CN117599228A - Multifunctional dressing patch for eyes - Google Patents
Multifunctional dressing patch for eyes Download PDFInfo
- Publication number
- CN117599228A CN117599228A CN202410092163.0A CN202410092163A CN117599228A CN 117599228 A CN117599228 A CN 117599228A CN 202410092163 A CN202410092163 A CN 202410092163A CN 117599228 A CN117599228 A CN 117599228A
- Authority
- CN
- China
- Prior art keywords
- layer
- hydrophobic
- polylactic acid
- glycolic acid
- acid copolymer
- 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
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 125000002091 cationic group Chemical group 0.000 claims description 15
- 229920000642 polymer Polymers 0.000 claims description 13
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 6
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- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 3
- 229960003942 amphotericin b Drugs 0.000 claims description 3
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- 229960003405 ciprofloxacin Drugs 0.000 claims description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 3
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- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 claims description 3
- 229960003255 natamycin Drugs 0.000 claims description 3
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F9/00—Methods 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
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
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- A—HUMAN NECESSITIES
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
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- A—HUMAN NECESSITIES
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- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
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- A—HUMAN NECESSITIES
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
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- A—HUMAN NECESSITIES
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
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- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/43—Hormones, e.g. dexamethasone
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a multifunctional ophthalmic dressing patch which comprises a transparent porous permeation layer, an antibacterial drug layer, a first porous permeation layer, an anti-inflammatory drug layer, a second porous permeation layer, an oxygen release layer and a transparent hydrophobic protection layer which are sequentially stacked; the antibacterial drug layer is a polymer film or hydrogel modified by a cationic polymer and loaded with hydrophobic antibiotic polylactic acid-glycolic acid copolymer nano particles; responsive release of the antibacterial agent under acidic and/or microbial polysaccharide degrading enzyme conditions; the anti-inflammatory drug layer is a polymer film or hydrogel loaded with hydrophobic anti-inflammatory drug phenylborate/polylactic acid-glycolic acid copolymer nano particles, and the anti-inflammatory drug is released in a responsive way under the condition of ROS generated by inflammation. The invention is not only used for preventing the infection and inflammation problems after eye surgery, but also can relieve the symptoms of dry eyes, corneal edema, cornea neovascularization, conjunctival congestion, infection, inflammatory reaction and the like caused by overuse or unhealthy eyes of daily use.
Description
Technical Field
The invention belongs to the field of medical treatment, and particularly relates to a multifunctional ophthalmic dressing patch which is particularly used for preventing postoperative infection and inflammation of eyes and relieving symptoms such as dry eyes, corneal edema, corneal neovascularization, conjunctival congestion, infection and inflammatory reaction caused by daily unhealthy eyes.
Background
In order to avoid secondary infections of the eyes caused by air pollution, medical instrument pollution and other approaches after eye operations such as cataract extraction, glaucoma operation, vitreoretinal operation and the like, related patients usually need to continuously and frequently apply antibacterial and anti-inflammatory drugs to the eyes. However, due to the excessively high frequency of administration and complex drug categories, patient compliance is poor, which can lead to frequent post-ocular infection events and even blindness. In addition, symptoms such as dry eyes, corneal edema, conjunctival congestion, infection and inflammation can be caused under daily conditions such as long-time computer office work and unhealthy eye habits. The release of the conventional antibacterial anti-inflammatory application has an uncontrollable or partially controllable release function, and can not carry out logic sequential response release on different processes of diseases, such as subacidity of acute wounds, alkaline microenvironment caused by microbial chronic infection, high Reactive Oxygen Species (ROS) expression period with inflammation in the later period of infection, and the like. Therefore, there is a need for a new multifunctional ophthalmic dressing patch that can provide a long-lasting logistic response to drug release to prevent post-operative infections and improve ocular symptoms without affecting vision.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a multifunctional ophthalmic dressing patch which adopts a combination technology of long-acting logical response release of antibacterial drugs, anti-inflammatory drugs and hypoxia improvement, and can prevent infection and relieve eye symptoms for patients after eye surgery and people with daily unhealthy eye habits. The antibacterial drug is responsively released under the action of acute wound acidic environment and chronic wound microorganism secretase, when the disease progresses to an inflammatory phase, the antibacterial drug is stimulated to release through ROS, and when the oxygen is simultaneously opened, the antibacterial-anti-inflammatory drug gradually releases oxygen, relieves local hypoxia and regulates the pH of the wound.
