The purpose of this invention is to provide a kind of anticancer, analgesic injection, this injection not only to cancerous pain, carcino-matous hemorrhage, to improve patient's life quality effective, the effect that the tumor body is dwindled.
FUFANG KUSHEN ZHUSHEYE of the present invention is prepared from following method:
Prescription: Radix Sophorae Flavescentis 1000-1500 gram Smilax lanceaefolia Roxb. Var.opaca A.DC. 400-800 gram
Preparation technology: above two flavor medicated powder are broken into coarse powder, and mixing is put in the percolation cylinder, according to " percolation in appendix of Chinese pharmacopoeia nineteen ninety version under fluid extract and the extractum item carries out percolation.
Add and be equivalent to dose 3-8 0.5-3% acetic acid dipping doubly 30-50 hour, preferred 48 hours, then carry out percolation, collect the liquid of filtering, emit solution, concentrating under reduced pressure (below 75 ℃) is extremely an amount of, (being no more than 1000ml), device is deposited in addition.Medicinal residues add 3-8 and doubly measure water for injection, decoct each 0.5-2 hour 2 times, filter, merging filtrate is concentrated into an amount of (being no more than 1000ml), put coldly, centrifugal, supernatant and sour concentrated solution merge, be adjusted to about 800-1200ml, add ethanol precipitation 2 times, make solution alcohol content reach 50-70% earlier, leave standstill filtration, centrifugal, the supernatant decompression recycling ethanol, be concentrated into 300-600ml, add ethanol again and make pure content 80-95%, the same processing, (160 ℃ were heated 2 hours to add the injection active carbon, activation) an amount of, heated 15 minutes, constantly jolting is put cold, filter, 20%NaOH transfers PH to 7; Cold putting spent the night, and filters, and transfers PH to 11 again.Handle with method, transfer PH to 5, handle, transfer PH to 8 with NaOH again with method with 20% acetic acid; Add the injection water transfer to 1000ml, the microporous membrane sucking filtration, embedding (every 2ml), sterilize 100 ℃ 30 minutes promptly.
Injection of the present invention is compared with existing FUFANG KUSHEN ZHUSHEYE, and mice is had the obvious suppression effect because of the plan pain reaction that physical property and chemical irritation cause.To mice transplanted tumor S180 (sarcoma), the growth of H22 (hepatocarcinoma) has the obvious suppression effect; Mouse cell immunity and humoral immune function due to the tumor lowly all there is potentiation.And tangible anastalsis arranged.
FUFANG KUSHEN ZHUSHEYE of the present invention is compared with existing lightyellow sophora root injection, owing to reasonable recipe, produced new pharmacological action, promptly cyclophosphamide is suppressed tumor obvious synergistic effect is arranged, toxicity to heavy dose of cyclophosphamide has tangible Attenuation, shows the raising hemopoietic function of bone marrow aspect of leukocyte increasing.
Experimental example 1 FUFANG KUSHEN ZHUSHEYE clinical experiment report
According to the result of preclinical pharmacology, toxicological test summary and I clinical trial phase, FUFANG KUSHEN ZHUSHEYE has been carried out the research of II clinical trial phase.In this stage, we use this medicine treatment pulmonary carcinoma, gastric cancer, hepatocarcinoma totally 204 examples according to " clinical trial protocol " requirement, establish positive controls (chemotherapeutics treatment commonly used) simultaneously in addition and carry out controlled observation research.
Test objective
By the II clinical trial phase, further estimate the effectiveness of FUFANG KUSHEN ZHUSHEYE, and toxicity.
Physical data and case are selected
The object of including this test in has three kinds of pulmonary carcinoma, gastric cancer and primary hepatocarcinoma (to call hepatocarcinoma in the following text) totally 294 routine common cancers, is to have lost operation opportunity or middle and advanced stage case that operations research could not excise and perform the operation the back compound recipe, comprising:
1, pulmonary carcinoma 135 examples are divided into two groups, i.e. compound light-yellow sophora root injection for curing group at random, (to call the treatment group in the following text) 105 examples and positive control (chemotherapeutics treatment group commonly used is to call matched group in the following text) 30 examples, treatment is organized in 105 examples, man's 84 examples, women 21 examples, maximum 64 years old age, minimal ages 26 years old, average 54.2 years old, in matched group 30 examples, man's 23 examples, women 7 examples, maximum 64 years old age, minimal ages 31 years old, average 53.6 years old.In 135 examples, 81 examples are made a definite diagnosis through pathology, and 24 examples are made a definite diagnosis through the cytology, and are surplus respectively by CT (24 example) and X line (6 example) diagnosis.
