Inventors: Belle L. Chou et al.

BACKGROUND OF THE INVENTION

1. Field of the Invention

[0001] The exempl ary embodi ment(s) of the present i nventi on general I y rel ates to an el astomeri c flexible article for application to a person'sskin. More specifically, the exempl ary

embodi ment(s) of the present i nventi on rel ates to a ski n barri er enhanoi ng coati ng for an i nsi de surface of an article, in particular a glove, with a skin pH lowering natural composition.

2. Background

[0002] A principal problem is higher vulnerability to skin disease when the skin barrier is depl eted. Occupati onal dermati ti s i s a common type of ski n di sease spreadi ng i n many i ndustri es worldwide. Irritant contact dermatitisand allergic contact dermatitis are the highest rated diseases in the industries. Disruption of natural skin barrier function, due to chemical contact and frequent use of soaps, hand washers, alcoholic sanitizers and detergents result in removal of epidermal barrier lipids, and natural moisturizing factors (NMF), which lead to loss of skin moi sture and ski n pH al terati ons (from aci di c to basi c), and I eavi ng ski n unprotected to external allergens.

[0003] The ski n barri er i s deri ved by anucl eate, corni f i ed, outermost I ayers of the epi dermi s, collectively known as the stratum corneum. It is known that the stratum corneum is composed of a mixture of lipids and proteins, such asceramides, cholesterol s, free fatty acids, filaggrin and keratin respectively.

[0004] Skin pH is one key factor involved in skin barrier homeostasis. Several physiological mechani sms contri bute to the f ormati on of the aci d mantel resul ti ng i n the f ormati on of a ski n barrier at an acidic pH. The proposed physiological mechani sms for the stratum corneum acidification descri bes: (1 ) Phosphol i pids to free fatty acids (FFA) pathway; (2) Na ⁺ /H ⁺ exchange (NHE1); (3) Histidineto frans-Urocanic acid (UCA) pathway; and (4) Sweat and sebum gland secretions. Formation of free fatty acids, frans-Urocanic acid, and monovalent ion exchange, contributes to pH reduction in the stratum corneum, and maintaining the desired skin pH at 5- 5.5. This pH iscritical for a healthy skin barrier, retards the entry of pathogenic mi croorgani sms through the ski n, and prevents the occurrence of ski n di seases.

[0005] During the epidermal differentiation, free fatty acids particularly, medium and long chain fatty aci ds are derived from I amel I ar-phosphol i pi ds by an enzymati c degradati on and exi sts i n the extracel I ul ar spaces i n between the corneocytes mai ntai ni ng the pH of the stratum corneum. Apart from thisfunction, free fatty acids also contri bute to the flexibility of the stratum corneum.

[0006] NHE1 is a transport protein of the monovalent cations in keratinocytecell membranes and has been shown to regul ate i ntracel I ul ar pH by el ectroneutral exchange of extracel I ul ar Na ⁺ ion for intracellular H ⁺ ion, thereby creating an acidic pH in the border between stratum granul osum and stratum corneum. Thi s f aci I i tates the cerami de I i pi d f ormati on by aci d sphi ngomyel i nase and β-gl ucocerebrosidase, thus enhanci ng the ski n barrier function through a healthy lipid layer.

[0007] During epidermal differentiation, Histidineamino acid, resulting from Filaggrin proteolysis, isfurther converted into irans-Urocanicacid, by catalysisof hi stidase enzyme, in corneocytes. irans-Urocanicacid, is another important factor which regulates the stratum corneum pH.

[0008] Sweat and sebum gl and secretes I acti c aci d and I i pi ds on to the outer ski n surface, where the I i pi ds are further converted to free fatty aci ds by the acti on of ski n mi crof I ora, thus contri buti ng to mai ntai n an ad di c ski n pH .

