CZ20003301A3 - Disposable absorption article containing dermatological component with enzyme inhibitor - Google Patents

Abstract

The present invention provides an absorbent article having at least one the part contains a dermatological component with an enzyme inhibitor, which is at least partially transferred from the device to the user's skin in normal contact, movement of the user and / or body heat. The enzyme inhibitor is transferred on the skin with the dermatological component and is available on skin / urine and skin / faeces interfaces, where they inhibit enzymatic activity on the skin and reduces or prevents the formation inflammation. Re-applying similarly modified resources the user's skin provides the available source from which he can an enzyme inhibitor smoothly migrating to the skin and providing it proactive protection against harmful enzymes in treatment and / or prevention of diaper dermatitis.

Description

A disposable absorbent composition comprising a dermatological component with an enzyme inhibitor

Technical field

The invention relates to absorbent articles such as diapers, training pants, incontinence pads, feminine hygiene articles and the like, which comprise a dermatological component containing an enzyme inhibitor, particularly on a surface in contact with the user. During normal wear of the composition, the enzyme inhibitor is transferred with the dermatological component to at least a portion of the skin of the user where it can inactivate the fecal enzymes and reduce the redness and inflammation that may result after prolonged exposure of the skin to body products.

BACKGROUND OF THE INVENTION

A diaper rash is a common form of irritation and inflammation in those parts of the baby's body that are commonly covered by a diaper. This condition is also called diaper dermatitis. Although this condition is certainly most common in children, it does not occur only in children. Any individual suffering from incontinence to the extent that it requires the use of absorbent articles may develop the disease. Susceptible individuals include newborns, old people, severely ill or non-ambulatory individuals. 21 C.F.R. 333 503 defines a diaper rash as "an inflammatory skin disease in the diaper region (dyke, buttocks, lower abdomen and inner thighs) caused by one or more of the following factors: moisture, occlusion, abrasion, sustained contact with urine or faeces or both, or mechanical or chemical • 9 · 9 · 9 · 9 · 9 · 9 · 9 · 9 · 9 9 9 9 9

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9999 9999 99 99 irritation. ”As a general rule, doctors consider a diaper rash or dermatitis to be in its lightest stage of contact irritation due to dermatitis due to extensive skin contact with urine or faeces or both. Among the most commonly mentioned factors related to diaper rash are ammonia, stool enzymes, bacteria, bacterial products, urine pH and Candida albicans.

Many types of disposable absorbent articles are available, such as diapers, training pants, incontinence articles, sanitary napkins and the like, which have a high absorption capacity for urine and other body secretions. Disposable articles of this type typically comprise some type of liquid pervious topsheet, absorbent core and liquid impervious backsheet. Although these types of absorbent structures can be highly effective in absorbing fluids, they cannot absorb stool. Typically, the stool is trapped between the outer surface of the liquid-permeable topsheet and the skin of the wearer, most of which will adhere to the wearer's skin. Thus, the skin is exposed to the stool, often for a long time, and is sensitive to the irritating substances present in the stool that create or contribute to the formation of a diaper rash.

Because enzymes are present in plants, soil, bacteria, milk, dairy products and almost all animal tissues, as well as in the digestive juices of the gastrointestinal tract, they are almost always present in the diaper area that has been contaminated with human excretions. Enzymes present in stool include proteolytic enzymes, lipases and other esterases and diesterases, ureases and other enzymes including amylases, elastases, nucleases, etc. Although the relative proportions of different types of enzymes causing skin irritation are unknown, there is evidence that at least proteolytic and lipolytic enzymes in the stool, which are of intestinal and / or pancreatic origin, have a direct effect on the development of skin inflammation in diaper dermatitis.

Studies with inhibitors designed to inhibit the enzymatic activity of different classes of proteases have shown that serine proteases, cysteine proteases, and metalloproteases are very likely to be responsible for the overall proteolytic activity of stool. It is known that serine proteases, particularly trypsin and chymotrypsin, are almost always present in large amounts in the faeces of healthy young children and less, but a detectable amount is present in the faeces of healthy adults. Lipases, including esterases, which hydrolyze triglycerides in the diet are also present in normal faeces and are capable of hydrolyzing triglycerides and other glycerides found on human skin, thereby creating irritating fatty acids and glycerol by-products. When the skin is exposed to enzymes such as lipases and proteases present in body secretions, the skin components that contain proteins and proteins can be damaged, resulting in irritation and inflammation. In addition, breaching the skin barrier allows other urine and stool components, ammonia, bacteria, etc. that would otherwise not be irritating, to penetrate through the damaged skin barrier, causing further irritation and possible infection.

It is known that bile salts are also present in body exudates. Bile salts normally act to form lipid emulsions in the body, thereby ensuring the action of lipases at the lipid / water interface. Bile salts are also active when they are excreted in the faeces and

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9 9 9999999 99 99 other excretions and can act as coenzymes and enhance the activity of lipases that attack lipids in the stratum corneum of the skin that is exposed to body excretions.

The irritant effects of fecal enzymatic activity on the skin are usually potentiated when urine is present and / or when the skin is covered. The formation of ammonium hydroxide by the urinary bacterial urease enzyme results in an increase in pH, e.g. to values of 7.0 and above, in which the activity of proteases and other enzymes, such as lipases present in the faeces, increases. E.g. the optimal pH range for urease is 6.4-6.9, for trypsin 7.8-8.2 and for lipases 7.5-9.5. If the pH exceeds 7.0, free ammonia is released from the urine, which is another irritant toxic compound affecting the skin. Urine itself can also contribute to the formation of a diaper rash by moisturizing the environment. Water, especially water in the form of urine, is particularly effective in reducing the skin barrier, thereby increasing the susceptibility of the skin to irritation by stool enzymes. Since urine and faeces are commonly present in the absorbent at one time, and skin exposure for several hours is not uncommon, suitable conditions and sufficient time are present to produce such interactions and consequent skin damage. Another factor that contributes to enhancing the enzymatic activity of stool is its alkaline pH. For example, it is well known that although the stools of naturally breastfed babies are usually acidic, stools of artificially breastfed babies are generally alkaline with a pH ranging from slightly alkaline (pH 7.2 7.5) to strongly alkaline (pH 8.7 and higher) . Thus, especially artificially breastfed babies are prone to developing diaper dermatitis due to increased enzyme activity in stool due to higher pH.

• · · · · · ·

In view of the effect of alkaline pH on the increased activity of enzymes in the faeces, several attempts have been made to maintain the pH of the skin using pH modifying agents, such as buffering agents or weak acids, in an absorbent or as additives in topically applied dermatological agents. It is believed that effectively maintaining the pH of the skin at its natural low pH (i.e., from 3.0 to 5.5) can counteract the irritant effect of ammonia and reduce the activity of stool enzymes. However, reducing the enzymatic activity of the skin in this manner is quite difficult when the stool is directly on the skin.

Certain anti-enzyme components have been added to topically applied formulations for the treatment and prevention of diaper rash caused by prolonged contact of human skin with body secretions. For example, U.S. Pat. No. 4,556,560 discloses compositions comprising water-soluble lipase inhibitors, preferably metal salts, such as zinc chloride in a barrier vehicle such as polyethylene glycol. When the lipase inhibitor is inserted into the diaper topsheet or absorbent core, it is best if it is in an aqueous or volatile medium such as ethanol to facilitate transmission to the skin after wetting the diaper with urine. U.S. Patent No. 5,091,193 discloses diaper changing skin application compositions containing a chelating agent such as folic acid, ethylenediaminetetraacetic acid (EDTA) and the like, which limit the availability of metals that urease and proteases require as cofactors for activity. The composition may further comprise a lipase substrate, such as a fatty alcohol ester or added antienzyme, saturated or unsaturated, linear or branched, zinc salt of a C 2 -C 22 fatty acid. Or an aminoacyl acid such as propionylcysteine, propionylhydroxyproline or caproylcysteine.

While preparations for treating diaper dermatitis containing certain inhibitors of enzyme activity have been described, the possibility of treating or preventing diaper dermatitis in which dermatological preparations containing enzyme inhibitors are contained in absorbent compositions with automatic transmission to the skin of the wearer during normal wear of the treated composition or the use, preferably repeatedly, automatically maintains sufficient levels of enzyme inhibitors in a selected area of the user's skin, thereby providing protection against faecal penetration and enzyme activity. In addition, absorbent compositions having a dermatological component have not previously been disclosed comprising, on a surface contacting a user, immobilized enzyme inhibitors (at room temperature), especially in the topsheet from which the dermatological component and enzyme inhibitor are transferred to the user's skin upon heating the dermatological component to body temperature.

SUMMARY OF THE INVENTION

The invention provides an absorbent composition, a portion of which comprises a dermatological component comprising an enzyme inhibitor, and wherein the dermatological component including the enzyme inhibitor is at least partially transferred from the composition to the skin of the user of the composition during normal contact, user movement and / or body heat. The enzyme inhibitor is any substance which reduces the activity of one or more enzymes, preferably at about the IC _5, as determined below, is not more than 500 micromolar (μΜ). Suitable enzyme inhibitors for use in the composition are protease inhibitors, lipase inhibitors, elastase inhibitors, urease inhibitors, amylase inhibitors and the like, as well as bile salt inactivators that would otherwise act as lipase cofactors. The dermatological component typically contains from about 0.001% to about 50% of the enzyme inhibitor, more preferably from about 0.01% to about 25%, more preferably from about 0.1% to about 10%, and most preferably from about 0.1% to about 5%.

The nature of the dermatological component containing the enzyme inhibitor may vary considerably, but in one proposed embodiment it is solid or semi-solid at room temperature (20 ° C). In the preferred embodiment, the dermatological component still contains about 5% to 95% of a plasticizer that is plastic or liquid at 20 ° C. Further, the dermatological component should contain about 5% to 95% of a substance capable of immobilizing the emollient in the composition and having a melting point of at least about 35 ° C. The part of the absorbent composition comprising the dermatological component with the enzyme inhibitor should preferably be a surface in contact with the user, preferably a liquid-permeable topsheet.

Since the enzyme inhibitor is transmitted to the skin with the dermatological component, it is therefore available at the skin / urine and skin / stool interfaces where it inhibits enzymatic activity on the skin and reduces or prevents the development of inflammation. Reusing similarly formulated compositions offers an available source from which enzyme inhibitors pass smoothly onto the skin where they accumulate and provide proactive protection against harmful enzymes in the treatment and / or prevention of diaper dermatitis.

Overview of Figures in the Drawings φ φ φ φ φ φ • φ

Φ Φ 1 • ·· <

Figure 1 is a schematic illustration of an absorbent article in the form of a diaper according to the present invention.

Figure 2 is a side view showing the location of the skin analog used in the dermatological component transfer assay and / or the protease inhibitor transfer assay.

Figure 3 is a plan view showing the location of the skin analog used in the dermatological component transfer assay and / or the protease inhibitor transfer assay.

DETAILED DESCRIPTION OF THE INVENTION

I. Definitions

The term "comprising" as used herein means that various components, components or steps may be used together in the practice of the present invention. Accordingly, the term 'including' also includes the narrower terms 'composed primarily of' and 'composed of'.

The term &quot; treated composition &quot; as used herein means that the absorbent article has a dermatological component on its surface or is at least capable of moving towards the user-contacting surface.

The term "surface in contact with the user" of the absorbent article is one or more surfaces of any component of the device that touches the user during wear. The user's contact surfaces include, but are not limited to, portions of the topsheet, the limb, and the limb.

cuffs, waistband, side stripes, lanyards, etc. that touch the wearer during wear.

The term "dermatological component" as used herein means any component containing an enzyme inhibitor that is transferred to the skin of the user of the formulated composition due to normal contact, movement of the user and / or body heat when worn normally.

The term "IC ₅₀ " means the inhibitory concentration (eg micromolar concentration, μΜ) of a substance (inhibitor) that reduces the level of enzyme cleavage by 50% when measuring enzyme activity by standard in vitro assays. below. IC ₅₀ is calculated using the equation IC ₅₀ o = (I) / ((v / v) -1), where (I) is the inhibitory concentration tested, v is the substrate cleavage level in the absence of inhibitor and Vj is the substrate cleavage level in the presence of inhibitor . As described below, the IC50 of an enzyme inhibitor can be measured using a purified enzyme method or a fecal enzyme method.

Other terms are defined herein when they are first used.

All percentages, coefficients and ratios used herein are by weight unless otherwise specified.

II. Enzyme inhibitors

Enzyme activity inhibitors are well known and are classified as competitive inhibitors (which compete with the substrate for binding to the active site of the enzyme) and non-competitive inhibitors (which inactivate the enzyme by binding to a site other than the active site). Many enzymes, such as metalloproteases, are inactivated by substances that bind to the enzyme metal group. Chelating agents are potent inhibitors of other enzymes that require the presence of metal ions such as calcium, cobalt, copper, magnesium, manganese, sodium, potassium, or zinc for activation. Since enzymes are proteins, antibodies against specific enzymes are also effective as enzyme inhibitors.

The enzyme inhibitors suitable for the absorbent compositions described herein typically have an IC ₅₀ value of up to about 500 µΜ, preferably up to about 250 µΜ, and most preferably up to about 100 µΜ. It will be appreciated that certain inhibitors (eg, EDTA) will have higher IC 50 values, but will still be useful in the absorbent compositions described herein. Materials for which the molecular weight cannot be determined will reduce the enzyme activity by at least 50% at a concentration not exceeding about 5% by weight in the dermatological component. Representative methods of measuring enzyme inhibitory activity are mentioned below.

Any type of enzyme inhibitor may be utilized in a dermatological component transferable to the skin of a user of the absorbent composition of the present invention, including any naturally occurring inhibitor of vegetable, microbial and / or animal origin (including human) and synthetically prepared chemical inhibitors. Enzyme inhibitors may be hydrophilic or hydrophobic in nature and may therefore be soluble in water or a hydrophobic vehicle. Enzyme inhibitors are usually present in the dermatological component at a concentration of from about 0.001% to about 50% by weight, preferably from about 0.01% to about 25%, more preferably from about 0.1% to about 10%, and most preferably from about 0% to about 10%. , 1% to 5%. Because of the variety of inhibitors

For the enzymes used in the invention, the effective concentration of each inhibitor must be determined separately, as is conventional in the art.

Enzyme inhibitors may be used alone or as a mixture of enzyme inhibitors, such as a "cocktail" of inhibitors, in a single absorbent composition. In addition, various enzyme inhibitors may be used in the dermatological component at different locations in a single absorbent article.

Due to the variety of enzymes present in stool and other body secretions, substances that inhibit certain classes of enzymes (eg, proteases) can also be expected to inhibit enzymes that break down substrates other than those (eg, proteins and peptides). Thus, inhibitors that inhibit proteases can also inhibit lipases and other esterases, amylases and / or ureases, and vice versa.

Preferably, inhibitors of the enzymes and / or coenzymes most commonly found in faeces or other body secretions are added to the dermatological component of the inventive absorbent article. Most preferred enzyme inhibitors are proteolytic enzyme inhibitors such as trypsin, chymotrypsin, aminopeptidase and elastase; lipases; bile salts; amylases; and / or urease.

Examples of suitable protease inhibitors for use in the present invention which are believed to inhibit the type of protease shown in parentheses are, but are not limited to, a soybean trypsin inhibitor and other trypsin inhibitors of plant origin, such as a limestone protease inhibitor ( Phaseolus limensis)

A protease inhibitor from maize and the like; Bowman-Birk inhibitor (serine and trypsin-like protease inhibitor); a pancreatic trypsin inhibitor such as a bovine pancreatic basic trypsin inhibitor and other pancreatic trypsin inhibitors obtained from animals; egg white trypsin inhibitor (serine and trypsin-like protease inhibitor); ovomucoids containing ovoinhibitors, such as chicken or turkey egg white (trypsin and chymotrypsin inhibitors); chymostatin (a serine and chymotrypsin-like protease inhibitor); aprotinin (serine protease inhibitor); leupeptin and analogues thereof such as propionyl-leupeptin, Ν-α-t-BOC-deacetylleupeptin (a serine and cysteine protease inhibitor); bestatin and analogs thereof such as epibestatin and nitrobestatin (aminopeptidase and metalloprotease inhibitors); amastatin and analogs thereof, such as epiamastatin (aminopeptidase inhibitor); antipain (trypsin inhibitor); antithrombin III (serine protease inhibitor); hirudin (a thrombin-like serine protease inhibitor); cystatin (a cysteine protease inhibitor of egg white); E-64 (trans-epoxysuccinyl- _L- leucylamido- (4-guanidino) butane) and analogs thereof (cysteine protease inhibitor); and ₂ macroglobulin (universal endoprotease inhibitor); oci-antitrypsin (trypsin inhibitor); pepstatin and analogs thereof, such as acetylpepstatin, pepstatin A, Nle-Sta-Ala-Sta (an aspartyl protease inhibitor); apstatin (aminopeptidase P inhibitor); (2R) -2-mercaptomethyl-4-methylpentanoyl-b- (2-naphthyl) -Ala-Ala amide (matrix metalloprotease inhibitor); (2R) -2-mercaptomethyl-4-methylpentanoyl-Phe-Ala amide (matrix metalloprotease inhibitor); N-acetylLeu-Leu-methioninal (calpain inhibitor); N-acetyl-Leu-Leunorleucinal (calpain inhibitor); p-aminobenzoyl-Gly-Pro- _D -Leu-DAla hydroxamic acid (matrix metalloprotease inhibitor); 2 (R) (N- (4-Methoxyphenylsulfonyl) -N- (3-pyridylmethyl) amino) -3-methylbutano-hydroxamic acid (metalloprotease inhibitor); L1-chloro-3- (4-tosylamido) -7-amino-2-heptanone-HCl (TLCK), L-1-chloro-3- (4-tosylamido) -4-phenyl-2-butanone (TPCK), tranexamic acid, glycerrhizinic acid acid, 18-p-glycerretinic acid and the corresponding salts, stearylglycerretinate, colloidal oat extracts, elhibin, zinc salts, iodoacetate, phenylmethylsulfonylfluoride, phosphoramidone, 4- (2-aminoethyl) -benzenesulfonylfluoride HCl, 3,4-dichloroisocoumarin, quercetin and the like and the like. .

