CN105395786A - New use of pharmaceutical composition - Google Patents

New use of pharmaceutical composition Download PDF

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CN105395786A
CN105395786A CN201510899068.2A CN201510899068A CN105395786A CN 105395786 A CN105395786 A CN 105395786A CN 201510899068 A CN201510899068 A CN 201510899068A CN 105395786 A CN105395786 A CN 105395786A
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王瑞峰
海丽娜
王金华
潘晓娟
雷娜
沈燕
孟杨
秦文杰
李明花
李安平
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Beijing Zhendong Biotechnology Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/489—Sophora, e.g. necklacepod or mamani
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

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Abstract

The invention provides new medical use of compound sophora flavescens injection, and the use refers to application in preparation of drugs treating colorectal cancer, in particular to the application in drugs treating advanced colorectal cancer. The compound sophora flavescens injection provided by the invention has precise prescription and remarkable curative effect, is especially suitable for treatment of advanced rectal cancer symptoms, can be used for single treatment, and also can be used in combination with surgery, radiotherapy or chemotherapy. Clinical test shows that the Chinese medicinal composition provided by the invention has an effective rate up to 96.8% and a cure rate up to 61.3%.

Description

A kind of novelty teabag of Pharmaceutical composition
Technical field
A kind of novelty teabag of the open Chinese medicine compound lightyellow sophora root injection (trade (brand) name: rock relaxes) of the present invention.Described novelty teabag is at preparation treatment colorectal cancer, the particularly novelty teabag of advanced colorectal cancer disease medicament.
Background technology
Colon cancer and rectal cancer be generically and collectively referred to as colorectal cancer, i.e. so-called colorectal cancer, refer to the malignant change that colorectal mucosa epithelium occurs under the multiple carcinogenic factor effect such as environment or heredity, the i.e. malignant tumor of colorectal mucosa epithelium genesis, be one of modal malignant tumor of digestive tract, be in the 3rd of global malignant tumor, and along with growth in the living standard, the change of dietary structure, the sickness rate of colorectal cancer is in lasting rising.Operative treatment is the prefered method for the treatment of of colorectal cancer, and within 5 years, survival rate is only about 50%.Current western medical treatment colorectal cancer be perform the operation, radiotherapy, chemotherapy be first-selection.But rectal cancer due to early symptom not obvious, time many patients make a definite diagnosis, majority has been middle and advanced stage patient, carry out operative treatment and no doubt can excise cancerous protuberance, but also have cancer embolus in residual cancer or regional lymph node metastasis or blood vessel to exist, the raising of reacting for whole body therapeutic and body defenses of performing the operation is like water off a duck's back.By adopting treatment by Chinese herbs Combined with Radiotherapy chemotherapy to control symptom in late period, can relief of symptoms, symptom management, and toxic and side effects is little.
Colorectal cancer in Chinese medicine more belongs to the category such as " mass in the abdomen ", " spouting bleeding from anus ".Its cause of disease mostly is eating and drinking without temperance, and addiction to greasy and sweet foods, scorching or unclean thing, cause the dysfunction of the spleen, damp and hotly accumulates malicious tenesmus large intestine, thermal burn intestinal network, poison evil become carbuncle and gradually carcinoma occurs.According to theory of Chinese medical science, for the pathogeny of rectal cancer, suitable bowel relieving removing toxic substances, invigorating spleen and kidney, heat clearing away eliminating stagnation, carry out dialectical composition of prescription, to reach the object for the treatment of both the principal and secondary aspects of a disease.
FUFANG KUSHEN ZHUSHEYE is that scientific composition, is prepared from, has clearing away heat-damp and promoting diuresis, removing pathogenic heat from blood and toxic substance from the body under modern Chinese medicine injection technological guidance, effect of removing obstruction for relieving pain by Radix Sophorae Flavescentis, Smilax lanceaefolia Roxb. Var.opaca A.DC. under Traditional Chinese medical theory instructs.FUFANG KUSHEN ZHUSHEYE is national secondary Chinese medicine protection kind, is applied to cancerous protuberance pain, hemorrhage clinically for many years.CN1062181C discloses FUFANG KUSHEN ZHUSHEYE for the treatment of pulmonary carcinoma, hepatocarcinoma, gastric cancer and the effect alleviating cancerous pain; CN1876016A discloses the effects such as FUFANG KUSHEN ZHUSHEYE anti entity tumour, adjuvant chemotherapy medicine efficacy enhancing and toxicity reducing, analgesia, hemostasis, leukocyte increasing, raising immunity, anti-hepatitis.We have carried out inside and outside to the therapeutical effect of this medicine in colorectal cancer and have explored and clinical research.Result shows: the growth of FUFANG KUSHEN ZHUSHEYE to Human colorectal cancer cells strain SW480 and HT29 has obvious inhibitory action, to LOVO cell proliferation in vitro, there is suppression in various degree and lethal effect, to the infiltration of Human colorectal carcinoma SW480 transplanted tumor, transfer there is obvious inhibitory action.Clinical experiment shows: alone or treat rectal cancer with chemotherapeutics coupling, FUFANG KUSHEN ZHUSHEYE is evident in efficacy, disease progression can be delayed, improve symptom, and toxic and side effects is comparatively light, the indexs such as case fatality rate, life cycle, median survival interval, progression of disease phase and quality of life all have obvious improvement.
