WO2018122710A1

WO2018122710A1 - Ocular pad and method for warming a periocular area

Info

Publication number: WO2018122710A1
Application number: PCT/IB2017/058335
Authority: WO
Inventors: Daniela ZELASCHI; Shujing YU
Original assignee: Touch Medical Device Jiashan Co Ltd; NTC SRL
Current assignee: Touch Medical Device Jiashan Co Ltd; NTC SRL
Priority date: 2016-12-28
Filing date: 2017-12-22
Publication date: 2018-07-05
Anticipated expiration: 2019-06-28
Also published as: EP3562447A1; IT201600131691A1; MA47161A

Abstract

The present invention relates to an ocular pad comprising a pocket containing a gel material which reversibly changes color when heated above a threshold temperature. Said pad is particularly suitable for warming a periocular area.

Description

OCULAR PAD AND METHOD FOR WARMING A PERIOCULAR AREA

Many common ocular conditions are currently treated by warming the periocular area corresponding to the affected eyes to be treated. Examples of such conditions are Meibomian Gland Dysfunction (MGD) , dry eye, chalazion, sore eyes and blepharitis. In particular, the dry eye (DE) is a common condition with symptoms that impact patients' quality of life. Said condition is perceived to be as distressing as chest pain and imposes considerable healthcare costs, up to US$1.1 million per 1,000 persons annually, and productivity costs. The MGD is a chronic abnormality of the meibomian glands (MGs) . It may cause eye discomfort and affect tear film stability which leads to poorer visual function, faster tear evaporation and ocular surface damage. MGD is thought to be a major cause of dry eye that affects 46.2-69.3% Asians and 3.5-19.9% Caucasians .

Meibomian glands are large sebaceous glands that are located as separate gland strands in parallel arrangement within the tarsal plates of the eyelids. Their oily product, meibum, is secreted via a holocrine mechanism during which meibocytes are transformed into the meibum. Following production in the gland acini, meibum is transported through the ductal system via the connecting duct and the central duct towards the orifice at the free eyelid margin close to the inner eyelid border. Meibum is a complex mixture of various lipids and minor protein components as well as other components of the meibocytes, which form a clear liquid at body temperature. It is transported within the gland by the force of secretory pressure from continuous secretion and by muscular action of the orbicularis muscle and Riolans muscles during blinking. After it is delivered onto the posterior eyelid margin, meibum moves from the posterior eyelid margin reservoir onto the tear meniscus and is pulled as a thin layer onto the pre-ocular tear film every time the eyelid opens. During closure of the eyelid, it is compressed and a small part is continuously renewed. Meibum also has a barrier function against the spillage of tears over the inner border of the eyelid and against the entry of skin lipids (sebum) from the free eyelid margin.

Moreover, obstructive meibomian gland dysfunction (MGD) is a common source of complaint among patients with dry eye syndrome and its prevalence increases with age. The main clinical consequence of obstructive MGD is evaporative DE syndrome. Moreover, chronic obstruction of the meibomian glands may also result in degeneration of the secretory gland tissue that can lead to a secondary hypo-secretion even if the primary obstruction is later resolved by therapeutic approaches. Risk factors in the pathogenesis of obstructive MGD include age, hormonal disturbances and environmental influences (e.g., contact lenses) . Furthermore, qualitative alterations in the composition of the meibum may lead to hyper-keratinization of the ductal epithelium and increased viscosity of the meibum. This can result in obstruction of the duct and orifice leading to a lack of meibum on the eyelid margin and tear film with downstream hyper-evaporative DE syndrome. At the same time, obstruction leads to a stasis of meibum inside the meibomian gland with increased pressure and resulting dilatation of the ducts and in atrophy of the acini with rarefaction of the secretory meibocytes and gland dropout. Stasis can also increase the growth of commensal bacteria, their production of oil degrading enzymes and release of toxic mediators. These factors can act as self- enforcing feedback loops that aggravate the primary hyper-keratinization and compositional disturbance of meibum and can hence lead to a progressive MGD.

