CN103405721B - Pharmaceutical composition for inhibiting tumor metastasis and application thereof - Google Patents
Pharmaceutical composition for inhibiting tumor metastasis and application thereof Download PDFInfo
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Abstract
The invention discloses a pharmaceutical composition for inhibiting tumor metastasis and an application thereof. The pharmaceutical composition comprises the following Chinese medicinal raw materials in parts by weight: 1-4 parts of radix euphorbiae lantu, 40-52 parts of Oldenlandia diffusa, 40-52 parts of felwort, 20-30 parts of curcuma zedoary, 20-30 parts of burdock, 12-20 parts of herba epimedii, 12-20 parts of Poria cocos and 12-20 parts of loranthus parasiticus. The pharmaceutical composition disclosed by the invention has a remarkable effect for inhibiting tumor metastasis.
Description
Technical field
The invention belongs to technical field of Chinese medicine, be specifically related to a kind of pharmaceutical composition and application thereof of anti metastasis.
Background technology
According to World Health Organization (WHO) (WHO) statistics, the eighties in 20th century, the annual new cancered patient about 7,000,000 in the whole world, died from cancer person about 5,000,000 people every year.At the beginning of the fifties, China's cancer mortality accounts for the 9th or the 10th of whole cause of the death, and the seventies, China's cancer mortality leapt to the 3rd.Statistics in 1991, the cancer mortality of China some big and medium-sized cities resident has occupied the 1st of whole cause of the death.Annual new cancer stricken about 1,600,000 people of China, die from cancer person about 1,300,000 people.Above-mentioned data shows: the cancer morbidity of the whole world and China is obviously increasing year by year.In addition, when China's cancer patient is gone to a doctor, end-stage patients still occupy the majority, and have the advantages that lose operation and wait radical cure chance, therapeutic effect poor.Numerous medical personnels strengthen the research of oncotherapy, grasp and improve the therapeutic effect of existing various treatment means, and to reduction cancer mortality, reduce relapse rate, the quality of life of improving cancer patient is significant.By the level of present China cancer mortality, the whole nation just has 2 people to die from cancer for every 1 minute, people more than 2 800 being had every day to be seized life by cancer, within 1 year, having the city of a population of one million to be destroyed by being equivalent to one.Visible, cancer is commonly encountered diseases, frequently-occurring disease, to people's life and health person of having serious threat, is also huge on the impact of the development of the national economy.In the U.S., annual treatment of cancer expense 83,000,000,000 dollars, accounts for 14% of national medical expense.Almost everyone experiences the threat of cancer.Because the whole world is every year because the number of cancer mortality is up to 6,300,000 people, and China is every year because the number of cancer mortality has reached 1,300,000 people, and cancer patient every year with 3% speed increase, be equivalent to just have 1 family to be subject to the threat of cancer in every 200 families.
Chemotherapy is an important means of current Therapeutic cancer, and chemotherapeutics, while killing cancerous cell, also exists toxicity to organism normal cell.In recent years, along with continuing to bring out of PTS, the reasonable application of Combination chemotherapy, the curative effect of chemotherapy is enhanced, but these medicines simultaneously normal tissue organ have infringement or toxic action, thus reduce body's immunity, occur a series of toxicities such as bone marrow depression, affect the curative effect of chemotherapy, even force chemotherapy to stop.Clinical research shows, when chemotherapy according to the toxicity symptom of the body constitution of patient, cancer staging and appearance, be aided with treatment by Chinese herbs, effectively can strengthen the effect of chemotherapy, can avoid or alleviate again the toxicity of chemicotherapy to a certain extent, extend the life cycle of patient and improve the life quality of patient.And Chinese medicine is as the advantageous resource of China, some medicine has obvious antitumor action, from the traditional natural drug of China, therefore screens high-efficiency low-toxicity, antitumor drug tool that targeting is strong is of great significance.
Summary of the invention
The present invention according to Traditional Chinese medical theory, through to a large amount of screenings of drug component, restructuring, trial, made by a large amount of animal experiment study again.Therefore, the object of the invention is to, by prescription again after studying conventional medicament pharmacology, provide a kind of pharmaceutical composition of anti metastasis.
The object of the present invention is achieved like this:
A pharmaceutical composition for anti metastasis, is prepared from by the traditional Chinese medicinal material raw materials comprising following weight portion: Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 1-4 part, Herba Hedyotidis Diffusae 40-52 part, Radix Gentianae 40-52 part, Rhizoma Curcumae 20-30 part, Fructus Arctii 20-30 part, Herba Epimedii 12-20 part, Poria 12-20 part, Herba Taxilli 12-20 part.