Chelating agents have been found to be useful as protease and urease inhibitors at concentrations from 0.1% to about 2%. Examples of chelating agents are phytic acid, nitrilotriacetic acid, EDTA, diethylenetriaminopentaacetic acid, hydroxyethylethylenediaminetriacetic acid and their respective salts, described in U.S. Pat. No. 5,091,393 filed by Enjolras on Feb. 25, 1992, which is incorporated herein by reference.

For use in the absorbent compositions of the present invention, we prefer protease inhibitors that have an inhibitory effect that is not limited to one class of proteases. Such compounds include, but are not limited to, hexamidine and its salts, pentamidine and its salts, benzamidine and its salts and derivatives, p-aminobenzamidine and its salts and derivatives, and guanidinobenzoic acid and its salts and derivatives such as those described in U.S. Pat. No. 5,376,655 to Imaki et al. On December 27, 1994, which is incorporated herein by reference. Other protease inhibitors proposed are the guanidinobenzoic acid polymer derivatives described in U.S. Patent Application Serial No. 09 / 041,196 (T. L. Underiner et al.), Which were filed concurrently with this application.

* »> · · ·> · ·>>>>>>>>>>>>>>>>>>>>> · · · · · ····

For use with the present invention, we prefer the following protease inhibitors: soybean trypsin inhibitor, aprotinin, hexamidine (eg hexamidine diisothionate), p-aminobenzamidine, leupeptin, pepstatin A, chymostatin and polymer derivatives of guanidinobenzoic acid (described in the present application US 09/041 196 , which is incorporated herein by reference). The most suitable protease inhibitors are soybean trypsin inhibitor, hexamidine, p-aminobenzamidine and the preceding polymeric guanidinobenzoic acid derivatives.

It is known that urease is inhibited in the presence of trace amounts of heavy metal ions such as silver, copper and the like. Thus, trace amounts (as little as 0.001% or less) of salts of these metals are good inhibitors of urease. Other suitable urease inhibitors include, but are not limited to, acetylhydroxamic acid and derivatives thereof, such as cinamoylhydroxyamic acid and other alkylhydroxamic acids, respective salts and derivatives; phosphoramidate and its derivatives. Such compounds are competitive urease inhibitors at a concentration of about 2 micromolar (μΜ). Chelating agents have been found to be good inhibitors of both proteases and ureases at a concentration of from 0.1% to about 2%. Examples of chelating agents are phytic acid, nitrilotriacetic acid, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminopentaacetic acid, hydroxyethylethylenediaminetriacetic acid, and the corresponding salts thereof, described in U.S. Patent 5,091,193, which is incorporated herein by reference. Other urease inhibiting compounds are disclosed in U.S. Patent 3,952,862 to Kraskin, which is incorporated herein by reference and includes amino acid compounds such as hydroxyalkylamino acids, sulfhydrylamino acids, aminosulfonic acids, compounds.

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9

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Amino acid amino acids such as methoxyethyl imino diacetic acid, ethylene bis- (oxypropylaminodioacetic acid), ethylene bis- (oxyethyl imino diacetic acid), aminomethylphosphonic acid (Ν, di-diacetic acid) and the like and aminopolycarboxylic acid compounds, including acids and salts of diethylenetriaminopentaacetic acid (DTPA), N-hydroxyethylenediaminotriacetic acid (HEDTA) and the like.

Other suitable urease inhibitors are described in U.S. Patent 5,409,903 to Polak et al. On April 25, 1995, which is incorporated herein by reference. This patent discloses urease inhibitors such as divalent magnesium phosphate, dialdehyde polysaccharides and zeolite, used alone, in combination with or with calcium, calcium acetate, calcium chloride, calcium gluconate and calcium lactate or the like with magnesium, magnesium chloride and magnesium citrate compounds .

Suitable lipase inhibitors are, inter alia, water-soluble metal salts such as cadmium, cobalt, copper, iron, molybdenum, silver, lanthanum, tin and zinc. Examples of lipase inhibiting compounds are described in U.S. Patent 4,556,560, incorporated herein by reference, and include zinc chloride, zinc acetate, zinc nitrate trihydrate, zinc nitrate hexahydrate, ferrous chloride, ferrous chloride tetrahydrate, ferric chloride, ferric chloride monohydrate, chloride ferric hexahydrate, ferric lactate, ferric lactate, ferric malate, ferrous nitrate, ferric nitrate hexahydrate, ferric nitrate 9H ₂ 0, ferrous sulphate and its hydrates, ferric sulphate and its hydrates, copper sulphate pentahydrate, tin chloride, cobalt chloride and lanthanum chloride, zinc salts of saturated and unsaturated monocarboxylic acids of 6 to 12 carbons, a block of propylene oxide and ethylene oxide copolymers (eg marketed under the name Pluronic® and Tetronic® of BASF Corp.), glycerol triesters of fatty acids of 2 to 20 carbons such as e.g., triacetin and the like Lipase receptors are disclosed in US 5,091,193, incorporated herein by reference, and include fatty alcohol esters such as saturated or unsaturated, linear or branched alkyl of 10 to 20 carbon, lactate or propionate, saturated or unsaturated, linear or branched zinc salts of 2 to 22 carbons, such as those formed with propionic acid, isobutyric acid, caproic acid, undecylenic acid and the like, zinc salts of aminoacylated acids such as propionylcysteine, propionylhydroxyproline or caproylcysteine and the like have been found. such lipase inhibitors are from 0.01% to about 10%.

Other suitable lipase inhibitors described in our patent application EP97 / 120 699 (G. Palumbo et al.) Are specific esters which act as a replacement substrate for faecal lipases and thus are competitive lipase inhibitors. The formulas of these esters are:

where R 1 and each R ₂ are independently C 2 -C 22 acyl groups or alkyl, alkenyl, arylalkyl, hydroxyalkyl groups · 9 9 9 9 9 99

9 9 9 9 9 9 9 9 9

9 9 9 9 9 9 9 9 9 ♦ · ···· · ······ i / 9 9 · · · · · · ··· ··· ····· from 1 to 24 carbon atoms or hydrogen, whereby at least one R or R _{2 is} such an acyl group, R _3, R _4, R _5, R _6, R 7, Rs and R ₉ are either alkyl, alkenyl, arylalkyl, hydroxyalkyl, alkoxy from 1 to 24 carbons, hydroxy or hydrogen; R 10 and R 11 are either alkyl, alkenyl, arylalkyl, hydroxyalkyl, alkoxy groups of 2 to 24 carbons, hydroxy groups or hydrogen; A and B may be C1-C6 linear or branched alkylene, alkenylene, alkoxylene, hydroxyalkylene groups; x values range from 0 to 15; the values of y are either 0 or 1, provided that when x = 2 and y = 0, at least one R 2 is an alkyl, alkenyl, aryalkyl, hydroxy alkyl of 1 to 24 carbons, or a hydrogen atom.

Other examples of lipase inhibitors are described in U.S. Patent 5,643,873, which is incorporated herein by reference, and includes: (2S, 3S, 5S) -5 ((S) -2-formamido-4-methyl-valeryloxy) -2 -hexyl-3-hydroxy-hexadecanoic acid 1,3 lactone, also known as tetrahydrolipstatin; (2S, 3S, 5S, 7Z, 10Z) -5 - ((S) -2-Formamido-4-methyl-valeryloxy) -2-hexyl-3-hydroxy-7,10-hexadecadiene 1,3 acid lactone, known also as lipstatin; 1- (trans-4-isobutylcyclohexyl) -2- (phenylsulfonyloxy) ethanone, also known as FL-386; 4-Methylpiperidine-1-carboxylic acid 4-phenoxyphenyl ester, also referred to as WAY121898; N- (3-chloro-4- (trifluoromethyl) phenyl) -N '- (3- (trifluoromethyl) phenyl) urea, also known as BAY-N-3176; N-formyl-Lvaline- (S) -1 - (((2S, 3S) -3-hexyl-4-oxo-2-oxetanyl) methyl) hexyl ester, also known as valillactone; (2S, 3S, 5S, 7Z, 10Z) -5 - ((S) -2-acetamido-3-carbamoylpropionyloxy) -2-hexyl-3-hydroxy-7,10-hexadecadiene lactone, also known as esterastin; (3S, 4S) -4 - ((1S, 5R, 7S, 8R, 9R, E) 8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3 -undecenyl) -3-methyl -2-oxetanone, also known as ebelactone A; (3S, 4S) -3-ethyl-4 ((1S, 5R, 7S, 8R, 9R, E) -8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl) -2-oxetanone, also known as ebelactone B; and 1,6-di (O (carbamoyl) cyclohexanone oxime) hexane, also known as RHC 80267.

Examples of bile salt inhibitors that are coenzymes of lipolytic enzymes and are suitable lipase inhibitors in said absorbent composition include, inter alia, the cationic compounds described in patent application EP 97 / 120,700 filed Nov. 26, 1997 by reference. The formulas name G. Palumbo et al., Which is included herein are: ³

Ra - N - r,

RM (I) or

R.

^R 1

4r ₅ ~ n —r ^ • R «

ΜΓ

Rtm or amphoteric compound of preferably acidic origin having the formula at its isoelectric point:

íl M

R -N ^{+ R} io -BH -A (III) for the preparation of ingredients for the treatment, prevention or suppression of lipolytic dermatitis, wherein R, R2, R3 and R4 are independently C1-C22 alkyl, alkenyl, aryl, arylalkyl, amidoalkyl, ( poly) alkoxy, hydroxyalkyl or acyl groups or two or more R 1, R ₂ , R 3 and R ₄ together form one or more ring structures;

• 9 • 9 9

4 ··

R ₅ , R ₆ and A are independently C 1 -C 22 alkylene, alkenylene, (poly) alkoxylene, hydroxy alkylene, arylalkylene or amidoalkylene groups; R ₇ and R ₈ are independently C 1 -C 4 alkyl, alkenyl, alkoxy or hydroxyl groups or a hydrogen atom; R ₉ and R ₁₀ are independently C 1 -C 22 alkyl, alkenyl, aryl, arylalkyl, amidoalkyl, (poly) alkoxy, hydroxyalkyl or acyl groups or two or more R 1, R ₉ and R ₁₀ together form one or more ring structures; The BH group is a proton donor; x is from 2 to 4; and M 'is the opposite ion.

Another example of a suitable bile salt inhibitor is cholestyramine, described in C. Michael White et al., Entitled "Cholestyramine Ointment to Treat Buttocks Rash and Anal Excoriation in an Infant," The Annals of Pharmacotherapy 30: 954956, Sept. 1996.

P-guanidinobenzoic acid derivatives, especially esters thereof, have been described as esterase inhibitors. Such inhibitors are suitable for the dermatological component of the absorbent composition of the invention and are described in U.S. Patent 5,376,655 filed by Imaki et al. 27 Mar:

12, 1994, which is incorporated herein by reference.

Suitable amylase inhibitors and / or glucosidase amylase inhibitors include those described in U.S. Patent 5,643,874, which is incorporated herein by reference, and includes O-4,6-dideoxy-4 - (((1S (1a, 4a, 5p, 6a) () - 4,5,6-trihydroxy-3- (hydroxymethyl) -2-cyclohexen-1-yl) amino) -? D-glucopyranosyl- (1? 4) O? D-glucopyranosyl- (1-> 4) D-glucose, also known as acarbose; 2 (S), 3 (R), 4 (S), 5 (S) tetrahydroxy-N- (2-hydroxy-1- (hydroxymethyl) ethyl) -5- (hydroxy20) 9) methyl) -1 (S) -cyclo-hexamine, known as voglibose; 1,5-dideoxy-1,5 - ((2-hydroxyethyl) imino) -D-glucitol, also known as miglitol;

1,5-dideoxy-1,5- (2- (4-ethoxycarbonylphenoxy) ethylimino) -Dlucitol, known as emiglitate; 2,6-dideoxy-2,6-imino-7- (β-D-glucopyranosyl) -D-glycero-L-guloheptitol, also known as MDL-25637;

1,5-dideoxy-1,5- (6-deoxy-1-O-methyl-α-D-glucopyranosyl-6-imino) D-glucitol, also known as camiglibose; 1,5,9,11,14-pentahydroxy-3-methyl-8,13-dioxo-5,6,8,13-tetrahydro-benzonaphthacene-2-carboxylic acid, known as pradimicin Q; or also as adiposine; and 1,2dideoxy-2- (2 (S), 3 (S), 4 (R) -trihydroxy-5-hydroxymethyl-5-cyclohexen-1 (S) -amino) -L-glucopyranose, known as salbostatin . Other suitable amylase inhibitors include tendamistat, crops and plant derived substances, particularly wheat, rice, corn, barley and other cereal grains, beans and seaweed.

III. Absorbents

The term "absorbent" is used herein to refer to a product that absorbs and retains body exudates. The term "disposable" is used herein to describe an absorbent article that is not intended to be laundered or otherwise restored or reused. Examples of disposable absorbent articles are feminine hygiene articles such as sanitary towels, sanitary towels and tampons, diapers, incontinence pads and pads, exercise pants and the like.

A typical disposable absorbent composition comprises a top of a liquid pervious layer, a bottom impermeable layer, and an absorbent core positioned between the top and bottom layers. Disposable absorbent articles and components therefor, including

99 99 »

The topsheet, the backsheet, the absorbent core and any of the individual layers of these portions have a body-facing surface and a garment-facing surface. As used herein, the term &quot; body-facing surface &quot; means that the surface of the device or a portion thereof is to be worn towards the wearer's body, while the &quot; garment-facing surface &quot; is on the opposite side and should be worn towards the garment.

The following section generally describes absorbent core, topsheet and backsheet materials that are suitable for disposable absorbent articles. This general description applies to portions of the specific absorbent composition shown in Figure 1 and described below, in addition to the other absorbent compositions generally described herein.

The absorbent core is usually capable of absorbing or retaining fluids (eg, blood, urine and / or other body exudates). The absorbent core is generally compressible, malleable and does not irritate the wearer &apos; s skin. The absorbent core can be manufactured in a variety of sizes and shapes (eg, rectangular, oval, hourglass, "T", dog bone, asymmetric, etc.). In addition, the absorbent core, in addition to the absorbent components, may also comprise any of a wide variety of liquid absorbent materials, such as pulp. Examples of other suitable absorbent materials used for the absorbent core are cellulose wadding; mixed polymers such as coform; chemically stiffened, modified or cross-linked cellulose fibers; synthetic fibers such as crimped polyester fibers, peat, laminated paper, absorbent foams, absorbent sponge materials, superabsorbent polymers including composites, absorbent gel

4 4 4 4 4 4 4 44 • Materials or some similar material, combinations of materials or mixtures thereof.

The configuration and construction of the absorbent core may vary (e.g., the absorbent core may have different straddling zones and / or a profile that is thicker in the center; hydrophilic gradients; absorbent component gradients; superabsorbent gradients or regions of lower average density or lower average base weight, eg receiving regions or may be composed of one or more layers or structures). However, the total absorbent capacity of the absorbent core should correspond to the proposed loading and intended use of the absorbent article. Further, the size and absorbent capacity of the absorbent core must be appropriate for a variety of uses, such as diapers, incontinence pads, sanitary napkins, sanitary napkins, and adapted to a variety of users from infants to adults. The absorbent core may also include other absorbent components that are frequently used in absorbent articles, such as a backfill layer, an absorbent urine hold layer, or an additional topsheet to enhance user comfort.

