CN106389393A - Biological protein glue-triamcinolone acetonide slow release agent as well as preparation method and application of slow release agent - Google Patents
Biological protein glue-triamcinolone acetonide slow release agent as well as preparation method and application of slow release agent Download PDFInfo
- Publication number
- CN106389393A CN106389393A CN201611040732.9A CN201611040732A CN106389393A CN 106389393 A CN106389393 A CN 106389393A CN 201611040732 A CN201611040732 A CN 201611040732A CN 106389393 A CN106389393 A CN 106389393A
- Authority
- CN
- China
- Prior art keywords
- triamcinolone acetonide
- solution
- releasing agent
- slow releasing
- aprotinin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention provides a biological protein glue-triamcinolone acetonide slow release agent as well as a preparation method and application of the slow release agent. The slow release agent comprises biological protein glue, aprotinin and triamcinolone acetonide, wherein the biological protein glue is used as a medicine carrier, the aprotinin is used as a slow solvent, and triamcinolone acetonide is taken as an effective medicine component. The prepared biological protein glue-triamcinolone acetonide slow release agent is directly sprayed to a corresponding surgical region of a digestive tract by virtue of an endoscope and is capable of playing a durable anti-inflammatory role, so that the formation of postoperative scars is reduced, the postoperative esophageal stenosis is prevented, and the life quality of a patient is effectively improved.
Description
Technical field
The present invention relates to slow releasing preparation field, particularly to biological fibrin glue-Triamcinolone Acetonide slow releasing agent and preparation method and
Application.
Background technology
The esophageal carcinoma is initiated by the malignant tumor of Esophageal Mucosa epithelium, and the sickness rate of the esophageal carcinoma is pernicious in the world
The 8th is occupied, mortality rate is the 6th in tumor.China is one of esophageal carcinoma country the most occurred frequently, domestic annual esophageal carcinoma neopathy
Example more than 220,000, death about 200,000, usual patient with esophageal carcinoma advances to middle and advanced stage when making a definite diagnosis, and overall 5 years survival rates are not
Foot 20%, and the early stage esophageal carcinoma generally can be effected a radical cure through endoscopic minimally-invasive treatment, survival rate can exceed 95% within 5 years.At present, scope
Lower mucosectomy (Endoscopic mucosal resection EMR) and Endoscopic submucosal dissection (endoscopic
Submucosal dissection ESD) be the early stage esophageal carcinoma primary treatment regimen.But, EMR and ESD would generally destroy
Esophageal patient's mucous layer, leads to esophagostenosiss.Research shows, the mucous membrane of esophagus more than 3/4ths weeks is peeled off, and postoperative esophaguses are narrow
Narrow incidence rate is up to 88-100%, causes serious impact to the quality of life of patient.
Expand narrow positions by mechanical means, can release for patient painful within a short period of time.But, esophagostenosiss
Easily recur, multiple interventional therapy need to be carried out, this undoubtedly can increase the damage of digestive tract inwall and the generation of complication, leads to scar
Trace is formed, and forms esophagostenosiss.Esophagostenosiss are the mucous layer inflammatory reactions because the destruction of muscularis propria and fibrosiss lead to
Disappearance will avoid the infringement of muscularis propria and excess fibrosis thus preventing esophagostenosiss.Steroid hormone can reduce dried meat ammonia
The activation of acyl hydroxylase, promotes the activation of collagenase to react thus reducing the content of tissue collagen to reduce inflammation.Based on this
Theory, finds that the injection of Triamcinolone Acetonide under the postoperative scope of ESD can effectively prevent the generation of esophagostenosiss.But, local class is solid
The injection of alcohol medicine generally requires multiple medication under the auxiliary of intervening equipment, and this misery that undoubtedly can increase patient and economy are born
Load, the wound surface scope of different operations, injection system and injection dosage, also bring along different curative effect, meanwhile, multiple injection meeting
There is the risk puncturing bleeding.