Preferably, the pharmaceutical composition of above-mentioned anti metastasis is prepared from by the traditional Chinese medicinal material raw materials of following weight portion: Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 2-3 part, Herba Hedyotidis Diffusae 45-50 part, Radix Gentianae 45-50 part, Rhizoma Curcumae 23-27 part, Fructus Arctii 23-27 part, Herba Epimedii 15-18 part, Poria 15-18 part, Herba Taxilli 15-18 part.
Further preferably, the pharmaceutical composition of above-mentioned anti metastasis is prepared from by the traditional Chinese medicinal material raw materials of following weight portion: the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 2 parts, Herba Hedyotidis Diffusae 48 parts, Radix Gentianae 48 parts, Rhizoma Curcumae 25 parts, Fructus Arctii 25 parts, Herba Epimedii 16 parts, 16 parts, Poria, Herba Taxilli 16 parts.
Further preferably, the pharmaceutical composition of above-mentioned anti metastasis is oral formulations.Again further preferably, described oral formulations is tablet, capsule, granule, oral liquid.
Found by experimental study, the pharmaceutical composition anti metastasis be made up of the Chinese crude drug of said ratio evident in efficacy.Therefore, second object of the present invention is to provide a kind of new medical use, the application of namely above-mentioned compositions in the medicine of preparation anti metastasis.The application of preferably above-mentioned compositions in the medicine preparing melanoma transfer.
The preparation method of the Chinese medicine oral liquid that the present invention relates to comprises the steps:
(1) get Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 1-4 part of recipe quantity, Herba Hedyotidis Diffusae 40-52 part, Radix Gentianae 40-52 part, Rhizoma Curcumae 20-30 part, Fructus Arctii 20-30 part, Herba Epimedii 12-20 part, Poria 12-20 part and Herba Taxilli 12-20 part, clean roguing, dry, pulverize;
(2) above-mentioned graininess medical material is added water cover powder 2cm again, soak 1-1.2h, pull medical material out and put during multi-functional extractions is filled with and decoct with water secondary, the water of first time totalling medical material 8-10 times amount, decoct 2h, get decocting liquid, filter, second time adds up the water of medical material 6-8 times amount, decoct 1h, get twice decocting liquid to merge, filter, when being concentrated into 90 DEG C, relative density is the concentrated solution of 1.15g/mL;
(3) concentrated solution is set to 0-5 DEG C of deepfreeze 24h, cold preservation liquid is added the filter aid kieselguhr of 0.3%, filter, filtrate reconcentration contains 5-6g crude drug amount to every milliliter, set to 0-5 DEG C of deepfreeze 24h, cold preservation liquid is filtered, add or pack after not adding correctives and obtain oral liquid.
According to Chinese medicine Historical Data Data About, pharmacologically active and the source of the traditional Chinese medicinal material raw materials that the present invention adopts are as follows:
The Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae): the effect with removing fluid-retention by purgation, removing mass parasite killing.Edema abdominal distention; Expectorant carnivorism amasss; Trusted subordinate's pain; Lump in the abdomen; Tuberculosis; Scabies.Select the root of Isolated From Thymelaeaceae Species Stellera chamaejasme L. Stellera chamaejasmeL. [Passerina chamaejasmeFisch.].
Herba Hedyotidis Diffusae: latin name Herba Hedyotis Diffusae, has the effect of heat-clearing and toxic substances removing, dampness removing; Cure mainly: dyspnea and cough due to lung-heat; Laryngopharynx swelling and pain; Intestinal carbuncle; Furuncle and phyma skin infection; Venom; The puckery pain of pyretic stranguria; Edema; Dysentery; Intestinal is scorching; Jaundice due to damp-heat; Cancerous protuberance.Be selected from the dry herb of Maguireothamnus speciosus Herba Hedyotidis Diffusae Hedyotis diffusa Willd..
Radix Gentianae: heat clearing and damp drying; Eliminating pathogen in the liver is calmed the frightened.Jaundice due to damp-heat; Urine leaching pain; Swelling of the vulva pudendal pruritus; Damp-heat vaginal discharge; The feeling of fullness in the head headache of liver and gall excess-fire; Conjunctival congestion and swelling pain; Deaf ear swells; Hypochondriac pain bitter taste; Calentura convulsion with spasms.Derive from the root welding technology of gentianaceae plant Radix Gentianae (Gentiana scabra Bge.).
