WO2013086731A1 - Appareil d'amenée - Google Patents

Appareil d'amenée Download PDF

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Publication number
WO2013086731A1
WO2013086731A1 PCT/CN2011/084106 CN2011084106W WO2013086731A1 WO 2013086731 A1 WO2013086731 A1 WO 2013086731A1 CN 2011084106 W CN2011084106 W CN 2011084106W WO 2013086731 A1 WO2013086731 A1 WO 2013086731A1
Authority
WO
WIPO (PCT)
Prior art keywords
nanofibre
strands
polymer
channels
spinneret
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.)
Ceased
Application number
PCT/CN2011/084106
Other languages
English (en)
Inventor
Christopher BRANFORD- WHITE
Limin Zhu
Deng-guang YU
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LONDON METROPOLITAN UNIVERSITY (LMU)
Original Assignee
LONDON METROPOLITAN UNIVERSITY (LMU)
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by LONDON METROPOLITAN UNIVERSITY (LMU) filed Critical LONDON METROPOLITAN UNIVERSITY (LMU)
Priority to PCT/CN2011/084106 priority Critical patent/WO2013086731A1/fr
Publication of WO2013086731A1 publication Critical patent/WO2013086731A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0061—Electro-spinning characterised by the electro-spinning apparatus
    • D01D5/0069—Electro-spinning characterised by the electro-spinning apparatus characterised by the spinning section, e.g. capillary tube, protrusion or pin
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/28—Formation of filaments, threads, or the like while mixing different spinning solutions or melts during the spinning operation; Spinnerette packs therefor
    • D01D5/30—Conjugate filaments; Spinnerette packs therefor
    • D01D5/32—Side-by-side structure; Spinnerette packs therefor