[0009] A solution to skin barrier depletion resulting in higher vulnerability to skin disease has been to coat the i nsi de of gl oves wi th natural i ngredi ents. However, these natural i ngredi ents are non-sel ecti va These natural i ngredi ents al so do not acti vel y regul ate ski n barri er bi ol ogi cal mechani sms to determi ne the pH of the stratum corneum. Furthermore, most of the pri or sol uti ons are hydrophi I i c i n nature maki ng i t di ff i cult to penetrate through the hydrophobi c epi dermi s I ayer of the ski n. Thi s further reduces the desi red effects of such natural i ngredi ents as they are not penetrati ng i nto the acti ve si tes i nsi de the I ayers of the ski n.

[0010] A nother sol uti on to thi s probl em i s al oe coated gl oves; however, the al oe i s si mpl y for moisturizing the skin and is not actively regulating the pH level of the skin. As such, the prior solutions have failed to provide an effective and efficient means of regulating skin pH to an optimum level for enhancing the barrier function of the skin.

[0011] Accordi ngl y , there i s a need for a coati ng that can be appl i ed to an d astomeri c arti cl e, such asa glove, the coating comprising a mixture of active ingredients that can actively regulate skin pH to enhance the barrier function of the skin.

SUMMARY

[0012] Accordi ng to an embodi ment of the present i nventi on, there i s an el astomeri c arti cl e havi ng an i nsi de surface contai ni ng a coati ng of a ski n pH bal and ng natural compositi on comprising a dried solution of active ingredients including liposome encapsulated amino acids, liposome encapsulated monovalent cations, and free fatty acida

[0013] Accordi ng to another embodiment of the present invention, thedried solution on the el astomeri c arti cl e i s di ssol vabl e on ski n and the I i posomes enhance absorpti on of the acti ve i ngredi ents i nto the ski n. I n a further embodi ment, the acti ve i ngredi ents reduce ski n pH by 0.2 - 0.5 units.

[0014] Accordi ng to yet another embodi ment of the present i nventi on, there i s an el astomeri c, fluid impermeable glove comprising a skin pH balancing composition coated and dried on an inside surface of the glove. The skin pH balancing composition comprises: a plurality of active i ngredi ents compri si ng ami no acids, free fatty acids, and monoval ent cati ons where the ami no aoi d and the monoval ent cati ons are encapsul ated i n I i posomes. The mol ar rati o of the free fatty acids to the ami no aci ds to the monoval ent cati ons to the I i posomes i s pref erabl y 2: 3: 1 : 1 and the active ingredients reduce skin pH by 0.2-0.5 unite

[0015] Accordi ng to yet another embodi ment of the present i nventi on, there i s a method of manuf acturi ng a f I ui d i mpermeabl e el astomeri c arti cl e compri si ng a ski n pH bal and ng composition. The method, according to an embodiment, comprises preparing a skin pH balancing composition including encapsulating ami no acids within liposomes and encapsulating monovalent cations within liposomes and mixing the liposome encapsul ated amino acids and liposome encapsul ated monovalent cations, with a free fatty acid, water, and an emulsifying agent; and applying the skin pH balancing composition to an inside surface of the article.

[0016] These features, advantages and other embodiments of the present invention are further made apparent, i n the remai nder of the present document, to those of ordi nary ski 11 i n the art. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more fully describe embodiments of the present invention reference is made to the accompanyi ng drawi ngs. These drawi ngs are not to be consi dered I i mitati ons i n the scope of the i nventi on, but are merel y i 11 ustrati va

[0018] FIG. 1 illustrates a cross sectional view of an el astomeric article comprising a coating contai ni ng active i ngredi ents on an i nsi de surface of the arti cl e i n contact with a user' s ski n, accordi ng to an embodi ment of the present i nventi on.

[0019] Fl G. 2 i s a detai I vi ew taken from Fl G. 1 i 11 ustrati ng the acti ve i ngredi ents enteri ng the ski n, accordi ng to an embodi ment of the present i nventi on.

[0020] Fl G. 3 i 11 ustrates the target si tes of the acti ve i ngredi ents, whi ch compri se free fatty aci ds, monoval ent cati ons, and ami no aci ds i n the epi dermi s, accordi ng to an embodi ment of the present invention.