Rhizoma Curcumae: circulation of qi promoting removing blood stasis, removing food stagnancy pain relieving.For Dan abdominal mass mass in the abdomen, blood stasis amenorrhea, food stagnation distending pain; Early cervical carcinoma.Select the rhizome of zingiberaceous plant C. kwangsinensis Curcuam kwangsiensis S.G.Leset C.F.Liang.
Fructus Arctii: the effect with dispelling wind and heat pathogens, lung qi dispersing rash, sore-throat relieving eliminating stagnation, removing toxic substances and promoting subsidence of swelling, cure mainly cough due to pathogenic wind-heat, laryngopharynx swelling and pain, macule not thoroughly, rubella pruritus, sore swollen toxin.Be selected from the dry mature fruit of feverfew Fructus Arctii Arctium lappa L..
Herba Epimedii: kidney-replenishing, bone and muscle strengthening, wind-damp dispelling.For impotence and seminal emission, muscles and bones flaccidity is soft, rheumatic arthralgia, numbness contracture; Climacteric hypertension.Select the dried leaves of Berberidaceae plant Herba Epimedii (Epimedium brevicornum Maxim.).
Poria: there is diuretic, effect of eliminating dampness by diuresis diuresis.Cure mainly dysuria; Edema distension; Phlegm retention cough with dyspnea; Vomiting; Insufficiency of the spleen lack of appetite; Have loose bowels; Palpitation and restlessness; Insomnia forgetfulness; Seminal emission nebulousurine.Select the dry sclerotia of On Polyporaceae Poria Poria cocos (Schw.) Wolf.
Herba Taxilli: invigorating the liver and kidney; Bone and muscle strengthening; Wind-damp dispelling; Antiabortive.Main soreness of waist and knee joint; Muscles and bones flaccidity is weak; Limbs are hemiplegia; Rheumatic arthralgia; Head is wrong dizzy; Frequent fetal movement, metrostaxis.For rheumatic arthralgia, soreness of the waist and knees, muscles and bones is unable, metrorrhagia through many, blood leaking in gestation, frequent fetal movement; Hypertension.Select the dry stem and branch with leaf of Loranthaceae plant Herba Taxilli Taxillus chinensis (DC.) Danser.
Inventor is shown by experimental study, and pharmaceutical composition anti metastasis determined curative effect of the present invention, obviously can suppress the growth of B16 cell in C57BL/6 Mice Body after gavage model mice.It has blood vessel dilating, increases the effect of wall of micrangium permeability and tissue fluid generation, does not increase the probability of tumor cell blood and/or lymph metastasis.On the contrary, pharmaceutical composition of the present invention makes its blood and lymph metastasis probability obviously reduce.Pharmaceutical composition anti metastasis Be very effective of the present invention, and without toxicity.
Detailed description of the invention
Be below specific embodiments of the invention, technical scheme of the present invention is done to describing further, but protection scope of the present invention be not limited to these embodiments.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
Embodiment 1
Crude drug prescription: the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 2 kilograms, Herba Hedyotidis Diffusae 48 kilograms, Radix Gentianae 48 kilograms, Rhizoma Curcumae 25 kilograms, Fructus Arctii 25 kilograms, Herba Epimedii 16 kilograms, 16 kilograms, Poria, Herba Taxilli 16 kilograms.
Preparation method:
(1) get the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) of recipe quantity, Herba Hedyotidis Diffusae, Radix Gentianae, Rhizoma Curcumae, Fructus Arctii, Herba Epimedii, Poria and Herba Taxilli, clean roguing, dry, pulverize;
(2) above-mentioned graininess medical material is added water cover powder 2cm again, soak 1-1.2h, pull medical material out and put during multi-functional extractions is filled with and decoct with water secondary, first time totalling medical material 10 times amount water, decoct 2h, get decocting liquid, filter, second time adds up the water of medical material 8 times amount, decoct 1h, get twice decocting liquid to merge, filter, when being concentrated into 90 DEG C, relative density is the concentrated solution of 1.15g/mL;
(3) concentrated solution is set to 0-5 DEG C of deepfreeze 24h, cold preservation liquid is added the filter aid kieselguhr of 0.3%, filter, filtrate reconcentration containing 6g crude drug amount, sets to 0-5 DEG C of deepfreeze 24h to every milliliter, is filtered by cold preservation liquid, packs and obtain oral liquid.
