CN109663116B

CN109663116B - Traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy, traditional Chinese medicine decoction-free granules and application

Info

Publication number: CN109663116B
Application number: CN201910092998.5A
Authority: CN
Inventors: 刘华为; 马战平; 李猛; 王志梅; 黄刚; 山萌
Original assignee: Shaanxi Traditional Chinese Medicine Hospital
Current assignee: Shaanxi Traditional Chinese Medicine Hospital
Priority date: 2019-01-30
Filing date: 2019-01-30
Publication date: 2021-06-25
Anticipated expiration: 2039-01-30
Also published as: CN109663116A

Abstract

The invention relates to a traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy, traditional Chinese medicine decoction-free granules and application, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw material medicines: 6-15 parts of ginger processed pinellia, 10-15 parts of dried ginger, 6-15 parts of exocarpium citri grandis, 10-15 parts of white poria, 3-12 parts of fructus aurantii immaturus in rice water, 10-15 parts of pogostemon cablin, 2-4 parts of ginger-processed coptis, 3-5 parts of wine-processed radix scutellariae, 15-30 parts of reed rhizome, 5-12 parts of bamboo shavings, 5-9 parts of perilla leaf, 9-15 parts of radix codonopsis pilosulae and 2-6 parts of raw licorice. The traditional Chinese medicine decoction-free granules consist of single traditional Chinese medicine formula granules in parts by weight. Application of traditional Chinese medicine composition and traditional Chinese medicine decoction-free granules in preparation of medicines for treating nausea and vomiting caused by chemotherapy. The invention has the functions of replenishing qi to invigorate the spleen, harmonizing the stomach and lowering adverse qi, and relieving distension and fullness; regulating immunity, and inhibiting tumor growth; the composition is used together with chemotherapeutic drugs to achieve synergistic sensitization and relieve vomiting symptoms; regulating digestive tract function.

Description

Traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy, traditional Chinese medicine decoction-free granules and application

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy, traditional Chinese medicine decoction-free granules and application.

Background

Worldwide, malignancy is second only to heart disease as the second leading cause of death. Chemotherapy is one of the core modes of malignant tumor treatment, and nausea and vomiting (CINV) caused by Chemotherapy are common adverse reactions, which seriously affect the life quality and the overall treatment of patients.

Current research status of CINV:

1. and (4) classification: the disease is divided into 5 types of acute, delayed, prospective, explosive and refractory.

Acute nausea and vomiting: typically occurs from minutes to hours of administration and peaks at 5-6 hours post-administration, but remits within as much as 24 hours.

Delayed nausea and vomiting: it occurs much after 24 hours of chemotherapy, and usually lasts for several days when chemotherapy is applied to cisplatin, carboplatin, cyclophosphamide and adriamycin.

③ anticipatory nausea and vomiting: refers to nausea and vomiting that occur in a patient after experiencing uncontrolled CINV at the time of a previous chemotherapy, before the start of the next chemotherapy, is a conditioned reflex, mainly due to psychological, etc. factors.

Fourthly, explosive vomiting: means that emesis occurs even if prophylactic treatment is performed, and "rescue treatment" is required.

Refractory vomiting: refers to the failure of the previous chemotherapy cycle to use prophylactic and/or rescue antiemetic therapy, while vomiting still occurs in the subsequent chemotherapy cycle.

2. Emetic grading of antitumor drugs: generally, anti-tumor drugs can be classified into 4 emetic risk grades, such as high emetic risk (HEC, such as cisplatin and cyclophosphamide), medium emetic risk (MEC, such as oxaliplatin and irinotecan), low emetic risk (such as gemcitabine and taxoids), and slight emetic risk, and the occurrence rates of emesis if not treated for prevention are respectively more than 90%, 30% -90%, 10% -30% and less than 10%.

3. High incidence of CINV and great influence: comprehensive literature reports that the incidence of CINV is 70-80%, wherein the incidence of the expected nausea and vomiting accounts for 10-44%. Mild to moderate vomiting often results in a rather irritable mood of the patient, moderate to severe vomiting may affect the daily diet and nutrition of the patient, even cause electrolyte disorders, and even be forced to discontinue chemotherapy, affecting the quality of life and overall treatment of the patient.

4. Western medicines are expensive and have great side effects: western medicines such as 5-HT₃Although the receptor antagonist and the NK-1 receptor antagonist have outstanding curative effects, the receptor antagonist and the NK-1 receptor antagonist have the problems of high price, large side effect, unclear long-term adverse reaction and the like. In addition, although the existing antiemetic drugs applied to clinic are more in variety, the antiemetic drugs with high efficiency and multiple target points are less.

The chemotherapy drug can kill tumor cells, and can be used as a toxic substance to damage normal tissue cells of the body, so that the body tissues and organs are damaged and affected to different degrees, thereby generating great side effects, particularly easily causing gastrointestinal tract dysfunction, seriously affecting the life quality of patients and reducing the chemotherapy compliance. Therefore, a drug is urgently needed to relieve or treat nausea and vomiting caused by tumor chemotherapy drugs, and guarantee smooth tumor treatment is provided.

Disclosure of Invention

Nausea and Vomiting (CINV) caused by chemotherapy belongs to the field of vomiting in the traditional Chinese medicine, and belongs to the patients with dysfunction of ascending and descending of the spleen and stomach and incoordination between the gallbladder and the stomach. The symptoms include nausea, emesis, singultus, abdominal discomfort, chest distress, palpitation, dysphoria, and constipation (constipation or unformed). A white or yellow and greasy tongue coating and a wiry, slippery or wiry and slow pulse.

