CN104958762A - Lucentis eye vitreous intracavity slow release medicine for 33G syringe needle injection - Google Patents
Lucentis eye vitreous intracavity slow release medicine for 33G syringe needle injection Download PDFInfo
- Publication number
- CN104958762A CN104958762A CN201510371614.5A CN201510371614A CN104958762A CN 104958762 A CN104958762 A CN 104958762A CN 201510371614 A CN201510371614 A CN 201510371614A CN 104958762 A CN104958762 A CN 104958762A
- Authority
- CN
- China
- Prior art keywords
- lucentis
- component
- polyethylene glycol
- phosphate buffer
- solution
- 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.)
- Granted
Links
- 229940076783 lucentis Drugs 0.000 title claims abstract description 33
- 238000002347 injection Methods 0.000 title claims abstract description 29
- 239000007924 injection Substances 0.000 title claims abstract description 29
- 239000003814 drug Substances 0.000 title abstract description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 102
- 239000000243 solution Substances 0.000 claims abstract description 53
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 33
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 21
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 21
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 11
- 239000008363 phosphate buffer Substances 0.000 claims description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 19
- 230000008569 process Effects 0.000 claims description 19
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 18
- 239000004698 Polyethylene Substances 0.000 claims description 18
- 229920000573 polyethylene Polymers 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000002671 adjuvant Substances 0.000 claims description 10
- 150000002334 glycols Chemical class 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 2
- 239000002953 phosphate buffered saline Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 10
- 239000007943 implant Substances 0.000 abstract description 9
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 3
- 239000011259 mixed solution Substances 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 230000004962 physiological condition Effects 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- 239000000499 gel Substances 0.000 abstract 2
- 239000002253 acid Substances 0.000 abstract 1
- 239000007853 buffer solution Substances 0.000 abstract 1
- 230000001276 controlling effect Effects 0.000 abstract 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 230000035484 reaction time Effects 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 229940086542 triethylamine Drugs 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 17
- 229940079593 drug Drugs 0.000 description 15
- 239000007788 liquid Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 229920003020 cross-linked polyethylene Polymers 0.000 description 7
- 239000004703 cross-linked polyethylene Substances 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 230000003000 nontoxic effect Effects 0.000 description 7
- 210000001525 retina Anatomy 0.000 description 6
- 201000005667 central retinal vein occlusion Diseases 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 208000004644 retinal vein occlusion Diseases 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 210000004127 vitreous body Anatomy 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010038491 Renal papillary necrosis Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000002137 anti-vascular effect Effects 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940125645 monoclonal antibody drug Drugs 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses lucentis eye vitreous intracavity slow release medicine for 33G syringe needle injection. The lucentis eye vitreous intracavity slow release medicine for 33G syringe needle injection is characterized by comprising a component A and a component B, the component A is a homogeneous mixed solution formed by lucentis and biodegradable medicinal polyethylene glycol auxiliary materials, and the component B is a peptides cross-linking agent. After being injected into the eye vitreous chamber, the component A and the component B can form a gel implant very quickly and prevent the lucentis from quickly releasing, and therefore the medicine releasing slowing effect is achieved, and the medicine administration interval is prolonged. A reaction can be achieved on the physiological conditions, in other words, the reaction can be conducted in normal saline or a buffer solution with the pH value of 7.4, special organic solvent or strong acid conditions needed by a traditional implant or gels is not needed, safety is high, and hurt to the human tissue is effectively avoided; the reaction time can be effectively regulated by controlling the four arm-polyethylene glycol (peg)-maleic imide concentration of the solution and the triethyl amine concentration of the solution, and the lucentis eye vitreous intracavity slow release medicine can be used for very thin 33G syringe needle injection.
Description
Technical field
The present invention relates to a kind of vitreum intracavity injection medicine preparation, particularly a kind of 33G needle injection Lucentis vitreum intracavity slow releasing pharmaceutical.
