Lipophilic Carrier Composition for Solubilizing Lipophilic Bioactive Botanical Extracts, Methods of Solubilizing Lipophilic Bioactive Botanical Extracts, and Methods of Using Solubilized Lipophilic Bioactive Botanical Extracts

BACKGROUND

Skin is a complex living tissue, which is composed of two main layers: the dermis and the epidermis. The epidermis is the outer layer of the skin, and is organized in layers of cells called keratinocytes that progressively differentiate to form the outermost layer of the epidermis, known as the stratum corneum. Fully differentiated keratinocytes, known as corneocytes, are devoid of nuclei and are filled with insoluble keratin fibers. They are arranged like bricks and separated by lipid-rich layers in an array that is often referred to as the brick-and-mortar model of the stratum corneum. In addition to protecting the inner layers of the skin from deleterious chemicals and harmful radiation, the stratum corneum acts as a barrier to the passage of hydrophilic compounds. Metabolically active keratinocytes, which form the remainder of the epidermis, and cells that respond to external stimuli are located below the stratum corneum. The dermis lies below the epidermis and is constituted mainly of fibroblasts, which are metabolically active cells that can respond to signals coming from upper layers of the skin and from the external environment.

Bioactive botanical extracts, having beneficial effects on the skin, e.g., photoprotection, anti-aging, moisturizing, antioxidant, astringent, anti-irritant, and antimicrobial properties, are being increasingly used in the cosmetic industry and are featured in a growing variety of cosmetic formulations and products available in the marketplace. Such bioactive botanical extracts and mixtures of botanical extracts are often obtained by extracting biomasses in solvents that are compatible with cosmetic uses. For safety, environmental and economic reasons, water is generally the extraction solvent of choice and the extractions result in water soluble, or hydrophilic, biological active ingredients. Generally these extracts are formulated in a cosmetically acceptable carrier for application to the skin. Because they have been obtained through water extraction, these extracts are hydrophilic and can be easily added to hydrophilic gels and toiletries or to the water phase of an emulsion. However, because of their hydrophilic nature, the active ingredients in these extracts may have difficulty penetrating the lipophilic stratum corneum barrier of the skin. This decreased penetration generally is thought to lead to decreased efficacy. While means for facilitating the passage of hydrophilic active ingredients through the stratum corneum's lipophilic barrier exist, e.g., incorporation into liposomes or other vehicles having lipophilic characteristics, these means generally involve additional transformation of the active ingredients and may affect their efficacy.

The cosmetics industry is therefore becoming more interested in lipophilic bioactive botanical extracts. Due to their lipophilic nature and enhanced physiological compatibility relative to hydrophilic compounds, lipophilic bioactive extracts are thought to have enhanced ability to penetrate the skin's lipophilic stratum corneum barrier and thus improved biological efficacy resulting from a better ability to reach the metabolically active cells in the dermis and lower layers of the epidermis.

Lipophilic bioactive botanical extracts are known. Unfortunately, because of their physico-chemical properties, in particular their lipophilic nature, many of such lipophilic bioactive botanical extracts have the disadvantage that they do not lend themselves to easy incorporation in an effective amount into cosmetic formulations because, inter alia, they are not readily soluble in cosmetic formulation media and their solubilization requires conditions, such as excessive processing, e.g., stirring, sonication or mixing, elevated temperatures or aggressive solvents, that often result in their degradation, or conditions that are not compatible with cosmetic uses, or conditions that may be deleterious to other compounds present in the formulation.

Another major challenge in providing high quality cosmetic products based on “natural” ingredients such as bioactive botanical extracts is their poor stability in formulations. Many bioactive botanical extracts do not tolerate processing and storage conditions that are generally acceptable for more stable synthetic ingredients.

A further challenge in providing high quality cosmetic products using “natural” ingredients is the poor stability of certain vegetable oils used in cosmetic formulations. Due to their poor stability, unsaturated vegetable oils do not tolerate processing conditions, storage conditions, or the presence of other reactive ingredients in formulations that are generally acceptable for more stable synthetic ingredients. For example, some seed derived polyunsaturated oils, those containing essential fatty acids in particular, have been shown to improve the structure and function of cell membranes, improve skin barrier function and enhance skin penetration. However, because these oils contain high amounts of unsaturated fatty acids, which are in part responsible for those properties, they are also very vulnerable to oxidation. The labile olefin moiety characteristic of these oils is very easily oxidized upon exposure to oxygen, especially at elevated temperatures. As a result, it is often the case that, by the time products containing these oils reach the consumer, the benefits of such oils have been lost. Although microencapsulation technology has been proposed to protect such oils from oxidation, investment in new apparatus is generally required to utilize such technology and the process is generally time consuming and expensive. Furthermore, depending upon the microencapsulation used, the skin bioavailability of oil components may be hampered.

There remains a need in the cosmetics industry to provide a means of incorporating lipophilic bioactive botanical extracts into a variety of topical dermatological, pharmaceutical and cosmetic preparations that is cost-effective and compatible with standard equipment while preserving the integrity and beneficial properties of these materials, particularly the beneficial properties of the oil components of these materials.

The present invention provides a simple and cost-effective solution to this need by providing a lipophilic bioactive botanical extract presolubilized in an oxidation stable and cosmetically acceptable vegetable oil carrier (i.e., a lipophilic carrier composition). The inventive lipophilic carrier composition is oxidation stable and can readily be incorporated into a variety of cosmetic formulations, improving the processing time and providing a more shelf stable product.

SUMMARY OF THE INVENTION

In one embodiment, the present invention provides a lipophilic carrier composition comprising a lipophilic bioactive botanical extract, a vegetable oil, a solubilization system, and, optionally, an antioxidant, where the vegetable oil is present in a stable, relatively unoxidized state. In certain embodiments, the vegetable oil is resistant to oxidation such that the Rancimat induction time for the lipophilic carrier composition according to ISO Method no. 6886-2006 is greater than 3 hours, greater than 4 hours, greater than 5 hours, greater than 7 hours, greater than 10 hours, greater than 15 hours, or greater than 20 hours.

In another embodiment, the present invention provides a lipophilic carrier composition comprising a lipophilic bioactive botanical extract, a vegetable oil, a solubilization system, and, optionally, an antioxidant, where the lipophilic carrier composition is produced by a method comprising:

- (a) combining the solubilization system and the lipophilic bioactive botanical extract to form a mixture;
- (b) maintaining the temperature of the mixture between 40-100° C. under a nitrogen or other inert gas atmosphere until the lipophilic bioactive botanical extract is dissolved;
- (c) cooling the mixture of step (b);
- (d) adding the vegetable oil; and
- (e) agitating the mixture formed by the addition of the vegetable oil in step (d) until a homogeneous composition is obtained.

In some embodiments, the mixture of step (c) is cooled to about room temperature.

If the antioxidant is part of the lipophilic carrier composition, it may be added along with the vegetable oil in step (d) or it may be added after the vegetable oil but before step (e). Generally, the antioxidant is dissolved in a cosmetically acceptable alcohol before addition.

In another embodiment, the present invention provides a lipophilic antioxidant composition comprising an antioxidant, a vegetable oil, and a solubilization system, but not comprising a lipophilic bioactive botanical extract, where the vegetable oil is present in a stable, relatively unoxidized state. In certain embodiments, the vegetable oil is resistant to oxidation such that the Rancimat induction time for the lipophilic antioxidant composition according to ISO Method no. 6886-2006 is greater than 3 hours, greater than 4 hours, greater than 5 hours, greater than 7 hours, greater than 10 hours, greater than 15 hours, or greater than 20 hours.

- (a) combining the solubilization system and the antioxidant to form a mixture;
- (b) maintaining the mixture at a temperature that is higher than room temperature under a nitrogen or other inert gas atmosphere such that the antioxidant is dissolved;
- (c) reducing the temperature of the mixture of step (b) to room temperature;
- (d) adding the vegetable oil to the mixture of step (c); and
- (e) agitating the mixture formed by the addition of the vegetable oil in step (d) until a homogeneous composition is obtained.

In some embodiments, the temperature that is higher than room temperature of step (b) is between 40-100° C. In some embodiments, the temperature that is higher than room temperature of step (b) is between 40-50° C., between 50-60° C., between 60-70° C., between 70-80° C., between 80-90° C., or between 90-100° C.

In certain embodiments, the solubilization system comprises a branched, long chain alcohol such as octyldodecanol, a cosmetically acceptable alcohol such as ethanol, and one or more fatty acid esters of a branched, long chain alcohol, for example, octyldodecyl oleate and/or octyldodecyl stearoyl stearate. In certain embodiments, the branched, long chain alcohol in the fatty acid esters is the same branched, long chain alcohol as the unesterified branched, long chain alcohol. In other embodiments, the branched, long chain alcohol in the fatty acid esters is a different branched, long chain alcohol from the unesterified branched, long chain alcohol. In certain embodiments, the fatty acids of the esters are resistant to oxidation. For example, in certain embodiments, the fatty acids do not contain a double bond. In other embodiments, the fatty acids contains only one double bond. Suitable fatty acids include monounsaturated fatty acids such as myristoleic acid (14:1), palmitoleic acid (16:1), sapienic acid (16:1), oleic acid (18:1), elaidic acid (18:1), vaccenic acid (18:1), eicosenoic acid (20:1), and erucid acid (22:1). Other suitable fatty acids include saturated fatty acids such as caprylic acid (8:0), capric acid (10:0), lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), lignoceric acid (24:0), and cerotic acid (26:0).

The solubilization system enables the complete dissolution of lipophilic bioactive botanical extracts therein. The solubilization system thus allows for the convenient incorporation of lipophilic active ingredients such as those found in lipophilic bioactive botanical extracts into a vegetable oil, thus forming a lipophilic carrier composition comprising the solubilization system, lipophilic bioactive botanical extract, and vegetable oil, without exposing the vegetable oil to elevated temperatures or extended processing time. As is known in the art, elevated temperatures and extended processing times can lead to the undesired oxidation of vegetable oils. Thus, the lipophilic carrier composition of the present invention contains the vegetable oil in a stable, relatively unoxidized state. The ability to provide lipophilic bioactive botanical extracts in combination with a stable, relatively unoxidized vegetable oil is an advantageous feature of the present invention.

The lipophilic carrier composition can conveniently be used to store and distribute lipophilic active ingredients and to formulate topical cosmetic, pharmaceutical, and dermatologic formulations while maintaining the bioactivity of the lipophilic bioactive botanical extract and preventing oxidation of the vegetable oil and other oxidizable components of the formulation made from the lipophilic carrier composition.