[0021] Fl G. 4 i 11 ustrates a I i posome surroundi ng monoval ent cati ons, accordi ng to an

embodiment of the present invention.

[0022] Fl G. 5 i 11 ustrates a I i posome surroundi ng hydrophi I i c ami no aci ds, accordi ng to an embodiment of the present invention.

[0023] Fl G. 6 i 11 ustrates the penetrati on of monoval ent cati ons and ami no aci ds surrounded by I i posomes i n the stratum corneum, accordi ng to an embodi ment of the present i nventi on.

[0024] Fl G. 7 i 11 ustrates a I i posome rel easi ng encapsul ated ami no acids i n the stratum corneum, accordi ng to an embodi ment of the present i nventi on.

[0025] Fl G. 8 i 11 ustrates a I i posome rel easi ng encapsul ated monoval ent cati ons at the i nterf ace between the stratum granulosum and the stratum corneum, according to an embodiment of the present invention. [0026] Fl G. 9 i 11 ustrates a method of maki ng an el astomeri c arti cl e havi ng a preparati on of a ski n pH bal and ng natural compositi on i ncl udi ng a method of process ng the acti ve i ngredi ents i n the preparation applied to the article, according to an embodiment of the present invention.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

[0027] The descri pti on above and bel ow and the drawi ngs of the present document focus on one or more currentl y preferred embodi ments of the present i nventi on and al so descri be some exemplary optional features and/or alternative embodi ments of the present invention. The descri pti on and drawi ngs are for the purpose of i 11 ustrati on and not I i mi tati on. Those of ordi nary skill in the art would recognize variations, modifications, and alternatives. Such variations, modifications, and alternatives are also within the scope of the present invention. Section titles are terse and are for conveni ence onl y .

[0028] Throughout the descri pti on and drawi ngs, exampl e embodi ments of the present i nventi on are given with reference to specific configurations. It will be appreciated by those of ordinary skill in the art that the present invention can be embodied in other specific forms. Those of ordi nary ski 11 i n the art woul d be abl e to practi ce such other embodi ments of the present i nventi on without undue experi mentati on. The scope of the present i nventi on, for the purpose of the present patent document, i s not I i mi ted merel y to the sped f i c exampl e embodi ments of the present invention or alternatives of theforegoing description.

[0029] A n embodi ment of the present i nventi on i s an el astomeri c arti d e havi ng an i nsi de surface 3 and an outsi de surface 4. The i nsi de surface 3 can al so be referred to as the i nner surface and the i nner surf ace/i nsi de surface 3 i s the ski n-f ad ng or ski n contacti ng surface of the wearer/user when the arti d e i s worn on i n use. The el astomeri c f I exi bl e arti d e can be a gl ove, such as a di sposabl e, fluid i mpermeabl e exami nati on type gl ove or di sposabl e protecti ve gl ove 2. A n el astomeri c f I exi bl e arti cl e, accordi ng to some embodi ments of the present i nveriti on i s a disposable protective glove, but other forms of articles may also be used, such as protective arti cl es worn on, or to cover, a porti on of the ski n. The el astomeri c f I exi bl e arti cl e can be made of a material selected from nitrile butadiene latex, natural rubber latex, polychloroprene, polyurethane, polyisoprene, PVA, acrylic, butyl, silicone rubber, fluoro-elastomer, and PVC, or combinations thereof, where the inside surface 3 of the glove 2 iscoated with a mixture of natural i ngredi ents faci I i tati ng the reducti on of ski n pH .

