CN105125592A - Medicine containing toad venom lipid-soluble substances and preparation method thereof - Google Patents
Medicine containing toad venom lipid-soluble substances and preparation method thereof Download PDFInfo
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Abstract
The invention provides medicine containing toad venom lipid-soluble substances and a preparation method thereof. According to the toad venom lipid-soluble substances, the weight sum of bufalin, cinobufagin and resibufogenin is larger than 50% of the total weight of the toad venom lipid-soluble substances. The preparation method of the toad venom lipid-soluble substances includes the steps that toad venom herbs are smashed, then absolute ethyl alcohol is added, the amount of the absolute ethyl alcohol is 5-50 times that of the herbs, heating reflux is performed on the mixture for 1 h in a water bath of 60 DEG C, then the mixture is cooled to indoor temperature, suction filtration is performed, dry extract is obtained after filtrate is evaporated to dryness, purified water is added into the extract for ultrasonic suspending, the amount of the purified water is 5-30 times that of the extract, and extracting is performed through chloroform, wherein the amount of chloroform is 5-50 times that of the mixture. The invention further provides a medicine composite and a preparation method thereof. The medicine composite is a toad venom extract lipid microsphere oral solution and is used for treating gastrointestinal tumors.
Description
Technical field
The present invention relates to medical art, specifically it is a kind of extracting method containing Venenum Bufonis lipoclastic, and lipid microsphere oral solution.
Background technology
In recent years, cancer becomes first killer of the new century mankind gradually.According to World Health Organization (WHO) (WHO) report, there are 2,460 ten thousand cancer patients in the current whole world; To the year two thousand twenty, estimate to reach 3,000 ten thousand.Within 2005, have 7,600,000 people to die from cancer, death toll accounts for 13% of the whole world 5,800 ten thousand population, and to the year two thousand twenty, cancer will cause more than 1,000 ten thousand people dead every year.The number of cancer deaths nearly 1,900,000 of China in 2005,1,200,000 people's life-spans were wherein lower than 70 years old.Expert expects, the number to the year two thousand twenty death because of cancer stricken will more than 4,000,000.
Cancerous pain is the most common and unmanageable symptom of cancer patient, is also the key factor affecting patients ' life quality.Application " three ladder medicine analgesias " controls the scheme of cancer pain, although curative effect is relatively more definite, life-time service analgesics toxic and side effects is large, and additive, dependency by force, and is subject to the restriction of patient tolerability, causes some patients's analgesic effect not good enough.
Chinese medicine has effect of its uniqueness in therapeutic field of tumor.Venenum Bufonis has history that is long-term for oral administration or external application for curing cancer in China, and achieves good clinical effectiveness.Pharmacodynamic study shows, Venenum Bufonis is mainly used in treating digestive system tumor, as hepatocarcinoma, gastric cancer, colon cancer, the esophageal carcinoma etc., its active anticancer is than paclitaxel, the anticarcinogen strong ten times such as amycin and camptothecine of current Clinical practice, even Radix Achyranthis Bidentatae, and have no side effect, this is undoubtedly for the treatment of digestive system tumor provides better selection.Venenum Bufonis is the ear rear gland of Bufonidae animal Bufo siccus BufoBufogargarizansCantor or Bufo melanostictus BufomelanostictusSchneide etc. and the white serosity of skin gland secretion, forms through dry processing.Property sweet, acrid, warm, poisonous.Can detoxify, detumescence, heart tonifying, pain relieving.Treatment skin ulcer, carbuncle, the diseases such as carbuncle on the back.Research confirms that Venenum Bufonis anticancer analgetic effective ingredient is greasiness soluble compound, and wherein resibufogenin, Toadpoison Medicine, cinobufagin content are more, and activity is stronger.
Existing research is just studied for Venenum Bufonis crude drug or simple Venenum Bufonis ethanol extract, and in preparation, the concentration of effective ingredient is low, clinical need be large with volume, this brings very large inconvenience to patient, limits Clinical practice.Simultaneously because Chinese medicine ingredients is complicated, other impurity contained in preparation may play to effective ingredient itself effect increasing or weaken drug effect.Therefore, the invention provides a kind of extracting mode of Bufodienolides liposoluble constituent, wherein resibufogenin, Toadpoison Medicine, cinobufagin content are greater than 50%.
