A nasal traditional Chinese medicine composition for adjuvant tumor therapy and its preparation method

Abstract

This invention discloses a nasal administration of traditional Chinese medicine composition for adjuvant cancer treatment and its preparation method, comprising the following raw materials in parts by weight: each part is 1 gram, including 5-10 parts of Phellinus linteus, 4-9 parts of Ganoderma lucidum, 5-10 parts of Panax notoginseng, 3-8 parts of Cremastra appendiculata, 4-9 parts of Ligustrum lucidum, 1-5 parts of Cordyceps sinensis, 8-14 parts of Prunus persica, 2-5 parts of scallion, 3-15 parts of bitter almond, 8-15 parts of jujube, 3-6 parts of pepper, 50-60 parts of gypsum, 2-8 parts of Croton tiglium, 0.2-0.5 parts of arsenic trioxide, 1-5 parts of calomel, and 2-4 parts of ginger. This invention utilizes nasal inhalation via the mucous membrane for administration, achieving effects such as inhibiting tumor cells, enhancing the body's immune function, shortening the treatment cycle, and reducing side effects, making it suitable for adjuvant treatment of various cancers.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to a nasal administration of traditional Chinese medicine composition for adjuvant tumor treatment and its preparation method. Background Technology

[0002] Nasal administration is a modern route of drug delivery, used to treat both local nasal diseases and systemic diseases through absorption via the nasal mucosa. Currently, formulations used for systemic diseases include salmon calcitonin nasal spray for treating osteoporosis. Furthermore, due to the unique anatomical connection between the nasal cavity and brain tissue, nasal administration can cross the blood-brain barrier for brain-targeted delivery, used for central analgesia and mood regulation, such as fentanyl nasal spray for pain relief. Therefore, nasal administration has unique advantages, serving as a method for local, systemic, and even direct brain delivery.

[0003] Traditional Chinese medicine also includes nasal administration. Aromatherapy preparations are solid or liquid fragrances that combine various medicinal ingredients to achieve specific therapeutic effects. Scientific research shows that odors can directly promote or inhibit nerve excitation, thereby regulating the mind and treating diseases. Therefore, volatile preparations made by combining the medicinal properties of Chinese herbs—namely, olfactory therapy—are one of the methods of treating and preventing diseases in traditional Chinese medicine.

[0004] However, existing fragrances are mostly used for purposes such as refreshing the mind or treating insect bites. They typically involve adding fragrances during the processing of medicinal herbs, relying on the volatility of these fragrances to achieve their intended effect. However, since the therapeutic effects of these fragrances are primarily preventative, they generally do not provide significant relief for malignant diseases such as tumors. Furthermore, traditional fragrances are prone to gelatinization during processing due to high temperatures, which can affect their effectiveness.

[0005] According to existing technology reports, in 1983, Yang Maoquan used arsenic trioxide combined with toad, croton, and white pepper to grind into a fine powder, and then pounded it together with red dates (pitted) and scallions to form pills. After wrapping the pills in gauze, they were inserted into the middle nasal meatus on the affected side, which achieved an effective treatment for lymph node tuberculosis. This fully demonstrates the feasibility of using traditional Chinese medicine for nasal administration to treat systemic diseases.

[0006] In previous research, the inventors developed a scented balm (CN 116531481 A, cited in its entirety here for reference) that promotes sleep, reduces mosquito bites, and enhances biological activity. The balm comprises the following components: 1-5 parts Cordyceps sinensis, 8-14 parts peach kernel, 2-5 parts scallion, 3-15 parts bitter almond, 8-15 parts jujube, 3-6 parts pepper, 50-60 parts gypsum, 2-8 parts croton seed, 0.2-0.5 parts arsenic, 1-5 parts calomel, 2-4 parts ginger, and 90-105 parts spring mineral water. However, in later applications, the inventors found that the scented balm's effects were not significant. It could only be used in daily life as a consumer product and could not be applied in the treatment of diseases, particularly lacking technical effectiveness in adjuvant cancer therapy.

[0007] The inventors also previously used the corresponding nasal delivery products for health maintenance. The ingredients were: 6-10 parts bitter almonds, 10-15 parts jujubes, 1-5 parts cordyceps, 2-6 parts American ginseng, 10-15 parts peach kernels, 2-5 parts scallions, 2-4 parts pepper, 8-12 parts goji berries, 50-60 parts gypsum, and 90-105 parts water. However, the health benefits of these products were limited, offering no absolute advantage over oral health supplements, and lacking unique technological advancements. In particular, because these products only contained tonifying herbs like jujubes and cordyceps, and blood-activating and cough-suppressing herbs like peach kernels and almonds, their effects were very limited. In practical application, the inventors verified that they did not have an adjunctive therapeutic effect on cancer patients.

[0008] In previous research, the inventors also used the corresponding nasal drug delivery products for the treatment of tumors, namely, they provided a method for treating tumors by nasal inhalation and sweating detoxification (CN103372101A and CN103372100A, which are incorporated herein by reference in their entirety). The raw materials are 0.2-1 parts cordyceps, 0.001-0.005 parts arsenic, 8-23 centipedes, 3-15 parts peach kernels, 3-15 parts apricot kernels, 3-10 parts wolfberries, 3-6 blister beetles, 0.5-1 part croton seeds, and 3-16 parts pepper; it also includes 3-16 parts scallions, 3-16 parts ginger, and 3-6 parts garlic by weight. However, the above-mentioned products use animal-derived drugs such as centipedes and blister beetles, which have a distinctive fishy odor that is difficult for patients to accept. Furthermore, blister beetles are highly irritating to the nasal cavity, causing side effects such as nasal congestion, nasal obstruction, and nosebleeds. As a result, patient compliance is poor, which greatly limits their clinical application.

[0009] It is evident that the existing technology of using nasal administration of traditional Chinese medicine for tumor treatment still has technical defects such as large side effects, poor treatment effect, and unclear therapeutic effect. There is an urgent need to provide an effective traditional Chinese medicine composition with fewer side effects for adjuvant tumor treatment. Summary of the Invention

[0010] The purpose of this invention is to provide a nasal administration of a traditional Chinese medicine composition for adjuvant cancer therapy and its preparation method. This invention utilizes nasal inhalation via the mucous membrane, achieving effects such as inhibiting tumor cells, enhancing the body's immune function, shortening the treatment cycle, and reducing side effects. It is suitable for adjuvant therapy of various cancers. Compared with existing technologies, it has fewer side effects, a clear therapeutic effect, and better therapeutic efficacy. It can also appropriately reduce the dosage of other anti-tumor drugs, or reduce the dosage of radiotherapy and chemotherapy.