Content of the invention
For above-mentioned problems of the prior art, the invention provides biological fibrin glue-Triamcinolone Acetonide slow releasing agent and
Preparation method and application, by scope direct spraying slow releasing agent at the corresponding operative region of digestive tract, can play lasting antiinflammatory and make
With, reduce postoperative scar and formed, prevention of postoperative esophagostenosiss, it is effectively improved patients ' life quality.
The present invention provide a kind of technical scheme be：A kind of biological fibrin glue-Triamcinolone Acetonide slow releasing agent, slow releasing agent comprises to give birth to
Thing albumin glue, aprotinin, Triamcinolone Acetonide, wherein, the mass fraction of biological fibrin glue is 1.8%～4.0%, the quality of aprotinin
Fraction is 0.08%～0.10%, and the mass fraction of Triamcinolone Acetonide is 0.09%～0.33%.
The preparation method of above-mentioned slow releasing agent, has steps of,
1) take aprotinin, dissolving is configured to the aprotinin solution that mass concentration is 10%；
2) take Triamcinolone Acetonide, dissolving is configured to the Triamcinolone Acetonide solution that concentration is 10mg/ml；
3) it is respectively configured bioprotein main body sol solution, catalyst solution, wherein, bioprotein main gel solution concentration is
50～90mg/ml, catalyst solution concentration is 500IU/ml；
4) take 1 debulking step 3) the bioprotein main body sol solution that configures, 0.01 debulking step 1) aprotinin that configures is molten
Liquid, 0.125～0.375 debulking step 2) the Triamcinolone Acetonide solution that configures, mix；
5) take 1 debulking step 3) catalyst solution that configures, 0.01 debulking step 1) configure aprotinin solution, 0.125
～0.375 debulking step 2) the Triamcinolone Acetonide solution that configures, mix；
6) by step 4), step 5) mixed liquor mixing, condense, obtain biological fibrin glue-Triamcinolone Acetonide slow releasing agent.
Above-mentioned steps 1) use physiological saline solution aprotinin, step 2) use sterilized water for injection solution Triamcinolone Acetonide.
Above-mentioned slow releasing agent is in the purposes of the biological sustained release profile in vivo test Cinacort Span of preparation simulation.
The present invention provide another kind of technical scheme be：A kind of biological fibrin glue-Triamcinolone Acetonide slow releasing agent, slow releasing agent includes
Biological fibrin glue, Triamcinolone Acetonide, wherein, the mass fraction of biological fibrin glue is 2.5%～4.5%, and the quality of Triamcinolone Acetonide is divided
Number is 0.13%～0.38%.
The preparation method of above-mentioned slow releasing agent, has following steps：
1) take Triamcinolone Acetonide, dissolving is configured to the Triamcinolone Acetonide solution that concentration is 10mg/ml；
2) with step 1) the Triamcinolone Acetonide solution that configures makees solvent, and configuration concentration is the bioprotein master of 50～90mg/ml
Body sol solution；
3) configuration concentration is the catalyst solution of 500IU/ml；
4) by step 2) gained bioprotein main body sol solution and step 3) gained catalyst solution equal-volume mixes, coagulates
Knot, obtains biological fibrin glue-Triamcinolone Acetonide slow releasing agent.
Above-mentioned steps 1) dissolve Triamcinolone Acetonide with sterilized water for injection.
Above-mentioned slow releasing agent treats the purposes in the preparation of postoperative stenosis in preparation for preventing and treating digestive endoscope.
The invention has the advantages that：
Biological fibrin glue extracts from biological tissue, by multiple coercibility such as Fibrinogen, thrombin and thrombin
Albumen forms, and itself has hemostasis, wound closure, bonding breach, the effect of promotion healing.Biological fibrin glue implants
Afterwards, according to local fibrinolytic and biological fibrin glue volume, can be absorbed by tissue degradation in 8～18d, toxic and side effects are less,
There is not foreign body residue problem, it is to avoid the problem needing second operation to take out after some biomaterials implantation.
Triamcinolone Acetonide belongs to steroid hormone, is applied to prevent esophaguses ESD postoperative stenosis.
