WO2021083919A1

WO2021083919A1 - Composition containing prebiotic bacteria and licochalcone a

Info

Publication number: WO2021083919A1
Application number: PCT/EP2020/080215
Authority: WO
Inventors: Heike FÖLSTER; Stefan Gallinat; Daniel Richter; Petra SCHÖNDIENST; Svenja Lügger
Original assignee: Beiersdorf Ag
Priority date: 2019-10-28
Filing date: 2020-10-28
Publication date: 2021-05-06
Also published as: EP4051222A1; DE102019007505A1

Abstract

The invention relates to a cosmetic or dermatological composition containing: at least one prebiotically active bacteria strain which has a positive influence on skin health when settling on the skin; and licochalcone A. The invention further relates to a method for the cosmetic or dermatological treatment of the skin, wherein the composition according to the invention is applied to the skin. The invention also relates to a process for preparing the cosmetic or dermatological composition according to the invention.

Description

Beiersdorf Aktiengesellschaft Hamburg

Composition with probiotic bacteria and licochalcone A.

The present invention relates to a cosmetic or dermatological composition which comprises at least one probiotic bacterial strain which has a positive effect on skin health when it settles on the skin, and licochalcone A. The invention also relates to a method for the cosmetic or dermatological treatment of the skin, in which the composition of the present invention is applied to the skin. The invention also relates to a method for producing the cosmetic or dermatological composition of the present invention.

The desire to look beautiful and attractive is inherently rooted in people. Even if the ideal of beauty has changed in the course of time, striving for a flawless appearance has always been the goal of people, as a personable appearance increases their self-esteem and the attraction to others. The condition and appearance of the skin play an important part in a beautiful and attractive appearance.

Cosmetic and dermatological compositions for improving skin health are extensively described in the prior art. In recent years there has been increasing speculation that disorders of the skin health caused by infections, stress, improper nutrition, medication, environmental factors or the like could be traced back to undesired changes in the natural skin microbiome.

Treatment approaches have therefore been proposed in which the skin microbiome is improved through the targeted settlement of metabolically active, probiotically effective bacterial strains by restoring or maintaining the microbiome homeostasis. US 2018/0104283 A1 describes a method in which bacterial strains naturally occurring on the skin are supplied to the skin in order to displace potentially pathogenic microorganisms. WO 2016/172196 A1 describes a method for treating acne in a patient, in which live C. acnes strains are settled on the patient's skin. However, it has repeatedly proven difficult to establish a sufficient amount of the metabolically active bacterial strains on the skin. Since the skin is densely populated by bacteria, bacteria that are applied to the skin must first establish themselves in the microbiome, which is difficult due to the limited nutrients and the complex interactions within the various bacteria in the microbiome.

This regularly leads to bacteria applied to the skin being displaced by the microorganisms of the existing skin flora. For this reason, attempts have been made to allow the bacteria applied to the skin to grow by initially pushing back the existing skin flora with a disinfectant or an antibiotic. However, such measures represent a relatively difficult intervention in the microbiome, which can result in lasting undesirable or even pathological shifts in the microbiome.

It was therefore the object of the present invention to provide compositions and methods with which probiotic bacterial strains which have a positive effect on skin health can be settled in sufficient quantities on the skin and integrated into the microbiome.

The object is surprisingly achieved by a cosmetic composition which comprises or consists of at least the following components: a) at least one probiotically active bacterial strain which has a positive effect on the health of the skin when it settles on the skin; b) Licochalcone A or a derivative thereof.

It was found that the simultaneous administration of probiotic strains of bacteria with licochalcone A leads to the fact that the probiotic bacteria strains can be integrated significantly better into the existing skin microbiome.

