Cosmetic composition against hair loss

Abstract

A cosmetic composition is provided to promote hair growth and prevent hair loss, the cosmetic composition essentially comprising melatonin, dihydroquercetin glucoside and / or epigallocatechin gallate glucoside. The product is applied to the scalp, for example, using a spray applicator.

Description

Technical field

[0001] The present invention relates to a cosmetic composition for stimulating hair growth, combating hair loss and thinning, wherein essentially plant extracts from Larix Europaea wood extract and Camellia sinensis leaf extract are used in combination with melatonin. The composition is applied topically to the scalp. Technical background

[0002] A full head of hair is an aesthetic factor in a person's appearance. Therefore, hair loss or thinning hair often causes psychological distress and can visually indicate a lack of health and well-being to others. Furthermore, it can manifest psychological problems in the individual, as they may feel disadvantaged compared to the norms of their environment.

[0003] The pathogenesis of androgenetic alopecia plays a particularly important role. Androgenetic alopecia can be triggered by androgens (e.g., testosterone) or by genetic predisposition. It manifests as a progressive shortening of the hair growth phase and progressive miniaturization of the hair follicles (regressive metamorphosis). Androgenetic hair loss (alopecia androgenetica or androgenetic alopecia (AGA), androgen-induced hair loss) is actually a normal part of aging. Like all hormones, testosterone is broken down and metabolized by enzymes. The resulting dihydrotestosterone (DHT) is the biologically active form of testosterone. DHT leads to increased affinity of the receptors in the hair follicle, resulting in hair loss. Approximately 80% of men and 50% of women worldwide are affected.In men, the onset of androgenetic alopecia (AGA) is characterized by a receding hairline at the temples, resulting in a receding hairline. As the condition progresses, increasing thinning of the hair occurs in the crown area. In women, AGA begins along the center part of the scalp. This is followed by increasing thinning of the hair in the crown area. AGA typically begins after menopause. Treatment of hormone-dependent tumors, such as breast cancer, with aromatase inhibitors can also lead to androgenetic alopecia in younger women. A family history of hair loss suggests a hereditary hypersensitivity of the hair follicles to the steroid hormone dihydrotestosterone (DHT). The growth phase (anagen phase) of the hair is shortened. This leads to hair loss, as well as a shortening and alteration of the hair shaft and progressive thinning of the scalp hair, i.e., alopecia.Male and female patterns of alopecia can be distinguished. Male pattern alopecia is genetically determined, and testosterone levels also play a significant role. During menopause, estrogen levels drop, but testosterone, which triggers androgenic alopecia, remains constant, so its effect predominates. Similar disturbances are observed with the use of hormonal contraceptives and medically indicated hormone therapy. Another aspect of hair loss is diffuse hair loss. Diffuse hair loss (diffuse alopecia, telogen effluvium) refers to increased hair loss across the entire scalp. This type of hair loss occurs more frequently in women. The causes are varied, for example...Hormonal fluctuations, thyroid disorders, iron deficiency, infections, scalp conditions, lupus, stress, or unbalanced diets such as radical diets, the influence of certain medications like beta-blockers or statins, metabolic disorders such as diabetes mellitus, Crohn's disease, bulimia, anorexia, or anemia can all contribute to seasonal hair loss. Seasonal hair loss occurs regularly. It actually corresponds to a natural cycle and is usually temporary. It is therefore a natural, physiological phenomenon, as it is in numerous other living organisms that experience seasonal cycles, such as plants, skin, and hair. Hair also protects against weather conditions and external factors, including UV radiation. Like animals, humans naturally lose hair. However, some people experience hair loss during the changing of the seasons.In most cases, hair loss occurs in spring and autumn when temperature fluctuations are more pronounced and put stress on the scalp and hair follicles. Therefore, attempts have been made in the past to combat hair loss and thinning. Over time, numerous topical preparations have been proposed, with varying degrees of success in combating hair loss (see the review article by Feroze Kaliyadan, "Androgenetic Alopecia - Medical Management" in Clinical Dermatology Review 2022; Vol. 6; pages 75-79; DOI: 10.4103 / cdr.cdr_27_21). Known active ingredients include minoxidil, a potassium channel opener whose hair growth-promoting effect has not yet been fully elucidated, and finasteride, an inhibitor of steroid 5α-reductase, whose hair growth-promoting effect has also not yet been fully elucidated. They are often effective but also have side effects.Melatonin has also been proposed to stimulate hair growth; see Bae S, Yoon YG, Kim JY, Park IC, An S, Lee JH, 2022. “Melatonin increases growth properties in human dermal papilla spheroids by activating AKT / GSK3β / β-Catenin signaling pathway.” PeerJ 10:e13461 http: / / doi.org / 10.7717 / peerj.13461. Mesotherapy, which is primarily based on alternative, more traditional approaches, is also known. Furthermore, platelet-rich plasma (PRP) therapy is available. PRP treatment stimulates the hair follicles from within, supposedly preventing thinning, brittle, dry, and fragile hair. The platelet-rich plasma supposedly stops the follicles from dying and switches them from the shedding to the growth phase, thereby restoring hair volume. Laser therapies, i.e.,The effects of radiation of a specific frequency have been proposed, as well as the administration of dietary supplements to stimulate hair growth from within. However, in most cases, the actual mechanism of action of the ingredients in these current approaches to stimulating hair growth is either unknown or not precisely understood. Therefore, the effectiveness and success of these methods are often dependent on the individual, and while success is possible, it unfortunately often occurs rather randomly and is thus inconsistent. Improvement is needed.

