CN113694172A - Ginger and bamboo medicine pair with antiemetic and anticancer effects and preparation method thereof - Google Patents
Ginger and bamboo medicine pair with antiemetic and anticancer effects and preparation method thereof Download PDFInfo
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- CN113694172A CN113694172A CN202111156798.5A CN202111156798A CN113694172A CN 113694172 A CN113694172 A CN 113694172A CN 202111156798 A CN202111156798 A CN 202111156798A CN 113694172 A CN113694172 A CN 113694172A
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- antiemetic
- anticancer
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Medical Informatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the technical field of traditional Chinese medicines and preparation thereof, and relates to a ginger and bamboo medicine pair with antiemetic and anticancer effects and a preparation method thereof, wherein the components comprise a ginger extract and a bamboo shavings extract, and the weight ratio of the ginger extract to the bamboo shavings extract is (1: 10) - (10: 1); the ginger extract and the bamboo shavings extract are optimally combined in a medicine pair mode originally invented by an inventor, so that the composition can inhibit cancers and postoperative nausea and vomiting, has double advantages of anticancer effect, produces an anticancer and antiemetic effect exceeding the expected anticancer and antiemetic effect in an anticancer and antiemetic model, and is non-toxic; the invention has simple components, low cost, no toxic or side effect, safety, reliability and wide market prospect.
Description
The technical field is as follows:
the invention belongs to the technical field of traditional Chinese medicines and preparation thereof, and relates to a ginger and bamboo medicine pair with antiemetic and anticancer effects and a preparation method thereof.
Background art:
the american cancer research association (AACR) recently released cancer progression report predicts that by 2035 new cases of cancer will increase from 1520 ten thousand to 2400 ten thousand worldwide annually. Chemotherapy, while effective as an important therapeutic tool, has limited its full use in the treatment of cancer due to toxic side effects resulting from non-specific damage to healthy cells. The possibility of nausea and vomiting during cancer treatment and cancer pain drug control and after surgery, especially the possibility of acute malignant vomiting of highly vomiting-causing risk drugs such as cisplatin>90 percent. Nausea and vomiting are likely to cause metabolic disorders, malnutrition and weight loss, and are one of the important causes of fear of chemotherapy, decreased quality of life and decreased compliance. The current authoritative guideline recommends a classical prevention regimen for acute emesis with highly emetogenic risk chemotherapy drugs as 5-HT3Antagonist + dexamethasone + NK1Combinations of receptor antagonists or the addition of lorazepam/olanzapine. Even with the antiemetic regimen recommended by the guidelines, 28% of patients do not achieve complete remission. And the antiemetic scheme is expensive and has adverse reactions such as constipation, somnolence, dizziness/headache, diarrhea, insomnia and the like. In addition, single-target inhibition by chemotherapeutic agents often results in resistance that results in discontinuation or failure of the treatment. There is a great need to develop low toxicity, multi-target natural replacement therapies.
The natural Chinese herbal medicine has great development potential and has the advantages of integral and multi-target regulation, but the prescription components are complex, the effective components are difficult to screen, and the internationalization of the traditional Chinese medicine is not facilitated. The medicine pair is the minimum unit of the traditional Chinese medicine formula, has simple formula and less interference factors, and is the essence of the traditional Chinese medicine prescription-sending medicine.
The traditional Chinese medicine ginger (Zingier) is known as 'holy medicine for vomiting'. Gingerol is an active ingredient for resisting emesis. Modern studies have demonstrated that gingerol can inhibit the release of 5-HT and P substance from enterochromaffin cells, and acts on emesis-related 5-HT3And NK1And the like, simultaneously influence the expression of a plurality of substances such as CCK (cholecystokinesis), CGRP (calcitonin gene-related peptide), MTL (motilin), and the like, and are natural low-toxicity antiemetics with multiple target points.