The Venenum Bufonis Injection going through clinically at present to use is aqueous injection, and its main component is indoles alkaloid.And a large amount of results of study shows that the anti-tumor activity of Venenum Bufonis liposoluble constituent is stronger, be mainly bufadienolide compound, its larger bio-toxicity seriously constrains its clinical practice, carries out by the new formulation research reduced for the purpose of Venenum Bufonis and active ingredient bio-toxicity thereof significant.
Many researchers, from multi-angle research improvement pharmaceutical dosage form, makes it while performance pharmacological action, lowers toxic and side effects.Seen that at present the Venenum Bufonis related preparations of research report comprises transdermal absorption formulation, microsphere, Benexate Hydrochloride, injection, tablet, capsule, solid lipid nanoparticle etc., but above-mentioned preparation on stream owing to being difficult to suitability for industrialized production, the different all unrealized final industrialization of factor such as safety is low, toxicity is high, drug effect is poor.
The existing research overwhelming majority studies for Venenum Bufonis crude drug or simple Venenum Bufonis ethanol extract, and in preparation, the concentration of effective ingredient is low, clinical need be large with volume, this brings very large inconvenience to patient, limits Clinical practice.Simultaneously because Chinese medicine ingredients is complicated, other impurity contained in preparation may play to effective ingredient itself effect increasing or weaken drug effect.Therefore, the purity of Chinese medicine preparation effective ingredient needs to improve.
For reducing toxicity and the zest of Venenum Bufonis liposoluble extract and monomer, CN1985851A patent provides a kind of lipide microsphere injection containing Venenum Bufonis extract.The toxicity of effective reduction Venenum Bufonis liposoluble extract or monomer whose and zest, but Venenum Bufonis lipid nanoparticle and lipide microsphere injection are injection emulsion, require higher to adjuvant, inevitably sterol is there is in oil phase adjuvant, easy initiation toxicity, there is cost higher, the shortcoming that safety is poor.
The invention provides a kind of Orally taken emulsion of Bufodienolides liposoluble constituent, its advantage is: 1, adopt preparation means pharmaceutical pack to be wrapped in O/W type Emulsion in oil phase, avoid directly stimulating digestive tract.2, due to its specified particle diameter scope, impact tentatively distributes in vivo, avoids effective ingredient absorbed by heart and reduce toxicity, improves medicine tumor bulk concentration simultaneously.3, the oil phase generally meeting medicinal requirements can be adopted, the sterol in oil phase is not limited, is more suitable for suitability for industrialized production; 4, while providing necessary nutrition to patient, due to sterol a certain amount of in its oil phase, to patient's cholesterol levels and rehabilitation useful.5, due to the reduction of its toxic and side effects, useful for the antitumous effect increasing dosages larger, this treatment for tumor is significant.6, there is auxiliary analgesia at performance antitumor, Nutrition is provided, more meet tumor patient treatment multi-aspect demand, significant to oncotherapy.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of Venenum Bufonis lipoclastic, and the pharmaceutical composition using prepared Venenum Bufonis lipoclastic as active component is provided further.
For this reason, the invention provides a kind of Venenum Bufonis lipoclastic, wherein the weight sum of Toadpoison Medicine, cinobufagin and resibufogenin three kinds of compositions is greater than 50% of Venenum Bufonis lipoclastic gross weight.
Further, Toadpoison Medicine 9.0% ~ 11.0%, cinobufagin 13.5% ~ 16.8%, the resibufogenin 22.5% ~ 27.5% of Venenum Bufonis lipoclastic of the present invention wherein containing following percentage by weight.
