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02/28/08 | 1 views | #20080050318 | Prev - Next | USPTO Class 424 | About this Page  424 rss/xml feed  monitor keywords

Use of a combination of components with an inhibitory synergistic effect on calcium channels to prevent or treat wrinkles and fine lines

USPTO Application #: 20080050318
Title: Use of a combination of components with an inhibitory synergistic effect on calcium channels to prevent or treat wrinkles and fine lines
Abstract: Disclosed herein is a composition for topical application to skin, comprising, in a physiologically acceptable medium (i) at least one peptide comprising at least one amino acid sequence derived from the amino acid sequence of the protein SNAP 25, and (ii) at least one calcium-channel inhibitor. Further disclosed is the use of this combination in a composition suitable for topical application to the skin, as an agent for preventing or treating wrinkles and fine lines, such as expression wrinkles, as well as a cosmetic treatment process comprising applying to the skin the composition. (end of abstract)
Agent: Finnegan, Henderson, Farabow, Garrett & Dunner LLP - Washington, DC, US
Inventor: Beatrice Renault
USPTO Applicaton #: 20080050318 - Class: 424 59 (USPTO)

The Patent Description & Claims data below is from USPTO Patent Application 20080050318.
Brief Patent Description - Full Patent Description - Patent Application Claims  monitor keywords

[0001]This application claims benefit of U.S. Provisional Application No. 60/427,575, filed Nov. 20, 2002.

[0002]Disclosed herein is a composition that is suitable for topical application to skin, comprising, in a physiologically acceptable medium, (i) at least one peptide comprising at least one amino acid sequence derived from the amino acid sequence of the protein SNAP 25, and (ii) at least one calcium-channel inhibitor.

[0003]Women, and even men, currently have a tendency to wish to look youthful for as long as possible and consequently seek to fade out the signs of aging on the skin, which are reflected in particular by wrinkles and fine lines. In this respect, the media and the fashion world report about products intended to keep the skin radiant and wrinkle-free for as long as possible, which are signs of youthful skin, and all the more so since the physical appearance acts on the psyche and/or on the morale.

[0004]Up until now, wrinkles and fine lines have been treated using cosmetic products containing active agents acting on the skin, for example, by moisturizing it or by improving its cell renewal or alternatively by promoting the synthesis, or preventing the degeneration, of the elastic fibers which make up skin tissue.

[0005]Although these treatments make it possible to act on the wrinkles and fine lines caused by chronological or intrinsic ageing, and also on those caused by photo-ageing, they have no effect on expression wrinkles, which require an intervention on the contractile component of the wrinkles present in the skin.

[0006]Expression wrinkles are produced by mechanisms that differ from those generating lines due to ageing.

[0007]More precisely, expression wrinkles are produced by the stress exerted on the skin by the facial muscles which produce facial expressions. Depending on the shape of the face, the frequency of expressions and the existence of any tics, expression wrinkles can appear in childhood. Age and some environmental factors such as exposure to the sun do not have any effect on their genesis but can make them deeper and render them permanent.

[0008]Expression wrinkles are characterized by the presence of furrows at the periphery of the orifices, namely the nose (nasogenic furrows), the mouth (parabuccal lines and bitterness lines) and the eyes (crows feet) around which the facial muscles are located, and also between the eyebrows (glabellar lines or frown lines) and on the forehead.

[0009]Specifically, it has been shown that the facial skin muscles, in particular striated muscle fibers, which are under the direct control of the neuromuscular impulse, can play an essential role in the formation of expression wrinkles, and that modulating the neuromuscular impulse can attenuate expression wrinkles and also provide a "smoothing" effect on the skin's microrelief.

[0010]Moreover, it is believed that the phenotype of certain fibroblasts located along the tension lines created under the effect of contraction of facial muscles when making a facial expression is progressively modified under the effect of the contractions, endowing the fibroblasts, named myofibroblasts, with particular contractile properties related to striated muscle properties.

