WO2012105823A1

WO2012105823A1 - Cosmetic non therapeutic use of extracts from ficus deltoidea

Info

Publication number: WO2012105823A1
Application number: PCT/MY2011/000008
Authority: WO
Inventors: Jens Bitzer; Philipp Wabnitz; Matthias Gehling; Peter Reinemer
Original assignee: Biotropics Malaysia Berhad
Priority date: 2011-02-02
Filing date: 2011-02-02
Publication date: 2012-08-09
Also published as: MY178073A

Abstract

The present invention is focused on the use of a topic dermatologic composition for improving the cosmetic appearance of skin, comprising improving the microcirculation in skin by applying said composition to skin where the composition comprises a hydrophilic extract from Ficus deltoidea or parts thereof.

Description

Cosmetic non therapeutic use of extracts from Ficus deltoidea

Summary of the invention

The present invention relates to the use of a topic dermatologic composition for improving the cosmetic appearance of skin, comprising improving the microcirculation in skin by applying said composition to skin where the composition comprises a hydrophilic extract from Ficus deltoidea or parts thereof, as well as to related aspects.

Background of the invention

Extracts of Ficus deltoidea and their use are well known in the art. Zunoliza (Int J Pharm & Clin Res 2009, 1(3) 100-105; Pharmacognosy Res. 2009, 1 (4): 216-223) describes the preparation of an extracts of the leaves possessing anti-inflammatory and anti-oxidative properties. Other anti-oxidative activities of aqueous extracts were reported by Hakiman (J Med Plants Res 2009, 3(3): 120-131. Sulaiman (Fitoterapia 2008, 79(7-8): 557-561 ) evaluated the anti nociceptive activity of an aqueous leaf extract for treating conditions associated with painful conditions. All of these described activities are not the subject matter of the present invention.

Some market products such as Minyak Mas Cotek (Delto Medicama Platation; www.delto.com.my) claim benefits such as reducing the blood sugar level, regulating blood pressure, reducing nerves and joints pain, removing toxin in our body, improving blood circulation, reducing cholesterol and blood lipids, delaying menopause, reducing piles pain, relieving nausea, improving migraine condition, womb contraction after birth, increasing and recovering sexual desire.

WO2010019864 discloses the use of extracts of the latex originated from the genus Ficus in pharmaceutical and/or nutraceutical treatment of angiogenic diseases which are commonly but not necessarily accompanied by inflammatory processes. [In the end the focus is on rutin]. Within the scope of the invention is the treatment of psoriasis. Inflammation and/or Psoriasis are not the subject matter of the present application.

General Description of the Invention

It has now been found surprisingly that hydrophilic extracts from Ficus deltoidea plant material (including whole plants or parts thereof, e.g. root, the rhizome, the stem, leaves, flowers, seeds, floral buds or fruit bodies) show an improving effect on skin appearance.

It is, without that this is intended to limit the scope of the present invention, assumed that this

l effect can be explained mainly by an opening effect on sphincter muscles that usually control the blood flow through skin arteries, thus leading to an enhanced microcirculation throughout the skin where the composition according to the invention is applied. A number of possible mechanisms are assumed to contribute to this effect:

