CN106924331B - Application of Aidi preparation in preparation of medicine for treating neuroblastoma - Google Patents
Application of Aidi preparation in preparation of medicine for treating neuroblastoma Download PDFInfo
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Abstract
The invention discloses an application of an Aidi preparation in preparing a medicine for treating neuroblastoma, the Aidi preparation of the invention is composed of four medicines of cantharis, ginseng, astragalus and acanthopanax; the Aidi preparation has stronger neuroblastoma resistance, obvious curative effect, small side effect and safer clinical medication, provides a new treatment way for the treatment of neuroblastoma and expands the clinical application of the Aidi preparation.
Description
Technical Field
The invention relates to a new application of an Aidi preparation, in particular to an application of the Aidi preparation in preparing a medicine for treating neuroblastoma.
Background
Neuroblast (NB) originates from an embryonic tumour of primitive neural crest cells of the sympathetic nervous system, with the sympathetic chain, adrenal medulla, being the most common primary site. NB is one of the most common solid tumors of children, accounts for 8% -10% of all children tumors, accounts for 28% of the incidence rate of the total cancers of the infants, and is the malignant tumor with the highest incidence rate of the infants. NB has a high mortality rate which accounts for 15% of all pediatric malignant tumor deaths, the morbidity is mostly below 5 years of age, and about 1% of family history exists. About 3000 new cases of new diseases occur in China every year, and nearly half of neuroblastoma occurs in infants within 2 years of age. Neuroblastoma belongs to a neuroendocrine tumor, can originate from any nerve ridge part of the sympathetic nervous system, and has main metastasis routes of lymph and blood circulation. Regional lymph node infiltration occurs in about 35% of patients with localized lesions, with hematogenous metastases occurring primarily in the bone marrow, bone, liver and skin, and brain and lung metastases at terminal stage or recurrence. Neuroblastoma is complex and diverse in clinical manifestations, high in malignancy degree, rapid in disease progression, easy to generate metastasis in early stage, poor in prognosis and low in long-term survival rate, and most of children patients (more than 50%) are in a high-risk state in late stage after diagnosis.
The Aidi preparation is prepared by extracting extract with medicinal value as effective component from Mylabris, Ginseng radix, radix astragali and radix Acanthopanacis Senticosi as main raw materials. Has the functions of clearing away heat and toxic material, removing blood stasis and dissipating stagnation, wherein the Aidi injection is recorded in 20 volumes of standards issued by the Ministry of health.
Patent CN03117114.1, invention patent named "Chinese medicinal injection for treating tumor and its preparation method", patent CN200510003151.3 named "preparation method of Chinese medicinal preparation for treating tumor" disclose Aidi preparation with Mylabris, Ginseng radix, radix astragali and radix Acanthopanacis Senticosi as prescription and its preparation method.
The prior art shows that the Aidi preparation has good treatment effect on malignant tumors. The Aidi preparation has good curative effect on primary liver cancer, lung cancer, rectal cancer, malignant lymphoma and gynecological malignant tumors reported in the current research, but no report related to neuroblastoma exists. The diagnosis of neuroblastoma is often in the late stage, and the treatment difficulty is large. Traditional surgery, chemotherapy and radiotherapy are three main means for treating neuroblastoma, and surgery excision and chemotherapy are generally advocated for localized tumors. The patients who can not be resected after the operation adopt the strategies of firstly chemotherapy, then the operation, then the chemotherapy or the radiotherapy after the diagnosis is confirmed. However, the existing medicines for treating neuroblastoma have poor effects, serious adverse reactions and poor prognosis.
Disclosure of Invention
The invention aims to provide application of an Aidi preparation in preparing a medicine for treating neuroblastoma.