The topsheet is usually pliable, soft and does not irritate the user's skin. Further, the topsheet is liquid pervious, allowing liquids (e.g., blood and / or urine) to readily pass through it. A suitable topsheet may be made of a variety of materials, eg, wool and non-woven materials (eg, a nonwoven web of fibers), including non-woven materials with apertures; polymers such as porous thermoplastic film, porous plastic film and hydroformed thermoplastic films; porous foams; reticulated foams; crosslinked thermoplastic films and thermoplastic scars. Suitable wool and non-innocent materials are natural fibers (eg, wood or cotton fibers), synthetic fibers (eg, polymer fibers such as polyester, polypropylene or polyethylene fibers), or materials formed from a combination of natural and synthetic fibers. If the topsheet is an innocent material, the material may be treated by a variety of known techniques. The net may be made, for example, by spinning, carding, hot blowing, wetting, wet forming, a combination of the above or the like. The topsheet should contain a dermatological component with an enzyme inhibitor, regardless of whether it is made of wool or non-innocent material; below.

The backsheet is liquid impermeable (e.g., blood and / or urine) and typically comprises a thin plastic layer, although other impermeable flexible materials may also be used. The term "flexible" is used for materials that are compliant and easily change shape according to the shape and curves of the human body. The backsheet prevents exudates absorbed and retained in the absorbent core from wetting the articles in contact with the absorbent article, such as bedsheets, pants, pajamas and underwear. Thus, the backsheet may comprise a wool or non-innocent material, a polymer coating, such as a thermoplastic layer of polyethylene or polypropylene, or composite materials, such as a coated non-innocent material. A suitable backing is a polyethylene film having a thickness of from 0.012 mm to about 0.051 mm. Suitable polyethylene films are manufactured by Clopay Corporation of Cincinnati, Ohio under the designation PI8-1401 and Tredegar Film Products of Terre Haute, Indiana under the designation XP-39385. The backsheet is typically convex and / or matt machined to give the appearance of a fabric. Further, the backsheet should be permeable to vapors from the absorbent core (i.e., the backsheet is breathable) although it is impermeable. The size of the backsheet is determined by the size of the absorbent core and its selected shape.

The backsheet and topsheet are positioned, respectively, adjacent the surface of the absorbent core applied to the garment and body. The absorbent core is typically bonded to the topsheet, the backsheet, or both, by one of the fasteners (not shown in Figure 1) that are commonly used in the art. However, embodiments of the absorbent article can be seen if some or all of the absorbent core is not attached to either the topsheet, the backsheet, or both.

The backsheet and / or topsheet may be affixed to the absorbent core or a continuous adhesive layer, a sample adhesive layer, or a series of individual lines, spirals or adhesive points. Suitable adhesives are manufactured by H.B. Fuller Company in St. Paul in Minnesota under the designation HL-1258 or H-2031. The fasteners preferably form the adhesive fiber web described in U.S. Patent 4,573,986, issued to Minetola et al. Mar. 4, 1986, which is incorporated herein by reference. An example of a bonding method is a network of fibers consisting of a plurality of adhesive lines twisted into a spiral as described in U.S. Patent 3,911,173 filed by Sprague, Jr. et al. Oct. 7, 1975, U.S. Patent No. 4,785,996, filed by Zwieker et al. On Nov. 22, 1978, and U.S. Patent 4,482,666, filed on June 27, 1989 by Werenicz. Each of these patents is incorporated herein by reference. Thermal joints, pressure joints, ultrasonic joints may also be used as fasteners.

9 9 9 · · 9 9 9 9

9999 99 99 joints, dynamic mechanical joints or other suitable fasteners or combinations thereof known in the art.

The proposed disposable absorbent article is a diaper that comprises at least one portion of an enzyme inhibitor, and more preferably the user-contacting surface thereof is treated with a dermatological component containing the enzyme inhibitor. As used herein, the term diaper means an absorbent article which is generally used by children and incontinent persons and which is worn around the lower torso. In other words, the term diaper includes diapers, training pants, adult incontinence, and the like.

Figure 1 is a drawing of a diaper 50 that is shown in an expanded state (i.e., not contracted by elastic portions) and without some portions so that its structure is clearly visible and is rotated with its outer surface toward the viewer. The diaper 50 of Figure 1 is typically comprised of a permeable topsheet 520, an impermeable backsheet 530 associated with the topsheet 520, an absorbent core 540 having a garment facing surface 542, a body facing surface 544, a side edge 546, waist edges 548, and The diaper 50 typically further comprises elastic thigh cuffs 550 and a differently shaped elastic waist portion 560 and generally differently shaped clamping means 570.

The diaper 50 shown in Figure 1 has an outer surface 52, an inner surface 54 that corresponds to a body facing surface opposite the outer surface 52, a first waist region 56, a second waist region 58, and a perimeter 51 defined by the outer edges of the diaper 50, where the longitudinal edges are designated 55 and the end edges 57. (V • · · · ·

9 9 9

9 9 9

99999 9

9 9

9 9 9

99

9 · · 9 9 9

9 9 9

Typically, the diaper is divided into two waist regions and a crotch region which is located therebetween, but in this application only the waist division of the diaper 50 into the waist regions containing the original crotch region is used for simplicity). The surface facing the body 54 of the diaper 50 is that portion of the diaper 50 that abuts the wearer's body during wear. The surface facing the body 54 is typically formed by at least a portion of the topsheet 520 and other portions that may be attached to the topsheet 520, such as the thigh cuff 550, as well as areas not belonging to the topsheet but touching the wearer, such as the waist portion 560, the side portions, and the like. The outer surface 52 includes a portion of the diaper 50 that faces away from the body of the wearer (i.e., the outer surface 52 is typically at least a portion of the backsheet 530 and other portions that may be attached thereto). . The first waist region 56 and the second waist region 58 extend between the end edges 57 of the periphery 51 and the transverse centerline 53 of the diaper 50. Also shown in Figure 1 is a longitudinal centerline 59.

Figure 1 shows a proposed embodiment of a diaper 50 in which the topsheet 520 and the backsheet 530 have a length and width greater than the dimensions of the absorbent core 540. The elastic thigh cuffs 550 and the backsheet 530 extend beyond the edges of the absorbent core 540 thereby forming the periphery 51 of the diaper 50.

The diapers of the present invention may be made in a number of known embodiments in which the absorbent cores are adapted to the present invention. Exemplary embodiments are generally described in U.S. Patent 3,860,003 (Buell) filed Jan. 14, 1975, U.S. Patent 5,151,092 (Buell et al.), September 29, 1992, and U.S. Patent 5,221,274 (Buell et al.). All of these patents are incorporated herein by reference. * • • • φ φ φ φ φ

An embodiment of a diaper to which the present invention can be readily adapted is described in U.S. Patent 5,554,145 filed by Roe et al., The disclosure of which is incorporated herein by reference.

The topsheet 520, which is particularly suitable for use in diaper 50, is carded and thermally bonded in a manner conventional in the art. An acceptable topsheet is comprised of long polypropylene fibers having a denier of about 2.2. As used herein, the long fibers are those having a length of at least 15.9 mm. The weight of the topsheet should be from about 14 to about 25 grams per square meter. A suitable topsheet is manufactured by Veratec, Inc., Division of the International Paper Company, Mass. under the designation P-8.

The topsheet 520 of the diaper 50 is typically made of a hydrophilic material that facilitates rapid passage of fluid (eg, urine) through the topsheet. If the topsheet is made of a hydrophobic material, at least portions of the topsheet must be treated to be hydrophilic and allow fluids to rapidly pass through the topsheet. This will reduce the likelihood that body exudates will flow out of the topsheet instead of being absorbed from the topsheet by the absorbent core. The topsheet may become hydrophilic upon impregnation with a surfactant. Suitable methods of impregnating the surfactant include spraying the surfactant on the topsheet and immersing the surfactant in the surfactant. A more detailed description of such treatment and hydrophilicity is given in U.S. Patent Nos. 4,988,344 and 4,988,345, both of which were filed by Reising et al.

January 29, 1991, incorporated herein by reference.

The topsheet may also be in the form of a film having apertures, which is preferred in feminine hygiene absorbent articles.

4 4

Apertured films are suitable because they are permeable to body fluids but do not absorb and tend to return fluid with subsequent wetting of the skin. This means that the surface of the film that touches the body remains dry, thereby reducing body contamination and creating a better user experience. Suitable films are described in U.S. Patent 3,929,135 (Thompson) filed December 30, 1975, U.S. Patent 4,324,246 (Mullane et al.) Filed Apr. 13, 1982, U.S. Patent 4,342,314 (Radel et al.) 3 No. 8, 1982, U.S. Patent 4,463,045 (Ahr et al.), Filed Jul. 1984 and U.S. Pat. No. 5,006,394 (Baird), filed May 9, 1984;

Each of these patents is incorporated herein by reference.

Recommended films with micro-holes for topsheets are described in U.S. Patent 4,609,518 (Curro et al.) Filed September 2, 1986 and U.S. Patent 4,629,643 (Curro et al.) Filed December 16, 1986, which are incorporated herein by reference. by reference. The proposed topsheet for use in feminine hygiene products is the film described in one or more of the aforementioned patents and marketed by The Procter & Gamble Company of Cincinnati, Ohio under the designation DRIWEAWE®.

The body-facing surface of the film may be hydrophilic, allowing body fluids to pass through the topsheet faster than if it were not hydrophilic, thereby reducing the likelihood that the fluid will drain from the topsheet instead of being absorbed. In the proposed embodiment, the surfactant is incorporated into the polymeric material of the topsheet film as described in U.S. Pat. Statutory Invention Registration H1670 (Aziz et al.), Issued Jul. 1, 1997, which is incorporated herein by reference. In other embodiments (not shown) of the present invention, the absorbent article may be provided with accessories enhancing contact between the topsheet and the skin of the wearer. V • 4 • 4 4

44444 4

4 ·

4 4

4 4 4

In one embodiment, the absorbent article is provided with elastic portions as described in U.S. Patent 4,892,536 to DesMarais et al.

January 9, 1990, U.S. Patent 4,990,147 (Freeland) February 5, 1991, and U.S. Patent No. 07,993,198 (Freeland et al.), December 18, 1992, which lift the topsheet to improve contact with the perianal area of the user . In another embodiment, described in U.S. Patent 5,171,236 to Drier et al., Filed Dec. 15, 1992, the diaper is provided with a series of joints that lift the topsheet. In yet another embodiment described in U.S. Pat. Statuory Invention Registration H1687, filed in Roe et al on Oct. 7, 1997, the absorbent article is provided with a buttock protecting portion that lifts the topsheet into the wearer's groove.

In the proposed embodiment of the diaper described herein, the backsheet 530 has an hourglass shape and extends beyond the absorbent core by at least 1.3 cm to 6.4 cm over the entire periphery of the diaper.

The absorbent core 540 may be of any size or shape compatible with the diaper 50. One proposed embodiment of the diaper 50 has an asymmetric T-shaped absorbent core 540 with tabs in the first waist region, but generally a rectangular shape in the second waist region. Examples of absorbents that can be used to form absorbent cores of the compositions are described, for example, in U.S. Patent 4,610,678 (Weisman et al.), Filed Sep. 9, 1986, U.S. Patent 4,673,402 (Weisman et al.), Filed 16. U.S. Patent 4,888,231 (Angstadt), issued December 19, 1989; and U.S. Patent 4,834,735 (Alemany et al.), Filed May 30, 1989. The absorbent core may further comprise a dual absorbent core system comprised of an absorbent / distribution device. cores of chemically stiffened fibers, which are placed above the absorbent core, 9 9 9 9 9

2Λ · 9,999 9 9 · 99,99 9

J 9 9 9 9 9 9 9 9 9 9 · 99 9 9999 99 99 retention core, this system is described in more detail in U.S. Pat. No. 5,234,423 (Alemany et al.) Filed Aug. 10, 1993 and U.S. Pat. No. 5,147,345 (Young, LaVon and Taylor) filed Sep. 15, 1992. All of these patents are incorporated herein by reference.

In the proposed embodiment, the diaper 50 further includes elastic thigh cuffs 550 to provide better fluid and body exudation, an elastic waist portion 560 for improved adherence and grip, and clamping means 570 that form a side connection that maintains the first waist region 56 and the second waist region 58 so as to overlap, thereby creating a lateral pull around the periphery of the diaper that maintains the diaper on the wearer. The diaper 50 may also include, in the waist regions 56 and 58, elastic waist strips (not shown) and / or elastic side portions (also not shown) that provide greater comfort and adhesion as well as more efficient use of the diaper 50.

The elastic thigh cuffs 550 may have a number of different embodiments, including those described in U.S. Patent 3,860,003, U.S. Patent 4,909,803 (Aziz et al.) Filed Mar. 20, 1990, U.S. Patent 4,695,278 (Lawson) filed Sep. 22, 1990. 1987 and U.S. Patent 4,795,454 (Dragoo) filed Jan. 3, 1989, the disclosures of which are incorporated herein by reference. Absorbent compositions having elastic cuffs treated with a component that may be useful herein are described in U.S. Patent Application Serial Nos. 08 / 766,386 and 08 / 840,039 assigned to U.S. Pat.

12, 1996 and 24, 4, 1997, which are incorporated herein by reference.

The elastic waist feature is comprised of an elastic waistband (not shown), which may be formed in a variety of different embodiments, including those described in U.S. Patent 4,515,595 (Kievit et al.).

Filed May 7, 1985, U.S. Patent 5,026,364 (Robertson) filed June 25, 1991, and U.S. Pat. No. 5,151,092 (Buell et al.) Filed Sep. 29, 1992, the disclosures of which are incorporated herein by reference. are incorporated herein by reference.

The elastic side sections may be formed in a number of different embodiments. Examples of diapers with elastic side portions disposed within the diaper ears are disclosed in U.S. Patent 4,857,067 (Wood et al.) Filed Aug. 15, 1989; U.S. Patent 4,383,781 (Sciaraffa et al.) Filed March 3, 1983; USA. No. 4,938,753 (Van Gompel et al.), Filed Jul. 3, 1990, and U.S. Patent 5,151,092 (Buell et al.), Filed Sep. 29, 1992, which are incorporated herein by reference.

Examples of clamping means 570 are described in U.S. Patent 4,846,815 (Scripps) July 11, 1989, U.S. Patent 4,894,060 (Nestegard) filed January 16, 1990, U.S. Patent 4,946,527 (Battrell) filed August 7, 1990 U.S. Patent 3,848,594 (Buell), filed Nov. 19, 1974, U.S. Patent 4,662,875 (Hirotsu et al.), filed May 5, 1987, and U.S. Patent No. 5,151,092 (Buell et al.), filed Sep. 29, 1974. 1992, their disclosures are incorporated herein by reference.

The diaper 50 is generally applied by applying one of the diaper waist regions, preferably the other waist region 58, to the wearer's back and extending the remainder of the diaper between the wearer's legs so that the other waist region, preferably the waist region 56, is applied forward. Then, clamping means are used to secure the diaper sideways.

Of course, any type of absorbent article can be used to utilize an enzyme inhibitor and / or a transfer system to transfer the inhibitor to the skin of a user during wear of the composition. Thus, the above description is for illustrative purposes only.

The present invention may also use training pants as an absorbent composition comprising an enzyme inhibitor. As used herein, the term training pant refers to a disposable garment having fixed sides and leg openings and adapted for children or adults. The training panties are worn so that the user pushes the legs into the leg openings and the panties are stretched towards the bottom of the wearer's torso. Suitable training pants are described in U.S. Patent 5,246,433 (Hasse et al.) Filed Sep. 21, 1993, U.S. Patent 5,569,234 (Buell et al.) Filed Oct. 29, 1996, U.S. Patent No. 4,940,464 (Van Gompel) et al., filed July 10, 1990, and U.S. Patent 5,092,861 (Nomura et al.) filed March 3, 1992, the disclosures of which are incorporated herein by reference.

Other disposable absorbent compositions which can be used in the present invention are incontinence agents. The term incontinence agent is used for mats, underwear, absorbent pads, bedding and the like, whether used by adults or other incontinent persons. Suitable incontinence agents are described in U.S. Pat. No. 4,253,461 (Strickland et al.), Filed Mar. 3, 1981; 4,597,760 and 4,597,761 (Buell); No. 4,704,115, U.S. Pat. No. 4,909,802 (Ahr et al.), U.S. Pat. No. 4,964,860 (Gipson et al.), Filed Oct. 23, 1990; No. 5,304,161 (Noel et al.), Filed Apr. 19, 1994. Descriptions of these patents are incorporated herein by reference.