After Triamcinolone Acetonide is mixed with bioprotein main gel, then mix with catalyst, simulation occurs organism blood coagulation anti-
Should, form gelatinous fibrin polymer, Triamcinolone Acetonide is evenly distributed in this fibrin polymer.Fibrin is many
Aggressiveness has stable and specific spongy three dimensional structure, and surface area is larger, can extend the autolysis time and release with Triamcinolone Acetonide
Put the time, be built in three dimensional structure between multiple cells, form the structure of similar semipermeable membrane, Triamcinolone Acetonide is evenly distributed on fibre
The polymeric each cell of fibrillarin is interior, can along Concentraton gradient direction from semipermeable membrane constantly between cell to exosmosis, realize slow
Release the purpose of Triamcinolone Acetonide, be persistently administered at corrective surgery region, effectively prevent traditional treatment means and pass through intervening equipment
Assist the defect of multiple medication.Additionally, biological fibrin glue also has the advantages that crushing resistance, shape-plastic, in conjunction with gastral
Pipeline feature, is highly suitable for digestive tract medication.
When slow release Triamcinolone Acetonide in simulation organism in normal saline, the aprotinin adding during preparing slow releasing agent
For slowing down albumin glue rate of set, so that Triamcinolone Acetonide is evenly distributed in biological fibrin glue, Triamcinolone Acetonide can be effectively ensured and delay
The ride comfort released.
The biological fibrin glue that the present invention prepares-Triamcinolone Acetonide slow releasing agent, can play lasting antiinflammatory action, reduce postoperative
Cicatrization, effectively prevents Postoperative Esophagus Stenosis, reduces postoperative complication.For once daily, reduce treatment patients'
Number of times, mitigates patient burden, is effectively improved the quality of life of patient.
Biological fibrin glue used by the present invention, purchased from Shanghai Laishi Blood Product Co., Ltd's (catalyst：Every bottle
1000IU, 2ml/ bottle, main gel：Every bottle of 100-180mg, 2ml/ bottle)；Triamcinolone acetonide acetate injection (5ml: 50mg), is purchased from
Tianjin KingYork Amino Acid Co., Ltd.；Aprotinin, purchased from Shanghai Yaxin Biotech Co., Ltd.；The desk-top constant temperature of THZ-9213 type
Agitator, purchased from Shanghai leap medical apparatus and instruments factory；Sterilized water for injection, purchased from Kelun Pharm Ind Co., Ltd., Sichuan；Physiology
Saline, purchased from Xinan Pharmaceutical Co., Ltd..
Figure of description
Fig. 1 is chromatographic determination figure, in figure, and A is the chromatogram of normal saline+aprotinin solution, and B notes for triamcinolone acetonide acetate
Penetrate the chromatogram of liquid, C is the chromatogram of Triamcinolone Acetonide+normal saline+aprotinin solution；
Fig. 2 is slow releasing agent Triamcinolone Acetonide releasing curve diagram in 37 DEG C of normal saline, in figure, and containing the bent peace of 2.5mg how A represents
Moral slow releasing agent, B represents the slow releasing agent of Triamcinolone Acetonide containing 5.0mg, and C represents the slow releasing agent of Triamcinolone Acetonide containing 7.5mg.
Specific embodiment
In order that the objects, technical solutions and advantages of the present invention become more apparent, with reference to embodiment, to the present invention
It is further elaborated.It should be appreciated that specific embodiment described herein, only in order to explain the present invention, is not used to limit
Determine the present invention.