Embodiment 2
Crude drug prescription: the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 3 kilograms, Herba Hedyotidis Diffusae 40 kilograms, Radix Gentianae 42 kilograms, Rhizoma Curcumae 21 kilograms, Fructus Arctii 30 kilograms, Herba Epimedii 12 kilograms, 20 kilograms, Poria, Herba Taxilli 20 kilograms.
Preparation method:
(1) get the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) of recipe quantity, Herba Hedyotidis Diffusae, Radix Gentianae, Rhizoma Curcumae, Fructus Arctii, Herba Epimedii, Poria and Herba Taxilli, clean roguing, dry, pulverize;
(2) above-mentioned graininess medical material is added water cover powder 2cm again, soak 1-1.2h, pull medical material out and put during multi-functional extractions is filled with and decoct with water secondary, first time totalling medical material 8 times amount water, decoct 2h, get decocting liquid, filter, second time adds up the water of medical material 8 times amount, decoct 1h, get twice decocting liquid to merge, filter, when being concentrated into 90 DEG C, relative density is the concentrated solution of 1.15g/mL;
(3) concentrated solution is set to 0-5 DEG C of deepfreeze 24h, cold preservation liquid is added the filter aid kieselguhr of 0.3%, filter, filtrate reconcentration containing 5g crude drug amount, sets to 0-5 DEG C of deepfreeze 24h to every milliliter, is filtered by cold preservation liquid, packs and obtain oral liquid.
Embodiment 3
Crude drug prescription: the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 1 kilogram, Herba Hedyotidis Diffusae 52 kilograms, Radix Gentianae 45 kilograms, Rhizoma Curcumae 30 kilograms, Fructus Arctii 22 kilograms, Herba Epimedii 20 kilograms, 12 kilograms, Poria, Herba Taxilli 16 kilograms.
Preparation method:
(1) get the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) of recipe quantity, Herba Hedyotidis Diffusae, Radix Gentianae, Rhizoma Curcumae, Fructus Arctii, Herba Epimedii, Poria and Herba Taxilli, clean roguing, dry, pulverize;
(2) above-mentioned graininess medical material is added water cover powder 2cm again, soak 1-1.2h, pull medical material out and put during multi-functional extractions is filled with and decoct with water secondary, first time totalling medical material 8 times amount water, decoct 2h, get decocting liquid, filter, second time adds up the water of medical material 6 times amount, decoct 1h, get twice decocting liquid to merge, filter, when being concentrated into 90 DEG C, relative density is the concentrated solution of 1.15g/mL;
(3) concentrated solution is set to 0-5 DEG C of deepfreeze 24h, cold preservation liquid is added the filter aid kieselguhr of 0.3%, filter, filtrate reconcentration containing 6g crude drug amount, sets to 0-5 DEG C of deepfreeze 24h to every milliliter, is filtered by cold preservation liquid, packs and obtain oral liquid.
Embodiment 4, Chinese medicine are on the impact of spontaneous B16F10 melanoma metastasis mouse model
Cellar culture B16F10 melanoma cell, 4-5 days before experiment, by 1:10 passage in Tissue Culture Flask, in order to avoid not exclusively merging excessively appears in Growth of Cells.Each culture bottle is approximately containing 6-8 × 10
6cell, the cell of trophophase of taking the logarithm, discards culture fluid, cleans, add 1mL 0.25% pancreatin+0.02% EDTA Digestive system, put into cell culture incubator, after 1-3 min, rap culture bottle and make cell detachment with PBS.Add 10mL DMEM, blow and beat cell with pipet, obtain single cell suspension, proceed to 50mL polypropylene centrifuge tube.Centrifuge cell (1200 rpm × 10min), then washes twice with PBS.Use trypan blu e counting cells, adjustment cell concentration is 1 × 10
7/ mL, for subsequent use.
Cleaning grade C57BL/6 mice (female, 5-6 age in week, 16-20g), only 200 μ l dose inoculations are subcutaneous in mice left upper extremity armpit with every.Within the 6th day after inoculation, be divided into following two groups at random according to the large young pathbreaker mice of the upper primary tumor of left foot pad:
Model control group (12): the purified water of gavage 150mL/kg Mouse Weight;
Chinese drug-treated group (12): Chinese medicine oral liquid prepared by gavage embodiment 1, dosage is 100mL/kg Mouse Weight;
After last administration the 2nd day, draw materials when namely inoculating the 20th day.Before two groups of each administrations of mice and all use the most major diameter (L) of vernier caliper measurement tumor and most minor axis (W) before finally drawing materials, by formula L × W
2× 0.52 calculates gross tumor volume (V), and by (Vn-Vn-
1)/Vn-
1calculate tumor growth index, n is pendulous frequency.