A presolubilized lipophilic bioactive botanical extract for use in the present invention may be made by a method comprising combining a solubilization system with a lipophilic bioactive botanical extract and, if necessary to dissolve the lipophilic bioactive botanical extract, heating the mixture to a temperature between 40-100° C. under a nitrogen or other inert gas atmosphere. In some embodiments, the mixture is heated to a temperature between 40-50° C., between 50-60° C., between 60-70° C., between 70-80° C., between 80-90° C., or between 90-100° C. In some embodiments, the inert gas is selected from the group consisting of noble gases such as argon, xenon, neon, and helium. In some embodiments, a mixture of nitrogen and another inert gas is used. In alternative embodiments, rather than using an inert gas to prevent oxidation, a vacuum is used to prevent contact with air, and thus prevent oxidation.

The present invention also provides a method of making a lipophilic carrier composition comprising combining the solubilization system with the lipophilic bioactive botanical extract and, if necessary to dissolve the lipophilic bioactive botanical extract, heating the mixture to a temperature between 40-100° C. under a nitrogen or other inert gas atmosphere until the extract is dissolved, then cooling the mixture to room temperature, adding a vegetable oil, and then, optionally, adding an antioxidant extract dissolved in a cosmetically acceptable alcohol. The mixture is then agitated until a homogeneous composition is obtained.

The lipophilic active carrier compositions of the invention can be used to prepare cosmetics having extended shelf life, for the convenient storage and distribution of a lipophilic biological extract, for use as a base or ingredient in a variety of cosmetic compositions, and for preserving the biological activity of additional ingredients included in products produced using the inventive lipophilic active carrier composition (e.g., unsaturated fatty acids, polyphenols, additional liposoluble actives).

The invention also provides a method of protecting skin against erythema and/or skin barrier function loss due to exposure of the skin to radiation or chemical stress using the inventive lipophilic active carrier compositions disclosed herein. Such methods of protecting skin generally involve applying a cosmetic or pharmaceutical formulation produced by incorporating a lipophilic carrier composition of the present invention into a base cream before the insult that results in erythema and/or skin barrier function loss. Thus, included in the present invention are methods of protecting skin against erythema and/or skin barrier function loss by applying a cosmetic or pharmaceutical formulation produced by incorporating a lipophilic carrier composition of the present invention into a base cream to skin that is at risk of suffering radiation or chemical stress. Such “at risk” skin might include, e.g., the skin of a person who contemplates exposing his or her skin to a significant amount of strong sunlight, e.g., by spending a day at the beach. Other “at risk” skin might include the skin of a person who is exposed to chemical stress (e.g., by occupational exposure to chemical aggressors or by frequent use of soaps or cleansers).

A method of treating skin that has developed erythema and/or skin barrier function loss due to exposure of the skin to radiation or chemical stress using the lipophilic active carrier compositions disclosed herein is also provided. Such methods of treating skin generally involve applying a cosmetic or pharmaceutical formulation produced by incorporating a lipophilic carrier composition of the present invention into a base cream after the insult that results in erythema and/or skin barrier function loss.

Of course, cosmetic or pharmaceutical formulations produced by incorporating a lipophilic carrier composition of the present invention into a base cream may be utilized by applying such formulations to the skin both before and after an insult.

The invention also provides methods of treating age spots using the inventive lipophilic active carrier compositions disclosed herein. Such methods of treating age spots generally involve applying a cosmetic or pharmaceutical formulation produced by incorporating a lipophilic carrier composition of the present invention into a base cream to an area of skin containing age spots. Thus, included in the present invention are methods of treating age spots by applying a cosmetic or pharmaceutical formulation produced by incorporating a lipophilic carrier composition of the present invention into a base cream to skin containing age spots. In some embodiments, the cosmetic or pharmaceutical formulation is applied to an area of skin including the age spots and surrounding areas of skin. In some embodiments, the cosmetic or pharmaceutical formulation is applied directly to the age spots and not also to the surrounding skin areas. In some embodiments, the age spots are on the face, the upper body or chest area, the legs, the hands, or the arms. In some embodiments, the cosmetic or pharmaceutical formulation comprises an extract from Paeonia suffruticosa root and Ribes nigrum seed oil.

Furthermore, the clinical advantages of using cosmetic and similar formulations made from the lipophilic active carrier compositions of the present invention over formulations containing i) only a vegetable oil, ii) a vegetable oil with a solubilization system but without the lipophilic bioactive extract or iii) a simple placebo representing the formulation base are shown herein.

The present invention provides a lipophilic carrier composition comprising Cnidium monnieri fruit extract, Echium plantagineum seed oil, ethanol, octyldodecanol, octyldodecyl oleate, and octyldodecyl stearoyl stearate. The present invention also provides a lipophilic carrier composition comprising Paeonia suffruticosa root extract, Ribes nigrum seed oil, ethanol, octyldodecanol, octyldodecyl oleate, and octyldodecyl stearoyl stearate.

DETAILED DESCRIPTION

The term “topical” as used herein refers to the route of administration of a cosmetic composition that involves direct application to the body part being treated, e.g., the skin, hair or nails. Examples of topical application include application to the skin of creams, lotions, gels, ointments or other semisolids to rub-on, solutions to spray, or liquids to be applied by an applicator. Rinse-off applications with washes, cleansers, or shampoos are also examples of topical application. Typically, areas of the body suitable for application of the cosmetic compositions include the skin of the face, throat, neck, scalp, chest, back, ears, hands, arms, and other skin sites where dermatological conditions may occur.

The term “cosmetic” is intended to encompass compositions that improve the health and/or appearance of skin and hair and is used interchangeably with dermatologic and naturopathic, cosmeceutical, pharmaceutical, nutraceutical and other similar terms.

As used herein, “room temperature” refers to a temperature of about 18-25° C., preferably 20-22° C.

As used herein, “homogeneous composition” refers to a composition that is a single phase that appears clear or translucent by visual inspection.

In the various embodiments discussed herein the vegetable oil is preferably one with beneficial pharmacological, cosmetic or dermatological properties. Most preferably the vegetable oil has a high level of polyunsaturated fatty acids, e.g., at least about 25%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95%.

Vegetable oils which can be used in the present invention include any cosmetically compatible vegetable oil derived from a botanical source, such as a plant. Various parts of a plant may be used to obtain the vegetable oil, e.g., leaves, stems, bark, flowers, seeds, fruits, spores or roots. The vegetable oil may be obtained by conventional methods, e.g., by cold-press extraction and the like. Preferably the vegetable oil has beneficial pharmaceutical, cosmetic, or dermatological properties. Vegetable oils that include a significant proportion of polyunsaturated oils, such as the essential fatty acids omega-3 and omega-6, as well as omega-5 and omega-9 fatty acids, are particularly suitable for use in the inventive compositions and methods. In certain embodiments, the omega-3 fatty acids comprise alpha-linolenic acid (ALA) and its longer chain derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the omega-6 fatty acids comprise linoleic acid (LA) and its longer chain derivatives such as gamma-linolenic acid (GLA) and arachidonic acid (AA). Topical application of some polyunsaturated fatty acids have been shown to have bioactivity, e.g., to improve the structure and function of cell membranes and improve skin barrier function. Improving skin barrier function reduces transepidermal water loss, leaving skin more hydrated, moisturized, and protected. The amount of vegetable oil used in the inventive compositions described herein is not particularly limited. A formulations scientist will readily be able to determine the appropriate amount of vegetable oil in the composition to achieve the desired properties in the composition. Typical embodiments of the invention include lipophilic carrier compositions comprising a vegetable oil in an amount from about 10-50%.

Vegetable oils that are well suited for the invention include Ribes nigrum (black currant) seed oil, Echium plantagineum (purple viper's bugloss) seed oil, baobab seed oil, black cumin seed oil, borage oil, burit fruit oil, calophyllum oil, elderberry seed oil, evening primrose oil, flax seed oil, gevuina nut oil, goji seed oil, hemp seed oil, jobs tears seed oil, jojoba oil, kiwi seed oil, neem oil, olive oil, passion fruit oil, pitanga seed oil (orange, red and purple varieties), pumpkin seed oil, raspberry seed oil, rose hip oil, sacha inchi seed oil, safflower oil, sea buckthorn seed oil, sesame oil, soybean oil, sunflower seed oil and walnut oil. Vegetable oils particularly suited for use in the invention include Ribes nigrum (black currant) seed oil, Echium plantagineum (Purple Viper's Bugloss) seed oil or a combination thereof. Suitable vegetable oils for use in the present invention include those in the following table.

TABLE 1

Unsaturated
Polyunsaturated

Name of oil
FA (%)
FA (%)
Major constituents
Color
Origin

Apricot Kernel Oil
95%
29%
Oleic, linoleic,
clear to light
Middle East

palmitic
yellow

Baobab Seed Oil
70%
35%
Oleic, linoleic,
golden yellow
Southern

palmitic, stearic

Africa

Blackcurrant Seed
87%
76%
Linoleic, a-linolenic,
Clear yellow
Eastern

Oil

g-linolenic, oleic,

Europe

palmitic

Black Cumin Seed
78%
58%
Linoleic, oleic,
yellow to
Middle East

Oil

margaric, cis-11,14-
amber

eicosadienoic acid,

stearic

Borage Oil
85%
69%
Oleic, linoleic, g-
Dark green
North America

linolenic, palmitic

and Eastern

Africa

Burit Fruit Oil
82%
3%
Oleic, palmitic,
Red-Orange
Brazil

linoleic, linolenic,

stearic,

Calophyllum Oil
71%
31%
Oleic, linoleic,
clear green
Pacific Islands

stearic, palmitic

Elderberry Seed Oil
94%
80%
Linoleic, a-linolenic,
deep dark
North America

g-linolenic oleic,
green

erucic, palmitic,

stearic

Evening Primrose
92%
81%
Oleic, linoleic, g-
yellow
Northern Asia

Oil

linolenic, palmitic

Flax Seed Oil
91%
72%
Linoleic, a-linolenic,
light yellow
South America

oleic, palmitic

Gevuina Nut Oil
82%
32%
Oelic, palmitoleic,
light yellow
Chile

linoleic, a-linolenic

Goji Seed Oil
90%
71%
Linoleic, Oleic,
Orange-yellow
Asia

linolenic

Hemp Seed Oil
92%
80%
Linoleic, a-linolenic,
Olive green
Northern Asia

palmitic, g-linolenic,

stereadonic

Jobs Tears Seed Oil
86%
36%
Oleic, linoleic,
NA
Asia

palmitic

Jojoba Oil
90%
6%
Gadoleic, erucic,
pale yellow
Middle East &

oleic, linoleic,

South America

lignoceric, palmitic

Kiwi Seed Oil
91%
76%
a-Linolenic, linoleic,
yellow to
New Zeland

oleic, stearic,
amber

palmitic

Neem Oil
64%
18%
Linoleic, oleic,
browny
Central Asia

stearic, palmitic

Olive Oil
84%
8%
Oleic, Palmitic,
Light to
Western

linoleic
medium green
Europe and

Middle East

Passion Fruit Oil
90%
78%
Linoleic, oleic,
Light
South

palmitic, stearic, a-

America,

linolenic

Pitanga Seeds
61%
47%
Palmitic, linoleic, a-
NA
South

(orange) Oil

linoleic, oleic

America,

Southeast

Asia, and

Australia.

