Traditional Chinese medicine preparation for treating pancreatic cancer in combination with gemcitabine and improving hepatorenal toxicity

Abstract

The application discloses a traditional Chinese medicine preparation for treating pancreatic cancer and improving liver and kidney toxicity in combination with gemcitabine, which is prepared from radix codonopsis, poria cocos and ganoderma lucidum, and is used for tonifying qi and invigorating the spleen, supplementing without being too harsh, supplementing the acquired constitution, treating various deficiencies, and achieving the purpose of supporting the healthy and cultivating the root, and is the monarch drug. Kadsura japonica and oldenlandia diffusa clear heat and resolve toxicity, remove stasis and resolve mass; and coix seed benefits water and removes dampness, and are the minister drugs. Bupleurum smoothes the liver and resolves depression, regulates qi movement, and fructus aurantii enters the middle-jiao spleen and stomach, moves qi and resolves mass, the two drugs lift clear and descend turbid, and make the qi movement smooth; frankincense, myrrh and dried toad skin relieve pain; atractylodes rhizome invigorates the spleen and dries dampness; pinellia ternata regulates qi and harmonizes the center, and is combined as the auxiliary drug; and licorice root regulates all drugs, and is the minister drug. The whole formula supports the healthy and resists cancer, attacks and supplements, and considers the symptoms and the root cause. More importantly, the liver and kidney toxicity caused by the treatment of pancreatic cancer by using gemcitabine can be improved, the treatment dose does not need to be reduced or the treatment does not need to be interrupted, and the purpose of effectively treating pancreatic cancer is achieved.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine preparation, and more particularly to a traditional Chinese medicine preparation that can be used in combination with gemcitabine to treat pancreatic cancer and improve liver and kidney toxicity. Background Technology

[0002] Pancreatic cancer is a highly malignant tumor with a poor prognosis, and its pathogenesis remains unclear. Currently, chemotherapy is the main clinical treatment for pancreatic cancer, with gemcitabine (GEM) being widely used as a first-line chemotherapy drug. However, gemcitabine can cause liver and kidney toxicity in pancreatic cancer treatment, leading patients to reduce the dosage or even discontinue treatment until the toxic reactions subside. This significantly limits its clinical efficacy. Summary of the Invention

[0003] The present invention aims to solve the above-mentioned technical problems existing in the prior art and provide a traditional Chinese medicine preparation that can be used in combination with gemcitabine to treat pancreatic cancer and improve liver and kidney toxicity.

[0004] The technical solution of this invention is: a traditional Chinese medicine preparation that can be used in combination with gemcitabine to treat pancreatic cancer and improve liver and kidney toxicity. It is an aqueous extract of traditional Chinese medicine, comprising the following components and their mass fractions: Ganoderma lucidum 10-40, Codonopsis pilosula 7.5-30, Poria cocos 7.5-30, Scutellaria barbata 15-60, Hedyotis diffusa 15-60, Coix lacryma-jobi 15-60, Boswellia carterii 2.5-10, Commiphora myrrha 2.5-10, Atractylodes macrocephala (fried) 5-20, Citrus aurantium 5-20, Bupleurum chinense 5-20, Pinellia ternata (processed) 3-12, and Glycyrrhiza uralensis 3-12.

[0005] This invention utilizes Codonopsis pilosula, Poria cocos, and Ganoderma lucidum together to invigorate Qi and strengthen the spleen, providing nourishment without being drastic, thus replenishing the source of acquired constitution and treating various deficiencies to achieve the goal of supporting the body's vital energy and strengthening its foundation. These are the principal herbs. Scutellaria barbata and Hedyotis diffusa clear heat, detoxify, and resolve stagnation; Coix lacryma-jobi promotes diuresis and eliminates dampness, serving as assistant herbs. Bupleurum chinense soothes the liver, relieves depression, and regulates Qi; Citrus aurantium enters the middle Jiao (spleen and stomach), promoting Qi circulation and resolving stagnation. These two herbs ascend clear Qi and descend turbid Qi, ensuring smooth Qi flow; Frankincense, Myrrh, and Toad Skin relieve pain; Atractylodes macrocephala strengthens the spleen and dries dampness; Pinellia ternata regulates Qi and harmonizes the middle Jiao, serving as adjuvant herbs; Glycyrrhiza uralensis harmonizes all the herbs, serving as guiding herbs. The entire formula combines herbs to support the body's vital energy and fight cancer, addressing both the root cause and the symptoms. More importantly, it can improve the liver and kidney toxicity caused by gemcitabine treatment for pancreatic cancer, eliminating the need to reduce the treatment dose or interrupt treatment, thus achieving effective treatment of pancreatic cancer. Attached Figure Description

[0006] Figure 1 This is a schematic diagram showing the changes in body weight of mice in each experimental group treated for pancreatic cancer from day 1 to day 14.

