Nasal administration traditional Chinese medicine composition for tumor treatment or adjuvant treatment and preparation method of nasal administration traditional Chinese medicine composition

Abstract

The invention discloses a nasal administration traditional Chinese medicine composition for tumor treatment or adjuvant treatment and a preparation method of the nasal administration traditional Chinese medicine composition. The medicine is prepared from 5-10 parts of phellinus igniarius, 4-9 parts of lucid ganoderma, 5-10 parts of pseudo-ginseng, 3-8 parts of edible tulip, 4-9 parts of glossy privet fruit, 1-5 parts of cordyceps sinensis, 8-14 parts of peach kernel, 2-5 parts of green Chinese onion, 3-15 parts of semen armeniacae amarae, 8-15 parts of Chinese date, 3-6 parts of pepper, 50-60 parts of gypsum, 2-8 parts of croton, 0.2-0.5 part of arsenic, 1-5 parts of calomel and 2-4 parts of fresh ginger. A nasal inhalation mucous membrane administration mode is adopted, the effects of inhibiting tumor cells, improving the immunity of the body, shortening the treatment cycle, relieving side effects and the like can be achieved, and the medicine is suitable for treatment and adjuvant treatment of various tumors.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to a nasal Chinese medicine composition for tumor treatment or adjuvant treatment and a preparation method thereof. Background Art

[0002] Nasal administration is one of the modern drug administration routes. It can be used to treat local nasal diseases and can also be used to treat systemic diseases through drug absorption through the nasal mucosa. Currently, the preparations used for systemic diseases include salmon calcitonin spray for the treatment of osteoporosis. Moreover, due to the special anatomical structure of the nasal cavity connecting to the brain tissue, nasal administration can also cross the blood-brain barrier for brain-targeted administration, which can be used for central analgesia, emotional regulation, etc., such as fentanyl nasal spray for analgesia. It can be seen that nasal administration has its unique advantages in drug administration. It can be used for local administration, systemic administration, and even has the advantage of direct administration to the brain.

[0003] Traditional Chinese medicine also has a nasal dosage form. Scents are solid or liquid flavors that achieve the corresponding functions of drugs through the combination of multiple drugs. Scents can achieve certain therapeutic purposes through the combination of drugs. Scientific research shows that smells can directly promote or inhibit nerve excitement to achieve the purpose of regulating the spirit and treating diseases. Therefore, volatile medicines prepared by combining the medicinal properties of Chinese medicinal materials, namely olfactory medicines, are one of the means of treating and preventing diseases in traditional Chinese medicine.

[0004] However, existing scent agents are mostly used for purposes such as refreshing the mind with fragrance or mosquito bites. Usually, certain spices are added during the processing of the formula ingredients and Chinese herbal medicines, and the volatility of the spices is used to achieve the purpose of use. However, since the therapeutic effect of these spices is mainly prevention, they generally cannot play a good therapeutic effect on malignant diseases such as tumors. On the other hand, traditional scent agents are prone to gelatinization when the ingredients are separated due to high temperature during the processing process, which affects the use effect when used.

[0005] It is reported in the prior art that in 1983, Yang Maoquan used arsenic in combination with toad, croton, and white pepper to grind into fine powder, and pounded them into pills with red dates (pitted) and green onion. The pills were wrapped with gauze and inserted into the middle nasal cavity on the affected side, achieving effective results in treating lymph node tuberculosis, which fully demonstrated the feasibility of nasal administration of traditional Chinese medicine for the treatment of systemic diseases.

[0006] The inventor has invented a scent ointment (CN 116531481 A, the entire text of which is incorporated herein by reference) that promotes sleep, reduces mosquito bites, and improves biological activity in previous studies. The ointment comprises the following components: 1-5 parts of cordyceps sinensis, 8-14 parts of peach kernels, 2-5 parts of green onions, 3-15 parts of bitter almonds, 8-15 parts of jujubes, 3-6 parts of pepper, 50-60 parts of gypsum, 2-8 parts of croton seeds, 0.2-0.5 parts of arsenic, 1

[0007] -5 parts, ginger 2-4 parts, spring mineral water 90-105 parts. However, the inventor found in the later application that the above scent ointment has no significant technical effect and can only be used in daily life as a daily necessity, but cannot be used in the field of disease treatment, especially for the treatment or auxiliary treatment of tumors.

[0008] The inventor has also used the corresponding nasal administration product for health care, and its raw materials are: 6-10 parts of bitter almonds, 10-15 parts of jujubes, 1-5 parts of cordyceps sinensis, 2-6 parts of American ginseng, 10-15 parts of peach kernels, 2-5 parts of green onions, 2-4 parts of pepper, 8-12 parts of wolfberries, 50-60 parts of gypsum, and 90-105 parts of water. However, the health care function of the above-mentioned products is limited, and there is no absolute advantage compared with oral health care products, and there is also a lack of unique progress in technology. In particular, since the above-mentioned products only contain tonic drugs such as jujubes and cordyceps and blood circulation and cough relieving drugs such as peach kernels and almonds, the effects are very single. The inventor has verified in practical applications that they do not have a therapeutic or auxiliary therapeutic effect on tumor patients.

[0009] In previous studies, the inventors have also used corresponding nasal administration products for the treatment of tumors, that is, a method for treating tumors by nasal inhalation, sweating and detoxification (CN103372101A and CN103372100A, the entire text of which is incorporated herein by reference), the raw materials of which are 0.2-1 parts of cordyceps, 0.001-0.005 parts of arsenic, 8-23 centipedes, 3-15 parts of peach kernels, 3-15 parts of almonds, 3-10 parts of wolfberries, 3-6 blister beetles, 0.5-1 parts of croton, and 3-16 parts of pepper; it also includes 3-16 parts of onions, 3-16 parts of ginger, and 3-6 parts of garlic by weight. However, the above-mentioned products use animal drugs such as centipedes and blister beetles, which have a special fishy smell that is difficult for patients to accept. In addition, blister beetles are highly irritating to the nasal cavity, causing side effects such as nasal mucosal congestion, nasal congestion, and nosebleeds. Patients' compliance is poor, and their clinical application is greatly limited.

