CN1634119A - Liquid embolism agent for intracranial aneurysm and its preparing process - Google Patents
Liquid embolism agent for intracranial aneurysm and its preparing process Download PDFInfo
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- CN1634119A CN1634119A CN200410065732.5A CN200410065732A CN1634119A CN 1634119 A CN1634119 A CN 1634119A CN 200410065732 A CN200410065732 A CN 200410065732A CN 1634119 A CN1634119 A CN 1634119A
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- pseudobulbus bletillae
- aneurysm
- suppository
- thromboembolism
- polysaccharose
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Abstract
The invention relates to an intracranial aneurysm liquid suppository, which is prepared by mixing polysaccharide extract of bletilla striata, a crude medicinal herb with cellulose diacetate polymeride by a finite proportion, wherein the development composition is IohexoI, the dissolvent composition is dimethyl sulphoxide as organic solvent. The invention also relates to the process for preparing the liquid suppository. The liquid suppository can be applied to the interventional therapy of intracranial aneurysm.
Description
One, technical field
The invention belongs to biological pharmacy technical field, relate to a kind of liquid embolism agent for intracranial aneurysm and preparation method thereof.
Two, background technology
Intracranial aneurysm is the neurosurgery common disease, and main causes of death are hemorrhage and early stage complication [people such as Hop JW, " Stroke ", the 28th volume, 660-664 page or leaf (1997)].Zhi Liao unique method was to adopt surgery operation of opening cranium folder to close aneurysm in the past.Yet the shortcoming of surgery operation of opening cranium is fairly obvious: 1, and the patient's ratio that can undergo surgery is limited: or because of age, the health person of being not suitable for, or repeatedly SAH, the higher person of HH classification, or vasospasm person is arranged, operation risk is all very big; 2, surgical clamp is closed has very big blind area: be difficult to approaching or can't press from both sides fully close for back circulation or giant aneurysm etc.; 3, the surgical operation rehabilitation is slow, and the relapse rate height brings painful big to the patient.And recent two decades comes, and along with reaching its maturity of interventional therapy in the blood vessel, increasing doctor begins to select this low-risk, and Wicresoft hinders, and effectively remedies the new method of operative treatment blind area.Till 1992, all do not needed to adopt operation of opening cranium in the aneurysm of European countries 80% and only used intervention embolization [people such as Vinuela, " Interventional Neuroradiology ", 63-75 page or leaf (1992)].
The basic skills that has been used as interventional therapy mainly contains three kinds: can shirk sacculus, electrolysis can be shirked turn (GDC), and liquid embolizing agent.The sacculus of being reinstated can be difficult to the aneurysm that surgical clips closes to some and carries out thromboembolism the earliest, but its defective is also clearly: 1, can not carry out thromboembolism at the tumor shape, and easily cause aneurysm rupture; 2, sacculus easily bounces back, necessary filling silicone fluid or firming agent (HEMO) in it; 3, sacculus and delivery conduit pliability are poor, are difficult to operation.The GDC that has obtained at present domestic and international clinical practice then has two bigger technical restrictions: 1, and the GDC compression is recurred with aneurysm, and can cause the pressure symptom of brain essence or cranial nerve, this more normal appearance in wide neck and big or giant aneurysm; 2, the GDC metal material has any biological inert, and thrombosis is difficult for forming people such as [, " interventional radiology magazine ", the 12nd the 3rd phase of volume, 233-235 page or leaf (2003 years)] Zhang Xin in the tumor.The treatment principle of liquid embolizing agent is to contact with the blood in tumor chamber by entering the tumor chamber, the rapid disperse of solvent, and embolization material is condensed into solid thromboembolism aneurysm in very short time.Compared with above two kinds of methods, liquid embolizing agent has easily and flows, and is easy to control, many irreplaceable advantages such as good biocompatibility, the suitable liquid embolism materials be developed to advanced subject for interventional radiology.