Summary of the invention
A kind of novelty teabag of the open FUFANG KUSHEN ZHUSHEYE of the present invention.
The novelty teabag that the present invention relates to is at preparation treatment colorectal cancer, the particularly novelty teabag of advanced colorectal cancer disease medicament.
The crude drug of FUFANG KUSHEN ZHUSHEYE of the present invention consists of:
Radix Sophorae Flavescentis 1000 ~ 1500 weight portion Smilax lanceaefolia Roxb. Var.opaca A.DC. 400 ~ 800 weight portion.
The crude drug of FUFANG KUSHEN ZHUSHEYE of the present invention preferably consists of:
Radix Sophorae Flavescentis 1400 weight portion Smilax lanceaefolia Roxb. Var.opaca A.DC. 600 weight portion.
The preparation method of FUFANG KUSHEN ZHUSHEYE of the present invention comprises the steps:
Two taste crude drug are ground into coarse powder, mixing, put in diacolation jar, add 0.5 ~ 3% acetic acid being equivalent to dose 3 ~ 8 times to flood 30 ~ 50 hours, then carry out percolation, collection is filtered liquid, reducing pressure less than 75 DEG C, it is appropriate to be concentrated into, another device is deposited, medicinal residues add 3 ~ 8 times amount waters for injection, decoct secondary, each 0.5 ~ 2 hour, merging filtrate, be concentrated into appropriate, let cool, centrifugal, supernatant and sour concentrated solution merge, be adjusted to 800 ~ 1200 parts by volume, add alcohol settling 2 times, solution alcohol content is first made to reach 50 ~ 70%, hold over night, centrifugal, supernatant decompression recycling ethanol, be concentrated into 300 ~ 600 parts by volume, adding ethanol again makes alcohol content reach 80 ~ 95%, the same process, inject with active carbon appropriate, heat treated, filter, with sodium hydroxide adjust pH to 6 ~ 8, placed liquid, filter, adjust pH to 9 ~ 11 again, same treatment, pH to 4 ~ 6 are adjusted with acetic acid, same treatment, pH to 7 ~ 9 are adjusted again with sodium hydroxide, inject and be adjusted to 1000 parts by volume with water, microporous membrane sucking filtration, embedding, sterilizing, obtain.
The preparation method of FUFANG KUSHEN ZHUSHEYE of the present invention preferably includes following steps:
Two taste crude drug are ground into coarse powder, mixing, put in diacolation jar, add 1% acetic acid being equivalent to dose 5 times and flood 48 hours, then carry out percolation, collection is filtered liquid, reducing pressure less than 75 DEG C, it is appropriate to be concentrated into, another device is deposited, medicinal residues add 5 times amount waters for injection, decoct secondary, each 1 hour, merging filtrate, be concentrated into appropriate, let cool, centrifugal, supernatant and sour concentrated solution merge, be adjusted to 1000 parts by volume, add alcohol settling 2 times, solution alcohol content is first made to reach 65%, hold over night, centrifugal, supernatant decompression recycling ethanol, be concentrated into 500 parts by volume, adding ethanol again makes alcohol content reach 90%, the same process, inject with active carbon appropriate, heat treated, filter, with sodium hydroxide adjust pH to 7, placed liquid, filter, adjust pH to 11 again, same treatment, pH to 5 is adjusted with acetic acid, same treatment, pH to 8 is adjusted again with sodium hydroxide, inject and be adjusted to 1000 parts by volume with water, microporous membrane sucking filtration, embedding, sterilizing, obtain.
The ratio of weight portion of the present invention and parts by volume is grams per milliliter.
Following experimental example and embodiment are used for further illustrating but are not limited to the present invention.
Pharmacodynamic experiment
Pharmacodynamic study result of the test shows, pharmaceutical composition of the present invention has obvious inhibitory action to human colorectal cancer cell line SW480 and HT29, to the in-vitro multiplication of LOVO cell, there is suppression in various degree and lethal effect, have obvious inhibitory action to the growth of Human colorectal carcinoma SW480 transplanted tumor cell.
experimental example 1.
