CN106924331A - A kind of application of Aidi preparation in treatment neuroblast tumor medicine is prepared - Google Patents
A kind of application of Aidi preparation in treatment neuroblast tumor medicine is prepared Download PDFInfo
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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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/254—Acanthopanax or Eleutherococcus
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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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
Abstract
The invention discloses a kind of application of Aidi preparation in treatment neuroblast tumor medicine is prepared, Aidi preparation of the invention is made up of Chinese blister beetle, ginseng, the Radix Astragali and wilsonii four traditional Chinese medicine;There is Aidi preparation of the invention stronger anti-neuroblastoma to act on, and significantly, Small side effects, clinical application is safer, for the treatment of neuroblastoma provides new therapy approach and has expanded the clinical practice of Aidi preparation for curative effect of medication.
Description
Technical field
The present invention relates to a kind of new opplication of Aidi preparation, it is specifically related to a kind of Aidi preparation and exists
Prepare the application in treatment neuroblast tumor medicine.
Background technology
Neuroblast tumour (neuroblastoma, NB) originates from the original of stomodaeal nervous system
The embryonal tumors of neural crest cell, sympathetic chain, adrenal medella are most common primary
Position.NB is one of most common entity tumor of children, accounts for all pediatric tumors
8%~10%, the 28% of the total cancer morbidity of baby is accounted for, it is pernicious swollen baby's incidence of disease highest
Knurl.NB case fatality rate is high, accounts for the 15% of all Children Malignant Tumor death case fatality rate, its morbidity
Mostly less than 5 years old, about 1% family history.The annual neopathy of China 3000 or so, has
Nearly there is the infant within 2 years old in the neuroblastoma of half.Neuroblastoma belongs to
In neuroendocrine, any neural spine position of stomodaeal nervous system can be originated from,
Its main route of metastasis is lymph and blood.About 35% has local pouring in Focal lesion patient
Infiltration is fawned on, hematogenous metastasis takes place mostly in marrow, bone, liver and skin, whole latter stage or recurrence
When can have brain and Lung metastases.Neuroblastoma complicated clinical manifestation is various, and grade malignancy is high,
Disease progression is rapid, and early stage easily shifts, and locates after the diagnosis of most infants (being more than 50%)
In late period high-risk status, prognosis is poor, and long-term surviving rate is low.
Aidi preparation is, with Chinese blister beetle, ginseng, the Radix Astragali and wilsonii as primary raw material, to extract its tool
The preparation that the extract for having medical value is made as active ingredient.There is clearing heat and detoxicating, dispersing blood stasis
The effect of dissipating bind, wherein ad pro injection are recorded in Ministry of Public Health's ministry standard 20.
Patent CN03117114.1, entitled " traditional medicine Injectio for the treatment of tumour and its making
The patent of invention and patent CN 200510003151.3 of method ", entitled " one kind is treated swollen
It is place that the preparation method of the Chinese medicine preparation of knurl " is disclosed with Chinese blister beetle, ginseng, the Radix Astragali and wilsonii
Side Aidi preparation with and preparation method thereof.
The prior art indicate that, Aidi preparation has good therapeutic effect to malignant tumour.At present
Reported for work out in research Aidi preparation to primary carcinoma of liver, lung cancer, the carcinoma of the rectum, malignant lymphoma,
The treatment of gynecologic malignant tumor has good curative effect, but not to the correlation report of neuroblastoma
Road.Neuroblastoma is medical to belong to late period often, and treatment difficulty is larger.Traditional operation, chemotherapy,
Radiotherapy is three big Main Means of neuroblastoma treatment, and typically limitation tumour is advocated first
Surgery excision, then chemotherapy.Unresectable person after making a definite diagnosis using first chemotherapy, rear operation,
The strategy of chemotherapy or plus radiotherapy again.But the effect of drugs for the treatment of neuroblastoma is not at present
Good, adverse reaction is serious, and prognosis is poor.
The content of the invention
The purpose of invention is to provide a kind of Aidi preparation in treatment neuroblast tumor medicine is prepared
Application.