[0030] I n one embodi ment of the present i nventi on, the i nsi de surface 3 of the di sposabl e gl ove 2 can contai n a coati ng 6 compri si ng a mi xture of natural acti ve i ngredi ents extracted from pi ant based materi al s. The acti ve i ngredi ents can be made from a combi nati on of medi urn fatty aci ds (M FA), long fatty acids (LFA), rich natural oils, amino acids, for example, histidine, and sodium and potassium monovalent ions. The mixture of medi urn fatty acids and long fatty acids may include I auric acid, palmitic acid, stearic acid, oleic acid, linoleicacid, alpha-linolenicacid, and combi nati ons thereof. These i ngredi ents can be sel ected from one or more of the fol I owi ng sources listed in Table 1

Tabl e 1. Natural sources of the active i ngredi ents

[0031] FIG. 1 illustrates a cross sectional view of an article, such as a glove 2, in contact with a user' s ski n, the gl ove 2 compri ses a coati ng 6 compri si ng acti ve i ngredi errts, accordi ng to an embodiment of the present invention. The cross sectional view shows the article having an i ndetermi nate or vari abl e I ength and thi ckness as wel I as a magni f i ed vi ew of the coati ng thi ckness for reference purposes. The gl ove 2 compri ses an el astomeri c I ayer 8 havi ng an i nsi de surface 3 that faces the user' s ski n and an outsi de surface 4 that faces the external envi ronment. The coati ng 6 is appl ied to the i nside surface 3 as a dri ed coati ng and comes i n contact with the ski n of a user. Once the gl ove 2 is worn and comes i n di rect contact with the user's ski n, the coati ng 6 di ssol ves due to the warm and moi st envi ronment created i nsi de the gl ove 2. Thi s facilitates the active ingredients, particularly B-free fatty acids 14, A-amino acids 12 and C- monovalent cations 16 to absorb into the skin and regulate the natural skin's pH for a healthy ski n barri er (not shown, see Fl G. 2) . The concentrati on of the acti ve i ngredi ents of the coati ng 6 can rangefrom 5-16%, more preferably 10-12% with a ratio of freefatty acids: amino acids: monovalent cations: liposomes to approximately 2:3: 1:1.

[0032] Fl G. 2 i s a detai I ed vi ew of Fl G. 1 at 100, i 11 ustrati ng the acti ve i ngredi ents, A-ami no acids 12, B-free fatty acids 14, C- monovalent cations 16, D-liposomes 18, according to an embodi ment of the present i nvention. The coati ng 6 compri si ng the active i ngredi errts are absorbed i nto the user' s outer ski n I ayer, the stratum corneum 20 i n the epi dermi & The A-ami no acids 12 and C-monovalent cations 16 are encapsulated within D-liposomes 18, which can penetrate i nto the user's ski n. The I i posomes enhance the absorption of the active i ngredi ents i nto the ski n. The D-l i posomes 18 can be phosphati dyl chol i nes extracted from pi ants. The epi dermis compri ses the: stratum basal e, stratum spinosum, stratum granulosum 22, stratum corneum 20. The stratum corneum 20 is the target site of the active ingredients in the present invention.

[0033] Fl G. 3 i 11 ustrates the stratum corneum 20 and stratum granul osum 22, whi ch can be target sites of B-free fatty acids 14, C-monovalent cations 16, and A -ami no acids 12 in the epi dermi s, accordi ng to an embodi ment of the present i nventi on. As i 11 ustrated i n Fl G . 3, B-free fatty aci ds 14 parti cul arl y, medi urn chai n fatty aci ds and I ong chai n fatty aci ds i n the coati ng 6 penetrate the epidermis of the ski n through the i ntercel I ular spaces of the stratum corneum 20. The lower pH of the B-free fatty acids 14 reduces the overal I pH of the stratum corneum 20. FIG. 3 also illustrates C-monovalent cations 16 such as Na ⁺ ions in the extracellular space exchanging with intracellular H+ ion by the transport channel called NHE1 located in the cell I i ni ng of kerati nocyte eel I membranes. C-monoval ent cati ons such as K ⁺ i ons can also be used. The sodium-hydrogen antiporter 1 (NHE1), which isatransport protein of C-monovalent cation 16 i n kerati nocyte celI membranes has been shown to regul ate i ntracd I ul ar pH by el ectroneutral exchange of extracel I ul ar Na ⁺ i on for i ntrace! I ul ar H ⁺ i on, creati ng an aci di c pH i n the border between the stratum granul osum 22 and stratum corneum 20. Thi s f aci I i tates the cerami de I i pi d formation by the low pH dependent enzymes (i .a acid sphingomyelinase and β- glucocerebrosidase), thus enhancing the skin barrier function through adense lipid layer.

