CN117679477A - Traditional Chinese medicine composition for treating qi and yin deficiency syndrome after malignant tumor radiotherapy - Google Patents
Traditional Chinese medicine composition for treating qi and yin deficiency syndrome after malignant tumor radiotherapy Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine composition for treating qi and yin deficiency after malignant tumor radiotherapy, which is prepared from the following raw materials in parts by weight: 10-30 parts of raw astragalus, 1-10 parts of raw bighead atractylodes rhizome, 1-20 parts of raw rehmannia root, 10-30 parts of raw coix seed, 1-5 parts of peppermint and 1-3 parts of watermelon frost. The formula of the traditional Chinese medicine composition contains raw astragalus, raw rehmannia, raw bighead atractylodes rhizome and raw coix seed, so the name is 'four-raw soup'. The 'Sisheng decoction' has the effects of supplementing qi and nourishing yin, and is used for the adjuvant treatment of qi and yin deficiency after tumor radiotherapy, and the curative effect is clear.
Description
Technical Field
The invention relates to a traditional Chinese medicine composition for adjuvant therapy of qi and yin deficiency after tumor radiotherapy.
Background
At present, malignant tumor is one of the diseases with the highest harm to human health and mortality. Radiotherapy is an important means for treating tumors in modern medicine, and has a series of toxic and side effects on organisms while killing tumor cells, and the symptoms are peripheral leucopenia, bone marrow depression, debilitation, sweating, canker sore, inappetence, nausea, vomiting and the like. The occurrence of the toxic and side effects of the radiotherapy reduces the treatment effect of the radiotherapy on one hand, and a large number of patients cannot tolerate the radiotherapy on the other hand, so that the treatment course of the radiotherapy cannot be successfully completed, which is unfavorable for the treatment of tumors. The toxic and side effects of the radiotherapy are that the western medicine mostly adopts leucocyte medicines and supplements nutrition agents, but the effect is often limited, and the problem can not be well solved.
Because of the gradual consumption of qi and blood of malignant tumor patients, the deficiency of yin fluid, especially of late stage tumor patients, is quite prominent in contradiction between the positive and the negative. According to the etiology analysis of traditional Chinese medicine, X-rays and gamma-rays used for tumor radiotherapy can be classified as heat evil, heat toxin, fire evil and the like, and the pathogenesis of toxic and side effects of the tumor radiotherapy is that the heat toxin invades a human body, yin (blood) is injured, qi is consumed, yin is injured, qi-yin deficiency is the most common condition after radiotherapy and chemotherapy of a tumor patient, so qi-tonifying and yin-nourishing are fundamental principles of enhancing organism immunity and relieving toxic and side effects of radiotherapy and chemotherapy of malignant tumors. In view of huge cardinality of patients with tumor radiotherapy, the formula of the traditional Chinese medicine compatibility with the principles of tonifying qi and nourishing yin is adopted to improve the deficiency of both qi and yin after tumor radiotherapy, so that the traditional Chinese medicine compatibility can meet clinical needs and has wide prospect.
At present, the Chinese patent medicine for improving the toxic and side effects of the tumor radiotherapy and defining the indications is very at least, and needs to be solved urgently.
Disclosure of Invention
Aiming at the requirements of prevention and treatment of toxic and side effects of tumor radiotherapy, according to the embodiment of the invention, a traditional Chinese medicine composition for treating qi-yin deficiency after malignant tumor radiotherapy is expected to be provided.