The eyelid warming, usually achieved with simple warm compresses, is regarded as the mainstay of the clinical treatment of ocular conditions [see Geerling G, Tauber J, Baudouin C, Goto E, Matsumoto Y, O'Brien T, et al . ; "The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction", Invest. Ophthalmol. Vis. Sci. 2011; 52 ( 4 ) : 2050-2064 ] . Alternatively, the eyelid warming is reached by different methods, such as: warmed towel or cotton, eyelid warming masks, and other improvised methods of heating, like warmed seeds or even hard boiled eggs. However, the efficacy of all these methods is affected by lack of standardization, in terms of duration and maintenance of temperature, and by a scarce compliance, due also to the difficulty in handling such heating means. Furthermore, when using such methods the user can have handling difficulties, often leading to lack of compliance.

Furthermore, such heating means known in the art require to be heated before the application on the eyelid. However, the absence of a system which allows to control the temperature may cause failure of the treatment, since the patient can apply on the eyelid a vehicle that he/she subjectively judges warm, but that has not reached the right temperature for efficacy, making the treatment, often cumbersome, totally ineffective. Medium term consequence will be that the patient will no longer comply with the warming treatment, having had proof of inefficacy.

In view of the above, the Applicant has faced the problem to find a heating device suitable for warming a periocular area, allowing the user to know when the device has reached the therapeutic temperature and is consequently ready to be applied on said area in order to alleviate or treat ocular conditions.

To solve the above problem, an ocular pad is provided which can be applied on the periocular area and comprises a pocket containing a gel material which reversibly changes color when heated above a threshold temperature. Particularly, when the pad reaches a temperature suitable for the application to the periocular area, particularly a therapeutically effective temperature, reversible color change in the gel material is observed.

Therefore, according to a first object, the present invention relates to an ocular pad comprising a pocket containing a gel material which comprises a thermochromic dye which reversibly changes color when heated above a threshold temperature ranging from 40°C to 45°C.

Advantageously, when the pad of the invention reaches the suitable temperature under heating, it changes color noticeably, thus allowing the user to have an immediate visual confirmation that the device is ready to be applied, since it has reached a therapeutically effective warm temperature. Thus, the control of the temperature, for example by a thermometer, is not necessary, having as a result a more convenient, quick and user friendly procedure.

Another advantage lies in that the pad of the present invention allows to standardize the application on the periocular area. Furthermore, the use of the pad is very easy, so that it is suitable for the domestic use. Moreover, the small size of the pad makes it portable.

BRIEF DESCRIPTION OF THE DRAWINGS

Several embodiments of the present invention will now be described by way of example only, with reference to the accompanying drawing in which:

Figure 1 shows a schematic view of the pad according to the invention.

In Fig. 1, a pad (1) is shown having a pocket (2) made of polymeric material, which contains the gel material. The pocket (2) is closed by a rim (3) obtained by hot welding the plastic edges. Moreover, the pad (1) preferably has a flap (4) which is conveniently shaped to allow an easy handling of the pad (1) during heating and during application on the periocular area.

Further characteristics and advantages of the present invention will be evident from the following detailed description.

DETAILED DESCRIPTION

For the purposes of the present invention, the expression "periocular area" means the whole periocular area or a partial area thereof, such as, for example, the eyelids (upper and/or lower) .

According to a preferred embodiment of the present invention, the thermochromic dye is a thermochromic leuco-dye. More preferably, the thermochromic dye comprises a fluoran-based dye and a developer. Preferably, the weight ratio between the fluoran-based dye and the developer ranges from 30:70 to 70:30, more preferably from 40:60 to 60:40.

