CN115232264A - Hot-melt pressure-sensitive adhesive for transdermal delivery of hydrophilic drugs and medical patch - Google Patents
Hot-melt pressure-sensitive adhesive for transdermal delivery of hydrophilic drugs and medical patch Download PDFInfo
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- CN115232264A CN115232264A CN202210716531.5A CN202210716531A CN115232264A CN 115232264 A CN115232264 A CN 115232264A CN 202210716531 A CN202210716531 A CN 202210716531A CN 115232264 A CN115232264 A CN 115232264A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F287/00—Macromolecular compounds obtained by polymerising monomers on to block polymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7076—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising ingredients of undetermined constitution or reaction products thereof, e.g. rosin or other plant resins
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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
- A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
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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
- A61L15/20—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
- 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
- A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
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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
- A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
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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
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
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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
- A61L15/42—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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J11/00—Features of adhesives not provided for in group C09J9/00, e.g. additives
- C09J11/02—Non-macromolecular additives
- C09J11/04—Non-macromolecular additives inorganic
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J151/00—Adhesives based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Adhesives based on derivatives of such polymers
- C09J151/006—Adhesives based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Adhesives based on derivatives of such polymers grafted on to block copolymers containing at least one sequence of polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J7/00—Adhesives in the form of films or foils
- C09J7/30—Adhesives in the form of films or foils characterised by the adhesive composition
- C09J7/35—Heat-activated
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J7/00—Adhesives in the form of films or foils
- C09J7/30—Adhesives in the form of films or foils characterised by the adhesive composition
- C09J7/38—Pressure-sensitive adhesives [PSA]
- C09J7/381—Pressure-sensitive adhesives [PSA] based on macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- C09J7/385—Acrylic polymers
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K2201/00—Specific properties of additives
- C08K2201/002—Physical properties
- C08K2201/005—Additives being defined by their particle size in general
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J2301/00—Additional features of adhesives in the form of films or foils
- C09J2301/30—Additional features of adhesives in the form of films or foils characterized by the chemical, physicochemical or physical properties of the adhesive or the carrier
- C09J2301/302—Additional features of adhesives in the form of films or foils characterized by the chemical, physicochemical or physical properties of the adhesive or the carrier the adhesive being pressure-sensitive, i.e. tacky at temperatures inferior to 30°C
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J2301/00—Additional features of adhesives in the form of films or foils
- C09J2301/30—Additional features of adhesives in the form of films or foils characterized by the chemical, physicochemical or physical properties of the adhesive or the carrier
- C09J2301/304—Additional features of adhesives in the form of films or foils characterized by the chemical, physicochemical or physical properties of the adhesive or the carrier the adhesive being heat-activatable, i.e. not tacky at temperatures inferior to 30°C
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J2301/00—Additional features of adhesives in the form of films or foils
- C09J2301/40—Additional features of adhesives in the form of films or foils characterized by the presence of essential components
- C09J2301/408—Additional features of adhesives in the form of films or foils characterized by the presence of essential components additives as essential feature of the adhesive layer
Abstract
The invention provides a hot-melt pressure-sensitive adhesive and a medical patch for transdermal administration of hydrophilic drugs. In order to remarkably improve the loading capacity and the hydrophilic drug slow-release capacity of the hot-melt pressure-sensitive adhesive, hydrophilic monomer methacrylic acid sulfobetaine is grafted to the SIS copolymer by an ultraviolet polymerization method, and then black talc is added to prepare the novel SBMA-g-SIS hot-melt pressure-sensitive adhesive. The graft modified SIS copolymer can establish a stable colloid system due to the amphipathy, has a lower micelle monomolecular exchange speed, and simultaneously is added with black talc with good adsorption performance, so that the hydrophilic drug loading capacity and the drug slow-release capacity of the pressure-sensitive adhesive are greatly improved by the synergy of the two. And the amphiphilic SIS copolymer has good compatibility with tackifying resin, and the adhesive property of the pressure-sensitive adhesive is improved.
Description
Technical Field
The invention belongs to the technical field of adhesives, relates to a hot-melt pressure-sensitive adhesive, and particularly relates to a hot-melt pressure-sensitive adhesive for transdermal delivery of hydrophilic drugs, a medical drug delivery patch and a preparation method thereof.