Pharmaceutical composition of the present invention is to the influence research of human colorectal cancer cell line SW480 and HT29
MTT method (mtt assay) is adopted to measure drug combination preparation of the present invention (by the preparation of embodiment 1 method) the growth inhibited effect to Human colorectal cancer cells strain SW480 and HT29, with culture fluid in contrast.Take the logarithm trophophase cell, be inoculated in 96 well culture plates, every hole adds 100 l of cell suspension (5000, every hole cell).Medicine group gradient dilution is join in culture plate after variable concentrations, and every hole adds medicinal liquid 100 microlitre, and often kind of concentration establishes 3 multiple holes, after mixing, culture plate is placed in CO gently 2in incubator, 37 DEG C, volume fraction is the CO of 5% 2under condition after continuous culture 48h, every hole adds 10 pi of MTT solution (5g/L, normal saline), continues to cultivate 4h.Careful sucking-off culture fluid before measuring, every hole adds DMSO150 microlitre, slowly vibrates, and the rear microplate reader of dissolving completely to be crystallized measures OD value and calculates its suppression ratio under wavelength 570nm.
Suppression ratio=(1-experimental group OD value/matched group OD value) × 100%
Observe the cytotoxicity of medicine to human colorectal cancer cell line SW480 and HCT-29
The results are shown in Table 1:
table 1 medicine is to the cytotoxicity (n=3) of SW480 and HT29 cell strain
Result shows, this medicine has obvious inhibitory action to Human colorectal cancer cells strain SW480 and HT29 under the dosage conditions of 100mg/ml.
experimental example 2
FUFANG KUSHEN ZHUSHEYE (by the preparation of the embodiment 1 method) impact on colon cancer LOVO cell proliferation in vitro.
By the survival rate of 6h, 24h, 48h, 72h, 96h, 120hLOVO cell after the FUFANG KUSHEN ZHUSHEYE effect of MTT colorimetric determination variable concentrations, compare with blank cell, calculate the suppression ratio of cell proliferation.
Result shows: the propagation of FUFANG KUSHEN ZHUSHEYE to LOVO cell of variable concentrations has suppression in various degree and lethal effect, and presents obvious dose-dependence.The performance showed increased such as 2mg/ml FUFANG KUSHEN ZHUSHEYE group has obvious time dependence, and along with the prolongation of time, cell floats, broken, dead; 1,0.5, the effect of 0.25mg/ml FUFANG KUSHEN ZHUSHEYE group from 6h-72h, the inhibitory action of cell growth in obviously increasing situation, but when action time is more than 72h, weakens the inhibitory action of LOVO cell proliferation gradually.
Apoptosis rate with flow cytomery after variable concentrations FUFANG KUSHEN ZHUSHEYE effect LOVO cell and cell cycle distribution situation.Result display is as drug effect 6h, and each concentration FUFANG KUSHEN ZHUSHEYE and matched group more all occur that G1, S phase blocks trend; Lmg/ml, 2mg/ml FUFANG KUSHEN ZHUSHEYE group effect 24h, enters the cytosis of G2/M phase compared with matched group; 2,1,0.5mg/m1 dosing group effect 48h enter the G2/M phase cell comparatively matched group all have increase.
table 2 variable concentrations, different time rock relax the proliferation inhibition rate after to colon cancer LOVO cytosis
（n=18，x±s）
Control 2mg/mlOM（%） 1mg/mlOM（%） 500ug/mlOM（%） 250 ug/mlOM（%）
6h 0.00 34.42±9.65** 17.74±7.54* 10.24±11.48 7.93±4.02*
24h 0.00 54.36±6.97** 27.51±8.79** 7.83±0.74** 5.78±4.08
48h 0.00 67.64±7.87** 34.90±5.11** 11.99±2.94** 11.21±4.64*
72h 0.00 78.71±4.36** 47.77±14.21** 13.54±1.7** 7.12±3.51*
96h 0.00 85.76±3.96** 45.22±22.68** 12.72±5.58* 8.74±6.02
120h 0.00 89.22±2.47** 40.90±5.93** 6.06±5.15 0.90±3.00
Note: compared with matched group, * * P < 0.01, * P < 0.05
table 3 variable concentrations rock relaxes on the impact of LOVO cell cycle distribution
（n=3，x±s）
Note: compared with matched group, * * P < 0.01, * P < 0.05
experimental example 3
The impact that FUFANG KUSHEN ZHUSHEYE (by the preparation of embodiment 2 method) is expressed human colon carcinoma SW480 transplanted tumor E-cadherin.
