WO2000064528A1 - Systeme d'apport de medicaments - Google Patents

Systeme d'apport de medicaments Download PDF

Info

Publication number
WO2000064528A1
WO2000064528A1 PCT/US2000/011570 US0011570W WO0064528A1 WO 2000064528 A1 WO2000064528 A1 WO 2000064528A1 US 0011570 W US0011570 W US 0011570W WO 0064528 A1 WO0064528 A1 WO 0064528A1
Authority
WO
WIPO (PCT)
Prior art keywords
drug
flow
delivery system
agent
altering agent
Prior art date
Application number
PCT/US2000/011570
Other languages
English (en)
Inventor
Charles E. Austin
Original Assignee
Situs Corporation
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 Situs Corporation filed Critical Situs Corporation
Priority to AU48080/00A priority Critical patent/AU4808000A/en
Publication of WO2000064528A1 publication Critical patent/WO2000064528A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

Definitions

  • the present invention relates to drug delivery systems. More specifically, the invention relates to drug delivery systems comprising a drug in liquid form in combination with a flow-altering agent which allows controlled delivery of the drug.
  • Drugs can be administered to patients in a variety of formulations, including solids, liquids, aerosols, creams and ointments.
  • drugs are combined with other substances that act to prolong drug activity, reduce side effects, increase efficacy, facilitate handling, or to simply make them more palatable.
  • One example of combining a drug with another substance in a solid formulation to make a tablet for oral administration is E-mycin, a broad spectrum antibiotic used to treat a variety of bacterial infections (Knoll Laboratories, Mount Olive, l ⁇ IJ).
  • E-mycin requires a special coating to protect the drug from the inactivating effects of gastric acidity and to permit efficient absorption of the antibiotic in the small intestine.
  • Fluma ⁇ ne an antiviral agent used to treat strains of influenza (Forest Laboratories, New York, NY). Flumanne is combined with sodium saccharin, sorbitol and flavoring agents to increase its palatabi t ⁇ .
  • liquid drug formulations such as syrups and solutions
  • properties of both the drug and the substance(s) with which it is combined must be considered. These properties, including density, solubility, pH, thermal and electrical conductivity, and viscosity, affect the manner in which the drug formulation is administered, and ultimately determine the safety and efficacy of the drug formulation in treating the patient. Viscosity of liquid drug formulations is another important parameter.
  • Viscosity-reducing agents have been used in ophthalmic compositions due to the high viscosity of the polymers used to regulate the absorption of drug in the eye (see, for example, U.S. Patent Nos. 5,795,913, 5,710,182, 5,698,219 and 5,679,665).
  • 5,540,912 utilize the viscosity of the liquid or semi-liquid carrier in which large drug particles are mixed to promote the uniform suspension of the drug and to regulate the rate at which the drug will diffuse through the mixture
  • the formulation of the drug will vary depending on the concentration of the drug in the carrier, and lattice or pore structure of the carrier matrix
  • the references discussed above assume the driving force of the drug within the suspension is diffusion, and examines the formulation as two different species, the carrier and the drug.
  • the viscosity of the carrier is altered to affect the movement of the drug within the carrier, not the movement of the drug and carrier as a mixture.
  • the rate at which a drug is delivered to a patient is often critical to the efficacy of the treatment. If a drug is delivered at a rate which is too low, its pharmaceutical effectiveness may be compromised. In contrast, if a drug is administered too quickly, it may be toxic or have other adverse effects.
  • the rate of drug delivery is often controlled by administering the drug with a driving force to ensure that the proper dosage is supplied to the patient. This driving force may take the form of a pressure source, or any other suitable source of energy for driving a fluid.
  • the rate of drug delivery will be affected by the nature of the driving force, the properties of the drug mixture and the flow path of the mixture.
  • One embodiment of the present invention is a drug delivery system, comprising: a drug in liquid form; an agent which alters the flow characteristics of the drug when combined with the drug; an energy source configured to pressurize the drug and the flow altering agent; and a flow path through which the drug is delivered.
  • the flow-altering agent is a viscosity enhancing agent.
  • the viscosity enhancing agent is selected from the group consisting of glycerol, propylene glycol, carboxymethylcellulose and hydroxypropylmethylcellulose.
  • the drug is used to treat a bladder disorder selected from the group consisting of urge incontinence, bladder infection, interstitial cystitis, pain, neuralgia and cancer.