Elevated thromboxane levels are associated with a number of disease states, including dermal pressure ulcers. (Wang, N.-Z., Urry, D. W., Swaim, S. F., Gillette, R. L, Hoffman, C. E., Hinkle, S.H., Coolman, S. L, Luan, C.-X., Xu, J., Kemppainen, B. W. Skin concentrations of thromboxane synthetase inhibitor after topical application with bioelastic membrane. J. Vet. Pharmacol. Therap. 27, 37-43). Thromboxane levels in skin can be reduced by the inhibition of Thromboxane synthase, the enzyme that produces Thromboxane A2 from Prostaglandin H2 (Swaim, S. F., Vaughn, D. M., Ridell, K. P., Powers, R. D., Use of a thormboxane synthtase inhibitor in the presence of dermal pressure. Am. J. Hosp. Palliat. Care (1992) 9: 21-3). The use of Thromboxan synthase inhibitors to preserve dermal microcirculation has been demonstrated (M. C. Robson, E. J. Del Beccaro, and J. P. Heggers, The Effect of Prostaglandins on the Dermal Microcirculation After Burning, and the Inhibition of the Effect by Specific Pharmacological Agents Plastic and Reconstructive Surgery, 63(6):781-787, 1979 and E. J. Del Beccaro, M. C. Robson, J. P. Heggers, and R. Swaminathan, The Use of Specific Thromboxane Inhibitors to Preserve the Dermal Microcirculation After Burning, Surgery, 87(2): 137-141 , 1980). Such condition has been demonstrated to be beneficial in increasing survival length of skin flaps (Ono I, Ohura T, Murazumi M, Sakamura R, Chiba S. (1990). A study on the effectiveness of a thromboxane synthetase inhibitor (OKY-046) in increasing the survival length of skin flaps. Plast Reconstr Surg. 1990 Dec;86(6): 1164-73; Banic A, Kouris K, Rajacic N, Nazzal M, al-Ghussain NM, Thulesius O. (1991 ). Effect of Ridogrel, a thromboxane receptor blocker and synthesis inhibitor on plasma and red blood cell flow in an arterial skin flap in sheep. Scand J Plast Reconstr Surg Hand Surg. 1991 ;25(1 ):9-14), anti-iching (Andoh T, Nishikawa Y, Yamaguchi- Miyamoto T, Nojima H, Narumiya S, Kuraishi Y. (2007). Thromboxane A2 induces itch- associated responses through TP receptors in the skin in mice, J Invest Dermatol. 2007 Aug;127(8):2042-7. Epub 2007 Apr 12.), and wound healing (Friedhoff, Lawrence T. (New York, NY) Bolton, Laura L. (Metuchen, NJ), Method of treating skin injuries using thromboxane A2 receptor antagonists, US patent 4925873). Topical application of Thromboxane synthase inhibitors has been demonstrated to be beneficial for protection of skin from pressure lesions and injury (Kemppainen BW, Urry DW, Swaim SF, Sartin EA, Gillette RL, Hinkle SH, Coolman SL, Luan CX, Xu (2004). Bioelastic membranes for topical application of a thromboxane synthetase inhibitor for protection of skin from pressure injury: a preliminary study. Wound Repair Regen. 2004 Jul-Aug;12(4):453-60.).

Selective Phosphodiesterase III inhibitors have been demonstrated to improve microcirculation and the survival of ischemic flaps (lchioka S, Nakatsuka T, Sato Y, Shibata M, Kamiya A, Harii K., Amrinone, a selective phosphodiesterase III inhibitor, improves microcirculation and flap survival: a comparative study with prostaglandin E1 , J Surg Res. 1998 Feb 15;75(1 ):42-8; Ono I, Gunji H, Suda K, Kaneko F., Effects of cilostazol lotion on blood flow in rabbit skin. J Dermatol Sci. 1994 Apr;7(2):79-83; J. Boldt, Ch. Knothe, B. Zickmann, E. Schindler, W. A. Stertmann, G. Hempelmann, Circulatory effects of the PDE- inhibitors piroximone and enoximone, Br J clin Pharmac 1993; 36: 309-314). Selective Phosphodiesterase V inhibitors have also been demonstrated to improve cutaneous microcirculation and to be beneficial for postoperative skin flap viability (Park JW, Mrowietz C, Chung N, Jung F., Sildenafil improves cutaneous microcirculation in patients with coronary artery disease: a monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study. Clin Hemorheol Microcirc. 2004;31 (3): 173-83; Hart K, Baur D, Hodam J, Lesoon-Wood L, Parham M, Keith K, Vazquez R, Ager E, Pizarro J., Short- and long-term effects of sildenafil on skin flap survival in rats. Laryngoscope. 2006;1 16(4):522-8.). In addition, mixed PDE inhibitors like sildenafil which inhibit both PDE III and PDE V activity, have been shown to induce lipolysis, improve skin microcirculation and tissue hypoxia, all conditions to improve the symptoms of cellulite, a significant cosmetic problem for post- adolescent women (Altabas K, Altabas V, Berkovic MC, Rotkvic VZ,. From cellulite to smooth skin: is Viagra the new dream cream? Med Hypotheses. 2009 Jul;73(1 ):1 18-9. Epub 2009 Feb 28.) Mild beta-adrenergic antagonism has been additionally demonstrated to be beneficial in cardioprotection and a reduction in vasoconstriction, which is attributed to anti-platelet activity or reduction in thromboxane-induced vasoconstriction. Studies with strong beta-adrenergic and mild beta-adrenergic blockade have demonstrated that mild beta-adregeneric blockade may be particular useful to leverage the benefits without causing a pronounced beta- adrenergic blockade (Campbell, W..B., Callahan, K.S., Johnson, A.R., Graham, R.M., Anti- Platelet activity of beta-adrenergic antagonists: inhibition of thromboxane synthesis and platelet Aggregation in patients receiving long-term propranolol treatment. The Lancet, (1981 ) 318: 1382-1384). Surprisingly it was found that extracts of Ficus deltoidea have advantages against the prior art which were not foreseeable for a skilled person in the art, said extracts exhibit a strong inhibition activity against phosphodiesterases 3 and 5 (PDE3 and PDE5), and against thromboxane A synthase 1 (TBXAS1 ), as well as mild inhibition activity against beta-2 adrenergic receptor and beta-3 adrenergic receptor (ADRB2 and ADRB3).

