MXPA00008934A - Disposable absorbent article having a skin care composition containing an enzyme inhibitor - Google Patents
Disposable absorbent article having a skin care composition containing an enzyme inhibitorInfo
- Publication number
- MXPA00008934A MXPA00008934A MXPA/A/2000/008934A MXPA00008934A MXPA00008934A MX PA00008934 A MXPA00008934 A MX PA00008934A MX PA00008934 A MXPA00008934 A MX PA00008934A MX PA00008934 A MXPA00008934 A MX PA00008934A
- Authority
- MX
- Mexico
- Prior art keywords
- skin
- composition
- inhibitor
- article
- skin care
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 342
- 210000003491 Skin Anatomy 0.000 title claims abstract description 226
- 239000002250 absorbent Substances 0.000 title claims abstract description 134
- 230000002745 absorbent Effects 0.000 title claims abstract description 134
- 239000002532 enzyme inhibitor Substances 0.000 title claims abstract description 76
- 102000004190 Enzymes Human genes 0.000 claims abstract description 45
- 108090000790 Enzymes Proteins 0.000 claims abstract description 45
- 230000002255 enzymatic Effects 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 127
- 239000003112 inhibitor Substances 0.000 claims description 119
- -1 fatty acid ester Chemical class 0.000 claims description 101
- 239000003974 emollient agent Substances 0.000 claims description 58
- 239000003795 chemical substances by application Substances 0.000 claims description 53
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 32
- 239000000194 fatty acid Substances 0.000 claims description 32
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 32
- 102000004882 lipase Human genes 0.000 claims description 30
- 108090001060 lipase Proteins 0.000 claims description 30
- 239000004367 Lipase Substances 0.000 claims description 28
- 235000019421 lipase Nutrition 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000011780 sodium chloride Substances 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 150000002191 fatty alcohols Chemical class 0.000 claims description 23
- 150000004665 fatty acids Chemical class 0.000 claims description 21
- 229940088598 Enzyme Drugs 0.000 claims description 20
- 230000003100 immobilizing Effects 0.000 claims description 20
- 229920001296 polysiloxane Polymers 0.000 claims description 20
- 229940040461 Lipase Drugs 0.000 claims description 19
- 229960001915 hexamidine Drugs 0.000 claims description 19
- 235000019271 petrolatum Nutrition 0.000 claims description 19
- OQLKNTOKMBVBKV-UHFFFAOYSA-N Hexamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCCOC1=CC=C(C(N)=N)C=C1 OQLKNTOKMBVBKV-UHFFFAOYSA-N 0.000 claims description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 17
- 238000002844 melting Methods 0.000 claims description 17
- 150000001298 alcohols Chemical class 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 15
- 108010065511 Amylases Proteins 0.000 claims description 14
- 102000013142 Amylases Human genes 0.000 claims description 14
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- 235000019418 amylase Nutrition 0.000 claims description 14
- 239000005720 sucrose Substances 0.000 claims description 14
- 239000004264 Petrolatum Substances 0.000 claims description 13
- 229940066842 Petrolatum Drugs 0.000 claims description 13
- 239000002753 trypsin inhibitor Substances 0.000 claims description 13
- 239000004382 Amylase Substances 0.000 claims description 12
- 230000000875 corresponding Effects 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- KCXVZYZYPLLWCC-UHFFFAOYSA-N edta Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 10
- 239000000284 extract Substances 0.000 claims description 10
- IAYPIBMASNFSPL-UHFFFAOYSA-N oxane Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 10
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 7
- 239000003833 bile salt Substances 0.000 claims description 7
- 239000012530 fluid Substances 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 7
- 239000002601 urease inhibitor Substances 0.000 claims description 7
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- 150000003751 zinc Chemical class 0.000 claims description 6
- WPANETAWYGDRLL-UHFFFAOYSA-N 4-aminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(N)C=C1 WPANETAWYGDRLL-UHFFFAOYSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
- 229940015001 Glycerin Drugs 0.000 claims description 5
- 240000007842 Glycine max Species 0.000 claims description 5
- 235000010469 Glycine max Nutrition 0.000 claims description 5
- FAXGPCHRFPCXOO-LXTPJMTPSA-N Pepstatin Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 claims description 5
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- 239000000454 talc Substances 0.000 claims description 5
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- 229910052623 talc Inorganic materials 0.000 claims description 5
- XLOMVQKBTHCTTD-UHFFFAOYSA-N zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 5
- GYDJEQRTZSCIOI-LJGSYFOKSA-N (1r,4r)-4-(aminomethyl)cyclohexane-1-carboxylic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims description 4
- MRXDGVXSWIXTQL-LROMGURASA-N (2S)-2-[[(1S)-1-[(6S)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-2-[[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)[C@H]1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-LROMGURASA-N 0.000 claims description 4
- GDBQQVLCIARPGH-ULQDDVLXSA-N (2S)-2-acetamido-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 claims description 4
- FCEQRBOTYXIORK-UHFFFAOYSA-N 2-(diaminomethylideneamino)benzoic acid Chemical compound NC(=N)NC1=CC=CC=C1C(O)=O FCEQRBOTYXIORK-UHFFFAOYSA-N 0.000 claims description 4
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 claims description 4
- 239000005995 Aluminium silicate Substances 0.000 claims description 4
- PZZYQPZGQPZBDN-UHFFFAOYSA-N Aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 claims description 4
- 235000007319 Avena orientalis Nutrition 0.000 claims description 4
- 244000075850 Avena orientalis Species 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- 229950002499 Fytic acid Drugs 0.000 claims description 4
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 claims description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 4
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- 229940039717 Lanolin Drugs 0.000 claims description 4
- YFCUZWYIPBUQBD-ZOWNYOTGSA-N N-[(3S)-7-amino-1-chloro-2-oxoheptan-3-yl]-4-methylbenzenesulfonamide;hydron;chloride Chemical compound Cl.CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 YFCUZWYIPBUQBD-ZOWNYOTGSA-N 0.000 claims description 4
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- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
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- UNBMQQNYLCPCHS-VYNDPHDASA-N Ebelactone B Chemical compound CC[C@@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)\C=C(/C)C[C@H](C)[C@@H]1OC(=O)[C@H]1CC UNBMQQNYLCPCHS-VYNDPHDASA-N 0.000 claims description 3
- LPLVUJXQOOQHMX-MYOOOWEVSA-N Glycyrrhizic acid Natural products O=C(O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@H](C(=O)O)O2)[C@@H](O[C@@H]2C(C)(C)[C@H]3[C@@](C)([C@H]4C(=O)C=C5[C@](C)([C@]4(C)CC3)CC[C@]3(C)[C@H]5C[C@](C(=O)O)(C)CC3)CC2)O1 LPLVUJXQOOQHMX-MYOOOWEVSA-N 0.000 claims description 3
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- URAYPUMNDPQOKB-UHFFFAOYSA-N Triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 3
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- DJWUNCQRNNEAKC-UHFFFAOYSA-L Zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 claims description 3
- HGMSJMJPXGGEBP-UHFFFAOYSA-N [4-[3-(4-ethylphenyl)butyl]phenyl]-trimethylazanium Chemical compound C1=CC(CC)=CC=C1C(C)CCC1=CC=C([N+](C)(C)C)C=C1 HGMSJMJPXGGEBP-UHFFFAOYSA-N 0.000 claims description 3
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- 239000001087 glyceryl triacetate Substances 0.000 claims description 3
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- VGGGPCQERPFHOB-RDBSUJKOSA-N (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-RDBSUJKOSA-N 0.000 claims description 2
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- WWGVIIVMPMBQFV-MUGJNUQGSA-N [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]heptan-2-yl] (2S)-2-formamido-3-methylbutanoate Chemical compound CCCCCC[C@H]1[C@H](C[C@H](CCCCC)OC(=O)[C@@H](NC=O)C(C)C)OC1=O WWGVIIVMPMBQFV-MUGJNUQGSA-N 0.000 claims description 2
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- KREXGRSOTUKPLX-UHFFFAOYSA-N octadecanoic acid;zinc Chemical compound [Zn].CCCCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O KREXGRSOTUKPLX-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- 125000003944 tolyl group Chemical group 0.000 description 1
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- RZLVQBNCHSJZPX-UHFFFAOYSA-L zinc sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O RZLVQBNCHSJZPX-UHFFFAOYSA-L 0.000 description 1
- JGPSMWXKRPZZRG-UHFFFAOYSA-N zinc;dinitrate;hexahydrate Chemical compound O.O.O.O.O.O.[Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O JGPSMWXKRPZZRG-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides an absorbent article, at least a portion of which comprises a skin care composition that comprises an enzyme inhibitor and is at least partially transferred from the article to the skin of a wearer of the article as a result of normal contact, wearer motion and/or body heat. The enzyme inhibitor is transferred to the skin with the skin care composition and is available at the skin/urine and skin/feces interfaces to inhibit enzymatic activity on the skin and to reduce or prevent the occurrence of inflammation. Repeated application of similar treated articles to the wearer's skin provides an available source with which the enzyme inhibitor transfers onto the skin continuously over time and accumulates to provide a proactive defense against harmful enzymes for the treatment and/or prevention of diaper dermatitis.
Description
ABSORBENT DISPOSABLE ARTICLE THAT HAS A COMPOSITION FOR CARE OF THE SKIN CONTAINING AN ENZYME INHIBITOR
BACKGROUND OF THE INVENTION
The invention relates to absorbent articles such as diapers, trainers, incontinence briefs for adults, feminine hygiene products and the like, which incorporate a skin care composition comprising an enzyme inhibitor, preferably on a contact surface. with the user. During normal use of the article the enzyme inhibitor with the skin care composition is transferred to at least a portion of the user's skin where it is available to inactivate fecal enzymes and reduce the redness and inflammation that may occur to Continuation of prolonged exposure of the skin to body wastes. The diaper rash is a common form of irritation and inflammation of those parts of a baby's body normally covered by a diaper. This condition is also referred to as diaper rash, cover dermatitis, cover rash and scalding. Although certainly more common in babies, this condition, in reality, is not limited to babies. Any individual who suffers from incontinence to the extent that the use of absorbent articles is required may develop this condition. Susceptible individuals vary from newborns to the elderly, to critically ill or non-ambulatory individuals. Section 333.503 of Title 21 of the Code of Federal Regulations defines a diaper rash as "an inflammatory condition of the skin in the diaper area (perineum, buttocks, lower abdomen, and inner thighs) caused by one or more of the following factors: humidity, occlusion, excoriation, continuous contact with urine or feces, or both, or mechanical or chemical irritation. " It is generally accepted by the medical profession that the true diaper rash or diaper rash is a condition, which is, in its simplest stages, an irritant contact dermatitis that results from extended skin contact with urine, or feces. , or both. Among the most commonly accepted factors linked to diaper rash are ammonia, fecal rash is ammonia, faecal enzymes, bacteria, the products of bacterial action the pH of urine, and Candida albicans. Many types of disposable absorbent products, such as diapers, trainers, adult incontinence devices, sanitary napkins, pantyhose, and the like, are available and have a high capacity to absorb urine and other exudates from the body. Disposable products of this type generally comprise some type of liquid-permeable top sheet material, an absorbent core, and a liquid-impermeable backsheet material. Although these types of absorbent structures can be highly efficient for absorbing liquids, they can not absorb bowel movements. Typically, the bowel movement is trapped between the outer surface of the liquid-permeable topsheet and the wearer's skin, much of which adheres to the wearer's skin. In this way the skin is exposed to contact with feces, often for prolonged periods of time, and is susceptible to irritants present in the feces that may produce or contribute to the diaper rash. Because enzymes are widely distributed in plants, humus, bacteria, milk, milk products, and almost all animal tissues, as well as digestive juices in the gastrointestinal tract, these are almost always present in the diaper area where has been messed up by human waste. The enzymes present in feces include proteolytic enzymes, lipases and other esterases and diesterase, ureases and other enzymes including amylases, elastases, nucleases, and the like. Although the relative contribution of different types of enzymes to skin irritation is unknown, there is evidence that at least proteolytic and lipolytic fecal enzymes, of intestinal and / or pancreatic origin, play a direct role in causing skin irritation. and inflammation of the diaper rash. Studies with inhibitors designed to inhibit the enzymatic activity of various classes of proteases have shown that serine proteases, cysteine proteases, and metalloproteases were most likely responsible for the total proteolytic activity of faeces. It is known that trypsin and chymotrypsin of serine proteases, in particular, are almost always present in measurable amounts in the raw in normal stools of young children, and minor but detectable amounts are present in the normal stools of adults. Lipases, including esterases that hydrolyze food triglycerides, are also found in normal stools and are able to hydrolyse the triglycerides and other glycerides found in human skin to form the irritating fatty acid and glycerol byproducts. In this way, when the skin is exposed to enzymes such as lipases and proteases present in the exudates of the body, the components that contain lipids and components that contain protein from the skin, especially the barrier layer (stratum corneum), can be decomposed resulting in irritation and inflammation of the diaper rash. In addition, disturbance of the skin barrier allows other components of urine and feces, ammonia, bacteria and the like, which otherwise can not be irritating on their own, to migrate through the compromised barrier of the skin. skin to produce additional irritation and possible infection. It is known that bile salts are also present in body exudates. These bile salts are normally known to emulsify the lipids in the body to ensure that the lipase enzymes are capable of performing at the lipid / water interface. Bile salts are also active when excreted in feces and other exudates and are available to act as coenzymes and increase the activity of lipases that attack lipids in the stratum corneum of the skin that is exposed to exudates from the body. The irritant effects of fecal enzyme activity on the skin are likely to be amplified if urine is present and / or if the skin is clogged. The production of ammonium hydroxide by the action of the urease of the bacterial enzyme in the urine results in an increase in pH, for example at levels of 7.0 and above, in which the enzymatic activity of proteases and other enzymes such as Lipases present in the stool increases. For example, the optimum pH varies for urease activity is from 6.4 to 6.9, for trypsin from 7.8 to 8.2, and for lipases from 7.5 to 9.5. At a pH higher than 7.0, free ammonia is released from the urine as an additional toxic irritant to the skin. The urine itself can also contribute to the diaper rash by adding moisture to the diaper environment. Water, and particularly water in the form of urine, is especially effective in decreasing the barrier properties of the skin, thereby increasing the susceptibility of the skin to irritation by the fecal enzyme. Since urine and feces are commonly present in the absorbent article at the same time, exposure to the skin for several hours is not an uncommon, adequate condition, enough time is available for this interaction and the resulting damage to the skin that happens. An alkaline pH in the stool is an additional contributory factor for the increased enzymatic activity of the feces. For example, it is well known that although stools from breastfed babies are usually acidicFaecal feces of bottle-fed and spoon-fed infants are generally alkaline, with a pH ranging from slightly alkaline (pH 7.2 to 7.5) to very alkaline (pH 8.7 and above). In this way bottle-fed and spoon-fed infants in particular may have a tendency to develop the diaper rash due to the increased pH activity of faecal enzymes. In view of the contribution of the alkaline pH to increase the activity of the faecal enzyme, several attempts have been made to maintain the pH of the skin by the use of pH control agents, such as regulating agents or ammonia-neutralizing acidic agents, in an absorbent article as ingredients in topically applied skin care products. It is considered that effectively maintaining the pH of the skin in its neutral acid state (ie, from about 3.0 to about 5.5) can counteract the irritant effects of ammonia and reduce the activity of faecal enzymes. Reducing the enzymatic activity in the skin by this approach, however, is potentially difficult in the situation where the alkaline feces are deposited directly on the skin immediately after the bowel movement. Certain anti-enzyme compounds have been included in the topically applied compositions for the treatment or prevention of diaper rash caused by prolonged contact of human skin with body wastes. For example, U.S. Patent No. 4,556,560 describes compositions containing water-soluble lipase inhibitors that are preferably metal salts such as zinc chloride in a barrier-type carrier such as polyethylene glycol. If incorporated into a diaper core or topsheet, the lipase inhibitor is preferably in an aqueous or volatile carrier such as ethanol to be transferred to which when the diaper is wetted with urine. U.S. Patent No. 5,091, 193 discloses compositions for application to the skin at the time of diaper change which contain a chelating agent such as phytic acid, ethylenediamine tetraacetic acid, (EDTA) and the like, which restrict the availability of metals that ureases and proteases require as cofactors for activity. The composition may further include a lipase inhibitor such as an ester of a fatty alcohol or an additional anti-enzyme, such as the zinc salt of a saturated fatty acid of 2 to 2 to 22 carbon atoms, saturated or unsaturated, linear or branched, or an amino acid, acylated such as propionylcysteine, propionylhydroxyproline or caproylcysteine. Although diaper rash treatment compositions have been described to include certain inhibitors of enzyme activity, there has been no prior description of a diaper rash treatment or prevention regimen by which skin care compositions containing enzyme inhibitors are included in the absorbent articles for automatic transfer to the skin of a user during normal use of the treated article, or that the use, preferably repeated use, of the absorbent articles automatically transfers sufficient levels of the inhibitors of enzyme to the selected regions of the user's skin to provide a defense against faecal penetration and enzymatic activity. In addition, there has been no prior description of the absorbent articles having a skin care composition containing an immobilized enzyme inhibitor (at room temperature) on a user interface, preferably a topsheet, wherein the composition for skin care and the enzyme inhibitor are transferred to the user's skin when the skin care composition is heated to body temperature.
BRIEF DESCRIPTION OF THE INVENTION
The invention provides an absorbent article, at least a portion of which comprises a composition for skin care comprising an enzyme inhibitor, wherein the composition for skin care, including the enzyme inhibitor, is at least Partially transferred from the article to the skin of the user of the article as a result of normal contact, user movement and / or body heat. The enzyme inhibitor can be any material that inhibits the activity of one or more enzymes, preferably an IC 50, as defined below, of no more than about 500 μM. Enzyme inhibitors useful for use in the article of the invention include, but are not limited to, protease inhibitors, lipase inhibitors, elastase inhibitors, urease inhibitors, amylase inhibitors, and the like, and also include salt inactivators. biliary which would otherwise act as cofactors for the lipase activity. The composition for skin care preferably comprises from about 0.001% to about 50% of the enzyme inhibitor, typically from about 0.01% to about 25%, more typically from about 0.1% to about 10%, and very typically from about 0.1% to about 5%. The nature of the skin care composition comprising the enzyme inhibitor can vary widely, but in a preferred embodiment it is solid or semi-solid at room temperature (20 ° C). In a particularly preferred embodiment, the skin care composition will further comprise from about 5% to about 95% of an emollient having a plastic or fluid consistency at 20 ° C. Most preferably, the skin care composition further comprises from about 5% to about 95% of an agent that is capable of immobilizing the emollient in the article and having a melting point of at least about 35 ° C. Preferably, the part of the absorbent article incorporating the skin care composition comprising the enzyme inhibitor is a user interface, which is more preferably a liquid permeable topsheet. Since the enzyme inhibitor is transferred to the skin with the skin care composition, the inhibitor is available at the skin / urine and skin / stool interface to inhibit the enzymatic activity on the skin and reduce or prevent it the occurrence of inflammation. The repeated application of treated articles similar to the user's skin provides an available source with which the enzyme inhibitor transfers onto the skin continuously over time and accumulates to provide a proactive defense against harmful enzymes for the treatment and / or prevention of diaper rash
BRIEF DESCRIPTION OF THE DRAWINGS
Although the specification concludes with the claims particularly pointing out and claiming the present invention, it is believed that the present invention will be better understood from the following description along with the accompanying drawings, in which like reference numbers identify identical elements, and where : Figure 1 is a schematic illustration of an absorbent article in the form of a diaper according to the present invention. Figure 2a is a side view showing the placement of the skin analogue used in the transfer test of the skin care composition and / or the protease inhibitor transfer test. Figure 2b is a plan view showing the placement of the skin analogue used in the transfer test of the skin care composition and / or the protease inhibitor transfer test.