The aim of the invention is realized by the following technical scheme: a multifunctional dressing patch for eyes comprises a transparent porous permeation layer, an antibacterial drug layer, a first porous permeation layer, an anti-inflammatory drug layer, a second porous permeation layer, an oxygen release layer and a transparent hydrophobic protection layer which are sequentially stacked;
the antibacterial drug layer is a polymer film or hydrogel modified by a cationic polymer and loaded with hydrophobic antibiotic polylactic acid-glycolic acid copolymer nano particles; responsive release of the antibacterial agent under acidic conditions and/or microbial polysaccharide degrading enzyme conditions;
the anti-inflammatory drug layer is a polymer film or hydrogel loaded with hydrophobic anti-inflammatory drug phenylborate/polylactic acid-glycolic acid copolymer nano particles, and the anti-inflammatory drug is released in a responsive way under the condition of ROS generated by inflammation.
Further, when the antimicrobial drug released by the antimicrobial drug layer has inhibited microbial infection or no inflammatory symptoms are manifested, the antimicrobial drug layer may form a permeation barrier preventing permeation release of the upper anti-inflammatory drug layer, the anti-inflammatory drug layer preventing permeation of oxygen;
the oxygen slow release layer releases oxygen when the anti-inflammatory layer and the antibacterial layer are simultaneously opened.
Further, the transparent porous layer, the first porous layer and the second porous layer are made of methyl methacrylate, polytetrafluoroethylene and silicone hydrogel.
Further, the preparation method of the cationic high molecular polymer modified hydrophobic antibiotic loaded polylactic acid-glycolic acid copolymer nanoparticle comprises the following steps:
1) Dissolving polylactic acid-glycolic acid copolymer and hydrophobic antibiotic in organic solvent, and mixing uniformly;
2) Evaporating the organic solvent under vacuum condition to obtain a polylactic acid-glycolic acid copolymer polymer film;
3) Hydrating the obtained polylactic acid-glycolic acid copolymer polymer film with a cationic high molecular polymer and physiological saline containing polyvinyl alcohol under the ultrasonic action to obtain a cationic high molecular polymer modified hydrophobic antibiotic-loaded PLGA (polylactic acid-glycolic acid copolymer) nanoparticle suspension;
the hydrophobic antibiotic: the mass ratio of the polylactic acid-glycolic acid copolymer to the cationic high molecular polymer is 1: (1-100) 0.1-10);
the organic solvent is one or more of dichloromethane, acetone, DMSO, methanol or ethanol;
the cationic polymer is one or more of chitosan, cationic guar gum and cellulose-based polycation;
the hydrophobic antibiotic is one or more of azithromycin, ciprofloxacin, lincomycin, amphotericin B and natamycin.
Further, the preparation method of the hydrophobic anti-inflammatory drug loaded phenylborate/polylactic acid-glycolic acid copolymer nanoparticle comprises the following steps:
1) Dissolving phenylborate, polylactic acid-glycolic acid copolymer and hydrophobic anti-inflammatory drug in an organic solvent, and uniformly mixing;
2) Evaporating the organic solvent under vacuum condition to obtain a polylactic acid-glycolic acid copolymer polymer film;
3) Hydrating the obtained polylactic acid-glycolic acid copolymer polymer film with physiological saline containing polyvinyl alcohol under the action of ultrasound to obtain a phenylborate/polylactic acid-glycolic acid copolymer nanoparticle suspension carrying a hydrophobic anti-inflammatory drug;
the hydrophobic anti-inflammatory drug: phenylboronate: the mass ratio of the polylactic acid-glycolic acid copolymer is 1: (0.1-10), 1-100;
the hydrophobic anti-inflammatory drug is one or more of glucocorticoid, dexamethasone, aspirin and acetaminophen;
the organic solvent is one or more of dichloromethane, acetone, DMSO, methanol or ethanol.
Further, the oxygen slow release layer is a fluorocarbon compound loaded with oxygen.
Further, the transparent hydrophobic protective layer is made of acrylic ester copolymer and polyurethane.
