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CN105879126A - Super-lubricating serum albumin punctal plug and preparation method thereof - Google Patents

Super-lubricating serum albumin punctal plug and preparation method thereof Download PDF

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Publication number
CN105879126A
CN105879126A CN201610176245.9A CN201610176245A CN105879126A CN 105879126 A CN105879126 A CN 105879126A CN 201610176245 A CN201610176245 A CN 201610176245A CN 105879126 A CN105879126 A CN 105879126A
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serum albumin
solution
punctal plug
preparation
buffer
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CN201610176245.9A
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Inventor
汪伟
李丹
何铭锋
朱家喜
俞益雷
李绿巍
许利利
朱明华
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Hangzhou Yahui Biotechnology Co Ltd
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Hangzhou Yahui Biotechnology Co Ltd
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Priority to CN201610176245.9A priority Critical patent/CN105879126A/en
Publication of CN105879126A publication Critical patent/CN105879126A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007Methods or devices for eye surgery
    • A61F9/00772Apparatus for restoration of tear ducts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04Macromolecular materials
    • A61L31/043Proteins; Polypeptides; Degradation products thereof
    • A61L31/047Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Plastic & Reconstructive Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses a super-lubricating serum albumin punctal plug and a preparation method of the super-lubricating serum albumin punctal plug. The punctal plug provided by the invention is provided with a main body (2), a first section (1), a second section (3) and a super-lubricating coating (4). After the super-lubricating serum albumin punctal plug is soaked by a hydrophilic polymer solution, a hydrophilic macromolecular coating is formed on the surface of the serum albumin punctal plug through chemical reaction, when the hydrophilic macromolecular coating contacts water, hydrophilic groups of the water-soluble polymers are combined with water and rapidly swell, the lubricating property is good, thus the injury caused to the soft tissue when the punctal plug is implanted is reduced, the pain is alleviated, the occurrence of complications is prevented, and therefore, the super-lubricating serum albumin punctal plug is particularly suitable for the clinical application.