Embodiment one：Prepare biological fibrin glue-Triamcinolone Acetonide slow releasing agent
1) configure aprotinin solution
Take 100mg aprotinin, with 900 μ l physiological saline solutions in aseptic no enzyme environment, fully mix, obtain aprotinin
Solution；
2) configure bioprotein main body sol solution
According to the Fibrin Glue operation instructions bought, dissolve main gel with supporting main body sol solution, obtain
Bioprotein main body sol solution；
3) configure catalyst solution
According to the Fibrin Glue operation instructions bought, with supporting calcium chloride solution catalyst-solvent (blood coagulation
Enzyme), obtain catalyst (thrombin) solution；
4) take the first supporting syringe, extraction step 2) the bioprotein main body sol solution 1ml that configures, step 1) configuration
Aprotinin solution 10 μ l, 0.125ml triamcinolone acetonide acetate injection, mix；Take the second supporting syringe, extraction step 3)
The catalyst solution 1ml of configuration, step 1) aprotinin solution 10 μ l, 0.125ml triamcinolone acetonide acetate injection of configuring, mixes
Even；The cone head part of the first syringe, the second syringe is securely attached to connect on needle stand, then the nozzle peace by each syringe
It is contained on the conehead connecting needle stand, after checking non-loosening seepage, push the first syringe, the second syringe, injection prepares simultaneously
In good thin transparent bag (thin transparent bag floor space is 2.0cm × 2.0cm), rapid condensation forms biological fibrin glue-Triamcinolone Acetonide
Slow releasing agent (2.5mg containing Triamcinolone Acetonide).
Embodiment two：Prepare biological fibrin glue-Triamcinolone Acetonide slow releasing agent
1) configure aprotinin solution
Take 100mg aprotinin, with 900 μ l physiological saline solutions in aseptic no enzyme environment, fully mix, obtain aprotinin
Solution；
2) configure bioprotein main body sol solution
According to the Fibrin Glue operation instructions bought, dissolve main gel with supporting main body sol solution, obtain
Bioprotein main body sol solution；
3) configure catalyst solution
According to the Fibrin Glue operation instructions bought, with supporting calcium chloride solution catalyst-solvent (blood coagulation
Enzyme), obtain catalyst (thrombin) solution；
4) take the first supporting syringe, extraction step 2) the bioprotein main body sol solution 1ml that configures, step 1) configuration
Aprotinin solution 10 μ l, 0.25ml triamcinolone acetonide acetate injection, mix；Take the second supporting syringe, extraction step 3)
The catalyst solution 1ml of configuration, step 1) aprotinin solution 10 μ l, 0.25ml triamcinolone acetonide acetate injection of configuring, mix；
The cone head part of the first syringe, the second syringe is securely attached to connect on needle stand, then the nozzle of each syringe is installed
On the conehead connecting needle stand, after checking non-loosening seepage, push the first syringe, the second syringe, injection is ready to simultaneously
Thin transparent bag in (thin transparent bag floor space be 2.0cm × 2.0cm), rapid condensation form biological fibrin glue-Triamcinolone Acetonide and delay
Release agent (5.0mg containing Triamcinolone Acetonide).
Embodiment three：Prepare biological fibrin glue-Triamcinolone Acetonide slow releasing agent
1) configure aprotinin solution
Take 100mg aprotinin, with 900 μ l physiological saline solutions in aseptic no enzyme environment, fully mix, obtain aprotinin
Solution；
2) configure bioprotein main body sol solution
According to the Fibrin Glue operation instructions bought, dissolve main gel with supporting main body sol solution, obtain
Bioprotein main body sol solution；
3) configure catalyst solution
According to the Fibrin Glue operation instructions bought, with supporting calcium chloride solution catalyst-solvent (blood coagulation
Enzyme), obtain catalyst (thrombin) solution；
4) take the first supporting syringe, extraction step 2) the bioprotein main body sol solution 1ml that configures, step 1) configuration
Aprotinin solution 10 μ l, 0.375ml triamcinolone acetonide acetate injection, mix；Take the second supporting syringe, extraction step 3)
The catalyst solution 1ml of configuration, step 1) aprotinin solution 10 μ l, 0.375ml triamcinolone acetonide acetate injection of configuring, mixes
Even；The cone head part of the first syringe, the second syringe is securely attached to connect on needle stand, then the nozzle peace by each syringe
It is contained on the conehead connecting needle stand, after checking non-loosening seepage, push the first syringe, the second syringe, injection prepares simultaneously
In good thin transparent bag (thin transparent bag floor space is 2.0cm × 2.0cm), rapid condensation forms biological fibrin glue-Triamcinolone Acetonide
Slow releasing agent (7.5mg containing Triamcinolone Acetonide).