Pitanga Seeds (red)
52%
45%
Linoleic, palmitic,
NA
South

Oil

oleic, a-linoleic,

America,

palmitoleic

Southeast

Asia, and

Australia.

Pitanga Seeds
61%
47%
Linoleic, palmitic,
NA
South

(purple) Oil

oleic, a-linoleic,

America,

palmitoleic

Southeast

Asia, and

Australia.

Pumpkin Seed Oil
84%
57%
Linoleic, oleic,
dark green to
Syria, Austria

palmitic, stearic
dark red
and Slovenia

Raspberry Seed Oil
96%
84%
Linoleic, a-linolenic,
gold to reddish
North America

oleic
color

Rose Hip Oil
94%
79%
Linolenic, linoleic,
Amber
South America

oleic, palmitic.

Sacha inchi seed oil
94%
85%
a-Linoleic, linoleic,
intense yellow
Amazon river

Oleic, palmitic,
to golden

stearic
amber

Safflower Oil
88%
75%
Linoleic, oleic,
light yellow
South Amercia

palmitic

Sea buckthorn seed
83%
67%
Linoleic, a-linolenic,
golden
Europe and

oil

oleic, palmitic,

Asia

stearic, vaccenic

Sesame Oil
87%
45%
Oleic, linoleic,
Light yellow
Eastern Africa

palmitic, stearic

& Southern

Africa

Soybean oil
83%
57%
Linoleic, oleic, a-
NA
USA, Brazil,

linolenic, palmitic

China

Sunflower Seed Oil
77%
66%
Linoleic, oleic,
slightly amber
North America

palmitic, stearic

Walnut Oil
84%
56%
Linoleic, oleic,
light green
Eastern

palmitic

Europe.

Lipophilic bioactive botanical extracts for use in the present invention are not particularly limited and include any lipophilic extract derived from a botanical source that has beneficial effects on the skin. The term botanical, as used herein, is intended to include material derived from organisms such as plants as well as fungi, algae, marine plant organisms, microorganism fermentation broths and other biological sources of cosmetic ingredients. Examples of various plant tissues include, but are not limited to whole plants, leaves, bark, roots, root bark, fruits, flowers, seeds, and pollen. The lipophilic bioactive botanical extract or compounds therefrom may be obtained by methods known in the art, e.g., by extraction with organic solvents, e.g., lipophilic organic solvents, or combinations of water and organic solvents, or by supercritical fluid carbon dioxide (SCF-CO₂) extraction with, or without, the addition or the presence of water.

Lipophilic bioactive botanical extracts include those having beneficial pharmaceutical, cosmetic, or dermatological properties. However, hydrophobic powders, waxes and other extracts having physico-chemical properties that require an inconvenient amount of cosmetically acceptable solvent, inconvenient amount of processing time, or elevated temperatures in order to incorporate the extract into a cosmetic formulation are particularly well suited for use in the inventive compositions and methods. Suitable lipophilic bioactive botanical extracts include those antioxidants listed in Table 2 that provide, in addition to antioxidant activity, a health benefit such as the health benefits listed in Table 2 under “Health Applications.” Thus, the categories of lipophilic bioactive botanical extracts and antioxidants are not intended to be mutually exclusive. Typical embodiments of the invention include lipophilic carrier compositions comprising a lipophilic bioactive botanical extract or extracts in an amount from about 0.1-5%, about 0.3-4%, about 0.5-3%, about 0.7-3%, or about 1-2% (w/w). In other embodiments, the lipophilic carrier composition comprises a lipophilic bioactive botanical extract in an amount from about 0.1-0.3%, about 0.3-0.5%, about 0.5-0.7%, about 0.7-1%, about 1.1-1.3%, about 1.3-1.5%, about 1.5-1.7%, about 1.7-2%, about 2.1-2.3%, about 2.3-2.5%, about 2.5-2.7%, about 2.7-3%, about 3.1-3.3%, about 3.3-3.5%, about 3.5-3.7%, about 3.7-4%, about 4.1-4.3%, about 4.3-4.5%, about 4.5-4.7%, or about 4.7-5% (w/w).

Lipophilic bioactive botanical extracts that are particularly well suited to this invention are Cnidium monnieri fruit extract (enriched in the compound osthol) and Paeonia suffruticosa root extract (enriched in the compound paeonol) or a combination thereof. Use of these extracts has been found to protect against erythema and/or skin barrier function loss due to exposure of the skin to radiation or chemical stress.

Suitable antioxidants for use in the present invention are not particularly limited and may be antioxidants or free radical scavengers such as vitamins, synthetic antioxidants, or plant-derived antioxidants that protect at least the vegetable oil from endogenous oxidation and/or oxidation induced or accelerated by heat, radiation or the addition of pro-oxidant compounds, thus extending shelf life and expanding compatibility of bioactive ingredients in the inventive compositions and formulations that include the inventive compositions. A list of suitable antioxidants appears in Table 2 below.

TABLE 2

Liposoluble antioxidant actives and lipophilic bioactive botanical compounds

Antioxidant/

lipophilic

bioactive

botanical

Health
Other

compound
Molecular family
Source(s)
Applications
Applications
Ref.

Ascorbyl-
Ester formed from
Synthesis
Immune booster;
To increase the
Cort, Antioxidant activity of

palmitate
ascorbic acid and

joint protection;
shelf life of
tocopherols, ascorbyl palmitate,

palmitic acid

promotes healing,
vegetable oils and
and ascorbic acid and their mode

stimulates
potato chips
of action. J Am Oil Chem Soc.

collagen synthesis

1974 Jul; 51(7): 321-5.

Apigenin
Biflavone

Ampelopsis

Antioxidant,
Topical anti-
Arsić et al, Preparation of novel

grossedentata

radical scavenger,
inflammatory;
apigenin-enriched, liposomal and

stems; Allium
anti-inflammatory,
substitute for
non-liposomal, antiinflammatory

sativum;
carbohydrate
corticoid therapy
topical formulations as substitutes

Coriander fruit;
metabolism

for corticosteroid therapy.

Rosemary
promoter,

Phytother Res. 2011

immunity system

Feb; 25(2): 228-33.

modulater.

Induces

autophagia; potent

inhibitor of

CYP2C9;

monoamine

transporter

activator

Baicalein
Flavone
Roots of
Cardiovascular
Atopic dermatitis
Yun et al, Therapeutic effects of

Scutellaria

protective; lowers

Baicalein on atopic dermatitis-

baicalensis &
blood pressure;

like skin lesions of NC/Nga mice

Oroxylum

anti-thrombotic,

induced by dermatophagoides

indicum

anti proliferative

pteronyssinus. Int

and anti-

Immunopharmacol. 2010

mitogenic;

Sep; 10(9): 1142-8

antioxidant;

Srinivas NR, Baicalin, an

prostaglandin

emerging multi-therapeutic agent:

antagonis; free

pharmacodynamics,

radical scavenger;

pharmacokinetics, and

eNOS inhibition:

considerations from drug

ICAM

development perspectives.

expression↓

Xenobiotica. 2010

May; 40(5): 357-67

Betulinic acid
Pentacyclic
Bark of several
Anti-retroviral,
To protect foods
Bracco et al, Production and use

triterpenoid
species of plants,
anti-malarial, and
against oxidative
of natural antioxidants. Journal of

principally the
anti-inflammatory
rancidity.
the American Oil Chemists'

white birch; also
properties;

Society 1981, 58 (6): 686-690

present in
potential

rosemary extracts
anticancer agent,

by inhibition of

topoisomerase

Biochanin A
Phenolic

Ganoderma

Potent ligands of
Skin
Moon et al, Dietary flavonoids:

(isoflavone)

lucidum, red
the human aryl
photoprotection
effects on xenobiotic and

clover, soy, alfalfa
hydrocarbon

carcinogen metabolism. Toxicol

sprouts, peanuts,
receptor; inhibits

In Vitro. 2006 Mar; 20(2): 187-210.

chickpea and in
CYP19 expression

Lin et al, Topical isoflavones

other legumes.
and aromatase

provide effective photoprotection

activity; anti-

to skin. Photodermatol

inflammatory;

Photoimmunol Photomed. 2008

↓NfkB

Apr; 24(2): 61-6.

translocation;

chemopreventive;

Bixin
Carotenoid
Seeds of the fruit
NA
To protect
Castro et al, The effects of

of Achiote (Bixa

unsaturated lipids
colorifico on lipid oxidation,

orellana) tree

from oxidation;
colour and vitamin E in raw and

also used as a
grilled chicken patties during

natural colorant by
frozen storage. Food Chemistry

the food industry
2011, 124 (1): 126-131

Boldine
Alkaloid
Boldo tree &
Antioxidant, cyto-
Skin lightening
O'Brien et al, Boldine and its

Lindera aggregata

protective, anti-
agent.
antioxidant or health-promoting

tumour promoting,
Improves the
properties. Chem Biol Interact.

anti-inflammatory,
oxidative stability
2006 Jan 5; 159(1): 1-17.

anti-diabetic, anti-
of bullfrog oil
Méndez et al, Fatty acid

atherogenic

composition, extraction,

actions,

fractionation, and stabilization of

vasorelaxing,

bullfrog (Rana catesbeiana) oil.

immunomodulator

Journal of the American Oil

Chemists' Society (1998) 75(1):

79-83

Caffeic acid
Hydroxycinnamic
Burdock,
Anti-inflammatory
To reduce
Eymard et al, Assessment of

acid
hawthorn,
and anti-cancer,
oxidation of fatty
washing with antioxidant on the

artichoke, pear,
UV-protection;
fish (mackerel)
oxidative stability of fatty fish

basil, thyme,
lipoxygenase
during storage
mince during processing and

oregano, apple,
inhibitor

storage. J Agric Food Chem.

coffee beans

2010, 58(10): 6182-9.