Therefore the extracts of the invention are useful in the improvement of the microcirculation (especially through capillaries) and capillarisation of the skin, improvement of the feeding of the skin, improvement of the supply of the skin with nutrition, moisture and oxygen, improvement of the skin colouring/coloring and complexion, vitalization of skin, reduction of fatigue appearance of the skin, and improvement of a healthy appearance of the skin. This effect is surprising as WO 201019864 describes inhibition of angiogenesis with lipophilic extracts of Ficus spp. - which would rather be expected to lead to a decrease in the provision of blood to the skin.

Detailed description of the invention

The invention, in a first embodiment, relates to the use of a topic dermatologic composition for improving the cosmetic appearance of skin, comprising improving the microcirculation in skin by applying said composition to skin, where the composition comprises a hydrophilic extract from Ficus deltoidea plants or Ficus deltoidea plant parts. In another embodiment, the invention relates to the use according to the preceding paragraph, where the improving of the cosmetic appearance is a more fresh and/or vital visual appearance of skin.

In yet another embodiment, the invention relates to the use according to any of the two preceding paragraphs, where the improving of the cosmetic appearance is a more rosy appearance of skin.

In yet a further embodiment, the invention relates to the use according to any one of the preceding three paragraphs, where the improving of the cosmetic appearance is (= manifests itself in) a more smooth, supple and/or soft appearance of skin in case of touch.

A further embodiment of the invention relates to the use according to any one of the preceding four paragraphs, where the improving of the cosmetic appearance is a more juvenile appearance of the skin. Another embodiment of the invention relates to the use according to any one of the preceding five paragraphs, where the hydrophilic extract is obtained using a solvent for extraction that has an E_T(30) value of 45 kcal/mol or higher at 25 °C and 1 bar. Another version of the embodiment in the preceding paragraph relates to the use where the E_T(30) value of the solvent used for extraction is 48 kcal/mol or higher.

A further embodiment of the invention relates to the use according to any one the preceding two paragraphs, where the solvent for extraction is an aqueous solvent; yet another specific embodiment of this embodiment is where the solvent used for extraction consists essentially of water or a mixture of water with a d-C₈-alkanol with one or more hydroxy groups, especially a Ci-C₈-alkanol, Ci-C₈-alkandiol or (VCe-alkantriol, e.g. water, ethanol/water, isopropanol/water, monopropylene-glycol/water or glycerol/water, where the vol/vol ration (V/V) of the alkanol to water may e.g. be in the range from 3 to 97 to 97 to 3, e.g. from 25 to 75 to 96 to 4.