Background technology
Epidemiological study result shows, more than 75 years old population ages macular degeneration related (age-related macular degeneration, AMD) prevalence can up to 47.3%; In the diabetics of more than 40 years old, 37% suffers from diabetic renal papillary necrosis (diabetic retinopathy, DR); The incidence rate of central retinal vein occlusion (central retinal vein occlusion, CRVO) new vessels is afterwards up to 15-20%.Although the Therapeutic Method of above-mentioned retina relevant disease and effect make some progress in recent years, their curative effect is subject to a great extent how to the restriction of this difficult problem of the oculi posterior segment such as retina, choroid tissue transhipment effective dose of medicine thing.
At present, treatment retina relevant disease, that commonly uses clinically mainly contains 4 kinds of route of administration: Formulations for systemic administration: by inside and outside two-layer blood-retina barrier effect, drug absorption enters eye inner tissue as the dose such as retina, vitreous body very few (entering vitreous body drug concentration often less than 10% of blood plasma drug concentration), do not reach active drug concentration, strengthen dosage and can play the effect that part improves ophthalmic retinal tissue drug concentration, but also may cause serious whole body toxic and side effects simultaneously.Eye table administration (based on eye drip): run off fast at eye table by medicine, aqueous barrier etc. affects, and after conventional eye drop solutions eye drip, medicine is difficult to reach active drug concentration at retinal tissue.Periocular injections: compare Formulations for systemic administration and the administration of eye table, this administration more easily arrives eye inner tissue, and less than intravitreal wound, but because of choroidal blood Circulation, medicine is easily eliminated fast, for maintaining active drug concentration, must repeatedly inject, patient compliance is poor.Intravitreal: intravitreal is one of the most widely used route of administration in retinal diseases treatment, and medicine directly enters eye inner tissue, and in tissue, drug level can reach higher level.But, the potential risk that intravitreal has it intrinsic and side effect, easily cause detachment of retina, hemorrhage, endophthalmitis and cataract etc., and to the disease needing long term administration to treat, usually repeatedly will carry out intravitreal, potential risk and side effect increase further.
Lucentis (ranibizumab, trade name Lucentis) is for needing an exemplary of intravitreal administration.Lucentis is a kind of anti-vascular endothelial growth factor monoclonal antibody drug, ratifies intra-ocular applications, is widely used in the disease related with intraocular neovascularizations such as treatment moist AMD, DR, CRVO.Lucentis belongs to macromolecular monoclonal antibody bio-pharmaceutical, due to ocular physiology barrier action, conventional eye table administration cannot effectively absorb to tissue performance therapeutical effect such as retinas, can only be main administering mode with intravitreal at present, and long-term intravitreal continuously, not only increase the risk that intraocular injection complication occurs, and the compliance of patient also can reduce.And the syringe needle carrying out intravitreal is thicker, the complication caused is more serious.Weigh the advantages and disadvantages, usually need monthly inject once clinically at present, patient needs injection continuously to inject with the progress of symptom management even all the life for several years usually.
For reducing the severe complication that vitreous chamber puncture injection causes, using the syringe needle of the diameter thinner (namely G-value is larger) of syringe needle to carry out intravitreal is clinical development trend, and the 30G syringe needle current clinical ophthalmology having been selected successively thinner 33G syringe needle replace tradition to use is injected.In addition, use medicine to be prepared into slow releasing agent, also can effectively reduce the intravitreal frequency.But all there is technological deficiency in various degree in slow releasing agent conventional at present, as the Authorization Notice No. patent of invention that is CN 101390825B the solid implant invented cannot carry out Conventional glass body cavity drug administration by injection, especially 33G needle injection cannot be used, need clinically to carry out Operation, administration process is complicated, and wound is large; And microsphere is large because of particle diameter, needs major diameter injection needle to carry out intravitreal, cannot use superfine 33G needle injection; , because particle size is little, there is building-up effect in the preparations such as liposome nano granule, is not easy dispersion, very easily blocking syringe needle, also cannot use superfine 33G needle injection when injecting; And the slow releasing agents such as the in-situ gel such as conventional gel, chitosan are for reaching slow releasing function, need the macromolecular material of high molecular as chitosan etc., solution viscosity is large, and superfine 33G syringe needle also cannot be used to inject.
Summary of the invention
For the problems referred to above, the object of this invention is to provide a kind of Lucentis vitreum intracavity release thing for superfine 33G needle injection, can prolong drug effect, reduce administration number of times, reduce glass chamber repeatedly inject the untoward reaction caused.