A kind of ideal liquid embolizing agent should possess following condition: 1, and excellent biological compatibility; 2, can produce effective blood vessel embolism and bring out thrombosis; 3, nontoxic, no teratogenesis, carcinogenesis; 4, low concentration, low viscosity, easy to control, easy conduit by different size; 5, under the X line, can develop; 6, do not drift about after entering the tumor chamber to far-end.The intravascular fluid body embolism materials of experiment and clinical use is various in style in recent years, report that more is the positive butyl ester of alpha-cyanoacrylate (NBCA), cellulose acetate polymer (cellulose acetate polymer, CAP), polypropylene cyanogen (polyacrylonitrile, PAN), ethylene and vinyl alcohol polymer EVAL (ethylene vinyl copolymer) and EVOH (ethylene vinyl alcoholcopolymer) be several.The application shortcoming of these materials is also clearly: have adhesiveness as NBCA, easily make microtubular and blood vessel adhesion, shortcoming such as each thromboembolism focus amount is few; Traditional CAP solution does not have well to solve the technical barrier of control tumor intracavity far-end drift.The most sophisticated at present liquid embolizing agent ONYX then is the mixture that the following vinyl alcohol copolymer (EVOH), dimethylsulfoxide solvent and micronize tantalum powder three form.It has stronger polymerism, and basic adhesion conduit, and the case report of thromboembolism success is at home and abroad all arranged.But there is the problem of uncontrollable tumor intracavity far-end drift equally in ONYX itself, in the imported product of clinical practice, then be to have adopted parent artery placement shutoff sacculus to solve, so both strengthened cost, introduced new foreign body again in vivo at the aneurysm eck.In addition, ONYX can not be applied to can't be with the aneurysm of sacculus sealing, and also will be at first in the treatment of tumor neck place placing rack during for the aneurysm of non-constant width neck, and then inject after placing balloon occluder tumor neck, this has all limited the range of application of this liquid embolizing agent greatly.[people such as Song Donglei, " Chinese clinical neuroscience ", the 11st 4 phases of volume, 383-386 page or leaf (2003 years)].
Three, summary of the invention
Technical problem to be solved by this invention is to disclose a kind of liquid embolizing agent that is used for the intracranial aneurysm interventional therapy, polyoses extract that it comprises effective thromboembolism composition is the natural drug Pseudobulbus Bletillae (Rhizoma Bletillae) and cellulose diacetate polymer, develop to and be divided into iohexol, solvent composition is a dimethyl sulfoxine.
The present invention relates to the preparation method of liquid embolizing agent.
The invention still further relates to the processing method of development composition in the liquid embolizing agent.
Effectively the polyoses extract of the natural drug Pseudobulbus Bletillae (Rhizoma Bletillae) of one of thromboembolism composition is from orchid Pseudobulbus Bletillae (Rhizoma Bletillae) tuber.Relevant studies show that, Pseudobulbus Bletillae polysaccharose have the blood coagulation of promotion and thrombosis, promote vascular endothelial growth, effects such as blood vessel and digestive tract ulcer healing.
Two kinds of effective thromboembolism compositions are dissolved in the organic solvent dimethyl sulfoxine with form of mixtures among the present invention.
Development composition iohexol is to obtain after the commodity iohexol inj is handled.Processing method has two kinds, and a kind of is that the commodity iohexol inj is carried out lyophilization; Another kind is to adopt the mode of distilling under reduced pressure to concentrate to the commodity iohexol inj.
The preparation of liquid embolizing agent of the present invention may further comprise the steps:
1, the pure product preparation of Pseudobulbus Bletillae polysaccharose: get the natural drug Pseudobulbus Bletillae (Rhizoma Bletillae), carry out the preliminary extracting of polysaccharide component, and through removing albumen, ion-exchange chromatography and gel permeation chromatography obtain the pure product of Pseudobulbus Bletillae polysaccharose extract;
2, development composition preparation:, get iohexol white solid powder with the lyophilizing of commodity iohexol inj;
3, the liquid embolizing agent preparation: take by weighing Pseudobulbus Bletillae polysaccharose extract and cellulose diacetate in the ratio range, be dissolved in the organic solvent dimethyl sulfoxine under the heating condition, the cooling back adds the development composition, and dissolving back cold preservation is standby.