Another embodiment of the invention refers to the use according to any one the preceding eight paragraphs, where the dermatologic composition is an oil, an ointments, a tincture, a cream, a gel, a solution, a lotion, a spray, a powder, a shampoo, a soap, a cosmetic pencil or a perfume. A more specific embodiment here relates to the case where the dermatologic composition is an ointment, a cream, a gel or a solution.

In a further embodiment, the invention relates to a method of treatment of the skin of a human in need thereof to improve the microcirculation in order to improve the feeding of the skin, improvement of the supply of the skin with nutrition, moisture and oxygen, improvement of the skin colouring/coloring and complexion, vitalization of skin, reduction of fatigue appearance of the skin, and improvement of a healthy appearance of the skin, said method comprising (topically) administering an effective amount of a dermatologic composition comprising a hydrophilic extract from Ficus deltoidea plants or Ficus deltoidea plant parts as defined in any one of the preceding nine paragraphs.

The following definitions of more general terms, as well as definitions given already above, can replace the more general terms in any of the embodiments of the invention, in any combination, thus leading to more specific embodiments all of which are also comprised by the present invention.

"Microcirculation" (not to be confused with commonly used "improved blood circulation"), in particular "dermal microcirculation", according to the present disclosure describes an improved blood flow through the capillaries of skin, presumed to be based mainly on an increased opening (relaxation) of precapillary sphincters which contain muscle fibers that allow them to contract so that the blood flow can be stopped or started, or more generally adjusted, by these sphincters, e.g. in certain areas of the skin. When the sphincters are open, blood flows freely to the capillary beds of body tissue. When the sphincters are closed, blood is not allowed to flow through the capillary beds.

"Improving the microcirculation" especially refers to enhancement of the microcirculation by at least partly relaxing the precapillary sphincters.

The extracts according to the invention are hydrophilic extracts that may be obtained by using sufficiently polar solvents, e.g. the solvents mentioned in the claims. One possible way t \o define the polarity of solvents is the characterization by their E_T(30) values. This is due to the fact that these E_T(30) values are a common way to describe the hydrophilic or hydrophobic nature of solvents and soluents. For example, water has an E_T(30) of 63.1. The E_T(30) method is based on a method published by Reichart et al. and makes use of the stabilisation of the ground state of the betaine dye 2,6-diphenyl-4-(2,4,6- triphenyl-1-pyridinio)phenolate, CAS Nummer 10081-39-7, R: 22-24/25, in apolar solvents leading to a higher energy for the transition from the ground state (HOMO) to the first excited state (LUMO) of the molecule (see K. Dimroth, J Lieb Ann d Chemie (1963) 661(1): 1 - 37, DOI 10.1002/jlac.19636610102). The extraction leading to the hydrophilic extract can, for example, start from whole plants or plant parts (collectively referred to also a plant material) as defined above, e.g. from leaves. The plant material may be used without prior treatment or after e.g. drying, chopping, milling or grinding or combinations of two or more thereof. The extract may be prepared by any extraction method known in the art, however, the condition being that it is a hydrophilic extraction.

Hydrophilic extraction means that preferably a solvent as defined above is used. Alternatively, also supercritical fluids, such as nitrous oxide, sulphur dioxide, fluorocarbons or especially carbon dioxide, with or without one or more organic modifiers, e.g. co-solvents such as methanol or ethanol, halogenated hydrocarbons such as chloroform, which allow to adjust the solvating power, can be used for extraction. In a further embodiment of the invention, the extraction can be followed by a further step for enrichment, e.g. solvent partition (e.g. of an extract filled up with water and partitioned between a hydrophilic phase, e.g. with water and/or one or more polar organic solvents, and a hydrophobic phase, e.g. an essentially apolar solvent forming a separate phase in the presence of water, e.g. an alkane, such as pentanes or hexanes, or an only weekly polar solvent, such as an ester, e.g. ethyl acetate, an ether, e.g. ethyl ether, or a halogenated hydrocarbons, such as methylene chloride, and/or by chromatography, e.g. preparative high performance chromatography. Preferably, if organic solvents are used, the extract is further extracted after optional concentration e.g. by evaporation extracted with a solvent not miscible with water to remove impurities into the organic phase.

