Transdermal Pharmaceutical Composition

• US 20070264345A1
• Filed: 10/06/2004
• Published: 11/15/2007
• Est. Priority Date: 10/09/2003
• Status: Active Grant

• Current Assignee: Richter Gedeon Vegyeszeti Gyar Rt.
• Original Assignee: Richter Gedeon Vegyeszeti Gyar Rt.
• Inventors: Bodis, Attila, Lapis, Erzsebet, Pannonhalmine Csoka, Ildiko, Illes, Janos, Kissne Csikos, Emoke, Eros, Istvan, Francsicsne Czinege, Erzsebet, Soonse Csanyi, Erzsebet
• Granted Patent: US 7,728,042 B2
• Time in Patent Office: Days
• US Class Current: 424/488
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/1274 Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/06 Anabolic agents androgens A61P5/26
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/30 : Oestrogens
• CPC Class Codes: A61P 5/34 : Gestagens
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

The invention relates to a liquid crystal gel containing polyoxyethylene-glyceryl-trioleate, propylene-glycol, iso-propyl myristate and a hyaluronic acid salt or complex for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics. The invention also relates to transdermal pharmaceutical composition consists of an estrogen and a progestin component as well as a liquid crystal gel containing polyoxyethylene-glyceryl-trioleate, propylene-glycol, isopropyl myristate and a hyaluronic acid salt or complex. The invention can be applied for transdermal hormone replacement therapy and for other trans-dermal depending on the active principles included.

Claims

1. Liquid crystal gel for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics characterized in that the gel containing polyoxyethyleneglyceryl-trioleate, propylene-glycol, isopropyl myristate and a hyaluronic acid salt or complex.

2. The liquid crystal gel for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics according to claim 1 characterized in that the amount of polyoxyethylene-glyceryl-trioleate in the gel varies between 26.7 and 40% (w/w) of the total weight of the gel.

5. The liquid crystal gel for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics according to any of claims 1-4 characterized in that the amount of propylene-glycol added to the gel varies between 13.3 and 20% (w/w) of the total weight of the gel.

8. The liquid crystal gel for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics according to any of claims 1-7 characterized in that the ratio of polyoxyethylene-glyceryl-trioleate and propylene-glycol is 2:

1.

9. The liquid crystal gel for use in the manufacture of transdermal pharmaceutical compositions and healing -cosmetics according to any of claims 1-8 characterized in that the amount of isopropyl-myristate added to the gel varies between 5 and 35% (w/w) of the total weight of the gel.

12. The liquid crystal gels for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics according to any of claims 1-11 characterized in that sodium-hyaluronate is applied as hyaluronic acid salt.

13. The liquid crystal gels for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics according to any of claims 1-11 characterized in that hyaluronic acid zinc complex is applied as hyaluronic acid complex.

14. The liquid crystal gel for use in the manufacture of transdermal pharmaceutical compositions and healing cosmetics according to any of claims 12-13 characterized in that the amount of sodium-hyaluronate or hyaluronic acid zinc complex in the gel varies between 0.01 and 2% (w/w) of the total weight of the gel.

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17. Transdermal pharmaceutical composition characterized in that the composition consists of an estrogen and progestin component as well as a liquid crystal gel containing polyoxyethylene-glyceryl-trioleate, propylene-glycol, isopropyl myristate and a hyaluronic acid salt or complex.

18. The pharmaceutical composition according to claim 17 characterized in that the estrogen component is estradiol.

20. The pharmaceutical composition according to any of claims 17-19 characterized in that the progestin component is gestodene.

22. The pharmaceutical composition according to any of claims 17-19 characterized in that the progestin component is etonogestrel.

24. The pharmaceutical composition according to any of claims 17-19 characterized in that the progestin component is levonorgestrel.

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26. Method of treatment for transdermal hormone replacement therapy characterized in that a pharmaceutical composition consists of an estrogen and a progestin component as well as a liquid crystal gel containing polyoxyethylene-glyceryl-trioleate, propylene-glycol, isopropyl myristate and a hyaluronic acid salt or complex is applied onto the surface to be treated.