Further, the antibacterial drug layer, the first porous permeation layer, the anti-inflammatory drug layer, the second porous permeation layer and the oxygen release layer are annular.
Further, the multifunctional eye dressing patch is arranged in an arc shape.
Further, when not in use, a hydrophobic protective layer is attached to the surface of the transparent porous permeation layer; when in use, the hydrophobic protective layer is removed, and the protective layer is directly covered on the surface of the cornea of the eyeball without affecting vision.
Compared with the prior art, the invention has the beneficial effects that:
(1) The structure of the eye dressing patch is similar to that of a contact lens, but the eye dressing patch can be applied to the cornea surface of an eyeball when in use, and is convenient to use, and the eye dressing patch is characterized in that a multifunctional layer capable of releasing antibacterial drugs, anti-inflammatory drugs and oxygen slow release for a long time is added in a non-optical area, so that postoperative infection can be effectively prevented, further infection and inflammation are avoided, or eye discomfort symptoms caused by daily unhealthy eyes are relieved.
(2) The multifunctional dressing responds to drug release by having disease progression logic. When the cornea microenvironment is normal, the functional layer formed by the hydrophobic antibacterial/anti-inflammatory drug loaded nanoparticles may form a permeation barrier preventing the excessive or unnecessary release of the internal drug. When the cornea micro-environment becomes acidic in an acute wound caused by microorganisms or trauma, the cationic polymer of the antibacterial drug layer ionizes at the moment, so that the release of the antibacterial drug is quickened, and pathogens are killed or invasion of the pathogens is prevented. When a microorganism causes chronic wounds, the microenvironment is alkaline, but a large amount of aggregated microorganisms secrete polysaccharide degrading enzymes, so that polysaccharide macromolecules of the nano particles are broken down, the quick release of the antibacterial drugs is promoted, and the microorganisms are killed. As the wound progresses to the inflammatory phase, phenylboronates in the anti-inflammatory nanoparticle structure in the anti-inflammatory drug layer break at the massive ROS generated, thereby responsively accelerating the release of the anti-inflammatory drug and inhibiting inflammation. In addition, only when the disease development is in a serious stage, namely the antibacterial drug layer and the anti-inflammatory drug layer are both started to release, the oxygen slow-release layer at the uppermost layer can break through the two first permeation barriers, so as to reach the cornea area, improve the hypoxia and promote the recovery of local microenvironment. The invention utilizes the nanocrystallization drug loading technology and the functional layer structure design to reasonably and logically release antibacterial drugs, anti-inflammatory drugs and oxygen in response, and can prevent or treat eye diseases for a long time by organically combining three angles of killing pathogens, improving inflammation and reducing hypoxia. (3) Compared with frequently used bactericidal and anti-inflammatory eye drops, the eye dressing patch provided by the invention belongs to a long-acting local administration technology, can improve the drug effect and reduce the use time cost. (4) The hydrophobic protective layer of the surface layer can prevent harmful substances such as external pathogens, dust and the like from damaging eyes.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the description of the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort to a person skilled in the art.
Fig. 1 is a schematic structural diagram of a multifunctional ophthalmic dressing patch according to an embodiment of the present invention;
fig. 2 is a top view of a multifunctional ophthalmic dressing patch according to an embodiment of the present invention;
fig. 3 is a schematic diagram of a front anatomical structure of a multifunctional ophthalmic dressing patch according to an embodiment of the present invention.
Reference numerals in the drawings: 1. the cornea of the eyeball; 2. multifunctional ophthalmic dressing; 3. a non-optical region; 4. an optical region; 5. a transparent porous permeation layer; 6. an antibacterial drug layer; 7. a first porous layer; 8. an anti-inflammatory drug layer; 9. a second porous layer; 10. an oxygen slow release layer; 11. transparent hydrophobic protective layer.
Detailed Description
Reference will now be made in detail to exemplary embodiments, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, the same numbers in different drawings refer to the same or similar elements, unless otherwise indicated. The implementations described in the following exemplary examples do not represent all implementations consistent with the invention. Rather, they are merely examples of apparatus consistent with aspects of the invention as detailed in the accompanying claims.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in this specification and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any or all possible combinations of one or more of the associated listed items.
It should be understood that although the terms first, second, third, etc. may be used herein to describe various information, these information should not be limited by these terms. These terms are only used to distinguish one type of information from another. For example, first information may also be referred to as second information, and similarly, second information may also be referred to as first information, without departing from the scope of the invention. The word "if" as used herein may be interpreted as "at … …" or "at … …" or "responsive to a determination", depending on the context.
The present invention will be described in detail with reference to the accompanying drawings. The features of the examples and embodiments described below may be combined with each other without conflict.
Referring to fig. 1-3 in combination, fig. 1 is a schematic structural diagram of a multifunctional dressing patch for eyes, similar to a contact lens, attached to a cornea surface according to an embodiment of the present invention; comprises a transparent porous permeation layer 5, an antibacterial drug layer 6, a first porous permeation layer 7, an anti-inflammatory drug layer 8, a second porous permeation layer 9, an oxygen release layer 10 and a transparent hydrophobic protection layer 11 which are sequentially stacked.
The release function of the long-acting logic response of the drug is specifically as follows: the antibacterial drug layer 6 is a polymer film or hydrogel modified by a cationic polymer and loaded with hydrophobic antibiotic polylactic acid-glycolic acid copolymer nano particles; can responsively release the antibacterial drug under acidic conditions and/or microbial polysaccharide degrading enzyme conditions; the anti-inflammatory drug layer 8 is a polymer film or hydrogel loaded with hydrophobic anti-inflammatory drug phenylborate/polylactic acid-glycolic acid copolymer nano particles, and can release the anti-inflammatory drug in a responsive way under the condition of ROS generated by inflammation. When the antimicrobial drug released by the antimicrobial drug layer 6 has inhibited microbial infection or no inflammatory symptoms are present, the antimicrobial drug layer 6 forms a permeation barrier preventing permeation release of the upper layer of the anti-inflammatory drug, and the anti-inflammatory drug layer 8 prevents permeation of oxygen; the oxygen-releasing layer 10 releases oxygen only when the anti-inflammatory drug layer 8 and the antibacterial drug layer 6 are simultaneously turned on.
Fig. 2 is a top view of a multifunctional ophthalmic dressing patch provided in the embodiment of the present invention, where the multifunctional ophthalmic dressing patch 2 may be divided into a non-optical area 3 and an optical area 4, where the non-optical area 3 is adhered with various functional layers (i.e. an antibacterial drug layer 6, a first porous permeation layer 7, an anti-inflammatory drug layer 8, a second porous permeation layer 9 and an oxygen release layer 10), so as not to affect the normal viewing function of the optical area (4) where the vision is located, specifically, the antibacterial drug layer 6, the first porous permeation layer 7, the anti-inflammatory drug layer 8, the second porous permeation layer 9 and the oxygen release layer 10 are annular, and the transparent porous permeation layer 5 of the first layer and the transparent hydrophobic protection layer 11 of the uppermost layer are made of transparent materials; preferably, the transparent porous permeation layer 5 is made of methyl methacrylate, polytetrafluoroethylene and silicone hydrogel, and the transparent hydrophobic protection layer 11 is made of acrylate copolymer and polyurethane.
Fig. 3 is a schematic view of a front anatomical structure of a multifunctional ophthalmic dressing patch according to an embodiment of the present invention, including: the transparent porous permeation layer 5 covered on the cornea 1 of the eyeball is sequentially stuck with the antibacterial drug layer 6 in the non-optical area 3, the antibacterial drug layer 8 is stuck after the isolation of the first porous permeation layer 7, the antibacterial drug/the anti-inflammatory drug/the oxygen is gradually and slowly released to the cornea surface through the second porous permeation layer 9 and the oxygen release layer 10, thereby preventing or infecting the infection after the operation or the unhealthy eye, the inflammation symptom, finally sticking the hydrophobic protection layer 11 integrally, preventing the injury of harmful substances such as external pathogens, dust and the like to the eyes and protecting the external leakage of the multifunctional drug. When the multifunctional dressing patch 2 is used, the release function of the long-acting logic responsiveness of the medicine can be realized only by attaching the multifunctional dressing patch 2 to the cornea surface conveniently and quickly, and the eye vision is not affected.
The transparent porous layer 5, the first porous layer 7 and the second porous layer 9 are made of methyl methacrylate, polytetrafluoroethylene and silicone hydrogel. They are all organic polymer materials, have the characteristics of hydrophilicity, transparency, porosity and the like, and are suitable for preparing dressing patches
The antibacterial drug layer 6 can be a polymer film or hydrogel modified by a cationic polymer and loaded with hydrophobic antibiotic PLGA nano particles, various hydrophobic antibiotic molecules can be wrapped inside the PLGA polymer, and chitosan wrapped outside can be ionized or degraded under the action of an acidic condition or a microbial polysaccharide degrading enzyme, so that the capability of acidic or microbial infection responsive release is realized, and under normal conditions, a compact permeation barrier is formed, and the action time of patch sterilization or infection prevention is prolonged.
The anti-inflammatory drug layer 8 is a polymer film or hydrogel loaded with hydrophobic anti-inflammatory drug phenylborate/PLGA nano particles, has the effect of prolonging the anti-inflammatory treatment or prevention time of the dressing patch like 6, and can release the anti-inflammatory drug in the inflammatory phase response.
The preparation method of the cationic high molecular polymer modified hydrophobic antibiotic loaded polylactic acid-glycolic acid copolymer nanoparticle comprises the following steps:
1) Dissolving polylactic acid-glycolic acid copolymer and hydrophobic antibiotic in organic solvent, and mixing uniformly;
2) Evaporating the organic solvent under vacuum condition to obtain a polylactic acid-glycolic acid copolymer polymer film;
3) Hydrating the obtained polylactic acid-glycolic acid copolymer polymer film with a cationic high molecular polymer and physiological saline containing polyvinyl alcohol (PVA) under the ultrasonic action to obtain a cationic high molecular polymer modified hydrophobic antibiotic-loaded PLGA nanoparticle suspension; preferably, the mass concentration of the polyvinyl alcohol in the physiological saline containing the polyvinyl alcohol is 0.1% -10%;
the hydrophobic antibiotic: the mass ratio of the polylactic acid-glycolic acid copolymer to the cationic high molecular polymer is 1: (1-100) 0.1-10);
the cationic polymer is one or more of chitosan, cationic guar gum and cellulose-based polycation;
the hydrophobic antibiotic is one or more of azithromycin, ciprofloxacin, lincomycin, amphotericin B and natamycin.
The preparation method of the hydrophobic anti-inflammatory drug loaded phenylborate/polylactic acid-glycolic acid copolymer nanoparticle comprises the following steps:
1) Dissolving phenylboronate, PLGA and a hydrophobic anti-inflammatory drug in an organic solvent, and uniformly mixing;
2) Evaporating the organic solvent under vacuum condition to obtain a polylactic acid-glycolic acid copolymer polymer film;
3) Hydrating the obtained PLGA polymer film with physiological saline containing polyvinyl alcohol under the ultrasonic action to obtain phenylborate/PLGA nanoparticle suspension loaded with a hydrophobic anti-inflammatory drug; preferably, the mass concentration of the polyvinyl alcohol in the physiological saline containing the polyvinyl alcohol is 0.1% -10%;
the hydrophobic anti-inflammatory drug: phenylboronate: the mass ratio of the polylactic acid-glycolic acid copolymer is 1: (0.1-10), 1-100;
the hydrophobic anti-inflammatory drug is one or more of glucocorticoid, dexamethasone, aspirin and acetaminophen;
the organic solvent is one or more of dichloromethane, acetone, DMSO, methanol or ethanol.
The oxygen slow release layer 10 is a fluorocarbon compound loaded with oxygen, on one hand, can slowly release oxygen, relieve local hypoxia, avoid generation of new blood vessels, and on the other hand, can release oxygen in a targeted direction towards the cornea due to the effect of the hydrophobic layer 11, and does not leak to the outside. And oxygen release must be accomplished through increased permeation clearance when the anti-inflammatory and antibacterial layers are simultaneously released.
The multifunctional layer is adhered to the non-optical area 3, so that the optical area 4 for external observation by eyes is avoided, and the eyesight of a user is not affected.
The multifunctional layers are mutually adhered according to the sequence of the invention, and the direct interaction of various medicines can be effectively prevented through the porous permeable layer.
The main body of the multifunctional ophthalmic dressing patch is in an arc shape, so that the multifunctional ophthalmic dressing patch can be attached to the cornea surface of an eyeball more conveniently, and discomfort during use is reduced.
The multifunctional eye dressing patch 2 has the integral structure similar to that of a contact lens, and when the multifunctional eye dressing patch 2 is used, the dressing patch 2 is worn in a contact lens mode;
when the multifunctional ophthalmic dressing patch 2 is not used, a hydrophobic protective layer (the material adopted by the hydrophobic protective layer comprises acrylic ester copolymer and polyurethane) can be attached to the surface of the transparent porous permeation layer 5, so that the loss of medicines is prevented. When the multifunctional eye dressing patch is used, the hydrophobic protective layer below the transparent porous permeable layer 5 is removed, and the antibacterial drug layer 6 and the anti-inflammatory drug layer 8 in the multifunctional eye dressing patch 2 can exchange water with each porous permeable layer under the action of the eye water environment and release the water to the cornea surface. In normal cornea microenvironment, the antibacterial and anti-inflammatory drug layers can form a permeation barrier due to the presence of nanoparticles, avoiding premature release of the internal drug during non-disease periods. However, when acute wounds or chronic infected wounds exist, the micro environment is changed to be acidic or the condition of the over-expressed microbial polysaccharide degrading enzyme, the antibacterial drug can be released in response. Further with the advent of the inflammatory phase, the massive production of ROS stimulates the anti-inflammatory drug layer to release anti-inflammatory drugs to improve the inflammatory condition. While the oxygen slow release layer 11 can release high concentration oxygen loaded in the interior through the permeation gap when the oxygen slow release layer and the oxygen slow release layer are opened, so as to stabilize the pH of the microenvironment and improve the local hypoxia. The three are combined with each other to prevent and improve ocular discomfort and inflammation caused by unhealthy eyes in response to infection after ocular surgery. The medicine in the dressing patch can use broad-spectrum antibacterial and anti-inflammatory medicines, has simple overall structure but rich functions, can prolong the service life of the medicine, has higher stability and practicability, and has certain popularization value.
Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure herein. This application is intended to cover any variations, uses, or adaptations of the application following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the application pertains. The specification and examples are to be regarded in an illustrative manner only.
It is to be understood that the present application is not limited to the precise arrangements and instrumentalities shown in the drawings, which have been described above, and that various modifications and changes may be effected without departing from the scope thereof.
Claims (10)
1. The multifunctional ophthalmic dressing patch is characterized by comprising a transparent porous permeation layer, an antibacterial drug layer, a first porous permeation layer, an anti-inflammatory drug layer, a second porous permeation layer, an oxygen release layer and a transparent hydrophobic protection layer which are sequentially stacked;
the antibacterial drug layer is a polymer film or hydrogel modified by a cationic polymer and loaded with hydrophobic antibiotic polylactic acid-glycolic acid copolymer nano particles; responsive release of the antibacterial agent under acidic conditions and/or microbial polysaccharide degrading enzyme conditions;
the anti-inflammatory drug layer is a polymer film or hydrogel loaded with hydrophobic anti-inflammatory drug phenylborate/polylactic acid-glycolic acid copolymer nano particles, and the anti-inflammatory drug is released in a responsive way under the condition of ROS generated by inflammation.
2. The patch of claim 1, wherein when the antimicrobial drug released by the antimicrobial drug layer has inhibited microbial infection or no inflammatory condition is manifested, the antimicrobial drug layer forms a permeation barrier to prevent permeation of the upper anti-inflammatory drug layer from releasing, and the anti-inflammatory drug layer prevents permeation of oxygen;
the oxygen slow release layer releases oxygen when the anti-inflammatory layer and the antibacterial layer are simultaneously opened.
3. The multi-purpose ophthalmic dressing patch of claim 1, wherein the transparent porous layer, the first porous layer and the second porous layer comprise methyl methacrylate, polytetrafluoroethylene and silicone hydrogel.
