New! View global litigation for patent families

US20070191815A1 - Biosynchronous transdermal drug delivery - Google Patents

Biosynchronous transdermal drug delivery Download PDF

Info

Publication number
US20070191815A1
US20070191815A1 US11162517 US16251705A US2007191815A1 US 20070191815 A1 US20070191815 A1 US 20070191815A1 US 11162517 US11162517 US 11162517 US 16251705 A US16251705 A US 16251705A US 2007191815 A1 US2007191815 A1 US 2007191815A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
drug
system
morning
symptoms
time
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.)
Abandoned
Application number
US11162517
Inventor
Guy DiPierro
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.)
Chrono Therapeutics Inc
Original Assignee
Chrono Therapeutics Inc
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

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M35/00Devices for applying, e.g. spreading, media, e.g. remedies, on the human body ; Introducing media, e.g. remedies, into the body by diffusion through the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/04Nitro compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465Nicotine; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0002Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M39/00Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/22Valves or arrangement of valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M2037/0007Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023Drug applicators using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0061Methods for using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/02General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0266Shape memory materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/33Controlling, regulating or measuring
    • A61M2205/3331Pressure; Flow
    • A61M2205/3337Controlling, regulating pressure or flow by means of a valve by-passing a pump
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/50General characteristics of the apparatus with microprocessors or computers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0092Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/20Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Abstract

Systems and methods for synchronizing the administration of compounds with the human body's natural circadian rhythms and addiction rhythms to counteract symptoms when they are likely to be at their worst by using an automated and pre programmable transdermal or other drug administration system.

