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

• US 8,252,321 B2
• Filed: 10/31/2007
• Issued: 08/28/2012
• Est. Priority Date: 09/13/2004
• Status: Active Grant

• Current Assignee: Morningside Venture Investments Ltd. (Morningside Group Ltd.)
• Original Assignee: Chrono Therapeutics Inc.
• Inventors: Dipierro, Guy, Giannos, Steven A.
• Primary Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US11/981,672
• Publication Number:
  US 20080220092A1
• Time in Patent Office: 1,763 Days
• Field of Search: None
• US Class Current: 424/449
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/428 : condensed with carbocyclic rings
• CPC Class Codes: A61K 31/435 : having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/4436 : containing a heterocyclic ring having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/4439 : containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/445 : Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4453 : only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 31/4458 : only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/4468 : having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/465 : Nicotine; Derivatives thereof
• CPC Class Codes: A61K 31/47 : Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/473 : ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/485 : Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/4965 : Non-condensed pyrazines
• CPC Class Codes: A61K 31/498 : Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/4985 : Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/505 : Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/55 : having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/704 : attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7072 : having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/708 : having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• CPC Class Codes: A61K 9/0014 : Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/7023 : Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/7084 : Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61M 2005/14268 : with a reusable and a disposable component
• CPC Class Codes: A61M 2037/0007 : 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
• CPC Class Codes: A61M 2037/0023 : Drug applicators using microneedles
• CPC Class Codes: A61M 2205/3337 : Controlling, regulating pressure or flow by means of a valve by-passing a pump
• CPC Class Codes: A61M 2205/3368 : Temperature
• CPC Class Codes: A61M 2205/50 : with microprocessors or computers
• CPC Class Codes: A61M 2205/502 : User interfaces, e.g. screens or keyboards
• CPC Class Codes: A61M 2205/8206 : battery-operated
• CPC Class Codes: A61M 37/00 : Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 : by using microneedles
• CPC Class Codes: A61M 37/0092 : using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61M 39/22 : Valves or arrangement of valves A61M39/02, A61M39/0247, A61M39/16 take precedence; regulating valves in infusion systems A61M5/16881; in devices worn by the patient for the reception of urine, faeces, catamenial or other discharge, or in colostomy devices A61F5/4405
• CPC Class Codes: A61M 5/14248 : of the skin patch type
• CPC Class Codes: A61N 1/30 : Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Systems and methods for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and treating hyperglycemia, Alzheimer'"'"'s disease, sleep disorders, Parkinson'"'"'s disease, Attention Deficit Disorder and nicotine addiction involve synchronizing and tailoring the administration of nutraceuticals, medications and other substances (for example, stimulants) in accordance with the body'"'"'s natural circadian rhythms, meal times and other factors. Improved control of blood glucose levels, extended alertness, and weight control, and counteracting of disease symptoms when they are at their worst are possible. An automated, pre-programmable transdermal administration system is used to provide pulsed doses of medications, pharmaceuticals, hormones, neuropeptides, anorexigens, pro-drugs, stimulants, plant extracts, botanicals, nutraceuticals, cosmeceuticals, phytochemicals, phytonutrients, enzymes, antioxidants, essential oils, fatty acids, minerals, vitamins, amino acids, coenzymes, or other physiological active ingredient or precursor. The system can utilize a pump, pressurized reservoir, a system for removing depleted carrier solution, or other modulated dispensing actuator, in conjunction with porous membranes or micro-fabricated structures.

Claims

1. A method for delivering an active substance 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 active substance, an electronic programmable timing mechanism, a mechanism for causing the active substance to be delivered transdermally in response to the timing mechanism by passive absorption, and an expandable waste reservoir for controlled discontinuance of the delivery of the active substance; and

providing timing routines implemented by the timing mechanism, wherein the timing routines are selected to deliver the active substance by passive absorption at a time, rate, sequence and/or cycle that is synchronized with a biological rhythm of the human or animal; and

removing the active substance from the skin of the human or animal via the expandable waste reservoir to discontinue delivery of the active substance,

wherein the device is maintained in contact with the skin during removal of the active substance via the expandable waste reservoir.

2. The method of claim 1, wherein the active substance is selected from the group consisting of glibenclamide, glipizide, rosiglitazonc, metoformin, dextroamphetamine, ephedrine, adrifina, ampakine, tacrine, donepezil, rivastigmine, galantamine, memantine, selegiline, ropinirole, apomorphine, pramipexole, biperiden, bromocriptine, levodopa, methylphenidate, dextro-amphetamine, bupropion, nitroglycerin, indomethacin, valdecoxib, tulobuterol, clonidine, oxybutynin, zolmitriptan, miglitol, entanyl, fluorouracil, doxorubicin, cisplatin, zidovudine, gabapentin, triprolidine, fentanyl, diclofenac, theophyline, carbidopa, entacapone metaprolol and caffeine.

3. The method of claim 1, wherein the active substance is for a purpose selected from the group consisting of fatigue management, treating obesity, weight loss, weight management, nutraceutical delivery, treating hyperglycemia, managing alzheimer'"'"'s disease, treating a sleep disorder, treating parkinson'"'"'s disease, treating an attention deficit disorder, treating nicotine addiction, treating cancer, treating headache, pain management, treating asthma, treating angina, treating hypertension, treating depression, treating epilepsy, treating AIDS, treating a cold and treating a flu.

4. The method of claim 2, wherein the active substance is for a purpose selected from the group consisting of fatigue management, treating obesity, weight loss, weight management, delivery of nutraceuticals, treating hyperglycemia, managing alzheimer'"'"'s disease, treating a sleep disorder, treating parkinson'"'"'s disease, treating an attention deficit disorder, treating nicotine addiction, treating cancer, treating headache, pain management, treating asthma, treating angina, treating hypertension, treating depression, treating a cold and treating a flu.

