantity (x ± s)
| Group | Pipe forms quantity |
| The culture fluid group | 152±6.2 |
| Blank serum group | 154±8.3 |
| 1 group of pastille serum | 64±9.8 |
| 2 groups of pastille serum | 58±10.1 |
3: pastille serum is to the inhibitory action of human migration of vascular endothelial cells ability.
1, preparation chemotactic factor
Get the NIH3T3 cell that goes down to posterity and grew fine in back second day.The soft rinsing of serum-free DMEM 2 times.Serum-free DMEM, 5%CO2 cultivates 24-48hours for 37 ℃.The collecting cell supernatant.Centrifugal (12000g, 4 ℃, 10min).Supernatant bacteriological filtration (0.22um filter membrane), (20 ℃) are preserved in packing.
2, Matrigel invasion and attack experiment
The Matrigel 25ul (virgin rubber is pressed 1: 2 dilution proportion with DMEM) that gets dilution adds chamber on the Transwell plate, covers whole polyester film surface, hatches 30min for 37 ℃, makes Matrigel aggregate into glue.The 4th generation human umbilical vein endothelial cell (HUVEC) suspension is seeded to the chamber by 30000/250ul density, PBS washing 3 digestion and harvestings from culture bottle.DMEM makes single cell suspension with serum-free, and 5 * 105cells/ml sets 2 groups of culture fluid group, blank serum group, 1 group of pastille serum and pastille serum, all does 3 multiple holes for every group.The preparation of blank serum, pastille serum 1 and pastille serum 2 is with embodiment 3.Add the culture fluid of 10ul, blank serum, pastille serum 1 and pastille serum 2 respectively.The chamber adds the chemotactic factor of 500ul step 1 preparation under the Transwell plate.5%CO2 cultivated 24 hours for 37 ℃.Wipe the cell of gel and polyester film upper surface gently with the wet cotton swab of DMEM.The careful taking-up gone up the chamber, and ice-cold methanol is fixed 30 minutes.Haematoxylin dyeing 1 minute.Gradient alcohol dehydration (80%, 95%, 100%, 100%), dimethylbenzene is transparent.Carefully polyester film is cut from last chamber, place resinene mounting on the microscope slide.The cell (400 *) under high power lens that is attached to the polyester film lower surface is got 6 visuals field countings average and take pictures (Fig. 2) at random.Repeated experiments 2 times.The result is as shown in table 4, and 2 groups of vascular endothelial cells of 1 group of pastille serum and pastille serum pass through the quantity that Matrigel migrates to the poly-carbon ester film lower surface of Transwell plate and significantly are lower than culture fluid group and blank serum group (p＜0.01).
Table 4: culture fluid group, blank serum group and two pastille serum group vascular endothelial cells perforation cell quantity (x ± s)
| Group | The perforation cell quantity |
| The culture fluid group | 61.5±4.26 |
| Blank serum group | 63.4±5.31 |
| 1 group of pastille serum | 52.2±4.11 |
| 2 groups of pastille serum | 49.3±5.1 |
Embodiment 5: the Chinese medicine compound tablet that the present invention relates to is to the influence of the tumor-blood-vessel growth and the tumor growth of colorectal cancer animal model
Results human colon cancerous cell line LoVo cell is made cell suspension with PBS, and the right side thigh portion that is seeded to big BALB/cAnN-nu/nu nude mice of 8 weeks with 2,000,000/200ul is subcutaneous.When treating the tumor bulk-growth, be divided into three groups at random, 5 every group, be designated as medication group 1, medication group 2 and matched group to the 5mmX5mm size.5 slices/time in the tablet that the oral day by day embodiment 1 of medication group 1 is provided, 2 times/day, 12 hours at interval, administration was 10 days altogether.3 slices/time in oral day by day embodiment 2 tablet that provides of medication group 2,2 times/day, 12 hours at interval, administration was 10 days altogether.Matched group gives not contain the adjuvant of effective composition.Successive administration 60 days is every the major diameter and the minor axis of record tumor body.During the medication, untoward reaction does not appear in mice.After putting to death mice, take out tumor, detect the quality of tumor.Use the microvessel density that CD34 dyeing SABC method detects matched group and two treatment group tumors.The result shows, two medication group tumor bodies dwindle than matched group, the growth difference that obviously slows down has statistical significance (P＜0.01) (Fig. 3), volume and quality that two treatment groups are taken out the tumor piece all are lower than matched group, difference has statistical significance (P＜0.01), microvessel density be starkly lower than matched group (P＜0.01) (table 5, Fig. 4).