The preparation method of Venenum Bufonis lipoclastic of the present invention is as follows:
The dehydrated alcohol of medical material 5 ~ 50 times amount will be added after Venenum Bufonis pulverizing medicinal materials, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, dry extract is obtained after filtrate evaporate to dryness, after extract being added the ultrasonic suspendible of purified water of 5 ~ 30 times amount, with the chloroform extraction of 5 ~ 50 times amount, the extraction of its Chinese crude drug and extraction are the known technology of industry technology personnel.
Preferably, the preparation method of Venenum Bufonis lipoclastic of the present invention is as follows:
By adding the dehydrated alcohol of medical material 5 ~ 25 times amount after Venenum Bufonis pulverizing medicinal materials, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, dry extract is obtained, after extract being added the ultrasonic suspendible of purified water of 5 ~ 20 times amount, with the chloroform extraction of 5 ~ 40 times amount after filtrate evaporate to dryness.
Preferred, the preparation method of Venenum Bufonis lipoclastic of the present invention is as follows:
By adding the dehydrated alcohol of medical material 5 ~ 15 times amount after Venenum Bufonis pulverizing medicinal materials, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, dry extract is obtained, after extract being added the ultrasonic suspendible of purified water of 5 ~ 10 times amount, with the chloroform extraction of 5 ~ 30 times amount after filtrate evaporate to dryness.
Most preferred Venenum Bufonis lipoclastic of the present invention, is characterized in that, containing Toadpoison Medicine 10.3%, cinobufagin 16.7%, resibufogenin 26.1%.Its preparation method, step is as follows:
Venenum Bufonis fine medicinal material powder is obtained after Venenum Bufonis pulverizing medicinal materials is also crossed 200 mesh sieves, weigh fine powder, add the dehydrated alcohol of 5 times amount, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, filtrate evaporate to dryness, the dry thing of filtrate puts the dry 24h of 60 DEG C of vacuum drying ovens, obtains Venenum Bufonis extract, get Venenum Bufonis extract, after adding the ultrasonic suspendible 1h of purified water of 10 times amount, then extract extracts by the chloroform adding suspension 30 times amount, gets organic layer by its evaporate to dryness after extraction, the dry thing of gained to be put in 60 DEG C of baking ovens dry 48 hours, obtains.
The present invention further provides containing the pharmaceutical composition of Venenum Bufonis lipoclastic of the present invention as active constituents of medicine, described compositions comprises Venenum Bufonis lipoclastic, fat-soluble medium, glycerol, surfactant and water.
Venenum Bufonis lipoclastic in compositions of the present invention is preferably the Venenum Bufonis lipoclastic wherein containing Toadpoison Medicine, cinobufagin and resibufogenin prepared by the inventive method, also can be the Venenum Bufonis lipoclastic that market is bought, as derived from the Venenum Bufonis lipoclastic of Venenum Bufonis, or the Venenum Bufonis lipoclastic of synthetic.
Typically, pharmaceutical composition of the present invention, the weight percentage of each component is as follows:
All the other are water.
Fat-soluble medium described in the present composition refers to a large class physiological acceptability material, no matter is mineral oil, vegetable oil, animal oil, quintessence oil or artificial oil, or its mixture.Therefore, fat-soluble medium is in order to refer to the material with very different chemical character of a wide region.When with type or functional classification oil, as mineral oil source comprises fat or cerul hydrocarbon, the fat of aromatic hydrocarbon or mixing and aromatic radical hydrocarbon from oil.Also the oil of petroleum derivation is comprised, as refined paraffin wax wet goods in mineral oil classification.In vegetable oil classification, oil is mainly derived from seed or nut, and comprises drying oil as Semen Lini and Oleum Verniciae fordii; Semi-drying oil is as safflower oil and soybean oil; Non-drying oil as Oleum Ricini, Oleum Gossypii semen and Oleum Cocois and can be used as soap class as Petiolus Trachycarpi oil and Oleum Cocois.In animal oil classification, oil usually from as sebum, Adeps Sus domestica and stearic fat.Aqueous animal oil comprises fish oil, oleic acid, spermaceti wet goods.They are usually containing abundant fatty acid.Aqueous animal oil comprises some vegetable oil, as olive oil, and Oleum Gossypii semen, corn oil and Oleum Arachidis hypogaeae semen, also comprise the fish oil that some are special, they are widely used as medicine owing to being rich in vitamin, as morrhua liver, shark hepatic wet goods.Aqueous fatty oil is as single, double, triglyceride, or its mixture is preferred oil.According to the present invention, the triglyceride of medium chain are also available oil, are preferably long-chain fat acid glyceride, medium chain length fatty acid triglyceride, or its mixture.