Vomiting, disorder of qi movement of middle energizer and dysfunction of qi movement of gallbladder and stomach are the basic pathogenesis. The chemotherapy medicament is a drug poison and has the characteristics of disturbing qi and blood of a human body and influencing the normal operation of viscera functions; chemotherapy medicine damages spleen and stomach, causes dysfunction of spleen and stomach transportation and transformation, abnormal ascending and descending, endogenous turbid phlegm, nausea and vomiting due to stomach qi descending, and hiccup due to adverse rising of stomach qi and diaphragm movement; incoordination between the spleen and stomach can lead to the rise of gallbladder qi, gallbladder dysfunction, qi stagnation, phlegm generation, turbid phlegm internal disturbance, disturbance of heart spirit, chest distress, palpitation, and dysphoria; incoordination between the gallbladder and stomach, gastric and abdominal discomfort; impaired function of the spleen and stomach may lead to weakness of the spleen and stomach, resulting in constipation, wiry and smooth pulse, and other symptoms.

The invention aims to disclose a traditional Chinese medicine composition for treating CINV according to the traditional Chinese medicine and western medicine symptoms of the CINV.

The invention aims to disclose a traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy.

The second purpose of the invention is to disclose the application of the traditional Chinese medicine composition.

The third purpose of the invention is to disclose a traditional Chinese medicine decoction-free granule for treating nausea and vomiting caused by chemotherapy.

The fourth purpose of the invention is to disclose the application of the Chinese medicinal decoction-free granules.

The purpose of the invention is realized by the following technical scheme:

a traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy is prepared from the following raw material medicines in parts by weight: 6-15 parts of ginger processed pinellia, 10-15 parts of dried ginger, 6-15 parts of exocarpium citri grandis, 10-15 parts of white poria, 3-12 parts of fructus aurantii immaturus in rice water, 10-15 parts of pogostemon cablin, 2-4 parts of ginger-processed coptis, 3-5 parts of wine-processed radix scutellariae, 15-30 parts of reed rhizome, 5-12 parts of bamboo shavings, 5-9 parts of perilla leaf, 9-15 parts of radix codonopsis pilosulae and 2-6 parts of raw licorice.

The traditional Chinese medicine composition of the technical scheme is characterized in that the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 15 parts of ginger processed pinellia tuber, 15 parts of dried ginger, 15 parts of exocarpium citri grandis, 15 parts of white poria, 12 parts of fructus aurantii immaturus from rice washing, 15 parts of patchouli, 4 parts of ginger-processed coptis root, 5 parts of wine-processed scutellaria baicalensis, 30 parts of reed rhizome, 12 parts of bamboo shavings, 9 parts of perilla leaf, 15 parts of radix codonopsis pilosulae and 6 parts of raw liquorice.

The application of the traditional Chinese medicine composition in the technical scheme in preparing the medicine for treating nausea and vomiting caused by chemotherapy.

The traditional Chinese medicine decoction-free granules for treating nausea and vomiting caused by chemotherapy comprise the following single traditional Chinese medicine formula granules in parts by weight: 6-15 parts of ginger processed pinellia, 10-15 parts of dried ginger, 6-15 parts of exocarpium citri grandis, 10-15 parts of white poria, 3-12 parts of fructus aurantii immaturus in rice water, 10-15 parts of pogostemon cablin, 2-4 parts of ginger-processed coptis, 3-5 parts of wine-processed radix scutellariae, 15-30 parts of reed rhizome, 5-12 parts of bamboo shavings, 5-9 parts of perilla leaf, 9-15 parts of radix codonopsis pilosulae and 2-6 parts of raw licorice.

The traditional Chinese medicine decoction-free granules in the technical scheme are characterized in that the traditional Chinese medicine decoction-free granules are prepared from the following single traditional Chinese medicine formula granules in parts by weight: 15 parts of ginger processed pinellia tuber, 15 parts of dried ginger, 15 parts of exocarpium citri grandis, 15 parts of white poria, 12 parts of fructus aurantii immaturus from rice washing, 15 parts of patchouli, 4 parts of ginger-processed coptis root, 5 parts of wine-processed scutellaria baicalensis, 30 parts of reed rhizome, 12 parts of bamboo shavings, 9 parts of perilla leaf, 15 parts of radix codonopsis pilosulae and 6 parts of raw liquorice.

The application of the traditional Chinese medicine decoction-free granules in the technical scheme in preparing medicines for treating nausea and vomiting caused by chemotherapy.

Aiming at the fact that 'disorder of qi activity of middle jiao and qi dysfunction of gallbladder and stomach' are basic pathogenesis of CINV, the invention adopts a treatment method of 'conditioning qi activity and promoting qi transformation', and the traditional Chinese medicine treatment mechanism of the invention is as follows:

ginger pinellia tuber and dried ginger are selected as monarch drugs, pinellia tuber is pungent, warm and toxic, and has the effects of eliminating dampness and phlegm, lowering adverse qi and preventing vomiting, relieving distension and fullness and eliminating stagnation, and ginger can restrict the toxicity; the dried ginger is pungent and hot, warms middle-jiao to dispel cold, returns yang to dredge vessels, warms lung to eliminate retention, can warm and disperse cold evil in lung to promote lung qi to descend, enables water passage to be adjusted and phlegm retention to be changed, and can warm spleen and stomach to expel dampness and turbidity to insulate the source of phlegm; the two medicines are monarch medicines together, and the medicines are used together to enhance the dissipation function of damp turbidity caused by internal depression and phlegm dampness formed by the damp turbidity so as to ventilate;