[0011]It is further known that the skin muscles of the face are under the control of motor nerve afferences of the facial nerve and that, moreover, the interlobular septa of the hypoderm contain within them fibers that constitute a striated muscle tissue. In the peripheral nervous system, the junction between a nerve and a striated muscle constitutes the neuromuscular plate, upstream of which is the afferent nerve pathway, known as the motor neuron. Moreover, cell membranes of each nerve fiber, and also of muscle cells, comprise numerous ion channels, and especially calcium channels, or chlorine channels, which can allow the controlled passage of Ca.sup.2+ or Cl.sup.-, respectively.

[0012]Variations in the intracellular Ca.sup.2+ concentration are involved in initiating electrical and mechanical phenomena, for example, depolarization or contraction of smooth or striated muscle, hormonal secretion and activation of enzymes.

[0013]In particular, the increase in the calcium concentration is considered the cause of muscle contraction, and its decrease is considered to cause relaxation.

[0014]It is generally accepted that during the contraction phase, the thin actin filaments slide between the thick myosin filaments, thus resulting in shortening of the sarcomeres and consequently a contractile movement of the cell and of the fiber as a whole.

[0015]With respect to skeletal striated muscle, in the relaxed state, the actin is not accessible to the myosin bridges because it is associated with another protein complex consisting of troponin and myosin.

[0016]When calcium binds to the troponin-myosin complex, the actin molecules become accessible and the contractile phenomenon can then begin. The troponin molecule undergoes a conformational change that reveals the ATPase activity of the heads of the myosin molecule in the thick filaments, thus initiating contraction. The hydrolysis of the ATP to ADP and phosphate provides the chemical energy allowing the filaments to slide.

[0017]The role of Ca.sup.2+ in the contractile proteins of striated muscle is thus an activating (de-inhibiting) role on the ATPase activity.

[0018]Relaxation of the striated muscle takes place when the transverse tubules and the cell membrane are repolarized, thus allowing the cellular intracytoplasmic Ca.sup.2+ concentration to return to a value of 10.sup.-7 M, below the activation threshold of intracellular enzymes such as ATPase (activation threshold which is in the range of 1 to 2 concentration logarithms higher).

[0019]In the contraction of smooth muscle fibers, calcium is not an activator per se: it combines with calmodulin, and the calcium-calmodulin complex activates MLCK (myosin light chain kinase), forming therewith a ternary complex. This complex converts the myosin into phosphorylated myosin, which combines with actin, resulting in a contraction of the smooth fibers.

[0020]The contraction-relaxation cycle can be caused by variations in the cytoplasmic calcium concentration ranging from 10.sup.-7 M (inactive) to 10.sup.-5 M (active).

[0021]Regulating the intracellular cytoplasmic Ca.sup.2+ concentration is only possible because the cytoplasmic calcium effluxes correct the cytoplasmic influxes. The intracytoplasmic Ca.sup.2+ exchanges take place either with respect to intracellular storage vesicles or with respect to the exterior of the cell. In both cases, the Ca.sup.2+ is not available in the cytoplasm. These exchanges can be ensured only by expelling intracellular cytoplasmic calcium via one or more "active" mechanisms capable of surmounting the electrochemical potential gradient mentioned above.

[0022]Two types of mechanisms can intervene: a calcium pump, which actively expels the cations at the expense of the hydrolysis of ATP, and a movement of Ca.sup.2+ coupled to a movement of Na.sup.+. In most cells, the ATP-dependent calcium pump operates more efficiently in the presence of calmodulin, which can increase its affinity.

[0023]In order to better describe the changes in permeability to calcium, it is currently common to consider that this permeability corresponds (i) to the opening of calcium channels that are dependent on the membrane potential, or voltage-operated channels (VOCs), which open during depolarization and allow calcium to enter the cell, or (ii) to the activation of membrane receptors.

[0024]Three types of VOCs are known: a channel that opens at a low potential, the T channel (Transient channel), and two types of channels that open at a high potential, the L channels (Long channels) and N channels (channels present in the neurons).

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