CN103191146B - Efficient painless drug for treating local tumor ablation - Google Patents
Efficient painless drug for treating local tumor ablation Download PDFInfo
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- CN103191146B CN103191146B CN201310140677.0A CN201310140677A CN103191146B CN 103191146 B CN103191146 B CN 103191146B CN 201310140677 A CN201310140677 A CN 201310140677A CN 103191146 B CN103191146 B CN 103191146B
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- polidocanol
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Abstract
The invention discloses an efficient painless drug for treating local tumor ablation. The efficient painless drug is mixed solution of absolute ethyl alcohol and lauromacrogol, wherein the ratio of lauromacrogol is 0.1-99.9%, and the ratio of absolute ethyl alcohol is 99.9%-0.1% according to the volume fraction. The efficient painless drug for treating local tumor ablation, which is injected into local tumor under guide of an ultrasonic imaging technique, is the mixed solution of absolute ethyl alcohol and lauromacrogol according to the volume ratio of 19/1 to 99/1; and volume ratio of absolute ethyl alcohol to lauromacrogol preferably is 99/1 or 19/1; the efficient painless drug for treating local tumor ablation is applied to preparation of the drug for treating ablation by being injected to the tumor under guide of the ultrasonic imaging technique; the sufferer has no adverse reaction such as pain in an operation; and the postoperation color Doppler ultrasonic review finds out that the tumor echo is increased, blood flow signals are obviously reduced, and the indexes of a part of patients with rising alpha fetal protein are obviously reduced by review.
Description
Technical field
The present invention relates to a kind of tumor local ablation therapy medicine, dehydrated alcohol direct killing tumor and polidocanol is utilized to destroy tumor vessel, the reaction of induction local immunity, reach multipath antitumor action, and without untoward reaction such as pain in injection process, there is efficiently painless antitumor advantage.
Background technology
Tumor chemical ablation has the advantages such as easy and simple to handle, untoward reaction is light, low cost, and wherein percutaneous Ethanol Injection (percutaneous ethanol injection, PEI) most is representative.The main mechanism of PEI treatment causes tumor cell rapid dehydration, protein coagulation in high concentration ethanol injection tumor, and make tumor cell degeneration, necrosis, for the hepatocarcinoma of small volume, the small liver cancer curative effect being especially less than 3 cm is obvious.But because drug dispersion is uneven after simple dehydrated alcohol intratumor injection, need multiple injection to treat, the tumor that partial volume is larger is difficult to thorough deactivation, cause recurring in the future.In addition, pain is the common untoward reaction of PEI, and the larger pain of dehydrated alcohol consumption is more obvious, and some patients cannot be stood and abandoning cure.
Polycinnamic alcohol injection (aqueous solution of 1% polidocanol) is mainly used in the sclerotherapy of the hemorrhage emergency treatment hemostasis of esophageal variceal vein under scope and cirso-clinically.After polidocanol intravenous injection, can injured blood vessel endothelium, promote thrombosis, and injection site generation aseptic inflammation, necrosis can be made.In addition, polidocanol is a kind of ether compound, has regional anesthesia analgesia effect.Clinical research in recent years shows, polycinnamic alcohol injection also has good curative effect to diseases such as cyst, hemangioma and venous malformations.Part research adopts polycinnamic alcohol injection intratumoral injection hysteromyoma also to have certain curative effect, but general curative effect is not good enough, and relevant polycinnamic alcohol injection intratumoral injection malignant tumor has not yet to see report.
Summary of the invention
The object of this invention is to provide a kind of dehydrated alcohol and the polidocanol efficiently painless tumor local ablation therapy medicine as Mixtard.
The object of the present invention is achieved like this, described efficiently painless tumor local ablation therapy medicine, for the mixed liquor of dehydrated alcohol and polidocanol, with the ratio of volume fraction polidocanol for 0.1% ~ 99.9%, the ratio of dehydrated alcohol is 99.9% ~ 0.1% scope.As long as the mixed liquor that dehydrated alcohol and polidocanol are made into according to the above ratio can reach effect of the present invention.
Described guides bet to be mapped to the efficiently painless tumor local ablation therapy medicine of tumor by local, for dehydrated alcohol and polidocanol are the mixed liquor of 19/1 ~ 99/1 by volume at the ultrasonic image technology that waits.As long as the mixed liquor that dehydrated alcohol and polidocanol are made into according to the above ratio can reach effect of the present invention.
Certainly above-mentioned dehydrated alcohol and the volume ratio of polidocanol are preferably 99/1 or 19/1, then painless tumor local ablation therapy effect is better.
Efficiently painless tumor local ablation therapy medicine of the present invention is in the ultrasonic application waiting image technology to guide bet to be mapped to tumor to carry out in ablation medicine of preparation; Be particularly useful for the most of entity tumor of human body, as after hepatocarcinoma, renal carcinoma, thyroid carcinoma, breast carcinoma, peritoneum and the local ablation therapy of soft tissue innocent and malignant tumour.