The inventor engages in the anti-tumor research of traditional Chinese medicines for a long time, combines the theoretical analysis of traditional Chinese medicine and the long-term clinical practice, and proposes a traditional Chinese medicine composition for treating qi-yin deficiency syndrome after malignant tumor radiotherapy, which is prepared from the following raw materials in parts by weight: 10-30 parts of raw astragalus, 1-10 parts of raw bighead atractylodes rhizome, 1-20 parts of raw rehmannia root, 10-30 parts of raw coix seed, 1-5 parts of peppermint and 1-3 parts of watermelon frost. Preferably: 10-20 parts of raw astragalus, 1-6 parts of raw bighead atractylodes rhizome, 1-10 parts of raw rehmannia root, 10-20 parts of raw coix seed, 1-3 parts of peppermint and 1-2 parts of watermelon frost. And preferably: 15-20 parts of raw astragalus, 3-6 parts of raw bighead atractylodes rhizome, 5-10 parts of raw rehmannia root, 15-20 parts of raw coix seed, 1-2 parts of peppermint and 1-2 parts of watermelon frost. Most preferably: 20 parts of raw astragalus, 6 parts of raw bighead atractylodes rhizome, 10 parts of raw rehmannia root, 20 parts of raw coix seed, 2 parts of peppermint and 1.3 parts of watermelon frost. The present group Fang Fangyi was analyzed as follows:
astragalus root has sweet taste and slight warmth, and can nourish qi and raise yang, benefit defensive qi and strengthen superficies, promote tissue regeneration, promote diuresis and remove edema. "the lung is the most effective in invigorating qi, and the exterior is known as qi-tonifying herbs. The raw materials have the effects of clearing heat and promoting the production of body fluid, and the preparation of materia medica: the recipe is effective in strengthening exterior, inducing diaphoresis, stopping sweating, warming and separating skin and muscle, strengthening skin and muscle space, purging yin fire, and relieving muscle heat … … ". Sheng Di Huang is sweet and bitter in nature, cool and clear heat, promote the production of body fluid, nourish yin and nourish blood. Can be used for treating fever due to yin deficiency, diabetes, hematemesis, epistaxis, metrorrhagia, menoxenia, fetal movement, constipation due to yin injury, etc. Raw astragalus root, radix astragali, with the recipe of dried rehamnnia root, radix rehmanniae, is a monarch drug in the recipe. The bighead atractylodes rhizome is bitter and sweet in taste and warm in nature, enters spleen and stomach meridians, supplements qi to invigorate spleen, eliminates dampness to promote diuresis, and is matched with astragalus to invigorate qi of spleen and stomach, so that the acquired essence of the spleen and stomach is nourished, and qi and blood are biochemically active. Materia medica true: bai Zhu is bitter and sweet in flavor, and can dry dampness and invigorate spleen, and can slow spleen and promote fluid production. It is the first herb to tonify qi of spleen, with the actions of strengthening food and removing food retention. The coix seed is cool in nature, sweet in taste, light in weight, capable of strengthening spleen, excreting dampness, removing arthralgia and relieving diarrhea, capable of being used for treating edema, beriberi, dysuria and the like, has a direct anti-tumor effect in modern researches, and the bighead atractylodes rhizome and coix seed can strengthen spleen, replenish qi, enable qi and blood to be biochemically active, and are ministerial drugs in the recipe. The mint is used for dispelling wind-heat, clearing lung and soothing liver, clearing heat and purging fire, and relieving swelling and pain, is used for treating tonsillitis and pharyngitis caused by lung and stomach fire and steaming upwards, and has the symptoms of red and swollen throat, aphtha of mouth and tongue, swelling of gum and the like, and is matched with watermelon frost for clearing heat and detoxicating, and relieving swelling and pain, and is used for assisting in the recipe. The whole formula has the effects of tonifying qi and yin, and protecting the spleen and stomach, so as to resist the toxic and side effects of radiotherapy.
The formula of the traditional Chinese medicine composition contains raw astragalus, raw rehmannia, raw bighead atractylodes rhizome and raw coix seed, so the name is 'four-raw soup'. The preparation of the traditional Chinese medicine composition is free from special parts, is supplemented with common pharmaceutical excipients, and can be prepared into common dosage forms such as oral liquid (hereinafter also called four-raw soup or four-raw soup oral liquid), granules, tablets and the like in the pharmacy by adopting a conventional preparation method in the field.
The traditional Chinese medicine composition 'Sisheng decoction' has the advantages of low cost of raw materials, simple and convenient preparation, convenient application, good clinical application effect, high patient acceptance, no toxic or side effect, long-term administration, and wide market prospect in view of a plurality of patients receiving radiotherapy tumors. The subsequent test examples will demonstrate that the four-generation soup contains factors that promote proliferation and differentiation of bone marrow hematopoietic stem cells.
Detailed Description
The invention will be further illustrated with reference to specific examples. These examples should be construed as merely illustrative of the present invention and not limiting the scope of the present invention. Various changes and modifications to the present invention may be made by one skilled in the art after reading the description herein, and such equivalent changes and modifications are intended to fall within the scope of the present invention as defined in the appended claims.
Example 1
Prescription: 200g of raw astragalus, 60g of raw bighead atractylodes rhizome, 100g of raw rehmannia root, 200g of raw coix seed, 20g of peppermint and 13g of watermelon frost.