As far as the fluoran-based dye is concerned, it is preferably selected from: 3-diethylamino- 6-methyl- 7,2, 4-xylidinofluoran, 3-dimethylamino-7- methoxyfluoran, 3-diethylamino- 6-methoxyfluoran, 3- diethy1amino-7-methoxyfluoran, 3-diethylamino-7- chlorofluoran, 3-diethylamino- 6-methyl-7-chlorofluoran, 3-diethylamino-6, 7-dimethylfluoran, 3- (N-ethyl-p- toluidino) -7-methylfluoran, 3-diethylamino-7-N-acetyl- N-methylamino ) fluoran, 3-diethylamino-7-N- methylaminofluoran, 3-diethylamino-7- dibenzylaminofluoran, 3-diethylamino-7- (N-methyl-N- benzylamino) fluoran, 3-diethylamino-7- (N-chloroethyl-N- methylamino) fluoran, 3-diethylamino-7-N- diethylaminofluoran, 3- (N-ethyl-p-toluidino) -6-methyl- 7-phenylaminofluoran, 3- (N-ethyl-p-toluidino) -6-methyl- 7- (p-toluidino) fluoran, 3-diethylamino- 6-methyl-7- pheny1aminofluoran, 3-dibutylamino- 6-methyl-7- phenylaminofluoran, 3-diethylamino-7- (2- carbomethoxyphenylamino ) fluoran, 3- (N-ethyl-N- isoamylamino ) - 6-methyl-7-phenylaminofluoran, 3- (N- cyclohexyl-N-methylamino ) - 6-methyl-7- phenylaminofluoran, 3-pyrrolidino- 6-methyl-7- phenylaminofluoran, 3-piperidino- 6-methyl-7- phenylaminofluoran, 3-diethylamino- 6-methyl-7- xylidinofluoran, 3-diethylamino-7- (o- chlorophenylamino ) -fluoran, 3-butylamino-7- (o- chlorophenylamino ) fluoran, 3-pyrrolidino- 6-methyl-7-p- butylphenylaminofluoran, 3- (N-methyl-N-n-amylamino ) - 6- methyl-7-phenylaminofluoran, 3- (N-ethyl-N-n-amylamino ) - 6-methyl-7-phenylaminofluoran, 3- (N-methyl-N-n- hexylamino) - 6-methyl-7-phenylaminofluoran, 3- (N-ethyl- N-n-hexylamino ) - 6-methyl-7-phenylaminofluoran, 3- (N- ethyl-N-beta-ethylhexylamino ) -6-methyl-7- phenylaminofluoran or mixtures thereof, more preferably 3-diethylamino- 6-methyl-7 , 2, 4-xylidinofluoran .

According to a preferred aspect, the developer is a phenolic compound preferably selected from: isopropylidenediphenol (bisphenol A) , p-octylphenol , p- tert-butylphenol , p-phenylphenol , p- hydroxyacetophenone, alpha-naphthol , beta-naphthol , p- tert-octylcatechol, 2 , 2 ' -dihydroxybiphenyl , l,l-bis(p- hydroxyphenyl ) butane, 2 , 2-bis ( 4-hydroxyphenyl ) heptane, 2 , 2-bis ( 3-methyl-4-hydroxyphenyl ) propane, 2,2- bis (3,5- dimethyl-4-hydroxyphenyl ) propane, 2, 2-bis (3, 5-dichloro- 4-hydroxyphenyl ) propane, bis ( 4-hydroxyphenyl ) sulfone, bis ( 3 , 4-dihydroxyphenyl ) sulfone, bis ( 4-allyl-4- hydroxyphenyl ) sulfone, 4-hydroxy-4 ' -isopropoxydiphenyl sulfone, 1 , 1-bis ( 4-hydroxyphenyl ) cyclohexane, bis (4- hydroxyphenyl ) ether, p-hydroxybenzoic acid, ethyl p- hydroxybenzoate, butyl p-hydroxybenzoate, benzyl p- hydroxybenzoate, butyl bis ( 4-hydroxyphenyl ) acetate, 1,1, 3-tris ( 2-methyl-4-hydroxy-5-tert- butylphenyl ) butane, 1, 1, 3-tris ( 2-methyl-4-hydroxy-5- cyclohexylphenyl ) butane, bis [2- 4- hydroxyphenylthio ) ethoxy] methane and dimethyl 4- hydroxyphthalate or mixtures thereof, more preferably isopropylidenediphenol (bisphenol A) , benzyl p- hydroxybenzoate or mixtures thereof, even more preferably isopropylidenediphenol (bisphenol A) .

As above-mentioned the color change is reversible. The qualitative color change depends on the thermochromic dye used. For example, when the threshold temperature is exceeded, the color of the gel material can change from orange or green to yellow.

According to a preferred embodiment, the thermochromic dye is in the form of droplets microencapsulated in a protective coating. The droplets have preferably an average size from 1 μπι to 10 μπι. Microencapsulation of the thermochromic dye can be obtained according to well known techniques (see e.g. the handbook by A. Kondo and J. Wade van Valkenburg, Eds., Microcapsule Processing and Technology', Marcel Dekker (1979) ) .

Preferably, the threshold temperature ranges from

41.5°C to 43.5°C. Advantageously, due to color reversibility, the pad can be effectively used many times, to make the system economically sustainable.