Composition advantage of the present invention is very significant: Pseudobulbus Bletillae polysaccharose is in suppository, and the viscosity of utilization itself has played the thromboembolism effect on the one hand; Owing to possess thromboplastic biological nature, quickened the formation of thrombosis on the other hand; Pseudobulbus Bletillae polysaccharose also possesses the function that promotes vascular endothelial cell growth in addition, achieves many things at one stroke.The cellulose diacetate polymer has good effect of embolization as the liquid embolic material of classics.Develop to branch and removed water in the commodity iohexol inj after treatment, avoided the destruction of water suppository stability.
The proportioning that the present invention taked is that the inventor tests in a large number to grope to sum up and draws, each amounts of components is: in per 16 milliliters of dimethyl sulfoxines, the polyoses extract 0.1-0.3 gram and cellulose diacetate polymer 0.5-0.7 gram that contain the natural drug Pseudobulbus Bletillae (Rhizoma Bletillae), and 4 milliliters of contrast agent liquid iodophor mykol or solid-state iohexol 2.0-2.5 gram.
Preferably implement the present invention down at 30 ℃-40 ℃.
The present invention on the one hand, has solved well and need not to stop the far-end drift under the auxiliary material situations such as sacculus, support, and formed effective thromboembolism and bring out thrombotic technical barrier in the scope of tumor chamber by to the groping of thromboembolism condition; On the other hand, the natural drug polyoses extract in the thromboembolism composition has fabulous biocompatibility and short thrombotic effect.The present invention satisfies the condition that a ideal liquid embolizing agent should possess, and has reached the safety of better effect of embolization and Geng Gao.
Four, description of drawings
Fig. 1 (a) gets single eluting sugar peak for Pseudobulbus Bletillae polysaccharose half pure product through gel permeation chromatography.
Fig. 1 (b) is the pure product infrared spectrum of Pseudobulbus Bletillae polysaccharose figure.
Fig. 2 is the photo of the full liquid of external model aneurysm under the DSA supervision.
Fig. 3 carries out the intubate thromboembolism for DSA monitors down to the external model aneurysm.
Fig. 4 (a) and Fig. 4 (b) are the outward appearance that external thromboembolism finishes artery tumor model.
Fig. 5 (a) and Fig. 5 (b) monitor the aneurysmal photo of animal model down for DSA.
Fig. 6 prepares to carry out the X-ray photograph of thromboembolism for animal model aneurysm intubate is put in place.
Fig. 7 is the X-ray photograph when the animal model aneurysm is carried out thromboembolism.
Fig. 8 (a) and Fig. 8 (b) are for finishing to withdraw from conduit to animal model aneurysm thromboembolism, and tumor chamber thromboembolism is abundant, the X-ray photograph that parent artery is unimpeded.
Five, the specific embodiment
The preparation of 1 liquid embolizing agent
Get the commercially available Chinese medicine Pseudobulbus Bletillae (Rhizoma Bletillae), fully pulverized the back decocting in water 3 hours, seethe with excitement 8-10 time, three layers of filtered through gauze are got filtrate, add the two volumes dehydrated alcohol, and precipitation is spent the night; Centrifugal supernatant discarded is got the precipitation sucking filtration after three times repeatedly, is dissolved in distilled water, Sevag method protein precipitation impurity people such as [, " Carbohydr Chem ", the 5th volume page 5 (nineteen sixty-five)] Staub, and repeated multiple times to Coomassie brilliant blue method detects no albumen; The absolute ether extraction, the lyophilizing of water intaking phase gets the Pseudobulbus Bletillae polysaccharose crude product; Crude product is through DE-52 ion exchange column (Whatman product) chromatography, anthrone-sulfuric acid process detect single eluting peak, lyophilizing gets Pseudobulbus Bletillae polysaccharose half pure product; Half pure product are through Sephadex G-200 solvent resistant column (Pharmacia product) chromatography, anthrone-sulfuric acid process detect single eluting peak, see Fig. 1 (a).Lyophilizing gets the pure product of Pseudobulbus Bletillae polysaccharose, and infrared spectrum detects polysaccharide and consists of glucose and mannose, sees Fig. 1 (b).