Aidi preparation of the invention is constituted by from Chinese blister beetle, ginseng, the Radix Astragali and wilsonii.Mainly
Contain the extract with medical value extracted from Chinese blister beetle, ginseng, the Radix Astragali and wilsonii
As active ingredient.Calculate in parts by weight, Aidi preparation of the present invention is by weight ratio:
It is by 0.5-5 parts, ginseng 25-100 parts, Radix Astragali 50-200 parts of Chinese medicine material Chinese blister beetle and thorn five
Plus 100-200 parts extracted be prepared from.
Preferably proportioning is:Chinese blister beetle 1-2 parts, ginseng 30-70 parts, Radix Astragali 75-125 parts, thorn
Slender acanthopanax 125-175 parts.
Most preferably proportioning is:1.5 parts of Chinese blister beetle, 50 parts of ginseng, 100 parts of the Radix Astragali, wilsonii
150 parts.
In use, medicine of the invention can be added one or more as needed pharmaceutically may be used
With the carrier for receiving, such as diluent, filler, adhesive, excipient, disintegrant, surface
Activating agent, sorbefacient and lubricant etc., are made various Aidi preparations.
Foregoing Aidi preparation preferably with injection, tablet, pill, capsule, granule,
The form of emulsion, solution or suspending agent is used, more preferably injection.Above-mentioned formulation can be pressed
It is prepared by the conventional method according to pharmaceutical field.
The method of administration of foregoing Aidi preparation is oral, percutaneous, vein or intramuscular injection.
In the preparation method of Aidi preparation of the present invention, its effective component extracts can be according to patent
Number extracted for the method for CN03117114.1, it is also possible to according to Patent No.
Method in CN200510003151.3 is extracted, and can also be carried out with conventional method
Extract.
Aidi preparation of the present invention, its active ingredient Chinese blister beetle is the big spot in Meloidae insect south
The black mylabris cichorii Mylabris cichorii Linnaeus of Chinese blister beetle Mylabris phalerata Pallas or yellow
Hirudo leech, property is pungent, heat, very toxic, the effect of malicious phagedenoma of being become thin with blood-breaking, attacked;People
It is the dry root of Araliaceae ginseng Panax ginseng C.A.Mey. to join, sweet, slight bitter,
Tepor, with reinforcing vital energy, reinforces the spleen to benefit the lung, and promote the production of body fluid beneficial blood, calms the nerves and increases effect of intelligence;The Radix Astragali
It is legume astragalus mongolicus Astragalus membranaceus
(Fisch.) dry root of Bge.var.mongholocus (Bge.) or Astragalus membranacus, it is solid with tonifying Qi
Table, diuretic and maintain drug, apocenosis, effect of expelling pus and promoting granulation;Wilsonii is Araliaceae wilsonii
Acanthopanax senticosus (Rupr.et Maxim.) Harms's dries root and rhizome or stem,
With the effect for replenishing qi to invigorate the spleen, tonifying the kidney to relieve mental strain.Four share with clearing heat and detoxicating, dispersing blood stasis dissipating bind
Effect.
The active component of Aidi preparation is Chinese blister beetle, ginseng, the Radix Astragali and wilsonii, and Chinese blister beetle can be used for
For many years stubborn dermatitis, wei lump in the abdomen lump, dislike dead flesh of sore etc.;Ginseng can be used for vigour collapse card, the lung spleen heart
Syndrome of deficiency of kidney qi, pyreticosis deficiency of vital energy injury thirst and diabete;The Radix Astragali can be used for treatment deficiency of vital energy weak, deficiency of food
Loose stool, the sinking of qi of middle-jiao, exterior deficiency spontaneous perspiration;Wilsonii can be used for the insufficiency of both the spleen and the kindey, physically weak weak, food
It is intended to depressed, soreness of waist and knee joint, insomnia and dreamful sleep etc..Above-mentioned four kinds of medicines have tonifying middle-Jiao and Qi, promote the production of body fluid
Effect of blood-nourishing, can promote body growth, play the role of anti-oxidant, enhancing immune.Therefore,
Aidi preparation has significant curative effect to treatment neuroblastoma knurl, and its Small side effects is clinical
Medication is safer.The further experimental study of the applicant finds that Aidi preparation really can be used for
Prepare the medicine for the treatment of neuroblastoma.