[0010] It can be seen that the existing technology of using nasal Chinese medicine for tumor treatment still has technical defects such as large side effects, poor therapeutic effect, and unclear therapeutic effect. There is an urgent need to provide an effective Chinese medicine composition with small side effects for tumor treatment or adjuvant treatment. Summary of the invention

[0011] The purpose of the present invention is to provide a nasal Chinese medicine composition for tumor treatment or adjuvant treatment and a preparation method thereof. The present invention adopts a nasal inhalation mucosal administration method, which can achieve the effects of inhibiting tumor cells, improving the body's immune ability, shortening the treatment cycle, reducing side effects, etc., and is suitable for the treatment or adjuvant treatment of various tumors. Compared with the prior art, it has the technical effects of small side effects, clear therapeutic effects, and better therapeutic effects, and can also appropriately reduce the dosage of other anti-tumor drugs, or reduce the dosage of radiotherapy and chemotherapy.

[0012] In order to achieve the above object, the present invention adopts the following technical solutions:

[0013] A Chinese medicine composition for nasal administration for tumor treatment or adjuvant treatment, characterized in that it is made of the following raw materials in parts by weight: 1 gram per part, 5-10 parts of mulberry linterus, 4-9 parts of ganoderma lucidum, 5-10 parts of Panax notoginseng, 3-8 parts of Aralia scabra, 4-9 parts of Ligustrum lucidum, 1-5 parts of Cordyceps sinensis, 8-14 parts of peach kernel, 2-5 parts of green onion, 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, 0.2-0.5 parts of arsenic, 1-5 parts of calomel, and 2-4 parts of ginger.

[0014] Through years of clinical practice and research, the inventors have realized that many tumors are related to blood disorders in traditional Chinese medicine. Based on the above understanding, the technical solution of the present invention innovatively adopts Phellinus and Panax notoginseng as the main medicine of this prescription. Both have the dual effects of promoting blood circulation and removing blood stasis, stopping bleeding and reducing swelling. They have a full range of unique therapeutic effects on lumps or blood stasis caused by complex causes such as accumulation of masses and masses (including solid tumors or non-solid tumors called tumors in Western medicine). When combined with conventional means such as surgery, radiotherapy and chemotherapy to treat tumors, they can be effectively used for the treatment or adjuvant treatment of tumor diseases, shorten the treatment cycle, enhance the efficacy, and relieve the pain of patients.

[0015] Furthermore, the technical scheme of the present invention also adopts Tripterygium wilfordii to reduce swelling and disperse nodules, and Piper nigrum to warm the middle and relieve pain, thereby enhancing the reducing swelling and relieving pain effects of Panax notoginseng; adopts Peach Kernel to promote blood circulation and remove blood stasis, thereby increasing the blood circulation effects of Phellinus igniarius and Panax notoginseng; adopts Cordyceps sinensis to stop bleeding and resolve phlegm, thereby enhancing the hemostatic effects of Phellinus igniarius and Panax notoginseng, and all of them are assistant drugs.

[0016] Furthermore, the technical solution of the present invention also adopts Ganoderma lucidum to nourish deficiency, eliminate phlegm and relieve cough, bitter almond to relieve cough and asthma, and ginger to warm the middle and relieve cough, further eliminating the adverse reactions of nasal administration; adopts Ligustrum lucidum to nourish liver and kidney, and jujube to replenish qi, further enhancing the patient's immunity and restoring the normal function of the body. Croton is used to remove water, reduce swelling, eliminate phlegm and ulcer, arsenic to rob phlegm and ulcer to remove rot, light powder to attack poison and heal ulcer, and green onion to detoxify and promote yang, further targeting the etiology and pathogenesis of tumors to attack poison and eliminate phlegm and enhance positive energy. The above drugs are adjuvants.

[0017] Furthermore, the technical solution of the present 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 drug inside as a guiding drug.

[0018] The present invention innovatively adjusts the compatibility structure of the nasal Chinese medicine composition, combines Phellinus igniarius and Panax notoginseng for nasal administration for the first time as the main medicine for the treatment or auxiliary treatment of tumors, and reasonably combines the ministerial medicine, the guiding medicine and the adjuvant medicine, and reasonably and effectively cooperates the above main, ministerial, guiding and adjuvant medicines to achieve the comprehensive treatment principles of regulating blood, reducing swelling and relieving pain, removing phlegm and relieving cough, replenishing deficiency and attacking toxins, and fully exerts the treatment or auxiliary treatment effect for tumors. Compared with the prior art, the nasal Chinese medicine composition has the technical effects of small side effects, clear therapeutic effects and better therapeutic effects.

[0019] In addition, it is well known to those skilled in the art that the weight ratio of the raw materials has a certain influence on the efficacy of the Chinese medicine composition. In a non-limiting way, the inventors have found through a large number of exploratory experiments that the Chinese medicine composition for nasal administration within the above-mentioned weight ratio relationship can basically achieve the technical effect of treating or assisting the treatment of tumors, while the Chinese medicine composition for nasal administration outside the said weight ratio relationship is usually difficult to exert the technical effect of treating or assisting the treatment of tumors.

[0020] Further preferably, the Chinese medicine composition for nasal administration is made of the following raw materials in parts by weight: 1 gram per part, 6-9 parts of Phellinus igniarius, 5-8 parts of Ganoderma lucidum, 6-9 parts of Panax notoginseng, 4-7 parts of Psoralea corylifolia, 5-8 parts of Ligustrum lucidum, 2-4 parts of Cordyceps sinensis, 9-13 parts of peach kernel, 3-5 parts of green onion, 7-12 parts of bitter almond, 10-13 parts of jujube, 4-6 parts of pepper, 52-58 parts of gypsum, 4-7 parts of croton, 0.3-0.4 parts of arsenic, 2-4 parts of calomel, and 2-4 parts of ginger. That is to say, within the preferred weight ratio, compared with other weight ratios that can basically achieve the treatment or adjuvant treatment of tumors, the Chinese medicine composition for nasal administration can achieve the preferred technical effects of the treatment or adjuvant treatment of tumors, such as lower side effects and better therapeutic effects (such as better inhibition of tumor cells, stronger immunity enhancement, better shortening of treatment cycles, etc.).