With the lyophilizing of commodity iohexol inj, get iohexol white solid powder.Under aseptic technique, take by weighing pure product of Pseudobulbus Bletillae polysaccharose and cellulose diacetate, heating in water bath also remains under 55 ℃-65 ℃, and magnetic agitation makes it to be dissolved in fully the organic solvent dimethyl sulfoxine.Be cooled to room temperature, add development composition iohexol, stir once more, extremely transparent uniform solution is completed into.Since after the thromboembolism principle of liquid embolizing agent is the contact water, the rapid disperse of dimethyl sulfoxine, effectively embolization material is condensed into solid in very short time, and therefore the whole process of operation avoids suppository to contact with water or aqueous phase solution.
Liquid embolizing agent preparation finishing back cold preservation was used preceding 37 ℃ of heating in water bath 10-15 minutes in 4 ℃ of refrigerators.
The external model experiment (one) of 2 liquid embolizing agents
External model is made up of three parts: intracranial parent artery, aneurysm and heart.Parent artery is the silica gel tube simulation of 3mm by internal diameter, and aneurysm is by the made ball-type cavity simulation of the silica gel tube of 4mm, and the blood-pumping function of heart is simulated by water pump, and " blood vessel " inner blood is simulated by normal saline.Parent artery and aneurysm are embedded in the curved groove that carves on the veneer.
The building method of external model is: at first the long internal diameter of clip 1.6cm is the silica gel tube of 4mm, puts into after the steel ball burning heat with internal diameter 5mm to make it to expand, and with the taking-up of steel ball from the segment silica gel tube, the other end is sealed after the cooling again, becomes the tumor chamber; Be to cut an osculum on the silica gel tube of 3mm at internal diameter,, but will reserve duct entry the adhesion that coincide with it of tumor chamber opening.Water flowing leak detection in pipe after several minutes.Water pump provides the interior normal saline of pipe to keep mobile pressure, requires flow velocity to arrive 320ml/min at 280ml/min.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, and cellulose diacetate 1.1 grams do not add the Pseudobulbus Bletillae polysaccharose extract.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, the injecting fluid suppository, and initial 0.2-0.5ml suppository can pass through conduit smoothly, promotes slowly afterwards, and suppository glue flowability is not good, and the phenomenon of adhesion conduit is arranged.Continue to promote suppository, at its contact " blood " 10-15 conduit took place after second and stop up.
The external model experiment (two) of 3 liquid embolizing agents
External model makes up with embodiment 2.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, and cellulose diacetate 0.4 gram does not add the Pseudobulbus Bletillae polysaccharose extract.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, the injecting fluid suppository, but promotion solidify immediately after its contact " blood " with mobile good, washed away by " blood flow " and the far-end drift phenomenon take place.
The external model experiment (three) of 4 liquid embolizing agents
External model makes up with embodiment 2.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, and Pseudobulbus Bletillae polysaccharose extract 0.3 gram does not add cellulose diacetate.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, the injecting fluid suppository, but promotion but after its contact " blood ", do not solidify with mobile good, washed away by " blood flow " at once and the far-end drift phenomenon take place.
The external model experiment (four) of 5 liquid embolizing agents
External model makes up with embodiment 2.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, and Pseudobulbus Bletillae polysaccharose extract 0.7 gram does not add cellulose diacetate.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, the injecting fluid suppository, but promotion but after its contact " blood ", do not solidify with mobile good, washed away by " blood flow " at once and the far-end drift phenomenon take place.
The external model experiment (five) of 6 liquid embolizing agents
External model makes up with embodiment 2.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, pure product 0.4 gram of cellulose diacetate, Pseudobulbus Bletillae polysaccharose extract 0.1 gram.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, the injecting fluid suppository, but promotion but after its contact " blood ", solidify immediately with mobile good, quilt " blood flow " washes away and the far-end drift phenomenon takes place behind the 3-5s.