the ministerial drugs are pungent, bitter and warm in orange, dispel cold, eliminate dampness, promote qi circulation and eliminate phlegm; bitter, pungent and sour fructus Aurantii is slightly cold, and has effects in regulating qi-flowing, relieving epigastric distention, activating stagnancy, relieving flatulence, and lowering adverse qi of gallbladder and stomach, and can be soaked in rice swill to weaken its pungent and dry and intestine-smoothing effects, and enhance the effects of invigorating spleen and regulating stomach; the combination of orange peel and bitter orange can increase the ability of regulating qi and resolving phlegm. Bai Fu Ling is sweet, bland and mild, induces diuresis to alleviate edema, excretes dampness, invigorates spleen and calms heart, so it is used to eliminate phlegm. The patchouli has aromatic fragrance, is pungent and slightly warm, and can resolve dampness, stop vomiting and relieve summer-heat, and is combined with the pinellia ternate, so that the patchouli has the effects of resolving dampness with fragrance, and drying dampness with pungent warm, has the effects of regulating spleen and stomach and enhancing the capability of stopping vomiting;

the adjuvant drugs of the scutellaria baicalensis and the coptis chinensis are bitter and cold, clear heat and dry dampness, purge fire and detoxify, purge heat of long-standing depression of middle energizer and regulate qi activity of the middle energizer, the scutellaria baicalensis is processed with wine to relieve the bitter and cold property, and the coptis chinensis is processed with ginger to clear heat, harmonize stomach and stop vomiting; the scutellaria baicalensis and the coptis root are bitter and descend, the dried ginger is pungent, and the medicines are used together to play the effects of pungent flavor and bitter flavor descending, so that the spleen can ascend the clear, the stomach can descend the turbid, and the qi movement is regulated smoothly to reduce the occurrence of nausea and vomiting, so that the effects of ascending one body and descending one body are achieved, and the qi movement is regulated; one warm and one cold, coordinating yin and yang. Rhizoma phragmitis is sweet and cold, and has the effects of clearing heat and purging fire, promoting fluid production to quench thirst, relieving restlessness, stopping vomiting and promoting urination so as to improve the effects of clearing and relieving vomiting. The bamboo shavings are sweet and slightly cold, clear heat and resolve phlegm, relieve restlessness and stop vomiting; the bamboo shavings are matched with the pinellia ternate, so that the effects of reducing phlegm and harmonizing stomach, preventing vomiting and relieving restlessness are enhanced when the bamboo shavings are warm and cool. Folium Perillae is pungent and warm, has effects in dispelling cold, relieving exterior syndrome, regulating qi-flowing, and relieving epigastric distention, and can relieve chest stuffiness, promote diaphragmasis, and promote qi movement;

the guiding drugs are ginseng and liquorice, so that the spleen and stomach qi can be benefited, and the qi is sufficient to dissipate moisture; secondly, the clear qi is increased, the turbid qi is decreased when the clear qi is increased, the effects of strengthening the spleen, tonifying qi and promoting gasification are achieved, and the liquorice can harmonize the other medicines;

the formula of the invention is in keeping the pathogenesis, has precise and appropriate compatibility and concentrated drug efficacy, and the compatibility of the medicines can help the deficiency of vital qi, clear and dissipate the turbid phlegm pathogen, and regulate the functions of the spleen, the stomach and the gallbladder, thereby playing the roles of strengthening the vital qi, relieving stuffiness and lowering adverse qi together.

The single traditional Chinese medicine formula granules used in the traditional Chinese medicine decoction-free granules are pure traditional Chinese medicine product series which are prepared by taking traditional Chinese medicine decoction pieces which meet processing specifications as raw materials and carrying out extraction, concentration, separation, drying, granulation and packaging refining by modern pharmaceutical technology. The purpose of pushing the product is to be used as a substitute of the traditional Chinese medicine decoction piece for clinical formula. The product has the advantages of completely consistent effective components, taste, channel tropism, indication and efficacy with those of traditional Chinese medicine decoction pieces. Therefore, the traditional Chinese medicine decoction piece not only keeps all the characteristics of the original traditional Chinese medicine decoction pieces, namely can meet the requirements of doctors on treatment based on syndrome differentiation, can be added or subtracted according to the symptoms, has strong medicine property and high medicine effect, but also has the advantages of no need of decoction, direct taking, small dosage, rapid action, complete components, exact curative effect, safety, sanitation, convenience in carrying and storage, easiness in dispensing, suitability for industrial production and the like. The single Chinese medicinal formula granule is separated from the traditional Chinese medicinal decoction pieces, and has more superiority than the traditional Chinese medicinal decoction pieces.

The chemical components of Chinese medicine are the material basis of the pharmacological action of Chinese medicine. The traditional Chinese medicine decoction-free granules (hereinafter referred to as ludwigia octovalvis warm half granules) for treating CINV have the main effects of tonifying qi and strengthening spleen, harmonizing stomach and lowering adverse qi, and relieving distension and fullness, and are used for treating the basic pathogenesis of 'disorder of qi activity of middle jiao and qi stagnation of gallbladder and stomach' of CINV. Modern pharmacological research proves that each component of the medicine has certain functions of regulating the immunity of the organism and inhibiting the growth of tumor; the composition has synergistic effect with chemotherapeutic drugs, and has effects of relieving emesis and regulating digestive tract function. Modern pharmacological research data show that:

the qi-tonifying and spleen-invigorating effects of the traditional Chinese medicine are mainly focused on the effects of regulating the immunity of the organism and inhibiting the growth of tumors of the effective components;

the stomach harmonizing and adverse qi lowering effects are that the synergistic sensitization is realized when the composition is used together with chemotherapeutic drugs, and the vomiting symptom is relieved;

(III), the actions of relieving stuffiness and relieving fullness are related to the regulation of the function of the digestive tract.