[0021] Most preferably, the Chinese medicine composition for nasal administration is made of the following raw materials in weight: 1 gram per portion, 8 parts of Phellinus igniarius, 7 parts of Ganoderma lucidum, 8 parts of Panax notoginseng, 6 parts of Psoralea corylifolia, 7 parts of Ligustrum lucidum, 3 parts of Cordyceps sinensis, 11 parts of peach kernel, 4 parts of green onion, 10 parts of bitter almond, 12 parts of jujube, 5 parts of pepper, 55 parts of gypsum, 5 parts of croton, 0.3 parts of arsenic, 3 parts of calomel, and 3 parts of ginger. That is to say, through a large number of experimental explorations, it can be known that in the most preferred weight ratio relationship, compared with other weight ratio relationships, the Chinese medicine composition for nasal administration can achieve the best technical effect for the treatment or adjuvant treatment of tumors, such as the lowest side effect and the best therapeutic effect (such as the best effect of inhibiting tumor cells, the strongest effect of enhancing immunity, the best shortening of treatment cycle, etc.).

[0022] Further preferably, the pepper may be white pepper. The inventors have found that white pepper has a stronger aroma, can better take advantage of nasal administration, is less irritating, and is better used for the treatment or adjuvant treatment of tumors.

[0023] Further preferably, the jujube is pitted jujube flesh. The inventors have found that pitted jujube is easier to crush and mix, preventing the hard particles of the pit from irritating the nasal cavity.

[0024] Further preferably, the peach kernel is a stewed peach kernel, which reduces the toxic side effects of the peach kernel, prolongs the shelf life of the drug, and ensures the stability of the drug quality.

[0025] Further preferably, the bitter almonds are stewed bitter almonds, which reduce the toxic side effects of bitter almonds.

[0026] Further preferably, the gypsum is raw gypsum. The inventors have found that the use of raw gypsum can better clear away internal heat and effectively balance and reduce the toxicity of highly toxic drugs such as arsenic, croton, and calomel.

[0027] Further preferably, the croton is raw croton. It is generally believed that raw croton has an erosive effect when used externally alone. In the present invention, by rationally combining raw croton with other drugs such as gypsum, ganoderma lucidum, bitter almond and ginger, its irritation is significantly reduced, and it can effectively play a therapeutic or adjuvant therapeutic role for tumors.

[0028] As a further description of the above technical solution, in order to better prepare the Chinese medicine composition for nasal administration, the raw materials can also use solvents to extract the raw materials. The inventors have found that using water as a solvent can effectively dissolve the active ingredients, and has low irritation and stable drug quality.

[0029] Further preferably, the Chinese medicine composition for nasal administration contains the following raw materials in parts by weight: 90-105 parts of water. More preferably, it contains the following raw materials in parts by weight: 100 parts of water.

[0030] In order to achieve the purpose of providing a preparation method, the present invention adopts the following technical scheme: specifically comprising the following steps:

[0031] S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension material A;

[0032] S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B;

[0033] S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

[0034] As a further description of the above technical solution:

[0035] The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

[0036] It should be noted that, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0037] 1. The technical solution of the present invention innovatively adopts Phellinus igniarius and Radix Notoginseng as the monarch medicine of this prescription, giving full play to the dual effects of both of promoting blood circulation and removing blood stasis, stopping bleeding and reducing swelling, and can be effectively used for the treatment or adjuvant treatment of tumors, inhibiting tumor cells, enhancing immunity, shortening the treatment cycle, enhancing the therapeutic effect, and alleviating the pain of patients. Reasonable selection of Tripterygium wilfordii, pepper, peach kernel, Cordyceps sinensis, etc. as ministerial medicines enhances the therapeutic effect of the monarch medicine. And it is possible to produce irritating taste and improve drug efficacy by trace amounts of croton, arsenic, light powder, etc., cooperate with Tripterygium wilfordii, peach kernel, jujube, pepper, bitter almond and Cordyceps sinensis, etc., to improve overall biological activity. The whole side cooperates to achieve the comprehensive treatment principle of regulating blood, reducing swelling and relieving pain, removing phlegm and relieving cough, replenishing deficiency, and attacking toxic substances, and effectively plays the treatment or adjuvant treatment effect for tumors.

[0038] 2. The present invention uses an innovative administration method for the treatment or adjuvant treatment of tumors. The administration method is directly introduced into the nasal cavity, sprayed into the nasal cavity, or combined with a breathing mask or static dispersion, that is, the nasal inhalation mucosal administration method is adopted. The administration method is unique, which reduces the treatment burden and psychological pressure of tumor patients, and the patient compliance is high. In the process of tumor treatment or adjuvant treatment, it can inhibit tumor growth and improve the body's immune ability. It is suitable for various tumors, has significant therapeutic effects, and is not easy to relapse.

[0039] 3. The present invention optimizes the weight ratio of the raw materials. Through preliminary exploratory experiments, it is found that the Chinese medicine composition for nasal administration within the above weight ratio can basically achieve the technical effect of tumor treatment or adjuvant treatment. The above weight ratio is significantly better than other weight ratios.

[0040] 4. In the present invention, the precipitated medicinal properties are increased by heating the Class B raw materials in the preparation method, the gelatinization strength is lowered, the toxicity of the original medicinal materials is effectively reduced, and the use effect is improved. DETAILED DESCRIPTION

[0041] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0042] Example 1

[0043] A Chinese medicine composition for nasal administration for tumor treatment or adjuvant treatment is prepared from the following raw materials: 1 gram per portion, 10 parts of mulberry linterus, 9 parts of ganoderma lucidum, 10 parts of notoginseng, 8 parts of yam, 9 parts of glossy privet, 1 part of cordyceps sinensis, 8 parts of peach kernel, 2 parts of green onion, 3 parts of bitter almond, 8 parts of jujube, 3 parts of pepper, 50 parts of gypsum, 2 parts of croton, 0.2 parts of arsenic, 1 part of calomel, and 2 parts of ginger. 90 parts of mineral water are used as solvent.

[0044] The preparation method of the Chinese medicine composition specifically comprises the following steps:

[0045] S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension material A;

[0046] S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B;

[0047] S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

[0048] The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

[0049] Example 2

[0050] A Chinese medicine composition for nasal administration for the treatment or adjuvant treatment of tumors is prepared from the following raw materials: 1 gram per portion, 5 parts of Phellinus igniarius, 4 parts of Ganoderma lucidum, 5 parts of Panax notoginseng, 3 parts of Psoralea corylifolia, 4 parts of Ligustrum lucidum, 2 parts of Cordyceps sinensis, 10 parts of peach kernel, 3 parts of green onion, 5 parts of bitter almond, 10 parts of jujube, 4 parts of pepper, 53 parts of gypsum, 4 parts of croton, 0.4 parts of arsenic, 2 parts of calomel, and 3 parts of ginger. 95 parts of mineral water are used as solvent.