Other reprocessing is possible, e.g. by filtering (e.g. through paper, sintered glass, charcoal (also allowing for decoloration) or silica).

The extraction can be made at lowered or elevated or ambient temperature, e.g. in the range from -20 °C to the boiling point of the solvent or solvent mixture employed, e.g. from 20 °C to said boiling point. The extraction may be improved by moving the solvent and/or the plant material, e.g. by stirring, or by ultrasound, or by milling and/or chopping during extraction, or the like.

Extracts of the invention can be prepared using plants or especially plant parts of Ficus deltoidea which is synonymous to Ficus diversifolia, Ficus triangularis, Ficus lutescens, Ficus landonii, Ficus motleyana, Ficus oligoneura, Ficus ovoidea, Ficus retusa, Ficus sideroxyfolia, Ficus spathulata, Synoecia diversifolia, Synoecia grandifolia, Urostigma oligoneuron, Urostigma ovoidum, Erythrogyne lutescens. Ficus deltoidea is also known as mistletoe fig, cherry banyan, delta fig, fig shrub, mistletoe rubber plant, rusty leaved bush fig, mas cotek, emas cotek, secotek emas, Mistelfeigenbaum, Mistelfeige, tabat barito, ara jelatih, ara bimbilang, kayu menupang.

Ficus deltoidea is indigenous to the southern Philippines southward and westward to Southeast Asia, Malaysia, and Indonesia (F. Starr, K. Starr, I. Loope, Plants of Hawaii (species reports) 2003: "Ficus deltoids" http://www.hear.orq/starr/hiplants/reports/index.html, a project at "Hawaiian Ecosystems at Risk project (HEAR)"). F. deltoidea cherishes warmth and humidity and is quite intolerant of draughts, which is why it is commonly found in Malaysia's rainforests. The plant has male and female species which can be differentiated by the shape of the leaves: those of the male being smaller, thinner, and tapering in shape with red specks at the back while the female leaves are thicker and more roundish with golden specks found on the front and black spots at the back. The topic dermatologic (cosmetic) compositions according to the invention are for external application on the skin of humans.

"Cosmetic" especially refers to a non-therapeutic use, that is, a use not for treatment of a disease or condition for its cure or symptome reduction but merely to improve the aesthetic appearance of an individual.

For topical administration to the skin, the compositions with the lipophilic extract from Ficus deltoidea are preferably provided as ointments, tinctures, creams, gels, solution, lotions; sprays; aerosols, dry powders, suspensions, shampoos, hair soaps, perfumes or the like.

In fact, any conventional topic composition can be utilized in this invention. Among the preferred compositions comprising the extract used according to the invention are those in the form of an ointment, gel, cream or lotion. The cosmetic composition for topical administration to the skin can be prepared by mixing the aforementioned extract with non-toxic, therapeutically inert, solid or liquid carriers customarily used in such preparations. These preparations preferably comprise 0.01 to 99 percent by weight, especially 0.02 to 50.0 percent by weight, preferably 0.05 to 10 percent by weight, e.g. 0.05 to 2 percent by weight of the extract, based on the total weight of the composition.

In preparing the topical compositions described above, customary additives such as preservatives, thickeners, perfumes and the like used in the art of cosmetic compounding of topical preparation can be used. Cream-base cosmetic compositions containing the active agent, used in accordance with this invention, can be composed of aqueous emulsions containing a fatty acid alcohol, semi-solid petroleum hydrocarbon, ethylene glycol and an emulsifying agent.

Ointment formulations comprising the extract in accordance with this invention, for example, can comprise admixtures of a semi-solid petroleum hydrocarbon or fats with a solvent dispersion of the active material. Cream compositions comprising the extract for use in this invention can, for example, comprise emulsions formed from a water phase, e.g. using a humectant, a viscosity stabilizer and water, an oil phase of a fatty acid alcohol, a semi-solid petroleum hydrocarbon and an emulsifying agent and a phase containing the active agent dispersed in a aqueous stabilizer-buffer solution. Stabilizers may be added to the topical composition. Any conventional stabilizer can be utilized in accordance with this invention. For example, fatty acid alcohol components function as a stabilizer. These fatty acid alcohol components are derived from the reduction of a long-chain saturated fatty acid containing at least 14 carbon atoms. Alternatively gels can be used utilising standard gel carriers.