  • the drug is selected from the group consisting of oxybutynm, an antibiotic, a diagnostic agent and an anticancer drug.
  • the drug is delivered at a rate of between about 0.05 and about 100 cc/day.
  • the flow path includes an aperture.
  • the present invention also provides a drug delivery system, comprising: an energy source; a drug in liquid form within a reservoir operatively connected to the energy source; and a flow altering agent in combination with the drug.
  • the flow-altering agent is a viscosity enhancing agent.
  • the delivery rate of the drug is between about 0.05 and 100 cc/day.
  • the energy source pressurizes the drug.
  • the present invention also provides a drug delivery system, comprising: a pressurized drug in liquid form; and a viscosity altering agent in combination with the drug, wherein the viscosity-altering agent effects a rate at which the pressurized drug is delivered
  • a drug delivery system comprising: a drug in liquid form stored within a pressurized reservoir; a viscosity altering agent in combination with the drug, and a flow path within the pressurized reservoir through which the drug is delivered at a rate of between about 0.05 and about 100 cc/day.
  • the flow path is an aperture
  • the present invention also provides a method for delivering a drug, comprising the steps of: combining a drug in liquid form and a viscosity-altering agent; pressurizing the drug and the viscosity-altering agent; pressurizing the drug and the viscosity-altering agent; and delivering the drug through a valve at a rate of between about 0.05 and about 100 cc/day.
  • the flow altering agent is a viscosity enhancing agent
  • Another embodiment of the invention is the use of a liquid drug in combination with a flow-altering agent in the preparation of a medicament for intravesical delivery
  • the flow-altering agent is a viscosity enhancing agent.
  • the delivery is accomplished by infusing the drug through a flow regulator and then into the bladder of a patient.
  • the present invention provides a controlled drug delivery system comprising an energy source and a drug in liquid form which comprises a flow-altering agent.
  • the flow-altering agent affects the rate at which the drug is delivered by changing the dynamic properties of the liquid drug mixture.
  • the flow-altering agent is a viscosity enhancing agent.
  • a viscosity enhancing agent is a material that is either (a) added primarily to enhance viscosity, and not for another pharmacological or formulation purpose, or (b) increases the viscosity by at least 0.5, and preferably by at least 1 centipoise.
  • a viscosity-altering agent can be added to the drug by the physician to alter the drug delivery rate thereof.
  • a drug in condensed form solid or liquid
  • a solution comprising a viscosity-altering agent is added to the infuser Addition of the solution inflates the infuser, generating an internal pressure on the drug solution, and activates the drug, resulting in inflation of the infuser and activation of the drug.
  • the drug delivery system of the invention can be used to treat, for example, bladder disorders and diseases including urge incontinence, interstitial cystitis, bladder infection, cystitis, and bladder cancer.
  • the system may be useful in treating diseases affecting the surrounding tissues and organs such as recurrent or chronic urinary tract infection (UTI), lower urinary tract symptom (LUTS), endomet ⁇ osis, prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer.
  • the system may be able to deliver pharmaceutical compounds to treat systemic conditions such as chronic pain and neuralgia.
  • Drugs contemplated for these uses include, for example, anticholinergics (such as, for example, oxybutynm), vanilloids, hepa ⁇ n, antibiotics, hormones, alpha blockers, diagnostic agents, anticancer drugs, chemotherapeutics compounds, antidepressants narcotics, analgesics and non- steroidal anti-inflammatory drugs (NSAID) and the like.
  • anticholinergics such as, for example, oxybutynm
  • vanilloids such as, for example, oxybutynm
  • hepa ⁇ n antibiotics
  • hormones such as, for example, alpha blockers
  • diagnostic agents such as, anticancer drugs, chemotherapeutics compounds, antidepressants narcotics, analgesics and non- steroidal anti-inflammatory drugs (NSAID) and the like.
  • NSAID non- steroidal anti-inflammatory drugs
  • the net result of changing the dynamic properties of the drug solution is to affect the flow of the drug solution.
  • Flow is governed by laws relating the physical and dynamic properties of the fluid.
  • the Navier-Stokes equation relates the flow to the forces acting upon the fluid as functions of the physical properties of the fluid such as the density and viscosity.
  • the addition of a viscosity-altering agent affects the coefficient of viscosity of the drug solution.
  • the Navier Stokes equation reduces to a simple relationship where the flow rate is directly proportional to the pressure and inversely proportional to the coefficient of viscosity.