• • • •

Other disposable absorbent articles which can be used in the present invention are feminine hygiene articles, such as a sanitary napkin. Suitable feminine hygiene products are described in U.S. Patent 4,556,146 (Swanson et al.), Filed December 3, 1985, U.S. Patent 4,589,876 (Van Tilberg), filed April 27, 1993, U.S. Patent 4,687,478 (Van Tilburg). U.S. Patent 4,950,264 (Osborn) filed Aug. 18, 1997; 1990, U.S. Patent No. 5,009,653 (Osborn) filed April 23, 1991, U.S. Patent No. 5,267,992 (Van Tilburg) filed December 7, 1993, U.S. Patent No. 5,389,094 (Lavash et al.) Filed February 14, 1995 , U.S. Pat. No. 5,413,568 (Roach et al.), filed May 9, 1995, U.S. Pat. No. 5,460,623 (Emenaker et al.), filed Oct. 24, 1995, U.S. Pat. No. 5,489,283 (Van Tilburg), filed May 6, 1995. No. 2, 1996, U.S. Patent No. 5,569,231 (Emenaker et al.), Filed Oct. 29, 1996, and U.S. Patent No. 5,620,430 (Bamber), filed Apr. 15, 1997. Descriptions of these patents are incorporated herein by reference.

IV. Enzyme inhibition testing

Standard assays for enzyme activity in vitro and inhibition of enzyme activity are well known. Reagents for performing these assays are commercially available. In general, a simple system is composed of an enzyme-specific substrate which, when hydrolyzed by the enzyme, forms a colored product. Enzyme activity is measured spectrophotometrically as the degree of color product development (i.e., the level of color change) over a specified period of time. Inhibition of enzyme activity is shown to be a measurable decrease in the level of color change over the same period of time in the presence of an inhibitor. The following are examples of methods that can be used to determine the inhibitory activity of enzyme inhibitors in a) purified enzymes known from stool, and b) enzyme activity of stool alone. However, these methods are not the only ones, and therefore other methods, other substrates, other inhibitors and the like can be used to test activity against a wide variety of stool enzymes.

For each of the following sample purified protease assays, stool protease assays, purified lipase assays, stool lipase assays, purified urease assays, stool urease assays, purified amylases and stool amylases assays, an IC ₅₀ can be determined for each inhibitor tested according to the following equation:

IC ₅₀ = [I] / [(v / v) -1) J, where [I] is the concentration of inhibitor tested, v is the substrate cleavage level in the absence of inhibitor, and Vj is the substrate cleavage level in the presence of inhibitor.

v and Vj are measured as changes in absorbance (optical density, OD) at a given wavelength / time (e.g., minutes).

A. Testing of purified proteases

1. Purified Trypsin

To test the efficacy of protease inhibitors against purified trypsin, 0.05 ml of putative inhibitor and 0.125 ml of 32 nM trypsin (eg, Sigma, St. Louis, MO, Cat. No. T6424) are placed in a microcycle in trypsin buffer (50 mM TRIS, 20 mM). CaCl ₂ , pH 8.2). The cuvette is allowed to incubate at 25 ° C for about 10 minutes. To this mixture was added 0.025 mL of substrate (4 mM Cbz-arginine-pnitroanilide, e.g., Sigma, St. Louis, MO, Cat. No. C4893) to the cuvette at

4 44 44 44

444 44 44 4444

4444 4 4444

4 4444 4 4 444444 j *> ··· 4 4 4444

No. 4,444,444,444 with trypsin buffer, mix, and after 10 minutes absorbance is measured at 25 ° C at 405 nm. The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Values V i and v of inhibitor concentration are used to calculate IC ₅₀ according to the above equation.

2. Purified chymotrypsin

To test the efficacy of protease inhibitors against purified chymotrypsin, 0.05 ml of the putative inhibitor and 0.125 ml of 16 nM chymotrypsin (e.g., Sigma, St. Louis,

MO, Cat. No. C8946) in chymotrypsin buffer (50 mM TRIS, 10 mM CaCl ₂ , pH 7.6). The cuvette is allowed to incubate at 25 ° C for about 10 minutes. To this mixture, 0.025 ml of substrate (0.6 mM N-succin-ala-ala-pro-phe-p-nitroanilide, eg Sigma, Cat. No. S7388) is added to the cuvette in chymotrypsin buffer, mixed and after 10 minutes. absorbance at 25 ° C at 405 nm is measured. The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Values V i and v of inhibitor concentration are used to calculate IC ₅₀ according to the above equation.

3. Purified Leucine Aminopeptidase · Purified Leucine Aminopeptidase

9 9 9 9 9 9 9 9 9 ar · · 9999 9 9 9 9 9 9 9 9 · 9 «· · · · · · · ··· 9999 99 99

To test the efficacy of protease inhibitors against purified leucine aminopeptidase (LAP), 0.05 ml of the putative inhibitor and 0.125 ml of 0.06 U / ml LAP (e.g., Sigma,

St. Louis, MO, Cat. No. L5006) in LAP buffer (50 mM sodium phosphate, pH 7.2). The cuvette is allowed to incubate at 25 ° C for about 10 minutes. To this mixture, 0.025 ml of substrate (2.4 mM L-leucine-pnitroaniline, e.g. Sigma, St. Louis, MO, Cat. No. L9125) is added to the cuvette in LAP buffer, mixed, and absorbance is measured after 10 minutes at 25 ° C at 405 nm. The level of substrate cleavage in the presence of inhibitor (vj) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Vi and v values and inhibitor concentrations are used to calculate the IC 50 according to the above equation.

B. Testing of specific stool proteases

The following is a general description of a method of obtaining a stool sample that is suitable for use in testing stool proteases. However, any person skilled in the art will be able to obtain appropriate stool samples for use in any of the stool specific protease assays (ie, lipase, urease and amylase).

For the purpose of creating positive controls to ensure that the stool sample collection exhibits the enzymatic activity required to evaluate the activity of protease inhibitors, the following procedure is performed for each of the stool protease assays. The collected stool (at least five different samples) is taken to be free of urine and contamination and mixed with water in a weight ratio

4 · ·· 44 · 4 i 4 4 4 4 44 4 4 4 4

4 4 4 4

4,444 4 4,44444

3/4 · 4 44 444

4,444,444 44,444 (w / w) e.g. 1:50. The mixture is then thoroughly mixed so that a homogenous suspension can be obtained by homogenization or sonication. The stool suspension is used as a source of protease activity as described below and will have a substrate conversion level in the absence of inhibitor ranging from 0.005 OD405 per minute to 0.020 OD405 per minute. (To ensure perfect linearity, the final absorbance should not exceed 1.5 OD ₄₀ 5 units). If the stool activity is outside this range, then it is not possible to accurately determine the IC50 values of the putative protease inhibitors. However, the range of enzyme activity can be adjusted by increasing or decreasing the dilution factor for each enzyme. If this is not possible, another group should be chosen to obtain the samples.

1. Stool trypsin activity

To test the efficacy of protease inhibitors against trypsin in the stool, inhibitor and trypsin buffer (50 mM TRIS, mM CaCl 2, pH 8.2) are placed in the cuvette to give a final volume of 0.8 ml. To this mixture was added 0.1 mL of substrate (3 mM Cbz-arginine-pnitroanilide) to the cuvette. The cuvette is mixed by rotation and incubated at 25 ° C for 5 minutes. About 0.1 ml of stool suspension is added to the cuvette, mixed and measured at 25 ° C for absorbance at 405 nm minus absorbance at 490 nm for 5 minutes. (Absorbance at 490 nm is a correction factor for background absorbance caused by stool particles, ie interference). The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance difference curve (ie, absorbance at 405 nm minus absorbance at 490 nm) with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance difference versus time curve. Values in; and v and inhibitor concentrations [I] are used to calculate the IC 50 according to the above equation.

2. Stool chymotrypsin activity

To test the efficacy of the protease inhibitors against chymotrypsin in the faeces, the inhibitor and chymotrypsin buffer (50 mM TRIS, 10 mM CaCl ₂ , pH 7.6) are placed in the cuvette to give a final volume of 0.92 ml. To this mixture was added 0.04 mL of substrate (1.25 mM N-succal-ala-pro-phe-p-nitroanilide) to the cuvette. The cuvette is mixed by rotation and incubated at 25 ° C for 5 minutes. About 0.04 mL of stool suspension is added to the cuvette, mixed and measured at 25 ° C for absorbance at 405 nm minus absorbance at 490 nm for 5 minutes. The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance difference curve (ie, absorbance at 405 nm minus absorbance at 490 nm) with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance difference versus time curve. Values v, a, and inhibitor concentration [I] are used to calculate the IC ₅₀ according to the above equation.

3. LAP activity in stool

To test the efficacy of anti-LAP protease inhibitors in the stool, inhibitor and LAP buffer (50 mM sodium phosphate, pH 7.2) are placed in the cuvette so that the final volume is 0.95 ml. To this mixture was added 0.03 mL of substrate (6 mM L-leucine-p-nitroanilide) to the cuvette. The cuvette is mixed by rotation and incubated at 25 ° C for 5 minutes. About 0.02 ml of stool suspension is added to the cuvette, mixed and measured at 5 minutes at

25 ° C absorbance at 405 nm minus absorbance at 490 nm. The level of substrate cleavage in the presence of inhibitor (vj) is the slope of the absorbance difference curve (ie, absorbance at 405 nm minus absorbance at 490 nm) with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance difference versus time curve. Values vj and v of inhibitor concentration [I] are used to calculate the IC ₅₀ according to the above equation.

The protease inhibitory activity of the selected protease inhibitors used in the absorbent compositions of the invention was determined using the purified protease and stool protease assays described above and the test results are shown in Table 1.

Tabuka 1

IC50 řuM) Purified proteases Specific nroteázv stool TrvDsin Chvmotrvosin LAP * TrvDsin Chvmotrvosin LAP * Inhibitor soybean trypsin inhibitor 0.25 0,026 > 10 <0.01 0.06 > 20 aprotinin 0.168 1 > 20 0.01 0.22 > 20 hexamidine diisothionate 2.5 > 1000 256 2.3 > 1000 130 p-amino-benzamidine 13.8 > 500 > 500 20 May > 500 > 500 leupeptin 0.14 > 500 > 500 0.11 > 500 > 500 pepstatin A 324 4.9 > 500 > 500 300 > 500 chymostatin > 500 <0.12 > 500 > 500 0.02 > 500 TLCK 78.3 > 500 > 500 200 > 500 > 500 glycyrrhyzic acid 45 > 500 > 500 > 300 > 300 > 300 EDTA > 125,000 > 125,000 > 1250 00 100 ALIGN! 100 ALIGN! > 3000 4- (2-Aminoethyl) benzenesulfonyl fluoride hydrochloride 45.7 190 > 500

* LAP = leucine aminopeptidase ** TLCK = L-1-chloro-3- (4-tosylamido) -7-amino-2-heptanone-HCl *** EDTA - ethylenediaminetetraacetic acid

Table 1 shows that each of the compounds inhibits at least one protease by the purified stool and / or stool protease assay method.

D. Purified Lipase Testing

To test the efficacy of lipase inhibitors, 0.05 ml of the putative inhibitor and 0.125 ml of 160 nM pancreatic lipase (e.g. Sigma, St. Louis, MO, Cat. No. L0382) are added to a microvoid in 50 mM TRIS buffer containing 1 mM CaCl ₂ pH 8.0. The cuvette is incubated at 25 ° C for 10 minutes. About 0.025 mL of substrate (1.25 mM p-nitrophenol caprylate, e.g., Sigma, St. Louis, MO, Cat. No. NO752) is added to the cuvette and allowed to incubate for an additional 5 minutes. After 10 minutes, absorbance was measured at 405 nm at 25 ° C. The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Values V i and v of inhibitor concentration [I] are used to calculate the IC ₅₀ according to the above equation.

E. Faecal lipase testing

To test the efficacy of lipase inhibitors against faecal lipase, inhibitor and lipase buffer (50 mM TRIS buffer containing 1 mM CaCl ₂ pH 8.0) are added to the cuvette to a final volume of 0.8 ml. To this mixture was added 0.1 mL of substrate (1.25 mM pnitrophenol caprylate) to the cuvette. The cuvette is mixed by inverting and left to leave.

Incubate at 25 ° C for 5 minutes at 1 ° C. Thereafter, 0.1 ml of faeces suspension is added to the cuvette, mixed and measured after 5 minutes at 25 ° C absorbance at 405 nm minus absorbance at 490 nm. (Absorbance at 490 nm is a correction factor for background absorbance caused by stool particles, ie interference). The level of substrate cleavage in the presence of inhibitor (V i) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Values Vj and v and inhibitor concentration [I] are used to calculate the IC50 according to the above equation.

F Testing of purified urease activity.

To test for urease inhibitor activity, 0.05 ml of the putative inhibitor and 0.125 ml of 0.08 U / ml urease are added to the microvoid, Jack Bean (Sigma U2125 Catalog) in 45 mM sodium phosphate buffer pH 6.8. The cuvette is allowed to incubate at 25 ° C for about 10 minutes. To this mixture was added 0.025 mL of substrate (300 mM urea, e.g., Sigma U0631) and the mixture was allowed to incubate for an additional 5 minutes. Ammonia release is immediately measured using a commercial ammonia detection kit (Sigma Diagnostics, St. Louis, MO, Procedure 171).

G. Testing urease activity

To test the effectiveness of urease inhibitors against urease from faeces, the inhibitor and urease buffer (45 mM sodium phosphate, pH 6.8) are added to the cuvette to a final volume of 0.8 ml. To this mixture was added 0.1 mL of substrate (375 mM urea) to the cuvette. Mix the cuvette

invert and incubate at 25 ° C for about 5 minutes. To this mixture was added 0.1 mL of stool suspension, mixed and allowed to incubate for an additional 5 minutes. Ammonia release is then immediately measured using a commercial ammonia detection kit (Sigma Diagnostics, Procedure 171).

H. Testing Purified Amylase Activity

Amylase activity was determined using the 577 Sigma Diagnostics procedure. To test the efficacy of amylase inhibitors, 0.010 ml of a putative inhibitor and 0.010 ml of human salivary aamylase (Sigma No. A0521, 100 to 2000 U / L, as measured by Sigma Diagnostics procedure 577) in water are added to the cuvette. The cuvette is incubated at 37 ° C for 10 minutes. To this mixture was added 1.00 ml amylase substrate and allowed to incubate for a further 2 minutes. After 2 minutes, absorbance at 405 nm was measured at 37 ° C. The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Values V i and v of inhibitor concentration [I] are used to calculate the IC ₅₀ according to the above equation.

I. Testing of amylase activity from stool

Amylase activity was determined using the 577 Sigma Diagnostics procedure. To test the efficacy of amylase inhibitors against stool amylases, 0.010 ml of the putative inhibitor and 0.010 ml of stool suspension (100 to 2000 U / l, as measured by Sigma Diagnostics) are added to the cuvette.

4Q · ··· · + -} procedure 577). The cuvette is allowed to incubate at 37 ° C for 10 minutes. To this mixture was added 1.00 ml of amylase substrate, mixed and allowed to incubate for a further 2 minutes. After 2 minutes at 37 ° C

X absorbance at 405 nm minus absorbance at 490 nm. The level of substrate cleavage in the presence of inhibitor (vi) is the slope of the absorbance curve at 405 nm with respect to time. The same procedure is repeated without adding the putative inhibitor. The level of substrate cleavage in the absence of inhibitor (v) is the slope of the absorbance curve at 405 nm with respect to time. Values in; and v and inhibitor concentrations [I] are used to calculate the IC 50 according to the above equation.

V. Dermatological component

Dermatological ingredients suitable for use in the absorbent compositions of the present invention are described in U.S. Patent Nos. 08/926 532 and 08/926 533, both filed Sep. 10, 1997, U.S. Pat. No. 5,607,760 filed Mar. 4, 1997, U.S. Pat. No. 5,609,587 U.S. Patent 5,635,191, filed June 3, 1997, and U.S. Patent 5,643,588, filed July 1, 1997, the disclosures of which are incorporated herein by reference. The dermatological component is, as mentioned, transferred to the skin of the user of the treated composition during normal contact, movement of the user and / or by heat of the body. That is, the transfer of the dermatological component containing the enzyme inhibitor begins after application of the composition to the user and continues for the period of wear. Accordingly, the enzyme inhibitor is typically present on the skin of the user prior to the attack of body secretions.

In addition to its function of providing a minimum inhibitory concentration of the enzyme inhibitor to the skin of the user, the dermatological component may also contain ingredients that, for example, reduce stool adhesion to the skin, create a skin / stool barrier (e.g. stool adherence), but remain relatively impermeable, but breathable, or have other beneficial effects on the skin (e.g., soften the skin, improve or maintain skin quality), etc. The dermatological component may take a number of forms such as emulsion, solution, cream, ointment, balsam, suspension, gel and the like.

