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(12) Patent Application Publication (10) Pub. No.: US 2015/0290181 A1 Lee Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2015/0290181 A1 Lee Et Al US 201502901 81A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0290181 A1 Lee et al. (43) Pub. Date: Oct. 15, 2015 (54) COMBINATION OF EFFECTIVE (52) U.S. Cl. SUBSTANCES CAUSING SYNERGISTIC CPC ............. A6 IK3I/445 (2013.01); A61 K3I/I66 EFFECTS OF MULTIPLE TARGETING AND (2013.01); A61 K3I/505 (2013.01); A61 K USE THEREOF 36/38 (2013.01); A61K 45/06 (2013.01); A61 K 36/744 (2013.01); A61K 36/69 (2013.01); (75) Inventors: Doo Hyun Lee, Seoul (KR); Sunyoung A61K 31/198 (2013.01); A61K 36/40 Cho, Gyeonggi-do (KR) (2013.01); A61 K36/884 (2013.01) (73) Assignee: VIVOZONE, INC., Seoul (KR) (57) ABSTRACT Disclosed are a combination of active components inducing (21) Appl. No.: 14/128,616 synergistic effects of multi-targeting and a use thereof. More particularly, disclosed are a functional food composition, a (22) PCT Filed: Jun. 28, 2012 cosmetic composition, a pain-suppressive composition, and a composition for treatment or prevention of pruritus or atopic (86). PCT No.: PCT/KR2O12/OOS145 dermatitis, which comprise as active components, two or S371 (c)(1), more components selected from a group consisting of (a) a (2), (4) Date: Jan. 16, 2014 5-hydroxytryptamine subtype 2 (5-HT2) receptor antagonist; (b) a P2X receptor antagonist; and (c) any one of a glycine (30) Foreign Application Priority Data receptor agonist, a glycine transporter (GlyT) antagonist, a gamma-aminobutyric acid (GABA) receptor agonist, and a Jun. 28, 2011 (KR) ........................ 10-2011-0063.289 GABA transporter 1 (GAT1) antagonist. The multi-targeting composite composition (specifically, natural Substances com Publication Classification posite composition) has synergistic effects, and thus a treat ment using a combination of respective components may (51) Int. Cl. achieve increased biological effects, in which mechanisms A6 IK3I/445 (2006.01) targeted by respective components are involved. Thus, the A 6LX3L/505 (2006.01) multi-targeting composite composition may not only remark A6 IK36/68 (2006.01) ably control pain but may also increase effects of alleviating A6 IK36/884 (2006.01) symptoms of skin diseases such as itching and atopic derma A6 IK36/744 (2006.01) titis; preventing or improving depression, refreshment, pore A6 IK 36/69 (2006.01) minimization, improving wrinkles, skin regeneration, skin A6 IK3I/98 (2006.01) health, recovery of skin condition, skin whitening, preventing A6 IK 36/40 (2006.01) or improving athlete's foot, recovery of Scalp health and A6 IK3I/66 (2006.01) regeneration of scalp, promoting hair growth, preventing gray A6 IK 45/06 (2006.01) hair, and improving dental and periodontal diseases, etc. Patent Application Publication Oct. 15, 2015 Sheet 3 of 5 US 2015/0290181 A1 3883: 8:38:::::: 3:3:::::: x 8 x 833 338.83 8 is :x: 8x8: Patent Application Publication Oct. 15, 2015 Sheet 4 of 5 US 2015/0290181 A1 FIG 4 3:3888: fri:it:8338 +*:::::::::::::: 3::iffiti. isis. r:3: FIG 5 ::::: ' RE.88:88 seat cits Patent Application Publication Oct. 15, 2015 Sheet 5 of 5 US 2015/0290181 A1 'ehicle 2ml of mangosteen (2-3) + 1 g of Palmijiwhang Pills - - - - - - - (n=3) 88 8xxx xxxx xxxxx xxxx x: Vehicle 0.5g of Palmijiwhang Pills 1 g of Palmijiwhang Pills (n=4) (n=4). (f=4) US 2015/0290 181 A1 Oct. 15, 2015 COMBINATION OF EFFECTIVE basic components. However, Such formulations as described SUBSTANCES CAUSING SYNERGISTIC above also need a cosmetic composition having more various EFFECTS OF MULTIPLE TARGETING AND and higher efficacy and a toxicity problem still needs to be USE THEREOF solved for safety in skin. 0006. In view of the foregoing, recently, a lot of studies TECHNICAL FIELD into natural Substances having efficacy against diseases have been actively carried out. For example, Nelumbinis Semen 0001. The present invention relates to a combination of extract has been used to treat depression; a method of pro active components inducing synergistic effects of multi-tar ducing Seanol-based cream for pain treatment and anti-in geting and a use thereof, and more specifically, to a functional flammation is known; salt, Phyllostachys migra Munro food composition, a cosmetic composition, a pain-Suppres extract, and the like have been provided to prevent and treat sive composition, and a composition for treatment or preven skin inflammations (Korean Patent Application Laid-open tion of pruritus or atopic dermatitis, which comprise as active No. 10-2009-0113462); Reynoutria elliptica extract, San components, two or more components selected from a group guisorba officinalis L. extract, Coptis chinensis extract, and consisting of (a) a 5-hydroxytryptamine subtype 2 (5-HT2) the like have been provided to improve atopic dermatitis receptor antagonist; (b) a P2X receptor antagonist; and (c) (Korean Patent Application Laid-open No. 10-2007 any one of a glycine receptor agonist, a glycine transporter 0079497); and a combination of Glycyrrhiza uralensis Fis (GlyT) antagonist, a gamma-aminobutyric acid (GABA) cher, green tea, Asiasari