  • a relatively low viscosity agent having a viscosity coefficient in the range of about 0.1 to about 1.0 centipoise
  • a relatively high viscosity agent providing a coefficient of viscosity in the range of about 1 to about 100 centipoise
  • the viscosity of the liquid drug composition is increased by at least about 1, 2, or 3 centipoise, or alternatively by at least about 5, 10, or 15 centipoise.
  • One significant advantage of the apparatus and method of the present invention is that a single device with a single design may be manufactured by a single manufacturing process which has many applications for drug delivery at a variety of desired flow rates.
  • the flow rate is simply adjusted by the physician by the selection of an appropriate flow-altering agent which is combined with the drug
  • the addition of one or more flow altering agents to a concentrated drug now makes metered drug delivery from an energy source, such as a pressurized source, simple and reproducible, a method which was not previously feasible.
  • the flow altering agent is a viscosity altering agent which increases the viscosity of the liquid drug and changes the dynamic character of the fluid flow, thus slowing down its rate of delivery.
  • Viscosity-enhancing agents contemplated for use in the present invention include glycol cosolvents such as glycerol or propylene glycol; cellulosic viscosity-enhancing agents such as carboxymethylcellulose, hydroxypropylmethylcellulose; or any other viscosity enhancing agent well known in the art.
  • a viscosity decreasing agent such as water or other aqueous solution is added which actually increases the flow rate.
  • a drug in solid form i.e., powdered or lyophi zed
  • a pharmaceutically acceptable excipient or diluent such as phosphate buffered saline (PBS) or lactated Ringer's solution and a viscosity-altering agent.
  • FIG. 1 A schematic diagram of a drug delivery system 2 of the invention is shown in Figure 1.
  • An energy source 4 acts on liquid drug reservoir 6 which contains a viscosity altering agent.
  • the liquid drug then flows through valve 8 at a controlled rate.
  • the energy source may be a spring, piston, syringe, balloon, gravitational source, and the like, that generates a pressure on the liquid.
  • the drug reservoir is an elastic membrane that, when inflated, generates a pressure on the liquid drug.
  • the liquid drug exits the drug reservoir through a flow controller or flow rest ⁇ ctor/regulator (e.g. valve) that controls the rate of flow of the drug out of the reservoir.
  • a flow controller or flow rest ⁇ ctor/regulator e.g. valve
  • the drug reservoir may be any shaped article capable of holding a liquid drug in combination with a flow-altering agent, and configured with an energy source such that the source exerts pressure on the liquid drug contained within the article.
  • the drug delivery system may also comprise a valve assembly for accurately metering the dosage of a drug.
  • the system also comprises a flow path through which the drug is delivered at a rate of about 0.05 to about 100 cc/day, more preferably between about 0.25 and about 50 cc/day.
  • the flow path comprises an aperture.
  • the aperture is preferably a valve or microflow valve.
  • the viscosity of the liquid drug is between about 0.1 and about 100 centipoises (cps); more preferably between about 1 and about 10 cps; and most preferably, between about 1 and 5 cps.
  • the viscosity of any desired liquid drug solution and its flow rate from a reservoir can be determined using standard analytical techniques.
  • the drug delivery system comprises an energy source; a drug in liquid form within a reservoir operably connected to the energy source; and a flow-altering agent in combination with the drug.
  • the drug delivery system comprises a drug in liquid form stored within a pressurized source; a flow-altering agent in combination with the drug; and an aperture within the pressurized source through which the drug is delivered at a rate of about 0.05 to about 100 cc/day
  • the flow altering agent is a viscosity enhancing agent
  • the drug delivery method comprises the steps of combining a drug in liquid form and a flow altering agent, pressurizing the drug and the flow altering agent, and delivering the drug through a microflow valve at a rate of about 0 05 to about 100 cc/day
  • the pressurized drug delivery system and method of the invention may be used to deliver any desired drug to any desired location
  • a drug such as oxybutynm chloride, which is used to treat urge incontinence, is placed in the drug reservoir of an intravesical infuser such as the one described in U. S. Patent Application Serial No 09/041,475, in combination with glycerol, to decrease the flow rate of oxybutynm chloride through the flow restricted exit port of the infuser This allows prolonged drug release over time and reduces the number of times the infuser must be refilled with drug It should be noted that the present invention is not limited to only those embodiments describe in the Detailed

