Composition and dressing with nitric oxide

a technology of nitric oxide and composition, applied in the field of composition and dressing with nitric oxide, can solve the problems of short half-life, inability to target or selectivity, and inability to achieve high concentrations of toxic substances,

Inactive Publication Date: 2011-11-17
PQ SILICAS UK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

One object of the present invention, amongst others, is to provide a composition, for use in skin dressings, which provides delivery of nitric oxide to the skin over an extended period of time. An object of the invention is to provide a dressing composition having an anti-pathogenic effect. Another object of the invention is to provide a safe and convenient topical, targeted delivery system for nitric oxide, which overcomes some of the problems in the prior art.

Problems solved by technology

The delivery of NO as a gas is fraught with problems, and its short half-life, once released into the body, is a further problem in its use as for treatment.
NO is toxic in high concentrations and may have negative effects if applied in excessive amounts to the body.
The various known NO releasing agents have problems such as lack of targeting ability or selectivity, potentially carcinogenic or toxic by-products, need for specific activation, difficulties in manufacture or difficulties with controlled release.

Method used

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  • Composition and dressing with nitric oxide
  • Composition and dressing with nitric oxide
  • Composition and dressing with nitric oxide

Examples

Experimental program
Comparison scheme
Effect test

example 1

A zinc ion-exchanged zeolite was prepared by slurrying 40 g of a commercial sodium zeolite A (zeolite Doucil 4A from PQ Silicas UK Ltd.—mean particle diameter typically 3 to 5 μm) in 4 litres of 0.05 molar zinc acetate solution for 24 hours. The resulting ion exchanged zeolite was filtered, washed with water and dried at 300° C. under vacuum for 3 hours.

Referring to formula IV, corresponding to formula III above but with M′=Zn and hence g=2, M=Na, and with x=2 for zeolite 4A, y=0.

w(ZnO).z(Na2O).Al2O3.xSiO2  IV

the resulting zeolite as measured by XRF had w 0.65 and z=0.58.

The dry zeolite was loaded with nitric oxide by exposure to dry NO gas at a pressure of 2 bar at 25° C. Excess NO was allowed to escape and the NO loaded zeolite was flushed with a flow of dry nitrogen gas to remove any NO which was physisorbed rather than adsorbed.

NO levels were measure using a Sievers NOA 280i chemiluminescence NO analyser. The NO was released by passing nitrogen gas of known humidity over the loa...

example 2

A homogeneous ointment was prepared from 6.6 grams of Zeolite-NO prepared as for Example 1 and 13.4 grams of Emulsifying Ointment (BP) supplied by Boots Company PLC (50% by weight white soft paraffin BP and 20% by weight liquid paraffin BP with 30% by weight emulsifying wax). The resulting ointment is referred to below as “Ointment A”.

A hydrocolloid preparation was prepared from 5 grams of Blanose 7H4FX (Polyisobuthylene) and 1 gram of SCMC blended with 4 grams of the Zeolite-NO of Example 1 in a dry nitrogen atmosphere. The hydrocolloid preparation is referred to below as “Hydrocolloid B”

The rate of release of NO from samples of Ointment A and Hydrocolloid B levels were measured using a Sievers NOA 280i chemiluminescence NO analyser. In each case, a sample of either 0.4 grams of Ointment A or 0.3 grams of Hydrocolloid B was placed in a sealed glass vial (internal volume 4.55 mls), so that in each case the amount of NO initially in the vial was approximately the same for Hydrocolloi...

example 3

Zeolite 1

4 grams of zeolite 4A (Doucil 4A from PQ Silicas UK Ltd.—mean particle diameter 3 to 5 μm) was slurried in 400 mls of 0.05M zinc acetate solution for 24 hours. The slurry was then filtered, washed and dried. The resultant product was analysed by XRF (x-ray fluorescence) analysis.

Zeolite 2

This example is as for Example A 1 but zinc sulphate was used as the soluble salt and a more concentrated solution and shorter exchange time were used. 22.5 grams of zinc sulphate heptahydrate was dissolved in 60 grams of deionised water. 13 grams of zeolite 4A was first slurried in 22.5 grams of deionised water. The pH of the slurry was 11.4. The zeolite slurry was then added to the zinc sulphate solution. The mixture was slurried for 30 minutes washed and dried. The product was analysed by XRF.

Zeolite 3 (According to the First Method)

The procedure of example B was repeated, except that prior to adding the zeolite slurry to the zinc sulphate solution, the pH of the zeolite slurry was reduc...

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Abstract

A dressing composition for use as a skin dressing comprises an elastomeric-adhesive composition, and a zeolite comprising releasably adsorbed nitric oxide. The zeolite may comprise a transition metal cation such as Co, Fe, Mn, Ni, Cu, Zn, Ag or a mixture thereof as an extra-framework metal cation, preferably Zn. The elastomeric adhesive composition may be a hydrocolloid-adhesive composition comprising, hydrocolloid and elastomer. The dressing composition releases nitric oxide, which may have beneficial effects, when used on wounds or moist skin, with a substantially constant release rate over a long period of time. A dressing including a layer of the dressing composition has a backing layer and may have a release liner removably attached to the skin-contacting surface of the dressing layer.

Description

INTRODUCTIONThe present invention relates to compositions for use in dressings for application onto skin, for instance as dressings for the treatment of wounds, pre-treatment of skin, ostomy seals, neuropathy treatment, treatment of fungal disorders, transdermal drug release and the like. In particular, it relates to compositions comprising elastomeric adhesive and zeolite wherein the zeolite comprises releasably adsorbed nitric oxide.BACKGROUNDThe 1998 Nobel Prize for Physiology or Medicine was awarded in 1998 for the discovery that endogenous nitric oxide is responsible for endothelium-dependent smooth muscle relaxation. Nitric oxide (NO) is also a vasodilator, and increases blood flow through blood vessels. Nitric oxide is also an important factor in controlling and preventing platelet adhesion in the blood and may consequently act against thrombus formation. It also plays an important role in the immune system, inflammatory reaction mechanisms and in neurotransmission.The delive...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61L15/18A61K33/34A61K33/32A61K33/38A61K33/26A61K33/30A61P17/02A61P15/10A61P15/00A61P9/08A61P17/00A61P25/00A61P29/00A61K33/00A61K33/06
CPCA61L15/18A61L15/44A61L15/58A61L2300/114A61L2300/602A61L26/0004A61L26/0052A61L26/0066A61L2300/802A61P15/00A61P15/10A61P17/00A61P17/02A61P25/00A61P29/00A61P9/08A61P3/10
Inventor ARAYA, ABRAHAMMINIHAN, ALAN REGINALDROBBINS, PAUL MATTHEWBRODERICK, SONYA THERESAWARING, MICHAEL J.
Owner PQ SILICAS UK
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