Surfactant described in the present composition can be any surfactant, comprises phospholipid, polyoxyethylene sorbitan fatty acid ester, poloxalkol class, enuatrol, oleic acid, cholic acid, sodium cholate, deoxycholic acid, sodium deoxycholate and composition thereof.
Wherein said phospholipid is selected from lecithin, fabaceous lecithin, and composition thereof.
Described polyoxyethylene sorbitan fatty acid ester is selected from Tween20, Tween40, Tween60, Tween80, Tween85, or its mixture.
The preferred surfactant of the present invention is selected from: lecithin, fabaceous lecithin, enuatrol, oleic acid, Tween80, pluronic F-68, or its mixture.
Pharmaceutical composition of the present invention is the pharmaceutical preparation of liquid form, and described preparation comprises injection, suspensoid, oral solution, liniment, lotion, nasal drop, ear drop, gargarism, mixture etc.Preferred pharmaceutical composition of the present invention is lipid microsphere oral solution.
The present invention's preferred lipid microsphere oral administration solution agent prescription consists of:
| Raw material | Percentage by weight |
| Venenum Bufonis lipoclastic | 0.2-0.5％ |
| Vegetable oil | 15-25％ |
| Surfactant | 1.5-5％ |
| Glycerol | 3-5％ |
| All the other are water |
The present invention's preferred lipid microsphere oral administration solution agent prescription consists of:
| Supplementary material | Percentage by weight |
| Venenum Bufonis lipoclastic | 0.2-0.4％ |
| Soybean oil | 15-25％ |
| Ovum Gallus domesticus Flavus lecithin | 1.5-2.5％ |
| Pluronic F-68 | 0.5-0.8％ |
| Deoxycholic acid | 0.1-0.3％ |
| Glycerol | 3-5％ |
The preparation method of lipid microsphere oral solution of the present invention is as follows:
Phospholipid and Venenum Bufonis lipoclastic are joined in the oil phase of soybean oil composition, heated and stirred, to dissolving, obtains the pastille oil phase clarified; Be added in suitable quantity of water by pluronic F-68, deoxycholic acid and glycerol, heated and stirred makes dissolving, obtained aqueous phase, under the stirring of high speed dispersor, joined by aqueous phase in oil phase, rotating speed is 15000rpm, continues to stir 10min, obtained colostrum, by colostrum with salt acid for adjusting pH value to 7-8, be settled to full dose with water, be transferred in high pressure homogenizer, with 1200bar pressure homogenizing, after bottling and get final product.
The most preferred Venenum Bufonis lipoclastic of the present invention is through screening acquisition, and screening process asks for an interview embodiment.
Compared to the prior art, the present invention has the following advantages:
1, decrease digestive tract is directly stimulated.
2, toxicity is reduced.
3, improve the stability of medicine, yield, purity and antitumous effect.
4, there is auxiliary analgesia, the effect of nutrition is provided.
Beneficial effect of the present invention investigate and data as follows:
One, the experiment exam of GI irritation, antitumous effect and toxicity
The present invention carries out the strain of human colon carcinoma HCT-8 tumor with reference to cell toxicant series antineoplastic medicament non-clinical study technological guidance principle method to test medicine Bufo siccus lipid microsphere oral administration solution (being called for short by reagent), people gastric cancer BGC803 tumor strain nude mice carries out experimental observation through administration tumor suppression growth, GI irritation and toxicity.
