WO1992010933A1

WO1992010933A1 - Improvements in and relating to articles providing a vapour phase activity

Info

Publication number: WO1992010933A1
Application number: PCT/GB1991/002293
Authority: WO
Inventors: Alfred Emil Lauchenauer
Original assignee: Institut Fur Antibakteriologie Ifa; Evans, David, Charles
Priority date: 1990-12-24
Filing date: 1991-12-20
Publication date: 1992-07-09
Also published as: AU9132491A; GB9028057D0

Abstract

An article which is capable of dispensing an active agent in the vapour phase, which article comprises a matrix having, at least in part, an active agent dispersed therethrough; wherein the rate of release of said agent from a surface of the matrix is dependent upon the rate of diffusion of the agent through the matrix and the rate of effusion of the agent from said surface.

Description

I__PROV__MENTS IN AND RELATING TO ARTICLES PROVIDING A VAPOUR PHASE ACTIVITY

DESCRIPTION

The present invention relates to articles providing a vapour phase activity and has particular reference to articles having a controlled release rate of a active agent.

It is generally well-known to treat articles with an active agent which is volatile at room temperature and pressure and thus imparts to the article a vapour phase activity. Particular applications for this treatment include the treatment of articles with substances having a injurious effect on microorganisms such, for example, as biocidial agents, fungicides and pesticides. It is also known to treat articles with insecticides such that, over a period of time, the insecticide is dispensed as a vapour into the atmosphere thereby to maintain the region surrounding the article free from insects. Articles which are commonly treated with such active agents include shoe insoles, carpets, floor mats and the like. The active agent can be applied to the article in solution by spraying or painting the solution onto the article and, where the article is a woven or non-woven textile material, the active agent solution forms a film or layer on the yarns or filaments of the material.

Where the article to be treated with active agent is a foamed article such as a shoe insole, the article can be saturated with a solution containing the active agent thereby to fill the interstices within the foam with the active agent solution.

In such articles treated with active agent solution, however, the active agent is held in the liquid phase and, thus, the rate of dispensing of active agent into the vapour phase is dependent only upon the area of contact between the active agent and the tmosphere. The rate of delivery of active agent, therefore, exhibits a max-unum when the article is first exposed to the atmosphere e.g. by unwrapping, and declines over a period of time. In the particular examples of shoe insoles and carpets, while for a short time the amount of active ingredient is sufficient to have a positive biocidal, fungistatic or bacteriostatic effect, this declines very rapidly having regard to the fairly rigorous physical conditions of compression and expansion, and to the fairly humid conditions produced in a shoe while it is being worn. In the case of other treated articles, the decline in the rate of release of active agent may be further exacerbated by wetting or cleeuiing. Furthermore, the active agent is delivered from the treated article into the vapour phase whether the article is in use or not.

According to one aspect of the present invention, therefore, there is provided an article which is capable of dispensing an active agent in the vapour phase, and comprising a matrix having, at least in part, an active agent dispersed therethrough; wherein the rate of release of said agent from a surface of the matrix is dependant upon the rate of diffusion of the agent through the matrix and the rate of effusion of the agent from said surface. The article comprising a matrix in accordance with the present invention may include em active agent having a preventative, and preferably curative, effect on microorganisms , not only when such microorganisms are in direct contact with the matrix containing the active ingredient, but also in the vapour phase. Active agents which may be incorporated into the matrix, in accordance with the present invention, include bacteriocides, fungicides, insecticides, all of which have a vapour pressure sufficient for the active agent to be effective in the vapour phase.

The active agent may be a biocide to prevent deleterious effects of microorganisms, e.g. fungi decomposition of perspiration, and to prevent odour formation. Deodourizing agents of the type well known in the prior art, odour destroying agents and medicated agents, such as those suitable for the prevention and curing of athletes foot and the like, are preferred.

The diffusion rate of the active agent through the matrix may be influenced by the chemical composition of the matrix. In particular, the inteπnolecular structure of the matrix material, such as the degree of cross-linking between the polymer molecules and/or the degree of swelling of the matrix by the absorption of water may effect the rate of diffusion of the active agent.

The rate of diffusion of the active agent through the matrix material may be controlled by additives to the matrix. Additives which may be included in the matrix include materials which form adducts with the agent (e.g. by bonding, or by complex or salt formation), thereby decreasing the rate of diffusion of the agent through the matrix; anionic or cationic additives; compounds which form salts with the active agent; or additives which repell the agent, thereby facilitating diffusion through the matrix.