In order that those of ordinary skill in the art are better understood from the present invention, below by way of experimental example
The composition and preparation method of Aidi preparation of the present invention is expanded on further, and Aidi preparation is being controlled
Treat the experimental study in neuroblast tumor medicine.It should be noted that:Following examples are only
The explaination present invention, rather than the limitation present invention.
Test example
Test example 1:The activity research of the outer nerve-cell tumor of Aidi preparation antibody
1.1 materials and reagent
1.1.1 medicine name and source:Ad pro injection, takes from embodiment 1-7 by different prescriptions
The obtained ad pro injection of proportioning.Injection vincristine sulphate, Shanxi Dong Taisheng pharmacy of shaking has
Limit company;Cis-platinum, vinorelbine is Jiangsu Haosen Pharmaceutical Co., Ltd.
Compound method:Above medicine is made into respective concentration with serum free medium.
1.1.2 cell line
Neuroblastoma SH-SY5Y cells, neuroblastoma SK-N-SH cells, purchase
From Unite States Standard biology product collecting center (ATCC), neuroblastoma N2a cells, purchase
In Chinese Academy of Sciences's Shanghai school of life and health sciences cell resource center, according to the specification culture for being provided.
1.1.3 reagent and instrument
DMEM/F12(1:1) culture medium, hyclone (Gibco companies of the U.S.), penicillin (10
Ten thousand u/L), streptomysin (100mg/L), CO2 incubators, ELx800 types ELIASA (U.S. Bio-Tek
Company).
1.2 research methods
1.2.1 cell culture
With containing 10% hyclone, 100,000 u/L penicillin and 100mg/L streptomysins
DMEM/F12(1:1) culture medium, the routine passage culture in 37 DEG C, 5%CO2 incubators
SH-SY5Y cells, SK-N-SH cells and N2a cells.
1.2.2 cell inhibitory rate is determined
Take the logarithm growth period SH-SY5Y cell, SK-N-SH cells and N2a cells, respectively
Cell suspension is made, (edge hole is used to be inoculated in 96 orifice plates with 40000ml-1 cell densities
Sterile phosphate buffer (PBS) is filled), it is incubated 5 hours in 5%CO2,37 DEG C,
Medicine sets 5-7 concentration respectively, and each concentration sets 2 multiple holes, and continuous action is after 36 hours,
The μ l of 0.5%MTT solution 20 are added per hole, continues to cultivate 5 hours.Terminate culture, carefully
Nutrient solution in hole is sucked, 150 μ l dimethyl sulfoxide (DMSO)s (DMSO) are added per hole, be placed in shaking table
Upper low-speed oscillation 10min, makes crystal fully dissolve.With ELIASA at 490nm wavelength
Determine optical density (OD).Blank is replaced with fresh serum-free media.Calculate medicine suppression
Rate processed and half-inhibition concentration (IC50):
Drug inhibition rate (%)=(blank OD- medication OD)/blank OD × 100%
Half-inhibition concentration (IC50):Refer to the concentration of inhibitor when being suppressed half, i.e. apoptosis is thin
Corresponding concentration when the ratio between born of the same parents and whole cell numbers are equal to 50%.Inducibility is stronger, the number
Value is lower.
