A traditional chinese medicine composition for pancreatic cancer

Abstract

The application discloses a traditional Chinese medicine composition for treating pancreatic cancer, which comprises the following medicinal materials in parts by weight: 1-20 parts of Chinese cork tree, 1-15 parts of ginkgo, 1-10 parts of evodia, 1-10 parts of tripterygium, 1-15 parts of two-edged needle, 1-15 parts of radix astragali, and 1-10 parts of jujube. The application further discloses a medicine taking the traditional Chinese medicine composition as raw materials and a preparation method of the medicine. In addition, the application further discloses application of the traditional Chinese medicine composition or the medicine in preparation of a medicine for treating pancreatic cancer.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for pancreatic cancer. Background Technology

[0002] Although pancreatic cancer has a low incidence rate, its prognosis is extremely poor, with a 5-year survival rate of only 7.2% to 9%. Due to its insidious onset and atypical early symptoms, the early diagnosis rate of pancreatic cancer is less than 5%; approximately 60% of patients have metastasized at initial diagnosis, and about 30% are in the locally advanced stage at initial diagnosis. The incidence of pancreatic cancer in my country has also been on the rise in recent years.

[0003] Modern medicine treats pancreatic cancer primarily based on its stage, with treatment options including surgery, neoadjuvant therapy, chemotherapy, interventional therapy, radiotherapy, immunotherapy, molecularly targeted therapy, and comprehensive treatment. In the early stages of the disease, surgery is the preferred and most effective method, with a 5-year survival rate of up to 58% for early-stage pancreatic cancer patients. However, due to its insidious onset, more than half of pancreatic cancer patients are already out of the surgical window when diagnosed. For locally unresectable / metastatic pancreatic cancer, while chemotherapy is the primary treatment, its clinical efficacy is relatively limited once drug resistance develops. While the advent of targeted drugs and immunotherapy has led to significant progress in the treatment of many tumors, progress in pancreatic cancer treatment has been slow, and further exploration is needed to develop more effective treatment methods for pancreatic cancer.

[0004] For advanced pancreatic cancer, most traditional Chinese medicine practitioners believe that the disease is located in the pancreas, related to the spleen and stomach, and involves the liver and gallbladder. Its root cause is related to spleen and stomach weakness and liver qi stagnation, while its manifestations include damp-heat, blood stasis, qi stagnation, and phlegm accumulation. The combination of deficiency and accumulation of pathogenic factors eventually leads to cancer. The disease is often a mixture of deficiency and excess, with the root cause being weak and the manifestation strong. It is often caused by lingering toxins and heat, which over time depletes yin and blood, or by deficiency of both the liver and spleen leading to spleen deficiency and qi stagnation, or blood stasis in the liver and spleen. The pancreas has a rich blood supply and is surrounded by numerous tissues and organs, abundant in blood and qi. If damp-heat, phlegm, blood stasis, and qi stagnation accumulate over time, the combination of deficiency and accumulation of pathogenic factors eventually leads to cancer.

[0005] Given the complex and often contradictory nature of pancreatic cancer patients, Traditional Chinese Medicine (TCM) treatment often employs the principle of supporting the body's resistance and eliminating pathogenic factors, addressing both the root cause and the symptoms. Common methods for treating the symptoms include soothing the liver and strengthening the spleen, resolving blood stasis and eliminating accumulations, and clearing heat and dampness. Common methods for treating the root cause include strengthening the spleen and replenishing qi, nourishing yin and generating fluids, and tonifying qi and nourishing blood. For example, Chinese invention patent application CN116672415A (publication date September 1, 2023) discloses a TCM composition for pancreatic cancer, consisting of: 5-15 parts Bupleurum chinense, 10-20 parts Scutellaria baicalensis, 10-20 parts Pinellia ternata, 20-30 parts Coix lacryma-jobi, 10-20 parts Citrus aurantium, 10-20 parts Magnolia officinalis, 20-30 parts Paeonia lactiflora, and 10-20 parts Rheum palmatum. In this formula, Bupleurum is the principal herb, Scutellaria baicalensis and Rheum palmatum are the assistant herbs, and Paeonia lactiflora, Pinellia ternata, Magnolia officinalis, and Coix lacryma-jobi are the adjuvant herbs, working together to clear heat, dry dampness, regulate qi, and promote circulation. Another example is Chinese invention patent application CN114887004A (publication date August 12, 2022), which discloses a traditional Chinese medicine composition for treating pancreatic cancer. It is made from 30-40 parts of Hedyotis diffusa, 15-20 parts of chicken gizzard lining, 6-10 parts of prepared Rheum palmatum, 20-30 parts of Coix lacryma-jobi, 20-30 parts of Dioscorea opposita, 15-30 parts of Eriocaulon buergerianum, 10-20 parts of Atractylodes macrocephala, 6-10 parts of Glycyrrhiza uralensis, and 10-20 parts of Citrus reticulata. In this formula, Hedyotis diffusa and chicken gizzard lining are the principal herbs, prepared Rheum palmatum, Eriocaulon buergerianum, and Coix lacryma-jobi are the assistant herbs, Dioscorea opposita, Atractylodes macrocephala, and Citrus reticulata are the adjuvant herbs, and Glycyrrhiza uralensis is the guiding herb. Both of the above compositions embody the treatment principles and formulation principles of clearing heat and dampness, promoting blood circulation and removing blood stasis.

[0006] Although drug researchers and clinicians are dedicated to the research and development of treatments for pancreatic cancer, according to GLOBOCAN statistics, in 2020, there were 490,000 new cases and 460,000 deaths from pancreatic cancer globally, ranking 14th and 4th respectively among all malignant tumors; the incidence of pancreatic cancer is showing a year-on-year upward trend. It is projected that by 2030, pancreatic cancer will become the second leading cause of death from malignant tumors. Therefore, the clinical need for pancreatic cancer treatment is far from being met. Summary of the Invention

[0007] To overcome the shortcomings of existing technologies, this invention provides a traditional Chinese medicine composition for treating pancreatic cancer. Preliminary pharmacodynamic experiments have demonstrated that the traditional Chinese medicine composition of this invention has a significant inhibitory effect on the growth of human pancreatic cancer cell lines (AsPC-1, BxPC-3, and PANC1) xenografts, suggesting its potential for treating pancreatic cancer.