Carriers for the agent may be added to the matrix to assist diffusion of the agent through the matrix.

The rate of effusion of the active agent from a surface of the matrix may be influenced by the structure and configuration of the surface and by the rate of diffusion of the active agent through the matrix to the surface. Other factors influencing the rate of effusion of the agent from the surface of the matrix include the size of the surface of the matrix relative to the bulk of the matrix material, the circulation of air over the matrix surface where effusion takes place, and reabsorption of the active agent onto the matrix surface.

The matrix may form a slow release system for the active agent to dispense the active agent at a substantially constant rate over an extended period of time, and may be formed from polymeric materials such as copolymers and mixed polymers of vinylic, acrylic, and acetate monomers, halogenated vinylic and acrylic monomers, and polyurethanes. Alternatively, the matrix material may be formed from natural or synthetic latex or rubber. In one embodiment of the present invention, the matrix material is a stable gel produced in accordance with United States Patent Specification No. 4,491,479.

The matrix containing the active agent may be a shaped 3 dimensional article, a film, a laininate, a foam or, alternatively, the matrix may be printed, coated or padded onto a suitable substrate.

The article, in accordance with the present invention, may be a self supporting film or layer which includes, at least in part, the matrix material, or the article may be a sheet of foamed rubber or latex matrix layer. Alternatively, an article in accordance with the present invention may be a woven or non-woven textile material to which the matrix containing the active agent is printed coated or padded, or may be a foamed polymer having interstices occupied by the matrix material having the active agents dispersed therethrough.

In a further variation of the present invention, the article can be a laminated material comprising a resilient, flexible or self-supporting film or layer of matrix material and one or more layers of non-active agent containing material. An article in accordance with the present invention, may comprise one or more layers of matrix material containing active agent. Particular e___bod_L__-ents of the present invention include shoe insoles and floor coverings such as carpets, mats and the like.

A shoe insole, may comprise a shaped, resilient matrix layer having upper and lower layers juxtaposed the resilient layer. Preferably the upper and lower layers are bonded around the peripheral edge of the shaped resilient layer in order to encapsulate the same. The upper and lower layers may be wholly permeable, or partially permeable, to air and vapour; the upper and lower layers may comprise wholly, or in part, a semi-permeable membrane or a cellular structure. The resilient layer preferably has a thickness suitable to provide comfort in use. In this embodiment of the present invention, the resilient layer may be a resilient, self-supporting matrix layer having the active ingredients dispersed therethrough or, alternatively, may be a foamed polymeric material having the matrix disposed in the interstices of the foam. The surface of the insole may be formed of a textile material; the resilient matrix layer may be formed from a porous material provided with the slow-release system contained therein or attached thereto; the lower layer of the insole may be a layer of low porosity. Preferably, the resilient matrix layer should be sufficiently durable to provide a wear life at least over the period of dispensing of the active ingredient from the matrix.

In the case of carpets and mats, the matrix layer may be a resilient, self-supporting layer or a sheet of foamed polymeric material having the matrix disposed in the interstices of the foam, and laminated to the underside of the textile carpet material.

In a variation of the present invention, the matrix material may be supplied as a spray or aerosol for applying the matrix to an article. Where the article treated is a woven or non-woven textile material, the matrix may form a yarn coating; alternatively, where the matrix is sprayed onto a surface of low porosity, the matrix may form a thin surface film or lamina. The matrix, in accordance with the invention, may include an indicator to provide an indication of the amount of the active agent still present in the matrix i.e. to indicate when the article comprising the matrix requires replacement, i.e. when the effective dispensing of the active agent from the matrix of the article has ceased.

The rate of release of active agent from the matrix, according to the present invention, may be promoted by conditions prevalent during use of the article such, for example, as humidity, temperature and pressure.