The transfer of the effective concentration of the enzyme inhibitor from the absorbent composition to the skin and the effective amount of the dermatological component applied or transferred to the surfaces of the composition touching the wearer depends primarily on the dermatological component used. The amount of the component should be at least 0.0078 mg / cm ² to 12 mg / cm ² , preferably 0.16 mg / cm ² to 6 mg / cm ^2, and most preferably 0.6 mg, at least on the user-contacting surface area. / cm ² to 4 mg / cm ² . However, these ranges are merely illustrative and the skilled artisan will appreciate that the nature of the component determines the amount that must be applied to deliver a sufficient concentration of the enzyme inhibitor and that the desired amount is detectable by routine experimentation.

The amount of dermatological component applied to the absorbent article is an important factor of the present invention, but more important is the amount of component transferred to the skin of the user during use of one or more of the compositions so treated. Although the amount of dermatological component containing an enzyme inhibitor transferred to the skin depends to some extent on the nature of the component used and the activity of the enzyme inhibitor, relatively small amounts can still be transferred that are still sufficient to produce a minimum inhibitory concentration of the enzyme inhibitor on the skin. This is particularly true for the proposed components described in Example 1.

Given the level of dermatological component that is transferred to the user while wearing one modified absorbent composition for 3 hours (typical wear time) and especially for the proposed dermatological components described in Example 1, it is suggested that it be transferred to the skin within three hours of wear time. at least 0.0016 mg / cm ² , preferably at least 0.0078 mg / cm ^2, and most preferably at least 0.016 mg / cm ^{2 of the} dermatological component. The usual transferred amount of dermatological component by one formulated composition over a three hour wear period is from 0.0016 mg / cm ² to 0.78 mg / cm ² , preferably from 0.0078 mg / cm ² to 0.47 mg / cm ^2, and most preferably from 0.016 mg / cm ² to 0.31 mg / cm ² .

For long-term use of the formulated compositions (replacement is usually done every 3 to 4 hours during the day and also before bedtime), such as for 24 hours, components that are transferred to the skin of the user within 24 hours in an amount of at least 0 , 0047 mg / cm ^2, more preferably at least 0.016 mg / ^cm2 and most preferably at least 0.047 mg / cm. The amount of component transferred within 24 hours is usually from 0.0047 mg / cm ² to 2.79 mg / cm ² , more usually from 0.016 mg / cm ² to 10 mg / cm ^2, and most often from 0.047 mg / cm ² to 0, 93 mg / cm ² . The procedure for determining the amount of dermatological component transferred to the skin during wear of the treated composition is described below.

Obviously, among the numerous substances suitable for dermatological ingredients containing the skin-transfer enzyme inhibitor of the invention, those substances considered to be safe and effective dermatological agents have been logically selected. These substances belong to Category I as defined in U.S. Pat. Food and Drug Administration (FDA), (21 CFR § 347), which now includes: allantoin, aluminum hydroxide gel, calamine, cocoa butter, dimeticone, fish oil (in combination), glycerin, kaolin, petrolatum, lanolin, mineral oil, shark oil, white petrolatum, talc, starch, zinc acetate, zinc carbonate, zinc oxide and the like. categories defined by U.S. Pat. Food and Drug Administration (FDA), which now includes: live yeast derivatives, aldioxa, aluminum acetate, microporous cellulose, cholecalciferol, colloidal oat flour, cysteine hydrochloride, dexpantenol, peruvian balsamic oil, protein hydrolysates, racemated methionine, sodium bicarbonate, vitamin bicarbonate etc.

A number of dermatological ingredients listed in the FDA are now commonly used in commercially available dermatological products such as A and D Ointment®, Vaseline®, Petroleum Jelly, Desitin® Diaper Rash Ointment and Daily Care® ointment, Gold Bond® Medicated Baby Powder, Aquaphor Healing Ointment, Baby Magic® Baby Lotion, Johnson's Ultra Sensitive® Baby Cream. An effective concentration of enzyme inhibitor can be incorporated into any of these commercial products and applied to the absorbent composition to form a modified composition of the present invention.

It will be described below that dermatological ingredients suitable for transferring enzyme inhibitors to the skin of a user are preferably, but not necessarily, those with a melting profile that allows them to remain stationary on the surface touching the skin at room temperature. It is easy to transfer to the user at body temperature and not to liquefy when stored in extreme conditions. In this regard, the components are at least partially transferable to the skin due to contact, movement of the user and / or body heat. Since the component is generally immobilized on the surface of the device touching the wearer, relatively low levels of the component are sufficient to produce the desired effects on the skin. Furthermore, it may be necessary to use special packaging materials for the formulated compositions of the present invention.

In the proposed embodiment, the dermatological components are water-in-oil emulsions wherein the enzyme inhibitor is in the aqueous phase. However, the dermatological component itself may be solid or more often semi-solid at 20 ° C, i.e. at ambient temperature. The term semisolid means that the component has rheological properties typical of pseudo-formable or malleable liquids. If there is no friction, the components may have the appearance of a semi-solid, but may liquefy as friction increases. This is because the component contains primarily both solid and liquid parts. The viscosity of the dermatological component containing the enzyme inhibitor should be from 1.0 x 10 ⁴ to 1.0 x 10 ⁶ g / cm.s, preferably from 5.0 x 10 ⁴ to 5.0 x 10 ⁶ g at zero friction. cm.s. By zero viscosity is meant viscosity measured at a very low friction level (e.g., 1.0 s ^-1 ) using a suitable viscometer (e.g., CSL 100 model from TA Instruments of New Castle, DE). One skilled in the art will appreciate that components other than those of high melting point (see below) may be used which will have a comparable viscosity which can be measured by extrapolating the viscosity curve relative to the friction level for such a component to zero friction at about 20 °. C. The proposed components are at least semi-solid at room temperature to prevent the component from passing into the absorbent composition prior to use. In addition, they have • 4 ·

The final melting point (100% liquefaction) above possible unfavorable storage conditions, which may be higher than 45 ° C (eg a warehouse in Arizona, a truck in Florida, etc.). Examples of ingredients having these features are described in detail in U.S. Patent 5,643,588, U.S. Patent 5,607,760, U.S. Patent 5,609,587, and U.S. Patent 5,635,191. The proposed ingredients have the following melting profiles:

Property Proposed range The most unfavorable range % liquid at room temperature (20 ° C) 2-50 3-25 % liquid at body temperature (37 ° C) 25-95 30-90 final melting point (° C) > 38 > 45

The proposed components containing the enzyme inhibitor do not tend to flow at ambient temperature and pass to a greater extent into undesirable areas of the composition to which they have been applied. That is, less dermatological component is required to achieve the expected therapeutic and protective effect.

In order to prevent the components from moving inside the composition to undesirable locations, the components must be immobilized by maximizing their viscosity. Unfortunately, in some cases, a higher viscosity may reduce the transfer of the component to the wearer's skin. Thus, an equilibrium must be achieved which allows both the component to be retained on the surface of the composition and its transfer to the skin of the user. Suitable viscosities of these components are in the range of from 0.05 to 5 g / cm.s, preferably from 0.05 to 3 g / cm.s, and preferably from 0.05 to 1 g / cm.s, measured at &lt; · · · · · · · · · · · · · · · · · · · · · · · · · ·

60 ° C with a rotary viscometer (a suitable viscometer is Model 4357 from Lab Line Instruments, Inc. of Melrose Park, IL). The viscometer operates at 60 rpm using shaft # 2.

In addition to the dermatological components modified to have a therapeutic and / or protective effect on the skin and the positive effect of enzyme inhibitors, the other active ingredients of these components are one or more preservatives or emollients. The term emollient as used herein is reserved for a substance that protects against moisture and irritation, softens, soothes, softens, coat, lubricate, moisturize, protect and / or cleanse the skin. (It will be appreciated that many of the materials mentioned above are emollients.) In the proposed embodiment, these emollients are malleable or liquid at ambient temperature, i.e., 20 ° C.

Examples of suitable plasticizers for use in the present invention are, inter alia, petroleum derived plasticizers, sucrose fatty acid esters, polyethylene glycol and derivatives thereof, wetting agents, fatty acid esters, alkyl ethoxylates, ethoxylate fatty acid esters, fatty alcohol, polysiloxane, propylene glycol and derivatives thereof , glycerol and derivatives thereof, including glyceride, acetoglyceridových and of ethoxylated fatty acid glycerides Cl ₂ C ₂ 8, triethylene glycol and derivatives thereof, whale fat and or other waxes, fatty acids, fatty alcohol esters, especially those having 12 to 28 carbon atoms in its chain, such as stearic acid, propoxylated fatty alcohols, other fatty acid esters of polyhydroxy alcohols, lanolin and its derivatives, kaolin and its derivatives, any dermatological agent mentioned above or mixtures of these plasticizers. Suitable petroleum emollients include those hydrocarbons or mixtures thereof having a chain length of from 16 to 32 carbons. Petroleum hydrocarbons of this chain length include mineral oil and petrolatum. The term mineral oil usually refers to a less viscous hydrocarbon mixture having from 16 to 20 carbons. Vaseline usually refers to a more viscous mixture of 16 to 32 carbons. Vaseline and mineral oil are preferred emollients for use in the dermatological component of the present invention.

Suitable fatty acid ester plasticizers include those derived from C ₁₂ -C ₂₈ fatty acids, more preferably C ₁₆ -C ₂₂ saturated fatty acids, and short chain alcohols (C 1 -C ₈ , more preferably C 1 -C ₃ ). Suitable examples of such esters are methyl palmitate, methyl stearate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, ethylhexyl palmitate, and mixtures thereof. Změkěovadla Suitable fatty acid ester type may also be obtained from the esters of fatty alcohols, long chain (C ₂ -C _28, more preferably C _i2 CIO) fatty acids having shorter chain, e.g., lactic acid, such as lauryl lactate and cetyl lactate.

Suitable alkyl ethoxylate type plasticizers are C ₁₂ -C ₂₂ fatty alcohol ethoxylates having an average degree of ethoxylation of from 2 to 30. These plasticizers are selected from the group consisting of lauryl, cetyl and stearyl ethoxylates or mixtures thereof having an average degree of ethoxylation of from 2 to 23 Illustrative examples of such alkyl ethoxylates are laureth-3 (laurylethoxylate with an average degree of ethoxylation of 3), laureth-23 (with an average degree of ethoxylation of 23), ceteth-10 (cetyl alcohol ethoxylate with an average degree of ethoxylation of 10) and steareth-10 (stearyl alcoholethoxylate with an average degree of ethoxylation) 10). These alkyl ethoxylate plasticizers are generally used in combination with petroleum derived plasticizers, such as petrolatum, in a weight ratio of the alkyl ethoxylate plasticizer to the petroleum derived plasticizer from 1: 1 to 1: 5, more preferably from 1: 1 to 5: 1. 2 to 1: 4.

Suitable fatty alcohol type emollients are fatty alcohols, C ₂ -C _22, more preferably fatty alcohols, C ₆ -C _eighth Illustrative examples are cetyl alcohol, stearyl alcohol and mixtures thereof. These plasticizers are generally used in combination with petroleum softeners, such as petrolatum, in a weight ratio of fatty alcohol softener to petroleum softener of from 1: 1 to 1: 5, preferably from 1: 1 to 1: 2.

Other suitable plasticizers are the polysiloxane compounds. Generally, those polysiloxane materials whose monomeric siloxane unit has the following structure are suitable for use in the present invention:

R *

SIL ² wherein R ¹ and R ² may, independently for each monomer unit, hydrogen or alkyl, aryl, alkenyl, alkaryl, arakyl, cycloalkyl, halogenated hydrocarbon, or other radical. All these residues can be replaced. The residues R ¹ and R ^{2 of} each individual monomer unit may be different from the respective groups of the adjacent unit. In addition, the polysiloxane may have a linear chain, branched chain, or cyclic structure. Residues R ¹ a · «· ··

R may independently be other groups such as siloxanes, polysiloxanes, silanes and polysilanes. The radicals R ¹ and R ² may contain any of a number of organic groups including alcohol, carboxylic acid, phenyl, and amine groups.

Examples of alkyl radicals are methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl, octadecyl and the like. Examples of alkenyl radicals are vinyl, allyl and the like. Examples of aryl radicals are phenyl, diphenyl, naphthyl, etc. Examples of alkaryl radicals are toyl, xylyl. , ethylphenyl and the like. Examples of aralkyl radicals are benzyl, alpha-phenylethyl, beta-phenylethyl, alpha-phenylbutyl and the like. Examples of cycloalkyl radicals are cyclobutyl, cyclopentyl, cyclohexyl and the like. etc.

The viscosity of suitable polysiloxanes can vary widely, as can the viscosity of siloxanes in general, and therefore the siloxanes can be flowable or can be adjusted to become flowable. That is, their viscosity ranges from 5 centistokes (measured at 37 ° C with a glass viscometer) to 20,000,000 centistokes, but is not limited to these values. The polysiloxanes should have a viscosity at 37 ° C ranging from 5 to 5,000 centistoke, preferably from 5 to 2,000 centistoke, most preferably from 100 to 1,000 centistoke. High viscosity, non-flowable polysiloxanes can be effectively applied to the absorbent composition by, for example, forming an emulsion of polysiloxanes in the surfactant or forming a solution of siloxanes with a solvent such as hexane, which is mentioned by way of example only.

The various methods of applying polysiloxane plasticizers to absorbent articles will be discussed in more detail below.

Polysiloxane compounds proposed for use in the present invention are described in U.S. Patent 5,059,282. Among the most suitable polysiloxane compounds are polymethylsiloxane compounds having a phenyl group (eg, Dow Corning 556 Cosmetic-Grade Fluid: polymethylphenylsiloxane) or or cetyl or stearyl group demethicones such as For example, Dow 2502 and Dow 2503 polysiloxane fluids. In addition to these phenyl or alkyl substitutions, an effective substitution by amine, carboxyl, hydroxyl, ether, polyether, aldehyde, ketone, amide, ester, and thiol groups can also be effected. Of the range of active substituents, phenol, amino, alkyl, carboxyl and hydroxyl groups are preferred, but phenol groups are most preferred.

Suitable fatty ester plasticizers are the polyol polyesters described in U.S. Patent 5,609,587. Examples of polyols are, inter alia, polyhydric compounds such as pentaerythritol, sugars such as raffinose, maltodextrose, galactose, sucrose, glucose, lactose, mannose. and erythrose, and sugar alcohols such as erythritol, xylitol, malitol, mannitol and sorbitol. Fatty acid esters and / or other organic moieties having from 2 to 30 carbons are formed from such polyols. Although it is not necessary for all hydroxyl groups of the polyols to be esterified, the proposed polyol polyester plasticizers have almost all (eg at least 85%) hydroxyl groups esterified. Particularly suitable are sucrose polyol polyesters such as sucrose polycotonate, sucrose polysojate, and sucrose polysojate, and the like. And sucrose polybehenate. Also mixtures of these polyol polyesters are suitable plasticizers for the present invention.

Suitable hydrating components are glycerin, propylene glycol, sorbitol, trihydroxystearin and the like.

The amount of emollient that may be included in the dermatological component depends on a number of factors, such as the type of emollient involved, the desired skin effect, other components of the component, etc. The component contains emollients from 0 to 100% by weight. However, the suggested range is from 10 to 95%, preferably from 20 to 80%, and most preferably from 40 to 75% by weight.

Another beneficial component of an enzyme inhibitor-containing dermatological component may be a substance that is capable of immobilizing the component (including an enzyme inhibitor, a proposed emollient and / or other preservative) in a desired area within or on the formulated composition. Since some of the proposed component components are malleable or liquid at 20 ° C, they will tend to flow or migrate even when exposed to only slight friction. When deposited on a user-contacting surface or other area of the absorbent article in a dissolved or liquid state, they usually do not remain in that area as they tend to move and overflow into the unwanted area of the device.

If any of the components of the dermatological component are moved into the interior of the composition, this may have an adverse effect on the absorbance of the core of the composition due to the hydrophobic properties, e.g. This also means that a greater amount of dermatological component must be applied to the composition to achieve the desired effect. Increasing the content of the dermatological component not only increases the cost, but also enhances the undesirable effect on the absorbance of the core of the composition and the unwanted transfer of the component during processing of the treated composition.

The immobilizing agent counteracts the tendency of the components of the dermatological component to move or drain by retaining them on the surface or area of the composition to which they have been applied. This is partly because the immobilizing agent increases the melting point and / or viscosity of the component above the values of the moving components.