Example IV：Prepare biological fibrin glue-Triamcinolone Acetonide slow releasing agent
1) configure bioprotein main body sol solution
According to the Fibrin Glue operation instructions bought, take bioprotein main gel, noted with triamcinolone acetonide acetate
Penetrate liquid and make solvent, dissolving obtains bioprotein main body sol solution；
2) configure catalyst solution
According to the Fibrin Glue operation instructions bought, with supporting calcium chloride solution catalyst-solvent (blood coagulation
Enzyme), obtain catalyst (thrombin) solution；
3) take the first supporting syringe, the second syringe, extract isopyknic step 1 respectively) bioprotein that configures
Main body sol solution and step 2) catalyst solution that configures, the cone head part of the first syringe, the second syringe is firmly connected
On connecting needle stand, then the nozzle of each syringe is arranged on the conehead connecting needle stand, after checking non-loosening seepage, pushes away simultaneously
Squeeze the first syringe, the second syringe, inject (thin transparent bag floor space is 2.0cm × 2.0cm) in ready thin transparent bag,
It is rapidly condensed into white tremelloid biological fibrin glue-Triamcinolone Acetonide slow releasing agent.
Embodiment five：Prepare biological fibrin glue blank control group
1) configure aprotinin solution
Take 100mg aprotinin, with 900 μ l physiological saline solutions in aseptic no enzyme environment, fully mix, obtain aprotinin
Solution；
2) configure bioprotein main body sol solution
According to the Fibrin Glue operation instructions bought, dissolve main gel with supporting main body sol solution, obtain
Bioprotein main body sol solution；
3) configure catalyst solution
According to the Fibrin Glue operation instructions bought, with supporting calcium chloride solution catalyst-solvent (blood coagulation
Enzyme), obtain catalyst (thrombin) solution；
4) take the first supporting syringe, extraction step 2) the bioprotein main body sol solution 1ml that configures, step 1) configuration
Aprotinin solution 10 μ l, 0.25ml normal saline, mix；Take the second supporting syringe, extraction step 3) catalysis that configures
Agent solution 1ml, step 1) aprotinin solution 10 μ l, 0.25ml normal saline of configuring, by the first syringe, the second syringe
Cone head part is securely attached to connect on needle stand, then the nozzle of each syringe is arranged on the conehead connecting needle stand, checks no
After loose leaky, push the first syringe, the second syringe simultaneously, inject (thin transparent bag bottom surface in ready thin transparent bag
Amass as 2.0cm × 2.0cm), rapid condensation forms biological fibrin glue blank control group (without Triamcinolone Acetonide).
External slow release experiment：
The biological fibrin glue that embodiment one, two, three, five is prepared is respectively placed in four beakers, and each beaker is respectively
Add normal saline 5ml, with THZ-9213 type Desk type constant-temperatureoscillator oscillator in 37 DEG C of constant temperature oscillations, every 12h (i.e. 12h, 24h,
36h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 156h, 168h) draw release liquid 5ml, and supplement life
Reason saline 5ml, continues vibration.
Chromatography：
Chromatographiccondition：Chromatographic column (Water × BridgeC18,4.6mm × 15mm, 5 μm)；Mobile phase is water：Methanol
=30: 70；Sample size：20μl；Column temperature：30℃；Detection wavelength：240nm；Flow velocity：1ml/min.
Specificity is tested
By above-mentioned chromatographiccondition, chromatography measures normal saline+aprotinin solution, triamcinolone acetonide acetate note respectively
Penetrate liquid, Triamcinolone Acetonide+normal saline+aprotinin solution, and obtain chromatogram as shown in Figure 1.By observing Fig. 1 gained chromatographic peak
Understand, preferably, Triamcinolone Acetonide retention time is about 8.6min to this test method specificity, is not detected by other materials to biological egg
The interference that in white glue, Triamcinolone Acetonide measures.