Description

  • [0001]
    This application claims the benefit of U.S. Provisional Application No. 60/609,418 filed on September 13, 2004 which is incorporated herein by reference. This application also relates to PCT application No. PCT/IB2004/002947 entitled Transdermal Drug Delivery Method and System filed on Sep. 13, 2004 which is incorporated herein by reference.
  • FIELD OF THE INVENTION
  • [0002]
    The present invention relates, in general, to controlled drug delivery methods and systems, and, more specifically, to systems and methods for biosynchronous transdermal drug delivery in which drugs, pharmaceuticals, and other bioactive substances are delivered transdermally into a body in a manner that is synchronized with biological processes and/or biological rhythms so as to improve performance of the substance in the body.
  • RELEVANT BACKGROUND
  • [0003]
    In the field of drug delivery, it is recognized that supplying the drug in a correct temporal pattern is an important attribute of any drug delivery methodology. Controlled release drug delivery systems are intended to improve response to a drug and/or lessen side effects of a drug. The term “controlled release” refers generally to delivery mechanisms that make an active ingredient available to the biological system of a host in a manner that supplies the drug according to a desired temporal pattern. Controlled release drug delivery may be implemented using instantaneous release systems, delayed release systems, and sustained release systems. In most cases, controlled release systems are designed to maintain a sustained plasma level of an active ingredient in a drug within a human or animal host over a period of time.
  • [0004]
    Instantaneous release refers to systems that make the active ingredient available immediately after administration to the biosystem of the host. Instantaneous release systems include continuous or pulsed intravenous infusion or injections. Such systems provide a great deal of control because administration can be both instantaneously started and stopped and the delivery rate can be controlled with great precision. However, the administration is undesirably invasive as they involve administration via a puncture needle or catheter. ‘Delayed release’ refers to systems in which the active ingredient made available to the host at some time after administration. Such systems include oral as well as injectable drugs in which the active ingredient is coated or encapsulated with a substance that dissolves at a known rate so as to release the active ingredient after the delay. Unfortunately, it is often difficult to control the degradation of the coating or encapsulant after administration and the actual performance will vary from patient to patient. Sustained Release generally refers to release of active ingredient such that the level of active ingredient available to the host is maintained at some level over a period of time. Like delayed release systems, sustained release systems are difficult to control and exhibit variability from patient to patient. Due to the adsorption through the gastrointestinal tract, drug concentrations rise quickly in the body when taking a pill, but the decrease is dependent on excretion and metabolism, which can not be controlled. In addition, the adsorption through the gastrointestinal tract in many cases leads to considerable side effects (such as ulcers), and can severely damage the liver.
  • [0005]
    Transdermal drug delivery has developed primarily for sustained release of drugs in situations where oral sustained release systems are inadequate. In some cases, drugs cannot be effectively administered orally because the active ingredients are destroyed or altered by the gastrointestinal system. In other cases the drug may be physically or chemically incompatible with the coatings and/or chelating agents used to implement sustained release. In other cases a transdermal delivery system may provide sustained release over a period of days or weeks whereas orally administered drugs may offer sustained performance over only a few hours. A wide variety of active substances can be delivered through transdermal systems so long as the active substance can be provided in a form that can cross the skin barrier.
  • [0006]
    In most cases transdermal delivery systems are passive, taking the form of a patch that is adhesively attached to the host. The patch includes a quantity of the active substance, along with a suitable carrier if need be, absorbed in a sponge or similar system. Once applied, the active ingredient diffuses into the host through the skin at a rate determined by the concentration of the active substance and the diffusivity of the active substance. However, a variety of physical and chemical processes at the skin/patch boundary affect the delivery rate and may eventually inhibit drug delivery altogether. Active transdermal delivery systems have been developed to help regulate the delivery rate by providing mechanisms to improve drug delivery over time by “pumping” the active ingredient. One such system is described in U.S. Pat. No. 5,370,635 entitled “DEVICE FOR DELIVERING A MEDICAMENT” which describes a system for delivering a medicament and dispensing it to an organism for a relatively long period of time, for example at least a few days. The device can be adapted for positioning on the surface of the skin of a human or possibly an animal body in order to apply a medicament thereto from the outer side thereof.
  • [0007]
    Conventional transdermal systems circumvent the disadvantages of the adsorption through the gastrointestinal tract, but they do not optimize or tailor the dosing regiment to offset peak symptoms. In addition the constant transdermal delivery of a drug can lead to severe side effects, including debilitating sleep disorders and ever increasing tolerance.
  • [0008]
    Timed delivery is most often used to maintain a sustained level of a drug in the body. A significant focus of current research in drug delivery has been to determine the influence of a patient's circadian or other biological rhythms on drug efficacy and efficiency. This research demonstrates that certain disease symptoms follow a daily pattern, with peak symptoms at certain times of the day. It has been widely acknowledged that hormones, neurotransmitters and other intra-body compounds are released in different amounts at different times of the day pursuant to daily patterns. The Wall Street Journal reported on May 27, 2003 that ‘Doctors are increasingly looking at the clock when it comes to prescribing medicine, instructing patients not only to what drug to use but also precisely when to take it. The new approach stems from a growing body of research that demonstrates that certain diseases tend to get worse at certain times of the day, By synchronizing medications with a patient's body clock, many physicians believe that the drugs will work more effectively and with fewer side effects. In some cases, the improvements have been so pronounced that doctors have been able to reduce dosages.” Similarly, American Pharmacy reports that ‘Circadian physiologic processes alter drug absorption, distribution, metabolism, and excretion. As a result, drug doses need to be adjusted to meet the differing needs of target organs or tissues at various times of the day. See, L. Lamberg, American Pharmacy, 1991; N831(11): 20-23. Doctors have responded to this growing body of research by prescribing a carefully timed drug administration regimen to optimize treatment.
  • [0009]
    Recently, an orally administered drug for arthritis treatment has suggested a chronotherepeutic approach using a delay release system where the delay is scheduled to release the active ingredient at the beginning of an interleukin 6 cascade that is believed to cause early morning stiffness in rheumatoid arthritis patients. By attempting to synchronize the drug delivery with a biological cycle it is believed that low doses may be used to achieve desired results. However, this system does not overcome the limitations of delayed release systems described above. Although it is possible to meet the requirements of chronopharmacology with pills, this requires an enormous amount of discipline by the patient to comply with the treatment regiment. As illustrated above, to achieve optimal results, many patients may need to wake up during the night to take their medication.
  • [0010]
    Hence, what is needed is a reliable means of delivering multiple drugs in precisely timed and measured doses-without the inconvenience and hazard of injection, yet with improved performance as compared to orally-delivered drugs.
  • [0011]
    Currently, patient compliance (taking the proper dosages at the prescribed times) is a critical problem facing caregivers and pharmaceutical firms alike. Studies show that only about half of patients take medications at the times and in the dosages directed by their physician. It is reported that each year, 125,000 deaths and up to 20% of all hospital and nursing home admissions result from patient non compliance. It is estimated that non-compliance results in additional healthcare costs in excess of $100 billion per year in United States. These figures are even more pronounced for the elderly. Hence, a need exists for systems and methods that increase patient compliance for administration of a variety of drugs.
  • [0012]
    Additional advantages and novel features of this invention shall be set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the following specification or may be learned by the practice of the invention. The advantages of the invention may be realized and attained by means of the instrumentalities, combinations, compositions, and methods particularly pointed out in the appended claims.
  • SUMMARY OF THE INVENTION
  • [0013]
    Briefly stated, the present invention involves synchronizing the administration of compounds with the human body's natural circadian rhythms and addiction rhythms to counteract symptoms when they are likely to be at their worst by using an automated and pre programmable transdermal or other drug administration system.
  • [0014]
    Specifically, this invention describes a method to maximize the efficiency of compound administration, decrease negative side effects and increase the efficacy of pharmacological therapy by synchronizing and tailoring the administration of certain compounds to match these circadian rhythms.
  • [0015]
    Thus based on an analysis of the human body's circadian rhythms, the invention delivers varying dosages at varying times, pursuant to a pre-programmed dosage profile. This ensures that peak drug concentrations are present in the bloodstream to offset peak disease and addiction symptoms arising from variances and fluctuation in the body's natural circadian rhythms. Further, these methods ensure that less of a drug is in the bloodstream when disease and addiction symptoms are at there lowest.
  • [0016]
    The present invention describes methods for treating diseases, addictions and disorders in humans. These methods involve synchronizing and tailoring the administration of compounds with the body's natural circadian rhythms to counteract symptoms when they are likely to be at their worst by using an automated and pre programmable transdermal drug administration system.
  • [0017]
    More specifically, these methods synchronize and tailor drug administration to the human body's circadian rhythms to deliver varying dosages at varying times. This ensures that peak drug concentrations are present in the bloodstream to offset peak disease and addiction symptoms arising from variances and fluctuation in the body's natural circadian rhythms. Further, these methods ensure that less of a drug is in the bloodstream when disease and addiction symptoms are at there lowest. This minimizes negative side effects, and increases efficacy of the dosing regimen.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0018]
    FIG. 1 shows an exemplary device useful for implementing the present invention;
  • [0019]
    FIG. 2A and FIG. 2B illustrate comparative drug release profiles demonstrating operation of the present invention;
  • [0020]
    FIG. 3 is a schematic illustration of a drug delivery device in accordance with the present invention;
  • [0021]
    FIG. 4 is a schematic illustration of an alternative drug delivery device in accordance with the present invention
  • [0022]
    FIG. 5 shows an exemplary administration profile for a stimulant delivery system;
  • [0023]
    FIG. 6 shows an exemplary administration profile for a nicotine delivery system;
  • [0024]
    FIG. 7 shows an exemplary administration profile for a nitroglycerine delivery system tailored to treat variant angina attacks; and
  • [0025]
    FIG. 8 illustrates an exemplary administration profile for a nitroglycerine delivery system tailored to treat stress-induced angina attack.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • [0026]
    The reality of circadian rhythms in animals including humans is well known. Biological rhythms are periodic fluctuations in biological characteristics over time, which also include circadian as well as seasonal variations. Circadian, or approximately 24-hour, rhythms include the production of biological molecules such as cortisol and adrenaline, the regulation of body temperature and heart rate, changes in characteristics of blood, such as stickiness, and behaviors such as wakefulness, sleep and periods of activity.
  • [0027]
    Research demonstrates that certain disease symptoms follow a daily pattern, with peak symptoms at certain times of the day. It has been widely acknowledged that hormones, neurotransmitters and other intra-body compounds are released in different amounts at different times of the day pursuant to daily patterns. It is believed that the failure of current transdermal systems to synchronize drug administration with the body's natural rhythms often lead to (i) severe side effects, including debilitating sleep disorders (in the context of nighttime nicotine administration, for example), (ii) ever increasing tolerance (in the case of nitroglycerin and other pharmaceuticals for example), (iii) more expensive therapies, since more of a compound is needed since body rhythm tailored dosing is not implemented. In addition, many addictions follow a daily pattern consistent with one's circadian rhythms. For example, according to studies performed, immediately upon waking, smoker's have peak nicotine cravings. These peak cravings return after each meal, due to the interplay of serotonin release as a trained response to the culmination of a meal. Our methods precisely time the administration of drugs so that they reach peak levels when symptoms are likely to be at their worst, and efficacy is greatly improved.
  • [0028]
    The present invention involves precisely timing the administration of drugs so that they reach peak levels in synchronization with times when symptoms are likely to be at their worst, or times at which the drugs are believed to be more effective in the body and/or better tolerated by the patient. The present invention is described in terms of a particular example drug delivery system that provides automated and precise control over dosing, with single-dose capability, (once while people sleep) or capability to administer separate and varying-sized doses many times throughout a multiple day period. The particular implementation is consistent with a commercial development of a miniaturized, automated and programmable non-invasive drug delivery system called the ChronoDose™ system being developed by the assignee of the present invention. The system enables controlling of the amount of drug exposed to the skin in a controlled time dependent way according to a programmed administration schedule that implements a desired dosage profile. In this manner the present invention enables one to precisely control and vary the time of drug release and the amount of each dose, pursuant to an easily set pre-programmed dosage profile.
  • [0029]
    Research demonstrates that for certain symptoms, conditions and diseases, drug effects can be optimized when administered in a defined (and often varying) dosage at predefined times. This is known as Chrono-Pharmacology. To illustrate the importance of Chrono-Pharmacology consider the following facts:
      • Asthma attacks are 100 times more likely between 4:00 and 6:00 AM.
      • Heart attacks and strokes are most likely to occur around 6:00 AM.
      • Variant Angina attacks occur30 times more often in the middle of the night between 2:00 AM and 4:00 AM.
      • Smokers experience the highest cravings immediately upon waking up
      • Lethargy and difficulty getting out of bed is highest immediately upon waking up early in the morning
      • Cold and flu symptoms peak during night time and early morning hours, when cold medications are wearing off
  • [0036]
    In accordance with the present invention, substances with proven or suspected chrono-pharmacological efficiency are integrated into a miniaturized, automated, programmable watch-like device, such as device 100 shown in FIG. 1. The delivery system 100 shown in FIG. 1 can be used for a variety of active compositions, and is small, fully automated and programmable. This system consists of a re-usable wristwatch-like device 101 to control the time and dosage of drug delivery; and a small, disposable, ‘reservoir’ 103, which is about the size of a quarter or ½ dollar coin in a particular example, that the user can simply pop-in to place on the watch-like platform. This reservoir patch lasts, for example, up to 72 hours, depending on the application. Shorter and longer reservoir lifetimes are contemplated. The device is readily adapted to be worn on the forearm, ankle, or other convenient body location.
  • [0037]
    In a particular application the replaceable reservoir can include a description of an administration schedule that can be used to manually or automatically program device 100 with an administration schedule. For example, written schedule can be printed on or affixed to the reservoir 101 or electrically programmed using volatile or non-volatile memory. In this manner a dosing profile can be prescribed and filled by a pharmacy in much the same manner as a conventional drug prescription is handled today.