1.3 result of the tests
The ad pro injection of vincristine, cis-platinum and different component is to ex vivo nerve blastoma
SH-SY5Y cells, SK-N-SH cells and N2a cells have inhibitory action, wherein by reality
Apply example 1 and ad pro injection inhibitory action is weaker than vincristine and cis-platinum obtained in embodiment 7;
Ad pro injection inhibitory action is better than vincristine and cis-platinum as obtained in embodiment 2-6;Ai Di
(embodiment 4) to ex vivo nerve blastoma SH-SY5Y cells, SK-N-SH cells and
The inhibitory action of N2a cells is most strong.Concrete outcome is shown in Table 1:
The vincristine of table 1, cis-platinum and Aidi preparation ex vivo nerve blastoma SH-SY5Y are thin
Born of the same parents, SK-N-SH cells and N2a cell inhibitory rates (%) and half-inhibition concentration (IC50) are tied
Really
1.4 experiment conclusions
The ad pro injection of vincristine, cis-platinum and different component is alone female to ex vivo nerve thin
Born of the same parents knurl SH-SY5Y cells, SK-N-SH cells and N2a cells have inhibitory action, wherein
Ai Di (embodiment 1) drug component is minimum, and its inhibitory action is less than vincristine and cis-platinum;Chinese mugwort
Enlightening (embodiment 7) drug component highest, its inhibitory action is less than vincristine and cis-platinum on the contrary.
Ad pro injection inhibitory action is better than vincristine and cis-platinum as obtained in embodiment 2-6, herein
In the range of ad pro injection prescription proportioning all there is the outer neuroblastoma of significant antibody
SH-SY5Y cells, SK-N-SH cells and N2a cel l proliferations;Ai Di (embodiments
4) to ex vivo nerve blastoma SH-SY5Y cells, SK-N-SH cells and N2a cells
Inhibitory action it is most strong, this be most preferred ad pro injection prescription proportioning.
Test example 2:Aidi preparation is studied the interior curative effect of neuroblastoma
2.1 materials and reagent:
2.1.1 medicine name and source:Ad pro injection, takes from embodiment 1-7 by different prescriptions
The obtained ad pro injection of proportioning;Injection vincristine sulphate, Shanxi Dong Taisheng pharmacy of shaking has
Limit company;Cis-platinum, vinorelbine is Jiangsu Haosen Pharmaceutical Co., Ltd.
2.1.2 experimental animal and cell
Cleaning grade BALB/c mouse, is provided by Mountain Western Medicine S University's Experimental Animal Center;Nerve
Blastoma N2a cells, are purchased from Chinese Academy of Sciences's Shanghai school of life and health sciences cell resource center.
2.1.3 reagent and instrument
DMEM/F12(1:1) culture medium, hyclone (Gibco companies of the U.S.), penicillin (10
Ten thousand u/L), streptomysin (100mg/L), inverted microscope, CO2 incubators, pipette, inhale ear
Ball, alcolhol burner.
2.2 test methods
2.2.1 cell culture
N2a cells are inoculated in containing 10% hyclone, 100U/ml streptomysins and 100U/ml
In the DMEM nutrient solutions of penicillin, in 37 DEG C, the 5%CO2 incubators of saturated humidity
Secondary Culture.
2.2.2 the preparation of injection cell suspension
Selection exponential phase cell, through digestion, piping and druming, adds nutrient solution etc. to be made unicellular hanging
Liquid.
2.2.3 model is set up and is administered
BALB/c mouse intraperitoneal injection N2a cell lines, treat knurl volume growth to 100~200
After between mm3, by animal be randomly divided into saline control group (NS groups), vincristine group,
Cis-platinum group and Ai Di groups.Every group 10, the daily intraperitoneal injection injection sulfuric acid of vincristine group
Vincristine 0.025mg/kg, 2 times/week, continuous two weeks.The daily intraperitoneal injection cis-platinum of cis-platinum group
5mg/kg, 1 times/week, continuous two weeks.The daily same time intraperitoneal injection Aidi injection of Ai Di groups
Liquid 50ml with 0.9% sodium chloride or 5~10% 400~450ml of glucose injection (after being diluted
Use), continuous two weeks.The daily same time intraperitoneal injection NS2ml of control group.2-3 is surveyed weekly
Secondary knurl volume, claims mouse weight, record data.Calculate gross tumor volume (V), relative tumour volume (RTV)
With tumour inhibiting rate (IR).