Description

A kind of super lubrication serum albumin Punctal plug and preparation method thereof
Technical field
The invention belongs to medical instruments field, be specifically related to a kind of super lubrication serum albumin lacrimal point Plug and preparation method thereof.
Background technology
Tear film has the structure of complexity, for protecting the surface of eyes.Tear film comprises three Primary layer: the lipid layer in outside, the mucin layer of inner side, and lipid layer and mucin layer it Between water-bearing layer.Each layer has specific function.Lipid layer prevents tear from steaming from ocular surface Send out.Water-bearing layer is cornea oxygen supply, and comprises other chemical compositions critically important to healthy eye. Mucin layer maintains the reciprocal action between lipid layer and water-bearing layer, and prevents tear on cornea Beading.
" xerophthalmia " is to stand due to the not enough disease of the normal tear fluid film cornea moistening that caused of disorder Disease.This disease comprises diversified S&S, from there being the light, interrupted of foreign body sensation Burn and/or swipe, to cornea and conjunctival disease (keratitis sicca (KCS)) The famine of water-bearing layer secretion.
Xerophthalmia can have multiple concrete cause and facilitate factor, including dry environment, surrounding air The pollutant of propagation, autoimmune disorder etc., a lot of reasons is all relevant to two basic causes. First, the tear stains of lachrymal gland may block or possible malfunction, to such an extent as to can not have q.s Tear arrive eyes.Although the tear of the second lachrymal gland and tear stains transmissibility q.s is to eyes, But tear can form dry eye condition from the too fast outflow of eyes.Initially, lacrimal point is by sealing Or closed by electricity or laser burn.Although these methods can provide acceptable knot Really, but they are irreversible, unless accepted Plastic renovation operation.Owing to being sometimes difficult to really Determining xerophthalmia is to be caused by too much flowing out or produced by very few tear, and this method may Unnecessary wound can be brought, such as epiphora to patient.To this end, have been developed for temporary or forever Property closes the device of lacrimal point for a long time.After Lacrimal plug, partially enclosed tear discharge line, add The natural tear of its lubrication of eye surface.This treatment can be permanently effective alleviation xerophthalmia Shape.For many people, lacrimal passage Embolization can effectively reduce, and even exempts making of artificial tears With.MEDENNIUM company of U.S. SmartPlug Punctal plug, by hydrophobicity acrylic acid Material manufactures.Absorbable collagen Punctal plug (the Tears Naturale of Alcon companyTM Collagen Punctal Plug) and the silica gel tear of nonabsorable of Lacrimedics company Point plug (Blue OPAQUE Herrick Lacrimal Plug) etc..
Human serum albumin (Human Serum Albumin or HSA) is that in blood plasma content is Many protein, accounts for the 40%-60% of Total plasma protein.The molecular structure of human albumin in Within 1975, illustrate that [Meloun B, Mor á vek, L., Kostka are V.1975.Complete amino acid sequence of human serum albumin.FEBS Letters. 58:134-137.], for the single chain polypeptide containing 585 amino acid residues, molecule contains 17 Disulfide bond.Human serum albumin is the main component constituting blood plasma, its physiological function mainly dimension Hold plasma colloid osmotic pressure, also have carrier function (Sun Shiguang, Yu Minglian, Wang Jianmin etc., The clinical practice mistaken ideas of people's serum albumin and countermeasure thereof, PLA's Acta Pharmaceutica Sinica, 2009, 25(4):366-368).Human serum albumin makes nano-particle and by state as pharmaceutical carrier Inside and outside widely studied (Yu Yaoyu, Li Jian, Li Lihong, Qu Youzhi, Yu Jia, Deng Jianping, Gao Guodong, Zhang Wenbin, Jiao Derang, the preparation of magnetic albumin nanoparticle and physical property thereof Analyze, Chinese Clinical neurosurgery magazine, 2011,16:609-611;Zhang Liangke, marquis's generation Auspicious, Song Xiangrong, Lu Yi, the preparation of a kind of albumin nano granular and evaluation, Chinese Pharmaceutical Journal, 2007,42:365-367;Elmer J,Cabrales P,Wang Q,Zhang N,Palmer AF, Synthesis and biophysical properties of polymerized human Serum albumin, Biotechnol Prog, 2011,27:290-296;Jain S,Mathur R, Das M, Swarnakar NK, Mishra AK, Synthesis, pharmacoscintigraphic evaluation and antitumor efficacy of methotrexate-loaded,folate-conjugated,stealth albumin Nanoparticles, Nanomedicine (London), 2011,6:1733-1754).With To albumin research gradually deeply, its range of application is constantly expanded.
Summary of the invention
It is an object of the invention to provide the serum albumin Punctal plug of a kind of super lubrication, can avoid Damage to soft tissue in Punctal plug implantation process, to expand serum albumin at medical apparatus and instruments The range of application in field.
The invention provides the preparation method of a kind of serum albumin biomaterial, including walking as follows Rapid:
(1), sero-abluminous solution system is dissolved in preparation: contain in every bulk solution The trifluoroethanol (v/v) of 75%-94.95%, the inorganic base (v/v) of the 0.01M-2.0M of 5%-20%, The beta-mercaptoethanol (v/v) of 0.05%-5%;
(2), by serum albumin it is dissolved in above-mentioned solution, containing 5%-30% in final solution (w/v) serum albumin;
(3), serum albumin solution is stood, after question response is complete, outwell supernatant liquid, will Lower floor has the serum albumin solution of bigger viscosity and joins in mould, after solidification to be dried, Opening mould, being dipped into by solidification material containing concentration is the electrophilic of 0.5%~45% (w/v) In the hydrophilic polymer solution of functional group, it is dried after cleaning, prepares serum albumin biology material Material.
For avoiding any ambiguity, the term w/v used for various solution compositions means weight Volume ratio, refers to that unit volume solution is contained within a certain percentage rate combination by weight, such as The human serum albumin (w/v) of 5% refers in 100ml bulk solution containing described in 10g Component.And term v/v means volume ratio, refer to that unit volume solution is contained within by volume A certain percentage rate combines, and the trifluoroethanol (v/v) of such as 75% refers at 100ml volume molten Liquid contains the described trifluoroethanol of 60ml.Other corresponding numerical rangies are by that analogy.
In said method, described sero-abluminous source can be people, cattle, horse, sheep, The serum albumin of the animals such as mouse, preferably human serum albumin.Serum albumin can be led to Cross the recombinant expressed production of genetic engineering, or can extract from people or animal blood slurry.
In said method step (1), dissolve every volume in sero-abluminous solution system molten Liquid preferably comprises the trifluoroethanol (v/v) of 80%-90%, the 0.01M-2.0M's of 8%-15% Inorganic base (v/v), the beta-mercaptoethanol (v/v) of 1%-5%.
In said method step (1), the inorganic base in described solution is selected from ammonia, hydroxide Sodium, sodium carbonate, sodium bicarbonate, disodium hydrogen phosphate, sodium phosphate etc. or its mixture, preferably ammonia Water;The preferably molar concentration of inorganic base is 0.01-1M, more preferably 0.1-0.2M.
In said method step (2), preferably containing 10%-20% (w/v) in final solution Serum albumin.
In said method step (3), preferably by serum albumin solution 10-40 DEG C of standing 1-60 hour, preferably stand 12-48 hour at 20-30 DEG C, more preferably stand 20-40 in room temperature Hour.
In said method step (3), preferably serum albumin solution is joined after mould 10-40 DEG C dry 1-60 hour, preferably dry 12-48 hour at 20-30 DEG C, more preferably in room Temperature is dried 20-40 hour.
In said method step (3), the described hydrophilic polymer containing electrophilic functional group Succinimidyl propionate base Polyethylene Glycol, the poly-second of succinimidyl succinate base can be selected from Glycol, Succinimidyl glutarate base Polyethylene Glycol, the poly-second of butanimide decanedioic acid ester group Glycol, pentaerythritol polyethylene glycol ether four succinimidyl glutarate, tetramethylolmethane Polyethylene Glycol In ether four butanimide succinic acid, pentaerythritol polyethylene glycol ether four butanimide decanedioic acid One or more, preferably succinimidyl succinate base Polyethylene Glycol.Hydrophilic polymer The molecular weight of thing is 1000~1000000, preferably 50000-200000.
The effect of hydrophilic polymer solution is the serum albumin biomaterial surface in solidification Hydrophilic polymeric coating layer, upon contact with water, water solublity high score is formed by chemical reaction The hydrophilic group of son is combined rapid swelling with water so that serum albumin biomaterial has excellent Greasy property.
In said method step (3), serum albumin solidification material is molten at hydrophilic polymer In liquid soak after, preferably cleaned to pH be 6.0~8.0.Cleanout fluid maybe can maintain selected from water Any one buffer solvent that pH value of solution is 6.0-8.0, concentration is 1-100mmol/L, optionally From phosphate buffer, disodium hydrogen phosphate-citrate buffer solution, TRIS, glycyl-glycine, N-bis-(ethoxy) glycine, phosphate sodium dihydrogen buffer solution, disodium hydrogen phosphate buffer, vinegar Acid sodium buffer, sodium carbonate buffer, sodium phosphate buffer, lysis buffer, arginine Buffer or its mixture;The pH value range of buffer agent is preferably 6.5-7.5;Buffer agent Concentration is preferably 5-50mmol/L, more excellent for 10-30mmol/L.Preferably cleaning solution is Deionized water or phosphate buffer.After cleaning at 25~80 DEG C after drying, serum albumin is prepared Biomaterial.After more preferably cleaning at 30~50 DEG C after drying, serum albumin biology material is prepared Material.