Carnosic Acid &
Phenolic diterpene
Rosemary & Sage
Antioxidant;
Protects skin cells
Reuter et al, Sage extract rich in

carnosol

leaves
inhibits lipid
against UV-
phenolic diterpenes inhibits

peroxidation;
induced erythema
ultraviolet-induced erythema in

protects from
Used as a
vivo. Planta Med. 2007

carcinogens
preservative (anti-
Sep; 73(11): 1190-1.

microbial) or
Weckesser et al, Screening of

antioxidant in food
plant extracts for antimicrobial

and nonfood
activity against bacteria and

products (e.g.
yeasts with dermatological

toothpaste,
relevance. Phytomedicine. 2007

mouthwash and
Aug; 14(7-8): 508-16.

chewing gum)
Collins & Charles, Antimicrobial

activity of Carnosol and Ursolic

acid. Food Microbiology (1987)

4(4): 311-315

b-Carotene
Carotenoid
Sweet potatoes,
Anti-oxidant; anti-
Protection of skin
Krinsky & Johnson, Carotenoid

carrots, goji,
cancer; supports
from ozone-
actions and their relation to health

melon
eye health and
induced
and disease. Mol Aspects Med.

(cantaloupe),
immune functions;
inflammation;
2005 Dec; 26(6): 459-516.

mangoes, apricots,
protection from
protection of skin
Valacchi et al, Beta-carotene

Persimmon,
free radicals;
from infra-red-
prevents ozone-induced

spinach, kale, and
cardio protection;
induced free
proinflammatory markers in

many others
bone health
radicals;
murine skin. Toxicol Ind Health.

treatment of
2009 May-Jun; 25(4-5): 241-7.

melasma;

food coloring

Crocetin
Carotenoid

Crocus flower and
Improves quality
To improve the
Botsoglou et al, Effect of dietary

dicarboxylic acid

Gardenia

of sleep; energy
oxidative stability
saffron (Crocus sativus L.) on the

jasminoides fruits,
booster;
of egg yolks of
oxidative stability of egg yolk.

and pistil of
neuroprotective;
hens (fed with
Br Poult Sci. 2005

saffron
anti-tumor
saffron); also used
Dec; 46(6): 701-7.

as a natural

colorant

Cryptoxanthin
Carotenoid
Petals & flowers
Provitamin A;
Associated with
Namitha & Negi Chemistry and

(xanthophyll)
of plants in the
Anti-oxidant; Free
better skin
biotechnology of carotenoids Crit

genus Physalis,
radical scavenger;
hydration (in men
Rev Food Sci Nutr. 2010

orange rind,
helps repair DNA;
only)
Sep; 50(8): 728-60

papaya, egg yolk,
chemopreventive;

Boelsma et al, Human skin

butter, apples,
anti-cancer;

condition and its associations

squash, pumpkins,
benefits

with nutrient concentrations in

tangerine
rheumatoid

serum and diet. Am J Clin Nutr.

arthritis

2003 Feb; 77(2): 348-55.

Curcumin
Phenolic

Curcuma longa

Anti-tumor, anti-
To improve
Rungphanichkul et al,

(Turmeric)
inflammatory &
transdermal
Preparation of curcuminoid

anti-oxidant,
delivery
niosomes for enhancement of

chemopreventive &
Acne; skin aging;
skin permeation. Pharmazie. 2011

chemotherapeutic;
psoriasis
Aug; 66(8): 570-5.

inhibits iNOS,

Lima et al, Curcumin induces

COX & LOX,

heme oxygenase-1 in normal

induces HO-1;

human skin fibroblasts through

epigenetic agent

redox signaling: relevance for

anti-aging intervention. Mol Nutr

Food Res. 2011 Mar; 55(3): 430-42

Jurenka, Anti-inflammatory

properties of curcumin, a major

constituent of Curcuma longa: a

review of preclinical and clinical

research. Altern Med Rev. 2009

Jun; 14(2): 141-53. Review

Emodin
Anthraquinone
Himalayan
Anti-
NA
El-Shemy et al, Antitumor

rhubarb &
inflammatory,

properties and modulation of

buckthorn & Aloe
anti-tumor,

antioxidant enzymes' activity by

vera leaf, Frangula
antipsychotic,

Aloe vera leaf active principles

bark
profibrinolytic &

isolated via supercritical carbon

wound healing;

dioxide extraction. Curr Med

inhibits NFkB

Chem. 2010; 17(2): 129-38.

activation &

Review

ICAM expression;

CK2 inhibitor;

anti-herpes

Epigallocatechin
Flavanol
Mainly from green
Anti-tumor, anti-
To protect
Huang & Frankel, Antioxidant

gallate

tea
HIV, anti-
liposomes against
Activity of Tea Catechins in

inflammatory,
oxidative rancidity
Different Lipid Systems, Journal

weight control

of Agricultural and Food

Chemistry 1997, 45 (8): 3033-3038

Ferulic acid
Hydroxycinnamic
Seeds of coffee,
Anti-tumor, bone
Most effective in
Kikuzaki et al, Antioxidant

acid
apple, artichoke,
health,
protecting linoleic
properties of ferulic acid and its

peanut, and
cardiovascular
acid from auto-
related compounds. J Agric Food

orange; seeds and
health, UV
oxidation
Chem. 2002, 50(7): 2161-8.

cell walls of
protection

commelinid plants

(rice, wheat, oats,

and pineapple)

Honokiol &
Biphenyl
Cones, bark, and
Antioxidative,
Reduces UVB-
Park et al, In vitro antibacterial

Magnolol
neolignans
leaves of
anti-inflammatory,
induced
and anti-inflammatory effects of

Magnolia

anti-tumor, anti-
inflammation &
honokiol and magnolol against

grandifloris

angiogenic, anti-
skin cancer;

Propionibacterium sp. Eur J

diabetic, anti-
Anti-acne; anti-
Pharmacol. 2004 Aug 2; 496(1-3):

microbial, anti-
aging skin cream
189-95.

fungal, anti-

Vaod et al, Honokiol, a

neurodegeneration,

phytochemical from the Magnolia

anti-depressant,

plant, inhibits

pain control,

photocarcinogenesis by targeting

hormonal

UVB-induced inflammatory

regulation,

mediators and cell cycle

cardiovascular and

regulators: development of

liver protective

topical formulation.

properties;

Carcinogenesis. 2010

Modulation of the

Nov; 31(11): 2004-11

NFkB signaling

Shen et al, Honokiol and

pathway

magnolol as multifunctional

antioxidative molecules for

dermatologic disorders.

Molecules. 2010 Sep

16; 15(9): 6452-65

Lee et al, Therapeutic

applications of compounds in the

Magnolia family. Pharmacol

Ther. 2011 May; 130(2): 157-76

Lutein
Carotenoid
Spinach, turnip
Macular
Protection of
Lee & Mi, Effects, quenching

greens, romaine
degeneration,
soybean oil from
mechanisms, and kinetics of

lettuce, eggs, red
cataracts, visual
photo-oxidation
carotenoids in chlorophyll-

pepper, pumpkin,
performance

sensitized photooxidation of

mango, papaya,

soybean oil . . . Agric. Food Chem.,

oranges, kiwi,

1990, 38 (8): 1630-1634

peaches, squash,

legumes,

brassicates,

prunes, sweet

potatoes,

honeydew melon,

rhubarb, plum,

avocado, pear

Luteolin
Biflavonoid

Reseda luteola,
Strong antioxidant
Topical anti-
Baolin et al, Topical application

Achillea

and radical
inflammatory;
of luteolin inhibits scratching

millefolium,
scavenger; anti-
anti-pruritus
behavior associated with allergic

Chamomillae

cancer; fights

cutaneous reaction in micee.

requtita, Cynara
allergies, anti-

Planta Med. 2005

scolymus, Thymus
inflammatory;

May; 71(5): 424-8.

vulgaris, Erigeron
cataract;

canadensis,
competitive

Propolis, etc.
inhibitor of

xanthine oxidase;

inhibits lipid

peroxidation

Lycopene
Carotenoid
Vietnam Gac,
Anti-cancer,
Most powerful
Montesano et al, Pure lycopene

tomatoes,
neuroprotective,
carotenoid
from tomato preserves extra

Grapefruit,
cardioprotection,
quencher of
virgin olive oil from natural

Watermelon,
male fertility
singlet oxygen;
oxidative events during storage. J

guava, apricots,

used to preserve
Agric Food Chem, 2006, 83(11):

carrots, autumn

oils
933-941

olive

Moronic acid
Triterpenic acid

Rhus javanica (a
Anti-HIV activity;
NA
Donglei et al, Anti-AIDS Agents

sumac), mistletoe,
also active against

69. Moronic Acid and Other

frankincense,
herpes simplex

Triterpene Derivatives as Novel

olibanum
virus 1

Potent Anti-HIV Agents. Journal

of Medicinal Chemistry 2006, 49

(18): 5462-9.

Oleanolic acid
Triterpenic acid
Olive leaf,
Anti-
For protection of
Guinda et al, Supplementation of

american
inflammatory,
vegetable oils
oils with oleanolic acid from the

pokeweed, honey
chemoprevention,

olive leaf (olea europaea),

mesquite, garlic,
anti angiogenic

European Journal of Lipid

java apple, cloves,

Science and Technology 106 (1):

and many other

22-26, 2004

Syzygium species.

Paprika
Phenolic acid
Fruits of
Anti-inflammatory
To increase oil
Yang

(capsaicin)

Capsicum annuum

and analgesic;
stability during
http://www.springerlink.com/

(chili peppers).
animal repellent;
frying
content/?Author=Cheul-Young+Yang

anti bacterial

et al, Capsaicin and tocopherol

in red pepper seed oil enhances

the thermal oxidative stability

during frying, Journal of Food

Science and Technology,

2010, 47(2): 162-165

Phytoene
Carotenoid
In most fruits and
UV absorber anti-
Sunscreen
L. von Oppen-Bezalel (2009).

(colorless)
vegetables; also in
inflammatory,
stabilizer
“Lightening, Boosting and

algae (Dunaliella)
DNA & collagen

Protecting with Colorless

protection, anti-

Carotenoids”. Cosmetics &

pigmentation

Toiletries magazine 124 (3): 66-75.

Phytofluene
Carotenoid
Tomatoes and
UV absorber, anti-
Sunscreen
L. von Oppen-Bezalel (2007).