Caulis Bambusae In Taeniam (Bambusae Caulis In Taenias) is a dry intermediate layer of stem of perennial evergreen arbor or shrub of Gramineae, bark of green stalk, and stem of Maackia longituba or Phyllostachys glauca. The caulis bambusae in taeniam is sweet and cold in nature, and has the effects of clearing heat, eliminating phlegm, relieving restlessness, stopping vomiting and the like. The records of Ben Cao Jing Shu (materia Medica) record that vomiting of sour water is all due to heat. Vomiting when yang-yin is hot; warm qi, cold and heat, also cause pathogenic factors, exogenous pathogenic factors and yang-deficiency syndrome. Zhu Ru, sweet in flavor and cold in nature, can relieve yang-heat and vomiting caused by pathogenic qi receding to stop . "
At present, no research report on antiemetic and anticancer effects of the combination of ginger and bamboo shavings as a medicine is found. Western medicines have great toxic and side effects and are also common in allergic reactions. And natural, low-toxicity and potent drugs are more needed for patients with cancer or postoperative infirmity. The traditional Chinese medicine is usually prepared from a plurality of medicines, so that the curative effect strength is enhanced, and the toxic and side effects are reduced. Ginger and bamboo shavings have the effects of antiemetic and the like, but the single medicine acting on antiemetic and anticancer can not achieve the expected treatment effect clinically. The ginger and bamboo innovative medicine combination can generate excellent curative effect according to a certain proportion. Therefore, the invention develops a natural ginger and bamboo medicine pair which has high efficiency, low toxicity and low price and has the double treatment advantages of resisting cancer and inhibiting nausea and vomiting. The inventor searches for various ratio drug pair formulas according to the theory of traditional Chinese medicine, and continuously researches and tests to finally obtain the optimal drug pair composition of the invention.
The invention content is as follows:
the invention aims to overcome the defects of the prior art and find a natural ginger and bamboo medicine pair which has the advantages of inhibiting cancers and postoperative nausea and vomiting and has double advantages of treatment and a preparation method thereof.
In order to achieve the purpose, the invention provides a ginger and bamboo medicine pair with an antiemetic and anticancer effect, which comprises ginger extract and bamboo shavings extract, wherein the weight ratio of the ginger extract to the bamboo shavings extract is (1: 10) - (10: 1).
The invention also provides a preparation method of the ginger and bamboo medicine pair with the antiemetic and anticancer effects, which specifically comprises the following steps:
(1) preparing a ginger extract: adopting a water decoction method, peeling and mashing whole ginger, soaking the ginger in a distilled water beaker with the weight of 10 times of that of the ginger for 60min, heating the beaker on an electric furnace with an asbestos screen to 100 ℃ and decocting for 60min, filtering silk cloth, storing filtrate, adding distilled water with the weight of 6 times of that of decoction dregs into the filtered decoction dregs, soaking, decocting and filtering the decoction dregs in the same method, mixing the two filtrates, heating and concentrating the mixture to a minimum volume, filtering the mixture by using an ultrafiltration membrane, and drying the mixture for 36h at 70 ℃ by using a vacuum drying oven under reduced pressure to obtain brown yellow powder so as to obtain the ginger extract containing gingerol;
(2) bamboo shavings extract: pulverizing caulis Bambusae in Taenia, sieving, extracting by water decoction or percolation method, wherein the percolation method comprises recovering ethanol or ethyl acetate with volume concentration of 30-60% or their mixture at a temperature below 60 deg.C under reduced pressure, concentrating, and drying to obtain caulis Bambusae in Taenia extract;
(3) weighing the ginger extract and the bamboo shavings extract according to the weight ratio of (1: 10) - (10: 1), and uniformly mixing to complete the preparation of the ginger bamboo medicinal pair with the antiemetic and anticancer effects.
Compared with the prior art, the ginger extract and the bamboo shavings extract are optimally combined in a medicine pair mode originally invented by an inventor, the ginger extract and the bamboo shavings extract are proved to have the effects of inhibiting vomit caused by chemotherapeutic drugs and resisting tumors, and the dosage ratio of the ginger extract to the bamboo shavings extract to the prescription is determined through a large number of experiments, so that the ginger bamboo shavings extract has excellent synergistic effect on the composition; repeated experimental study shows that the ginger and bamboo medicine produce good synergistic effect on the ginger extract and the bamboo shavings extract (1: 10) - (10: 1), can inhibit cancer and postoperative nausea and vomiting, has double advantages of anticancer effect, produces more than expected anticancer and antiemetic effects in an anticancer and antiemetic model, and is nontoxic. The traditional Chinese medicine composition is different from various traditional Chinese medicine formulas, and has the advantages of simple components, low cost, no toxic or side effect, safety, reliability and wide market prospect.