The preparation method comprises the following steps: decocting radix astragali, rhizoma Atractylodis Macrocephalae, radix rehmanniae, semen Coicis, and herba Menthae with water for 3 times, 10 times, 8 times, 2h, 1.5h, and 1h, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to relative density of 1.20-1.30 (50-60deg.C), adding ethanol to total ethanol content of 60-70%, stirring, standing for 24h, filtering, recovering ethanol from the filtrate until no ethanol smell, diluting with water, stirring, refrigerating for 24h, filtering, adding watermelon frost and appropriate amount of protein sugar to dissolve uniformly, adding water to 1000ml, filtering, packaging, and sterilizing with steam at 100deg.C for 30 min.
Example 2
Prescription: 600g of raw astragalus, 50g of raw bighead atractylodes rhizome, 200g of raw rehmannia, 50g of raw coix seed, 50g of peppermint and 30g of watermelon frost.
The preparation method comprises the following steps: decocting radix astragali, rhizoma Atractylodis Macrocephalae, radix rehmanniae, semen Coicis, and herba Menthae with water for 3 times, 10 times, 8 times, 2h, 1.5h, and 1h, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to relative density of 1.20-1.30 (50-60deg.C), adding ethanol to total ethanol content of 60-70%, stirring, standing for 24h, filtering, recovering ethanol from the filtrate until no ethanol smell, diluting with water, stirring, refrigerating for 24h, filtering, adding watermelon frost and appropriate amount of protein sugar to dissolve uniformly, adding water to 1000ml, filtering, packaging, and sterilizing with steam at 100deg.C for 30 min.
Example 3
Prescription: 50g of raw astragalus, 200g of raw bighead atractylodes rhizome, 60g of raw rehmannia root, 100g of raw coix seed, 10g of peppermint and 20g of watermelon frost.
The preparation method comprises the following steps: decocting radix astragali, rhizoma Atractylodis Macrocephalae, radix rehmanniae, semen Coicis, and herba Menthae with water for 3 times, 10 times, 8 times, 2h, 1.5h, and 1h, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to relative density of 1.20-1.30 (50-60deg.C), adding ethanol to total ethanol content of 60-70%, stirring, standing for 24h, filtering, recovering ethanol from the filtrate until no ethanol smell, diluting with water, stirring, refrigerating for 24h, filtering, adding watermelon frost and appropriate amount of protein sugar to dissolve uniformly, adding water to 1000ml, filtering, packaging, and sterilizing with steam at 100deg.C for 30 min.
Example 4
Prescription: 50g of raw astragalus, 50g of raw bighead atractylodes rhizome, 60g of raw rehmannia root, 300g of raw coix seed, 60g of peppermint and 5g of watermelon frost.
The preparation method comprises the following steps: decocting radix astragali, rhizoma Atractylodis Macrocephalae, radix rehmanniae, semen Coicis, and herba Menthae with water for 3 times, 10 times, 8 times, 2h, 1.5h, and 1h, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to relative density of 1.20-1.30 (50-60deg.C), adding ethanol to total ethanol content of 60-70%, stirring, standing for 24h, filtering, recovering ethanol from the filtrate until no ethanol smell, diluting with water, stirring, refrigerating for 24h, filtering, adding watermelon frost and appropriate amount of protein sugar to dissolve uniformly, adding water to 1000ml, filtering, packaging, and sterilizing with steam at 100deg.C for 30 min.
Pharmacological test experimental study of the bone marrow suppression effect of the anti-radiotherapy of the traditional Chinese medicine composition
1. Materials and pharmaceutical products
1.1. Kunming mice, 18-20 g, male and female halves, supplied by Shanghai university of medical science animal center, eligibility number: medical word 02-22-1.
1.2. Prepared as in example 1, 3g/ml crude drug was used for filtration and sterilization before cell culture, and the culture broth was adjusted to the original volume with 1640 and pH was adjusted to 7.4. Blood nourishing drink is produced by Jilin Changbai mountain pharmaceutical factories.
RPMI-1640 medium: the powder type product of Tokyo pharmaceutical Co., ltd., japan was prepared with ultrapure water. Adding penicillin and streptomycin 10 ten thousand each u /L、Heps 2.38g/L、NaHCO 3 2g/L, L-Glu 0.3g/L, etc., and positive pressure filtration sterilization.