The Aidi preparation of the present invention consists of cantharis, ginseng, astragalus root and acanthopanax root. Mainly contains an extract with medicinal value extracted from cantharis, ginseng, astragalus and acanthopanax as an effective component. According to the weight portion, the Aidi preparation of the invention is prepared from the following components in parts by weight: is prepared by extracting 0.5 to 5 parts of Chinese medicinal raw materials of cantharis, 25 to 100 parts of ginseng, 50 to 200 parts of astragalus and 100 plus 200 parts of acanthopanax.
The preferable mixture ratio is as follows: 1-2 parts of cantharis, 30-70 parts of ginseng, 75-125 parts of astragalus root and 175 parts of acanthopanax 125-.
The most preferable mixture ratio is as follows: cantharis 1.5 parts, ginseng 50 parts, astragalus 100 parts and acanthopanax 150 parts.
When in use, the medicament of the invention can be added with one or more pharmaceutically acceptable carriers, such as diluent, filler, adhesive, excipient, disintegrant, surfactant, absorption enhancer, lubricant and the like, according to the needs to prepare various Addie preparations.
The aforementioned edi preparation is preferably used in the form of an injection, tablet, pill, capsule, granule, emulsion, solution or suspension, and more preferably an injection. The preparation can be prepared according to the conventional method in the field of pharmacy.
The aforementioned route of administration of the Addie preparation is oral, transdermal, intravenous or intramuscular injection.
In the preparation method of the Aidi preparation, the effective component extract can be extracted according to the method disclosed in the patent No. CN03117114.1, or the method disclosed in the patent No. CN200510003151.3, or the conventional method.
The active ingredient cantharis of the Aidi preparation is a dried body of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus of Meloideae, which is a dry body of Mylabris phalerata Pallas or Mylabris phalerata Linnaeus, is pungent in property, hot and toxic, has the effects of breaking blood, removing emaciation, attacking toxin and corroding sore; the Ginseng radix is dried root of Panax ginseng C.A.Mey. of Araliaceae, has sweet, slightly bitter and slightly warm taste, and has effects of invigorating primordial qi, invigorating spleen, benefiting lung, promoting fluid production, benefiting blood, tranquilizing mind, and improving intelligence; radix astragali is dried root of Astragalus membranaceus Bge. var. mongholicus (Bge.) or Astragalus membranaceus Bge of Leguminosae, and has effects of invigorating qi, consolidating exterior, promoting urination, removing toxic substance, expelling pus, healing sore, and promoting granulation; the radix Acanthopanacis Senticosi is dried root, rhizome or stem of Harms of Acanthopanax senticosus (Rupr. et Maxim.) of Araliaceae, and has effects of invigorating qi, invigorating spleen, invigorating kidney and tranquilizing mind. The four drugs are used together to have the effects of clearing away heat and toxic materials, removing blood stasis and resolving hard mass.
The active ingredients of the Aidi preparation are cantharis, ginseng, radix astragali and acanthopanax, wherein the cantharis can be used for treating stubborn dermatitis, abdominal mass, sore and dead muscle and the like; ginseng radix can be used for treating syndrome of collapse due to qi deficiency, syndrome of qi deficiency of lung, spleen, heart and kidney, thirst due to deficiency of qi and body fluid due to febrile disease, and diabetes; radix astragali can be used for treating qi deficiency, debilitation, anorexia, loose stool, collapse of middle-warmer energy, and exterior deficiency spontaneous perspiration; radix Acanthopanacis Senticosi can be used for treating spleen and kidney yang deficiency, asthenia, anorexia, soreness of waist and knees, insomnia and dreaminess, etc. The four medicines have effects of invigorating spleen, replenishing qi, promoting fluid production, nourishing blood, promoting organism growth, resisting oxidation, and enhancing immunity. Therefore, the Aidi preparation has obvious curative effect on neuroblastoma, small side effect and safer clinical medication. Further experimental research of the applicant finds that the Aidi preparation can be used for preparing a medicament for treating neuroblastoma.
In order to make the person skilled in the art better understand the present invention, the following experimental examples further illustrate the composition and preparation method of the edi preparation of the present invention, and the experimental study of the edi preparation in the drug for treating neuroblastoma. It should be noted that: the following examples are merely illustrative of the invention and are not intended to be limiting thereof.