The traditional Chinese medicine composition and the traditional Chinese medicine decoction-free granules respectively have the following effects aiming at the three points:

the qi-tonifying and spleen-invigorating effects of the traditional Chinese medicine are mainly focused on the effects that the effective components have the effects of regulating the immunity of the organism and inhibiting the growth of tumors:

the chemotherapy medicament can damage the healthy energy of the human body while killing tumor cells, so as to cause weakness of the spleen and the stomach and insufficient healthy energy, therefore, the traditional Chinese medicines for tonifying qi and spleen can help healthy energy, regulate the immunity of the organism, strengthen the spleen to stop the source of phlegm and inhibit the growth of tumors.

(1) The pinellia ternata extract can inhibit tumor growth and reproduction by enhancing phagocytic function and secretion of reticuloendothelial system, and induce tumor cell apoptosis to play a role in resisting cancer. Pinellia ternata extract pair S₁₈₀、H₂₂The EAC has inhibitory effect and can induce SH-SY5Y and PCI₂Apoptosis, p-PCI₂Has growth and proliferation inhibiting effects. The methanol-extracted pinellia ternata polysaccharide fraction has polymorphonuclear leukocyte inducing ability, which is presumed to lead to a tumor-destroying cellular response by activating polymorphonuclear leukocytes.

(2) The Zingiberis rhizoma extract has biphasic regulating effect on organism immunity, and time-dependent effect on cytokine enhancement, and Interleukin (IL) -l, IL-3, IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) of monolayer cells are significantly increased in the presence of low concentration Zingiberis rhizoma extract, while higher concentration does not have the enhancement. The extract of Zingiberis rhizoma exerts cytotoxicity by promoting apoptosis and inhibits tumor proliferation.

(3) The flavonoid active components in exocarpium Citri Grandis, naringenin, apigenin, rhoifolin, etc. have effect in inhibiting tumor cell growth. Naringenin can reduce lung tumor size, slow tumor growth speed, and inhibit breast tumor metastasis; the obtained cauliflower can induce apoptosis by changing cell cycle, inhibit growth of gastric cancer multidrug-resistant cell, and increase apoptosis rate with concentration increase and time extension.

(4) Pachyman can increase the content of immune factors IL-2 and TNF-alpha in mouse serum, increase IL-2, TNF-alpha, IL-6, IFN-gamma titer, improve lymphocyte and macrophage functions, and induce anti-Peyer's knot and CD3 in mesenteric lymph node⁺、CD19⁺The change of the cell proportion promotes the biosynthesis of IgA, IgG and IgM in mouse serum. Pachyman can enhance the activity of tumor necrosis factor and natural killer cell activity, the tumor necrosis factor is a kind of polysaccharide secreted by macrophage, it can directly participate in the killing of monocyte to tumor cell, and through inhibiting the activity of gene transcription, reduce the expression level of mcy gene mRNA specifically, make HLA mRNA expression level increase, enhance the activity of cellular immune system especially CTL, play a role in killing tumor cell indirectly.

(5) Patchouli alcohol can enhance humoral immune response to play a role in immune regulation by activating a mononuclear phagocyte system, can inhibit colon cancer cells HCT116 and SW480 in vitro, can inhibit expression of histone deacetylase 2 and activity of histone deacetylase, and can down-regulate protooncogene (cmyc) and activate transcription factor NF-B channel, thereby inhibiting cell differentiation, promoting apoptosis and playing a role in anti-tumor.

(6) The berberine plays an anti-tumor role by killing tumor cells, inhibiting the proliferation of the tumor cells, inducing the apoptosis and inhibiting the invasion and the metastasis of the cells. The berberine can inhibit the degradation of the inhibitory protein of the nuclear factor kB in the lung cancer cells, so that the generation of IL-1 beta and TNF-alpha is increased, the apoptosis of the lung cancer cells is promoted, and the berberine has a treatment effect on the lung cancer; berberine also acts to reduce the invasive potential of lung cancer cells by down-regulating matrix metalloproteinases and urokinase-type plasminogen activator.

(7) The scutellaria can improve the immunity of the organism and enhance the resistance of the body to viruses; the flavonoids of Scutellariae radix can regulate amino acid metabolism by influencing Cyclooxygenase (COX) and Lipoxygenase (LOX) pathways to exert antitumor effect.

(8) The Perillae herba has effects of enhancing immunity of mouse, stimulating production and release of IL-2 and IgM, and inhibiting cancer cell proliferation and inducing cancer cell apoptosis.

(9) The Codonopsis pilosula polysaccharide can enhance phagocytic function of reticuloendothelial system, increase spleen index, promote generation of hemolysin, and regulate organism immunity. The radix Codonopsis polysaccharide can make cell nucleus solid and condensed and apoptosis corpuscle appear, and has inhibitory effect on hepatocarcinoma cell SMMC-7721.

(10) The glycyrrhiza polysaccharide can effectively stimulate the proliferation and the activity of T lymphocytes to achieve the effect of enhancing resistance, and also has the effects of promoting the generation of immune globulin and inhibiting the activity of complement; glycyrrhetinic acid can exert anticancer effect by inducing tumor cell apoptosis, inhibiting tumor cell invasion, inducing tumor cell differentiation, inhibiting tumor multidrug resistance, etc.

(12) The refined polysaccharide in fructus Aurantii can regulate immunity. Nobiletin has good anti-tumor effect. Rhizoma Phragmitis polysaccharide has effects of resisting lipid peroxidation, resisting tumor in vitro, and improving lipid metabolism disorder. The bamboo shavings polysaccharide has the functions of regulating immunity in vitro and enhancing the immunity of organisms.