The external model experiment (six) of 7 liquid embolizing agents
External model makes up with embodiment 2.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, pure product 0.8 gram of cellulose diacetate, Pseudobulbus Bletillae polysaccharose extract 0.3 gram.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, the injecting fluid suppository, and initial the promotion slowly, suppository glue flowability is not good, and the phenomenon of adhesion conduit is obvious.Very fast generation conduit stops up.
The external model experiment (seven) of 8 liquid embolizing agents
External model makes up with embodiment 2.
According to embodiment 1 described method obtaining liq suppository, each amounts of components is to contain iohexol white solid powder 2.4 grams in per 16 milliliters of dimethyl sulfoxines, pure product 0.6 gram of cellulose diacetate, Pseudobulbus Bletillae polysaccharose extract 0.1 gram.
In external model, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, and " blood flow " fills " tumor chamber ".The injecting fluid suppository, but suppository glue promotion bleaches in the time in 40s-50s after the contact " blood " fully with mobile good.
Open DSA Digital Subtraction radiography and monitor, carry out external thromboembolism experiment.The 1.5F conduit is inserted the tumor chamber, open current, test speed is 300ml/min, and " blood flow " fills " tumor chamber ", sees Fig. 2.The start injection liquid embolizing agent, development effect is clear, but suppository glue promotion bleaches in the time in 17s-24s after the contact " blood " fully with mobile good.See Fig. 3.
Thromboembolism 20 routine aneurysm model altogether, each example are all selected to withdraw from microtubular behind thromboembolism 80% cavity, and it is rapid to withdraw from process, conduit mouth adhesion, the drift of suppository parent artery far-end or suppository all do not take place be spilled over to endovascular phenomenon.Close radiography after thromboembolism finishes and monitor, observe " tumor chamber " full white colloid, it is moderate to touch hardness, and " tumor chamber " mouth is no thread residual, sees Fig. 4 (a) and Fig. 4 (b).This result shows that effect of embolization of the present invention is ideal in the external model.
Hemangioma model experiment in the animal body of 9 liquid embolizing agents
Laboratory animal:
Choose two of adult healthy rabbit, body weight is respectively 2.6, and 3.0kg is male.
Method:
Adopt the vein transplantation method to make up animal blood vessels tumor model, step is as follows: get 6 hours rabbit of fasting, the pentobarbital (25mg/kg) of auricular vein injection 1% makes its general anesthesia, employing is the median incision to the breastbone upper limb from the thyroid cartilage lower edge, appear the total vein of left side neck, separate and intercept the vein of one section 1-2cm, be soaked in the heparin saline standby.The medisection platysma appears and separates the about 3-4cm of bilateral carotid.The left carotid far-end cuts off after the near-end ligation with the blocking-up of interim blocking-up folder.Form the tunnel at the trachea rear, the broken ends of fractured bone of the near-end of left carotid is placed the right side by the tunnel.Right carotid near-end and far-end temporary interruption.Place operating microscope, carry out reconstructing blood vessel, further venous pocket is coincide into the about 7-9mm of diameter, two kinds of dissimilar aneurysm model of the top aneurysm of the about 4-6mm of tumor neck and side aneurysm with the noinvasive suture.Carry out the radiography evaluation after 5-7 days.Two rabbits form 4 in aneurysm altogether, and wherein top aneurysm and side aneurysm are each two, all form good.
For exploring the maximum magnitude that is suitable for prescription in the body, according to embodiment 6 schemes preparation suppository.