[0034] FIG. 3 also illustrates A-amino acids 12, particularly Histidine, which converts into frans-Urocanic acid, by catalysis of the histidase enzyme, in the cells of the stratum corneum 20. frans-Urocanic acid, is another important factor in regulating the pH of stratum corneum 20.

[0035] FIG. 4 ill ustrates C-monovalent cations 16 encapsulated inside a hydrophobic carrier cal I ed a D-l i posome 18. D-l i posome 18 f aci I i tates the hydrophi lie C- monovaJ ent cati ons 16 penetration into the target site, which is the interface between the stratum granulosum 22 and the stratum corneum 20. FI G. 5 illustrates hydrophilicA-amino acids 12 encapsulated inside a hydrophobi c carri er caJ I ed a D-l i posome 18, ready to penetrate through the hydrophobi c i ntercel I ul ar route of the stratum corneum 20.

[0036] FIG. 6 illustrates the penetration of monovalent cations and amino acids surrounded by liposomes 18 in the stratum corneum 20, according to an embodiment of the present invention. The I i posomes 18 encapsul ati ng the A-ami no acids 12 target the stratum corneum 20 and the I i posomes 18 encapsul ati ng the C-monoval ent cati ons 16 target the i nterf ace between the stratum granulosum 22 and the stratum corneum 20.

[0037] Fl G. 7 i 11 ustrates the D-l i posomes 18 rel easi ng encapsulated A-ami no acids 12 i n the stratum corneum 20, accordi ng to an embodi ment of the present i nventi on. Thi s i s done when the D-l i posomes 18 di ssol ve i n the i ntercel I ul ar I i pi ds of the stratum corneum 20. The chemi cal and physi cal structures of these I i posomes are si mi I ar to that of the I i pi d membrane i n the ski n barrier, and so offer additional protection to the skin.

[0038] Fl G. 8 i 11 ustrates I i posomes 18 rel easi ng encapsulated C- monoval ent cati ons 16 at the i nterf ace between the stratum granulosum 22 and the stratum corneum 20, accordi ng to an embodi ment of the present i nventi on . Thi s i s done when the D-l i posomes 18 di ssol ve i n the i ntercel I ul ar I i pi ds of the stratum corneum 20.

[0039] FIG. 9 ill ustrates one method 300 of processing the active ingredients and its application to an el astomeri c arti cl e, accordi ng to an embodi ment of the present i nventi on. A-ami no ad ds 12 are encapsulated within D-l i posomes 18 (step 310) and C-monoval ent cations 16 are encapsulated withi n D-l i posomes 18 (step 312). I n performi ng the above encapsulation, the rate of adding A-ami no acids 12 and C-monovalent cations 16 into D-l i posomes 18 is kept at about 50 mL per minute with a reaction temperature in the range of 40°C- 50° C, at a mixing speed of about 500-600 rounds per mi nuta The process of encapsul ati on i s conti nued for 30-40 mi nutes.

[0040] The above mentioned encapsulated A-ami no acids 12 and C-monovalent cations 16 are mixed with a free fatty acid source and water. Additionally, this step can be done in the presence of an emulsifying agent 28 (step 314). The B-f ree fatty acids 14 can be selected from a group I i sted i n Tabl e 1 and a I i kel y materi al . To attai n a homogeneous mi xture, hydrophi I i c and hydrophobic ingredients in the active ingredient mixture are mixed together with an emulsifying agent 28, which provides a fundamental outcome for a uniform coating. The emulsifying agent 28 can be sel ected from the fol I owi ng range or as appropri ate gum arabi c, soya I eci thi n, and bee wax. In preparing the final active ingredient mixture above, the mixing is carried out at preferably 1000-1500 rounds per minute, for duration of preferably up to 60 minutes. In an embodiment, the duration of mixing the encapsulated amino acids 12 and the encapsulated monoval ent cati ons 16 i s about 45 to 60 mi nutes. The fol I owi ng f ormul as i n Tabl e 2 i 11 ustrate di f f erent composi ti ons re! ated to embodi ments of the present i nventi on. Formul as I and 11 have a I ower dryi ng temperature I eavi ng no resi dues, and no sti cki ness i n the i nsi de surface 3 of the gl ove 2, and the ease of coati ng i s much better compared to Formul a 111. Formul as I and 11 were sel ected for further proceedi ngs based on ease of processi ng.