It is preferred to lock the immobilizing agent on the user-contacting surface or in the area of the composition to which it is applied. This can be achieved by using immobilizing agents which rapidly solidify upon application to the composition. Further, external cooling of the composition by fans, fans, and the like can be used to accelerate crystallization of the agent.

The immobilizing agent should have a melting profile such that the component is solid or semi-solid at ambient temperature. Therefore, the proposed immobilizing agents should have a melting point of at least 35 ° C. At this temperature, the immobilizing agent will not tend to move or flow. The proposed immobilizing agents have a melting point of at least 40 ° C. Typically, the immobilizing agent has a melting point in the range of 50 ° C to 150 ° C.

The immobilizing agents may be selected from a variety of agents if the inhibitory properties of the dermatological component have a positive effect on the skin described herein. It has been found that some plasticizers or plasticizer classes have melting properties that are suitable as immobilizing agents. Such substances can fulfill the functions of both plasticizer and immobilizing agent. Proposed immobilizing agent will belong to the group comprising fatty alcohols, C14-C22 fatty acids, C12 -C22 fatty alcohol ethoxylates, C12-C22 and mixtures thereof, having an average degree of ethoxylation of 2 to 30 Proposed immobilizing agents include fatty alcohols, C ₆ Cig most preferably high melting point crystalline materials selected from the group consisting of cetyl alcohol, stearyl alcohol, behenyl alcohol, and mixtures thereof. (The linear structure of these substances may accelerate solidification on the treated absorbent composition.) Mixtures of cetyl alcohol and stearyl alcohol are preferred. Another suggested immobilizing agents include fatty acids, C ₆ -C _8, preferably from the group consisting of palmitic acid, stearic acid and mixtures thereof. Mixtures of palmitic acid and stearic acid are preferred. Other proposed immobilizing agents include C ₁₆ -C ₁₈ fatty alcohol ethoxylates with an average degree of ethoxylation of from 5 to 20. Fatty alcohols and fatty acids should be linear. It is important that these proposed immobilizing agents, such as C16-C18 fatty alcohols, increase the level of crystallization of the component, thereby accelerating crystallization on the surface of the substrate.

Other types of immobilizing agents that may be used herein are polyhydroxy fatty acid esters, polyhydroxy fatty acid amides, and mixtures thereof. The proposed esters and amides have three or more free hydroxyl groups on the polyhydroxyl

group and are generally non-ionic in nature. Because of the possible skin sensitization of the users of the formulations to which the component has been applied, these esters and amides should be relatively mild and non-irritating to the skin.

O

II

The R-CPolyhydroxy fatty acid esters suitable for use in the present invention have the following formula:

_γ n

wherein R is a hydrocarbon group of C5-C31, typically a linear chain _C7 -C19 alkyl or alkenyl, more preferably straight chain C ₉ -C ₇ alkyl or alkenyl, most preferably straight chain Cn-C ₇ alkyl or alkenyl, or mixtures thereof. Y is a polyhydroxy hydrocarbon group having a hydrocarbon chain having at least 2 free hydroxyls directly linked to the chain and n is at least 1. Suitable Y groups can be derived into polyols such as glycerol, pentaerythritol, sugars such as raffinose, maltodextrose, galactose , sucrose, glucose, xylose, fructose, maltose, lactose, mannose and erythrose, sugar alcohols such as erythritol, xylitol, malitol, mannitol and sorbitol and sugar alcohol anhydrides such as sorbitan.

One class of suitable polyhydroxy fatty acid esters includes some sorbitan esters, especially C ₁ -C ₂ saturated fatty acid esters. These sorbitan esters usually contain, due to the way in which they are produced, what they are: · ······ · «· · yeah · mixtures of mono-, di-, tri-, etc. esters. Illustrative examples of suitable sorbitan esters are sorbitan palmitates (eg, SPAN 40), sorbitan stearates (eg, SPAN 60), and sorbitan behenates that include one or more mono-, di- and tri-ester variants of such sorbitan esters, eg, sorbitan mono di- and tri-palmitate, sorbitan mono-, di- and tri-stearate, sorbitan mono-, di- and tri-behenate as well as mixtures of sorbitan mono-, di- and tri-esters of fatty acids. Mixtures of various sorbitan esters can also be used, such as sorbitan palmitates with sorbitan stearates. Particularly suitable sorbitan esters are sorbitan stearates, generally as mixtures of mono-, di- and tri-esters (plus some tetraesters), such as SPAN 60 and sorbitan stearates sold under the trade name GLYCOMUL-S by Lonza, Inc. Although these sorbitan esters generally contain mixtures of mono-, di- and tri- esters, plus some tetraesters, usually the mono- and di-esters predominate in these mixtures.

Another class of suitable polyhydroxyesterů fatty acids comprises glyceryl monoesters some particular glyceryl monoesters of saturated fatty acids, C ₆ -C ₂ 2, such as e.g. glyceryl monostearate, glyceryl monopalmitate, and glyceryl. Glyceryl monoester mixtures, as well as sorbitan esters, usually contain some di- and triesters. However, in order to be useful in the present invention, these compositions should preferably contain glyceryl monoesters.

Another class of suitable polyhydroxy fatty acid esters comprises sucrose fatty acid esters, in particular C12-C22 sucrose fatty acid esters. Particularly suitable are sucrose monoesters and diesters, as well as sucrose mono- and distearates and sucrose mono- and dilaurates.

The polyhydroxy fatty acid amides suitable for use in the present invention have the following formula:

OR ^{1 -} 2 HIR — C — N — Z wherein R ¹ is H, a C 1 -C 4 hydrocarbon, 2-hydroxyethyl, 2-hydroxypropyl, methoxyethyl, methoxypropyl or mixtures thereof, in particular C 1 -C 4 alkyl, methoxyethyl or methoxypropyl, more preferably C 1 or C2 alkyl or methoxypropyl, most preferably Ci alkyl (i.e., methyl) or methoxypropyl and R ² is a hydrocarbon group of C5-C31, typically a straight chain _C7-C19 alkyl or alkenyl, more preferably straight chain C9 -C17 alkyl or alkenyl, most preferably linear a C11-C17 alkyl or alkenyl chain or mixtures thereof; and Z is a polyhydroxyl hydrocarbon having a linear chain with at least 3 hydroxyl groups directly linked to the chain. See U.S. Patent 5,174,927, which describes these polyhydroxy fatty acid amides and their preparation.

The group Z is derived from a reducing sugar in a reductive amination reaction, preferably glycityl. Suitable reducing sugars are glucose, fructose, maltose, lactose, galactose, mannose and xylose. In addition to these sugars, high dextrose corn syrup, high fructose corn syrup and high maltose corn syrup may also be used. From these corn syrups, a mixture of sugar components may be formed for the Z group.

The group Z is selected from the group consisting of -CH ₂ - (CHOH) _n CH ₂ OH, - CH ₂ (CH ₂ OH) - [(CHOH) _{n -} ] - CH ₂ OH, -CH ₂ OH-CH ₂ (CHOH) ₂ (CHOR ³ ) - (CHOH) -CH 2 OH, wherein n is an integer from 3 to 5 and R ³ is H or a cyclic or aliphatic monosaccharide. Particularly suitable are glycityls wherein n is 4, especially -CH 2 - (CHOH) ₄ -CH ₂ OH.

In the above formula, R ¹ may be, for example, N-methyl, Nethyl, N-propyl, N-isopropyl, N-butyl, N-2-hydroxyethyl, N-methoxypropyl or N-2-hydroxypropyl. R ² may be selected, for example, to form cocamides, stearamides, oleamides, lauramides, myristamides, capricamides, palmitamides, tallowamides and the like. 1-deoxymanityl, 1-deoxymaltotriotityl and the like.

The most suitable polyhydroxy fatty acid amides have the following general formula:

O R1

OH

AND

CH

_R2-C-N-CH2

CH ₂ —OH wherein R ¹ is methyl or methoxypropyl, R ² is a linear chain C ₁ -C ₁₇ alkyl or alkenyl group. These include N-lauryl-N-methyl glucamide, N-lauryl-N-methoxypropyl glucamide, N-cocoyl-Nmethyl glucamide, N-cocoyl-N-methoxypropyl glucamide, N-palmityl • · • »

N-methoxypropyl glucamide, N-tallowyl-N-methyl glucamide or Ntallowyl-N-methoxypropyl glucamide.

As previously noted, some immobilizing agents need an emulsifier to dissolve in the plasticizer. This applies in particular to certain glucamides, such as N-alkyl-N-methoxypropyl glucamides having an HLB value of at least 7. Suitable emulsifiers are generally those having an HLB value of less than 7. In this respect, it has been found that sorbitan esters such as e.g., sorbitan stearate having an HLB value of 4.9 or less are suitable for dissolving glucamide immobilizing agents in petrolatum. Other suitable emulsifiers are steareth-2 (polyethylene glycol ethers of stearyl alcohol which are formed according to the formula CH ₃ (CH 2) 17 (OCH ₂ CH 2) _n OH where the average value of n is 2, sorbitan tristearate, isosorbide laurate and glyceryl monostearate. For example, a mixture of about 1.1 N-cocoyl-N-methyl glucamide and petrolatum, which does not normally dissolve into a single-phase mixture, is added after adding 20% Steareth-2 and sorbitan tristearate. as an emulsifier dissolved in a single phase mixture.

Other types of additives that may be used as immobilizing agents, either alone or in combination with the aforementioned immobilizing agents, are waxes such as carnauba palm wax, natural wax, beeswax, candelila, paraffin, ceresin, esparto, ouricuri, rust wax, isoparaffin and other known extracted and mineral waxes. The high melting point of these substances allows the component to be immobilized on the desired surface or area of the composition. Microcrystalline waxes are also good immobilizing agents. Microcrystalline waxes help to lock low molecular weight hydrocarbons within the dermatological component. Paraffin wax is suitable. An example of an alternative immobilizing agent is a paraffin wax such as Parrafin S.P. 434 from Strahl and Pitsch lne.

The amount of immobilizing agent to be contained in the ingredient depends on a number of factors, including the content of the active ingredients (eg plasticizers), the type of immobilizing agent concerned, if used, the other components of the ingredient, whether an emulsifier is needed to dissolve the immobilizing agent in the other ingredients. and other similar factors. When the immobilizing agent is used, its content in the component is generally 5 to 90%. Preferably, the immobilizing agent content of the component is from 5 to 50%, preferably from 10 to 40%.

It is desirable that at least a portion of the topsheet of the composition be made of a hydrophilic material to facilitate fluid transfer (e.g., urine). Furthermore, it is also desirable that the dermatological component be sufficiently wettable to allow rapid transfer of fluids through the topsheet. Hydrophobic dermatological components may also be used, but only to the extent that the necessary properties of the topsheet are not impaired. (One possibility is, for example, applying a component to only a portion of the topsheet.) This will reduce the likelihood that body exudates will flow out of the treated topsheet before they can be absorbed through the topsheet into the absorbent core.

If a hydrophilic component is desired, it may be necessary to add a hydrophilic surfactant (or a mixture of hydrophilic surfactants) to improve wettability.

surfactants), depending on the respective components used in the ingredient. Ala, some immobilizing agents such as N-cocoyl-N-methoxypropyl glucamide have HLB values above 7 and are sufficiently wettable even without the addition of a hydrophilic surfactant. Other immobilizing agents such as e.g. the fatty alcohols, C ₆ -C ₈ with HLB values below 7 for improving wettability may require addition of hydrophilic surfactant. Similarly, a hydrophilic surfactant must be added to a hydrophobic emollient, such as petrolatum, if the component is required to be hydrophilic. Of course, it is of no importance to address wettability if the user-contacting surface is not the topsheet of the device or if the desired properties of the topsheet are provided by other means (e.g., partial deposition).

Suitable hydrophilic surfactants should be miscible with other components of the dermatological component to form mixtures. Because of the possible hypersensitivity of the skin of users of absorbent articles having a dermatological component applied, these surfactants should be relatively soft and non-irritating. These hydrophilic surfactants should be nonionic so as not to irritate the skin but also to avoid adverse effects on other parts of the formulated composition. E.g. reduction of tensile strength, quality of adhesive joints, etc.

Suitable nonionic surfactants should be immobile upon application of the component to the composition and have HLB values of from 4 to 20, preferably from 7 to 20. In order to be immobile, these non-ionic surfactants generally have a melting point above which the absorbent articles are exposed during storage, transport, sale and use, e.g. at least 30 ° C. In this regard, nonionic surfactants generally have melting points similar to those previously described as immobilizing agents.

Suitable nonionic surfactants for use in the formulations applied to the composition, at least in the effluent area, are the alkyl glycosides, alkyl glycoside ethers described in U.S. Pat. No. 4,011,389, alkyl polyethoxy esters such as Pegosperse 1000MS from Lonza, Inc., Fair Lawn, New Jersey, ethoxy sorbitan mono-, di- and / or tri-esters of C ₁₂ -C ₁₈ fatty acids with an average degree of ethoxylation of from 2 to 20, preferably from 2 to 10, such as TWEEN 60 (sorbitan stearic esters with an average degree of ethoxylation of 4); condensation products of aliphatic alcohols with 1 to 54 moles of ethylene oxide. The alkyl chain of the aliphatic alcohol is generally linear in configuration and contains from 8 to 22 carbon atoms. Particularly suitable are the condensation products of alcohols having an alkyl group containing from 11 to 22 carbon atoms with 2 to 30 moles of ethylene oxide per mole of alcohol. Examples of such ethoxylated alcohols are 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 with alkyl chains of 10-14 carbon atoms) with 6 moles of ethylene oxide. A number of suitable ethoxylated alcohols are commercially available, including Tergitol 15-S-9 (a 9 mole ethylene oxide condensation product of Cn-C18 linear alcohols) sold by The Union Carbide Corporation, KYRO EOB (a 9 mole ethylene oxide condensation product of C13-C15). Procter & Gamble Co., NEODOL surfactants from Shell Chemical Co., in particular NEODOL 25-12 (condensation product of linear alcohols C12-C15 with 12 moles of ethylene oxide) and NEODOL 23-6.5T (condensation product of linear alcohols C12-C13

Β ··· «Β

6 »β β Β Β ,5 Β Β ,5 Β Β Β 6 6 6 6 6 6 6 6 ,5 6 ,5 ,5 ,5 ,5 ,5 ,5 ,5 6 6 6 6 6 6 6 ,5 6 ,5 ,5 6 ,5 6 ,5 ,5 6 6) to BASF Corp., in particular PLURAFAC A-38 (the condensation product of a C 18 linear alcohol with 27 moles of ethylene oxide). (Some hydrophilic surfactants, especially ethoxylated alcohols such as NEODOL 25-12, may act as alkyl ethoxylate plasticizers). Other suitable examples of ethoxy alcohol surfactants are Brij surfactants and mixtures thereof, especially Brij 72 (i.e. Steareth-2) and Brij 76 (i.e. Steareth-10). Furthermore, mixtures of ethoxylated cetyl alcohol and stearyl alcohol with an average degree of ethoxylation of from 10 to 20 can also be used as hydrophilic surfactants.

Another surfactant suitable for use in the ingredient is Aerosol OT, a sodium sulfosuccinic acid dioctyl ester sold by the American Cyanamid Company.

Other suitable surfactants are silicone copolymers such as General Electric SF 1188 (a copolymer of polydimethylsiloxane and a polyoxyalkylene ether) and General Electric SF 1228 (a silicone copolymer of polyether). These silicone surfactants may be used in combination with the other types of hydrophilic surfactants mentioned above, such as ethoxylated alcohols. It has been found that these silicone surfactants are already effective at a concentration of 0.1%, preferably up to 0.25 to 1.0% by weight of the component.

If a hydrophilic component is desired, the amount of hydrophilic surfactant required to increase the wettability of the component to the desired level depends in part on the HLB value and the amount of immobilizing agent, if used, the HLB value used. · 9 9 9 9 9 9 9 9 9 9 9

1 2 3 4 5 «« »·»

W 9 9

9 9 999 9999 99 9 9 surfactant and other similar factors. To increase the wettability, the component may contain from 0.1 to 50% of a hydrophilic surfactant. However, to increase wettability, the component typically contains from 1 to 25%, preferably from 10 to 20%, of a hydrophilic surfactant.

The component may contain other components commonly present in emulsions, ointments, solutions, suspensions, etc. of this type. These components include water, viscosity modifiers, perfumes, disinfectant antibacterial agents, antiviral agents, vitamins, pharmaceuticals, coating agents, deodorants, opacifiers, astrigents, solvents, preservatives, etc. In addition, stabilizers, such as cellulose derivatives, proteins and lecithin. All of these are well known in the art as additives and can be used in the appropriate amounts in these ingredients.

