CN1062181C - Compound sophora flavescens injection - Google Patents

Compound sophora flavescens injection Download PDF

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Publication number
CN1062181C
CN1062181C CN97112532A CN97112532A CN1062181C CN 1062181 C CN1062181 C CN 1062181C CN 97112532 A CN97112532 A CN 97112532A CN 97112532 A CN97112532 A CN 97112532A CN 1062181 C CN1062181 C CN 1062181C
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injection
treatment
examples
transfer
concentrated
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CN1171960A (en
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张志文
张明远
燕章文
张明理
周钟鸣
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Shanxi Zhendong Pharmaceutical Co ltd
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JINJING PHARMACEUTICAL INDUSTRY Co Ltd SHANXI PROV
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Abstract

The present invention discloses a compound lightyellow sophora root injection which is prepared from lightyellow sophora root and white Poria. The injection can be used for resisting tumor, relieving cancer pain and stopping bleeding, and has the synergism and detoxicating effect on chemotherapeutic drugs for tumor.

Description

FUFANG KUSHEN ZHUSHEYE
The present invention relates to a kind of cancer that is used for the treatment of,, improve the injection that patient's life quality has good therapeutic effect, belong to drug world particularly to cancerous pain, carcino-matous hemorrhage.
Radix Sophorae Flavescentis belongs to heat clearing and damp drying class Chinese medicine, has dampness, detoxifcation, parasiticidal effect.It has been known routine techniques that Radix Sophorae Flavescentis is made injection, but the antitumaous effect of lightyellow sophora root injection does not appear in the newspapers always.CN1050326 discloses a kind of manufacture method of bitter injection of bitter cassia holo-element, and this injection is to be raw material with Radix Sophorae Flavescentis and Cortex Cinnamomi, extracts active ingredient respectively and makes.Though this medicine has certain anticancer analgetic effect, its tumour inhibiting rate is relatively low.And a hot temperature is very unreasonable on prescription.
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.
Embodiment:
Prescription: Radix Sophorae Flavescentis 1400 gram Smilax lanceaefolia Roxb. Var.opaca A.DC. 600 grams
Method for making: above two flavor medicated powder are broken into coarse powder, and mixing is put in the percolation cylinder, add 1% acetic acid that is equivalent to 6 times of doses and soaked 48 hours clearly, then carry out percolation, collect the liquid of filtering and emit solution, concentrating under reduced pressure (below 75 ℃) is to 400ml, and device is deposited in addition, and medicinal residues add 6 times of amount waters for injection, decoct 2 times, each 1 hour, filter, merging filtrate is concentrated into 400ml, puts cold, centrifugal, supernatant and sour concentrated solution merge, and are adjusted to about 1000ml.Add ethanol precipitation 2 times, make solution alcohol content reach 65%, standing over night earlier, centrifugal, the supernatant decompression recycling ethanol is concentrated into 400ml, add ethanol again and make that to contain alcohol amount be 90%, the same processing adds (the 160 ℃ of heating 2 hours of injection active carbon, activation) an amount of, heated constantly jolting 15 minutes, put coldly, 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 20%NaOH again with method with 20% acetic acid; Add the injection water transfer to 1000ml, the microporous membrane sucking filtration, every 2ml of embedding, sterilize 100 ℃ 30 minutes.

Claims (5)

1, a kind of FUFANG KUSHEN ZHUSHEYE is characterized in that the raw material for preparing this injection is:
Radix Sophorae Flavescentis 1000-1500 gram Smilax lanceaefolia Roxb. Var.opaca A.DC. 400-800 gram.
2, FUFANG KUSHEN ZHUSHEYE according to claim 1 is characterized in that the raw material for preparing this injection is:
Radix Sophorae Flavescentis 1400 gram Smilax lanceaefolia Roxb. Var.opaca A.DC. 600 grams.
3, FUFANG KUSHEN ZHUSHEYE according to claim 1 is characterized in that this injection is to be prepared from following method:
Two flavor raw material powders are broken into coarse powder, and mixing is put in the percolation cylinder, adds to be equivalent to dose 3-8 0.5-3% acetic acid dipping doubly 30-50 hour, then carry out percolation, collect the liquid of filtering, emit solution, decompression is concentrated into an amount of below 75 ℃, device is deposited in addition, and medicinal residues add 3-8 and doubly measure water for injection, decoct 2 times, each 0.5-2 hour, filter merging filtrate, be concentrated in right amount, put cold, centrifugal, supernatant and sour concentrated solution merge, and are adjusted to 800-1200ml, add ethanol precipitation 2 times, make solution alcohol content reach 50-70% earlier, standing over night, centrifugal, the supernatant decompression recycling ethanol is concentrated into 300-600ml, adds ethanol again and makes pure content reach 80-95%, the same processing, it is an amount of to add the injection active carbon, heats 15 minutes, constantly jolting is put coldly, filters, transfer PH to 7 with NaOH, cold putting spent the night, and filters, transfer PH to 11 again, handle, transfer PH to 5 with acetic acid with method, handle with method, transfer PH to 8 with NaOH again, add the injection water and transfer to 1000ml, the microporous membrane sucking filtration, embedding, sterilization.
4, according to the FUFANG KUSHEN ZHUSHEYE of claim 3, it is characterized in that flooding the used acetate concentration of raw material is 1%.
5, according to the compound light-yellow sophora root injection fluid injection of claim 3, the pure content when it is characterized in that extracting the concentrated solution ethanol precipitation twice is respectively 65% and 90%.
CN97112532A 1997-07-16 1997-07-16 Compound sophora flavescens injection Expired - Lifetime CN1062181C (en)

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CN1296036C (en) * 2005-02-04 2007-01-24 张海峰 Compound light-yellow sophora root freeze-drying injection and preparation thereof

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CN100375630C (en) * 2005-06-13 2008-03-19 北京正大绿洲医药科技有限公司 Compound drop pills with flavescent sophora root and its preparation method
CN101822770A (en) * 2010-04-29 2010-09-08 北京振东光明药物研究院有限公司 Medicinal composition with anti-tumor effect and application thereof
CN104352477A (en) * 2014-11-04 2015-02-18 湖南利诺生物药业有限公司 Traditional Chinese medicine pain-relieving capsule and preparation method thereof
CN104606607A (en) * 2015-01-27 2015-05-13 刘军花 Medicament for nursing cancer pain
CN105395786A (en) * 2015-12-09 2016-03-16 北京振东生物科技有限公司 New use of pharmaceutical composition
CN113577182A (en) * 2021-09-15 2021-11-02 山西振东健康生物科技股份有限公司 Traditional Chinese medicine extract and preparation method and application thereof

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Address after: Shanxi Changzhi Guangming Road Zhendong Science Park zip code: 047100

Patentee after: Shanxi Zhendong Pharmaceutical Co.,Ltd.

Address before: Su Zhen, Changzhi County, Shanxi Province: 047105

Patentee before: Shanxi Zhendong Jinjing Pharmaceutical Co.,Ltd.

C56 Change in the name or address of the patentee
CP01 Change in the name or title of a patent holder

Address after: 047100 Shanxi County of Changzhi province science and Technology Park Zhendong road light

Patentee after: SHANXI ZHENDONG PHARMACEUTICAL Co.,Ltd.

Address before: 047100 Shanxi County of Changzhi province science and Technology Park Zhendong road light

Patentee before: Shanxi Zhendong Pharmaceutical Co.,Ltd.

CX01 Expiry of patent term
CX01 Expiry of patent term

Granted publication date: 20010221