2, gastric cancer 90 examples, treatment is organized in 60 examples, male 49 examples, women 11 examples, maximum ages 65 example, minimal ages 34 years old, average 58.9 years old, diseased region C district 24 examples, M district 14 examples, A district 22 examples.Male 21 examples in matched group 30 examples, women 9 examples, maximum 64 years old age, minimal ages 32 years old, average 54.4 years old, diseased region C district 12 examples, M district 7 examples, A district 11 examples, all case all obtains pathological diagnosis through scope.
3, hepatocarcinoma 69 examples, treatment are organized male 33 examples in 39 examples, women 6 examples, maximum 64 years old age, minimal ages 33 years old, average 54.5 years old, 8 examples are diagnosed by hepatic tissue pathology in 39 examples, and 6 examples are by the extrahepatic tissue pathological diagnosis, and 15 examples of surplusing are diagnosed by CT+AFP, in matched group 30 examples, male 26 examples, women 4 examples, maximum 63 years old age, minimal ages 36 years old, average 56.8 years old, in 30 examples by hepatic tissue pathology diagnosis person 9 examples, extrahepatic tissue pathological diagnosis 4 examples, 17 examples of surplusing are diagnosed by CT+AFP.
Test method
With standard compliant case, include test in, divide two groups at random, the treatment group is single treats with FUFANG KUSHEN ZHUSHEYE, consumption 16-20ml adds in the 200ml physiologic dose brine, vein splashes into, and every day 1 time, 10 is a course of treatment, logotype 2-4 course of treatment, need not any other anticarcinogen except that general symptomatic treatment, matched group adopt chemotherapeutics list commonly used with or unite use, and suit the medicine to the illness, Supporting Therapy.All case is monitored leukocyte, hepatic and renal function, electrocardiogram, observation gastrointestinal reaction etc. before and after treatment and in the treatment.After treatment finishes, evaluation curative effect, relatively two groups result.
Result of the test
1, efficacy assessment standard: comprise the objective curative effect universal standard of tumor, 0-4 degree pain indexing, Karnofaky performance status point system etc.See " clinical trial protocol " for details.
2, efficacy analysis:
2.1 the objective efficacy analysis of cancer: all have in the case and can estimate tumor kitchen range person, be respectively 71 examples, 52 examples, 28 examples in treatment group pulmonary carcinoma, gastric cancer, hepatocarcinoma, matched group is respectively 24 examples, 27 example and 28 examples.Analysis result sees Table 1,2,3
The objective efficacy analysis that table 1 pulmonary carcinoma is two groups
The treatment group | Matched group |
| The example number | % | The example number | % |
CR PR S P | 7 34 25 5 | 9.9 47.9 35.2 7.0 | 3 11 8 2 | 12.5 45.8 33.3 8.4 |
Effective percentage | | 57.8 | | 58.3 |
Total routine number | 71 | | 24 | |
Compare no significant difference P>0.05 for two groups
The objective efficacy analysis that table 2 gastric cancer is two groups
The treatment group | Matched group |
| The example number | % | The example number | % |
CR PR S P | 2 21 18 11 | 3.8 40.4 34.6 21.2 | 1 10 12 4 | 3.7 37.0 44.5 14.8 |
Effective percentage | | 42.2 | | 40.7 |
Total routine number | 52 | | 27 | |
Compare no significant difference P>0.05 for two groups
The objective efficacy analysis that table 3 pulmonary carcinoma is two groups
The treatment group | Matched group |
| The example number | % | The example number | % |
CR PR S P | - 10 11 10 | 32.2 35.5 32.2 | - 8 10 10 | 28.6 35.7 35.7 |
Effective percentage | | 32.2 | | 28.6 |
Total routine number | 31 | | 28 | |
Compare no significant difference P>0.05 for two groups
From table 1,2,3 as can be seen: lung cancer therapy group effective percentage (CR+PR) 57.8%, 58.3%, two group of no significant difference of matched group effective percentage (CR+PR).
Curing gastric cancer group effective percentage (PR) 42.2%, 40.7%, two group of no significant difference of matched group effective percentage (CR+PR).