[0008] To achieve the above-mentioned technical effects, the present invention adopts the following technical solution:

[0009] A traditional Chinese medicine composition for pancreatic cancer, comprising the following medicinal materials in parts by weight:

[0010] 1-20 parts of Phellodendron bark, 1-15 parts of Ginkgo, 1-10 parts of Evodia fruit, 1-10 parts of Tripterygium wilfordii, 1-15 parts of Zanthoxylum nitidum, 1-15 parts of Achyranthes bidentata, and 1-10 parts of jujube.

[0011] Preferably, the traditional Chinese medicine composition for pancreatic cancer comprises the following medicinal materials in parts by weight:

[0012] 5-15 parts of Phellodendron bark, 5-12 parts of Ginkgo biloba, 1-8 parts of Evodia rutaecarpa, 3-10 parts of Tripterygium wilfordii, 5-12 parts of Zanthoxylum nitidum, 5-12 parts of Achyranthes bidentata, and 3-8 parts of Ziziphus jujuba.

[0013] More preferably, the traditional Chinese medicine composition for pancreatic cancer comprises the following medicinal materials in parts by weight:

[0014] 10-15 parts of Phellodendron bark, 8-12 parts of Ginkgo biloba, 3-6 parts of Evodia rutaecarpa, 3-8 parts of Tripterygium wilfordii, 8-12 parts of Zanthoxylum nitidum, 8-12 parts of Achyranthes bidentata, and 3-8 parts of Ziziphus jujuba.

[0015] More preferably, the traditional Chinese medicine composition for pancreatic cancer comprises the following medicinal materials in parts by weight:

[0016] 11-13 parts of Phellodendron bark, 9-11 parts of Ginkgo biloba, 4-6 parts of Evodia rutaecarpa, 4-6 parts of Tripterygium wilfordii, 9-11 parts of Zanthoxylum nitidum, 9-11 parts of Achyranthes bidentata, and 4-6 parts of Ziziphus jujuba.

[0017] As a particularly preferred embodiment, the present invention provides a traditional Chinese medicine composition for pancreatic cancer, comprising the following parts by weight of medicinal materials:

[0018] 12 parts of Phellodendron bark, 10 parts of Ginkgo biloba, 5 parts of Evodia rutaecarpa, 5 parts of Tripterygium wilfordii, 10 parts of Zanthoxylum nitidum, 10 parts of Achyranthes bidentata, and 5 parts of Ziziphus jujuba.

[0019] As a preferred embodiment, the traditional Chinese medicine composition for pancreatic cancer provided by the present invention is composed of Phellodendron bark, Ginkgo, Evodia fruit, Tripterygium wilfordii, Zanthoxylum nitidum, Achyranthes bidentata, and jujube, with the weight parts of each medicinal material as defined above.

[0020] Optionally, the *Phellodendron chinense* in the traditional Chinese medicine composition of the present invention can be replaced by *Phellodendron chinense* derived from the dried bark of the Rutaceae plant *Phellodendron chinense* Schneid. The dried bark of *Phellodendron chinense* is also commonly known as "Sichuan *Phellodendron chinense*".

[0021] Another object of the present invention is to provide a medicine, wherein the raw materials of the above-mentioned traditional Chinese medicine composition may include or exclude pharmaceutically acceptable excipients.

[0022] The pharmaceutically acceptable excipients described in this invention include, but are not limited to: (1) diluents, such as starch, powdered sugar, dextrin, lactose, pregelatinized starch, microcrystalline fiber, inorganic calcium salts (such as calcium sulfate, calcium hydrogen phosphate, pharmaceutical calcium carbonate, etc.), mannitol, vegetable oil, polyethylene glycol, etc.; (2) binders, such as distilled water, ethanol, starch paste, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose and ethyl cellulose, hydroxypropyl methyl cellulose, etc.; (3) disintegrants, such as dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, croscarmellose, croscarmellose sodium, etc.; (4) lubricants, such as magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol, magnesium lauryl sulfate, etc.; (5) solvents, such as water, ethanol solutions, etc.

[0023] The drug is any clinically acceptable formulation.

[0024] Preferably, the drug is an oral preparation.

[0025] Preferably, the oral preparation is selected from decoctions, powders, capsules, tablets, honey pills, water-honey pills, water pills, concentrated pills, paste pills, wax pills, granules, oral liquids, or drop pills; more preferably, it is a decoction or granules.

[0026] A third objective of this invention is to provide a method for preparing the aforementioned drug, comprising preparing each medicinal material according to the stated weight proportions, and preparing a clinically acceptable formulation by adding or omitting pharmaceutically acceptable excipients according to conventional formulation methods in the art.

[0027] The conventional formulation methods in this art include pulverization, sieving, extraction with a suitable solvent (e.g., decoction with water), concentration and / or drying of the extract, and purification of the extract (liquid). These methods are familiar to and readily chosen by those skilled in the art.

[0028] Furthermore, the present invention also provides the use of the above-mentioned traditional Chinese medicine composition, the above-mentioned drug, or the drug prepared according to the above-mentioned preparation method in the preparation of a drug for treating pancreatic cancer.

[0029] In particular, the present invention provides the use of the above-mentioned traditional Chinese medicine composition, the above-mentioned drug, or the drug prepared according to the above-mentioned preparation method in the preparation of a drug for treating locally advanced / advanced unresectable pancreatic cancer, metastatic pancreatic cancer, and pancreatic cancer that has recurred after surgery.

[0030] In this instruction manual, the "parts by weight" of each component refers to the ratio of the amounts of each component, not the actual unit of mass. Depending on the actual situation, a unit of weight can be any mass, such as 1 part by weight can be 1g, 500g, or 1kg, or even 10g, 15g, 30g, etc.

[0031] The medicinal properties, meridian tropism, functions and indications of each herb in the traditional Chinese medicine composition of this invention, as well as the formula explanation of this composition, are as follows:

[0032] Phellodendron amurense Rupr is the dried bark of the Phellodendron amurense plant, belonging to the Rutaceae family. It is bitter and cold in nature; it enters the kidney and bladder meridians. It has the functions of clearing heat and drying dampness, purging fire and eliminating steaming heat, and detoxifying and healing sores. It is used for damp-heat diarrhea, jaundice with dark urine, leukorrhea and vulvar itching, painful urination due to heat, beriberi with weakness and paralysis, bone steaming fever, night sweats, seminal emission, sores and carbuncles, eczema and damp sores.

[0033] Ginkgo seeds are the dried, mature seeds of the ginkgo biloba L. plant, belonging to the Ginkgoaceae family. They have a sweet, bitter, and astringent taste, and are neutral in nature; they enter the lung and kidney meridians. They have the effects of astringing the lungs and relieving asthma, stopping leukorrhea and reducing urination, and are often used for cough with excessive phlegm, leukorrhea, enuresis, and frequent urination.