The present invention is the improvement to the agent of common Lucentis intravitreal, by Lucentis, biodegradable medical polyethylene glycol class adjuvant and GPQ peptide class cross-linking agent, be prepared into the vitreum intracavity slow releasing pharmaceutical for superfine 33G needle injection with slow releasing function.The present invention comprises component A and B component, and component A is the mixed solution of the homogenizing that Lucentis and biodegradable medical polyethylene glycol class adjuvant are formed jointly, and B component is peptide class cross-linking agent solution.Before injection, only need extract isopyknic component A and B component with the syringe of joining 33G syringe needle, mixing can carry out the injection of vitreum intracavity gently.Component A and B component are common liq in after mixing 10 minutes, after being injected into vitreum intracavity, because medical polyethylene glycol class adjuvant forms gel implant under the effect of peptide class cross-linking agent, retardance Lucentis discharges fast, thus play slow releasing pharmaceutical effect, extend delivery time.
Know-why of the present invention: biodegradable medical polyethylene glycol class adjuvant is four arms-Polyethylene Glycol-maleimide, four maleimide active groups are connected with above each peg molecule, the aminoacid sequence of peptide class cross-linking agent is GCRDQGWIGQPGDRCG, after four arms-Polyethylene Glycol-maleimide mixes in the solution with peptide class cross-linking agent, cysteine residues generation Michael addition reaction in amido link in four arms-Polyethylene Glycol-maleimide and peptide class cross-linking agent and being cross-linked, thus viscosity is sharply increased and final formation gel implant, this reaction can realize in physiological conditions, namely be react in the buffer of 7.4 at normal saline or pH value, without the need to the special organic solvent required for conventional implants or gel or strong acidic condition, safety is high, effectively avoid damaging tissue.The Effective Regulation response time is got final product by the four arms-Polyethylene Glycol-maleimide concentration in control solution and the triethylamine concentration in solution, to realize before 33G needle injection, with during injection or common injection, the implant that cross-linking reaction generates gel type occurring after entering vitreous chamber.
The concrete technical scheme of the present invention is as follows:
A kind of 33G needle injection Lucentis vitreum intracavity slow releasing pharmaceutical, it is characterized in that comprising component A and B component, described component A is the mixed solution that Lucentis and biodegradable medical polyethylene glycol class adjuvant form homogenizing jointly, and B component is peptide class cross-linking agent solution.
Biodegradable medical polyethylene glycol class adjuvant in described component A is four arms-Polyethylene Glycol-maleimide, molecular weight polyethylene glycol is 1000 ~ 2000 dalton, four arms-Polyethylene Glycol-maleimide mass concentration is in the solution 40mg/ml-80mg/ml, and four arms-Polyethylene Glycol-maleimide and the mass ratio both Lucentis are 0.2:0.8-0.5:0.5.
Described component A adopts phosphate buffered saline.
Peptide class cross-linking agent in described B component is GPQ peptide, aminoacid sequence is GCRDQGWIGQPGDRCG, GPQ peptide is dissolved in the phosphate buffer containing triethylamine, the mass concentration of GPQ peptide in phosphate buffer is 64mg/ml-128mg/ml, triethylamine concentration is 2mM-20mM, and pH value is adjusted to 7.0-7.4.
Preparation method of the present invention is as follows: (1) gets aseptic biodegradable medical polyethylene glycol class adjuvant, aseptically dissolve with phosphate buffer, then add Lucentis powder, after dissolving, quantitative filling is in the cillin bottle of aseptic process, is mixed with component A solution; (2) getting triethylamine is dissolved in phosphate buffer, with sodium hydroxide adjust pH to 7.0-7.4, obtains the phosphate buffer containing triethylamine; Get after the above-mentioned phosphate buffer containing triethylamine of GPQ peptide fully dissolves, after dissolving, quantitative filling is in the cillin bottle of aseptic process, is mixed with B component solution.
When the present invention uses, adopt the syringe of 33G syringe needle to extract component A liquid and the B component liquid of equivalent volumes, then syringe is shaken gently the liquid of mixing the inside, within 10 minutes, be injected into vitreous chamber.