Test examples
Test example 1: activity study of Adi preparation antibody against external neuroblastoma
1.1 materials and reagents
1.1.1 drug name and Source: aidi injection is prepared from Aidi injection prepared in different formula ratios in examples 1-7. Vincristine sulfate for injection, shanxi zhendongtaisheng pharmaceutical ltd; cisplatin, vinorelbine, is manufactured by Jiangsu Haussen pharmaceutical Co.
The preparation method comprises the following steps: the above medicines are prepared into corresponding concentrations by serum-free culture medium.
1.1.2 cell lines
Neuroblastoma SH-SY5Y cells and neuroblastoma SK-N-SH cells were purchased from American Standard Collection for Biometrics (ATCC) and neuroblastoma N2a cells were purchased from cell resources center of Shanghai institute of Life sciences, the department of Central sciences, and cultured according to the provided instructions.
1.1.3 reagents and instruments
DMEM/F12(1:1) medium, fetal bovine serum (Gibco, USA), penicillin (10 ten thousand u/L), streptomycin (100mg/L), CO2 incubator, ELx800 type enzyme-linked immunosorbent assay (Bio-Tek, USA).
1.2 methods of investigation
1.2.1 cell culture
SH-SY5Y cells, SK-N-SH cells and N2a cells were subcultured conventionally in DMEM/F12(1:1) medium containing 10% fetal bovine serum, 10 wumu/L penicillin and 100mg/L streptomycin at 37 ℃ in a 5% CO2 incubator.
1.2.2 determination of cell inhibition Rate
SH-SY5Y cells, SK-N-SH cells and N2a cells in logarithmic growth phase are respectively prepared into cell suspensions, the cell suspensions are inoculated on a 96-well plate (the edge holes are filled with sterile Phosphate Buffer Solution (PBS)) at the cell density of 40000ml & lt-1 & gt, the 96-well plate is incubated for 5 hours at the temperature of 5% CO2 and 37 ℃, the drug concentration is respectively set to be 5-7, each concentration is set to be 2 multiple wells, 20 mu l of 0.5% MTT solution is added into each well after 36 hours of continuous action, and the culture is continued for 5 hours. The culture was terminated, the culture medium was carefully aspirated from the wells, 150. mu.l of dimethyl sulfoxide (DMSO) was added to each well, and the mixture was shaken on a shaker at a low speed for 10min to dissolve the crystals sufficiently. The Optical Density (OD) was measured at 490nm wavelength with a microplate reader. The blank was replaced with fresh serum-free medium. Drug inhibition and median inhibitory concentration (IC50) were calculated:
drug inhibition (%) - (blank OD-applied OD)/blank OD × 100%
Median inhibitory concentration (IC 50): refers to the concentration of inhibitor at which half of the inhibitor is inhibited, i.e., the concentration at which the ratio of apoptotic cells to the total number of cells equals 50%. The stronger the induction capacity, the lower the value.
1.3 test results
Vincristine, cisplatin and Addie injection of different compositions all have inhibitory effect on neuroblastoma SH-SY5Y cell, SK-N-SH cell and N2a cell in vitro, wherein the Addie injection prepared according to example 1 and example 7 has weaker inhibitory effect than vincristine and cisplatin; the Addie injection prepared according to examples 2-6 had a stronger inhibitory effect than vincristine and cisplatin; addi (example 4) showed the strongest inhibitory effect on in vitro neuroblastoma SH-SY5Y cells, SK-N-SH cells and N2a cells. Specific results are shown in table 1:
TABLE 1 vincristine, cisplatin and Addie formulations in vitro neuroblastoma SH-SY5Y cells, SK-N-SH cells and N2a cell inhibition (%) and half maximal inhibitory concentration (IC50) results
1.4 conclusion of the experiment
The single use of vincristine, cisplatin and Addie injection with different components all has inhibitory effect on in vitro neuroblastoma SH-SY5Y cell, SK-N-SH cell and N2a cell, wherein Addie (example 1) has the lowest drug component, and the inhibitory effect is lower than that of vincristine and cisplatin; addi (example 7) had the highest drug composition, and its inhibitory effect was rather lower than vincristine and cisplatin.