DETAILED DESCRIPTION OF THE INVENTION
Definitions As used herein, the term "comprising" means that the various components, ingredients or steps may be employed together to practice the present invention. Accordingly, the term "comprising" embraces the more restrictive terms "consisting essentially of", and "consisting of". As used herein, the term "user contact surface" of an absorbent article is one or more surfaces of any component of the article that can make contact with the user's body at some time during the period of use. Body contacting surfaces include, but are not limited to, portions of the topsheet, leg cuffs or elastics, waist region, side panels, and the like, which can make contact with the wearer during use. As used herein, the term "skin care composition" refers to any composition that contains an enzyme inhibitor that is transferred to the skin of a user of an article treated as a result of normal, movement contact. of the user and / or body heat when the item is being used. As used herein, the term "IC50" means the inhibitory concentration (e.g., a micromolar concentration, μM) of a substance (inhibitor) that reduces the rate of cleavage of the substrate by an enzyme by 50%, as measured by the test In vitro standard of the enzyme activity described below. The IC5o is calculated according to the equation IC50 = [l] / [(v / v,) - 1], where [I] is the concentration of the inhibitor tested, v is the rate of unfolding of the substrate in the absence of the inhibitor and v, is the rate of unfolding of the substrate in the presence of the inhibitor. As further described below, the IC50 of an enzyme inhibitor according to the invention can be measured by a Purified Enzyme Method or by a Fecal Enzyme Method. Other terms are defined here where they are initially discussed. All percentages, proportions and ratios used here are by weight unless otherwise specified.
II. Enzyme Inhibitors Inhibitors of enzyme activity are well known and are typically classified as competitive inhibitors (which compete with the substrate for binding at the active site on the enzyme) and non-competitive inhibitors (which bind to another site different from the site). active to inactivate the enzyme). Many enzymes, such as metalloproteases, are inhibited by substances that bind with a metal group in the enzyme. Chelating agents are effective inhibitors of other enzymes that require the presence of metal ions, such as calcium ions, cobalt, copper, magnesium, manganese, sodium, potassium, or zinc, for activation. Since enzymes are proteins, antibodies raised against specific enzymes are also effective enzyme inhibitors. Enzymatic inhibitors useful in the absorbent articles described herein will typically have an IC50 value of no greater than about 500 μM, more typically not greater than about 250 μM, and even more typically no greater than about 100 μM. It will be understood that certain enzyme inhibitors (e.g., EDTA) will have higher IC 50 values but will become useful in the absorbent articles described herein. For materials for which molecular weight can not be determined, these materials will typically reduce the activity of the enzyme by at least 50% at a concentration in the skin care composition of no greater than about 5 weight percent. Representative methods for measuring the inhibitory activity of the enzyme are discussed below. Without limitation, any type of enzyme inhibitor may be employed in the skin care compositions transferable to the skin of the user from the absorbent articles of the present invention, including any inhibitor of natural occurrence of plant, microbial and / or animal origin (including human) and synthetically manufactured chemical inhibitors. The inhibitors of the enzyme can be hydrophilic or hydrophobic in nature and can thus be soluble in water or soluble in a hydrophobic vehicle. The enzyme inhibitors are preferably present in the skin care composition in a concentration of from about 0.001% to about 50% by weight, typically from about 0.01% to about 25%, more typically from about 0.1% by weight. about 10%, and very typically from about 0.1% to about 5%. Because of the variety of enzyme inhibitors employed in the invention, the effective concentration of each inhibitor must be determined separately, as is known to those skilled in the art. The enzyme inhibitors can be used simply or as a mixture of enzyme inhibitors such as a cocktail of inhibitors in an individual absorbent article. In addition, different enzyme inhibitors may be employed in the skin care compositions at different locations in an individual absorbent article. Because of the wide diversity of enzymes present in faeces and other body exudates, it is reasonably predictable that materials such as those described below which inhibit certain classes of enzymes (e.g., proteases) also inhibit enzymes that unfold substrates. different from those specified. For example, proteins and peptides). Therefore, inhibitors that inhibit proteases can also inhibit lipases and other esterases, amylases and / or ureases and vice versa. Inhibitors of enzymes and / or coenzymes very often found in fecal esus or other exudates of the body are preferred in the skin care compositions in the absorbent articles of the invention. In this manner, enzyme inhibitors are preferably inhibitors of proteolytic enzymes such as trypsin, chymotrypsin, aminopeptidase and elastase; lipases, bile salts; amylases; and / or ureases. Suitable exemplary protease inhibitors for use in the invention that are believed to inhibit the type of protease indicated in parentheses include, but are not limited to, soybean trypsin inhibitor and other trypsin inhibitors derived from plants such as inhibitor lime seed protease, corn protease inhibitor and the like; Bowman-Birk inhibitor (trypsin-like protease inhibitor, serine); pancreatic trypsin inhibitor such as inhibitor of pancreatic basic trypsin of bovine and other animal-derived pancreatic trypsin inhibitors; White egg trypsin inhibitor (trypsin-like protease inhibitor, serine); ovomucosides containing ovoinhibitors such as chicken white egg or turkey (trypsin inhibitors and chymotrypsin); chymostatin (chymotrypsin-like protease inhibitor, serine); aprotinins (serine protease inhibitor); leupeptin and its analogs such as propionyl-leupeptin, N-alpha-t-BOC deacetylleupeptin (inhibitor of serine and cysteine protease); bestatin and its analogues such as epibestatin and nitrobestatin (aminopeptidase metalloprotease inhibitor); amastatin and its analogues such as epiamastatin (aminopeptidase inhibitor); antipain (trypsin inhibitor); antithrombin III (serine protease inhibitor); hirundin (serine protease inhibitor type thrombin); cystatin (white egg cystatin protease inhibitor); E-64 (trans-epoxysuccinyl-L-leucylamido- (4-guanidino) -butane) and its analogs (cysteine protease inhibitor); alpha2-macroglobulin (universal endoprotease inhibitor); alpha antitrypsin (trypsin inhibitor); pepstatin and its analogs such as acetyl pepstatin, pepstatin, A, Nle-Sta-Ala-Sta (aspartyl protease inhibitor); apstatin (P aminopeptidase inhibitor); (2R) -2-mercaptomethyl-4-methylpentanoyl-b- (2-naphthyl) -Ala-Ala amide (metalloprotease matrix inhibitor); (2R) -2-mercaptomethyl-4-methylpentanoyl-Phe-Ala amide (inhibitor of metalloprotease matrix); N-acetyl-Leu-Leu-methionine (calpain inhibitor); N-acetyl-Leu-Leu-norleucinal (calpain inhibitor); p-aminobenzoyl-Gly-Pro-D-Leu-D-Ala hydroxamic acid (metalloprotease matrix inhibitor); 2 (R) - [N- (methoxyphenylsulfonyl) -N- (3-pyridylmethyl) amino] -3-methylbutane-hydroxamic acid (metalloprotease inhibitor); L-1-chloro-3- [4-tosylamido] -7-amino-2-heptanone-HC1 (TLCK), L-1-chloro-3- [4-tosylamido] -4-phenyl-2-butanone (TPCK ), tranexamic acid, glycyrrhizic acid, 18-ß-glyceryltinic acid and its corresponding salts, stearialglycyrretinate, oval colloidal extracts, elhibin, zinc salts, iodoacetate, phenylmethylsulfonyl fluoride, phosphoramidon, 4- (2-aminoethyl) -benzensulfonyl fluoride HC1, 3,4-dichloroiso-coumarin, corcetin, and the like, and mixtures thereof. It has also been found that chelating agents are useful as inhibitors of both proteases and ureases at a concentration of about 0.1% to about 2%. Exemplary chelating agents are phytic acid, nitrilotriacetic acid, EDTA, diethylene triamine pentacetic acid, hydroxyethyl ethylene diamine triacetic acid, and the corresponding salts, disclosed in U.S. Patent No. 5,091, 193 issued to Enjolras on February 25, 1992, the disclosure of which is hereby incorporated by reference. Among the preferred protease inhibitors for use in the absorbent articles of the invention are compounds that exhibit the inhibitory activity that is not necessarily restricted to a single protease class. These compounds include, but are not limited to, hexamidine and its salts; pentamidine and its salts; benzamidine and its salts and derivatives, p-aminobenzamidine and its salts and derivatives; and guanidinobenzoic acid and its salts and derivatives such as those disclosed in U.S. Patent No. 5,376,655 issued to Imaki et al. on December 27, 1994, the disclosure of which is hereby incorporated by reference. Other preferred protease inhibitors include polymeric guanidinobenzoic acid derivatives disclosed and made in our co-pending United States patent application Serial No. 09/041, 196, filed March 12, 1998, in the name of T.L. Underiner and others, co-represented with the present application, the disclosure of whose co-pending application is hereby incorporated by reference. Protease inhibitors which are preferred in the practice of the invention are the soybean trypsin inhibitor, aprotinin, hexamidine (for example, hexamidine diisethionate), p-aminobenzamidine, leupeptin, pepstatin A, chymostatin and polymeric derivatives of the acid guanidinobezoic (disclosed and made in our co-pending United States patent application Serial No. 09/041, 196, incorporated by reference above). Particularly preferred protease inhibitors are the soybean trypsin inhibitor, hexamidine, p-aminobenzamidine and the above polymeric guanidinobenzoic acid derivatives. Ureases are known to be inhibited in the presence of residual amounts of heavy metal ions, such as those of silver, copper and the like. In this way, residual amounts (as little as 0.001% or less) of the salts of these metals are useful as urease inhibitors. Other exemplary inhibitors of urease activity include, but are not limited to, acetyl hydroxamic acid and its derivatives, such as cinamoyl hydroxamic acid and other hydroxamic alkyl acids, salts and corresponding derivatives; phosphoroamidate and its derivatives. These compounds are competitive inhibitors of urease at a concentration of approximately 2 micromolar (μM). Chelating agents have also been found to be useful as inhibitors of both proteases and ureases at a concentration of about 0.1% to about 2%. Exemplary chelating agents are phytic acid, nitrilotriacetic acid, ethylenediamine tetraacetic acid (EDTA), diethylene triamine pentacetic acid, hydroxyethyl ethylene diamine triacetic acid, and the corresponding salts, disclosed in U.S. Patent No. 5,091, 193 incorporated by reference. previously. Other urease inhibitor compounds are disclosed in U.S. Patent No. 3,935,862 issued to Kraskin on February 3, 1976, the disclosure of which is hereby incorporated by reference, and include amino acid compounds, such as acids hydroxyalkylamino, sulfhydryl amino acid, aminosulfonic acids, aminophosphonic acid compounds and amino ether acids such as methoxyethyliminodiacetic acid, ethylene bis (oxypropylamin diacetic acid), ethylene bis (oxyethyliminodiacetic acid), amino methyl phosphonic acid (N, N-diacetic), and the like, and aminopolycarboxylic acid compounds, including the acids and salts of diethylenetriaminepentaacetic acid (DTPA), N-hydroxyethylenediaminetriacetic acid (HEDTA), and the like. Other suitable urease inhibitors are disclosed in U.S. Patent No. 5,409,903 issued to Polak et al. On April 25, 1995, the disclosure of which is hereby incorporated by reference. This patent discloses dibasic magnesium phosphate, dialdehyde polysaccharides and zeolite, used alone in combination with each other or with the compounds of calcium, calcium acetate, calcium chloride, calcium gluconate and calcium lactate, as well as magnesium compounds , magnesium chloride and magnesium chloride, for the inhibition of ureases. Suitable lipase inhibitors include, but are not limited to, salts of water-soluble metals, such as cadmium, cobalt, copper, iron, molybdenum, silver, lanthanum, tin and zinc. Lipase inhibitor compounds are disclosed in U.S. Patent No. 4,556,560, herein incorporated by reference, and include zinc chloride, zinc acetate, zinc nitrate trihydrate, zinc nitrate hexahydrate, zinc sulfate. , zinc sulfate heptahydrate, zinc sulfate hexahydrate, iron chloride (ll), iron chloride tetrahydrate (ll), iron chloride (III), iron chloride monohydrate (III), iron chloride hexahydrate (lll), iron lactate (ll), iron lactate (lll), iron malate (lll), iron nitrate (ll), iron nitrate hexahydrate (III), iron nitrate nonahydrate (III), iron sulphate (ll) and its hydrates, iron sulphate (III) and its hydrates, copper sulphate pentahydrate, tin chloride, cobalt chloride and lanthanum chloride, zinc salts of both saturated and unsaturated monocarboxylic acids they have from about 6 to about 12 carbon atoms, copolymers of block of propylene oxide and ethylene oxide (for example, marketed as Pluronic® and Tetronic® by BASF Corp.), glycerol triesters of fatty acids having from about 2 to about 20 carbons such as triacetin, and the like. Other useful lipase inhibitors are disclosed in U.S. Patent No. 5,091, 193, hereby incorporated by reference, and include esters of fatty alcohols, such as saturated or unsaturated, linear or branched alkyl acetate, lactate or propionate containing 10 to 20 carbon atoms; zinc salts of saturated or unsaturated, linear or branched fatty acids of 2 to 22 carbon atoms, such as those formed with propionic acid, isobutyric acid, caproic acid, decilentic acid, and the like; zinc salts and adylated amino salts, such as propionylcysteine, propionyl hydroxyproline or caproylcysteine, and the like. Lipase inhibitors, such as the above, have been found to be useful at a concentration of from about 0.01% to about 10%. Still other useful lipase inhibitors, disclosed in our co-pending patent application EP 97 / 120,699, filed on November 26, 1997 in the name of G. Palumbo et al., The disclosure of which is hereby incorporated by reference, include ester-specific agents that act as a substitute substrate for fecal lipases and therefore are competitive inhibitors of lipase. These esters have the formulas:
R-: (I) R Ro
C = O c = o O or R 10 R 1 1 (II)
wherein R-, and each R2 are independently an acyl group with 2 to 22 carbon atoms, or an alkyl, alkenyl, arylalkyl, hydroxyalkyl group with 1 to 24 carbon atoms or hydrogen, whereby at least one of R, and R2 is such an acyl group, R3, R4. Rs, Re, R7l R8, and Rg are independently alkyl, alkenyl, arylalkyl, hydroxyalkyl, alkoxy groups of 1 to 24 carbon atoms, hydroxy group or hydrogen; R10 and Rn are independently an alkyl, alkenyl, arylalkyl, hydroxyalkyl, alkoxy groups of 2 to 24 carbon atoms, a hydroxy group or hydrogen; A and B are independently alkylene, alkenylene, alkoxylene, linear or branched hydroxyalkylene groups of C -, - C6; the values of x are independently from 0 to 15; the values of y are independently 0 or 1, provided that when x = 2 and y = 0, at least one R 2 is an alkyl, alkenyl, arylalkyl, hydroxyalkyl group with 1 to 24 carbon atoms or hydrogen. Still further examples of lipase inhibitors are those disclosed in U.S. Patent No. 5,643,874, hereby incorporated by reference, which include: (2S.3S, 5S) -5 ((S) - acid lactone) 2-formamido-4-methyl-valeryloxy] -2-hexyl-3-hydroxy-hexadecane, also known as tetrahydrolipstatin; 1, 3-acid lactone (2S, 3S, 5S, 7Z, 10Z) -5 - [(S) -2-formamido-4-methyl-valeryloxy] -2-hexyl-3-hydroxy-7, 10 -hexadecadienoic, also known as lipstatin; 1- (trans-4-isobutylcyclohexyl) -2- (phenylsulfonyloxy) ethanone, also known as FL-386; 4-phenoxyphenyl ester of 4-methylpiperidine-1-carboxylic acid, also known as WAY-121898; N- [3-chloro-4- (trifluoromethyl) phenyl-] N '- [3- (trifluoromethyl) -phenyl] urea, also known as BAY-N-3176; N-formyl-L-valine- (S) -1 - [[(2S, 3S) -3-hexyl-4-oxo-2-oxethanyljmethylhexyl ester, also known as valilactone; (2S, 3S, 5S, 7Z, 10Z) -5 - [(S) -2-Acetamido-3-carbamoylpropionyloxy] -2-hexyl-3-hydroxy-7,10-hexadecadienic acid lactonate, also known as esterastine; (3S, 4S) -4 - [(1S, 5R, 7S, 8R, 9R, E) -8-hydroxy-1, 3,5,7,9-pentamethyl-6-oxo-3-undecenyl] -3- methyl-2-oxatanone, also known as ebelactone A; (3S, 4S) -3-ethyl-4 - [(1S, 5R, 7S, 8R, 9R, E) -8-hydroxy-1, 3,5,7,9-pentamethyl-6-oxo-3- undecenyl] -2-oxatanone, also known as ebelactone B; and 1,6-di (O- (carbamoyl) cyclohexanone oxime) hexane, also known as RHC80267. Exemplary inhibitors of bile salts that are coenzymes for lipolytic enzymes and are useful as inhibitors of the lipase enzyme in the absorbent articles of the invention include, but are not limited to, cationic compounds disclosed in our copending European patent application 97 / 120,700, filed on November 26, 1997 in the name of G. Palumbo, and others, the disclosure of which is hereby incorporated by reference. These compounds have the formulas:
R4 - N- RI R-. MY)
di) or an amphoteric compound and preferably an acid source, the amphoteric compound and its isoelectric point having the formula:
R 10 (III)
for the preparation of a composition for the treatment, prevention or reduction of lipolytic dermatitis of the external skin, wherein R ^ R2, R3 and R are independently a C1-C22 alkyl, alkenyl, aryl, arylalkyl, amidoalkyl, (poly ), alkoxy, hydroxyalkyl, or acyl groups, or two or more of the groups of R ^ R2, R3 and R together form one or more ring structures; R5, R6 and A are independently an alkylene of C 1 -C 22, alkenylene, (poly) alkoxylene, hydroxyalkylene, arylalkylene or amidoalkylene groups; R7 and R8 are independently a CrC4 alkyl, alkenyl, alkoxy group or a hydroxy group or hydrogen; R9 and Rio are independently a C? -C22 alkyl, alkenyl, aryl, arylalkyl, amidoalkyl, (poly) alkoxy, hydroxyalkyl, or acyl groups, or two or more of the groups R1-R9 and R10 together form one or more structures ring; BH is a proton donor group; x is from 2 to 4; and M is a counter ion. Another exemplary inhibitor of the appropriate bile salt is cholestyramine, described in the publication by C. Michael White et al., Entitled "Cholestyramine Ointment to Treat Buttocks Rash and Anal Excoriation in Children", The Annals of Pharmacotherapy 30: 954-956 , September 1996. The p-guanidinobenzoic acid derivatives, especially the esters of p-guanidinobenzoic acid, have been described as esterase inhibitors. These inhibitors are useful in the skin care compositions of the absorbent articles of the invention and are described in U.S. Patent Application No. 5,376,655 issued to Imaki et al. On December 27, 1994, the disclosure of which is incorporated herein by reference. which is hereby incorporated by reference. Suitable amylase inhibitors and / or glycosidase amylase inhibitors include those described in U.S. Patent No. 5,643,874, herein incorporated by reference, and include O-4,6-dideoxy-4 - [[[1 S- (1, 4a, 5β, 6)] - 4,5,6-trihydroxy-3- (hydroxymethyl) -2-cyclohexan-1-yl] amino] - - D-glucopyranosyl- (1 - »4 ) OaD-glucopyranosyl- (1 -> 4) -D-glucose, also known as acarbose;
2 (S), 3 (R), 4 (S), 5 (S) -tetrahydroxy-N- [2-hydroxy-1- (hydroxymethyl) -etl] -5- (hydroxymethyl) -1 ( S) -cyclohexamine, also known as voglibose; 1, 5-dideoxy-1, 5 - [(2-hydroxyethyl) imino] -D-glucitol, also known as miglitol; 1,5-dideoxy-1, 5- [2- (4-ethoxycarbonylphenoxy) -ethylimino] -D-glucitol, also known as emiglitate; 2,6-dideoxy-2,6-imino-7 (β-D-glucopyranosyl) -D-glycero-L-guloheptitol, also known as MDL-25637; 1,5-dideoxy-1, 5- (6-deoxy-1-O-methyl-a-D-glucopyranos-6 -limino) -D-glucitol, also known as camiglibose; 1, 5,9,1,1, 14-pentahydroxy-3-methyl-8,13-dioxo-5,6,8,13-tetrahydrobenzo [a] -naphthacene-2-carboxylic acid, also known as pradimycin Q; also known as adiposine; and 1,2-dideoxy-2- [2 (S), 3 (S), 4 (R) -trihydroxy-5- (hydroxymethyl) -5-cyclohexen-1 (S) -ylamino] -L-glucopyranose, also known as salbostatin. Other suitable amylase inhibitors include tendamistat, trestatins, and those derived from plants, especially oats, rice, corn, barley and other cereal grains, seeds and seaweed.