[0034] Evodia rutaecarpa is the dried, nearly mature fruit of Evodia rutaecarpa (Juss.) Benth., a plant in the Rutaceae family. It has a pungent and bitter taste, and is warm in nature; it enters the liver, spleen, stomach, and kidney meridians. It has the functions of dispelling cold and relieving pain, suppressing nausea and vomiting, and tonifying yang and stopping diarrhea. It is used for Jueyin headache, cold hernia abdominal pain, cold-damp beriberi, menstrual cramps, abdominal distension and pain, vomiting and acid regurgitation, and early morning diarrhea.

[0035] Tripterygium wilfordii Hook.f., a plant in the Celastraceae family, is a rhizome with a bitter and cool nature. It enters the liver and kidney meridians and has the effects of dispelling wind and dampness, promoting blood circulation and unblocking collaterals, reducing swelling and relieving pain, and killing parasites and detoxifying. It is commonly used for various skin diseases such as rheumatism, leprosy, stubborn tinea, eczema, scabies, dermatitis, and rashes.

[0036] Zanthoxylum nitidum (Roxb.) DC., a plant in the Rutaceae family, is a dried root. It tastes bitter and pungent, and is neutral in nature; it enters the liver and stomach meridians. It has the effects of promoting blood circulation and removing blood stasis, regulating qi and relieving pain, dispelling wind and unblocking collaterals, and detoxifying and reducing swelling. It is used for injuries from falls and blows, stomachache, toothache, rheumatic pain, and snake bites; externally, it is used to treat burns and scalds.

[0037] Achyranthes bidentata Bl., a plant in the Amaranthaceae family, is the dried root of the plant. It tastes bitter, sweet, and sour, and is neutral in nature; it enters the liver and kidney meridians. It has the effects of dispelling blood stasis and promoting menstruation, tonifying the liver and kidneys, strengthening tendons and bones, promoting urination and relieving strangury, and guiding blood downwards. It is used for amenorrhea, dysmenorrhea, lower back and knee pain, weakness of tendons and bones, strangury, edema, headache, dizziness, toothache, canker sores, hematemesis, and epistaxis.

[0038] Jujube is the dried, ripe fruit of the jujube (Ziziphus jujuba Mill.), a plant in the Rhamnaceae family. It has a sweet taste and warm properties; it enters the spleen, stomach, and heart meridians. It has the effects of tonifying the middle energizer and replenishing qi, nourishing blood and calming the mind. It is used for spleen deficiency with poor appetite, fatigue, loose stools, and hysteria in women.

[0039] Among the above seven medicinal materials, taking "clearing heat and drying dampness, dissipating stasis and relieving pain" as the main principles, Phellodendron amurense Rupr. is the monarch drug, which is bitter in taste and cold in nature, and has the effects of clearing heat and drying dampness, purging fire and removing steaming. Huang Yuanyu mentioned in "Commentary on Medical Formulas of Zhang Zhongjing" that "Phellodendron amurense Rupr. purges the dampness-heat of the earthly branch, clears the stagnant steaming of the ethereal branch, regulates heat and relieves tenesmus, and treats jaundice, abdominal fullness, and typhoid fever." In the middle and advanced stages of pancreatic cancer, dampness blocks the middle jiao, the qi mechanism is abnormal, stagnates and transforms into heat, and dampness-heat intersects and obstructs, forming cancerous tumors, or dampness-heat steams the liver and gallbladder, forming jaundice. Academician Tong Xiaolin, a contemporary doctor, believes that Phellodendron amurense Rupr. is the key drug for regulating the dampness-heat state. In "Prescriptions of Universal Relief", most of the compound prescriptions of Phellodendron amurense Rupr. can disperse stasis and eliminate masses and treat mass accumulation. Tripterygium wilfordii Hook. f. is the ministerial drug, which is bitter, pungent, and highly toxic, and can dispel wind and dampness, activate blood circulation and dredge collaterals, and relieve swelling and pain. Achyranthes bidentata Blume is also the ministerial drug, which can tonify the liver and kidney, remove blood stasis and dredge menstruation, and guide blood downward. Zanthoxylum nitidum (Roxb.) DC. is also the ministerial drug, which is bitter and pungent in nature and flat in taste, and can promote qi and relieve pain, activate blood circulation and remove stasis, and dispel wind and dredge collaterals. The combination of Tripterygium wilfordii Hook. f., Achyranthes bidentata Blume, and Zanthoxylum nitidum (Roxb.) DC. can activate blood circulation and dredge collaterals, activate blood circulation and relieve pain, and exert the effect on cancer pain. Ginkgo biloba L. is the adjuvant drug, which is sweet, bitter, and flat in nature, and can astringe the lung qi, arrest cough and asthma, and treat leukorrhea and gonorrhea. In the formula, it is combined with Phellodendron amurense Rupr. to clear heat and dry dampness and relieve dampness toxin. Evodia rutaecarpa (Juss.) Benth. is the adjuvant drug, which is pungent, bitter, and hot in nature, and can dispel cold and relieve pain, lower adverse qi and stop vomiting, and assist yang and stop diarrhea. Evodia rutaecarpa (Juss.) Benth. is a highly hot drug. In the traditional Chinese medicine composition of the present invention, firstly, it can help relieve the pain of patients through its analgesic effect; secondly, when combined with Phellodendron amurense Rupr., it can relieve vomiting and acid regurgitation when dampness-heat is excessive and the spleen and stomach decline in the later stage; thirdly, it is the drug for counteracting the adverse effect. Most late-stage cancer patients have weak spleen and stomach, and Evodia rutaecarpa (Juss.) Benth. is the drug for counteracting the adverse effect to prevent the cold-natured drugs such as Phellodendron amurense Rupr. from damaging the stomach and causing adverse effects. Jujube is the guiding drug, which can replenish the middle qi and harmonize the spleen and stomach. The whole formula targets the pathological factors of dampness-heat and blood stasis in pancreatic cancer, improves the clinical symptoms of patients with the syndrome of dampness-heat accumulation and blood stasis obstruction in pancreatic cancer, and improves the quality of life of patients.