The inhibition effect of the Addie injection prepared according to the embodiment 2-6 is stronger than that of vincristine and cisplatin, and the formula proportion of the Addie injection in the range has obvious proliferation effects on antibody ectoneuroblastoma SH-SY5Y cells, SK-N-SH cells and N2a cells; aidi (example 4) has the strongest inhibitory effect on in vitro neuroblastoma SH-SY5Y cells, SK-N-SH cells and N2a cells, and is the most preferable prescription ratio of Aidi injection.
Test example 2: in vivo efficacy study of Adi formulations on neuroblastoma
2.1 materials and reagents:
2.1.1 drug name and Source: aidi injection prepared from examples 1-7 according to different formulation ratios; vincristine sulfate for injection, shanxi zhendongtaisheng pharmaceutical ltd; cisplatin, vinorelbine, is manufactured by Jiangsu Haussen pharmaceutical Co.
2.1.2 Experimental animals and cells
Clean-grade BALB/c mice, provided by the Experimental animals center of Shanxi university of medical; neuroblastoma N2a cells, purchased from cell resources center of Shanghai Life sciences of the Chinese academy of sciences.
2.1.3 reagents and instruments
DMEM/F12(1:1) medium, fetal bovine serum (Gibco, USA), penicillin (10 ten thousand u/L), streptomycin (100mg/L), inverted microscope, CO2 incubator, pipette, suction bulb, alcohol lamp.
2.2 test methods
2.2.1 cell culture
N2a cells were inoculated in DMEM medium containing 10% fetal calf serum, 100U/ml streptomycin and 100U/ml penicillin and subcultured at 37 ℃ in a 5% CO2 incubator saturated in humidity.
2.2.2 preparation of cell suspensions for injection
Selecting cells in logarithmic growth phase, digesting, beating, adding culture solution, etc. to obtain single cell suspension.
2.2.3 model establishment and drug delivery
Injecting the N2a cell strain into the abdominal cavity of a BALB/c mouse, and randomly dividing the animals into a normal saline control group (NS group), a vincristine group, a cis-platinum group and an Addie group after the tumor volume grows to be between 100-200 mm 3. Each group contains 10 vincristine groups, which are administered by intraperitoneal injection daily with vincristine sulfate 0.025mg/kg for 2 times per week for two weeks. Cisplatin 5mg/kg is intraperitoneally injected into the cisplatin group daily for 1 time per week for two weeks. 50ml of Aidi injection (diluted with 400-450 ml of 0.9% sodium chloride or 5-10% glucose injection) is intraperitoneally injected into Aidi group at the same time every day for two weeks. Control group was i.p. injected with NS2ml at the same time daily. Tumor volumes were measured 2-3 times a week, mice weighed, and data recorded. Tumor volume (V), Relative Tumor Volume (RTV) and tumor Inhibition Rate (IR) were calculated.
Tumor volume (V) ═ 1/2 xa (major axis) × b2 (major axis)
For Tumor Volume (RTV) ═ Vt/V0 (where V0 is the tumor volume measured at the time of group administration and Vt is the tumor volume at each measurement)
Tumor Inhibition Rate (IR)% (1-vincristine group or edi group or cisplatin group average tumor weight/NS group average tumor weight) × 100%
2.2.4 test results
Vincristine and Addie have certain therapeutic effect on neuroblastoma, and can obviously inhibit neuroblastoma growth. Wherein the Aidi injection prepared according to example 1 and example 7 has a weaker therapeutic effect on neuroblastoma than vincristine and cisplatin; the Aidi injection prepared according to the embodiments 2-6 has more remarkable treatment effect than vincristine and cisplatin; edi (example 4) showed the best therapeutic effect on neuroblastoma; addi (examples 6-7) was most toxic due to the highest drug component, resulting in symptoms of lassitude and vomiting in mice; in addition, cisplatin administration resulted in drug-related death in one mouse.
