Gum pad for delivery of medication to mucosal tissues

• US 6,319,510 B1
• Filed: 02/22/2000
• Issued: 11/20/2001
• Est. Priority Date: 04/20/1999
• Status: Expired due to Term

• Current Assignee: Alayne Yates
• Original Assignee: Alayne Yates
• Inventors: Yates, Alayne
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US09/510,470
• Time in Patent Office: 637 Days
• Field of Search: 424/404, 424/402
• US Class Current: 424/404
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 15/04 for inducing labour or abortion; Uterotonics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

The Gum Pad is a laminate composed of: (a) a synthetic base or backing layer which is configured to be held in place on the gingiva (gums) in the mouth; (b) an intermediate, reservoir layer for containing medication therein; and (c) a semi-permeable outer layer facing outwardly toward oral mucosal tissues in the mouth which will allow saliva to enter and dissolve the medication in the reservoir layer into solution and pass the diffused saliva-medication solution outwardly to the oral mucosal tissues. The backing layer is placed on the gum so that the semi-permeable outer layer faces outwardly toward the buccal mucosa. Saliva enters the semi-permeable layer and dissolves the medication in the reservoir layer, then diffuses outwardly through the semi-permeable layer to the mucosal tissues in the mouth where it is readily absorbed into the circulatory system. The Gum Pad can be used for the topical or systemic delivery of a wide range of pharmaceutical and nutritional agents, for the treatment of a variety of human disorders and diseases.

Claims

1. A gum pad for use in the mouth of a person comprising:

(a) a nonporous first layer;

(b) a second layer adjacent said nonporous first layer having a medication capable of being liquified by saliva retained in said second layer;

(c) a semi-permeable third layer covering said second layer and sealed to said first layer to form a pocket enclosing said second layer,

(d) wherein said semi-permeable third layer is permeable to saliva such that the saliva can penetrate therethrough to liquify the medication retained in said second layer and transport it by liquid diffusion back through said semi-permeable third layer; and

wherein said first layer is made of a stable and flexible material and has an outer surface adapted to be installed in place on the gum in the mouth of the person using the gum pad, with said third layer facing outwardly toward oppositely facing mucosal tissues in the mouth.

2. A gum pad according to claim 1, wherein the outer surface of said first layer has an adhesive compound applied to it for adhering to the gum when installed for use.

3. A gum pad according to claim 1, wherein the medication retained in said second layer is mixed or compounded with a material selected from the group consisting of:

water soluble exipient matrix;

water soluble hydrogel matrix; and

free flowing lipophilic particles.

4. A gum pad according to claim 1, wherein said third layer is a semi-permeable membrane made of a type of material selected from the group consisting of:

thin polymer film containing pores;

nonwoven fibers bonded together having inter-fiber pores; and

foam layer with open cells as pores.

5. A gum pad according to claim 4, wherein said semi-permeable third layer has a porosity of about 30 to 70 volume %, and a fluid permeability greater than about 2×

10<sup>−

4</sup> cm mil/atm hr, so as to be readily permeable to saliva and saliva transport of medication dissolved therein.

6. A gum pad according to claim 1, wherein the medication retained in said second layer is selected from the group consisting of:

uncharged molecules;

molecular complexes;

pharmacologically acceptable salts, acids, amines or organic cations;

derivatives of esters, amides, or ethers;

biologically active polypeptides or proteins; and

nutritional supplements.

7. A gum pad according to claim 1, wherein the medication retained in said second layer is selected from the group consisting of:

anticonvulsants;

anxiolytics;

anesthetics;

analgesics;

peptides;

antiemetics; and

beta-adrenergic blockers.

8. A gum pad according to claim 1, used for topical treatment of tissue in the mouth of a person using the gum pad, wherein said first layer is made of a stable and flexible material and has an outer surface adapted to be installed in place on a supporting tissue area and said third layer faces outwardly toward the tissues to be treated topically in the mouth.

9. A gum pad according to claim 1, wherein gum pad has an elongated, generally tubular shape with bulb shaped ends, said first layer has a flat outer surface, and said third layer has a curved outer surface, such that the gum pad can be installed between the buccal mucosa and the gums of the teeth at a front part of the upper and/or lower jaw of the mouth extending to posterior areas of the jaw.

19. A gum pad according to claim 1, wherein chitosan is applied as an adhesive on the external surface of the first layer of the gum pad.

20. A gum pad according to claim 1, wherein the first layer is composed of a naturally self-adherent hydrophilic polymeric resin that adheres to the mucosa.

21. A gum pad according to claim 1, wherein the medication is mixed with a material selected from the group comprising:

free flowing liposomes;

liposome-protein conjugates; and

proliposomes.

22. A gum pad according to claim 1, wherein the medication is in a form selected from the group consisting of:

a soluble powder adhering to a fibrous web;

liquid sprayed on a fibrous web; and

emulsion coated on the fibrous web.