lll. Absorbent Articles As used herein, the term "absorbent article" refers to a device that absorbs and retains exudates from the body. The term "disposable" is used herein to describe absorbent articles, which are not intended to be washed or otherwise restored or reused as an absorbent article after a single use. Examples of disposable absorbent articles include feminine hygiene garments such as sanitary napkins, panty liners and tampons, diapers, incontinence briefs, diaper carriers, trainers, and the like. Disposable absorbent articles typically comprise a liquid permeable topsheet, a liquid impermeable backsheet and an absorbent core positioned between the topsheet and the backsheet. Disposable absorbent articles and their components, including the topsheet, backsheet, absorbent core and any individual layer of these components, have a body-facing surface and a garment-facing surface. As used herein, "body-facing surface" represents that surface of the article or component that is intended to be used toward or adjacent to the user's body, while the "surface facing the garment" is on the side opposite and is intended to be worn towards or positioned adjacent to the garment or underwear of the wearer when the disposable absorbent article is worn. The following description generally discusses absorbent core, top sheet and backsheet materials that are useful in disposable absorbent articles. It should be understood that this general description applies to these components of the specific absorbent articles shown in Figure 1, and further described below, in addition to those of other disposable absorbent articles, which are generally described herein. In general, the absorbent core is capable of absorbing or retaining liquids (e.g., menstruation, urine and / or other body exudates). The absorbent core can preferably be compressed, is conformable and non-irritating to the wearer's skin. The absorbent core can be manufactured in a wide variety of shapes and sizes (eg, rectangular, oval, hourglass shaped, "T" shaped, dog bone shaped, asymmetrical, etc.). In addition to the absorbent composites, the absorbent core can include any of a wide variety of liquid materials commonly used in absorbent articles such as shredded wood pulp, which is generally referred to as air felt. Examples of other absorbent materials suitable for use in the absorbent core include crimped cellulose filler; meltblown polymers including co-form; chemically hardened, modified or cross-linked cellulosic fibers; synthetic fibers such as crimped polyester fibers; peat, tissue paper; including tissue paper wrappers and tissue paper laminates; absorbent foams; absorbent sponges; super absorbent polymers; absorbent gelling materials; or any equivalent material or combinations of materials or mixtures thereof. The configuration and construction of the absorbent core can be varied (for example, the absorbent core can have zones of variable gauge and / or have a profile in order to be thicker in the center, hydrophilic gradients, gradients of absorbent composites, gradients super absorbent; or areas of lower average density and lower average basis weight, eg, acquisition zones, and may comprise one or more layers or substrates). The total absorbent capacity of the absorbent core, however, must be compatible with the design load and intended use of the absorbent article. In addition, the size and absorbent capacity of the absorbent core can be varied to suit different uses such as diapers, incontinence pads, protective pantyhose, regular sanitary napkins, and night sanitary napkins, and to suit users ranging from babies to adults. The absorbent core may also include other absorbent components that are generally used in absorbent articles, for example, a dusting layer, a penetration or acquisition layer, or a secondary top sheet to increase user comfort. The top sheet is preferably pleasant, soft feeling, and non-irritating to the wearer's skin. In addition, the topsheet is permeable to liquid, allowing liquids (eg, menstruation and / or urine) to easily penetrate through its thickness. A suitable topsheet can be manufactured from a wide variety of materials such as woven and non-woven materials (e.g., a non-woven web of fibers), including apertured non-woven materials; polymeric materials such as thermoplastic films formed with apertures, apertured plastic films, and hydroformed thermoplastic films; porous foams, cross-linked foams; crosslinked thermoplastic films; and thermoplastic canvases. Suitable woven and nonwoven materials may be composed of natural fibers (e.g., wood or cotton fibers), synthetic fibers (e.g., polymer fibers such as polyester, polypropylene or polyethylene fibers) or a combination thereof. natural and synthetic fibers. When the top sheet comprises a nonwoven web, the web can be manufactured from a wide number of known techniques. For example, the web can be spunbonded, carded, wet-laid, meltblown, hydroentangled, hydroformed, hydrophobic, combinations of the foregoing, or the like. If it is composed of a woven or nonwoven material, the topsheet preferably comprises skin care compositions comprising the enzyme inhibitor (s), as described below. The backsheet is impervious to liquids (eg, menstruation and / or urine) and preferably comprises a thin plastic film, although other flexible liquid impervious materials may also be used. As used herein, the term "flexible" refers to materials that are pleasing and will easily conform to the shape and general contours of the human body. The backsheet prevents the exudates absorbed and contained in the absorbent core from wetting articles that are in contact with the absorbent article such as bedding, pants, pajamas, underwear. The backsheet in this manner may comprise a woven or non-woven material, polymeric films such as polyethylene or polypropylene thermoplastic films., or composite materials such as a nonwoven material coated with films. A suitable backing sheet is a polyethylene film having a thickness of about 0.012 mm to about 0.051 mm. Exemplary polyethylene films are manufactured by Clopay Corporation of Cincinnati, OH, under the designation P18-1401 and by Tredegar Film Products of Terre Haute, IN, under the designation XP-39385. The backsheet is preferably engraved or finished in matte to provide a clothing type appearance. In addition, the backsheet may allow the vapors to escape from the absorbent core (i.e., the backsheet is breathable), while still preventing exudates from passing through the backsheet. The size of the backing sheet is dictated by the size of the absorbent core and the exact design of the selected absorbent article. The back sheet and the top sheet are positioned adjacent to the garment facing surface and the body facing surface, respectively, of the absorbent core. The absorbent core is preferably bonded with the backsheet, the top sheet, or both, in a manner known as through attachment means (not shown in Figure 1) such as those well known in the art. However, embodiments of the absorbent articles are contemplated wherein portions or the entire absorbent core is separated from either the topsheet, the backsheet or both. For example, the backsheet and / or the top sheet may be secured to the absorbent core or to each other through a uniform continuous layer of adhesive, a patterned adhesive layer, or a separate line arrangement, spirals, or dots of adhesives. The adhesives that have been found to be satisfactory are manufactured by H. B. Fuller Company of St. Paul, MN under the designation HL-1258 or H-2031. The attachment means preferably comprises a network of open-pattern filaments of adhesive as described in De. E. U. A. 4,573,986, issued to Minetola et al., March 4, 1986, and which is incorporated herein by reference. An illustrative attachment means of an open-pattern filament network comprises several lines of adhesive filaments intertwined in a spiral pattern as illustrated by the apparatus and method shown in US Patent 3,911, 173, issued to Sprague, Jr. October 7, 1975; U.S. Patent No. 4,785,996, issued to Zwieker et al., November 22, 1978; and U.S. Patent No. 4,842,666, issued to Werenicz on June 27, 1989. Each of these patents is incorporated herein by reference. Alternatively, the joining means may comprise heat joints, pressure joints, ultrasonic joints, dynamic mechanical joints, or any other suitable joining means or combinations of these joining means as is well known in the art. The preferred disposable absorbent article of the invention, at least a portion of which has an enzyme inhibitor incorporated therein and, more preferably, having a contact surface with the body treated with a skin care composition containing a enzyme inhibitor, it's a diaper. As used herein, the term "diaper" refers to an absorbent article generally worn by infants, and incontinent persons, which is worn around the wearer's lower torso, in other words, the term "diaper" includes diapers for infants. , trainers, incontinence devices for adults and the like. Figure 1 is a plan view of the diaper 50 useful in the invention in its non-contracted planar state (i.e., with elastic-induced contraction pulled) with the portions of the structure cut to more clearly show the construction of the diaper 50 and with the portion of the diaper 50 that faces away from the wearer (outer surface) facing the visor. As shown in Figure 1, the diaper 50 preferably comprises a liquid-permeable top sheet 520, a liquid-impermeable backsheet 530 bonded to the topsheet 520, an absorbent core 540 positioned between the topsheet 520 and the sheet back 530, absorbent core 540 having a garment facing surface 542, body facing surface 544, side edges 546, waist edges 548, and tabs 549. Diaper 50 preferably further comprises elastic cuffs for legs 550 , and multiple elastic waist feature pleats designated 560, and a fastening system generally designated 570. The diaper 50 is shown in Figure 1 having an outer surface 52, an inner surface 54 corresponding to the body facing surface , which is exposed to the outer surface 52, a first waist region 56, a second waist region 58, and a periphery 51, which is defined by the outer edges of the diaper 50 where the longitudinal edges are designated 55 and the end edges are designated 57. (Although those skilled in the art will recognize that a diaper is usually described in terms of having a pair of diapers. waist regions and a crotch region between the waist regions, in this application, for simplicity of terminology, the diaper 50 is described as having only waist regions including a portion of the diaper that could typically be designated as part of the region crotch). The surface facing the body 54 of the diaper 50 comprises that portion of the diaper 50 that is positioned adjacent the wearer's body during use. The body facing surface 54 is generally formed of at least a portion of the topsheet 520 and other components that can be attached to the topsheet 520, such as leg cuffs 550, as well as any region to which the sheet The upper can not extend, but which remains in contact with the user, such as the waist accessory 560, side panels, and the like. The outer surface 52 comprises that portion of the diaper 50 that is positioned away from the wearer's body (i.e., the outer surface 52 generally formed by at least a portion of the backing sheet 530 and other components that can be attached to the sheet backup 530). The first waist region 56 and the second waist region 58 extend, respectively, from the end edges 57 of the periphery 51 to the lateral center line 53 of the diaper 50. Figure 1 also shows the longitudinal centerline 59. Figure 1 shows a preferred embodiment of the diaper 50, wherein the top sheet 520 and the backsheet 530 have length and width dimensions generally greater than those of the absorbent core 540. The elastic leg cuffs 550 and the backsheet 530 extend beyond the edges of the absorbent core 540 to thereby form the periphery 51. of the diaper 50. The diapers of the present invention can have a number of well-known configurations, with the absorbent cores thereof being adapted for the present invention. The illustrative configurations are generally described in the patent of US Pat. No. 3,860,003, issued to Buell on January 14, 1975.; U.S. Patent No. 5,151,092, issued to Buell et al. on September 29, 1992; patent of E. U. Á. 5,221, 274 issued to Buell et al. On June 22, 1993. Each of these patents is incorporated herein by reference. Another diaper configuration to which the present invention can be readily adapted is described in U.S. Patent No. 5,554,145 issued to Roe et al. On September 10, 1996, the disclosure of which is incorporated herein by reference. A topsheet 520, which is particularly suitable for use in the diaper 50, is carded and thermally bonded through means well known to those skilled in the art of fabrics. A satisfactory topsheet for the present invention comprises polypropylene fibers of mediated length having a denier value of about 2.2. As used in the present invention, the term "medium length fibers" refers to those fibers that have a length of at least about 15.9 mm. Preferably, the topsheet has a basis weight of about 15 to about 25 grams per square meter. A suitable topsheet is manufactured by Veratec, Inc., a Division of International Paper Company, of Walpole, MA, under the designation P-8. The topsheet 520 of the diaper 50 is made of a hydrophilic material to promote rapid transfer of liquids (eg, urine) through the topsheet. If the topsheet is made of a hydrophobic material, at least the portions of the upper surface of the topsheet are treated to make hydrophilic, so that liquids will be transferred through the topsheet more rapidly. This reduces the likelihood that body exudates will flow out of the top sheet instead of being drawn through the top sheet and absorbed by the absorbent core. The topsheet can be made hydrophilic by treating it with a surfactant. Suitable methods for treating the topsheet with a surfactant include spraying the material of the topsheet with the surfactant and immersing the material in the surfactant. A more detailed discussion of such treatment and hydrophilicity is contained in US Patent 4,988,344 issued to Reising and others on January 29, 1991 and US Patent 4,988,345 issued to Reising on January 29, 1991, each of which it is incorporated here by reference. Alternatively, the topsheet may be in the form of a film formed with openings, which is preferred in feminine hygiene absorbent articles, the films formed with openings are useful as they are permeable to body fluids and not yet absorbent and have a reduced tendency to allow liquids to pass back and rewet the user's skin. In this way, the surface of the formed film that is in contact with the body remains dry, thus reducing the spots on the body and creating a more comfortable feeling for the user. Suitable formed films are described in U.S. Patent 3,929,135 issued to Thompson on December 30, 1975; U.A. Patent 4,324,246 issued to Mullane et al. on April 13, 1982; U.A. Patent 4,342,314 issued to Radel et al. on August 3, 1982; U.A. Patent 4,463,045, issued to Ahr et al. on July 31, 1984; and U.S. Patent No. 5,006,384, issued to Baird on April 9, 1991. Each of these patents is incorporated herein by reference. The upper sheets of film formed with particularly preferred micro-apertures are described in US Pat. No. 4,609,518, issued to Curro et al. On September 2, 1986 and US Pat. No. 4,629,643, issued to Curro et al. On December 16, 1986; which are incorporated herein by reference. The preferred topsheet for use in feminine hygiene products is the formed film described in one or more of the above patents and sold as sanitary napkins by Procter & amp;; Gamble Co. of Cincinnati, OH as "DRI-WEAVE®". The surface facing the body of the formed film topsheet can be hydrophilic in order to help the body fluids transfer through the topsheet more rapidly than if the body surface were not hydrophilic in order to decrease the likelihood that the liquid will flow into the topsheet instead of flowing into and being absorbed by the absorbent structure. In a preferred embodiment, the surfactant is incorporated into the polymeric materials of the formed film topsheet as described in U. S. Statutory Invention Registration H1670 for Aziz et al., Published on the 1st. July 1997, which is incorporated herein by reference. Alternatively, the surface that gives the body of the topsheet can be made hydrophilic by treating it with a surfactant such as is described in U.S. Patent No. 4,950,254, hereby incorporated by reference. In alternative embodiments (not shown) of the present invention, the absorbent article may be provided with means for improving contact between the topsheet and a user's skin. In one such embodiment, the absorbent article can be provided with elastic means, as described in U.S. Patent No. 4,892,536 issued to the name of DesMarais et al., On January 9, 1990, in the U.S. Patent. No. 4,990,147 issued to Freeland on February 5, 1991, and in United States Patent Application Serial No. 07 / 993,198 filed in the name of Freeland and others on December 18, 1992, which lift the superior sheet to improve contact with the perianal region of the user. In another embodiment, described in U.S. Patent No. 5,171, 236, issued in the name of Drier et al. On December 15, 1992, a diaper is provided with a separation means for lifting the topsheet. In yet another embodiment, described in the US Statutory Invention Registration H1687, published in the name of Roe et al. On October 7, 1997, the absorbent article is provided with a glute locking device that lifts the upper sheet the groove of Buttocks of a user. In a preferred embodiment of a diaper as described herein, the backsheet 530 has a modified hourglass shape extending beyond the absorbent core at a minimum distance of about 1.3 cm to about 6.4 cm around the entire periphery of the diaper. The absorbent core 540 can take any size or shape that is compatible with the diaper 50. A preferred embodiment of the diaper 50 has a modified, asymmetric, T-shaped absorbent core 540 having tabs in the first waist region but a generally rectangular in the second waist region. Illustrative absorbent materials for use as the absorbent core of articles useful in the methods herein are described in, for example, U.S. Patent No. 4,610,678 issued to Weisman et al., September 9, 1986; U.S. Patent No. 4,673,402, issued to Weisman et al. on June 16, 1987; U.A. Patent 4,888,231 issued to Angstadt on December 19, 1989; and US Patent 4,834,735 issued to Alemany et al. on May 30, 1989. The absorbent core can further comprise the dual core system containing an acquisition / distribution core of chemically hardened fibers placed on an absorbent storage core as detailed. in U.S. Patent 5,234,423, issued to Alemany et al., on August 10, 1993; and in U.S. Patent No. 5,147,345 issued to Young, LaVon and Taylor on September 15, 1992. All of these patents are incorporated herein by reference. In a preferred embodiment, the diaper 50 further comprises elastic leg cuffs 550 to provide improved containment of liquids and other body exudates.; a 560 elastic waist accessory that provides improved fit and containment; and a fastening system 570, which forms a lateral closure that maintains the first waist region 56 and the second waist reaction 58 in an overlapping configuration, so that lateral stresses are maintained around the circumference of the diaper to maintain the diaper on the user. The diaper 50 may also comprise elastic waistbands (not shown) and / or elastic side panels (not shown) in the waist regions 56 and 58 to provide an elastically extending aspect that provides a more comfortable and contour fit and a more effective application of the diaper 50. The elastic leg cuffs 550 can be constructed in a number of different configurations, including those described in the aforementioned U.S. Patent No. 3,860,003; U.A. Patent 4,909,803, issued to Aziz et al. on March 20, 1990; U.S. Patent No. 4,695,278 issued to Lawson et al. on September 22, 1987; and U.S. Patent No. 4,795,454 issued to Dragoo on January 3, 1989, each being incorporated herein by reference. Absorbent articles having elastic cuffs that are treated with a composition that may be useful herein are described in the co-pending US patent application No. 08 / 766,386 and 08 / 840,039, filed December 3, 1996 and 24 April 1997, respectively, both incorporated herein by reference. The waist elastic attachment preferably comprises an elastic waist band (not shown) that can be constructed in a number of different configurations including those described in the patent of US Pat. No. 4,515,595 issued to Keivit et al., May 7, 1985; U.S. Patent No. 5,026,364 issued to Robertson on June 25, 1991; and the above-cited U.S. Patent No. 5,151,092 issued Buell et al. on September 29, 1992, the descriptions of which are incorporated herein by reference. Elastic side panels can be constructed in a number of configurations. Examples of diapers with elastic side panels placed on the tabs (flaps) of the diaper are described in U.S. Patent No. 4,857,067 issued to Wood et al. On August 15, 1989; U.A. Patent 4,381, 781 issued to Sciaraffa et al. on May 3, 1983; U.S. Patent No. 4,938,753 issued to Van Gompel et al., July 3, 1990; and U.S. Patent No. 5,151,092 issued to Buell et al. on September 29, 1992; the descriptions of which are incorporated herein by reference. Illustrative fastening systems 570 are described in U.S. Patent No. 4,846,815 issued to Scrips on July 11, 1989; U.S. Patent No. 4,894,060 issued to Nestegard, January 16, 1990; U.S. Patent No. 4,946,527 issued to Battrell, August 7, 1990; U.A. Patent 3,848,594 issued to Buell, November 19, 1974; patent of E. U. A. B1 4,662,875 issued to Hirotsu, and others on May 5, 19987; and U.S. Patent No. 5,151,092 issued to Buell et al. on September 29, 1992; the descriptions of which are incorporated herein by reference.
The diaper 50 is preferably applied to a wearer by placing one of the waist regions of the diaper, preferably the second waist region 58, under the user's back and pulling the rest of the diaper between the user's legs, so that the other region of waist, preferably the first waist region 56, is placed across the front of the user, the fastening system 570 is then applied to effect a lateral closure. Of course, it will be recognized that any absorbent article design can be used in the present invention to incorporate an enzyme inhibitor and / or a delivery system to deliver the inhibitor to a user's skin during use of the article, as described further further, it may be used in the present invention. The above description is merely illustrative. The present invention may also employ trainers as an absorbent article comprising a protease inhibitor. The term "trainers" as used herein, refers to disposable garments having fixed sides and leg openings designed for baby or adult users. Trainers (also referred to in the art as "put" products) are placed in place on the wearer by inserting the wearer's legs into the leg openings and slipping the trainer shorts into place around the wearer's lower cough. Suitable trainers are described in U.S. Patent No. 5,246,433 issued to Hasse et al. On September 21, 1993; U.S. Patent No. 5,569,234, issued to Buell et al., on October 29, 1996; U.S. Patent No. 4,940,464 issued to Van Gompel et al., July 10, 1990; and U.S. Patent No. 5,092,861 issued to Nomura et al., March 3, 1992, the descriptions of which are incorporated herein by reference. Another disposable absorbent article for use in the present invention is an incontinence article. The term "incontinence article" refers to pads, • undergarments (pads that remain in place through a suspension system of some kind, such as a band or the like), inserts for absorbent articles, capacity enhancers for absorbent articles, trusses, bed pads, and the like, regardless of whether they are worn by adults or other incontinent persons. Suitable incontinence articles are described in U.S. Patent No. 4,253,461 issued to Strickland et al., March 3, 1981; U.A. Patent Nos. 4,597,760 and 4,597,761 issued to Buell on the 1st. July 1986; the aforementioned U.S. Patent 4,704,115; U.A. Patent 4,909,802 issued to Ahr, et al., on April 16, 1987; U.S. Patent No. 4,964,860 issued to Gipson et al. on October 23, 1990; and in the patent of E. U. A. 5,304, 161, issued in the name of Noel and others on April 19, 1994. The descriptions of each of these references are incorporated herein by reference. Another disposable absorbent article for use in the present invention is a feminine hygiene article, such as a sanitary napkin. Suitable feminine hygiene articles are described in U.S. Patent No. 4,556,146 issued to Swanzon et al. On December 3, 1985; U.S. Patent No. B14,589,879 issued to Van Tilberg, April 27, 1993; U.S. Patent No. 4,687,478 issued to Van Tilburg on August 18, 1997; U.S. Patent No. 4,950,264 issued to Osborn Ill, on August 21, 1990; U.S. Patent No. 5,009,653, issued to Osborn III, on April 23, 1991; U.S. Patent No. 5,267,992 issued to Van Tilburg on December 7, 1993; U.S. Patent No. 5,389,094 issued to Lavash et al., February 14, 1995; U.S. Patent No. 5,413,568 issued to Roach et al. on May 9, 1995; U.S. Patent No. 5,460,623 issued to Emenaker et al. on October 24, 1995; U.S. Patent No. 5,489,283, issued to Van Tilburg on February 6, 1996; U.S. Patent No. 5,569,231, issued to Emenaker on October 29, 1996; and U.S. Patent No. 5,620,430 issued to Bamber on April 15, 1997, the descriptions of each of these patents is incorporated herein by reference.
IV. Enzyme Inhibition Test Standard in vitro tests for enzyme activity and inhibition of enzyme activity are well known. The reagents used to conduct these tests are usually available commercially. In general, a simple system comprises a specific enzyme substrate which, when hydrolyzed by the enzyme, produces a colored product. The activity of the enzyme is measured spectrophotometrically as the degree of development of the colored product (ie, the rate of color change) over a predetermined period of time. Inhibition of enzyme activity is exhibited as a measurable decrease in the rate of color change during the same period of time in the presence of an inhibitor. The following are exemplary methods that can be used to determine the inhibitory activity of enzyme inhibitors against a) known purifying enzymes that exist in feces, and b) the enzyme activity of the stools themselves. These methods are not intended to be limiting, however, other methods, other substrates, other inhibitors and the like may be used to test activity against a wide variety of fecal enzymes, as is known to one skilled in the art. For each of the following Purified Protease tests, Purified Lipase tests, Fecal Lipase tests, Purified Urease tests, Fecal Urease tests, Purified Amylase tests, and Fecal Amylase tests, the IC50 for each of the inhibitors tested can be calculated according to the following equation: iC5o = [l] / [(v / Vi) -1] where: [I] is the concentration of the tested inhibitor, v is the rate of unfolding of the substrate in the absence of inhibitor and v, is the rate of unfolding of the substrate in the presence of the inhibitor. In the methods, v and vi are measured as the change in absorbance (optical density, OD) at a given wavelength / time (for example, in minutes).
A. Purified Protease Methods 1. Purified Trypsin To test the efficacy of protease inhibitors against purified trypsin, 0.05 mL of a putative inhibitor and 0.125 mL of 32 nM trypsin were added (eg, Sigma, St. Louis, MO, catalog number T6424) in the trypsin regulator (50 mM TRIS, 20 mM CaCl 2, pH 8.2) to a microcuvette. The cuvette is incubated at 25 ° C for 10 minutes. For this mixture, 0.025 mL of substrate (4 mM Cbz-argigin-p-nitroanilide, eg, Sigma, St. Louis, MO, catalog number C4893) is added in the trypsin buffer to the cuvette, mixed, and absorbance at 405 nm measured over 10 minutes at 25 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against time. The rates v, and v, and the concentration of the inhibitor [I] are used to calculate the IC50 according to the equation expressed above.
2. Purified chymotrypsin To test the efficacy of protease inhibitors against purified chymotrypsin, 0.05 mL of a putative inhibitor and 0.125 mL of 16 nM motripsin are added (eg, Sigma, St. Louis, MO, catalog number C8946) in the chymotrypsin regulator (50 mM TRIS, 10Mm CaCl2, pH 7.6) to a microcuvette. The cuvette is incubated at 25 ° C for 10 minutes. To this mixture, 0.025 mL of the substrate (0.6 mM N-Succ-Ala-Ala-Pro-Phe-p-nitroanilide, for example, Sigma catalog number S7388) is added in the chymotrypsin buffer to the cuvette, mixed, and the absorbance at 405 nm measured for 10 minutes at 25 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against time. The rates v, and v, and the inhibitor concentration [I] are used to calculate the IC50 according to the equation expressed above.
3. Purified Leucine Aminopeptidase To test the efficacy of protease inhibitors against purified leucine aminopeptidase (LAP), 0.05 of a putative inhibitor and 0.125 mL of 0.06 U / mL LAP are added (eg, Sigma, St. Louis, MO , catalog number L5006) in a LAP regulator (50 mM sodium phosphate, pH 7.2) to a microcuvette. The microcuvette is incubated at 25 ° C for 10 minutes. For this mixture, 0.025 mL of the substrate is added (2.4mM L-leucine-p-nitroaniline, eg, Sigma, St. Louis, MO, catalog number L9125) in the LAP regulator to the cuvette are mixed, and measured the absorbance at 405 nm for 10 minutes at 25 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against time. The rates v, and v, and the inhibitor concentration [I] are used to calculate the IC50 according to the equation expressed above.
B. Specific Faecal Protease Methods The following is a general description of a method for obtaining a suitable stool sample for use in the Fecal Protease Methods. However, one skilled in the art will be able to adapt the method to obtain stool samples suitable for use in any of the Specific Fecal Protease Methods listed below (ie, lipase, urease and amylase) without undue experimentation. For purposes of establishing a positive control to ensure that fecal samples from the background sample exhibit the enzymatic activity required to determine the protease inhibitory activity, the following procedure was followed for each of the faecal protease methods. Fecal bottom feces of babies (at least five different bags) are collected in a manner to keep them free of urine and contamination and mixed with water to obtain a mixture by weight by weight (w / w) (eg, 1). : 50 p / p). This mixture is then mixed vigorously to obtain a homogeneous suspension by homogenization or sonication. The fecal background suspension is used as a source of protease activity as described below and will exhibit a substrate transfer rate in the absence of the inhibitor on the scale of 0.005 OD405 per minute at 0.020 OD 05 per minute. (Also, to ensure complete linearity the final absorbance should not exceed 1.5 OD405 units). If the background activity of babies is out of this scale, it is not possible to accurately determine the IC50 values for putative protease inhibitors. However, the scale of the activity of the enzyme can be adjusted by increasing or decreasing the dilution factor according to each enzyme. If this is not possible, a group of different subjects should be used to obtain the sample background.
1. Faecal trypsin activity To test the efficacy of protease inhibitors against trypsin activity in feces, the inhibitor and the trypsin regulator (50nM TRIS, 20mM CaCl2, pH 8.2) are added in a cuvette to obtain a final volume of 0.8 mL. To this mixture, 0.1 mL of the substrate (3mM cbz-arginine-p-nitroanilide) is added to the cuvette. The cuvette is mixed by inversion and incubated at 25 ° C for 5 minutes. A volume of 0.1 mL of the faecal suspension is added to the cuvette, mixed and the absorbance at 405 nm minus the absorbance at 490 nm are measured for 5 minutes at 25 ° C. (Absorbance at 490 nm is a correction factor for background absorbance due to particulate fecal material, ie, "interference"). The rate of unfolding of the substrate in the presence of the inhibitor (v,), is the curve of a graph related to the excess absorbance (ie, the absorbance at 405 nm minus the absorbance at 490 nm) against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the excess absorbance against time. The rates v, and v, and the concentration of the inhibitor [I] are used to calculate the IC5o according to the equation expressed above.
2. Fecal chymotrypsin activity To test the efficacy of protease inhibitors against the activity of chymotrypsin in stool, the inhibitor and regulator of chemotripsins (50 mM TRIS, 10 mM CaCl2, pH 7.6.) Is added in a cuvette. obtain a final volume of 0.92 mL. To this mixture, 0.04 mL of the substrate (1.25 mM N-Succ-Ala-Ala-Pro-Phe-p-nitroanilide) is added to the cuvette. The cuvette is mixed by inversion and incubated at 25 ° C for 5 minutes. A volume of 0.04 mL of the faecal suspension is added to the cuvette, mixed and the absorbance measured at 405 nm minus the absorbance at 490 nm for 5 minutes at 25 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the excess absorbance (ie, the absorbance at 405 nm minus the absorbance at 490 nm) against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the excess absorbance against time. The rates v, and v, and the inhibitor concentration [I] are used to calculate the IC50 according to the equation expressed above. 3. Faecal LAP activity To test the efficacy of protease inhibitors against LAP activity in faeces, the inhibitor and the LAP regulator (50 mM sodium phosphate, pH 7.2) are added in a cuvette to obtain a final volume of 0.95 mL. To this mixture, 0.03 mL of the substrate (6 mM L-Leucine-p-nitroanilide) is added to the cuvette. The cuvette is mixed by inversion and incubated at 25 ° C for 5 minutes. A volume of 0.02 mL of the faecal suspension is added to the cuvette, the absorbance at 405 nm minus the absorbance at 490 nm is mixed and measured for 5 minutes at 25 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the excess absorbance (ie, the absorbance at 405 nm minus the absorbance at 490 nm) against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the excess absorbance against time. The rates, v, and v, and the concentration of the inhibitor [I] are used to calculate the IC50 according to the equation expressed above.
Using the purified protease and faecal protease tests described above, the protease inhibition activity of the exemplary protease inhibitors employed in the absorbent articles of the invention was tested and the test results are illustrated in Table I.
TABLE 1 Clso Values (uM) Purified Proteases Specific Faecal Proteases Thymosine Chymotrypsin LAP * Trypsin Chymotrypsin LAP *
Trypsin Inhibitor 0.25 0.026 > 10 < 0.01 0.06 > 20 soybeans Aprotina 0.168 1 > 20 0.01 0.22 > twenty
Hexamidine 2.5 > 1000 256 2.3 > 1000 130
Diisetionata p-Aminobenzamidine 13.8 > 500 > 500 20 > 500 > 500
Leupeptin 0.14 > 500 > 500 0.1 1 > 500 > 500
Pepstatin A 324 4.9 > 500 > 500 300 > 500
Chymostatin > 500 < 0.12 > 500 > 500 0.2 > 500
TLCK ** 78.3 > 500 > 500 200 > 500 > 500
Glycyrrhizic acid 45 > 500 > 500 > 300 > 300 > 300
EDTA *** > 125,000 > 125,000 s • 125,000 100 100 > 3000
4 - (2- 47.5 190> 500 aminoetiyl) -benzenesulfonyl fluoride hydrochloride
* LAP = Leucine Aminopeptidase ** TLCK = HCl of L-1-chloro-3- [4-tosylamido] -7-amino-2-heptanone *** EDTA = Ethylenediamine Tetracetic Acid
As illustrated in Table 1, each of the exemplary compounds inhibit at least one of the proteases tested by the purified Protease and / or Fecal Specific Protease methods employed.
D. Purified lipase method To test the efficacy of lipase inhibitors, 0.05 ml of a putative inhibitor and 0.125 ml of 160 nM pancreatic lipase (e.g., Sigma, St. Louis, MO, catalog number L0382) in a 50 mM TRIS buffer containing 1 mM CaC12, pH 8.0, to a microcuvette. The cuvette is incubated at 25 ° C for 10 minutes. To this mixture is added 0.025 ml of the substrate (p-nitrophenol caprilat 1.25 mM, eg, Sigma, St. Louis, MO, catalog number N0752) to the cuvette and the mixture is incubated for an additional 5 minutes. The absorbance at 405 nm is then measured during the 10 minutes at 25 ° C: The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against time. The rates, v, and v, and the concentration of the inhibitor [I] are used to calculate the IC5o according to the equation expressed above.
E. Fecal lipase activity To test the efficacy of lipase inhibitors against lipase activity in the fecal eses, the lipase inhibitor and regulator (50mM TRIS buffer containing 1 mM CaC12, pH 8.0) is added to a bucket to obtain a final volume of 0.8 ml. To this mixture, 0.1 ml of the substrate (p-nitrophenol caprylate 1.25 mM) is added to the cuvette. The cuvette is mixed by inversion and incubated at 25 ° C for 5 minutes. A volume of 0.1 ml of the faecal suspension is added to the cuvette, mixed and the absorbance measured at 405 nm minus the absorbance at 490 nm for 5 minutes at 25 ° C. (Absorbance at 490 nm is a correction factor for background absorbance due to particulate fecal material (ie, "interference"). The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time The same procedure is repeated without the putative inhibitor The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against the The rates, v, and v, and the concentration of the inhibitor [I] are used to calculate the IC5o according to the equation expressed above.
F. Purified urease activity To test the efficacy of urease inhibitors, 0.05 ml of a putative inhibitor and 0.125 ml of 0.08 U / ml Jack Bean urease (Sigma catalog U2125) are added in 45 mM sodium phosphate buffer. , pH of 6.8, to a microcuvette. The cuvette is incubated at 25 ° C for 10 minutes. To this mixture, 0.025 ml of the substrate (300 mM urea, eg, Sigma U0631) is added to the cuvette and the mixture is incubated for an additional 5 minutes. The release of ammonia is determined immediately using a commercially available ammonia detection kit (Sigma Diagnostics, St. Louis, MO, Procedure 171).
G. Fecal urease activity To test the efficacy of urease inhibitors against urease activity in fecal eses, the inhibitor and the urease buffer (45 mM sodium phosphate pH 6.8) are added to a cuvette. to obtain a final volume of 0.8 ml. To this mixture 0.1 ml of the substrate (375 mM urea) is added to the cuvette. The cuvette is mixed by inversion and incubated at 25 ° C for 5 minutes. A volume of 0.1 ml of faecal suspension is added to the cuvette, mixed and incubated for an additional 5 minutes. The release of ammonia is determined immediately using a commercially available ammonia detection kit from (Sigma Diagnostics, Procedure 171). H. Activity of purified amylase The activity of amylase is determined using the Sigma 577 diagnostic procedure. To test the efficacy of amylase inhibitors, 0.010 ml of a putative inhibitor and 0.010 ml of human salivary-amylase are added. (Sigma # A0521; 100 to 2000 U / L, as measured by Sigma Diagnostics, Procedure 577) in water to a bucket. The cuvette is incubated at 37 ° C for 10 minutes. To this mixture, 1.00 ml of the amylase substrate is added to the cuvette and the mixture is incubated for an additional 2 minutes. Absorbance is measured at 405 nm for 2 minutes at 37 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against time. The rates, v, and v, and inhibitor concentration [I] are used to calculate the IC50 according to the equation expressed above.
I. Fecal amylase activity Amylase activity is determined using the Sigma 577 diagnostic procedure. To test the efficacy of amylase inhibitors against amylase activity in fecal eses, 0.010 ml of a putative inhibitor and 0.010 ml of fecal suspension (100 to 2000 U / L, as measured by the 577 procedure of Sigma Diagnostics) are added to a cuvette. The cuvette is incubated at 37 ° C for 10 minutes. To this mixture, 1.00 ml of the amylase substrate is added to the cuvette and the mixture is incubated for an additional 2 minutes. The absorbance at 405 nm minus the absorbance at 490 nm is measured for 2 minutes at 37 ° C. The rate of unfolding of the substrate in the presence of the inhibitor (v,) is the curve of a graph related to the absorbance at 405 nm against time. The same procedure is repeated without the putative inhibitor. The rate of unfolding of the substrate in the absence of the inhibitor (v) is the curve of a graph related to the absorbance at 405 nm against time. The rates, v, and v, and inhibitor concentration [I] are used to calculate the IC50 according to the equation expressed above.
V. Skin Care Compositions Skin care compositions suitable for use in the absorbent articles of the invention are described in US patent applications Nos. 08 / 926,532 and 08 / 926,533, each filed. on September 10, 1997; U.S. Patent No. 5,607,760 issued March 4, 1997; U.S. Patent No. 5,609,587 issued March 11, 1997; U.S. Patent No. 5,635,191, issued June 3, 1997; and U.S. Patent No. 5,643,588 issued on the 1st. July 1997, descriptions of each are incorporated herein by reference. As indicated, the skin care composition is transferred to the skin of a user of an article treated by normal contact, user movement and / or body heat. As such, the transfer of the skin care composition containing the enzyme inhibitor begins upon application of the article to the user, and continues through the period of use. In this way, the enzyme inhibitor is generally present on the skin before the insult by exudates from the body. In addition to its function as a vehicle for delivering a minimum concentration of an enzyme inhibitor to a user's skin, the skin care composition comprising the enzyme inhibitor may also comprise ingredients that, for example, reduce adhesion. stool to the skin (for example, to improve the ease of cleaning the bowel movement), provide a barrier function of skin / stool (for example, to cover the skin to prevent adherence of stool), while remaining relatively impermeable to liquid but permeable to steam, or which provides other therapeutic benefits to the skin (e.g., improved skin smoothness, maintaining or improving skin health) and the like. The skin care composition can be in a variety of forms, including, but not limited to, emulsions, lotions, creams, ointments, bran, suspensions, encapsulations, gels, and the like. In order to provide an effective concentration of the enzyme inhibitor to the skin through an absorbent article over time, an effective amount of the skin care composition applied to or migrates to one or more of the contact surfaces. with the user of the article depends, to a certain degree, on the particular composition used. The amount of the composition on at least a portion of the user interface of the absorbent article preferably ranges from about 0.0078 mg / cm2 to about 12 mg / cm2, preferably around 0.16 mg / cm2 to 6 mg / cm2 , most preferably around 0.6 mg / cm2 to about 4 mg / cm2. However, these scales are, by way of illustration, and those skilled in the art will recognize that the nature of the composition will dictate the level that must be applied to provide an effective concentration of the enzyme inhibitor and that the desirable level can be ascertained at through routine experimentation in view of the current description. Although the amount of the skin care composition applied to the absorbent article is an important aspect of the present invention, more important is the amount of composition transferred to the user's skin during the use of one or more treated articles. Although the amount of the composition containing the enzyme inhibitor delivered to the skin will depend to some degree on the nature of the composition employed and the potency of the enzyme inhibitor, relatively low amounts may be delivered, while still providing an effective minimum concentration. of the enzyme inhibitor to the skin. This is particularly true for preferred compositions, such as described in Example 1. With respect to the level of the skin care composition that is transferred to the user during the use of a treated absorbent article used for a period of about 3 hours. hours (a typical use time), particularly for preferred skin care compositions such as those described in Example 1, where at least about 0.0016 mg / cm2, preferably at least about 0.0078 mg / cm2, most preferably at least 0.016 mg / is preferred. cm2 of the composition, is transferred to the skin during a period of use of 3 hours. Typically, the amount of the composition delivered by a treated article will be from about 0.0016 mg / cm2 to about 0.78 mg / cm2, preferably around 0.0078 mg / cm2 to about 0.47 mg / cm2, most preferably around 0.16 mg / cm2 a 0.31 mg / cm2, during a period of use of 3 hours. For continuous use of treated articles (in other words, changes that occur according to normal usage patterns, typically including changes every 3 to 4 hours during the day and a recent article before sleeping at night) such as during a 24 hour period, it will be preferred that at least about 0.0047 mg / cm2 preferably at least about 0.016 mg / cm2, most preferably at least about 0.047 mg / cm2 of the composition be transferred to the user's skin during the period 24 hours Typically, the amount of composition delivered after a 24 hour period, where treated articles are applied at each change, will be from about 0.0047 mg / cm2 to about 2.79 mg / cm2, preferably from about 0.016 mg / cm2 to about 1.5 mg / cm2 and typically very preferably around 0.047 mg / cm2 to about 0.93 mg / cm2. A method for determining the amount of the skin care composition transferred to the skin during the use of the treated article is described below. It will be recognized that the numerous materials useful in the skin care compositions containing enzyme inhibitors supplied to the skin according to the invention, those which have been considered safe and effective skin care agents are logical materials for used in the present. Such materials include Category I assets as defined by the US Food and Drug Administration's (FDA) Tentative Final Monograph on Skin Protectant Drug Products for Over-the-Counter Human Use (21 CFR § 347), which currently includes: allantoin, gel aluminum hydroxide, calamine, cocoa butter, dimethicone, cod liver oil (in combination) glycerin, kaolin, petrolatum, lanolin, mineral oil, shark liver oil, white petrolatum, talc, topical starch, zinc acetate, zinc carbonate, zinc oxide, and the like. Other potentially useful materials are category III assets as defined by the US Food and Drug Administration (FDA) Tentative Final Monograph on Skin Protectant Drug Products for Over-the-Counter Human Use (21 CFR § 347), which currently includes: cell derivatives of live yeast, aldioxa, aluminum acetate, microporous cellulose, cholecalciferol, colloidal oat flour, cysteine hydrochloride, dexpanthenol, Peruvean balsam oil, protein hydrolyzates, racemic methionine, sodium bicarbonate, vitamin A, and Similar. Many of FDA's monographed skin care ingredients are currently used in commercially available skin care products such as A &D® Ointment, Vaseline® Petroleum Jelly, Desitin® Diaper Rash Ointment and Daily Care® ointment, Gold Bond® Medicated Baby Powder, Aquaphor® Healing Ointment, Baby Magic® Baby Lotion, and Johnson's Ultra Sensitive® Baby Cream. An effective concentration of an enzyme inhibitor can be incorporated into any of these commercial products and applied to absorbent articles to create treated articles for use in the present invention. As discussed below, skin care compositions useful for transferring enzyme inhibitors to the skin of the user preferably, although not necessarily, have a melting profile so that they are relatively immobile and are located on the contact surface with the user of the article at room temperature, are easily transferable to the user at body temperature and are not yet completely liquid under Extreme storage conditions. In this regard, the compositions are at least capable of partially transferring to the skin through normal contact, user movement, and / or body heat. Since the composition is preferably substantially immobilized on the contact surface of the user of the article, relatively low levels of the composition are required to impart the desired skin care benefits. In addition, special barrier materials or wrappers are unnecessary for packing treated articles useful in the methods of the present invention. In a preferred embodiment, the skin care compositions useful herein are water-in-oil emulsions, wherein the enzyme inhibitor is in the aqueous phase. However, the same skin care composition can be solid or more often semi-solid, at 20 ° C, that is, at room temperature. By "semi-solid" it means that the composition has a typical rheology of pseudoplastic or plastic liquids. When no shear is applied, the compositions may have the appearance of a semi-solid, but may be made to flow as the shear rate increases. This is due to the fact that, while the composition contains mainly solid components, it also contains a liquid component. Preferably, the compositions containing an enzyme inhibitor of the present invention have a shear viscosity of zero of between 1.0 x 108 centipoises and about 1.0 x 108. Most preferably, the shear viscosity of zero is between 5.0 x 106 centipoises and approximately 5.0 x 107 centipoises As used herein, the term "zero shear viscosity" refers to a viscosity measured at very slow shear rates (e.g., 1.0 seconds ~ 1) using a pressure viscometer. plate and cone (a suitable instrument available from TA Instruments of New Castle, DE with model number CSL 100). One skilled in the art will recognize means other than high melting point components (as discussed below) that can be used to provide comparable measured viscosities for these compositions comprising these means can be measured by extrapolating a plot of viscosity versus stress rate cutting for the compositions for a shear rate of zero at a temperature of about 20 ° C. Preferred compositions are at least semi-solid at room temperature to minimize the migration of the composition before using the article. In addition, the compositions preferably have a final melting point (100% liquid) above the potential "stressor" storage conditions that may be greater than 45 ° C (for example, in a warehouse in Arizona, on a truck in Florida , etc.). Representative compositions having these melting characteristics are described in detail in U.S. Patent No. 5,643,588, U.S. Patent 5,607,760 U.S. Patent 5,609,587, and U.S. Patent 5,635, 191 the descriptions of each are incorporated herein by reference. Specifically, the preferred compositions will have the following melting profile: Feature Very Preferred Preferred Scale% liquid at temperature 2-50 3-25 ambient (20 ° C). % of liquid at temperature 25-95 30-90 of the body (37 ° C).
Final melting point (° C) > 38 > Four. Five
Being solid or semisolid at room temperature, the preferred compositions containing the enzyme inhibitors do not tend to flow and migrate to a significant extent to undesired sites of the article in which it is applied. This means that less composition is required for skin care to impart desirable therapeutic, protective and / or conditioning benefits. To improve the immobility of the preferred compositions, the viscosity of the formulated compositions should be as high as possible to avoid flow into the article to an undesired site. Unfortunately, in some cases, higher viscosities can inhibit the transfer of the composition to the wearer's skin. Therefore, an equilibrium must be achieved so that the viscosities are high enough to maintain the composition located on the surface of the article, but not so high as to prevent transfer to the user's skin. Suitable viscosities of the compositions will typically range from about 5 to about 500 centipoise, preferably about 5 to 300 centipoise, most preferably about 5 to 100 centipoise, measured at 60 ° C using a rotational viscometer (a suitable viscometer that is available at Lab Line Instruments, Inc. of Melrose Park, IL, as model 4537). The viscometer is operated at 60 rpm using a No. 2 spindle. For skin care compositions designed to provide a therapeutic and / or protective benefit to the skin in addition to the benefit derived from the enzyme inhibitor, an active ingredient in these Compositions is one or more skin protectants or emollients. As used herein, the term "emollient" is a material that protects against moisture or irritation, softens, covers, lubricates, moistens, protects and / or cleanses the skin. (It will be recognized that several of the monograph assets listed above are "emollients", depending on the term used here). In a preferred embodiment, said emollients will have a plastic or liquid consistency at room temperature, that is, around 20-25 ° C. Representative emollients useful in the present invention include, but are not limited to, emollients that are petroleum based, sucrose esters of fatty acids; polyethylene glycol and its derivatives; humectants; fatty acid ester type; alkyl ethoxylate type; fatty acid ethoxylates ester; type of fatty alcohol; polyoxyloxane type; propylene glycol and its derivatives; glycerin and its derivatives; including glyceride, acetoglycerides and ethoxylated glycerides of fatty acids of 12 to 28 carbon atoms; triethylene glycol and its derivatives; Whale sperm wax and other waxes; fatty acids or fatty alcohol ethers, particularly those having from 12 to 28 carbon atoms in their fatty chain, such as stearic acid and methyl stearyl ether; propoxylated fatty alcohols; other fatty esters of polyhydroxy alcohols; lanolin and its derivatives; kaolin and its derivatives; any of the monografied skin care agents listed above; mixtures of these emollients. Suitable petroleum-based emollients include those of hydrocarbons, or mixtures of hydrocarbons, having chain lengths of 16 to 32 carbon atoms; Petroleum-based hydrocarbons having these chain lengths include mineral oil (also known as "liquid petrolatum") and petrolatum (also known as "mineral wax", "petroleum jelly" and "mineral jelly"). Mineral oil usually refers to less viscous petrolatum mixtures usually refers to more viscous hydrocarbon mixtures. Petrolatum and mineral oil are particularly preferred emollients for the compositions of the present invention. Suitable fatty acid ester emollients include those derived from fatty acids of 12 to 28 carbon atoms, preferably saturated fatty acids of 16 to 22 carbon atoms, and short chain monohydric alcohols. { C-- C8, preferably C -? - C-3). Representative examples of such esters include methyl palmitate, methyl stearate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, ethylhexyl palmitate and mixtures thereof. Suitable fatty acid ester emollients can also be derived from esters, longer chain fatty alcohols (C 2 -C 28, preferably C 12 -C 16) and shorter chain fatty acids, for example, lactic acid, such as lauryl lactate and cetyl lactate. Suitable alkyl ethoxylate emollients include fatty alcohol ethoxylates of 12 to 22 carbon atoms having an average degree of ethoxylation of about 2 to about 30. Preferably, the fatty alcohol ethoxylate emollient is selected from the group consisting of lauryl. , cetyl and stearyl ethoxylates, and mixtures thereof, having an average degree of ethoxylation ranging from about 2 to 23. Representative examples of said alkyl ethoxylates include laureth-3 (a lauryl ethoxylate having an average degree of ethoxylation of 3), laureth -23 (a lauryl ethoxylate having an average degree of ethoxylation of 23), cetet-10 (a cetyl alcohol ethoxylate having an ethoxylation degree of 10), and steareth-10 (a stearyl alcohol ethoxylate having an average degree of ethoxylation of 10). When employed, these alkyl ethoxylate emollients are typically used in combination with petroleum-based emollients, such as petrolatum, at a weight ratio of alkyl ethoxylate emollient to petroleum-based emollient of about 1: 1 to about 1. : 5, preferably around 1: 2 to 1: 4. Suitable fatty alcohol emollients include fatty alcohols of 12 to 22 carbon atoms, preferably fatty alcohols of 16 to 18 carbon atoms. Representative examples include cetyl alcohol and stearyl alcohol, and mixtures thereof. When employed, these fatty alcohol emollients are typically used in combination with petroleum-based emollients, such as petrolatum, at a weight ratio of fatty alcohol emollient to petroleum-based emollient of about 1: 1 to about 1. : 5, preferably around 1: 1 to 1: 2. Other suitable types of emollients for use herein include polysiloxane compounds. In general, polysiloxane materials suitable for use in the present invention include those having monomeric siloxane units of the following structure:
R1
wherein R1 and R2 for each monomeric independent siloxane unit can independently be hydrogen or any of alkyl, aryl, alkenyl, alkaryl, aralkyl, cycloalkyl, halogenated hydrocarbon or other radical. Any of said radicals can be substituted or unsubstituted; the radicals R1 and R2 of any particular monomer unit may differ from the corresponding functionalities of the next adjacent monomer unit; in addition, the polysiloxane can be either a straight chain, a straight chain, a branched chain, or have a cyclic structure, the radicals R1 and R2 can independently be other silaceous functionalities such as, but not limited to siloxanes, polysiloxanes, silanes and polysilanes. The radicals R1 and R2 can contain any of a variety of organic functionalities including, for example, functionalities of alcohol, carboxylic acid, phenyl, and amine. Illustrative alkyl radicals are methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl, octadecyl, and the like. Illustrative alkenyl radicals are vinyl, allyl, and the like. Exemplary aryl radicals are phenyl, diphenyl, naphthyl, and the like. Illustrative alkaryl radicals are tolyl, xylyl, ethylphenyl, and the like. Illustrative aralkyl radicals are benzyl, alpha phenylethyl, beta phenylethyl, alpha-phenylbutyl, and the like. Illustrative cycloalkyl radicals are cyclobutyl, cyclopentyl, cyclohexyl, and the like. Illustrative halogenated hydrocarbon radicals are chloromethyl, bromoethyl, tetrafluoroethyl, fluoroethyl, trifluoroethyl, trifluorotolyl, hexafluoroxylyl, and the like. The viscosity of polysiloxanes useful in the present invention can vary as widely as the viscosity of the polysiloxanes in general varies, so long as the polysiloxane can flow or be flowable for application to the absorbent article. This includes, but is not limited to, viscosity as low as 5 centistokes (at 37 ° C as measured by a glass capillary viscometer according to ASTM standard method D-445) to approximately 20,000,000 centistokes. Preferably, the polysiloxanes have a viscosity at 37 ° C ranging from about 5 to about 5,000 centistokes, preferably about 5 to 2,000 centistokes, most preferably about 100 to 1, 000 centistokes. The highly viscous polysiloxanes, which by themselves are resistant to flow, can be effectively deposited on the absorbent articles by methods such as, for example, emulsification of the polysiloxane in surfactant or the provision of the polysiloxane in solution with the aid of a solvent , such as hexane, listed for illustrative purposes only. Particular methods for applying polysiloxane emollients to absorbent articles are discussed in more detail below. Preferred polysiloxane compounds for use in the present invention are described in U.S. Patent No. 5,059,282, issued to Ampulski et al., On October 22, 1991, which is incorporated herein by reference. Particularly preferred polysiloxane compounds for use as emollients of the compositions of the present invention include phenyl-functional polymethylsiloxane compounds (e.g., Dow Corning 556 Cosmetic-Grade Fluid: polyphenylmethylsiloxane) and dimethicones functionalized with cetyl or stearyl such as polysiloxane liquids. Dow 2502 and Dow 2503, respectively. In addition to such substitutions with phenyl-functional or alkyl groups, an effective substitution can be made with amino, carboxyl, hydroxyl, ether, polyether, aldehyde, ketone, amide, ester, and thiol groups. Of these effective substituent groups, the family of the groups comprising phenyl, allyl, carboxyl, amino and hydroxyl groups are more preferred than others; most preferred are amino and phenyl-functional groups. Suitable fatty ester emollients also include polyol polyester esters as described in U.S. Patent No. 5,609,587, issued to Roe on March 11, 1997, the disclosure of which is incorporated herein by reference. Exemplary polyols include, but are not limited to, polyhydric compounds such as pentaerythritol; sugars such as raffinose, maltodextrose, galactose, sucrose, glucose, xylose, fructose, maltose, lactose, mannose and erythrose; and sugar alcohols such as erythritol, xylitol, malitol, mannitol and sorbitol. Said polyols are esterified with fatty acids and / or other organic radicals having at least two carbon atoms and up to 30 carbon atoms. Although it is not necessary that all of the hydroxyl groups of the polyol be esterified, the preferred polyester polyol emollients of the present invention have substantially all of the esterified hydroxyl groups (eg, at least about 85%). Particularly preferred are polyol sucrose polyesters such as sucrose polycotonate, sucrose polysorbate, and sucrose polybehenate. Mixtures of said polyol polyesters are also suitable emollients for the present invention. Suitable humectants include glycerin, propylene alcohol, sorbitol, dihydroxystearin, and the like. When present, the amount of emollient that can be included in the composition will vary depending on a variety of factors, including the particular emollient involved, the desired skin benefits, the other components in the composition, and the like. The composition will typically comprise about 0 to 100% of the emollient. Preferably, the composition will comprise from about 10 to about 95%, more preferably from about 20 to about 80%, and most preferably about 40 to 75% by weight of the emollient. Another optional preferred component of skin care compositions containing an enzyme inhibitor useful in the present invention is an agent capable of immobilizing the composition (including the enzyme inhibitor) the preferred emollient and / or other conditioning agents / protection for the skin) at the desired site in or on the treated article. Since certain preferred emollients in the composition have a plastic or liquid consistency at 20 ° C, they tend to migrate, even when subjected to modest shear stress. When applied to a user interface or other site of an absorbent article, especially in a molten or fused state, the emollient will not primarily remain in or on the treated region. Rather, the emollient will tend to migrate and flow into unwanted regions of the article. Specifically, if any component in the skin care composition migrates into the interior of the article, it can cause undesired effects on the absorbency of the article core due to the hydrophobic characteristics of, for example, emollients and other agents of the invention. skin conditioning used in the compositions useful in the present invention. It also means more composition for skin care has to be applied to the article to obtain the desired therapeutic and / or protective benefits. By increasing the level of the composition for skin care not only the cost increases, but it also exacerbates the undesirable effect on the absorbency of the core of the article and the undesired transfer of the composition during the processing / conversion of the treated articles. .
The immobilizing agent counteracts this tendency of the components of the skin care composition to migrate or flow by keeping the emollient mainly located on the surface or in the region of the article to which the composition is applied. It is believed that this is due, in part, to the fact that the immobilization agent raises the melting point and / or viscosity of the composition above that of the moving components. It is also advantageous to "lock" the immobilization agent on the contact surface with the body or the region of the article to which it is applied. This can be achieved by using immobilization agents, which are quickly fixed (ie, solidified) after application to the article. In addition, outside the cooling of the treated article through blowers, fans, cold rollers, etc., can accelerate the crystallization of the immobilization agent. The immobilizing agent will preferably have a melting profile that will provide a composition that is solid or semi-solid at room temperature. In this regard, the preferred immobilizing agents will have a melting point of at least about 35 ° C. This is due to the same immobilization agent that will not tend to emigrate or flow. Preferred immobilizing agents will have melting points of at least about 40 ° C. Typically, the immobilization agent will have a melting point on the scale of about 50 ° to 150 ° C. When used, the immobilization agents useful herein may be selected from a number of agents, provided that the enzyme inhibition properties of the skin care composition provide the skin benefits described herein. . It will be recognized that certain emollients or classes of emollients will have fusion characteristics such that they are suitable as immobilization agents. These materials can function as both emollient and immobilization agents. Preferred immobilizing agents will comprise a number selected from the group consisting of fatty alcohols of 14 to 22 carbon atoms, fatty acids of 12 to 22 carbon atoms and fatty alcohol ethoxylates of 12 to 22 carbon atoms having an average degree of ethoxylation ranging from 2 to about 30, and mixtures thereof. Preferred immobilizing agents include fatty alcohols of 16 to 18 carbon atoms, most preferably crystalline high melt materials selected from the group consisting of cetyl alcohol, stearyl alcohol, behenyl alcohol, and mixtures thereof. (The linear structure of these materials can accelerate solidification on the treated absorbent article). Also preferred are mixtures of cetyl alcohol and stearyl alcohol. Other preferred immobilizing agents include fatty acids of 16 to 18 carbon atoms, most preferably selected from the group consisting of palmitic acid, stearic acid, and mixtures thereof. Mixtures of palmitic acid and stearic acid are particularly preferred. Still other preferred immobilizing agents include fatty alcohol ethoxylates of 16 to 18 carbon atoms having an average degree of ethoxylation ranging from about 5 to about 20. Preferably, the fatty alcohols, fatty acids, and fatty alcohols are linear. Importantly, these preferred immobilization agents such as fatty alcohols of 16 to 18 carbon atoms increase the rate of crystallization of the composition by causing the composition to crystallize rapidly on the surface of the substrate. Other types of immobilization agents that may be used herein include polyhydroxy fatty acid esters, polyhydroxy fatty acid amides, and mixtures thereof. Preferred amide esters will have three or more free hydroxy groups on the polyhydroxy moiety and are typically non-ionic by character. Due to the possible sensitivity of the skin of those who use articles to which the composition is applied, these esters and amides must also be relatively mild and non-irritating to the skin. The polyhydroxy fatty acid esters suitable for use in the present invention will have the formula:
wherein R is a hydrocarbyl group of 5 to 31 carbon atoms, preferably alkyl or alkenyl of 7 to 9 straight chain atoms, most preferably alkyl or alkenyl of 9 to 17 carbon atoms preferably straight chain, alkyl or alkenyl of to 17 straight-chain carbon atoms, or mixtures thereof; Y is a polyhydroxyhydrocarbyl moiety having a hydrocarbyl chain with at least two free hydroxyls directly connected to the chain; and n is at least 1. Suitable Y groups can be derivatives of polyols such as glycerol, pentaerythritol; sugars such as raffinose, maltodestrose, galactose, sucrose, glucose, xylose, fructose, maltose, lactose, mannose and erythrose; sugar alcohols such as erythritol, xylitol, malitol, mannitol and sorbitol; and anhydrides of sugar alcohols such as sorbitan. A class of polyhydroxy fatty acid esters suitable for use in the present invention comprises certain sorbitan esters, preferably sorbitan esters of saturated fatty acids of 16 to 22 carbon atoms. Due to the manner in which they are typically manufactured, these sorbitan esters usually comprise mixtures of mono, di, tri, etc., esters. Representative examples of suitable sorbitan esters include sorbitan palmitates (e.g., SPAN 40), sorbitan stearates (e.g., SPAN 60), and sorbitan behenates, which comprise one or more of the mono, di, and triester versions thereof. sorbitan esters, for example, sorbitan mono, di and tripalmitate, mono, di, and sorbitan tristearate, sorbitan mono, di and tribehenate, as well as sorbitan mono, di and tri-esters of tallow fatty acid mixed together. Mixtures of different sorbitan esters, such as sorbitan palmitates with sorbitan stearates, can also be used. Particularly preferred sorbitan esters are sorbitan stearates, typically as a mixture of mono, di and triesters (plus some tetraester) such as SPAN 60, and sorbitan stearates sold under the trade name GLYCOMUL-S by Lonza, Inc. From Fair Lawn NJ. Although these sorbitan esters typically contain mixtures of mono, di and triesters plus some tetraester, the mono and diester are usually the predominant species in these mixtures.
Other classes of polyhydroxy fatty acid ester suitable for use in the present invention comprise certain glyceryl monoesters, preferably glyceryl monoesters of saturated fatty acids of 16 to 22 carbon atoms such as glyceryl monostearate, glyceryl monopalmitate, and glyceryl behenate. Again, as with sorbitan esters, the glyceryl monoester mixtures will typically contain some di and triester. However, said mixtures must predominantly contain the glyceryl monoester species which is useful in the present invention. Another class of polyhydroxy fatty acid esters suitable for use in the present invention comprises certain fatty acid esters of sucrose, preferably saturated fatty acid esters of 12 to 22 carbon atoms of sucrose. Sucrose monoesters and diesters are particularly preferred and include sucrose mono- and distearate and sucrose mono- and dilaurate. The polyhydroxy fatty acid amides suitable for use in the present invention will have the formula: wherein R 1 is H, hydrocarbyl of 1 to 4 carbon atoms, 2-hydroxyethyl, 2-hydroxypropyl. , methoxyethyl, methoxypropyl, or a mixture thereof, preferably alkyl of 1 to 4 carbon atoms, methoxyethyl or methoxypropyl, most preferably alkyl of 1 to 2 carbon atoms or methoxypropyl, and most preferably alkyl of 1 carbon atom (is say, methyl) or methoxypropyl; and R2 is a hydrocarbyl group of 5 to 31 carbon atoms, preferably alkyl or alkenyl of 7 to 19 straight carbon atoms, preferably straight chain C9-C17 alkyl or alkenyl, and most preferably alkyl or alkenyl of 11 to 17 straight-chain carbon atoms, or mixtures thereof; and Z is a polyhydroxyhydrocarbyl moiety having a linear hydrocarbyl chain with at least 3 hydroxyls directly connected to the chain. See, U.S. Patent No. 5,174,927, issued to Honsa on December 29, 1992 (incorporated herein by reference), which discloses these polyhydroxy fatty acid amides, as well as their preparation. The Z portion will preferably be derived from a reducing sugar in a reduction of reductive amination; most preferably glycityl. Suitable reducing agents include glucose, fructose, maltose, lactose, galactose, mannose and xylose. Corn syrup with a high content of dextrose, corn syrup with a high fructose content, and corn syrup with a high maltose content, as well as the individual sugars listed above can be used. These syrups can produce mixtures of sugar components for the Z portion. The Z portion will preferably be selected from the group consisting of -CH2- (CHOH) n -CH2OH, -CH (CH2OH) - [(CHOH) n.1 ] -CH2OH, -CH2OH-CH2- (CHOH) 2 (CHOR3) (CHOH-CH2OH, where n is an integer from 3 to 5, R3 is H or a cyclic or aliphatic monosaccharide, glycyls are very preferred, wherein In the above formula, R can be, for example, methyl, ethyl, propyl, isopropyl, butyl, 2-hydroxyethyl, methoxypropyl or 2-hydroxypropyl; R2 can be selected from the group consisting of -CH2- (CHOH) 4 -CH2OH. select to provide, for example, cocamides, stearamides, oleamides, lauramides, myristamides, capricamides, palmitamides, seboamides, etc. The Z portion can be 1-deoxyglucitide, 2-deoxyfuctilityl, 1-deoxymaltityl, 1-deoxymaltityl, 1-deoxygalactityl, 1-deoxyanityl, 1-deoxy-thiotriotityl, etc. The highly preferred polyhydroxy fatty acid amides have the formula:
O R1 OH II I I R2- C- - CH2- -CH- -CH2-OH
wherein R 1 is methyl or methoxypropyl; R2 is a straight chain alkyl or alkenyl group of 1 to 17 carbon atoms. These include N-lauryl-M-methyl glucamide, N-lauryl-N-methoxypropyl glucamide, N-cocoyl-N-methyl glucamide, N-cocoyl-N-methoxypropyl glucamide, N-palmitoyl-N-methoxypropyl glucamide, N-seboil -N-methyl glucamide, or N-tallowyl-N-methoxypropyl glucamide. As previously noted, some of the immobilization agents may require an emulsifier for solubilization in the emollient. This is particularly the case for certain glucamides such as N-alkyl-N-methoxypropyl glucamides having HLB values of at least about 7. Suitable emulsifiers will typically include those having HLB values below about 7. In this regard, previously described sorbitan esters, such as sorbitan stearates, having HLB values of about 4.9 or less, have been found useful for solubilizing these glucamide immobilization agents in petrolatum. Other suitable emulsifiers include Steareth-2 (polyethylene glycol ethers of stearyl alcohol which conform to the formula CH3 (CH2) 17 (OCH2CH2) nOH, where n has an average value of 2), sorbitan tristearate, isosorbide laurate, and glyceryl monostearate. The emulsifier can be included in an amount sufficient to solubilize the immobilizing agent in the emollient, so that a substantially homogeneous mixture is obtained. For example, a mixture of approximately 1: 1 of N-cocoyl-N-methyl glucamide and petrolatum that normally does not melt into a single phase mixture will melt into a single phase mixture after the addition of 20% of a 1: 1 mixture of Steareth-2 and sorbitan tristearate as the emulsifier. Other types of ingredients that can be used as immobilizing agents, either alone or in combination with the above-mentioned immobilization agents, include waxes such as carnauba, osoquerite, beeswax, candelite, paraffin, ceresin, esparto, ouricuri, wax prayer, isoparaffin, and other mined waxes and minerals. The high melting point of these materials can help immobilize the composition on the desired surface or the site on the article. In addition, microcrystalline waxes are effective immobilization agents. Microcrystalline waxes can help "close" low molecular weight hydrocarbons within the skin care composition. Preferably, the wax is a paraffin wax. An example of a particularly preferred alternative immobilization agent is a paraffin wax such as Parrafin SP 434 from Strahl and Pitsch Inc. of West Babylon, N. Y. 1704. The amount of the optional immobilization agent that can be included in the composition will depend on a variety of factors, including the active (eg, emollients) involved, the particular immobilizing agent involved, if any, the other components in the composition, if an emulsifier is required to solubilize the immobilizing agent in the other components, and similar factors. When present, the composition will typically comprise about 5 to 90% of the immobilizing agent. Preferably, the composition will comprise from about 5 to about 50%, most preferably about 10 to 40% of the immobilizing agent. It is highly desirable that at least a portion of the topsheet of the article be made of a hydrophilic material to promote the rapid transfer of liquids (eg, urine) through the topsheet. Similarly, it may be desirable that the composition be sufficiently wettable to ensure that liquids will be transferred through the topsheet rapidly. Alternatively, hydrophobic skin care compositions can be used, provided that they are applied in such a way that the properties that handle the fluid of the upper sheet are adequately maintained. (For example, as discussed further, the non-uniform application of the composition to the topsheet is a means to achieve this goal). This decreases the likelihood that body exudates will flow out of the top sheet treated with the composition instead of being drawn through the top sheet and absorbed by the absorbent core. When a hydrophilic composition is desired, depending on the particular components used in the composition, a hydrophilic surfactant (or a mixture of hydrophilic surfactants) may or may not be required to improve the wettability. For example, some immobilization agents, such as N-cocoyl-N-methoxypropyl glucamide have HLB values of at least about 7 and are sufficiently wettable without the addition of a hydrophilic surfactant. Other immobilizing agents such as fatty alcohols of 16 to 18 carbon atoms having HLB values below about 7 may require the addition of a hydrophilic surfactant to improve the wettability when the composition is applied to the upper sheets of the Article. Similarly, a hydrophobic emollient, such as petrolatum, may require the addition of a hydrophilic surfactant if a hydrophilic composition is desired. Of course, the concern with regard to wetting capacity is not a factor when a contact surface with the user, under consideration, is different from the upper sheet of the article or when the fluid handling properties of the upper sheet are adequately maintained. through other means (for example, non-uniform application). Suitable hydrophilic surfactants will preferably be miscible with other components of the skin care composition in order to form combined blends. Due to the possible skin sensitivity of those who use disposable absorbent products to which the composition is applied, these surfactants must also be relatively mild and non-irritating to the skin. Typically, these hydrophilic surfactants are nonionic to be only non-irritating to the skin, but also to avoid other undesirable effects on any other structure within the treated article. For example, reductions in tensile strength of the fabric sheet, adhesive bonding strengths, and the like. Suitable nonionic surfactants may be substantially non-migrating after the composition is applied to the articles and will typically have HLB values in the range of about 4 to about 20, preferably about 7 to 20. To be non-migratory, these Nonionic surfactants will typically have melting temperatures higher than the temperatures commonly encountered during storage, shipping, sale and use of disposable absorbent products, for example, at least about 30 ° C. In this regard, these nonionic surfactants will preferably have melting points similar to those of the previously described immobilization agents. Nonionic surfactants suitable for use in compositions that will be applied to the articles, at least in the liquid discharge region of the diaper, include alkyl glycosides; alkyl glycoside ethers as described in the patent of E. U. A. 4,01 1, 389, issued to Langdon et al., March 8, 1977, which is incorporated herein by reference; alkyl polyethoxylated esters such as Pegosperse 1000MS (available from Lonza, Inc., Fair Lawn, NJ), ethoxylated sorbitan mono, di, and / or triesters of fatty acids of 12 to 18 carbon atoms having an average degree of ethoxylation of about 2 to about 20, preferably about 2 to 10, such as TWEEN 60 (sorbitan esters of stearic acid having an average degree of ethoxylation of about 20), and TWEEN 61 (sorbitan esters of stearic acid having an average degree of ethoxylation about 4), and the condensation products of aliphatic alcohols with from about 1 to about 54 moles of ethylene oxide. The alkyl chain of the aliphatic alcohol is typically a straight chain (linear) configuration and contains from about 8 to about 22 carbon atoms. Particularly preferred are the condensation products of alcohols having an alkyl group containing from about 8 to about 22 carbon atoms with 2 to about 30 moles of ethylene oxide per mole of alcohol (on average). Examples of such ethoxylated alcohols include the condensation products of myristyl alcohol with 7 moles of ethylene oxide per mole of alcohol, the condensation products of coconut alcohol (a mixture of fatty alcohols having alkyl chains varying in length from 10 to 14 atoms) carbon) with approximately 6 moles of ethylene oxide. A number of suitable ethoxylated alcohols are commercially available, including TERGITOL 15-S-9 (the condensation product of linear alcohols of 11 to 15 carbon atoms with 9 moles of ethylene oxide), sold by Union Carbide Corporation of Danbury, CT.; NEODOL commercial name surfactants sold by Shell Chemical Co., of Houston, TX, in particular NEODOL 25-12 (condensation product of linear alcohols of 12 to 15 carbon atoms with an average of 12 moles of ethylene oxide) and NEODOL 23-6.5T (condensation product of linear alcohols of 12 to 13 carbon atoms with an average of 6.5 moles of ethylene oxide that has been distilled to remove certain impurities) and especially the surfactants with commercial name of PLURAFAC sold by BASF Corp. Of Mt. Olive, NJ, in particular PLURAFAC A-38 (a condensation product of a straight-chain alcohol of 18 carbon atoms with 27 moles of ethylene oxide). (Certain of the hydrophilic surfactants, in particular the ethoxylated alcohols such as NEODOL 25-12, may also function as alkylethoxylate emollients). Other examples of preferred ethoxylated alcohol surfactants include the ICI class of Brij surfactants and mixtures thereof, Brij 72 (ie Steareth-2) and Brij 76 (ie Steareth-10) being especially preferred. Also, mixtures of cetyl alcohol and ethoxylated stearyl alcohol at an average degree of ethoxylation of about 10 to about 20, can be used as the hydrophilic surfactant. Another type of surfactant suitable for use in the composition includes Aerosol OT, a dioctyl ester of sodium sulfosuccinic acid sold by Cytec Industries, Inc. of Morristown, NJ. Another type of surfactant suitable for use in the composition includes silicone copolymers such as General Electric SF 1 188 (a copolymer of a polydimethylsiloxane and a polyoxyalkylene ether) and General Electric SF 1228 (a silicone polyether copolymer). These silicone surfactants can be used in combination with other types of hydrophilic surfactants discussed above, such as the ethoxylated alcohols. These silicone surfactants have been found to be effective at concentrations as low as 0.1%, most preferably about 0.25 to 1.0% by weight of the composition. When a hydrophilic composition is desired, the amount of hydrophilic surfactant required to increase the wettability of the composition to a desired level will depend in part on the value of HLB and the level of immobilization agent, if any, used, the value of HLB of the surfactant agent used and similar factors. The composition may comprise from about 0.1 to about 50% of the hydrophilic surfactant when it is necessary to increase the wetting properties of the composition. Preferably, the composition comprises about 1% to about 25%, most preferably about 10 to 20% of the hydrophilic surfactant when it is necessary to increase the wettability. The compositions may comprise other components typically present in emulsions, creams, ointments, lotions, powders, suspensions, etc., of this type, these components include water, viscosity modifiers, perfumes, disinfectant antibacterial actives, antiviral agents, vitamins, pharmaceutical actives. , film foamers, deodorants, opacifiers, astringents, solvents, preservatives, and the like. In addition, stabilizers may be added to improve the storage life of the composition such as cellulose derivatives, proteins and lecithins. All of these materials are well known in the art as additives to such formulations and may be employed in appropriate amounts in the compositions for use herein. If water-based skin care compositions are used, a preservative will be necessary. Suitable preservatives include propylparaben, methylparaben, benzyl alcohol, benzylconium chloride, tribasic calcium phosphate, DTH, or acids such as citric, tartaric, maleic, lactic, malic, benzoic, salicylic, and the like. Suitable viscosity-increasing agents include some of the agents described as effective immobilizing agents. Other suitable viscosity-increasing agents include alkyl galactomannan, silica, talc, magnesium silicate, sorbite, colloidal silicon dioxide, magnesium aluminum silicate, zinc stearate, wood wax alcohol, sorbitan sesquatose, cetyl hydroxyethyl cellulose and other modified celluloses. Suitable solvents include propylene glycol, glycerin, cyclomethicone, polyethylene glycols, hexylene glycol, diol, and multiple hydroxy-based solvents. Suitable vitamins include A, D-3, E, B-5 and E acetate.
SAW. Treatment of Articles with the Composition To prepare the absorbent articles to carry out the methods of the present invention, the skin care composition containing the enzyme inhibitor is applied so that during use, at least some portion of the composition will be transferred from the treated article to the user's skin. That is, the skin care composition is either applied directly to one or more body contact surfaces, or is applied in alternate or medium locations so that the skin care composition is readily available for transfer. of one or more contact surfaces of the body during use without the intervention of the user / the one providing the care. (For example, materials placed below the contact surface of the body, encapsulated compositions, etc.). Of course, to effect the supply of the composition towards those regions of the body more susceptible to skin roughness, it will be preferred to include the composition in the portion of the upper sheet and cuffs that will be in contact with the buttocks, the genitals, of the user, in the anal regions during use. In addition, the composition can be applied to other regions of the article to supply one or more of the user's hips, abdomen, back, waist, sides, thighs, etc. Suitable methods include spraying, printing (e.g., flexographic printing), coating (e.g., contact slot coating, engraving coating), extruding, or combinations of these application techniques, e.g., spraying the care composition of the skin on the rotating surface, such as a roller surface, which then transfers the composition to the desired portion of the article. The skin care composition containing the enzyme inhibitor can also be applied as a solid material through any of a variety of methods, eg, extrusion. When applied to the topsheet of the article, the manner of applying the composition to the article should be such that the topsheet is not saturated with the composition, at least in the region corresponding to the liquid discharge region of the article, if the composition is hydrophobic by nature. If the topsheet becomes saturated with the composition in the liquid discharge region, there is a greater potential for the composition to block the openings in the topsheet, reducing the ability of the topsheet to transmit the liquid to the underlying absorbent core, also, saturation of the topsheet is not required to obtain the therapeutic and / or protective benefits. Similarly, saturation of other components of the treated article may be unnecessary or desired to transfer the composition sufficient for the desired benefits on the skin. Particularly suitable methods and application will apply the composition primarily to the external surface of the topsheet of the article. The minimum level of the composition containing the enzyme inhibitor that will be applied to the user's contact surface of the article is an effective amount to provide the therapeutic, protective and / or conditioning benefits for the skin when the composition is supplied in accordance with the present invention. The level of the composition applied will depend on several factors, including the treated article component, the relative amount of the surface area of the contact surface with the user not treated with the composition, the content of the composition and the like. In general, with compositions that are relatively hydrophobic and will be applied essentially to the entire topsheet, the composition is preferably applied to the topsheet of the article in an amount ranging from about 0.016 mg / cm2 to about 2.33 mg / cm2., most preferably around 0.16 mg / cm2 to 1.55 mg / cm2. It will be recognized that higher levels of skin care composition can be applied to other components of the article, where the properties of fluid handling are not impacted (e.g., cuffs, waist band, side panels, etc.). .). It will also be recognized that for compositions that are relatively hydrophilic, higher addition levels may be used on the topsheet without adversely affecting the handling properties of the liquid to an unacceptable extent. Conversely, higher levels of a hydrophilic composition may be undesirable when applied to components (eg, cuffs, waist) other than the topsheet, to prevent the penetration of exudates to the edges of the article, which may result in as a result of a leak. Since the composition is preferably and substantially immobilized on the surface of the treated region, relatively small amounts of the composition are added to deliver an effective amount of the enzyme inhibitor. It is believed that the ability to use low levels to impart the desired benefits on the skin is due to the fact that the composition is continuous, and automatically supplied as the articles are used. As indicated, the ability to use relatively low levels of the composition for skin care allows the top sheet of the article to maintain its liquid transfer properties in the liquid discharge region. The composition can be applied non-uniformly to the contact surface with the body of the article. By "non-uniform" it is meant that the amount, site, distribution pattern, etc., of the composition may vary over the user's contact surface, and may also vary over specific regions of the article. For example, to maintain the liquid handling performance of the topsheet, it may be desired to apply the composition non-uniformly to the topsheet, particularly if the composition is hydrophobic in nature. In this regard, portions of the treated surface of the article (and its regions) may have greater or lesser amounts of the composition, including portions of the surface that have no composition therein. When the composition is relatively hydrophobic, in said preferred embodiment, the surface of the topsheet will have regions where the composition is not applied, particularly in areas of the topsheet corresponding to the crotch region of the article. As used herein, the crotch region of the article is the rectangle, defined below, that is longitudinally and parallel centered around the crotch point of the article. The "crotch point" is determined by placing the article on a user in a standing position and then placing an extension filament around the legs in a configuration of number 8. The point in the article corresponding to the point of intersection of the filament It is considered as the crotch point of the article. (It is understood that the crotch point is determined by placing the absorbent article on a user in the intended manner and determining where, the crossed filament, will make contact with the article). With respect to incontinence devices (eg diapers, incontinence articles for adults), the length of the crotch region corresponds to 40% of the total length of the absorbent article (ie, in a dimension of Y). With respect to sanitary napkins, the length of the crotch region corresponds to 80% of the total length of the absorbent article. The width of the crotch region is equivalent to the width of the wider absorbent core component as measured at the crotch point, (as used herein), the components of "absorbent core" are those materials involved with the acquisition, transportation, distribution and / or storage of body fluids. As such, the term, absorbent core does not include the topsheet or the backsheet of the absorbent article). By way of illustration, for an incontinence article having a length of 50.8 cm in a core width in the crotch region of 10.16 cm, the crotch region is the rectangle, centered over the crotch point, having a length of 20.3 cm and a width of 10.16 cm. Surprisingly, although the topsheet or other components comprising the composition are treated non-uniformly (e.g., microscopic or macroscopic regions where composition is not applied), during the use of the article, the composition is transferred to the user even in regions of the skin corresponding to untreated regions within the topsheet or other components. The amount and uniformity of the composition transferred from the skin is believed to depend on several factors, including, for example, the application pattern of the skin care composition, the contact of the user's skin to the surface of the article. treated, the friction created during the time between the skin of the wearer and the treated region, the heat generated from the wearer to improve the transfer of the composition, the properties of the composition, the materials constituting the composition, and the like. When the composition is applied non-uniformly, any pattern can be used, including, for example, the application of small drops (obtained through, for example, spraying) discrete drops (obtained through, for example, printing by engraving) , strips running in a longitudinal or lateral direction of the article (obtained through the contact groove coating), spirals running in the longitudinal or lateral direction, etc., pattern impressions, etc. In those embodiments wherein the top sheet comprises discrete, untreated regions, the percentage of open area of the top sheet region that corresponds to the crotch region of the article can vary widely. (As illustrated herein, the "percentage of open area" of the topsheet is determined, (i) by measuring the surface area of the top sheet covering the crotch region, (ii) by measuring the surface area total of the untreated region in this portion of the topsheet and (ii) dividing the measurement (ii) between the measurement between the measurement (i) As used herein, "untreated" means a region of the top sheet having less than about 0.016 mg / cm 2 of the composition In this regard, the percentage of the open area can be from about 1% to about 99%, from about 5% to about 95%, from about 10% to about 90%, from about 15% to about 85%, from about 20% to about 80%, from about 25% to about 75%, from about 30% to about 70%, or from about 35% to about 65%. percentage of The open area required to achieve the desired effect of the composition and the desired liquid handling properties of the topsheet will be dictated greatly by the characteristics of the composition (in particular the contents of the composition and its relative hydrophobic / hydrophilic properties) . One skilled in the art will appreciate that the percentage of desired open area will be easily determined through routine experimentation. In general, with compositions that are relatively hydrophobic and that are to be applied such that the regions of the topsheet are not coated with the composition, the composition is preferably applied to the topsheet of the article in an amount ranging from about 0.0078. mg / cm2 at approximately 5.43 mg / cm2, preferably from about 0.16 mg / cm2 to about 3.88 mg / cm2, most preferably from about 0.62 mg / cm2 to about 3.1 mg / cm2. It will be recognized that for compositions that are relatively hydrophilic, higher addition levels may be used without adversely impacting the liquid handling properties of the topsheet to an unacceptable extent. Of course, for items that have a relatively high percentage of open areas in the crotch, they can be obtained at higher levels of addition without adversely affecting the handling of liquid by the topsheet.
In a preferred embodiment for carrying out the present methods, the topsheet of the articles used will comprise strips of the composition running in the longitudinal direction of the article. These longitudinal strips (or spirals) are separated by longitudinal strips where little or no composition is applied to the topsheet. In these embodiments, each strip of the composition will typically have a width of approximately 0.254 cm approximately 1.90 cm, very typically around 0.254 cm to 1.27 cm, and the width of the strips containing no composition will typically be approximately 0.254 cm a approximately 2.54 cm, very typically around 0.381 to 1.27 cm. These are applicable to typical diaper designs for babies. For larger products such as adult incontinence products, these scales may be higher. The composition of skin care can also be applied in non-uniform patterns over other components of the article. In these cases, the open area is calculated by the rectangle defined by the perimeters of the skin care composition. The composition can be applied to the article at any point during assembly. For example, the composition can be applied to the disposable and finished absorbent product before it is packaged. The composition can also be applied to a given component (eg top sheet, cuffs, sides, waist, etc.), at the convergence site or by the material supplier, before it is combined with other starting materials for form a finished disposable absorbent product. Again, the composition can be applied to other areas of the article so that the composition will migrate towards one or more contact surfaces with the body during use. The composition is typically applied from a melt bath thereof to the article. Since, in a preferred embodiment, the composition melts at a temperature significantly above room temperature, it is usually applied as a hot composition to the article. Typically, the composition is heated to a temperature in the range of about 35 to about 150 ° C. Preferably about 40 to about 100 ° C, before being applied to the article. The enzyme inhibitor can be added to the composition before or after heating. If added before heating, the temperature at which the composition is heated is selected so as not to inactivate the enzyme inhibitor. Alternatively, the enzyme inhibitor can be added to the preheated composition when it has been cooled to a temperature that does not affect the enzyme inhibitor, but is sufficiently liquid to be applied to the article. Once the molten composition has been applied to the article, it is allowed to cool and solidify. Preferably, the application process is designed to assist in the cooling / fixing of the composition. When applying the compositions to articles, methods such as contact groove coating, spraying, engraving coating, exton coating methods are preferred. One method involves slot coating the composition on the topsheet of the article after the topsheet is assembled with the other starting materials to a finished product.
Vile. Test Methods A. Transfer of Skin Care Composition and Enzyme Inhibitor to User's Skin Abstract This method uses a material analogous to removable skin that is placed on a user's skin for a controlled period of time . After the skin analogue has been removed, it is extracted using an appropriate solvent and the amount of skin care composition or amount of a protease inhibitor deposited thereon is determined using known analytical methods. The method is described for use with baby diapers comprising skin care compositions that both contain and do not contain protease inhibitors as defined herein. One skilled in the art will recognize appropriate changes for other skin care compositions, protease inhibitors, absorbent articles or user types.
Subjects Approximately equal numbers of male and female babies should be selected using the following inclusion and exclusion criteria. Sufficient babies must be selected to ensure that there are at least 15 subjects per condition and time of transfer that complete all aspects of the test.
Inclusion Criteria a. Healthy baby b. Carriers of care proposed not to use lotions, creams, powders or other preparations for the skin in the diaper area during the period of the test. c. Babies who use disposable diapers all the time. d. Providers of care proposed to give a bath to the baby at night before the study and not again until after completing the study. and. The care provider proposed to have babies who do not swim from the night before the study until after completing the study.
Exclusion Criteria The baby has been ill for the last 4 days.
b. Diarrhea (soft stools) at any time during the four days before the test. c. A drug that can increase the frequency of bowel movements (eg, oral antibiotics, antifungal agents, corticosteroids) d. Damaged skin in or around the test site (eg, from sunburn, active skin lesions, or the like). and. Known allergies or irritation of adhesive ingredients or skin care.
Materials In vivo transfer Skin analogue: Dermatological tape, TEGADERM tape No. 1622W available from 3M Health Care, St. Paul, MN. Sample container: Glass jar with a closure available from VWR Scientific, West Chester, PA with catalog number 15900-242. Tape release powder: Baby powder (comprising only talc and fragrance) available from Johnson & Johnson, New Brunswick, NJ. Surgical gloves: Available from Best Manufacturing Co., Menlo GA, as product 6005PFM.
Extraction and Analysis of Skin Care Composition Extraction Solvent: Dichloromethane, available from Sigma-Aldrich of St. Louis, MO, as 27956-3. Stearyl alcohol: Aldrich 25876-8 1-Hexadecanol: Aldrich 25874-1 Assortment flask: 10 ml Gas chromatography: Flame ionization detector, Hewlett Packard Model 5890, is very suitable. Column: Capillary column: Chrompack CP Sil-5 CB, 2 meters by 0.25 mm internal diameter, 0.12 micron thick film of the fused silica capillary (without substitutions). Instrumental data: They must be able to determine in a reproducible way peak areas of interest. System
Extraction and Analysis of an Inhibitor (for example, protease) Sample Enzyme (for example, Hexamidine) Extraction Solvent: Dichloromethane, available from Sigma-Aldrich of St. Louis, MO, as 27956-3. Assortment flask: 10 ml Column: Hwelett Packard Zorbax SB-CN 5-micron narrow hole, 2.1 x 150 mm, with a Waters Bondapack Cn 10 micron, 3.9 x 20mm backrest column.
Instrumental data: They must be able to determine in a reproducible way peak areas of interest. System
In Vivo Transfer Method A. Confirm from the subject's care provider that the subject has been bathed within at least 24 hours and that no lotions, powders, etc. have been applied to the diaper region of the subject's skin from the bath. B. Use surgical gloves, place the subject on the table and remove his diaper. O Flip the subject over his stomach. D. Remove the release liner from a TEGADERM tape and lightly brush with the talc J &baby Powder on the adhesive surface (use surgical gloves, or similar, during application to avoid contamination of the tape). Provide sufficient powder so that there is a small dust cover over the entire tape except the edges. (This step is performed to prevent the tape from adhering very aggressively to the baby's skin). E. Figures 2a and 2b illustrate the placement for the TEGADERM tape, shown in those figures as tape 700. Apply tape 700 to the right seat of the child. The tape 700 is to be applied at the highest point on the child's seat immediately adjacent to, but not in, the gluteal groove of the child. A second tape 700 may be applied to measure the transfer at two increments of time or the effect of an additional diaper. If a second tape is used, tape the tape 700 over the left seat using the procedure described above. F. Change diapers according to the following protocol: 3 hours transfer time a diaper; 6 hours transfer time 2 diapers (change every 3 hours); 24 hours of transfer time lib by the care provider. For 24-hour transfer times, the following additional instructions should be followed: 1. Use only water and a damp cloth to clean the diaper area during the end of the test. Do not use baby towels. Avoid touching the area around the tape with your hands or any cleaning implement. 2. Do not use skin care products (lotions, ointments, creams, soap, etc.) during the term of the test. 3. Do not bathe the subject during the test. 4. Use only the test diapers. Record the time of each diaper change. 5. Record the time of any bowel movement and clean the subject with water and a cleaning cloth. G. Record the time of each diaper that was applied for all the test diapers. H. Return to the subject near the end of the predetermined transfer time. I. Remove the test diaper. If the child has had a bowel movement, the study staff should remove the tape 700 and discard it (the subject is then observed in the test and the data from that subject is not included in the analysis).
If the subject has urinated, the tape 700 will be acceptable for analysis as described below. J. Personnel in the test facility should wear surgical gloves and remove the tape 700 by tearing the edge of the tape 700 with tweezers and moderately peeling the remaining portion of the tape 700 from the skin. K. Color the used tape 700 in one of the glass jars and close with the lid.
Make sure the jar is properly marked for subsequent sample identification. L. At the end of the test collect all the samples in the jars for analysis as described below.
1. Extraction and Analysis of the Composition Test samples for the
Skin Care This method is designed to be used with the preferred skin care composition, skin care composition of Table 4. A person skilled in the art will recognize what adaptations may be necessary to extract and analyze the level of skin care. the other compositions for skin care. In the beginning: 1) one of the main ingredients of the composition is extracted from the skin analog using an appropriate solvent; 2) gas chromatographic techniques or other appropriate quantitative analytical techniques are then used to determine the level of the main ingredient in the extract; 3) the amount of the skin care composition is calculated per unit area based on the amount of the main ingredient in the extraction and the area of the tape.
Internal Standard Solvent / Extraction Prepare an internal standard solvent / extraction by accurately loading 100 + 2 mg of 1-hexadecanol into a small beaker. Dissolve 1-hexadecanol in dichloromethane and transfer to a 1-liter volumetric flask. Rinse the beaker three more times with dichloromethane transferring each rinse portion to the volumetric flask. Fill the volumetric flask to the volume and mix well. This solution will be used to supply the internal standard and extract the skin care composition from the tapes. When not in use, this container must be kept tightly capped to avoid evaporation of the solvent.
Caation Standard _ Prepare a caation standard of known concentration by accurately loading (± 0.1 mg) 10 + 1 mg of the stearyl alcohol into a 100 ml volumetric flask.
Record the weight of the stearyl alcohol used. Add the internal standard / extraction solvent to the flask and mix to dissolve. Fill to the volume and mix well. When not in use, this container must be kept hermetically sealed to avoid evaporation of the solvent. This solution will be used to determine the relative response of stearyl alcohol to the internal standard of 1-hexadecanol for instrument caation.
Preparation and Caation of Gas Chromatography All equipment must be installed, operated and maintained in accordance with the manufacturer's recommendations. Install the column and check all gas flows with the column oven at 100 ° C and injection port and detector at operating temperatures. Gas chromatography will be operated under the following conditions: Carrier gas: Hydrogen (helium can be used); flow rate 1.5 ml / minute. Injection Port: 325 ° C; slot ventilation flow 30 ml / minute; septum purge 2 ml / minute; straight through the lining with glass wool plug; Merlin microsello. Injection volume: 2 μl slot. FID detector: 350 ° C; set gas flows according to the manufacturer's suggestions. Typical gas flows are 400 ml / minute for air, 30 ml / minute for hydrogen and 30 ml / minute for the auxiliary gas (formation). Column Oven: 100 ° C in ramp at 15 ° C / minute at 325 ° C; keep for 10 minutes.
Ensure that all connections are hermetically sealed and free of leakage. Turn on the detector and allow it to stabilize. Condition the column at 325 ° C for 30 minutes. Clean the syringe with dichloromethane as needed. The syringe should also be rinsed with dichloromethane several times after each injection. Perform several blank operations with dichloromethane injections to ensure that a good baseline is obtained and that no unusual spikes are present in the chromatogram. If strange peaks are present or the baseline is not adequate, stop the problem and correct the errors. Calibrate the instrument using the previously prepared calibration standard. Consult the manufacturer's instructions for the data system for the appropriate sequence of operations. Calculations should be performed in a manner similar to that described in the calculations section below in order to provide the desired result.
Sample Analysis Procedure 1) Remove the lid of the sample jar and add 10 ml of the extraction solvent solution / internal standard using the assortment flask. Replace the lid and shake the contents to ensure that the tape 700 is not adhered to the sides of the jar and is completely submerged in the solvent. Repeat this for all samples. 2) Allow the samples to settle 16 hours (typically overnight).
3) Shake the contents of the jug to mix. Using a transfer pipette, transfer an aliquot of the sample extract to an appropriately labeled autosampler bottle. Cover the bottle, replace the lid of the jar and hold until completing the analyzes. Repeat this for all samples.
4) Place the flasks in the autosampler in random order and start the analyzes using the gas chromatography conditions described above. The first bottle should be a dichloromethane template. Several "verification" standards (approximately every 20 samples) must be placed throughout the operation to verify correct operation. 5) At the end of the operation, check each chromatogram to ensure the proper analysis. If you suspect a problem, detect and correct. Re-analyze the samples as necessary.
Calculations The total micrograms of stearyl alcohol in each sample extract were calculated based on the relative response of the stearyl alcohol peak to that of the internal 1-hexadecanol standard. The ratio of the peak areas is multiplied by the relative response factor (determined at the time of calibration of the instrument) and the micrograms of the internal standard in the extract to produce the total μg of stearyl alcohol in a sample.
Instrument Calibration Determine the instrumental relative response factor for stearyl alcohol and the internal standard based on stearic alcohol areas and 1-hexadecanol peaks in the standard calibration chromatogram.
Area? Nst Weigh Response Factor (Rf) = XX 10 Weight tnst Areas where Area? Nst GC peak area for the internal standard Areasa Peak area GC for stearyl alcohol Weight mst Micrograms of the internal standard used to prepare the internal standard solvent / extraction. WeightSa Micrograms of the stearyl alcohol used to prepare the calibration standard.
Sample Calculations Calculate the total micrograms of stearyl alcohol in each sample using the peak areas of the sample chromatogram in the following equation: Areasa Weight? Nst Total μg SA = X Rf X
Where Area? Nst GC peak area for the internal standard Areasa GC peak area for stearyl alcohol Weight? Nst Micrograms of the internal standard used to prepare the internal standard solvent / extraction.
Report the amount of composition for skin care transferred in mg / cm2, where:
0. 001 X μg of stearyl alcohol Transferred Composition = (concentration of stearyl alcohol in the composition) X (tape area)
For the method described above, the concentration of stearyl alcohol in the composition is 41% and the tape patch measures 4.4 cm by 4.4 cm.
Transferred composition = (0.001 X μg stearyl alcohol) / (0.41 X 4.4 cm X 4.4 cm) 0.000126 X μg stearyl alcohol (mg / cm2)
2. Extraction and Analysis of the Test Sample for the Protease Inhibitor This method is designed to be used with the skin care composition containing a protease inhibitor of Table 1. One skilled in the art will recognize that adaptations may be necessary for extract and analyze the level of other protease inhibitors. In principle: 1) the protease inhibitor is extracted from the skin analogue using an appropriate solvent; 2) then HPLC or other quantitative analytical techniques are used to determine the level of the inhibitor in the extract; 3) the amount of a protease inhibitor is calculated per unit area based on the amount of the inhibitor in the extract and the area of the tape.
Standard preparation To prepare a standard solution of 10 ug / mL of hexamidine, weigh 0.10 grams +/- 0.02 grams of reactive grade hexamidine diisetionate and dissolve it in a mobile phase HPLC solution (10% acetic acid) glacial and 17.5% methanol). Prepare additional hexamidine standards by aliquoting the standard solution of 10 ug / mL as shown in Table 2 and diluting to a volume in 100 mL flasks with the mobile phase HPLC solution.
TABLE 2 Preparation of the Standards *
Sample preparation 1. Place the transfer ribbon sample in a 40 mL glass bottle. 2. Add 10 mL of dichloromethane to the bottle using a dispensing flask, and tightly cap the vial. 3. Secure the bottle in a wrist-action shaker and shake for 30 minutes. 4. Remove the bottle from the agitator, remove the cap from the bottle and add 10 mL of the mobile phase HPLC solution to the bottle. Re-cap the bottle and place the bottle securely on the wrist action shaker. 5. Shake the sample for 30 minutes to dissolve hexamidine in the aqueous phase. 6. Allow the vial / sample to rest and the layers separate for at least 30 minutes before proceeding. 7. After the sample has separated, remove the aqueous (upper layer) from the bottle with a disposable syringe and filter the aqueous phase through a 0.45 micron filter into an HPLC sample vial.
Analysis of the sample 1. Chromatograph standards and samples under the conditions described in Table 3. TABLE 3 Chromatographic conditions
Calculations 1. Standard concentration (mg / mL): S, (mg / mL) = W (mg) / 100 * (W100) (1) W = hexamidine weight for the standard reserve solution V ^ volume of the solution of reserve hexamidine used to prepare the standard (Table 1)
2. Calibration curve A. Tabulate the mg / mL of hexamidine in each standard (S,) and the responses (peak areas or peak heights), R "for each of the standard solutions. B. Construct a calibration curve to perform the least squares adjustment of equation 2 for the data.
R¡ = mS, + b (2)
3. Test sample A. Calculate the amount of hexamidine (H ^ in the sample that is extracted using the measured response R and the calibration equation: H = (Rb) / m (3) B. Calculate the amount of hexamidine (h) ) in the samples in milligrams according to equation 4. H = H1 * 10 (4) C. Divide the amount of hexamidine (H) by the area of the tape to determine the concentration of hexamidine per unit area of the analog of skin.
VIII. Specific Examples The following are specific illustrations of (a) treatment of diaper upper sheets with the skin care compositions and (b) methods of the present invention using articles comprising those top sheets. Similar approaches can be used to treat other components to provide the treated articles for use in the present methods.
Example 1 Preparation and testing of an absorbent article having a top sheet comprising a composition for skin care and an enzyme inhibitor
A. Preparation of the composition for skin care.
Composition 1 A skin care composition is made by mixing together the following components: 99 parts of a base (ie, liquid) molten composition containing 85 parts of SEFA cotonate (sucrose polycotonate made by Procter &Gamble Co., Cincinnati, OH) and 15 parts of SEFA behenate (sucrose polybehenate made by Procter &Gamble Co., Cincinnati, OH) with 1 part acetohydroxamic acid (Sigma Chemicals, St. Louis, MO). Composition 2 A skin care composition is made by mixing together the following components: 99 parts of a base (ie, liquid) melt composition containing 85 parts of petrolatum (available from Witco Corp., Greenwich, CT as White Protopet); 41 parts of stearyl alcohol (available from Procter &Gamble Co., Cincinnati, OH as C01897); and 1 part aloe extract (available from Madis Botanicals, Inc., S. Hackensack, NJ as Veragel Lípoid in Kaydol), with 1 part tranexamic acid (Sigma Chemicals). Composition 3 A skin care composition is prepared as in composition 2, except that triacetin is used (Sigma Chemicals instead of tranexamic acid) Composition 4 A skin care composition is made by mixing together the following components: 9 parts of a base (ie, liquid) molten composition containing 58 parts of petrolatum (available from Witco Corp., Greenwich, CT as White Protopet); 41 parts of stearyl alcohol (available from Procter &Gamble Co., Cincinnati, OH as C01897), and 1 part of aloe extract (available from Madis Botanicals, Inc., S. Hackensack, NJ as Veragel Lipoid in Kaydol), with 1 part of the hot inhibitory composition (ie, 60oC) which contains 9 parts of Tween 61 (ICI surfactants) and 1 part of hexamidine diisetionate (available from Laboratories Serobilogiques, Pulnoy, France as Elestab HP100).
B. Preparation of a treated article by contact slot coating. A composition selected from Table I is placed in a heated tank that operates at a temperature of 170 ° C. The composition is subsequently applied with a contact applicator (using, for example, a Meltex EP45 thermal fusion adhesive applicator head having 5 slots and operating at a temperature of 170 ° F) on the top sheet of an article in a pattern in strips where the strips run in the longitudinal direction of the article. Specifically, 5 strips are applied, measuring each strip 0.25 inches wide (ie, in the lateral direction of the articles) and 1.75 inches long at an added level = 7.7 mg / in2 (12 g / m2, 1.19 mg / cm2). The distance between the strips is 0.31 inches.
Example 2 Method to improve skin health An active incontinent adult weighing 165 Ibs. who consistently uses absorbent articles and who persistently has light erythema uses an adult incontinence product analogous to the diaper of Example 1 for a period of at least about 5 days. The subject's article is changed according to the user's routine patterns, (the typical patterns of change consist of changes every four to five hours during the day and the application of a new item before sleep). No intervention by the user, in the form of manual application of skin protection products or moisture repellents, occurs during this period. At the end of the 5th. period day, the subject was observed to have reduced or resolved the erythema.
Example 3: Method for improving skin health A diaper is placed on a 32-pound baby who exhibits rash by light diaper and erythema for a period of at least about 5 days using the diaper of Example 1 during the night when sleeping only . (That is, an untreated article is used throughout the day). The baby's diaper is changed according to the caregiver's routine patterns. There is no intervention by the caregiver, in the form of manual application of skin protector or moisture repellent, during this period. At the end of the 5 day period, it was observed that the subject has reduced or resolved the rash or erythema.
EXAMPLE 4 METHOD FOR MAINTAINING SKIN HEALTH A baby weighing 25 pounds who does not exhibit a rash from a diaper or erythema is diagnosed with otitis media and systemic antibiotics are of course prescribed. Based on experience with conventional (untreated) diapers, the caregiver expects the baby to develop the erythema and / or diaper rash that results from loose bowel movements. As a result, diapers such as those described in Example 1 are used continuously throughout the period of administration of the antibiotic. There is no intervention by the caregiver, in the form of manual application of skin protectors or moisture repellent, during this period. During the entire period of antibiotic administration, the subject did not exhibit erythema or rash per diaper.
Disclosures of all patents, patent applications (and any of the patents issued thereon, as well as any of the corresponding published foreign patent applications), and publications mentioned throughout this description are hereby incorporated by reference here. However, it is not expressly admitted that any of the documents incorporated by reference herein teach or disclose the present invention. Although the particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. Therefore, attempts are made to protect all these changes and modifications within the scope of the invention in the appended claims.
Claims (10)
1. An absorbent article, at least a part of which comprises a composition for skin care comprising an enzyme inhibitor, characterized in that the skin care composition comprising the enzyme inhibitor is at least partially transferred from the article towards the skin of a user of the article as a result of normal contact, user movement, and / or body heat.
2. The article according to claim 1, characterized in that the enzyme inhibitor is selected from a protease inhibitor, a lipase inhibitor, a bile salt inactivator, an elastase inhibitor, a urease inhibitor, an inhibitor of amylase, or a mixture thereof.
3. The article according to claim 1 or 2, characterized in that the composition for skin care is solid or semi-solid at 20 ° C.
4. The article according to claim 1, 2 or 3, characterized in that the skin care composition comprises from 5% to 95% of an emollient having a plastic or fluid consistency at 20 ° C, and preferably comprises in addition to 5% to 95% of an agent capable of immobilizing the emollient within the article and having a melting point of at least 35 ° C.
5. The article according to any of claims 1 to 4, characterized in that the part of the article is a contact surface with the user, preferably the upper sheet.
6. The article according to any of claims 1 to 5, characterized in that the skin care composition comprising the enzyme inhibitor is applied to the top sheet in such a way that one or more regions of the top sheet are not treated with the skin care composition; preferably, the skin care composition comprising the enzyme inhibitor is applied to the top sheet in the form of a plurality of strips that are separated by a plurality of strips that do not have a skin care composition.
7. The article according to any of claims 1 to 6, characterized in that the composition for skin care comprises from 0.001% to 50% of the enzyme inhibitor, preferably from 0.1% to 10% of the enzyme inhibitor.
8. The article according to any of claims 1 to 7, characterized in that the enzyme inhibitor has an IC 0 not greater than 500 μM. The article according to claim 1, wherein the skin care composition further comprises a member selected from the group consisting of oil-based emollients, fatty acid ester type emollients; emollients of the alkyl ethoxylate type; emollients of fatty acid ester ethoxylates, emollients of the fatty alcohol type; emollients of the polysiloxane type; fatty acids of sucrose ester; polyethylene glycol and derivatives thereof, sorbitol and derivatives thereof, trihydroxystearin and derivatives thereof; humectants; dimethicone; petrolatum, propylene glycol and derivatives thereof; glycerin and derivatives thereof; triethylene glycol and derivatives thereof; spermaceti or other waxes; fatty acids, fatty alcohol ethers; propoxylated fatty alcohols; fatty esters of polyhydroxy alcohols, lanolin and their derivatives; kaolin and its derivatives; allantoin; aluminum hydroxide gel; calamine, cocoa butter, cod liver oil; kaolin; lanolin; mineral oil; shark liver oil; white petrolatum; talcum powder; topical starch; zinc acetate; zinc carbonate, zinc oxide; live yeast cell derivatives; aldioxa; aluminum acetate; microporous cellulose, 'colecalciferol; colloidal oatmeal; cysteine hydrochloride; dexpanthenol; Peruvian balsam oil; protein hydrosylates; racemic methionine; sodium bicarbonate, vitamin A, D3, E, B5 and E acetate; and mixtures thereof. 10. The article according to claim 1, characterized in that at least 0.0016 mg / cm2, preferably at least 0.0078 mg / cm2, more preferably 0.0016 mg / cm2 to 0.78 mg / cm2 of the skin care composition containing the enzyme inhibitor is transferred to the skin of the patient. user during the use of the article treated with the composition for skin care. 1 1. An absorbent article, at least a part of which comprises a composition for skin care that is solid or semi-solid at 20 ° C and comprising (i) from 0.001% to 50% of an enzyme inhibitor , (ii) from 5% to 95% of an emollient having a plastic or fluid consistency at 20 ° C, and (iii) from 5% to 95% of an agent capable of immobilizing the emollient in the article, characterized in that the Immobilization agent has a melting point of at least 35 ° C. The article according to claim 1, wherein the enzyme inhibitor is selected from the group consisting of: soybean trypsin inhibitor and other trypsin inhibitors derived from plants; inhibitor Bowman-Birk; pancreatic trypsin inhibitor; ovomucosides; Chymostatin; aprotinins; leupeptin and its analogues; bestatin and its analogues; antipain; antithrombin III; hirundin; cystatin; a2-macroglobulin; arantitrypsin; Pepstatin and its analogues; TLCK; TPCK; tranexamic acid and its salts, glycyrrhizic acid and its salts, 18-β-glycyrrhetinic acid and its salts; stearialglicirretinate; oat colloidal extracts; elhibin; 4- (2-aminoethyl) -benzensulfonylfluoride HCl; corcetin; phytic acid and its salts; ethylenediamine tetraacetic acid, (EDTA) and its salts; hexamidine and its salts; pentamidine and its salts; benzamidine and its salts and derivatives, p-aminobenzamidine and its salts and derivatives; and guanidinobenzoic acid and its salts and derivatives, including its polymeric derivatives; alkyl hydroxamic acids and corresponding salts and derivatives; phosphoramidate and its derivatives; salts of metals soluble in water; zinc salts of monocarboxylic acids, both saturated and unsaturated; glycerol triesters of fatty acids, such as triacetin, copolymers of bolck of propylene oxide and ethylene oxide; chlorhexidine; cholestyramine; acarbose; voglibose; emiglitato; camiglibosa; pradimicin Q; salbostatin; tendamistat; trestatins; inhibitors derived from plants, especially those of oats, rice, corn; barley and other grains of cereals, seeds, and seaweed; tetrahydrolipstatin; lipstatin; valilactone; esterastine; ebelactone A and B; 1, 6-di (0- (carbamoyl) cyclohexanone oxime) hexane; and mixtures thereof. 13. A method for reducing the enzymatic activity of a faecal enzyme on a part of the skin of a user of an absorbent article, comprising the steps of (i) providing an absorbent article, at least a portion of which comprises a composition for skin care comprising an enzyme inhibitor, and (ii) transferring a part of the skin care composition to the wearer's skin during the use of the article.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/041,266 | 1998-03-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00008934A true MXPA00008934A (en) | 2001-07-09 |
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