Advantage of the present invention is: efficiently painless tumor local ablation therapy medicine of the present invention, it guides bet to be mapped to tumor by local by the ultrasonic image technology that waits, and the tissue coagulation effect utilizing dehydrated alcohol powerful and polidocanol destroy the multipath ablated tumor such as tumor vessel, the reaction of induction local inflammation.In addition, the regional anesthesia analgesia effect of polidocanol significantly can alleviate the pain reaction that percutaneous ethanol injectionl causes, and improves Ethanol Injection amount, improves the compliance of patient treatment, reaches more thoroughly tumor inactivating efficacy.The present invention is applicable to the most of entity tumor of human body, as after hepatocarcinoma, renal carcinoma, thyroid carcinoma, breast carcinoma, peritoneum and the local ablation therapy of soft tissue innocent and malignant tumour.
Accompanying drawing explanation
Fig. 1 is rabbit VX2 tumor Contrast-enhanced Ultrasound figure after dehydrated alcohol and polidocanol mixed liquor are treated.
Fig. 2 is rabbit VX2 cancer pathology inspection figure after dehydrated alcohol and polidocanol mixed liquor are treated
.
Detailed description of the invention
1, the preparation of Mixtard medicine
Aseptically, accurate absorption dehydrated alcohol and polidocanol, by volume ratio is 19/1(V/V) fully mixing acquisition Mixtard (namely volume fraction is 95% ethanol+volume fraction is 5% polidocanol mixed liquor), 4 DEG C save backup.
2, medicine analgesic test
Get Kunming mouse 32, weight 18 ~ 22g, male and female half and half, be divided into 4 groups at random: saline control group (A), 2% lignocaine matched group (B), polycinnamic alcohol injection group (C), 95% ethanol+5% polidocanol mixed liquor group (D).Adopt microsyringe to mice left hind foot lift hemostasis above-mentioned relative medicine 10 μ l, within 5 minutes, tailing edge needle track injects 1% formalin 10 μ l again, observes mice pain and reacts 2 minutes, calculate integration.Lick, sting or tremble 3 points, foot; Carry 2 points, foot; Touch bottom surface but do not bear a heavy burden, during walking, walking lamely 1 point; Normal heavy burden, walking 0 point freely.As a result, polidocanol group analgesic activity is the most obvious, compares with matched group, difference have statistical significance (
p<0.05) (table 1).
Table 1 different disposal analgesic effect compares
*compare with A group,
p﹤ 0.05;
#compare with B group,
p﹤ 0.05
3, Mixtard and dehydrated alcohol melt liver tissues of rats effect and compare
Male regular grade SD rat 18, weight is about 250g, is divided into 2 groups at random, Mixtard group and dehydrated alcohol group, after ether inhalation anesthesia, opens ventrad liver tissues of rats injectable drug 0.1ml.After 7 days, rat is put to death in ether inhalation anesthesia, dissects rat liver, measures necrosis of liver tissue volume.The average Necrosis volume of Mixtard group is (0.265 ± 0.077) cm
3, apparently higher than (0.013 ± 0.005) cm of dehydrated alcohol group
3(
p<0.01).
4, Mixtard and dehydrated alcohol melt rat liver cancer comparitive study
Kunming mouse 40, male, 18 ~ 22g, right side axillary fossa subcutaneous vaccination rat liver cancer H22 cell.After 7 days, high frequency ultrasound measures gross tumor volume, chooses tumor volume about 0.1 cm
3mice 32, is divided into 4 groups at random, is respectively normal saline group (A), dehydrated alcohol group (B), polycinnamic alcohol injection group (C), Mixtard group (D).After mice ether inhalation anesthesia, under high frequency ultrasound guides, injection relative medicine, volume injected is 0.1ml, administration 1 time in every 3 days, successive administration 4 times, observes tumor-bearing mice life span.As a result, Mixtard group life span is the longest, average out to 31.5 days (table 2).