[0051] The preparation method of the Chinese medicine composition specifically comprises the following steps:

[0052] S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension material A;

[0053] S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B;

[0054] S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

[0055] The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

[0056] Example 3

[0057] A Chinese medicine composition for nasal administration for the treatment or adjuvant treatment of tumors is prepared from the following raw materials: 1 gram per portion, 8 parts of mulberry linterus, 7 parts of ganoderma lucidum, 8 parts of notoginseng, 6 parts of yam, 7 parts of glossy privet, 3 parts of cordyceps, 11 parts of peach kernel, 4 parts of green onion, 10 parts of bitter almond, 12 parts of jujube, 5 parts of pepper, 55 parts of gypsum, 5 parts of croton, 0.3 parts of arsenic, 3 parts of calomel, and 3 parts of ginger. 100 parts of mineral water are used as solvent.

[0058] The preparation method of the Chinese medicine composition specifically comprises the following steps:

[0059] S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension material A;

[0060] S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B;

[0061] S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

[0062] The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

[0063] Example 4

[0064] A Chinese medicine composition for nasal administration for the treatment or adjuvant treatment of tumors is prepared from the following raw materials: 1 gram per portion, 9 parts of mulberry linterus, 6 parts of ganoderma lucidum, 9 parts of notoginseng, 6 parts of yam, 7 parts of glossy privet, 5 parts of cordyceps, 14 parts of peach kernel, 5 parts of green onion, 15 parts of bitter almond, 15 parts of jujube, 6 parts of pepper, 60 parts of gypsum, 8 parts of croton, 0.5 parts of arsenic, 5 parts of calomel, and 4 parts of ginger. 105 parts of mineral water are used as a solvent.

[0065] The preparation method of the Chinese medicine composition specifically comprises the following steps:

[0066] S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension material A;

[0067] S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B;

[0068] S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

[0069] The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

[0070] Example 5

[0071] A Chinese medicine composition for nasal administration for the treatment or adjuvant treatment of tumors is prepared from the following raw materials: 1 gram per portion, 7 parts of mulberry linterus, 8 parts of ganoderma lucidum, 7 parts of notoginseng, 6 parts of yam, 7 parts of glossy privet, 1 part of cordyceps, 8 parts of peach kernel, 2 parts of green onion, 3 parts of bitter almond, 8 parts of jujube, 3 parts of pepper, 50 parts of gypsum, 2 parts of croton, 0.2 parts of arsenic, 1 part of calomel, and 2 parts of ginger. 100 parts of mineral water are used as solvent.

[0072] The preparation method of the Chinese medicine composition specifically comprises the following steps:

[0073] S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension material A;

[0074] S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B;

[0075] S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

[0076] The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

[0077] In order to study the technical effects of the present invention, the inventor commissioned the School of Pharmacy of Heilongjiang University of Chinese Medicine to conduct a pharmacodynamic study and multiple-dose toxicity test on the nasal Chinese medicine composition for the treatment or adjuvant treatment of tumors in Example 3 of the present invention.

[0078] Experimental Example 1: Study on the protective effect on cyclophosphamide-type immunosuppressed mice

[0079] Specifically, a test on the protective effect on cyclophosphamide-induced immunosuppressive mice was conducted, and the differences in immune ability between the group receiving the Chinese medicine composition of the present invention and the model group were compared by measuring the spleen index, the content of leukocytes, lymphocytes, immunoglobulins, and cytokines in serum, as follows:

[0080] 1. Experimental materials:

[0081] 1. Administration group: the Chinese medicine composition for nasal administration for the treatment or adjuvant treatment of tumors in Example 3;

[0082] 2. Cyclophosphamide, manufacturer: Jiangsu Hengrui Co., Ltd., batch number: 23021525;

[0083] 3. Animals: ICR mice, provided by Liaoning Changsheng Biotechnology Co., Ltd., quality certificate: SCKX(Liao)2020-0001.

[0084] 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.

[0085] 2. Test methods and results

[0086] 1. Modeling method

[0087] Fifty ICR male six-week-old mice were taken and kept at 24±2℃ for one week. 40 mice were injected intraperitoneally with cyclophosphamide (CTX, 60mg / kg·d) for 3 consecutive days on the first day of the experiment, and then injected every 3 days. After cyclophosphamide was prepared, the injection was completed within 1 hour to ensure the drug effect. The remaining 10 mice were used as blank control groups and injected with an equal volume of saline at the same time.

[0088] 2. Experimental Grouping

[0089] The model mice were randomly divided into 4 groups, each with 10 mice, namely the model group, the low-dose group 1.21 g / Kg / d of the Chinese medicine composition of the present invention, the medium-dose group 2.42 g / Kg / d, and the high-dose group 4.84 g / Kg / d. The experiment was replicated in three batches.

[0090] 3. Medication and material collection

[0091] The drug was administered by nasal inhalation. In order to better simulate the clinical medication form, this experiment used a homemade fully enclosed device for drug administration, which included a glass mouse cage, an air circulation pump, an electric blanket, a wind speed adjustment device, and a drug tube with holes. When administering the drug, turn on the power, and deliver the wind source through the air circulation pump. One end of the drug tube with holes is open and connected to the pipeline, and the other end is connected to the glass mouse cage with holes. The circulating wind blows the drug into the glass mouse cage, and the mice inhale the drug in gas form autonomously. The blank control group and the model group were not given any drug, but air was given in the same device as a control.

[0092] (1) Peripheral blood leukocyte count

[0093] The eyeballs were removed to obtain whole blood, and the number of white blood cells and lymphocytes in the blood of mice was detected using a complete blood cell analyzer. The results are shown in the table below.

[0094] Effects on peripheral blood leukocyte count and lymphocyte count

[0095]

[0096] Note: **P<0.01 compared with the blank group, **P<0.01 compared with the model group, # P<0.05, ## P<0.01.

[0097] The results showed that compared with the blank control group, the number of white blood cells and lymphocytes in the model group mice were significantly reduced, and the difference was statistically significant (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 each administration group was increased compared with the model group, among which the low dose (P<0.05), medium dose and high dose (P<0.05) were significantly different from the model group. The number of lymphocytes in each administration group was increased compared with the model group, and the medium dose (P<0.05) and high dose groups (P<0.01) were significantly different from the model group, indicating that the administration of the Chinese medicine composition of the present invention has a callback effect on the immunosuppression of mice caused by cyclophosphamide.