The specific implementation mode is as follows:
the present invention will be described in detail below with reference to specific examples.
Example 1:
the embodiment relates to a ginger and bamboo medicine pair with antiemetic and anticancer effects, which comprises ginger extract and bamboo shavings extract (hereinafter referred to as ginger and bamboo medicine pair), wherein the weight ratio of the ginger extract to the bamboo shavings extract is 2: 5.
the preparation method of the ginger and bamboo medicine pair for stopping vomiting and resisting cancer, which is related by the embodiment, specifically comprises the following process steps:
(1) preparing a ginger extract: the preparation method comprises the steps of adopting a water decoction method, peeling and mashing whole ginger, soaking in a distilled water beaker with the weight of 10 times of that of the ginger for 60min, heating the beaker on an electric furnace with an asbestos screen to 100 ℃ and decocting for 60min, filtering silk cloth, storing filtrate, adding distilled water with the weight of 6 times of that of decoction dregs into filtered decoction dregs, soaking, decocting and filtering in the same method, heating and concentrating the filtrate obtained in two times, filtering with an ultrafiltration membrane, and drying under reduced pressure for 36h at 70 ℃ by adopting a vacuum drying oven to obtain brown yellow powder, thus obtaining the ginger extract containing gingerol.
(2) Preparing the bamboo shavings extract: pulverizing caulis Bambusae in Taenia, sieving, extracting with 30 vol% ethanol by percolation method, recovering under reduced pressure below 60 deg.C, concentrating, and drying to obtain caulis Bambusae in Taenia extract.
(3) The ginger extract and the bamboo shavings extract are mixed according to the weight ratio of 2: 5, weighing, and uniformly mixing to obtain the rhizoma zingiberis recens bamboo medicine pair with effects of inhibiting chemotherapy and postoperative emesis and resisting cancer.
The ginger and bamboo drug pair for inhibiting chemotherapy and postoperative vomiting and having anticancer effect in this embodiment can also be prepared into capsules containing 100-500mg of ginger and bamboo drug pair by the preparation process in the prior art, or prepared into tablets containing 100-500mg of ginger and bamboo drug pair by the wet granulation process in the prior art for oral administration.
Example 2:
the ginger and bamboo medicine pair with the functions of inhibiting chemotherapy and postoperative vomiting and resisting cancer comprises ginger extract and bamboo shavings extract, wherein the ginger extract and the bamboo shavings extract are mixed according to a weight ratio of 3: 2, mixing the components.
Example 3:
in this example, for vomiting caused by cisplatin, a common anticancer drug, the drug delivery therapy using the ginger and bamboo medicine, the related pharmacodynamic tests are as follows:
1. test materials:
(1) caulis Bambusae in Taenia purchased from Dryokshood of Qingdao, rhizoma Zingiberis recens purchased from Shandong, and identified as dry intermediate layer of stem of caulis Bambusae in Gramineae, caulis Bambusae in Taeniam or herba Lophatheri and tuber of rhizoma Zingiberis recens of Zingiberaceae by technical division of pharmaceutical academy of Qingdao university.
(2) Gingerol is prepared by the preparation method described in Chinese patent ZL 201210038339.1.
(3) Cisplatin (cissplatin), produced by the eastern Shandong Qilu pharmaceutical factory, lot number: 903005CE, 20 mg/count.
Ondansetron hydrochloride injection, olsacon pharmaceutical, lot number: 090102, 2 ml: 4 mg.
(4) The weight of healthy adult minks (1.3-1.8) kg is 1.3-1.8, male minks are provided by Qingdao special breeding animal breeding center to avoid influence of estrogen on emesis determination index, each animal is independently placed in a 75cm x 50cm iron cage, natural light is irradiated for 24h day and night, and drinking water is freely taken before experiment.