Table 5: the tumor quality of matched group and two medication groups and microvessel density (x ± s)
| Group | Tumor quality (g) | Microvessel density (individual) |
| Matched group | 10.52±3.46 | 46.48±5.37 |
| |
4.28±1.12 * | 19.52±3.62 * |
| Medication group 2 | 3.85±1.09 * | 15.35±2.89 * |
The Kruskal-Wallis check,
*Expression has significance (p＜0.01) with the matched group comparing difference
Embodiment 6: the Chinese medicine compound tablet that the present invention relates to is to PATIENTS WITH LARGE BOWEL serum copper zinc level and excretory influence thereof
1. clinical case is selected, is divided into groups and treatment
Select 40 routine colorectal cancer patients, M-F is 1.5: 1,62.3 years old mean age, withdraws 2 weeks of medicine of element metabolism such as influencing copper, zinc, ferrum, calcium after being admitted to hospital without exception.2 weeks and medication overall process are taken food without exception and are unified the low copper diet of regulation before medication.Be divided into 2 groups at random, be designated as treatment group 1 and treatment group 2,5 slices/time in the tablet that the oral day by day embodiment 1 of treatment group 1 is provided, every day 3 times, 4 weeks of administration; 5 slices/time in the tablet that the oral day by day embodiment 2 of treatment group 2 is provided, every day 3 times, 4 weeks of administration.Alternative is selected 20 routine non-malignant patients and is matched group, the low copper diet of unified regulation of taking food without exception in 2 weeks before detection.
2. the serum copper zinc level detects
Respectively at treatment (treating preceding 1 day) on the 0th, the 7th, 14,21 with gathered the venous blood 2ml of two treatment group patients and corresponding time point matched group on the 28th, separation of serum is put-20 ℃ of preservations.Use atomic absorption spectrophotometer and measure Copper in Serum zinc content.
3. copper zinc content detection in the feces
Respectively at treatment (treating preceding 1 day) on the 0th, the 7th, 14,21 with gathered 24 hours feces of two treatment group patients and corresponding time point matched group on the 28th, it is stirred evenly respectively, leave and take a little specimen at random, after claiming its quality, putting into bellows removes specimen moisture major part under 70 ℃ of temperature, put into thermostatic drying chamber taking out after the barbecue carbonization in 2 hours under the 240-260 ℃ of high temperature, claim its weight again.The carbonization specimen is ground foam, mixing, take by weighing the HNO3/HCLO4 solution 2ml that 50mg added 3: 1,, prepare pale brown color settled solution 80 ℃ of water-baths 1 hour, add deionized water to the 10ml mixing, use atomic absorption spectrophotometer to measure the content of copper, zinc in the feces.Adopt SPSS10.0 software, the definite probabilistic method of F check, x2 check or four fold table.
4. result
Shown in table 6 and table 7, serum copper ion level significantly reduces (p＜0.01) before the treatment after the two treatment group medications, and the serum zinc ion concentration then significantly increases (p＜0.01) before the treatment.The copper content of discharging in the feces after the two treatment group medications significantly increases (p＜0.01) before the treatment, and the zinc content of discharge then significantly reduces (p＜0.01) before the treatment.
Table 6: treat the 0th, 7,14,28 day two treatment group and matched group serum copper zinc content (x ± s)
*With comparison in corresponding the 0th day, difference had significance (p＜0.01)
*Compare with matched group, difference has significance (p＜0.01)
5
Table 7 the: treat (x ± s) of copper zinc content in the 0th, 7,14,28 day two treatment group and the matched group feces
*With comparison in corresponding the 0th day, difference had significance (p＜0.01)
*Compare with matched group, difference has significance (p＜0.01)
Embodiment 7: the Chinese medicine compound tablet that the present invention relates to is to human result of treatment for colorectal cancer
Claims (15)
1. pharmaceutical composition that treats and/or prevents malignant tumor, its main component comprises: Radix Et Rhizoma Rhei, Rhizoma Coptidis, Rhizoma Curcumae Longae, Herba Lysimachiae, Rhizoma Alismatis, Rhizoma Curcumae.
2. according to the pharmaceutical composition of claim 1, the dosage form of described pharmaceutical composition is tablet, pill, capsule, powder, granule, injection or oral liquid.
3. according to the pharmaceutical composition of claim 2, the dosage form of wherein said compositions is the Chinese medicine compound tablet.