Linearity curve equation
Sterilized water for injection configuration concentration (X) is used to be 0.05 μ g/ml, 0.10 μ g/ml, 1.00 μ g/ml, 10.00 μ g/ respectively
Ml, the Triamcinolone Acetonide solution of 5 Concentraton gradient of 50.00 μ g/ml, carry out chromatography mensure by above-mentioned chromatographiccondition,
With peak area Y as dependent variable, concentration X (μ g/ml) is independent variable, calculates to obtain regression equation by linear regression：Y=63362X-
10006 (r=0.9999, n=5).Chromatographic peak area is brought into regression equation calculation respective concentration C, and calculates concentration deviation (D
=(C-X) * 100%), lowest detectable limit is determined in 5% with deviation.Result shows, Triamcinolone Acetonide is in 0.05～50 μ g/mL model
Enclose interior linearly good.
Precision Experiment
The Triamcinolone Acetonide solution being 5 μ g/ml with sterilized water for injection configuration concentration.Carry out color by above-mentioned chromatographiccondition
Analysis of spectrum measures.Measure 3 times every 3h in odd-numbered day, measure 3 batches altogether；In the daytime in same timing daily 3 times, METHOD FOR CONTINUOUS DETERMINATION
3d, it the results are shown in Table 1.In a few days average relative standard's deviation (RSD) is 0.95%, and average relative standard's deviation (RSD) is in the daytime
0.77%.
Table 1：Precision test result (n=3)
Stability experiment
Appoint the same release liquid taking the experiment of external slow release, put into refrigerator and be incubated in 4 DEG C, respectively at 0,2,4,6,8,10,15,
Carry out chromatography detection by above-mentioned chromatographiccondition, according to its Triamcinolone Acetonide of regression equation calculation obtaining when 20,30d
Content, result display RSD=0.83% (n=9), show that release liquid is stable in 30d.
Repeated experiment
Take same release liquid, be divided into 6 parts, be configured to 6 parts of parallel sampless, carry out chromatography by above-mentioned chromatographiccondition
Detection, according to the content of its Triamcinolone Acetonide of regression equation calculation obtaining, result shows RSD=1.01%, (n=6), shows this
Method repeatability is good.
Release in vitro rate
According to above-mentioned chromatographiccondition, chromatography external SR test gained release liquid, calculates to obtain chromatographic peak face respectively
Long-pending, substitute into the regression equation obtaining, obtain each sample solution concentration.Obtain the tired of Triamcinolone Acetonide further according to preparation formula
Long-pending release rate, preparation=(∑ CV)/M, wherein C is Qu An in each sample release liquid being obtained according to regression equation calculation
How moral concentration, V is each sample release liquid volume, and M is the quality being dissolved into Triamcinolone Acetonide in biological fibrin glue.To add up release rate
For vertical coordinate (Y-axis), with the time as abscissa (X-axis), do a vitro cumulative release rate curve as shown in Figure 2.As shown in Figure 2,
Biological fibrin glue-Triamcinolone Acetonide slow releasing agent can be continual and steady in normal saline under conditions of ambient temperature is 37 DEG C
Release, slow release duration is up to 120h.Show slow release effect in biological fibrin glue for the Triamcinolone Acetonide have good stability and when
Effect property.
Application method：
The biological fibrin glue that example IV is prepared-Triamcinolone Acetonide slow releasing agent loads the supporting spray equipment of scope
Interior, scope pipeline stretches into along endoscopic biopsy duct, and scope pipeline collar extension is connected with spray equipment, and scope pipeline internal orifice is under direct-view
Corresponding people digest road appointed part, you can to appointed part sprayed biological albumin glue-Triamcinolone Acetonide slow releasing agent.
Claims (8)
1. a kind of biological fibrin glue-Triamcinolone Acetonide slow releasing agent is it is characterised in that slow releasing agent comprises biological fibrin glue, aprotinin, song
An Naide, wherein, the mass fraction of biological fibrin glue is 1.8%～4.0%, the mass fraction of aprotinin is 0.08%～
0.10%, the mass fraction of Triamcinolone Acetonide is 0.09%～0.33%.