[0040] Among the above seven medicinal materials, Phellodendron amurense Rupr. for clearing heat and resolving dampness, Tripterygium wilfordii Hook. f., and Achyranthes bidentata Blume for activating blood circulation and removing stasis have already appeared in the traditional Chinese medicine composition for treating pancreatic cancer. For example, the Chinese invention patent with the publication number CN108355110B (publication date: January 8, 2021) discloses a traditional Chinese medicine composition composed of 23 Chinese medicinal materials including Phellodendron amurense Rupr. The Chinese invention patent application with the publication number CN1069379A (publication date: July 11, 2017) discloses a pharmaceutical composition for treating pancreatic head cancer, including Achyranthes bidentata Blume, Sargassum fusiforme (Harv.) Setch., Fritillaria thunbergii Miq., Endothelium corneum gigeriae galli, Poria cocos (Schw.) Wolf, Lonicera japonica Thunb., Forsythia suspensa (Thunb.) Vahl, Gardenia jasminoides Ellis, Paeonia lactiflora Pall., Salvia miltiorrhiza Bunge, Rehmannia glutinosa Libosch., Citrus reticulata Blanco, Vaccaria segetalis (Neck.) Garcke, and Glycyrrhiza glabra L. However, Ginkgo biloba L. and Zanthoxylum nitidum (Roxb.) DC. are less used in the treatment of pancreatic cancer, especially there is no report on their use as important ministerial and adjuvant drugs in the treatment of pancreatic cancer. Therefore, the formula of the traditional Chinese medicine composition for treating pancreatic cancer described in the present invention is novel and unique. Although there are only seven medicinal materials, it has a significant inhibitory effect on the growth of transplanted tumors of human pancreatic cancer cell lines (AsPC-1, BxPC-3, and PANC1); suggesting that the traditional Chinese medicine composition described in the present invention can be used clinically to treat pancreatic cancer. Detailed Implementation

[0041] The present invention will be described below with reference to specific embodiments. Those skilled in the art will understand that these embodiments are for illustrative purposes only and do not limit the scope of the invention in any way.

[0042] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, all medicinal materials and reagents used in the following examples are commercially available products.

[0043] Example 1 A traditional Chinese medicine composition for pancreatic cancer

[0044] The raw material composition of the traditional Chinese medicine composition described in this embodiment is (1 part = 1 kg):

[0045] 20 parts of Phellodendron bark, 10 parts of Ginkgo biloba, 5 parts of Evodia rutaecarpa, 8 parts of Tripterygium wilfordii, 10 parts of Zanthoxylum nitidum, 10 parts of Achyranthes bidentata, and 6 parts of jujube.

[0046] Example 2 A traditional Chinese medicine composition for pancreatic cancer

[0047] The raw material composition of the traditional Chinese medicine composition described in this embodiment is (1 part = 1 kg):

[0048] 12 parts of Phellodendron bark, 10 parts of Ginkgo biloba, 5 parts of Evodia rutaecarpa, 5 parts of Tripterygium wilfordii, 10 parts of Zanthoxylum nitidum, 10 parts of Achyranthes bidentata, and 5 parts of Ziziphus jujuba.

[0049] Example 3 A traditional Chinese medicine composition for pancreatic cancer

[0050] The raw material composition of the traditional Chinese medicine composition described in this embodiment is (1 part = 1 kg):

[0051] 12 parts of Phellodendron bark, 8 parts of Ginkgo biloba, 4 parts of Evodia rutaecarpa, 8 parts of Tripterygium wilfordii, 8 parts of Zanthoxylum nitidum, 8 parts of Achyranthes bidentata, and 6 parts of Ziziphus jujuba.

[0052] Example 4 A traditional Chinese medicine composition for pancreatic cancer

[0053] The raw material composition of the traditional Chinese medicine composition described in this embodiment is (1 part = 1 kg):

[0054] 5 parts of Phellodendron bark, 5 parts of Ginkgo biloba, 3 parts of Evodia rutaecarpa, 3 parts of Tripterygium wilfordii, 5 parts of Zanthoxylum nitidum, 5 parts of Achyranthes bidentata, and 10 parts of jujube.

[0055] Example 5 A capsule

[0056] Take the traditional Chinese medicine composition from Example 1, mix it, grind it into a fine powder, pass it through a 100-mesh sieve, and fill it into capsules, 0.4g of raw medicine per capsule, and you will get the product.

[0057] Dosage and administration: Take 2-4 capsules three times a day with warm water.

[0058] Example 6 A granule

[0059] Take the traditional Chinese medicine composition from Example 2, mix it, grind it into a fine powder, pass it through a 200-mesh sieve, add an appropriate amount of dextrin as a filler, granulate and compress it into granules, 6g / bag, and package it to obtain the final product.

[0060] Dosage and administration: Take 6g three times a day with warm water.

[0061] Example 7 A tablet

[0062] Take the traditional Chinese medicine composition of Example 3, add 5 to 10 times the weight of the medicinal materials to water and decoct twice, each time for 30 minutes to 1 hour. Combine the decoctions, concentrate, add an appropriate amount of dextrin, granulate, and compress into tablets to obtain the final product.

[0063] Example 8 A type of honey pill

[0064] Take the traditional Chinese medicine composition from Example 4, mix it, grind it into a fine powder, pass it through a 60-100 mesh sieve, add an appropriate amount of refined honey, and prepare it into small honey pills according to conventional methods, 3g / 10 pills.

[0065] Dosage and administration: Take 3 grams three times a day with warm water.

[0066] Example 9 A decoction

[0067] Weigh each medicinal material according to the following mass measurements:

[0068] 12g of Phellodendron bark, 10g of Ginkgo, 5g of Evodia fruit, 5g of Tripterygium wilfordii, 10g of Zanthoxylum nitidum, 10g of Achyranthes bidentata, and 5g of Jujube.

[0069] Mix all the medicinal herbs together, add 5-10 times their weight of water, heat to a boil and simmer for 25 minutes, then filter while hot. Add 5-10 times their weight of water to the dregs, heat to a boil and simmer for 20-30 minutes, then filter while hot. Combine the two decoctions to obtain the final product. Divide into 2-3 doses and consume within one day.

[0070] Experimental Example Pharmacodynamic experiments

[0071] 1. Materials

[0072] 1.1 Experimental drugs:

[0073] (1) Traditional Chinese medicine composition:

[0074] ① Granule 1: The traditional Chinese medicine composition of the present invention, light yellow powder (after grinding); prepared according to the method described in Example 6 (the raw material composition and dosage ratio are the same as those of the traditional Chinese medicine composition in Example 2), where 1 part = 1 g.