  • [0038]
    An exemplary implementation shown in FIG. 3 comprises a collapsible drug reservoir, an expandable waste reservoir, a micro-pump, electronics for automation, a display, and a highly permeable membrane. An exemplary system is described in a PCT application No. PCT/IB2004/002947entitled TRANSDERMAL DRUG DELIVEDRY METHOD AND SYSTEM filed on Sep. 13, 2004 which is incorporated herein by reference. The drug reservoir will contain about 3 ml of drug formulation. A tiny, miniaturized pump is activated at pre-programmed times and releases a pre-defined amount of drug formulation into the drug chamber, where the formulation comes into contact with highly permeable membrane. This membrane rests on the skin, and provides for even diffusion of the drug over the device's drug absorption surface area. This membrane works effectively with, and can be coated with, an adhesive. In operation, when the administration of the drug needs to be discontinued, the remaining drug formulation is either removed from the membrane area via a waste chamber, containing a hydrophilic substance (hydrogel) or the device is taken off.
  • [0039]
    In an implementation shown in FIG. 4, a pressurized drug reservoir is used which minimizes or eliminates need for a micropump. Electronics control a valve that allows controlled quantities of the drug to be applied to the drug chamber where the formulation comes into contact with highly permeable membrane.
  • [0040]
    The construction and use of transdermal patches for the delivery of pharmaceutical agents is known. See, for example, U.S. Pat. No. 5,370,635 entitled “DEVICE FOR DELIVERING A MEDICAMENT” the disclosure of which is incorporated herein by reference. Such patches may be constructed using a saturated media, pressurized reservoirs, or unpressurized reservoirs with micropumps for continuous, pulsatile, or on-demand delivery of an active material. For example, a pharmaceutically acceptable composition of an active material may be combined with skin penetration enhancers including, but not limited to, oleic acid, amino acids, oleyl alcohol, long chain fatty acids, propylene glycol, polyethylene glycol, isopropanol, ethoxydiglycol, sodium xylene sulfonate, ethanol, N-methylpyrrolidone, laurocapram, alkanecarboxylic acids, dimethylsulfoxide, polar lipids, N-methyl-2-pyrrolidone, and the like, which increase the permeability of the skin to the active material and permit the active material to penetrate through the skin and into the bloodstream. Pharmaceutically acceptable compositions may be combined with one or more agents including, but not limited to, alcohols, moisturizers, humectants, oils, emulsifiers, thickeners, thinners, surface active agents, fragrances, preservatives, antioxidants, vitamins, or minerals. Pharmaceutically acceptable compositions may also be combined with a polymeric substance including, but not limited to, ethylcellulose, hydroxypropyl cellulose, ethylene/vinylacetate, polyvinyl pyrrolidone, and the like, to provide the composition in gel form, which may be dissolved in solvent such as methylene chloride, evaporated to the desired viscosity, and then applied to backing material to provide a patch. The backing can be any of the conventional materials such as polyethylene, ethyl-vinyl acetate copolymer, polyurethane and the like.
  • [0041]
    Example substances include caffeine and a variety of over-the-counter and prescription stimulants (for treating fatigue, sleep disorders, attention deficit disorders and a variety of other conditions), nicotine (for smoking cessation), nitroglycerin (for treating heart attack and strokes), fentanyl (for treating chronic pain), albutamol (for treating asthma), and selegiline (for treating depression, attention deficit disorder or Parkinson's disease). We have carefully identified these specific drugs and diseases because they have the following attributes: (i) Chrono-Pharmacology is critical to optimized dosing but is not being implemented because no automated transdermal system exists, and (ii) these drugs can be transdermally absorbed passively (i.e., without the need for ultrasound or electrical stimulation or other permeation enhancers). Exemplary chrono-pharmacological systems that can make use of the present invention are summarized in Table 1
    DISEASES/
    CONDITION CHRONOPHARMACOLOGY
    Morning Adrenaline is lowest in the morning, making waking
    Lethargy uncomfortable and difficult for many people. This can
    be treated by administering OTC Stimulant before
    waking
    Smoking Nicotine at night creates sleeping disorders
    Cessation (nightmares), but cravings are the highest after
    waking up. This can be treated by administering
    Nicotine before waking up.
    Angina Angina (variant) attacks occur 30 (thirty) times more
    often between 2:00 a.m. and 4:00 a.m. This can be
    treated by administering larger nitroglycerin doses
    in early morning
    Asthma Asthma attacks are 100 times more likely between 4:00
    a.m. and 6:00 a.m. Adrenaline and Cortisol are
    virtually absent at night. This can be treated by
    administering albutamol in early morning
    Colds Heaviest symptoms overnight and in the morning. This
    and Flu can be treated by administering Cold/Flu medicine
    during the night.
    Heart Heart attacks and strokes are most likely between
    Attacks 6:00 a.m. and Noon. This can be treated by adminis-
    and tering Anticoagulants before waking up.
    Strokes
    Pain Neurological pain is worst between 3 A.M and 8 A.M.
    This can be treated by administering pain medication
    during sleep.
    Depression Selegiline at night can create sleeping disorders
    (nightmares), but depression symptoms are high
    immediately upon waking up. This can be treated by
    administering Selegiline before waking up.
    Rheumatoid Worst upon awakening. Cortisol and anti-inflammatory
    Arthritis hormones are very low at night This can be treated by
    administering medication delivered before waking up.
    Supplements Vitamins and supplements are best administered in low
    doses over the course of the day to be most effective.
  • [0042]
    Using this system the present invention can pre-program the times and amount of each dosage by precisely controlling the amount of drug exposed to the skin during each dosing. This feature is advantageous when a drug is best administered during sleep, e.g., 1 to 2 hours before waking up. The present invention precisely counteracts peak disease symptoms and increase patient compliance.
  • [0043]
    The present invention represents the first true non-invasive chrono-pharmacological drug delivery device. While current transdermal applications are restricted to the dosage profile shown in FIG. 2 a, the automated implementation of the present invention can be programmed for a variety of drug delivery patterns to achieve customized patient dosing regiments for optimal therapy (FIG. 2 b). There are many advantages for a controlled transdermal release of an active material such as a drug. As used herein, the term ‘controlled’ or ‘sustained’ release of an active material includes continuous or discontinuous, linear or non-linear release of the active material according to a programmed schedule. Among the advantages of controlled release are the convenience of a single application for the patient, avoidance of peaks and valleys in systemic concentration which can be associated with repeated injections, the potential to reduce the overall dosage of the active material, lower body stress, and the potential to enhance the pharmacological effects of the active material. A lower, sustained dose can also prevent adverse affects that are occasionally observed with infusion therapy. In addition to significantly reducing the cost of care, controlled release drug therapy can free the patient from repeated treatment or hospitalization, thus offering the patient greater flexibility and improving patient compliance. A controlled release formulation of certain drugs also provides an opportunity to use the drug in a manner not previously exploited or considered. The present invention is particularly advantageous when (i) known chrono-pharmacological information shows that a drug's effects can optimized when administered in a defined dosage at a predefined time or times, and/or (ii) patient compliance with the dosing regimen is greatly increased due to automation, (doses required at inopportune times, when sleeping, for example).
  • [0000]
    Applications—ArisePatch™
  • [0044]
    A contemplated consumer product is the ArisePatch™. Most people experience difficulty and discomfort when waking early in the morning. According to a 2002 National Sleep Foundation poll 49% of US adults age 18-29 have trouble waking in the morning and 41% of US adults age 30-64 have trouble waking in the morning. There are 165,000,000 adults in the US alone age 18-64, meaning approximately 74,250,000 US adults age 18-64 have trouble waking in the morning.
  • [0045]
    The ArisePatch implementation of the present invention allows individuals, while asleep, to have an over-the-counter (OTC) or prescription stimulant automatically administered during a 1-2 hour pre-wake-up period. FIG. 5 illustrates an exemplary stimulant administration profile showing a blood plasma level of ephedrine in nanograms per milliliter on the vertical axis, with time on the horizontal axis. Stimulant concentrations will reach peak levels immediately prior to having to wake. Immediately upon waking up the individual will be alert and feel well rested. The ArisePatch™ will eliminate the typical discomfort or difficulty associated with getting up early. This functionality is attractive to employed people getting up for work to ensure punctuality, and just about anyone who wants to offset morning discomfort associated with a late night, jet lag, or sickness.
  • [0000]
    Applications—Smoking Cessation
  • [0046]
    Nicotine replacement has been the most frequently used therapy to support smokers in their effort to quit. Smokers report that the craving for a cigarette is greatest immediately upon waking in the morning. The time elapsed between wakening and the first cigarette is the best indicator of addiction. For most smokers this time only a few minutes.
  • [0047]
    Current nicotine patches cause severe sleep disturbances by releasing nicotine steadily throughout the night to ensure sufficient morning nicotine levels to offset the strong morning craving. It is widely accepted that current nicotine patches have a detrimental and common side effect—sleeping disorders, and insomnia, including persistent nightmares. Therefore, users are often forced to remove the patch in the evening before they go to bed. This eliminates sleep disturbances, but results in nicotine levels that are insufficient to offset the strong morning craving. This is a major drawback to current nicotine patches and many users relapse, resulting in a less efficient smoking cessation therapy. Current patches present the user with a difficult decision, choosing between nightmares and relief from the strong morning cravings.
  • [0048]
    An exemplary product contemplated by the present invention is called Nicotine ChronoDose™ system. In accordance with the present invention, the system can begin to administer nicotine(or nicotine analogs or any other smoking cessation compound including but not limited to Zyban) automatically during a one hour period immediately prior to waking. This will relieve the smoker's peak craving upon waking without causing nightmares and insomnia. We believe that this system clearly provides a superior method for smoking cessation.
  • [0049]
    A more advanced nicotine replacement system than that described above is worn for three days at a time and is programmed to release nicotine in a daily rhythmic pattern such as shown in FIG. 6 to offset peaks in a smoker's cravings. FIG. 6 illustrates an exemplary nicotine administration profile showing a blood plasma level of nicotine in nanograms per milliliter on the vertical axis, with time on the horizontal axis. This implementation will reduce nicotine dependency by administering pre-programmed levels of nicotine pursuant to typical smoking patterns. For instance many smokers report that cravings for a cigarette are greatest upon waking up, after lunch, mid afternoon, after dinner and before bedtime. This implementation of the present invention will automatically release larger doses of nicotine to offset peak cravings and no nicotine when cravings are typically at a minimum. The present invention may be delivered in a pre-programmed manner for each treatment regimen. The only involvement by the user will be the replacement of the ‘reservoir’ every three days, and the replacement of the platform housing as needed.
  • [0050]
    This implementation represents a tremendous move forward in nicotine replacement therapy, and is far superior to the old-technology systems that simply release the same amount of nicotine all day and night. With the present invention, one can systematically decrease a smoker's tolerance without increasing dependence (the result of a constant flow) and better wean a smoker off nicotine. This will allow the smoker to better ‘tailor-down’ and decrease the amount of nicotine he needs to quit. Modern smoking cessation is much more than nicotine replacement therapy. Programs also include weight control, diet and psychological support. The present invention fits well into these programs, since it addresses the key component of being able to quit smoking by efficiently countering the withdrawal symptoms while doing away with the negative side effects of current nicotine replacement therapy systems, namely sleep disturbance.
  • [0000]
    Applications—Cold and Flu treatment
  • [0051]
    Cold and flu symptoms are worst from midnight until the early morning because the concentration of cortisol is lowest at that time. Current night time cold and flu medication end up losing efficacy by early morning when cold and flu symptoms are highest. Therefore people suffering from a cold or flu are often unpleasantly awoken by an increase in symptoms, cutting sleep short. Set and put on before bedtime, the present invention will automatically deliver a larger dose of medication and immuno-boosters in the early morning hours to more effectively combat the peak cold and flu symptoms that occur in the morning. Users will experience less severe cold and flu symptoms during the morning hours, will not have their sleep cycle cut short, and will wake up feeling symptom-free. This implementation uses prescription or OTC cold medicine alone or optionally in combination with certain transdermally efficacious vitamins and immune system boosters to provide a total solution to cold and flu ailments. This is the first cold therapy that combines OTC medicine with supplemental immuno-boosters in a comprehensive and automated manner. Our system will treat the cold symptoms directly and boost the body's immune system to help it heal naturally.
  • [0052]
    In a particular application, the Cold and Flu automated transdermal drug delivery system utilizes OTC cold medicine, Vitamin C, Echinacea, and Zinc to provide a total solution to cold and flu ailments, and all while you sleep. Cold and flu symptoms are worst in the middle of the night and early morning because the hormone cortisol, a key inflammation fighter, is missing at that time. Cold and flu symptoms are worst from midnight until the early morning because the concentration of cortisol is lowest at that time. Current night time cold and flu medication end up losing efficacy by early morning when cold and flu symptoms are highest. Therefore people suffering from a cold or flu are often unpleasantly awoken by an increase in symptoms, cutting sleep short
  • [0053]
    Set and put on before bedtime, the Cold and Flu automated transdermal drug delivery system utilizes our proprietary technology to automatically deliver a larger dose of medication and immuno-boosters in the early morning hours to more effectively combat the peak cold and flu symptoms that occur in the morning. Users will experience less severe cold and flu symptoms during the morning hours, will not have their sleep cycle cut short, and will wake up feeling symptom-free.
  • [0054]
    Our system not only combats statistically proven peak nighttime and early morning cold symptoms by releasing OTC cold medicine, but actually helps your body to heal by boosting its immune system through Vitamin C, Echinacea and Zinc supplementation in small but distinct doses all night long.
  • [0055]
    Our Cold/Flu system releases these combination of compounds every 2 hours throughout the night, with a higher dosage of compounds being released in the morning to combat these proven middle of the night and early morning symptoms, which are the worst of the day.
  • [0056]
    Cold and flu symptoms are worst in the middle of the night and early morning because the hormone cortisol, a key inflammation fighter, is missing at that time. Our system utilizes its core competitive advantage by pre-programming our System to release more medicaments precisely at that time to offset these peak symptoms. Current cold and flu medications end up losing efficacy by early morning when cold symptoms peak, so the user either has sleep cut short due to the onset of these symptoms, or wakes up out of slumber feeling sick with peak symptoms. Our system will ensure that a while a person is actually sleeping, a sufficient dose of cold and flu medicine is freshly delivered to offset these peak morning symptoms.
  • [0000]
    Applications—Weight Control, Vitamin and Herbal Supplementation
  • [0057]