Gross tumor volume (V)=1/2 × a (major diameter) × b2 (footpath wide)
To gross tumor volume (RTV)=Vt/V0 (tumour bodies measured when V0 is packet administration in formula
Product, gross tumor volume when Vt is measurement every time)
(1- vincristine group or Ai Di groups or the average knurl weight of cis-platinum group/NS groups are flat for tumour inhibiting rate (IR) %=
Equal knurl weight) × 100%
2.2.4 result of the test
Vincristine and Ai Di have certain therapeutic effect to neuroblastoma, can be substantially
Suppress the growth of neuroblastoma.Wherein, the Ai Di as obtained in embodiment 1 and embodiment 7
Parenteral solution is weaker than vincristine and cis-platinum to the therapeutic effect of neuroblastoma;By embodiment
Ad pro injection therapeutic effect obtained in 2-6 is more more significantly than vincristine and cis-platinum;Ai Di is (real
Apply example 4) it is best to the therapeutic effect of neuroblastoma;Ai Di (embodiment 6-7) is due to medicine
Component highest, toxicity is maximum, causes mouse lassitude and symptoms of emesis occur;Additionally, suitable
A mouse is caused drug-associated occur after platinum administration dead.
The vincristine of table 1, cis-platinum and Ai Di are treated to neuroblastoma N2a cell growth inhibitions
Effect
Note:d0:First time administration time;dn:20 days after first administration
2.3 conclusion (of pressure testing)s
Vincristine, cis-platinum and Ai Di have to neuroblastoma when being administered alone and significantly control
Therapeutic effect, can substantially suppress the growth of neuroblastoma;Wherein, as obtained in embodiment 1
Ad pro injection drug component is minimum, and the therapeutic effect to neuroblastoma is weaker than vincristine
And cis-platinum;The ad pro injection drug component highest as obtained in embodiment 7, toxic and side effect is maximum,
Therapeutic effect to neuroblastoma is weaker than vincristine and cis-platinum on the contrary;By embodiment 2-6
Obtained ad pro injection therapeutic effect is more more significantly than vincristine and cis-platinum;Ai Di (is implemented
Example 4) it is best to the therapeutic effect of ex vivo nerve blastoma.In sum, Ai Di (embodiments
4) for most preferably prescription is matched, best therapeutic effect can be reached.
Test example 3:Treatment of the Aidi preparation to neuroblastoma
1st, case selection:For the child patient of the neuroblastoma for having classical symptom, lead to
Cross biopsy, bone marrow aspiration and urine VMA/HVA to make a definite diagnosis, filter out and clarify a diagnosis as neural mother is thin
Born of the same parents' knurl infant 18.According to UICC TNM stages, in III phase 2, IV phase 16.
18 patients are randomly divided into two groups, treatment group 10, man 5, female 5, age
The 18-59 months, average 38 months, in III phase 1, IV phase 9;Control group 8, man 4
Example, female 4, the month at age 19-56, average 36.6 months, in III phase 1, IV phase 7
Example.So patient KPS scorings are respectively less than 60.Two groups in age, sex, the course of disease, the state of an illness
Aspect is respectively provided with comparativity.According to the specific state of an illness of patient when entering group before treatment, carry out X-ray,
The inspection such as CT, MRI, bone scanning, bone marrow cell, the tumor presence of accurate evaluation patient.
The inspection such as blood routine, blood biochemistry checking, electrocardiogram and (or) echocardiogram is done, assessment is suffered from
Person's basal conditions.The estimated existence of patient is more than 3 months.
2nd, treatment method:Control group gives injects vincristine 0.05mg/kg, drip-feed,
D1,2,20~80mg/kg of endoxan, drip-feed d1,2 are respectively with 1 time;More soft ratio
Star 15mg/ (m2 times), drip-feed, d1,2 are respectively with 1 time;Fluorouracil 10mg/kg,
Drip-feed, d3,8,9, cytarabine 3mg/kg, drip-feed, d3,8,9, often
It is within 3~4 weeks 1 course for the treatment of.Treatment group's vein is added dropwise ad pro injection 100ml (with 0.9% chlorination
Used after sodium or 5~10% 400~450ml of glucose injection dilutions)/day, the course for the treatment of 15 days,
It is a cycle, the course for the treatment of of 2 cycle one.
3rd, decision method:Curative effect is evaluated by RECIST evaluation criterions:Complete incidence graph (CR),
(PR) is alleviated in part, stabilization (SD), is in progress (PD) and unchanged (NC).Calculated with CR+PR
Efficient (RR), disease control rate (DCR) is calculated with CR+PR+SD.Quality of life assessment
Scored with KPS scorings as standard, after treatment and rise more than 10 points to improve, be within 10 points
Stabilization, reduces more than 10 points to reduce.
4th, result
4.1 short term effects:Efficient (CR+PR) is 70%, disease control in treatment group 10
Rate (CR+PR+SD) processed is 90%;Control group effective percentage (CR+PR) is 62.5%, disease control
Rate (CR+PR+SD) processed is 75%;Treatment group's short term effect is better than control group.Two groups are treated in the recent period
Imitate to compare and be shown in Table 1.
1 two groups of patient's short term effects of table compare
4.2 recent qualities of life:Having 7 (70%) patients ' life qualities in treatment group is improved,
Quality of life is improved as 4 (50%) in control group, and treatment group's patients ' life quality is better than control
Group.Two groups of recent qualities of life of patient are relatively shown in Table two.
2 two groups of recent qualities of life of patient of table compare
Group | Number of cases | Improve (%) | Stabilization (%) | Decline (%) |
Treatment group | 10 | 7 (70%) | 2 (20%) | 1 (10%) |
Control group | 8 | 4 (50%) | 2 (25%) | 2 (25%) |
4.3 discuss:Understand from the above, the curative effect for the treatment of group and the quality of life of patient are excellent
In control group, Aidi preparation is better than vincristine and ring phosphorus as quality neuroblast tumor medicine
Acid amides, Doxorubicin drug combination.Aidi preparation has good to malignant nerve blastoma
Curative effect and potential therapeutic value.
Specific embodiment
Embodiment 1:The preparation (low component) of ad pro injection
Raw material:Chinese blister beetle 4g, ginseng 200g, Radix Astragali 450g, wilsonii 900g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Embodiment 2:The preparation of ad pro injection
Raw material:Chinese blister beetle 5g, ginseng 250g, Radix Astragali 500g, wilsonii 1000g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Embodiment 3:The preparation of ad pro injection
Raw material:Chinese blister beetle 10g, ginseng 300g, Radix Astragali 750g, wilsonii 1250g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Embodiment 4:The preparation of ad pro injection
Raw material:Chinese blister beetle 15g, ginseng 500g, Radix Astragali 1000g, wilsonii 1500g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Embodiment 5:The preparation of ad pro injection
Raw material:Chinese blister beetle 20g, ginseng 700g, Radix Astragali 1250g, wilsonii 1750g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Embodiment 6:The preparation of ad pro injection
Raw material:Chinese blister beetle 50g, ginseng 1000g, Radix Astragali 2000g, wilsonii 2000g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Embodiment 7:The preparation (component high) of ad pro injection
Raw material:Chinese blister beetle 60g, ginseng 1100g, Radix Astragali 2100g, wilsonii 2100g
Preparation method:Chinese blister beetle medicinal material is taken, is crushed, with the ethanol heating and refluxing extractions 5 of 400ml 100%
Secondary, extraction time is respectively:2h, 1h, 0.5h, 0.5h, 0.5h, filtration, the dregs of a decoction are standby,
Extract solution is adjusted to pH8-9 with 4% sodium hydroxide solution, and ethanol is recovered under reduced pressure, filtration, adds water
1000ml is diluted to, pH6-7 is adjusted to 12% hydrochloric acid solution, stood, refrigeration, centrifugation filter
Cross, supernatant is adjusted to pH8-9 with 4% sodium hydroxide solution, standby;Ginseng section is taken, is used
The ethanol heating and refluxing extraction 3h of 480ml 60%, filtration, the dregs of a decoction are standby, and extract solution is recovered under reduced pressure