BALB/c-nu nude mice is adopted to test.Experimental design each per os gavage Test Drug Dosages is 2mg/kg, weekly per os gastric infusion 6 times, successive administration 3 weeks.Separately establish Fluorouracil Injection group (being called for short positive drug group 1), Venenum Bufonis extract lipide microsphere injection (being called for short positive drug group 2) and enteric coating Venenum Bufonis micropill (being called for short positive drug group 3), calculate positive drug group dosage, intravenous administration 2 times weekly.Successive administration 3 weeks.Often organize and establish 10 nude mices.
Within during administration every 3 ~ 4 days, measure tumor bearing nude mice body weight, calculate tumor proliferation rate (T/C%).Experiment Continuous Observation 22-23 days.The 3 dead each experimental group tumor bearing nude mices in natural gift other places after last administration, complete stripping tumor and stomach intestinal tissue, weigh.
Two, analgesic activity experiment exam
1. by temperature control hot plate with regulate at 55 ± 0.5 DEG C, put into large beaker and fix.After putting into mice to the time of licking between metapedes be the pain sensation response time.
2. get female white mice 2, labelling, weighs.Before administration, the pain sensation response time of two Mus is first tested.Get pain the response time in 10 ~ 30s mice as test use.
3. use and carry out administration on an empty stomach to mice respectively by reagent and different positive drug group calculating dosage, 60min surveys pain sensation reaction upon administration.In testing, as analgesia reaction in 60s, should take out immediately, and in 60s.Observe the performance before and after mice administration, and carefully record result, calculate the threshold of pain improve percentage rate=(after medicine the pain sensation response time-medicine before the pain sensation response time) before/medicine the pain sensation response time × 100%, the threshold of pain improves that percentage rate is higher shows that analgesic effect is more obvious.
Experimental result is as follows:
Detailed description of the invention:
Further illustrate the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1
The extraction of Venenum Bufonis medical material
Venenum Bufonis fine medicinal material powder is obtained after Venenum Bufonis pulverizing medicinal materials is also crossed 200 mesh sieves, weigh fine powder, add the dehydrated alcohol of 5 times amount, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, filtrate evaporate to dryness, the dry thing of filtrate puts vacuum drying oven (60 DEG C) dry 24h, obtains Venenum Bufonis extract.
Embodiment 2
The extraction of Venenum Bufonis medical material
Venenum Bufonis fine medicinal material powder is obtained after Venenum Bufonis pulverizing medicinal materials is also crossed 200 mesh sieves, weigh fine powder, add the dehydrated alcohol of 15 times amount, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, filtrate evaporate to dryness, the dry thing of filtrate puts vacuum drying oven (60 DEG C) dry 24h, obtains Venenum Bufonis extract.
Embodiment 3
The extraction of Venenum Bufonis medical material
Venenum Bufonis fine medicinal material powder is obtained after Venenum Bufonis pulverizing medicinal materials is also crossed 200 mesh sieves, weigh fine powder, add the dehydrated alcohol of 10 times amount, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, filtrate evaporate to dryness, the dry thing of filtrate puts vacuum drying oven (60 DEG C) dry 24h, obtains Venenum Bufonis extract.
Embodiment 4
Venenum Bufonis extract extracts
Weigh Venenum Bufonis extract, after adding the ultrasonic suspendible 1h of purified water of 5 times amount, extract extracts by the chloroform adding suspension 5 times amount again, organic layer is got by its evaporate to dryness after extraction, the dry thing of gained to put in baking oven (60 DEG C) dry 48 hours, obtains Venenum Bufonis extract (i.e. Venenum Bufonis lipoclastic of the present invention).
Embodiment 5
Venenum Bufonis extract extracts
Weigh Venenum Bufonis extract, after adding the ultrasonic suspendible 1h of purified water of 8 times amount, extract extracts by the chloroform adding suspension 15 times amount again, organic layer is got by its evaporate to dryness after extraction, the dry thing of gained to put in baking oven (60 DEG C) dry 48 hours, obtains Venenum Bufonis extract (i.e. Venenum Bufonis lipoclastic of the present invention).