4. according to each pharmaceutical composition among the claim 1-3, it is characterized in that the component of said composition and parts by weight are: Radix Et Rhizoma Rhei 5-10, Rhizoma Coptidis 5-10, Rhizoma Curcumae Longae 5-10, Herba Lysimachiae 10-20, Rhizoma Alismatis 5-10, Rhizoma Curcumae 5-10.
5. according to each pharmaceutical composition among the claim 1-3, it is characterized in that the component of said composition and parts by weight are: Radix Et Rhizoma Rhei 6, Rhizoma Coptidis 6, Rhizoma Curcumae Longae 9, Herba Lysimachiae 15, Rhizoma Alismatis 5, Rhizoma Curcumae 9.
6. according to each pharmaceutical composition among the claim 1-3, wherein also comprise one or more pharmaceutically acceptable carriers, described carrier comprises diluent, filler, excipient, binding agent, wetting agent, collapses and release agent, absorption enhancer, surfactant, absorption carrier, lubricant, flavouring agent and/or sweeting agent.
7. according to each pharmaceutical composition among the claim 1-3, the route of administration of described compositions is oral administration, administered intramuscular or intravenous administration.
8. according to each pharmaceutical composition among the claim 1-3, the dosage form of wherein said pharmaceutical composition is a tablet, pill or capsule, described tablet, pill or capsule are prepared from by the following method: get Radix Et Rhizoma Rhei 6g, Rhizoma Coptidis 6g, Rhizoma Curcumae Longae 9g, Herba Lysimachiae 15g, Rhizoma Alismatis 5g, Rhizoma Curcumae 9g, with Rhizoma Alismatis, Herba Lysimachiae, Rhizoma Curcumae Longae, Rhizoma Curcumae decocts twice in described ratio and 3g Radix Et Rhizoma Rhei water, filter the rear filtrate standing over night, be condensed into thick extractum, again Rhizoma Coptidis 6g and residue 3g Radix Et Rhizoma Rhei are pulverized and above-mentioned extractum mixing, add appropriate amount of auxiliary materials and granulate, formulation method prepares tablet routinely, pill or capsule.
9. according to each preparation of drug combination method among the claim 1-8, described preparation method comprises the steps: to get Radix Et Rhizoma Rhei, Rhizoma Coptidis, Rhizoma Curcumae Longae, Herba Lysimachiae, Rhizoma Alismatis, Rhizoma Curcumae in each described ratio among the claim 1-8, Rhizoma Alismatis, Herba Lysimachiae, Rhizoma Curcumae Longae, Rhizoma Curcumae are decocted twice in described ratio and Radix Et Rhizoma Rhei water, filter the rear filtrate standing over night, be condensed into thick extractum, again Rhizoma Coptidis and remaining Radix Et Rhizoma Rhei are pulverized and above-mentioned extractum mixing, add appropriate amount of auxiliary materials and granulate, formulation method is prepared into tablet, pill or capsule routinely.
10. pharmaceutical composition that treats and/or prevents malignant tumor, its main component comprises: emodin extract, berberine extract, curcumin extraction, Herba Lysimachiae extract, Rhizoma Alismatis total triterpenes extract, Rhizoma Curcumae extract.
11. according to the pharmaceutical composition of claim 10, the dosage form of described pharmaceutical composition is tablet, pill, capsule, powder, granule, injection or oral liquid.
12. pharmaceutical composition according to claim 11, described tablet, pill or capsule are prepared from by the following method: with emodin extract 0.25g, berberine extract 0.25g, curcumin extraction 0.25g, Herba Lysimachiae extract 0.625g, Rhizoma Alismatis total triterpenes extract 0.625g, Rhizoma Curcumae extract 0.625g mixing, add appropriate amount of auxiliary materials and granulate, formulation method prepares tablet, pill or capsule routinely.
13. according to each preparation of drug combination method among the claim 10-12, described preparation method comprises the steps: to get emodin extract, berberine extract, curcumin extraction, Herba Lysimachiae extract, Rhizoma Alismatis total triterpenes extract, Rhizoma Curcumae extract mixing in each described ratio among the claim 10-12, add appropriate amount of auxiliary materials and granulate, formulation method is prepared into tablet, pill or capsule routinely.
14. be used for the treatment of and/or prevent application in the medicine of malignant tumor in preparation according to each pharmaceutical composition of claim 1-13.