One or more further additives may be present in the compositions used according to the invention, e.g. preservatives, bactericides, substances impeding foaming, colorants, e.g. dyes or pigments, thickeners (e.g. silica, aluminium silicates, polysaccharides or their derivatives, e.g. xanthane or guar gum or hydroxypropylmethylcellulose), moisturizers (including urea, lactic acid, pyrrolidone carbonic acid, hyluronic acid, polysaccharides rich in fucose, and/or glycerol), fats, oils, waxes or other customary additives, such as polyols, alcohols, polymers, foam stabilizers, electrolytes, other organic solvents, silicones (e.g. cyclomethicon, hexamethylcyclotrisiloxane, polydimethylsiloxane, poly(methylphenyl- siloxane)), perfumes, UV protectors, such as metal oxides which may also be coated, e.g. Ti0₂, or organic UV absorbers, such as methylene bis-benztriazolyl tetramethylbutylphenol or 4-(tert.-butyl)-4'-methoxydibenzoylmethane) and the like. Among the antoioxidants, conventional antioxidants or mixtures of conventional antioxidants can be incorporated into the topical preparations containing the aforementioned active agent. Among the conventional antioxidants which can be utilized in these preparations are included N-methyl-a-tocopherolamine, tocopherols, butylated hydroxyanisole, butylated hydroxytoluene, ethoxyquin, vitamin C, ascorbyl palmitate, vitamin A and the like.

The amount of further additives can in total be 0 to 99 % by weight, e.g. from 0.1 to 60 % by weight.

The following Examples serve to illustrate the invention without limiting its scope:

Examples: Abbreviations cAMP cyclic adenosine monophosphate

cGMP cyclic guanosine monphosphate

TR-FRET Time-Resolved Fluorescence Resonance Energy Transfer Tris tris(hydroxymethyl)aminomethane

HBSS Hank's Balanced Salt Solution

Example 1 : Extraction and Extracts

A) 25 g milled leaves from F. deltoidea were extracted once with 200 ml water at 40°C for 20 min using ultrasound. Another 25 g sample was suspended in 200 ml water and extracted for 30 min under reflux with stirring. Both extracts were separated by filtration from the plant material and evaporated to dryness in vacuo. The extract yields were determined to 3057 mg using water/ultrasound and to 1870 mg using boiling water.

B) Other samples were extracted according the following procedure: For each experiment 20 g milled leaves from F. deltoidea (male and female originated) were extracted with 200 ml of different solvents in different proportions under the conditions presented in Table 1. a) Samples processed in water or mixtures of water with ethanol or 2-propanol

The solvents were removed by evaporation and the remaining water phases were filled up with water to a volume of 50 ml (crude extract) followed by twofold extraction in liquid / liquid separation with 50 ml n-heptane. An aliquot (20 ml of the total) of each crude extract sample was taken as reference sample. The different phases of the liq./liq. separation and the reference samples were evaporated to dryness and the extract yields were determined. b) Samples processed in mixtures of water with monopropylene-glycol or glycerol

These samples were not further processed since monopropylene-glycol or glycerol can not be separated from water by simple evaporation. The resulting solutions were evaporated to dryness. An aliquot 20 ml of the monopropylene-glycol solution was evaporated to dryness in vacuo under warming to 50°C in a speed vac. The glycerol containing samples were not evaporable to a constant mass.

Table 1 : Extracts prepared according Process B, conditions of preparation and yields extract solvent method of extraction yield

[mg]

1 ethanol/water (30/70) ultrasound; 40°C for 30 min. 3021

2 ethanol/water (70/30) ultrasound; 40°C for 30 min. 2707

3 ethanol/water (95/5) ultrasound; 40°C for 30 min. 993

4 isopropanol/water (30/70) ultrasound; 40°C for 30 min. 3620

5 isopropanol/water (70/30) ultrasound; 40°C for 30 min. 2406

6 monopropylene-glycol/water (30/70) ultrasound; 40°C for 30 min. 2317

7 monopropylene-glycol/water (70/30) ultrasound; 40°C for 30 min. 2210

8 glycerol/water (30/70) ultrasound; 40°C for 30 min. n.d.

