US-12616730-B2 - Topical composition comprising an extract of combined herbs comprising longanae arillus for the treatment or alleviation of skin ulcer and the use thereof

Abstract

The present invention is related to a topical pharmaceutical composition and cosmetic composition comprising a combined herb extract of Longanae Arillus, Ligustici Tenuissimi Rhizomaand Polygalae radix as an active ingredient to treat and alleviate skin ulcer.

Inventors

• Ok Nam PARK

Assignees

• MEDIHELPLINE CO., LTD
• Ok Nam PARK

Dates

Publication Date

20260505

Application Date

20210310

Priority Date

20200313

Claims (4)

1. 1 . A topical pharmaceutical composition comprising a combined herb extract of Longanae arillus, Ligustici tenuissimi rhizoma , and Polygalae radix as active ingredients in therapeutically effective amounts to treat and alleviate skin ulcer, wherein said combined herb extract is in the form of an aqueous ethanolic extract; wherein the extraction comprises extracting the herbs with 10-90% (v/v) ethanol in water; and wherein said combined herb extract consists of a mixture of each extract of Longanae arillus, Ligustici tenuissimi rhizoma , and Polygalae radix based on a dried weight (w/w) ratio respectively of (1-3):(1-3):(1-3).
2. 2 . The topical pharmaceutical composition according to claim 1 , wherein said skin ulcer is selected from a decubitus ulcer or diabetic ulcer.
3. 3 . A method of treating or alleviating skin ulcer in a mammal comprising topically administering to said mammal an effective amount of the topical pharmaceutical composition of claim 1 .
4. 4 . The method of treating or alleviating skin ulcer of claim 3 , wherein the skin ulcer is selected from decubitus ulcer or diabetic ulcer.

Description

TECHNICAL FIELD The present invention relates to a topical composition comprising the extract of combined herbs comprising Longanae Arillus for the treatment or alleviation of skin ulcer and the use thereof. BACKGROUND ART Skin wound is caused by trauma, bruises, and tear, and wound healing is the process of repairing damaged tissue for the integrity of the skin (Pazyar N, Yaghoobi R, Rafiee E. Mehrabian A, Feily A (2014) Skin Wound Healing and Phytomedicine: A Review. Skin Pharmacol Physiol. 27: pp. 303-310.). Wound healing occurs in four stages of sequential and continuous process: hemostasis, inflammation, proliferation, and remodeling (Demidova-Rice T N, Hamblin M R. Herman I M (2012) Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 1: Normal and Chronic Wounds: Biology, Causes, and Approaches to Care. Advances in Skin & Wound Care. 25:304-314). This process is very complex but sophisticated through efficient interaction between various cells, proteins, and cytokines, and chronic wounds are formed if the wound healing process is not carried out properly due to various causes. For example, chronic wounds are known to be stagnant in the inflammatory stage, causing excessive inflammatory reactions, resulting in abnormal increases in pro-inflammatory cytokine and MMPs (Eming S A, Krieg T, Davidson J M (2007) Inflammation in Wound Repair: Molecular and Cellular Mechanisms. Journal of Investigative Dermatology. 127:514-525.). Also, the expression of growth factors is reduced, and the process of vasogenesis and the formation of granulation tissue are not done properly (Frank S, Hubner G, Breier G, Longaker M T. Greenhalgh D G, Werner S (1995) Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes. Journal of Biological Chemistry. 270: pp. 12607-12613.; Goldman R (2004) Growth Factors and Chronic Wound Healing: Past, Present, and Future. Advances in Skin & Wound Care. 17: pp. 24-35.). A chronic wound is characterized that the wound has not healed naturally within three months and occurs in patients with diabetes and vascular disease. (Nunan R, Harding K G, Martin P (2014) Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity. Disease Models & Mechanisms. 7:1205-1213.) Among the chronic wounds, the largest number of patients with diabetic foot ulcers is about 400 million worldwide, 20 to 30 percent of whom are at lifetime risk of developing diabetic foot ulcers. (Armstrong D G, Boulton A J M, Bus S A (2017) Diabetic Foot Ulcers and Their Recurrence. New England Journal of Medicine. 376: pp. 2367-2375.). Chronic wounds are formed by way of being not processing to the further proliferation stage, which is caused by the stagnation at the inflammatory stage, molecular biologically and for such reason, the abnormal gene expression and interaction occur thereafter (Bannon P, Wood S, Restivo T, Campbell L, Hardman M J, Mace K A (2013) Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice. Disease Models & Mechanisms. 6:1434-1447.). It has been reported that the pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 etc and MMPs (matrix metalloproteinases) are expressed as the inflammatory phase continues, whereas the expression of various growth factors such as PDGF, VEGF, and IGF etc, is decreased (Trengove N J, Bielefeldt-Ohmann H, Stacey M C (2001) Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair and Regeneration. 8: pp., 13-25.; Armstrong D G, Jude E B (2002) The Role of Matrix Metalloproteinases in Wound Healing. Journal of the American Podiatric Medical Association. 92: pp., 12-18.). MMPs (matrix metalloproteinases) controlled by TIMPs (tissue inhibitors of metalloproteinases), decompose extracellular substrates and enables re-epithelialization. (Martins V L, Caley M. O'Toole E A (2013) Matrix metalloproteinases and epidermal wound repair. Cell and Tissue Research. 351:255-268) In particular, the research on MMP-9 is the most active among MMPs, and it is known to have the most harmful effects on chronic wounds (Jones J I, Nguyen T T, Peng Z, Chang M (2019) Targeting MMP-9 in Diabetic Foot Ulcers. Pharmaceuticals. 12:79.; Reiss M J. Han Y P, Garcia E, Goldberg M, Yu H, Garner W L (2010) Matrix metalloproteinase-9 delays wound healing in a murine wound model. Surgery. 147:295-302). Recently, a chronic wound caused by various etiology such as diabetic skin ulcers, bedsores, radiation ulcers, venous ulcers, excessive steroid use, and aging etc. give rise to experiencing problems in the normal skin injury recovery process due to the difficulty of being treated effectively. The recovering process of skin injury is suppressed due to various causes, and an abnormal inflammation in the inflammatory stage, the early stage of wound recovery, delays the progress to the proli