15. according to the application of claim 14, wherein said malignant tumor comprises entity tumor and hematological system tumor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101111533A CN101322825A (en) | 2007-06-15 | 2007-06-15 | Medicament composition for treating malignant tumour |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101111533A CN101322825A (en) | 2007-06-15 | 2007-06-15 | Medicament composition for treating malignant tumour |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101322825A true CN101322825A (en) | 2008-12-17 |
Family
ID=40186625
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101111533A Pending CN101322825A (en) | 2007-06-15 | 2007-06-15 | Medicament composition for treating malignant tumour |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101322825A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130202723A1 (en) * | 2012-02-07 | 2013-08-08 | Yu-Te Liu | Method of producing a chinese herbal composition for treating terminal cancer patients with constipation |
| CN110327446A (en) * | 2019-08-15 | 2019-10-15 | 安徽中医药大学第一附属医院 | It is a kind of to treat hepatolenticular degeneration liver fibrosis Chinese medicine composition and application |
| US11033579B2 (en) | 2015-09-24 | 2021-06-15 | Innolife Co., Ltd. | Use of trientine to deliver copper to ischemic tissue |
-
2007
- 2007-06-15 CN CNA2007101111533A patent/CN101322825A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130202723A1 (en) * | 2012-02-07 | 2013-08-08 | Yu-Te Liu | Method of producing a chinese herbal composition for treating terminal cancer patients with constipation |
| US11033579B2 (en) | 2015-09-24 | 2021-06-15 | Innolife Co., Ltd. | Use of trientine to deliver copper to ischemic tissue |
| US12076340B2 (en) | 2015-09-24 | 2024-09-03 | Innolife Co., Ltd. | Use of trientine to deliver copper to ischemic tissue |
| CN110327446A (en) * | 2019-08-15 | 2019-10-15 | 安徽中医药大学第一附属医院 | It is a kind of to treat hepatolenticular degeneration liver fibrosis Chinese medicine composition and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102861284B (en) | Traditional Chinese medicine compound preparation for treating non-small cell lung cancer and preparation method thereof | |
| CN103386078B (en) | A kind of Chinese medicine composition is preparing the application in treating colon cancer drug | |
| CN101850032B (en) | Anti-tumor traditional Chinese medicine composition and preparation method and application thereof | |
| CN1618446A (en) | Medicine for treating diabetes, and its prepn. method | |
| CN106361830B (en) | Rhubarb powder and preparation method thereof | |
| CN101322825A (en) | Medicament composition for treating malignant tumour | |
| CN103463554B (en) | A kind of treat malignant tumor pharmaceutical composition and preparation method and purposes | |
| CN112755160A (en) | Traditional Chinese medicine composition for improving postoperative prognosis of breast cancer and application thereof | |
| CN102858359B (en) | Medicinal composition comprising alcohol-soluble and water-insoluble licorice extract, pharmaceutical preparation, pharmaceutical application, therapeutic method, and preparative method thereof | |
| CN101011543B (en) | Antineoplastic medicine composition | |
| CN1943718B (en) | A Chinese traditional medicinal composition and its preparation method | |
| CN100406026C (en) | Medicine for treating chronic gastritis and gastric carcinoma, and its prepn. method | |
| CN103826651A (en) | Medical composition containing stauntonia hexaphylla extract | |
| CN102631492B (en) | Chinese medicinal composition for improving immunity and resisting fatigue | |
| CN1298351C (en) | Chinese medicine oral preparaton for treating urinary system infestation and its preparation method | |
| CN100409862C (en) | Chinese medicinal composition for treating viral infection of upper respiratory tract and preparing process thereof | |
| CN104605344A (en) | Health food for enhancing immunity and preparation method of health food | |
| CN111298061B (en) | Traditional Chinese medicine composition for clearing heat and detoxicating, removing stasis and resolving masses and preparation method thereof | |
| CN1186052C (en) | Medicine for treatment of pelvic inflammation, its preparation and preparing method | |
| CN103156891A (en) | Preparation method of akebia fruit active components and preparation method of preparation of akebia fruit active components and application in preparation of antineoplastic medicines of preparation of foreknowledge sub-active components | |
| CN102068537B (en) | The preparation of Pericarpium Citri Reticulatae Radix Glycyrrhizae prevents and treats the health food of nasopharyngeal carcinoma and the production method of medicine | |
| CN102631486B (en) | Health care composition | |
| CN101690794B (en) | Antitumor medicament, preparation method and quality control method | |
| CN106215164A (en) | Fructus Phyllanthi pharmaceutical composition and preparation method thereof, preparation and anti-Ai Yingyong | |
| CN104474133B (en) | The Chinese medicine composition and its preparation and preparation method of improvement tumor microenvironment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20081217 |