23. A gum pad according to claim 1, wherein the medication is mixed with an exipient matrix made from a material selected from the group consisting of:

cellulose product;

polysaccharides; and

conventional matrix material.

24. A gum pad according to claim 1, wherein the medication is mixed with a hydrogel matrix made from a material selected from the group consisting of:

cellulose derivatives;

polymers and co-polymers;

gums, including alginate gum; and

polytetrafluoroethylene web.

25. A gum pad according to claim 1, wherein the medication is mixed with an additive material selected from the group consisting of:

sweeteners;

flavoring agents;

buffers;

surfactants;

enzyme inhibitors;

co-solvents; and

permeants.

26. A gum pad according to claim 1, wherein the medication is provided in a concentration sufficient to cause an osmotic gradient across the semi-permeable third layer when diluted with saliva.

27. A gum pad according to claim 1, wherein the medication is mixed with a hydrogel matrix and contains material selected from the group consisting of:

enzymes;

antibodies;

proteins; and

peptides.

36. A gum pad according to claim 1, wherein the semi-permeable third layer is a membrane formed from a material selected from the group consisting of:

cellulose;

cellulose derivatives;

gums;

semi-permeable polymers; and

high flux membrane material.

37. A gum pad according to claim 1, wherein the medication is mixed with a matrix in the second layer, and the second layer is enclosed by laminating the edges of the first layer and a semi-permeable membrane third layers.

38. A gum pad according to claim 1, wherein the medication contains a freeze dried material, and the gum pad is enclosed in a sealed, waterproof envelope.

54. A medication delivery method according to claim 20, wherein said second layer has a total volume of less than about 4.0 cm³, the concentration of the medication is in the range of about 0.005% to about 25% by weight of a total dispersion the medication is carried in, and the medication can be delivered through the mucosal tissue into the human circulatory system within a matter of a few minutes or more, and may be maintained as desired for a number of hours.

55. A medication delivery method according to claim 20, wherein the medication retained in said second layer is selected from the group consisting of:

uncharged molecules;

molecular complexes;

pharmacologically acceptable salts, acids, amines or organic cations;

derivatives of esters, amides, or ethers;

biologically active polypeptides or proteins; and

nutritional supplements.

10. A medication delivery method of delivering medication into the human circulatory system from within the mouth of a person, said method comprising the steps of:

(a) providing a pad having a nonporous first layer, a second layer for retaining a medication therein, and a semi-permeable third layer covering the second layer and sealed to said first layer so as to form a sealed pocket enclosing said second layer;

(b) impregnating said second layer with medication to be delivered into the human circulatory system; and

(c) placing said pad on a supporting part within the mouth of the person with said semi-permeable third layer facing outwardly toward mucosal tissue in the mouth so as to permit saliva within the mouth to Penetrate into said semi-permeable third layer and liquify the medication in said second layer and transport it by diffusion through said semi-permeable third layer for absorption into the mucosal tissue,

wherein the medication retained in said second layer is selected from the group consisting of;

anticonvulsants;

anxiolytics;

anesthetics;

analgesics;

peptides;

antiemetics; and

beta-adrenergic blockers.

11. A medication delivery method according to claim 10, wherein said medication is vigabratin used to treat seizures, and the medication delivered by said method has effect within 20 minutes.

12. A medication delivery method according to claim 10, wherein said medication is aprazolam used to treat anxiety, and the medication delivered by said method has effect within 2-10 minutes.

13. A medication delivery method according to claim 10, wherein said medication is midazolam used as a sedative, and the medication delivered by said method has effect within 10 minutes.

14. A medication delivery method according to claim 10, wherein said medication is fentanyl used to alleviate pain, and the medication delivered by said method has effect within 10-20 minutes.

15. A medication delivery method according to claim 10, wherein said medication is oxytocin used to induce labor, and the medication delivered by said method has effect within 5-10 minutes.

16. A medication delivery method according to claim 10, wherein said medication is dronabinol used to relieve nausea, and the medication delivered by said method has effect within 30 minutes.

17. A medication delivery method according to claim 10, wherein said medication is propanolol used to treat stage fright, and the medication delivered by said method has effect within 28 minutes.

18. A method of treating human systemic disease or disorder by delivery of medication into the human circulatory system through mucosal tissue within the mouth of a person, comprising the steps of:

(a) providing a pad having a medication soluble by saliva retained therein with a semi-permeable outer layer covering the medication retained in the pad, said semi-permeable outer layer facing outwardly toward mucosal tissue within the mouth of the person;

(b) placing said pad on a supporting part within the mouth of the person with said semi-permeable third layer facing outwardly toward mucosal tissue in the mouth so as to permit saliva within the mouth to penetrate into said semi-permeable third layer and liquify the medication in said second layer; and

(c) permitting saliva within the mouth to penetrate into the pad through said semi-permeable outer layer to liquify the medication retained therein; and

(d) transporting the medication dissolved in the saliva by diffusion through said semi-permeable outer layer for absorption into the mucosal tissue within the mouth of the person where it can enter into the human circulatory system.