    In yet another application, a series of weight loss vitamins and supplements is administered in small distinct doses many times over a multiple day period. Vitamins and supplements are absorbed by the body in small dosages. Contrary to popular belief, once-a-day products are not maximally effective because excess dosages are excreted unused. This implementation of the present invention precisely controls the timing and dosage of small but distinct amounts of vitamins and supplements during a 24 hour period to ensure that vitamins and supplements are constantly bio-available for optimal absorption and cellular function. Greater doses are automatically released prior to mealtimes to counter appetite cravings, resulting in a much more effective diet program.
  • [0000]
    Applications—Angina
  • [0058]
    Research shows that variant angina occurs 30 times more often between 2:00 a.m. and 4:00 a.m. (‘critical angina phase’) than at any other time of the day. Nitroglycerin effectively combats angina attacks, if administered in optimal doses. Current nitroglycerin patches exist, but they can only release a constant amount of nitroglycerine steadily over time. Current patches cannot tailor the release of nitroglycerine to optimize treatment by releasing more nitroglycerine precisely during the critical angina phase to offset these peak symptoms.
  • [0059]
    In addition, nitroglycerine loses its effectiveness and requires higher and higher dosages when administered constantly. Our bodies become tolerant to it. Current systems cannot stop or decrease the release of nitroglycerine when disease symptoms are lowest. Thus, these current ‘dumb’ patches cannot offset the critical angina phase by releasing more of the drug, nor can they shut down or stop nitroglycerine administration when the body doesn't need it. It is a ‘one dose fits all’ type of scenario once each “dumb” patch is applied to the patient.
  • [0060]
    The method in accordance with the present invention utilizes an automated transdermal system in order to transdermally administer more nitroglycerine during the critical angina phase to ensure adequate offset of these symptoms and less nitroglycerine when it is not needed so that no tolerance builds up. Our method utilizes a ‘smart’ patch medicine system at this time to offset these peak critical phases in the disease cycle arising due to the human body's circadian rhythm.
  • [0061]
    The preprogrammable automated transdermal system is worn around the wrist like a watch (or the forearm arm or ankle) and releases nitroglycerine in optimal dosages at times that are optimally synchronized. This is pursuant to a pre-programmed and tailored dosage profile. Current nitroglycerin patches only have the capability to release a constant dose of nitroglycerin over a period of time. Current nitroglycerin patches simply cannot alter or vary dosages to increase dosages at different times of the day, and decrease dosages at other times of the day.
  • [0062]
    The nitroglycerin system in accordance with the present invention has three primary advantages over current nitroglycerin patches. First, the system utilizes its core competitive advantage to automatically and precisely release nitroglycerin in peak amounts to offset the peak symptoms of morning attacks occurring during the critical angina phase. Current nitroglycerine patches have release rates that stay constant and do not increase to offset critical phases, and do not decrease as symptoms decrease. Second, our system solves the tolerance issue by releasing less (or no) nitroglycerin in off-peak hours, and then releasing nitroglycerin at just the right time so that it is present during critical periods, without increasing tolerance. Third, our system accomplishes 1 and 2 above automatically, without the need for a patient to wake up to take a drug at this critical phase, which does away with the need for any increased patient compliance.
  • [0063]
    As a result we believe that our nitroglycerin system represents an ideal delivery system for patients who use nitroglycerin regularly for the treatment and/or the prevention of heart attacks and strokes. Patient compliance regarding the timing and dose of heart attack medication is crucial. Patient non-compliance with physician's instructions for this is often a cause of re-hospitalization, according to the US Department of Health and Human Services. The system solves this problem, and will decrease the need for re-hospitalization by dramatically increasing patient compliance.
  • [0064]
    This system can be either an ‘wear each night and remove in the morning’ system, whereby it only releases nitroglycerine automatically to offset the critical angina phase in the morning, or a ‘total solution’ system, that is worn for a period of 24 hours to several days, and that administers nitroglycerine in tailored amounts and at tailored times as synchronized with the body's circadian rhythm (and conveniently taken off while showering or swimming).
  • [0065]
    The system is an innovative new drug therapy for angina. With its superior advantage of optimized and automated time and dose administration synchronized with our circadian rhythms, the system in accordance with the present invention ensures that nitroglycerin will circulate in the bloodstream exactly when the patient needs it, and without any build up tolerance. For these reasons, our system is superior to current steady release nicotine patches. Our system's increased advantages are extremely relevant for those patients with moderate to severe angina.
  • [0066]
    FIG. 7 shows an exemplary administration profile for a nitroglycerine delivery system tailored to treat variant angina attacks or angina pectoris. This type of angina attack has a peak frequency in many patients between the hours of 2:00 and 4:00 AM. This is a particularly difficult time to wake up to take a drug such as nitroglycerine. In accordance with the present invention an administration profile substantially like that shown in FIG. 7 is automatically administered. In FIG. 7 the vertical axis indicates blood plasma level in nanograms per milliliter, and the horizontal axis indicates time from 10:00 PM through the night to 8:00 AM.
  • [0067]
    FIG. 8 illustrates an exemplary administration profile for a nitroglycerine delivery system tailored to treat stress-induced angina attack. In FIG. 8 the vertical axis indicates blood plasma level in nanograms per milliliter, and the horizontal axis indicates time from 12:00 AM through the day until about 4:00 PM. The administration profile shown in FIG. 8 provides a high blood plasma concentration throughout the waking hours of a day when stress is likely occur.
  • [0000]
    Applications—Asthma
  • [0068]
    The automated transdermal asthma system automatically administers a morning dose of albuterol, tolobuterol, salmeterol, beta 2 agonist or any other antiarrhythmic drug (an ‘Asthma drug’) to combat the peak symptom of morning asthma attacks known as the ‘morning dip’.
  • [0069]
    Asthma attacks occur 100 (one hundred) times more often between the hours 4 A.M. and 6 A.M., when most people are asleep. This is due to the early morning deterioration of respiratory function known as ‘morning dip’, which is the time of day that respiratory function is at its lowest. These early morning asthma attacks cause great distress to sufferers and care providers. The morning dip represents the dip in respiratory function at this time when asthma attacks are 100 times more likely to occur. Our system effectively combats the morning dip by releasing more Asthma drug at this time to offset this peak morning symptom . In other words, our ‘smart’ patch varies the level of drug in the bloodstream so that drug concentrations are highest when respiratory function is at its lowest.
  • [0070]
    Current ‘dumb’ asthma patches exist, but they can only release a constant amount of drug steadily over time. Current patches cannot tailor the release of drug to optimize treatment by releasing more drug precisely during the morning dip to offset these peak critical symptoms.
  • [0071]
    The Asthma system has two primary advantages over current patches. First, the system of the present invention utilizes its core competitive advantage to automatically and precisely release albuterol or other asthma drugs in peak amounts to offset the peak symptoms associated with the morning dip. Current patches have release rates that stay constant and do not increase to offset this peak critical phases, and do not decrease as symptoms decrease. Second, our system accomplishes 1 and 2 above automatically, without the need for a patient to wake up to take a drug at this critical phase, which does away with the need for any increased patient compliance.
  • [0072]
    The automated transdermal system for Asthma is worn around the wrist like a watch (or the forearm arm or ankle) and releases albuterol or other Asthma drugs in optimal dosages at times that are optimally synchronized, especially to offset the morning dip, pursuant to a pre-programmed and tailored dosage profile. Current Asthma patches only have the capability to release a constant dose over a period of time. Current Asthma patches simply cannot alter or vary dosages to increase dosages at different times of the day, and decrease dosages at other times of the day.
  • [0073]
    The system is an innovative new drug therapy for asthma. With its superior advantage of optimized and automated time and dose administration synchronized with our circadian rhythms, our system ensures that albuterol or another asthma drug will circulate in increased amounts in the bloodstream exactly when the patient needs it. For these reasons, our system is superior to current steady release patches. Our system's increased advantages are extremely relevant for those patients with moderate to severe asthma.
  • [0000]
    Applications—Hypertension
  • [0074]
    The clondine automated transdermal system utilizes clondine, (or another hypertension drug) an effective drug that combats high blood pressure. The clondine automated transdermal drug delivery system has an automated morning release of Clondine to combat the peak symptom of morning heart attacks.
  • [0075]
    Blood pressure differs at different times of the day. Blood pressure surges upon waking, and is lower by 20 to 30 per cent while sleeping. Our preprogrammed automatic transdermal system utilizes its core competitive advantage by releasing clondine in a tailored fashion to counter high blood pressure when symptoms are highest, while releasing less clondine when symptoms are less severe.
  • [0076]
    Current clondine patches release the drug consistently over time. It cannot release more of the drug when symptoms are worst. People die most when the symptoms peak. Having the advantage of administering more of the drug when a patient needs it the most can mean the difference between life and death, especially in patients with moderate to severe high blood pressure.
  • [0077]
    The automated transdermal system for hypertension has two primary advantages over current patches. First, our system utilizes its core competitive advantage to automatically and precisely release clondine or other hypertension drugs in peak amounts to offset the peak symptoms associated with the dangerous morning symptoms. Current hypertension patches have release rates that stay constant and do not increase to offset this peak critical phases, and do not decrease as symptoms decrease. Second, our system accomplishes 1 and 2 above automatically, without the need for a patient to wake up to take a drug at this critical phase, which does away with the need for any increased patient compliance.
  • [0000]
    Applications—Depression, Alzheimer's, Attention Deficit
  • [0078]
    The selegiline automated transdermal system utilizes selegiline, an effective MAO inhibitor for the treatment of depression, Alzheimer's and Attention Deficit Disorder.
  • [0079]
    The selegiline automated transdermal drug delivery system gives an automated morning release of selegiline to combat the peak symptom of morning depression without the side effect of sleep disturbances.
  • [0080]
    The system in accordance with the present invention is applied before bed. It does not release the drug until an hour or 2 before morning, so symptom of morning depression would be corrected by our system without subjecting the patient to sleep disturbances.
  • [0081]
    Primary negative side effects of the selegiline patches are abnormal dreams, insomnia, and difficulty sleeping. We believe that by specifically refraining from administering selegiline at night, and utilizing our system's core competitive advantage to turn it on an hour or so before waking, we can do away with this negative side effect and still offset the critical phase of morning symptoms of depression. It has been reported that patients have increased symptoms of depression upon waking if the critical amount of Selegiline is not circulating through their system. Our system utilizes its core competitive advantage to provide a compelling solution to this problem. Our system is applied before bed, it would not release the drug until an hour or two before morning, so symptom of morning depression would be corrected by our system without subjecting the patient to sleep disturbances
  • [0082]
    Current Oral Selegiline produces horrible side effects. There is a new Selegiline patch coming out on the market, but it to produces sleep disturbances. It is believed that the system in accordance with the present invention would be superior to conventional Selegiline product delivery systems.
  • [0000]
    Applications—In General
  • [0083]
    The present invention is particularly useful in applications in which it is necessary and/or desirable to start the administration of a drug, stop the administration of a drug, and/or increase/decrease the dosage of a drug at a time when it is inconvenient or impossible for a patient to initiate the necessary actions. This is particularly useful for a wide variety of drug administration applications that benefit when administration is started, stopped, or changed while a person is sleeping. As chronotherapy knowledge increases, it is contemplated that a wide variety of applications will be discovered in which benefit is realized by starting, stopping and/or changing the drug administration while a patient sleeps.
  • [0084]
    In each of the examples, treatment is continued as needed to provide superior symptomatic relief, prevent exacerbation of symptoms, and/or prevent and/or delay progression of the disease state or condition in the patient, or until it is no longer well tolerated by the patient, or until a physician terminates treatment. For example, a physician may monitor one or more symptoms and/or serum levels of active material and/or metabolic by-product(s) in a patient being treated according to this invention and, upon observing attenuation of one or more symptoms for a period of time, conclude that the patient can sustain the positive effects of the above-described treatment without further administration for a period of time. When necessary, the patient may then return at a later point in time for additional treatment as needed.
  • [0085]
    As used herein, ‘day’ means a 24-hour period. Thus, for example, ‘for at least three consecutive days’ means for at least a 72-hour period. During or after the treatment, a physician may monitor one or more symptoms and/or serum levels in the patient and, upon observing an improvement in one or more of the parameters for a period of time, conclude that the patient can sustain the positive effects of the treatment without further administration of the active material for a period of time.
  • [0086]
    In order to use an active material for therapeutic treatment (including prophylactic treatment) of mammals including humans according to the methods of this invention, the active material is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition. According to this aspect of the invention there is provided a pharmaceutical composition comprising an active material in association with a pharmaceutically acceptable diluting substance or carrier, wherein the active material is present in an amount for effective treating or preventing a particular condition. While individual needs may vary, determination of optimal ranges for effective amounts of an active ingredient (alone or in combination with other drugs) within the ranges disclosed herein is within the expertise of those skilled in the art. Accordingly, ‘effective amounts’ of each component for purposes herein are determined by such considerations and are amounts that improve one or more active ingredient functions and/or ameliorate on or more deleterious conditions in patients and/or improve the quality of life in patients.
  • [0087]
    The present invention also provides pharmaceutical kits for treating a particular symptom, condition and/or disease and/or improving a particular biological function, comprising one or more containers comprising one or more active compositions in accordance with this invention. Such kits can also include additional drugs or therapeutics for co-use with the active composition for treatment or prevention of a particular symptom, condition and/or disease and/or improving a particular biological function . In this embodiment, the active composition and the drug can be formulated in admixture in one container, or can be contained in separate containers for simultaneous or separate administration. The kit can further comprise a device(s) for administering the compounds and/or compositions, such as device 100 shown in FIG. 1, and written instructions in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which instructions can also reflect approval by the agency of manufacture, use or sale for human administration.
  • [0088]
    Although the invention has been described and illustrated with a certain degree of particularity, it is understood that the present disclosure has been made only by way of example, and that numerous changes in the dosages, administration profiles, timing, as well as the combination and arrangement of parts can be resorted to by those skilled in the art without departing from the spirit and scope of the invention, as hereinafter claimed.