(colorless)
other fruits &
inflammatory,
stabilizer
“UVA, A Main Concern in Sun

vegetables; also in
DNA & collagen

Damage: Protection from the

algae (Dunaliella)
protection, anti-

Inside and Outside with

pigmentation

Phytoene, Phytofluene, the

Colorless Carotenoids and more”.

SÖFW-Journal.

Quercetin
Flavonol
Citrus fruits,
Antihistamine and
To reduce the
Kiokias et al, In Vitro Activity of

apples, onions,
anti-inflammatory;
oxidative
Vitamins, Flavonoids, and

parsley, sage, tea,
may help protect
deterioration of
Natural Phenolic Antioxidants

and red wine,
against heart
cottonseed o/w
Against the Oxidative

olive oil, grapes,
disease and
emulsions
Deterioration of Oil-Based

dark cherries, and
cancer.

Systems. Crit Rev Food Sci Nutr.

dark berries

2008, 48(1): 78-93

Reticuline
Alkaloid

Lindera aggregate;
Vasorelaxant
Hair growth
Nakaoji et al, Norreticuline and

roots of Polyalthia

reticuline as possible new agents

cerasoides

for hair growth acceleration. Biol

Pharm Bull. 1997

May; 20(5): 586-8.

Rosmarinic acid
Phenolic acid
Found in many
Antiviral,
To slow rancidity
Frankel et al, Antioxidant

plants, including
antibacterial, anti-
in food, fats, and
Activity of a Rosemary Extract

rosemary, basil,
inflammatory,
oils.
and Its Constituents, Carnosic

peppermint, lemon
hepatoprotective,

Acid, Carnosol, and Rosmarinic

balm (Melissa
antispasmodic

Acid, in Bulk Oil and Oil-in-

officinalis), and

Water Emulsion. J. Agric. Food

fennel.

Chem., 1996, 44 (1): 131-135

Salvigenin
Flavone

Rosmarinus

Anti-oxidant, anti-
Topical anti-
Kuo et al, Anti-inflammatory

officinalis leaves
inflammatory,
inflammatory
effects of supercritical carbon

& Salvia
anti plasmodial

dioxide extract from Rosmarinus

leriaefolia

officinalis leaves. J Agric Food

Chem. 2011 Apr 27; 59(8): 3674-85

Tanshinone IIA
Diterpenoid
Found in Salvia
Anti-oxidant, anti-
NA
Li et al, Tanshinone IIA Inhibits

naphthoquinone

miltiorrhiza &
inflammatory,

Growth of Keratinocytes through

Aquilaria sinensis;
Inhibits AP-1

Cell Cycle Arrest and Apoptosis:

part of the Chinese
activity;

Underlying Treatment

medicine Tanshen
antagonist of

Mechanism of Psoriasis.

PPARγ; anti

Evid Based Complement Alternat

obesity; anti

Med. 2012; 2012: 927658.

psoriasis; anti

angiogenic;

improves

circulation;

cardioprotective

Thymoquinone
Quinone

Nigella sativa

anti-cancer,
Inhibits corneal
Ragheb et al, The protective

(cumin) &
analgesic
angiogenesis
effect of thymoquinone, an anti-

Thymus vulgaris

anticonvulsant,

oxidant and anti-inflammatory

L. aerial flowering
angiogenesis

agent, against renal injury: a

parts & Satureja
inhibitor; histone

review. Saudi J Kidney Dis

montana

deacetylase

Transpl. 2009 Sep; 20(5): 741-52.

inhibitor; strong

Review.

anti-oxidant;

protects against

renal injury;

analgesic

Ursolic acid
Pentacyclic
Apples, basil,
Cardioprotective,
Anti-wrinkle
Sultana N., Clinically useful

triterpene acid
bilberries,
anticancer,

anticancer, antitumor, and

cranberries, elder
cytotoxic,

antiwrinkle agent, ursolic acid

flower,
antitumor,

and related derivatives as

peppermint,
antioxidant, anti-

medicinally important natural

rosemary,
inflammatory,

product. J Enzyme Inhib Med

lavender, oregano,
anti-HIV, acetyl

Chem. 2011 26(5): 616-42

thyme, hawthorn,
cholinesterase, α-

prunes
glucosidase,

antimicrobial, and

hepatoprotective

Vanillic acid
Phenolic acid

Angelica sinensis,
Anti-oxidant; anti-
inhibition of
Chou et al, Antioxidative

Origanum vulgare,
diabetic;
alpha-melanocyte-
characteristics and inhibition of

Allium cepa,
hepatoprotective
stimulating
alpha-melanocyte-stimulating

Allium sativum,

hormone-
hormone-stimulated

Armoracia

stimulated
melanogenesis of vanillin and

rusticana, &

melanogenesis;
vanillic acid from Origanum

Aspalathus

Preservation of

vulgare. Exp Dermatol. 2010

linearis

fresh food
Aug; 19(8): 742-50.

Verbascoside
Phenylethanoid

Buddleja davidii

antioxidant, anti-
Promotes skin
Vertuani et al, Activity and

(acteoside)
glycoside
cell cultures
inflammatory,
repair and
stability studies of verbascoside,

photoprotective
ameliorates skin
a novel antioxidant, in dermo-

and
inflammation;
cosmetic and pharmaceutical

chelating, antiproliferative
↑GST activity
topical formulations. Molecules.

2011 Aug 18; 16(8): 7068-80

Vitexin
Biflavonoid

Ampelopsis

Anti-oxydant,
Inhibition of
Kim et al, Vitexin, orientin and

grossedentata

anti-tumor, anti-
adipogenesis;
other flavonoids from Spirodela

stems; Jatropha
inflammatory,
Anti-glycation

polyrhiza inhibit adipogenesis in

curcas leaves;
hypotensive,
activity
3T3-L1 cells. Phytother Res.

hawthorn herb;
antispasmodique;

2010 Oct; 24(10): 1543-8.

Arnebia

anti-histamine

Prabhakar et al, Pharmacological

hispidissima;
activity

investigations on vitexin. Planta

Fenugreek;

Med. 1981 Dec; 43(4): 396-403.

Ochrocarpus

Peng et al, Inhibitory effect of

longifolius; Acer

mung bean extract and its

palmatum

constituents vitexin and

isovitexin on the formation of

advanced glycation endproducts.

Food Chemistry (2008) 106 (2):

475-481

Vitamin E
Vitamin
Wheat germ oil,
Anti-
Anti-wrinkle,
Thiele & Ekanayake-

sunflower oil, nuts
inflammatory,
photoprotective,
Mudiyanselage,

and nut oils, leafy
cardioprotective,
and skin barrier
Vitamin E in human skin: organ-

vegetables,
anti-tumor
stabilizing
specific physiology and

avocado,

properties
considerations for its use in

asparagus, kiwi,

To increase oil
dermatology. Mol Aspects Med.

broccoli, pumpkin

stability
2007 28(5-6): 646-67.

mangoes, sweet

Kiokias et al, In Vitro Activity of

potatoes, papayas

Vitamins, Flavonoids, and

Natural Phenolic Antioxidants

Against the Oxidative

Deterioration of Oil-Based

Systems. Crit Rev Food Sci Nutr.

2008, 48(1): 78-93

Zeaxanthin (lutein
Carotenoid
Leaves of most
Anti-oxidant; eye
Food dye
Lien et al, Nutritional influences

isomer)

green plants; also
health; macular
UV protection for
on visual development and

paprika, saffron
degeneration;
skin; inhibits skin
function. Prog Retin Eye Res.

cataracts
lipid peroxidation
2011 May; 30(3): 188-203

Palombo et al, Beneficial long-

term effects of combined

oral/topical antioxidant treatment

with the carotenoids lutein and

zeaxanthin on human skin: a

double-blind, placebo-controlled

study. Skin Pharmacol Physiol.

2007; 20(4): 199-210

When present, antioxidants may be present in an amount that increases the Rancimat induction time (according to the ISO Method no. 6886-2006) to greater than 3 hours, greater than 4 hours, or greater than 5 hours, or more. Natural antioxidants may be selected from botanical extracts known to have antioxidant activity. Typically, amounts from about 0.1-2% (w/w) of such extracts are sufficient to impart the desired stability to a lipophilic carrier composition. Preferably, amounts from 0.2% to 2.0% or from 0.5% to 1.5% (w/w) are present in the inventive lipophilic carrier compositions. Suitable antioxidants for use with the present invention include natural or synthetic caffeic acid and carnosic acid and mixtures thereof. Preferably, the antioxidants are Rosmarinus officinalis (rosemary) leaf extract and/or Solidago virgaurea (goldenrod) extract. Most preferable is a combination of Rosmarinus officinalis extract and Solidago virgaurea extract. When used in normal daily conditions, oils or any compounds used in formulations may be exposed to light (UV) or a combination of light, heat, and air. Furthermore, they may also be in contact with other compounds having pro-oxidative properties. In such conditions, various types of reactive oxygen species or free radicals may be generated. Antioxidants usually target specific types of reactive oxygen species or free radicals. To ensure broader protection (especially of the vegetable oil), rosemary and goldenrod extracts together may be suitable.

Nevertheless, rosemary extract and goldenrod extract may also be used separately. For example, either only 0.1% of rosemary extract (and no solidago extract) or only 0.1% of solidago extract (and no rosemary extract) in the lipophilic carrier composition may be used.

The solubilizing system of the present invention preferably includes a cosmetically acceptable alcohol such as ethanol, and preferably also octyldodecanol and a fatty acid ester of octyldodecanol, e.g., octyldodecyl oleate and/or octyldodecyl stearoyl stearate. In some embodiments, the solubilization system comprises ethanol at 2-20% (w/w) of the total solubilization system, octyldodecanol at 20-40% (w/w) of the total solubilization system, a first fatty acid ester of octyldodecanol at 20-55% (w/w) of the total solubilization system, and, optionally, a second fatty acid ester of octyldodecanol at 20-55% (w/w) of the total solubilization system.

Preferably, the amounts of the components of the solubilization system are chosen such that, when the solubilization system is used to prepare a lipophilic carrier composition, the ethanol is present in an amount from 2-15%, 2-10%, 2-7%, 3-10%, or 4-8% (w/w) of the lipophilic carrier composition. Preferably, the octyldodecanol is present in the lipophilic carrier composition in an amount from 15-35%, 15-30%, 20-30%, or 25-30% (w/w) of the lipophilic carrier composition. Preferably, octyldodecyl oleate is present in an amount from 15-25%, 15-20%, or 20-25% (w/w) of the lipophilic carrier composition. Preferably, octyldodecyl stearoyl stearate is present in an amount from 5-15%, 5-10%, or 10-15% (w/w) of the lipophilic carrier composition.