1.4. Granulocyte stimulating factor Hui Er blood (G-CSF): is a product of kylin corporation of Japan (KIRIN), a liquid agent, 75. Mu.g/piece, and is prepared to a desired concentration under aseptic conditions before use.
1.5. Fetal Calf Serum (FCS): is manufactured by GIBCO corporation of America.
1.6. Bone marrow source: the rib resected by the operation patient without blood system diseases is provided by Shanghai Zhongshan hospital.
2. Experimental method
2.1. Establishing an acute radiation injury model: mice (mouse) 137 The Cs-gamma rays are irradiated in a whole body for one time, the irradiation doses are respectively 2Gy, 4Gy and 7.5Gy, and the dose rate is 1.12Gy/min.
2.2. The treatment method comprises the following steps: the treatment group starts to feed the four-raw-soup oral liquid for the first time after 4 hours after illumination, and the dosage is 0.3 ml/time and 2 times/day. Wherein mice receiving 2Gy, 4Gy irradiation are treated for 14 days, and 7.5Gy irradiation are treated for 7 days; the mice in the negative control group and the positive control group respectively begin to be irrigated with double distilled water and blood nourishing drinks with the same volume as the four-raw-soup oral liquid after 4 hours of irradiation.
2.3. Bone marrow nucleated cell count: mice receiving 7.5Gy were sacrificed by cervical scission 10 days after irradiation, one of the hind limb femur of each mouse was aseptically removed, their bone marrow was flushed with 2ml of 1640 culture medium, and a single cell suspension of bone marrow was prepared with a 4-gauge needle for nucleated cell counting.
G-CFU assay: mice receiving 2Gy and 4Gy were sacrificed at 21 days after irradiation, hind limb femur bone marrow was prepared into single cell suspension, and after bone marrow nucleated cell counting, a culture system was prepared according to the composition ratio described in literature (Tang Peixian. Hematopoietic cell culture technique, western: shanxi science and technology Press, 1985:93-107), and after thoroughly mixing, 1 ml/dish was poured into a 33mm diameter dish, and 6 dishes were repeated. Pouring the dish, standing at room temperature for a while, and then adding 5% CO 2 Culturing in an incubator at 37 ℃ and saturated humidity for 7 days, counting the yield of G-CFU per dish under a light microscope, and respectively carrying out in-situ photography and photography after staining fixation. Counting criteria: a cell mass consisting of 50 or more cells is counted as a colony.
2.5. Counts of endogenous spleen nodules: mice receiving 7.5Gy were sacrificed by cervical scission 10 days after irradiation, spleens were removed, fixed in picric acid saturated solution (Bouin's fixative) for 6h, and then off-white round nodules were removed to visually count the convex surfaces of the spleens. The special person count was fixed for each experiment.
2.6. Preparation of human bone marrow cell suspension: extruding bone marrow liquid from the surgically resected rib with a sterile rongeur, diluting with 1640 culture solution, fully mixing, centrifuging (500 g,10 min), removing upper fat and liquid, adding a proper amount of culture solution, fully mixing, slowly dripping into a test tube containing an equivalent lymphocyte separating liquid (specific gravity 1.077), centrifuging (500 g,20 min) for layering, taking out a middle nucleated cell layer, washing for two times, diluting with a proper amount of culture solution, and preparing single cell suspension through a No. 4 needle head for standby.
3. Experimental results
Specific results are shown in tables 1-4, and the numerical values are expressed by X+ -s.
In the test example, the change of the number of the bone marrow nucleated cells is observed first, and the four-generation decoction is found to obviously increase the number of the bone marrow nucleated cells of the irradiated mice, the increasing amplitude of the four-generation decoction exceeds that of a positive control medicine 'blood nourishing drink' (Table 1), which is completely consistent with the influence of the four-generation decoction on the peripheral blood white cell count, so that the four-generation decoction has the effects of protecting the bone marrow nucleated cells and relieving the radiation injury degree.
The experimental results in table 2 show that the four-generation decoction has good protection effect on bone marrow hematopoietic progenitor cells of the mice under control, and the curative effect is better than that of blood nourishing decoction, which indicates that the mice treated by the four-generation decoction also contain a considerable amount of homotypic cell colonies (namely, the granulocyte hematopoietic progenitor cells with clonality) which can be re-planted and parasitized in vitro in bone marrow after being irradiated. The soup is presumed to have an effect of protecting hematopoietic stem cells or stimulating differentiation of hematopoietic stem cells into hematopoietic progenitor cells.