[0011] To achieve the above objectives, the present invention adopts the following technical solution:

[0012] A nasal administration traditional Chinese medicine composition for adjuvant tumor treatment, characterized in that it is made from the following raw materials in parts by weight: each part is 1 gram, including 5-10 parts of Phellinus linteus, 4-9 parts of Ganoderma lucidum, 5-10 parts of Panax notoginseng, 3-8 parts of Cremastra appendiculata, 4-9 parts of Ligustrum lucidum, 1-5 parts of Cordyceps sinensis, 8-14 parts of Prunus persica, 2-5 parts of scallion, 3-15 parts of bitter almond, 8-15 parts of jujube, 3-6 parts of pepper, 50-60 parts of gypsum, 2-8 parts of Croton tiglium, 0.2-0.5 parts of arsenic, 1-5 parts of calomel, and 2-4 parts of ginger.

[0013] Through years of clinical research, the inventors have recognized that many types of tumors are related to blood imbalances in Traditional Chinese Medicine (TCM). Based on this understanding, the technical solution of this invention innovatively uses Sanghuang (Phellinus linteus) and Sanqi (Panax notoginseng) as the principal herbs in this prescription. Both herbs have the dual effects of promoting blood circulation, removing blood stasis, stopping bleeding, and reducing swelling. They have a comprehensive and unique therapeutic effect on lumps or obstructions caused by complex etiologies such as masses and accumulations (including solid tumors or non-solid tumors as defined in Western medicine). When used in conjunction with conventional methods such as surgery, radiotherapy, and chemotherapy to treat tumors, they can be effectively used as adjuvant therapy for tumor diseases, shortening the treatment cycle, enhancing efficacy, and reducing patient suffering.

[0014] Furthermore, the technical solution of this invention also uses *Cremastra appendiculata* to reduce swelling and dissipate nodules, and pepper to warm the middle and relieve pain, thereby enhancing the swelling-reducing and pain-relieving effects of *Panax notoginseng*; it uses peach kernel to invigorate blood and remove blood stasis, thereby increasing the blood-invigorating effects of *Phellinus linteus* and *Panax notoginseng*; and it uses cordyceps sinensis to stop bleeding and resolve phlegm, thereby enhancing the hemostatic effects of *Phellinus linteus* and *Panax notoginseng*, all of which are used as assistant herbs.

[0015] Furthermore, the technical solution of this invention also employs Ganoderma lucidum to replenish deficiency, eliminate phlegm, and relieve cough; bitter almond to relieve cough and asthma; and ginger to warm the middle and relieve cough, further eliminating adverse reactions of nasal administration; it employs Ligustrum lucidum to nourish the liver and kidneys; and jujube to replenish the middle and boost qi, further enhancing the patient's immunity and restoring normal bodily functions. It also employs Croton tiglium to promote diuresis, reduce swelling, eliminate phlegm, and erode sores; arsenic trioxide to eliminate phlegm, erode sores, and remove necrotic tissue; calomel to attack toxins and astringe sores; and scallion to detoxify and promote yang, further targeting the pathogenesis of tumors to attack toxins, eliminate phlegm, and enhance the body's resistance. All of the above drugs serve as adjuvants.

[0016] Furthermore, the technical solution of this invention also uses gypsum to clear internal heat and effectively balance and reduce the toxicity of highly toxic drugs such as arsenic, croton, and calomel, and guides the drugs internally as an adjuvant.

[0017] This invention innovatively adjusts the compatibility structure of the nasal administration Chinese medicine composition, and for the first time combines Sanghuang and Sanqi for nasal administration as the principal drug for adjuvant cancer treatment. It also rationally combines the assistant, guiding, and adjuvant drugs to achieve a comprehensive therapeutic effect, including regulating blood circulation, reducing swelling and pain, eliminating phlegm and relieving cough, tonifying deficiency, and attacking toxins. This fully exerts its adjuvant effect on cancer treatment, resulting in a more effective and less side-effect-prone nasal administration Chinese medicine composition compared to existing technologies.

[0018] Furthermore, those skilled in the art know that the weight ratio of the active pharmaceutical ingredient has a certain influence on the efficacy of the traditional Chinese medicine composition. Without limitation, the inventors have found through a large number of exploratory experiments that the nasal administration traditional Chinese medicine composition within the above weight ratio can basically achieve the technical effect of adjuvant tumor treatment, while nasal administration traditional Chinese medicine compositions outside the above weight ratio usually cannot exert the technical effect of adjuvant tumor treatment.

[0019] Further preferably, the nasal administration traditional Chinese medicine composition is made from the following raw materials in parts by weight: 1 gram per part, 6-9 parts of Phellinus linteus, 5-8 parts of Ganoderma lucidum, 6-9 parts of Panax notoginseng, 4-7 parts of Cremastra appendiculata, 5-8 parts of Ligustrum lucidum, 2-4 parts of Cordyceps sinensis, 9-13 parts of Prunus persica, 3-5 parts of scallion, 7-12 parts of Prunus armeniaca, 10-13 parts of Ziziphus jujuba, 4-6 parts of pepper, 52-58 parts of gypsum, 4-7 parts of Croton tiglium, 0.3-0.4 parts of arsenic trioxide, 2-4 parts of calomel, and 2-4 parts of ginger. In other words, within the preferred weight ratio, compared with other weight ratios that can basically achieve the desired effect for adjuvant tumor treatment, the nasal administration traditional Chinese medicine composition can achieve the preferred technical effects for adjuvant tumor treatment, such as fewer side effects and better therapeutic effects (e.g., better inhibition of tumor cells, stronger immune-enhancing effects, and shorter treatment cycles).