[0007] Figure 2 This is a schematic diagram showing the changes in tumor volume in each experimental group of pancreatic cancer treated for 1-14 days.

[0008] Figure 3 This is a schematic diagram of tumor quality after treatment of pancreatic cancer in each experimental group.

[0009] Figure 4 This is a schematic diagram showing the tumor size after treatment of pancreatic cancer in each experimental group.

[0010] Figure 5 These are HE-stained images of tumor tissue sections from each experimental group after treatment for pancreatic cancer.

[0011] Figure 6 These are HE-stained images of liver and kidney sections from each experimental group after treatment for pancreatic cancer. Detailed Implementation

[0012] A traditional Chinese medicine preparation that can be used in combination with gemcitabine to treat pancreatic cancer and improve liver and kidney toxicity is prepared by taking 20g of Ganoderma lucidum, 15g of Codonopsis pilosula, 15g of Poria cocos, 30g of Scutellaria barbata, 30g of Hedyotis diffusa, 30g of raw Coix lacryma-jobi, 5g of Boswellia carterii, 5g of Commiphora myrrha, 10g of stir-fried Atractylodes macrocephala, 10g of Citrus aurantium, 10g of Bupleurum chinense, 6g of processed Pinellia ternata, and 6g of Glycyrrhiza uralensis. The mixture is then soaked in 10 times its weight of water for 2 hours, boiled, and decocted for 2 hours. The mixture is filtered while hot to obtain the filtrate. The remaining dregs are then treated with 10 times their weight of water using the same method. The filtrates are then combined and concentrated using a rotary evaporator to 132.5ml, resulting in a medicinal water extract with a concentration of 1.45g / mL.

[0013] experiment: 1. Cell lines The mouse pancreatic cancer PANC02 cell line was purchased from Procell, catalog number CL-0736.

[0014] 2. Laboratory animals Twenty male C57BL / 6 mice, 6 weeks old and weighing 20–21.5 g, were provided by Liaoning Changsheng Biotechnology Co., Ltd. Animal Production Certificate No.: SYXK(Liaoning)2024-0002. The laboratory animals were raised and managed according to SPF-grade animal management requirements.

[0015] 3. Modeling A mouse subcutaneous xenograft model of mouse pancreatic cancer PANC02 cells was established. The mouse pancreatic cancer cell line PANC02 was passaged in vitro, and the cells were prepared into a suspension by trypsin digestion. 1.5 × 10⁻⁶ cells were then added to the suspension. 6 One (0.1 mL) cell suspension was inoculated subcutaneously in the right hind limb of a mouse, and the tumor formation was observed and recorded daily.

[0016] 4. Grouping and Intervention Twenty C57BL / 6 mice were acclimatized for one week and then randomly divided into four groups using a random number table: a control group, a compound group (the traditional Chinese medicine preparation described in this invention), a gemcitabine group (100 mg / mL), and a combination group (the traditional Chinese medicine preparation described in this invention + gemcitabine), with five mice in each group. Fourteen days after modeling, the tumor volume was approximately 100 mm². 3 Intervention began at a specific time. The control group received oral administration of physiological saline (0.2 mL / 10 g per mouse, the same volume was used throughout the treatment) once a day. The gemcitabine group received intraperitoneal injection (0.1 mL / 10 g per mouse, the same volume was used throughout the treatment) once every 3 days. The traditional Chinese medicine group and the combined treatment group received traditional Chinese medicine preparations by oral administration once a day, while the combined treatment group also received intraperitoneal injection of gemcitabine once every 3 days. The intervention lasted for 14 days, and the body weight and tumor volume of the tumor-bearing mice were measured and recorded daily.

[0017] 5. Detection methods for pancreatic cancer treatment in various experimental groups according to embodiments of the present invention. After administration, the body weight of the mice was measured daily, and a curve showing the change in body weight over time was plotted to evaluate the changes in body weight after administration.

[0018] After starting medication, measure the length and width of the tumor daily, according to the formula: Tumor volume = (length * width) 2 ) / 2 Calculate the tumor volume and plot the curve of tumor volume change over time.

[0019] After the experiment, all tumor-bearing mice were euthanized, and tumor tissue was isolated, weighed, photographed, and used to create a tumor mass chart. The isolated tumor tissue was then washed with physiological saline, fixed with paraformaldehyde, and sent to Wuhan Saiwei Biotechnology Co., Ltd. for sectioning. The sections were then retrieved and stained with hematoxylin and eosin (HE).

[0020] 6. A method for detecting the improvement of gemcitabine-induced hepatotoxicity and nephrotoxicity by the pharmaceutical formulation in this invention. The serum of each experimental group was tested for liver and kidney function using the Mindray BS-240 Vet instrument. The specific testing steps and methods were performed according to the kit instructions.

[0021] The separated liver and kidney tissues were washed with physiological saline, fixed with paraformaldehyde, and sent to Wuhan Saiwei Biotechnology Co., Ltd. for sectioning. After the sections were retrieved, they were stained with hematoxylin and eosin (HE).