9 glycerol/water (70/30) ultrasound; 40°C for 30 min. n.d.

Example 2: Biological activities a) Assay PDE3

According to literature (see Hidaka H and Asano T. Biochim Biophys Acta. 429:485, 1976. Nicholsen CD et al. Trends Pharmacol Sci. 12:19, 1991.) Human platelets PDE3 was used. Test compound and/or vehicle were preincubated with 10 pg/ml enzyme in Tris-HCI buffer pH 7.5 for 15 minutes at 25°C. The reaction was initiated by addition of 1 μΜ cAMP and 0.01 μΜ [³H]cAMP for another 20 minute incubation period and was terminated at 100°C. The resulting [³H]AMP was converted to [³H]Adenosine by addition of snake venom nucleotidase and was separated by AG1-X2 resin (Fa. Bio-Rad Laboratories GmbH, Munich, Germany, product category 140). An aliquot was removed and counted to determine the amount of [³H]Adenosine formed.

Since enzyme activity may change from lot to lot, the concentration used was adjusted if necessary. (Assay number 152000, Ricerca Biosciences, LLC, Taipei, Taiwan) b) Assay PDE5

Human platelet phosphodiesterase PDE5 is used. Test compound and/or vehicle was preincubated with 35 pg/ml enzyme in Tris-HCI buffer pH 7.5 for 15 minutes at 25°C. The reaction was initiated by addition of 1 μΜ cGMP and 0.01 μΜ [³H]cGMP for another 20 minute incubation period and was terminated at 100°C. The resulting [³H]GMP was converted to [3H]Guanosine by addition of snake venom nucleotidase and was separated by AG1-X2 resin. An aliquot was removed and counted to determine the amount of [³H]Guanosine formed. Compounds were screened at 10 μ .

Since enzyme activity may change from lot to lot, the concentration used was adjusted if necessary. Same ref. as PDE3. (assay number 156000, Ricerca Biosciences, LLC, Taipei, Taiwan) c) Assays ADRB2

According to literature Ref: (see Brodde OE et al. J Cardiovasc Pharmacol. 6(6): 1184, 1984. Hopkinson HE et al. Br J Pharmacol. 131(1 ): 124, 2000.)

Human adrenergic β2 (beta 2) receptors expressed in CHO cells were used. Test compound and/or vehicle was incubated with the cells (2.5 x 10⁵ cell/ml) in modified HBSS pH 7.4 buffer for 20 minutes at 37°C. The reaction was evaluated for cAMP levels by TR-FRET. Test compound-induced cAMP increases by 50 percent or more (>50%) relative to the 0.3 μΜ procaterol control response indicated possible adrenergic β2 receptor agonist activity. Test compound induced inhibition of the 0.01 μΜ procaterol-induced cAMP response by 50 percent or more (>50%) indicates receptor antagonist activity. Compounds were screened at given concentrations (cf. Table 2). These same concentrations were concurrently applied to a separate group of treated cells and evaluated for possible compound-induced cytotoxicity only if significant inhibition of cAMP release was observed. (Assay number 302150, Ricerca Biosciences, LLC, Taipei, Taiwan) d) Assay TBXAS2 According to literature (see Borsch-Haubold AG et al. J Biol Chem. 273(44):28766, 1998. lizuka K et al. J Med Chem. 24(10): 1139, 1981.) Human platelet thromboxane A2 synthase is used. Test compound and/or vehicle was preincubated with 10 pg/ml enzyme in Tris-HCI buffer pH 7.4 for 15 minutes at 25°C. The reaction was initiated by addition of 10 μΜ prostaglandin H2 for another 3 minute incubation period and terminated by further addition of 1 N HCl. An aliquot was removed and the amount of thromboxane B2 formed was determined spectrophotometricaliy by EIA kit (Enzyme-linked Immunosorbent Assay). Since enzyme activity may change from lot to lot, the concentration used was adjusted if necessary. (Assay number 194020, Ricerca Biosciences, LLC, Taipei, Taiwan) e) Results of the PDE3. PDE5. TBXAS2 and ADBR2 assays

Two extracts according to Example 1 (their origin is explained in table 2) were tested at 100 pg/ml and in dilution at 10 pg/ml in each of the above described assays (except PDE5). Table 2: results of the PDE3, PDE5, TBXAS2 and ADBR2 assays

ADRB2

Sample cone. PDE3 POE5 TBXAS2

Ant

[% inh.] [% inh.] [% inh.] [% resp.]