[0020] Most preferably, the nasal administration traditional Chinese medicine composition is made from the following raw materials in parts by weight: 1 gram per part, 8 parts of Phellinus linteus, 7 parts of Ganoderma lucidum, 8 parts of Panax notoginseng, 6 parts of Cremastra appendiculata, 7 parts of Ligustrum lucidum, 3 parts of Cordyceps sinensis, 11 parts of Prunus persica, 4 parts of scallion, 10 parts of Prunus armeniaca, 12 parts of Ziziphus jujuba, 5 parts of pepper, 55 parts of gypsum, 5 parts of Croton tiglium, 0.3 parts of arsenic trioxide, 3 parts of calomel, and 3 parts of ginger. In other words, through extensive experimentation, it has been found that, compared with other weight ratios, the nasal administration traditional Chinese medicine composition achieves the best technical effect for adjuvant cancer treatment, such as the lowest side effects and the best therapeutic effect (e.g., the best effect in inhibiting tumor cells, the strongest effect in enhancing immunity, and the best effect in shortening the treatment cycle).

[0021] Further preferably, the pepper can be white pepper. The inventors have found that white pepper has a richer aroma, which allows it to better leverage the advantages of nasal administration, is less irritating, and is better suited for adjuvant cancer treatment.

[0022] Further preferably, the jujubes are pitted jujube flesh. The inventors have found that pitted jujubes are easier to crush and mix, preventing the hard particles of the jujube pits from irritating the nasal cavity.

[0023] More preferably, the peach kernels are blanched peach kernels. Blanching peach kernels reduces the toxic side effects of peach kernels, extends the shelf life of the medicine, and ensures the stability of the medicine's quality.

[0024] More preferably, the bitter almond is a blanched bitter almond. Blanching reduces the toxic side effects of bitter almonds.

[0025] More preferably, the gypsum is raw gypsum. The inventors have found that using raw gypsum can better clear internal heat and effectively balance and reduce the toxicity of highly toxic drugs such as arsenic, croton, and calomel.

[0026] More preferably, the croton seed is raw croton seed. Raw croton seed is generally considered to have an ulcer-causing effect when used alone externally. In this invention, by rationally combining raw croton seed with other drugs such as gypsum, Ganoderma lucidum, bitter almond, and ginger, its irritant properties are significantly reduced, and it can effectively play a role in adjuvant therapy for tumors.

[0027] As a further description of the above technical solution, in order to better prepare the nasal administration traditional Chinese medicine composition, the raw materials can also be extracted using a solvent. The inventors have found that using water as a solvent can effectively dissolve the active ingredients, and has low irritation and stable drug quality.

[0028] More preferably, the nasal administration herbal composition contains the following raw material in parts by weight: 90-105 parts water. More preferably, it contains the following raw material in parts by weight: 100 parts water.

[0029] To achieve the objective of providing a preparation method, this invention adopts the following technical solution, specifically including the following steps:

[0030] S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material.

[0031] S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B.

[0032] S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

[0033] As a further description of the above technical solution:

[0034] The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

[0035] It should be noted that, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0036] 1. This invention innovatively uses Sanghuang (Phellinus linteus) and Sanqi (Panax notoginseng) as the principal herbs in this prescription, fully leveraging their dual effects of promoting blood circulation, removing blood stasis, stopping bleeding, and reducing swelling. This makes them effective for adjuvant cancer treatment, inhibiting tumor cells, enhancing immunity, shortening the treatment cycle, improving efficacy, and alleviating patient suffering. The invention also rationally selects other herbs such as Shancigu (Pseudobulbus Cremastrae), pepper, peach kernel, and Cordyceps sinensis as assistant herbs to enhance the efficacy of the principal herbs. Furthermore, trace amounts of Croton tiglium, arsenic, and calomel can produce a pungent taste and enhance efficacy, which, combined with Shancigu, peach kernel, jujube, pepper, bitter almond, and Cordyceps sinensis, improves overall bioactivity. The comprehensive formula achieves the principles of regulating blood circulation, reducing swelling and relieving pain, eliminating phlegm and relieving cough, tonifying deficiency, and attacking toxins, effectively playing a role in adjuvant cancer treatment.

[0037] 2. This invention utilizes an innovative drug delivery method for adjuvant cancer therapy. Drug delivery is achieved through direct nasal inhalation, nasal spray, or administration via a face mask or by allowing the drug to dissipate naturally. This unique method reduces the treatment burden and psychological stress for cancer patients, resulting in high patient compliance. In adjuvant cancer therapy, it can inhibit tumor growth and enhance the body's immune system. It is suitable for various types of cancer, with significant efficacy and a low recurrence rate.

[0038] 3. This invention optimizes the weight ratio of the active pharmaceutical ingredients. Preliminary exploratory experiments have shown that the nasal administration of the traditional Chinese medicine composition within the above weight ratio can essentially achieve the technical effect for adjuvant tumor treatment. The above weight ratio is significantly superior to other weight ratios.

[0039] 4. In this invention, by heating and processing the raw materials of type B in the preparation method to increase the precipitation of medicinal properties, the gelatinization strength is lower, which effectively reduces the toxicity of the original medicinal materials and improves the effect of use. Detailed Implementation

[0040] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0041] Example 1

[0042] A nasal administration traditional Chinese medicine composition for adjuvant tumor treatment is made from the following raw materials: 1 gram per part, 10 parts of Phellinus linteus, 9 parts of Ganoderma lucidum, 10 parts of Panax notoginseng, 8 parts of Cremastra appendiculata, 9 parts of Ligustrum lucidum, 1 part of Cordyceps sinensis, 8 parts of Prunus persica, 2 parts of scallion, 3 parts of bitter almond, 8 parts of jujube, 3 parts of pepper, 50 parts of gypsum, 2 parts of Croton tiglium, 0.2 parts of arsenic trioxide, 1 part of calomel, and 2 parts of ginger. 90 parts of mineral water are used as the solvent.

[0043] The preparation method of the traditional Chinese medicine composition specifically includes the following steps:

[0044] S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material.

[0045] S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B.

[0046] S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

[0047] The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

[0048] Example 2

[0049] A nasal administration traditional Chinese medicine composition for adjuvant tumor treatment is made from the following raw materials: 1 gram per part, 5 parts of Phellinus linteus, 4 parts of Ganoderma lucidum, 5 parts of Panax notoginseng, 3 parts of Cremastra appendiculata, 4 parts of Ligustrum lucidum, 2 parts of Cordyceps sinensis, 10 parts of Prunus persica, 3 parts of scallion, 5 parts of bitter almond, 10 parts of jujube, 4 parts of pepper, 53 parts of gypsum, 4 parts of Croton tiglium, 0.4 parts of arsenic trioxide, 2 parts of calomel, and 3 parts of ginger. 95 parts of mineral water are used as the solvent.

[0050] The preparation method of the traditional Chinese medicine composition specifically includes the following steps:

[0051] S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material.