[0075] ② Granule 2: Control traditional Chinese medicine composition, light yellow powder (after grinding); raw material composition (1 part = 1 g): 10 parts of Dalbergia odorifera, 8 parts of Corydalis yanhusuo, 10 parts of Salvia miltiorrhiza, 10 parts of Spatholobus suberectus, 8 parts of Sophora flavescens, 10 parts of Swertia mileensis, 10 parts of Morus alba root bark, 10 parts of Isatis indigotica, 3 parts of Glycyrrhiza uralensis; the above 9 flavors are mixed and ground into fine powder, passed through a 200-mesh sieve, and an appropriate amount of dextrin is added as a filler, granulated and pressed into granules.

[0076] The above two kinds of granules were received on February 21, 2022, and stored dry in a cool cabinet. When used, they were ground into fine powder and prepared into a stock solution of 2.00 mg / mL with standard dilution water, and used immediately after preparation.

[0077] (2) Chemotherapeutic drugs

[0078] Gemcitabine, white powder, CAS No. 122111-03-9, purchased from J&K Scientific Ltd., stored in the shade. Prepared into a stock solution of 10.0 mg / mL with standard dilution water, and used immediately after preparation.

[0079] 1.2 Experimental animals

[0080] ① Wild-type AB strain zebrafish, reproduced by natural paired mating, 30 tails in each experimental group, with an age of 3 dpf, used for the determination of the maximum test concentration (MTC) of the traditional Chinese medicine composition of the present invention.

[0081] ② Wild-type AB strain zebrafish, reproduced by natural paired mating, 30 tails in each experimental group, with an age of 2 dpf, used for the evaluation of the anti-pancreatic cancer anti-tumor growth effect and migration effect of the traditional Chinese medicine composition of the present invention.

[0082] All zebrafish were raised in fish-raising water at 28 °C (water quality: 200 mg of instant sea salt was added to every 1 L of reverse osmosis water, with a conductivity of 450 - 550 μS / cm; pH of 6.5 - 8.5; hardness of 50 - 100 mg / LCaCO3). The license number for the use of experimental animals is: SYXK(Zhe)2022-0004, and the feeding management meets the requirements of international AAALAC certification (certification number: 001458).

[0083] 1.3 Experimental equipment:

[0084] Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan); needle puller (PC-10, Narishige, Japan); microinjector (IM300, Narishige, Japan); precision electronic balance (CP214, OHAUS, USA); 6-well plate (Nest Biotech, China); CO2 incubator (3111, Thermo Fisher Scientific, USA); double-person single-sided clean bench (SW-CJ-215KS, Shanghai Sujing Industrial Co., Ltd., China).

[0085] Dimethyl sulfoxide (DMSO, batch number 20171016, Sinopharm Chemical Reagent Co., Ltd., China); methylcellulose (batch number C2004046, Shanghai Aladdin Biochemical Technology Co., Ltd., China); RPMI 1640 medium (batch number 8121695, Thermo Fisher Scientific (China) Co., Ltd., China); ExCell fetal bovine serum (batch number 12A089, ExCellBio, China); CM-DiI (batch number 2335589, Thermo Fisher Scientific (China) Co., Ltd., China); D-Hanks (batch number 20210830, Beijing Solarbio Technology Co., Ltd., China); 0.25% Trypsin-EDTA (batch number 2186962, Thermo Fisher Scientific (China) Co., Ltd., USA); Pen Steep (batch number 2321152, Gibco, USA).

[0086] 2. Methods

[0087] (1) Concentration group

[0088] Experiment 1: Model control group;

[0089] Experimental Group 2: Positive control drug gemcitabine 0.01 μg / tail;

[0090] Experimental Group 3: The herbal composition of this invention (granules 1) was 55.6 μg / mL;

[0091] Experimental Group 4: The herbal composition of this invention (granules 1) was 167 μg / mL;

[0092] Experimental Group 5: The herbal composition of this invention (granules 1) 500 μg / mL;

[0093] Experimental Group 6: Control Chinese herbal medicine composition (granules 2) 111 μg / mL;

[0094] Experimental Group 7: Control Chinese herbal medicine composition (granules 2) 333 μg / mL;

[0095] Experimental Group 8: Control Chinese herbal medicine composition (granules 2) 1000 μg / mL.

[0096] (2) Model making

[0097] Human pancreatic cancer cells (AsPC-1, BxPC-3, and PANC1) were labeled with CM-DiI and microinjected into the yolk sacs of 2dpf wild-type AB strain zebrafish, with approximately 200 cells transplanted per fish, to establish a zebrafish tumor transplantation model.

[0098] (3) Experimental methods

[0099] ① Measurement of MTC

[0100] Wild-type AB strain zebrafish (3dpf) were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Except for the normal control group, all other concentration groups were administered water-soluble samples (125, 250, 500, 1000, and 2000 μg / mL concentrations). A normal control group was also included. Each well contained 3 mL of sample. After treatment at 35℃ for 48 h, the MTC of different treatment groups relative to normal zebrafish was measured.

[0101] ②Evaluate the inhibitory effect of the traditional Chinese medicine composition of the present invention on the growth of pancreatic cancer (AsPC-1, BxPC-3 and PANC1).

[0102] Human pancreatic cancer cells (AsPC-1, BxPC-3, and PANC1) were labeled with CM-DiI and microinjected into the yolk sacs of 2-day-flush (dpf) wild-type AB strain zebrafish, with approximately 200 cells per fish, to establish a zebrafish tumor transplantation model. The model zebrafish were cultured at 35°C to 3 days post-flop (dpf). At 3dpf, zebrafish with good tumor cell uniformity were selected under a microscope and randomly assigned to 6-well plates (30 fish per well). Different drug groups (concentrations listed in the concentration group section) were administered water-soluble solutions, while the positive control gemcitabine was injected intravenously at a dose of 100 ng / fish. A model control group was also included, with 3 mL per well. After 48 hours of treatment at 35°C, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were acquired using NIS-ElementsD 3.20 advanced image processing software, and the fluorescence intensity of human pancreatic cancer cells was analyzed. The statistical analysis results of this index were used to evaluate the anti-tumor growth efficacy of the samples. Statistical results are expressed as mean ± SE.

[0103] ③Evaluate the inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of pancreatic cancer (AsPC-1, BxPC-3 and PANC1).