28. A method according to claim 18, wherein the semi-permeable third layer is a membrane selected to control release of the medication mixed with a hydrogel matrix, and prevent over-expansion of the hydrogel matrix.

29. A method according to claim 18, wherein the medication is mixed with a hydrogel matrix, and the rate of medication release from the hydrogel matrix is controlled by the selection of the hydrogel material and addition of cross-linking agents.

30. A method according to claim 29, wherein the hydrogel material and cross-linking agents are selected such that large and/or water soluble molecules of medication are delivered over an extended period of time.

31. A method according to claim 18, wherein the medication material is prepared by freeze-drying or freeze-etching for heat sensitive medications and for rapid medication delivery.

32. A method according to claim 31, wherein cryoprotectants, auxiliary agents, or exipient matrix material are added during freeze-drying or freeze etching.

33. A method according to claim 31, wherein the shelf-life of the freeze-dried medication is prolonged by mixing the medication material with hydrogel matrix and cryoprotectants, and by vacuum storage at a low temperature.

34. A method according to claim 18, wherein the semi-permeable third layer is composed of an osmosis or reverse-osmosis membrane.

35. A method according to claim 18, wherein the semi-permeable third layer is a membrane that is insoluble in saliva and does not react to medications or additives.

39. A human disease treatment method according to claim 18, wherein the gum pad is used for a treatment selected from the group consisting of:

preventing gum deterioration;

treating periodontal disease;

preventing heart attacks and strokes;

regulating cardiovascular function;

treating bacterial or viral infection;

boosting immune response;

suppressing appetite;

improving digestion;

relieving pain; and

moderating metabolic and organic conditions.

40. A human disease treatment method according to claim 18, wherein upon the medication in the second layer absorbing saliva and flowing out through the third layer of the gum pad, the medication is absorbed by the mucosa, enters the capillaries and is transported through circulatory system.

41. A human disease treatment method according to claim 18, wherein two or more gum pads are applied simultaneously or sequentially to enable continuous medication delivery.

42. A human disease treatment method according to claim 18, wherein the dosage of the medication is adjusted by changing the colloidal state of the medication in the second layer and the time interval over which the medication is delivered.

43. A human disease treatment method according to claim 18, wherein the gum pad is removable by the patient if any adverse effects are noted.

44. A human disease treatment method according to claim 18, wherein the gum pad is used with pre-operative patients, nauseated patients, patients who are non-compliant, or patients who fear needles.

45. A human disease treatment method according to claim 18, wherein the gum pad is used to deliver medication selected from the group consisting of:

vitamins;

herbs;

plant extracts; and

other nutritional products.

46. A human disease treatment method according to claim 18, wherein the gum pad is used to deliver water-insoluble medications which, when released systemically, is converted by metabolic processes to a biologically active form.

47. A human disease treatment method according to claim 18, wherein the gum pad is used to deliver a fat soluble medication selected from the group consisting of:

liposomes;

liposome-protein conjugates; and

proliposomes.

48. A human disease treatment method according to claim 18, wherein the medication is a peptide that would otherwise be destroyed in the gut or liver.

49. A human disease treatment method according to claim 18, wherein the gum pad can be readily removed from the patient for rapid cessation of drug delivery if toxicity occurs.

50. A human disease treatment method according to claim 18, wherein the gum pad can be readily adjusted for rapid correction when patients are under or over-medicated.

51. A human disease treatment method according to claim 18, wherein the medication is selected for delivery to the central nervous system (CNS) from the group consisting of:

stimulants;

respiratory stimulants;

sedatives;

hypnotics;

anti-convulsants;

analgesics;

opioid agonists/antagonists;

anti-migraine;

anti-emetic/vertigo;

anti-anxiety;

anti-depressant;

anti-psychotic;

anti-Parkinsons; and

agents to counteract or treat movement disorders.

52. A human disease treatment method according to claim 18, wherein the medication is a peripherally or centrally CNS-active material selected from the group consisting of:

hormones;

neurohormones;

neuroprotectants;

neurotransmitters, their agonists and antagonists;

neuromodulators;

adenosine derivatives;

enzymes;

enzyme inhibitors;

genes;

nucleotides;

immune system components;

signal transduction peptides;

biomarkers;

growth factors; and

agents that affect growth factor receptors.

53. A human disease treatment method according to claim 18, wherein the medication is selected from the group consisting of:

vitamins;

essential oils;

natural hormones;

nutritional supplements;

plant extracts; and

nutraceuticals.