2. a kind of method preparing slow releasing agent described in claim 1 is it is characterised in that have steps of,
1) take aprotinin, dissolving is configured to the aprotinin solution that mass concentration is 10%；
2) take Triamcinolone Acetonide, dissolving is configured to the Triamcinolone Acetonide solution that concentration is 10mg/ml；
3) be respectively configured bioprotein main body sol solution, catalyst solution, wherein, bioprotein main gel solution concentration be 50～
90mg/ml, catalyst solution concentration is 500IU/ml；
4) take 1 debulking step 3) the bioprotein main body sol solution that configures, 0.01 debulking step 1) configure aprotinin solution,
0.125～0.375 debulking step 2) the Triamcinolone Acetonide solution that configures, mix；
5) take 1 debulking step 3) catalyst solution that configures, 0.01 debulking step 1) configure aprotinin solution, 0.125～
0.375 debulking step 2) the Triamcinolone Acetonide Solutions Solution that configures, mix；
6) by step 4), step 5) mixed liquor mixing, condense, obtain biological fibrin glue-Triamcinolone Acetonide slow releasing agent.
3. according to claim 2 preparation method it is characterised in that step 1) use physiological saline solution aprotinin, step 2)
With sterilized water for injection solution Triamcinolone Acetonide.
4. slow releasing agent described in claim 1 is in the purposes of the biological sustained release profile in vivo test Cinacort Span of preparation simulation.
5. a kind of biological fibrin glue-Triamcinolone Acetonide slow releasing agent is it is characterised in that slow releasing agent comprises biological fibrin glue, Triamcinolone Acetonide,
Wherein, the mass fraction of biological fibrin glue is 2.5%～4.5%, and the mass fraction of Triamcinolone Acetonide is 0.13%～0.38%.
6. a kind of method preparing slow releasing agent described in claim 5 is it is characterised in that there are following steps：
1) take Triamcinolone Acetonide, dissolving is configured to the Triamcinolone Acetonide solution that concentration is 10mg/ml；
2) with step 1) the Triamcinolone Acetonide solution that configures makees solvent, and configuration concentration is the bioprotein main gel of 50～90mg/ml
Solution；
3) configuration concentration is the catalyst solution of 500IU/ml；
4) by step 2) gained bioprotein main body sol solution and step 3) gained catalyst solution equal-volume mixes, condenses, obtain
To biological fibrin glue-Triamcinolone Acetonide slow releasing agent.
7. according to claim 6 preparation method it is characterised in that step 1) dissolve Triamcinolone Acetonide with sterilized water for injection.
8. slow releasing agent described in claim 5 treats the purposes in the preparation of postoperative stenosis in preparation for preventing and treating digestive endoscope.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611040732.9A CN106389393A (en) | 2016-11-23 | 2016-11-23 | Biological protein glue-triamcinolone acetonide slow release agent as well as preparation method and application of slow release agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611040732.9A CN106389393A (en) | 2016-11-23 | 2016-11-23 | Biological protein glue-triamcinolone acetonide slow release agent as well as preparation method and application of slow release agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106389393A true CN106389393A (en) | 2017-02-15 |
Family
ID=58082970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611040732.9A Pending CN106389393A (en) | 2016-11-23 | 2016-11-23 | Biological protein glue-triamcinolone acetonide slow release agent as well as preparation method and application of slow release agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106389393A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1376514A (en) * | 2002-04-09 | 2002-10-30 | 中国人民解放军第四军医大学 | Injection-type bone morphogenetic protein using fibrin as carrier |
| CN101797377A (en) * | 2009-02-11 | 2010-08-11 | 北京赛生药业有限公司 | Fibrin sealant and preparation method thereof |
| CN104902937A (en) * | 2012-12-11 | 2015-09-09 | 世元世龙技术株式会社 | Tissue sealant in which collagen and fibrin are mixed, and method for preparing same |
