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 10,258,738 B2
• Filed: 04/21/2017
• 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:
  US15/494,392
• Publication Number:
  US 20170224911A1
• Time in Patent Office: 725 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 method for treating a human with Parkinson'"'"'s disease comprising:

delivering an active pharmaceutical ingredient (API) for treating Parkinson'"'"'s disease, symptoms associated with Parkinson'"'"'s disease, or symptoms associated with treatments for Parkinson'"'"'s disease dissolved in a solvent to a skin-interface membrane of a transdermal drug delivery device coupled to a skin of the human;

absorbing the active pharmaceutical ingredient from the skin-interface membrane transdermally into the human; and

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

2. The method of claim 1, wherein the API comprises one or more of the following:

dopamine precursors, dopa decarboxylase inhibitors, Levodopa/carbidopa mixtures, Levodopa/carbidopa/entacapone mixtures, Levodopa/benserazide mixtures, dopamine agonists, anticholinergics, MAO-B inhibitors, COMT inhibitors, dopaminergic agonists, Ampakines Istradefylline (KW-6002), S-(−

)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923), Sarizotan, bornaprine, budipine, ethopropazine, lazabemide, memantine, modafinil, talampanel, altinicline, brasofensine, safinamide, droxidopa, quinagolide, terguride, riluzole, talipexole, piroheptine, bifeprunox, spheramine, sumanirole, lisuride hydrogen maleateor, and orphenadrine.

3. The method of claim 1, wherein the API comprises levodopa.

4. The method of claim 3, wherein the API includes a Levodopa/carbidopa mixture, Levodopa/carbidopa/entacapone mixture, or Levodopa/benserazide mixture.

5. The method of claim 1, wherein the API comprises one or more of the following:

Carbidopa, bromocriptine, pergolide, pramipexole, rotigotine, ropinirole, cabergoline, apomorphine, lisuride, piribedil, selegiline, Amantadine, memantine, and safinamide.

6. The method of claim 1, 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.

7. The method of claim 1, wherein delivering the API dissolved in the solvent to the skin-interface membrane of the transdermal drug delivery device coupled to the human includes delivering the API at a time, rate, sequence and/or cycle that is synchronized with a biological rhythm of the human.

8. The method of claim 1, wherein delivering the API dissolved in the solvent to the skin-interface membrane of the transdermal drug delivery device coupled to the human includes delivering the API at a time, rate, sequence and/or cycle that is selected to reduce dyskinesia in the human.

9. The method of claim 1, further comprising:

repeating the delivering, absorbing and moving steps to modulate and control dosing to create a consistently therapeutically effective blood plasma concentration of the active pharmaceutical ingredient in the human.

10. The method of claim 1, further comprising:

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

11. The method of claim 2, wherein the API further comprises levodopa.

12. The method of claim 10, wherein the API includes levodopa and the peaks and troughs of the blood plasma concentration of levodopa are between about 1.4 to about 2.0 μ

g/ml.

13. The method of claim 1, wherein the API is for a purpose of treating dyskinesia.

14. The method of claim 1, further comprising:

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

15. The method of claim 1, wherein delivering the API 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.

16. The method of claim 1, wherein the transdermal drug delivery device includes a reservoir with the API dissolved in the solvent and further comprising:

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

17. The method of claim 1, wherein delivering the API dissolved in the solvent to the skin-interface membrane of the transdermal drug delivery device coupled to the skin of the human begins during a one hour period immediately prior to the human'"'"'s waking to transdermally administer the API to the human.

18. The method of claim 1, wherein the delivery step comprises delivering a first dosage of API to the human to raise the human'"'"'s blood plasma concentration of API from a first level to a second level higher than the first level.

19. The method of claim 18 wherein the first dosage is delivered while the human is asleep.

20. The method of claim 18, wherein delivering the first dosage of API to the human is at a time around 7:

30 a.m. to 10;

00 a.m.

21. The method of claim 18, wherein delivering the first dosage of API to the human is at a time around 10:

00 a.m. to 12;

00 p.m.

22. The method of claim 18, wherein the delivery step further comprises reducing or stopping delivery of API to the human to reduce the human'"'"'s blood plasma concentration of API from the second level to a third level lower than the second level, then delivering a second dosage of API to the human to increase the human'"'"'s blood plasma concentration of API from the third level to a fourth level higher than the third level.

23. The method of claim 22, wherein the second dosage of API to the human is at a time around 1:

00 p.m. to about 3;

00 p.m.

24. The method of claim 22, wherein the second dosage of API to the human is at a time around 3:

00 p.m. to about 5;

00 p.m.

25. The method of claim 22, wherein the delivery step further comprises reducing or stopping delivery of API to the human to reduce the human'"'"'s blood plasma concentration of API from the fourth level to a fifth level lower than the fourth level, then delivering a third dosage of API to the human to increase the human'"'"'s blood plasma concentration of API from the fifth level to a sixth level higher than the fifth level.

26. The method of claim 25, wherein the third dosage of API to the human is at a time around 6:

00 p.m. to about 8;

00 p.m.

27. The method of claim 25, wherein the API comprises Levodopa.