Claims (18)

  1. 1. A method for delivering a bioactive agent to a human or animal comprising:
    providing a transdermal drug delivery device coupled to the human or animal, the delivery device having a source of the bioactive agent, a programmable timing mechanism, and a mechanism for causing the bioactive agent to be delivered transdermally in response to the timing mechanism; and
    timing routines implemented by the timing mechanism, wherein the timing routines are selected to deliver the bioactive agent at a time, rate, sequence and/or cycle that is synchronized with a biological rhythm of the human or animal.
  2. 2. The method of claim 1 wherein the bioactive agent comprises a stimulant and the timing routines are selected to deliver the stimulant immediately before the human or animal wakes up.
  3. 3. The method of claim 1 wherein the bioactive agent comprises nicotine and the timing routines are selected to deliver the nicotine at times that are associated with nicotine cravings.
  4. 4. The method of claim 3 wherein at least one of the selected times corresponds to a time at which the human or animal experiences a morning nicotine craving.
  5. 5. The method of claim 1 wherein the bioactive agent comprises an antihistamine and the timing routines are selected to deliver the antihistamine while the human or animal sleeps.
  6. 6. The method of claim 1 wherein the bioactive agent comprises a stimulant and the timing routines are selected to deliver the stimulant immediately before the human or animal wakes up.
  7. 7. A method for treating a symptom, condition, and/or disease comprising:
    identifying a drug suitable for treating a particular symptom, condition and/or disease;
    identifying a biologically superior time for administering a drug;
    programming a time-programmable transdermal drug delivery system with a schedule selected to synchronize with the identified biologically superior time; and
    causing the time-programmable transdermal drug delivery system to deliver the active ingredient according to the programmed schedule.
  8. 8. A programmable transdermal drug delivery device comprising:
    an interface for coupling to the skin of a host;
    a reservoir storing a quantity of an active composition;
    valve mechanism for supplying a quantity of the active composition from the reservoir to the interface in response to a control signal; and
    a timing mechanism coupled to the valve mechanism and configured to generate the control signal according to a programmed administration schedule.
  9. 9. The device of claim 7 wherein the valve mechanism controls a rate at which the active composition is supplied in response to the control signal.
  10. 10. The device of claim 7 further comprising a mechanism for removing the active composition from the interface in response to the control signal.
  11. 11. The device of claim 7 further comprising a mechanism for removing carrier materials from the interface.
  12. 12. A kit comprising a first container comprising a pharmaceutical formulation of an active material, said formulation comprising an amount of active material effective to treat a symptom, condition, and/or disease, wherein said first container is adapted to coupled to a programmable transdermal drug delivery system.
  13. 13. The kit of claim 11 wherein the first container includes a specification of an administration schedule that is used to program the programmable transdermal drug delivery system.
  14. 14. A method for delivering a drug to a human or animal comprising:
    providing a transdermal drug delivery device coupled to the human or animal, the delivery device having a source of the drug, a programmable timing mechanism, and a mechanism
    for causing the drug to be delivered transdermally in response to the timing mechanism; and
    timing routines implemented by the timing mechanism, wherein the timing routines are selected to deliver the drug at a time when the human or animal is expected to be asleep.
  15. 15. The method of claim 13 wherein the timing routines initiate drug delivery at a time when the human or animal is expected to be asleep.
  16. 16. The method of claim 13 wherein the timing routines terminate drug delivery at a time when the human or animal is expected to be asleep.
  17. 17. The method of claim 13 wherein the timing routines increase the dosage of drug delivered at a time when the human or animal is expected to be asleep.
  18. 18. The method of claim 13 wherein the timing routines decrease the dosage of drug delivered at a time when the human or animal is expected to be asleep.
US11162517 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery Abandoned US20070191815A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US60941804 true 2004-09-13 2004-09-13
US11162517 US20070191815A1 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
PCT/US2005/032672 WO2006031856A3 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
US11162517 US20070191815A1 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
CA 2580329 CA2580329C (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
US11162525 US7780981B2 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
EP20050796698 EP1802258A4 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
JP2007531458A JP5254616B2 (en) 2004-09-13 2005-09-13 Biological synchrony (biosynchronous) transdermal drug delivery
US12835693 US20100280432A1 (en) 2004-09-13 2010-07-13 Biosynchronous transdermal drug delivery
US14162156 US20140200525A1 (en) 2003-10-27 2014-01-23 Biosynchronous transdermal drug delivery
US14746704 US9555227B2 (en) 2004-09-13 2015-06-22 Biosynchronous transdermal drug delivery
US14746689 US9555226B2 (en) 2003-10-27 2015-06-22 Transdermal drug delivery method and system
US15385638 US20170100572A1 (en) 2003-10-27 2016-12-20 Transdermal drug delivery method and system
US15385665 US20170100573A1 (en) 2004-09-13 2016-12-20 Biosynchronous transdermal drug delivery

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US13892006 Continuation US8673346B2 (en) 2003-10-27 2013-05-10 Transdermal drug delivery method and system

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14162156 Continuation US20140200525A1 (en) 2003-10-27 2014-01-23 Biosynchronous transdermal drug delivery

Publications (1)

Publication Number Publication Date
US20070191815A1 true true US20070191815A1 (en) 2007-08-16

Family

ID=38024536

Family Applications (8)

Application Number Title Priority Date Filing Date
US11162517 Abandoned US20070191815A1 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
US11162525 Active 2027-10-31 US7780981B2 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
US12835693 Abandoned US20100280432A1 (en) 2004-09-13 2010-07-13 Biosynchronous transdermal drug delivery
US14162156 Abandoned US20140200525A1 (en) 2003-10-27 2014-01-23 Biosynchronous transdermal drug delivery
US14746689 Active US9555226B2 (en) 2003-10-27 2015-06-22 Transdermal drug delivery method and system
US14746704 Active US9555227B2 (en) 2003-10-27 2015-06-22 Biosynchronous transdermal drug delivery
US15385665 Pending US20170100573A1 (en) 2003-10-27 2016-12-20 Biosynchronous transdermal drug delivery
US15385638 Pending US20170100572A1 (en) 2003-10-27 2016-12-20 Transdermal drug delivery method and system

Family Applications After (7)

Application Number Title Priority Date Filing Date
US11162525 Active 2027-10-31 US7780981B2 (en) 2004-09-13 2005-09-13 Biosynchronous transdermal drug delivery
US12835693 Abandoned US20100280432A1 (en) 2004-09-13 2010-07-13 Biosynchronous transdermal drug delivery
US14162156 Abandoned US20140200525A1 (en) 2003-10-27 2014-01-23 Biosynchronous transdermal drug delivery
US14746689 Active US9555226B2 (en) 2003-10-27 2015-06-22 Transdermal drug delivery method and system
US14746704 Active US9555227B2 (en) 2003-10-27 2015-06-22 Biosynchronous transdermal drug delivery
US15385665 Pending US20170100573A1 (en) 2003-10-27 2016-12-20 Biosynchronous transdermal drug delivery
US15385638 Pending US20170100572A1 (en) 2003-10-27 2016-12-20 Transdermal drug delivery method and system

Country Status (5)

Country Link
US (8) US20070191815A1 (en)
EP (1) EP1802258A4 (en)
JP (1) JP5254616B2 (en)
CA (1) CA2580329C (en)
WO (1) WO2006031856A3 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060062838A1 (en) * 2004-09-13 2006-03-23 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery
US20070042026A1 (en) * 2005-03-17 2007-02-22 Wille John J Prophylactic and therapeutic treatment of topical and transdermal drug-induced skin reactions
US20080220092A1 (en) * 2004-09-13 2008-09-11 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like
US20100169260A1 (en) * 2008-12-30 2010-07-01 Searete Llc Methods and systems for presenting an inhalation experience
USRE46217E1 (en) 2005-05-24 2016-11-29 Chrono Therapeutics Inc. Portable drug delivery device including a detachable and replaceable administration or dosing element
US9724483B2 (en) 2008-12-30 2017-08-08 Gearbox, Llc Method for administering an inhalable compound

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100260669A1 (en) * 2004-05-13 2010-10-14 Anthony Joonkyoo Yun Treatment of Seasonal Conditions Through Modulation of the Autonomic Nervous System
US7459469B2 (en) * 2004-11-10 2008-12-02 Targacept, Inc. Hydroxybenzoate salts of metanicotine compounds
CN101472893A (en) * 2006-05-09 2009-07-01 塔加西普特公司 Polymorph forms of (2S)-(4E)-N-methyl-5- (3-isopropoxypyridin) yl]-4-penten-2-amine for the treatment of central nervous system disorders
EP2133338A1 (en) * 2006-05-09 2009-12-16 AstraZeneca AB Salt forms of (2S)-(4E)-N-Methyl-5-[(5-Isopropoxy)pyridin-3-yl]-4-penten-2-amine
JP2009545357A (en) * 2006-08-02 2009-12-24 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ Apparatus for monitoring the state of and / or patient for treatment decision support
WO2008032238A3 (en) * 2006-09-13 2008-11-06 Paul A J Ackermans Device for automatic adjustment of the dose of melatonin and/or delivery of melatonin
US20080107719A1 (en) * 2006-11-08 2008-05-08 Sukhon Likitlersuang Transdermal drug delivery system
US20080152709A1 (en) * 2006-12-22 2008-06-26 Drugtech Corporation Clonidine composition and method of use
WO2008091592A1 (en) * 2007-01-22 2008-07-31 Targacept, Inc. Intranasal, buccal, and sublingual administration of metanicotine analogs
KR20100052490A (en) * 2007-07-31 2010-05-19 아스트라제네카 아베 Transdermal administration of (2s)-(4e)-n-methyl-5-(3-(5-isopropoxypyridin)yl)-4-penten-2-amine
WO2009026139A1 (en) * 2007-08-17 2009-02-26 Isis Biopolymer Llc Iontophoretic drug delivery system
US20100121307A1 (en) * 2007-08-24 2010-05-13 Microfabrica Inc. Microneedles, Microneedle Arrays, Methods for Making, and Transdermal and/or Intradermal Applications
JP2011517578A (en) * 2007-12-10 2011-06-16 アイシス バイオポリマー,インク. Iontophoretic drug delivery device and software application
EP2141620A1 (en) * 2008-07-01 2010-01-06 Boehringer Mannheim Gmbh Insulin pump and method for controlling a user interface of an insulin pump
EP2419085A4 (en) * 2009-04-14 2013-04-24 Univ California Improved oral drug devices and drug formulations
US20110092881A1 (en) * 2009-05-08 2011-04-21 Isis Biopolymer Inc. Iontophoretic device with contact sensor
US20100286590A1 (en) * 2009-05-08 2010-11-11 Isis Biopolymer Llc Iontophoretic device with improved counterelectrode
US8641671B2 (en) 2009-07-30 2014-02-04 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
US8703802B2 (en) 2010-05-20 2014-04-22 Targacept, Inc. Process for the preparation of aryl substituted olefinic amines
DE102010030502A1 (en) 2010-06-24 2011-12-29 HSG-IMIT-Institut für Mikro- und Informationstechnologie Quellstoffaktor and conveying device, in particular to in a medical active substance
US8623409B1 (en) 2010-10-20 2014-01-07 Tris Pharma Inc. Clonidine formulation
US20150051548A1 (en) * 2012-03-13 2015-02-19 Becton Dickinson France Method of Manufacture for a Miniaturized Drug Delivery Device
US9539201B2 (en) 2012-04-20 2017-01-10 KAT Transdermals LLC Selegiline transdermal system
US9265458B2 (en) 2012-12-04 2016-02-23 Sync-Think, Inc. Application of smooth pursuit cognitive testing paradigms to clinical drug development
US20140207047A1 (en) * 2013-01-22 2014-07-24 Chrono Therapeutics, Inc. Transdermal drug delivery system and method
US9380976B2 (en) 2013-03-11 2016-07-05 Sync-Think, Inc. Optical neuroinformatics
US9492608B2 (en) 2013-03-15 2016-11-15 Tandem Diabetes Care, Inc. Method and device utilizing insulin delivery protocols
WO2017079758A1 (en) * 2015-11-06 2017-05-11 Bkr Ip Holdco Llc Modified transdermal delivery device or patch and method of delivering insulin from said modified transdermal delivery device