Background
The Hot Melt Pressure Sensitive Adhesive (HMPSA) has double performances of hot melt and pressure sensitive, is coated in a molten state, and can be quickly bonded by applying light pressure after being cooled. The hot-melt pressure-sensitive adhesive does not contain organic solvent, does not pollute the environment, is simple to manufacture and convenient to use, and has wide application in the field of medical treatment and health.
The HMPSAs based on the SIS thermoplastic elastomer mainly comprise styrene-isoprene-styrene triblock (SIS) copolymer, tackifying resin and plasticizer, have the property of vulcanized rubber at room temperature, and have plasticity at high temperature. The SIS-based HMPSAs exhibit excellent lipophilic drug-loading ability and self-crystallization inhibition, can effectively deliver lipophilic drugs to the skin, and are therefore suitable for the preparation of medical patches.
However, SIS belongs to a hydrophobic material, so that hydrophilic drugs are difficult to load, and the SIS has poor moisture absorption and air permeability and is easy to cause skin allergy due to strong hydrophobicity, so that the application of the SIS in a transdermal drug delivery patch is greatly limited. Thus, researchers have introduced hydrophilic functional groups into SIS using in situ epoxidation to prepare epoxidized SIS (ESIS). However, ESIS is still less hydrophilic and the effect of loading hydrophilic drugs is not ideal. And the poor compatibility between the epoxy group and the tackifying resin can weaken the adhesive property of the HMPSAs, so that the adhesive property of the corresponding medical patch is poor.
Therefore, a hot melt pressure sensitive adhesive for hydrophilic drug loading and good adhesion performance is needed, and is applied to medical patches for hydrophilic drug transdermal delivery.
Disclosure of Invention
The invention provides a hot-melt pressure-sensitive adhesive for transdermal administration of hydrophilic drugs and a medical patch thereof. The technical principle of the invention is as follows: grafting a hydrophilic monomer methacrylic acid Sulfobetaine (SBMA) to the SIS copolymer by an ultraviolet polymerization method, and adding hydrophilic black talc into a hot melt adhesive to prepare the novel SBMA-g-SIS hot melt pressure sensitive adhesive. The graft modified SIS copolymer can establish a stable colloid system due to the amphipathy, has a lower micelle monomolecular exchange speed, and simultaneously is added with black talc with good adsorption performance, so that the hydrophilic drug loading capacity and the drug slow-release capacity of the pressure-sensitive adhesive are greatly improved by the synergy of the two. And the amphiphilic SIS copolymer has good compatibility with tackifying resin, and the adhesive property of the pressure-sensitive adhesive is improved.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides an SBMA-g-SIS copolymer (sulfobetaine-grafted styrene-isoprene-styrene triblock copolymer) prepared as follows:
dissolving a photoinitiator and sulfobetaine methacrylate (SBMA) in an organic solvent, adding a styrene-isoprene-styrene triblock copolymer (SIS), completely swelling (about 20-28h is needed, and 24h is needed in one embodiment of the invention), taking out the swollen matter, placing the swollen matter in an ultraviolet lamp for grafting reaction, after the reaction is completely finished (900-1200W, preferably 1000W for grafting reaction for 8-15min, preferably 10 min), volatilizing the solvent (usually at room temperature), and obtaining the SBMA-g-SIS copolymer (sulfobetaine methacrylate grafted styrene-isoprene-styrene triblock copolymer); the mass ratio of the sulfobetaine methacrylate to the styrene-isoprene-styrene triblock copolymer is 1-9 (preferably 7; the mass ratio of the photoinitiator to the methacrylic acid sulfobetaine is 0.3-1:35 (preferably 0.5; the volume ratio of the organic solvent is 1.5-3:1 (preferably 2.3).
The photoinitiator is a photoinitiator which initiates polymerization through a hydrogen abstraction reaction. Further, the photoinitiator is a mixture of benzophenone and benzoin dimethyl ether (mass ratio of 1. In a preferred embodiment of the invention, a mass ratio of 1:2 with benzoin dimethyl ether, but those skilled in the art know that various photoinitiators which initiate polymerization by hydrogen abstraction reaction can give SBMA-g-SIS copolymers of the present invention.