4. The multifunctional ophthalmic dressing patch according to claim 1, wherein the preparation method of the cationic high molecular polymer modified hydrophobic antibiotic-loaded polylactic acid-glycolic acid copolymer nanoparticle comprises the following steps:
1) Dissolving polylactic acid-glycolic acid copolymer and hydrophobic antibiotic in organic solvent, and mixing uniformly;
2) Evaporating the organic solvent under vacuum condition to obtain a polylactic acid-glycolic acid copolymer polymer film;
3) Hydrating the obtained polylactic acid-glycolic acid copolymer polymer film with a cationic high molecular polymer and physiological saline containing polyvinyl alcohol under the ultrasonic action to obtain a cationic high molecular polymer modified hydrophobic antibiotic-loaded PLGA (polylactic acid-glycolic acid copolymer) nanoparticle suspension;
the hydrophobic antibiotic: the mass ratio of the polylactic acid-glycolic acid copolymer to the cationic high molecular polymer is 1: (1-100) 0.1-10);
the organic solvent is one or more of dichloromethane, acetone, DMSO, methanol or ethanol;
the cationic polymer is one or more of chitosan, cationic guar gum and cellulose-based polycation;
the antibacterial drug is a hydrophobic antibiotic, and the hydrophobic antibiotic is one or more of azithromycin, ciprofloxacin, lincomycin, amphotericin B and natamycin.
5. The multifunctional ophthalmic dressing patch according to claim 1, wherein the preparation method of the hydrophobic anti-inflammatory drug-loaded phenylborate/polylactic acid-glycolic acid copolymer nanoparticle comprises the following steps:
1) Dissolving phenylborate, polylactic acid-glycolic acid copolymer and hydrophobic anti-inflammatory drug in an organic solvent, and uniformly mixing;
2) Evaporating the organic solvent under vacuum condition to obtain a polylactic acid-glycolic acid copolymer polymer film;
3) Hydrating the obtained polylactic acid-glycolic acid copolymer polymer film with physiological saline containing polyvinyl alcohol under the action of ultrasound to obtain a phenylborate/polylactic acid-glycolic acid copolymer nanoparticle suspension carrying a hydrophobic anti-inflammatory drug;
the hydrophobic anti-inflammatory drug: phenylboronate: the mass ratio of the polylactic acid-glycolic acid copolymer is 1: (0.1-10), 1-100;
the hydrophobic anti-inflammatory drug is one or more of glucocorticoid, dexamethasone, aspirin and acetaminophen;
the organic solvent is one or more of dichloromethane, acetone, DMSO, methanol or ethanol.
6. The multi-purpose ophthalmic dressing patch of claim 1, wherein the oxygen slow release layer is an oxygen-loaded fluorocarbon.
7. The multifunctional ophthalmic dressing patch of claim 1, wherein the transparent hydrophobic protective layer comprises an acrylate copolymer or polyurethane.
8. The multi-functional ophthalmic dressing patch of claim 1, wherein the antimicrobial drug layer, the first porous permeation layer, the anti-inflammatory drug layer, the second porous permeation layer, and the oxygen-eluting layer are annular.
9. The patch of claim 1, wherein the patch is configured in an arcuate configuration.
10. The patch according to claim 1, wherein a hydrophobic protective layer is attached to the surface of the transparent porous layer when not in use; when in use, the hydrophobic protective layer is removed, and the protective layer is directly covered on the surface of the cornea of the eyeball without affecting vision.
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| CN113413237A (en) * | 2021-06-01 | 2021-09-21 | 温州医科大学 | Surface-modified artificial lens with degradable drug sustained-release coating with concentric ring patterns and preparation method thereof |
| KR20230171242A (en) * | 2022-06-13 | 2023-12-20 | 한국기계연구원 | Multi-layered wound dressing patch and manufacturing method thereof |
| CN218842014U (en) * | 2022-10-27 | 2023-04-11 | 安徽医科大学 | Corneal contact lens with medicine slow-release function |
| CN115678046A (en) * | 2022-11-24 | 2023-02-03 | 华中科技大学 | Oxygen-producing double-network hydrogel, preparation method and application |
| CN116808286A (en) * | 2023-08-09 | 2023-09-29 | 北京化工大学 | Inflammatory response on-demand anti-inflammatory hydrogel medical dressing for skin wound healing and preparation method thereof |
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