[0052] S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B.

[0053] S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

[0054] The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

[0055] Example 3

[0056] A nasal administration traditional Chinese medicine composition for adjuvant tumor treatment is made from the following raw materials: 1 gram per part, 8 parts of Phellinus linteus, 7 parts of Ganoderma lucidum, 8 parts of Panax notoginseng, 6 parts of Cremastra appendiculata, 7 parts of Ligustrum lucidum, 3 parts of Cordyceps sinensis, 11 parts of Prunus persica, 4 parts of scallion, 10 parts of Prunus armeniaca, 12 parts of Ziziphus jujuba, 5 parts of pepper, 55 parts of gypsum, 5 parts of Croton tiglium, 0.3 parts of arsenic trioxide, 3 parts of calomel, and 3 parts of ginger. 100 parts of mineral water are used as the solvent.

[0057] The preparation method of the traditional Chinese medicine composition specifically includes the following steps:

[0058] S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material.

[0059] S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B.

[0060] S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

[0061] The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

[0062] Example 4

[0063] A nasal administration traditional Chinese medicine composition for adjuvant tumor treatment is made from the following raw materials: 1 gram per part, 9 parts of Phellinus linteus, 6 parts of Ganoderma lucidum, 9 parts of Panax notoginseng, 6 parts of Cremastra appendiculata, 7 parts of Ligustrum lucidum, 5 parts of Cordyceps sinensis, 14 parts of Prunus persica, 5 parts of scallion, 15 parts of Prunus armeniaca, 15 parts of jujube, 6 parts of pepper, 60 parts of gypsum, 8 parts of Croton tiglium, 0.5 parts of arsenic trioxide, 5 parts of calomel, and 4 parts of ginger. 105 parts of mineral water are used as the solvent.

[0064] The preparation method of the traditional Chinese medicine composition specifically includes the following steps:

[0065] S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material.

[0066] S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B.

[0067] S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

[0068] The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

[0069] Example 5

[0070] A nasal administration traditional Chinese medicine composition for adjuvant tumor treatment is made from the following raw materials: each part is 1 gram, including 7 parts of Phellinus linteus, 8 parts of Ganoderma lucidum, 7 parts of Panax notoginseng, 6 parts of Cremastra appendiculata, 7 parts of Ligustrum lucidum, 1 part of Cordyceps sinensis, 8 parts of Prunus persica, 2 parts of scallion, 3 parts of bitter almond, 8 parts of jujube, 3 parts of pepper, 50 parts of gypsum, 2 parts of Croton tiglium, 0.2 parts of arsenic trioxide, 1 part of calomel, and 2 parts of ginger. 100 parts of mineral water are used as the solvent.

[0071] The preparation method of the traditional Chinese medicine composition specifically includes the following steps:

[0072] S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material.

[0073] S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B.

[0074] S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

[0075] The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

[0076] In order to study the technical effects of the present invention, the inventors commissioned the School of Pharmacy of Heilongjiang University of Traditional Chinese Medicine to conduct pharmacodynamic studies and multiple-dose toxicity tests on the nasal administration of the traditional Chinese medicine composition for adjuvant tumor treatment in Example 3 of the present invention.

[0077] Experimental Example 1: Study on the protective effect of cyclophosphamide on immunosuppressed mice

[0078] Specifically, a protective effect experiment was conducted on mice with cyclophosphamide-induced immunosuppression. The differences in immune capacity between the treatment group and the model group were compared by measuring spleen index, serum leukocytes, lymphocytes, immunoglobulins, and cytokine levels. Details are as follows:

[0079] I. Experimental Materials:

[0080] 1. Dosing group: The nasal administration of traditional Chinese medicine composition for adjuvant tumor therapy in Example 3;

[0081] 2. Cyclophosphamide, Manufacturer: Jiangsu Hengrui Medicine Co., Ltd., Batch No.: 23021525;

[0082] 3. Animals: ICR mice, provided by Liaoning Changsheng Biotechnology Co., Ltd., quality certificate: SCKX(Liaoning)2020-0001.

[0083] 4. Mouse immunoglobulin IgG / A / E / M assay kit, Jiangsu Jingmei Biotechnology Co., Ltd.; cytokine IL-1 / 2 assay kit, purchased from Nanjing Jiancheng Bioengineering Institute.

[0084] II. Experimental Methods and Results

[0085] 1. Modeling Method

[0086] Fifty six-week-old male ICR mice were housed at 24 ± 2 ℃ for one week. Forty mice were then injected intraperitoneally with cyclophosphamide (CTX, 60 mg / kg•d) on day 1 for three consecutive days, followed by injections every three days thereafter. To ensure optimal drug efficacy, the cyclophosphamide was administered within one hour of preparation. The remaining ten mice served as a blank control group, receiving an equal volume of physiological saline intraperitoneally simultaneously.

[0087] 2. Experimental Grouping

[0088] Mice were randomly divided into four groups of 10 each: a model group, a low-dose group (1.21 g / kg / d, containing the herbal composition of this invention), a medium-dose group (2.42 g / kg / d), and a high-dose group (4.84 g / kg / d). The experiment was replicated in three batches.

[0089] 3. Administration of medication and collection of materials

[0090] To better simulate clinical drug administration, a self-made, fully enclosed device was used for nasal inhalation administration. This device included a glass cage, an air circulation pump, an electric blanket, a fan speed regulator, and a perforated drug tube. During administration, the power was turned on, and the air circulation pump supplied air. One end of the perforated drug tube was open and connected to the pipeline, while the other end, also perforated, was connected to the glass cage. The circulating air delivered the drug into the cage, and the mice inhaled the gaseous drug spontaneously. The blank control group and the model group received no drug, but were given air in the same device as a control.

[0091] (1) Peripheral blood leukocyte count measurement

[0092] Whole blood was collected by enucleating the eyeballs, and the number of white blood cells and lymphocytes in the mouse blood was detected using a complete blood cell count analyzer. The results are shown in the table below.