[0004] Several hair parameters are important for assessing the stage of pathogenesis. "Hair density" refers to the number of hairs growing per square centimeter of scalp. Normally, there are between 80,000 and 120,000 hairs on the head, with the highest density at the crown. Ethnic variations exist. Another parameter is "hair thickness." An average human hair is approximately 0.05 to 0.08 mm thick. Fine hair is described as measuring 0.02 to 0.04 mm. Hair thins with age. Ethnic differences can also be observed.

[0005] A reliable, technically and methodologically objective assessment of the therapeutic benefit of an application is based on the TrichoScan method, in which a cohort of men with androgenetic alopecia in stage I or II (Hamilton / Norwood scale) have the test substance applied to their scalp over a specific period, preferably 6 months. Following application, the anagen / telogen ratio (A / T ratio) is of particular importance for assessing hair loss. It measures the proportion of actively growing hairs (anagen phase) to resting hairs (shedding phase). A normal hair growth cycle is indicated by an A / T ratio of 4 or higher. If the ratio is below 4, this indicates that more hairs are in the telogen phase, leading to increased hair loss.

[0006] Against this background, it is therefore an object of the present invention to provide a cosmetic composition for stimulating hair growth, combating hair loss and thinning, which is used as a topical care product, is easy to manufacture and apply, and which offers advantages over conventional products. In particular, it is an object to optimally supply the hair follicles so that stronger hair growth occurs as quickly and stably as possible.

[0007] The present invention therefore relates to a cosmetic composition according to the main claim. Particular embodiments are defined in the dependent claims. The invention also relates to combinations with further measures for promoting hair growth, as well as a method for producing the cosmetic composition and a container for applying it. Description of the drawing Fig. Figure 1 illustrates a cross-section through the scalp and shows the points of attack of the active ingredients of the cosmetic composition according to the invention. Description of the embodiments

[0008] The cosmetic composition according to the invention essentially comprises a mixture of the active ingredients melatonin, dihydroquercetin glucoside (DHQG; also called taxifolin glucoside) and / or epigallocatechin gallate (EGCG), and further additives and excipients. The action of the aforementioned active ingredients achieves the following effects, which together create a significantly improved promotion of hair growth and / or hair quality.

[0009] Fig.Figure 1 illustrates a cross-section of the scalp, particularly the hair follicle. It has been determined that EGCG2 is primarily active in the basal layer of the epidermis by controlling the activity of interleukin 8 (IL-8). The sebaceous and sweat glands are also favorably regulated, ensuring optimal growth in this layer of the scalp. DHQG acts somewhat deeper in the skin layer, particularly at the site of stem cells in the outer root sheath (ORSc) and also affects the fibroblasts in the dermal papilla. The hair shaft is an environment of enzymatic reactions, such as those involving serotonin N-acetyltransferase. As a result, the hair shaft is strengthened and reinforced. It is a more recent finding that melatonin is synthesized in the hair follicle (see Fischer et al.). in International Journal of Trichology, 2012, Vol. 4, page 236 ff. In addition, the hair follicle also has various melatonin receptors.Melatonin can, for example, have a positive effect on seborrhea or seborrheic dermatitis. Other possible mechanisms include the elimination of reactive oxidative stress (ROS), which affects hair growth through a variety of external and internal factors.