5. The method of claim 1 whereby permeation through the skin is assisted using one or more from the group comprising:

micro-fabricated structures, heat, sonophoresis, and a chemical permeation enhancer.

6. The method of claim 1 wherein the active substance comprises a stimulant and the timing routines are selected to deliver the stimulant immediately before the human or animal wakes up.

7. The method of claim 1 wherein the active substance comprises nicotine and the timing routines are selected to deliver the nicotine at times that are associated with nicotine cravings.

8. The method of claim 7 wherein at least one of the selected times corresponds to a time at which the human or animal experiences a morning nicotine craving.

9. The method of claim 1 wherein the active substance comprises an antihistamine and the timing routines are selected to deliver the antihistamine while the human or animal sleeps.

10. The method of claim 1 wherein the active substance comprises nicotine and the timing routines are selected to deliver the stimulant immediately before the human or animal wakes up.

18. The method of claim 1, wherein the source of the active substance comprises an active substance reservoir and an administration reservoir, wherein the active substance reservoir is separated from the administration reservoir.

11. A method for treating a symptom, condition, and/or disease comprising:

identifying an active substance suitable for treating a particular symptom, condition and/or disease;

identifying a biologically superior time for modulating the administration of the active substance;

programming an electronic time-programmable transdermal drug delivery system with a schedule selected to synchronize with the identified biologically superior time for modulating;

causing the time-programmable transdermal drug delivery system to deliver the active substance by passive absorption according to the programmed schedule, the drug delivery system including an expandable waste reservoir for controlled discontinuance of the delivery of the active substance; and

removing the active substance from the skin of the human or animal via the expandable waste reservoir to discontinue delivery of the active substance,

wherein the system is maintained in contact with the skin during removal of the active substance via the expandable waste reservoir.

12. The method of claim 11, wherein the disease is selected from the group consisting of aging, fatigue, obesity, hyperglycemia, alzheimer'"'"'s disease, a sleep disorder, parkinson'"'"'s disease, attention deficit disorder, nicotine addiction, cancer, headache, migraine, pain, epilepsy, AIDS, asthma, angina, hypertension, depression, cold and flu.

13. The method of claim 11, wherein the active substance is selected from the group consisting of glibenclamide, glipizide, rosiglitazone, metoformin, dextroamphetamine, ephedrine, adrifina, ampakine, tacrine, donepezil, rivastigmine, galantamine, memantine, selegiline, ropinirole, apomorphine, pramipexole, biperiden, bromocriptine, levodopa, methylphenidate, dextro-amphetamine, bupropion, nitroglycerin, indomethacin, valdecoxib, tulobuterol, clonidine, oxybutynin, zolmitriptan, miglitol, entanyl, fluorouracil, doxorubicin, cisplatin, zidovudine, gabapentin, triprolidine, fentanyl, diclofenac, theophyline, carbidopa, entacapone metaprolol and caffeine.

14. A method for delivering an active substance 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 active substance, an electronic programmable timing mechanism, an expandable waste reservoir for removing carrier solution and/or remaining active substance, and a mechanism for causing the active substance to be delivered transdermally in response to the timing mechanism by passive absorption;

programming a timing routine to be implemented by the timing mechanism to deliver the active substance, wherein the timing routine is selected from the group consisting of;

(a) a timing routine to deliver the active substance at a time when the human or animal is asleep or is expected to be asleep;

(b) a timing routine to deliver the active substance at a time when the human or animal is awake or is expected to be awake;

(c) a timing routine to deliver the active substance at a time when the human or animal is waking up or is expected to be waking up;

(d) a timing routine to deliver the active substance in during or near mealtime;

(e) a timing routine to increase a dosage of the active substance at a preprogrammed time;

(f) a timing routine to decrease a dosage of the active substance at a preprogrammed time;

(g) a timing routine to terminate delivery of the active substance at a preprogrammed time;

(h) a timing routine to increase delivery of the active substance in response to a signal representative of a change in a physiological condition;

(i) a timing routine to deliver the active substance in response to a signal indicative of a demand by the human or animal; and

(j) a timing routine to deliver the active substance at regular intervals; and

removing the carrier solution and/or remaining active substance from the skin of the human or animal via the expandable waste reservoir to discontinue delivery of the active substance to the human or animal,

wherein the device is maintained in contact with the skin during removal of the carrier solution and/or remaining active substance via the expandable waste reservoir.

15. The method of claim 14, wherein the active substance is a nutraceutical.

16. The method of claim 14, wherein the active substance is for a purpose selected from the group consisting of fatigue management, treating obesity, weight loss, weight management, delivery of nutraceuticals, treatment of hyperglycemia, managing alzheimer'"'"'s disease, treating a sleep disorder, treating parkinson'"'"'s disease, treating an attention deficit disorder, treating nicotine addiction, treating cancer, treating headache, pain management, treating asthma, treating angina, treating hypertension, treating depression, treating epilepsy, treating AIDS, treating a cold and treating a flu.

17. The method of claim 14, wherein the active substance is selected from the group consisting of glibenclamide, glipizide, rosiglitazone, metoformin, dextroamphetamine, ephedrine, adrifina, ampakine, tacrine, donepezil, rivastigmine, galantamine, memantine, selegiline, ropinirole, apomorphine, pramipexole, biperiden, bromocriptine, levodopa, methylphenidate, dextro-amphetamine, bupropion, nitroglycerin, indomethacin, valdecoxib, tulobuterol, clonidine, oxybutynin, zolmitriptan, miglitol, entanyl, fluorouracil, doxorubicin, cisplatin, zidovudine, gabapentin, triprolidine, fentanyl, diclofinac, theophyline, carbidopa, entacapone metaprolol and caffeine.