[0093] Effects on peripheral blood leukocyte and lymphocyte counts

[0094]

[0095] Note: Comparison of each dosage group with the blank group Comparison of each dose group with the model group

[0096] The results showed that compared with the blank control group, the number of white blood cells and lymphocytes in the model group mice was significantly reduced, with statistically significant differences (P<0.01), indicating that the model group mice had low immune function and the model was successfully established. The number of white blood cells in all treatment groups was increased compared with the model group, with significant differences observed in the low-dose (P<0.05), medium-dose, and high-dose (P<0.05) groups compared to the model group. The number of lymphocytes in all treatment groups was increased compared with the model group, with significant differences observed in the medium-dose (P<0.05) and high-dose (P<0.01) groups compared to the model group, indicating that the herbal composition of this invention has a reversing effect on the immunosuppression induced by cyclophosphamide in mice.

[0097] (2) Measurement of mouse immune organ index

[0098] The spleen was removed, the blood was absorbed with a cotton ball, and it was weighed. The immune organ index was calculated using the following formula. The results are shown in the table below.

[0099] Spleen index (g / g) = Spleen weight / Body weight × 100%

[0100] Effects on spleen index, an immune organ

[0101]

[0102] Note: Comparison between each dose group and the model group .

[0103] The results showed that, compared with the model group, the spleen index of mice in the treatment group was increased. Among them, the spleen index of the medium-dose (P<0.05) and high-dose (P<0.01) groups showed significant differences, indicating that the traditional Chinese medicine composition of the present invention has an immune-enhancing effect.

[0104] (3) Detection of T lymphocyte subsets in mouse peripheral blood

[0105] After a 12-hour fast following the last administration, blood was collected by enucleation and anticoagulated with heparin. Plasma was collected by centrifugation and stored at -20 °C for cytokine assay. Cell pellets were resuspended in PBS to their original volume, mixed, and aliquoted into 50 μL tubes. FITC-labeled anti-mouse CD4 and CD8 monoclonal antibodies were added to each tube (10 μL / tube), mixed thoroughly, and incubated at 4 °C for 10 min. 50 μL of erythrocyte lysis buffer was added to each tube, and the mixture was vortexed for 10 min. Then, 2 mL of distilled water was added to each tube, and the mixture was vortexed for 2 min. The tubes were incubated at 37 °C for 12 min until clear. The mixture was centrifuged at 2000 r / min for 10 min, the supernatant was discarded, and 500 μL of PBS was added. The results were analyzed by flow cytometry. The results are shown in the table below.

[0106] Effects of peripheral blood T lymphocyte subsets

[0107]

[0108] Note: Comparison of each dosage group with the blank group Comparison of each dose group with the model group .

[0109] The results showed that, compared with the blank control group, the model group mice had CD4 + T cell levels (P<0.01) were significantly decreased, and CD8 levels were also significantly reduced. + The significantly elevated T cell levels (P<0.01) indicated that the model group mice had impaired immune function, and the model was successfully established. CD4 levels were significantly increased in mice of each treatment group. + T cell levels were increased in all groups compared to the model group, with significant differences observed in the medium-dose and high-dose groups (P<0.01) compared to the model group. CD8+ levels were also increased in mice in each treatment group. + The levels of T cells were lower in both groups compared to the model group, and the medium-dose group (P<0.05) and high-dose group (P<0.01) showed significant differences compared to the model group. This indicates that the herbal composition of the present invention can adjust the abnormal distribution of T cell subsets in immunocompromised mice and has a certain promoting and regulating effect on T cell immune function.

[0110] (4) Determination of mouse immune molecule content

[0111] Twelve hours after the last administration of medication, 1 mL of blood was collected from the retro-orbital venous plexus of the mice before sacrifice. The blood was allowed to stand, centrifuged at 3000 r / min for 10 min, and serum was collected. Spleen tissue was mixed with physiological saline at a ratio of 1:9, thoroughly homogenized, and centrifuged at 3000 r / min for 10 min. The levels of serum immunoglobulins IgG, IgA, IgE, and IgM, and spleen IL-1 and IL-2 were measured, all strictly following the kit instructions. After colorimetric development, OD values ​​were read at 450 nm using an automated microplate reader, and the corresponding data were obtained by plotting a standard curve. The results are shown in the table below.

[0112] Effects on the content of immune molecules

[0113]

[0114] Note: Comparison of each dosage group with the blank group Comparison of each dose group with the model group .

[0115] The results showed that the serum levels of IgG, IgA, IgE, and IgM in the model group mice were significantly lower than those in the control group (P<0.01), and the levels of IL-1 (P<0.05) and IL-2 (P<0.01) in the spleen were significantly lower than those in the control group, indicating that the model group was successfully established. Compared with the model group, the IgG levels in the medium-dose and high-dose groups (P<0.05) were significantly increased in all treatment groups; the serum IgA levels in the medium-dose (P<0.05) and high-dose (P<0.01) groups were significantly increased; the serum IgE levels in the high-dose group (P<0.05) were significantly increased; the serum IgM levels in the medium-dose (P<0.05) and high-dose (P<0.01) groups were significantly increased; the spleen IL-1 levels in the high-dose group (P<0.05) were significantly increased; and the IL-2 levels in the medium-dose and high-dose groups (P<0.05) were significantly increased. These results indicate that the herbal composition of this invention enhances humoral immunity in cyclophosphamide-induced immunosuppressed mice.

[0116] Experimental Example 2: The present invention also observed the effect of the traditional Chinese medicine composition in Example 3 of the present invention on subcutaneous xenografts of Hepa1-6 liver cancer in mice. The specific results are as follows:

[0117] I. Experimental Materials: C57BL / 6 strain mice, provided by Liaoning Changsheng Biotechnology Co., Ltd., quality certificate: SCKX(Liaoning)2020-0001. Mouse hepatocellular carcinoma cells Hepa1-6 were purchased from Wuhan Shangen Biotechnology Co., Ltd.

[0118] II. Experimental Methods

[0119] Hepa1-6 cells were cultured in high-glucose DMEM medium supplemented with 10% fetal bovine serum, 1 mM sodium pyruvate, and 1% penicillin and streptomycin. The cells were stored in a 5% CO2 incubator at 37°C, with the medium changed every 2-3 days until 80% cell confluence was achieved. Once cell confluence reached 70-80%, the old medium was discarded, and the cells were washed twice with 2 mL PBS. The cells were then digested with trypsin at 37°C for 3 min, followed by stopping the digestion with complete medium and centrifugation. The cells were washed twice with PBS, reconstituted with PBS, counted, and diluted 3 × 10⁶ cells / mL. 6 In 100 µL of phosphate buffered saline.