Advantage of the present invention: this reaction can realize in physiological conditions, namely be react in the buffer of 7.4 at normal saline or pH value, without the need to the special organic solvent required for conventional implants or gel or strong acidic condition, safety is high, effectively avoids damaging tissue.The Effective Regulation response time is got final product by the four arms-Polyethylene Glycol-maleimide concentration in control solution and the triethylamine concentration in solution, to realize before 33G needle injection, with during injection or common injection, the implant that cross-linking reaction generates gel type occurring after entering vitreous chamber.
Detailed description of the invention
The present invention is further described below by specific embodiment.
embodiment 1:
(1) aseptic daltonian four arms of molecular weight 1000-Polyethylene Glycol-maleimide 80mg is got, aseptically dissolve with pH7.4 phosphate buffer 1 ml, then add Lucentis powder 20mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
(2) triethylamine 2.98mg is taken, be dissolved in 10ml pH7.4 phosphate buffer, with sodium hydroxide adjust pH to 7.4, preparation is the phosphate buffer of 2mM containing triethylamine, take GPQ peptide 64mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
(3) when using, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 10 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 15 days degradable one-tenth and aminoacid.
embodiment 2:
Get aseptic daltonian four arms of molecular weight 2000-Polyethylene Glycol-maleimide 80mg, aseptically dissolve with pH7.4 phosphate buffer 1 ml, then add Lucentis powder 20mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
Take triethylamine 2.98mg, be dissolved in 10mlpH7.4 phosphate buffer, with sodium hydroxide adjust pH to 7.4, it is the phosphate buffer of 2mM that preparation claims containing triethylamine, take GPQ peptide 64mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
During use, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 15 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 20 days degradable one-tenth and aminoacid.
embodiment 3:
Get aseptic daltonian four arms of molecular weight 1000-Polyethylene Glycol-maleimide 80mg, aseptically dissolve with pH7.4 phosphate buffer 1 ml, then add Lucentis powder 80mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
Take triethylamine 2.98mg, be dissolved in 10ml pH7.4 phosphate buffer, with sodium hydroxide adjust pH to 7.4, preparation is the phosphate buffer of 2mM containing triethylamine, take GPQ peptide 64mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
During use, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 10 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 15 days degradable one-tenth and aminoacid.
embodiment 4:
Get aseptic daltonian four arms of molecular weight 1000-Polyethylene Glycol-maleimide 80mg, aseptically dissolve with pH7.4 phosphate buffer 1 ml, then add Lucentis powder 40mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
Take triethylamine 2.98mg, be dissolved in 10ml pH7.4 phosphate buffer, with sodium hydroxide adjust pH to 7.4, preparation is the phosphate buffer of 2mM containing triethylamine, take GPQ peptide 64mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
During use, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 10 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 15 days degradable one-tenth and aminoacid.
embodiment 5:
Get aseptic daltonian four arms of molecular weight 1000-Polyethylene Glycol-maleimide 80mg, aseptically dissolve with pH7.4 phosphate buffer 1 ml, then add Lucentis powder 20mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
Take triethylamine 2.98mg, be dissolved in 10ml pH7.4 phosphate buffer, with sodium hydroxide adjust pH to 7.4, preparation is the phosphate buffer of 2mM containing triethylamine, take GPQ peptide 128mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
During use, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 12 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 15 days degradable one-tenth and aminoacid.
embodiment 6:
Get aseptic daltonian four arms of molecular weight 1000-Polyethylene Glycol-maleimide 80mg, aseptically dissolve with pH7.0 phosphate buffer 1 ml, then add Lucentis powder 20mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
Take triethylamine 2.98mg, be dissolved in 10ml pH7.0 phosphate buffer, with sodium hydroxide adjust pH to 7.0, preparation is the phosphate buffer of 2mM containing triethylamine, take GPQ peptide 64mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
During use, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 10 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 15 days degradable one-tenth and aminoacid.
embodiment 7:
Get aseptic daltonian four arms of molecular weight 1000-Polyethylene Glycol-maleimide 80mg, aseptically dissolve with pH7.4 phosphate buffer 1 ml, then add Lucentis powder 20mg, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with A bottle solution.