The stomach harmonizing and adverse qi lowering effects are that the synergistic sensitization is realized when the composition is combined with chemotherapeutic drugs, and the vomiting symptom is relieved:

the stomach-harmonizing and adverse-rising qi-lowering traditional Chinese medicines can smooth the middle-jiao qi, and vomit is relieved when the spleen and stomach transportation and transformation functions are normal; the qi-machine of the spleen and the stomach is regulated to be normal, the qi-machine of the gallbladder and the stomach are normal, and the drug is used together with the chemotherapeutics to enhance the sensitivity and improve the curative effect.

(1) The pinellia alcohol extract can inhibit cancer cells from pumping out of the cells by down-regulating the expression of cell membrane pump glycoprotein p170, can partially reverse the drug resistance of multidrug resistance cell line K562/A02 cells to anticancer drugs, and improve the curative effect; and can effectively relieve symptoms of nausea, emesis, and food intake decrease caused by chemotherapy drugs. Pinellia ternata plays a role in stopping vomiting by inhibiting vomiting centers and activating vagal efferent activities, and ingredients of the function in stopping vomiting are related to methionine, glycine, alkaloid, glucuronide and the like.

(2) The chemical component 6-gingerol of the dried ginger reduces the apoptosis of Survivin protein to inhibit tumor cells by down-regulating the expression of birc-5 mRNA, has the killing and chemotherapy sensitization effects on the human hepatoma cell strain HepG-2 cells, and has more obvious effect in a low-oxygen and low-sugar environment.

(3) The berberine can induce SKOV3 cell apoptosis, down-regulate Bcl-2 and Survivin genes and up-regulate Bax gene expression, and can also recover methylation state of hMLH1 promoter, enhance hMLH1mRNA expression and synergistically enhance the anti-tumor effect of the anti-cancer drug.

(4) The radix Codonopsis and radix astragali extract has certain enhancing effect on paclitaxel for inhibiting generation of lung cancer tumor microvessels and inhibiting tumor metastasis, and can also reduce chemotherapy toxic and side effects, and high dose of radix Codonopsis and radix astragali injection can inhibit chemotaxis of lung cancer cells on vascular endothelial cells.

(5) The compound polysaccharide of pachyman, wogonin and chemotherapy medicine can improve curative effect, and relieve side effects of chemotherapy medicine such as nausea and emesis. Perilla iso-ketone (IK) has obvious synergistic sensitization effect on radiotherapy of liver cancer cells. The patchouli n-hexane extract has certain resistance to emesis.

(III), the functions of relieving distension and fullness are related to the regulation of the functions of the digestive tract:

chemotherapy drugs damage the spleen and stomach, causing spleen deficiency, and distention and fullness are the most common complications of patients with spleen deficiency after chemotherapy. The patients often have the symptoms of poor appetite, fullness and distention in the stomach and the like, and the traditional Chinese medicine has unique curative effect on regulating the functions of the digestive tract.

(1) The pinellia ternata extract has the effect of resisting ulcer by reducing gastric secretion, reducing free acidity and total acidity of gastric juice, inhibiting activity of pepsin, promoting gastric mucosa repair and the like; it has bidirectional regulating effect on isolated intestinal canal, and can act on acetylcholine receptor to produce contraction effect, and inhibit intestinal canal contraction caused by acetylcholine, histamine, and barium chloride.

(2) The dried ginger has slight stimulation to the digestive tract, can enhance the intestinal tension, rhythm and peristalsis, and promote the digestive function of the stomach and the intestine.

(3) The fructus aurantii has a bidirectional regulating effect on gastrointestinal smooth muscles, can excite the gastrointestinal smooth muscles, strengthen gastrointestinal peristalsis, and can reduce the tension and spasmolysis of the gastrointestinal smooth muscles; fructus Aurantii exerts inhibitory effects through cholinergic receptors, 5-hydroxytryptamine mediated and direct effects on smooth muscle.

(4) The patchouli aqueous extract and the deoiling aqueous extract can inhibit the normal intestinal propulsion of mice and the intestinal propulsion caused by neostigmine, increase gastric acid secretion, enhance the activity of pepsin serum amylase and the function of pancreatic secretase, while the patchouli volatile oil has no influence on the intestinal propulsion, reduces the gastric acid secretion and improves the digestion function.

(5) The total alkaloids of Coptidis rhizoma can reduce free radicals in vivo, relieve lipid peroxidation, inhibit iNOS overexpression, maintain NO content of gastric mucosa at normal level, and protect gastric mucosa.

(6) The Scutellariae radix decoction has effect in inhibiting small intestine movement, and relieving small intestine smooth muscle spasm. The codonopsis pilosula polysaccharide can effectively relieve inflammatory reaction, protect intestinal villi and crypt, and improve intestinal mucosa symptoms caused by chemotherapy drugs. The liquiritin has the functions of resisting ulcer activity, regulating gastrointestinal tract function and improving body function.

The invention has the following beneficial effects:

1. has effects of invigorating qi, invigorating spleen, regulating stomach function, lowering adverse qi, relieving oppression and distention.

2. Has effects in regulating immunity and inhibiting tumor growth.

3. Has the effects of synergistic sensitization and relieving emesis symptom when used together with chemotherapeutic drugs.

4. Has the effect of regulating digestive tract function.

The specific implementation mode is as follows:

in order to facilitate understanding of the technical scheme of the invention, the following will further describe the traditional Chinese medicine composition, the traditional Chinese medicine decoction-free granule and the application for treating nausea and vomiting caused by chemotherapy, in combination with specific test examples.

Example 1: the preparation of the traditional Chinese medicine composition comprises the following steps:

weighing 6g of ginger processed pinellia tuber, 10g of dried ginger, 6g of exocarpium citri grandis, 10g of white poria, 3g of fructus aurantii immaturus in rice water, 10g of patchouli, 2g of ginger processed coptis, 3g of wine-processed scutellaria baicalensis, 15g of reed rhizome, 5g of bamboo shavings, 5g of perilla leaf, 15g of radix codonopsis and 2g of raw liquorice.

Example 2: the preparation of the traditional Chinese medicine composition comprises the following steps:

weighing 10g of ginger processed pinellia tuber, 12g of dried ginger, 10g of exocarpium citri grandis, 12g of white poria, 7g of fructus aurantii immaturus in rice water, 12g of patchouli, 3g of ginger processed coptis, 4g of wine-processed scutellaria baicalensis, 20g of reed rhizome, 8g of bamboo shavings, 7g of perilla leaf, 12g of radix codonopsis and 4g of raw liquorice.

Example 3: the preparation of the traditional Chinese medicine composition comprises the following steps:

weighing 15g of ginger processed pinellia tuber, 15g of dried ginger, 15g of exocarpium citri grandis, 15g of white poria, 12g of fructus aurantii immaturus in rice water, 15g of patchouli, 4g of ginger processed coptis, 5g of wine-processed scutellaria baicalensis, 30g of reed rhizome, 12g of bamboo shavings, 9g of perilla leaf, 15g of radix codonopsis and 6g of raw liquorice.

Example 4: the preparation of the traditional Chinese medicine decoction-free granules:

weighing the following single traditional Chinese medicine formula granules by weight: 6g of ginger processed pinellia tuber, 10g of dried ginger, 6g of exocarpium citri grandis, 10g of white poria, 3g of fructus aurantii immaturus in rice water, 10g of patchouli, 2g of ginger processed coptis, 3g of wine-processed scutellaria baicalensis, 15g of reed rhizome, 5g of bamboo shavings, 5g of perilla leaf, 15g of codonopsis pilosula and 2g of raw liquorice.

The single traditional Chinese medicine formula granule in the embodiment is purchased from Jiangyin Tianjiang pharmaceutical industry Co.

Example 5: the preparation of the traditional Chinese medicine decoction-free granules:

weighing the following single traditional Chinese medicine formula granules by weight: 10g of ginger processed pinellia tuber, 12g of dried ginger, 10g of exocarpium citri grandis, 12g of white poria, 7g of fructus aurantii immaturus from rice washing, 12g of patchouli, 3g of ginger processed coptis, 4g of wine-processed scutellaria baicalensis, 20g of reed rhizome, 8g of bamboo shavings, 7g of perilla leaf, 12g of codonopsis pilosula and 4g of raw liquorice.

Example 6: preparation of Chinese medicine decoction-free granule

Weighing the following single traditional Chinese medicine formula granules by weight: 15g of ginger processed pinellia tuber, 15g of dried ginger, 15g of exocarpium citri grandis, 15g of white poria, 12g of fructus aurantii immaturus in rice water, 15g of patchouli, 4g of ginger processed coptis, 5g of wine-processed scutellaria baicalensis, 30g of reed rhizome, 12g of bamboo shavings, 9g of perilla leaf, 15g of codonopsis pilosula and 6g of raw liquorice.

The beneficial effects of the traditional Chinese medicine decoction-free granules (hereinafter referred to as the rue-cao-wen-half granules) for treating nausea and vomiting caused by chemotherapy are illustrated by specific test examples as follows:

test example 1: the common reed rhizome warm half granule is clinically applied as follows:

firstly, the diagnosis standard of nausea and vomiting (CINV) caused by chemotherapy adopts the medicine treatment:

western diagnostic criteria: reference is made to the "guidelines for the prevention and treatment of emesis related to tumor therapy (2014 edition)" published by CRPC and ASMC.

Defining: accompanying nausea and vomiting during tumor chemotherapy.

Types of CINV: acute, delayed, anticipatory, explosive and refractory 5 types.

The traditional Chinese medicine diagnosis standard is as follows: according to the partial principle of the guiding principle of clinical research on new Chinese medicines (2002 edition) of the medical and political administration of the Ministry of public health of the people's republic of China on the attenuation and/or synergism of new Chinese medicines on radiotherapy and chemotherapy, the Ministry of health of the people's republic of China's traditional Chinese medicine industry standard ' diagnosis and treatment effect standard of internal medicine syndrome of traditional Chinese medicine ' (ZY/T001.1-94), national high-grade Chinese medicine academy planning teaching material Chinese medicine internal science (ninth edition) ' emesis ', and the Ministry of clinical diagnosis and treatment term syndrome of traditional Chinese medicine (national standard of the Ministry of China) are formulated on the basis of the clinical experience and questionnaire survey of the well-known traditional Chinese medicine Liu.

The core pathogenesis is as follows: the qi movement of the middle energizer is disturbed and qi transformation of the gallbladder and stomach is obstructed.

The main symptoms are: nausea, vomiting;

the secondary symptoms are as follows: hiccup, abdominal discomfort, chest distress, palpitation, dysphoria, constipation (constipation or unformed);

tongue pulse: a white or yellow and greasy tongue coating and a wiry, slippery or wiry and slow pulse.

The principal symptoms are essential, and the secondary symptoms 1 can be diagnosed by combining the tongue pulse.

(II) CINV curative effect judgment standard:

nausea and vomiting are divided into an acute phase, defined as within 24 hours of the start of chemotherapy, and a delayed phase, defined as between 24 and 120 hours of the start of chemotherapy. Emesis Complete Remission (CR) is stated to be emesis-free and no rescue medication is used; complete nausea remission (CR) is stated as a nausea score (visual analog scale) VAS ≦ 5 mm.

(III) the CINV effective cases treated by the ludwigia prostrata warm half granules:

case one: xian Ma, male, 60 years old, Shanxi province Yangyang city Jingyang county credit union family hospital, hospitalization number 241305

Initial diagnosis time: 6 and 30 months in 2017.

The main complaints are: lung cancer was confirmed for 1 week.

The current medical history: the patient has no obvious reason to cough before 1 week and has short breath, is diagnosed as lung malignant tumor (adenocarcinoma) by combining related examination, and is treated by 1-cycle chemotherapy medicaments, and the specific scheme of the chemotherapy medicaments is as follows: docetaxel (d1-d3) and cisplatin (d1-d3), nausea, vomiting and abdominal discomfort appear after chemotherapy, and symptoms are not relieved after oral administration of related antiemetic drugs (not detailed), so that the patients are required to be treated by the traditional Chinese medicine at present. The symptoms are as follows: nausea, vomiting, hiccup, abdominal discomfort, cough, a small amount of white and sticky sputum, difficulty in expectoration, blood streaks in the sputum, chest distress, shortness of breath, hypodynamia, anorexia, poor night rest, small convenient adjustment, dry stool. A pale-red tongue with white coating and a wiry and slippery pulse.

History of the past: the traditional history of type 2 diabetes is 5 years, the metformin tablet and glipizide tablet are orally taken at present, and the blood sugar is controlled; lacunar cerebral infarction for 2 months.

Traditional Chinese medicine diagnosis: the internal cancer belongs to the syndrome of lung-spleen qi deficiency and incoordination between gallbladder and stomach.

And (3) Western diagnosis: 1. lung malignancy (adenocarcinoma); 2. diabetes mellitus; 3. lacunar cerebral infarction.

Therapeutic method: tonifying lung and spleen, regulating stomach function and promoting gallbladder function.

The traditional Chinese medicine comprises the following components: the ludwigia octovalvis warm half granules are prepared by the following specific medicines: 15g of ginger processed pinellia tuber, 15g of dried ginger, 15g of red tangerine peel, 15g of tuckahoe, 12g of bitter orange, 15g of wrinkled gianthyssop herb, 4g of ginger-processed coptis root, 5g of wine-processed scutellaria root, 30g of reed rhizome, 12g of bamboo shavings, 9g of perilla leaf, 15g of codonopsis pilosula and 6g of raw liquorice. 6 doses are taken with water, and one dose is taken every day in two times.

The time of the return visit: 7 month and 6 days 2018

Patients complain of 6 doses of the medicine and then symptoms of nausea, vomiting, hiccup and abdominal discomfort are relieved, cough and shortness of breath are relieved, fatigue is relieved, blood streak is not existed in phlegm, normal eating is realized, usual night rest is realized, convenient adjustment is realized, the tongue is pale red, the tongue coating is white, and the pulse is string and smooth.

The traditional Chinese medicine comprises the following components: the ludwigia octovalvis warm half granules are prepared by the following specific medicines: 15g of ginger processed pinellia tuber, 15g of dried ginger, 15g of red tangerine peel, 15g of tuckahoe, 12g of bitter orange, 15g of wrinkled gianthyssop herb, 4g of ginger-processed coptis root, 5g of wine-processed scutellaria root, 30g of reed rhizome, 12g of bamboo shavings, 9g of perilla leaf, 15g of codonopsis pilosula and 6g of raw liquorice. 7 doses of the medicine are taken with water, and one dose is taken every day in two times.

And (3) return visit: the patient complains about the 7 doses and basically disappears the symptoms of digestive tract and respiratory tract discomfort such as nausea, vomit, cough, short breath and the like.

Case two: leibozan, male, No. 201 of 68 years old, Yanan city pagoda area, Zhenhuang village, No. 242245 of hospitalization

Initial diagnosis time: 7 and 10 months in 2017.

The main complaints are: the lung cancer is diagnosed for more than 1 month, and the hemoptysis lasts for 2 days.

The current medical history: the patient has no obvious inducement to cough and expectoration with headache and shortness of breath before 1 month, is diagnosed as lung malignant tumor (small cell carcinoma) by combining with related examination, and is treated by 1-cycle chemotherapy medicaments, and the specific chemotherapy scheme is as follows: etoposide (d1-d3), cisplatin (d1-d3), nausea, vomiting, abdominal discomfort after chemotherapy, and slight relief of symptoms after oral administration of related drugs (not detailed). The patient had no obvious reason to have hemoptysis before 2 days, is fresh red in color and about 10ml in volume, and is now required to be treated with the traditional Chinese medicine. The symptoms are as follows: nausea, vomiting, hiccup, abdominal discomfort, cough, a small amount of white and sticky sputum, good luck of sputum, blood-streaked sputum, chest distress, shortness of breath, fatigue, good appetite, regular night rest, small convenient adjustment, dry stool. A dark tongue with white coating and a wiry and slippery pulse.

History of the past: lacunar infarction for 1 year.

And (3) Western diagnosis: 1. malignant tumors of the lung (small cell carcinoma); 2. lacunar cerebral infarction.

The traditional Chinese medicine comprises the following components: the ludwigia octovalvis warm half granules are prepared by the following specific medicines: 15g of ginger processed pinellia tuber, 15g of dried ginger, 15g of red tangerine peel, 15g of tuckahoe, 12g of bitter orange, 15g of wrinkled gianthyssop herb, 4g of ginger-processed coptis root, 5g of wine-processed scutellaria root, 30g of reed rhizome, 12g of bamboo shavings, 9g of perilla leaf, 15g of codonopsis pilosula and 6g of raw liquorice. 3 doses are taken with water, and one dose is taken every day in two times.