The present invention another object is that and utilizes said method to prepare serum albumin biomaterial. Preferably, a kind of serum albumin Punctal plug is prepared according to specific mould, according to described The Punctal plug that mould prepares has main body (2), first segment (1) second sections (3) With super lubricant coating (4), as shown in Figure 1.First segment (1) leans against outside lacrimal point, anti- Only Punctal plug is slipped in lacrimal ductule, and it is fixed that the second sections (3) rises after Punctal plug inserts lacrimal point Position effect, the damage in implantation process to tissue avoided by super lubricant coating (4).
Punctal plug body of the present invention is slender cylinder, and described cylinder diameter is Between 0.5~4.5mm, height is 0.2~3mm.More preferably cylinder diameter is 0.8~2mm Between, height is 1.5~2.5mm.
The first segment 1 of Punctal plug of the present invention and the second sections 3 are a diameter of 0.7~5.5mm, more preferably first segment 1 and second sections 3 of Punctal plug is a diameter of 1~2.5mm.
The super lubricant coating (4) of Punctal plug of the present invention is by the lacrimal point described in step (3) Plug mould prepares shape after serum albumin Punctal plug soaks in hydrophilic polymer solution Become.Chemical reaction is passed through after hydrophilic polymer solution soaking in serum albumin Punctal plug surface Form hydrophilic polymeric coating layer, upon contact with water, the hydrophilic group of water soluble polymer Be combined rapid swelling with water, there is excellent greasy property, can decrease Punctal plug implant time pair The damage of soft tissue, eases the pain, it is therefore prevented that the generation of complication.It is additionally, since recombined human Serum albumin is derived from blood of human body or uses genetic engineering recombinant expressed, and in human blood Serum albumin consistent, immunoreation will not be caused.It addition, the serum that the present invention provides is white Albumen Punctal plug production method is quality controllable, is suitable for large-scale industrial production.
Accompanying drawing explanation
Fig. 1 super lubrication serum albumin Punctal plug schematic cross-section.Fig. 1 has first segment Section the 1, second sections 3, main body 2 and super lubricant coating 4.First segment 1 Lean against outside lacrimal point, prevent Punctal plug to be slipped in lacrimal ductule, the second sections 3 play the role of positioning after Punctal plug inserts lacrimal point, and super lubricant coating 4 is avoided To the damage organized in implantation process.
Detailed description of the invention
Embodiment 1
Sero-abluminous solution system is dissolved in preparation: take each component according to percent by volume, 0.1M ammonia 10%, 1% mercaptoethanol, remaining is trifluoroethanol, and stirring makes it be sufficiently mixed; Serum albumin is dissolved in above-mentioned solution, containing 25% (w/v) in final serum albumin solution Serum albumin, gently with bar magnet stir 30 minutes, bleed 30 minutes with vacuum pump and cause gas Bubble eliminates;Serum albumin solution room temperature is stood, after 48h, outwells supernatant liquid, under inciting somebody to action Layer has the serum albumin solution of bigger viscosity and joins in mould, dried in air at room temperature Night;Mould is opened, after taking-up, is dipped into succinimidyl propionate base polyglycol solution In, concentration is 10% (w/v), cleans to pH=7.0 with deionized water, is dried at 25 DEG C, Prepare super lubrication serum albumin Punctal plug.
Embodiment 2
Sero-abluminous solution system is dissolved in preparation: take each component according to percent by volume, 0.1M ammonia 10%, 1% mercaptoethanol, remaining is trifluoroethanol, and stirring makes it be sufficiently mixed; Serum albumin is dissolved in above-mentioned solution, containing 35% (w/v) in final serum albumin solution Serum albumin, gently with bar magnet stir 30 minutes, bleed 30 minutes with vacuum pump and cause gas Bubble eliminates;Serum albumin solution room temperature is stood, after 48h, outwells supernatant liquid, under inciting somebody to action Layer has the serum albumin solution of bigger viscosity and joins in mould, dried in air at room temperature Night;Mould is opened, after taking-up, is dipped into succinimidyl propionate base polyglycol solution In, concentration is 10% (w/v), cleans to pH=7.0 with deionized water, is dried at 37 DEG C, Prepare super lubrication serum albumin Punctal plug.
Embodiment 3
Sero-abluminous solution system is dissolved in preparation: take each component according to percent by volume, 0.1M ammonia 10%, 1% mercaptoethanol, remaining is trifluoroethanol, and stirring makes it be sufficiently mixed; Serum albumin is dissolved in above-mentioned solution, containing 45% (w/v) in final serum albumin solution Serum albumin, gently with bar magnet stir 30 minutes, bleed 30 minutes with vacuum pump and cause gas Bubble eliminates;Serum albumin solution room temperature is stood, after 48h, outwells supernatant liquid, under inciting somebody to action Layer has the serum albumin solution of bigger viscosity and joins in mould, dried in air at room temperature Night;Mould is opened, after taking-up, is dipped into succinimidyl succinate base Polyethylene Glycol molten In liquid, concentration is 10% (w/v), cleans to pH=7.0 with deionized water, is dried at 37 DEG C, Prepare super lubrication serum albumin Punctal plug.

