CN103191146B - Efficient painless drug for treating local tumor ablation - Google Patents

Abstract

The invention discloses a high-efficiency and painless drug for local ablation of tumors, which is a mixture of absolute ethanol and lauromacrogol, the proportion of lauromacrogol is 0.1% to 99.9% in terms of volume fraction, and the proportion of absolute ethanol is 99.9% %~0.1% range. The efficient and painless local tumor ablation drug injected into the tumor under the guidance of ultrasound and other imaging techniques is a mixture of absolute ethanol and lauromacrogol in a volume ratio of 19/1 to 99/1. The volume ratio of said absolute ethanol to lauromacrogol is preferably 99/1 or 19/1. The application of the highly efficient and painless local tumor ablation therapy drug is injected into tumors for ablation therapy drug under the guidance of image technology such as preparation of ultrasound. The patient had no adverse reactions such as pain during the operation. Postoperative color Doppler ultrasonography re-examination found that the tumor echo was increased, the blood flow signal was significantly reduced, and the re-examination indicators of some patients with elevated alpha-fetoprotein were significantly reduced.

Description

A highly efficient and painless drug for local ablation of tumors

technical field

The invention relates to a drug for local ablation of tumors, which uses absolute ethanol to directly kill tumors and lauromacrogol to destroy tumor blood vessels and induce local immune responses to achieve multi-channel anti-tumor effects, and has no adverse reactions such as pain during the injection process, and is highly effective. Painless anti-tumor advantage.

Background technique

Tumor chemical ablation has the advantages of simple operation, mild adverse reactions, and low cost, among which percutaneous ethanol injection (PEI) is the most representative. The main mechanism of PEI treatment is that high-concentration ethanol is injected into the tumor to cause rapid dehydration of tumor cells, protein coagulation, denaturation and necrosis of cancer cells. However, due to the uneven diffusion of the drug after intratumoral injection of pure anhydrous ethanol, multiple injections are required, and some large tumors are difficult to be completely inactivated, resulting in recurrence in the future. In addition, pain is a common adverse reaction of PEI. The greater the dosage of absolute ethanol, the more obvious the pain. Some patients could not bear it and gave up treatment.

Lauromacrogol injection (1% lauromacrogol aqueous solution) is mainly used clinically for emergency hemostasis of esophageal variceal bleeding and sclerotherapy of varicose veins under endoscopy. After intravenous injection of lauromacrogol, it can damage the vascular endothelium, promote thrombus formation, and cause aseptic inflammation and necrosis at the injection site. In addition, lauromacrogol is an ether compound that has local anesthetic and analgesic effects. Clinical studies in recent years have shown that lauromacrogol injection also has a good curative effect on diseases such as cysts, hemangiomas and venous malformations. In some studies, intratumoral injection of lauromacrogol injection has a certain effect on uterine fibroids, but the overall curative effect is not good, and there is no report about intratumoral injection of lauromacrogol injection in the treatment of malignant tumors.

Contents of the invention

The purpose of the present invention is to provide a kind of efficient and painless local tumor ablation treatment drug which is mixed with absolute ethanol and lauromacrogol.

The purpose of the present invention is achieved in that the highly efficient and painless local tumor ablation treatment drug is a mixed solution of absolute ethanol and lauromacrogol, and the ratio of lauromacrogol in volume fraction is 0.1% to 99.9%, The proportion of absolute ethanol is in the range of 99.9% to 0.1%. As long as the mixed solution of absolute ethanol and lauromacrogol is made according to the above ratio, the effect of the present invention can be achieved.

The highly efficient and painless local tumor ablation treatment drug injected into the local tumor under the guidance of imaging techniques such as ultrasound is a mixture of absolute ethanol and lauromacrogol in a volume ratio of 19/1 to 99/1. As long as the mixed solution of absolute ethanol and lauromacrogol is made according to the above ratio, the effect of the present invention can be achieved.

Of course, the above-mentioned volume ratio of absolute ethanol to lauromacrogol is preferably 99/1 or 19/1, and the effect of painless tumor local ablation therapy is better.

The high-efficiency and painless tumor local ablation therapy drug described in the present invention is injected into the tumor for ablation therapy drug under the guidance of imaging technology such as preparation of ultrasound; it is especially suitable for most solid tumors in the human body, such as liver cancer, kidney cancer, and thyroid cancer , Breast cancer, retroperitoneal and soft tissue benign and malignant tumors local ablation therapy.

The advantages of the present invention are: the highly efficient and painless local tumor ablation treatment drug of the present invention can be injected into the local tumor under the guidance of ultrasound and other imaging techniques, and the strong tissue coagulation effect of absolute ethanol and lauromacrogol can be used to destroy tumor blood vessels, Induce local inflammatory response and other ways to ablate tumor. In addition, the local anesthesia and analgesic effect of lauromacrogol can significantly reduce the pain response caused by the injection of absolute ethanol, increase the injection volume of absolute ethanol, improve the compliance of patients with treatment, and achieve a more thorough tumor inactivation effect. The present invention is suitable for local ablation treatment of most solid tumors in human body, such as liver cancer, kidney cancer, thyroid cancer, breast cancer, retroperitoneum and soft tissue benign and malignant tumors.

Description of drawings

Figure 1 is a contrast-enhanced ultrasonography image of rabbit VX2 tumor after treatment with the mixture of absolute ethanol and lauromacrogol.

Fig. 2 is a pathological examination diagram of rabbit VX2 tumor after treatment with the mixture of absolute ethanol and lauromacrogol .