Liver cancer treatment group effective percentage (PR) 32.2%, 28.6%, two group of no significant difference of matched group efficient (PR).
The curative effect of three kinds of cancers compares, and best with pulmonary carcinoma, gastric cancer is taken second place, and hepatocarcinoma is taken second place again.
2.2 the treatment analysis of cancerous pain:
Have the above pain person of 2 degree, pulmonary carcinoma, gastric cancer, hepatocarcinoma are respectively 78 examples, 41 example and 26 examples in the treatment group.Be respectively 19 examples, 21 example and 22 examples in the matched group.Its total remission rate treatment group is followed successively by 93.0%, 97.5% and 100.0% after treating.Matched group is followed successively by 47.3%, 28.6% and 50.0%.Treatment group and matched group relatively have significant difference P<0.01.See Table 4.5.6
The efficacy analysis of two groups of treatments of table 4 pulmonary carcinoma pain
The example number | Alleviate fully | Part is alleviated | Total remission rate |
The example number | % | The example number | % | The example number | % |
Treatment group matched group | 78 19 | 55 3 | 70.5 15.7 | 16 6 | 22.5 31.6 | 71 9 | 93.0 47.3 |
Compare significant difference P<0.01 for two groups
The efficacy analysis of two groups of treatments of table 5 gastric cancer pain
The example number | Alleviate fully | Part is alleviated | Total remission rate |
Example number % | Example number % | Example number % |
Treatment group matched group | 41 21 | 28 68.3 | 12 29.2 6 28.6 | 40 97.5 6 28.6 |
Compare significant difference P<0.01 for two groups
The efficacy analysis of two groups of treatments of table 6 hepatocarcinoma pain
The example number | Alleviate fully | Part is alleviated | Total remission rate |
Example number % | Example number % | Example number % |
Treatment group matched group | 26 22 | 19 73.0 6 27.2 | 7 27.0 5 22.7 | 26 100.0 11 50.0 |
Compare significant difference P<0.01 for two groups
2.3 performance status observed result
All case has all been done the scoring of Karnofgky method before and after treatment, and the result shows that each treatment group all has rising in various degree.Matched group does not then have tangible rising, sees Table 7.8.9
Karnofgky appraisal result before and after two groups of treatments of table 7 pulmonary carcinoma
The example number | Meansigma methods before the treatment | Treatment back meansigma methods | Appreciation rate (%) |
105 matched groups 30 are organized in treatment | 62 69 | 74.0 61.0 | 19.4 |
Karnofgky appraisal result before and after two groups of treatments of table 8 gastric cancer
The example number | Meansigma methods before the treatment | Treatment back meansigma methods | Appreciation rate (%) |
60 matched groups 30 are organized in treatment | 54 56 | 76 58 | 40.7 3.6 |
Karnofgky appraisal result before and after two groups of treatments of table 9 hepatocarcinoma
The example number | Meansigma methods before the treatment | Treatment back meansigma methods | Appreciation rate (%) |
39 matched groups 30 are organized in treatment | 55 60 | 75 65 | 36.4 8.3 |
2.4 toxic reaction observed result
2.4.1 influence to bone marrow
Pulmonary carcinoma: treatment is organized in 105 examples, and leukopenia (4 * 10 is arranged before the treatment
9/ L is following) person's 23 examples, account for 21.0%.Be reduced to 11 examples after the treatment, account for 10.4%, point out no bone marrow toxicity.And in matched group 30 examples, the treatment proleukocyte is all 4 * 10
9More than/the L, treatment back leukocyte is lower than 4 * 10
9/ L person 12 examples, accounting for 40.0% (12/30) prompting has tangible bone marrow toxicity reaction.
Gastric cancer: treatment is organized in 60 examples, the treatment before from cell 4 * 10
9Following person's 4 examples of/L, treatment back 2 examples recover normal, surplus no change.The treatment proleukocyte all in normal range, has 11 examples to drop to 4 * 10 in matched group 30 examples after the treatment
9/ L following (11/30) does not have bone marrow toxicity in the results suggest treatment group, and matched group then has tangible bone marrow toxicity reaction performance.
Hepatocarcinoma: treatment group and matched group, in the treatment and after the treatment, do not have significant change in the treatment group, and 8 examples (8/30) leukopenia to 4 * 10 are arranged in the matched group all in normal range at the treatment proleukocyte
9Below/the L, wherein there are 2 examples to reduce to 3 * 10
9Below/the L, treatment still has 4 examples to be lower than normal value after finishing for two weeks.Illustrate that treatment group avirulence performance contrast then has significantly toxic reaction.