After total body exposure to sublethal doses of 7-7.5 Gy, partially surviving CFU-S in bone marrow migrate to the spleen to form nodules (CFU-S), which are self-contained and therefore referred to as endogenous CFU-S. As shown in Table 3, the present test shows that the number of CFU-S on day 10 of the four-born decoction treatment is significantly higher than that of the negative and positive control groups after the mice are irradiated with 7.5Gy, which means that the four-born decoction can increase the transfer of endogenous multipotent hematopoietic stem cells to the spleen. It is believed that 7.5Gy irradiated mice, while killing some hematopoietic stem cells, the remaining or damaged hematopoietic stem cells may retain and restore their ability to self-replicate due to the effects of tetragenic soup.
The results of in vitro experiments using human bone marrow cells also showed that the four-raw soup at a concentration of 0.1 ml/dish had a significant effect in promoting the formation of G-CFU (Table 4).
In summary, this experiment reveals the mechanism of action of the four-way decoction to reduce the radiation response: the decoction contains factors for promoting proliferation and differentiation of bone marrow hematopoietic stem cells.
TABLE 1 influence of Tetrakistrodon decoction oral liquid on bone marrow nucleated cell content 10 days after 7.5Gy irradiation (x 10) 3 One femur)
Note that: p < 0.05 p < 0.01 compared to negative control group compared to positive control group Δ p＜0.05
TABLE 2 influence of four-raw decoction oral liquid on the colony formation of bone marrow-derived hematopoietic progenitor cells (colony/dish) 21 days after irradiation of mice
Note that: p < 0.05 p < 0.01 compared to negative control group compared to positive control group Δ p＜0.05
TABLE 3 Effect of IV soup oral liquid on the number of 10 days (CFU-S) after 7.5Gy irradiated mice (colony/spleen)
Note that: p < 0.05 p < 0.01 compared to negative control group compared to positive control group Δ p＜0.05
TABLE 4 influence of decoction oral liquid on human bone marrow G-CFU yield (colony/dish)
Note that: p < 0.05 p < 0.01 compared to negative control group compared to positive control group Δ p＜0.05。
Claims (6)
1. The traditional Chinese medicine composition for treating the qi-yin deficiency syndrome after malignant tumor radiotherapy is characterized by being prepared from the following raw materials in parts by weight: 10-30 parts of raw astragalus, 1-10 parts of raw bighead atractylodes rhizome, 1-20 parts of raw rehmannia root, 10-30 parts of raw coix seed, 1-5 parts of peppermint and 1-3 parts of watermelon frost.
2. The traditional Chinese medicine composition for treating qi and yin deficiency syndrome after malignant tumor radiotherapy according to claim 1, wherein the raw material medicines and the weight parts thereof are as follows: 10-20 parts of raw astragalus, 1-6 parts of raw bighead atractylodes rhizome, 1-10 parts of raw rehmannia root, 10-20 parts of raw coix seed, 1-3 parts of peppermint and 1-2 parts of watermelon frost.
3. The traditional Chinese medicine composition for treating qi and yin deficiency syndrome after malignant tumor radiotherapy according to claim 1, wherein the raw material medicines and the weight parts thereof are as follows: 15-20 parts of raw astragalus, 3-6 parts of raw bighead atractylodes rhizome, 5-10 parts of raw rehmannia root, 15-20 parts of raw coix seed, 1-2 parts of peppermint and 1-2 parts of watermelon frost.
4. The traditional Chinese medicine composition for treating qi and yin deficiency syndrome after malignant tumor radiotherapy according to claim 1, wherein the raw material medicines and the weight parts thereof are as follows: 20 parts of raw astragalus, 6 parts of raw bighead atractylodes rhizome, 10 parts of raw rehmannia root, 20 parts of raw coix seed, 2 parts of peppermint and 1.3 parts of watermelon frost.
5. The Chinese medicinal composition for treating deficiency of both qi and yin after radiotherapy of malignant tumor according to any one of claims 1 to 4, wherein the Chinese medicinal composition is an oral liquid.
6. The Chinese medicinal composition for treating deficiency of both qi and yin after radiotherapy of malignant tumor according to any one of claims 1 to 4, wherein the Chinese medicinal composition is a tablet.
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