Thus, in one embodiinent of the present invention, an article may be stored in a environment of low humidity and the matrix composition be selected such that in such any environment, the rate of release of active agent from the matrix is low or almost zero. In use, in an area of relatively higher humidity, however, the rate of release of active agent from the matrix of the article may be increased by absorption of water into the matrix wherein the water may act as a carrier in the matrix for the agent and/or the water may result in swelling of the matrix material. Where the article in accordance with the invention is a shoe insole or a floor covering, which is subject, in use, to repeated compression and expansion by walking on the article, the article may include a resilient porous or foamed layer which, under conditions of repeated compression and expansion, produces a "pumping" effect which serves to enhance the circulation of the active agent in the vapour phase. In the particular case of a shoe insole, where the active agent may be a fungicide for the treatment of e.g. athletes foot, such a pumping motion may advantageously be used to effect circulation of the vapour phase active agent between the toes of the shoe wearer.

Where an article, in accordance with the present invention, is used in an environment of relatively high temperature, the high temperature may increase the rate of diffusion and effusion of the active agent through and from the matrix. In a preferred embodiinent of the present invention, the rate of diffusion and effusion may be strongly temperature dependent and, thus, when the article is stored in a relatively cold environment the rate of dispensing of the active agent from the matrix is low.

The following is a description by way of example only of the methods of carrying the invention into effect:-

EXAMPLE 1

A shoe insole was made having: (a) a surface layer consisting of a woven cotton fabric, (b) a porous inner layer providing bulk and cushioning properties, and made of a polyurethane foam 5 millimetres thick having a density of 150 to 200 grams per litre and a compressibility such that it was compressed by the feet of the wearer of the shoe (standing) by 40% to 60% in the areas of highest pressure, and (c) a bottom layer consisting of a nonwoven fabric of nylon fibres substantially orientated parallel to the length of the insole.

The cotton surface layer (a) was treated with a solution containing 50 grams per litre of Elotex WS 45, which is a highly hydrophobic polyvinylacetate. to prevent diffusion of aqueous solutions into the porous material of the inner layer. The purpose of this treatment is to prevent wetting of the inner layer in case the cotton surface layer has adsorbed and stored liquid perspiration. The Elotex solution also contained 30 grams per litre of an agent capable of destroying odours and preventing the growth of micro-organisms such as bacteria and fungi (Synodor, 50% aqueous solution) .

The porous and bulking inner layer was treated with a solution containing 100 grams per litre of xilix, which is an agent having biocidal action in the solid, liquid and vapour phase. The aqueous solution also contained an acrylic binder. The purpose of the binder is to hold the biocidal agent in place in a relatively high concentration, and to adjust the rate of release to the desired level.

In another test, the biocidal agent was applied from a foamed aqueous dispersion also containing an acrylic binder capable of being gelled in a foam configuration. The application of the foamed formulation was by spreading a layer of the foam to a thickness of 7 millimeters upon the surface of the polyurethane foam sheet (which travelled on a screen-like conveyor belt); sucking the foam into the polyurethane foam by passing it over a vacuum slot; and thereafter gelling the acrylic binder in foamed form.

The foamed configuration of the binder holding the biocidal agent was found to provide a larger surface area of the slow release interface and hence better control over release rates.

The three components of the insole were laminated together and cut into pieces of proper size and shape.

EXAMPLES 2 TO 18

Further examples of the invention are set forth in Table 1 below:

TABLE 1 Continued

Non aqueous gel FP cast in form of corrugated sheet to extend release period

Polyurethane FP yarn coating, Dispersion yarn integrated into web by weft insertion technique

Examples 19 to 35

Further examples of the invention are set forth in Table 2 below with reference to the following explanatory notes:-

(1) Matrix material

Formulations I, and V

A matrix material in the form of a film (thickness 2 mm) containing 10% of Fenpropimorph was prepared from an aqueous dispersion containing:-

800 parts of an acrylic dispersion, such as that coπanerically available under the trade name Primal LE 1126

140 parts of water

80 parts of Fenpropimorph (Maag) (emulsified)

Formulation II:

A matrix material in the form of a film was prepared as per Formulations I and V, but a polyurethane dispersion such as that commerically available under the trade name Wi__mington Urethane was used instead of an acrylic dispersion.