When drawing materials, complete excision tumor, weighs after filter paper blots; Get liver, spleen, lung, cerebral tissue and draining lymph node at different levels, routine prepares paraffin section, and HE dyes, and observes the impact of drug on tumor cell blood and lymph metastasis.Occur that metastasis is for the hematogenous metastasis positive with liver, spleen, lung, brain, in regional nodes, occur that non-spreading property metastasis is that lymph metastasis is positive.
After off-test, can be found out by statistical results, gavage Chinese medicine obviously can suppress the growth of B16 cell in C57BL/6 Mice Body.Chinese drug-treated group and matched group tumor are heavily respectively (5.01 ± 1.16) g and (7.27 ± 1.43) g, and between the two, difference has statistical significance (P<0.01).From tumor growth index, its inhibitory action is more obvious at the experiment initial stage, and along with tumor constantly grows, inhibition strength gradually weakens, and two groups of tumor volume difference are then day by day obvious.
In addition, in matched group 12 tumor-bearing mices, 10 find that there is lymphatic metastasis, the rate of transform 83.3%.Wherein 1 tumor body is comparatively large, and cover with whole axillary fossa, cannot differentiate lymph node, but offside axillary fossa has a positive lymph nodes, all the other individualities have 1 ~ 4 lymph node positive respectively.Chinese drug-treated group has 4 examples lymphatic metastasis to occur, the rate of transform 33.3%, the number of metastatic lymph node 1 ~ 3.The tumor cell invading lymph node is not gathered into cancer nests, and rapid differentiation and maturation, synthesize a large amount of melanin granules, do not synthesize melanic juvenile cell and seldom see.And in tumor body, but often have large stretch of juvenile cell to exist.
Secondly, matched group 12 mices are showed no liver, brain metastes; Lung metastases 3 example, the rate of transform 25.0%, metastasis is minimum, is no more than a high power field.Spleen shifts 9 examples (comprising above-mentioned 3 routine Lung metastases), the rate of transform 75.0%, wherein 4 routine naked eyes visible spleen dorsal part section blackening, and form has no obvious change.Under mirror, the distribution of metastasis is without evident regularity, and like in the majority along spleen trabeculae distribution person, and cell volume is comparatively large, and the oncocyte volume be deep in excess syndrome’of the spleen matter is little, and Maturity is high.Shift not obvious under splenic capsule, may be relevant with its compact structure.From the number of cases of transfer and looking down upon greatly of metastasis, the generation of spleen transfer occurs prior to Lung metastases.Chinese drug-treated group is visible spleen transfer under only finding 3 routine mirrors, and the rate of transform 25.0%, does not find obvious Lung metastases.Chinese drug-treated group is compared with matched group, and hematogenous metastasis and lymph metastasis rate all obviously reduce (P< 0.05).
Claims (6)
1. a pharmaceutical composition for anti metastasis, is characterized in that: described compositions is prepared from by the traditional Chinese medicinal material raw materials of following weight portion: Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 2-3 part, Herba Hedyotidis Diffusae 45-50 part, Radix Gentianae 45-50 part, Rhizoma Curcumae 23-27 part, Fructus Arctii 23-27 part, Herba Epimedii 15-18 part, Poria 15-18 part, Herba Taxilli 15-18 part.
2. the pharmaceutical composition of anti metastasis according to claim 1, is characterized in that: described compositions is prepared from by the traditional Chinese medicinal material raw materials of following weight portion: the Radix Euphorbiae Fischerianae (Radix Euphorbiae Ebracteolatae) 2 parts, Herba Hedyotidis Diffusae 48 parts, Radix Gentianae 48 parts, Rhizoma Curcumae 25 parts, Fructus Arctii 25 parts, Herba Epimedii 16 parts, 16 parts, Poria, Herba Taxilli 16 parts.
3. the pharmaceutical composition of anti metastasis according to claim 1 and 2, is characterized in that: described compositions is oral formulations.
4. the pharmaceutical composition of anti metastasis according to claim 3, is characterized in that: described oral formulations is tablet, capsule, granule, oral liquid.
5. the pharmaceutical composition of anti metastasis according to claim 1 and 2, is characterized in that: described tumor is melanoma.
6. the application of the compositions described in claim 1 or 2 in the medicine preparing melanoma transfer.
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| CN111053762B (en) * | 2019-12-26 | 2023-02-07 | 内蒙古民族大学 | Application of stellera chamaejasme B in preparation of medicine for treating melanoma |
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