Ethanol, concentrate adds water to volume for 150ml, upper macroporous absorbent resin, and add water 5 times of wash-out
Column volume, then eluted with 80% ethanol, 5 times of column volumes, eluent is collected, ethanol is reclaimed, it is dense
Contracting, filtration is standby;The Radix Astragali, wilsonii medicinal material are taken, is merged with ginseng, the Chinese blister beetle dregs of a decoction, plus
24960ml decoctings are boiled 5 times, and extraction time is respectively:3h, 2h, 1h, 0.5h, 0.5h,
Collecting decoction, filtration is concentrated into volume for 1560ml, and filtering, supernatant adds ethanol, makes
Alcohol content reaches 60%, and pH7, refrigeration, filtering, supernatant are adjusted with 7% sodium hydroxide solution
Again plus ethanol, alcohol content is made to reach 60%, ethanol is reclaimed in refrigeration, filtering, adds water to 1200ml,
PH4~5 are adjusted with 12% hydrochloric acid solution, 0.3% activated carbon boiling decoloring 40min, centrifugation is added
Filtering;Supernatant merges with ginseng, Chinese blister beetle extract solution, injects water to 10000ml, adjusts
Section liquid PH value is 3, and filtering, embedding, sterilizing obtain final product Aidi injection preparation 1000,
Dosage is 10ml/ branch, and every is 0.008~0.030mg containing cantharidin (C10H12O4).
Claims (6)
1. application of a kind of Aidi preparation in treatment treatment neuroblast tumor medicine is prepared, it is characterised in that:The Aidi preparation by 0.5-5 weight portions Chinese blister beetle, the ginseng of 25-100 weight portions, the wilsonii of the Radix Astragali of 50-200 weight portions and 100-200 weight portions extracts and is prepared from.
2. application of a kind of Aidi preparation according to claim 1 in treatment neuroblast tumor medicine is prepared, it is characterised in that:The Aidi preparation is extracted by the wilsonii of the Chinese blister beetle of 1-2 weight portions, the ginseng of 30-70 weight portions, the Radix Astragali of 75-125 weight portions and 125-175 weight portions and is prepared from.
3. application of a kind of Aidi preparation according to claim 2 in treatment neuroblast tumor medicine is prepared, it is characterised in that:The Aidi preparation is extracted by the wilsonii of the Chinese blister beetle of 1.5 weight portions, the ginseng of 50 weight portions, the Radix Astragali of 100 weight portions and 150 weight portions and is prepared from.
4. the application according to a kind of any described Aidi preparations of claim 1-3 in treatment neuroblast tumor medicine is prepared, it is characterised in that:The Aidi preparation is injection, freeze-dried powder, tablet, pill, capsule, granule, emulsion, solution or suspending agent.
5. application of a kind of Aidi preparation according to claim 4 in treatment neuroblast tumor medicine is prepared, it is characterised in that:The Aidi preparation is injection.
6. the application according to a kind of any described Aidi preparations of claim 1-3 in treatment neuroblast tumor medicine is prepared, it is characterised in that:The method of administration of the Aidi preparation is oral, percutaneous, vein or intramuscular injection.
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CN109846922A (en) * | 2017-11-30 | 2019-06-07 | 贵州益佰制药股份有限公司 | Application of the Aidi preparation in preparation treatment chronic obstructive emphysema drug |
CN115607587A (en) * | 2021-07-16 | 2023-01-17 | 贵州益佰制药股份有限公司 | Application of Aidi preparation in preparing medicine for treating herpes zoster |
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CN109846922A (en) * | 2017-11-30 | 2019-06-07 | 贵州益佰制药股份有限公司 | Application of the Aidi preparation in preparation treatment chronic obstructive emphysema drug |
CN115607587A (en) * | 2021-07-16 | 2023-01-17 | 贵州益佰制药股份有限公司 | Application of Aidi preparation in preparing medicine for treating herpes zoster |
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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