In a second aspect, the invention provides a hot melt pressure sensitive adhesive matrix containing the SBMA-g-SIS copolymer, wherein the hot melt pressure sensitive adhesive matrix comprises the following components in parts by mass:
the tackifying resin is one or a mixture of more than two of polymerized rosin, terpene resin, petroleum resin or modified resin thereof (preferably polymerized rosin); the plasticizer is naphthenic oil, chlorinated paraffin or epoxidized soybean oil (preferably naphthenic oil).
Further, the invention provides a preparation method of the black talc powder with the particle size of 300-400nm, wherein the black talc powder with the particle size of 300-400nm is prepared by the following method:
crushing, ball-milling and sieving black talc powder (in Guangfeng region of Shanghai province in Jiangxi), and adding the black talc powder into the obtained black talc powder according to the volume ratio of 1:1, ball-milling for 6-18 h by a wet method at 700r/min, centrifugally washing the obtained sample by deionized water (3 times), drying the obtained precipitate, grinding, and sieving by a 200-mesh sieve to obtain the black talc powder with the particle size of 300-400nm.
Preferably, the volume of the mixed solution of the ethanol and the deionized water is 1.5-3mL/g (preferably 2 mL/g) by mass of the black talcum powder.
Further preferably, the hot-melt pressure-sensitive adhesive matrix comprises or consists of the following components in parts by mass:
in a third aspect, the invention provides a preparation method of the hot-melt pressure-sensitive adhesive matrix, which is characterized in that the method comprises the following steps: mixing SBMA-g-SIS copolymer, plasticizer and black talcum powder with the particle size of 300-400nm according to the formula amount, heating to 180 ℃, and stirring to be clear and transparent; adding a formula amount of tackifying resin, cooling to 150 ℃, and stirring until the mixture is clear and transparent to obtain the hot-melt pressure-sensitive adhesive matrix.
In a fourth aspect, the invention provides a hot-melt pressure-sensitive adhesive using the hot-melt pressure-sensitive adhesive matrix as a carrier, wherein the hot-melt pressure-sensitive adhesive consists of the hot-melt pressure-sensitive adhesive matrix and a hydrophilic drug.
The hydrophilic drugs include, but are not limited to, hydrophilic antibacterial drugs, traditional Chinese medicine extracts, hydrophilic analgesic drugs, and the like. The addition amount of the hydrophilic drug is preferably the maximum drug loading of the hot-melt pressure-sensitive adhesive matrix, so that the drug is not precipitated in the glue, and generally does not exceed 10%.
According to the embodiment of the invention, chlorhexidine acetate is adopted to demonstrate the loading capacity of the hydrophilic drug, the grafted SBMA-g-SIS copolymer is greatly improved in drug loading and adhesive property compared with the ungrafted SIS, and the black talc powder is used for further improving the drug loading and adhesive property of the hot-melt pressure-sensitive adhesive base. In one embodiment of the invention, the maximum drug loading of chlorhexidine acetate can be up to 6.7%, but depending on the drug choice, the maximum drug loading may vary somewhat.
Particularly preferably, the hot-melt pressure-sensitive adhesive consists of the following components in parts by mass:
the tackifying resin is one or a mixture of more than two of polymerized rosin, terpene resin, petroleum resin or modified resin thereof (preferably polymerized rosin); the plasticizer is naphthenic oil, chlorinated paraffin or epoxidized soybean oil (preferably naphthenic oil).
Most preferably, the hot-melt pressure-sensitive adhesive comprises or consists of the following components in parts by mass:
in view of the increased polarity of the modified SIS copolymer, a tackifying resin compatible with SBMA-g-SIS is preferred, including but not limited to one or a mixture of two or more of polymerized rosin, terpene resin, petroleum resin or modified resin thereof, and the like.
Similarly, plasticizers compatible with SBMA-g-SIS, including but not limited to naphthenic oils, chlorinated paraffins, epoxidized soybean oil, and the like, are preferred.
In a fifth aspect, the present invention further provides a preparation method of the above hot melt pressure sensitive adhesive, where the method is: mixing SBMA-g-SIS copolymer, plasticizer and black talcum powder with particle size of 300-400nm according to the formula amount, heating to 180 ℃, and stirring to be clear and transparent; adding a formula amount of tackifying resin, cooling to 150 ℃, and stirring to be clear and transparent to obtain the hot-melt pressure-sensitive adhesive.
Preferably, the invention also provides a preparation method of the hot melt pressure sensitive adhesive, wherein the hot melt pressure sensitive adhesive comprises the following components in parts by mass:
the tackifying resin is polymerized rosin, terpene resin, petroleum resin or modified resin thereof (preferably polymerized rosin); the plasticizer is naphthenic oil, chlorinated paraffin or epoxidized soybean oil (preferably naphthenic oil);
the method comprises the following steps:
mixing SBMA-g-SIS copolymer, plasticizer and black talcum powder with particle size of 300-400nm according to the formula amount, heating to 180 ℃, and stirring to be clear and transparent; adding a formula amount of tackifying resin, cooling to 150 ℃, and stirring to be clear and transparent; and cooling to 130 ℃, adding a formula amount of hydrophilic medicine, and fully stirring until the mixture is clear and transparent to obtain the hot-melt pressure-sensitive adhesive.
In a sixth aspect, the invention also provides an application of the hot-melt pressure-sensitive adhesive matrix or the hot-melt pressure-sensitive adhesive in a patch, especially a patch in the field of medicine, and various medical patches can be prepared according to requirements.
The drug-loaded hot melt pressure-sensitive adhesive can be used for preparing a medical paster for transdermal delivery of hydrophilic drugs, and is prepared by coating the drug-loaded pressure-sensitive adhesive on a polyurethane film or a non-woven fabric backing. The medical patch can be used as antibacterial adhesive film, wound plaster, analgesic and antiinflammatory patch, etc.
Specifically, the invention provides an application of the hot-melt pressure-sensitive adhesive in preparation of a medical patch.
Further, the application is as follows: the medical patch is a medical patch, and the medical patch comprises a flaky base material and a hot-melt pressure-sensitive adhesive coated on the flaky base material.
Further, the sheet-shaped substrate is a back lining polyurethane film, non-woven fabric or medical release paper.
Preferably, the hot melt pressure sensitive adhesive comprises an antimicrobial drug.
The medical patch has a peel strength of 276-301gf/cm, a tack energy of > 5 days, and is free from residual adhesive upon peeling. When the chlorhexidine acetate is used as a model drug, the effective antibacterial time is more than 120h. The application of the plaster is that the plaster can be used as an antibacterial sticking membrane, a band-aid and an analgesic and anti-inflammatory plaster.
Compared with SIS-based hot melt pressure sensitive adhesive, the invention has the beneficial effects that: SBMA is added into the hot-melt pressure-sensitive adhesive for hydrophilic modification, and black talc is added for auxiliary action, so that the hot-melt pressure-sensitive adhesive has remarkable innovativeness and performance advantages: the addition of SBMA obviously improves the hydrophilicity of SIS, and the SIS copolymer after grafting modification can form a stable colloid system due to the amphipathy of the SIS copolymer, has lower micelle monomolecular exchange speed, and synergistically promotes the loading, slow release capacity and adhesion performance of pressure-sensitive adhesive hydrophilic drugs together with hydrophilic black talc with good adsorption performance; SBMA has a wide compatibility, which enhances the compatibility of the SIS copolymer with tackifying resin, thus further improving the adhesive performance of the pressure sensitive adhesive. The pressure sensitive adhesive can be used in medical patch products, such as dressings, surgical films, plaster patches, and the like, and can facilitate transdermal delivery of hydrophilic drugs.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1: preparation of SBMA-g-SIS-based hot melt pressure sensitive adhesive
SBMA-g-SIS-based drug-loaded hot-melt pressure-sensitive adhesive is synthesized according to the proportion in the following table, and SIS-based drug-loaded hot-melt pressure-sensitive adhesive prepared from commercial SIS copolymer (SIS 1209, the tomb petrochemical industry) is used as a control group.
0.5g of a photoinitiator (benzophenone and benzoin dimethyl ether, mass ratio 1; and (2) putting 30g of SIS copolymer powder (SIS 1209, the tombarthite, the styrene content is 30%) into the mixed solution for swelling for 24h, taking out the swollen matter, placing the swollen matter in a position 30cm under an ultraviolet lamp with the power of 1000W for grafting reaction for 10min, and volatilizing the solvent at room temperature to obtain the SBMA-g-SIS copolymer.
Uniformly stirring the SBMA-g-SIS copolymer and plasticizer naphthenic oil (KN 4006, xinjiang kramey) at 180 ℃; adding tackifying resin polymerized rosin (140 parts by weight of Guangzhou Yunlin), uniformly stirring at 150 ℃, adding 0.4 part by weight of chlorhexidine acetate (hydrophilic antibacterial drug), and fully stirring at 130 ℃ until the mixture is clear and transparent to obtain the drug-loaded hot-melt pressure-sensitive adhesive.
TABLE 1 formula of drug-loaded modified SIS-based hot-melt pressure-sensitive adhesive
Example 2: preparation of medical Patches
The 8 pressure-sensitive adhesives prepared in example 1 were mixed at a ratio of 0.2g/cm 2 The amount of the coating is uniformly coated on the medical release paper(Wuxi Zixu, 120 g) on the anti-sticking surface. The medical operation film is prepared by covering a polyurethane film on the surface of a pressure-sensitive adhesive layer, rolling, standing for 1-7 days, and transferring the medical pressure-sensitive adhesive layer coated on medical release paper to the polyurethane film (0.015 mm, kaissima, japan); a medical plaster is prepared by covering non-woven fabric (Shandong Shuntai, 013) on the surface of pressure sensitive adhesive layer, rolling, standing for 1-7 days to transfer the medical pressure sensitive adhesive layer coated on the medical release paper to the non-woven fabric. Then, cutting, folding, packaging and irradiating for sterilization to obtain the finished product of the medical patch.
Example 3: evaluation of tackiness of medical Patch
The invention tests the adhesion performance and the drug release performance of the control group and the No. 1-7 patch coated with the drug-loaded hot-melt pressure-sensitive adhesive in example 2. The adhesion properties include the permanent adhesion and the peel strength (1 Cr18Ni9Ti steel plate) tested using the national standards GB/T4851-1998 and GB2792-81, respectively. The results are shown in the following table. Therefore, the prepared 1-7# group pressure-sensitive adhesive patches have good viscosity which is higher than that of a control group, which shows that the SBMA-g-SIS-based pressure-sensitive adhesive enhances the compatibility with tackifying resin and improves the adhesive property. In addition, there was no adhesive residue when the patch was peeled off.
Table 2 results of adhesion test of medical patch
Example 4: drug sustained-release test for medical patch
The invention uses chlorhexidine acetate as a hydrophilic model drug to measure the drug release rate of the medical paster. A drug release test was performed using 40% (v/v) ethanol/water solution as a receiving medium for drug release, and the control group and No. 1-7 drug-loaded medical patches prepared in example 2 were removed with the anti-adhesion film of the patch facing the receiving reservoir and the diffusion area of 0.627cm 2 The volume of the receiving pool is 5ml; the temperature of the receiving pool is ensured to be 37 +/-0.5 ℃, and the stirring speed is 700r/min. Timing is started, 0.4mL of sample in the receiving pool is taken at 1h, 12h, 48h, 96h and 120h respectively, and blank receiving with the same temperature and the same quantity is supplemented at the same timeMedia, at least three sets of parallel experiments were performed for each test. The result is shown in table 3, the SBMA-g-SIS based pressure sensitive adhesive medical patch has a stable colloid system due to the amphiphilic modified block copolymer, and the micelle monomolecular exchange speed is lower, so that the medicine release speed to the environment is reduced, and under the condition of the same content of elastomer, the medicine release speed of the hot melt pressure sensitive adhesive medical patch containing the modified SIS base is lower than that of the patch containing only the SIS base. As can be seen from Table 3, the higher the content of the modified SIS copolymer, the slower the drug release rate of the medical patch, and the longer the administration effect. Meanwhile, the contents of the tackifying resin and the plasticizer also have certain influence on the release rate of the medicament.
TABLE 3 comparison of drug Release Effect of medical Patches
Example 5: drug loading testing of medical patches
Because the drug-loaded SBMA-g-SIS-based hot melt pressure sensitive adhesive of the 7# formula in the example 1 has the best adhesiveness and the better performance of the sustained-release drug, gradually increased black talc powder is added into the formula, and the drug-loaded amount of the pressure sensitive adhesive is measured by taking the prepared pressure sensitive adhesive as a substrate. And the SIS-based drug-loaded hot-melt pressure-sensitive adhesive prepared by using a 7# formula and taking a commercially available SIS-based copolymer as an elastomer is used as a control group 1.
The superfine black talcum powder is prepared by crushing, ball-milling (dry-milling) and sieving black talcum (in Guangfeng region of Shanghai province in Jiangxi), wherein 80mL of the black talcum powder with the volume ratio of 1:1, performing wet ball milling for 6-18 h at 700r/min in a ball mill, taking out a sample, washing with deionized water, centrifuging for three times, taking out the solid at the lower layer in a centrifugal tube, drying, grinding and sieving (200 meshes) to obtain the ultrafine black talcum powder with the average particle size of 300-400nm.
Uniformly stirring 6 parts by weight of SBMA-g-SIS copolymer, 7 parts by weight of plasticizer and different amounts of black talcum powder at 180 ℃; adding 7 parts by weight of tackifying resin, uniformly stirring at 150 ℃, then respectively adding the chlorhexidine acetate which is increased gradually, fully stirring at 130 ℃ until the mixture is clear and transparent to obtain the drug-loaded hot-melt pressure-sensitive adhesive, and judging the maximum drug-loading rate of the drug-loaded hot-melt pressure-sensitive adhesive according to whether the drug is precipitated. As can be seen from Table 4, when 1 part by weight of black talc is added into the formula, the maximum drug loading of the SBMA-g-SIS-based hot-melt pressure-sensitive adhesive is 1.5 parts by weight, while the maximum drug loading of the SIS-based hot-melt pressure-sensitive adhesive of the control group is 0.4 part by weight, so that the addition of the SBMA and the black talc obviously improves the hydrophilicity of the SIS, thereby improving the loading of the hot-melt pressure-sensitive adhesive on hydrophilic drugs.
Table 4 drug loading test results for medical patches
Example 6: evaluation of tackiness of medical Patch
The control group 1 and SBMA-g-SIS groups 1 to 6 prepared in example 5 were prepared into medical patches by the method of example 2, and adhesion performance tests were conducted. The adhesion properties include the permanent adhesion and the peel strength, which are tested using the national standards GB/T4851-1998 and GB2792-81, respectively. The results are shown in the following table. Therefore, the prepared SBMA-g-SIS groups 1-6 medical patches have good viscosity which is higher than that of a control group, and the bonding performance of the SBMA-g-SIS base pressure sensitive adhesive and the pressure sensitive adhesive doped with the ultrafine black talcum powder is improved. In addition, no adhesive residue is left when the patch is torn off.
TABLE 5 tack test results for medical patches
Example 7: evaluation of antibacterial Properties of medical Patches
The control group 1 and SBMA-g-SIS groups 1, 2, 4, and 6 prepared in example 5 were prepared as medical patches by the method of example 2, cut into disks with a diameter of 25mm, and the inhibition zones were measured for escherichia coli (e.coli ATCC25922, available from ATCC) and staphylococcus aureus (s.aureus ATCC6538, available from ATCC) according to the method described in GB/T20944.1-2007. After incubating the dish in an incubator at 37 ℃ for 48h, the zone diameter was determined. The results are shown in Table 5. As can be seen, the bacteriostatic effect of the SBMA-g-SIS group is higher than that of the control group, on one hand, the drug loading is higher than that of the control group, and on the other hand, the slow release effect is related to the slow release effect.
TABLE 6 bacteriostatic effect test of pressure-sensitive adhesive
Claims (10)
1. An SBMA-g-SIS copolymer, characterized in that said SBMA-g-SIS copolymer is prepared by the following method:
dissolving a photoinitiator and methacrylic acid sulfobetaine in an organic solvent, adding a styrene-isoprene-styrene triblock copolymer, taking out a swelling material after complete swelling, placing the swelling material in an ultraviolet lamp for grafting reaction, and volatilizing the solvent after complete reaction to obtain the SBMA-g-SIS copolymer; the mass ratio of the methacrylic acid sulfobetaine to the styrene-isoprene-styrene triblock copolymer is 1-9; the mass ratio of the photoinitiator to the methacrylic acid sulfobetaine is 0.3-1:35; the volume ratio of the organic solvent is 1.5-3:1, and the volume of the organic solvent is 2-5mL/g based on the mass of the styrene-isoprene-styrene triblock copolymer.
2. The SBMA-g-SIS copolymer of claim 1, wherein: the photoinitiator is a mixture of benzophenone and benzoin dimethyl ether or a mixture of 4-acryloyloxy benzophenone and 4-vinyl-4' -methoxy benzophenone.
3. A hot melt pressure sensitive adhesive matrix comprising the SBMA-g-SIS copolymer according to claim 1, wherein the hot melt pressure sensitive adhesive matrix comprises the following components in parts by mass:
the tackifying resin is one or a mixture of more than two of polymerized rosin, terpene resin, petroleum resin or modified resin thereof; the plasticizer is naphthenic oil, chlorinated paraffin or epoxidized soybean oil.
4. A method of preparing a hot melt pressure sensitive adhesive matrix according to claim 3, wherein the method comprises: mixing SBMA-g-SIS copolymer, plasticizer and black talcum powder with the particle size of 300-400nm according to the formula amount, heating to 180 ℃, and stirring to be clear and transparent; adding a formula amount of tackifying resin, cooling to 150 ℃, and stirring until the mixture is clear and transparent to obtain the hot-melt pressure-sensitive adhesive matrix.
5. A hot-melt pressure-sensitive adhesive with the hot-melt pressure-sensitive adhesive matrix as the carrier according to claim 3, characterized in that: the hot-melt pressure-sensitive adhesive consists of the hot-melt pressure-sensitive adhesive matrix and a hydrophilic medicine.
6. The hot melt pressure sensitive adhesive of claim 5, wherein: the hot-melt pressure-sensitive adhesive comprises the following components in parts by mass:
7. the hot-melt pressure-sensitive adhesive according to claim 6, wherein the hot-melt pressure-sensitive adhesive comprises the following components in parts by mass:
8. the process for preparing a hot melt pressure sensitive adhesive according to claim 5, wherein the process comprises:
mixing SBMA-g-SIS copolymer, plasticizer and black talcum powder with particle size of 300-400nm according to the formula amount, heating to 180 ℃, and stirring to be clear and transparent; adding a formula amount of tackifying resin, cooling to 150 ℃, and stirring until the mixture is clear and transparent; and cooling to 130 ℃, adding a formula amount of hydrophilic medicine, and fully stirring until the mixture is clear and transparent to obtain the hot-melt pressure-sensitive adhesive.
9. Use of the hot melt pressure sensitive adhesive according to claim 5 in the manufacture of a medical patch.
10. The use of claim 9, wherein: the medical patch comprises a sheet-shaped substrate and a hot-melt pressure-sensitive adhesive coated on the sheet-shaped substrate.
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Citations (4)
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|---|---|---|---|---|
| JPH0770545A (en) * | 1993-09-01 | 1995-03-14 | I C S Kk | Pressure-sensitive adhesive composition |
| CN104449488A (en) * | 2014-11-05 | 2015-03-25 | 大连理工大学 | Grafted styrene series thermoplastic elastomer-based hot melt pressure sensitive adhesive and preparation method thereof |
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| CN114106361A (en) * | 2020-08-25 | 2022-03-01 | 苏州至善新材料科技有限公司 | Polypropylene material loaded with zwitterionic polymer coating and preparation method thereof |
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Patent Citations (4)
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|---|---|---|---|---|
| JPH0770545A (en) * | 1993-09-01 | 1995-03-14 | I C S Kk | Pressure-sensitive adhesive composition |
| CN104449488A (en) * | 2014-11-05 | 2015-03-25 | 大连理工大学 | Grafted styrene series thermoplastic elastomer-based hot melt pressure sensitive adhesive and preparation method thereof |
| CN104927062A (en) * | 2015-06-01 | 2015-09-23 | 大连理工大学 | Thermoplastic elastomer made of styrene-isoprene-styrene block polymer grafted polyoxyethylene ether as well as amphiphilic hot-melt pressure-sensitive adhesive |
| CN114106361A (en) * | 2020-08-25 | 2022-03-01 | 苏州至善新材料科技有限公司 | Polypropylene material loaded with zwitterionic polymer coating and preparation method thereof |
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| 童潇: "pH敏感型两亲性热熔压敏胶的制备及评价", 《中国优秀硕士学位论文全文数据 工程科技I辑》, no. 8, pages 016 - 148 * |
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