Select healthy SPF level BALB/c mouse 2, female, age 4-6 week, body weight 20 ± 2g; Healthy SD rat 40, body weight (180 ± 15) g.40 healthy SD rats, after modeling success, are divided into 4 groups by the method for table of random number grouping, often organize 10: A group: model control group by inoculation human colon carcinoma SW480 orthotopic transplantation tumor; B group: positive controls; C group: FUFANG KUSHEN ZHUSHEYE high dose group; D group: FUFANG KUSHEN ZHUSHEYE low dose group.Fasting 24h after inoculation, starts drug treatment after diet water 7d.A group: model control group, presses 10ml/kg.qd coloclysis with sterilized water for injection; B group: positive controls, lumbar injection 5-FU, dosage is 50mg/kg.qod; C group: FUFANG KUSHEN ZHUSHEYE high dose group, 2ml (8g)/qd. body weight coloclysis; D group: FUFANG KUSHEN ZHUSHEYE low dose group, 2ml (0.8g)/qd. body weight coloclysis, hangs leakproof by the feet.After often organizing equal successive administration 14d, de-neck puts to death each group of rat, dissects and peels off tumor tissue and weigh, win thymus, spleen is weighed, calculate tumour inhibiting rate, thymus index, index and spleen index respectively.Adopt EnvisionTM two step method to analyze the expression of E-cadherin in transplanted tumor tissue, inquire into the impact that FUFANG KUSHEN ZHUSHEYE infiltrates Human colorectal carcinoma SW480 transplanted tumor, shifts, and Primary Study is carried out to wherein mechanism of action.
Result is as follows:
The change of 1.SD rat ordinary circumstance
Before modeling, all rats enliven, and hair color is smooth, and feed water is normal, and stool is in coccoid, and upgrowth situation is good.Inoculate in latter 6 days, outward appearance is without significant change, and activity, diet, stool are all normal, and after each group rat inoculation SW480 transplanted tumor block, tumor formation rate is 100%.Modeling starts after 7 days to give drug enema process, FUFANG KUSHEN ZHUSHEYE high and low dose group and positive controls (5-FU group) rat hypogastric region inoculation position can be laid one's hand on and the substantive enclosed mass of soybean grain size, out-of-shape, surface irregularity, tight with surrounding tissue adhesion, mobility is poor; With growing up of tumor body, the body weight of FUFANG KUSHEN ZHUSHEYE high and low dose group and positive controls rat all comparatively before increase to some extent, lazy dynamic, Mus hair is matt, times of defecation increases, loose stool, slit liquid just; Day feed discharge reduction, liveness reduces gradually; Model group rats tumor bulk-growth is accelerated, and partial rat occurs lazy dynamic, drowsiness, flocks together, hogback, perpendicular hair, Mus hair are not bright and clean, feed discharge reduction, loose stool, weight loss.Modeling is after 14 days, and losing weight appears in model group rats, and the feed water yield is comparatively front obviously to be reduced, the dirty and messy tarnish of chaeta.There is depilation phenomenon in positive controls, chaeta loosens dirty and messy, body weight comparatively before obviously alleviate, comparatively model group loses weight obviously, often together crowded, and FUFANG KUSHEN ZHUSHEYE is respectively organized, and rat body weight is obviously comparatively front to be increased, the day feed water yield increases, and liveness increases.Testing positives matched group has 1 rat dead because of dyscrasia, has 1 rat because of the improper death of coloclysis in model group.
2. the change of various rat body weight before and after administration
To compare respectively after rat inoculation SW480 transplanted tumor the 7th day and the body weight change of the 15th day after administration, the results are shown in following table.
table 4: before and after administration SD rat body weight change (g, )
Group Animal number of cases (n) 7th day (g) 15th day (g)
Model control group 9 198.15±8.37 242.13±6.45
Positive controls 9 198.18±8.17 236.56±4.73 ※▲
FUFANG KUSHEN ZHUSHEYE high dose group 10 198.92±8.02 252.32±5.35 ▲
FUFANG KUSHEN ZHUSHEYE low dose group 10 198.81±8.45 248.85±5.61 ▲
Note: contrast ※ P<0.01 with model group; Dosage group contrast ▲ P<0.01 each with FUFANG KUSHEN ZHUSHEYE
From above table, respectively organize rat body weight comparison in difference before administration without statistically meaning (P>0.05).After administration, FUFANG KUSHEN ZHUSHEYE high and low dose group, positive controls rat body weight difference compared with model group have significant difference (P<0.01); With FUFANG KUSHEN ZHUSHEYE high and low dose group ratio, positive controls rat body weight obviously alleviates (P<0.01), and FUFANG KUSHEN ZHUSHEYE high and low dose group rat body weight increases, show that FUFANG KUSHEN ZHUSHEYE can improve the general survival condition of rat to a certain extent.