In certain embodiments, the solubilization system may contain different components from those described above. In such embodiments, the solubilization system is such that the lipophilic bioactive botanical extract may be dissolved therein, if necessary by the use of elevated temperatures (e.g., 40-100° C.), and remain dissolved as the temperature is lowered to about room temperature, at which point the vegetable oil is added. The solubilization system allows for the combining of bioactive botanical extract and vegetable oil in one composition, without unacceptable oxidation of the fatty acids in the vegetable oil.

Lipophilic bioactive botanical extracts can be solubilized in a lipophilic carrier composition comprising a vegetable oil using a solubilizing system as described above. In one embodiment, a first phase is prepared by combining the lipophilic bioactive botanical extract and the solubilizing system to form a mixture. The mixture is then heated to between 40° C. and 100° C. under a nitrogen atmosphere until complete solubilization of the extract, as judged by visual inspection. The solution is then cooled, preferably to a temperature of about 35-40° C., about 30-35° C., about 25-30° C., about 20-25° C., or about 15-20° C., the vegetable oil is added, and the mixture is cooled to room temperature, if not already at room temperature. A second phase is prepared separately by dissolving the antioxidant extracts in a cosmetically compatible alcohol, e.g., ethanol, and the resulting mixture is then agitated at room temperature until the extracts are dissolved. The first and second phases are then combined together under agitation until a homogenous mixture is obtained.

In certain embodiments, the lipophilic carrier composition of the present invention comprises more than one lipophilic bioactive botanical extract, more than one vegetable oil, or more than one antioxidant. In certain embodiments, the lipophilic carrier composition comprises two lipophilic bioactive botanical extracts, two vegetable oils, or two antioxidants.

TABLE 3

Representative ranges of ingredients suitable for certain embodiments

of lipophilic bioactive botanical extracts solubilized with vegetable oils

(lipophilic carrier compositions).

Percentages represent w/w of the total lipophilic carrier composition.

Vegetable Oil
20-40%

Octyldodecanol
15-35%

Octyldodecyl Oleate,
15-25%

Octyldodecyl Stearoyl Stearate
5-15%

Lipophilic bioactive botanical extract
0.1-5.0%

Ethanol
2-15%

Antioxidant
0.01-2.0%

In certain embodiments, the vegetable oil is present at 20-25%, 25-30%, 30-35%, or 35-40% (w/w). In certain embodiments, the octyldodecanol is present at 15-20%, 20-25%, 25-30%, or 30-35% (w/w). In certain embodiments, the octyldodecyl oleate is present at 15-20% or 20-25% (w/w). In certain embodiments, the octyldodecyl stearoyl stearate is present at 5-10% or 10-15% (w/w). In certain embodiments, the lipophilic bioactive botanical extract is present at 0.1-0.5%, 0.5-1%, 1-2%, 2-3%, 3-4%, or 4-5% (w/w).

The presolubilized extracts in lipophilic carrier compositions are easily incorporated into a wide variety of product types that include but are not limited to solid and liquid compositions intended for topical use such as lotions, creams, gels, sticks, sprays, shaving creams, ointments, cleansing liquid washes and solid bars, pastes, powders, mousses, masks, peels, makeup, and wipes. The compositions may be used in conjunction with other devices such as skin abrading, skin massaging, or electro-stimulation devices, light-therapy devices, ultrasound devices, radio frequency devices, thermal/cooling devices, iontophoresis devices, and micro-penetration devices.

EXAMPLES

To assess the efficacy of skin protective, soothing and repairing effects as well as the oxidation stability of a cosmetic topical product incorporating the inventive lipophilic carrier compositions, the following generic formulations were prepared. In a first embodiment, a lipophilic bioactive botanical extract of Cnidium monnieri fruit in a lipophilic carrier composition that included Echium plantaginium seed oil was used to prepare a cosmetic formulation that was evaluated for skin protective, soothing and repairing effect upon exposure to a chemical agent.

In a second embodiment, a lipophilic bioactive botanical extract of Cnidium monnieri fruit in a lipophilic carrier composition that included Echium plantaginium seed oil was used to prepare a cosmetic formulation that was evaluated for skin protective, soothing and repairing effect upon exposure to ultraviolet radiation.

The following general formulations were prepared in order to assess the stability and efficacy of the inventive compositions:

TABLE 4

Formulations

Ingredients
Formula 1
Formula 2
Formula 3
Formula 4

Total
100.00
100.00
100.00
100.00

Trade

INCI Name
Name

Water Phase (Phase A):

Water

96
95.3
95.3
95.3

Sodium Polyacrylate
Cosmedia
0.6
0.6
0.6
0.6

SP

Preservative
Euxil K300
0.4
0.4
0.4
0.4

Oil Phase (Phase B):

Cetearyl Alcohol
Hydrenol D
2
2
2
2

Ceteareth-20
Eumulgin
1
1
1
1

B2

Active (Part C):

Part C1

Lipophilic bioactive extract‡

0
0
0
0.01

Octyldodecanol

0
0
0.63
0.62

Octyldodecyl Oleate

0
0
0.39
0.39

Octyldodecyl Stearoyl

0
0
0.18
0.18

Stearate

Part C2

Vegetable Oil†

0
0.7
0.7
0.7

Rosemary leaf extract

0
0
0.002
0.002

Goldenrod Extract

0
0
0.002
0.002

Ethanol

0
0
0.096
0.096

Total Oil Loading:

3.00
3.70
3.70
3.70

Total Water Loading:

97.00
96.30
96.30
96.30

Exemplified lipophilic bioactive botanical extract: Example 6: Cnidium monnieri Fruit Extract; Example 7: Paeonia suffruticosa Root extract.

^†Exemplified Vegetable Oil Example 6: Echium plantagineum seed oil; Example 7: Ribes nigrum (black currant) seed oil.

Comparative Example 1
Method of Preparing Base Cream Formula 1

Phase A and Phase B (see Table 4) were prepared separately by weighing their ingredients at room temperature, warming the ingredients to 75° C., and then combining the respective ingredients of the two phases with stirring. The phases were then warmed to about 75° C. and combined with agitation until homogenous.

Comparative Example 2
Method of Preparing Formula 2, Base Cream Plus Vegetable Oil

Comparative Example 3
Method of Preparing Formula 3, Base Cream, Vegetable Oil Plus Solubilization System and Antioxidants

Phase A and Phase B were prepared separately by weighing their ingredients at room temperature, warming the ingredients to 75° C., and then combing the respective ingredients of the two phases with stirring. The phases were then warmed to about 75° C. and combined with agitation until homogenous. Part C was prepared by separately combining the respective ingredients of Parts C1 (lipophilic bioactive extract is not included) and C2 with stirring and then combining Parts C1 and C2 at room temperature. Part C was then added to the mixture of Phase A and Phase B and homogenized.

Example 4
Method of Preparing Formula 4, Active Cream Incorporating Inventive Presolubilized Lipophilic Bioactive Botanical Extract in a Lipophilic Carrier Composition

A presolubilized lipophilic bioactive botanical extract was prepared as follows: Part C was prepared by first combining the lipophilic bioactive botanical extract in a mixture of octyldodecanol, octyldodecyl oleate, and octyldodecyl stearoyl stearate while heating to between 65-70° C. under a nitrogen atmosphere until complete solubilization of the extract resulting in a clear or translucent solution. The solution was then cooled to 45° C., the vegetable oil was added, and the mixture was cooled to room temperature. A mixture of the antioxidants dissolved in ethanol was then added to the cooled solution with agitation. This presolubilized lipophilic bioactive botanical extract in a lipophilic carrier composition (Part C) was then combined with a base cream of Formula 1 (comparative example 1) and homogenized.

Example 5
Protective Effect of Antioxidants

Experiments were performed using the Rancimat method (Method: ISO 6886-2006) to assess the efficacy of a lipophilic carrier composition comprising Rosmarinus officinalis leaf extract and Solidago virgaurea (Goldenrod) extract to protect oil derived from Echium plantagineum seeds or from Ribes nigrum seeds from oxidation when the oil and the antioxidants are present in the lipophilic carrier composition. In the Rancimat method, a sample of oil is heated under atmospheric pressure, and air is allowed to bubble through the oil at a selected temperature. Under these conditions, a lipoperoxidative reaction occurs and the short-chain volatile acids produced thereby are recovered and measured conductometrically in distilled water. The time required to produce a sudden increase in conductivity, due to the formation of volatile acids, determines an induction time which can be defined as a measure of the oxidative stability of the oil. A Metrohm Rancimat model 743® (Herisau, Switzerland) was used. Results obtained showed that the presence of Rosmarinus officinalis leaf extract and Solidago virgaurea extract protected the oil derived from Echium plantagineum seeds (Table 5) or from Ribes nigrum seed extract (Table 6) from degradation induced by heat and air contact. Furthermore, it was demonstrated that the addition of other ingredients of the lipophilic carrier composition, e.g., a Cnidium monnieri fruit extract or a Paeonia suffruticosa root extract, does not negatively affect the stability of Echium plantagineum oil or Ribes nigrum oil towards oxidation.

TABLE 5

Effect of various components of the Echium plantagineum seed oil-based compositions on Rancimat time.

octyldodecyl

Echium

oleate,

Rosmarinus

Solidago

Cnidium

plantagineum

octyldodecyl

officinalis

virgaurea

monnieri

seed oil (%)
Octyldodecanol
stearoyl
Ethanol
(Rosemary) leaf
(Goldenrod)
Fruit
Rancimat

Source 1
Source 2
(%)
stearate (%)
(%)
extract (%)
extract (%)
Extract (%)
time (hr)

100
—
—
—
—
—
—
—
0.3

—
100
—
—
—
—
—
—
0.1

35
—
29.5
30
4.8
—
—
—
3.3

35
—
29.5
30
4.8
0.1
0.1
—
19.6

35
—
29.5
30
4.8
0.1
0.1
0.5
20.4

TABLE 6

Effect of various components of the Ribes nigrum (black currant) seed oil-based compositions on Rancimat time.

octyldodecyl

Ribes nigrum

oleate,

Rosmarinus

Solidago

Paeonia

(Black Currant)

octyldodecyl

officinalis

virgaurea

suffruticosa

seed oil (%)
Octyldodecanol
stearoyl
Ethanol
(Rosemary) leaf
(Goldenrod)
Root
Rancimat

Source 1
Source 2
(%)
stearate (%)
(%)
extract (%)
extract (%)
extract (%)
time (hr)

100
—
—
—
—
—
—
—
0.2

—
100
—
—
—
—
—
—
0.1

35
—
29
30
4.8
—
—
—
7.4

35
—
29
30
4.8
0.1
0.1
—
30.7

35
—
29
30
4.8
0.1
0.1
1.0
33.4

Summary of Clinical Trials

Several lipophilic bioactive botanical extracts solubilized using the solubilization system described herein and present in a lipophilic carrier composition comprising vegetable oil were tested in human clinical trials for efficacy. These tests showed safety and efficacy in preventing and treating skin erythema and lessening the reduction of the skin barrier function after exposure to radiation and chemical stress.