[0120] Six- to eight-week-old C57BL / 6 mice were housed under natural conditions for one week, provided with normal water and food, to acclimatize. A mouse axillary tumor xenograft model was established using Hepa1-6 cell injection. After anesthesia, the mice were placed supine on a operating table. Hair was removed from a 3cm × 3cm area in the right forelimb axilla using a shaver. 3 × 10-1 cells were then injected into the xenograft. 6100 μL of Hepa1-6 cell culture was subcutaneously injected into the right forelimb axilla of mice. Twelve days after inoculation, a visible mass and the presence of tumor cells on pathological examination were used as the criteria for successful tumor implantation.

[0121] After successful modeling, mice were randomly divided into 6 groups of 10 mice each: a blank control group, a model group, a low-dose group, a medium-dose group, a high-dose group, and a cyclophosphamide (positive control) group. Nasal inhalation was used for drug administration. To better simulate clinical drug administration, a self-made fully enclosed device was used. This device included a glass mouse cage, an air circulation pump, an electric blanket, a fan speed regulator, and a perforated drug tube. During administration, the power was turned on, and the air circulation pump delivered air. One end of the perforated drug tube was open and connected to a pipe, while the other end was perforated and connected to the glass mouse cage. The circulating air delivered the drug to the glass mouse cage, and the mice inhaled the gaseous drug spontaneously. The blank control group and the model group did not receive the drug but were given air in the same device as a control.

[0122] Three dosage groups were designed based on 1, 2, and 4 times the clinical dose per kilogram of body weight, and administered according to body weight: low dose 1.21 g / kg, medium dose 2.42 g / kg, and high dose 4.84 g / kg; the positive control group received an intraperitoneal injection of cyclophosphamide 0.02 g / kg, once daily.

[0123] During the experiment, the mice were observed daily, including their fur, mental state, diet, water intake, defecation, and activity. Their general condition was evaluated weekly. Mice underwent an acclimatization period of one week. Tumor size was recorded every three days using calipers, and tumor inhibition rate and tumor weight were calculated.

[0124] V (tumor volume) = major diameter × minor diameter 2 / 2

[0125] Tumor growth inhibition rate (%) = (mean tumor mass of control group - mean tumor mass of treatment group) / mean tumor mass of control group × 100%

[0126] III. Experimental Results

[0127] The experimental results of the effect of the traditional Chinese medicine composition of this invention on the tumor volume of Hepa1-6 tumor-bearing mice are shown in the table below. On day 12 after Hepa1-6 liver cancer cells were injected into the armpits of C57BL / 6 mice, obvious masses were visible to the naked eye and tumor cells were visible upon pathological examination, indicating that the Hepa1-6 tumor-bearing mouse model was successfully established on day 12. On day 12 of modeling, there was no significant difference in tumor volume among the groups (P > 0.05); on days 15 and 18, there were significant differences in tumor volume between the low- and medium-dose groups and the positive group (P < 0.05), and significant differences in tumor volume between the high- and positive groups and the model group (P < 0.05, P < 0.01); on days 21, 24, 27, and 30, there were significant differences in tumor volume between the low-, medium-, and high-dose groups and the model and positive groups (P < 0.05, P < 0.01), and significant differences in tumor volume between the positive group and the model group (P < 0.01).

[0128] Experimental results show that the herbal composition of the present invention at low, medium, and high doses, as well as in the positive control group, can reduce the tumor volume of Hepa1-6 tumor-bearing mice, exhibiting tumor-suppressing effects, with the positive control group showing the best tumor-suppressing effect. The reduction in tumor volume in Hepa1-6 tumor-bearing mice becomes more pronounced with increasing dosage of the herbal composition of the present invention, indicating that the herbal composition of the present invention has a dose-dependent effect on the proliferation of Hepa1-6 liver cancer.

[0129] Effects on tumor volume in Hepa1-6 tumor-bearing mice

[0130]

[0131] Note: Compared with the model group Compared to the positive group (cyclophosphamide)

[0132] The experimental results of the effects of the traditional Chinese medicine composition of this invention on tumor weight and tumor inhibition rate in Hepa1-6 tumor-bearing mice are shown in the table below. After dissection, the tumors of the Hepa1-6 tumor-bearing mice were obtained and their weight was measured. There were significant differences in tumor weight between the low-, medium-, and high-dose groups and the model group (P < 0.01), and a significant difference in tumor weight between the positive control group and the model group (P < 0.01). The tumor inhibition rates of the low-, medium-, and high-dose groups and the positive control group of the traditional Chinese medicine composition of this invention were 23.14%, 41.04%, 43.67%, and 68.12%, respectively.

[0133] Table 9. Effects of the herbal composition of the present invention on tumor weight and tumor inhibition rate in Hepa1-6 tumor-bearing mice.

[0134]

[0135] Note: Compared with the model group Compared to the positive group (cyclophosphamide)

[0136] Experimental results show that the herbal composition of the present invention and the positive control group both have an inhibitory effect on the proliferation of Hepa1-6 liver cancer. Among them, the positive control group has the highest tumor inhibition rate and the most obvious tumor inhibition effect. The tumor inhibition rate of the herbal composition of the present invention against Hepa1-6 liver cancer gradually increases with the increase of dosage, indicating that the herbal composition of the present invention has a tumor inhibition effect and its inhibition of the proliferation of Hepa1-6 liver cancer is dose-dependent.

[0137] Experimental Example 3: Effects on mouse breast cancer cells 4T1

[0138] 1. Cell Culture

[0139] 1.1 Cell cryopreservation

[0140] Remove the cells to be cryopreserved from the CO2 incubator and place them in a clean bench to discard the old culture medium. Add 3 mL of preheated PBS (37°C) and vortex twice, then digest and centrifuge. Discard the supernatant and add 1 mL of serum-free cell cryopreservation medium to resuspend the cells. Transfer the cell suspension to cryovials and label them. Incubate overnight at -80°C, and the next day transfer to liquid nitrogen for long-term storage.

[0141] 1.2 Cell resuscitation

[0142] First, preheat the water bath to 37°C. Prepare 15 mL sterile centrifuge tubes on a clean bench and add 4 mL of 1640 complete culture medium. Then, remove the cells to be revived from liquid nitrogen and quickly place them in the 37°C water bath, shaking constantly to rapidly thaw them. Transfer the thawed cell suspension to a centrifuge tube pre-filled with 4 mL of complete culture medium, gently mix by pipetting, and centrifuge at 1000 rpm for 5 min. Remove the supernatant, resuspend the cells in 1 mL of complete culture medium, and seed them into T-25 cell culture flasks containing 5 mL of 1640 complete culture medium. Incubate in a 5% CO2, 37°C incubator, changing the culture medium the next day.