The rabbit fasting is 6 hours before the thromboembolism operation, with ketamine 15mg/ml and atropine 0.04mg/ml as general anesthesia before medication, animal lies on the back and is fixed in operating-table, instil 1% pentobarbital (25mg/kg) of auricular vein keeps general anesthesia.Carry out radiography, observe aneurysm model once more, all right.One side groin cropping, sterilization behind separation subcutaneous tissue and the muscle, exposes and separates femoral artery, and puncture femoral artery antetheca is sent into seal wire and conduit in the lumen of vessels.Carry out radiography once more and monitor, wire catheter is delivered to common carotid artery along arteries, searching model tumor chamber inlet also enters.Extract seal wire, the microtubular mouth is stabilized in the tumor chamber by 3/4 position, lining.Beginning is with the fltting speed injecting fluid suppository of per minute 0.2ml/min.Wherein one top aneurysm and side aneurysm enter at suppository that 4-5 thromboembolism glue all took place taken out of the tumor accent and waft and brim with phenomenon with the far-end that blood flow washes away by blood flow after second behind the tumor chamber, should not continue injection; Similar phenomenon also takes place in the side aneurysm of another animal, but top aneurysm thromboembolism is good, treats to select to withdraw from microtubular, the opening part noresidue of tumor chamber behind the tumor chamber thromboembolism 80%.Ligation is subsequently sewed up.Stitching finishes a back animal is done the video observation, finds that its top aneurysm still exists, full blood in it, and thromboembolism glue does not exist.Supposition is after microtubular withdraws from, and the phenomenon that washed away by blood flow also takes place the glue of injection.
Hemangioma model experiment in the animal body of 10 liquid embolizing agents
Laboratory animal;
Choose 12 of adult healthy rabbit, body weight 2.5-3.5kg is male.Be divided into first at random, second, the third three groups, every group is 4, corresponds to behind the thromboembolism 24 hours respectively, 2 weeks behind 1 week and the thromboembolism behind the thromboembolism.
Method:
Method according to embodiment 9 makes up the hemangioma model, and 12 rabbits form 30 in aneurysm altogether, and wherein the top aneurysm is 11, and 19 in side aneurysm all forms good.
According to embodiment 8 schemes preparation suppository.
The rabbit fasting is 6 hours before the thromboembolism operation, with ketamine 15mg/ml and atropine 0.04mg/ml as general anesthesia before medication, animal lies on the back and is fixed in operating-table, instil 1% pentobarbital (25mg/kg) of auricular vein keeps general anesthesia.Carry out radiography, observe the hemangioma model once more, all right.See Fig. 5 (a) and Fig. 5 (b).One side groin cropping, sterilization behind separation subcutaneous tissue and the muscle, exposes and separates femoral artery, and puncture femoral artery antetheca is sent into seal wire and conduit in the lumen of vessels.Carry out radiography once more and monitor, wire catheter is delivered to common carotid artery along arteries, searching model tumor chamber inlet also enters.Extract seal wire, the microtubular mouth is stabilized in the tumor chamber by 3/4 position, lining, see Fig. 6.Beginning is seen Fig. 7 with the fltting speed injecting fluid suppository of per minute 0.2ml/min.Treat to select to withdraw from microtubular behind the tumor chamber thromboembolism 80%, Fig. 8 (a) and Fig. 8 (b) are seen in the opening part noresidue of tumor chamber.Ligation is subsequently sewed up, and returns cage to raise.
The result:
1, animal ordinary circumstance: no abnormal change.
2, imageology is observed: the X-ray sheet shows that all rabbit carotid aneurysm chamber models are all entirely shut, and tumor chamber opening part is not seen thread residual, and the parent artery far-end is not seen the suppository drift.
3, specimen is observed substantially: all tumor chambeies are all firmly clogged by solid matter, are creamy white, and are slightly faint yellow.The first group is seen the suppository smooth surface, occupies the tumor cavity volume more than 80%, near tumor chamber opening part thrombosis is arranged, and the hardness ratio sponge is harder; The second group sees that suppository combines closely with the tumor chamber, occupies tumor cavity volume 90% or is full of whole tumor chamber, and hardness obviously increases; See that suppository is full of whole tumor chamber for third group, no gap, suppository hardness height, tumor chamber opening thrombosis situation is obvious, but does not protrude into parent artery fully.
4, pathological observation: light microscopic Carapax et Plastrum Testudinis group is seen suppository and tumor intracavity portion good knitting, and also has the space between the cervical region of tumor chamber, and thrombosis is arranged in it; Second group suppository and tumor intracavity portion merge closely, with tumor chamber cervical region local little space are only arranged, and are full of by thrombosis, visible fusiform cells in the thrombosis, the endotheliocyte of simultaneously visible atrophy; See that suppository and tumor chamber merge fully for third group, the tumor chamber visible endotheliocyte of cervical region is discontinuous, and a small amount of inflammatory cell infiltration is arranged, and the collagen fiber cell is arranged.The parent artery surrounding tissue does not have inflammatory cell infiltration.