Claims (10)

1. a preparation method for serum albumin biomaterial, comprises the steps:
(1), sero-abluminous solution system is dissolved in preparation: contain in every bulk solution The trifluoroethanol (v/v) of 75%-94.95%, the inorganic base (v/v) of the 0.01M-2.0M of 5%-20%, The beta-mercaptoethanol (v/v) of 0.05%-5%;
(2), by serum albumin it is dissolved in above-mentioned solution, containing 5%-30% in final solution (w/v) serum albumin;
(3), serum albumin solution is stood, after question response is complete, outwell supernatant liquid, will Lower floor has the serum albumin solution of bigger viscosity and joins in mould, after solidification to be dried, Opening mould, being dipped into by solidification material containing concentration is the electrophilic of 0.5%~45% (w/v) In the hydrophilic polymer solution of functional group, it is dried after cleaning, prepares serum albumin biology material Material.
Preparation method the most according to claim 1, it is characterised in that: the white egg of described serum White source is the serum albumin of the animals such as people, cattle, horse, sheep, mouse.
Preparation method the most according to claim 1, it is characterised in that: described method step (1) In, the inorganic base in described solution selected from ammonia, sodium hydroxide, sodium carbonate, sodium bicarbonate, Disodium hydrogen phosphate, sodium phosphate etc. or its mixture.
Preparation method the most according to claim 1, it is characterised in that: described method step (3) In, serum albumin solution is stood 1-60 hour at 10-40 DEG C.
Preparation method the most according to claim 1, it is characterised in that: described method step (3) In, the described hydrophilic polymer containing electrophilic functional group is selected from succinimidyl propionate base Polyethylene Glycol, succinimidyl succinate base Polyethylene Glycol, Succinimidyl glutarate base Polyethylene Glycol, butanimide decanedioic acid ester group Polyethylene Glycol, pentaerythritol polyethylene glycol ether four Succinimidyl glutarate, pentaerythritol polyethylene glycol ether four butanimide succinic acid, season penta One or more in tetrol polyglycol ether four butanimide decanedioic acid.
Preparation method the most according to claim 1, it is characterised in that: described method step (3) In, the described hydrophilic polymer containing electrophilic functional group is succinimidyl succinate base Polyethylene Glycol.
Preparation method the most according to claim 1, it is characterised in that: described method step (3) In, after serum albumin solidification material soaks in hydrophilic polymer solution, cleaned to PH is 6.0~8.0;Cleanout fluid is selected from water maybe can maintain pH value of solution to be 6.0-8.0, concentration is Any one buffer solvent of 1-100mmol/L, optionally from phosphate buffer, disodium hydrogen phosphate- Citrate buffer solution, TRIS, glycyl-glycine, N-bis-(ethoxy) glycine, Phosphate sodium dihydrogen buffer solution, disodium hydrogen phosphate buffer, sodium-acetate buffer, sodium carbonate buffer Liquid, sodium phosphate buffer, lysis buffer, Arginine buffer or its mixture.
8. a serum albumin Punctal plug, it is by the method system described in any one of claim 1-7 Standby and obtain, described Punctal plug has main body (2), first segment (1), the second sections (3) With super lubricant coating (4).
Serum albumin Punctal plug the most according to claim 8, it is characterised in that: described Punctal plug body is slender cylinder, and described cylinder diameter is 0.5~4.5mm, and height is 0.2~3mm.
Serum albumin Punctal plug the most according to claim 8, it is characterised in that: described The super lubricant coating (4) of Punctal plug is by the Punctal plug mould described in claim 1 step (3) Prepare and formed after serum albumin Punctal plug soaks in hydrophilic polymer solution.
CN201610176245.9A 2016-03-24 2016-03-24 Super-lubricating serum albumin punctal plug and preparation method thereof Pending CN105879126A (en)

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CN111558093A (en) * 2020-05-19 2020-08-21 温州医科大学附属眼视光医院 Lacrimal passage suppository capable of being degraded in medium and long periods and preparation method thereof

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109731137A (en) * 2019-03-13 2019-05-10 成都氢润医疗科技有限公司 The preparation method of albumin coating with biological functions and material with biological functions
CN109731137B (en) * 2019-03-13 2021-05-07 陕西师范大学 Preparation method of albumin coating with biological anti-fouling function and material with biological anti-fouling function
CN111558093A (en) * 2020-05-19 2020-08-21 温州医科大学附属眼视光医院 Lacrimal passage suppository capable of being degraded in medium and long periods and preparation method thereof

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