Embodiment 6
Venenum Bufonis extract extracts
Weigh Venenum Bufonis extract, after adding the ultrasonic suspendible 1h of purified water of 10 times amount, extract extracts by the chloroform adding suspension 30 times amount again, organic layer is got by its evaporate to dryness after extraction, the dry thing of gained to put in baking oven (60 DEG C) dry 48 hours, obtains Venenum Bufonis extract (i.e. Venenum Bufonis lipoclastic of the present invention).
Three, extraction effect experiment exam
Carry out further screening experiment to embodiment 1-6, the selection result is as follows:
The extract of embodiment 1-3 is carried out combination extraction according to the method for embodiment 4-6, and be prepared into different Venenum Bufonis lipoclastics respectively, measure the content of each component and the total content of three kinds of components, measurement result is as shown in the table:
Embodiment 7
Pharmaceutical composition
Prescription:
Preparation technology:
1. the phospholipid of recipe quantity and Venenum Bufonis extract are joined in the oil phase of soybean oil composition, under 60 DEG C of conditions, heated and stirred is to dissolving, and obtains the pastille oil phase clarified, for subsequent use;
2. be added in appropriate purified water by the pluronic F-68 of recipe quantity, deoxycholic acid and glycerol, 60 DEG C of heated and stirred make dissolving, obtained aqueous phase, for subsequent use;
3. under the stirring of high speed dispersor, joined by aqueous phase in oil phase, rotating speed is 15000rpm, continues to stir 10min, obtained colostrum, for subsequent use;
4. by colostrum with about salt acid for adjusting pH value to 7.5, be settled to full dose by purified water, be cooled to about 30 DEG C, be transferred in high pressure homogenizer, with 1200bar pressure homogenizing 15 times.
5. bottle, inflated with nitrogen, sealing, 121 DEG C of autoclaving 15min, are down to room temperature after taking-up, obtain final product.
Embodiment 8
Pharmaceutical composition
Prescription:
Preparation technology:
1. the phospholipid of recipe quantity and Venenum Bufonis extract are joined in the oil phase of soybean oil composition, under 60 DEG C of conditions, heated and stirred is to dissolving, and obtains the pastille oil phase clarified, for subsequent use;
2. be added in appropriate purified water by the pluronic F-68 of recipe quantity, deoxycholic acid and glycerol, 60 DEG C of heated and stirred make dissolving, obtained aqueous phase, for subsequent use;
3. under the stirring of high speed dispersor, joined by aqueous phase in oil phase, rotating speed is 15000rpm, continues to stir 10min, obtained colostrum, for subsequent use;
4. by colostrum with about salt acid for adjusting pH value to 7.5, be settled to full dose by purified water, be cooled to about 30 DEG C, be transferred in high pressure homogenizer, with 1200bar pressure homogenizing 15 times.
5. bottle, inflated with nitrogen, sealing, 121 DEG C of autoclaving 15min, are down to room temperature after taking-up, obtain final product.
Embodiment 9
Pharmaceutical composition
Prescription:
Preparation technology:
1. the phospholipid of recipe quantity and Venenum Bufonis extract are joined in the oil phase of soybean oil composition, under 60 DEG C of conditions, heated and stirred is to dissolving, and obtains the pastille oil phase clarified, for subsequent use;
2. be added in appropriate purified water by the pluronic F-68 of recipe quantity, deoxycholic acid and glycerol, 60 DEG C of heated and stirred make dissolving, obtained aqueous phase, for subsequent use;
3. under the stirring of high speed dispersor, joined by aqueous phase in oil phase, rotating speed is 15000rpm, continues to stir 10min, obtained colostrum, for subsequent use;
4. by colostrum with about salt acid for adjusting pH value to 7.5, be settled to full dose by purified water, be cooled to about 30 DEG C, be transferred in high pressure homogenizer, with 1200bar pressure homogenizing 15 times.
5. bottle, inflated with nitrogen, sealing, 121 DEG C of autoclaving 15min, are down to room temperature after taking-up, obtain final product.