Formulation III:

A film consisting of a non- aqueous gel was prepared according to US Patent No. 4,491,479 as follows:

100 grams of Natrosol 250 HHR were stirred into 900 grams of anchydrons glycerine, to which 100 grams of Fenpriporrrorph had previously been added. The mixture was then heated to about 100°C and became more viscous due to the Natrosol gradually dissolving and forming a glycerine gel. When the viscosity had reached a level suitable for casting a film onto a release film, such as a fluorocarbon coated textile belt, a film 3 millimeters thick was cast. To complete gel formation, the film on the belt was heated to 150°C until all Natrosol has dissolved (about 2 minutes) . Formulation IV:-

A matrix material in the form of a film was prepared as described for Formulations I and V, but a polyvinyl acetate dispersion was used instead of an acrylic dispersion.

In particular Examples 19 to 36 were prepared as follows:-

Example 19, Formulation I: as described above

Example 20, Formulation I b: as I, but crosslinker (Knittex LE, 100 parts) and crosslinker catalyst added, (13 parts diammonium phosphate in 67 parts of water) .

Example 21, Formulation I b. as I, but cationic surfactant added (65 parts of Polyavin) Example 22, Formulation I c: As I, but anionic surfactant added (65 parts of Nekal BX 10%)

Example 23, Formulation I d: As I, but agent showing down diffusion of aqueous media through porous substrates like films added (100 parts of Elotex WS 45, Ebnother) .

Example 24, Formulation II: As described above.

Example 25, Formulation III As described above.

Example 26, Formulation III a: As Formulation III, except that 10 g/litre of Nekal BX (anionic agent) were added to the glycerine. Example 27, Formulation III a: As Formulation III, except that lOg of Polyavin (cationic active agent) were added to the glycerine.

Example 28, (Formulation II c): Same as Formulation III, except that 50 g of pine oil (bactericide with vapour phase action) were added to the glycerine.

Example 29: (Formulation IV): As described above.

Example 30: As Formulation I, but the (Formulation V b): matrix was foamed by blowing air through a filter plate (Nr.2) immersed in the dispersion. Example 31 (Formulation Vb) As Formulation I, but the dispersion was padded onto a terry towel fabric.

Example 32 (Formulation I e) As formulation I, but 10% of β-pinene (bacteriostatic active in vapour phase) added in emulsion foxa instead of Fenpropimorph.

Example 33: (Formulation I f) As Formulation I e, with thymol instead of ^β-pinene (thymol is a vapour-active bacteriostatic agent) .

Example 34 (Formulation I g): As Formulation I e, with turpentine oil substituted for β-pinene static active in the vapour phase). Example 35: (Formulation I h) As Formulation I, but Dienochlor ( "Pentac^M, Sandoz substituted for Fenpropimorph; Pentac is an akaricide and is active in the vapour phase) . [The vapour phase action on mites feeding on freshly planted beans was used as criterion for effects achieved].

Example 36: (Formulation I): As Formulation I, but the matrix was cast as a film with a "waffle-like" structure.

(2) FPM = Fenpropimorph, which is commercially available from Maagofdielsdorf, Switzerland;

Dienochlor ("Pentac") is commercially available from Sandoz of Basel, Switzerland. (3) Effect observed:

In each example, the film was placed in a stoppered 100 cc glass jar, together with a petri dish containing pre-germinated Trichophyton menta grophytes, or microsporum gypsenus La 2397 and Thrichphyton baton-rongei La 792, on Sabou rand agar disposed remote from the film. The vapour phase active ingredient present in the formulation could, thus, act on the fungus or bacteria only in the vapour phase, and never by direct contact.

Examples 19 to 31, 36

The effect of FPM in the vapour phase on Trichophyton menta grophytes (causing Tinnea pedis, athlete's foot) in a closed vessel was measured, the fungus having been pre-germinated and then exposed to vapour given off by the substrate containing FPM. "100%" means total control; "0%" means no influence at all on fungus growth. Examples 32 to 34

The influence of the vapour phase action of the agents listed on microsporum gypsenus La 2397 and Thrichphyton baton-rongei La 792 was measured. The effect on the growth of the bacteria after exposure to the vapour of the agent was the criterion by which the influence was measured. ("100%" = no growth, 0% growth in absence of vaporous agent) .