TABLE 1 vincristine, cisplatin and Addie effect on neuroblastoma N2a cell growth inhibition
Note: d 0: a first time of administration; dn: 20 days after the first dose
2.3 conclusion of the test
The vincristine, the cisplatin and the Addie have obvious treatment effect on the neuroblastoma when being singly administered, and can obviously inhibit the growth of the neuroblastoma; wherein, the Aidi injection prepared according to the embodiment 1 has the lowest drug component and the treatment effect on neuroblastoma is weaker than that of vincristine and cisplatin; the Addie injection prepared according to the embodiment 7 has the highest medicinal component and the largest toxic and side effect, and the treatment effect on neuroblastoma is weaker than that of vincristine and cisplatin; the Aidi injection prepared according to the embodiments 2-6 has more remarkable treatment effect than vincristine and cisplatin; addi (example 4) showed the best therapeutic effect on in vitro neuroblastoma. In summary, Addie (example 4) is the most preferred formulation ratio to achieve the best therapeutic effect.
Test example 3: treatment of neuroblastoma with Addie formulation
1. Case selection: for the child patient with typical symptoms of neuroblastoma, the diagnosis is confirmed by biopsy, bone marrow aspiration and urine VMA/HVA, and 18 children with definite diagnosis of neuroblastoma are screened. According to UICC TNM staging, 2 cases in stage III and 16 cases in stage IV. The 18 patients were randomly divided into two groups, 10 treatment groups, 5 men and 5 women, age 18-59 months, average 38 months, stage III of 1 case, stage IV of 9 cases; the control group had 8 cases, 4 cases in men and 4 cases in women, aged 19-56 months, averaged 36.6 months, and had 1 case in stage III and 7 cases in stage IV. The patient KPS scores were all less than 60. The two groups were comparable in age, sex, course of disease, and disease condition. Before treatment, according to the specific disease condition of the patients when the patients are put into the group, the patients are examined by X-ray, CT, MRI, bone scanning, bone marrow cytology and the like, and the tumor condition of the patients is accurately evaluated. The basic condition of the patient is evaluated by performing examinations such as blood routine examination, blood biochemical examination, electrocardiogram and/or echocardiography. The patient is expected to survive for more than 3 months.
2. The treatment method comprises the following steps: the control group is injected with vincristine 0.05mg/kg, and is used for intravenous drip d1 and 2, cyclophosphamide 20-80 mg/kg, and intravenous drip d1 and 2 are respectively used for 1 time; doxorubicin 15mg/(m2 · dose), i.v. instillation, 1 for each of d1, 2; 10mg/kg of fluorouracil, d3, 8 and 9 for intravenous drip, 3mg/kg of cytarabine, d3, 8 and 9 for intravenous drip, and 1 course of treatment is every 3-4 weeks. 100ml of aidi injection (diluted with 0.9% sodium chloride or 400-450 ml of 5-10% glucose injection) is added into the vein of the treatment group, the treatment course lasts for 15 days, one period is provided, and 2 periods are one treatment course.
3. The judging method comprises the following steps: the efficacy was assessed according to RECIST evaluation criteria: complete Remission (CR), Partial Remission (PR), Stable (SD), Progression (PD) and No Change (NC). The effective rate (RR) was calculated as CR + PR, and the Disease Control Rate (DCR) was calculated as CR + PR + SD. The evaluation of life quality takes KPS score as standard, the score is increased by more than 10 points after treatment to improve, the score is stable within 10 points, and the score is reduced by more than 10 points to reduce.