The present invention screens adjuvant, and the selection result display uses the following formulation efficacy of the present invention best:
| supplementary material | percentage by weight |
| venenum Bufonis lipoclastic | 0.2-0.4% |
| soybean oil | 15-25% |
| ovum Gallus domesticus Flavus lecithin | 1.5-2.5% |
| pluronic F-68 | 0.5-0.8% |
| deoxycholic acid | 0.1-0.3% |
| glycerol | 3-5% |
| all the other are water. |
Four, formulation efficacy experiment exam
Recipe determination method is: lipid microsphere oral administration solution prepared by different auxiliary material same procedure in calorstat 40 DEG C place 3 months, measure the total content of three kinds of active components, result is as follows:
Result shows, and effect of the present invention is optimum.
Claims (10)
1. a Venenum Bufonis lipoclastic, is characterized in that, containing Toadpoison Medicine 9.0% ~ 11.0%, cinobufagin 13.5% ~ 16.8%, resibufogenin 22.5% ~ 27.5%.
2. Venenum Bufonis lipoclastic according to claim 1, is characterized in that, containing Toadpoison Medicine 10.3%, cinobufagin 16.7%, resibufogenin 26.1%.
3. the preparation method of Venenum Bufonis lipoclastic according to claim 1, it is characterized in that, step is as follows:
By adding the dehydrated alcohol of medical material 5 ~ 50 times amount after Venenum Bufonis pulverizing medicinal materials, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, obtain dry extract after filtrate evaporate to dryness, after extract being added the ultrasonic suspendible of purified water of 5 ~ 30 times amount, obtain with the chloroform extraction of 5 ~ 50 times amount.
4. the preparation method of Venenum Bufonis lipoclastic according to claim 2, it is characterized in that, step is as follows:
Venenum Bufonis fine medicinal material powder is obtained after Venenum Bufonis pulverizing medicinal materials is also crossed 200 mesh sieves, weigh fine powder, add the dehydrated alcohol of 5 times amount, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, filtrate evaporate to dryness, the dry thing of filtrate puts the dry 24h of 60 DEG C of vacuum drying ovens, obtains Venenum Bufonis extract, get Venenum Bufonis extract, after adding the ultrasonic suspendible 1h of purified water of 10 times amount, then extract extracts by the chloroform adding suspension 30 times amount, gets organic layer by its evaporate to dryness after extraction, the dry thing of gained to be put in 60 DEG C of baking ovens dry 48 hours, obtains.
5. containing the pharmaceutical composition of Venenum Bufonis lipoclastic described in claim 1 as active constituents of medicine, described compositions comprises the Venenum Bufonis lipoclastic of claim 1 or 2, fat-soluble medium, glycerol, surfactant and water, it is characterized in that, the weight percentage of each component is as follows:
6. pharmaceutical composition according to claim 4, is characterized in that, described fat-soluble medium is selected from mineral oil, vegetable oil, animal oil, quintessence oil or artificial oil, or its mixture, comprises the oil of petroleum derivation in its mineral oil in fluid, as refined paraffin wax wet goods.In vegetable oil, oil is mainly derived from seed or nut, comprises drying oil as Semen Lini and Oleum Verniciae fordii; Semi-drying oil is as safflower oil and soybean oil; Non-drying oil as Oleum Ricini, Oleum Gossypii semen and Oleum Cocois and can be used as soap class as Petiolus Trachycarpi oil and Oleum Cocois, in animal oil, grease separation is from sebum, Adeps Sus domestica and stearic fat, aqueous animal oil comprises fish oil, oleic acid, sperm oil, the triglyceride of medium chain, long-chain fat acid glyceride, medium chain length fatty acid triglyceride, or its mixture.
Wherein said surfactant is selected from: phospholipid, polyoxyethylene sorbitan fatty acid ester, poloxalkol, pluronic F-68, enuatrol, oleic acid, cholic acid, sodium cholate, deoxycholic acid, sodium deoxycholate and composition thereof;
Wherein said phospholipid is selected from lecithin, fabaceous lecithin, and composition thereof, described polyoxyethylene sorbitan fatty acid ester is selected from Tween20, Tween40, Tween60, Tween80, Tween85, or its mixture.