Example 6
Echium Plantaginium-Based Active Cream with Cnidium Monnieri Fruit Extract

Formulas 1-4 as described above were prepared, wherein the lipophilic bioactive botanical extract was Cnidium monnieri fruit extract and the vegetable oil was Echium plantaginium seed oil.

The skin protective, soothing and repairing effect of a cosmetic topical product incorporating the presolubilized Cnidium monnieri fruit extract in a lipophilic carrier composition comprising Echium plantaginium seed oil upon exposure of the skin to a chemical agent was evaluated by applying topical treatments (2 mg/cm²) of each of Formulas 1 through 4.

Example 6
A Skin Protective Effect Upon Exposure to Chemical Agent

The test was carried out on a panel of 10 healthy volunteers. Selected skin areas were kept untreated and unexposed to the chemical agent as controls. Other skin areas were treated with the relevant formulation for a period of 10 days (from Day 1 to Day 10) preceding exposure to the chemical agent.

On Day 11, a solution of sodium lauryl sulfate (SLS) was applied to the skin using Finn chambers to chemically aggress the skin. Finn chambers were kept in contact with the skin for 20±4 hours. On Day 12, the Finn chambers were removed and skin erythema and the skin barrier function were assessed to measure the protective effect of the treatment with the formulations. The skin barrier function was assessed by the measurement of trans-epidermal water loss (TEWL) using the TEWAMETER 300® (Courage+Khazaka, electronic GmbH) apparatus and skin erythema was measured using the MEXAMETER® MX 18 (Courage+Khazaka, electronic GmbH) apparatus. Results are shown in Tables 7 and 8.

Application of the Echium Plantaginium Active Cream with Cnidium Monnieri Fruit Extract prior to the application of the SLS-containing Finn chambers resulted in a reduction of the SLS-induced increase in TEWL (Table 7). This demonstrated that the Echium Plantaginium Active Cream with Cnidium Monnieri Fruit Extract (made with a lipophilic carrier composition of the present invention) can protect the skin barrier function from a chemical aggression.

TABLE 7

Effect of a topical composition incorporating a presolubilized

Cnidium monnieri fruit extract in a lipophilic carrier composition

comprising Echium plantagineum seed oil on the prevention of

chemically-induced skin barrier damage - reduction of TEWL increase

when cream formulations produced with the lipophilic carrier

composition are applied as a preventive treatment.

Chemically-induced

increase in TEWL (%)¹

Control (untreated skin)
400.5

Formula 1: base cream
350.6

Formula 2: Formula 1 with
319.3 (p = 0.020) vs Placebo⁵

Echium plantagineum seed oil
(p = 0.011) vs Active cream⁶

Formula 3: Formula 2 with
331.3 (p = 0.028) vs Placebo³

antioxidants and solubilization system
(p = 0.016) vs Active cream⁴

Active Cream Formula 4: Formula 3 with
289.9 (p < 0.002) vs Placebo²

presolubilized Cnidium monnieri

fruit extract

¹Compared to non-chemically stressed skin (baseline)

²Statistically significant when compared to Placebo cream

³Statistically significant when compared to Placebo cream

⁴Statistically significant when compared to Active cream

⁵Statistically significant when compared to Placebo cream

⁶Statistically significant when compared to Active cream

The measurement of skin erythema (Table 8) also demonstrated that the application of the Echium plantaginium Active Cream with Cnidium monnieri Fruit Extract can protect from chemically-induced skin erythema.

The above results demonstrate that a topical composition comprising a lipophilic carrier composition of the present invention that was produced using a presolubilized Cnidium monnieri fruit extract provided better protection against an increase in TEWL than the same composition lacking certain ingredients present in the inventive composition.

TABLE 8

Effect of a topical composition incorporating a presolubilized

Cnidium monnieri fruit extract in a lipophilic carrier composition

comprising Echium plantagineum seed oil on chemical agent-induced

skin erythema when applied as a cream formulation produced with

the lipophilic carrier composition as a preventive treatment

Chemically-induced increase

in skin erythema (%)¹

Control (untreated skin)
59.0

Formula 1: base cream
51.2

Formula 2: Formula 1 with
43.8 (p = 0.030) vs Placebo⁵

Echium plantagineum seed oil
(p = 0.004) vs Active cream⁶

Formula 3: Formula 2 with
41.3 (p = 0.002) vs Placebo³

antioxidants and solubilization system
(p = 0.033) vs Active cream⁴

Active Cream Formula 4: Formula 3 with
36.8 (p < 0.001) vs Placebo²

presolubilized Cnidium monnieri fruit

extract

¹Compared to non-chemically stressed skin (baseline)

²Statistically significant when compared to Placebo cream

³Statistically significant when compared to Placebo cream

⁴Statistically significant when compared to Active cream

⁵Statistically significant when compared to Placebo cream

⁶Statistically significant when compared to Active cream

The above results demonstrate that a topical composition comprising a lipophilic carrier composition of the present invention that was produced using a presolubilized Cnidium monnieri fruit extract provided better protection against chemically-induced skin erythema than the same composition lacking certain ingredients present in the inventive composition.

Example 6B
Skin Soothing and Repairing Effect after Exposure to Chemical Agent

In another experiment, some skin areas were treated only upon removal of the SLS-containing Finn chambers (Day 12). In this case, skin was post-treated with one application (2 mg/cm²) of the Placebo cream prepared according to Formula 1 or the Echium Plantaginium Active Cream with Cnidium Monnieri Fruit Extract prepared according to Formula 4. The repairing effect of the treatments was assessed for skin barrier function and for skin erythema at time 30 minutes, 1 hour, 2 hours and 24 hours after the topical application of the cream formulations. The skin barrier function and erythema were assessed as described in Example 6A above. Results are shown in Tables 9 and 10 and reveal that applying the active cream formulation after the chemical stress with SLS significantly reduces the extent of skin barrier damage. This demonstrates the therapeutic action of the active cream formulation in promoting skin barrier function. The data on skin erythema in Table 10 also demonstrate that the therapeutic application of the active cream formulation can help repair chemically-induced skin erythema.

TABLE 9

Effect of a topical composition incorporating a presolubilized

Cnidium monnieri fruit extract in a lipophilic carrier composition

comprising Echium plantagineum seed oil on chemically-induced

skin barrier damage when cream formulations are applied after

chemical damage. The therapeutic effect was measured at various

time periods after the cream formulation application.

Reduction of chemically-induced skin increase in

TEWL upon product application (%)

After

After 30 min
After 1 hour
After 2 hour
24 hour

Control
−1.3
−6.4
−11.2
−23.2

(untreated

skin)

Base cream:
−8.1
−8.4
−13.2
−20.6

Formula 1

Active cream:
−18.5
−24.4
−24.5
−28.8

Formula 4
(p = 0.005)¹
(p = 0.007)¹
(p = 0.006)¹
(p = 0.009)¹

¹Statistically significant when compared to Placebo cream

TABLE 10

Effect of a topical composition incorporating a presolubilized

Cnidium monnieri fruit extract in a lipophilic carrier composition

comprising Echium plantagineum seed oil on chemically-induced

skin erythema when cream formulations are applied after chemical

damage. The therapeutic effect was measured at various time

periods after the cream formulation application

Reduction of chemically-induced skin

erythema upon product application (%)

After

After 30 min
After 1 hour
After 2 hour
24 hour

Control
3.7
4.1
4.4
2.4

(untreated

skin)

Base cream:
−4.3
−5.5
−5.6
−6.1

Formula 1

Active cream:
−5.2
−6.7
−7.0
−9.2

Formula 4
(p = 0.463)²
(p = 0.510)²
(p = 0.394)²
(p = 0.032)¹

¹Statistically significant when compared to Placebo cream

²Not statistically significant when compared to Placebo cream

The data shown in Tables 9 and 10 demonstrate that a topical composition comprising a lipophilic carrier composition of the present invention that was produced using a presolubilized Cnidium monnieri fruit extract provided better protection against an increase in TEWL as well as better protection against chemically-induced skin erythema than the same composition lacking certain ingredients present in the inventive composition.

Example 7
Ribes Nigrum-Based Active Cream with Paeonia Suffruticosa Root Extract

Formulas 1-4 as described above were prepared wherein the lipophilic bioactive botanical extract was Paeonia suffruticosa root extract and the vegetable oil was Ribes nigrum seed oil.

Example 7A
Skin Protective, Soothing Effect Upon UV Exposure

The skin protective, soothing and repairing effect of a cosmetic topical product incorporating the presolubilized Paeonia suffruticosa root extract in a lipophilic carrier composition comprising Ribes nigrum seed oil upon UV exposure (UVA+B using a solar simulator) was evaluated by applying topical treatments (2 mg/cm²) of each of Formulas 1 through 4.

The UV exposure intensity was calibrated to induce 1.5 MED. 1 MED, or Minimal Erythema Dose, corresponds to the minimum amount of UVB radiation required to produce redness 24 hours after skin exposure. The test was carried out on a panel of 10 healthy volunteers. Selected skin areas were kept untreated and unexposed to UV as controls. Other skin areas were treated with the relevant formulation for a period of 10 days (from Day 1 to Day 10) preceding UV exposure.

On Day 11, specific skin sites were exposed to UV. On Day 12, 20±4 hours after UV exposure, skin erythema and the skin barrier function were assessed to measure the protective effect of the treatments. The skin barrier function was assessed by the measurement of trans-epidermal water loss (TEWL) using the TEWAMETER 300® apparatus (Courage+Khazaka, electronic GmbH) and skin erythema was measured using the MEXAMETER® MX 18 apparatus (Courage+Khazaka, electronic GmbH). The results are reported in Tables 11 and 12.