[0098] (2) Determination of mouse immune organ index

[0099] The spleen was removed, the floating blood was absorbed with cotton balls and weighed, and the immune organ index was calculated according to the following formula. The results are shown in the table below.

[0100] Spleen index (g / g) = spleen weight / body weight × 100%

[0101] Effects on the immune organ spleen index

[0102]

[0103] Note: Compared with the model group, each dose group # P<0.05, ## P<0.01.

[0104] The results showed that compared with the model group, the spleen index levels of the mice in the drug-treated groups were all increased, among which the spleen index increases in the medium-dose (P<0.05) and high-dose (P<0.01) groups were significantly different, indicating that the Chinese medicine composition of the present invention has an immune-enhancing effect.

[0105] (3) Detection of T lymphocyte subsets in mouse peripheral blood

[0106] After the last administration, the eyeballs were removed and blood was collected after fasting for 12 hours, and heparin was used for anticoagulation. The plasma was centrifuged and stored at -20°C for cytokine determination. The precipitated cells were resuspended to the original volume with PBS, mixed and divided into test tubes, 50μL / tube. FITC-labeled anti-mouse CD4 and CD8 monoclonal antibodies were added, 10μL / tube, mixed thoroughly, and reacted at 4°C for 10min. 50μL of red blood cell lysing agent was added to each tube, oscillated and mixed for 10min, and 2mL of distilled water was added to each tube, oscillated and mixed for 2min, and placed in a 37°C incubator for 12min until transparent and clear, centrifuged at 2000r / min for 10min, the supernatant was discarded, 500μL of PBS was added, and analyzed by flow cytometry. The results are shown in the table below.

[0107] Effects on peripheral blood T lymphocyte subsets

[0108]

[0109]

[0110] Note: **P<0.01 compared with the blank group, **P<0.01 compared with the model group, # P<0.05, ## P<0.01.

[0111] The results showed that compared with the blank control group, the CD4 + The level of T cells (P<0.01) was significantly decreased, and CD8 + The level of T cells (P<0.01) increased significantly, indicating that the immune function of the mice in the model group was low and the model was successfully established. + Compared with the model group, the levels of T cells in the middle-dose group and the high-dose group (P<0.01) were significantly different from those in the model group. + The T cell levels were lower than those in the model group, and there were significant differences between the medium-dose group (P<0.05) and the high-dose group (P<0.01) compared with the model group, indicating that the Chinese medicine 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.

[0112] (4) Determination of mouse immune molecule content

[0113] After the last administration, fast for 12 hours. Before the mice were killed, 1 mL of blood was collected from the retroorbital venous plexus of the eyeball, and the blood was allowed to stand and centrifuged at 3000 r / min for 10 minutes to collect the serum. The spleen tissue was mixed with normal saline at a ratio of 1:9, fully ground into a homogenate, and centrifuged at 3000 r / min for 10 minutes. The levels of mouse serum immunoglobulins IgG, IgA, IgE, IgM, and spleen IL-1 and IL-2 were measured. All operations were carried out strictly in accordance with the instructions of the kit. After color development, the OD value was read at a wavelength of 450nm on an automatic microplate reader, and the corresponding index data was obtained by drawing a standard curve. The results are shown in the table below.

[0114] Effects on immune molecule content

[0115]

[0116]

[0117] Note: Compared with the blank group, *P<0.05, **P<0.01; compared with the model group,# P<0.05, ## P<0.01.

[0118] The results showed that the IgG, IgA, IgE, and IgM in the serum of the model group mice were significantly decreased compared with those in the control group (P<0.01), and the IL-1 (P<0.05) and IL-2 (P<0.01) in the spleen were significantly decreased compared with those in the control group, indicating that the model group was successfully established. Compared with the model group mice, the IgG content of the mice in the medium-dose group and the high-dose group (P<0.05) was significantly increased; the IgA serum content of the medium-dose group (P<0.05) and the high-dose group (P<0.01) was significantly increased; the IgE serum content of the high-dose group (P<0.05) was significantly increased; the IgM serum content of the medium-dose group (P<0.05) and the high-dose group (P<0.01) was significantly increased; the IL-1 content in the spleen of the high-dose group (P<0.05) was significantly increased; the IL-2 level of the medium-dose group and the high-dose group (P<0.05) was significantly increased. The above results show that the Chinese medicine composition of the present invention has the effect of enhancing the humoral immunity of immunosuppressed mice induced by cyclophosphamide.

[0119] Experimental Example 2: The present invention also observed the effect of the Chinese medicine composition in Example 3 of the present invention on subcutaneous transplanted tumors of mouse liver cancer Hepa1-6, and the specific results are as follows:

[0120] 1. Experimental materials: C57BL / 6 mice, provided by Liaoning Changsheng Biotechnology Co., Ltd., quality certificate: SCKX (Liao) 2020-0001. Mouse hepatocellular carcinoma cells Hepa1-6 were purchased from Wuhan Shanen Biotechnology Co., Ltd.

[0121] 2. Experimental Methods

[0122] Hepa1-6 cells were cultured in high-glucose DMEM medium supplemented with 10% fetal bovine serum, 1mM sodium pyruvate, and 1% penicillin and streptomycin, and stored in a 5% CO2, 37°C constant temperature incubator. The medium was replaced every 2-3 days until 80% of the cells were confluent. After the cell culture fusion reached 70-80%, the old medium was discarded, and the cells were washed twice with 2mL PBS. The cells were digested with trypsin at 37°C for 3min, and the digestion was terminated with complete medium and centrifuged. Washed twice with PBS, re-dissolved with PBS, counted, and the cells were diluted to 3×10 6 in 100 μL of phosphate-buffered saline.

[0123] C57BL / 6 mice of 6-8 weeks old were selected and raised under natural conditions for one week. They were given normal water and food to adapt to the environment. A mouse axillary tumor xenograft model was established by injection of Hepa1-6 cells. After anesthesia, the mice were placed supine on the operating table. A 3 cm × 3 cm area of ​​the right forelimb axillary of the mice was depilated with a shaver. 3 × 10 6 100 μL of Hepa1-6 cell solution was subcutaneously injected into the axilla of the right forelimb of the mouse. 12 days after inoculation, the tumor was successfully implanted when the mass was visible to the naked eye and tumor cells were found in pathological examination.