[0143] 1.3 Cell passage

[0144] When the cells reached 80%-90% confluence, the culture medium was discarded, and the cells were washed twice with 3 mL of PBS. The PBS was then removed, and 1 mL of 0.25% trypsin digestion solution was added for 2 min to digest the cells. Digestion was terminated by adding 2 mL of 1640 complete culture medium, and the cells were centrifuged at 1000 rpm for 5 min. The supernatant was discarded, and the cells were resuspended in 2 mL of 1640 complete culture medium. The cells were seeded at a ratio of 1:2 into culture flasks containing 5 mL of 1640 complete culture medium and cultured in a 5% CO2 incubator at 37 ℃.

[0145] 2. Preparation of the test sample

[0146] Take 0.50 g of the traditional Chinese medicine composition of Example 3 of the present invention, add 1640 basal culture medium to 10 ml, sonicate for 10 min, filter, and obtain 50 mg / ml drug-containing culture medium, and store at 4 ℃.

[0147] 3. Cytotoxicity test

[0148] The cytotoxicity of the traditional Chinese medicine composition of this invention was determined using the CCK-8 assay. 4T1 cells in logarithmic growth phase were digested with 0.25% trypsin for 2 min, then 1640 complete culture medium was added to terminate the digestion. The cells were centrifuged, reconstituted with 1640 complete culture medium, counted, and the cell suspension concentration was adjusted to 1.0 × 10⁻⁶. 5 Cells / mL, 100 μL per well, were seeded into a 96-well plate and incubated for 12 h. The culture medium was then discarded. A blank group (no cells, culture medium without drug), a control group (cells present, culture medium without drug), and a drug-treated group (cells present, culture medium containing the herbal composition of this invention at concentrations of 10, 20, 40, 80, 160, 320, and 640 μg / mL, respectively) were set up, with 100 μL per well and 6 replicates per group. Incubation was performed for 24 h and 48 h, respectively. 10 μL of CCK-8 solution was added to each well and reacted for 2 h. The OD value was measured at 450 nm using a microplate reader. The half-inhibition concentration (IC50) was calculated using GraphPad Prism 8.0.2 software.

[0149] Tumor inhibition rate (%) = [OD(control group) - OD(treatment group)] / [OD(control group) - OD(blank group)] × 100%

[0150] Cell viability (%) = [OD (drug-treated group) - OD (blank group)] / [OD (control group) - OD (blank group)] × 100%

[0151] 4. Results

[0152] The inhibitory effect of the herbal composition of this invention on breast cancer cells 4T1 was detected by the CCK-8 assay. The experimental results showed that when the concentration of the herbal composition of this invention was 10 μg / mL, 20 μg / mL, 40 μg / mL, 80 μg / mL, 160 μg / mL, 320 μg / mL, and 640 μg / mL, after 24 h of intervention, the inhibition rate of the herbal composition on breast cancer cells 4T1 was 0.21%, 3.84%, 5.91%, 14.17%, 63.28%, 86.87%, and 87.34%, respectively. After 48 h of intervention, the inhibition rate of the herbal composition on breast cancer cells 4T1 was 11.88%, 15.36%, 26.03%, 33.72%, 75.60%, 86.32%, and 99.18%, respectively. Therefore, the inhibitory effect of the herbal composition of this invention on breast cancer cells 4T1 is enhanced with increasing concentration.

[0153]

[0154] Accordingly, the same cell inhibition experiment was also conducted on CT26 colon cancer cells in this invention. The experimental steps will not be repeated here. The results showed that the herbal composition of this invention had IC50 values ​​for CT26 colon cancer cells at 24 h, 48 h, and 72 h. 50 The concentrations were 307.5 μg / mL, 64.48 μg / mL, and 58.23 μg / mL, respectively.

[0155] Clinical application effects:

[0156] This invention has not yet undergone randomized, controlled, double-blind clinical trials in accordance with drug regulatory requirements, but it has already been preliminarily applied in clinical practice, as detailed below:

[0157] (a) General Information

[0158] One hundred and fourteen cancer patients were selected, including 76 males and 28 females, aged 9-76 years (median age 51 years). Eighty-four patients had solid tumors (12 cases of colorectal cancer, 42 cases of lung cancer, 3 cases of liver cancer, 17 cases of breast cancer, and 10 cases of lymphoma), and 20 patients had leukemia. All patients were diagnosed with cancer at a tertiary hospital and received routine surgery and / or standard radiotherapy and chemotherapy. These patients were randomly divided into two groups: a control group and a drug group. The two groups were comparable in terms of tumor type, male-to-female ratio, and age distribution.

[0159] All cases were treated with the traditional Chinese medicine composition of Example 3 of this invention via nasal spray for a duration of one course of treatment (i.e., 3 months) or more, followed by a 3-month observation period after the treatment ended. The disease stages of the 104 cases are listed below:

[0160] Distribution of tumor course in this group of 104 cases

[0161]

[0162] (II) Treatment Methods

[0163] In addition to routine tumor surgery and / or radiotherapy and chemotherapy, all patients in the treatment group received the traditional Chinese medicine composition prepared in Example 3 of this application, which was placed in a nebulizer and inhaled through the nose and exhaled through the mouth. After inhaling 8g of the medicine, they underwent a sauna once every two days. The control group received the same inhalation paste as described in prior art CN116531481A, with the same dosage and method of administration.

[0164] (III) Treatment Results

[0165] Criteria for judging therapeutic efficacy:

[0166] Cure: Cancer cells disappear, tumor marker results decrease by more than 80%, immunity reaches normal level, no pain or other symptoms, and no recurrence is observed during follow-up observation for more than 3 months;

[0167] Significant effect: Cancer cells are reduced by more than 80%, tumor marker results are reduced by more than 50%, immunity is more than 80% of the normal level, and there is occasional mild pain.

[0168] Improvement: Cancer cells decreased by more than 20%, tumor marker results decreased by more than 20%, immunity was more than 30% of normal levels, and pain from the lesions was reduced;

[0169] Ineffective: Cancer cells reduced by less than 20% or not reduced, tumor marker results reduced by less than 20% or not reduced, immunity lower than 30% of normal level, and no change in lesion pain.