2. The test method comprises the following steps:
randomly dividing 24 minks into 4 groups, wherein each group comprises 6 minks, and the groups are respectively a model control group, a positive control group (ondansetron group), a gingerol group and a ginger bamboo drug group; the model control group is subjected to intragastric (ig) perfusion treatment by 5ml of physiological saline, the ondansetron group is subjected to ip pretreatment by 2mg/kg of ondansetron, the gingerol group is subjected to ig pretreatment by 10g/kg (equivalent to crude drug content), and the dendrocalamus group is subjected to ig pretreatment by 10g/kg (equivalent to crude drug content) of dendrocalamus latiflorus drug pairs (ginger extract and bamboo shavings extract are mixed according to the weight ratio of 2: 5); cisplatin 7.5mg/kg ip is given to each group after 30min of administration; the vomit response of the minks within 6h after the administration is observed, and the incidence rate, the vomit latency period, the retching and the vomit frequency of the minks are recorded.
3. Test results
The effect results of the Zhu Jiang on cisplatin are shown in Table 1, and compared with the model control group, the Zhu Jiang group can obviously reduce the vomit and vomit times and prolong the vomit latency (P < 0.01). The incidence of vomiting (P <0.01) can be reduced by the gingerol group, the bamboos drug group and the ondansetron of the positive control group, wherein the curative effect of the gingerol group and the bamboos drug group is equivalent to that of the ondansetron group in the aspects of prolonging the vomiting latency and reducing the vomit and the vomiting times. From the data, the curative effect of the ginger bamboo medicine on reducing the vomit and the vomit times is better than that of a single traditional Chinese medicine gingerol group, and the curative effect of the ginger bamboo medicine and the gingerol group is equivalent to that of the single traditional Chinese medicine in prolonging the vomit latency.
TABLE 1 influence of the Phyllostachys nigra drugs on the emetic action of cisplatin (7.5mg/kg, ip)
Note: compared with the model control group,aP＜0.05；bP＜0.01。
example 4:
this example is a pharmacodynamic study of the antitumor effect of the Phyllostachys nigra drug
1. Test materials:
(1) 96 Kunming mice with both male and female functions and the weight (20 +/-2) g are provided by the center of drug testing animals in Qingdao city. Before the experiment, people can take water freely and naturally illuminate day and night for 24 hours.
(2) Cyclophosphamide, a product of henry pharmaceutical products of Jiangsu province, Inc.
(3) Gingerol is prepared by the preparation method described in Chinese patent ZL 201210038339.1.
2. The test method comprises the following steps:
(1) for mouse S180Inhibition of sarcoma growth
Diluting the milky ascites with proper amount of sterile physiological saline solution into tumor cell suspension with the number of cells of 10 after passage of 5-7 days7The mice were inoculated with 48 mice (0.2 ml) subcutaneous iy in the right axilla (2X 10 tumor cells)6One). The inoculation day is randomly divided into 4 groups, each group comprises 12 negative control groups, positive drug cyclophosphamide groups, ginger bamboo drug pair high concentration groups (400mg/ml) and ginger bamboo drug pair low concentration groups (100 mg/ml); the negative control group was given 0.5ml of distilled water; cyclophosphamide is given to the positive drug group at 20mg/kg/d, and the ginger bamboo drug is given to the high and low concentration groups respectively ig and is given with water solution of ginger bamboo drug pair (ginger extract and bamboo shavings extract are mixed according to the weight ratio of 2: 5) at 0.5ml/d for treatment; the administration was continued for 10 days. Conventional breeding, drinking water and food limitation. The day after stopping the drug, all mice are killed after taking off the cervical vertebra, subcutaneous solid tumor masses are stripped, weighed, and the tumor inhibition rate (%) is calculated according to the following formula: tumor inhibition rate ═ average tumor weight (C) in control group-average tumor weight (T) in test group]Control group mean tumor weight (C).