[0124] After successful modeling, mice were randomly divided into 6 groups, 10 in each group, namely blank group, model group, low-dose group of Chinese medicine composition of the present invention, medium-dose group, high-dose group, and cyclophosphamide (positive group). The nasal inhalation and sniffing method was adopted. In order to better simulate the clinical medication form, this experiment adopted a homemade fully enclosed device for administration, which included a glass mouse cage, an air circulation pump, an electric blanket, a wind speed regulating device, and a perforated drug tube. During administration, the power supply was turned on, and the air source was delivered by the air circulation pump. One end of the perforated drug tube was open and connected to the pipeline, and the other end was connected to the glass mouse cage with holes. The circulating wind blew the drug into the glass mouse cage, and the mice inhaled the drug in the form of gas autonomously. The blank control group and the model group were not administered, but air was given in the same device as a control.

[0125] The drug-administered group was designed with three dosages calculated at 1, 2, and 4 times the clinical dosage per kilogram of body weight. The low dose was 1.21 g / kg, the medium dose was 2.42 g / kg, and the high dose was 4.84 g / kg. The positive group was intraperitoneally injected with 0.02 g / kg of cyclophosphamide once a day.

[0126] During the experiment, the condition of the mice was observed every day, including hair, mental state, diet, drinking water, defecation, and movement activities, and the general condition of the mice was evaluated once a week. The mice were adapted for one week, and the tumor size was recorded with a caliper every 3 days during the experiment, and the tumor inhibition rate and tumor weight were calculated.

[0127] V (tumor volume) = major diameter × minor diameter 2 / 2

[0128] Tumor growth inhibition rate (%) = (average tumor weight of the control group - average tumor weight of the drug group) / average tumor weight of the control group × 100%

[0129] 3. Experimental Results

[0130] The experimental results of the effect of the Chinese medicine composition of the present invention on the tumor volume of Hepa1-6 tumor-bearing mice are shown in the table below. On the 12th day after the C57BL / 6 mice were inoculated with Hepa1-6 liver cancer cells in the armpit, obvious masses were visible to the naked eye and tumor cells were visible by pathological examination, indicating that on the 12th day, the Hepa1-6 tumor-bearing mice model was successfully established. On the 12th day of modeling, there was no significant difference in tumor volume between the groups (P>0.05); on the 15th and 18th days, there was a significant difference in tumor volume between the low-dose and medium-dose groups and the positive group (P<0.05), and there was a significant difference in tumor volume between the high-dose and positive groups and the model group (P<0.05, P<0.01); on the 21st, 24th, 27th, and 30th days, there was a significant difference in tumor volume between the low-dose, medium-dose, and high-dose groups and the model group and the positive group (P<0.05, P<0.01), and there was a significant difference in tumor volume between the positive group and the model group (P<0.01).

[0131] The experimental results show that the low, medium and high doses of the Chinese medicine composition of the present invention and the positive group can reduce the tumor volume of Hepa1-6 tumor-bearing mice and have an anti-tumor effect, among which the positive group has the best anti-tumor effect. As the dose of the Chinese medicine composition of the present invention increases, the effect of reducing the tumor volume of Hepa1-6 tumor-bearing mice becomes more obvious, indicating that the Chinese medicine composition of the present invention has a dose-dependent effect on the proliferation of liver cancer Hepa1-6.

[0132] Effect on tumor volume of Hepa1-6 tumor-bearing mice (x±S)

[0133]

[0134] Note: Compared with the model group, P < 0.05*, P < 0.01**; compared with the positive group (cyclophosphamide), P < 0.05 # , P<0.01 ##

[0135] The experimental results of the effect of the Chinese medicine composition of the present invention on the tumor weight and tumor inhibition rate of Hepa1-6 tumor-bearing mice are shown in the table below. After the Hepa1-6 tumor-bearing mice were dissected, the tumor was obtained and the tumor weight was weighed. There was a significant difference in tumor weight between the low, medium and high dose groups and the model group (P < 0.01), and there was a significant difference in tumor weight between the positive group and the model group (P < 0.01). The tumor inhibition rates of the low, medium, high dose and positive groups of the Chinese medicine composition of the present invention were 23.14%, 41.04%, 43.67% and 68.12%, respectively.

[0136] Table 9 Effect of the Chinese medicine composition of the present invention on tumor weight and tumor inhibition rate in Hepa1-6 tumor-bearing mice

[0137]

[0138]

[0139]

[0140] Note: Compared with the model group, P < 0.05*, P < 0.01**; compared with the positive group (cyclophosphamide), P < 0.05 # , P<0.01 ##

[0141] The experimental results show that the Chinese medicine composition of the present invention and the positive group both have inhibitory effects on the proliferation of liver cancer Hepa1-6, among which the positive group has the highest tumor inhibition rate and the most obvious tumor inhibition effect; the tumor inhibition rate of the Chinese medicine composition of the present invention on liver cancer Hepa1-6 gradually increases with the increasing dose, indicating that the Chinese medicine composition of the present invention has an anti-tumor effect and is dose-dependent in inhibiting the proliferation of liver cancer Hepa1-6.

[0142] Experimental Example 3: Effects on Mouse Breast Cancer Cell Line 4T1

[0143] 1. Cell Culture

[0144] 1.1 Cell cryopreservation

[0145] Take out the cells to be frozen from the CO2 incubator, place them in a clean bench and discard the old culture medium, add 3mL of PBS preheated to 37℃, rotate and shake to rinse twice, digest and centrifuge, discard the supernatant, add 1mL of serum-free cell freezing solution to resuspend the cells, transfer the cell suspension to a cryopreservation tube, and mark it. Store in a -80℃ refrigerator overnight, and transfer to liquid nitrogen for long-term storage the next day.

[0146] 1.2 Cell recovery

[0147] First, preheat the thermostatic water bath to 37°C. Prepare a 15mL sterile centrifuge tube on the clean bench in advance and add 4mL1640 complete medium. Then take out the cells to be revived from the liquid nitrogen, quickly place them in a 37°C water bath, and shake them continuously to melt them quickly. Use a pipette to transfer the thawed cell suspension to a centrifuge tube pre-filled with 4mL of complete medium, gently blow and mix, and centrifuge at 1000rpm for 5min. Remove the supernatant, add 1mL of complete medium to resuspend the cells, inoculate them into a T-25 cell culture flask containing 5ml1640 complete medium, and culture them in a 5% CO2, 37°C constant temperature incubator. Replace the medium the next day.