TART.F, 2 Example 19 20 21 22 23 24

(a) Matrix I la lb Ic Id II material (1)

(b) Vapour Phase- FPM FPM FPM FPM FPM FPM active active Agent (2)

(c) Concentration 10% 10% 10% 10% 10% 10% of (%) of (b) on dry film weight

(d) Config¬ uration acrylic acrylic acrylic acrylic acrylic acylic film film film film film film (crosslinked)

(e) Con¬ centration (mg) of (b) 50 50 per litre of air

(f) Interaction 10 10 10 10 10 10 time (h)

(g) Effect fungi- fungi¬ fungi¬ fungi¬ fungi¬ fungi¬ expected cide cide cide cide cide cide

(h) Effect observed (3) 30% 100% 100% 100% 100% 100% Example 25 26 27 28 29

(a) Matrix III Ilia Illb IIIc IV material

(b) Vapour Phase- FPM FPM FPM FPM FPM active Agent

(c) Concentration 10% 10% 10% 10% 10% of (%) of

(b) on dry film weight TABLE 2 Continued

(d) Configuration film film film film film

(non (non (non aqueous aqueous aqueous gel) gel) gel)

(e) Concentration 50 5 5 50 (mg) of (b) per litre of air

(f) Interaction time (h) 10 10 10 10 10

(g) Effect expected fungi- fungi¬ fungi¬ fungi¬ fungi¬ cide cide cide cide cide

(h) Effect observed 100% 100% 100% 100% 100% Example

30 31 32 33 34 35 36

(a) Matrix material V a V b I I e I f I h I

(b) Vapour FPM FPM Beta Thymol tur- Dieno- FPM Phase- Pinen pentine chlor active oil ("Pentac' Agent

(c) Con¬ centration 10% 10% 10% 10% 10% 10% 10% of (%) (b) on dry film weight

(d) Con¬ figuration foamed padded film film on web onto with terry waffle¬ towel like structur

(c) Con¬ centration 50 50 50 50 50 (mg) of (b) per litre of air

(f) Inter¬ action time (h) 10 10 24 24 24 10 TABLE 2 Continued

(g) Effect fungi- fungi- bacteri- bacteri- bacteri- akari- fungi expected cide cide cide cide cide cide cide

(h) Effect 80% 80% 100% 100% 100% 90% 100 observed

The present invention seeks to prolong the period during which a quantity of treatment agent can be dispensed in the vapour phase by providing a slow release system for the release of the treatment agent at a substantially constant, active level over an extended period of time; further the invention seeks not to permit the exponential decay of the release rate of active agent vapour as has been experienced in the prior art.

Furthermore, the rate of diffusion of the active agent through the matrix, and the rate of effusion from a surface of the matrix, in accordance with the present invention as herein described, may be dependent upon the ambient conditions of humidity, temperature and/or pressure in the environment of use of the article and, thus, an article may be provided wherein active agent is substantially only released when the article is in use, and, when the article is not in use, the rate of delivery of active agent from the matrix is relatively low. The present invention also comprehends inter alia the following articles in which a matrix layer containing the active agent dispersed therethrough, in accordance with the invention, may be advantageously employed: Insoles for use in militar /heavy duty footwear, sports shoes, such as for use in professional sports, jogging etc, and everyday-wear shoes, floor or wall coverings, carpets, sleeping bags, packaging material and hospital supply articles.

In the case of shoe insoles, the active agent may be a fungicide used, for instance, to prevent or heal athletes foot, and the repeated compression and expansion of the resilient insole material can be utilized to provide a pumping action thereby to facilitate circulation of the active agent vapour around the inside of the shoe to contact skin areas not directly in contact with the insole e.g. between toes.

In the case of an insecticide active agent, it has been found that the control of insects is much more effective if a relatively small quantity of ^■ . 1 insecticide in the vapour phase is active over prolonged periods of time, instead of agents not active in the vapour phase which have to be applied to surfaces from time to time, and are effective only if in direct contact with the insects to be elduninated.

Claims

CLAIMS:

1. An article for dispensing an active agent in the vapour phase, which .article comprises a matrix having, at least in part, an active agent dispersed therethrough; wherein the rate of release of said agent from a surface of the matrix is dependant upon the rate of diffusion of the agent through the matrix and the rate of effusion of the agent from said surface.

2. An article as claimed in claim 1, wherein said active agent has a vapour pressure sufficient for the active agent to be effective in the vapour phase.

3. An article as claimed in claim 1 or claim 2, wherein said active agent is selected from bacteriocides, fungicides, insecticides, deodorizing agents.

4. An article as claimed in any preceding claim, wherein the diffusion rate of the active agent through the matrix is influenced by the chemical composition of the matrix.

