Aging of the skin is a complex phenomenon resulting from the interaction of several intrinsic and extrinsic factors. Intrinsic aging is an inevitable, genetically programmed process. Among extrinsic influences (e.g., wind, heat, cigarette smoke, chemicals, etc.), ultraviolet radiation appears to be the single most important factor associated with aging of the skin. The effect of ultraviolet radiation on elastic tissues results in elastosis, which is the accumulation of damaged elastin, resulting in reduced elasticity and resilience.
Elastin is a critical component of extracellular matrix, and is especially abundant in tissues subject to physical deformations, such as lungs, blood vessels and skin.
The effect of intrinsic aging on tissue elasticity of mucosal tissues (such as vaginal, oral, or rectal mucosal tissues) and of viscero-elastic tissues (that are lining body cavities such as the respiratory track, the gastrointestinal track, the urinal and bladder track, or the reproductive track) is very similar to the effect of intrinsic skin aging. Elastin fiber production in these tissues is reduced with aging, resulting in reduced responsiveness to stimuli. In the oral cavity, such changes can contribute to a decrease in the health of the gums (leading to reduced resistance to the pressure of food processing), increased gum bleeding, loose teeth, and a general decrease in the visual health parameters of the oral cavity. In the vagina, reduced elastin fiber production could result in stiffness and reduced sexual function, and uterine prolapse is associated with reduced elasticity of the female reproductive system. Reduced elasticity of the bladder can result in urine incontinence. Reduced elasticity of vessel walls can lead to vessel breakage and bruising. In the eye, degenerative changes in elastin fibers in Brunch's membrane can be responsible for deposition of drusen and macular degeneration.
Consequently, the reduction in elasticity of these tissues results in reduced quality of life and self esteem. Thus, it is desired to have a treatment that can prevent, retard, or reverse the intrinsic and extrinsic aging effects on tissue elasticity.
Triglycerides are a main constituent of vegetable oil and animal fats, and they play an important role in metabolism as energy sources. However, high triglyceride levels may be associated with a higher risk for atherosclerosis, heart disease, and stroke. (Forrester, J. S., Curr. Opin. Cardiology 2001, 16: 261-264). High triglyceride levels can also increase the risk of thrombosis, which can lead to myocardial infarction (Miller G. J., Atherosclerosis, 2005, 179:213-27). Hypertriglyceridemia is also a well known cause of acute pancreatitis, which can have life-threatening complications (Bae J. H. et al., Korean J Gastroenterol. 2005, 46:475-80). Current approaches for lowering triglycerides include diet and pharmacological agents, such as fibric acid derivatives, fish-oil, and CoA reductase inhibitors (Jonkers, I., et al., Am. J. Cardiovasc. Drugs 2001, 1:455-466).
Uric acid is an end product of purine metabolism. Purines are building blocks of RNA and DNA. Most uric acid produced in the body is excreted by the kidneys. An overproduction of uric acid occurs when there is excessive breakdown of cells, which contain purines, or an inability of the kidneys to excrete uric acid.
Hyperuricemia can play a role in the development of gout as well as many degenerative diseases, such as the Metabolic syndrome, which has been linked to a number of coronary heart diseases and increased mortality (Lee, M-Sh., et al., J. Clin. Nutr. 2005, 14:285:292). Hyperuricemia is also involved in the tumor lysis syndrome (TLS), which is a life-threatening constellation of metabolic derangements arising as a consequence of the release of intracellular metabolites by tumor cells as they undergo necrosis (Zeh, H J et al., J Immunother. 2005; 28:1-9). Uric acid and triglycerides were both found to be positively associated with C-reactive protein (CRP) levels (Garcia-Lorda P., et al., International Journal of Obesity (2005) 1-7).
Thus, it is desired to have a treatment that can prevent, retard, or reverse the negative cardiovascular effects induced by high blood levels of triglycerides and uric acid.
Malvaceae is a family of flowering plants that includes the mallows, cotton plants, okra plants, hibiscus, baobab trees, and balsa trees. The family traditionally consists of about 1,500 species in 75 genera. Malva sylvestris is a species from the Malva (mallow) genera. The leaves of Malva sylvestris, otherwise known as blue mallow, are rich in mucilage. The mucilage of M. sylvestris is made up of high molecular weight acidic polysaccharides (Classen B, et al., Planta Med 64(7): 640-44 (1988)). The leaf tea is traditionally believed to be useful as an anti-inflammatory, decongestant, humectant, expectorant, and laxative. It has also been used internally for soothing sore throats, laryngitis, tonsillitis, coughs, dryness of the lungs, and digestive upsets. Mallow is also used as a poultice for healing wounds and skin inflammations. In traditional medicine, mallow leaf tea is also used against abnormal growths of the stomach and to alleviate urinary infections (Bisset N G (ed). Malvae folium—Mallow leaf. In Herbal Drugs and Phyto-pharmaceuticals (1994, CRC Press, Stuttgart, pp 313-316). Studies on irritated mucus membranes have shown that the mucilage of Malva sylvestris binds to buccal membranes and other mucus membranes of the body (Schmidgall J, et al. Planta Med 66(1): 48-53(2000)).
Cotinus coggygria extract is traditionally believed to be useful as an anti-microbial treatment, used in the form of external washes. See, e.g., US Patent Applications Nos. 2002/0132021 where the extract is mentioned to be active against E. coli, Staphylococcus aureus and S. cerevisiae, as well as having anti-cancer activity. The dried leaf and twig of Cotinus coggygria is used in Chinese traditional medicine to eliminate “dampness” and “heat”, and as an antipyretic (Huang K. C., The Pharmacology of Chinese Herbs (CRS Press, 1999, pp 193-194). A yellow/orange dye can be obtained from the root and stem and can be used for fabric dying. The leaves and bark are a good source of tannins (Grieve M. A Modern Herbal. Dover Publications, Inc. NY, 1971, pp 779-781).
The present invention relates to the unexpected discovery that Malva sylvestris and Cotinus coggygria extracts, when ingested, are both effective for enhancing the elasticity of the skin, urogenital, blood vessel walls, and mucosal tissues, as well as reducing triglyceride and uric acid levels.