Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Diagnostic or test agent produces visible change on skin
Reexamination Certificate
2000-07-12
2004-06-29
Saunders, David (Department: 1644)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Diagnostic or test agent produces visible change on skin
C424S009810, C435S029000, C530S859000, C600S306000, C600S307000, C600S556000
Reexamination Certificate
active
06756032
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to test methods that can be used for clinical and non-clinical fundamental research and/or other studies to determine the consequences of a challenge to a responsive system, such as to determine the efficacy of an action, substance and/or product to prevent, induce, reduce or heal disease or injury to a responsive system. By using germane challenges to the specific responsive systems, the present invention of using a secondary challenge to enhance and/or prolong the effects of a primary challenge is amenable for use with challenges to multi-cellular and unicellular organisms such as animals, plant, fungi, bacteria, and the like, to organs of multi-cellular organisms such as epidermis, liver, heart and the like, and to tissues or individual cells or cell cultures such as isolated cells from multi-cellular organisms such as sperm, eggs, white blood cells, neurons, and the like or cultures of such cells. One embodiment of the present invention enhances and/or prolongs the effects of a primary challenge to human epidermis by using a different secondary challenge.
BACKGROUND OF THE INVENTION
Studies on the effects of a challenge (insult) to provoke a human physiological response are needed to understand the etiology of disease and to develop both preventative measures and efficacious treatments. For example, studying the effects of stool on the etiology of diaper rash is needed to develop and/or determine efficacy of products, medications and/or processes that effectively prevent and/or treat diaper rash, which continues to routinely occur among many diapered children. Despite the many studies done to date, the etiology of diaper rash and the mechanisms of various diaper rash preventative and curative agents is incompletely understood. In general, this can be said for most dermatological diseases, as well as many common diseases of other tissues, organs and organisms.
Clinical and non-clinical scientific studies of biological responses, such as of diaper rash and many other dermatological responses, are hindered when current methods and/or devices cannot detect weak responses and/or distinguish among multiple causes for an observed response (i.e., disentangle or interpret a confounded response). Such studies are further hindered when the response being studied, such as diaper rash, occurs with relatively low and unpredictable frequency among the general population.
A common procedure to enhance a weak or inconsistent response is to damage or prime the responsive system prior to challenging it, but the enhanced response is often confounded. For example, the scarification test (Frosch and Kligman, 1976, Contact-Dermatitis 2: 314-242) has long been used to study irritant responses by first physically scarring skin with a needle prior to challenging that damaged skin with substances suspected to have mild irritancy or a weak response. Studies of allergenic and sensitization responses of human skin have long applied this approach by first priming the responsive system with repeated challenges, often over several weeks, to study effects of a second challenge of the same or different type (e.g., Kaidbey and Kligman, 1980, Contact Dermatitis 6:161-169).
There are two concerns with first damaging or priming a responsive system to study responses of that system. First, the damage or modification to the responsive system can cause the responsive system to respond to a challenge by a different mechanism than would the same naïve (undamaged and/or unmodified) responsive system. Second, the degree or severity of the response to a second challenge by a responsive system that has already been damaged or modified can be completely erroneous compared to a naïve responsive system. For example, a second challenge to already damaged skin could result in a severe response when the response by naïve skin would have been nil. Moreover, when the subjects are infants there is heightened justifiable concern anytime a severe response is observed and researchers would rather avoid inducing severe responses by any available means.
A common procedure to minimize confounding of a response, particularly when trying to study mechanisms of disease progression and/or the effects of interventions on the disease or on a injury, is to control the challenge, such as by using direct patching methods in dermatology studies. Such methods, however, are often inadequate when the response occurs at low frequency in the study population and/or the tools used to assess the response are relatively insensitive. To overcome these problems, a direct patching method is often used to study dermatological responses. However, these methods, when they work, typically require lengthy and/or repeated exposures that can be excessive and/or irrelevant to the normal course of events. In addition, many researchers and/or subjects find current patching methods sufficiently inconvenient and costly in time and resources that development of abbreviated methods is desirable.
The present invention is a novel approach to study physiological responses, particularly where enhancing and/or prolonging a response to a challenge without changing the inherent nature of the response is desirable. The methods are useful when the response of interest needs to be studied under both highly controlled and poorly-controlled challenge scenarios. In addition, the present invention reduces the challenge duration needed to provoke an enhanced and/or prolonged response. A specific embodiment of the present invention accomplishes this by enhancing and/or prolonging the effects of the primary challenge (stool) to human epidermis by using a different secondary challenge (tape-stripping) to elicit enhanced and durable erythemic and increased transepidermal water loss (TEWL) responses. In addition, the response to the initial challenge typically corresponds closely to what normally occurs with subjects during their normal lives because the exposure duration is relevant to the common experience of the subjects. Moreover, the primary challenge is applied to healthy, non-damaged skin so that the response is not confounded with the skin's responses to any other pre-damage challenge.
SUMMARY OF THE INVENTION
The present invention relates to a test method to enhance and/or prolong the response of a primary challenge to a responsive system, so that the primary challenge can be better studied, by using a different secondary challenge that does not alter the mechanism by which the primary challenge affects the responsive system nor does it confound the response of the primary challenge. Further, the present invention typically: 1) reduces the exposure duration needed for the primary challenge to induce a response to one that is more relevant to normal exposure scenario(s) for the responsive system or subject, 2) reduces the number of subjects needed to observe statistically significant and/or clinically relevant effects, 3) is more convenient for the researchers, and 4) is minimally stressful to the responsive system or subjects. In addition, the primary and/or secondary challenge may be preceded by one or more interventions in studies designed to understand the etiology of the disease and/or determine the efficacy of a preventative measure. In addition, the secondary challenge may be preceded by and/or followed by one or more interventions in studies designed to determine the efficacy of a curative measure.
DETAILED DESCRIPTION OF THE INVENTION
As used herein, “study” refers to either clinical or non-clinical research with specified testable hypotheses. As used herein, “subject” refers to a human, lower animal species, or other specified organism participating in a study. As used herein, “responsive system” refers to any organism, organ, tissue, mass of cells, or individual cell(s) for which a change in activity, appearance, function, structure, or other condition can be provoked or induced. As used herein, “challenge” refers to the entity and/or process of provoking, moderating or otherwise influencing a physiological (inc
Baldwin Susan
Odio Mauricio
Osborne Scott Edward
Tepper Bruce Ernest
Hughett Eileen L.
Saunders David
Stone Kirsten K.
The Procter & Gamble & Company
Wei-Berk Caroline
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