4. Results
4.1 recent therapeutic effect: the effective rate (CR + PR) of 10 cases in the treatment group is 70 percent, and the disease control rate (CR + PR + SD) is 90 percent; the effective rate (CR + PR) of the control group is 62.5 percent, and the disease control rate (CR + PR + SD) is 75 percent; the treatment group has better recent curative effect than the control group. The two groups of recent therapeutic effects are shown in Table 1.
TABLE 1 comparison of the near term efficacy of the two groups of patients
4.2 recent quality of life: the quality of life of 7 patients (70%) in the treatment group is improved, the quality of life of 4 patients (50%) in the control group is improved, and the quality of life of the patients in the treatment group is better than that of the patients in the control group. The recent quality of life of the two groups of patients is compared in the second table.
TABLE 2 comparison of recent quality of Life of two groups of patients
| Group of | Number of examples | Improvement (%) | Stability (%) | Decrease (%) |
| Treatment group | 10 | 7(70％) | 2(20％) | 1(10％) |
| Control group | 8 | 4(50％) | 2(25％) | 2(25％) |
4.3 discussion: from the results, the curative effect of the treatment group and the life quality of the patient are better than those of the control group, and the Addie preparation as a quality neuroblastoma medicament is better than that of the combination of vincristine, cyclophosphamide and doxorubicin. The Aidi preparation has good curative effect and potential therapeutic value on malignant neuroblastoma.
Detailed Description
Example 1: preparation of Aidi injection (Low component)
Raw materials: mylabris 4g, Ginseng radix 200g, radix astragali 450g, and radix Acanthopanacis Senticosi 900g
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Example 2: preparation of Aidi injection
Raw materials: mylabris 5g, Ginseng radix 250g, radix astragali 500g, and radix Acanthopanacis Senticosi 1000g
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Example 3: preparation of Aidi injection
Raw materials: cantharis 10g, ginseng 300g, astragalus root 750g, acanthopanax root 1250g
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Example 4: preparation of Aidi injection
Raw materials: 15g of cantharis, 500g of ginseng, 1000g of astragalus root and 1500g of acanthopanax
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Example 5: preparation of Aidi injection
Raw materials: 20g of cantharis, 700g of ginseng, 1250g of astragalus root and 1750g of acanthopanax
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Example 6: preparation of Aidi injection
Raw materials: 50g of cantharis, 1000g of ginseng, 2000g of astragalus root and 2000g of acanthopanax
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Example 7: preparation of Aidi injection (high component)
Raw materials: mylabris 60g, Ginseng radix 1100g, radix astragali 2100g, and radix Acanthopanacis Senticosi 2100g
The preparation method comprises the following steps: pulverizing Mylabris, extracting with 400ml 100% ethanol under reflux for 5 times, wherein the extraction time is respectively as follows: 2h, 1h, 0.5h and 0.5h, filtering, keeping the residue for later use, adjusting the pH of the extracting solution to 8-9 by using 4% sodium hydroxide solution, recovering ethanol under reduced pressure, filtering, adding water to dilute to 1000ml, adjusting the pH to 6-7 by using 12% hydrochloric acid solution, standing, refrigerating, centrifugally filtering, adjusting the pH of the supernate to 8-9 by using 4% sodium hydroxide solution for later use; slicing Ginseng radix, extracting with 480ml 60% ethanol under heating and refluxing for 3 hr, filtering, collecting the residue, recovering ethanol from the extractive solution under reduced pressure, adding water to 150ml of the concentrated solution, loading onto macroporous adsorbent resin, eluting with water 5 times the column volume, eluting with 80% ethanol 5 times the column volume, collecting eluate, recovering ethanol, concentrating, and filtering; mixing radix astragali and radix Acanthopanacis Senticosi with the residues of Ginseng radix and Mylabris, adding 24960ml water, and decocting for 5 times, wherein the extraction time is respectively: 3h, 2h, 1h, 0.5h and 0.5h, merging decoction, filtering, concentrating to 1560ml in volume, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, adjusting the pH value to 7 with 7% sodium hydroxide solution, refrigerating, filtering, adding ethanol into supernate to enable the ethanol content to reach 60%, refrigerating, filtering, recovering ethanol, adding water to 1200ml, adjusting the pH value to 4-5 with 12% hydrochloric acid solution, adding 0.3% active carbon, boiling and decolorizing for 40min, and centrifugally filtering; mixing the supernatant with the extractive solution of Ginseng radix and Mylabris, adding injectable water to 10000ml, adjusting pH to 3, filtering, bottling, and sterilizing to obtain 1000 Aidi injection preparations with dosage of 10 ml/piece, wherein each piece contains cantharidin (C10H12O4) 0.008-0.030 mg.