Take triethylamine 29.8mg, be dissolved in 10ml pH7.4 phosphate buffer, with sodium hydroxide adjust pH to 7.4, preparation is the phosphate buffer of 20mM containing triethylamine, take GPQ peptide 64mg, be after the phosphate buffer of 2mM fully dissolves with 1ml containing triethylamine, after dissolving, fill is in the cillin bottle of aseptic process, is mixed with B bottle solution.
During use, the syringe with 33G syringe needle is used to extract A bottle solution (as 0.1ml) as required, extract isopyknic B bottle solution (as 0.1ml) again, only syringe gently need be shaken twice, or syringe is turned upside down and can mix solution twice, in 10 minutes, then complete vitreum intracavity inject.This injecting liquid drug can realize the medicament slow release of 10 days after vitreous chamber, and four arms that GPQ peptide is cross-linked-Polyethylene Glycol-maleimide, under the Degradation of protease, is absorbed by tissue at the nontoxic Polyethylene Glycol of 15 days degradable one-tenth and aminoacid.
Above-described embodiment only for technical conceive of the present invention and feature are described, can not limit the scope of the invention with this.All equivalent transformations of doing according to spirit of the present invention or modification, all should be encompassed in protection scope of the present invention.
Claims (8)
1. a 33G needle injection Lucentis vitreum intracavity slow releasing pharmaceutical, it is characterized in that comprising component A and B component, described component A is the intimate mixing solution that Lucentis and medical polyethylene glycol class adjuvant are formed jointly, and described B component is peptide class cross-linking agent solution.
2. slow releasing pharmaceutical as claimed in claim 1, it is characterized in that described medical polyethylene glycol class adjuvant is four arms-Polyethylene Glycol-maleimide, molecular weight polyethylene glycol is 1000 ~ 2000 dalton.
3. slow releasing pharmaceutical as claimed in claim 2, it is characterized in that the mass concentration of four described arms-Polyethylene Glycol-maleimide is 40mg/ml-80mg/ml, four arms-Polyethylene Glycol-maleimide and the mass ratio both Lucentis are 0.2:0.8-0.5:0.5.
4. slow releasing pharmaceutical as claimed in claim 1, is characterized in that described component A adopts phosphate buffered saline.
5. slow releasing pharmaceutical as claimed in claim 1, it is characterized in that described peptide class cross-linking agent is GPQ peptide, its aminoacid sequence is GCRDQGWIGQPGDRCG.
6. slow releasing pharmaceutical as claimed in claim 5, it is characterized in that described GPQ peptide is dissolved in the phosphate buffer containing triethylamine, the mass concentration of GPQ peptide in phosphate buffer is 64mg/ml-128mg/ml, and triethylamine concentration is 2mM-20mM, and its pH value is 7.0-7.4.
7. slow releasing pharmaceutical as claimed in claim 1, it is characterized in that the phosphate buffer commonly used, pH value is adjusted to 7.0-7.4.
8. the 33G needle injection preparation method of Lucentis vitreum intracavity slow releasing pharmaceutical as claimed in claim 1, it is characterized in that comprising the following steps: (1) gets aseptic biodegradable medical polyethylene glycol class adjuvant, aseptically dissolve with phosphate buffer, then Lucentis powder is added, after dissolving, quantitative filling is in the cillin bottle of aseptic process, is mixed with component A solution; (2) getting triethylamine is dissolved in phosphate buffer, with sodium hydroxide adjust pH to 7.0-7.4, obtains the phosphate buffer containing triethylamine; Get after the above-mentioned phosphate buffer containing triethylamine of GPQ peptide fully dissolves, after dissolving, quantitative filling is in the cillin bottle of aseptic process, is mixed with B component solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510371614.5A CN104958762B (en) | 2015-06-30 | 2015-06-30 | A kind of 33G needle injection intracavitary slow releasing pharmaceutical of Lucentis vitreum |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510371614.5A CN104958762B (en) | 2015-06-30 | 2015-06-30 | A kind of 33G needle injection intracavitary slow releasing pharmaceutical of Lucentis vitreum |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104958762A true CN104958762A (en) | 2015-10-07 |