[0148] 1.3 Cell passaging

[0149] When the cells grew to 80%-90%, the culture medium was discarded, 3 mL of PBS was added to rinse twice, PBS was aspirated and 1 mL of 0.25% trypsin digestion solution was added to digest for 2 min, 2 mL of 1640 complete culture medium was added to terminate the digestion, and the cells were centrifuged at 1000 rpm for 5 min; the supernatant was discarded and 2 mL of 1640 complete culture medium was added to resuspend the cells, and the cells were inoculated into a culture flask containing 5 ml of 1640 complete culture medium at a ratio of 1:2, and cultured in a 5% CO2, 37°C incubator.

[0150] 2. Preparation of test samples

[0151] Take 0.50 g of the Chinese medicine composition of Example 3 of the present invention, add 1640 basic culture medium to 10 ml, ultrasonicate for 10 min, filter, obtain 50 mg / ml drug-containing culture medium, and store at 4°C.

[0152] 3. Cytotoxicity Assay

[0153] The cytotoxicity of the Chinese medicine composition of the present invention was determined by CCK-8 method. 4T1 cells in the logarithmic growth phase were digested with 0.25% trypsin for 2 min, 1640 complete medium was added, digestion was terminated, centrifuged, re-dissolved with 1640 complete medium, counted, and the cell suspension concentration was adjusted to 1.0×10 5 / ml, 100 μL per well was inoculated in a 96-well plate and incubated for 12 h. The culture medium was aspirated and discarded. A blank group (without cells, and the culture medium did not contain drugs), a control group (with cells, and the culture medium did not contain drugs), and a drug-treated group (with cells, and the culture medium contained the Chinese medicine composition of the present invention, with concentrations of 10, 20, 40, 80, 160, 320 and 640 μg / mL, respectively) were set up, 100 μL per well, 6 replicates per group, incubated for 24 h and 48 h, respectively, 10 μL of CCK-8 solution was added to each well for reaction for 2 h, and the OD value was measured at 450 nm with an enzyme reader. The half inhibition concentration (Half Inhibition Concentration, IC50) of the drug was calculated by software GraphPad Prism8.0.2.

[0154] Tumor inhibition rate (%) = [OD (control group) - OD (drug group)] / [OD (control group) - OD (blank group)] × 100%

[0155] Cell activity (%) = [OD (drug group) - OD (blank group)] / [OD (control group) - OD (blank group)] × 100%

[0156] 4. Results

[0157] The CCK-8 method was used to detect the inhibitory effect of the Chinese medicine composition of the present invention on breast cancer cells 4T1. The experimental results showed that when the concentration of the Chinese medicine composition of the present invention was 10 μg / mL, 20 μg / mL, 40 μg / mL, 80 μg / mL, 160 μg / mL, 320 μg / mL, and 640 μg / mL, the inhibition rates of the product on breast cancer cells 4T1 were 0.21%, 3.84%, 5.91%, 14.17%, 63.28%, 86.87%, and 87.34% after 24 hours of intervention. The inhibition rates of the product on breast cancer cells 4T1 were 11.88%, 15.36%, 26.03%, 33.72%, 75.60%, 86.32%, and 99.18% after 48 hours of intervention. It can be seen that with the increase of concentration, the inhibitory effect of the Chinese medicine composition of the present invention on breast cancer cells 4T1 is enhanced.

[0158] Inhibitory effect on 4T1 cells at 24h and 48h (MEAN±SD, n=6)

[0159]

[0160] Correspondingly, the present invention also carried out the same cell inhibition experiment on colon cancer cell CT26. The experimental steps are not repeated here. The results show that the IC of the Chinese medicine composition of the present invention on colon cancer cell CT26 at 24h, 48h and 72h is 50 They were 307.5μg / mL, 64.48μg / mL and 58.23μg / mL respectively.

[0161] Clinical application effect:

[0162] The present invention has not yet carried out randomized, controlled, double-blind clinical trials in accordance with drug regulatory requirements, but has been initially applied in clinical practice, as follows:

[0163] (I) General Information

[0164] 104 patients with tumors were selected, including 76 males and 28 females; aged 9-76 years old, with a median age of 51 years old; 84 solid tumors (12 cases of intestinal cancer, 42 cases of lung tumors, 3 cases of liver cancer, 17 breast tumors, and 10 lymphomas), and 20 cases of leukemia. All cases were diagnosed with tumors in a tertiary hospital and received conventional surgery and / or standard radiotherapy and chemotherapy. The above cases were randomly divided into two groups, a control group and a drug group. The tumor types, male-female ratios, and age distributions between the two groups were basically balanced and comparable. All cases were administered the Chinese medicine composition of Example 3 of the present invention by nasal spray, and the duration was more than one course of treatment (i.e., 3 months), and the treatment was observed for another 3 months. The 104 cases are listed by stage of disease course as follows:

[0165] The distribution of tumor course in this group of 104 patients

[0166]

[0167] (II) Treatment methods

[0168] All cases received conventional tumor surgery and / or radiotherapy, chemotherapy treatment, the drug administration group used the Chinese medicine composition prepared in Example 3 of the present application, put it into the sprayer, inhaled through the nasal cavity, exhaled from the mouth, inhaled 8g of the medicine, and sweat steamed once every two days. The control group was administered with the smelling ointment in the prior art CN116531481A, with the same dosage and usage.

[0169] (III) Treatment outcomes

[0170] Criteria for judging efficacy:

[0171] Cure: Cancer cells disappear, tumor marker results decrease by more than 80%, immunity reaches normal level, no pain and other symptoms, and no recurrence during follow-up observation for more than 3 months;

[0172] Significantly effective: 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 slight pain;

[0173] Improvement: Cancer cells decreased by more than 20%, tumor marker results decreased by more than 20%, immunity was more than 30% of the normal level, and the pain of the lesions was alleviated;

[0174] Ineffective: Cancer cells decreased by less than 20% or did not decrease, tumor marker results decreased by less than 20% or did not decrease, immunity was less than 30% of the normal level, and there was no change in the pain of the lesions.

[0175] According to the above-mentioned efficacy judgment standard, the efficacy analysis of the drug of the present invention is shown in the following table.