Citations (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4379454A (en) * 1981-02-17 1983-04-12 Alza Corporation Dosage for coadministering drug and percutaneous absorption enhancer
US4545990A (en) * 1982-11-22 1985-10-08 L'oreal Anti-acne composition
US4708716A (en) * 1983-08-18 1987-11-24 Drug Delivery Systems Inc. Transdermal drug applicator
US4917895A (en) * 1987-11-02 1990-04-17 Alza Corporation Transdermal drug delivery device
US5242941A (en) * 1990-12-04 1993-09-07 State Of Oregon Methods of treating circadian rhythm disorders
US5273756A (en) * 1991-08-23 1993-12-28 Cygnus Therapeutic Systems Transdermal drug delivery device using a membrane-protected microporous membrane to achieve delayed onset
US5352456A (en) * 1991-10-10 1994-10-04 Cygnus Therapeutic Systems Device for administering drug transdermally which provides an initial pulse of drug
US5370835A (en) * 1991-11-21 1994-12-06 Willi Sturtz Maschinenbau GmbH Method of manufacturing rectangular frames
US5389679A (en) * 1992-01-21 1995-02-14 Alliger; Howard Method of treating small mouth ulcers with lactic acid
US5405614A (en) * 1992-04-08 1995-04-11 International Medical Associates, Inc. Electronic transdermal drug delivery system
US5505958A (en) * 1994-10-31 1996-04-09 Algos Pharmaceutical Corporation Transdermal drug delivery device and method for its manufacture
US5538503A (en) * 1993-09-15 1996-07-23 Henley; Julian L. Programmable apparatus for reducing substance dependency in transdermal drug delivery
US5616332A (en) * 1993-07-23 1997-04-01 Herstein; Morris Cosmetic skin-renewal-stimulating composition with long-term irritation control
US5785688A (en) * 1996-05-07 1998-07-28 Ceramatec, Inc. Fluid delivery apparatus and method
US5879322A (en) * 1995-03-24 1999-03-09 Alza Corporation Self-contained transdermal drug delivery device
US5932240A (en) * 1992-04-08 1999-08-03 Americare Technology, Inc. Multidose transdermal drug delivery system
US5993435A (en) * 1990-04-30 1999-11-30 Alza Corporation Device and method of iontophoretic drug delivery
US6068853A (en) * 1994-04-13 2000-05-30 Novartis Corporation Temporally controlled drug delivery systems
US6090404A (en) * 1994-01-13 2000-07-18 Lts Lohmann Therapie-Systeme Gmbh Estradiol penetration enhancers
US6129702A (en) * 1996-12-03 2000-10-10 Fraunhofer-Gesellschaft Zur Forderung Angewandten Forschung E.V. Medicament dosing system
US6165155A (en) * 1997-02-07 2000-12-26 Sarcos, Lc Multipathway electronically-controlled drug delivery system
US6211296B1 (en) * 1998-11-05 2001-04-03 The B. F. Goodrich Company Hydrogels containing substances
US6214379B1 (en) * 1998-04-02 2001-04-10 Kv Pharmaceutical Company Maximizing effectiveness of substances used to improve health and well being
US6374136B1 (en) * 1997-12-22 2002-04-16 Alza Corporation Anhydrous drug reservoir for electrolytic transdermal delivery device
US20020127256A1 (en) * 2001-03-01 2002-09-12 Howard Murad Compositions and methods for treating dermatological disorders
US6539250B1 (en) * 1999-12-15 2003-03-25 David S. Bettinger Programmable transdermal therapeutic apparatus
US20030065294A1 (en) * 2001-09-28 2003-04-03 Pickup Ray L. Cutaneous administration system
US6595956B1 (en) * 1998-03-23 2003-07-22 Joseph Gross Drug delivery device
US6638528B1 (en) * 2000-01-20 2003-10-28 Noven Pharmaceuticals, Inc. Compositions and methods to effect the release profile in the transdermal administration of active agents
US6723086B2 (en) * 2001-05-07 2004-04-20 Logiq Wireless Solutions, Inc. Remote controlled transdermal medication delivery device
US20040138074A1 (en) * 2002-05-01 2004-07-15 Nawaz Ahmad Warming and nonirritating lubricant compositions and method of comparing irritation
US20050034842A1 (en) * 2003-08-11 2005-02-17 David Huber Electroosmotic micropumps with applications to fluid dispensing and field sampling
US6861066B2 (en) * 2002-03-11 2005-03-01 Health Plus International Inc. Method for the delivery of a biologically active agent
US6887202B2 (en) * 2000-06-01 2005-05-03 Science Applications International Corporation Systems and methods for monitoring health and delivering drugs transdermally
US20050151110A1 (en) * 2004-01-14 2005-07-14 Minor Barbara H. Fluoroether refrigerant compositions and uses thereof
US20050238704A1 (en) * 2003-10-27 2005-10-27 Werner Zumbrunn Transdermal drug delivery method and system