3. the impact of medicine and tumour inhibiting rate heavy on SW480 transplanted tumor rat tumor
Drug enema, after 14 days, puts to death each group of rat weight by de-cervical approach, thorax abdomen ANER DIAN and 75% alcohol disinfecting, open abdominal cavity, carefully peel off tumor block.Model control group, FUFANG KUSHEN ZHUSHEYE low dose group gross tumor volume are large, and blood supplies, and quality is more crisp, and infiltrate intestinal wall, boundary is unclear, not easily separated, easily hemorrhage in separation process; And positive controls, FUFANG KUSHEN ZHUSHEYE high dose group gross tumor volume are less, blood is not for good enough, light with surrounding tissue infiltration degree, is easily separated, and goes out insufficiency of blood in separation process.Use filter paper suck dry moisture after peeling off tumor body, take tumor weight, to calculate tumor control rate.Tumor weight and the tumour inhibiting rate of each group are as follows.
table 5: medicine on the impact of SW480 transplanted tumor rat tumor weight ( )
Group Animal number of cases (n) Tumor heavy (g) Tumour inhibiting rate (g)
Model control group 9 1.734±0.418 ——
Positive controls 9 0.945±0.412 45.50%
FUFANG KUSHEN ZHUSHEYE high dose group 10 1.273±0.071 ▽ 26.59%
FUFANG KUSHEN ZHUSHEYE low dose group 10 1.465±0.186 ▼ 15.51%
Note: compare ▽ P<0.05 with positive controls, ▼ P<0.01
From above table, the average tumor of FUFANG KUSHEN ZHUSHEYE each dosage group is heavy lower than model group, the tumour inhibiting rate of FUFANG KUSHEN ZHUSHEYE high and low dose group and the tumour inhibiting rate of model group have significant difference, and wherein FUFANG KUSHEN ZHUSHEYE high and low dose group tumour inhibiting rate is respectively 26.59%, 15.51%; Compare with positive controls, FUFANG KUSHEN ZHUSHEYE high dose group tumor-inhibiting action more weak (P<0.05), low dose group the most weak (P<0.01); Positive controls (5-FU group) tumor-inhibiting action is the strongest.Illustrate that the growth of FUFANG KUSHEN ZHUSHEYE to SW480 transplanted tumor rat tumor body has inhibitory action thus.
4. medicine is on the impact of SW480 transplanted tumor immune organs of rats
Positive controls: naked eyes see rat chest gland, spleen severe atrophy, and dissect not easily complete separation, the thymus leaflet of partial rat is unclear, and color is canescence, and spleen is pale red.In FUFANG KUSHEN ZHUSHEYE high and low dose group, thymus, the spleen outward appearance of SD rat are lobulated, and demarcate clear with surrounding tissue, and color is greyish white, glossy, and volume is large.FUFANG KUSHEN ZHUSHEYE high and low dose group Thymus and spleen index is higher compared with the Thymus and spleen index of model group and positive controls.
Experimental data is as follows:
table 6: medicine on the impact of SW480 transplanted tumor Rats Spleen exponential sum thymus index ( )
Group Animal number of cases (n) Thymus index (mg/g) Index and spleen index (mg/g)
Model control group 9 1.282±0.104 2.180±0.181
Positive controls ● 9 0.919±0.187 1.930±0.125
FUFANG KUSHEN ZHUSHEYE high dose group ●☆ 10 1.388±0.130 2.252±0.138
FUFANG KUSHEN ZHUSHEYE low dose group ○☆ 10 1.251±0.118 2.179±0.152
Note: with model group ratio ● P<0.05, zero P<0.01; With positive controls than ☆ P<0.01
As seen from the above table, FUFANG KUSHEN ZHUSHEYE each dosage group SD rat chest gland index, comparatively model control group is high for index and spleen index, wherein FUFANG KUSHEN ZHUSHEYE high dose group has significant difference (P<0.01), low dosage (P<0.05); SD rat chest gland index in FUFANG KUSHEN ZHUSHEYE high and low dose group, index and spleen index comparatively positive controls have remarkable rising; SD rat chest gland index in positive controls (5-FU group), index and spleen index comparatively model control group obviously reduce, and have significant difference (P<0.01); Show that 5-FU has stronger damage effect to the spleen of SW480 transplanted tumor rat and thymus, cause spleen and atrophy of thymus gland, strike is to a certain degree caused to the immunologic mechanism of rat, and FUFANG KUSHEN ZHUSHEYE can impel thymus, the spleen growth of rat, and the immunologic function of body can be improved to a great extent, the anti-tumor capacity of enhancing body.
5. FUFANG KUSHEN ZHUSHEYE is on the impact of SW480 transplanted tumor rat liver transfer case
Get liver after de-neck puts to death rat, observe the hepatic metastasis situation of tumor, result is as follows
table 7: the comparison of each group rat liver transfer case after drug enema
Group Animal number of cases (n) Rat liver transfer number of cases (n)
Model control group 9 4
Positive controls 9 3 ◇
FUFANG KUSHEN ZHUSHEYE high dose group 10 1 ◆
FUFANG KUSHEN ZHUSHEYE low dose group 10 2 ◆
Note: with model group than ◇ P<0.05, with positive controls ratio ◆ P<0.01
As seen from the above table, each group of rat occurs that the quantity of hepatic metastasis is respectively, model control group 4, positive controls 3, FUFANG KUSHEN ZHUSHEYE high dose group 1, FUFANG KUSHEN ZHUSHEYE low dose group 2, after using X 2 test to carry out statistical analysis, shows between each group and occurs that the situation of Liver metastases there are differences.Compare with model group, rat liver transfer number of cases less (P<0.05) of positive controls; Compare with positive controls, rat liver transfer number of cases less slightly (P<0.01) of FUFANG KUSHEN ZHUSHEYE each dosage group, prompting FUFANG KUSHEN ZHUSHEYE, to the hepatic metastasis situation of SW480 transplanted tumor rat, serves inhibitory action to a certain extent.
6. medicine is on the impact of E-cadherin in SW480 transplanted tumor rat tumor tissue
After drug enema, in SW480 transplanted tumor rat tumor tissue, E-cadherin expression contents is as follows:
table 8: medicine is on the impact of E-cadherin in SW480 transplanted tumor rat tumor tissue
As seen from the above table, with model control group ratio, positive controls, FUFANG KUSHEN ZHUSHEYE high dose group E-cadherin express and obviously raise, and it is variant that FUFANG KUSHEN ZHUSHEYE low dose group E-cadherin expresses rising; FUFANG KUSHEN ZHUSHEYE high dose group and positive controls contrast without significant difference, also illustrate that FUFANG KUSHEN ZHUSHEYE and 5-FU express close affecting SW480 transplanted tumor rat E-cadherin.
experimental example 4
Clinical observation case is selected from the outpatient service year February in March, 2013 to 2014 with complete data and rectal cancer patient totally 62 examples of being in hospital, age 38-71 year, wherein man 33 example, female 29 example.
Diagnostic criteria:
(1) bowl evacuation habit changes, and has pus and blood or Mucous Stool, and with tenesmus, stool out-of-shape, there is difficult defecation in the later stage.
(2) anal-rectal tumor has local pain, podex neoplasm or fecal incontinence.
(3) digital rectal examination, can touch irregular masses on rectal wall, and fingerstall can contaminate pus and blood.Position the higher person is made rectoscope or sigmoidoscopy and biopsy and is made a definite diagnosis.
(4) x-ray inspection: clysis with barium shows local filling defect, mucosal damage, and intestinal wall is stiff, stenosis of bowel or block.
Therapeutic Method: use compositions FUFANG KUSHEN ZHUSHEYE of the present invention (by the preparation of embodiment 1 method).
Efficacy assessment standard:
Cure: good through root value criterion wound healing, without complication.Observe 5 years without recurrence.
Complete incidence graph: lump disappears, symptom takes a turn for the better, and maintains more than 1 month without metastasis.
Partial rcsponse: mass reduction >=50%, symptom alleviates, and maintains more than 1 month.
Therapeutic outcome: 62 routine patients, through the treatment of 3 courses for the treatment of, cure 38 examples, effective 13 examples, effective 13 examples, invalid 2 examples.Cure rate is 61.3%; Total effective rate is 96.8%.
Conclusion: the traditional Chinese medicine composition for treating rectal cancer that the present invention treats rectal cancer is evident in efficacy, can delay disease progression, improve symptom, and have no side effect
experimental example 5
FUFANG KUSHEN ZHUSHEYE is on advanced colorectal cancer patient median survival interval and the impact of quality of life.
Adopt Randomized controlled clinical study method, include advanced colorectal cancer patient 40 example in, 37 examples can be evaluated, treatment group 18 example, matched group 19 example, two groups all adopt chemotherapy (FOLFOX, FOLFRI scheme) to treat, treatment group adds with FUFANG KUSHEN ZHUSHEYE (by the preparation of embodiment 2 method) on this basis, treat after 3 months, carry out long term follow-up, observe the case fatality rate of patient, life cycle, median survival interval, progression of disease phase (timetoprogression, TTP) and quality of life.
The case fatality rate of result display treatment group and matched group is respectively 11.1% (2/18) and 42.1% (8/19); Life cycle is respectively (22.63 ± 7.34) individual month and (19.76 ± 8.28) individual month, and median survival interval is respectively 17 months and 13 months; TTP is respectively (17.76 ± 5.62) individual month and (12.68 ± 9.26) individual month, and statistical analysis all has statistical significance (P<0.05).TCM symptom score, quality of life and KPS mark before treatment group is treated and are respectively 15.59 ± 3.78,54.06 ± 3.96,64.71 ± 6.24, be respectively 10.53 ± 5.57,58.65 ± 4.03,69.41 ± 4.29 after treatment, before and after treatment, comparing difference all has statistical significance (P<0.05); 16.11 ± 3.99,54.06 ± 4.39 and 64.44 ± 5.11 are respectively before treatment of control group; Be respectively 19.61 ± 7.78,50.17 ± 8.26,60.00 ± 9.70 after treatment, treatment Life For The Residents of Three Gorges Reservoir Before and KPS scoring comparing difference have statistical significance (P<0.05), but trend is the direction to difference.
model case
Case 1
Liu so-and-so, female, 52 years old.Patient started before half a year to occur that times of defecation increases, random thoughts abdominal distention, and stool band blood, is diagnosed as colon cancer intestinal cancer at local hospital in the recent period.Namely perform an operation very soon, the state of an illness takes a turn for the better gradually, recurs after half a year, brings into use medicine of the present invention to treat, after 1 course for the treatment of, times of defecation obviously reduces, and no longer occurs the situation of having blood in stool, after adhering to 4 courses for the treatment of of use, malaise symptoms disappears, and repeatedly checks, and all recover normal.
Case 2
Zhao so-and-so, man, 68 years old.Suffer from rectal cancer late period, abdominal metastas, often stomachache, abdominal distention, lost best opportunity of operation, he has accepted the suggestion of hospital, adopts Chinese traditional treatment, after use 3 courses for the treatment of of medicine of the present invention, complication alleviates gradually, and health takes a turn for the better day by day, within 3 years, follows up a case by regular visits to patient and is still still living and in good health.
Case 3
Female, 45 years old, frequent micturition, urgent micturition, have blood in stool, leucorrhea abnormal, be diagnosed as rectal cancer through hospital, through chemicotherapy, occur that apparent side effect reacts, use medicine of the present invention, after 3 months check, symptom is significantly alleviated.
Case 4
Man, 40 years old, just, stomachache, defecation frequency increased, single quantity is few, difficult defecation, and stool such as to attenuate at the symptom, be diagnosed as colon cancer early stage, through January chemotherapy without being clearly better, be clearly better after using medicine of the present invention, multiple in good condition after May, and progressively take food, continue use after 6 months, health is rehabilitation gradually, can take care of oneself and work.
Detailed description of the invention
Embodiment 1.
The crude drug of FUFANG KUSHEN ZHUSHEYE consists of:
Radix Sophorae Flavescentis 1400 parts, Smilax lanceaefolia Roxb. Var.opaca A.DC. 600 parts.
Two taste crude drug are ground into coarse powder, mixing, put in diacolation jar, add 1% acetic acid being equivalent to dose 5 times and flood 48 hours, then carry out percolation, collection is filtered liquid, reducing pressure less than 75 DEG C, it is appropriate to be concentrated into, another device is deposited, medicinal residues add 5 times amount waters for injection, decoct secondary, each 1 hour, merging filtrate, be concentrated into appropriate, let cool, centrifugal, supernatant and sour concentrated solution merge, be adjusted to 1000 parts by volume, add alcohol settling 2 times, solution alcohol content is first made to reach 65%, hold over night, centrifugal, supernatant decompression recycling ethanol, be concentrated into 500 parts by volume, adding ethanol again makes alcohol content reach 90%, the same process, inject with active carbon appropriate, heat treated, filter, with sodium hydroxide adjust pH to 7, placed liquid, filter, adjust pH to 11 again, same treatment, pH to 5 is adjusted with acetic acid, same treatment, pH to 8 is adjusted again with sodium hydroxide, inject and be adjusted to 1000 parts by volume with water, microporous membrane sucking filtration, embedding, sterilizing, obtain.
Embodiment 2
The crude drug of FUFANG KUSHEN ZHUSHEYE consists of:
Radix Sophorae Flavescentis 1400 parts, Smilax lanceaefolia Roxb. Var.opaca A.DC. 600 parts.
By two taste crude drug according to the percolation (Chinese Pharmacopoeia 2010 editions annex IO) under fluid extract and extractum item, make solvent with 1% acetum, flood after 24 ~ 30 hours, percolation 24 hours, collect percolate, medicinal residues decoct with water secondary, each 1 hour, after filtrate and above-mentioned percolate merge, be concentrated into appropriate, adding ethanol makes alcohol content reach 60%, leave standstill, filter, reclaim ethanol, and concentrating under reduced pressure medicinal liquid, adding ethanol again makes alcohol content be 80%, leave standstill, filter, reclaim ethanol, and concentrating under reduced pressure medicinal liquid, adding ethanol again makes alcohol content be 90%, leave standstill, reclaim and eliminate ethanol, inject water to 80% of dosing amount, with 20% sodium hydroxide solution and 25% acetum adjust ph, add active carbon 4g, heat micro-boiling 20 minutes, let cool, filter, by 20% sodium hydroxide solution adjust ph, add 0.25% polyoxyethylene sorbitan monoleate, inject water to 1000ml, filter, embedding, sterilizing, obtain.
The ratio of weight portion of the present invention and parts by volume is grams per milliliter.
The above embodiment is only that the preferred embodiment of the present invention is described; not scope of the present invention is limited; under not departing from the present invention and designing the prerequisite of spirit; the various distortion that those of ordinary skill in the art make technical scheme of the present invention and improvement, all should fall in protection domain that claims of the present invention determine.