2.4.2 gastrointestinal reaction:
Pulmonary carcinoma: do not have 1 example before the treatment in the treatment group symptoms such as nausea and vomiting are arranged, the most appetite in treatment back have improvement.There are 27 examples (27/30) the varying degree nausea and vomiting to occur after the treatment of control group, 3 routine laxativeness (3/30), gastrointestinal reaction is obvious.
Gastric cancer: organize in 60 examples in treatment, have in various degree nauseating, vomiter's 19 examples to account for 31.6% before the treatment, improvement is in various degree all arranged in treatment and after the treatment, only have 6 examples to still have mild nausea after the treatment, before the treatment obvious decline is arranged.And before the treatment 7 examples of nausea and vomiting are in various degree arranged in the matched group, and account for 23.3%, (7/30) increases to 24 examples in treatment, account for to still have 9 routine symptoms to last till more than 1 week after 80.0% (24/30) treatment finishes, and other has 2 examples diarrhoea to occur.Illustrate that treatment has tangible gastrointestinal reaction.Table 10
Gastrointestinal reaction relatively in two groups of treatment front and back of table 10 gastric cancer and the treatment
Total routine number | Before the treatment | In the treatment | After the treatment |
Example number % | Example number % | Example number % |
60 matched groups 30 are organized in treatment | 19 31.6 7 23.3 | 17 28.3 24 80.0 | 6 10.0 9 30.0 |
Treatment finishes the two groups of remarkable P of comparing difference<0.01, back
Hepatocarcinoma: treatment is organized in 39 examples, mild nausea, vomiter's 9 examples (9/39) are arranged before the treatment, after treatment, have 7 examples to disappear, the person newly occurs, and in matched group 30 examples, 6 examples that mild nausea is arranged, idol has 2 examples of vomiting, and idol has diarrhoea person's 3 examples, in the treatment, the symptom of these cases all has and increases the weight of, and other has 14 examples the symptom newly to occur, illustrates that matched group has tangible gastrointestinal reaction.
2.4.3 hepatic and renal function and electrocardiogram change:
In pulmonary carcinoma, gastric cancer, three treatment groups of hepatocarcinoma, all do not have the reaction of hepatic and renal function and Electrocardiographic overt toxicity.And have indivedual cases slight toxic reaction performance once to occur in the contrast, behind symptomatic treatment, recover.
Discuss
By the clinical observation research to FUFANG KUSHEN ZHUSHEYE treatment pulmonary carcinoma, gastric cancer and hepatocarcinoma, we realize FUFANG KUSHEN ZHUSHEYE following characteristics:
1, reasonable clinical effectiveness is arranged, its objective effective percentage pulmonary carcinoma (CR+PR) is 57.8%, gastric cancer (CR+PR) is 42.2%, hepatocarcinoma (PR) is 32.2%, is 58.3% with matched group pulmonary carcinoma (CR+PR), gastric cancer (CR+PR) is 40.7%, hepatocarcinoma (PR) 28.6% curative effect close (P>0.05) is a tool new drug preferably in the present Chinese medicine anticarcinogen.
2, this medicine is in anticancer, the effect that has good alleviation cancerous pain again, its remission rate is up to 93-100%, complete remission rate is 68.3-70.5%, compare with matched group, marked difference (P<0.01) is arranged, and this is that other anticarcinogen is not available at present, for allowed the cancer patient that a new drug is not provided bitterly by 2000.
3, no obvious toxic-side effects: all find no any obvious toxic-side effects in the case, and most of case is after accepting this preparation for treating, patient's spirit, general states such as sleep, appetite also take a turn for the better thereupon, improved patient's life quality, thereby this preparation can be widely used in the treatment of middle and advanced stage cancer.
Conclusion
1, FUFANG KUSHEN ZHUSHEYE has sure anticarcinogenic effect, and its curative effect is close with chemotherapeutics commonly used.
2, except that anticarcinogenic effect, this preparation still has the effect of good alleviation cancerous pain, and pain relief rate height is that other cancer therapy drug institute is incomparable at present.
3, have no side effect, can extensively be adapted to the treatment of middle and terminal cancer.
4, can improve patient's general situation, improve patient's life quality.