As mentioned above, the composition according to the invention comprises, as a first component, at least one probiotic bacterial strain which, when it settles on the skin, has a positive effect on skin health. As used herein, “probiotically effective” means that the bacterial strain in question, when administered to humans in sufficient quantities, conveys health-promoting effects. In the present case, the term is used in connection with those bacterial strains that settle on the skin after administration, ie multiply through cell division, and have a positive effect on skin health through their presence in the skin flora. In the context of the present invention, bacteria of the genus Staphylococcus and Cutibacterium are particularly suitable as probiotically effective bacterial strains. These genera are those that are regularly represented in normal human skin flora. In a particularly preferred embodiment, the at least one probiotically effective bacterial strain belongs to a species which is selected from the group consisting of Staphylococcus epidermidis, Staphylococcus hominis and Cutibacterium acnes.

Staphylococcus epidermidis and Staphylococcus hominis are coagulase-negative, facultatively pathogenic, gram-positive bacteria that inhabit human skin and mucous membranes. Preferably, the at least one S. epidermidis strain and / or the at least one S. hominis strain is not an antimicrobial strain. S. epidermidis strains and S. hominis strains are known which have developed resistance to conventional antibiotics such as penicillin and therefore cannot be treated with appropriate preparations. It has been described in the literature that S. epidermidis strains and S. hominis strains are actively involved in the control of the growth of pathogenic agents such as S. aureus strains in the natural skin flora. For this reason, too, the establishment of non-pathogenic S. epidermidis strains leads to an improvement in skin health.

The species C. acnes refers to gram-positive, anaerobic, rod-shaped bacteria, which until 2016 were taxonomically grouped as Propionibacterium acnes. The species includes pathogenic and non-pathogenic representatives. According to current knowledge, pathogenic representatives of this species, C. acnes, contribute significantly to the development of acne in humans, while non-pathogenic strains are important for maintaining a stable microbiome composition. The species can be divided into three phylogenetically different types, which are referred to here as types I, II and III. Type I bacteria are further subdivided into subtypes IA, IB and IC. Subtype 1A is further divided into subgroups 1A1 and 1A2. Many non-pathogenic strains of C. acnes belong to (a) type I, subtype IA, subgroup IA2, (b) type I, subtype IB, or (c) type II.

It is therefore preferred that the composition according to the invention comprises at least one strain of the species C. acnes, this strain preferably belonging to (a) type I, subtype IA, subgroup IA2, (b) type I, subtype IB, or (c) type II heard. In a particular embodiment, the composition comprises one or more C. acnes strains of type I, subtype IA, subgroup IA2. In a further particular embodiment, it comprises the composition of one or more C. acnes strains of type I, subtype IB. In a further particular embodiment, the composition comprises one or more C. acnes strains of type II.

In a further particularly preferred embodiment, the composition according to the invention comprises in each case at least one strain of type I, subtype IA, subgroup IA2, at least one strain of type I, subtype IB, and at least one strain of type II. It is particularly preferred that the composition according to the invention comprises several strains of type I, subtype IA, subgroup IA2, in combination with several strains of type I, subtype IB, as well as several strains of type II.

It is preferred that the composition of the present invention comprises a total amount of probiotic bacteria in the range of 10 ⁴ -10 ¹¹ CFU / ml, and more preferably in the range of 10 ⁷ -10 ¹ ° CFU / ml.

In addition to the at least one probiotically effective bacterial strain, the composition according to the invention comprises the flavonoid licochalcone A or a derivative thereof as a second component. Licochalcone A has the following structure:

Llcecbateen A

Licochalcone A is a chemical compound that can be extracted from the root of Chinese liquorice (Glycyrrhiza inflata). It has anti-inflammatory, antibacterial, anti-parasitic and anti-cancer effects and is regularly used in cosmetic compositions to prevent skin irritation such as redness. It has been shown that licochalcone A improves the establishment of probiotic strains, such as strains of S. epidermidis, S. hominis or C. acnes, in the skin microbiome.

Licochalcone A is preferably used in an amount of from 0.0001 to 10% by weight, particularly preferably from 0.001 to 7.5% by weight and particularly preferably from 0.01 to 5% by weight or from 0.1 to 0.5% by weight based on the total weight of the composition. It is therefore advantageous to use licochalcone A or a derivative thereof in an amount of at least 0.0001% by weight, at least 0.001% by weight, at least 0.01% by weight, at least 0.1% by weight, at least 1.0% by weight, at least 2.0% by weight, at least 3.0% by weight, at least 4.0% by weight, or at least 5.0% by weight, based on the total weight the composition to use.

According to a particularly preferred embodiment, the composition of the present invention contains, in addition to the at least one probiotic bacterial strain and licochalcone A or a derivative thereof, also at least one protector strain of the genus Lactobacillus, which promotes the settlement of the probiotic bacterial strain.

Bacteria of the genus Lactobacillus are gram-positive, microaerophilic or anaerobic bacteria that are taxonomically assigned to the Lactobacillaceae family. These are gram-positive, usually rod-shaped bacteria that ferment sugar and carbohydrates into lactic acids. Bacteria of the genus Lactobacillus are particularly well known from the food industry, where they are often used as starter cultures in the manufacture of dairy products. The genus includes various species that can be used without restriction within the scope of the present invention.

Suitable species which can serve as protector strains in the compositions of the present invention include Lactobacillus delbrueckii, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus delbrueckii subsp. delbrueckii, Lactobacillus delbrueckii subsp. lactis, Lactobacillus acidophilus, Lactobacillus amylolyticus, Lactobacillus amylovorus, Lactobacillus aviaries, Lactobacillus bifermentans, Lactobacillus brevis, Lacto bacillus casei, Lactobacillus coryniformis, Lactobacillus crispatus, Lactobacillus crustorum, Lactobacillus curvatus, Lactobacillus dextrinicus, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus hilgardii , Lactobacillus iners, Lactobacillus jensenii, Lactobacillus mali, Lactobacillus oryzae, Lactobacillus panis, Lactobacillus para- buchneri, Lactobacillus paracasei, Lactobacillus paralimentarius, Lactobacillus paralimentarius, Lactobacillus paralimentarius, Lactobacillus ractobacillus, Lactobacillus salivacillus, Lactornobacillus, Lactobacillus, Lactnobacillus, Lactornacillus salivacillus Lactnobacillus, Lactobacillus salivacillus Lactobacillus oryzae, Lactobacillus oryzae, Lactobacillus.

In a preferred embodiment, the composition of the present invention comprises two or more protector strains, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 Lactobacillus strains. In a particularly preferred embodiment, it is the at least one protector strain which is added to the composition according to the invention to a strain of the species Lactobacillus plantarum or Lactobacillus rhamnosus. In a particularly preferred embodiment, the composition according to the invention comprises at least one strain of the species Lactobacillus plantarum and one strain of the species Lactobacillus rhamnosus. In a further preferred embodiment, the composition according to the invention comprises several strains of the species Lactobacillus plantarum and several strains of the species Lactobacillus rhamnosus.

The at least one protector strain which is an optional component of the composition of the present invention can produce an antibiotic substance. The antibiotic substance can be a bacteriocin that is produced by the Lacto bacillus and secreted into the surrounding medium. The protector strain preferably produces a bacteriocin which is selected from the group consisting of nisin, mersacidin, lactocin, acidocin B, and entereocin P. In a further preferred embodiment, the protector strain contained in the composition according to the invention produces 2 or more of the named bacteriocins .

It is preferred that the optional protector strain or strains are selected in terms of type and amount such that the at least one probiotically effective bacterial strain settles which is at least 2 times higher than the corresponding settlement of the Bacterial strain in the absence of the protector strain. It is even more preferable that the colonization of the at least one probiotic strain of bacteria should be at least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 75 times. times, at least 100 times, at least 500 times or at least 1000 times higher than the corresponding settlement of the bacterial strain in the absence of the protector strain.

The effect of the protector strains can be measured in simple assays in which the composition of the present invention, which comprises at least one probiotic strain of bacteria, at least one Lactobacillus strain, and licochalcone A or a derivative thereof, is compared with a negative control. A composition which largely resembles the composition to be examined, but does not contain a Lactobacillus strain, is preferably used as a negative control.

It is preferred that the composition of the present invention comprises a total amount of bacteria of the genus Lactobacillus in the range of 10 ⁴ -10 ⁹ CFU / ml, and more preferably in the range of 10 ⁶ ^{-10 8} CFU / ml. This means that the protector trunks Compared to the probiotic strains can be contained in the composition in much smaller amounts. Since the protector strains only have to provide the probiotic strains with a growth advantage in the early phase of colonization of the skin, their permanent settlement is not necessary. Accordingly, the protector strains can be applied to the skin in significantly lower inoculation densities.

In one embodiment of the present invention, after application of the composition according to the invention, there is no permanent establishment of the at least one protector strain in the skin flora of the subject to whom the composition is administered. This means that the at least one protector strain does not reproduce or only insufficiently reproduces on the skin of the subject. It is preferred that after 24 hours, preferably after 48 hours and more preferably after 72 hours, the at least one protector strain can no longer be detected on the skin of the subject, or only in a small amount.

In addition to the probiotic bacterial strains and licochalcone A or a derivative thereof, the composition according to the invention preferably also comprises at least one cosmetic auxiliary. This cosmetic auxiliary can be substances that are regularly used as auxiliary in cosmetic or dermatological products. These substances include antioxidants, solubilizers, vitamins, dyes, carriers, fillers, emulsifiers, humectants and the like. In a preferred embodiment, the cosmetic auxiliary is glycerol, panthenol, ubiquinone Q10 or hyaluronic acid.

Since the composition according to the invention is formulated for use on the skin, it will have a pH value which is in the neutral to slightly acidic range. Thus it is preferred that the composition have a pH of 4-8, and preferably 5-7.

The composition according to the invention is preferably an emulsion. This can be in the form of an oil-in-water emulsion or a water-in-oil emulsion.

In another embodiment, the water content in the composition is less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, and particularly preferably less than 0.5% (weight / Weight). In a particularly preferred embodiment In terms of form, the composition according to the invention is an anhydrous composition.

The composition according to the invention is preferably in the form of a gel, a cream, an ointment or a lotion.

The composition according to the invention preferably does not comprise any silicone oil, mineral oil or polyethylene glycol.

Cosmetic and dermatological compositions usually contain one or more preservatives. In the present case it is particularly advantageous to use lactic acid as a preservative.

In a further aspect, the present invention relates to a method for producing a cosmetic or dermatological composition as described above,

The method comprises steps in which a suspension or a lyophilizate of the probiotically active bacterial strain or the probiotically active bacterial strains is first produced. If Lactobacillus strains are to be used in the composition in addition to the probiotically active bacterial strain or strains, two separate suspensions can first be prepared, which are then mixed with one another. The first suspension contains the at least one probiotically effective bacterial strain, and the second suspension contains at least one Lac tobacillus strain. Both suspensions can be prepared by inoculating cell material in water or a suitable buffer. The two suspensions can then be mixed with one another and combined with licochalcone A and the other components of the cosmetic or dermatological composition.

If the composition of the present invention is produced with lyophilisates of the bacterial strains, a lyophilisate can first be produced which comprises the at least one probiotic bacterial strain, and separately therefrom a second lyophilisate which comprises the at least one Lactobacillus strain. The two lyophilisates can then either be mixed with one another and then brought into contact with licochalcone A.

However, from an economic point of view, it is particularly preferred that first suspensions of the bacterial strains are mixed with one another, which are then subjected to freeze-drying, so that a lyophilisate is obtained which contains all of the bacterial strains. Me contains which are to be incorporated into the cosmetic or dermatological composition of the present invention. This lyophilizate, which contains both at least one probiotically effective bacterial strain and at least one lactobacillus strain, is then mixed with licochalcone A and other cosmetic auxiliaries in order to provide the composition according to the invention.

Suitable methods for freeze-drying or lyophilization are well known to the person skilled in the art. Freeze drying involves freezing a product, such as a bacterial suspension, under reduced pressure and adding heat so that the frozen water in the product can be removed by sublimation. Most products can be dried to 1-5% residual moisture. In accordance with the invention, commercially available devices can be used for freeze-drying, such as the Lyovac ™ devices from GEA (Berlin, Germany), the Gamma 2-20 freeze dryer LCM-1 from Christ (Osterode am Harz, Germany) or the Christ Martin ™ Alpha 1-2 freeze dryer from Fisher Scientific GmbH (Schwerte, Germany).

In yet another aspect, the invention relates to a method for the cosmetic or dermatological treatment of the skin, comprising steps in which the above-described cosmetic or dermatological composition of the present invention is applied to the skin of a subject, preferably a human.

In a particularly preferred embodiment, the area of skin to which the invention composition is applied has been carefully cleaned beforehand. Such cleaning can be done with a surfactant-containing cleaning agent. Cleaning agents which comprise benzoyl peroxide are particularly suitable for this purpose, although other substances can also be used in this context.

In a particularly preferred embodiment, the composition is an anhydrous composition. In such a composition, the bacterial strains can be present in the form of a lyophilizate in an oil phase. Only after the composition has been applied to the skin does the lyophilizate come into contact with water, which leads to the activation of the growth and metabolic activity of the bacteria.

The oil phase can comprise oils customary in the field of cosmetics, such as, for example, lecithins, olive oil, sunflower oil, jojoba oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil and castor oil. In another embodiment of the present invention, the composition is an aqueous composition. This means that the composition contains at least one aqueous phase in which the bacterial strains can be activated under suitable conditions.

The compositions of the present invention may be in the form of a cosmetic preparation which is used as a mask. The mask composition of the present invention is preferably based on an anhydrous powder which comprises at least one alginate, at least one calcium salt and at least one oil. The bacteria can be present as a lyophilizate in the oil phase, as described above.

Claims

1. Cosmetic or dermatological composition, comprising a) at least one probiotic strain of bacteria which has a positive effect on the health of the skin when it settles on the skin; b) Licochalcone A or a derivative thereof.

2. Cosmetic or dermatological composition according to claim 1, characterized in that the at least one probiotically active bacterial strain belongs to a genus which is selected from the group consisting of Staphylococcus and Cutibacterium.

3. Cosmetic or dermatological composition according to claim 2, characterized in that the at least one probiotically active bacterial strain belongs to a species which is selected from the group consisting of Staphylococcus epidermidis, Staphylococcus hominis and Cutibacterium acnes.

4. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that licochalcone A or a derivative thereof is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition.

5. Cosmetic or dermatological composition according to claim 4, characterized in that licochalcone A or a derivative thereof is contained in an amount of 0.01 to 5% by weight based on the total weight of the composition.

6. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that the cosmetic composition is in the form of an oil-in-water emulsion or water-in-oil emulsion.

7. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that the cosmetic composition is in the form of a gel, a cream, an ointment or a lotion.

8. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that the cosmetic composition comprises no silicone oil, mineral oil or polyethylene glycol.

9. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that the total amount of probiotic bacteria in the cosmetic composition ^{comprises 10 4} -10 ¹¹ CFU / ml, and preferably 10 ⁷ -10 ¹ ° CFU / ml.

10. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that it also contains at least one cosmetic adjuvant.

11. Cosmetic or dermatological composition according to claim 10, characterized in that the at least one cosmetic auxiliary is selected from the group consisting of glycerol, panthenol, ubiquinone Q10 and hyaluronic acid.

12. Cosmetic or dermatological composition according to one of the preceding claims, characterized in that the composition further comprises lactic acid as a preservative.

13. A method for the cosmetic or dermatological treatment of the skin, characterized in that the composition according to any one of claims 1-12 is applied to the skin.

14. The method according to claim 13, characterized in that the skin is cleaned with a surfactant-containing cleaning agent before the cosmetic composition is applied.

15. The method according to claim 14, characterized in that the cleaning agent comprises benzoyl peroxide.

16. A method for producing a cosmetic or dermatological composition according to any one of claims 1-12, characterized in that a suspension or a lyophilizate which comprises the at least one probiotic bacterial strain is mixed with licochalcone A or a derivative thereof .