Family Cites Families (124)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4856188A (en) 1984-10-12 1989-08-15 Drug Delivery Systems Inc. Method for making disposable and/or replenishable transdermal drug applicators
US5865786A (en) 1983-08-18 1999-02-02 Drug Delivery Systems, Inc. Programmable control and mounting system for transdermal drug applicator
WO1986007269A1 (en) 1985-06-10 1986-12-18 Drug Delivery Systems Inc. Programmable control and mounting system for transdermal drug applicator
US4853854A (en) 1985-12-26 1989-08-01 Health Innovations, Inc. Human behavior modification which establishes and generates a user adaptive withdrawal schedule
US4772263A (en) 1986-02-03 1988-09-20 Regents Of The University Of Minnesota Spring driven infusion pump
US4917676A (en) 1986-11-20 1990-04-17 Ciba-Geigy Corporation User-activated transdermal therapeutic system
WO1988005643A1 (en) 1987-02-02 1988-08-11 Avl Ag Process and device for determining parameters of interest in living organisms
US5000956A (en) 1987-03-09 1991-03-19 Alza Corporation Prevention of contact allergy by coadministration of a corticosteroid with a sensitizing drug
US5049387A (en) 1987-03-09 1991-09-17 Alza Corporation Inducing skin tolerance to a sensitizing drug
US5013293A (en) 1987-05-28 1991-05-07 Drug Delivery Systems Inc. Pulsating transdermal drug delivery system
JPH01265021A (en) 1987-10-29 1989-10-23 Hercon Lab Corp Material for controlled radiation or supply of composition containing pharmaceutically active substance to animal tissue
US4885154A (en) 1988-03-01 1989-12-05 Alza Corporation Method for reducing sensitization or irritation in transdermal drug delivery and means therefor
US5472946A (en) 1988-04-08 1995-12-05 Peck; James V. Transdermal penetration enhancers
US5364630A (en) 1988-06-14 1994-11-15 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5028428A (en) 1988-08-09 1991-07-02 Estee Lauder Inc. Anti-irritant and desensitizing compositions and methods of their use
US5248501A (en) 1988-11-22 1993-09-28 Parnell Pharmaceuticals Drug delivery systems containing eriodictyon fluid extract as an excipient, and methods and compositions associated therewith
JP2638635B2 (en) 1989-01-31 1997-08-06 積水化学工業株式会社 Percutaneous absorption preparation
JPH02208813A (en) 1989-02-09 1990-08-20 Fuji Photo Film Co Ltd Thin film magnetic head
US4908213A (en) 1989-02-21 1990-03-13 Schering Corporation Transdermal delivery of nicotine
US5149719A (en) 1990-04-27 1992-09-22 Minnesota Mining And Manufacturing Company Composition for transdermal penetration of medicaments
US5130139A (en) 1990-07-06 1992-07-14 Alza Corporation Reduction or prevention of skin irritation by drugs
US5120545A (en) 1990-08-03 1992-06-09 Alza Corporation Reduction or prevention of sensitization to drugs
US5221254A (en) 1991-04-02 1993-06-22 Alza Corporation Method for reducing sensation in iontophoretic drug delivery
US5464387A (en) 1991-07-24 1995-11-07 Alza Corporation Transdermal delivery device
US5273755A (en) 1991-08-23 1993-12-28 Cygnus Therapeutic Systems Transdermal drug delivery device using a polymer-filled microporous membrane to achieve delayed onset
US5304739A (en) 1991-12-19 1994-04-19 Klug Reja B High energy coaxial cable for use in pulsed high energy systems
US6436078B1 (en) 1994-12-06 2002-08-20 Pal Svedman Transdermal perfusion of fluids
CA2129227A1 (en) 1992-01-31 1993-08-05 Christian Paul Valcke Method and apparatus for closed loop drug delivery
US5262165A (en) 1992-02-04 1993-11-16 Schering Corporation Transdermal nitroglycerin patch with penetration enhancers
EP0578796B1 (en) 1992-02-04 1998-01-14 Asulab S.A. Device for dispensing a medicament
CA2072040C (en) 1992-06-23 2002-06-11 Charles Borg Method and device to facilitate the cognitive development of alternative response behaviour
US5501697A (en) 1992-06-23 1996-03-26 Fisher; Gary R. Treatment device to aid in long-term cessation of smoking
US5252604A (en) 1992-07-10 1993-10-12 Hoffmann-La Roche Inc. Compositions of retinoic acids and tocopherol for prevention of dermatitis
WO1994004109A1 (en) 1992-08-25 1994-03-03 Cygnus Therapeutic Systems Printed transdermal drug delivery device
CA2114968A1 (en) 1993-02-25 1994-08-26 John Wille Transdermal treatment with mast cell degranulating agents for drug-induced hypersensitivity
US5843979A (en) 1993-02-25 1998-12-01 Bristol-Myers Squibb Company Transdermal treatment with mast cell degranulating agents for drug-induced hypersensitivity
US5516793A (en) 1993-04-26 1996-05-14 Avon Products, Inc. Use of ascorbic acid to reduce irritation of topically applied active ingredients
US5445609A (en) 1993-05-28 1995-08-29 Alza Corporation Electrotransport agent delivery device having a disposable component and a removable liner
US5451407A (en) 1993-06-21 1995-09-19 Alza Corporation Reduction or prevention of skin irritation or sensitization during transdermal administration of a irritating or sensitizing drug
US5377258A (en) 1993-08-30 1994-12-27 National Medical Research Council Method and apparatus for an automated and interactive behavioral guidance system
US5533971A (en) 1993-09-03 1996-07-09 Alza Corporation Reduction of skin irritation during electrotransport
US5997501A (en) 1993-11-18 1999-12-07 Elan Corporation, Plc Intradermal drug delivery device
US5393526A (en) 1994-02-07 1995-02-28 Elizabeth Arden Company, Division Of Conopco, Inc. Cosmetic compositions
US5876368A (en) 1994-09-30 1999-03-02 Becton Dickinson And Company Iontophoretic drug delivery device having improved controller
US5445823A (en) 1994-10-20 1995-08-29 The Procter & Gamble Company Dermatological compositions and method of treatment of skin lesions therewith
US5618557A (en) 1994-11-22 1997-04-08 E.R. Squibb & Sons, Inc. Prophylactic treatment of allergic contact dermatitis
US5686100A (en) 1994-11-22 1997-11-11 E.R. Squibb & Sons, Inc. Prophylactic and therapeutic treatment of skin sensitization and irritation
US5697896A (en) 1994-12-08 1997-12-16 Alza Corporation Electrotransport delivery device
DE4444238A1 (en) 1994-12-13 1996-06-20 Beiersdorf Ag Cosmetic or dermatological active compound combinations of cinnamic acid derivatives and flavone glycosides
FR2728793B1 (en) 1994-12-28 1997-02-07
US5601839A (en) 1995-04-26 1997-02-11 Theratech, Inc. Triacetin as a penetration enhancer for transdermal delivery of a basic drug
CA2233197A1 (en) 1995-09-28 1997-04-03 Becton, Dickinson And Company Iontophoretic drug delivery system, including reusable device
US5688232A (en) 1995-09-28 1997-11-18 Becton Dickinson And Company Iontophoretic drug delivery device having an improved controller
WO1997018782A1 (en) 1995-11-22 1997-05-29 Bristol-Myers Squibb Company Treatment with calcium channel blockers for drug-induced hypersensitivity
US5716987A (en) 1996-06-21 1998-02-10 Bristol-Myers Squibb Company Prophylactic and therapeutic treatment of skin sensitization and irritation
US5919156A (en) 1996-09-27 1999-07-06 Becton, Dickinson And Company Iontophoretic drug delivery system, including unit for dispensing patches
US5797867A (en) 1996-09-27 1998-08-25 Becton Dickinson And Company Iontophoretic drug delivery system, including method for activating same for attachment to patient
US5908301A (en) 1996-12-05 1999-06-01 Lutz; Raymond Method and device for modifying behavior
US6019997A (en) 1997-01-09 2000-02-01 Minnesota Mining And Manufacturing Hydroalcoholic compositions for transdermal penetration of pharmaceutical agents
US6018679A (en) 1997-01-29 2000-01-25 Novartis Finance Corp. Iontophoretic transdermal delivery and control of adverse side-effects
WO1998046093A1 (en) 1997-04-14 1998-10-22 Robert Lindburg Smoking control device
US6420622B1 (en) 1997-08-01 2002-07-16 3M Innovative Properties Company Medical article having fluid control film
US5786888A (en) * 1997-09-16 1998-07-28 Trw Inc. Pulsed radiation classifier and related method
KR100648536B1 (en) 1997-11-10 2006-11-24 셀러지 파마세우티칼스, 인크 Penetration enhancing and irritation reducing systems
US6059736A (en) 1998-02-24 2000-05-09 Tapper; Robert Sensor controlled analysis and therapeutic delivery system
US20040062802A1 (en) 1998-04-02 2004-04-01 Hermelin Victor M. Maximizing effectiveness of substances used to improve health and well being
WO2000074763A3 (en) 1999-06-04 2001-07-05 Georgia Tech Res Inst Devices and methods for enhanced microneedle penetration of biological barriers
US5967789A (en) 1998-07-30 1999-10-19 Smoke Stoppers International, Inc. Method and system for stopping or modifying undesirable health-related behavior habits or maintaining desirable health-related behavior habits
US6165165A (en) * 1998-10-02 2000-12-26 Genx International, Inc. Embryo-implanting catheter assembly and method for making the same
US6567785B2 (en) 1999-06-19 2003-05-20 John Richard Clendenon Electronic behavior modification reminder system and method
DE19958554C2 (en) 1999-07-02 2002-06-13 Lohmann Therapie Syst Lts Microreservoir system based on polysiloxanes and ambiphilic solvents and their production
US7376700B1 (en) 1999-08-23 2008-05-20 Wellcoaches Corporation Personal coaching system for clients with ongoing concerns such as weight loss
US6437004B1 (en) 2000-04-06 2002-08-20 Nicholas V. Perricone Treatment of skin damage using olive oil polyphenols
JP4098985B2 (en) 2000-05-19 2008-06-11 サビンサ コーポレーション Method of increasing the bioavailability of nutrients and pharmaceutical preparations using tetrahydropiperine and analogs and derivatives thereof
EP2363061A1 (en) 2000-06-16 2011-09-07 BodyMedia, Inc. System for monitoring and managing body weight and other physiological conditions including iterative and personalized planning, intervention and reporting capability
US6589229B1 (en) 2000-07-31 2003-07-08 Becton, Dickinson And Company Wearable, self-contained drug infusion device
DE10103158A1 (en) 2001-01-24 2002-08-01 Christian Von Falkenhausen Device for electricity-assisted introduction of active agents into the skin comprises at least two electrodes which are connected through galvanic conduction of the reservoir of the active agent
DE10105759C1 (en) 2001-02-08 2001-10-25 Lohmann Therapie Syst Lts Electrically and magnetically assisted charge carrier delivery device e.g. for transdermal application of pharmaceuticals, has electrical and magnetic fields applied to charge carrier reservoir layer
US6749587B2 (en) 2001-02-22 2004-06-15 Insulet Corporation Modular infusion device and method
JP2005506285A (en) 2001-02-27 2005-03-03 ザ リージェンツ オブ ザ ユニバーシティー オブ ミシガン Use of natural egfr inhibitors of the epidermal growth factor receptor retinoid therapy that activates, for the purpose of preventing the side effects due to soap and other irritants
FR2822377A1 (en) 2001-03-23 2002-09-27 Oreal Use of fibers as an anti-irritant agent in a cosmetic or dermatological composition
WO2002076401A3 (en) 2001-03-26 2003-02-27 Dana Farber Cancer Inst Inc Method of attenuating reactions to skin irritants
US20040019321A1 (en) 2001-05-29 2004-01-29 Sage Burton H. Compensating drug delivery system
US6576269B1 (en) 2001-09-06 2003-06-10 Alexander Y. Korneyev Treating open skin lesions using extract of sea buckthorn
GB0121628D0 (en) 2001-09-07 2001-10-31 Watmough David J Improved method and apparatus for transdermal drug delivery
FR2829644A1 (en) 2001-09-10 2003-03-14 St Microelectronics Sa Internet digital word watermarking transmission having symmetrical algorithm authentication key before transmission and authentication key watermarking phase and transmission watermarked words
US7615234B2 (en) 2001-09-11 2009-11-10 Glide Pharmaceutical Technologies Limited Drug delivery technology
US20060122577A1 (en) 2001-09-26 2006-06-08 Poulsen Jens U Modular drug delivery system
US7429258B2 (en) 2001-10-26 2008-09-30 Massachusetts Institute Of Technology Microneedle transport device
ES2284943T3 (en) 2001-11-16 2007-11-16 Medinnovation Ag Medical pump device.
US7311693B2 (en) 2001-11-26 2007-12-25 Nilimedix Ltd. Drug delivery device and method
JP2005525147A (en) * 2002-01-16 2005-08-25 エンカプサレイション システムズ,インコーポレーテッド Substance delivery device
US20070168501A1 (en) 2002-03-29 2007-07-19 Cobb Nathan K Method and system for delivering behavior modification information over a network
US7647099B2 (en) 2002-04-29 2010-01-12 Rocky Mountain Biosystems, Inc. Controlled release transdermal drug delivery
CA2512854C (en) 2002-06-28 2010-02-09 Alza Corporation A reservoir for use in electrotransport drug delivery
US7196619B2 (en) 2002-06-29 2007-03-27 Neil Perlman Habit cessation aide
US20040259816A1 (en) 2002-10-01 2004-12-23 Pandol Stephen J. Compositions comprising plant-derived polyphenolic compounds and inhibitors of reactive oxygen species and methods of using thereof
US7399401B2 (en) 2002-10-09 2008-07-15 Abbott Diabetes Care, Inc. Methods for use in assessing a flow condition of a fluid
US7887842B2 (en) 2003-02-07 2011-02-15 Teikoku Pharma Usa, Inc. Methods of administering a dermatological agent to a subject
WO2004073429A1 (en) 2003-02-21 2004-09-02 Francis Paul Galea Medication and smoking cessation watch
CA2520867A1 (en) 2003-04-02 2004-10-21 Colin E. Rowlings Pulsatile transdermally administered antigens and adjuvants
US8021334B2 (en) 2004-05-30 2011-09-20 Nilimedix Ltd. Drug delivery device and method
US20050048020A1 (en) 2003-07-07 2005-03-03 Wille John J. Novel topical delivery system for plant derived anti-irritants
US8589174B2 (en) 2003-12-16 2013-11-19 Adventium Enterprises Activity monitoring
US20050141346A1 (en) 2003-12-30 2005-06-30 Rawls David K. Smoking cessation device
WO2005079161A3 (en) 2004-02-25 2006-03-09 Marco Luzzatto Remote coaching service and server
US20050226921A1 (en) 2004-04-13 2005-10-13 Kortzebom Robert N Non-invasive analysis and controlled dosage transdermal active patch
US7019622B2 (en) 2004-05-27 2006-03-28 Research In Motion Limited Handheld electronic device including vibrator having different vibration intensities and method for vibrating a handheld electronic device
US7537590B2 (en) 2004-07-30 2009-05-26 Microchips, Inc. Multi-reservoir device for transdermal drug delivery and sensing
US20070250018A1 (en) 2004-08-12 2007-10-25 Hirotoshi Adachi Transdermal Drug Administration System with Microneedles
US8252321B2 (en) 2004-09-13 2012-08-28 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like
JP5254616B2 (en) * 2004-09-13 2013-08-07 クロノ セラピューティクス、インコーポレイテッド Biological synchrony (biosynchronous) transdermal drug delivery
US20060078604A1 (en) 2004-10-08 2006-04-13 Noven Pharmaceuticals, Inc. Transdermal drug delivery device including an occlusive backing
US8343538B2 (en) 2004-10-08 2013-01-01 Noven Pharmaceuticals, Inc. Compositions and methods for controlling the flux of a drug from a transdermal drug delivery systems
US8999356B1 (en) 2004-12-03 2015-04-07 Omp, Inc. Drug delivery system
US8231573B2 (en) 2005-02-01 2012-07-31 Intelliject, Inc. Medicament delivery device having an electronic circuit system
EP1843812A4 (en) 2005-02-01 2008-12-03 Intelliject Llc Devices, systems, and methods for medicament delivery
US20060188859A1 (en) 2005-02-22 2006-08-24 Haim Yakobi Method and system for computer implemented personal counseling
US20070042026A1 (en) 2005-03-17 2007-02-22 Wille John J Prophylactic and therapeutic treatment of topical and transdermal drug-induced skin reactions
US8372040B2 (en) * 2005-05-24 2013-02-12 Chrono Therapeutics, Inc. Portable drug delivery device including a detachable and replaceable administration or dosing element
US8566121B2 (en) 2005-08-29 2013-10-22 Narayanan Ramasubramanian Personalized medical adherence management system
EP1815919A1 (en) * 2006-02-03 2007-08-08 Uponor Innovation Ab Making an elongated product
US20140207047A1 (en) 2013-01-22 2014-07-24 Chrono Therapeutics, Inc. Transdermal drug delivery system and method
US20140207048A1 (en) 2013-01-24 2014-07-24 Chrono Therapeutics, Inc. Optimized bio-synchronous bioactive agent delivery system