(2) Inhibition assay for mouse Ehrlich ascites tumor (EAC)
48 mice were tested, and the mice were divided into groups, dosed, administered, and tested for the duration of the test and the test method (1) described above180Inhibition of sarcoma growth was the same.
3. And (3) test results:
compared with the control group, the ginger and bamboo drug pair is used for the high and low concentration group to form the group S180And EAC has the effects of inhibiting tumor, reducing tumor inflammatory reaction, obviously reducing tumor weight and having significance in difference. The test results are shown in tables 2 and 3.
TABLE 2 ginger and bamboo drug vs. mouse S180Effect of sarcoma
Note: compared with the control group, the compound of the formula,aP<0.05，bP<0.01。
TABLE 3 influence of the Phyllostachys nigra drug on mouse Ehrlich ascites tumor
Note: compared with the control group, the compound of the formula,aP<0.05，bP<0.01。
example 5:
the present example performed acute toxicity tests on the pair of Zhuang Zi, and the related data are as follows:
1. test animals:
kunming mouse, male and female, weight (20 + -2 g), provided by the center of the laboratory animal of drug testing institute in Qingdao city.
2. Medicine preparation:
ginger bamboo medicinal pair, tragacanth gum.
3. The test method comprises the following steps:
according to the 'new Chinese medicine research technical requirements' issued by the State drug administration of medicine supervision and administration in November and twelve days of nineteen years, the natural Chinese medicine pair of the invention is subjected to acute toxicity test. The LD cannot be determined due to the limitation of drug concentration and volume50Therefore, the maximum dose test was conducted. Taking 30 Kunming mice, half of each female, administering ginger and bamboo medicine pair (ginger extract and bamboo shavings extract mixed according to the weight ratio of 2: 5) water solution with the concentration of 1000mg/ml, each 0.8ml, ig, namely the maximum ig volume of the mice, observing the activity state, diet, feces, respiration, weight and death condition of the mice after administration, and continuously observing for 14 d.
4. The experimental results are as follows:
after the ig administration, the mice of each group have good growth, weight gain and normal behavior, and have no death and obvious reaction. After the animals were sacrificed, no abnormal phenomenon occurred in each major organ by visual observation.
The results show that the ginger and bamboo medicine of the invention is applied to the oral administration of the maximum dose, has no obvious damage to animals, does not discover the toxic reaction of the ginger and bamboo medicine to organisms, and is a safe and reliable medicine.
Claims (2)
1. A rhizoma Zingiberis recens-bamboo shoot pair with antiemetic and anticancer effects is characterized by comprising rhizoma Zingiberis recens extract and caulis Bambusae in Taenia extract at a weight ratio of (1: 10) - (10: 1).
2. The pair of ginger and bamboo drugs having antiemetic and anticancer effects according to claim 1, characterized in that the preparation method comprises the steps of:
(1) preparing a ginger extract: adopting a water decoction method, peeling and mashing whole ginger, soaking the ginger in a distilled water beaker with the weight of 10 times of that of the ginger for 60min, heating the beaker on an electric furnace with an asbestos screen to 100 ℃ and decocting for 60min, filtering silk cloth, storing filtrate, adding distilled water with the weight of 6 times of that of decoction dregs into the filtered decoction dregs, soaking, decocting and filtering the decoction dregs in the same method, mixing the two filtrates, heating and concentrating the mixture to a minimum volume, filtering the mixture by using an ultrafiltration membrane, and drying the mixture for 36h at 70 ℃ by using a vacuum drying oven under reduced pressure to obtain brown yellow powder so as to obtain the ginger extract containing gingerol;
(2) bamboo shavings extract: pulverizing caulis Bambusae in Taenia, sieving, extracting by water decoction or percolation method, wherein the percolation method comprises recovering ethanol or ethyl acetate with volume concentration of 30-60% or their mixture at a temperature below 60 deg.C under reduced pressure, concentrating, and drying to obtain caulis Bambusae in Taenia extract;
(3) weighing the ginger extract and the bamboo shavings extract according to the weight ratio of (1: 10) - (10: 1), and uniformly mixing to complete the preparation of the ginger bamboo medicinal pair with the antiemetic and anticancer effects.
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