Table 2. Coating Composition

[0041] The appl i cati on of the prepared mi xture to gl oves pref erabl y begi ns wi th gl oves that are clean and free of protein residue, powder, or other surface contaminants. Therefore, the step 316

1 s pref erabl y i ncl uded i n the method 300 to remove such contami nants. The prepared mi xture i s appl ied to the gloves 2 (step 318), for example, by means of sprayi ng the mixture on to the i nside surface 3 of the glove 2. Alternatively, gloves 2 can be immersed into a solution containing this acti ve i ngredi ent mi xture. I n the I atter method, the gl oves are i mmersed i n the mi xture for at I east

2 mi nutes to al low the mixture to absorb onto the i nside surface 3.

[0042] Active ingredients are attached to the inside surface 3 of the glove 2 through a control led dehydration process (step 320). Water in the solution mixture is caused to evaporate through hot ai r dryi ng. Coated gl oves 2 are dri ed i n a pre-heated oven at 45°C- 55°C more pref erabl y at 50°C, and the dryi ng process conti nues to about 30-40 mi nutes. The temperature of the hot ai r i s thoroughl y mai ntai ned at the above range to avoi d I oss of acti ve i ngredi ents i n the coati ng 6. Alternatively, steps 318 and 320 can be accompli shed by a hot air oven with a device to spray and tumble simultaneously during drying to distribute the mi xture of natural ingredients evenly on the insidesurface3 of glove2 to form auniform costing 6. After the dehydration process, a resul t i ng dri ed sol uti on of acti ve i ngredi ents adheres to the i nsi de surface of the gl ove 2 whi ch i s dissolvable on skin under the warm and moist environment created inside the glove 2 during use.

[0043] The use of a combi nati on of natural extracts wi thi n the scope of thi s i nventi on, wi 11 effectively improve skin barrier function or enhance its recovery rate by reducing skin pH by 0.2- 0.5 units. The measurement of skin pH following treatment with formulas I and I I, in accordance with the invention, is summarized below.

[0044] 60 femal e subj ects between the ages of 30-40, were sel ected from a factory setti ng, where thei r routi ne work i nvol ves weari ng gl oves. Subj ects were pi aced i n two groups of 30 each. [Each group' s ski n pH was exami ned for 30 days f ol I owi ng use of the coated gl ove. Gl oves were prepared with the coati ng 6 as per the Formul a I and 11 separatd y and di stri buted among the two groups Subj ects were advi sed to avoi d usi ng any topi cal appl i cati ons on the ski n duri ng the tri aJ and i nstructed to wear the coated gl oves on both hands. Ski n pH measurements were recorded after completion of eight hours of wearing gloves. Measurements were taken using skin pH probe 905 (Courage +Khazaka d ectronic GmbH). The mean val ues of ski n pH are shown i n Table 3 below. The results show that the Formula II coated glove has a significant skin pH reducti on capacity than the coati ng of Formul a I .

Table 3. Mean Skin pH (baseline vs. coated glove)

[0045] Whi le parti cul ar embodi ments of the present i nventi on have been shown and descri bed, it wi 11 be obvi ous to those of ski 11 s i n the art that based upon the teachi ngs herei n, changes and modifications may be made without departing from thisexemplary embodi ment(s) of the present i nventi on and i ts broader aspects. Therefore, the appended cl ai ms are i ntended to encompass within their soope all such changes and modifications as are within the true spirit and scope of thi s exempl ary embodi merrt(s) of the present i nventi on.