KITS AND IMPROVED COMPOSITIONS FOR TREATING LOWER URINARY TRACT DISORDERS

• US 20120196830A1
• Filed: 04/09/2012
• Published: 08/02/2012
• Est. Priority Date: 01/14/2005
• Status: Active Application

• Current Assignee: Parsons C. Lowell
• Original Assignee: Parsons C. Lowell
• Inventors: Parsons, C. Lowell
• Application Number:
  US13/442,101
• Publication Number:
  US 20120196830A1
• Time in Patent Office: Days
• US Class Current: 514/56
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/055 the aromatic ring being substituted by halogen
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/221 with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers

Abstract

Superior buffered formulations and their kits for treating lower urinary tract symptoms and disorders are provided in the invention. In particular superior buffered formulations have demonstrated improvement for treating lower urinary tract symptoms of patients experiencing severe pain and/or urgency of the bladder and associated areas of the lower urinary tract.

Claims

1. A pharmaceutical composition for treating or ameliorating a lower urinary tract disorder comprising:

(a) an anionic polysaccharide in a quantity sufficient to treat or ameliorate the lower urinary tract disorder;

(b) an acute-acting anesthetic in a quantity sufficient to treat or ameliorate the lower urinary tract disorder;

(c) a buffer that buffers the solution at a pH that ensures that a sufficient portion of the acute-acting anesthetic is present in an uncharged state so that the acute-acting anesthetic can cross the cell membranes, the buffer being present in a quantity such that the buffer has a buffering capacity equivalent to the buffering capacity of sodium bicarbonate such that, when the formulation is dissolved in a liquid for administration, the sodium bicarbonate is present at a concentration of about 0.20 M to about 0.45 M;

(d) optionally, an osmolar component that provides an isotonic or nearly isotonic solutions compatible with human cells and blood; and

(e) optionally, an additional component comprising one or more of the following in any combination;

(i) an antibacterial agent in a quantity sufficient to treat or ameliorate the lower urinary tract disorder;

(ii) an antifungal agent in a quantity sufficient to treat or ameliorate the lower urinary tract disorder; and

(iii) a vasoconstrictor in a quantity sufficient to treat or ameliorate the lower urinary tract disorder.

2. The pharmaceutical composition of claim 1 wherein the anionic polysaccharide is a glycosaminoglycan.

3. The pharmaceutical composition of claim 2 wherein the glycosaminoglycan is selected from the group consisting of hyaluronic acid, hyaluronan, chondroitin sulfate, pentosan polysulface, dermatan sulfates, heparin, heparan sulfates, and keratin sulfates.

4. The pharmaceutical composition of claim 3 wherein the glycosaminoglycan is heparin.

5. The pharmaceutical composition of claim 4 wherein the composition comprises from about 10,000 units to about 100,000 units of heparin per unit dose.

6. The pharmaceutical composition of claim 5 wherein the composition comprises about 40,000 units of heparin per unit.

7. The pharmacological composition of claim 1 wherein the acute-acting anesthetic is selected from the group consisting of benzocaine, lidocaine, tetracaine, bupivacaine, cocaine, etidocaine, flecamide, mepivacine, pramoxine, prilocalne, procaine, chloroprocaine, proparacaine, ropivacaine, dyclonine, dibucaine, propoxycaine, chlorixylenol, cinchocaine, dexivacaine, diamocaine, hexylcaine, levobupivacaine, propoxycaine, pyrrocaine, risocaine, rodocaine, and pharmaceutically acceptable derivatives and bioisosteres thereof.

8. The pharmaceutical composition of claim 7 wherein the acute-acting anesthetic is lidocaine.

9. The pharmaceutical composition of claim 1 wherein the buffer is selected from the group consisting of bicarbonate buffer, Tris (Tris(hydroxymethyl)aminomethane) buffer, MOPS (3-(N-morpholino)propanesulfonic acid) buffer, HEPES (N-(2-hydroxyethyl)piperazine-N′