27. The method of treatment according to claim 26 characterized in that the hormone replacement therapy is applied

a) for the treatment of moderate to severe vasomotor symptoms of as well as the hot flush, nocturnal sweating and palpitation due to post-menopausal estrogen deficiency;

b) for the treatment of the symptoms of urogenital atrophy, vaginal dryness, recurrent vaginitis, recurrent cystitis, painful intercourse and incontinence due to postmenopausal estrogen deficiency;

c) for the treatment of the psychic symptoms and decreased physical performance manifesting as tiredness, anxiety, panic, irritability, lethargy, depression, mood disorders, sleep disturbances, memory problems, difficulty in mental concentration and decreased libido due to post-menopausal estrogen deficiency;

d) for the treatment of estrogen deficiency due to primary ovary insufficiency or castration;

e) for the treatment of dysmenorrhoea related to hormonal disorders without organic alterations and with hypoplastic endometrium;

f) for the prevention of post-menopausal osteoporosis;

g) for the reduction of the size of uterine myoma and for the treatment of bleeding disorders in post-menopausal women;

h) for the alleviation of the symptoms of post-menopausal estrogen deficiency in unstable hypertension;

i) for the alleviation of the symptoms of post-menopausal estrogen deficiency in women with hypertriglyceridaemia;

j) for the alleviation of the symptoms of post-menopausal estrogen deficiency in women with a history of thromboembolism;

k) for the alleviation of the symptoms of post-menopausal estrogen deficiency in women with hyperandrogenic symptoms (androgenic type alopecia, hirsutism);

l) for the alleviation of the symptoms post-menopausal estrogen deficiency in the early post-operative period of surgical menopause;

m) for the alleviation of the symptoms of post-menopausal estrogen deficiency in postmenopausal women with type 2 diabetes;

n) for the alleviation of the symptoms of post-menopausal estrogen deficiency in women, who cannot tolerate the side-effects of oral drug administration;

o) for the alleviation of the symptoms of post-menopausal estrogen deficiency in women, who cannot tolerate the side-effects associated with transdermal patches;

p) for the alleviation of the symptoms of post-menopausal estrogen deficiency in women, who cannot tolerate the side-effects associated with the use of alcohol-based transdermal gel.

28. Transdermal pharmaceutical composition characterized in that the composition consists of one or more active agent components as well as a liquid crystal gel containing polyoxyethylene-glyceryl-trioleate, propylene-glycol, isopropyl myristate and a hyaluronic acid salt or complex.

29. The pharmaceutical composition according to claim 28 characterized in that the active agent component is ondansetron.

31. The pharmaceutical composition according to claim 28 characterized in that the active agent component is terbinafine.

33. The pharmaceutical composition according to claim 28 characterized in that the active agent component is fluconazole.

35. The pharmaceutical composition according to claim 28 characterized in that the active agent component is metronidazole.

37. The pharmaceutical composition according to claim 28 characterized in that the active agent component is fentanyl.

39. The pharmaceutical composition according to claim 28 characterized in that the active agent component is nandrolone decanoate.

41. The pharmaceutical composition according to claim 28 characterized in that the active agent component is nestorone.

43. The pharmaceutical composition according to claim 28 characterized in that the active agent component is norethisterone.

45. The pharmaceutical composition according to claim 28 characterized in that the active agent component is eperisone.

47. The pharmaceutical composition according to claim 28 characterized in that the active agent component is tolperisone.

49. The pharmaceutical composition according to claim 28 characterized in that the active agent component is vinpocetine.

51. The pharmaceutical composition according to claim 28 characterized in that the active agent component is ketamine.

53. The pharmaceutical composition according to claim 28 characterized in that the active agent component is vincristine.

55. The pharmaceutical composition according to claim 28 characterized in that the active agent component is vinblastine.

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