radix extract, and chitosan has been receptor agonist, and a GABA transporter 1 (GAT1) antago Suggested to prevent periodontal diseases. Such natural Sub nist. stances can solve a toxicity problem of conventional com pound-containing compositions and can be easily applied to BACKGROUND ART functional foods, cosmetics, medicines, and the like. There 0002 Conventionally, various diseases have been treated fore, natural Substances have been recently applied to medi and prevented by using a 'single target-single disease' cines, cosmetics, and functional foods in various ways. approach to control a specific hormone or to target a single 0007 Conventionally, however, it is general to produce a receptor. However, such an approach has not been Sufficient functional food composition based on descriptions of old to treat and prevent many diseases and may cause unexpected documents or experience or to produce a composition based side effects. on a known-mechanism and apply the composition to a clini 0003 For example, according to a current mechanism of cal test. There has not been a research study like the present action of antidepressants, symptoms of depression are invention on a specific combination of natural Substances or reduced or relieved by increasing the amount of 5-HT as a compounds inducing synergistic effects based on a specific neurotransmitter in a human body, and Such an antidepressant receptor-related mechanism. has many serious side effects Such as an increase in Suicide 0008 Meanwhile, pain is a kind of warning system telling rate, headache, diarrhea, melosalgia, a skin rash, palpitations, us that something is wrong in our body, and it is an essential repetitive spasms, hyperhidrosis, edema, hypoactive sexual symptom to maintain our normal life and can be typically desire disorders, erectile dysfunction, and the like. Further, classified into acute pain and chronic pain. corticosteroids have been used to treat atopic dermatitis, but 0009. Although a lot of neuropathologic studies on pain when discontinuing Such a treatment, there may be a risk of have been actively carried out and various studies into treat rebound effects (dramatic worsening in a diseased part after ments for pain have been carried out, even now, most treat discontinuing a medication). Therefore, nonsteroidal anti ments for paindepend on narcotic analgesics developed in the inflammatory drugs or antihistamines that do not contain past. hormones such as corticosteroids have been used. However, 0010. A nervous system in charge of pain has a very com Such drugs have weak efficacy, and, thus, it is difficult to plicated and parallel structure. A selective and potent drug on completely treat the diseases. a single target may have lower efficacy than expected and is 0004. In order to solve these problems, as a suggestion for more likely to cause serious side effects. Therefore, there is a another direction of drug development, various studies into need for development of a multi-target drug capable of simul multi-target drugs have been carried out. However, at present, taneously controlling a pain signal process, or a central sen only combination drugs including two or three drugs have sitization mechanism by adjusting multiple targets. been used mostly for anticancer treatments, but there is lim 0011 Pain relievers developed so far act on peripheral ited knowledge about how to combine various targets. nerves or central nerves and relieve pain and can be typically 0005 Meanwhile, recently, in order to treat or prevent classified into a nonsteroidal anti-inflammatory drug diseases, functional foods have been researched and pro (NSAID), a COX-2 inhibitor, an opiate, a morphinomimetic, duced in various forms such as functional foods or functional and flupirtine. It is reported that these pain relievers have beverages with the purposes of vitality promotion, obesity many side effects and an addiction problem. prevention, improvement in atopic dermatitis, skin health, 0012. Accordingly, there is a significant need to develop Scalp health, pain control, refreshment, and the like. In addi novel medicaments capable of solving different side effects tion to Such functional foods, cosmetic compositions have and the addiction problem of conventional pain relievers as been continuously researched and developed to achieve an well as relieving symptoms specific to pains. aesthetic purpose, a therapeutic purpose, and a preventive 0013 Although a molecular-biological mechanism of purpose in the fields of skin whitening, antiwrinkle, skin pain and functions of drug targets based on the above mecha elasticity, hair, and scalp. However, in most cases, by formu nism have been relatively clearly disclosed, there is still con lating various kinds of chemical components, efficacy corre siderable lack of understanding about a mechanism which sponding to such components is given to cosmetics, or vari results in pruritus (itching). However, since a significantly ous kinds of formulations are created by creatively processing similar aspect is expressed between mechanisms respec US 2015/0290 181 A1 Oct.
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