-(2-ethanesulfonic acid) buffer, ACES (2-[(2-amino-2-oxoethyl)amino]ethanesulfonic acid) buffer, ADA (N-(2-acetamido)2-iminodiacetic acid) buffer, AMPSO (3-[(1,1-dimethyl-2-hydroxyethyl)amino]-2-propanesulfonic acid) buffer, BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid) buffer, Bicine N,N-bis(2-hydroxyethylglycine) buffer, Bis-Tris (bis-(2-hydroxyethyl)imino-tris(hydroxymethyl)methane) buffer, CAPS (3-(cyclohexylamino)-1-propanesulfonic acid) buffer, CAPSO (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid) buffer, CHES (2-(N-cyclohexylamino)ethanesulfonic acid) buffer, DIPSO (3-[N,N-bis(2-hydroxyethyl)amino]-2-hydroxy-propanesulfonic acid) buffer, HEPPS(N-(2-hydroxyethyl piperazine)-N′

-(3-propanesulfonic acid) buffer, HEPSO(N-(2-hydroxyethyl)piperazine-N′

-(2-hydroxypropanesulfonic acid) buffer, MES (2-(N-morpholino)ethanesulfonie acid) buffer, triethanolamine buffer, imidazole buffer, glycine buffer, ethanolamine buffer, phosphate buffer, MOPSO (3-(N-morpholino)-2-hydroxypropanesulfonic acid) buffer, PIPES (piperazine-N,N′

-bis(2-ethanesulfonic acid) buffer, POPSO (piperazine-N,N′

-bis(2-hydroxypropaneulfonic acid) buffer, TAPS(N-tris[hydroxymethyl)methyl-3-aminopropanesulfonic acid) buffer, TAPSO (3-[N-tris(hydroxymethyl)methylamino]-2-hydroxy-propanesulfonic acid) buffer, TES N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid) buffer, tricine (N-tris(hydroxymethyl)methylglycine buffer), 2-amino-2-methyl-1,3-propanediol buffer, and 2-amino-2-methyl-1-propanol buffer.

10. The pharmaceutical composition of claim 9 wherein the buffer is a bicarbonate buffer.

11. The pharmaceutical composition of claim 10 wherein the bicarbonate buffer is sodium bicarbonate.

12. The pharmaceutical composition of claim 1 wherein the composition comprises the osmolar component.

13. The pharmaceutical composition of claim 12 wherein the osmolar component is selected from the group consisting of sodium chloride, dextrose, dextran 40, dextran 60, starch and mannitol.

14. The pharmaceutical composition of claim 13 wherein the osmolar component is sodium chloride.

15. The pharmaceutical composition of claim 8 wherein the quantity of lidocaine in the composition is such that a unit dose contains about 120 mg to the maximum safety tolerated dose of lidocaine.

16. The pharmaceutical composition of claim 15 wherein the quantity of lidocaine in the composition is such that a unit dose contains about 160 mg of lidocaine.

17. The pharmaceutical composition of claim 15 wherein the quantity of lidocaine in the composition is such that a unit dose contains about 200 mg of lidocaine.

18. The pharmaceutical composition of claim 1 wherein the lower urinary tract disorder is selected from the group consisting of bacterial cystitis, fungal/yeast cystitis, vulvar vestibulitis, vulvodynia, dyspareunia, and endometriosis in women;

prostatitis and chronic pelvic pain syndrome in men; and

radiation induced cystitis, chemotherapy-induced cystitis, interstitial cystitis, and overactive bladder in men and women.

19. A pharmaceutical composition for treating or ameliorating a lower urinary tract disorder comprising:

(a) 160 mg lidocaine per unit dose;

(b) 40,000 units of heparin per unit dose;

(c) 336 mg sodium bicarbonate per unit dose; and

(d) 20 mg sodium chloride per unit dose;

such that, in a final unit dose volume of 12 ml, lidocaine is present at 46 mM, heparin is present at 3333 units/ml, sodium bicarbonate is present at 0.33 M, and sodium chloride is present at about 28.5 mM.

20. A pharmaceutical composition for treating or ameliorating a lower urinary tract disorder comprising:

(a) 200 mg lidocaine per unit dose;

(b) 40,000 units of heparin per unit dose;

(c) 336 mg sodium bicarbonate per unit dose; and

(d) 20 mg sodium chloride per unit dose;

such that, in a final dose volume of 13 ml, lidocaine is present at 53 mM, heparin is present at 3077 units/ml, sodium bicarbonate is present at 0.305 M, and sodium chloride is present at 26.3 mM.