Respectively the group mouse survival time compares (d) to table 2
| Group | Arithmetic mean | Median survival interval |
| A group | 14.4 | 13 |
| B group | 21.8 | 20 |
| C group | 16.1 | 15 |
| D group | 31.5 | 31 |
5, Mixtard (95% ethanol+5% polidocanol mixed liquor) melts rabbit VX2 tumor efficiency with dehydrated alcohol and compares
Male New Zealand rabbits 24, weight 2.4 ~ 2.6 kg, right hind muscle layer inoculation VX2 tumor, the change of color Doppler ultrasonography monitoring gross tumor volume.After 12 days, choose gross tumor volume about 1.8 cm
3person carries out ablation experiment, is divided into 3 groups at random, often organizes 6, is respectively saline control group (A), dehydrated alcohol group (B), 95% ethanol+5% polidocanol mixed liquor group (C).After lotus tumor rabbit is fixing, under Color Doppler ultrasound guide, intratumor injection relative medicine, injectable drug volume is 2 times of gross tumor volume, repetitive therapy 1 time after 1 week.After the 14th day ultrasonic contrast observes tumor by local blood perfusion situation after treatment, put to death animal, get tumor and carry out histopathologic examination.Found that, dehydrated alcohol and 95% ethanol+5% polidocanol mixed liquor group gross tumor volume are (3.01 ± 0.78) cm
3, be significantly less than saline control group (8.20 ± 2.45) cm
3, be also less than dehydrated alcohol group (4.97 ± 1.07) cm
3, the whole tumor of ultrasonic contrast does not strengthen (see figure 1) substantially, and the large stretch of downright bad (see figure 2) of mixed liquor group tumor tissues is seen by histopathologic examination.
6, ultrasonic mediation dehydrated alcohol polidocanol mixed liquor local ablation therapy hepatocarcinoma companion portal vein tumor thrombus
Dehydrated alcohol and polidocanol, by volume ratio is 99/1(V/V) fully mixing acquisition Mixtard (namely volume fraction is 99% ethanol+volume fraction is 1% polidocanol mixed liquor).Hepatocarcinoma companion portal vein tumor thrombus patient 5 example, injects 99% above-mentioned ethanol+1% polidocanol mixed liquor in ultrasound guidance tumor and in cancer embolus and carries out ablation.In art, patient is without untoward reaction such as pain, and treatment smoothly.Postoperative color doppler ultrasonography check finds that tumor echo is increased, blood flow signal obviously reduces, part alpha-fetoprotein rising patient checks index and obviously reduces, late result still under observation, illustrate that the present invention guides bet to be mapped to tumor by local by the ultrasonic image technology that waits, the tissue coagulation effect utilizing dehydrated alcohol powerful and polidocanol destroy the multipath ablated tumor such as tumor vessel, the reaction of induction local inflammation.
Claims (1)
1. an efficient painless tumor local ablation therapy medicine, being the mixed liquor of dehydrated alcohol and polidocanol, is 99/1 or 19/1 with the volume ratio of the dehydrated alcohol described in volume fraction and polidocanol.
2. guide bet to be mapped to the efficiently painless tumor local ablation therapy medicine of tumor by local at Ultrasonography, be the mixed liquor of dehydrated alcohol and polidocanol, described dehydrated alcohol and the volume ratio of polidocanol are 99/1 or 19/1.
3. the application that the efficiently painless tumor local ablation therapy medicine described in claim 1 or 2 is being prepared Ultrasonography and guided bet to be mapped to tumor to carry out in ablation medicine.
4. application according to claim 3, is characterized in that described tumor is hepatocarcinoma, renal carcinoma, thyroid carcinoma, breast carcinoma or peritoneum innocent and malignant tumour.
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| CN103191146B true CN103191146B (en) | 2015-05-13 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103768090B (en) * | 2014-02-19 | 2015-11-25 | 南通大学附属医院 | A kind of medicine of Uterine Fibroids by Intervention Therapy |
| WO2016090143A1 (en) * | 2014-12-04 | 2016-06-09 | Autonomix Medical, Inc. | Systems and methods for treating cancer and/or augmenting organ function |
| US9351945B1 (en) * | 2015-02-27 | 2016-05-31 | John Daniel Dobak, III | Reduction of adipose tissue |
| CN113143955A (en) * | 2021-03-09 | 2021-07-23 | 厦门大学 | Modified lauromacrogol foam hardening agent, preparation method and application |
| CN114129714B (en) * | 2021-11-24 | 2023-04-28 | 苏州大学 | Pharmaceutical preparation and preparation method and application thereof |
| CN114159388A (en) * | 2021-12-17 | 2022-03-11 | 陕西天宇制药有限公司 | Application of lauromacrogol injection in preparation of medicine for treating bronchial cyst |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829078A (en) * | 2010-03-19 | 2010-09-15 | 福建医科大学附属协和医院 | Absolute ethyl alcohol injection containing docetaxel and application thereof in preparing medicaments for treating tumors under ultrasonic guidance |
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| CN101829078A (en) * | 2010-03-19 | 2010-09-15 | 福建医科大学附属协和医院 | Absolute ethyl alcohol injection containing docetaxel and application thereof in preparing medicaments for treating tumors under ultrasonic guidance |
Non-Patent Citations (1)
| Title |
|---|
| 超声引导下经皮穿刺聚桂醇治疗35例肾囊肿的疗效观察;朱晓伟;《中国民族民间医药》;20130415(第7期);52 * |
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