The application of the cosmetic topical product incorporating the presolubilized Paeonia suffruticosa root extract in a Ribes nigrum seed oil prior to the application of UV light resulted in a reduction of the UV-induced increase in TEWL (Table 11). The most favorable results were observed for the active cream formulation, which was produced by using the solubilization system of the present invention to presolubilize the Paeonia suffruticosa root extract, followed by addition of the Ribes nigrum seed oil to form a lipophilic carrier composition comprising both the Paeonia suffruticosa root extract and the Ribes nigrum seed oil. This lipophilic carrier composition was incorporated into the base formulation to give the active cream. These results demonstrate that the active cream formulation can protect against UV-induced skin barrier function loss.

The measurement of skin erythema (Table 12) demonstrated that the application of the active cream formulation can protect from UV-induced skin erythema.

TABLE 11

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier

composition comprising Ribes nigrum (black currant) seed oil

on the prevention of UV-induced skin barrier damage - reduction

of TEWL increase when cream formulations are applied as a

preventive treatment.

UV-induced increase

in TEWL (%)¹

Control (untreated skin)
79.5

Formula 1: placebo base cream
81.2

Formula 2: Formula 1 with Ribes
51.9 (p = 0.001) vs Placebo⁵

nigrum (black currant) seed carrier oil
(p = 0.612) vs Active cream⁶

Formula 3: Formula 2 with
50.7 (p = 0.002) vs Placebo³

antioxidants and solubilization system
(p = 0.705) vs Active cream⁴

Active Cream Formula 4: Formula 3
48.0 (p < 0.002)²

with presolubilized Paeonia

suffruticosa root extract

¹Compared to non-irradiated skin (baseline)

²Statistically significant when compared to Placebo cream

³Statistically significant when compared to Placebo cream

⁴Non-statistically significant when compared to Active cream

⁵Statistically significant when compared to Placebo cream

⁶Non-statistically significant when compared to Active cream

TABLE 12

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum (black currant) seed oil on UV-induced

skin erythema when applied as a cream formulation

as a preventive treatment.

UV-induced increase in

skin erythema (%)¹

Control (untreated skin)
62.1

Formula 1: base cream
57.3

Formula 2: Formula 1 with Ribes nigrum
44.4 (p = 0.012) vs Placebo⁵

(Black Currant) seed carrier oil
(p = 0.127) vs Active cream⁶

Formula 3: Formula 2 with antioxidants
36.5 (p = 0.014) vs Placebo³

and solubilization system
(p = 0.470) vs Active cream⁴

Active Cream Formula 4: Formula 3 with
33.0 (p < 0.002)²

presolubilized Paeonia suffruticosa root

extract

¹Compared to non-irradiated skin (baseline)

²Statistically significant when compared to Placebo cream

³Statistically significant when compared to Placebo cream

⁴Non-statistically significant when compared to Active cream

⁵Statistically significant when compared to Placebo cream

⁶Non-statistically significant when compared to Active cream

Example 7B
Skin Soothing and Repairing Effect after Uv Exposure

In another experiment, some skin areas were treated only after exposure of the skin to UV (Day 12). In this case, skin was post-treated with one application (2 mg/cm²) of the Placebo cream prepared according to Formula 1 or the Active Cream prepared according to Formula 4. The repairing effect of the treatments was assessed for skin barrier function and for skin erythema at time 30 minutes, 1 hour, 2 hours and 24 hours upon the topical application of the cream formulations. The skin barrier function and erythema were assessed as described above. Results are reported in Tables 13 and 14 and show that applying the active cream formulation after UV exposure significantly reduces the extent of skin barrier damage (Table 13). This provides evidence for the therapeutic action of the active cream formulation in promoting skin barrier function. The measurement of skin erythema (Table 14) also demonstrated that the therapeutic application of the active cream formulation can help repair damage from UV-induced skin erythema.

TABLE 13

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum (black currant) seed oil on UV-induced skin

barrier damage when cream formulations were applied after UV -

therapeutic effect measured at various time periods after the cream

formulation application.

Reduction of UV-induced skin increase in

TEWL upon product application (%)

After

After 30 min
After 1 hour
After 2 hour
24 hour

Control
−0.6
1.2
−0.8
−6.2

(untreated

skin)

Placebo Base
−10.1
−9.8
−12.3
−10.2

cream:

Formula 1

Active cream:
−16.7
−18.2
−19.7
−28.7

Formula 4
(p = 0.003)¹
(p = 0.001)¹
(p = 0.003)¹
(p < 0.001)¹

¹Statistically significant when compared to Placebo cream

TABLE 14

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum seed oil on UV-induced skin erythema

when cream formulations are applied after UV - therapeutic effect

measured at various time periods after the cream formulation application.

Reduction of UV-induced skin erythema

upon product application (%)

After

After 30 min
After 1 hour
After 2 hour
24 hour

Control
0.7
−1.1
−3.3
−11.0

(untreated

skin)

Placebo base
−6.2
−9.1
−10.3
−11.7

cream:

Formula 1

Active cream:
−8.7
−12.1
−16.3
−19.5

Formula 4
(p = 0.046)¹
(p = 0.010)¹
(p = 0.008)¹
(p = 0.007)¹

¹Statistically significant when compared to Placebo cream

Example 7C
Reduction of the Appearance of Age Spots (Melasma)

Another experiment demonstrated the efficacy of a cosmetic topical product incorporating the presolubilized Paeonia suffruticosa root extract in a lipophilic carrier composition comprising Ribes nigrum seed oil in reducing the appearance of age spots (also known as brown spots, liver spots, melasma, solar lentigo, freckles, senile freckles, lengitines or chloasma “mask of pregnancy”). Age spots are hyperpigmented skin areas that may arise from over UV-exposure, in pregnant women, or in subjects undergoing hormonal replacement therapies. Their visual appearance is due to an accumulation of melanocytes and/or an excessive production of melanin pigments and this phenomenon becomes more apparent with increasing age. The efficacy of the cosmetic topical products disclosed herein for the treatment of age spots was evaluated by applying topical treatments (2 mg/cm²) of each of Formula 1 (Placebo cream) and Formula 4 (Active cream).

The test was carried out on a panel of 15 healthy volunteers with visible age spots. Formulas 1 and 4 were tested as a split-face clinical protocol where each Formula was applied on separate sides of the face down up to the upper chest area, twice daily. Evaluation of age spot appearance was measured at Day 0 (baseline) and after 30 (Day 30) and 60 days (Day 60) of product applications. The MEXAMETER® MX 18 apparatus (Courage+Khazaka, electronic GmbH) was used to measure the age spot color based on specific light wave-length absorption by melanin-related chromophores. Results are expressed as variation of the melanin index. The Spectrophotometer CM-700d (Konica Minolta Optics, Inc) was chosen to measure the age spot color intensity by computing specific light wave-length reflection of L* parameter (skin brightness) and b* parameter (variation from blue to yellow color) as the Individual Typology Angle)(ITA°). An increase in ITA° is indicative of a color intensity reduction. A separate individual measurement of the L* parameter was also performed to assess variations in general skin color lightness.

As a more visual assessment of the effect the treatments, a skilled dermatologist evaluated, in a blind fashion, the visual reduction of age spot appearance and the increase in skin complexion (color homogeneity). The evaluation criteria were as follows:

TABLE 15

Dermatologist clinical evaluation at Day 30 and

Day 60 in comparison to baseline
Score

No variation
1

Slight improvement
2

Moderate improvement
3

Remarkable improvement
4

Topical applications of the Active cream statistically reduced the melanin index (age spot pigment density) and increased the lightening of age spots present in the face, neck, and upper chest areas (Table 16 and 17, respectively). Furthermore, treatment with the Active cream statistically improved the general skin lightness (Table 18). Dermatologist assessments have shown that a reduction of age spot color appearance (Table 19) and an improvement in skin complexion (Table 20) can be visually observed already after 30 days of treatment. Those results demonstrate that topical applications of a cosmetic product incorporating the presolubilized Paeonia suffruticosa root extract in a lipophilic carrier composition comprising Ribes nigrum seed oil reduces the color pigmentation and the visual appearance of age spots. Furthermore, a general improvement in skin complexion could be observed.

TABLE 16

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum seed oil on age spot melanin index -

MEXAMETER ® MX 18.

Variation in melanin index upon product

application in comparison to baseline (%)

Day 30

Placebo

Day 60

Treatment
cream
Active cream
Placebo cream
Active cream

Melanin index
−2.5
−14.4
−1.5
−18.1

variation (%)

p value
N/A
p = 0.025¹
N/A
p = 0.004¹

¹Statistically significant when compared to Placebo cream

TABLE 17

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum seed oil on age spot color intensity

reduction (ITA °) - Spectrophotometer CM-700d.

ITA ° variation upon product application

in comparison to baseline (%)

Day 30
Day 60

Treatment
Placebo cream
Active cream
Placebo cream
Active cream

ITA °
−2.6
+12.4
−3.7
+20.1

variation

(%)

p value
N/A
p = 0.019¹
N/A
p = 0.002¹

¹Statistically significant when compared to Placebo cream

TABLE 18

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum seed oil on face, neck and upper chest

skin area color brightness (L*) - Spectrophotometer CM-700d.

L* variation upon product application

in comparison to baseline (%)

Day 60

Day 30

Active

Treatment
Placebo cream
Active cream
Placebo cream
cream

L* parameter
−0.7
+2.5
−0.5
+4.2

variation (%)

p value
N/A
p = 0.003¹
N/A
p < 0.001¹

¹Statistically significant when compared to Placebo cream

TABLE 19

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum seed oil on age spot visual appearance -

dermatologist evaluation.

Proportion of subjects for which a

reduction in the visual appearance

of age spots was observed (%)

Day 60

Day 30

Active

Treatment
Placebo cream
Active cream
Placebo cream
cream

Proportion of
0.0
26.7
6.7
53.3

subjects (%)

TABLE 20

Effect of a topical composition incorporating a presolubilized

Paeonia suffruticosa root extract in a lipophilic carrier composition

comprising Ribes nigrum seed oil on the visual assessment of skin

complexion - dermatologist evaluation.

Proportion of subjects for which an

improvement of skin complexion was

visually observed (%)

Day 60

Day 30

Active

Treatment
Placebo cream
Active cream
Placebo cream
cream

Proportion of
0.0
13.3
6.7
33.3

subjects (%)

Lipophilic Carrier Composition for Solubilizing Lipophilic Bioactive Botanical Extracts, Methods of Solubilizing Lipophilic Bioactive Botanical Extracts, and Methods of Using Solubilized Lipophilic Bioactive Botanical Extracts

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CROSS-REFERENCE TO RELATED APPLICATIONS

Provisional Applications (1)