Claims (5)

1. the application of Chinese medicine composition in preparation treatment colorectal cancer medicine, the activated feedstock of its compositions consists of:
Radix Sophorae Flavescentis 1000 ~ 1500 weight portion, Smilax lanceaefolia Roxb. Var.opaca A.DC. 400 ~ 800 weight portion.
2. apply as claimed in claim 1, it is characterized in that composition material medicine wherein consists of: Radix Sophorae Flavescentis 1400 weight portion, Smilax lanceaefolia Roxb. Var.opaca A.DC. 600 weight portion.
3. apply as claimed in claim 1, it is characterized in that compositions is wherein prepared from by the following method:
Two taste crude drug are ground into coarse powder, mixing, put in diacolation jar, add 0.5 ~ 3% acetic acid being equivalent to dose 3 ~ 8 times to flood 30 ~ 50 hours, then carry out percolation, collection is filtered liquid, reducing pressure less than 75 DEG C, it is appropriate to be concentrated into, another device is deposited, medicinal residues add 3 ~ 8 times amount waters for injection, decoct secondary, each 0.5 ~ 2 hour, merging filtrate, be concentrated into appropriate, let cool, centrifugal, supernatant and sour concentrated solution merge, be adjusted to 800 ~ 1200 parts by volume, add alcohol settling 2 times, solution alcohol content is first made to reach 50 ~ 70%, hold over night, centrifugal, supernatant decompression recycling ethanol, be concentrated into 300 ~ 600 parts by volume, adding ethanol again makes alcohol content reach 80 ~ 95%, the same process, inject with active carbon appropriate, heat treated, filter, with sodium hydroxide adjust pH to 6 ~ 8, placed liquid, filter, adjust pH to 9 ~ 11 again, same treatment, pH to 4 ~ 6 are adjusted with acetic acid, same treatment, pH to 7 ~ 9 are adjusted again with sodium hydroxide, inject and be adjusted to 1000 parts by volume with water, microporous membrane sucking filtration, embedding, sterilizing, obtain.
4. apply as claimed in claim 1, it is characterized in that compositions is wherein prepared from by the following method:
Two taste crude drug are ground into coarse powder, mixing, put in diacolation jar, add 1% acetic acid being equivalent to dose 5 times and flood 48 hours, then carry out percolation, collection is filtered liquid, reducing pressure less than 75 DEG C, it is appropriate to be concentrated into, another device is deposited, medicinal residues add 5 times amount waters for injection, decoct secondary, each 1 hour, merging filtrate, be concentrated into appropriate, let cool, centrifugal, supernatant and sour concentrated solution merge, be adjusted to 1000 parts by volume, add alcohol settling 2 times, solution alcohol content is first made to reach 65%, hold over night, centrifugal, supernatant decompression recycling ethanol, be concentrated into 500 parts by volume, adding ethanol again makes alcohol content reach 90%, the same process, inject with active carbon appropriate, heat treated, filter, with sodium hydroxide adjust pH to 7, placed liquid, filter, adjust pH to 11 again, same treatment, pH to 5 is adjusted with acetic acid, same treatment, pH to 8 is adjusted again with sodium hydroxide, inject and be adjusted to 1000 parts by volume with water, microporous membrane sucking filtration, embedding, sterilizing, obtain, described weight portion and the ratio of parts by volume are grams per milliliter.
5. apply as claimed in claim 1, it is characterized in that compositions is wherein prepared from by the following method:
By two taste crude drug according to the percolation (Chinese Pharmacopoeia 2010 editions annex IO) under fluid extract and extractum item, make solvent with 1% acetum, flood after 24 ~ 30 hours, percolation 24 hours, collect percolate, medicinal residues decoct with water secondary, each 1 hour, after filtrate and above-mentioned percolate merge, be concentrated into appropriate, adding ethanol makes alcohol content reach 60%, leave standstill, filter, reclaim ethanol, and concentrating under reduced pressure medicinal liquid, adding ethanol again makes alcohol content be 80%, leave standstill, filter, reclaim ethanol, and concentrating under reduced pressure medicinal liquid, adding ethanol again makes alcohol content be 90%, leave standstill, reclaim and eliminate ethanol, inject water to 80% of dosing amount, with 20% sodium hydroxide solution and 25% acetum adjust ph, add active carbon 4g, heat micro-boiling 20 minutes, let cool, filter, by 20% sodium hydroxide solution adjust ph, add 0.25% polyoxyethylene sorbitan monoleate, inject water to 1000ml, filter, embedding, sterilizing, obtain.
CN201510899068.2A 2015-12-09 2015-12-09 New use of pharmaceutical composition Pending CN105395786A (en)

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CN1171960A (en) * 1997-07-16 1998-02-04 山西金晶药业有限公司 Compound sophora flavescens injection
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Publication number Priority date Publication date Assignee Title
CN1171960A (en) * 1997-07-16 1998-02-04 山西金晶药业有限公司 Compound sophora flavescens injection
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