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Selon cette invention, un système et un procédé d'apport de médicaments comprennent un médicament sous forme liquide combiné à un agent modifiant l'écoulement, de préférence un renforçateur de viscosité, et une source sous pression. L'agent modifiant la viscosité permet de réguler l'apport du médicament à partir de la source.
PCT/US2000/011570 1999-04-28 2000-04-27 Systeme d'apport de medicaments WO2000064528A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU48080/00A AU4808000A (en) 1999-04-28 2000-04-27 Drug delivery system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US30103399A 1999-04-28 1999-04-28
US09/301,033 1999-04-28

Publications (1)

Publication Number Publication Date
WO2000064528A1 true WO2000064528A1 (fr) 2000-11-02

Family

ID=23161649

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/011570 WO2000064528A1 (fr) 1999-04-28 2000-04-27 Systeme d'apport de medicaments

Country Status (2)

Country Link
AU (1) AU4808000A (fr)
WO (1) WO2000064528A1 (fr)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3840009A (en) * 1971-12-27 1974-10-08 Alza Corp Self-powered vapor pressure delivery device
US5540912A (en) 1992-03-30 1996-07-30 Alza Corporation Viscous suspensions of controlled-release drug particles
US5654000A (en) 1992-07-28 1997-08-05 Poli Industria Chimica S.P.A. Pharmaceutical compositions for transmucosal delivery of peptides
US5674895A (en) * 1995-05-22 1997-10-07 Alza Corporation Dosage form comprising oxybutynin
US5679665A (en) 1992-10-07 1997-10-21 Laboratorios Cusi, S.A. Pharmaceutical formulation comprised of polymyxintrimethoprim and an anti-inflammatory drug for ophthalmic and otic topical use
US5698219A (en) 1994-08-08 1997-12-16 Laboratorios Cusi, S.A. Nanoemulsion of the oil water type, useful as an ophthalmic vehicle and process for the preparation thereof
US5710182A (en) 1994-03-31 1998-01-20 Santen Oy Ophthalmic composition
US5747065A (en) * 1993-09-29 1998-05-05 Lee; Eun Soo Monoglyceride/lactate ester permeation enhancer for oxybutynin
US5780050A (en) 1995-07-20 1998-07-14 Theratech, Inc. Drug delivery compositions for improved stability of steroids
US5795913A (en) 1994-03-31 1998-08-18 Santen Oy Ophthalmic composition
WO1999024106A1 (fr) 1997-11-06 1999-05-20 Situs Corporation Infuseur intravesical