5. An article as claimed in any preceding claim, wherein the matrix includes additives to control the rate of diffusion of the active agent therethrough.

6. An article as claimed in claim 5, wherein said additives are selected from materials which form adducts with the agent, anionic or cationic additives, compounds which form salts with the active agent and additives which repell the agent thereby facilitating diffusion between the matrix.

«

7. An article as claimed in any preceding claim, wherein said matrix includes a carrier for the agent thereby to assist diffusion of the agent through the matrix.

8. An article as claimed in any preceding claim, wherein the rate of effusion of the active agent from said surface is influenced by the structure and configuration of the surface and by the rate of diffusion of the active agent through the matrix to the surface.

9. An article as claimed in any preceding claim, wherein said matrix forms a slow-release system for the active agent, and the active agent is dispensed from the matrix at a substantially constant rate over an extended period of time.

10. An article as claimed in any preceding claim, wherein said matrix material is formed of polymeric materials selected from copolymers and mixed polymers of vinylic, acrylic, and acetate monomers, halogenated vinylic and acrylic monomers and polyurethanes.

11. An article as claimed in any of claims 1 to 9, wherein said matrix is formed or natural or synthetic latex or rubber.

12. An article as claimed in any of claims 1 to 9, wherein said matrix material is a stable gel produced in accordance with United States Patent Specification No. 4,491,479.

13. An article as claimed in any preceding claim, wherein said matrix is in the form of a shaped three- dimensional article, a film, a laminate or a foam.

14. An article as claimed in any of claims 1 to 12, wherein said matrix is printed, coated or padded onto a suitable substrate.

15. An article as claimed in claim 14, wherein said substrate is a woven or non-woven textile material.

16. An article as claimed in any of claims 1 to 12, wherein said article is a self supporting film or layer or a sheet of foamed rubber or a latex material.

17. An article as claimed in any preceding claim, wherein said article is a foamed polymer having interstices which are occupied by said matrix material.

18. An article as claimed in any preceding claim, wherein the article is a laminated material comprising at least one layer of said matrix material and one or more layers of non-active agent containing material.

19. An article as claimed in any preceding claim, wherein said article is a shoe insole which comprises a shaped, resilient matrix layer and upper and lower layers juxtaposed the resilient layer.

20. An article as claimed in claim 19, wherein the upper and lower layers are bonded around the peripheral edge of the resilient layer in order to encapsulate the same.

21. An article as claimed in claims 19 or 20, wherein one or more of the upper and lower layers are wholly permeable, or partially permeable, to air and vapour.

22. An article as claimed in any of claims 19 to 21, wherein one or more of the upper and lower layers comprises a semi-permeable membrane or a cellular structure.

23. An article as claimed in any of claims 19 to 22, wherein said resilient layer has a thickness suitable to provide comfort in use.

24. An article as claimed in any of claims 19 to 23, wherein said insole includes a surface layer which is formed of a textile material.

25. An article as claimed in any of claims 19 to 24, wherein the lower layer of the insole has a low porosity.

26. An article as claimed in any of claims 1 to 18, wherein said article is a carpet or mat which comprises a resilient, self-supporting layer or a sheet of foamed polymeric material having the matrix disposed in the interstices of the foam and forms a lower or bottom layer of the carpet or mat.

27. An article as claimed in any preceding claim, wherein the matrix includes an indicator to indicate the amount of active agent which remains in the matrix.

28. An article as claimed in any preceding claim wherein the rate of release of active agent from the matrix is promoted by conditions prevalent during use of the article such as humidity, temperature and/or pressure.

29. An article as claimed in claim 28, wherein the matrix composition is selected such that the article can be stored in an environment of relatively low humidity such that the rate of release of active agent therefrom is low or almost zero and, in use, in an area of relatively high humidity, the rate of release of active agent from the matrix of the article is increased by absorption of water into the matrix.

30. An article as claimed in any preceding claim, wherein said article, in use, is subject to repeated compression and expansion; the article including a resilient porous or foamed layer which, under such conditions of repeated compression and expansion, produces a "pumping" effect which promotes circulation of the active agent dispersed in the vapour phase in and around said article.

31. An article as claimed in any preceding claim, wherein the rate of release of active agent from said matrix layer is temperature dependent, the rate of release of active agent being higher under conditions of high temperature.