[0176] The present invention is used for analysis of the therapeutic effect of tumor treatment or adjuvant therapy

[0177]

[0178] From the above results, it can be seen that the Chinese medicine composition for nasal administration for tumor treatment or adjuvant treatment provided by the present invention can significantly provide the cure rate, marked efficacy and effective rate for treating tumors on the basis of conventional tumors. And there was no recurrence after observing for another 3 months after medication. From the above experimental research results, it can be seen that the Chinese medicine composition for nasal administration for tumor treatment or adjuvant treatment provided by the present invention has a significant technical effect of improving the therapeutic effect of tumors.

[0179] Example 4: Multiple-dose toxicity test

[0180] 1. Test methods

[0181] The maximum dosage (108.0 g / kg) of the toxicity test of the Chinese medicine composition of Example 3 of the present invention was designed by using the clinical daily dose of 0.133 g / kg and the KM mice for a single inhalation. Three dosages were designed according to the kilogram body weight dose conversion, which were 0.336, 1.008, and 3.024 g / rat / d (about 2, 6, and 18 times the clinical daily dose of 0.133 g / kg for humans) and a control group. Each group of 40 SD rats, 20 males and 20 females, was administered once a day by inhalation, 7 days a week, for 13 consecutive weeks, and a recovery period of two weeks. During the test, the appearance signs, behavioral activities, body weight, food intake and other indicators of the rats were tested, and hematology, blood biochemistry, organ weight and histopathology were tested after three months of administration and the end of the recovery period.

[0182] 2. Test results

[0183] ① During the 13-week inhalation experiment of the Chinese medicine composition of Example 3 of the present invention, the rats in each dosage group had normal activities, lively behaviors, smooth fur, and no abnormal changes were observed in all physical signs compared with the control group.

[0184] ②Compared with the control group during the same period, no abnormal changes of toxicological significance were found in the food intake of animals in each drug-treated group.

[0185] ③There was no abnormal change in the body weight of animals in each medication group compared with that in the control group.

[0186] ④Compared with the control group during the same period, no abnormal changes of toxicological significance were found in hematological and blood biochemical indicators.

[0187] ⑤ No dose-related pathological changes were observed in the tissues and organs of the animals in each group. After the end of the administration and the recovery period, the weight of the liver and kidney in the high-dose group increased compared with the control group during the same period, and the difference was significant. There were no abnormal changes in the weight and organ coefficients of all organs in other groups with toxicological significance.

[0188] ⑥Except for the pathological changes in the liver and kidney tissues of some animals in the high-dose group, other tissues did not show dose-dependent pathological changes.

[0189] ⑦ No delayed toxic reactions were observed in the recovery period indicators, and no delayed pathological changes related to the drugs were observed.

[0190] 3. Experimental conclusion

[0191] Under this experimental condition, the Chinese medicine composition of Example 3 of the present invention was administered to SD rats through the respiratory tract for 13 weeks. No clear toxic target organs were found at the doses of 0.336 and 1.008 g / rat / d (about 2 and 6 times the daily dose to be used in human clinics), and the toxic target organs were found to be liver and kidney at the dose of 3.024 g / rat / d (about 18 times the daily dose to be used in human clinics). Therefore, it is safe at the clinical dose, and when used at high doses, attention should be paid to the monitoring of liver and kidney function.

[0192] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A Chinese medicine composition for nasal administration for tumor treatment or adjuvant therapy, characterized in that: The invention is prepared from the following raw materials in parts by weight: 1 gram per part, 5-10 parts of mulberry yellow, 4-9 parts of ganoderma lucidum, 5-10 parts of panax notoginseng, 3-8 parts of aconite, 4-9 parts of glossy privet, 1-5 parts of cordyceps, 8-14 parts of peach kernel, 2-5 parts of green onion, 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, 0.2-0.5 parts of arsenic, 1-5 parts of calomel and 2-4 parts of ginger.

2. The Chinese medicine composition for nasal administration 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 stewed peach kernel; and / or the bitter almond is stewed bitter almond; and / or the gypsum is raw gypsum; and / or the croton is raw croton.

3. The Chinese medicine composition for nasal administration according to claim 1, characterized in that: The invention also contains the following raw materials in parts by weight: each part is 1 gram, and 90-105 parts of water.

4. The Chinese medicine composition for nasal administration according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 1 gram per part, 6-9 parts of mulberry yellow, 5-8 parts of ganoderma lucidum, 6-9 parts of panax notoginseng, 4-7 parts of aconite, 5-8 parts of glossy privet, 2-4 parts of cordyceps, 9-13 parts of peach kernel, 3-5 parts of green onion, 7-12 parts of bitter almond, 10-13 parts of jujube, 4-6 parts of pepper, 52-58 parts of gypsum, 4-7 parts of croton, 0.3-0.4 parts of arsenic, 2-4 parts of calomel and 2-4 parts of ginger.

5. The Chinese medicine composition for nasal administration according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: each part is 1 gram, 8 parts of mulberry igneous plant, 7 parts of ganoderma lucidum, 8 parts of panax notoginseng, 6 parts of aconite root, 7 parts of glossy privet fruit, 3 parts of cordyceps sinensis, 11 parts of peach kernel, 4 parts of green onion, 10 parts of bitter almond, 12 parts of jujube, 5 parts of pepper, 55 parts of gypsum, 5 parts of croton, 0.3 parts of arsenic, 3 parts of calomel and 3 parts of ginger.

6. The method for preparing the Chinese medicine composition for nasal administration according to claims 1-5, characterized in that: The specific steps include: S1. Weigh the raw materials in the formula: mulberry linterus, green onion, bitter almond, jujube, pepper, gypsum, croton, ginger, fully grind into coarse powder, add water and calcine to obtain suspension A material; S2. Weigh the remaining raw materials: Ganoderma lucidum, Panax notoginseng, Tripterygium wilfordii, Fructus Ligustri Lucidi, Cordyceps sinensis, Prunus persica, arsenic, and calomel, fully grind them into coarse powder, calcine them until they are brown and fragrant, and then disperse them to obtain powdered material B; S3. Mix the suspension material A and the powdered material B, stir until they become a paste, and then fill.

7. The method for preparing the Chinese medicine composition for nasal administration according to claim 6, characterized in that: The specific sterilization treatment of the paste in step S3 is: after the pre-treatment of the medicinal materials, ultraviolet irradiation is performed for 30 minutes, and the production is carried out in a sterile workshop.

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