Extract 1 100 pg/ml 56 68 87 59

EtOH / water 30:70 extract,

extract table 1 ; 10 pg/ml 19 - 41 5

product of process B 1

^"Extract 2 ^{" " "} Wpg/ml 5Ϊ 42 79 68 ^{" "} hot water extract;

10 pg/ml 36 - 7 12 product of process A

Example 3: Skin Testing

2 female test persons are recruited and tested.

At the first day, a baseline measurement on four test fields at the forearms is carried out (3 test samples, one of which may be placebo, one untreated). A one time administration follows (2 mg/cm²). The fields are measured again 15, 30, 60, 90 and 120 min after administration. The measurement of the peripheral blood circulation uses Full Field Laser Perfusion Imaging (FLPI). This technique is based on the laser speckle contrast measuring technique and measures the random speckle pattern resulting from irradiation of the skin with low energy infrared laser light (class A). This speckle pattern changes due to the movement of blood cells in the region examined. The scattering light containing this movement information is detected by a CCD camera. The FLPI results are represented as mean blood circulation in the test region.

Using this test system, it can be shown that the hydrophiiic Ficus deltoidea extracts enhance the skin microcirculation.

Enhanced microcirculation leads inter alia to better nutrition and a higher load with blood, thus improving the skin appearance.

Claims

Claims:

1. The use of a topic dermatologic composition for improving the cosmetic appearance of skin, comprising improving the microcirculation in skin by applying said composition to skin, where the composition comprises a hydrophilic extract from Ficus deltoidea plants or Ficus deltoidea plant parts.

2. The use according to claim 1 , where the improving of the cosmetic appearance is a more fresh and/or vital visual appearance of skin.

3. The use according to claim 1 , where the improving of the cosmetic appearance is a more rosy appearance of skin.

4. The use according to any one of claims 1 to 3, where the improving of the cosmetic appearance is a more smooth, supple and/or soft appearance of skin in case of touch.

5. The use according to any one of claims 1 to 4, where the improving of the cosmetic appearance is a more juvenile appearance of the skin.

6. The use according to any one of claims 1 to 5, where the hydrophilic extract is obtained using a solvent for extraction that has an E_T(30) value of 45 kcal/mol or higher at 25 °C and 1 bar.

7. The use according to claim 6, where the E_T(30) value of the solvent is 48 kcal/mol or higher.

8. The use according to any one of claims 6 or 7, where the solvent for extraction is an aqueous solvent.

9. The use according to claim 8, where the solvent consists essentially of water or a mixture of water with a Ci-C₈-alkanol with one or more hydroxyl groups, especially a C^Ce-alkanol, Ci-C₈-alkandiol or CrCe-alkantriol.

10. The use according to any one of claims 1 to 9, where the dermatologic composition is an oil, an ointments, a tincture, a cream, a gel, a solution, a lotion, a spray, a powder, a shampoo, a soap, a cosmetic pencil or a perfume.

11. The use according to claim 10, where the dermatologic composition is an ointment, a cream, a gel or a solution.

12. A method of treatment of the skin of a human in need thereof to improve the microcirculation in order to improve the feeding of the skin, improvement of the supply of the skin with nutrition, moisture and oxygen, improvement of the skin colouring/coloring and complexion, vitalization of skin, reduction of fatigue appearance of the skin, and improvement of a healthy appearance of the skin, said method comprising administering an effective amount of a dermatologic composition comprising a hydrophilic extract from Ficus deltoidea plants or Ficus deltoidea plant parts as defined in any one of the preceding nine paragraphs.