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 10,258,778 B2
• Filed: 03/14/2017
• Issued: 04/16/2019
• Est. Priority Date: 09/13/2004
• Status: Expired due to Fees

• 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
• Application Number:
  US15/458,831
• Publication Number:
  US 20170182299A1
• Time in Patent Office: 763 Days
• Field of Search: None
• 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 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, nutraceuticals, 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 device for transdermal administration of an active substance, the device comprising:

a pressurized reservoir;

a solution comprising the active substance and a solvent disposed in the pressurized reservoir;

a porous skin interface adapted to receive the solution from the reservoir and to transfer the active substance to the skin; and

an evaporation channel defining a flow path for flow of evaporated solvent from the porous skin interface therethrough.

2. The device of claim 1, further comprising:

a solvent recovery element communicating with the skin interface and adapted to receive the evaporated solvent, wherein the solvent recovery element comprises a desiccant, absorbent material, or hydrophilic material.

3. The device of claim 1, further comprising:

a solvent recovery element communicating with the skin interface and adapted to receive the evaporated solvent and a vapor permeable material disposed between the skin interface and the solvent recovery element.

4. The device of claim 1, further comprising:

a piston disposed in the pressurized reservoir in contact with the solution.

5. The device of claim 1, further comprising:

a valve controlling flow of the solution from the pressurized reservoir to the skin interface.

6. The device of claim 5, further comprising:

a programmable control unit adapted to control the valve.

7. The device of claim 1, wherein the porous skin interface comprises adhesive.

8. The device of claim 1, further comprising:

a housing into which the pressurized reservoir, porous skin interface, and evaporation channel are incorporated.

9. The device of claim 1, further comprising:

an administration reservoir adapted to receive the solution from the pressurized reservoir and to communicate with the porous skin interface.

10. The device of claim 1, wherein the active substance comprises an opiate, and wherein the opiate comprises fentanyl, codeine, dihydrocodeine, hydrocodone, hydromorphone, Sufentanil, Nalbuphine, Buprenorphine, Hydromorphone or other opiate derivative.

11. The device of claim 1, further comprising:

a display.

12. The device of claim 1, wherein the device includes a disposable portion and a reusable portion, wherein the disposable portion and the reusable portion are adapted to be coupled together.

13. The device of claim 12, wherein the disposable portion includes the pressurized reservoir, the solution of the active substance and the solvent disposed in the pressurized reservoir, the porous skin interface, and the evaporation channel.

14. The device of claim 12, wherein the reusable portion includes a programmable control unit and a power source.

15. A method for delivering an active substance to a human comprising:

delivering the active substance dissolved in a solvent from a pressurized reservoir of a transdermal drug delivery device to a porous skin-interface membrane of the transdermal drug delivery device coupled to a skin of the human;

absorbing the active substance from the porous skin-interface membrane transdermally into the human; and

moving evaporated solvent from the skin-interface membrane through an evaporation channel of the transdermal drug delivery device.

16. The method of claim 15, further comprising:

repeating the delivering, absorbing and moving steps to modulate and control dosing to create a plurality of active substance blood plasma concentration peaks and troughs in the human.

17. The method of claim 15, wherein the active substance is an opiate, and wherein the opiate comprises fentanyl, codeine, dihydrocodeine, hydrocodone, hydromorphone, Sufentanil, Nalbuphine, Buprenorphine, Hydromorphone or other opiate derivative.

18. The method of claim 15, wherein delivering the active substance dissolved in the solvent to the skin-interface membrane of the transdermal drug delivery device coupled to the human includes delivering the active substance at a time, rate, sequence and/or cycle that is synchronized with a biological rhythm of the human.

19. The method of claim 15, wherein the method further includes moving solvent from the skin-interface membrane into a solvent removal element, and wherein the solvent removal element comprises a desiccant, absorbent material, or hydrophilic material.

20. The method of claim 15, wherein the active substance is an opiate, and wherein the opiate is for a purpose of chronic pain management.

21. The method of claim 15, wherein the active substance is an opiate, and wherein the opiate is for a purpose of acute pain management.

22. The method of claim 15 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.

23. The method of claim 15, wherein the delivery step comprises delivering a first dosage of active substance to the human to raise the human'"'"'s blood plasma concentration of active substance from a first level to a second level higher than the first level while the human is asleep.

24. The method of claim 23, wherein delivering the first dosage of active substance to the human is at a time around 3 a.m. to 8 a.m.

25. The method of claim 23, wherein the second level of the blood plasma concentration is about 2-8 ng/ml.

26. The method of claim 23, wherein the delivery step further comprises reducing or stopping delivery of active substance to the human to reduce the human'"'"'s blood plasma concentration of active substance from the second level to a third level lower than the second level, then delivering a second dosage of active substance to the human to increase the human'"'"'s blood plasma concentration of active substance from the third level to a fourth level higher than the third level.

27. The method of claim 26, wherein the second dosage of active substance to the human is at a time around 5 p.m. to about 3 a.m.

28. The method of claim 26, wherein the third level of the blood plasma concentration is about 1-3 ng/ml.

29. The method of claim 26, wherein the third level of the blood plasma concentration is around 8 a.m. to around 5 p.m.

30. The method of claim 26, wherein the fourth level of the blood plasma concentration is about 2-5 ng/ml.

31. The method of claim 26, wherein the active substance is fentanyl.

32. The method of claim 15, further comprising:

removing the transdermal drug delivery device after contacting the skin for greater than 24 hours.

33. The method of claim 15, wherein delivering the active substance dissolved in the solvent to the skin-interface membrane of the transdermal drug delivery device coupled to the skin of the human is performed immediately before the human wakes up.

34. The method of claim 15, wherein the transdermal drug delivery device includes a reservoir with the active substance dissolved in the solvent and further comprising:

moving a portion of the active substance dissolved in the solvent from the reservoir to the skin-interface membrane.