Definitions

  • the invention relates to delivery devices for contacting active ingredients, especially pharmaceuticals, with the surface of a patient's skin, and particularly those devices intended for transdermal drug delivery.
  • Transdermal drug delivery is known in the art, with pharmaceuticals delivered by the transdermal route through application of drug-impregnated "patches" that may be affixed to a patient's skin.
  • drug delivery include nicotine to aid smoking cessation, as well as opioids such as fentanyl and buprenorphine for continual pain relief, scopolamine for the treatment of motion sickness and estrogen for treatment of menopausal symptoms.
  • TDDS transdermal drug delivery systems
  • eletrospun nanofibre mats have attracted increasing interest for developing new TDDS due to their unique characteristics, including: (1) a high porosity with a very small pore size resulting from their three-dimensional continuous web structure; (2) a very small fibre diameter (typically having a diameter of less than about 1 micron) and a correspondingly very large surface area; (3) a relatively simple manufacturing process; (4) the ability to include excipients within composite nanofibres; (5) a choice of pharmaceutically-acceptable polymers from which to form the fibres; (6) the presence of nanometre-scale structures which lead to favourable clinical outcomes for drug transfer combined with the macroscopic structure of the mats that allows easy processing, stability, ease of shipping and application found with "conventional" transdermal patch structures.
  • Electrospun nanofibres can be "functionalized” (i.e. given specific capabilities such as drug-delivery) by the incorporation of functional molecules or building blocks in the filament-forming polymer matrix during their manufacture.
  • functional molecules or building blocks in the filament-forming polymer matrix during their manufacture.
  • nanofibres that combine different types of polymers in a single electrospinning process to produce drug-loaded fibres with multiple desired functions
  • Particular problems are: compatibility of the drug, solvent and polymers for successful electropinning; whether or not the polymers are thermo dynamically miscible; thermodynamic and kinetic aspects of mixing; and the behaviour of the functional materials when dissolved in solution.
  • Nanofibres have been shown to have valuable properties for assisting graft implantation, cellular proliferation, cellular alignment and therefore functionality of cell therapies. For example, aligned nanofibres have been shown to help promote neurite outgrowth for nerve repair.
  • Co-axial two-component nanofibres are also known. It is amongst the objects of the invention to attempt a solution to these problems.
  • the invention provides a nanofibre comprising two connected dissimilar polymer strands, each of said strands having at least a portion of its surface exposed on the surface of said nanofibre.
  • said strands lie adjacent each other, and more preferably said strands are connected along the majority of their length.
  • the polymers of each strand are dissimilar.
  • a filament- forming bioadhesive polymer may be used, such as polyethylene oxide (PEO), hydroxypropyl methyl cellulose (HPMC), chitosan, gelatin, carboxymethyl cellulose (CMC) such as Na-CMC and Xanthan gum.
  • PEO polyethylene oxide
  • HPMC hydroxypropyl methyl cellulose
  • CMC carboxymethyl cellulose
  • one of said strands comprises an adhesive polymer.
  • the other strand can be prepared from solutions of the active ingredient (such as a drug) and a polymer matrix tailored to achieve optimal sustained drug release profiles of the active pharmaceutical ingredients (API).
  • active ingredient such as a drug
  • polymer matrix tailored to achieve optimal sustained drug release profiles of the active pharmaceutical ingredients (API).
  • Such polymers include PLA (polylactic acid), PLGA (poly(lactic-co-glycolic acid)), PCL (polycaprolactone) and EVOH (Ethylene Vinyl Alcohol).
  • One of said strands therefore, preferably comprises a diffusible active ingredient.
  • a transdermal penetration enhancer may also be incorporated into one of the strands.
  • the invention provides a nanofibre as described herein in which one of said strands comprises an adhesive polymer and the other (if there are two strands) or another (if there are more than two strands) said strand comprises a polymer containing a diffusible active ingredient.
  • said active ingredient comprises a medicament.
  • the invention also provides a device for use in a method of transdermal delivery of a medicament comprising a mat of nanofibres as described herein.
  • said device further comprises a cover on one side of said mat.
  • the invention also provides apparatus for forming nanofibres as described herein.
  • the invention provides apparatus for forming a nanofiber described herein comprising a spinneret having: a first fluid channel for fluid delivery of a first polymer composition; a second fluid channel for fluid delivery of a second polymer composition; said channels each having an inlet and an outlet, the said outlets being arranged adjacent each other; and wherein the longitudinal axes of said channels are arranged to be angled towards each other at the outlet of each channel.
  • the angle between said channels is between 5 and 80 degrees, more preferably between 20 and 80 degrees, and most preferably between 45 and 70 degrees. More generally, the minimum angle between said channels should be 5, 10, 15, 20, 25 of 30 degrees, and the maximum angle should be 80, 75, 70, 65, or 60 degrees. The inventors have found that these ranges of angles provide stability in dual nanofibre formation.
  • said outlets are spaced apart by less than 1mm.
  • Figures 1 and 2 illustrate respective transverse and longitudinal cross-sections of embodiments of nano fibres of the present invention
  • FIGS 3 and 4 illustrate cross-sections of embodiments of spinnerets of the present invention
  • Figure 5 illustrates an electrospinning apparatus using a spinneret of the present invention
  • Figure 6 illustrates a drug delivery device of the present invention. Description of Preferred Embodiments
  • Figure 1 illustrates a transverse cross-section of a nanofibre of the present invention, generally indicated by 1.
  • the nanofibre is formed from two connected polymer strands (2, 3), each strand being formed of a different polymer composition.
  • the strands 2, 3 are connected along longitudinal edges at a mid-region 4 of the nanofibre.
  • the mid-region of the nanofibre may contain a mixture of the two polymer compositions.
  • Figure 2 illustrates a longitudinal cross-section of a short portion of the nanofibre of Figure 1, illustrating that the two strands 2, 3 forming the composite nanofibre 1 lie adjacent each other.
  • the strands are connected to each other along the majority of their length, and at least a portion of the surface 5, 6 of each strand 2, 3 is exposed on the surface of the nanofibre 1.
  • a typical width, w, of the nanofibres is less than 1 micron, most preferably about 500nm, in the range of 50 to 1000 nm.
  • the composition of one of the strands 2 comprises a filament- forming bioadhesive polymer such as polyethylene oxide (PEO), hydroxypropyl methyl cellulose (HPMC), chitosan gelatin, carboxymethyl cellulose (CMC) such as Na-CMC and Xanthan gum.
  • a filament- forming bioadhesive polymer such as polyethylene oxide (PEO), hydroxypropyl methyl cellulose (HPMC), chitosan gelatin, carboxymethyl cellulose (CMC) such as Na-CMC and Xanthan gum.
  • Figure 3 illustrates a cross-sectional view of a second aspect of the invention, being a spinneret suitable for producing nanofibres of the first aspect of the invention.
  • the spinneret generally indicated by 7, comprises a first fluid channel (e.g. a tube, or conduit) 8 having an inlet 9 and an outlet 10 and a second fluid channel 11 having an inlet 12 and an outlet 13.
  • the two outlets 10, 13 are arranged to discharge adjacent each other at a separation, X, of typically less than 1mm, as illustrated in Figure 4.
  • each channel As the channels 8, 11 approach the fluid exits 10, 13, the respective longitudinal axes 14, 15 of each channel are arranged to be angled towards each other such that during an electrospinning process using the spinneret, polymer compositions pumped through the respective channels impact on each other and coalesce to form a composite nanofibre of the first aspect of the present invention.
  • the angle ⁇ between the axes 14, 15 of the channels is preferably between 20 and 70 degrees.
  • the two exit channels are mounted independently of each other on movable supports, such that the separation and relative angular inclination of the exit channels may be varied to suit different polymer compositions.
  • Figure 5 illustrates a typical configuration of an electrospinning apparatus, generally indicated by 16, and comprising a spinneret 7 of the invention and an electrically conductive collector plate 17.
  • the spinneret 7 is preferably made of electrically- conductive material, such as stainless steel.
  • a high voltage is applied between the spinneret 7 and the collector plate 17.
  • a voltage of several kilo Volts (e.g. around 15kV) is typical for spinneret - collector plate separations of the order of 20cm. Appropriate voltages and separations may be determined by those skilled in the art of electrospinning, generally.
  • Two polymer solutions are passed through the spinneret by means of a pump (not illustrated). The first polymer solution is passed through exit nozzle 10 via inlet 9, and the second solution through exit nozzle 13 via inlet 12.
  • the potential difference between the emerging polymer streams and the collector plate causes the streams to accelerate towards the plate (as indicated by the arrow), with a consequent thinning of the strands.
  • the strands coalesce due to the angle of the exit channels, and a composite nanofibre of the present invention is formed.
  • Figure 6 illustrates a medicament delivery device, generally indicated by 18, comprising a mat of nano fibres 19 secured to a cover 20.
  • the cover has adhesive regions 21 around the mat 19, allowing the device to be secured to a patient's skin, thereby pressing the mat against the skin surface.
  • the high surface area of the nanofibres facilitates diffusion of medicament contained within the nanofibres to the skin surface, for transdermal delivery.
  • the inclusion of a biocompatible adhesive polymer within at least one strand of the nanofibres ensures close and continuing contact of the nanofibres with the skin.
  • Electro- spinning processes In this example, two polymer solutions were used for side- by side electrospinning.
  • the first polymer composition consisted of 1%:5%: 15% (w/v) of DS, PL and Eudragit in a mixed solvent of DMAc and methanol with a volume ratio of 80:20.
  • the second polymer composition consisted of 0.8%:4%: 10% (w/v) of DS, PL and PVP K60 in ethanol.
  • the polymer solutions were degassed with a SK5200H ultrasonicator (350W, Shanghai Jinghong Instrument Co., Ltd. (Shanghai, China) for 15 min before the spinning processes.
  • a high voltage power supply (Shanghai Sute Electrical Co., Ltd) was used to provide high voltages in the range of 0-60 kV.
  • the positive electrode of the high voltage power supply was connected to a "side-by-side" spinneret of the present invention, and made of stainless steel.
  • the grounded electrode was connected to a metal collector wrapped with aluminium foil.
  • the feed rate of two polymer solutions through the two fluid channels of the spinneret was controlled by means of two syringe infusion pumps (KDS 100, Cole- Parmer®, USA). Formed fibers were dried for over 24 h at 40 °C under vacuum (320 Pa) in a DZF-6050 electric vacuum drying oven (Shanghai Laboratory Instrument Work Co. Ltd, Shanghai, China) to facilitate the removal of residual organic solvent and moisture.
  • the applied high voltage was 15 kV and the flow rate of each polymer solution through the spinneret was 1.0 mL/h.
  • the fibre-collected distance was fixed at 20cm.
  • the electrospinning process was conducted under ambient conditions.
  • the morphology of the surface and the cross-sections of the nano-fiber mats were assessed using a S-4800 field emission scanning electron microscope (Hitachi, Japan).
  • the average fiber diameter was determined by measuring diameters of composite nano- fibers over 100 points from FESEM images using Image J software (National Institutes of Health, USA).
  • the fibre illustrated has a width of approximately 550 nm.
  • PVP K60 poly(ethylene oxide)
  • CA white powder
  • Ibuprofen (IBU) and borneol were purchased from Shanghai
  • Electro- spinning processes Again, two different polymer compositions were employed in the electrospinning process.
  • the first polymer composition consisted of 0.5%:2%:6% (w/v) borneol, PEO and PVP in a mixed solvent of water and methanol with a volume ratio of 80:20.
  • the second polymer composition consisted of 5%: 15% (w/v) of IBU, CA in a mixed solvent of acetone, ethanol and DM Ac with a volume ratio of 3 : 1 : 1.
  • the polymer solutions were degassed with a SK5200H ultrasonicator (350W, Shanghai Jinghong Instrument Co., Ltd. (Shanghai, China) for 15 min before the spinning processes.
  • SK5200H ultrasonicator 350W, Shanghai Jinghong Instrument Co., Ltd. (Shanghai, China
  • a high voltage power supply (Shanghai Sute Electrical Co., Ltd) was used to provide high voltages in the range of 0-60 kV.
  • the positive electrode of the high voltage power supply was connected to a side-by-side spinneret according to the first aspect of the invention, made of stainless steel.
  • the grounded electrode was connected to a metal collector wrapped with aluminium foil.
  • the feed rate of two polymer solutions through the spinneret was controlled by means of two syringe infusion pumps (KDS 100, Cole- Parmer®, USA). Formed fibres were dried for over 24 h at 40 °C under vacuum (320 Pa) in a DZF-6050 electric vacuum drying oven (Shanghai Laboratory Instrument Work Co. Ltd, Shanghai, China) to facilitate the removal of residual organic solvent and moisture.
  • the applied high voltage between the spinneret and the collector plate was 12 kV and the flow rate of each polymer composition through the spinneret was 1.0 mL/h. Fibres were collected at a fixed distance of 15cm between the spinneret and the metal collector plate. The electro-spinning process was conducted under ambient condition.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Textile Engineering (AREA)
  • Mechanical Engineering (AREA)
  • Nanotechnology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des nanofibres composites (1) comprenant deux brins (2, 3) de polymère dissemblables reliés ensemble. Au moins une partie de la surface (5, 6) de chacun des brins (2, 3) est découverte à la surface de la nanofibre composite (1). L'invention concerne également un appareil de formation de telles nanofibres, sous la forme d'une filière (7) comprenant des canaux inclinés (8, 11).
PCT/CN2011/084106 2011-12-16 2011-12-16 Appareil d'amenée Ceased WO2013086731A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2011/084106 WO2013086731A1 (fr) 2011-12-16 2011-12-16 Appareil d'amenée