| CN105194731A (en) * | 2015-10-27 | 2015-12-30 | 上海科医联创生物科技有限公司 | Formula and preparation method for gel support used for in-vitro construction of tissue-engineered cartilage |
-
2016
- 2016-11-23 CN CN201611040732.9A patent/CN106389393A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1376514A (en) * | 2002-04-09 | 2002-10-30 | 中国人民解放军第四军医大学 | Injection-type bone morphogenetic protein using fibrin as carrier |
| CN101797377A (en) * | 2009-02-11 | 2010-08-11 | 北京赛生药业有限公司 | Fibrin sealant and preparation method thereof |
| CN104902937A (en) * | 2012-12-11 | 2015-09-09 | 世元世龙技术株式会社 | Tissue sealant in which collagen and fibrin are mixed, and method for preparing same |
| CN105194731A (en) * | 2015-10-27 | 2015-12-30 | 上海科医联创生物科技有限公司 | Formula and preparation method for gel support used for in-vitro construction of tissue-engineered cartilage |
Non-Patent Citations (3)
| Title |
|---|
| 张爱知 等: "《实用药物手册》", 30 October 2002, 上海科学技术出版社 * |
| 武阿丽 等: "胃镜下扩张联合黏膜下注射曲安奈德治疗食管癌术后吻合口顽固性良性狭窄临床研究", 《陕西医学杂志》 * |
| 顾其胜: "《海藻酸盐基生物医用材料与临床医学》", 30 April 2015, 上海科学技术出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis | |
| Yao et al. | Bioinspired biliverdin/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing | |
| Yao et al. | Flexible two-layer dissolving and safing microneedle transdermal of neurotoxin: A biocomfortable attempt to treat Rheumatoid Arthritis | |
| WO2021143951A2 (en) | Colchicine soluble microneedle patch and preparation method therefor | |
| CN105596287B (en) | Active divergence type solubility micropin and preparation method thereof | |
| Mei-Dan et al. | The role of platelet-rich plasma in rotator cuff repair | |
| CN104994841B (en) | The biological degradability microballon that is improved comprising the high molecular anticarcinogen adsorption capacity of anionic property and its preparation method | |
| CN106620887A (en) | Production method for drug balloon | |
| Guo et al. | Novel nanostructured lipid carriers-loaded dissolving microneedles for controlled local administration of aconitine | |
| Jain et al. | Esophageal stricture prevention after endoscopic submucosal dissection | |
| Chen et al. | Electrospun composite nanofibers with all-trans retinoic acid and MWCNTs-OH against cancer stem cells | |
| CN108685927A (en) | Include the medical composition and its use of methylenum careuleum class compound and bioactive ingredients | |
| Huang et al. | Drug-loaded balloon with built-in NIR controlled tip-separable microneedles for long-effective arteriosclerosis treatment | |
| CN108686216A (en) | Include the medical composition and its use of chemical ablation agent and bioactive polysaccharide | |
| Zeki et al. | Disseminated injection of vincristine-loaded silk gel improves the suppression of neuroblastoma tumor growth | |
| Xu et al. | Fabrication of a controlled-release delivery system for relieving sciatica nerve pain using an ultrasound-responsive microcapsule | |
| Wang et al. | Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb | |
| CN103405751B (en) | Composition with cell repairing function and preparation method and application thereof | |
| Leng et al. | Size-tunable and biodegradable thrombin-functionalized carboxymethyl chitin microspheres for endovascular embolization | |
| Qian et al. | A novel fast-releasing formulation containing curcumin and anti-microbial peptide-encapsulated transdermal hydrogels into microneedles to reduce inflammation in the therapy of neonatal sepsis | |
| CN114129714A (en) | Medicinal preparation and preparation method and application thereof | |
| CN114159586A (en) | Submucosal injection marker carrier gel for endoscope and application thereof | |
| Zhang et al. | A novel natural polysaccharide dissolving microneedle capable of adsorbing pus to load EGCG for the treatment of acne vulgaris | |
| CN106309671B (en) | Longnan of Gansu Province Z-bungeanum Maxim extract components and preparation method thereof and detection method | |
| CN107686517A (en) | The preparation of filler under a kind of liquid collagen mucous membrane |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170215 |