Claims (6)
1. The application of an Aidi preparation in preparing a medicine for treating neuroblastoma is characterized in that: the Aidi preparation is prepared by extracting 0.5-5 parts by weight of cantharis, 25-100 parts by weight of ginseng, 50-200 parts by weight of astragalus and 100-200 parts by weight of acanthopanax.
2. The use of an Addie formulation according to claim 1 in the manufacture of a medicament for the treatment of neuroblastoma, wherein: the Aidi preparation is prepared by extracting 1-2 parts by weight of cantharis, 30-70 parts by weight of ginseng, 75-125 parts by weight of astragalus and 125-175 parts by weight of acanthopanax.
3. The use of an Addie formulation according to claim 2 in the manufacture of a medicament for the treatment of neuroblastoma, wherein: the Aidi preparation is prepared by extracting 1.5 parts by weight of cantharis, 50 parts by weight of ginseng, 100 parts by weight of astragalus and 150 parts by weight of acanthopanax.
4. Use of an Addie formulation according to any one of claims 1-3 in the manufacture of a medicament for the treatment of neuroblastoma, wherein: the Aidi preparation is injection, lyophilized powder for injection, tablet, pill, capsule, granule, emulsion, solution or suspension.
5. The use of an Addie formulation according to claim 4 in the manufacture of a medicament for the treatment of neuroblastoma, wherein: the Aidi preparation is an injection.
6. Use of an Addie formulation according to any one of claims 1-3 in the manufacture of a medicament for the treatment of neuroblastoma, wherein: the administration route of the Aidi preparation is oral administration, percutaneous, intravenous or intramuscular injection.
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| CN115607587B (en) * | 2021-07-16 | 2023-12-01 | 贵州益佰制药股份有限公司 | Application of Aidi preparation in preparation of medicament for treating herpes zoster |
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| CN1449799A (en) * | 2003-01-03 | 2003-10-22 | 贵州益佰制药股份有限公司 | Traditional Chinese medicine injection for treating tumor and preparation process thereof |
| CN1730020A (en) * | 2005-08-02 | 2006-02-08 | 贵州益佰制药股份有限公司 | Method for preparing Chinese medicinal formulation for treating tumor |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1449799A (en) * | 2003-01-03 | 2003-10-22 | 贵州益佰制药股份有限公司 | Traditional Chinese medicine injection for treating tumor and preparation process thereof |
| CN1730020A (en) * | 2005-08-02 | 2006-02-08 | 贵州益佰制药股份有限公司 | Method for preparing Chinese medicinal formulation for treating tumor |
Non-Patent Citations (3)
| Title |
|---|
| 以参芪扶正注射液为主的中成药对肿瘤病人生活质量的影响;李咏梅等;《宁夏医学杂志》;20041130;第26卷(第11期);第728-729页第1.1-1.2节以及第2节 * |
| 斑蝥胶囊联合化疗治疗晚期小儿肿瘤疗效观察;蒋林等;《中国现代医药杂志》;20120131;第14卷(第1期);第13页右栏表1以及第14页第3节 * |
| 黄芪多糖对人神经母细胞瘤SH-SY5Y细胞的增殖作用研究;高晓红等;《中国药房》;20150810;第26卷(第22期);摘要 * |
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