If a water-based dermatological component is used, a preservative must be used. Suitable preservatives are propylparaben, methylparaben, benzyl alcohol, benzylkonium, tribasic calcium phosphate, BHT or acids such as citric, tartaric, maleic, lactic, malic, benzoic, salicylic and the like. Suitable viscosity enhancing agents include some of the substances described as effective immobilizing agents. reagents. Other suitable viscosity enhancing agents are, for example, alkylgalactomannan, silica, talc, magnesium silicate, sorbitol, colloidal silicone dioxide, magnesium aluminum silicate, zinc stearate, wool wax alcohol, sorbiton, sesquioleate, cetylhydroxyethylcellulose and other cellulose. Suitable solvents are propylene glycol, glycerin, cyclomethicone, and the like.

999999 9 9

9 9 9 9 9

Polyethylene glycols, hexalenglycol, diol and polyhydroxy solvents. Suitable vitamins are A, D ₃ , E, B ₅ and E acetate.

VI. Applying the component to the composition

The absorbent article must be formulated so that the dermatological component containing the enzyme inhibitor, when worn, is at least partially transferred from the treated article to the skin of the wearer.

Thus, the dermatological component is applied either directly to one or more surfaces that touch the wearer or is applied elsewhere or otherwise so as to be readily available for transmission from one or more surfaces that touch the wearer during wear, independently of the wearer. him. (For example, substances deposited under the surface that touches the user, the encapsulated component, etc.) Of course, in order to streamline the component to the areas most heavily loaded, it is necessary to apply the component to the buttocks, genital, groin areas and anal areas. In addition, the component may be applied to other areas of the device to transfer to the hips, abdomen, back, waist, thighs, etc. Suitable methods include spraying, printing (eg flexographic printing), coating (eg slit coating, imprint coating) extrusion or a combination of these application methods, e.g., spraying a dermatological component on a rotating surface, such as a compression roller, which then transfers the component to the desired portion of the composition. The dermatological component containing the enzyme inhibitor may be applied as a solid by any of a number of procedures, eg extrusion.

»»

9 9 • ·

9 • »9 * * * *

«· ♦ ·· ♦ ··

If the component is hydrophobic in nature, it may happen that, when applied to the topsheet of the composition, the layer will not be fully saturated with the component in the region corresponding to the outlet area of the composition. If the topsheet is saturated with the component in the outlet area, there is a high risk that the component will block the topsheet openings, thereby reducing the ability of the topsheet to transfer fluids to the underlying absorbent core. Saturation of the topsheet is also undesirable to achieve a therapeutic and / or protective effect. Likewise, saturation of other components of the composition may not be desirable. Suitable methods of application are those in which the component is applied primarily to the outer surface of the topsheet of the composition.

The minimum amount of the enzyme inhibitor-containing component applied to the surface of the user-contacting composition of the invention corresponds to an amount sufficient to provide a therapeutic, protective and / or skin-enhancing effect. The amount of deposited component depends on various factors, including the composition to be treated, the relative surface of the user's surface not covered by the component, the composition of the component, etc. Generally speaking, if relatively hydrophobic components are used and are applied to the entire topsheet, components in the range from 0.016 mg / cm ² to 2.33 mg / cm ² , more preferably from 0.16 mg / cm ² to 1.55 mg / cm ² . It will be appreciated that a greater amount of dermatological component may be applied to other parts of the composition where the distribution of the fluid is not impaired (e.g., cuffs, waistband, side panels, etc.). It will further be appreciated that the relatively hydrophilic components may be applied to the topsheet in greater amounts without significantly affecting the distribution properties. Conversely, a larger amount of the hydrophilic component may be undesirable when applied to a portion (e.g., cuff, waist)

4 ·

4 «44

4 4 4 4 ·

44443 «4 4

4 4 4 4 • · * 4444444

4 4 4 4 4 4 4 other than the top layer, where exudates may be sucked to the edges and leaked.

Since the component is completely immobilized on the surface, only a small amount is sufficient to transfer an effective amount of the enzyme inhibitor. It is believed that these small amounts are sufficient to achieve the desired effect on the skin, since the ingredient is sustained, spontaneously released during wear. That is, the possibility of using relatively low levels of the dermatological component makes the topsheet of the device able to maintain its transfer properties in the area of fluid outflow.

The component may be non-uniformly applied to the wearer's surface. By non-uniform is meant that the amount, location, layout pattern, etc. of the component may be different on the user-contacting surface and may vary in other areas of the composition. For example, in order to maintain the distribution properties of the topsheet, it may be necessary to apply the component in a non-uniform manner, especially if it is of a hydrophobic nature. For this reason, some portions of the treated surface of the composition (and its region) must have greater or lesser amounts of the component, including portions to which the component is not applied. In one such embodiment, where the component is relatively hydrophobic, the topsheet surface has an area to which the component has not been applied, particularly in the region of the topsheet that corresponds to the crotch region. The crotch region of the device as used herein is a rectangle defined below that is centered longitudinally and transversely to the crotch point. The crotch point is determined when the user wears the device and stretches the fiber around the legs in the shape of an eight. The point of the device which corresponds to the penetration of the fibers is considered to be the point φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ (Obviously, the crotch point is determined by placing the absorbent article on the wearer in a determined manner and determining where the crossed fibers contact the article). For incontinence devices (e.g., diapers, adult incontinence devices), the crotch region length is 40% of the total length of the absorbent article (i.e., the y dimension). In sanitary napkins, the crotch region length is 80% of the total length of the absorbent article. The width of the crotch region is the same as the width of the widest portion of the absorbent core measured at the crotch point. (Parts of the absorbent core are substances that are involved in the absorption, transmission, distribution and / or storage of body fluids. The term absorbent core does not include the topsheet or backsheet of the absorbent article.) the crotch area is 10 cm, the crotch area is rectangular, centered on the crotch point and its length is 20 cm and the width is 10 cm.

Surprisingly, by non-uniform application of the component to the topsheet or portions thereof (e.g., microscopic or macroscopic areas where no component is applied), the component is transferred to the user even in areas of the skin that correspond to untreated topsheets or portions thereof. The amount and uniformity of the component transferred to the skin depends on a number of factors including, e.g., the method of applying the dermatological component, the skin contact of the user and the treated area, the friction that arises during wear between the user's skin and the treated area; the properties of the component, the substances which form the component, etc.

·

4 »4

4 4 4

4 4 4 4 4 • 44

4 4 ·

A variety of patterns may be used in non-uniform application of the component, including, for example, applying small drops (e.g., by spraying), tiny dots (e.g., engraved printing), longitudinal or transverse strips (formed by a tactile slot coating), spirals that longitudinal, etc., sample printing, etc. In these embodiments, where the topsheet comprises separate, untreated precursors, the extent of the open portion of the crotch region of the topsheet may vary considerably. (The extent of the open portion of the topsheet is determined by (i) measuring the surface of the topsheet belonging to the crotch area, (ii) measuring the total surface area of the untreated area in that portion of the topsheet, and (iii) dividing the measurement result from As used herein, the term unadjusted means that the topsheet region contains less than 0.0016 mg / cm ^{2 of} component In this respect, the range of open portion may be from 1% to 99%, from 5% to 95%, from 10% up to 90%, from 15% to 85%, from 20% to 80%, from 25% to 75%, from 30% to 70% or from 35% to 65%. The distribution properties of the topsheet are largely determined by the properties of the component (especially its composition and the ratio of hydrophobic and hydrophilic properties). The skilled artisan will appreciate that the desired extent of the open portion can be readily determined by simple experimentation.

Components that are relatively hydrophobic and are not to be applied to the topsheet regions are first applied to the topsheet of the composition in an amount of from 0.0078 mg / cm ² to 5.43 mg / cm ² , more preferably from 0.16 mg / cm 2 ² to 3.88 mg / cm ² and most preferably from 0.62 mg / cm ² to 3.1 mg / cm 2. It will be appreciated that the components that are relatively hydrophilic can be applied in large quantities without significantly affecting the distribution properties of the topsheet. Of course, compositions with a relatively high percentage of crotch open areas may also have larger amounts of component applied without significantly affecting the distribution properties of the topsheet.

In one proposed embodiment, the topsheet is coated with longitudinal strips of the component. These longitudinal strips (or spirals) are separated from each other by longitudinal strips where little or no component is applied. In these embodiments, each component strip generally has a width of from 3 mm to 20 mm, preferably from 3 mm to 13 mm, and the width of the non-component strips is usually from 3 mm to 26 mm, more preferably from 4 mm to 13 mm. These ranges are applicable to conventional diapers. For larger products, such as adult incontinence products, these ranges may be larger.

The dermatological component may also be applied to other parts of the composition in a non-uniform pattern. In these cases, the open area can be calculated from a rectangle determined by the circumference of the dermatological component.

The component may be applied to the composition at any time during folding. For example, the ingredient may be applied to the finished absorbent article prior to packaging. The component may also be applied to a given portion (eg, topsheet, cuffs, sidewalls, waist, etc.) at the exchange site or fabric supplier before being bonded to the other portions into the finished absorbent composition. The component may also be applied to other areas of the composition such that it will be possible to pass over the wearer on one or more surfaces contacting the user.

9 * '·

99 99

9

99999 9 • 9 9

9 9

9 9

9 9

9

As a rule, the component is applied to the composition in its heated state because its melting point is substantially higher than the ambient temperature. The component is usually heated to a temperature in the range of from 35 ° C to 150 ° C, more preferably from 40 ° C to 100 ° C, before application to the composition. The enzyme inhibitor may be added to the ingredient before or after heating. If added before heating, the temperature must be selected so as not to denature it. Alternatively, the enzyme inhibitor may be added to a preheated component which has already been partially cooled to a temperature that does not damage the enzyme inhibitor but is sufficient to deposit the component on the composition. The liquid component is allowed to cool and solidify after application to the composition. The deposition procedure of the component is usually modified so that cooling is active.

Slit coating, spraying, engraved coating and extrusion are preferred when applying the component to the composition. One of these methods is the slot coating of the topsheet of the composite finished composition.

VII. Methods of testing

A. Transfer of the dermatological component and enzyme inhibitor to the skin of the user

Overview

This procedure utilizes a removable skin analog that is placed on the wearer's skin for a period of time. The cutaneous analog is then removed and the amount of dermatological component or amount of protease inhibitor in the extract of the analog obtained by solvent is determined by conventional analytical procedures. This procedure is described

9

9999

9 9

9 9 · 9 • 9999 for use in diapers containing a dermatological component with an enzyme inhibitor. The skilled artisan can determine appropriate changes for other dermatological components, protease inhibitors, absorbent articles or types of users.

Tested individuals

According to the following characteristics, two approximately equal groups of male and female children should be selected. Sufficient children should be selected to ensure that no less than 15 individuals complete all parts of each test.

Conditions of inclusion

a. Healthy child.

b. A caregiver willing to avoid using solutions, creams, dusting powders or other dermatological preparations in the diaper area during the test.

c. Children who wear diapers throughout the day.

d. A caregiver willing to bathe the child the day before the test, not before it is completed.

e. The caregiver willing to refrain from swimming the child from the evening before the test until it is completed.

Exclusion conditions

a. The child has been ill during the last four days.

b. Diarrhea (loose stools) within four days prior to the test.

c. Medicines that may increase intestinal emptying (eg, oral antibiotics, antifungals, corticosteroids).

d. Damaged skin at or around the test site (eg, burns, active skin lesions, etc.).

494 4494

9 9 9 9

9 9 9

9 9

e. Known allergies or irritations from sticky or dermatological components.

Substances

In vivo transmission

Skin analogue:

Sample Dispenser Dermatological Tape - TEGADERM Tape 1622W available from 3M Health Cares, St. Paul, MN closure jar from VWR Scientific, West Chester, PA under the designation 15900242

Tape Release Powder: Baby powder (containing only talc and fragrance composition) to Johnson & Johnson, New Brunswick, NJ

Surgical Gloves: from Best Manufacturing Co., Menlo GA, under the designation 6005PFM

Extraction and analysis of dermatological component

Solvent:

Stearyl alcohol: 1-hexadecanol: Preparation vial: Gas chromatograph:

dichloromethane from Louis, MO, 27056-3 Aldrich 25876-8 Aldrich 25874-1 10 ml suitable for ionization Packard model 5890

Sigma-Aldrich

detector from Hewlett

· * Z z - - - - - - - - - - - - z ^{z z z z z z z z z z ν} ··· ·· · · · ··· · ··· ···· · ♦ ·· Column: Chrompack CP Sil-5 capillary column CB, 2 meters x 0.25 mm of silica

0.12 gm glass film (without replacements)

System instrumentation: it must be possible to redefine the areas with the highest values

Extraction and assay of a typical inhibitor (eg hexamidine) of an enzyme (eg protease)

Solvent:

dichloromethane from Sigma-Aldrich, St. St. Louis, MO, 27056-3

Preparation vial: 10 ml

Column: Hewlett Packard Zorbax SB-CN with narrow bore 5 gm, 2.1 x 150 mm with Waters Bondapack CN 10 gm, protective column

3.9 x 20 mm

System instrumentation: it must be possible to redefine the areas with the highest values

Way

In vivo transmission

A. Confirmation from the caregiver that the child has been bathed in the last 24 hours and that no solutions, dusting powders, etc. have been applied to the area covered by the diaper since.

B. Put on surgical gloves, place baby on table and remove diaper.

C. Turn the baby to the tummy.

D. Remove the liner from the TEGADERM tape and gently dust the adhesive surface with J&J Baby Powder (all done in surgical gloves to prevent soiling of the tape). Apply sufficient powder over the entire tape range except the edges. (This is done to prevent the tape from sticking too aggressively to the baby's skin).

E. Figures 2a and 2b show the location of the TEGADERM tape, referred to herein as the tape 700. The tape 700 is applied to the right buttock of the infant. The tape 700 is applied to the highest point of the baby's buttocks near the gluteal groove. To measure transmission over two time periods or to measure the effect of another diaper, a second tape 700 may be applied. If a second tape 700 is used, then it is applied to the left buttock in the same manner.

F. The diaper change is performed according to the following protocol: transmission time 3 hours - 1 diaper, transmission time 6 hours - 2 diapers (3 hour change), transmission time 24 hours ad lib caregiver. For a 24-hour transmission time, the following additional instructions must be followed:

1. Use only water and washcloth to clean the diaper area during the test. Do not use baby towels. Do not touch the area around the tapes with your hand or cleaning tool.

• 4 • 4 4 • • 444 4

4 4

4 4

4 4

444 44 4444

4 · 4,444 4 · »4 ·· 44

2. Do not use dermatological preparations (solutions, ointments, creams, soaps, etc.) during the test.

3. Do not bathe the child during the test.

4. Use only tested diapers.

5. Record the time of excretion and wash the baby with water and washcloth.

G. Record the time of application of each diaper tested.

H. Call the child before the specified transmission time.

I. Remove the test diaper. If the infant has evacuated the bowel, the tape 700 should be removed and discarded (the child has completed the test and data will not be included in the assay). If the baby has urinated, the tape 700 is acceptable for analysis as shown below.

J. The investigator removes the tape 700 by grasping its edge with tweezers and gently peeling it off the skin. All in surgical gloves.

K. Prepare a glass and mark the sample carefully for later identification.

L. When the test is complete, place all samples in the assay glasses described below.

1. Extraction and analysis of test samples of the dermatological component • 9 • 9 • 9 • 9 • 9 · Β ·

ΒΒ · ·

ΒΒ ΒΒ

This method is intended for testing the proposed dermatological component, the component of Table 4. The skilled artisan knows what adjustments are necessary to extract and analyze other dermatological components. In general: (1) one of the major parts of the dermatological component is extracted from the skin analogue using an appropriate solvent; the amount of the main part in the extract and the area of the tape.

Internal standard / solvent

Prepare the internal standard / solvent by accurately weighing 100 ± 2 mg of 1-hexadecanol into a small beaker. Dissolve 1-hexadecanol in dichloromethane and transfer to a graduated cylinder. Rinse the beaker 3 times with dichloromethane and always pour the contents into a graduated cylinder. Refill the cylinder volume and mix well. This solution will be used to create an internal standard and extract the dermatological component from the tapes. The solvent container should be tightly closed to prevent evaporation.

Standard calibration

Prepare a calibration standard of known concentration by accurately weighing (± 0,1 mg) 10 ± 1 mg of stearyl alcohol into a 100 ml graduated cylinder. Record the weight of stearyl alcohol used. Add the internal standard / solvent to the drum and mix until dissolved. Top up and mix again. The solvent container should be tightly closed to prevent evaporation. This solution will be used in the determination of each other. The response of stearyl alcohol and 1-hexadecanol internal standard when calibrating the instrument.

Preparation and calibration of gas chromatograph

Install the column and check the gas flow through the column at

100 ° C and injection port and detector at operating temperatures. The flow chromatograph will operate under the following conditions:

Carrier gas: hydrogen (helium may also be used), flow rate 1.5 ml / min.