The result shows that liquid embolizing agent of the present invention is complete for hemangioma model thromboembolism in the animal body, and far-end drift or blood vessel that suppository do not occur are interior residual, and tumor neck place thrombosis is good, and none example of animal is dead or occur unusual.The animal vivo test safety of liquid embolizing agent and effectively.
Claims (3)
1, a kind of liquid embolism agent for intracranial aneurysm is characterized in that being mixed by a certain percentage by polyoses extract and the cellulose diacetate polymer of the natural drug Pseudobulbus Bletillae (Rhizoma Bletillae), develops to be divided into iohexol, and solvent composition is a dimethyl sulfoxine.
2, the preparation method of the described intracranial aneurysm suppository of a kind of claim 1 is characterized in that carrying out according to the following steps:
(1) the pure product preparation of Pseudobulbus Bletillae polysaccharose: get the natural drug Pseudobulbus Bletillae (Rhizoma Bletillae), carry out the preliminary extracting of polysaccharide component, and through removing albumen, ion-exchange chromatography and gel permeation chromatography obtain the pure product of Pseudobulbus Bletillae polysaccharose extract;
(2) development composition preparation:, get iohexol white solid powder with the lyophilizing of commodity iohexol inj;
(3) liquid embolizing agent preparation: take by weighing Pseudobulbus Bletillae polysaccharose extract and cellulose diacetate in the ratio range, be dissolved in the organic solvent dimethyl sulfoxine under the heating condition, the cooling back adds the development composition, and dissolving back cold preservation is standby.
3, the described Pseudobulbus Bletillae polysaccharose preparation method of extract of a kind of claim 2 is characterized in that carrying out according to the following steps: get the commercially available Chinese medicine Pseudobulbus Bletillae (Rhizoma Bletillae), fully pulverized the back decocting in water 3 hours, and seethed with excitement 8-10 time, three layers of filtered through gauze are got filtrate, add the two volumes dehydrated alcohol, precipitation is spent the night; Centrifugal supernatant discarded is got the precipitation sucking filtration after three times repeatedly, is dissolved in distilled water, Sevag method protein precipitation impurity, and repeated multiple times to Coomassie brilliant blue method detects no albumen; The absolute ether extraction, the lyophilizing of water intaking phase gets the Pseudobulbus Bletillae polysaccharose crude product; Crude product is through DE-52 ion exchange column (Whatman product) chromatography, anthrone-sulfuric acid process detect single eluting peak, lyophilizing gets Pseudobulbus Bletillae polysaccharose half pure product; Half pure product are through Sephadex G-200 solvent resistant column (Pharmacia product) chromatography, anthrone-sulfuric acid process detect single eluting peak; It is standby that lyophilizing gets the pure product of Pseudobulbus Bletillae polysaccharose.
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| CN101195839B (en) * | 2007-12-28 | 2010-12-29 | 中华全国供销合作总社南京野生植物综合利用研究院 | Fine purification technique for bletilla striata polyoses glue |
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| CN102100933A (en) * | 2010-08-10 | 2011-06-22 | 微创医疗器械(上海)有限公司 | Embolic material composition and preparation method thereof |
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| CN103198202B (en) * | 2012-12-19 | 2017-05-17 | 首都医科大学 | Image simulation method for intracranial aneurysm interventional therapy stent implantation |
| CN111200976A (en) * | 2017-10-09 | 2020-05-26 | 微仙美国有限公司 | Plug for radioactive liquid |
| CN111200976B (en) * | 2017-10-09 | 2023-07-07 | 微仙美国有限公司 | Radioactive liquid embolism |
| CN112592446A (en) * | 2020-12-09 | 2021-04-02 | 澳门大学 | Three-dimensional macroporous frozen gel scaffold and preparation method and application thereof |
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