Patent Citations (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4379454A (en) * 1981-02-17 1983-04-12 Alza Corporation Dosage for coadministering drug and percutaneous absorption enhancer
US4545990A (en) * 1982-11-22 1985-10-08 L'oreal Anti-acne composition
US4708716A (en) * 1983-08-18 1987-11-24 Drug Delivery Systems Inc. Transdermal drug applicator
US4917895A (en) * 1987-11-02 1990-04-17 Alza Corporation Transdermal drug delivery device
US5993435A (en) * 1990-04-30 1999-11-30 Alza Corporation Device and method of iontophoretic drug delivery
US5242941A (en) * 1990-12-04 1993-09-07 State Of Oregon Methods of treating circadian rhythm disorders
US5273756A (en) * 1991-08-23 1993-12-28 Cygnus Therapeutic Systems Transdermal drug delivery device using a membrane-protected microporous membrane to achieve delayed onset
US5352456A (en) * 1991-10-10 1994-10-04 Cygnus Therapeutic Systems Device for administering drug transdermally which provides an initial pulse of drug
US5820875A (en) * 1991-10-10 1998-10-13 Cygnus, Inc. Device for administering drug transdermally with a controlled temporal change in skin flux
US5370835A (en) * 1991-11-21 1994-12-06 Willi Sturtz Maschinenbau GmbH Method of manufacturing rectangular frames
US5389679A (en) * 1992-01-21 1995-02-14 Alliger; Howard Method of treating small mouth ulcers with lactic acid
US5405614A (en) * 1992-04-08 1995-04-11 International Medical Associates, Inc. Electronic transdermal drug delivery system
US5932240A (en) * 1992-04-08 1999-08-03 Americare Technology, Inc. Multidose transdermal drug delivery system
US5616332A (en) * 1993-07-23 1997-04-01 Herstein; Morris Cosmetic skin-renewal-stimulating composition with long-term irritation control
US5538503A (en) * 1993-09-15 1996-07-23 Henley; Julian L. Programmable apparatus for reducing substance dependency in transdermal drug delivery
US6090404A (en) * 1994-01-13 2000-07-18 Lts Lohmann Therapie-Systeme Gmbh Estradiol penetration enhancers
US6068853A (en) * 1994-04-13 2000-05-30 Novartis Corporation Temporally controlled drug delivery systems
US5505958A (en) * 1994-10-31 1996-04-09 Algos Pharmaceutical Corporation Transdermal drug delivery device and method for its manufacture
US5879322A (en) * 1995-03-24 1999-03-09 Alza Corporation Self-contained transdermal drug delivery device
US5785688A (en) * 1996-05-07 1998-07-28 Ceramatec, Inc. Fluid delivery apparatus and method
US6129702A (en) * 1996-12-03 2000-10-10 Fraunhofer-Gesellschaft Zur Forderung Angewandten Forschung E.V. Medicament dosing system
US6165155A (en) * 1997-02-07 2000-12-26 Sarcos, Lc Multipathway electronically-controlled drug delivery system
US6374136B1 (en) * 1997-12-22 2002-04-16 Alza Corporation Anhydrous drug reservoir for electrolytic transdermal delivery device
US6595956B1 (en) * 1998-03-23 2003-07-22 Joseph Gross Drug delivery device
US6214379B1 (en) * 1998-04-02 2001-04-10 Kv Pharmaceutical Company Maximizing effectiveness of substances used to improve health and well being
US6211296B1 (en) * 1998-11-05 2001-04-03 The B. F. Goodrich Company Hydrogels containing substances
US6539250B1 (en) * 1999-12-15 2003-03-25 David S. Bettinger Programmable transdermal therapeutic apparatus
US6638528B1 (en) * 2000-01-20 2003-10-28 Noven Pharmaceuticals, Inc. Compositions and methods to effect the release profile in the transdermal administration of active agents
US6887202B2 (en) * 2000-06-01 2005-05-03 Science Applications International Corporation Systems and methods for monitoring health and delivering drugs transdermally
US20050182307A1 (en) * 2000-06-01 2005-08-18 Science Applications International Corporation Systems and methods for monitoring health and delivering drugs transdermally
US20020127256A1 (en) * 2001-03-01 2002-09-12 Howard Murad Compositions and methods for treating dermatological disorders
US6723086B2 (en) * 2001-05-07 2004-04-20 Logiq Wireless Solutions, Inc. Remote controlled transdermal medication delivery device
US6723077B2 (en) * 2001-09-28 2004-04-20 Hewlett-Packard Development Company, L.P. Cutaneous administration system
US20030065294A1 (en) * 2001-09-28 2003-04-03 Pickup Ray L. Cutaneous administration system
US6861066B2 (en) * 2002-03-11 2005-03-01 Health Plus International Inc. Method for the delivery of a biologically active agent
US20040138074A1 (en) * 2002-05-01 2004-07-15 Nawaz Ahmad Warming and nonirritating lubricant compositions and method of comparing irritation
US20050034842A1 (en) * 2003-08-11 2005-02-17 David Huber Electroosmotic micropumps with applications to fluid dispensing and field sampling
US20050238704A1 (en) * 2003-10-27 2005-10-27 Werner Zumbrunn Transdermal drug delivery method and system
US20050151110A1 (en) * 2004-01-14 2005-07-14 Minor Barbara H. Fluoroether refrigerant compositions and uses thereof

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9555226B2 (en) 2003-10-27 2017-01-31 Chrono Therapeutics Inc. Transdermal drug delivery method and system
US9555227B2 (en) 2004-09-13 2017-01-31 Chrono Therapeutics Inc. Biosynchronous transdermal drug delivery
US9669199B2 (en) 2004-09-13 2017-06-06 Chrono Therapeutics Inc. Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like
US20080220092A1 (en) * 2004-09-13 2008-09-11 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like
US7780981B2 (en) * 2004-09-13 2010-08-24 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery
US20100280432A1 (en) * 2004-09-13 2010-11-04 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery
US8252321B2 (en) 2004-09-13 2012-08-28 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like
US8741336B2 (en) 2004-09-13 2014-06-03 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, Alzheimer'S disease, sleep disorders, Parkinson'S disease, AIDS, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like
US20060062838A1 (en) * 2004-09-13 2006-03-23 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery
US20070042026A1 (en) * 2005-03-17 2007-02-22 Wille John J Prophylactic and therapeutic treatment of topical and transdermal drug-induced skin reactions
USRE46217E1 (en) 2005-05-24 2016-11-29 Chrono Therapeutics Inc. Portable drug delivery device including a detachable and replaceable administration or dosing element
US20100169260A1 (en) * 2008-12-30 2010-07-01 Searete Llc Methods and systems for presenting an inhalation experience
US9724483B2 (en) 2008-12-30 2017-08-08 Gearbox, Llc Method for administering an inhalable compound
US9750903B2 (en) 2008-12-30 2017-09-05 Gearbox, Llc Method for administering an inhalable compound

Also Published As

Publication number Publication date Type
JP2008512215A (en) 2008-04-24 application
CA2580329A1 (en) 2006-03-23 application
EP1802258A4 (en) 2015-09-23 application
US20060062838A1 (en) 2006-03-23 application
US20170100572A1 (en) 2017-04-13 application
US20100280432A1 (en) 2010-11-04 application
CA2580329C (en) 2015-01-06 grant
US9555227B2 (en) 2017-01-31 grant
US7780981B2 (en) 2010-08-24 grant
US20140200525A1 (en) 2014-07-17 application
US9555226B2 (en) 2017-01-31 grant
US20150283366A1 (en) 2015-10-08 application
JP5254616B2 (en) 2013-08-07 grant
WO2006031856A2 (en) 2006-03-23 application
US20170100573A1 (en) 2017-04-13 application
US20150283367A1 (en) 2015-10-08 application
EP1802258A2 (en) 2007-07-04 application
WO2006031856A3 (en) 2006-08-17 application

Similar Documents

Publication Publication Date Title
Coffey et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study
US6632217B2 (en) Implantable osmotic pump
Chien Novel drug delivery systems
Grond et al. Clinical pharmacokinetics of transdermal opioids
US6629949B1 (en) Micro infusion drug delivery device
Campbell et al. Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats
Ranade Drug delivery systems. 6. Transdermal drug delivery
US6471688B1 (en) Osmotic pump drug delivery systems and methods
US20100042137A1 (en) Acupuncture and acupressure therapies
US20060034904A1 (en) Transdermal delivery using emcapsulated agent activated by ultrasound and or heat
US6284765B1 (en) (+) naloxone and epinephrine combination therapy
Lehmann et al. Transdermal fentanyl: clinical pharmacology
Ashburn et al. The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat
US6358060B2 (en) Two-stage transmucosal medicine delivery system for symptom relief
Langer Transdermal drug delivery: past progress, current status, and future prospects
US20020035346A1 (en) Drug release (delivery system)
Jones et al. Opiate antagonist therapy for the pruritus of cholestasis: the avoidance of opioid withdrawal‐like reactions
Colacone et al. Continuous nebulization of albuterol (salbutamol) in acute asthma
US20060271020A1 (en) Portable drug delivery device including a detachable and replaceble administration or dosing element
US6284266B1 (en) Methods and apparatus for improved administration of fentanyl and sufentanil
US6465006B1 (en) Method for facilitating absorption of pharmaceutically active compounds
Choiniere et al. Patient‐controlled analgesia: a double‐blind study in burn patients
US20090042970A1 (en) Methods and devices for desmopressin drug delivery
US6756053B2 (en) Controlled heat induced rapid delivery of pharmaceuticals from skin depot
Smith et al. A comparison of propofol and remifentanil during monitored anesthesia care

Legal Events

Date Code Title Description
AS Assignment

Owner name: CHRONO THERAPEUTICS, INC., NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DIPIERRO, GUY;REEL/FRAME:017322/0577

Effective date: 20051129

AS Assignment

Owner name: CHRONO THERAPEUTICS, INC., NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DIPIERRO, GUY;REEL/FRAME:022943/0591

Effective date: 20090706