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2011/084106 WO2013086731A1 (fr) 2011-12-16 2011-12-16 Appareil d'amenée

Publications (1)

Publication Number Publication Date
WO2013086731A1 true WO2013086731A1 (fr) 2013-06-20

Family

ID=48611832

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2011/084106 Ceased WO2013086731A1 (fr) 2011-12-16 2011-12-16 Appareil d'amenée

Country Status (1)

Country Link
WO (1) WO2013086731A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108893995A (zh) * 2018-06-15 2018-11-27 阿斯福特纺织（漳州）有限公司 一种均衡型涤纶面料及其成型工艺

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05195406A (ja) * 1992-01-18 1993-08-03 Unitika Ltd 伸縮性長繊維不織布及びその製造方法
JP2002363828A (ja) * 2001-06-06 2002-12-18 Toray Ind Inc 貼合型複合繊維およびその製造方法
WO2008024141A2 (fr) * 2006-05-09 2008-02-28 Apogee Technology, Inc. Structures de nanofibres présentes sur des aspérités destinées à séquestrer, porter et transférer des substances
CN101336885A (zh) * 2008-08-08 2009-01-07 东华大学 一种中药纳米纤维毡的制备方法
CN101570917A (zh) * 2009-06-03 2009-11-04 东华大学 生物黏附载药纳米纤维膜的电纺制备方法
CN101805932A (zh) * 2010-04-16 2010-08-18 东华大学 一种电纺并列纺丝头装置及其方法
KR20100094256A (ko) * 2009-02-18 2010-08-26 부산대학교 산학협력단 다층의 나노섬유 시트로 이루어진 의료용 피부 패치
CN201738041U (zh) * 2010-04-16 2011-02-09 东华大学 一种电纺并列纺丝头装置
CN102433610A (zh) * 2011-08-29 2012-05-02 长春理工大学 一种制备磁光双功能两股并行复合纳米纤维束的方法

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05195406A (ja) * 1992-01-18 1993-08-03 Unitika Ltd 伸縮性長繊維不織布及びその製造方法
JP2002363828A (ja) * 2001-06-06 2002-12-18 Toray Ind Inc 貼合型複合繊維およびその製造方法
WO2008024141A2 (fr) * 2006-05-09 2008-02-28 Apogee Technology, Inc. Structures de nanofibres présentes sur des aspérités destinées à séquestrer, porter et transférer des substances
CN101336885A (zh) * 2008-08-08 2009-01-07 东华大学 一种中药纳米纤维毡的制备方法
KR20100094256A (ko) * 2009-02-18 2010-08-26 부산대학교 산학협력단 다층의 나노섬유 시트로 이루어진 의료용 피부 패치
CN101570917A (zh) * 2009-06-03 2009-11-04 东华大学 生物黏附载药纳米纤维膜的电纺制备方法
CN101805932A (zh) * 2010-04-16 2010-08-18 东华大学 一种电纺并列纺丝头装置及其方法
CN201738041U (zh) * 2010-04-16 2011-02-09 东华大学 一种电纺并列纺丝头装置
CN102433610A (zh) * 2011-08-29 2012-05-02 长春理工大学 一种制备磁光双功能两股并行复合纳米纤维束的方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108893995A (zh) * 2018-06-15 2018-11-27 阿斯福特纺织（漳州）有限公司 一种均衡型涤纶面料及其成型工艺
CN108950797A (zh) * 2018-06-15 2018-12-07 阿斯福特纺织（漳州）有限公司 一种高档涤纶面料的成型工艺

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