METHOD OF TREATMENT OF IRRITATION OF SKIN OR MUCOUS CELLS

Abstract

The present invention provides a method of treatment of irritation of skin or mucous cells. The method comprises applying topically a composition comprising a combination of: xylitol, myonisotiol or mannitol or any combination of these; glycerol and/or urea; water; in the absence of any oil in water or wax in water emulsion.

Claims

1. A method of treating irritation to mucous cells or skin cells, comprising: providing a composition comprising an aqueous solution of: xylitol, myoinositol or mannitol or any combination thereof; and, glycerol and/or urea; said aqueous solution containing less than 0.01% inorganic salts; and, administering topically said composition to a patient in need thereof.

2. The method according to claim 1, wherein said step of providing a composition comprises providing a composition comprising an aqueous solution of: 1.5-5.5% (w/v) xylitol, myoinositol or mannitol or any combination thereof; and, 0.9-2.0% (w/v) glycerol; said aqueous solution containing less than 0.01% (w/v) inorganic salts.

3. The method according to claim 1, wherein said method is a method for treating mucous cells.

4. The method according to claim 1, wherein said method is a method for treating skin cells.

5. The method according to claim 2, wherein said step of providing a composition comprises providing a composition comprising 1.5-3.0% xylitol and 0.9-1.8% glycerol.

6. The method according to claim 2, wherein said step of providing a composition comprises providing a composition comprising 1.8-3.6% myoinositol and 0.9-1.8% glycerol.

7. The method according to claim 2, wherein said step of providing a composition comprises providing a composition comprising 1.8-3.6% mannitol and 0.9-1.8% glycerol.

8. The method according to claim 1, wherein said step of providing a composition comprises providing a composition comprising 1-2% xylitol, 1.5-3% mannitol, and 0.9-1.8% glycerol.

9. The method according to claim 1, wherein said step of providing a composition comprises providing a composition comprising at least one viscosity enhancing agent.

10. The method according to claim 1, wherein said step of providing a composition comprises providing a composition comprising at least one pharmaceutically active agent.

11. The method according to claim 1, wherein said step of providing a composition comprises providing a composition comprising at least one pharmaceutically acceptable excipient, additive or preservative.

12. The method according to claim 1, wherein said step of providing a composition additionally comprises providing a composition characterized by a pH of between 4.0 and 6.0.

13. A method of treating a condition selected from the group consisting of: cell damage caused by preservatives, detergents or drugs, used in topical pharmaceutical cosmetic or veterinary compositions; and, irritation of the mucous membranes of the eye caused by allergies, chemical pollutants, or physical irritants and manifested by redness, tearing, burning, discomfort or itching; said method comprising: providing a composition consisting essentially of an aqueous solution of: 5-18% xylitol, myoinositol or mannitol or any combination thereof;

2. 5-10% glycerol and/or urea; optionally, at least one component selected from the group consisting of pharmaceutically acceptable excipients, pharmaceutically acceptable additives, preservatives, and viscosity enhancing agents; said aqueous solution containing less than 0.01% inorganic salt; and, administering topically the composition to a patient in need thereof.

14. The method according to claim 13, wherein said step of providing a composition comprises providing a composition comprising: a component selected from the group consisting of: an aqueous solution of 5-18% xylitol and 5-10% urea; an aqueous solution of 5-18% myoinositol and 5-10% urea; and, an aqueous solution of 5-18% mannitol and 5-10% urea; optionally, at least one component selected from the group consisting of pharmaceutically acceptable excipients, pharmaceutically acceptable additives, preservatives, and viscosity enhancing agents; said aqueous solution containing less than 0.01% inorganic salt.

15. The method according to claim 13, wherein said step of providing a composition additionally comprises providing a composition characterized by a pH of between 4.0 and 6.0.

16. The use of a composition comprising an aqueous solution of: xylitol, myoinositol or mannitol or any combination thereof; and, glycerol and/or urea; said aqueous solution containing less than 0.01% inorganic salts; in a topical treatment of mucous cells or skin cells.

17. The use according to claim 16 in a topical treatment of mucous cells.

18. The use according to claim 16 in a topical treatment of skin cells.

19. The use according to claim 16, wherein said composition is characterized by a pH of between 4.0 and 6.0.

20. The use of a composition consisting essentially of an aqueous solution of: 5-18% xylitol, myoinositol or mannitol or any combination thereof; 2.5-10% glycerol and/or urea; optionally, at least one pharmaceutically acceptable excipient, additive, preservative, or viscosity enhancing agent; said aqueous solution containing less than 0.01% inorganic salt; in a topical treatment of a condition selected from the group consisting of cell damage caused by preservatives, detergents or drugs, used in topical pharmaceutical cosmetic or veterinary compositions; and, irritation of the mucous membranes of the eye caused by allergies, chemical pollutants, or physical irritants and manifested by redness, tearing, burning, discomfort or itching.

21. The use according to claim 20 in a topical treatment of cell damage caused by preservatives, detergents or drugs, used in topical pharmaceutical cosmetic or veterinary compositions.

22. The use according to claim 20 in a topical treatment of irritation of the mucous membranes of the eye caused by allergies, chemical pollutants, or physical irritants and manifested by redness, tearing, burning, discomfort or itching.

23. The use according to claim 20, wherein said composition is characterized by a pH of between 4.0 and 6.0.

Description

EXAMPLES

Example 1

Moisturizing Eye Drops

[0035]

TABLE-US-00001 Sodium hyaluronate 0.03 gm.  Povidone 2.0 gm. Glycerol 1.0 gm. Mannitol 3.2 gm. Cetrimide 0.01 gm.  NaOH q.s. to pH 7.0 H.sub.2O to 100 ml.

Example 2

Moisturizing Eye Drops

[0036]

TABLE-US-00002 Glycerol 1.3 gm. Xylitol 2.2 gm. Benzalkonium Chloride 0.01 gm.  NaOH q.s. to pH 7.0 H.sub.2O to 100 ml.

Example 3

Moisturizing Eye Drops Unit Dose Form for Single Application

[0037]

TABLE-US-00003 Sodium hyaluronate 0.03 gm.  Povidone 2.0 gm. Glycerol 1.0 gm. Myoinositol 3.2 gm. Cetrimide 0.01 gm.  NaOH q.s. to pH 7.0 H.sub.2O to 100 ml.

Example 4

Moisturizing Anti-Inflammatory Eye Drops

[0038]

TABLE-US-00004 Glycerol 1.3 gm. Xylitol 2.2 gm. Sodium diclofenac 0.1 gm. NaOH q.s. to pH 7.2 H.sub.2O to 100 ml.

Example 5

Moisturizing Anti-Inflammatory Eye Drops Unit Dose for Single Application

[0039]

TABLE-US-00005 Glycerol 1.0 gm. Mannitol 1.6 gm. Xylitol 1.6 gm. Sodium diclofenac 0.1 gm. NaOH q.s. to pH 7.2 H.sub.2O to 100 ml.

Example 6

Moisturizing Gel for Skin

[0040]

TABLE-US-00006 Glycerol 8.0 gm. Mannitol 5.0 gm. Urea 5.0 gm. Glycine 5.0 gm. Methylparaben 0.1 gm. Propylparaben 0.01 gm.  Polyacrylate 980 adjusted to pH 4.5 0.7 gm. H.sub.2O to 100 ml

Example 7

Moisturizing Gel for Skin

[0041]

TABLE-US-00007 Glycerol 10.0 gm.  Xylitol 8.0 gm. Urea 5.0 gm. Glycine 5.0 gm  Methylparaben 0.1 gm. Propylparaben 0.01 gm.  Polyacrylate 980 adjusted to pH 4.5 0.7 gm. H.sub.2O to 100 ml

Example 8

Moisturizing Gel for Skin

[0042]

TABLE-US-00008 Glycerol 8.0 gm. Myoinositol 4.5 gm. Xylitol 3.5 gm  Urea 5.0 gm. Glycine 5.0 gm. Methylparaben 0.1 gm. Propylparaben 0.01 gm.  Polyacrylate 980 adjusted to pH 4.5 0.7 gm. H.sub.2O to 100 ml

Example 9

[0043] Moisturizing Gel with Phytosphingosine Suspension for Skin

TABLE-US-00009 Glycerol 8.0 gm. Xylitol 7.0 gm Polyethylene glycol 3350 2.0 gm Phospholipids 0.25 gm Phytosphingosine in suspension 0.2 gm. Polyacrylate 980 or 974 1.0 gm. Methylparaben 0.1 gm. Propylparaben 0.01 gm. H.sub.2O to 100 ml

[0044] Suitable preservatives, suspending agents, excipients and other additives can be incorporated. The preferred pH (to be adjusted) of the compositions of examples 6 to 9 is pH 4.0 to 6.0.

Methods:

Human Studies

[0045] a. 23 dry eye patients received in both eyes 5 drop of Fluorescein-Novesin mixture. After 30 seconds the right eye was treated with 1 drop from the treatment bottle. The patient was asked to blink 2-3 times, then the fluorescein BUT was measured. Afterwards the left eye was treated with 1 drop from the Control bottle, the patient was asked to blink 2-3 times. Then the fluorescein BUT was measured.