| CN104958762B CN104958762B (en) | 2019-03-12 |
Family
ID=54212960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510371614.5A Active CN104958762B (en) | 2015-06-30 | 2015-06-30 | A kind of 33G needle injection intracavitary slow releasing pharmaceutical of Lucentis vitreum |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104958762B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109549918A (en) * | 2017-09-22 | 2019-04-02 | 沈阳兴齐眼药股份有限公司 | Ophthalmic pharmaceutical composition, ophthalmic kit and medical application thereof |
-
2015
- 2015-06-30 CN CN201510371614.5A patent/CN104958762B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| RAVI VAISHYA等: "Long-Term Delivery of Protein Therapeutics", 《EXPERT OPIN DRUG DELIV.》 * |
| 汲婧等: "雷珠单抗治疗湿性年龄相关性黄斑变性的治疗方案", 《国际眼科纵览》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109549918A (en) * | 2017-09-22 | 2019-04-02 | 沈阳兴齐眼药股份有限公司 | Ophthalmic pharmaceutical composition, ophthalmic kit and medical application thereof |
| CN109549918B (en) * | 2017-09-22 | 2023-05-23 | 沈阳兴齐眼药股份有限公司 | Ophthalmic medicine composition, ophthalmic medicine box and medical application thereof |
| US12150946B2 (en) | 2017-09-22 | 2024-11-26 | Shenyang Xingqi Pharmaceutical Co., Ltd. | Ophthalmic pharmaceutical composition, ophthalmic kit, and pharmaceutical application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104958762B (en) | 2019-03-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6700348B2 (en) | Sustained drug delivery implant | |
| ES2345018T3 (en) | COMPOSITIONS AND PROCEDURES TO TREAT THE BACK SEGMENT OF THE EYE. | |
| JP7519413B2 (en) | Ophthalmic pharmaceutical composition, ophthalmic kit, and medical application thereof | |
| Iyer et al. | Long-acting intraocular Delivery strategies for biological therapy of age-related macular degeneration | |
| US9044436B2 (en) | Compositions and methods for the treatment of angiogenesis-related eye diseases | |
| Sarkar et al. | Nanodiagnostics and Nanotherapeutics for age-related macular degeneration | |
| JP2017061467A5 (en) | ||
| EP1924309A1 (en) | Ophthalmic syringe | |
| TW200826963A (en) | Water insoluble polymer matrix for drug delivery | |
| CN115487139B (en) | Puerarin gellan gum ionic in-situ gel eye drops and preparation method | |
| WO2023039168A1 (en) | Use of verteporfin to modulate wound healing after an ocular surgical procedure or ocular injury | |
| CN1835735B (en) | Drug delivery system for administering fine particle under tenon's capsule | |
| CN104958762B (en) | A kind of 33G needle injection intracavitary slow releasing pharmaceutical of Lucentis vitreum | |
| KR20210045434A (en) | Antibiotic solutions and injection methods to prevent eye infections | |
| CN104906587B (en) | A kind of Foscarnet sodium vitreum intracavitary slow releasing pharmaceutical | |
| US20080138350A1 (en) | Process for use of fluoroquinolones to reduce or modulate inflammation due to eye disease or ophthalmic surgery | |
| Vyas et al. | A Review on in situ gelling system for ophthalmic drug delivery | |
| WO2019191200A1 (en) | Method and formulation for producing anesthesia of internal aspect of eye wall by topical application | |
| EP4282402A1 (en) | Ophthalmic preparation for treating macular edema, optic neuritis and non-infectious endophthalmitis through eye drop administration | |
| CN104667287B (en) | Ophthalmic composition for treating camera oculi posterior neovascularization resulting and application thereof | |
| HK40074896A (en) | Ophthalmic pharmaceutical composition, ophthalmic kit, and medical application thereof | |
| WO2025007888A1 (en) | Ophthalmic pharmaceutical composition and preparation method therefor, ophthalmic kit containing ophthalmic pharmaceutical composition, and use | |
| Kim et al. | Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives. Pharmaceutics 2021, 13, 108 | |
| HK40064642A (en) | Ophthalmic pharmaceutical composition, ophthalmic kit, and medical application thereof | |
| KR20250065706A (en) | High concentration pharmaceutical composition of roflumilast for ophthalmic delivery |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |