Compositions for sebum control

Abstract

The present invention provides a composition for reducing lipid production in sebaceous gland cells or in the skin of a subject, the composition comprising a triterpenoid according to Formula (I) as described herein or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and a plant extract selected from extracts of plants of the genus Garcinia, Rubus, Strawberry, Ilex and Hedera.

Description

Technical Field

[0001] The present invention relates to a composition comprising a plant extract in combination with a triterpenoid compound, and the use of the composition in a method for reducing lipid production in sebaceous gland cells (sebocytes). Also provided is the use of the composition in a cosmetic method for reducing lipid production in the skin of an individual, and the use of the composition in a method for treating a skin disease or disorder associated with increased lipid production in sebaceous gland cells. Background Art

[0002] Sebum is an oily substance secreted by human sebaceous glands. Sebum is produced by sebocytes, which are highly specialized epithelial cells commonly found in the skin associated with hair follicles, although sebaceous glands not associated with hair follicles also exist.

[0003] Adult sebum typically includes triglycerides (-41%), wax monoesters (-25%), free fatty acids (-16%), and squalene (-12%) (Cheng et al., 2004). Other components such as keratin and cellular material may also be present.

[0004] Sebum forms an integral part of the epidermal barrier and the skin's immune system. Sebum is the natural moisturizer of the epidermis, helping to maintain its integrity. Sebum is important for maintaining the pH of the skin surface, which plays a role in protecting the skin from exogenous (pathogenic) microorganisms and promoting the growth of endogenous (resident) microbial communities. Sebaceous gland secretions in conjunction with apocrine glands (sweat glands) are also thought to play an important role in thermoregulation.

[0005] Sebocyte formation is controlled by multiple molecular pathways (e.g., Blimp1, Wnt, C-myc, Hedgehog), and sebum synthesis is strongly regulated by hormones, especially androgens such as testosterone.

[0006] Sebum is produced in a holocrine process in which sebocytes rupture and break down (disintegrate) while releasing sebum and cellular remnants. During terminal differentiation of sebocytes, metabolic activity is focused on the biosynthesis of lipids (lipogenesis), particularly the new synthesis of fatty acids and squalene.

[0007] Levels of sebum production (sebum secretion) vary from person to person and are affected by gender, age, physical activity, stress, certain medications, and illness. Oily skin is often observed during puberty due to hormonal changes that occur throughout adolescence.

[0008] Excessive sebum production is associated with cosmetic problems such as oily or shiny skin and poor makeup application, as well as medical problems. Excessive sebum production is seen in acne vulgaris, one of the most common skin diseases. Excessive sebum secretion (hyperseborrhea) is a scalp problem caused by excessive sebum production. Immediate symptoms of excessive sebum secretion include scalp itching and pain, but later symptoms are hair loss. Individuals with hyperseborrheic skin typically exhibit greater than 200 μg cm measured on the forehead. -2 Sebum levels in the skin (as discussed, for example, in WO 2020 / 263188). Dysregulated sebocyte differentiation is also a feature of some rare benign and malignant tumors.

[0009] Cosmetic treatments for excess lipid production generally do not address the underlying cause. Instead, cosmetic treatments generally provide immediate symptomatic relief, such as oily, enlarged pores, acne-prone skin, and irregular skin texture. For example, a common method of treating oily or shiny skin is to use a powder that provides an immediate masking effect by absorbing excess sebum on the skin surface. Alternatively, astringents and cleansers may be used.

[0010] Known methods for reducing lipids on the skin's surface are limited and produce few sustainable visible results over long periods of time. Long-term use of astringents and cleansers may aggravate the condition.

[0011] Therefore, there is a need to develop compositions and methods for reducing lipid production in sebaceous gland cells and the skin of an individual. Summary of the invention

[0012] Most generally, the present invention relates to a composition comprising a plant extract in combination with a triterpenoid. The inventors have discovered that such a composition provides an excellent lipid reduction effect in sebocytes.

[0013] The triterpenoids may be pentacyclic triterpenoids, such as oleanolic acid and hederagenin, or tetracyclic triterpenoids, such as cycloastragenol and elemenic acid.

[0014] Therefore, in a first aspect of the present invention, there is provided a composition comprising:

[0015] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0016] (b) a plant extract selected from extracts of plants of the genera Garcinia, Rubus, Fragaria, Ilex and Hedera,

[0017]

[0018] in:

[0019] -Y- is a covalent bond and -X- is -CH2-, -CH2CH2-, or -X- is absent and the carbon atom to which -X- is attached is bonded to H,

[0020] -Y- is -O-, and -X- is absent, and the carbon atom to which -X- is attached is bonded to H,

[0021] Dashed bonds indicate the presence of double or single bonds between ring carbon atoms, with only one double bond present within the ring.

[0022] R 1 , R 3 , R 3′ , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , and wherein -Y- is -O- and -X- is absent, R 8 and R 9 can form a heterocyclic ring together, and R 5 It is absent when the ring carbon to which it is attached is in a double bond;

[0023] R 2 and R 2 ' is independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 16 、CO2R 17 、OC(=O)R 18 , or R 2 and R 2 'Together represents =O;

[0024] R 11 and R 11' Independently selected from H, F, OH, SH, C 1-6Alkyl, I, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 19 、CO2R 21 、OC(=O)R 21 , or R 11 and R 11' Together they represent =O;

[0025] R C If not present, or if the ring carbon to which it is attached is not in a double bond, R C H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , or with R 12 Together they can form a carbon ring;

[0026] R D If not present, or if the ring carbon to which it is attached is not in a double bond, R D H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 21 and R 21 Independently selected from H, C 1-6 Alkyl and C 1-4 haloalkyl; and

[0027] n is 0 or 1.

[0028] Preferred features of the compositions, such as triterpenoids and plant extracts, are described below.

[0029] The inventors have found that the composition of the first aspect reduces lipid production in sebaceous gland cells.

[0030] Thus, in a second aspect of the invention there is provided a method for reducing lipid production in sebocytes, the method comprising contacting the sebocytes with a composition of the first aspect. The method may be in vivo or ex vivo, for example in vitro.

[0031] The inventors have found that the composition of the first aspect can reduce or improve cosmetic problems associated with excessive lipid production in the skin, such as oily or shiny skin, oily hair, enlarged skin pores, bad body odor, and reduced retention of makeup on the skin.

[0032] Thus, in a third aspect of the invention there is provided a cosmetic method for reducing lipid production in the skin of an individual, the method comprising contacting the skin with a composition of the first aspect.

[0033] The inventors have found that the composition of the first aspect is useful for treating or preventing medical problems associated with excessive lipid production in the skin, such as acne vulgaris and rosacea.

[0034] Thus, in a fourth aspect of the present invention there is provided a composition according to the first aspect for use in a method of treatment.

[0035] In a further related aspect of the invention there is provided a composition of the first aspect for use in a method of treating a skin disease or condition associated with overproduction of lipids in the skin, such as acne vulgaris and rosacea.

[0036] These and other aspects and embodiments of the invention are described in further detail below. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The present invention is described with reference to the drawings listed below.

[0038] Figure 1 AdipoRed for display TM Mean fluorescence intensity obtained by flow cytometry of dye-treated sebaceous gland cells. Cells were incubated for 3 days with the test composition. From left to right, DMSO (negative control), EGCG (positive control), salicylic acid (positive control), oleanolic acid, raspberry (Rubus idaeus) extract, and a combination of oleanolic acid and raspberry extract according to an embodiment of the present invention.

[0039] Figure 2 AdipoRed for display TM Mean fluorescence intensity obtained by flow cytometry of dye-treated sebaceous gland cells. Cells were incubated with the test composition for 3 days. From left to right, DMSO (negative control), EGCG (positive control), salicylic acid (positive control), oleanolic acid, Hedera helix extract, and a combination of oleanolic acid and Hedera helix extract according to an embodiment of the present invention.

[0040] Figure 3 AdipoRed for display TM Mean fluorescence intensity obtained by flow cytometry of dye-treated sebaceous gland cells. Cells were incubated with the test composition for 3 days. From left to right, DMSO (negative control), EGCG (positive control), salicylic acid (positive control), oleanolic acid, Ilex aquifolium extract, and a combination of oleanolic acid and Ilex aquifolium extract according to an embodiment of the present invention.

[0041] Figure 4 AdipoRed for display TM Mean fluorescence intensity of dye-treated sebaceous gland cells obtained by flow cytometry. Cells were incubated for 3 days with the test composition. From left to right, DMSO (negative control), EGCG (positive control), oleanolic acid, mangosteen (Garcinia mangostana) extract, and a combination of oleanolic acid and mangosteen extract according to an embodiment of the present invention.

[0042] Figure 5 AdipoRed for display TM Mean fluorescence intensity obtained by flow cytometry of dye-treated sebaceous gland cells. Cells were incubated for 3 days with the test composition. From left to right, DMSO (negative control), EGCG (positive control), beta-elemonic acid, raspberry extract, and a combination of beta-elemonic acid and raspberry extract according to an embodiment of the present invention.

[0043] Figure 6 AdipoRed for display TM Mean fluorescence intensity obtained by flow cytometry of dye-treated sebaceous gland cells. Cells were incubated for 3 days with the test composition. From left to right, DMSO (negative control), EGCG (positive control), cycloastragenol, raspberry extract, and a combination of cycloastragenol and raspberry extract according to an embodiment of the present invention.

[0044] Figure 7 AdipoRed for display TM Mean fluorescence intensity obtained by flow cytometry of dye-treated sebaceous gland cells. Cells were incubated with the test composition for 3 days. From left to right, DMSO (negative control), EGCG (positive control), oleanolic acid, Fragaria vesca extract, and a combination of oleanolic acid and Fragaria vesca extract according to an embodiment of the present invention.

[0045] In the figures, the following labels are used for comparisons in one-way (single-factor) analysis of variance (One-Way ANOVA):

[0046] *P value: <0.05 (statistically significant compared to DMSO)

[0047] **P value: <0.01 (statistically significant compared to DMSO)

[0048] ***P value: 0.001 (statistically significant compared to DMSO)

[0049] ****P value: <0.0001 (statistically significant compared to DMSO)

[0050] #P value: <0.05 (statistically significant compared with oleanolic acid)

[0051] ##P value: <0.01 (statistically significant compared with oleanolic acid)

[0052] ###P value: <0.001 (statistically significant compared with oleanolic acid)

[0053] ####P value: <0.001 (statistically significant compared with oleanolic acid) DETAILED DESCRIPTION

[0054] The present invention relates to a composition comprising a plant extract in combination with a triterpenoid compound, and the use of the composition in a method for reducing lipid production in sebaceous gland cells. Also provided is the use of the composition in a cosmetic method for reducing lipid production in the skin of an individual, and the use of the composition in a method for treating a skin disease or condition associated with increased lipid production in sebaceous gland cells.

[0055] The following preferred embodiments are applicable to all aspects of the invention as described above. The preferred embodiments may be combined in any combination.

[0056] Triterpenoids

[0057] The composition of the present invention comprises triterpenoids and plant extracts. The triterpenoids may be pentacyclic triterpenoids, such as oleanolic acid and hederagenin, or tetracyclic triterpenoids, such as cycloastragenol and elemenic acid.

[0058] Pentacyclic triterpenoids contain five fused carbon rings, and the rings are substituted. Tetracyclic triterpenoids contain four fused carbon rings, and the rings are substituted.

[0059] One of the fused carbon rings in the pentacyclic or tetracyclic triterpenoids may contain an internal carbon-carbon double bond. Thus, within the ring, double bonds exist between adjacent carbon ring atoms. In one embodiment, the fused ring is saturated.

[0060] In one embodiment, the triterpenoid is a triterpenoid that is not present in or otherwise derived from (obtained from) the plant extract with which it is used in combination.

[0061] The composition of the present invention comprises a triterpenoid compound according to formula (I):

[0062]

[0063] in:

[0064] -Y- is a covalent bond and -X- is -CH2-, -CH2CH2-, or -X- is absent and the carbon atom to which -X- is attached is bonded to H, or

[0065] -Y- is -O-, and -X- is absent and the carbon atom to which it is attached is bonded to H,

[0066] Dashed bonds indicate the presence of double or single bonds between ring carbon atoms, with only one double bond present within the ring.

[0067] R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , and wherein -Y- is -O- and -X- is absent, R 8 and R 9 can form a heterocyclic ring together, and R 5 It is absent when the ring carbon to which it is attached is in a double bond;

[0068] R 2 and R 2' Independently selected from H, F, OH, SH, C1-6 Alkyl, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 16 、CO2R 17 、OC(=O)R 18 , or R 2 and R 2' Together they represent =O;

[0069] R 11 and R 11' Independently selected from H, F, OH, SH, C 1-6 Alkyl, I, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 19 、CO2R 21 、OC(=O)R 21 , or R 11 and R 11' Together they represent =O;

[0070] R C In the absence of R, or in the case where the ring carbon to which it is attached is not in a double bond, C H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , or with R 12 Together they can form a carbon ring;

[0071] R D If not present, or if the ring carbon to which it is attached is not in a double bond, R D H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 ,

[0072] R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 and R 21 Independently selected from H, C 1-6 Alkyl and C1-4 haloalkyl; and

[0073] n is 0 or 1.

[0074] Alkyl is a monovalent saturated hydrocarbon group. Alkyl can be C 1-6 Alkyl groups, such as C 1-4 , C 1-3 or C 1-2 Alkyl, for example C1 alkyl (methyl). In this document, the prefix (for example C 1-6 ) represents the number of carbon atoms in the hydrocarbon backbone. Alkyl groups may be straight-chain or branched.

[0075] C 1-6 Examples of straight-chain alkyl groups include methyl (—Me), ethyl (—Et), n-propyl (—nPr), n-butyl (—nBu), n-pentyl (—Amyl), and n-hexyl.

[0076] C 1-6 Examples of branched alkyl groups include isopropyl (-iPr), isobutyl (-iBu), sec-butyl (-sBu), tert-butyl (-tBu), isopentyl, sec-pentyl, tert-pentyl, neopentyl, isohexyl, sec-hexyl, tert-hexyl, and neohexyl.

[0077] A haloalkyl group is an alkyl group in which one or more hydrogen atoms, for example one or all of the hydrogen atoms, are replaced by halogen atoms, for example F, Cl, Br and I. A haloalkyl group may be C 1-4 Haloalkyl, such as C 1-3 or C 1-2 The alkyl halide may be monohalogenated or perhalogenated. 1-4 ) represents the number of carbon atoms in the hydrocarbon backbone chain.

[0078] C 1-4 Examples of haloalkyl groups include chloromethyl (-CH2Cl), fluoromethyl (-CH2F), difluoromethyl (-CHF2), trifluoromethyl (-CF3), chloroethyl (-C2H4Cl), monofluoroethyl (-C2H4F), pentafluoroethyl (-C2F3), heptafluoropropyl (-C3F7) and nonafluorobutyl (-C4F9).

[0079] Hydroxyalkyl is an alkyl group in which one or more hydrogen atoms (e.g., one or more hydrogen atoms on a hydrogen atom) are replaced by a hydroxyl group (-OH). Hydroxyalkyl can be C 1-4 Hydroxyalkyl, such as C 1-3 or C 1-2 Hydroxyalkyl, for example C1 hydroxyalkyl. Hydroxyalkyl may be monohydroxyalkyl. In this document, the prefix (e.g. C 1-4 ) represents the number of carbon atoms in the hydrocarbon backbone chain.

[0080] C1-4 Examples of hydroxyalkyl groups include hydroxymethyl (-CH2OH) and hydroxyethyl (eg, -C2H4OH).

[0081] An alkenyl group is a monovalent unsaturated hydrocarbon group containing one or more carbon-carbon double bonds. 2-6 Alkenyl, such as C 2-5 , C 2-4 or C 2-3 As used herein, the prefix (e.g., C 2-6 ) represents the number of carbon atoms in the hydrocarbon backbone. The alkenyl group may be straight chain or branched. The alkenyl group may contain one or more, such as two or more, such as three or more carbon-carbon double bonds. In the case of the presence of two or more double bonds, these double bonds may be conjugated or non-conjugated.

[0082] C 2-6 Examples of straight chain alkenyl groups include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), 1-butenyl, 2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 1-hexenyl, and 2-, 3-, and 4-hexenyl.

[0083] C 2-6 Examples of branched alkenyl groups include isopropenyl (1-methylvinyl), isobutenyl (2-methyl-1-propenyl), 1-isopentenyl, (3-methyl-1-butenyl) and 2-isopentenyl (3-methyl-2-butenyl).

[0084] In a preferred embodiment, R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Not all are H.

[0085] In a preferred embodiment, R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Not all OH.

[0086] In a preferred embodiment, R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Not all CO2H.

[0087] In a preferred embodiment, selected from R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 At least four of the groups are H.

[0088] In a preferred embodiment:

[0089] R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8 ′、R 9 , R 9' , R 10 , and R 12 Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Fluoroalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 ;

[0090] R 2 and R 2' Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Fluoroalkyl, C 2-6 Alkenyl, OR 16 、CO2R17 、OC(=O)R 18 , or R 2 and R 2' Together they represent =O;

[0091] R 11 and R 11' Independently selected from H, F, OH, SH, C 1-6 Alkyl, I, C 1-4 Fluoroalkyl, C 2-6 Alkenyl, OR 19 、CO2R 21 、OC(=O)R 21 , or R 11 and R 11' Together they represent =O;

[0092] R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 and R 21 Independently selected from H, C 1-6 Alkyl and C 1-4 Fluoroalkyl; and

[0093] n is 1 or 2.

[0094] A fluoroalkyl group is an alkyl group in which one or more hydrogen atoms are replaced by fluorine atoms (i.e., F). 1-4 Fluoroalkyl, such as C 1-3 or C 1-2 Fluoroalkyl. As used herein, the prefix (e.g., C 1-4 ) represents the number of carbon atoms in the hydrocarbon backbone chain.

[0095] C 1-4 Examples of the fluoroalkyl group include monofluoromethyl (-CH2F), difluoromethyl (-CHF2), trifluoromethyl (-CF3), pentafluoroethyl (-C2F3), heptafluoropropyl (-C3F7), and nonafluorobutyl (-C4F9).

[0096] -Y- and -X- groups

[0097] In one embodiment, -Y- is a covalent bond and -X- is -CH2- or -CH2CH2-.

[0098] When -Y- is a covalent bond and -X- is -CH2-, a cyclopentenyl ring is formed.

[0099] When -Y- is a covalent bond and -X- is -CH2CH2-, a cyclohexyl ring is formed.

[0100] In one embodiment, -Y- is a covalent bond and -X- is absent, and the carbon atom to which -X- is attached is bonded to H.

[0101] In a preferred embodiment, -Y- is a covalent bond and -X- is -CH2CH2-. Thus, the compound of formula (I) is:

[0102]

[0103] In a preferred embodiment, -Y- is a covalent bond and -X- is -CH2-. Thus, the compound of formula (I) is:

[0104]

[0105] In one embodiment, -Y- is -O- and -X- is absent, and the carbon atom to which -X- is attached is bonded to H.

[0106] When -X- is absent and the carbon atom to which -X- is attached is bonded to H, a ring is not formed.

[0107] Double bond and R C and R D

[0108] In one embodiment, the compound of formula (I) is:

[0109]

[0110] In one embodiment, the compound of formula (I) is:

[0111]

[0112] In one embodiment, the compound of formula (I) is:

[0113]

[0114] In R C Where present, it may be H in one embodiment.

[0115] In one embodiment, when R C When present, it can be combined with R 12 Together with the carbon ring atoms to which they are attached, they form a carbon ring, such as C 3-6 The carbon ring may be a cyclopropane ring.

[0116] In R D If present, in one embodiment, it may be H or C 1-6 alkyl.

[0117] The value of n

[0118] In one embodiment, n is 0. The ring is thus a cyclopentyl ring. This is preferred in the case where -X- is absent and the carbon atom to which -X- is attached is bonded to H.

[0119] In one embodiment, n is 1. The ring is thus a cyclohexyl ring. This is preferred when -X- is -CH2-, -CH2CH2-.

[0120] R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Group

[0121] In a preferred embodiment:

[0122] R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Independently selected from H, F, OH, SH, OR 13 、CO2R 14 、OC(=O)R 15 , C 1-6 Alkyl, CF3, C2F5 and C 2-6 alkenyl; and

[0123] R 13 , R 14 and R 15 Independently selected from H, C 1-6 Alkyl, CF3 and C2F5.

[0124] In a preferred embodiment:

[0125] R 1 , R 3 , R 3' , R 4 , R5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Independently selected from H, F, OH, SH, OR 13 、CO2R 14 、OC(=O)R 15 , C 1-6 Alkyl, CF3 and C 2-6 alkenyl; and

[0126] R 13 , R 14 and R 15 Independently selected from H, C 1-6 Alkyl and CF3.

[0127] In a preferred embodiment:

[0128] R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Independently selected from H, F, OH, OR 13 、CO2R 14 、OC(=O)R 15 , C 1-6 Alkyl and C 2-6 alkenyl; and

[0129] R 13 , R 14 and R 15 Independently selected from H and C 1-6 alkyl.

[0130] In a preferred embodiment:

[0131] R 1 , R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9, R 9' , R 10 and R 12 Independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me.

[0132] In a preferred embodiment, R 4 is H or OH.

[0133] In the case where -Y- is -O- and -X- is absent, R 8 and R 9 Together with the carbon atom to which they are attached, they may form a heterocyclic ring. The heterocyclic ring may be tetrahydrofuran or tetrahydropyran. For example, cycloastragenol is a compound having a tetrahydrofuran group in a triterpene.

[0134] In a preferred embodiment:

[0135] R 1 and / or R 4 and / or R 10 For H.

[0136] In a preferred embodiment:

[0137] R 5 and / or R 6 and / or R 12 For me.

[0138] In a preferred embodiment:

[0139] R 7 is CO2H.

[0140] R 2 and R 2' Group

[0141] In a preferred embodiment:

[0142] R 2 and R 2' independently selected from H, OH, OMe, OEt, C 1-4 Alkyl, C 2-4 alkenyl, CO2H, CO2Me, CO2Et, OC(O)Me, and OC(O)Et, or R 2 and R 2' Together they represent =O.

[0143] In a preferred embodiment:

[0144] R 2 and R 2'is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, CO2H, CO2Me, and OC(O)Me, or R 2 and R 2' Together they represent =O.

[0145] R 11 and R 11' Group

[0146] In a preferred embodiment:

[0147] R 11 and R 11' independently selected from H, OH, OMe, OEt, C 1-4 Alkyl, C 2-4 alkenyl, CO2H, CO2Me, CO2Et, OC(O)Me and OC(O)Et, or R 2 and R 2' Together they represent =O.

[0148] In a preferred embodiment:

[0149] R 11 and R 11' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, CO2H, CO2Me, and OC(O)Me, or R 2 and R 2' Together they represent =O.

[0150] Preferred formula

[0151] In a particularly preferred embodiment, the triterpenoid compound is a compound of formula (IIa):

[0152]

[0153] in:

[0154] R 3 , R 3' , R 8 , R 8' , R 9 and R 9' independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me;

[0155] R 2 and R 2'is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me, or R 2A and R 2A 'Together means = O;

[0156] R 11 and R 11' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me, or R 11 and R 11' Together they represent =O;

[0157] X is -CH2-, -CH2CH2-; and

[0158] Dashed bonds indicate the presence of double or single bonds between ring carbon atoms.

[0159] In formula (IIa), where a dashed bond indicates a single bond, it is understood that the carbon ring atom is connected to H.

[0160] In one embodiment, double bonds exist between ring carbon atoms.

[0161] In one embodiment, -X- is -CH2CH 2- .

[0162] In one embodiment, -X- is -CH2-.

[0163] In a preferred embodiment:

[0164] R 1 , R 3 , R 6 and R 7 Independently selected from H, OH, OR 13 、CO2R 14 、OC(=O)R 15 , Me, Et and C 1-4 alkenyl; and

[0165] R 13 , R 14 and R 15 Independently selected from H, Me and Et.

[0166] In a preferred embodiment:

[0167] R 3 , R 3' , R 8 , R 8' , R11 and R 1A 'Independently selected from H, OH, Me, OMe, CH2OH and CO2H;

[0168] R 2 and R A’ is independently selected from H, OH, Me, OMe, CH2OH, CO2H and OC(O)Me, or R 2 and R 2' Together they represent =O;

[0169] R 9 and R 9' H, OH, Me, 1-methylvinyl, OMe, CH2OH, and CO2H.

[0170] In a particularly preferred embodiment, the triterpenoid compound is selected from compounds of formula (II) to (VII):

[0171]

[0172] In another embodiment, the triterpenoid compound is selected from the compound of formula (VIII):

[0173]

[0174]

[0175] In a particularly preferred embodiment, the triterpenoid compound is a compound of formula (IIb):

[0176]

[0177] in:

[0178] -Y- is a covalent bond or -O-,

[0179] Dashed bonds indicate the presence of double or single bonds between ring carbon atoms, with only one double bond present within the ring.

[0180] R 3 , R 3' , R 4 , R 5 , R 6 , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 and R 12 Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , and wherein -Y- is -O- and -X- is absent, R 8 and R 9 can form a heterocyclic ring together, and R 5 It is absent when the ring carbon to which it is attached is in a double bond;

[0181] R 2 and R 2' Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 16 、CO2R 17 、OC(=O)R 18 , or R 2 and R 2' Together they represent =O;

[0182] R C In the absence of R, or in the case where the ring carbon to which it is attached is not in a double bond, C H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , or with R 12 Together they can form a carbon ring;

[0183] R D If it is not present, or if the ring carbon to which it is attached is not in a double bond, R D H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 21 and R 21 Independently selected from H, C 1-6 Alkyl and C1-4 haloalkyl; and

[0184] n is 0 or 1.

[0185] In a preferred embodiment:

[0186] R 1 , R 3 , R 6 and R 7 Independently selected from H, OH, OR 13 、CO2R 14 、OC(=O)R 15 , Me, Et and C 1-4 alkenyl; and

[0187] R 13 , R 14 and R 15 Independently selected from H, Me and Et.

[0188] In a preferred embodiment:

[0189] R 3 , R 3' , R 8 , R 8' , R 11 and R 11' independently selected from H, OH, Me, OMe, CH2OH and CO2H;

[0190] R 2 and R 2' is independently selected from H, OH, Me, OMe, CH2OH, CO2H and OC(O)Me, or R 2 and R 2' Together they represent =O;

[0191] R 9 and R 9' H, OH, Me, 1-methylvinyl, OMe, CH2OH, and CO2H.

[0192] In another embodiment, the triterpenoid compound is selected from compounds of formula (IX) and (X):

[0193]

[0194] Preferred compounds

[0195] In a particularly preferred embodiment, the triterpenoid compound is selected from oleanolic acid, hederagenin, rotundic acid, ursolic acid, acetylcoursolic acid, 23-hydroxybetulinic acid (anemosapogenin), betulinic acid (betulinic acid), cycloastragenol and β-elemenic acid (elemenic acid).

[0196] The triterpenoid compound may be a pentacyclic triterpenoid compound.

[0197] The triterpenoid compound may be a tetracyclic triterpenoid compound.

[0198] The triterpenoid compound may be selected from oleanolic acid, betulinic acid, cycloastragenol and β-elemenic acid.

[0199] The triterpenoid compound may be selected from oleanolic acid, cycloastragenol and β-elemenic acid.

[0200] The triterpenoid compound may be selected from oleanolic acid and betulinic acid.

[0201] The triterpenoid compound may be selected from oleanolic acid, β-elemenic acid and cycloastragenol.

[0202] The triterpenoid compound may be oleanolic acid.

[0203] The triterpenoid compound may be β-elemenic acid.

[0204] The triterpenoid compound may be β-elemenic acid.

[0205] The triterpenoids described herein, such as those of formula (I), can be provided in free base form. Alternatively, the triterpenoids can be provided in the form of salts, such as pharmaceutically or cosmetically acceptable salts. Examples of pharmaceutically acceptable salts are discussed in Berge et al., 1977, "Pharmaceutically Acceptable Salts," J. Pharm. Sci., Vol. 66, pp. 1-19.

[0206] In some embodiments, the triterpenoids described herein are provided in a protonated form with a suitable counter anion.

[0207] Suitable counter anions include both organic and inorganic anions. Examples of inorganic anions include those derived from inorganic acids, including chloride (Cl - ), bromide ion (Br - ), iodide ion (I - ), sulfate (SO4 2- ), sulfite (SO3 2- ), nitrate (NO3 - ), nitrite (NO2- ), phosphate (PO4 3- ) and phosphite (PO3 3- ). Examples of organic anions include 2-acetoxybenzoate, acetate, ascorbate, aspartate, benzoate, camphorsulfonate, cinnamate, citrate, edisulphonate, ethanesulfonate, formate, fumarate, gluconate, glutamate, glycolate, hydroxymalate, carboxylate, lactate, laurate, lactate, maleate, malate, methanesulfonate, oleate, oxalate, palmitate, phenylacetate, benzenesulfonate, propionate, pyruvate, salicylate, stearate, succinate, sulfanilate, tartrate, toluenesulfonate and valerate. Examples of suitable polymeric organic anions include those derived from tannic acid and carboxymethylcellulose.

[0208] In some embodiments, the triterpenoids disclosed herein are provided in a deprotonated form together with a suitable counter cation.

[0209] Suitable counter cations include organic and inorganic cations. Suitable counter ions include both inorganic and organic cations. Examples of suitable inorganic cations include alkali metal ions such as Na + and K + , alkaline earth metal cations such as Ca 2+ and Mg 2 + , and other cations such as Al 3+ Examples of suitable organic cations include ammonium ions (i.e., NH4 + ) and substituted ammonium ions (e.g. NH3R + NH2R2 + 、NHR3 + 、NR4 + ). Examples of substituted ammonium ions include those derived from ethylamine, diethylamine, dicyclohexylamine, triethylamine, butylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, benzylamine, phenylbenzylamine, choline, meglumine, and tromethamine, as well as amino acids such as lysine and arginine. Common examples of quaternary ammonium ions are N(CH3)4 + .

[0210] Unless otherwise stated, a reference to a particular compound also includes its salt forms.

[0211] The triterpenoid compounds described herein may be provided in the form of a solvate (a complex of a solute (eg, a compound, a salt of a compound) and a solvent). Examples of solvates include hydrates such as monohydrates, dihydrates, and trihydrates.

[0212] The triterpenoids described herein may be provided in a desolvated form, for example, in a dehydrated form.

[0213] The compositions of the present invention may include an effective amount, such as a therapeutically or cosmetically effective amount, of a triterpenoid described herein, such as a triterpenoid of formula (I).

[0214] In some embodiments, the composition of the present invention includes triterpenoids in an amount of 0.0005% to 10% by weight, for example based on the total weight of the composition. In a preferred embodiment, the composition of the present invention includes triterpenoids in an amount of 0.1% to 5% by weight, for example 0.1% to 3% by weight, and for example 0.2% to 3% by weight, and more preferably 0.2% to 2% by weight.

[0215] The triterpenoid may be present in an amount of up to 2%, 3%, 5% or 10% by weight.

[0216] The triterpenoid may be present in an amount of at least 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, or 1.0% by weight.

[0217] Plant Extracts

[0218] The composition of the present invention comprises a plant extract. The plant extract is selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera.

[0219] The plant extract may be derived from any suitable species of the genera Garcinia, Rubus, Fragaria, Ilex and Hedera.

[0220] Suitable plant extracts are commercially available and may be purchased, for example, from BOCSCI (New York, USA).

[0221] Suitable species of plants belonging to the genus Garcinia include Garcinia mangostana (mangosteen).

[0222] Suitable species of plants belonging to the genus Rubus include Rubus idaeus (red raspberry). Raspberries are widely distributed throughout Europe and are native to, for example, the United Kingdom.

[0223] Suitable species of plants belonging to the genus Hedera include Hedera helix (commonivy). Ivy is widely distributed throughout Europe and is native to, for example, the United Kingdom.

[0224] Suitable species of plants belonging to the genus Ilex include Ilex aquifolium (common holly). Ilex aquifolium is widely distributed throughout Europe and is native to, for example, the United Kingdom.

[0225] Suitable species of plants belonging to the genus Fragaria include Fragaria vesca (wild strawberry) and Fragaria × ananassa (garden strawberry). Fragaria vesca is widely distributed throughout Europe and is native to, for example, the United Kingdom. Fragaria × ananassa is widely grown throughout Europe, including the United Kingdom.

[0226] The plant extract may be derived from any suitable part of a plant. Suitable parts of a plant include roots, stems, leaves, flowers, fruits and seeds.

[0227] Examples of suitable fruit extracts include raspberry fruit extract, mangosteen peel extract and Fragaria foetida fruit extract.

[0228] Examples of suitable leaf extracts include Ilex oleifera leaf extract.

[0229] Plant extracts can be prepared using any suitable extraction method. Suitable extraction methods include extraction using organic solvents and extraction using aqueous solvents (aqueous extraction).

[0230] Typically, plant extracts are aqueous extracts.

[0231] In another embodiment, the plant extract is selected from raspberry extract, mangosteen extract, ivy extract, ilex holly extract and fragaria extract.

[0232] In a preferred embodiment, the plant extract is selected from extracts of plants belonging to the genera Rubus and Fragaria. In a preferred embodiment, the plant extract is selected from raspberry extract and Fragaria idaeus extract.

[0233] In a preferred embodiment, the plant extract is selected from extracts of plants belonging to the genus Garcinia. In a preferred embodiment, the plant extract is a mangosteen extract.

[0234] In a preferred embodiment, the plant extract is selected from extracts of plants belonging to the genera Hedera and Ilex. In a preferred embodiment, the plant extract is selected from the group consisting of an ivy extract and an Ilex holly extract.

[0235] In a preferred embodiment, the plant extract is raspberry extract.

[0236] In another embodiment, the plant extract is an ivy extract.

[0237] In another embodiment, the plant extract is Ilex oleifera leaf extract.

[0238] In one embodiment, the plant extract is a mangosteen extract.

[0239] In another embodiment, the plant extract is Fragaria candidum extract.

[0240] The triterpenoid may not be present in or otherwise derived from the plant extract with which it is used in combination.

[0241] The compositions of the present invention may include an effective amount, such as a therapeutically or cosmetically effective amount, of a plant extract described herein.

[0242] The Rubus extract, such as raspberry extract, may include one or more, such as all, of the following compounds given in Table 1 in amounts within the given ranges. The extract herein may be a dry extract.

[0243] Table 1. Composition of raspberry solid plant extract

[0244] Compound Concentration range (μg / g=ppm) Adenine 0.7–7.1 Betaine 1.2–3.4 choline 5.4–18.4 Ellagic acid 21.9–439.8 Quercetin-3-glucuronide 0.2–21.4 p-Coumaric acid 0.2–9.2 Pipecolic acid 1.0–74.4 Tyramine 17–182.9

[0245] Raspberry extract may be obtained from raspberry fruit or may be obtainable from raspberry fruit. The extract may be obtained by extraction with water, concentration and spray drying.

[0246] The Fragaria extract, such as Fragaria foetida extract, may include, for example, one or more, such as all, of the following compounds given in Table 2 in an amount within a given range. The extract here may be a dry extract.

[0247] Table 2. Composition of solid plant extract of yellow-haired strawberry

[0248] Compound Concentration range (μg / g=ppm) Adenine 206 Betaine 238 choline 261 Ellagic acid 346 p-Coumaric acid 140 Pipecolic acid 244 Quercetin-3-glucuronide 306

[0249] The strawberry extract may be obtained from strawberry fruit or may be obtained from strawberry fruit. The extract may be obtained by extraction with water, concentration and spray drying.

[0250] An extract of the genus Hederagen, such as an ivy extract, may be characterized by the presence of triterpenoid saponins, for example in an amount of 2.5 to 6% by weight. The extract may contain one or more, for example all, of hederagenine C (e.g., in an amount in the range of 1.7 to 4.8% by weight), hederagenine D (e.g., in an amount in the range of 0.4 to 0.8% by weight), and hederagenine B (e.g., in an amount in the range of 0.1-0.2% by weight). Additionally or alternatively, the extract may contain α-hederagenine, for example, in an amount in the range of 0.1% to 0.3% by weight. Additionally or alternatively, the extract may contain hederagenin, for example, in an amount in the range of 0.1 to 1.5% by weight, for example, 0.89 or 0.9% by weight. Tatia et al. (Rev. Chim. 2019, 70, 1157) describe the presence of these characteristic compounds of ivy extracts.

[0251] In one embodiment, the ivy extract may be characterized as having a minimum content of hederacoside C of 3.0% by weight.

[0252] The ivy extract may be obtained from the whole plant or leaves of English ivy or may be obtained from the whole plant or leaves of English ivy. The extract may be obtained by extraction with water, concentration and drying.

[0253] Holly extracts, such as Holly extracts, may be characterized by the presence of ursolic acid and oleanolic acid. Ursolic acid may be present in an amount of 1.30% by weight. Oleanolic acid may be present in an amount of 0.50% by weight. Additionally or alternatively, the Holly extract may include amino acids, sugars, carotenoids, phenolic derivatives, fatty acids, flavonoids, anthocyanins, and triterpenes, such as α-amyrin, β-amyrin, ursolic alcohol, and erythrodiol. Palu et al. (Molecules 2019, 24, 4413) describe the presence of these characteristic compounds of Holly extracts.

[0254] The Ilex hollifolia extract may be obtained from the whole plant or leaves of English holly or may be obtained from the whole plant or leaves of English holly, such as leaves. The extract may be obtained by extraction with water, concentration and drying.

[0255] An extract of the genus Garcinia, such as a mangosteen extract, may be characterized by the presence of one or more, such as all, of α-mangostin, γ-mangostin, and gartanin. α-Mangostin may be present in an amount of 8.5-13.9 wt %. γ-Mangostin may be present in an amount of 6.0-8.3 wt %. Garcinia may be present in an amount of 8.1 to 17.3 wt %. Muchtaridi et al. (J. Appl. Pharm. Sci. 2017, 7, 125) describe the presence of such characteristic compounds of a mangosteen extract.

[0256] In some embodiments, the composition of the present invention includes a plant extract in an amount of 0.005% to 50% by weight, for example based on the total weight of the composition. In a preferred embodiment, the composition of the present invention includes a plant extract in an amount of 0.005% to 30% by weight, for example 0.05% to 10% by weight, more preferably 0.1% to 3% by weight.

[0257] The plant extract may be present in an amount of up to 2%, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 45% or 50% by weight.

[0258] The plant extract may be present in an amount of at least 0.005%, 0.01%, 0.05%, 0.1%, 0.5% or 1% by weight.

[0259] In one embodiment, triterpenoids may be substantially absent from the plant extract used in combination therewith, for example, may be absent from the plant extract used in combination therewith, or may otherwise be derived from the plant extract used in combination therewith. For example, in the case where the plant extract is a raspberry, ivy or holly leaf holly extract, these extracts are substantially free of triterpenoids, any or all of the triterpenoids of formula (I). For example, the total amount of triterpenoids in the plant extract may be less than 1% by weight, for example, less than 0.1% by weight, for example, less than 0.01% by weight. For example, the triterpenoids of formula (I) combined with the plant extract may be less than 1% by weight, for example, less than 0.1% by weight, for example, less than 0.01% by weight and present in the plant extract.

[0260] Composition

[0261] The compositions of the invention may be formulated for cosmetic or therapeutic use. Thus, the compositions of the invention may additionally comprise one or more pharmaceutical or cosmetic ingredients.

[0262] Pharmaceutically and cosmetically acceptable ingredients are those ingredients which are, within the scope of sound judgment, suitable for use in contact with the tissues of the subject in question (e.g., humans) without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each ingredient must also be compatible with the other ingredients of the composition.

[0263] In one embodiment, the composition comprises one or more ingredients selected from the group consisting of solvents, oils, surfactants, thickeners, humectants, and preservatives.

[0264] Examples of suitable solvents include water; monohydric alcohols such as ethanol, isopropanol, benzyl alcohol and phenylethyl alcohol; polyhydric alcohols such as ethylene glycol, propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol and erythritol; and glycol ethers such as ethylene glycol monomethyl ether and diethylene glycol monomethyl ether.

[0265] Examples of suitable oils include mineral oils, vegetable oils and waxes.

[0266] Examples of suitable vegetable oils include algae oil, annatto oil, argan oil, almond oil, apricot kernel oil, avocado oil, babassu oil, brazil nut butter, butter, cashew butter, castor oil, camellia oil, cherry kernel oil, cocoa butter, coconut oil, corn oil, cottonseed oil, fish oil, grapeseed oil, gardenia oil, ghee, hazelnut oil, jatropha oil, jojoba oil, kohlrabi oil, linseed oil, macadamia oil, corn oil, mango seed oil, mango butter, mineral oil, mink oil, olive oil, palm oil, palm kernel oil, peach kernel oil, peanut butter, peanut oil, plum kernel oil, pomegranate oil, rapeseed oil, rice bran oil, rosehip oil, sal oil, sesame oil, shea butter, soybean oil, squalene, sunflower oil, tea seed oil, walnut oil.

[0267] Examples of suitable waxes include bayberry wax, beeswax, carnauba wax (palm wax), candelilla wax, ceresin, jojoba fat, lanolin wax, montan wax, ozokerite, polyglyceryl-3-beeswax, polyglyceryl-6-pentanostearate, Japan wax, microcrystalline wax, paraffin, isoparaffin, petrolatum, squalene, oligomeric olefins, synthetic candelilla wax, synthetic carnauba wax, synthetic beeswax.

[0268] Surfactants (surface-active agents) can act as dispersants or wetting agents. Examples of suitable surfactants include anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric (zwitterionic) surfactants.

[0269] Examples of suitable anionic surfactants include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, sodium lauric acid monoglyceride sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, sarcosine), ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauroyl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, sodium tridecylbenzene sulfonate, and sodium dodecylbenzene sulfonate.

[0270] Examples of suitable cationic surfactants include behentrimonium chloride, cocotrimonium chloride, cetylethyldimethylammonium bromide, dibehenyldimethylammonium chloride, dihydrogenated tallow benzylmonium chloride, disoydimethylammonium chloride, ditallowdimethylammonium chloride, hydroxycetylhydroxyethyldimethylammonium chloride, hydroxyethylbehenamidopropyldimethylammonium chloride, hydroxyethylcetyldimethylammonium chloride, hydroxyethyltallowdimethylammonium chloride, myristalkonium chloride, PEG-2 oleylmethylammonium chloride, PEG-5 stearalkonium chloride, PEG-15 cocoyl quaternium 4, PEG-2 stearalkonium chloride ... 4), lauryltrimethylammonium chloride; quaternium-16; quaternium-18, lauryldimethylbenzylammonium chloride (lauralkonium chloride), olealkmoniumchloride, cetylpyridinium chloride, polyquaternium-5, polyquaternium-6, polyquaternium-7, polyquaternium-10, polyquaternium-22, polyquaternium-37, polyquaternium-39, polyquaternium-47, cetyltrimethylammonium chloride, dilauryldimethylammonium chloride, cetyldimethylbenzylammonium chloride (cetalkonium chloride), dicetyldimethylammonium chloride, soyatrimonium chloride and stearyloctyldimonium methosulfate (stearyloctyl dimonium methosulfate).

[0271] Examples of suitable nonionic surfactants include fatty alcohol ethoxylates, such as octaethylene glycol monododecyl ether and pentaethylene glycol monododecyl ether; alkylphenol ethoxylates (APE or APEO), such as nonoxynol-4, nonoxynol-7, nonoxynol-9, nonoxynol-14, nonoxynol-15, nonoxynol-18 and triton X-100; glycerol fatty acid esters, such as glyceryl monostearate and glyceryl monolaurate; sorbitan fatty acid esters, such as sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, polysorbate (Tween) 20, polysorbate 40, polysorbate 60 and polysorbate 80.

[0272] Examples of suitable amphoteric (zwitterionic) surfactants include cocamidopropyl hydroxysultaine, cocamidopropyl betaine, lauryl betaine, lauryl dimethylamine oxide, and myristamine oxide.

[0273] Examples of suitable thickeners (rheology modifiers) include gums such as alginates, carrageenan, gum arabic, gum arabic, gum ghatti, gum karaya, gum tragacanth, guar gum; guar hydroxypropyltrimonium chloride, xanthan gum or gellan gum; cellulose derivatives such as sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxymethylcarboxyethylcellulose, hydroxymethylcarboxypropylcellulose, ethylcellulose, sulfated cellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose; agar; pectin; gelatin; starch and its derivatives; chitosan and its derivatives such as hydroxyethylchitosan; synthetic polymers such as polyvinyl alcohol, PVM / MA copolymers, PVM / MA decadiene crosspolymers, poly(ethylene oxide)-based thickeners;

[0274] The humectant can act as a hygroscopic agent, increasing the amount of water absorbed or retained by the composition. Examples of suitable humectants include acetamide MEA, ammonium lactate, chitosan and its derivatives, colloidal oats, galactoarabinan, glucose glutamate (salt), glerecyth-7, glygeryth-12, glycereth-26, glyceryth-31, glycerol, lactamide MEA, lactamide DEA, lactic acid, methyl gluceth-10, methyl gluceth-20, panthenol, propylene glycol, sorbitol, polyethylene glycol, 1,3-butylene glycol, 1,2,6-hexanetriol, hydrogenated starch hydrolysate, inositol, mannitol, PEG-5 pentaerythritol ether, polyglyceryl sorbitol, xylitol, sucrose, sodium hyaluronate and sodium PCA.

[0275] Examples of suitable preservatives include methylparaben, propylparaben and sorbic acid, methyldibromoglutaronitrile (MDBGN), benzyl alcohol, imidazolidinyl urea 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,3-imidazolidinedione (DMDM hydantoin), methylchloroisothiazolinone and methylisothiazolinone, phenoxyethanol and sodium benzoate.

[0276] In one embodiment, the composition includes one or more ingredients selected from the group consisting of emollients, anti-inflammatory agents, antioxidants, and UV blockers.

[0277] Examples of suitable emollients include fatty esters such as isopropyl myristate, isopropyl palmitate, caprylic / capric triglyceride, cetyl lactate, cetyl palmitate, hydrogenated castor oil, glyceryl esters, hydroxycetyl isostearate, hydroxycetyl phosphate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, PPG-5-Ceteth-20, 2-ethylhexyl isononanoate, 2-ethylhexyl stearate, C12-C16 fatty alcohol lactates, isopropyl lanolinate, and 2-ethylhexyl salicylate.

[0278] Examples of suitable anti-inflammatory ingredients include inhibitors of cyclooxygenase (e.g., COX-1 or COX-2) or lipoxygenase (e.g., LOX-5) enzymes, such as ascorbic acid, ascorbic acid derivatives, vitamin E, vitamin E derivatives, tocotrienols, rutin, quercetin, hesperidin (Citrus sinensis), hesperidin (Citrus sinensis), diosmin (Citrussinensis), mangifera indica, mangostana (Garcinia mangostana), anthocyanidins (Vaccinium myrtillus), astaxanthin (Haematococcus algae), lutein (Tagetes patula), lycopene (Lycopersicum esculentum), resveratrol (Polygonum cuspidatum), tetrahydrocurcumin (Curcuma longa), rosmarinus officinalis), hypericin (Hypericumperforatum), ellagic acid (Punica granatum), chlorogenic acid (Vaccinium vulgaris), oleuropein (Oleaeuropaea), alpha-lipoic acid, glutathione, andrographolide (Andrographis paniculata), grape seed extract, green tea extract, polyphenols, pycnogenol (pine bark extract), white tea extract, black tea extract, (Andrographispaniculata), carnosine, and niacinamide.Other examples of suitable anti-inflammatory compositions may additionally be selected from Aesculus hippocastanum extract, esculin, aescin, yohimbine, Capsicum oleoresin, capsaicin, nicotinic acid, nicotinate esters, methyl nicotinate, benzyl nicotinate, ruscogenins (Butchers Broom extract; Ruscus aculeatus extract), diosgenin (Trigonel afoenumgraecum, fenugreek), Phyllanthus emblica extract, Centella asiatica extract, Boswellia serrata, sericoside, visnadine, thiocolchicoside, grape seed extract, ginger root extract (Zingiber officinale extract), serrata extract, ... officianale), piperine, vitamin K, melilot (Melilotusofficinalis extract), glycyrrhetinic acid, ursolic acid, Terminalia sericea extract, Siegesbeckia orientalis extract, Amni visnaga extract, Vitisvinifera extract, apigenin, phytosan, luteolin.

[0279] Examples of suitable antioxidant ingredients include ascorbic acid, ascorbic acid derivatives ascorbyl glucosamine, ascorbyl arginine, ascorbyl lysine, ascorbyl glutathione, ascorbyl nicotinamide, ascorbyl niacin, ascorbyl allantoin, ascorbyl creatine, ascorbyl creatinine, ascorbyl chondroitin, ascorbyl chitosan, ascorbyl carnosine, vitamin E, vitamin E derivatives, tocotrienols, rutin, quercetin, hesperidin (Citrus sinensis), hesperidin (Citrus sinensis), diosmin (Citrus sinensis), mangifera indica, mangostana (Garcinia mangostana), anthocyanidins (Vaccinium myrtillus), astaxanthin (Haematococcusalgae), lutein (Tagetes patula), lycopene (Lycopersicum esculentum), resveratrol (Polygonum cuspidatum), tetrahydrocurcumin (Curcuma longa), rosmarinic acid (Rosmarinusofficinalis), hypericin (Hypericum perforatum), ellagic acid (Punica granatum), chlorogenic acid (Vaccinium vulgaris), oleuropein (Olea europaea), alpha-lipoic acid, niacinamide lipoate, glutathione, andrographolide (Andrographis paniculata), carnosine, niacinamide, Potentilla erecta extract, polyphenols, grape seed extract, pycnogenol (pine bark extract), pyridoxine, magnolol, honokiol, paeonol, resacetophenone, quinacetophenone, arbutin, and kojic acid.

[0280] Examples of suitable UV blockers (sunscreen actives) include octyl methoxycinnamate (ethylhexyl p-methoxycinnamate), octyl salicylate oxybenzone (benzophenone-3), benzophenone-4, menthyl anthranilate, dioxybenzone, aminobenzoic acid, amyl dimethyl PABA, diethanolamine p-methoxycinnamate, ethyl 4-bis(hydroxypropyl)aminobenzoate, 2-ethylhexyl 1-2-cyano-3,3-diphenylacrylate, homomenthyl salicylate, glyceryl aminobenzoate, dihydroxyacetone, octyl dimethyl PABA, 2-phenylbenzimidazole-5-sulfonic acid, triethanolamine salicylate, zinc oxide, titanium oxide, and mixtures thereof.

[0281] Other ingredients suitable for use in the compositions include fragrances, pH adjusters, pigments, odor absorbers, antimicrobials, antifungals, chelating agents and sugars.

[0282] The compositions of the present invention are typically formulated for topical use.

[0283] The composition of the present invention can be formulated as a solution, liquid, emulsion (lotion), cream, milk, dispersion, gel or paste. Examples of suitable emulsions include two-phase emulsions comprising an aqueous phase and an oil phase, such as oil-in-water (O / W) type and water-in-oil (W / O) type, and complex emulsions, such as triple emulsions (O / W / O and W / O / W).

[0284] Compositions and preparations can be prepared by any method well known in the art. These methods include the step of combining triterpenoids and / or plant extracts with a carrier constituting one or more auxiliary components. Typically, preparations are prepared by uniformly mixing triterpenoids and / or plant extracts with a carrier (e.g., a liquid carrier, a finely broken solid carrier, etc.).

[0285] The compositions of the present invention may be formulated as both cosmetic and pharmaceutical products.

[0286] In one embodiment, a personal care product is provided comprising a composition of the present invention. Suitable personal care products include skin care products, hair care products, cleansing products, and cosmetic powders and liquids.

[0287] Examples of suitable skin care products include skin / hand lotions, skin / hand creams, skin / hand ointments, skin / hand pastes, toners, shaving gels, shaving creams, sunscreens, deodorants, antiperspirants, sunscreen lotions, aftersun products, aftershave products, body oils, bath oils, and foam baths. Examples of suitable hair care products include conditioners, hair straightening lotions, styling gels, styling creams, styling waxes, styling lotions, mousses, spray gels, hair tonics, sprays, and pomades. Examples of suitable cleaning products include liquid soaps, bar soaps, shower gels, skin cleansers, and shampoos. Examples of suitable cosmetic powders and liquids include blush, talcum powder, contour powder, eye shadow, foundation, face powder, lip powder, powder makeup (pressed cake), contour liquid (liquid bronzer), eyeliner, lip gloss, lipstick, and mascara.

[0288] Methods and uses for reducing lipid production

[0289] The composition of the present invention reduces the production of lipids in sebaceous gland cells.

[0290] The present invention also provides a method for reducing lipid production in sebaceous gland cells, the method comprising contacting the sebaceous gland cells with a composition of the present invention, such as a composition comprising:

[0291] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0292] (b) A plant extract selected from the group consisting of extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera.

[0293] Preferred features of the composition, such as the triterpenoids and plant extracts are as described above.

[0294] In one embodiment, the method for reducing lipid production in sebaceous gland cells is in vivo. In one embodiment, the method for reducing lipid production in sebaceous gland cells is ex vivo, such as in vitro.

[0295] In one embodiment, the method for reducing lipid production in sebaceous gland cells comprises contacting sebaceous gland cells with an effective amount of a composition of the present invention. An effective amount of the composition provides a detectable reduction in lipid production in sebaceous gland cells. Methods for detecting and quantifying the production of lipids in sebaceous gland cells include, for example, using a suitable lipid detection dye such as AdipoRed TM Fluorescence measurement.

[0296] In one embodiment, the method for reducing lipid production in sebaceous gland cells comprises contacting sebaceous gland cells with an amount of a composition of the present invention suitable for reducing the production of lipids by 10% or more, preferably 15% or more, more preferably 20% or more, even more preferably 20% or more, and most preferably 30% or more.

[0297] In one embodiment, the method for reducing lipid production in sebocytes reduces lipid production by 5% or more, preferably 10% or more, preferably 15% or more, more preferably 20% or more, even more preferably 20% or more, and most preferably 30% or more.

[0298] The present invention also provides a composition of the present invention, for example, comprising the following composition:

[0299] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0300] (b) a plant extract selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera,

[0301] For use in a method of reducing lipid production in sebaceous gland cells.

[0302] Preferred features of the compositions, such as triterpenoids and plant extracts are described above. Preferred features of the methods for reducing lipid production in sebaceous gland cells are also set out above.

[0303] The present invention also provides the use of the composition of the present invention, for example comprising the following composition, for reducing lipid production in sebaceous gland cells:

[0304] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0305] (b) A plant extract selected from the group consisting of extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera.

[0306] Preferred features of the composition, eg triterpenoids and plant extracts are as described above.Preferred features of the method for reducing lipid production in sebaceous gland cells also apply to the use of the composition for reducing lipid production in sebaceous gland cells.

[0307] Beauty methods and uses

[0308] The compositions of the present invention reduce lipid production in sebaceous gland cells, such as lipid production in the skin of an individual. Thus, the compositions of the present invention can reduce or ameliorate cosmetic problems associated with excessive lipid production in the skin. Cosmetic problems associated with excessive lipid production in the skin include oily or shiny skin, oily hair, enlarged skin pores, bad body odor, and reduced retention of cosmetics on the skin.

[0309] Thus, the present invention provides a cosmetic method for reducing lipid production in the skin of an individual, the method comprising contacting the skin with a composition of the present invention, for example a composition comprising:

[0310] (a) a triterpenoid compound according to formula (I) or a cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0311] (b) A plant extract selected from the group consisting of extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera.

[0312] Preferred features of the composition, such as the triterpenoids and plant extracts are as described above.

[0313] In one embodiment, the cosmetic method for reducing lipid production in the skin of a subject is not a method of treatment. In one embodiment, the cosmetic method for reducing lipid production in the skin of a subject is not a method of treating the human or animal body by therapy.

[0314] In one embodiment, the cosmetic method reduces lipid production in sebaceous gland cells in the skin of a subject.

[0315] In one embodiment, the skin is skin on the head, such as skin on the face, mouth, neck or scalp. In one embodiment, the skin is skin on the chest, back, arms, legs or hands.

[0316] Benefits of reducing lipid production in an individual's skin include reducing the oily appearance of the skin, controlling surface oil, minimizing skin pores, and reducing unwanted body odor. In one embodiment, the cosmetic method reduces lipid production in the skin, thereby achieving a benefit selected from reducing the oily appearance of the skin, controlling surface oil of the skin, minimizing skin pores, and reducing unwanted body odor.

[0317] In one embodiment, the individual is in need of a cosmetic treatment. An individual in need of a cosmetic treatment may have a condition associated with an overproduction of lipids in the skin, such as oily or shiny skin, oily hair, enlarged skin pores, and excessive body odor. In one embodiment, the individual has a cosmetic condition selected from the group consisting of oily or shiny skin, oily hair, enlarged skin pores, and excessive body odor.

[0318] The present invention also provides a composition of the present invention, for example, comprising the following composition:

[0319] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0320] (b) a plant extract selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera,

[0321] It is used in cosmetic methods for reducing lipid production in the skin of an individual.

[0322] Preferred features of the composition, eg, triterpenoids and plant extracts are as described above. Preferred features of the cosmetic method for reducing lipid production in the skin of an individual are also set out above.

[0323] The present invention also provides for use of a composition of the present invention, for example a composition comprising:

[0324] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0325] (b) A plant extract selected from the group consisting of extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera.

[0326] Preferred features of the composition, eg triterpenoids and plant extracts are as described above.Preferred features of the cosmetic method for reducing lipid production in the skin of an individual also apply to the use of the composition for reducing lipid production in the skin of an individual.

[0327] Medical treatments and uses

[0328] The compositions of the present invention reduce lipid production in sebaceous gland cells, such as lipid production in the skin of an individual. Therefore, the compositions of the present invention can be used to treat or prevent (prevent) medical problems associated with excessive lipid production in the skin. Medical problems associated with excessive lipid production in the skin include acne vulgaris and rosacea.

[0329] Therefore, the present invention provides compositions of the present invention, for example, compositions comprising:

[0330] (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and

[0331] (b) a plant extract selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera,

[0332] It is for use in a method of treatment, such as a method of treating the human or animal body by therapy.

[0333] In one embodiment, the method of treatment is a method of treating a condition (eg, a disease) associated with overproduction of lipids in the skin. In one embodiment, the method of treatment is a method of treating a condition associated with overproduction of lipids in sebaceous gland cells.

[0334] In one embodiment, the skin is skin on the head, such as skin on the face, mouth, neck or scalp. In one embodiment, the skin is skin on the chest, back, arms, legs or hands.

[0335] In one embodiment, the treatment is treatment of acne vulgaris. In one embodiment, the treatment is treatment of rosacea.

[0336] In one embodiment, treatment is administered to a subject in need of treatment.

[0337] The subject (patient) in need of treatment can be a mammal, such as a human.

[0338] The subject in need of treatment can be an adult or a juvenile.

[0339] In a preferred embodiment, the subject in need of treatment is a human, more preferably an adult.

[0340] Alternatively, the subject in need of treatment is a non-human animal used in laboratory research.

[0341] In one embodiment, the treatment is administered by any convenient route of administration. In a preferred embodiment, the treatment is administered topically (ie, at the site of desired effect).

[0342] In one embodiment, treating comprises administering a therapeutically effective amount of the composition to a subject in need of treatment.

[0343] Those skilled in the art will appreciate that the appropriate dosage of the compositions described herein may vary from patient to patient. Determining the optimal dosage will generally involve a balance between the level of therapeutic benefit and any risk or harmful side effects. The dosage level selected will depend on a variety of factors, including but not limited to, the activity of specific triterpenoids and plant extracts, the route of administration, the time of administration, the excretion rate of triterpenoids and plant extracts, the duration of treatment, other drugs, compounds and / or materials used in combination, the severity of the illness and the species, sex, age, body weight, condition, general health and previous medical history of the patient. The amount of triterpenoids and plant extracts and the route of administration will ultimately be determined by a physician, veterinarian or clinician, although the dosage will generally be selected to reach a local concentration at the site of action, the concentration achieving the desired effect without causing substantially harmful or harmful side effects.

[0344] Administration can be achieved in one dose (administration), continuously or intermittently (e.g., in appropriately spaced divided doses) throughout the course of treatment. Methods for determining the most effective mode of administration and dosage are well known to those skilled in the art and will vary with the formulation used for treatment, the purpose of the treatment, the target cell being treated, and the subject being treated. Single or multiple administrations may be performed, with the dosage level and pattern being selected by the treating physician, veterinarian, or clinician.

[0345] Other Preferences

[0346] Each and every compatible combination of the above-described embodiments is expressly disclosed herein, as if each and every combination were individually and expressly recited.

[0347] Various other aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure.

[0348] "And / or" when used herein should be considered as specific disclosure of each of the two specified features or components with or without the other. For example, "A and / or B" should be considered as specific disclosure of each of (i) A, (ii) B, and (iii) A and B, just as if each were listed individually herein.

[0349] Unless the context dictates otherwise, the descriptions and definitions of the features above are not limited to any particular aspect or embodiment of the invention, and apply equally to all aspects and embodiments described.

[0350] Example

[0351] Certain aspects and embodiments of the invention will now be described by way of example and with reference to the above-mentioned figures.

[0352] Material

[0353] Dimethyl sulfoxide (DMSO), epigallocatechin gallate (EGCG) and salicylic acid (SA) were purchased from Sigma-Aldrich. Oleanolic acid (OA), β-elemenonic acid and cycloastragenol were purchased from TargetMol (Boston, USA).

[0354] Raspberry extract (RI), ivy extract (HH), ilex holly extract (IA), fragaria extract (FV), and mangosteen extract (GM) were purchased from BOCSCI (New York, USA).

[0355] Primary sebaceous gland cells were derived from the forehead of a 48-year-old Chinese male. The same cell line was used in all experiments.

[0356] Characterization methods

[0357] Flow cytometry experiments were performed on a BD LSR Fortessa X-20 as follows: First, the cells were analyzed based on size and granularity using a lipid dye (AdipoRed TM ) of sebaceous gland cells stained with AdipoRed TM Signal intensity measurement. AdipoRed is measured using a 488nm FITC blue laser TM The signal was measured and the mean fluorescence intensity value of 10,000 cells was obtained. The mean fluorescence intensity is a measure of the average lipid content in 10,000 sebaceous gland cells. Cells treated with the composition of the present invention were compared with cells treated with the vehicle to determine the percentage of lipid reduction.

[0358] Primary sebaceous gland cell culture

[0359] Primary sebocytes were cultured in complete medium containing Y27632 (CCMY) at 37°C with 5% CO2 to 80% confluency, wherein the complete medium consisted of 3:1 DMEM (Gibco, 11995-065) / F12 (Gibco, 31765-035) supplemented with 10% fetal bovine serum (Hyclone, SV30160.03), 1x Penstrep (Gibco, 15140-122), 0.2 μg / mL epidermal growth factor (PeproTech, AF-100-15-1MG), 1 μg / mL hydrocortisone (Sigma-Aldrich, H0888), 10 -9M cholera toxin (Sigma-Aldrich, C8052-2MG) and 10 μM Y-27632 (Tocris, 1254 / 10). The cells were washed with PBS buffer [5 ml for 10 cm culture plate] and then incubated with 0.125% trypsin-EDTA (Gibco, 15400054) [2 ml trypsin for 10 cm culture plate] at 37°C for 5-10 minutes. When all cells were detached, neutralization medium consisting of DMEM containing 10% FBS and 1x Penstrep was added (2 mL neutralization medium for 10 cm culture plate), and the cells were transferred to a 15 mL conical tube and centrifuged at 1,000 rpm for 5 minutes.

[0360] After centrifugation, the cells were pelleted, the supernatant was discarded and the cells were resuspended in culture medium.

[0361] The cells were cultured in a 170 L CelCulture CO2 incubator (Esco Lifesciences).

[0362] Cells were counted by loading onto a hemacytometer, visualized using a CKX41 inverted microscope (Olympus) and counted manually.

[0363] General test plan

[0364] Test compositions were added to wells of a 24-well plate to achieve a final compound concentration of 10 μM (4 μL of 10 mM stock solution in DMSO into 396 μL medium) or a final extract concentration of 31.25 μg / mL (4 μL of 3,125 μg / mL stock solution in DMSO into 396 μL medium).

[0365] Primary sebaceous gland cells were cultured at 60 × 10 6 Cells (396 μL) were inoculated in culture medium. The cells were incubated at 37°C and 5% CO2 for 3 days. The culture medium was discarded and AdipoRed TM Dye (0.06% v / v in PBS) and incubate the cells at 37°C for 20 minutes. The staining solution is discarded, trypsin (0.125%; 250 μL) is added and the cells are incubated at 37°C for 5-10 minutes. When all cells are detached, fixative solution (250 μL, MEM without phenol red, 10% fetal bovine serum and 4% paraformaldehyde) is added and the cells are transferred to 5 mL polystyrene tubes. Prior to flow cytometry, the tubes are stored on ice. The mean fluorescence intensity of the lipid signal can be obtained from the flow cytometer graph, which is used to determine the inhibitory effect of the compound on sebaceous gland cells.

[0366] Example 1

[0367] The lipid-lowering effect of the composition of the present invention was measured against DMSO as a negative control and against known lipid-lowering compounds epigallocatechin gallate (EGCG) and salicylic acid (SA) as positive controls. The results are shown in Tables 3 and Figures 1 to 7 middle.

[0368] The results showed that the composition including triterpenoids (oleanolic acid (OA)) and plant extracts (rubus idaeus extract (RI), ivy extract (HI), ilex holly extract (IA), fragrans chinensis extract (FV) and mangosteen extract (GM)) provided improved lipid reduction compared to the individual compounds or extracts. The results demonstrated the synergistic effect of the composition relative to the individual compounds.

[0369] Table 3: Percent reduction in mean fluorescence intensity relative to DMSO

[0370]

[0371] References

[0372] Many publications are cited above to more fully describe and disclose the present invention and the state of the art to which the present invention belongs. The complete citations of these references are provided below. The entire contents of each of these references are incorporated herein.

[0373] Cheng et al., Int. J. Cancer Res.; Cell Biol., 2010; Vol. 42, pp. 181-185

[0374] Muchtaridi et al. J. Appl. Pharm. Sci. 2017, 7, 125

[0375] Palu et al. Molecules 2019, 24, 441 3

[0376] Tatia et al., Rev. Chim. 2019, 70, 1157

[0377] WO 2020 / 263188

Claims

1. A composition comprising: (a) a triterpenoid compound according to formula (I) or a pharmaceutically or cosmetically acceptable salt, prodrug, solvate, tautomer or stereoisomer thereof; and (b) a plant extract selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera, in: -Y- is a covalent bond and -X- is -CH2-, -CH2-CH2-, or -X- is absent and the carbon atom to which -X- is attached is bonded to H, or -Y- is -O-, and -X- is absent, and the carbon atom to which -X- is attached is bonded to H, Dashed bonds indicate the presence of double or single bonds between ring carbon atoms, with only one double bond present within the ring. R 1 , R 3 , R 3 ′、R 4 , R 5 , R 6 , R 7 , R 8 , R 8 ′、R 9 , R 9 '、R 10 and R 12 Independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , and when -Y- is -O- and -X- is absent, R 8 and R 9 can form a heterocyclic ring together, and R 5 It is absent when the ring carbon to which it is attached is in a double bond; R 2 and R 2 ' is independently selected from H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 16 、CO2R 17 、OC(=O)R 18 , or R 2 and R 2 'Together represents =O; R 11 and R 11 'Independently selected from H, F, OH, SH, C 1-6 Alkyl, I, C 1-4 Haloalkyl, C 2-6 Alkenyl, OR 19 、CO2R 21 、OC(=O)R 21 , or R 11 and R 11 'Together means = O; R C When not present, or when the ring carbon to which it is attached is not in a double bond, R C H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 、OC(=O)R 15 , or with R 12 Together they can form a carbon ring; R D When not present, or when the ring carbon to which it is attached is not in a double bond, R D H, F, OH, SH, C 1-6 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, C 2-6 Alkenyl, OR 13 、CO2R 14 , OC(=O)R 15 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 and R 21 Independently selected from H, C 1-6 Alkyl and C 1-4 haloalkyl; and n is 0 or 1.

2. The composition of claim 1, wherein: -Y- is a covalent bond and -X- is -CH2- or -CH2CH2-, and n is 1.

3. The composition of claim 1, wherein: -Y- is a covalent bond or -O-, and -X- is absent, and the carbon atom to which -X- is attached is bonded to H, and n is 0.

4. The composition of claim 1, wherein: R 1 , R 3 , R 3 '、R 4 , R 5 , R 6 , R 7 , R 8 , R 8 '、R 9 , R 9 '、R 10 and R 12 Independently selected from H, F, OH, SH, OR 13 、CO2R 14 、OC(=O)R 15 , C 1-6 Alkyl, CF3 and C 2-6 alkenyl; R 2 and R 2 'Independently selected from H, OH, OMe, OEt, C 1-4 Alkyl, C 2-4 alkenyl, CO2H, CO2Me, CO2Et, OC(O)Me and OC(O)Et, or R 2 , R 2 'Together form = O; R 11 and R 11 'Independently selected from H, OH, OMe, OEt, C 1-4 Alkyl, C 2-4 alkenyl, CO2H, CO2Me, CO2Et, OC(O)Me and OC(O)Et, or R 2 and R 2 'Together form = O; R 13 , R 14 and R 15 Independently selected from H, C 1-6 Alkyl and CF3; and n is 1 or 2.

5. The composition of claim 2, wherein: R 1 , R 3 , R 3 '、R 4 , R 5 , R 6 , R 7 , R 8 , R 8 '、R 9 , R 9 '、R 10 and R 12 Independently selected from H, F, OH, OR 13 、CO2R 14 、OC(=O)R 15 , C 1-6 Alkyl and C 2-6 alkenyl; R 2 and R 2 'Independently selected from H, OH, OMe, OEt, C 1-4 Alkyl, C 2-4 alkenyl, CO2H, CO2Me, CO2Et, OC(O)Me and OC(O)Et, or R 2 and R 2 'Together form = O; R 11 and R 11 'Independently selected from H, OH, OMe, OEt, C 1-4 Alkyl, C 2-4 alkenyl, CO2H, CO2Me, CO2Et, OC(O)Me and OC(O)Et, or R 2 , R 2 'Together form = O; R 13 , R 14 and R 15 Independently selected from H and C 1-6 Alkyl; and n is 1 or 2.

6. The composition of claim 5, wherein: R 1 , R 3 , R 3 '、R 4 , R 5 , R 6 , R 7 , R 8 , R 8 '、R 9 , R 9 '、R 10 and R 12 independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me; R 2 and R 2 ' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, CO2H, CO2Me and OC(O)Me, or R 2 , R 2 'Together means = O; R 11 and R 11 ' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, CO2H, CO2Me and OC(O)Me, or R 2 and R 2 'Together represents =0; and n is 1 or 2.

7. The composition of any one of claims 1 to 4, wherein: R 1 and / or R 4 and / or R 10 For H.

8. The composition of any one of claims 1 to 5, wherein: R 5 and / or R 6 and / or R 12 For me.

9. The composition of claim 6, wherein: R 7 is CO2H.

10. The composition of claim 1, wherein the triterpenoid compound is a compound of formula (IIa): in: R 3 , R 3 '、R 8 , R 8 '、R 9 and R 9 ' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me; R 2 and R 2 ' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me, or R 2 and R 2 'Together means = O; R 11 and R 11 ' is independently selected from H, OH, Me, Et, vinyl, allyl, 1-methylvinyl, OMe, OEt, CH2OH, CH2CH2OH, CO2H, CO2Me and OC(O)Me, or R 11 and R 11 'Together means = O; -X- is -CH2-, -CH2CH2-; and Dashed bonds indicate the presence of double or single bonds between ring carbon atoms.

11. The composition of claim 10, wherein: R 3 , R 3 '、R 8 , R 8 ′、R 11 and R 11 ' is independently selected from H, OH, Me, OMe, CH2OH and CO2H; R 2 and R 2 ' is independently selected from H, OH, Me, OMe, CH2OH, CO2H and OC(O)Me, or R 2 and R 2 'Together means = O; R 9 and R 9 ' is H, OH, Me, 1-methylvinyl, OMe, CH2OH and CO2H.

12. The composition of claim 1, wherein the triterpenoid is selected from compounds of formula (II) to (VII):

13. The composition of claim 12, wherein the triterpenoid compound is selected from the group consisting of oleanolic acid, hederagenin, ferruginic acid, ursolic acid, acetyldursolic acid, 23-hydroxybetulinic acid, betulinic acid (betulinic acid), cycloastragenol and β-elemenic acid (elemenic acid).

14. The composition of any one of claims 1 to 13, wherein the plant extract is selected from raspberry extract, mangosteen extract, ivy extract, ilex ilex leaf extract and fragaria extract.

15. The composition of claim 1, wherein the triterpenoid compound is oleanolic acid, and the plant extract is selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria, Ilex and Hedera, for example selected from raspberry extract, ivy extract, Ilex holly, mangosteen and Fragaria lutea.

16. The composition of claim 1, wherein the triterpenoid is β-elemenic acid, and the plant extract is an extract of a plant belonging to the genus Rubus, such as raspberry extract.

17. The composition of claim 1, wherein the triterpenoid is cycloastragenol, and the plant extract is an extract of a plant belonging to the genus Rubus, such as raspberry extract.

18. The composition of claim 1, wherein (i) the triterpenoid compound is hederagenin, and the plant extract is selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria and Ilex, for example, selected from raspberry extract, Ilex holly, mangosteen and Fragaria foetida; and (ii) the triterpenoid compound is ferric holly acid, and the plant extract is selected from extracts of plants belonging to the genera Garcinia, Rubus, Fragaria and Hederagen, for example, selected from raspberry extract, ivy extract, mangosteen and Fragaria foetida.

19. The composition of any one of claims 1 to 18, wherein the triterpenoid is present in an amount of 0.005% to 10% by weight, preferably 0.1% to 5% by weight, more preferably 0.1% to 3% by weight, for example 0.2% to 2% by weight.

20. The composition of any one of claims 1 to 19, wherein the plant extract is present in an amount of 0.005 to 50 wt%, preferably 0.005 to 30 wt%, such as 0.05 to 10 wt%, and more preferably 0.1 to 3 wt%.

21. The composition of any one of claims 1 to 20, further comprising one or more components selected from solvents, oils, surfactants, thickeners, humectants and preservatives.

22. The composition of any one of claims 1 to 20, further comprising one or more components selected from the group consisting of emollients, anti-inflammatory agents, antioxidants, and UV blockers.

23. A skin care product selected from skin / hand lotion, skin / hand cream, skin / hand gel, skin / hand ointment, skin / hand paste, toner, shaving gel, shaving cream, sunscreen, deodorant, antiperspirant, sunscreen lotion, aftersun product, aftershave product, body oil, bath oil and foam bath, the skin care product comprising the composition of any one of claims 1 to 20.

24. A hair care product selected from the group consisting of a conditioner, a hair detangling lotion, a styling gel, a styling cream, a styling wax, a styling lotion, a mousse, a spray gel, a hair tonic, a spray and a pomade, the hair care product comprising the composition of any one of claims 1 to 20.

25. A cosmetic method for reducing lipid production in the skin of an individual, the method comprising contacting the skin with a composition according to any one of claims 1 to 20.

26. A method for reducing lipid production in sebaceous gland cells or in the skin of a subject, the method comprising contacting the skin with a composition as claimed in any one of claims 1 to 20, wherein the method is not a therapeutic method.

27. A method for reducing lipid production in sebocytes, the method comprising contacting the sebocytes with the composition of any one of claims 1 to 20.

28. The composition of any one of claims 1 to 20 for use in reducing lipid production in sebocytes.

29. A composition as claimed in any one of claims 1 to 20 for use in a method of treatment.

30. A composition as claimed in any one of claims 1 to 20 for use in a method of treating a skin disease or condition associated with overproduction of lipids in the skin.

31. The composition for use of claim 30, wherein the disease or condition is selected from acne vulgaris and rosacea.

32. Use of a composition as claimed in any one of claims 1 to 20 for reducing lipid production in sebocytes.

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