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3840009A (en) * 1971-12-27 1974-10-08 Alza Corp Self-powered vapor pressure delivery device
US5540912A (en) 1992-03-30 1996-07-30 Alza Corporation Viscous suspensions of controlled-release drug particles
US5654000A (en) 1992-07-28 1997-08-05 Poli Industria Chimica S.P.A. Pharmaceutical compositions for transmucosal delivery of peptides
US5679665A (en) 1992-10-07 1997-10-21 Laboratorios Cusi, S.A. Pharmaceutical formulation comprised of polymyxintrimethoprim and an anti-inflammatory drug for ophthalmic and otic topical use
US5747065A (en) * 1993-09-29 1998-05-05 Lee; Eun Soo Monoglyceride/lactate ester permeation enhancer for oxybutynin
US5710182A (en) 1994-03-31 1998-01-20 Santen Oy Ophthalmic composition
US5795913A (en) 1994-03-31 1998-08-18 Santen Oy Ophthalmic composition
US5698219A (en) 1994-08-08 1997-12-16 Laboratorios Cusi, S.A. Nanoemulsion of the oil water type, useful as an ophthalmic vehicle and process for the preparation thereof
US5674895A (en) * 1995-05-22 1997-10-07 Alza Corporation Dosage form comprising oxybutynin
US5780050A (en) 1995-07-20 1998-07-14 Theratech, Inc. Drug delivery compositions for improved stability of steroids
WO1999024106A1 (fr) 1997-11-06 1999-05-20 Situs Corporation Infuseur intravesical

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BUYSE G ET AL: "INTRAVESICAL APPLICATION OF A STABLE OXYBUTYNIN SOLUTION IMPROVES THERAPEUTIC COMPLIANCE AND ACCEPTANCE IN CHILDREN WITH NEUROGENIC BLADDER DYSFUNCTION", JOURNAL OF UROLOGY,US,BALTIMORE, MD, vol. 160, no. 3, PART 02, September 1998 (1998-09-01), pages 1084 - 1087, XP000867368, ISSN: 0022-5347 *

Also Published As

Publication number Publication date
AU4808000A (en) 2000-11-10

Similar Documents

Publication Publication Date Title
US20210169822A1 (en) Transdermal drug delivery method and system
US4948587A (en) Ultrasound enhancement of transbuccal drug delivery
ES2282134T3 (es) Copolimeros de polioxialquileno que contienen vehiculos liquidos fluidos.
ES2527448T3 (es) Nuevas formulaciones para el tratamiento de la migraña
Langer Implantable controlled release systems
EP0059694B1 (fr) Dispositif d'administration de produits pharmaceutiques
EP0539215B1 (fr) Augmentation de la penetration des formulations pour application topique
CA2392006A1 (fr) Dispositifs microfabriques pour transport de molecules dans un fluide porteur
KR102373297B1 (ko) 피부 질병의 치료를 위한 조성물, 방법 및 시스템
UY25432A1 (es) Administracion de un agente activo en aerosol
WO2007133389A3 (fr) Appareil et méthode pour administration d'agents thérapeutiques et autres
KR880008800A (ko) 난용성 활성성분을 위한 치료계
PT984762E (pt) Configuracoes de controlador de debito para um dispositivo de administracao de agente activo
BR0108730A (pt) Sistema, dispositivo e método para administração de uma droga, bocal de um dispositivo de administração de droga, dispositivo para administração de doses unitárias múltiplas de uma droga, métodos para preparação de um sistema de administração de droga e de uma formulação de droga e para tratamento de um paciente que necessita de doses múltiplas de uma droga, formulação de droga e multiparticulados
DE602004029264D1 (de) Medizinprodukt mit arzneimittelzufuhrglied
JPS596843B2 (ja) 薬剤供給体の製造法
ES2041174T3 (es) Sistema intravenoso para suministrar un agente beneficioso.
GB2349818A (en) Spray dispenser for opioid antagonists
KR880002511A (ko) 전신작용을 나타내는 경구적 치료 시스템
JPH08502952A (ja) オキシブチニンの経皮投与
JP2659932B2 (ja) 経皮的および経粘膜的薬剤施用具
JP2017508749A5 (fr)
JP2009521976A5 (fr)
WO2000064528A1 (fr) Systeme d'apport de medicaments
Chandrasekaran et al. Therapeutic systems and controlled drug delivery

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ CZ DE DE DK DK DM DZ EE EE ES FI FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP