MXPA00008936A - Protease inhibitors in absorbent articles - Google Patents

Abstract

The invention provides an absorbent article, at least a portion of which has a protease inhibitor incorporated therein to decrease the activity of fecal proteases that may otherwise initiate or contribute to inflammation of the skin of a wearer of the article resulting in diaper rash or diaper dermatitis. Preferably the article further comprises a delivery system for releasably containing and delivering the protease inhibitor to at least a portion of the skin of the wearer. More preferably, the delivery system comprises a skin care composition and at least a portion of the composition, including the protease inhibitor, is automatically transferred from the article to the wearer's skin without manual intervention during normal usage of the article to form a defense against fecal proteases at the skin-feces interface. Most preferably, repeated application of similarly treated articles to the wearer's skin provides an available source from which the protease inhibitor continuously transfers onto the skin over time and accumulatesto provide a proactive defense against fecal proteases for the reduction or prevention of diaper dermatitis due to proteolytic enzymes.

Description

PROTEASE INHIBITORS IN ABSORBING ITEMS BACKGROUND OF THE INVENTION The invention relates to absorbent arycles such as diapers, trainers, incontinence diapers for adults, feminine hygiene products and the like. In particular, the absorbent articles of the invention contain faecal protease inhibitors and are useful for the prevention and treatment of diaper rash. 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 dermaitis, dermalitis due to cover, rash on the cover 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 range from newborns to elderly people, to critically ill or non-ambulatory individuals. Many types of disposable absorbent products, such as diapers, training pants, dispositions for the incontinence of adults, sanitary towels, panniers, 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 the absorption of liquids, it is well recognized that the long-term use of such absorbent articles can compromise the underlying skin in terms of over-hydration or exposure to skin irritants commonly found in exudates. of the body. 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. As discussed in U.S. Patent No. 4,556,560, Buckingham; United States Pat. No. 4,657,537, Zimmerer; Patent No. 4,685,909, Berg and Stewart; U.S. Patent No. 4,842,593, Jordan and Ryan; Andersen et al. (Dermatifis by spot 30: 152-158, 1994); U.S. Patent No. 4,842,593, MacFarlane et al .; Andersen et al. (Contact Dermatitis 30: 152-158, 1994); MacFarlane et al (J. Appl. Bacteriol., 64: 37-46, 1988); and Buckingham and Berg (Pediatric Dermatology 3: 107-112, 1986), there is evidence that proteolytic and lipolytic fecal enzymes, of inestinal and / or pancreatic origin, play a direct role in causing skin irritation and inflammation of the rash. by diaper. Studies with inhibitors designed to inhibit the enzymatic activity of various classes of proteases showed that serine proteases, cysteine proteases, and metalloproieases were most likely responsible for the total proteolytic activity of the fecal esus. It is known that trypsin and chymotrypsin of serine proteases, in particular, are almost always present in measurable gross quantities in the stools of normal small children, and minor but detectable amounts are present in normal adult stools. The irritant effects of faecal enzymatic activity on the skin are likely to be amplified if the urine is present and / or if the skin is clogged. The production of ammonium hydroxide mediates the action of the urease of the bacterial enzyme in the urine resulting in an increase in pH, for example at levels of 7.0 and above, in which the enzymatic activity of the proteases and orads enzymes such as lipases present in fecal eses is increased. For example, the optimum pH varies for urease aclivity 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 greater 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 faeces are commonly present in the absorbent article at the same time, exposure to the skin lasting 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 fecal eses is an additional contributory factor for the increased enzymatic activity of the fecal esses. For example, it is well known that although the fecal eses of breast-fed infants are usually acidic, the fecal eses of bottle-fed and spoon-fed infants are generally alkaline, with a pH ranging from slightly alkaline (pH 7.2). a 7.5) to very alkaline (pH of 8.7 and higher). 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 previously proposed causes of diaper rash, many aspects have been taken in an attempt to reduce or prevent its occurrence. Many of the more practical aspects attempt to address multiple causes or important cofactors. The reduction of skin hydration through frequent diaper changes, the use of moisture absorbing powders, the use of super absorbent materials, and the improvement of airflow in diapers, are well-known aspects. The use of artificial barriers is also highly practiced. The typical of spheres is the use of a topical cream, ointment, lotion or paste to provide some degree of physical barrier to the skin against fecal irritances or urine, regardless of its specific nature. However, barrier, while reducing the access of irritants to the skin, can be occlusive by itself and can be aesthetically unpleasant. In another approach, attempts have been made to maintain the pH of the skin by the use of pH control agents, such as regulating agents or acid-neutralizing ammonia agents, in an absorbent article as ingredients in skin care products. topically applied. 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 irritating 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 fecal esus is deposited directly on the skin immediately after the bowel movement.

Certain anti-enzyme compounds have been included in the topically applied compositions for the travail or prevention of diaper rash caused by prolonged contact of human skin with body wastes. For example, US 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. U.S. Patent No. 5,091,193 discloses compositions for application to the skin at the time of diaper change that contain a chelating agent such as phytic acid, ethylenediamine tetraacetic acid, (EDTA) and the like, which resolve the availability of the only ones that the ureases and the prophets require as cofactors for the 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. Cleaning towels having skin cleansing compositions that incorporate protease inhibitors have also been described to be used in place of toilet paper to clean the body excretions from the skin to prevent irritation. Although there appear to be multiple factors involved in the development of the diaper rash, it is likely that the physiological response of the skin to irritants such as fecal enzymes, ammonia, and the like may involve some common mechanics. For example, it is known that the production of cytokines by skin cells is a common response to the presence of irritants and to the percubation of the skin's outer barrier layer (the stratum corneum). The main type of cell that appears to be involved in the production of cytokines is keratinocyte, which is a type of cell found directly below the corneal stratum and is most likely initially found to be an irritant. It has been shown that keratinocyte secretes a wide variety of different cytokines, including the proinflammatory cytokine interleukin 1-alpha (IL-1a), in response to irritants. This cytokine and others include a cascade of events that can eventually lead to the physiological appearance of erythema, papules, excoriation and ulceration which are collectively described as diaper rash. Although compositions for the travail or prevention of diaper rash have been described to include certain inhibitors of urease, lipase and / or enzymatic protease activity, it has not been previously recognized that fecal proieases play an important role in inducing the response Initial cytokine of the keratinocytes leading to the cascade of the inflammatory response and that the inhibition of the proteases, in particular, provide a more specific means to avoid or treat the diaper rash than previously reported. In particular, there has been no prior description of a flushing regimen for the reduction or prevention of diaper dermatitis whereby protease inhibitors are incorporated directly into the absorbent articles such as diapers, and the like, or that effective amounts can be delivered. of the protease inhibitors automatically to the user's skin from the treated articles without manual intervention. Furthermore, it has not been previously recognized that the use, preferably repeated use, of the delivered absorbent articles can automatically transfer sufficient levels of the protease inhibitors to the selected regions of the user's skin to provide a proactive defense against penetration and activity. of fecal protease.

BRIEF DESCRIPTION OF THE INVENTION The invention provides an absorbent article, at least a portion of which is a prolease inhibitor incorporated therein to decrease the activity of faecal proteases which may otherwise initiate or contribute to the skin inflammation of a user of the Article resulting in diaper rash or diaper rash As used in the context of the invention, the term "protease inhibitor" means any substance that inhibits protease activity in one or more of the seven tests described below. in (i) an IC50, as defined below, of about 30 micromolar (μM) or less, typically from about 0.00001 μM to about 30 μM more typically from about 0.0001 μM to about 20 μM, even more typically from about 0.001 μM to about 10 μM, and very typically from about 0.01 μM to about 5 μM, as measured by a profane method purified as described below: (ii) at an IC 50 of about 90 μM or less, typically from about 0.00001 μM to about 90 μM, more typically from about 0.0001 μM to about 30 μM, even more typically from about 0.001 μM to about 10 μM , and very typically from about 0.01μM to about 5μM, as measured by a specific fecal protease method described below; or (iii) at an IC50 of less than 500μM, more typically less than about 300μM, and still more typically less than about 100μM as measured by a General Fecal Protease Method described below. The protease inhibitor incorporated in the article of the invention preferably inactivates one or more of the major types of proteases present in the faeces, ie, serine proteases, metalloproteases, cysteine proteases, and aspartyl proteases. Although any protease inhibitor or mixtures of protease inhibitors that meet the IC50 criteria set forth above can be employed in the absorbent article, it has been discovered and demonstrated here that the inhibition of serine protease activity in the faeces by use of a serine protease inhibitor such as the soybean trypsin inhibitor and hexamidine, in particular, significantly reduce the initial cytokine response by skin cells to the faeces. Exemplary protease inhibitors suitable for use in the absorbent articles of the invention include the soybean trypsin inhibitor and hexamidine, as well as aprotin, p-aminobenzamidine, leupeptin, pepstatin A, chymostatin, and the like. The article preferably comprises from about 0.0001% or about 30%, preferably from 0.0001% to about 10%, by weight of the protease inhibitor. The inhibitor can be presented pure, such as a powder, flakes, particles and the like, or it can be in a carrier vehicle such as a solution, suspension, dispersion, emulsion and the like. On the other hand, the inhibitor can be releasably contained by a microcapsule, an absorbent material, a cell, an adhesive, a skin care composition, a solid support, a nanophase particle structure, and the like. Preferably, the inhibitor in the absorbent article reduces the protease activity, as measured by the Test method of the absorbent article (described below), by at least about 10%, more preferably by at least about 20%, even more preferably by at least about 50%, and most preferably at least about 80%. Typically, the inhibitor in the absorbent article reduces the protease acfivity by about 10% to about 99%, more preferably by about 20% to about 99%, even more typically by about 50% to about 99%., and very typically by about 80% to about 99%. The absorbent article preferably further comprises a delivery system for releasably conferring and delivering the protease inhibitor to at least a portion of the user's skin of the article. The delivery system may be of any configuration, but not limited to, one containing the protease inhibitor powder, in the form of a particle or flake, or in a solution, a dispersion, a suspension, an emulsion, or the like. The delivery system may comprise a metal structure such as a microcapsule, an absorbent material, a particle nanophase structure, a cell, an adhesive, a solid support, or the like, or a composition such as a skin care composition. . Preferably, the delivery system places the protease inhibitor in close proximity to the skin during use of the article and, more preferably, on at least a portion of the user's skin of the article, such that the inhibitor can intercept the faecal proteases in the interface of the skin / fecal eses before they can penetrate the surface of the stratum corneum of the skin, reducing or avoiding in this way the acfivation of an inflammatory response. In a preferred embodiment of the invention, the delivery system comprises a skin care composition containing from about 0.01% to about 50%, preferably from about 0.05% to about 25%, especially about 0.1% to about 10% , by weight of the protease inhibitor. More preferably, at least a portion of the surface that is in contact with the user of the absorbent arycle comprises the skin care composition with the inhibitor in such a way that a part of the skin care composition including the inhibitor Proiease is automatically transferred from the article to the user's skin without manual intervention during normal use of the article to form a defense against faecal proteases at the fecal skin interface, most preferably, the repeated application of articles similarly brought to the skin of the user provides an available source from which the protease inhibitor is continuously transferred onto the skin over time and accumulates to provide a proactive defense against faecal proteases for the reduction or prevention of diaper rash. due to proteolytic enzymes. An advantage of the absorbent articles brought with the proiease inhibitor of the invention is that the inhibition of the faecal proleads and, therefore, the reduction of the irriiation of the skin due to the contac tion with the fecal eses, is a direct result of the inhibitor-enzyme isolation, rather than by any indirect means, such as a change in pH, the inactivation of a cofactor required for enzyme activity, or the presence of other skin health-improving compounds. Through the judicious selection of inhibitors that inactivate the major types of proteases present in fecal eses, a method is established for the treatment and / or prevention of diaper rash requiring a very low amount of the protease inhibitor in the article . In addition, the inhibitor-enzyme interaction of the invention is achieved at high levels of pH normally found in soiled diapers and other absorbent articles under unregulated conditions.

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 I. 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 "IC50" means the inhibitory concentration (e.g., a micromolar concentration, μM) of a substance (inhibitor) that reduces the substrate cleavage rate by a 50% protease, as measured by the assay In vitro standard of the protease activity described below. The IC50 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 a protease inhibitor according to the invention can be measured by a purified protease period, by a specific faecal protease method or by a general fecal protease method. Other terms are defined here where they are initially discussed.

All porceniajes, proportions and relationships used here are by weight unless otherwise specified.

II. The invention The invention provides an absorbent article containing a protease inhibitor which inhibits one or more of the proteases found in the faeces and satisfies any of the IC50 criteria for the inhibition activity against Iripsin, chemophripsin and / or aminopeptidase leucine in a purified Prozaza Assay, a specific fecal protease Assay, or a General Protease Assay described below. More particularly, the present invention provides an absorbent article containing a protease inhibitor having an IC 50 of about 30 μM or less, typically about 0.00001 μM to about 30 μM, more typically from about 0.0001 μM to about 20 μM, even more typically from about 0.001 μM to about 10 μM, and very typically from about 0.01 μM to about 5 μM, as measured by the purified Protease Method. The invention separately provides an absorbent article containing a protease inhibitor that has an IC 50 of about 90 μM or less, typically about 0.00001 μM to about 90 μM, more typically from about 0.0001 μM to about 30 μM, even more so typical from about 0.001 μM to about 10 μM, and very typically from about 0.01 μM to about 5 μM as measured by the Specific Fecal Protease Method. The invention further provides an absorbent article containing a protease inhibitor or a mixture of protease inhibitors having an IC50 of less than about 500 μM., more typically less than about 300 μM, and still more typically less than about 100 μM as measured by the General Fecal Protease Method. As used in the context of the invention, the term "treated article" refers to an absorbent article containing the protease inhibitor. In one embodiment of the invention, the prolease inhibitor is initially available in or is capable of migrating towards a part of the absorbing aryl which may be in contact with the fecal eses, or especially fecal faeces, for direct inhibition of activity. of fecal protease in that part of the article. As discussed below, the inhibitor may be initially in an active form or it may be initially non-active but capable of being activated by, for example, a foreign force such as moisture in the urine or faeces. In another embodiment of the invention, the absorbent article comprises a delivery system containing a protease inhibitor and which automatically, without manual intervention, supplies an effective amount of the inhibitor to at least a portion of a user's skin during the use of the article for the inhibition of faecal proteases in the skin barrier / fecal es. More preferably, the use or repeated use of similar articles having protease inhibitor delivery systems automatically transfers a sufficient level of the protease inhibitor to the selected regions of the user's skin before they are in contact with them. fecal to provide a proactive defense against the penetration and activity of faecal protease. It has been made theorized that faecal proteases fragment into proteinaceous substances present in the stratum corneum (outer barrier layer) of the skin, resulting in the production of cytokine by the underlying keratinocytes and the activation of a cascade inflammatory response that produces the symptoms of the rash by diaper. As demonstrated herein, the protease inhibitor substances for use in the absorbent articles of the present invention have the surprising ability to inhibit the induction of cytokine production by keratinocytes in the presence of fecal esus which is due to an interaction direct inhibitor-enzyme Although not bound to be bound or limited by theory, the presence of a protease inhibitor that satisfies the IC 50 cryogen for the aclvity described above is considered to be in concavity with the fecal eses within the article or in the The skin / es fecal reduces or prevents the occurrence of an initial insult by a fecal protease to the stratum corneum. Therefore, an absorbent arycle having a protease inhibitor incorporated therein or preferably having a delivery system that delivers the protease inhibitor in an effective concentration directly on the skin is useful in the treatment and / or prevention of Diaper rash It is well known that one of the most important functions of the skin is to act as a barrier to the discharge of physiological fluids, electrolytes and other components, as well as acfuar as a barrier to the entry of microbes, toxins and other inflammatory agents or harmful. In light of the discovery that fecal proteases contribute significantly to diaper dermatitis, it is considered that in addition to causing skin irritation due to digestive degeneration of the stratum corneum, the action that compromises this barrier allows other components of urine and faeces, ammonia, fatty acids and the like, which may otherwise not be irritant by themselves, migrate through the barrier of the compromised skin to produce additional irritation. For example, Candida albicans, which produces an asparyl prophase, is often found as a major component of human faecal secretions in individuals treated with antibiotics. This yeast thrives in moist environments found in dirty diapers and, if the skin barrier is disturbed, not only can the aspartyl protease contribute to further skin breakdown, but a serious infection of Candida can occur. Therefore, the inclusion of fecal protease inhibitors in absorbent articles, as described herein, helps to maintain the integrity of the stratum corneum barrier and effectively prevents the occurrence of secondary irritation and / or infection that can contribute to diaper rash lll. Protease inhibitors Protease is a common term used to represent a group of proteolytic enzymes that are capable of hydrolyzing proteins and peptides into fragments by unfolding or hydrolyzing the peptide bonds. Proteases can be subclassified into proteinaseas (endopeptidases) and peptidases (exopeptidases). The pepíidasas act in the peptide bonds adjacent to a free amino or carboxyl group in the exfremo of a protein and in this way unfold the protein from the outside. Among the main types of peptidases are carboxypeptidases, dipeptidases and aminopeptidases. The proteinaseas act on the peptide-specific inner bonds of the proteins and can be sub-classified into four types, namely, serine proteases, metalloproteases, cysteine proteases, and aspartyl proteases. Among the main types of proteasease are trypsin and chymotrypsin. Because proteases are widely distributed in plants, humus, bacteria, milk, milk products, and almost all the other animals, as well as digestive juices in the gastroinfestinal tract, these are almost always present in the diaper area. where it has been soiled by human waste. Each of the protease inhibitors included in the absorbent articles of the invention is a chemical substance that satisfies at least one of the seven criteria for the IC 50 described above and reversibly or irreversibly inhibits the hydrolytic action of one or more proteases included among the subclasses of previous functional proteases normally found in human faeces as well as proteases whose specific substrates are not as yet undefined. The protease inhibitors that can be employed in the embodiments of the invention include any inhibitor of natural occurrence of plants, microbes and / or of animal origin (including human) and the synthetic inhibitor synthetically manufactured that satisfies the criteria for the IC50 described above. . Exemplary inhibitors of protease that are believed to meet the IC50 criteria and that are believed to further inhibit the type of protease indicated in the parenthesis include, but are not limited to, soybean trypsin inhibitor and other derivative trypsin inhibitors of other plants such as lime seed protease inhibitor, corn protease inhibitor and the like; Bowman Brik inhibitor (serine-type protease inhibitor, trypsin); pancreatic trypsin inhibitor lal as an inhibitor of bovine pancreatic trypsin and other animal derived pancreatic trypsin inhibitors; white egg trypsin inhibitor (serine-type protease inhibitor, trypsin); Ovoinhibitors containing ovomucosae such as from the white egg of chicken or turkey (trypsin inhibitors and chymotrypsin); chymostatin (serine-type protease inhibitor, chymotrypsin); aprotinin (serine protease inhibitor); leupeptin and its lane analogues such as propionyl-leupeptin, N-t-BOC diacetylleupeptin (serine and cysteine protease inhibitor); bestatin and its analogues such as epibestatin and nitrobestatin (inhibitor of aminopeptidase metalloprofease); amastafin and its analogues such as epiamastain (aminopepidase inhibitor); antiparin (trypsin inhibitor); anti-lyrbin III (serine protease inhibitor); 4-sulfamoylphenyl-4-guanidinobenzoaio-methosphonate (trypsin inhibitor); camostal (trypsin inhibitor); elafin (elastase inhibitor); hirudin (serine protease inhibitor type thrombin); cisiafin (proinase inhibitor of white egg cysteine); E-64 (trans-epoxysuccinyl-L-leucylamido- (4-guanidino) -buíano) and its analogues (cisiein prozacide inhibitor); 2-macroglobulin (universal endoprotease inhibitor); 1-anti-syringe (inhibitor of ipsin); pepstatin and its analogs such as acetyl pepstafin, pepstafin A, Nle-Sta-Ala-Sta (aspartyl protease inhibitor), apstain (P aminopeptidase inhibitor); (2R) -2mercaptomethyl-4-melylpenianyl-b- (2-napyl) -Ala-Ala amide (matrix metalloprotease inhibitor); (2R) -2-mercaptomethyl-4-methylpentanoyl-Phe-Ala amide (matrix metalloprotease inhibitor); N-acetyl-Leu-Leu-methionine (calpain inhibitor); norleucinal N-acetyl-Leu-Leu (calpain inhibitor); para-aminobenzoyl-Gly-Pro- -Leu-D-Ala hydroxamic acid (matrix metalloprolease inhibitor); 2 (R) - [N- (4-methoxyphenylsulfonyl) -N- (3-pyridylmethyl) amino] -3-methylbane-hydroxamic acid (meifaloprotease inhibitor); 4- (2-aminoetyl) -benzenesulfonylfluoride hydrochloride (general protease inhibitor / broad spectrum); and mixtures of any of the above. Among the preferred protease inhibitors for use in the absorbent articles of the invention are compounds that exhibit inhibitory activity that is not necessarily restricted as 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, para-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 the polymeric guanidinobenzoic acid derivatives disclosed and elaborated in our co-pending United States patent application Serial No. 09 / 041,196, filed March 12, 1998 in the name of T.L. Underiner et al, copresented with the present application, the disclosure of whose co-pending application is hereby incorporated by reference. The protease inhibitors can be used singly or as a mixture of protease inhibitors fal as a "cockialyl" of inhibitors in an individual absorbent article. In addition, the different protease inhibitors can be used in different locations in an individual absorbent article. Because of the wide diversity of enzymes present in fecal escs, it is reasonably predictable that materials such as those described above that inhibit faecal proteases can also inhibit enzymes that unfold substrates other than proteins and peptides. Therefore, protease inhibitors that also inhibit lipases and ofras esterases, amylases, and / or ureases are within the scope of the embodiments of the invention if the inhibitor meets the IC50 criterion for protease inhibition activity as described above. The protease inhibitors that are preferred in the practice of the invention are the soybean trypsin inhibitor, the Bowman-Birk inhibitor, aprotin, hexamidine (eg, hexamidine diisephionate), para-aminobenzamidine, leupeptin, pepstalin A , Chymosfalin and Polymeric Derivatives of Guanidinobenzoic Acid (disclosed and prepared in our copending United States Patent Application Serial No. 09 / 041,196, incorporated by reference above.) Particularly preferred protease inhibitors are the soybean trypsin inhibitor. , hexamidine, para-aminobenzamide and the above polymeric derivatives of guanidinobenzoic acid.

IV. Absorbenite 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 on the premise to describe absorbent articles, which are not de-inked to be washed or otherwise restored or reused as an absorbent article after a single use. Examples of disposable absorbent articles include feminine hygiene articles such as sanitary napkins, panty liners and tampons, diapers, incontinence briefs, diaper socks, trainers, and the like. The protease inhibitors can be incorporated in any part or portions of any of the absorbent articles described herein. The delivery systems for the protease inhibitors are components of the absorbent articles and are discussed separately below. 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, the backsheet, the absorbent core and any individual layer of component spheres, 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 placed adjacent to the garment or undergarments of the wearer when the disposable absorbent arc is worn. The following description generally discusses the 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, asymmetric, 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, for example, acquisition zones; and may comprise one or more layers or substrates). The total absorbency of the absorbent core, however, must be comparable to the design load and the 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, panty tubes, 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 topsheet is preferably pleasant, of soft feel, and does not irritate 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 non-woven materials with aberrations; polymeric materials such as plastic films with aberrations (for example, hydroformed fermoplastic films); porous foams, cross-linked foams; crosslinked thermoplastic films; and thermoplastic films. Suitable woven and nonwoven materials may be composed of natural fibers (for example, wood or cotton fibers), synthetic fibers (for example, 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 band can be bonded by spun, carded, wet-washed, melt-blown, hydroentangling, hydroformed, hydro-open, combinations of the above, or the like. If it is composed of a non-woven or non-woven fabric, the topsheet preferably comprises skin care compositions comprising the protease inhibitor (s), as described below. The backsheet is impermeable 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 in the present, the term "flexible" refers to materials that are pleasant and will easily conform to the shape and general contours of the human body. The backsheet proves that the exudates absorbed and contained in the absorbent core dampen the aricles that are in contact with the absorbent article such as bedding, pamphlets, pajamas, under garments. The backing sheet may in this way comprise a woven or non-woven material, polymeric films such as polyethylene or polypropylene thermoplastic films, or composite materials as a non-woven 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. The illusive polyethylene films are manufactured by Clopay Corporation of Cincinnati, OH, under the designation P18-1401 and by Tredegar Film Producis of Terre Hauie, 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 placed adjacent to the surface facing the garment and the surface facing the body, respectively, of the absorbent core. The absorbent core is preferably bonded with the backsheet, the topsheet, or both, in a manner known as through bonding means (not shown in Figure 1) such as those well known in the art. However, embodiments of 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 topsheet can 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 USPatent 3,911,173, issued to Sprague, Jr. on 7 October 1975; U.S. Patent No. 4,785,996, issued to Zwieker et al., November 22, 1978; and the patent of E. U. A. 4,842,666, issued to Werenicz on June 27, 1989. Each of these patenis is incorporated herein by reference. Alternately, the joining means may comprise heat junctions, pressure bonds, ullrasonic junctions, 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 a prolease inhibitor and / or a delivery system for a prophase inhibitor incorporated therein and, more preferably, having a contact surface with the treated body with a skin care composition containing a protease inhibitor, it is 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 looks 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 creases of elasticity characteristic 560, and a system generally designated as 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 5 1, 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 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 typically could be designated as the backing portion. the crotch region). The surface facing the body 54 of the diaper 50 comprises that portion of the diaper 50 that is placed 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 center line 59.

Figure 1 shows a preferred embodiment of the diaper 50, wherein the topsheet 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 they 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; U.S. Patent No. 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 top sheet can be made hydrophilic by trapping it with a surfactant agent. Suitable methods for treating the topsheet with a surfactant include spraying the top sheet material with the surfactant and immersing the material in the surfactant. A more detailed discussion of such hydrophilic trafficking and characterization is given in US Pat. No. 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 can be in the form of a film formed with openings, which is preferred in absorbent articles of feminine hygiene, the films formed with openings are useful since they are permeable to body fluids and not yet absorbent and have a reduced leniency to allow liquids to pass back and rewet the user's skin. In this way, the surface of the formed film which 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; Patent of E. U. A. 4,324,246 issued to Mullane and others on April 13, 1982; US Pat. No. 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 patents of E. U. A. 5,006,384, issued to Baird on April 9, 1991. Each of these panes 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 & 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 tensio-active agent 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. In 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 still another modality, described in the U. S. Stafutory Inveníion Registraíion. H1687, published in the name of Roe et al. On October 7, 1997, the absorbenfe article is provided with a gluteal locking device that raises the upper lamina the groove of a user's glutes. 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 approximately 1.3 cm to approximately 6.4 cm around the entire periphery of the diaper. The absorbent core 540 can form 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, US Pat. 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; Patent of US Pat. No. 4,888,231 issued to Angsladt on December 19, 1989; and US Pat. No. 4,834,735 issued to Alemany and others, May 30, 1989. The absorbent core may further comprise the dual core system containing a core of acquisition / distribution 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 the U.S.A. 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 exudates from the body; a 560 elastic waist accessory that provides improved fit and containment; and a fastening system 570, which forms a lateral closure which maintains the first waist region 56 and the second cinientation reaction 58 in a configuration overlap, 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 most effective diaper application 50.

The elastic leg cuffs 550 can be constructed in a number of different configurations, including those described in the patents of E. U. A. No. 3,860,003 mentioned above; U.S. Patent No. 4,909,803, issued to Aziz et al. on March 20, 1990; U.S. Patent No. 4,695,278 issued to Lawson et al., September 22, 1987; and US Pat. 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 which may be useful herein are described in the co-pending US patent application No. 08 / 766,386 and 08 / 840,039, filed on December 3, 1996 and December 24, 1996. April 1997, respectively, both incorporated herein by reference. The waist elastic attachment preferably comprises an elastic waistband (not shown) which 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., 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.S. Patent No. 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., September 29, 1992; the descriptions of which are incorporated herein by reference. Illustrative fastening systems 570 are described in the patents of E. U. A. 4,846,815 issued to Scrips and July 111, 1989; patent of US Pat. No. 4,894,060 issued to Nesiegard on January 16, 1990; pafenfe of E. U. A. 4,946,527 issued to Batírell, on August 7, 1990; patent of E. U. A. 3,848,594 issued to Buell, November 19, 1974; Pa.ent of E. U. A. B1 4,662,875 issued to Hirotsu, and others on May 5, 1998; and patents of E. U. A. 5,151,092 issued to Buell and others 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 diaper regions of the diaper, preferably the second waist region 58, under the wearer's back and pulling the rest of the diaper over the wearer'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 a pro-aase inhibitor and / or a delivery system to deliver the inhibitor to a user's skin during the 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. The underpants (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 sliding the underpants into place around the wearer's lower trouser. Suitable trainers are described in U.S. Patent No. 5,246,433 issued to Hasse et al. On September 21, 1993.; Patent of US Pat. No. 5,569,234, issued to Buell and Oros, on October 29, 1996; U.S. Patent No. 4,940,464 issued to Van Gompel et al., July 10, 1990; and US Pat. No. 5,092,861 issued to Nomura and others on March 3, 1992, the descriptions of which are incorporated herein by reference. Another disposable absorbent article for use in the present invention is an incontinent arithmetic. 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 articles absorbents, irons, bed pads, and the like, regardless of whether they are used by adults or other inconvinent persons. Suitable inconfi- nence carriers are described in the U.S. Patent No. 4,253,461 issued to Strickland et al., March 3, 1981; pateníes of E. U. A. Nos. 4,597,760 and 4,597,761 issued to Buell the 1st. July 1986; the aforementioned U.S. Patent 4,704,115; patenfe of E. U. A. 4,909,802 issued to Ahr, et al., on April 16, 1987; Patent of US Pat. No. 4,964,860 issued to Gipson et al. on October 23, 1990; and in the context 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; patent of E. U. A. 5,009,653, issued to Osborn III, on April 23, 1991; Pa.le of E. U. A. 5,267,992 issued to Van Tilburg on December 7, 1993; Pa.le of E. U. A. 5,389,094 issued to Lavash et al. on 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.

V. Methods for Protease Inhibition Standard in vitro assays 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 for 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. For the assay or assay of the purified protease and faecal protease assays described below, the IC50 for each inhibitor tested is calculated according to the following equation: IC50 = [l] / [(v / v,) - 1] where: [I] is the concentration of the inhibitor tested, v is the rate of the 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. The following methods of purified protease and faecal protease were used to determine the inhibitory activity of putative protease inhibitors against a) known proteases existing in the faeces; and b) the activity of the protease of the fecal esses themselves; respectively. Any substance that satisfies the IC50 criterion described above for the inhibition activity in any of the following methods is considered as a protease inhibitor as defined herein. In the Methods, v and v, they are measured as the change in absorbance (optical density, OD) at a given wavelength / time (for example, minutiae).

A. Purified Proiease Means 1. Purified Trypsin To test the efficacy of the purified trypsin protease inhibitors were added 0.05 mL of a putative inhibitor and 0.125 mL of 32 nM trypsin (eg, Sigma, Yes. Louis, MO, catalog number T6424) in the syringe regulator (50 mM TRIS, 20 mM CaCl2, pH 8.2) to a microcuvette. The cuvette is incubated at 25 ° C for 10 minutes. For this mixture, 0.025 mL of subtracted (4 mM Cbz-argigin-p-nitroanilide, eg, Sigma, Yes. 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 slabs 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 chymotrypsin 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 the splitting of the subtracted 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 min. For this mixture, 0.025 mL of the substrate (2.4 mM L-leucine-p-nitroaniline, for example, Sigma, St. Louis, MO, catalog number L9125) is added in the LAP buffer to the cube, mixed, and measured the absorbance at 405 nm for 10 minutes at 25 ° C. The fasa of the 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 puíative 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 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.

B. Specific faecal proiease methods The following is a general description of a method to obtain a suitable fecal sample for use in Fecal Protease Methods. For purposes of establishing a positive approach to ensure that fecal eses of the background sample exhibit the enzymatic activity required to determine the inhibitory activity of the protease, the following procedure was followed for each of the faecal proiease masses. The fecal fundus eses 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) (for example, 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 subtracted transfer rate in the absence of the inhibitor in the range of 0.005 OD405 per minute to 0.020 OD405 per minute. (Also, to ensure complete linearity the final absorbance should not exceed 1.5 OD405 units). If the activity of the fecal fundus of babies is outside this scale, it is not possible to determine in an exacdy way 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. Fecal protein activity To test the efficacy of protease inhibitors against the activity of trypsin in the faeces, 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 subfrate (3mM cbz-arginine-p-nifroanilide) is added to the cuvette. The cuvette is mixed by inversion and incubated at 25 ° C for 5 min. 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 putafive inhibitor. The rate of the splitting of the subtracted in the absence of the inhibitor (v) is the curve of a graph related to the absorbance in excess against time. The iases v, and v, and the concentration of the inhibitor [I] are used to calculate the IC50 according to the equation expressed above. 2. Fecal chymosynthesis activity To test the efficacy of protease inhibitors against chymotrypsin activity in the fecal esses, the chymotrypsin inhibitor and regulator (50 mM TRIS, 10 mM CaCl2, pH 7.6.) Is added in a cuvette for 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 the sub-split 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. 3. Faecal LAP activity To test the efficacy of protease inhibitors against LAP activity in fecal eses, the inhibitor and the LAP regulator (50 mM sodium phosphate, pH 7.2) are added in a cuvette to obtain a volume final 0.95 mL. To this mixture, 0.03 mL of the substrate (6 mM L-Leucine-p-nit roanilide) is added to the cube. The cube is mixed by inversion and incubated at 25 ° C for 5 min. 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 phasing of the subtraction 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. Using the purified protease and faecal protease assays described above, the protease inhibitory 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 rLAP = Leucine Aminopeptidase As shown in Table 1, each of the exemplary inhibitors exhibits an IC50 acceptable for the inhibition of at least one of the proteases tested by the purified Protease Methods and / or specific faecal protease methods employed.

C. General Fecal Protease Methods The general method described above for obtaining a suitable fecal sample for use in Fecal Protease Methods can be readily adapted by an expert in the art to obtain the appropriate samples from the appropriate fecal esses to be used. in the general fecal proiease method listed below for undue experimentation. To test the efficacy of protease inhibitors against protease activity in the fecal eses, 50 μL of the inhibitor and 50 μL of the faecal suspension are added to a 1.5 mL microcentrifuge tube. The microcentrifuge tube is mixed by inversion and incubated at 25 ° C for 45 minutes. Then, 50 μL of the protease buffer (regular 200 mM TRIS containing 20 mM CaCl2, pH 7.8) is added to the microcentrifuge tube. The microcentrifuge tube is again mixed by inversion and incubated at 25 ° C for 45 minutes. Then, 50 μL of the protease substrate (0.4% casein-resorufin, eg, Boehringer Mannheim, Indianapolis, IN, catalog number 1,734,334) is added to the microcentrifuge tube. The microcentrifuge tube is again mixed by inverting at 37 ° C for 60 minutes so that the cleavage reaction of the substrate will take place. Then, 480 μL of ichloroacetic acid (5% w / v) is added to quench the reaction and precipitate any unreacted casein-resorufin. The microcentrifuge tube is mixed by inversion and incubated at 37 ° C for 145 minutes. The microcentrifuge tube is rotated to a relative centrifugal force (RCF) of 20,800 times the gravity for 5 min. Then, 400 μL of the supernatant is added to 600 μL of the assay regulator (0.5 M TRIS, pH 8.8) in a cuvette. The cuvette is mixed by inversion and the absorbance at 574 nm is measured. The same procedure is repeated without the puffative inhibitor. A is the absorbance at 574 nm in the absence of the inhibitor. A, is the absorbance at 574 nm in the presence of the inhibitor. Anfes to start the reaction, A and A, are almost zero. Therefore, the unfolding of the substrap in the presence of the inhibitor (v,) can be calculated by dividing the absorbance at 574 nm (A,) during the reaction time. The rate of unfolding of the substrate in the absence of the inhibitor (v) can be calculated by dividing the absorbance at 574 nm (A) during the reaction time. The rates v, and v, and the inhibitor concentration [I] are used to calculate the IC50 according to the equation expressed above. TABLE 2 D. Absorbent article testing method To determine the presence of a protease inhibitor in any part of an absorbent article (eg, the topsheet, the absorbent core, the backsheet and / or additional layers, the leg cuffs) , fasteners, side panels, inserted elements, or any combination of these), a small sample of the aricle is made from a desired part and an extraction of the inhibitor is carried out. As is known to one skilled in the art, a water-soluble inhibitor must be extracted with water or a water-based solvent, while a liquid-soluble inhibitor must be extracted with a lipid-based solvent. The following description is only an exemplary method for determining the presence of a protease inhibitor (trypsin) in the article and is not intended to be limited, since the method can be used to test the presence of inhibitors other than proteases, and other different methods can be devised by one skilled in the art without undue experimentation.

In a method for testing a topsheet of an article for a trypsin inhibitor, random 3A-inch punch cuts are made on the side of the diaper core. The top sheet is removed from the punch and placed in a 1.5 mL centrifugal bottle. The sample is soaked overnight in 0.75 mL of water or other extraction solvent such as the 50 mM TRIS buffer, 20 mM CaCl2, pH 8.2 described above. An aliquot (0.125 mL) of supernatant fluid is removed and a cuvette containing 0.025 mL of 160 nM human pancreatic trypsin freshly prepared in TRIS-HCI containing 20 mM CaCl2, pH 8.2 is added and incubated for 10 minutes at 25 ° C. . A conirol sample containing only the regulator is prepared in a similar manner in a second cuvette. The Cbz-arginine-p-nilroanilide subsfrate (0.025 mL of a 4 mM solution) is added to each cuvette and the test and control samples are incubated for 5 minutes. The change in absorbance at 405 nm for each sample is then monitored for 10 minutes. The expert will recognize that the profocol may be used to analyze the inhibition activity of prophase in other components of the article, such as the absorbent core and the like.

The absorbent article is considered to sample an inhibition activity of the pro-asease if the sample exíraclo exhibits at least a 10% reduction, preferably at least a 20% reduction, most preferably at least a 50% reduction, and most preferably at least 80% reduction in substrate hydrolysis by a protease compared to the conirol sample, only the regulator, as measured by the Test Method of the absorbent article. Typically, the reduction in hydrolysis of the substrate will be from about 10% to about 99%, more typically from about 20% to about 99%, even more typically from about 50% to about 99%, and very typically from about 80%. % to approximately 99%. It is also considered that the absorbent article shows the inhibition activity of the protease if the sample contains any prolease inhibiting substance, such as any of the protease inhibitors described above as well as substances that do not necessarily meet the IC50 crierium for activity. inhibitor of the protease described above, when measured by any of the methods of purified protease or faecal protease, for example, substances such as L-1-chloro-3- [4-tosylamido] -7-amino-2-heptanone- HCl (TLCK), L-1-chloro-3- [4-tosylamido] -4-phenyl-2-butanone (TPCK), tranexamic acid, and the like.

E. In Vitro skin test for the inhibition of IL-la production In an in vitro method to determine the efficacy of protease inhibitors to prevent the proinflammatory response of the skin by faeces and fecal enzymes, human keratinocytes are obtained from the epidermal tissue and cultured in a serum free medium in plastic culture containers containing a nylon mesh surface for a period of time until they are confluent. Then the mesh surface is raised to the interface of the liquid air in order to promote the differentiation and formation of the layers organized in multiple layers analogous to those found in vivo, including a well defined barrier layer of stratum corneum. Any cell culture system that promotes the growth and differentiation of keratinocytes can be employed, as described. A commercially available cell culture system suitable for use in the present invention is Epiderm (MatTek Corporation, Aschland, Massachusetts). Infant feces are collected in a manner to keep them free of urine contamination and diluted with phosphate buffered saline (PBS) (pH 7.2 to 7.4). The mixture is then mixed vigorously to obtain a homogeneous suspension by homogenization or sonication. To analyze the production of IL-1 due to the activity of the faecal enzyme, an aliquot of the homogenate is diluted with PBS and added to the surface of the control culture in a culture vessel. To analyze the inhibition of IL-1a production due to protease activity, a predetermined amount of a putative protease inhibitor is added to an otherwise diluted aliquot identical to the above homogenate by adding it to the surface of a test culture. . The crops are allowed to incubate in a controlled atmosphere. At the selected times, the control cultures are grown in the test cultures sprayed with the inhibitor, and the underlying culinary medium. The culture medium is analyzed for the presence of IL-1a by known methods. For example, an assay or assay suitable for IL-1 is an immuno-absorbing method of commercially available enzyme linkages such as R &amp Quantikine.; D Systems, Minneapolis, Minnesota. The percent reduction in the production of IL-1a due to the presence of the protease inhibitor is calculated as follows:% reduction = IL-1alpha from the control cultures minus IL-1alpha of the test cultures I L - 1 alpha from control cultures Using this standard assay, the soybean trypsin inhibitor and hexamidine diiseionion ("hexamidine") were tested to inhibit the inhibition of serine protease inhibitors. production of I L-1 alpha by culfive keratinocytes in the presence of fecal esses. The results showed that hexamidine, at concentrations of 1000 μM and 100 μM, reduced the production of I L-1 to Ifa from the skin culture trafficated with the fecal escales 51-88% and 5%, respectively. A concentration of 10 μM of the soybean trypsin inhibitor was sufficient to reduce the production of I L-1 alpha by 56-75%. The term treatment (90 ° C) of the fecal eses before the test for the production of IL-1alpha resulted in an almost complete elimination of the production of I L-1 alpha, suggesting that the agent or main agents involved in the evocation of the response of the cyclokine are the denaturing proteins. The results indicate that the serine protease trypsin inhibitors (see Table 1) were also effective in reducing the production of IL-1alpha from the cultures of the skin cells.

SAW. Incorporation of the inhibitors in absorbent articles 1. Vehicle The prolease inhibitor for use in the absorbent article of the invention can be water soluble or liquid soluble and can be incorporated into the nested absorbent article, such as in the powder form dry or particulate, or in the form of a suspension, dispersion, emulsion or the like solution in a pharmaceutically and dermatologically acceptable carrier vehicle that does not interfere with the activity of protease inhibition of the compound. The inhibitor can also be incorporated into another structure that is incorporated into the article during manufacture or assembly. For example, the inhibitor can be coated on or fixed or otherwise bonded to the nanophase particle structure or other solid support such glass, plastic or agarose beads, and the like, or contained within pressure-soluble microcapsules or capable of dissolve and the like, or contained in an absorbent material. The use of other types of incorporable elements to contain the inhibitor and the methods of its incorporation will be readily apparent to one skilled in the art. Carriers carrier for inhibitor include compositions which are in the form of lotions, creams, oils, ointments, powders, foams, or gels and the like and which may contain any of the ingredients commonly used in the art for these compositions. The compositions of the compositions will depend on the composition of the composition; in this way, for example, lotions will generally comprise ingredients other than powders. Compositions that are cosmetic in nature may further comprise a wide variety of optional ingredients such as non-occlusive moistening agents, wetting agents, gelling agents, neutralizing agents, perfumes, coloring agents, and the like. Other ingredients, such as ionizing agents and the like, which may be present in the composition are described more fully below under the "skin care compositions". It is preferable that compositions containing the protease inhibitor intended to be transferred to the skin have a pH of not less than about 4 and not more than about 7.5. 2. Incorporation The protease inhibitor employed in the absorbent articles of the invention is incorporated into the article in a configuration that does not by itself invade the normal function of the different structures of the arycle (eg, the absorbance of the core, the permeability of the liquid). of the upper sheet and the like). The inhibitor can be incorporated into any part or paries of the arycle including, but not limited to, the topsheet, the backsheet, the absorbent core, any secondary layer or layers between the core and the sheet layers, a leg cuff a lateral panel, a region of cinura, a fastener, an insertable element such as an absorbent material inserted in the absorbent arycle for the use of the aricle, specialized structures such as those used to contain the inlestinal stools (for example, " cavities "for bowel movements), and the like. The inhibitor can be incorporated into the nested article or, alternatively, the inhibitor can be contained in a delivery system described below that is incorporated in any of the anterior portions of the article and that binds the prolease inhibitor directly or indirectly to the skin of a user during normal use of the item. Any number of different protease inhibitors or mixtures of the protease inhibitors, whether or not incorporated in the delivery system, can be uniformly or non-uniformly distributed throughout the absorbent article. The absorbent arylum preferably contains the protease inhibitor at such a level that the inhibitor or a mixture of inhibitors comprises from 0.0001% to 30%, more preferably from 0.0001% to 10%, even more preferably from 0.001% to 5%, and especially from 0.001% to 1% by weight of the article. The protease inhibitor can be incorporated directly onto the surface of or into the structure of any type of topsheet, including woven, non-woven upper sheets and structure with openings, backsheets, and / or absorbent core materials, or other components of the article during manufacture or assembly by various methods that will be readily apparent to those skilled in the art. For example, the inhibitor may be applied, optionally after being dispersed in a liquid and semi-solid carrier vehicle, to the topsheet, to the absorbent core, or to the side of the core of the backsheet, by spraying, dipping, printing, soaking, or by otherwise contacting the selected structural element with the inhibitor and optionally its carrier vehicle. Among many other techniques that can be used are polymerization of injerfo or radical, or steam fraiamienio the structural elements in order to bind them to the inhibitor by hydrogen bonds that are easily inverted when the surfaces are wetted by the body waste to release the inhibitor. Preferably, the inhibitor is incorporated into at least a portion of the contact surface with the body of the article and is available for automatic transfer to the wearer's skin during normal conialation, during user movement and / or body heat during the use of the article. In an allergenic manner, the arycle also comprises a delivery system containing the protease inhibitor and, and during the use of the arycle, the delivery system delivers at least a portion of the inhibitor to the wearer's skin aulomatically. In each of these embodiments of the invention, the protease inhibitor is transferred to the skin, preferably before a bowel movement occurs, by availability to act at the interface of the skin / faeces after a bowel movement. In a more preferred embodiment, the delivery system is a skin care composition containing the protease inhibitor and various emollients and immobilizing agents, as described below, which is directly supplied from a conical surface with the user to the skin of the user to perform a barrier function to the fecal eses as well as the function of inhibiting fecal protease. Most preferably, the use or preferably repeated use of the articles in which the prolease inhibitor is transferred or delivered directly or indirectly to the skin of the user provides an accumulation of the protease inhibitor for the most effective prevention or reduction of the inflammation of the skin due to contact with faecal proteases. In another embodiment of the invention, the protease inhibitor is placed in the nested absorbency arycle or in a delivery system in such a manner and location that it is available to inactivate the pro-eases in the fecal eses, especially fecal faeces deposited in the feces. the article before transferring the fecal eses to the user's skin. In another embodiment of the invention, the protease inhibitor is placed in the absorbent tissue in a manner that is available to reduce or eliminate fecal protease activity in fecal fluids, or in urine contaminated with fecal eses, which can penetrate towards the absorbent interior of the article and that can, for any reason, subsequently enter into contact with the contact surface with the user. Again, the prolease inhibitor may initially be available or may be denigrated by a delivery system within the article.

Vile. SUPPLY SYSTEM Protease inhibitors, or compositions containing them, can be incorporated in a releasable manner in any delivery system known to those skilled in the art which directly or indirectly facilitates the transfer of the protease inhibitor to the skin of the user of the article. to protect it against irritation due to faecal prolapses in the skin of the fecal skin. The delivery system may contain the unmixed protease inhibitor, as a powder or particulate, or in a solution, suspension, dispersion, emulsion, or the like in a carrier vehicle or in a skin care composition. When released from the delivery system the protease inhibitor is free to migrate from the location of the delivery system in the article to the counted surface with the user to the skin of the user. The delivery system may be a component of any part or portions of the absorbent article including, but not limited to, the topsheet, the backsheet, the absorbent core, any intervening secondary layers or layers between the core and the layers thereof. foil, a leg cuff, a side panel, a waist region, a fastener, an insert such as an absorbent material inserted into the absorbent article for use during the use of the article, specialized structures such as those employed to contain the evacuations intestinal (for example, "cavities" for intestinal evacuation) and the like. Preferably the delivery system is placed close to the wearer's skin and, more preferably it is a component of the user interface of part of the article such as the topsheet, the side panels, the leg cuffs, the region of waist, bras and the like. Most preferably, the delivery system is a skin care composition described below that is incorporated in the topsheet. The delivery system may contain and / or deliver the protease inhibitor in any form such as those described above, including powder in the form of flakes or particles, in the form of a solution, suspension, dispersion, emulsion or the like in a carrier vehicle. Pharmaceutically and dermatologically acceptable. When the inhibitor is released by the delivery system, it may be in an active functional form such as in a solution, suspension, emulsion or the like, or it may be non-functional such as in the form of particulate powder and capable of acivising by the contact with moisture coming from urine and fecal eses or other known means. The types of delivery systems that are useful in the absorbent articles of the invention to facilitate automatic transfer of the prolease inhibitor from any part of the article to the skin of a user will be readily apparent to those skilled in the art. Exemplary delivery systems include, for example, pressure-rupturable or dissolvable microcapsules that are induced to eject the inhibitor or inhibitor composition upon dissolution due to contact with moisture from the urine or feces or rupture due to pressure of the body or manual breaking by a user before applying the article to a user. For example, a water-soluble film enclosing and delivering a powder when in contact with moisture is described in U.S. Patent No. 4,790,836 and would be a suitable material for use in microcapsules containing the protease inhibitor in Any shape such as a powder, particles, semi-solid liquid. Examples of pressure-breakable microcapsules suitable for containing the protease inhibitor are described in U.S. Patent No. 3,585,998. These microcapsules may be present in any part of the absorbent article, including the upper sheet. U.S. Patent No. 4,623,339 discloses an insertable layer that is removable from an absorbent article before use and capable of manually activating under pressure to expel a substance through the slits in the layer. The disclosures of each of the above patents are hereby incorporated by reference. Other delivery systems suitable for conferring the inhibitors or the inhibitory composition include, but are not limited to, "cells" in the arylum that are enclosed or partially enclosed recesses, in a regular or irregular manner, that release the inhibitor when in place the humidity, heat or pressure; and water soluble adhesives and other of these compositions that release the inhibitor upon contact with moisture, and the like.

Regardless of the delivery system used, the protease inhibitor or the composition containing the protease inhibitor upon release may be able to migrate from its original location, for example, it may be moved by the flow of urine, by moving the user, by pressure and the like, or because of a decrease in viscosity when exposed to body heat, to other regions in the absorbent article. Protease inhibitors that are hydrophilic or incorporated in vehicles that are hydrophilic can migrate in all hydrophilic structures of the absorbent article, such as through hydrophilic pores or other openings to allow urine to flow from the topsheet to the core. . However, preferably the delivery systems containing the protease inhibitors, or the compositions comprising the inhibitors, are placed close to the user's skin. In a preferred embodiment, the protease inhibitors are components of the dissolved, suspended or emulsified skin care compositions that can be placed anywhere within the article, but are preferably incorporated into the contact surface with the user of the product. absorbent article such as the topsheet, the side panel, the waist region, the leg cuffs, the fastening device and the like. Skin care compositions suitable for supplying the protease inhibitor are described below. In any of these preferred embodiments, the skin care composition preferably comprises from about 0.01% to about 50%, more preferably from about 0.5% to about 25%, and especially from about 1% to about 10% by weight of the protease inhibitor.

VIII. Skin Care Compositions Skin care compositions suitable for use in the preferred embodiments of the invention are described in US Patent Applications Serial Nos. 08 / 926,532 and 08 / 926,533, each filed on 10. September 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. In addition to its function as a vehicle for delivering an effective concentration of a protease inhibitor to a user's skin, the skin care composition comprising the protease 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 protease inhibitor to the skin through an absorbent article with the fime, an effective amount of the skin care composition containing the protease inhibitor that is applied to or migrated one or more than 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 approximately 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 protease inhibitor and that the desirable level can be ascertained at through rulinary 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 protease inhibitor supplied to the skin will depend to some degree on the nature of the composition employed, relatively low amounts may be provided, while still providing a minimum effective concentration of the protease inhibitor to the skin. . This is particularly true for preferred compositions, as described in Example 1. In order to defer the amount of protease inhibitor transferred to the skin of a user after using one or more írated articles, a method is provided below to determine the caníidad of the composition for the care of the skin transferred to the skin. With respect to the level of the skin care composition that is transferred to the user during the use of an absorbent article used for a period of approximately 3 hours (a typical time of use), particularly for compositions for the care of the patient. preferred skin such as those described in Example 1, it is preferred where at least about 0.0016 mg / cm2, preferably at least about 0.0078 mg / cm2, most preferably at least 0.016 mg / cm2 of the composition, is transferred to the skin for a period of 3 hours. Typically, the size of the composition supplied by an irradiated 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 the continued use of erythroid arteries (in other words, changes that occur according to normal use palos, which typically include changes every 3 to 4 hours during the day and a recent site before sleeping at night) such as during a 24 hour period, it is 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 compositional amount supplied after a 24-hour period, where 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. It will be recognized that the numerous materials useful in the skin care compositions containing protease 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 oatmeal, cysteine hydrochloride, dexpanthenol, Peruvean balsam oil, protein hydrolyzates, racemic methionine, sodium bicarbonate, vilamine 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 Jel ly, Desitin® Diaper Rash Ointment and Daily Care® ointment , Gold Bond® Medicated Baby Powder, Aquaphor® Healing Ointment, Baby Magic® Baby Lotion, and Johnson's Ulira Sensifive® Baby Cream. An effective concentration of a protease inhibitor can be incorporated into any of these commercial products and applied to absorbent articles to create arradicides for use in the present invention. As discussed below, skin care compositions useful for transferring protease inhibitors to the skin of the user preferably, but not necessarily, have a melting profile so that they are relatively immobile and are located on the contact surface. With the user of the temperafura ambienie article, they are easily transferable to the user at body temperature and are not yet completely liquid under extreme storage conditions. Preferably, the compositions are easily transferable to the skin through normal contact, user movement, and / or body heat. Since the composition is preferably substantially immobilized on the user's surface of the arcicle, relatively low levels of the composition were needed to impart the desired skin care benefits. In addition, special barrier materials or wraps are unnecessary to pack the durable items in the methods of the present invention. In a preferred embodiment, the skin care compositions useful herein are water emulsions in aceifeal, wherein the protease inhibitor is in solution or suspension in any of the aqueous phase or oily phase. However, the same composition for skin care can be solid or more often semi-solid, at 20 ° C, that is, at ambient temperature. By "semi-solid" it means that the composition has an ypheological rheology of pseudoplastic or plastic liquids. When no shear is applied, the compositions may have the appearance of a solid, but may be made to flow as the rate of shear stress 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 a protease inhibitor of the present invention have a zero stress viscosity of between 1.0 x 10 8 centipoise and about 1.0 x 108. Most preferably, the shear viscosity of zero is between 5.0 x 106 centipoise and approximately 5.0 x 107 centipoise 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 plate viscometer and cone (a suitable instrument available from TA Instruments of New Castle, DE with model number CSL 100). An expert in The technique will recognize means of 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 exporalating a graph of viscosity versus rate of cut stress for the compositions. for a shear rate of zero at a temperalure of approximately 20 ° C. Preferred compositions are at least semi-solid at room temperature to minimize the migration of the composition before using the article. further, 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, in a truck in Florida, etc.). Representative compositions having these melting characteristics are described in detail in the patent of US Pat. No. 5,643,588, US Pat. No. 5,607,760, U.S. Patent No. 5,609,587, and US Pat. No. 5,635,191, the descriptions of which are incorporated herein by reference. Specifically, the preferred compositions will have the following melting profile: Characteristic Preferred Scale Very Preferred % of liquid at temperalure 2-50 3-25 atmosphere (20 ° C). % of liquid at temperature 25-95 30-90 of the body (37 ° C).

Final melting point (° C) 38 45 Being solid or semisolid at room temperature, the preferred compositions containing the protease inhibitors do not tend to flow and migrate to a significant degree 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, proive and / or conditioning benefits. To improve the immobility of the preferred compositions before using the article, 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 proiective benefit to the skin in addition to the benefit derived from the pro-insane inhibitor, an active ingredient in esías The compositions are one or more pro-assicins or emollients of the skin. As used in the present, the term "emollient" is a maferial which promotes moisture or irritation, softens, covers, lubricates, moistens, pros 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 ambient lemperairy, that is, around 20-25 ° C. Representative emollients useful in the present invention include, but are not limited to, emollients which are petroleum based, sucrose esters of fatty acids; polyethylene glycol and its derivatives; humectants; fatty acid ester type; alkyl ethoxylate group; fatty acid ethoxylates; type of fatty alcohol; polyoxiloxane lipo; propylene glycol and its derivatives; glycerin and its derivatives; including glyceride, acetoglycerides and eryoxylated glycerides of fatty acids of 12 to 28 carbon atoms; trielilénico 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 monographied skin care agents listed above; mixtures of these emollients. Suitable emollients based on peiroleum include those of hydrocarbons, or mixtures of hydrocarbons, with chain lengths of 16 to 32 carbon atoms; Petroleum-based hydrocarbons with long chain lengths include mineral oil (also known as "liquid pelleting") and pelleting (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 straight chain monohydric alcohols (C? -C8, preferably d-C3). Representative examples of such esters include methyl palmitate, methyl stearate, isopropyl laurate, isopropyl myristate, isopropyl palmitalo, ethylhexyl palmitafo and mixtures thereof. Suitable fatty acid ester emollients can also be ester derivatives, longer chain fatty alcohols (C12-C28, preferably C12-C16) 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 efoxylate emollient is selected from the group consisting of lauryl. , ceil and esielil eperoxylates, 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 efoxylazole having an average degree of eryoxylation of 3), laureth -23 (a lauryl efoxylate having an average degree of ethoxylation of 23), celet-10 (a ethoxylate of cetyl alcohol having an ethoxylation degree of 10), and stearel-10 (an eioxylate of esophalic alcohol with an average degree of Elyoxylation of 10). When employed, the alkyl ethoxylamino emollients are typically used in combination with peiroleum-based emollients, such as petrolatum, at a weight ratio of an alkyl ethoxylate emollient to a 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 peiroleum-based emolienols, 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 in the present include polysiloxane compounds. In general, polysiloxane materials suitable for use in the present invention include those which have monomeric siloxane units of the following structure: R1 -Si- O- wherein R1 and R2 for each monomeric independent siloxane unit can be independently hydrogen or any of alkyl, aryl, alkenyl, alkaryl, aralkyl, cycloalkyl, halogenated hydrocarbon or other radical. Any of said radicals may be substituted or unsubstituted; the radicals R and R2 of any paricular monomer unit may differ from the corresponding functionalities of the next adjacent monomer unit; moreover, the polysiloxane can be either a reda chain, a solid chain, a branched chain, or have a cyclic structure, the radicals R1 and R2 can independently be functional 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 methyloyl, elyl, propyl, butyl, pentyl, hexyl, ocyl, decyl, ociadecyl, and the like. The alkenyl radicals are vinyl, allyl, and the like.

Exemplary aryl radicals are phenyl, diphenyl, naphthyl, and the like. Exemplary alkaryl radicals are folyl, xylyl, ethylphenyl, and the like. Aralkyl ilusory radicals are benzyl, alpha phenylethyl, beta phenylethyl, alpha-phenylbutyl, and the like. Illustrative cycloalkyl radicals are cyclobuLyl, cyclopenfilo, cyclohexyl, and the like. The haloaldehyde hydrocarbon radicals are chloromethyl, bromoethyl, lelrafluoroelyl, fluoroethyl, trifluoroethyl, trifluoroylolyl, 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, provided that the polysiloxane can flow or be flowable for application to the absorbent article. This includes, but was not limited to, viscosity as low as 5 cents (at 37 ° C as measured by a glass capillary viscometer according to ASTM standard method D-445) at approximately 20,000,000 centistokes. Preferably, the polysiloxanes have a viscosity at 37 ° C ranging from about 5 to about 5,000 centisfoques, preferably about 5 to 2,000 centisks, most preferably about 100 to 1,000 centis. The alpha-viscous polysiloxanes, which by themselves are resistant to flow, can be effectively deposited on the absorbent arycles through 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, crippled for illustrative purposes only. Particular methods for applying polysiloxane emollients to absorbent articles are discussed with more later disclosure. Preferred polysiloxane compounds for use in the present invention are disclosed in the U.S. Patent No. 5,059,282, issued to Ampulski and Oros, 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 dimefirdones functionalized with cetyl or stearyl fales as polysiloxane liquids. Dow 2502 and Dow 2503, respectively. In addition to such substitutions with phenyl-functional or alkyl groups, effective subsidation can be made with amino, carboxyl, hydroxyl, ether, polyether, aldehyde, ketone, amide, ester, and thiol groups. Of these effecive subsfitutional groups, the family of 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 polyesters 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 substantially have the esterified hydroxyl groups (for example, 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 the skin care compositions which contain a prolease inhibitor in the present invention is an agent capable of immobilizing the composition (including the inhibitor of prophase) the preferred emollient and / or other conditioning agents. / prophecy for the skin) in the desired location in or on the treated tissue. 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 corfanfe effort. When applied to a contact surface with the user or another site of an absorbent article, especially in a molten or fused state, the emollient will not primarily remain in or over the trafficated region. Rather, the emollient will tend to migrate and flow into unwanted regions of the article. Specifically, if the emollient 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 many of the emollients and other skin conditioning agents used in the compositions in the present invention. It also means that much more emolienle has to be applied to the aricle to obtain the desired therapeutic and / or protective benefits. By increasing the level of emollient not only does the cost increase, but it also exacerbates the undesirable effect on the absorbency of the core of the article and the undesirable transfer of the composition during the processing / conversion of the brought articles. The immobilization agent counteracts the emollient's tendency to migrate or flow maintaining 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 schedule raises the melting point and / or viscosity of the composition above that of the emollient. Since the agent the immobilizing agent is preferably miscible with the emollient (or solubilized in the emollient with the aid of an appropriate emulsifier), it traps the emollient on the surface of the counted surface with the body of the article to the region in the which is applicable The counter immobilizing agent is the origin of the emollient to migrate or flow 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 must be, in paríe, to the fact that the immobilization agent raises the melting point and / or viscosity of the composition above that of the emollient. Since the agent of the immobilization agent is preferably miscible with the emollient (or solubilized in the emollient with the aid of an appropriate emulsifier or dispersed therein), it traps the emollient on the surface of the contact surface with the body of the article. to the region in which it is applied. It is also venlajoso "irra" 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 of the cooling of the armature irradiated by blowers, winders, cold rollers, etc., can accelerate the crystallization of the immobilization agent. In addition to being miscible (or solubilized in) with the emollient, the immobilizing agent will have a melting profile that will provide a composition that is solid or semi-solid at ambient 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. The 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 immobilizing agents useful herein may be selected from a number of agents, provided that the protease inhibitory properties of the skin care composition provide the skin benefits described herein. . 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 with 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 alpha-melting materials selected from the group consisting of cetyl alcohol, beilelic alcohol, behenyl alcohol, and mixtures thereof. (The linear structure of these materials can accelerate the solidification on the absorbed article). Mixtures of cephyl alcohol and spharyl alcohol are also parlicularly preferred. 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 immobilization agents include fatty alcohol ethoxylates of 16 to 18 carbon atoms with 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, increased the rate of crystallization of the composition 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 soft 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 chain atoms reda, 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 hydroxyhydrocarbyl 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, maltodesfrose, galactose, sucrose, glucose, xylose, fructose, maltose, lacíosa, mañosa and eriírosa; sugar alcohols such as erythriol, xylitol, malitol, manifol and sorbiol; and anhydrides of sugar alcohols such as sorbifan. A class of polyhydroxy fatty acid esters suitable for use in the present invention comprises certain sorbifan esters, preferably sorbitan esters of saturated fatty acids of 16 to 22 carbon atoms. Due to the manner in which they are 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 tri-ester versions of these sorbitan esters, for example, mono, di, and sorbitan, mono, di, and triamine diols, sorbitan, mono, di and tribehenazo sorbitan, as well as mono, di and tri-esters of mixed tallow fatty acid sorbitan. Mixtures of different sorbitan esters can also be used, such as sorbifan palmiylates with sorbitan stearates. Preferred sorbitan esters are the 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. Of 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. You will hear classes of polyhydroxy fatty acid ester suitable for use in the present invention comprising glyceryl monoesters, preferably glyceryl monoesters of saturated fatty acids of 16 to 22 carbon atoms such as glyceryl monoeslearate, glyceryl monopalmitate, and glyceryl behenafo. Again, as with sorbitan esters, glyceryl monoester mixtures will typically contain some di and triéser. However, said mixtures should 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 sucrose fatty acid esters, 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: Or R1 R '-N- wherein R1 is H, hydrocarbyl of 1 to 4 carbon atoms, 2-hydroxiefile, 2-hydroxypropyl, meloxyethyl, 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 (ie, 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) ". , - CH2OH, -CH2OH-CH2- (CHOH) 2 (CHOR3) (CHOH-CH2OH, wherein n is an integer from 3 to 5, R3 is H or a cyclic or aliphatic monosaccharide, glycyls are very preferred, where n is 4, particularly -CH 2 - (CHOH) 4-CH 2 OH In the above formula, R 1 may be, for example, methyl, ethyl, propyl, isopropyl, butyl, 2-hydroxyethyl, methoxypropyl or 2-hydroxypropyl; R2 may be selected to provide, for example, cocamides, stearamides, oleamides, lauramides, myristamides, capricamides, palmitamides, seboamides, etc. The Z portion may be 1-deoxyglucitol, 2-deoxyfuctityl, 1-deoxyxallipyl, 1-deoxymaltytyl, - deoxygalactyl, 1-deoxyanityl, 1-deoxy-thiotriotityl, etc. The highly preferred polyhydroxy fatty acid amides have the formula: wherein R is methyl or methoxypropyl; R2 is a straight chain alkyl or alkenyl group of 11 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 CH 3 (CH 2) 17 (OCH 2 CH 2) n OH, where n has an average value of 2), sorbitan tristearate, sosorbide laurate , and glyceryl monostearate. The emulsifier may be included in an amount sufficient to solubilize the immobilizing agent in the emollient, so that a homogeneously 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 S. P. 434 from Strahl and Pitsch Inc. of West Babylon, N. Y, 11704. 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 immobilization agent involved, if there are some, the other components in the composition, if an emulsifier is required to solubilize the immobilization 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 may be used, provided they are applied so that the fluid handling properties of the topsheet 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 the exudates from the body will flow out of the topsheet with the composition instead of being extruded through the topsheet and absorbed by the absorbent core. When a hydrophilic composition is desired, depending on the parficular components used in the composition, a hydrophilic tensioactive agent (or a mixture of hydrophilic lens active agents) may or may not be required to improve the wettability. For example, some immobilization agents, such as N-cocoyl-N-meioxypropyl glucamide, have HLB values of at least about 7 and are sufficiently wettable without the addition of a hydrophilic surfactant. Other immobilization agents such as fatty alcohols of 16 to 18 carbon atoms with 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 film. 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 sensitivity of the skin 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 tensioactive agents are nonionic to only be non-irritating to the skin, but also to avoid other undesirable effects on any other structure within the traced article. For example, reductions in tensile strength of the fabric sheet, adhesive bonding strengths, and the like. Suitable non-ionic tensioactive agents can be subsidentally non-migrational after the composition is applied to the arycles and will have LHB values on the scale of approximately 4 to approximately 20, preferably around 7 to 20. To be non-migratory, these non-ionic surfactants will optically yield melting lemperaires greater 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 non-ionic agents should preferably have melting points similar to those of the immobilization agents previously described. Suitable nonionic non-ionic agents 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 US Pat. No. 4,011,389, 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 from 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 esoxylation of 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 ranging 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, Slearefh-2) and Brij 76 (ie, Sieraih-10) being especially preferred. Also, mixtures of cetyl alcohol and ethoxylated stearyl alcohol can be used at an average degree of ethoxylation of about 10 to about 20, such 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. Of the type of suitable surface active agent for use in the composition includes true silicone copolymers such as General Eledric SF 1188 (a copolymer of a polydimethylsiloxane and a polyoxyalkylene ether) and General Electric SF 1228 (a polyether copolymer of silicone). These silicone surfactants can be used in combination with other types of hydrophilic surfactants disclosed herein, as well as the epoxylated alcohols. These silicone phenolic agents have been found to be effective at low concentrations such 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 on the HLB value and the level of immobilization schedule, if any, used. 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 lipously present in emulsions, creams, ointments, lotions, powders, suspensions, etc., of this type, which components include water, viscosity modifiers, perfumes, disinfectant antibacterial actives, antiviral agents, vitamins, pharmaceuticals. , film foamers, deodorants, opacifiers, asfringeníes, 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, mefilaparaben, 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 enhancement agents include alkyl galactomannan, silica, falco, magnesium silica, sorbium, colloidal silicon dioxide, magnesium aluminum silicate, zinc stearate, wood wax alcohol, sorbitan sesquale, cefyl hydroxyethylcellulose and modified celluloses ofras. Suitable solvents include propylene glycol, glycerin, cyclomelicone, polyethylene glycols, hexylene glycol, diol, and multiple hydroxy-based solvents. Suitable vinylamines include A, D-3, E, B-5 and E acetyl.

IX. Trajectories of the Articles with the Skin Care Composition To prepare the absorbent articles of the present invention, the skin care composition comprising the proiease inhibitor is applied so as to last use, at least some portion of the skin. the composition will be transferred from the trapped article to the user's skin. That is, the skin care composition is either applied directly to one or more surfaces of the body, or is applied in alternate or medium locations so that the composition for skin care 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, in order to effect the supply of the composition towards those regions of the body that are more susceptible to faeces, 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 geniiales, user, in the anal regions during use. In addition, the composition can be applied to more regions of the article to supply one or more of the user's hips, abdomen, back, cinura, sides, thighs, etc. Suitable methods include spraying, printing (e.g., flexographic printing), coating (e.g., confaction slot coating, engraving coating), extrusion, or combinations of these application techniques, e.g., spraying the care composition 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 protease inhibitor can also be applied as a solid material through any of a variety of methods, for example, 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 in 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 irradiated article may be unnecessary or desired to transfer the composition sufficient for the desired benefits in the skin. Particularly suitable methods and application will apply the composition primarily to the outer surface of the topsheet of the article. The minimum level of the composition containing the proiease inhibitor that will be applied to the counted surface of the user of the article is an effective ability to provide 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 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 the skin care composition can be applied to other components of the article, where the properties of fluid handling are not impaired (eg, cuffs, band of cinienta, laleral panels, ele). It will also be recognized that for compositions that are relatively hydrophilic, higher addition levels may be used on the topsheet without adversely impacting 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 protease 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 confined, and aulomatically provided as the articles are used. As indicated, the ability to use relatively low levels of the composition for skin care allows the upper lamina of the arumulus to maintain its liquid transfer properties in the liquid discharge region. The skin care composition containing a protease inhibitor 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 desirable to apply the composition non-uniformly to the topsheet, particularly if the composition is hydrophobic by nature. To this respect, portions of the trailed 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 count on the article). With respect to inconsequential dispositions (eg, diapers, incontinence ar- rows for adults), the length of the crotch region corresponds to 40% of the total length of the absorbing ar- lecle (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 "absorbent core" components 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 arycle that has 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 on the crotch point, with a length of 20.3 cm and a width of 10.16 cm. Surprisingly, although the topsheet or other components comprising the proiease-containing composition are non-uniformly frosted (e.g., microscopic or macroscopic regions where no composition is applied), during the use of the article, the composition is transferred to the user even at regions of the skin that correspond to non-trailed 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 skin recount of the user's surface skin. trailed, the friction created during the time between the wearer's skin and the frayed region, the heat generated from the wearer to improve the transference 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 in this, the "percentage of open area" of the upper sheet is determined, (i) by measuring the surface area of the upper sheet covering the crotch region, (i) by measuring the total surface area of the untreated region in this portion of the upper sheet and (iii) dividing the measurement (ii) between the measurement between the measurement (i). As used herein, "untraced" means a region of the topsheet 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%, of about 20%. % to about 80%), from about 25% to about 75%, from about 30% to about 70%, or from about 35% to about 65%. The percentage of 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 hydrophobic properties). hydrophilic relalives). An expert in the field will appreciate that the desired open area portion will be easily determined through routine experimentation.

In general, with compositions that are relatively hydrophobic and that are to be applied so 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 about 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 articles 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 upper sheet. In a preferred embodiment of the present invention, the topsheet of the arycles 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 containing protease 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 that contain 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 incontinence products for adults, these scales can be more alphas. 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 contours of the skin care composition. The composition can be applied to the article at any time during the assembly. For example, the composition can be applied to the disposable absorbent product and to the finished product that 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 arycle. The proiease inhibitor can be added to the composition before or after heating. If heating is added, the temperalure at which the composition is heated is selected so as not to inactivate the protease inhibitor. Alternatively, the protease inhibitor can be added to the preheated composition when it has been cooled to a temperature that does not affect the protease 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 the articles, methods such as contact groove coating, spraying, engraving coating, extrusion 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.

X. Test Methods A. Transfer of Composition for Skin Care and User Protease Skin Inhibitor Summary 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 on the night before the study and not once after completing the study. and. The provider of the care proposed to have babies who do not swim from the night before the study until after completing the study.

Exclusion Criteria a. The baby has been sick 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 Analogous to the skin: Dermaphological tape, cinla TEGADERM No. 1622W available from 3M Healíh Care, St. Paul, MN. Sample container: Glass jar with a closure available from VWR Scienlific, West Chester, PA under 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 the Composition for Skin Care Extraction Solvent: Dichloromethane, available from Sigma-Aldrich of St. Louis, MO, as 27956-3.

Stearyl alcohol: Aldrich 25876-8 1 -Hexadecanol: Aldrich 25874-1 Malraz assortment: 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 of inferno diameter, 0.12 micrometers of film thickness of the fused silica capillary (without substitions). Instrumental data: They must be capable of reproducibly deferring peak areas of interest. System Extraction and Analysis of Protease Inhibitor (Hexamidine) Extraction Solvent: Dichloromethane, available from Sigma-Aldrich of St. Louis, MO, as 27956-3.

Suriido flask: 10 ml Column: Hwelefl Packard Zorbax SB-CN narrow hole of 5 microns, 2.1 x 150 mm, with a Waters Bondapack Cn 10 micron, 3.9 x 20mm backup column.

Instrumental data: Must be able to reproduce in a reproducible manner peak areas of interest. System In Vivo Transfer Method A. Confirm from the subject's care provider that the subject has been bathed for at least 24 hours and that no lotions, powders, efe have been applied to the diaper region of the subject's skin from the bathroom . B. Use surgical gloves, place the subject on the table and remove your diaper. C. Flip the subject over his stomach. D. Remove the release liner from a TEGADERM tape and lightly brush with the J &J baby powder on the adhesive surface (use surgical guans, or similar, during application to prevent cinnamine conlamination). Provide sufficient dust 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 the 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, apply the cinna 700 tape to the left aseníadera using the procedure described above. F. Change the diapers according to the following protocol: 3 hours of 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 default transfer time. Remove the test diaper. If the child has had a bowel movement, the study staff must remove the tape 700 and discard it (the clip is then observed in the test and the data of that item is not included in the analysis). If the sujelo 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 Composition Test samples for Skin Care This method is designed to be used with the preferred skin care composition, the skin care composition of Table 4. One skilled in the art will recognize what adaptations may be necessary to extract and analyze the level of the other skin care compositions. In the beginning: 1) one of the main ingredients of the composition is extracted from the skin analog using an appropriate solvent; 2) then gas chromatographic techniques or other appropriate quantitative analytical techniques are used to determine the level of the main ingredient in the extracta; 3) the amount of the skin care composition is calculated per unit area based on the caníidad of the principal ingredient in the extraction and the area of the tape.

Internal Escandar Solvent / Extraction Prepare a standard inferno / extraction solvent loading 100 ± 2 mg of 1-hexadecanol in a small beaker. Dissolve 1-hexadecanol in dichloromethane and transfer to a 1-liter volumetric flask. Rinse the beaker a further flush with dichloromethane by 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.

Calibration Standard Prepare a standard calibration calibration of known concentration by loading with accuracy (± 0.1 mg) 10 + 1 mg of stearyl alcohol in a 100 ml volumetric marem- ach. Regislate 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 the stearyl alcohol to the infernal standard of 1-hexadecanol for calibration of the instrument.

Preparation and Calibration 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 slot 2 μl. 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 injections of dichloromethane to ensure that a good baseline is obtained and no unusual peak is 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 instructions of the manufacturer of 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.

Mud Analysis Procedure 1) Remove the iapa from the sample jar and add 10 ml of the internal extraction / sizing solvent solution using the surfing malraz. Replace the lid and shake the contents to ensure that the tape 700 is not adhered to the sides of the jar and is also submerged in the solvenle. Repeat this for all the samples. 2) Allow the samples to settle for 16 hours (typically during the night). 3) Agifar 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 esfo 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 should be placed (approximately every 20 samples) 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 standard of 1-hexadecanoi. 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 instrument's relative response factor for stearyl alcohol and the internal standard based on the eslearyl alcohol areas and 1-hexadecanol peaks in the standard calibration chromatogram. Area? Nst Heavy Response Factor (Rf) = X X 10 Weight st Areasa Where Area? Nst GC peak area for inferno scoring Are asa GC peak area for stearyl alcohol Weight? Nst Micrograms of infernal standard used to prepare solvenle of internal / exlraction standard. Weight, Micrograms of the stearyl alcohol used to prepare the calibration standard.

Mud Calculations Calculate the folaleral micrograms of esopharyl alcohol in each sample using the peak areas of the sample chroma- ogram in the following equation: Areasa Weight¡nst Total μg SA = X Rf X Are 3? Nst 100 Where Area, nst Peak GC area for the infernal standard Are asa Peak GC area for stearyl alcohol Weight, nst Micrograms of the internal sizing 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 to extract and analyze the level of other protease inhibitors. In principle: 1) the protease inhibitor is extracted from the skin analog using an appropriate solvency; 2) HPLC techniques or quantitative analytical techniques are then used to determine the level of the inhibitor in the extract; 3) the amount of a prolease 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 3 and diluting to a volume in 100 mL flasks with the mobile phase HPLC solution.

TABLE 3 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 4.

TABLE 4 Chromatographic conditions Flow rate of the mobile phase: 0.25 mL / min. Mobile phase: 10% glacial acetic acid, 17.5% Calculations 1. Standard concentration (mg / mL): S, (mg / mL) = W (mg) / 100 * (Vn / 100) (1) W = hexamidine weight for standard reserve solution Vt = volume of the reserve hexamidine solution 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 quality of hexamidine (HT) 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 = HT * 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 skin analogue.

VII. 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 skin care composition and a protease inhibitor A. Preparation of the composition for skin care.

A skin care composition (composition A) is prepared by mixing together the following components: (i) 99 parts of a molten (i.e., liquid) base composition containing 58 parts of petrolatum (available from Witco Corp., Greenwich , CT as White Protopel); 41 pairs of stearyl alcohol (available from Procter &Gamble Co., Cincinnati, OH as CO1897); and 1 part aloe extract (available from Madis Botanicals, Inc., S. Hackensack, NJ as Veragel Lipoid at Kaydol), with (i) 1 part hexamidine diisetionate (available from Laboratories Serobilogiques, Pulnoy, France as Elestab HP100).

B. Preparation of a treated article by contact slot coating. Composition A 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 arylum in a paired lire 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 11.75 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.

C. Testing a treated article for the enzyme inhibition property This example describes a method for testing a diaper for the protease inhibitory activity. It is not intended that it be limited, since other parts of other absorbent articles may be sampled and other dissimilar methods may be used for solveni extraction and other subsystem and similar systems that may be used for the test. Ten random 3A inch punch holes are made in the core area of the absorbent article treated with composition A, as described in Section B above, and in a control article that contains no inhibitor. Each of the punched areas is then tested by the inhibition activity of ipsin as follows: The top sheet is removed from the punched section and placed in a 1.5 mL centrifugal flask. The sample is soaked overnight in 0.75 mL of water. An aliquot (0.125 mL) of the supernatant liquid is removed and added to a cube containing 0.025 mL of 160 nM human pancreatic trypsin in TRIS-HC1 containing 20 mM CaCl2, pH 8.2, and incubated for 10 min. At 25 ° C. . The Cbz-arginine-nitroanilidine subscrete (0.025 mL of a 4 mM solution) is added to each cuvette and the test and control samples are incubated for 5 minutes. The change in absorbance at 405 nm for each sample is then moniforeated for 10 minutes. The test results illustrated in Table 5 indicate that the absorbent article containing the inhibitor causes a reduction in measured trypsin activity (related to a control article which is identical except that it does not contain inhibitor) and is an article of the present invention.

TABLE 5 Example 2 Method to improve the health of the skin 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 routine routine of the user, (the typical patterns of change consist of changes every one to five hours during the day and the application of a new article before going to sleep). There is no intervention by the user, in the form of manual application of any type of skin protector or moisture repellent or diaper rash treatment products, which occur 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 a rash through a light diaper and erythema for a period of at least about 5 days using the diaper of Example 1 during the night when he sleeps 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 or products for the trafamienío of the diaper rash, which occur 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 HEALTH OF THE SKIN A baby weighing 25 lbs. Who does not exhibit a rash from a diaper or erythema is diagnosed with otilis media and is of course prescribed sysalmic aniolytics. Based on the experience with conventional diapers (not irritated), 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 amphibiotic administration period. There is no intervention by the caregiver, in the form of the manual application of skin props or replenish the skin with moisture or products for the travail of the diaper rash, during this period. At the time of administration of the antibiotic, the subject did not exhibit erythema or rash per diaper.

Disclosures of all patents, patent applications (and any of the patents that are issued thereon, as well as any of the published published foreign patent applications), and publications mentioned in 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 may 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 (20)

1. An absorbent article, at least one of which comprises a proiease inhibitor that has an IC 50 of 30 μM, or less, as measured by a purified Proiease Mass.

2. The arycle according to claim 1, characterized in that the IC50 is from 0.00001 μM to 30 μM, preferably from 0.0001 μM to 20 μM, most preferably from 0.001 μM to 10 μM.

3. An absorbent article, at least a part of which comprises a protease inhibitor having an IC50 of 90 μM or less, as measured by a specific fecal proiease method.

4. The article according to claim 3, characterized in that the IC50 is from 0.00001 μM to 90 μM, preferably from 0.0001 μM to 30 μM, more preferably from 0.001 μM to 10 μM.

5. An absorbent article, at least a part of which comprises a protease inhibitor characterized in that the protease inhibitor has an IC50 of 500 μM or less, as measured by a general method of faecal protease.

6. The article according to claim 5, characterized in that the IC50 is not higher than 500 μM, preferably not higher than 300 μM, more preferably not higher than 100 μM.

7. The article according to any of claims 1 to 6, characterized in that the protease inhibitor is selected from the group consisting of a serine protease inhibitor, a metalloprotease inhibitor, a cysteine protease inhibitor, an inhibitor of aspartyl protease, and mixtures thereof.

The article according to any of claims 1 to 7, characterized in that the protease inhibitor is selected from the group consisting of soy bean trypsin inhibitor; inhibitor of lime seed protease; corn protease inhibitor; inhibitor Bowman Birk, human pancreatic trypsin inhibitor; inhibitor of bovine pancreatic basic trypsin; white egg trypsin inhibitor; ovomucosae of white egg that contain ovoinhibitors; Chymostatin; Aprotinin; leupeptin and its analogues; bestatin and its analogues; amastatin and its analogues; antipain; antithrombin III; hirudin; cystatin; E-64 and its analogues; alpha2-macroglobulin; alfaT-antitripsin; pepstatin and its analogues; apstain; (2R) -2-mercaptomethyl-4-mephylpentanoyl-b- (2-naphthyl) -Ala-Ala amide; (2R) -2-mercaptomethyl-4-methylpentanoyl-Phe-Ala amide; N-acetyl-Leu-Leu-melioninal; N-acetyl-Leu-Leu-norleucinal; p-aminobenzoyl-Gly-Pro-D-Leu-D-Ala hydroxamic acid; 2 (R) - [N- (4-methoxyphenylsulfonyl) -N- (3-pyridylmethyl) amino] -3-mephylbufano-hydroxamic acid; hexamidine and its salts; pentamidine and its salts; benzamidine and its salts and derivatives; p-aminobenzamidine and its salts and derivatives; guanidinobenzoic acid and its salts and derivatives; and mixtures thereof.

9. The article according to claim 5 or 6, wherein the proiease inhibitor is 4- (2-amino-eyl) -benzenesulfonyl fluoride hydrochloride.

10. The article according to any of claims 1 to 9, characterized in that the article comprises from 0.0001% to 30%, by weight, of the protease inhibitor, preferably from 0.0001% to 10%, by weight, of the protease inhibitor. .

11. The article according to any of claims 1 to 10, an extract of at least a portion of which produces at least 10% reduction in the hydrolysis of the substrate by a protease in the Test Method of the absorbent article.

The article according to any of claims 1 to 11, further comprising a delivery system for containing the protease inhibitor and supplying the inhibitor to at least a portion of the skin of a user of the article.

13. The arycle according to claim 12, characterized in that the delivery system is a skin care composition characterized in that the skin care composition comprises 0.01% to 50%, by weight, of the protease inhibitor. , characterized in that at least one part of the skin care composition is transferred from the article to the skin of a user during the use of the article.

14. The arycle according to claim 12 or 13, characterized in that the composition for skin care comprises 0.05% to 25% > , by weight, of the protease inhibitor, preferably from 0.1% to 10%, by weight, of the prolease inhibitor.

15. The arycle according to any of claims 1 to 14, further comprising a surface that is in contact with the user, characterized in that at least a portion of the contact surface with the user comprises the composition for the care of the user. skin containing the protease inhibitor; preferably the contact surface with the user is the top sheet.

16. An absorbent article, an extract of at least a part of which produces at least a 10% reduction, preferably at least 20% > of reduction, more preferably from 50 to 90% reduction, in the hydrolysis of the substrate by a protease in the test method of the test article.

17. An absorbent article containing a substance selected from the group consisting of soy bean trypsin inhibitor; inhibitor of lime seed protease; corn protease inhibitor; inhibitor Bowman Birk, inhibitor of human pancreatic syrinx; inhibitor of bovine pancreatic basic trypsin; inhibitor of white egg syrup; ovomucosae of white egg that contain ovoinhibitors; chemoslafin; Aprotinin; leupepfina and its analogues; bestalin and its analogues; Amaslafina and its analogues; anipaya; aníiírombina lll; hirudin; cystatin; E-64 and its analogues; alpha2-macroglobulin; alpha-antitrypsin; pepstatin and its analogues; apstatin; (2R) -2-mercaptomethyl-4-methylpentanoyl-b- (2-naphthyl) -Ala-Ala amide; (2R) -2-mercaptomethyl-4-methylpentanoyl-Phe-Ala amide; N-acetyl-Leu-Leu-methioninal; N-acetyl-Leu-Leu-norleucinal; p-aminobenzoyl-Gly-Pro-D-Leu-o-Ala hydroxamic acid; 2 (R) - [N- (4-Methioxyphenylsulfonyl) - N - (3-pyridylmethyl) amino] -3-meitylbutanohydroxamic acid; 4- (2-amino-yl) -benzenesulfonyl fluoride hydrochloride; hexamidine and its salts; pentamidine and its salts; benzamidine and its salts and derivatives; p-aminobenzamidine and its salts and derivatives; guanidinobenzoic acid and its salts and derivatives; TLCK, TPCK, franexamic acid and mixtures thereof.

18. The article according to claim 17, characterized in that the substance is selected from the soybean trypsin inhibitor, aprotonin, hexamidine, p-aminobenzamidine, leupeptin, pepstaphin A, chymoslaline, guanidinobenzoic acid derivatives, and mixtures thereof. the same.

19. A method for reducing the activity of the proteolytic enzyme of a faecal prophase present in an absorbent article, comprising the steps of (i) incorporating a protease inhibitor into at least one part of an absorbable arycle in contact with the fecal eses.; and (i) applying the article to a user in such a way that the protease inhibitor is in contact with the fecal protease.

20. A method for reducing the activity of the proteolytic enzyme of faecal proteases on a part of the skin in contact with an absorbent article, comprising the steps of (i) releasably incorporating a protease inhibitor into a delivery system within the absorbent article characterized in that the delivery system is capable of supplying the inhibitor to at least a portion of the skin of a user of the article, and (ii) applying the absorbent article to the wearer's skin.