[0046] Materials: Control—0.9% NaCl (saline); surface tension 72 mN/m

[0047] Treatment=as Control+0.002% Tween 80; surface tension 49 mN/m (dyn/cm)

[0048] Results:

TABLE-US-00010 Left eye - Control Right eye - Treatment 7.7 ± 0.4 sec 12.7 ± 1.5 sec Paired differences 5.0 ± 1.4 sec (p~0.001)
b. Examination of Treatment, of Conjunctival Damage, in Dry Eye Syndrome.

[0049] One month study, use of the eye drops three times a day:

[0050] Left eye=essentially isotonic Glycerol (marketed product) (L).

[0051] Right eye=50% isotonic Glycerol+50% isotonic Xylitol (R).

TABLE-US-00011 Rose Bengal Score (Oxford Scale) Before One month Patient No. R L R L 1 3 3 1 2 2 2 3 0 2 3 2 3 0 2 4 3 3 1 2 5 1 3 1 2 mean 2.2 3.0 0.6 2

TABLE-US-00012 Personal Satisfaction Before One month Patient No. R L R L 1 0 0 2 1 2 0 0 2 1 3 0 0 2 1 4 0 0 2 1 5 0 0 2 1 mean 0 0 2 1 0 = not satisfied 1 = better 2 = much better

[0052] Essentially the same results were obtained, by using Myoinositol instead of Xylitol.

Animal Studies

[0053] a. 3 rabbits were treated for 3 months twice daily with eye drops, adjusted to pH 7.0. The average cross section of the epithelial corneal cells and the percentage of damaged cells were evaluated by electromicroscopy.

TABLE-US-00013 Cross section Damaged Treatment in μ.sup.2 cells % None 590 16 0.9% NaCl 542 28 0.01% Benzalkonium Chloride + 0.9% NaCl 538 29 0.01% Benzalkonium Chloride + 2.5% 699 14 Glycerol 0.01% Cetrimonium Bromide + 0.9% NaCl 591 27 0.01% Cetrimonium. Bromide + 2.5% Glycerol 625 19 0.1% Na.sub.2 EDTA + 0.9% NaCl 531 15 0.1% Na.sub.2 EDTA + 2.5% Glycerol 616 17 0.025% Polysorbate 80 + 0.9% NaCl 440 25 0.025% Polysorbate 80 + 2.5% Glycerol 600 18 2.5% Glycerol 605 17 0.01% Benzalkonium Chloride + 4.5% Xylitol 554 19 0.01% Benzalkonium Chloride + 5.4% 584 19 Myoinositol 0.01% Benzalkonium Chloride + 5.4% 570 21 Mannitol

[0054] b. Prevention of Dry Skin (Irritation) Caused by 2% Sodium Lauryl Sulphate (Method: Modification of Sagiv et al. Skin Res. Technol. 6, 37, 2000)

[0055] Daily topical application of molar or isotonic polyols in deionized water, half an hour before application of 2% sodium lauryl sulphate in deionized water (SLS), on one of the two shaved flanks of guinea pigs, for three consecutive days, was examined in order to prevent SLS induced “Dry skin syndrome”. Skin dryness and erythema were measured four days later in vivo:

TABLE-US-00014 Name Concentration Corneometer Mexameter Glycerol .sup. 1M 5.5 ± 1.9 (E) 4.1 ± 3.3 (E) Glycerol 0.3M  25.9 ± 1.7 (NE)  27.4 ± 2.2 (NE) Xylitol 0.3M 2.8 ± 1.0 (E) 0.2 ± 0.4 (E) Myoinositol 0.3M 0.3 ± 1.1 (E)  5.1 ± 0.9 (E?) Mannitol 0.3M 2.2 ± 1.6 (E) 1.7 ± 0.5 (E)

[0056] Treatment of Dry Skin Induced by 2% Sodium Lauryl Sulphate (Sagiv et al, Skin Res. Technol. 6, 37, 2000)

TABLE-US-00015 Name Concentration Corneometer Mexameter Glycerol .sup. 1M 3.2 ± 1.7 (E) 1.5 ± 3.0 (E) Glycerol 0.3M 3.3 ± 2.3 (E)  21.2 ± 0.9 (NE) Xylitol 0.3M 1.3 ± 1.1 (E) 1.2 ± 0.9 (E) Myoinositol 0.3M 0.7 ± 1.8 (E) 1.0 ± 0.9 (E) Mannitol 0.3M 1.4 ± 0.6 (E) −0.1 ± 0.3 (E)  E = Effective = No significant difference or little difference between the treated and untreated side. NE = Not effective = Very much and significant difference between the treated and untreated side.

[0057] It was claimed that to be sure in efficacy both the “Corneometer” and “Mexameter” measurements have to be “Effective” (Sagiv et al. Skin Res. Technol. 6, 37, 2000).

[0058] It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative examples and that the present invention may be embodied in other specific forms without departing from the essential attributes thereof, and it is therefore desired that the present embodiments and examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.