[0104] Human pancreatic cancer cells (AsPC-1, BxPC-3, and PANC1) were labeled with CM-DiI and microinjected into the yolk sacs of 2-day-fly (dpf) wild-type AB strain zebrafish, with approximately 200 cells per fish, to establish a zebrafish tumor transplantation model. The model zebrafish were cultured at 35°C to 3 days post-flop (dpf). At 3dpf, zebrafish with good tumor cell uniformity were selected under a microscope and randomly assigned to 6-well plates (30 fish per well). Different drug groups were administered water-soluble solutions (concentrations are listed in the concentration group section), and the positive control gemcitabine was injected intravenously at a dose of 100 ng / fish. A model control group was also included, with 3 mL per well. After 48 hours of treatment at 35°C, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were collected using ImageJ advanced image processing software to analyze the migration distance of human pancreatic cancer cells. The statistical analysis results of this index were used to evaluate the anti-tumor migration efficacy of the samples. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS 26.0 software. P < 0.05 indicated that the difference was statistically significant.

[0105] (4) Experimental Results

[0106] ① Measurement of MTC

[0107] The herbal composition of this invention did not induce death or toxicity phenotypes in zebrafish tumor models at a concentration of 500 μg / mL. Therefore, the MTC of the herbal composition of this invention for inhibiting the growth of human pancreatic cancer in zebrafish was determined to be 500 μg / mL. See Table 1 for details.

[0108] Table 1. Concentration-lethality results of the herbal composition of the present invention after treatment of normal zebrafish (n=30)

[0109]

[0110] ② The inhibitory effect of the traditional Chinese medicine composition of this invention on the growth of AsPC-1 xenograft tumors

[0111] The fluorescence intensity of gemcitabine 0.1 μg / tail zebrafish AsPC-1 xenograft was 138,821 pixels, which was significantly different from the model control group (375,611 pixels) (P<0.001), indicating that the positive control drug can significantly inhibit the growth of AsPC-1 xenografts.

[0112] The fluorescence intensities of zebrafish AsPC-1 xenografts at concentrations of 55.6, 167, and 500 μg / mL of the herbal composition (granules 1) of this invention were 180092, 161679, and 147356 pixels, respectively, all showing highly significant differences compared to the model control group (375611 pixels) (P<0.001). This indicates that the herbal composition of this invention has a significant inhibitory effect on the growth of zebrafish AsPC-1 xenografts, exhibiting a certain dose-response relationship. See Table 2 for details.

[0113] The fluorescence intensities of zebrafish AsPC-1 xenografts at concentrations of 111, 333, and 1000 μg / mL of the control herbal composition (particle 2) were 254523, 187568, and 201518 pixels, respectively. The 333 and 1000 μg / mL groups showed significant differences compared to the model control group (375611 pixels), with P < 0.001. However, the 111 μg / mL concentration group showed no statistically significant difference compared to the model group. Although the 333 and 1000 μg / mL dose groups of particle 2 showed significant differences compared to the model group (P < 0.01), the fluorescence intensities of tumor cells in the low-dose (111 μg / mL) and high-dose (1000 μg / mL) groups of particle 2 were significantly higher than those in the low-dose and high-dose groups of the herbal composition of this invention (both P < 0.05). This indicates that the herbal composition of this invention (particle 1) has a significantly stronger inhibitory effect on the growth of zebrafish AsPC-1 xenografts than the control herbal composition (particle 2). See Table 2 for details.

[0114] Table 2. Inhibitory effect of the traditional Chinese medicine composition of the present invention on the growth of zebrafish AsPC-1 xenograft tumors (n=10)

[0115]

[0116] Note: Compared with the model control group, **p<0.01, ***p≤0.001; compared with the corresponding dose level group of particle 1, # p<0.05.

[0117] ③ The inhibitory effect of the traditional Chinese medicine composition of this invention on the growth of BxPC-3 xenograft tumors

[0118] The fluorescence intensity of zebrafish BxPC-3 xenografts at a concentration of 0.01 μg / tail of gemcitabine was 135,425 pixels, which was significantly lower than that of the model control group (310,330 pixels) (P < 0.001), indicating that the positive control drug could significantly inhibit the growth of BxPC-3 xenografts.

[0119] The fluorescence intensities of zebrafish BxPC-3 xenograft tumors at concentrations of 55.6, 167, and 500 μg / mL of the herbal composition (granules 1) of this invention were 201723, 189799, and 152533 pixels, respectively, which were significantly different from the model control group (310330 pixels) (P<0.05, P<0.01, and P<0.001, respectively). This indicates that the herbal composition of this invention has a significant inhibitory effect on the growth of zebrafish BxPC-3 xenograft tumors, and the inhibitory effect shows a dose-response relationship. See Table 3 for details.

[0120] The fluorescence intensities of zebrafish BxPC-3 xenografts at concentrations of 111, 333, and 1000 μg / mL of the control herbal composition (granules 2) were 150082, 144907, and 183409 pixels, respectively. The low-dose group (111 μg / mL) and the medium-dose group (333 μg / mL) showed significant differences compared to the model control group (310330 pixels) (P<0.01), but the high-dose group (1000 μg / mL) showed no statistically significant difference compared to the model group. No dose-response relationship was observed between the three dosage groups and the inhibitory effect on BxPC-3 xenograft growth. Furthermore, the fluorescence intensity of the high-dose group of the control herbal composition (granules 2) was significantly higher than that of the high-dose group of the herbal composition (granules 1) of this invention (P<0.05). See Table 3 for details.

[0121] Table 3. Inhibitory effect of the traditional Chinese medicine composition of the present invention on the growth of zebrafish BxPC-3 xenograft tumors (n=10)

[0122]

[0123] Note: Compared with the model control group, **p<0.01, ***p≤0.001; compared with the corresponding dose level group of particle 1, # p<0.05.

[0124] ④ The inhibitory effect of the traditional Chinese medicine composition of this invention on the growth of PANC1 transplanted tumors

[0125] The fluorescence intensity of zebrafish PANC1 xenografts at a concentration of 0.01 μg / tail was 84,270 pixels, which was significantly lower than that of the model control group (211,616 pixels). This indicates that the positive control drug can significantly inhibit the growth of PANC1 xenografts.

[0126] The fluorescence intensities of zebrafish PANC1 xenografts at concentrations of 55.6, 167, and 500 μg / mL of the herbal composition (granules 1) of this invention were 125746, 112819, and 101909 pixels, respectively, which were all highly significant compared with the model control group (211616 pixels) (P<0.05, P<0.01, and P<0.001, respectively). This indicates that the herbal composition of this invention has a significant inhibitory effect on the growth of zebrafish PANC1 xenografts, and exhibits a certain dose-response relationship. See Table 4 for details.