According to a preferred aspect of the invention, the ocular pad is made of a polymeric material, which is flexible and soft so as to improve comfort during use. Such polymeric material may be selected from a large number of materials, such as polyvinylchloride (PVC) , polyethylene, polypropylene, polyesters, polyamides, and the like. The pocket in the pad may be obtained for instance by peripheral hot welding of two superimposed polymer sheets. The pocket is then filled with the gel material according to well known techniques .

The gel material preferably comprises a gelling agent, which is preferably selected from carboxymethyl cellulose or a salt thereof, particularly sodium carboxymethyl cellulose, agar powder, sodium polyacrylate, and the like.

The gel material preferably comprises water. Moreover, it preferably comprises a polyol, more preferably glycerin.

The gel material preferably may contain further ingredients such as: solvents, fillers, preservatives, UV stabilizers, antioxidants, and the like.

According to another object, the present invention relates to a method for warming a periocular area, comprising the following steps:

providing a pad as defined above;

heating the pad until a change of color in the gel material is observed;

placing the heated pad on the periocular area. The above method is particularly suitable to treat various ocular conditions, such as Meibomian Gland Dysfunction (MGD) , dry eye, chalazion, sore eyes and blepharitis .

According to a preferred aspect, the pad can be heated by dipping the same into hot water or putting the pad under hot running water. Alternatively, the pad can be heated by microwave, preferably for a time ranging from 10 to 15 sec. Preferably, the heating by microwave is carried out at 400-500 watt.

The pad can be of different shapes, such that allowing a suitable and convenient coverage of the periocular area. Moreover, in order to aid the user during the heating step, the pad is equipped with a flap enabling the patient to hold the pad during heating .

According to a preferred aspect, in order to reach a suitable temperature, the pad is heated for at least 3 minutes with hot water.

The pad can be of any suitable shape for application on the periocular area, such as substantially circular, oval, squared or lobated shape. The dimensions are of course suitable to the intended use. For instance for a circular shape the diameter is preferably from 3 to 8 cm, preferably from 4 to 6 cm. Preferably, the pad has a thickness from 0.3 cm to 3 cm, more preferably from 0,5 cm cm to 1,5 cm.

The present invention will now be further illustrated by means of the following examples, which are illustrative only and are not intended to limit in any sense the scope of the invention. Example 1

A pad was made by hot welding two layers of flexible PVC (free from phthalates) so as to form a pocket which was filled with a gel material having the following composition:

The above leuco-dye was in the form of microcapsules by using melamine formaldehyde resin as protective coating.

The pad as above was dipped into hot water until a change from green to yellow was observed.

In order to check reversibility of the color change, the pad was cooled to room temperature, thus observing a color change from yellow to green, and then repeatedly heated with hot water and cooled to room temperature for 28 times. The pad maintained substantially unaltered the ability to change its color from green to yellow and vice versa.

Claims

1. Ocular pad comprising a pocket containing a gel material which comprises a thermochromic dye which reversibly changes color when heated above a threshold temperature ranging from 40°C to 45°C.

2. Ocular pad according to claim 1, wherein the thermochromic dye is a thermochromic leuco-dye.

3. Ocular pad according to claim 1, wherein the thermochromic dye comprises a fluoran-based dye and a developer .

4. Ocular pad according to claim 3, wherein the the fluoran-based dye and the developer are in weight ratio ranging from 30:70 to 70:30, preferably from 40 : 60 to 60:40.

5. Ocular pad according to anyone of the preceding claims, wherein the thermochromic dye is in the form of droplets microencapsulated in a protective coating .

6. Ocular pad according claim 5, wherein the droplets have an average size from 1 μπι to 10 μπι.

7. Ocular pad according to anyone of the preceding claims, wherein the threshold temperature ranges from 41.5°C to 43.5°C.

8. Ocular pad according to anyone of the preceding claims, wherein the gel material comprises a gelling agent, preferably selected from carboxymethyl cellulose or a salt thereof, agar powder, sodium polyacrylate, and the like.

9. Ocular pad according to anyone of the preceding claims, wherein the gel material comprises water .

10. Ocular pad according to anyone of the preceding claims, wherein the gel material comprises a polyol, preferably glycerin.

11. Method for warming a periocular area, comprising the following steps:

providing a pad as defined in anyone of claims from 1 to 10;

heating the pad until a change of color in the gel material is observed;

placing the heated pad on the periocular area.