7. pharmaceutical composition according to claim 5, is characterized in that, be lipid microsphere oral solution, its formula consists of
8. pharmaceutical composition according to claim 7, is characterized in that, described lipid microsphere oral administration solution agent prescription consists of
9. pharmaceutical composition according to claim 8, is characterized in that, described lipid microsphere oral administration solution agent prescription consists of
Preparation technology:
1) phospholipid and Venenum Bufonis lipoclastic are joined in the oil phase of soybean oil composition, under 60 DEG C of conditions, heated and stirred is to dissolving, and obtains the pastille oil phase clarified, for subsequent use;
2) be added in partial purification water by pluronic F-68, deoxycholic acid and glycerol, 60 DEG C of heated and stirred make dissolving, obtained aqueous phase, for subsequent use;
3) under the stirring of high speed dispersor, joined by aqueous phase in oil phase, rotating speed is 15000rpm, continues to stir 10min, obtained colostrum, for subsequent use;
4) by colostrum with about salt acid for adjusting pH value to 7.5, be settled to full dose by purified water, be cooled to about 30 DEG C, be transferred in high pressure homogenizer, with 1200bar pressure homogenizing 15 times,
5) bottle, inflated with nitrogen, sealing, 121 DEG C of autoclaving 15min, are down to room temperature after taking-up, obtain final product;
The preparation method of wherein said Venenum Bufonis lipoclastic is as follows:
Venenum Bufonis fine medicinal material powder is obtained after Venenum Bufonis pulverizing medicinal materials is also crossed 200 mesh sieves, weigh fine powder, add the dehydrated alcohol of 5 times amount, reflux 1h in 60 DEG C of water-baths, let cool to room temperature, sucking filtration, filtrate evaporate to dryness, the dry thing of filtrate puts the dry 24h of 60 DEG C of vacuum drying ovens, obtains Venenum Bufonis extract, get Venenum Bufonis extract, after adding the ultrasonic suspendible 1h of purified water of 10 times amount, then extract extracts by the chloroform adding suspension 30 times amount, gets organic layer by its evaporate to dryness after extraction, the dry thing of gained to be put in 60 DEG C of baking ovens dry 48 hours, obtains.
10. the application in the medicine of preparation treatment digestive tract tumor of the Venenum Bufonis lipoclastic described in claim 1-9 or its pharmaceutical composition.
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| CN107233349A (en) * | 2017-07-07 | 2017-10-10 | 黄娇艳 | Application of the drug combination in the medicine for the treatment of leukaemia or lymthoma is prepared |
| CN107281190A (en) * | 2017-07-10 | 2017-10-24 | 黄志敏 | A kind of medicine for treating digestive tract ulcer |
| CN107595892A (en) * | 2017-08-29 | 2018-01-19 | 苏州大学 | Application of the toad cake extract in terms of T type calcium ion channel blockor medicines are prepared |
| CN109464469A (en) * | 2018-10-19 | 2019-03-15 | 江苏浦金药业有限公司 | A kind of extracting method of the dried venom of toads |
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| CN107281190A (en) * | 2017-07-10 | 2017-10-24 | 黄志敏 | A kind of medicine for treating digestive tract ulcer |
| CN107595892A (en) * | 2017-08-29 | 2018-01-19 | 苏州大学 | Application of the toad cake extract in terms of T type calcium ion channel blockor medicines are prepared |
| CN109464469A (en) * | 2018-10-19 | 2019-03-15 | 江苏浦金药业有限公司 | A kind of extracting method of the dried venom of toads |
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Address after: 100176 Beijing Beijing economic and Technological Development Zone, Chuang Chuang thirteen Street 31 hospital two District 7 Building 101 room. Applicant after: Beijing nukangda medicine Polytron Technologies Inc Address before: 100176 Beijing Daxing District Beijing economic and Technological Development Zone Yongchang road 3 No. 8 Yongchang science and Technology Plaza 505 room Applicant before: BEIJING NUOKANGDA PHARMACEUTICAL CO., LTD. |
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Application publication date: 20151209 |