[0127] The fluorescence intensities of zebrafish PANC1 xenografts at concentrations of 111, 333, and 1000 μg / mL of the control herbal composition (granules 2) were 111,168, 92,666, and 122,134 pixels, respectively. Although the 111, 333, and 1000 μg / mL groups showed highly significant differences compared to the model control group (211,616 pixels) (P < 0.01, P < 0.001, and P < 0.05, respectively), no dose-response relationship was observed in the inhibitory effects of the three dosage groups. See Table 4 for details.

[0128] Table 4. Inhibitory effect of the traditional Chinese medicine composition of the present invention on the growth of zebrafish PANC1 xenograft tumors (n=10)

[0129]

[0130] Compared with the model control group, **p<0.01, ***p≤0.001; compared with the same dose group of granule 1, # p<0.05.

[0131] ⑤ The inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of AsPC-1 xenografts

[0132] The fluorescence intensity of the migration distance of AsPC-1 xenografts in zebrafish with gemcitabine 0.1 μg / tail was 215,921 pixels, which was significantly different from that of the model control group (597,355 pixels) (P<0.001), indicating that the positive control drug can significantly inhibit the migration of AsPC-1 xenografts.

[0133] The fluorescence intensities of zebrafish AsPC-1 xenografts at concentrations of 55.6, 167, and 500 μg / mL of the herbal composition (granules 1) of this invention were 296038, 275429, and 225805 pixels, respectively, which were statistically different from the model control group (597355 pixels) (P<0.05, P<0.05, and P<0.001, respectively). This indicates that the herbal composition (granules 1) of this invention has a significant inhibitory effect on the migration of zebrafish AsPC-1 xenografts, and exhibits a certain dose-response relationship. See Table 5 for details.

[0134] The fluorescence intensities of zebrafish AsPC-1 xenografts at concentrations of 111, 333, and 1000 μg / mL of the control herbal composition (granules 2) were 310,782, 256,699, and 274,437 pixels, respectively. There was no statistically significant difference between the low-dose group (111 μg / mL) and the model control group. Although both the medium-dose group (333 μg / mL) and the high-dose group (1000 μg / mL) showed significant differences compared to the model control group (P < 0.01), the fluorescence intensity of the high-dose group (1000 μg / mL) was actually stronger than that of the medium-dose group (333 μg / mL). Therefore, the inhibitory effect of the control herbal composition on the migration of zebrafish AsPC-1 xenografts did not demonstrate a dose-response relationship.

[0135] Table 5. Inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of zebrafish AsPC-1 xenografts (n=10)

[0136]

[0137]

[0138] Note: Compared with the model control group, **p<0.01, ***p≤0.001.

[0139] ⑥ The inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of BxPC-3 xenografts

[0140] The fluorescence intensity of zebrafish BxPC-3 xenografts at a concentration of 0.01 μg / tail of gemcitabine was 351,202 pixels, which was significantly lower than that of the model control group (740,983 pixels) (P < 0.001), indicating that the positive control drug could significantly inhibit the migration of BxPC-3 xenografts.

[0141] The fluorescence intensities of zebrafish BxPC-3 xenograft tumors at concentrations of 55.6, 167, and 500 μg / mL of the herbal composition (granules 1) of this invention were 505796, 475527, and 350922 pixels, respectively, which were significantly different from the model control group (740983 pixels) (P<0.05, P<0.01, and P<0.001, respectively), and the inhibitory effect showed a dose-response relationship. This indicates that the herbal composition of this invention has a significant inhibitory effect on the migration of zebrafish BxPC-3 xenograft tumors. See Table 6 for details.

[0142] The fluorescence intensities of zebrafish BxPC-3 xenografts at concentrations of 111, 333, and 1000 μg / mL of the control herbal composition (granules 2) were 392,507, 325,166, and 542,004 pixels, respectively. The low-dose group (111 μg / mL) and the medium-dose group (333 μg / mL) showed significantly different fluorescence intensities compared to the model control group (740,983 pixels), with P < 0.001. However, the high-dose group (1000 μg / mL) showed no statistically significant difference compared to the model group (P > 0.05). Therefore, the inhibitory effect of the control herbal composition on the migration of zebrafish BxPC-3 xenografts did not demonstrate a dose-response relationship. See Table 6 for details.

[0143] Table 6. Inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of BxPC-3 xenograft tumors in zebrafish (n=10)

[0144]

[0145] Note: Compared with the model control group, **p<0.01, ***p≤0.001; compared with the same dose group of granule 1, # p<0.05.

[0146] ⑦ The inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of PANC1 transplanted tumors

[0147] The fluorescence intensity of zebrafish PANC1 xenografts at a concentration of 0.01 μg / tail was 84,270 pixels, which was significantly lower than that of the model control group (783,161 pixels). This indicates that the positive control drug can significantly inhibit the migration of PANC1 xenografts.

[0148] The fluorescence intensities of zebrafish PANC1 xenografts at concentrations of 55.6, 167, and 500 μg / mL of the herbal composition (granules 1) of this invention were 619402, 577890, and 504291 pixels, respectively, which were all highly significant compared with the model control group (783161 pixels) (P<0.05, P<0.01, and P<0.001, respectively). This indicates that the herbal composition of this invention has a significant inhibitory effect on the migration of zebrafish PANC1 xenografts, and the inhibitory effect shows a certain dose-response relationship. See Table 7 for details.

[0149] The fluorescence intensities of zebrafish PANC1 xenografts at concentrations of 111, 333, and 1000 μg / mL of the control herbal composition 1 (granules 2) were 610403, 346006, and 648440 pixels, respectively. Although these were all highly significant differences compared to the model control group (783161 pixels) (P<0.01, P<0.001, and P<0.05, respectively), the inhibitory effect of the three dosage groups did not show a dose-response relationship. Furthermore, the fluorescence intensity of the high-dose group of the control herbal composition 1 was significantly higher than that of the high-dose group of the herbal composition of this invention. See Table 7 for details.

[0150] Table 7. Inhibitory effect of the traditional Chinese medicine composition of the present invention on the migration of PANC1 xenograft tumors in zebrafish (n=10)

[0151]

[0152] Note: Compared with the model control group, **p<0.01, ***p≤0.001; compared with the same dose group of granule 1, # p<0.05.