Injection hole: 325 ° C, flow rate 30 ml / min, partition cleaning 2 ml / min, glass wool insert, Merlin micro seal.

Injection volume: 2 μΐ divided.

FID detector: 350 ° C, set gas flows according to manufacturer's instructions. Typical gas flow rates are 400 ml / min for air, 30 ml / min for hydrogen and 30 ml / min for auxiliary gas.

Column thermostat: 100 ° C with increments of 15 ° C / min to 325 ° C, takes minutes.

Make sure all connections are tight and do not pass.

Light the detector and let it stabilize. Leave the column at 325 ° C for 30 minutes. Clean the syringe with dichloromethane. The syringe should also be flushed several times after each injection. Perform a few blind rounds with dichloromethane until you get a good baseline without undue peaks. If improper peaks appear or the baseline is not good, try to correct the problem.

• • • •

Set the instrument to the calibration standard previously prepared. Follow the manufacturer's recommendations to determine the correct order of operations. Calculations should be performed in a similar way as described below.

Sample analysis procedure

1) Remove the sample glass lid and add 10 ml of solvent / internal standard solution using a dispenser. Close the lid and twist the contents until the tape 700 is not attached to the sides of the glass and is completely immersed in the solvent. Repeat with all samples.

2) Leave the samples for 16 hours (usually overnight).

3) Mix the contents of the glass. Using a pipette, transfer all sample extract to the labeled vial. Close the vial with the cap. Close the glass and leave it until the assay is complete. Repeat with all samples.

4) Put the vials in random order into the tester and start the assay under the conditions described above. The first ampoule should be a blank control with dichloromethane. Several control standards (about every 20th sample) should be included to verify measurement accuracy.

5) After each measurement, check each chromatogram to confirm that the assay is correct. If there is a problem, try to identify and fix the problem. If necessary, re-analyze the samples.

Calculations

The number of micrograms of stearyl alcohol in the extract of each sample is calculated based on the relative response of the peak of stearyl alcohol to the peak of the internal standard of 1-hexadecanol. The peak area ratio is multiplied by the relative reaction factor (determined during instrument calibration) and the micrograms of the internal standard in the extract to obtain the total pg of stearyl alcohol in the sample.

Instrument calibration

Determination of the relative reaction factor of the stearyl alcohol apparatus and of the internal standard, which are derived from the peak area of stearyl alcohol and 1-hexadecanol in the chromatogram of the calibration standard.

The reaction factor (R _c) = _inp ^plochavst weight hmotnostsa plochasa area where _VST = peak area for the internal standard.

area _sa = peak area for stearyl alcohol. mass _vs t ⁼ micrograms of internal standard used to prepare internal standard / extraction solvent.

mass _S a ⁼ micrograms of stearyl alcohol used for the preparation of the calibration standard

Sample calculations

The number of micrograms of stearyl alcohol in each sample is calculated from the peak area in the sample chromatogram according to the following equation:

area weight _V st

Number of pg SA = area _input

Rf

100 c 4 ··· 4 4 4 4 · · · ·

4 ·· 4 · 4444 · 4444 ·· · 4 4 4 44

444 44 4444

4 · 9 4444444 ·· ·· where area _vst = peak area of the internal standard.

area _sa = peak area of stearyl alcohol. weight ⁼ micrograms of internal standard used to prepare internal standard / extraction solvent.

Calculate the transferred amount of dermatological component in mg / cm ² where:

Folder transferred = _ο, οοϊ x pg stearyl alcohol_ (SA concentration in folder) x (tape area)

In the method described above, the stearyl alcohol concentration in the component is 41% and the tape dimensions are 4.4 cm x 4.4 cm.

Folder transferred = (0.001 x pg stearyl alcohol in the folder) / (0.41 x

4.4 cm x 4.4 cm) = 0.000126 x pg stearyl alcohol (mg / cm ² )

2. Extraction and assay of protease inhibitor in test sample

The method is adapted for use with a dermatological component containing the protease inhibitor of Table 1. The skilled artisan knows what adjustments are necessary to extract and analyze other protease inhibitors. In general: 1) the protease inhibitor is released from the skin analog by treatment with an appropriate solvent, 2) then HPLC or other quantitative analytical technique is used to determine the inhibitor level in the extract, 3) the amount of protease inhibitor is calculated as unit area tape.

Preparation of standards

To prepare a 10 µg / ml standard hexamidine solution, weigh 0.10 grams +/- 0.02 grams of hexamidine diisothionate and dissolve it in the mobile phase (10% crystalline acetic acid and 17.5% methanol) of the HPLC solution. Prepare additional hexamidine standards from a standard solution of 10 µg / ml, see Table 2, and make up to 100 ml with HPLC mobile phase solution.

Table 2

Preparation of standards *

standard standard solution hexamidine (ml) final volume (ml) nominal concentration (pg / ml) 1 5.0 100 ALIGN! 0.5 2 10.0 100 ALIGN! 1.0 3 25.0 100 ALIGN! 2.5 4 50.0 100 ALIGN! 5.0

Sample preparation

1. Place the test transfer tape in a 40 ml glass vial.

2. Add 10 ml of dichloromethane and close the vial tightly.

3. Shake the vial for 30 minutes.

4. Remove the vial from the shaker, remove the vial cap and add 10 ml of mobile phase HPLC solution. Close the vial and shake again.

5. Shake the sample for 30 minutes to dissolve hexamidine in the aqueous phase.

6. Allow sample to settle and separate layers for at least 30 minutes.

• 4 4 5 · 4 4 4

4 4 4 · · 4 · · 444444 4 · · · 4 ·

2 <· ♦ ♦ 4 4 4 4 4 4 4 4

7. After separating the sample, remove the water (top) layer with a syringe and filter through a 0.45 µm filter.

Sample analysis

Carry out the chromatography of standards and samples according to the conditions described in Table 3.

Table 3

Chromatographic conditions

Mobile phase flow: 0.25 ml / min Mobile phase: 10% crystalline acetic acid, 17.5% methanol Injection volume: 10 ml UV detector wavelength: 254 nm Sensitivity of UV detector: 1,000 AUFS UV detector filter: 2,0 s Time: 10.0 min

Calculations

1. Standard concentration (mg / ml):

Si (mg / ml) = W (mg) / 100 * (Vi / 100)

W = hexamidine mass for standard stock solution

Vi = volume of hexamidine stock solution used to prepare the standard (Table I)

2. Calibration curve

A. Create a table mg / mL of hexamidine in each standard (Si) and the responses (peak area or peak height) R _{i 5} for each of the solutions.

B. Create a calibration curve according to equation (2).

Ri = mSi + b (1)

3. Test samples

A. Calculate the amount of hexamidine (Hi) in the sample extracts using the measured response R and the calibration equation:

Hi = (R-b) / m

B. Calculate the amount of hexamidine (H) in the samples in mg according to equation 4.

H = Hi * 10

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 analog.

DETAILED DESCRIPTION OF THE INVENTION

The following are individual examples of (a) applying a dermatological component to the diaper topsheet and (b) methods of the present invention using compositions comprising these topsheets. A similar approach can be used to modify other parts of such a device.

• 4 44 4 4 • 4 4 ·· 4 · · 4 · 4

4 1 »9 9 4

9 9 9

Example 1

Preparation and testing of a topsheet absorbent composition comprising a dermatological component and an enzyme inhibitor

A. Preparation of dermatological components

Folder 1

The dermatological component is formed by mixing the following components: 99 parts of a heated (i.e. liquid) base composition comprising 85 parts of SEFA cotonate (sucrose polycotonate from Procter & Gamble Co., Cincinnati, OH) and 15 parts of SEFA behenate (sucrose polybehenate from Procter & Gamble Co) (Cincinnati, OH) with 1 part acetohydroxamic acid (Sigma Chemicals, St. Louis, MO).

Folder 2

The dermatological component is formed by mixing the following components: 99 parts of a heated (i.e. liquid) base composition comprising 58 parts of petrolatum (from Witco Corp., Greenwich, CT as White Protopet), 41 parts of stearyl alcohol (from Procter & Gamble Co., Cincinnati, OH as CO 1897) and 1 part aloe extract (from Madis Botanicals, Inc., S. Hackensack, NJ as Veragel Lipoid in Kaydol) with 1 part tranexamic acid (Sigma Chemicals).

Folder 3

The dermatological component is prepared in the same manner as component 2 except that triacetin is used instead of tranexamic acid.

«· 9 • · · · ·

Folder 4

The dermatological component is formed by mixing the following components: 9 parts of a heated (i.e. liquid) base composition comprising 58 parts of petrolatum (from Witco Corp., Greenwich, CT as White Protopet), 41 parts of stearyl alcohol (from Procter & Gamble Co., Cincinnati, OH as CO 1897) and 1 part aloe extract (from Madis Botanicals, Inc., S. Hackensack, NJ as Veragel Lipoid in Kaydol) with 1 part heated (i.e., 60 ° C) inhibitor component containing 9 parts Tween 60 (ICI Surfactants) and 1 part hexamidine diisothionate (from Laboratories Serobilogiques, Pulnoy, France as Elestab HP100).

B. Preparation of the composition by contact slot coating

The component of Table 1 is placed in a heating tank at an operating temperature of 77 ° C. Then, the component is applied by a contact applicator (e.g. Meltex EP45) to the topsheet of the composition in strips that run longitudinally. 5 strips, each 0.54 cm wide, are accurately applied. (i.e., in the transverse dimension of the composition) and a length of 25.4 cm and the applied amount is 1.19 mg / cm ² . The distance between the strips is 0.67 cm.

Example 2

A method of improving skin condition

An adult incontinence patient weighing 82.5 kg, uses absorbent articles and suffers from mild erythema, wears an adult incontinence article similar to that of Example 1 for at least 5 days. The composition is changed in a manner customary for the user (usually every 4-5 hours during the day and before bedtime).

«· *

During this time, there is no user intervention (eg application of dermatological products). At the end of these 5 days, erythema diminished or disappeared.

Example 3

A method of improving skin condition

A child weighing 16 kg, suffering from diaper rash and erythema, wears the diapers of Example 1 for at least 5 days per night (i.e., uses the untreated composition during the day). The caregiver replaces the diapers in the normal way. During this time, there is no intervention by the caregiver (eg application of dermatological products). At the end of these 5 days, a reduction or disappearance of the rash and erythema was observed.

Example 4

How to maintain skin condition

A child who weighs 12.5 kg and does not have a diaper rash or erythema is examined for otitis media and is prescribed treatment with systemic antibiotics. Based on experience with conventional (unadjusted) diapers, the caregiver assumes that the child develops erythema and / or diaper rash as a result of thinner stools. The diapers described in Example 1 are continuously worn while taking antibiotics. During this time, there is no user intervention (eg application of dermatological products). No erythema or diaper rash is observed in the infant while receiving antibiotics.

Descriptions of all patents, patent applications (and all patents relating to the subject matter, as well as relevant published foreign patent applications) and publications mentioned in this specification are incorporated herein by reference. However, it is not admitted that any of the documents disclosed herein describe the present invention.

Although particular embodiments of the present invention have been illustrated and described, it will be apparent to those skilled in the art that various other changes and modifications may be made without departing from the scope of the invention. It is therefore our intention to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims (13)

PATENT CLAIMS An absorbent composition, a portion of which comprises a dermatological component with an enzyme inhibitor, wherein the dermatological component containing the enzyme inhibitor is at least partially transferred from the composition to the skin of the user of the composition during normal contact, movement of the user and / or body heat. The composition of claim 1, wherein the enzyme inhibitor is selected from a protease inhibitor, a lipase inhibitor, a bile salt inactivator, an elastase inhibitor, a urease inhibitor, an amylase inhibitor, or a mixture thereof. Composition according to claim 1 or 2, characterized in that the dermatological component is solid or semi-solid at 20 ° C. Composition according to claim 1, 2 or 3, characterized in that the dermatological component comprises 5% to 95% of a plasticizer, which is malleable or liquid at 20 ° C and further preferably comprises 5% to 95% of an agent capable of immobilizing the plasticizer in the plasticizer. and having a melting point of at least 35 ° C. The device according to claims 1-4, characterized in that the portion provides a surface contacting the user, preferably a topsheet. A composition according to claims 1-4, characterized in that the dermatological component containing the enzyme inhibitor is applied to the topsheet such that one or more regions of the topsheet are untreated by the dermatological component and the dermatological component with the enzyme inhibitor is preferably applied. onto a topsheet in the form of strips separated by a row of strips without a dermatological component. Composition according to claims 1-6, characterized in that the dermatological component comprises from 0.001% to 50% of an enzyme inhibitor, preferably from 0.1% to 10%. The composition of claims 1-7, wherein the IC ₅₀ of the enzyme inhibitor is not greater than 500 µΜ. polysiloxane plasticizers, 9. The composition of claim 1 wherein the dermatological component further comprises a compound selected from the group consisting of a plasticizer of petroleum origin, a fatty acid ester plasticizer, an alkyl ethoxylate plasticizer, a fatty acid ester ethoxylate plasticizer, a fatty alcohol type, a sucrose ester plasticizer fatty acids, polyesters of ethylene glycol and its derivatives, sorbitol and its derivatives, trihydroxystearin and its derivatives, hydrating agents, demethicone, petrolatum, propylene glycol and its derivatives, glycerin and its derivatives, triethylene glycol and its derivatives, sperm fat and other waxes, fatty acids, fatty alcohol ethers, propoxylated fatty alcohols, polyhydroxy alcohol fatty esters, lanolin and its derivatives, kaolin and its derivatives, lanolin, mineral oil, shark liver oil, white petrolatum, talc, starch, zinc acetate, zinc carbonic acid ester, zinc oxide Derivatives of live yeast, aldioxa, aluminum acetate, microporous cellulose, cholecalciferol, colloidal oatmeal, cysteine hydrochloride, dexpanthanol, Peruvian balsam • · oil, protein hydrolysates, methionine, sodium bicarbonate, acetates vitamins A, D _3, E, B _5, and E and mixtures thereof. Composition according to claim 1, characterized in that at least 0.0016 mg / cm ² , more preferably at least 0.0078 mg / cm ^2, and most preferably from 0.0016 mg / cm ^{2, is} transferred to the skin of the user during wear of the treated composition. up to 0.78 mg / cm ^{2 of the} dermatological component. An absorbent composition, at least a portion of which comprises a dermatological component that is solid or semi-solid at 20 ° C and comprises (i) 0.001% to 50% enzyme inhibitor, (ii) 5% to 95% plasticizer, which is malleable or liquid at 20 ° C. And (iii) 5% to 95% of an agent capable of immobilizing the emollient in the composition, wherein the immobilizing agent has a melting point of at least 35 ° C. The composition of claim 1, wherein the enzyme inhibitor is selected from the group consisting of: soybean trypsin inhibitor and other trypsin inhibitors of plant origin, ovomucoids, chymostatin, aprotinin, leupeptin and analogs thereof, bestatin and analogs thereof, antipain, antithrombin III, hirudin, cystatin, and ₂ macroglobulin, α-antitrypsin, pepstatin and its analogues, TLCK, TPCK, tranexamic acid and its salts, glycyrhizic acid and its salts, stearylglycyrretinate, 18-3-glycyrrhizic acid and its salts, colloidal oat extracts , elhibin, 4- (2-aminoethyl) benzenesulfonyl fluoride HCl, quercetin, phytolic acid and its salts, ethylenediaminetetraacetic acid (EDTA) and its salts, hexamidine and its salts, pentamidine and its salts, benzamidine and its salts and derivatives, p-aminobenzidine and its salts and derivatives, guanidinobenzoic acid 99 9 9 9 9 9 9 9 99 9 9 9 9 9 9 9 And its salts and derivatives, including polymer derivatives, alkylhydroxamic acids and their respective salts and derivatives, phosphoramidate and its derivatives, water-soluble metal salts, zinc salts of saturated and unsaturated monocarboxylic acids, glycerol fatty acid esters, such as triacetin, copolymers of propylene oxide and ethylene oxide, chlorhexidine, cholestyramine, acarbose, voglibose, miglitol, emiglitate, camiglibose, pradimicin Q, salbostatin, tendamistat, alcohols, inhibitors of plant origin, mainly from wheat, rice, corn, barley , beans and seaweed, tetrahydrolipstatin, lipstatin, valilactone, esterastine, ebelactone A and B, 1,6-di (O- (carbamoyl) cyclohexanone oxime) hexane and mixtures thereof. A method for reducing the enzymatic activity of stool enzymes on a skin portion of an absorbent user comprising the steps of (i) forming an absorbent composition at least a portion of which comprises an enzyme inhibitor dermatological component and (ii) transferring a portion of the dermatological component to the skin of the wearer.