[0022] 7. Statistical methods All data were calculated using SPSS 16.0 software. Quantitative data were expressed as mean ± standard deviation (Mean ± SD). Independent samples t-tests were used for comparisons between groups, and p ≤ 0.05 was considered statistically significant.

[0023] 8. Experimental Results 8.1 Results of pancreatic cancer treatment in each experimental group The changes in body weight of mice treated with pancreatic cancer in each experimental group for 1-14 days are as follows: Figure 1 As shown in the figure. The results indicate that, compared with the control group, the gemcitabine group experienced the most significant weight loss. The combination of the traditional Chinese medicine preparation of this invention and gemcitabine can alleviate the gemcitabine-induced weight loss in mice. Tumor volume changes in each experimental group after 1-14 days of treatment for pancreatic cancer are as follows: Figure 2 As shown.

[0024] Tumor quality after treatment of pancreatic cancer in each experimental group was as follows: Figure 3 As shown, Figure 3 **p≤0.01, ***p≤0.001, ****p≤0.0001 compared with the control group.

[0025] Tumor size after treatment of pancreatic cancer in each experimental group is as follows: Figure 4 As shown HE staining images of tumor tissue sections after pancreatic cancer treatment in each experimental group are shown below. Figure 5 As shown. From Figure 5 It can be seen that the tumor cells in the control group had a high nucleus-to-cytoplasm ratio, with nested cells arranged neatly and tightly with clear boundaries, and no obvious signs of cell necrosis. However, in the compound group, gemcitabine group, and combination group, the tumor cell nuclei gradually shrank and became smaller, and the arrangement became loose; diffuse large-scale necrosis of tumor cells was found in the gemcitabine group and combination group.

[0026] The results showed that compared with the control group, the tumor volume and mass of all other experimental groups were reduced, with the most significant reduction observed in the combination group. The tumor inhibition rates of the compound group, gemcitabine group, and combination group were 44.90%, 81.92%, and 94.36%, respectively. The traditional Chinese medicine preparation of this invention has a certain inhibitory effect on tumor growth, but the inhibitory effect is stronger when used in combination with gemcitabine. Although the tumor inhibition rate of the compound + gemcitabine group was higher than that of the gemcitabine group, the difference was not statistically significant.

[0027] 4.2 The results of the detection of hepatotoxicity and nephrotoxicity caused by gemcitabine in each experimental group are shown in Table 1.

[0028] Table 1 Comparison of serum liver and kidney function indicators in mice of different groups

[0029] In Table 1, *p≤0.05, **p≤0.01, compared with the control group; # p≤0.05, ## p≤0.01, ### p≤0.001, compared with the gemcitabine group.

[0030] HE staining of liver and kidney tissues after treatment with pancreatic cancer in each experimental group is as follows: Figure 6As shown. From Figure 6 It can be seen that, compared with the control group, there were no significant differences in HE staining and serum liver and kidney function indicators in the compound group. In the gemcitabine group, HE staining revealed kidney damage, with a more pronounced glomerular capsule, partial adhesion to the glomeruli, dilated glomerular capillaries filled with blood cells, enlarged renal tubules, and blood cell infiltration. In the liver group, imaging centered on the central hepatic vein showed significant inflammatory cell aggregation, inflammatory infiltration, and hepatocyte necrosis. Simultaneously, serum liver and kidney function indicators showed a significant increase in all indicators compared to the control group. In the combined administration of the traditional Chinese medicine preparation and gemcitabine in the embodiment of this invention, the enlargement of the glomerular capsule and renal tubules was alleviated, hepatocyte necrosis was significantly reduced, inflammatory infiltration decreased, and all serum indicators decreased, showing statistically significant differences.

[0031] The results of various experiments show that the traditional Chinese medicine preparations of the present invention, when used in combination with gemcitabine, can treat pancreatic cancer and improve the liver and kidney toxicity caused by gemcitabine in the treatment of pancreatic cancer. There is no need to reduce the treatment dose or interrupt the treatment, thus achieving the goal of effectively treating pancreatic cancer.

Claims

1. A traditional Chinese medicine composition for treating pancreatic cancer and improving hepatotoxicity and nephrotoxicity when used in combination with gemcitabine, characterized in that... The traditional Chinese medicine composition comprises the following parts by weight of raw materials: Ganoderma lucidum 10-40, Codonopsis pilosula 7.5-30, Poria cocos 7.5-30, Scutellaria barbata 15-60, Hedyotis diffusa 15-60, Coix lacryma-jobi 15-60, Boswellia carterii 2.5-10, Commiphora myrrha 2.5-10, Atractylodes macrocephala (fried) 5-20, Citrus aurantium 5-20, Bupleurum chinense 5-20, Pinellia ternata (processed) 3-12, Glycyrrhiza uralensis 3-12. This traditional Chinese medicine composition is an aqueous extract.

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