Enzyme inhibitors

Details Enzyme inhibitors Enzyme inhibitors

2000-09-08

2003-04-01

Rao, Deepak R. (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Chalcogen in the nitrogen containing substituent

C544S093000, C544S094000

Reexamination Certificate

active

06541629

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel functional polymer conjugates which inhibit one or more proteolytic and/or lipolytic enzymes. The polymer conjugates described herein are suitable for use in any context wherein proteolytic and/or lipolytic enzyme inhibition is indicated, inter alia, treatment of diaper rash.
BACKGROUND OF THE INVENTION
Diaper rash is ubiquitous. It was once believed that contacting the skin with urine produced diaper rash, however, it is now understood that the irritation of tissue which manifests itself in “diaper rash” is primarily caused by endogenic proteolytic and/or lipolytic enzymes, inter alia, trypsin, chymotrypsin, elastase, pancreatic lipase, which comprise human feces. However, skin irritation is not limited to enzymes which comprise feces, for example, menstrual fluids, nasal fluids, colostomy fluids, dandruff, wound healing may all provide a source of enzymes which produce irritation.
Proteolytic and lipolytic enzyme inhibitors are known. An example of effective inhibitors are “suicide inhibitors” which irreversibly react with the active site of the target enzyme thereby destroying the enzyme's ability to function. Reversible enzyme inhibitors, although not permanently inactivating the target enzyme, are also considered sufficiently effective to inhibit the effects of unwanted enzyme exposure. One drawback of low molecular weight enzyme inhibitors is their propensity to be readily absorbed through skin tissue, thereby entering into human cells wherein normal cell catabolism can be interrupted.
There is a long felt need to provide a barrier against the pernicious enzymes which act to irritate human skin, especially enzymes which produce diaper rash.
SUMMARY OF THE INVENTION
The present invention meets the aforementioned needs in that it has been surprisingly discovered that proteolytic and/or lipolytic enzyme inhibitors can be effectively delivered to human skin wherein said inhibitors can function as a barrier to enzyme activity thereby preventing diaper rash. The enzyme inhibitors of the present invention are polymer conjugates which have an enzyme inhibitor component and a functionalized polymer component.
The enzyme inhibitor component comprises a heterocyclic ring template and an enzyme targeting unit. The functionalized polymer component comprises a moiety which acts as an anchoring template for one or more enzyme inhibitors while providing a means for delivering the conjugate molecule to human skin. The enzyme inhibitor component is optionally, but preferably, linked to the functionalized polymer component by a linking group.
A first aspect of the present invention relates to an enzyme inhibiting polymer conjugate which is capable of inhibiting one or more proteolytic enzymes having the formula:
wherein T is a heterocyclic unit; L is a linking group; [Poly] is a polymeric unit, i indicates the number of said heterocyclic units which comprise said conjugate and has the value of from 1 to 100; z is 0 or 1.
The present invention further relates to a process for preventing the formation of skin irritation which is due to the presence of proteolytic and/or lipolytic enzymes, said process comprises the step of contacting an effective amount of a polymer conjugate as described herein below to human skin.
These and other objects, features and advantages will become apparent to those of ordinary skill in the art from a reading of the following detailed description and the appended claims. All percentages, ratios and proportions herein are by weight, unless otherwise specified. All temperatures are in degrees Celsius (° C.) unless otherwise specified. All documents cited are in relevant part, incorporated herein by reference.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to the prevention of pernicious and otherwise unwanted skin conditions, inter alia, rash, irritation, which is caused by the contact of proteolytic and/or lipolytic enzymes with skin. Among the conditions which the present invention seeks to ameliorate is diaper rash. The present invention achieves the desired result by applying to the skin by a suitable means a sufficient amount of a polymer conjugate which inhibits the activity of one or more enzymes which are the cause of said unwanted skin condition.
The polymer conjugates of the present invention comprise an enzyme inhibitor component and a functionalized polymer component. The enzyme inhibitor component comprises a heterocyclic ring template and an enzyme targeting unit. Key to the effectiveness of the enzyme inhibitor is the fact that the inhibitor comprises “an enzyme specifying unit” which has been modified.
The enzyme inhibitor component comprises a unit which has the role of either providing specificity for a particular enzyme or assists in deactivating the targeted enzyme.
The conjugates of the present invention further comprise a functionalized polymer component which acts as a delivery template for one or more enzyme inhibitors while providing a means for anchoring the conjugate molecule to human skin. The functionalized polymer component is typically an amphiphilic polymer which is capable of being directly attached to the enzyme inhibitor component or of being attached thereto by a linking unit. The polymer component also provides the conjugate with a source of increased molecular weight which acts to inhibit the absorption of the enzyme inhibitor into skin tissue. The polymer component also acts to facilitate formulation of the enzyme inhibitor into carriers or facilitates deposition of the conjugate directly to skin or by way of a substrate, diaper top sheet, inter alia, to which the conjugate is applied.
The conjugates of the present invention also optionally comprise a linking unit which serves to tether the enzyme inhibitor portion of the conjugate to the polymeric component. Although the polymer may be bonded directly to the enzyme inhibiting heterocycle, preferably a linking group is present to facilitate preparation and attachment of the polymer thereto.
The polymer conjugates of the present invention are utilized in an effective amount. For the purposes of the present invention the term “effective amount” is defined herein as the amount necessary to provide a reduction in enzyme activity in at least one inhibition assay. Preferred assays which are described herein are, inter alia, “Fecal Protease Inhibition Assay”, “Skin Test of Inhibition of IL-1&agr; Production”. Suitable tests also include tests which differentiate the specificity of said enzyme inhibitor, for example, which differentiate the particular proteases obstructed by said inhibitor.
Polymer Conjugates
Enzyme Inhibitor Component
The enzyme inhibitor component of the present invention comprises one or more heterocyclic moieties, designated herein as T units. The heterocyclic moiety is further characterized in that it comprises a unit (enzyme modulator) which interacts with one or more protease or lipase enzymes. Said heterocyclic moieties further optionally comprise one or more enzyme differentiating units, R.
The heterocyclic moieties of the present invention comprise 2 fused rings; an “A ring” which is common to all of the conjugates and a “B ring” which can vary widely and is further described herein below. The A ring has the formula:
and is the ring which is preferably attached to the optional linking group or directly to the polymer component. It is this ring which is capable of reversibly reacting with a target enzyme via acylation. The acylating unit of the present heterocyclic moieties has a different configuration with respect to prior art acylating units. Key is the fact that the present invention provides for a conjugate which is not linked via the acylating unit itself and secondly the acylating unit is tied back into a ring. This key structural difference prevents the release of the acylating agent upon interaction with an enzyme or a hydrolyzing agent, inter alia, water, urine, body fluids.
The present invention overcomes any pejorative effects from pre-mature hydrol

Affiliated with

Also associated with

Rating

Enzyme inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Enzyme inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Enzyme inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3031979