Detailed ways

1. Preparation of mixed injection medicine

Under sterile conditions, accurately absorb absolute ethanol and lauromacrogol, and mix them thoroughly at a volume ratio of 19/1 (V/V) to obtain a mixed injection (that is, 95% ethanol by volume + 5% polyol by volume). cinnamyl alcohol mixture), and stored at 4°C for later use.

2. Drug analgesic test

Take 32 Kunming mice, weighing 18-22 g, half male and half male, and randomly divide them into 4 groups: normal saline control group (A), 2% lidocaine control group (B), lauromacrogol injection group ( C), 95% ethanol + 5% lauromacrogol mixture group (D). 10 μl of the above-mentioned corresponding drugs were subcutaneously injected into the foot pad of the left hind limb of the mice with a micro-injector, and 10 μl of 1% formalin was injected again along the needle track 5 minutes later, the pain response of the mice was observed for 2 minutes, and the score was calculated. 3 points for licking, biting or shaking the foot; 2 points for lifting the foot; 1 point for lightly touching the bottom but no weight bearing, 1 point for limp when walking; 0 point for normal weight bearing and free walking. As a result, the analgesic effect of the lauromacrogol group was the most obvious, and the difference was statistically significant compared with the control group ( P <0.05) (Table 1).

Table 1 Comparison of analgesic effects of different treatments

^* Compared with group A, P ﹤0.05; ^#Compared with group B, P ﹤0.05

3. Comparison of the effects of mixed injection and absolute ethanol on ablation of rat liver tissue

Eighteen male normal-grade SD rats, weighing about 250 g, were randomly divided into two groups, the mixed injection group and the absolute ethanol group. After ether inhalation anesthesia, 0.1 ml of the drug was injected into the liver tissue of the rats by laparotomy. Seven days later, the rats were killed by ether inhalation anesthesia, and the rat livers were dissected to measure the necrosis volume of the liver tissue. The average necrosis volume in the mixed injection group was (0.265±0.077) cm ³ , significantly higher than (0.013±0.005) cm ³ in the absolute ethanol group ( P <0.01).

4. Comparison of curative effect of mixed injection and absolute ethanol in ablation of liver cancer in mice

Forty Kunming mice, male, weighing 18-22 g, were subcutaneously inoculated with mouse liver cancer H22 cells in the right axilla. Seven days later, the tumor volume was measured by high-frequency ultrasound, and ³² mice with a tumor volume of about 0.1 cm3 were selected and randomly divided into 4 groups, namely normal saline group (A), absolute ethanol group (B), and lauromacrogol injection group ( C), mixed injection group (D). After the mice were anesthetized by ether inhalation, under the guidance of high-frequency ultrasound, the corresponding drugs were injected, with an injection volume of 0.1 ml, administered once every 3 days, and administered 4 times in a row, and the survival time of the tumor-bearing mice was observed. As a result, the mixed injection group had the longest survival time, with an average of 31.5 days (Table 2).

Table 2 Comparison of survival time of mice in each group (d)

Group Don't arithmetic mean median survival time Group A 14.4 13 Group B 21.8 20 Group C 16.1 15 Group D 31.5 31

5. Comparison of curative effect of mixed injection (95% ethanol + 5% lauromacrogol mixture) and absolute ethanol in ablation of rabbit VX2 tumor

Twenty-four male New Zealand rabbits, weighing 2.4-2.6 kg, were inoculated with VX2 tumors in the muscle layer of the right hindlimb, and the changes in tumor volume were monitored by color Doppler ultrasonography. After 12 days, subjects with a tumor volume of about 1.8 ^cm3 were selected for ablation therapy experiment, and were randomly divided into 3 groups, 6 rats in each group, which were normal saline control group (A), absolute ethanol group (B), 95% ethanol+5% Lauromacrogol mixed solution group (C). After the tumor-bearing rabbits were fixed, the corresponding drugs were injected into the tumor under the guidance of color Doppler ultrasound. The injection volume was twice the tumor volume, and the treatment was repeated once a week later. On the 14th day after the treatment, after observing the local blood perfusion of the tumor by contrast-enhanced ultrasound, the animals were sacrificed, and the tumor was collected for histopathological examination. The results showed that the tumor volume of the absolute ethanol and 95% ethanol + 5% lauromacrogol mixed solution group was (3.01±0.78) cm ³ , significantly smaller than that of the normal saline control group (8.20±2.45) cm ³ , and smaller than that of the absolute ethanol group (4.97±1.07) cm ³ , the entire tumor was basically not enhanced by contrast-enhanced ultrasound (see Figure 1), and histopathological examination showed large necrosis of the tumor tissue in the mixed solution group (see Figure 2).

6. Ultrasound-guided local ablation of ethanol lauromacrogol mixture in the treatment of liver cancer with portal vein tumor thrombus

Absolute ethanol and lauromacrogol are mixed thoroughly at a volume ratio of 99/1 (V/V) to obtain a mixed injection (that is, 99% ethanol by volume + 1% lauromacrogol by volume). Five cases of liver cancer with portal vein tumor thrombus were injected with the above-mentioned mixture of 99% ethanol and 1% lauromacrogol under ultrasound guidance for ablation treatment. During the operation, the patient had no adverse reaction such as pain, and the treatment went smoothly. Postoperative color Doppler ultrasound re-examination found that the tumor echo was increased, the blood flow signal was significantly reduced, and the re-examination indicators of some patients with elevated alpha-fetoprotein were significantly reduced, and the long-term curative effect was still under observation. To the local tumor, the strong tissue coagulation effect of absolute ethanol and lauromacrogol are used to destroy tumor blood vessels and induce local inflammatory reactions to ablate the tumor.

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.