The time of the return visit: 7 month and 13 days 2017

After the patient takes 3 doses of the medicine, the symptoms of nausea, vomiting, hiccup and abdominal discomfort are relieved, cough and shortness of breath are relieved, blood thread does not exist in phlegm, the patient can take the medicine for a long time, and the patient can be adjusted for convenience when the patient is at rest at night. A dark tongue with white coating and a wiry and slippery pulse.

Case three: yimin Fang in Lian lake area of xi' an city of Shaanxi province, No. 2640596 hospitalization

Initial diagnosis time: 24/5/2018.

The main complaints are: lung malignant tumor is diagnosed for more than 1 month.

The current medical history: the patient is diagnosed as lung malignant tumor (adenocarcinoma) by combining relevant examination and carrying out 1-cycle chemotherapy drug treatment on cough, small amount of white and sticky phlegm, dry throat, pharyngalgia, shortness of breath, asthma, acid regurgitation and heartburn before 1 month, and the specific scheme of the chemotherapy drugs is as follows: docetaxel 120mg (d1) and cisplatin 40mg (d1-d3), nausea, vomiting and abdominal discomfort appear after chemotherapy, and symptoms are not relieved after oral administration related medicines (not detailed) are treated, so the doctor can see the doctor by asking for traditional Chinese medicine treatment. The symptoms are as follows: nausea, vomiting, hiccup, abdominal discomfort, paroxysmal cough, a small amount of white and sticky phlegm, chest distress, shortness of breath, asthma, chest pain during acute cough, hypodynamia, anorexia, general night rest, small and convenient adjustment and unformed stool. A pale and dark tongue with white coating and a wiry and slow pulse.

History of the past: it is good for health.

Traditional Chinese medicine diagnosis: the internal cancer belongs to the syndrome of lung-spleen qi deficiency and incoordination between gallbladder and stomach;

and (3) Western diagnosis: malignant tumor of lung (adenocarcinoma).

The time of the return visit: 2018, 5 months and 27 days

Patients complain of 3 doses of the medicine and then symptoms of nausea, vomiting, hiccup, abdominal discomfort are relieved, cough and asthma are relieved, fatigue is relieved, the patients can take the medicine normally and take the medicine at night, the patients can adjust the condition conveniently, the tongue is light and dark, the tongue coating is white, and the pulse is wiry and smooth.

And (3) return visit: the patient complains about the 7 doses and basically disappears the digestive tract and respiratory tract discomforts such as nausea, vomit, cough, asthma and the like.

While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims; meanwhile, any equivalent changes, modifications and variations of the above embodiments according to the essential technology of the present invention are within the scope of the technical solution of the present invention.

Claims

1. The traditional Chinese medicine composition for treating nausea and vomiting caused by chemotherapy is characterized by comprising the following raw material medicines in parts by weight: 6-15 parts of ginger processed pinellia, 10-15 parts of dried ginger, 6-15 parts of exocarpium citri grandis, 10-15 parts of white poria, 3-12 parts of fructus aurantii immaturus in rice water, 10-15 parts of pogostemon cablin, 2-4 parts of ginger-processed coptis, 3-5 parts of wine-processed radix scutellariae, 15-30 parts of reed rhizome, 5-12 parts of bamboo shavings, 5-9 parts of perilla leaf, 9-15 parts of radix codonopsis pilosulae and 2-6 parts of raw licorice.

2. The traditional Chinese medicine composition according to claim 1, wherein the raw materials are in parts by weight: 15 parts of ginger processed pinellia tuber, 15 parts of dried ginger, 15 parts of exocarpium citri grandis, 15 parts of white poria, 12 parts of fructus aurantii immaturus from rice washing, 15 parts of patchouli, 4 parts of ginger-processed coptis root, 5 parts of wine-processed scutellaria baicalensis, 30 parts of reed rhizome, 12 parts of bamboo shavings, 9 parts of perilla leaf, 15 parts of radix codonopsis pilosulae and 6 parts of raw liquorice.

3. Use of the Chinese medicinal composition of claim 1 or 2 in the preparation of a medicament for the treatment of nausea and vomiting caused by chemotherapy.

4. The traditional Chinese medicine decoction-free granules for treating nausea and vomiting caused by chemotherapy are characterized by consisting of the following single traditional Chinese medicine formula granules in parts by weight: 6-15 parts of ginger processed pinellia, 10-15 parts of dried ginger, 6-15 parts of exocarpium citri grandis, 10-15 parts of white poria, 3-12 parts of fructus aurantii immaturus in rice water, 10-15 parts of pogostemon cablin, 2-4 parts of ginger-processed coptis, 3-5 parts of wine-processed radix scutellariae, 15-30 parts of reed rhizome, 5-12 parts of bamboo shavings, 5-9 parts of perilla leaf, 9-15 parts of radix codonopsis pilosulae and 2-6 parts of raw licorice.

5. The decoction-free Chinese medicinal granule according to claim 4, wherein the single Chinese medicinal granules comprise the following raw materials in parts by weight: 15 parts of ginger processed pinellia tuber, 15 parts of dried ginger, 15 parts of exocarpium citri grandis, 15 parts of white poria, 12 parts of fructus aurantii immaturus from rice washing, 15 parts of patchouli, 4 parts of ginger-processed coptis root, 5 parts of wine-processed scutellaria baicalensis, 30 parts of reed rhizome, 12 parts of bamboo shavings, 9 parts of perilla leaf, 15 parts of radix codonopsis pilosulae and 6 parts of raw liquorice.

6. The use of the decoction-free Chinese medicinal granule of claim 4 or 5 in the preparation of a medicament for treating nausea and vomiting caused by chemotherapy.