[0170] Based on the above-mentioned efficacy judgment criteria, the efficacy analysis of the drug of the present invention is shown in the table below.

[0171] Efficacy analysis of this invention for adjuvant tumor therapy

[0172]

[0173] The results above demonstrate that the nasal administration of traditional Chinese medicine for adjuvant tumor therapy provided by this invention significantly improves the cure rate, efficacy, and effectiveness in treating tumors, compared to conventional tumor treatments. Furthermore, no recurrence was observed after three months of treatment. These experimental results indicate that the nasal administration of traditional Chinese medicine for adjuvant tumor therapy provided by this invention possesses significant technical effects in improving tumor treatment efficacy.

[0174] Example 4: Repeated-dose toxicity test

[0175] 1. Test Methods

[0176] Using the clinically intended daily dose of 0.133 g / kg and the maximum dose (108.0 g / kg) from a single inhalation toxicity test of the traditional Chinese medicine composition of Example 3 of this invention in KM mice, three dosages were designed based on the dose per kilogram of body weight: 0.336, 1.008, and 3.024 g / rat / day (approximately 2, 6, and 18 times the human clinically intended daily dose of 0.133 g / kg), and a control group. Forty SD rats were used in each group (20 males and 20 females). The rats were administered the drug once daily by inhalation, 7 days a week, for thirteen consecutive weeks, with a two-week recovery period. During the experiment, the rats' physical appearance, behavior, weight, food intake, and other indicators were monitored. Hematological, blood biochemical, organ weight, and histopathological examinations were performed three months after administration and at the end of the recovery period.

[0177] 2. Test Results

[0178] ① During the thirteen-week inhalation experiment of the traditional Chinese medicine composition of Example 3 of the present invention, the rats in each dose group were normal in activity, lively in behavior, and had glossy fur. No abnormal changes were observed in any physical signs compared with the control group.

[0179] ② No abnormal changes in food intake were observed in the animals in each treatment group compared with the control group at the same time point, which were not toxicologically significant.

[0180] ③ No abnormal changes were observed in the body weight of animals in each treatment group compared with the control group.

[0181] ④ No abnormal changes in hematological and blood biochemical indicators were observed compared with the control group during the same period.

[0182] ⑤ No dose-related pathological changes were observed in the animal tissues and organs of any group under gross observation. After the administration and recovery period, the liver and kidneys of the high-dose group were significantly heavier than those of the control group at the same time point. There were no toxicologically significant abnormal changes in the weight and organ coefficients of any other organs among the other groups.

[0183] ⑥ Except for the pathological changes in the liver and kidney tissues of a few animals in the high-dose group, no other tissues showed dose-effect relationship pathological changes during microscopic examination.

[0184] ⑦ No delayed toxic reactions or drug-related delayed pathological changes were observed during the recovery period.

[0185] 3. Experimental Conclusions

[0186] Under the experimental conditions described in this study, SD rats were administered the test compound of Example 3 of this invention via their respiratory tract at 13 weeks of age. No identifiable target organs of toxicity were found at doses of 0.336 g / rat / day and 1.008 g / rat / day (approximately 2 and 6 times the intended daily human clinical dose, respectively). At a dose of 3.024 g / rat / day (approximately 18 times the intended daily human clinical dose), the liver and kidneys were identified as target organs of toxicity. Therefore, the compound is safe at clinical doses. However, when using high doses, monitoring of liver and kidney function is necessary.

[0187] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for nasal administration as adjuvant therapy for tumors, characterized in that, It is made from the following raw materials in parts by weight: each part is 1 gram, including 6-9 parts of Phellinus linteus, 5-8 parts of Ganoderma lucidum, 6-9 parts of Panax notoginseng, 4-7 parts of Pseudobulbus Cremastrae, 5-8 parts of Ligustrum lucidum, 2-4 parts of Cordyceps sinensis, 9-13 parts of Prunus persica, 3-5 parts of scallion, 7-12 parts of bitter apricot kernel, 10-13 parts of jujube, 4-6 parts of pepper, 52-58 parts of gypsum, 4-7 parts of croton seed, 0.3-0.4 parts of arsenic, 2-4 parts of calomel, and 2-4 parts of ginger; among which Phellinus linteus and Panax notoginseng are the principal herbs, and the tumor is caused by the accumulation of masses.

2. The nasal administration traditional Chinese medicine composition according to claim 1, characterized in that, The pepper is white pepper; and / or the jujube is pitted jujube flesh; and / or the peach kernel is blanched peach kernel; and / or the bitter almond is blanched bitter almond; and / or the gypsum is raw gypsum; and / or the croton is raw croton.

3. The nasal administration traditional Chinese medicine composition according to claim 1, characterized in that, It also contains the following ingredients by weight: 1 gram per part, and 90-105 parts water.

4. The nasal administration traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following raw materials in parts by weight: each part is 1 gram, including 8 parts of Phellinus linteus, 7 parts of Ganoderma lucidum, 8 parts of Panax notoginseng, 6 parts of Pseudobulbus Cremastrae sibiricum, 7 parts of Ligustrum lucidum, 3 parts of Cordyceps sinensis, 11 parts of Prunus persica, 4 parts of scallion, 10 parts of bitter almond, 12 parts of jujube, 5 parts of pepper, 55 parts of gypsum, 5 parts of Croton tiglium, 0.3 parts of arsenic, 3 parts of calomel, and 3 parts of ginger.

5. The method for preparing the nasal administration traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, Specifically, the following steps are included: S1. Weigh the raw materials according to the formula: Sanghuang, scallion, bitter almond, jujube, pepper, gypsum, croton, and ginger. Grind them into coarse powder and calcine them with water to obtain a suspension A material. S2. Weigh the remaining ingredients in the formula: Ganoderma lucidum, Panax notoginseng, Pseudobulbus Cremastrae, Ligustrum lucidum, Cordyceps sinensis, peach kernel, arsenic, and calomel. Grind them thoroughly into coarse powder, calcine them until they turn a dark yellow color and smell a fragrance, and then disperse them to obtain powdered material B. S3. Mix the suspended material A with the powdered material B, stir until a paste is formed, and then fill the container.

6. The method for preparing the nasal administration traditional Chinese medicine composition according to claim 5, characterized in that, The sterilization treatment of the paste in step S3 specifically involves: after the pretreatment of the medicinal materials, irradiation with ultraviolet light for 30 minutes, followed by production in a sterile workshop.

Images