[0153] (5) Discussion and Conclusion

[0154] The raw materials of the comparative traditional Chinese medicine composition (granule 2) are Dalbergia odorifera, Corydalis yanhusuo, Salvia miltiorrhiza, Spatholobus suberectus, Sophora flavescens, Gentiana scabra, Morus alba root bark, Isatis indigotica root, and Glycyrrhiza uralensis. In this formula, Dalbergia odorifera and Salvia miltiorrhiza are the principal herbs for promoting blood circulation and removing blood stasis; Gentiana scabra and Sophora flavescens are the assistant herbs for clearing heat and drying dampness; Corydalis yanhusuo, Spatholobus suberectus, Morus alba root bark, and Isatis indigotica root are the adjuvant herbs; and Glycyrrhiza uralensis root is the guiding herb. Together, they promote blood circulation, relieve pain, clear heat, and dry dampness. Compared with granule 1 (the traditional Chinese medicine composition of this invention), the drug combination in granule 2 emphasizes the use of blood-activating herbs (Dalbergia odorifera, Corydalis yanhusuo, Salvia miltiorrhiza, and Spatholobus suberectus), while using Gentiana scabra, Sophora flavescens, Morus alba root bark, and Isatis indigotica root for clearing heat, detoxifying, and removing dampness. Its formulation principle is similar to that of the traditional Chinese medicine composition of this invention, but with a greater emphasis on promoting blood circulation and removing blood stasis. The above experimental results show that in all zebrafish pancreatic cancer models, the traditional Chinese medicine composition (granules 1) of this invention significantly inhibited the growth and migration of transplanted tumors, and the inhibitory effect on tumors showed a certain dose-response relationship. While the control traditional Chinese medicine composition (granules 2) also inhibited the growth and migration of each transplanted tumor, it did not show a clear dose-response relationship. Furthermore, the inhibitory effect of the traditional Chinese medicine composition (granules 1) on the growth of AsPC-1 transplanted tumors was significantly stronger than that of the control traditional Chinese medicine composition 1 (granules 2).

[0155] In summary, the traditional Chinese medicine composition of this invention has a stronger inhibitory effect on pancreatic cancer growth than the control traditional Chinese medicine composition. Furthermore, the traditional Chinese medicine composition of this invention uses Evodia rutaecarpa to counteract the effects of Phellodendron chinense and jujube to tonify the middle energizer and replenish qi. When targeting the main symptoms of damp-heat accumulation and blood stasis, it does not harm the body's vital energy, making it more suitable for the treatment of pancreatic cancer and improving the patient's quality of life.

[0156] In summary, this invention provides a traditional Chinese medicine composition that can be used for pancreatic cancer. The composition includes Phellodendron bark, Ginkgo, Evodia fruit, Tripterygium wilfordii, Zanthoxylum nitidum, Achyranthes bidentata, and Jujube. The combined effects of these herbs clear heat and dry dampness, disperse blood stasis, and relieve pain. Pharmacological experiments have demonstrated that the traditional Chinese medicine composition of this invention has a significant inhibitory effect on the growth and migration of human pancreatic cancer (AsPC-1, BxPC-3, and PANC1) xenografts. This invention provides a new clinical treatment option for pancreatic cancer patients and physicians.

Claims

1. A traditional Chinese medicine composition for pancreatic cancer, comprising the following medicinal materials in parts by weight: 1-20 parts of Phellodendron bark, 1-15 parts of Ginkgo, 1-10 parts of Evodia fruit, 1-10 parts of Tripterygium wilfordii, 1-15 parts of Zanthoxylum nitidum, 1-15 parts of Achyranthes bidentata, and 1-10 parts of jujube.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following medicinal materials in parts by weight: 5-15 parts of Phellodendron bark, 5-12 parts of Ginkgo biloba, 1-8 parts of Evodia rutaecarpa, 3-10 parts of Tripterygium wilfordii, 5-12 parts of Zanthoxylum nitidum, 5-12 parts of Achyranthes bidentata, and 3-8 parts of Ziziphus jujuba.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition consists of the following medicinal materials in parts by weight: 10-15 parts of Phellodendron bark, 8-12 parts of Ginkgo biloba, 3-6 parts of Evodia rutaecarpa, 3-8 parts of Tripterygium wilfordii, 8-12 parts of Zanthoxylum nitidum, 8-12 parts of Achyranthes bidentata, and 3-8 parts of Ziziphus jujuba.

4. The traditional Chinese medicine composition according to claim 3, characterized in that, The traditional Chinese medicine composition consists of the following medicinal materials in parts by weight: 11-13 parts of Phellodendron bark, 9-11 parts of Ginkgo biloba, 4-6 parts of Evodia rutaecarpa, 4-6 parts of Tripterygium wilfordii, 9-11 parts of Zanthoxylum nitidum, 9-11 parts of Achyranthes bidentata, and 4-6 parts of Ziziphus jujuba.

5. The traditional Chinese medicine composition according to claim 4, characterized in that, The traditional Chinese medicine composition consists of the following medicinal materials in parts by weight: 12 parts of Phellodendron bark, 10 parts of Ginkgo biloba, 5 parts of Evodia rutaecarpa, 5 parts of Tripterygium wilfordii, 10 parts of Zanthoxylum nitidum, 10 parts of Achyranthes bidentata, and 5 parts of Ziziphus jujuba.

6. The traditional Chinese medicine composition according to any one of claims 1 to 5, characterized in that, The aforementioned *Phellodendron chinense* can be replaced by *Phellodendron chinense* derived from the dried bark of the Rutaceae plant *Phellodendron chinese Schneid.*.

7. A medicament, using the traditional Chinese medicine composition of any one of claims 1 to 6 as a raw material, further comprising pharmaceutically acceptable excipients.

8. The medicament according to claim 7, characterized in that, The drug is any clinically acceptable formulation.

9. The medicament according to claim 8, characterized in that, The drug is an oral preparation.

10. The medicament according to claim 9, characterized in that, The oral preparations are selected from decoctions, powders, capsules, tablets, honey pills, water-honey pills, water pills, concentrated pills, paste pills, wax pills, granules, oral liquids, or drop pills.

11. The medicament according to claim 10, characterized in that, The oral preparation is a decoction or granules.

12. A method for preparing a drug according to any one of claims 7 to 11, comprising preparing each medicinal material according to the stated weight proportions, adding pharmaceutically acceptable excipients according to conventional formulation methods in the art, and preparing a clinically acceptable formulation.

13. The use of the traditional Chinese medicine composition according to any one of claims 1 to 6, the drug according to any one of claims 7 to 11, or the drug prepared according to the preparation method according to claim 12 in the preparation of a drug for treating pancreatic cancer.

14. The use of the traditional Chinese medicine composition according to any one of claims 1 to 6, the drug according to any one of claims 7 to 11, or the drug prepared according to the preparation method according to claim 12 in the preparation of a drug for treating locally advanced / advanced unresectable pancreatic cancer, metastatic pancreatic cancer, and postoperative recurrent pancreatic cancer.

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