[0010] Oxidative stress (OS) is a phenomenon characterized by the overproduction of free radicals by the body in response to endogenous or exogenous stimuli, leading to the release of significant amounts of oxidative substances such as reactive oxygen species (ROS). This excess of ROS exceeds the absorption capacity of the body's antioxidant system, resulting in an imbalance between the oxidative and antioxidant systems. Under normal physiological conditions, the body itself generates free radicals, which are counteracted by the release of antioxidant enzymes such as superoxide dismutase (SOD). OS ensures that the body maintains fundamental regulatory capabilities by controlling several signaling pathways and transcription factors and is involved in physiological processes such as cell proliferation, tissue repair, inflammation, and immunity.However, if the oxidative capacity is too high and exceeds the capacity of the body's antioxidant system to neutralize free radicals, oxidatively active molecules accumulate in the body. These molecules directly or indirectly impair the normal function of proteins, lipids, and DNA, cause cell or tissue damage, and ultimately lead to various diseases, including alopecia. The skin, the largest organ in mammals, consists primarily of the epidermis and dermis and serves as the body's first line of defense against external stimuli, as well as an excretory organ and for regulating body temperature. As an important skin appendage, hair follicles (HFs) not only produce hair and regulate body temperature but also periodically generate and store hair follicle stem cells (HFSCs), which are crucial for wound healing and the remodeling of the skin's microenvironment.The hair follicle is essentially a tiny organ formed by the interaction of the dermis and epidermis, consisting of a connective tissue sheath, an inner root sheath (IRS), an outer root sheath (ORS), a hair bulb, and a hair shaft (HS). The morphogenesis of the hair follicle is divided into three phases: induction, organogenesis, and cytodifferentiation. Following this, the hair follicle undergoes cyclical growth, including the anagen, catagen, and telogen phases. Organogenesis induces oxidative damage to the hair shaft and disrupts the hair cycle, leading to pathological hair loss. The active ingredients of this cosmetic composition intervene in these processes, primarily at the following levels from the basal layer. EGCG2 is particularly active in the uppermost layer of the epidermis, especially the basal layer.In the root sheath, DHQG is the predominant hormone, while in the root itself, melatonin acts in two ways: by stimulating the expression of ORS cells and mesenchymal stem cells (MS). Melatonin activates growth in the hair follicle. Furthermore, melatonin stimulates cell proliferation in the hair root via melatonin receptors. It prolongs the anagen phase of the hair and is also a highly potent antioxidant.

[0011] Dihydroxyquercetin glucoside, or DHQG for short, is an active ingredient found in Larix Europaea wood extract and acts, among other things, as an antioxidant. It has been shown to have a regulatory effect, particularly on hair stem cells.

[0012] Epigallocatechin gallate 2, or EGCG2 for short, is an active ingredient known as Camellia sinensis leaf extract. Among other things, it acts as an antioxidant and is particularly effective in the upper layers of the skin, specifically in controlling the effects of interleukin 8 (IL-8). It's important to note that Camellia sinensis leaf extract is the INCI name for green tea extract, which also typically contains caffeine. Caffeine can stimulate blood circulation, and this effect may have a positive impact on hair growth.

[0013] It has been shown that even one of DHQG or EGCG2 alone exerts a beneficial effect according to the mechanism described above. The combination of both substances, according to the composition of the invention, especially in combination with melatonin, can be advantageous.

[0014] Melatonin, as explained above, has a dual function: firstly, it controls the expression of ORS cells, i.e., it acts on the ORS bulge stem cells in the outer root sheath. Secondly, melatonin also acts on the expression of mesenchymal stem cells (MS). Therefore, due to the components of the cosmetic composition according to the invention described above, there are a total of four mechanisms at work. These mechanisms can act independently of one another, but together, as has been demonstrated, produce an unexpectedly beneficial effect by significantly stimulating hair growth and largely suppressing hair loss and thinning. It should be noted that an antioxidant effect can be assumed for all three components, but in addition, a specific effect at the aforementioned locations on the hair shaft and hair root can be attributed to each individual active ingredient.

[0015] The present invention uses a cosmetic composition whose components are used in the areas listed below, wherein all partial and percentage values ​​in this description and the claims are based on weight unless otherwise stated, and all related numerical values ​​are to be read with a tolerance of + / - 10% of the stated value due to the use of extracts: DHQG, i.e., dihydroquercetin glucoside, or taxifolin glucoside, is present in the cosmetic composition according to the invention as so-called Larix Europaea Wood Extract. Larix Europaea Wood Extract is the INCI name for larch bark extract, in particular from the bark (or wood) of the European larch (Larix europaea), although other raw materials could also be used. For example, the bark extract of the Siberian larch (Larix sibirica) is also suitable. EGCG2 is epigallocatechin gallate, which is contained in Camellia Sinensis Leaf Extract (green tea extract) and is present in the present invention as a glucoside.

[0016] In the present invention, both DHQG and EGCG2 are used as standard plant extracts, namely Larix Europaea Wood Extract and Camellia Sinensis Leaf Extract, respectively. The following areas are recommended for the present cosmetic composition: Larix Europaea Wood Extract 0.01 to 10%, preferably 0.01 to 0.5%, more preferably 0.05 to 2%, especially 0.1 to 1%. Camellia Sinensis Leaf Extract: 0.001 to 1%, preferably 0.001 to 0.5%, more preferably 0.005 to 0.2%, especially 0.01 to 0.1%. Glycine, zinc chloride and sodium metabisulfite can optionally be added to the mixture of both components or the individual components in the following quantities. Glycine can be used in an amount of 0.01 to 10%, preferably 0.01 to 0.5%, more preferably 0.05 to 2%, and especially 0.1 to 1%. Zinc chloride can be used in an amount of 0.001 to 1%, preferably 0.001 to 0.5%, more preferably 0.005 to 0.2%, and especially 0.01 to 0.1%. Sodium metabisulfite can be used in an amount of 0.001 to 5%, preferably 0.01 to 2.5%, more preferably 0.03 to 1% and most especially 0.05 to 0.5%.

[0017] The four or five active ingredients mentioned above can be present as a mixture in a glycerin / water base (hereinafter simply referred to as the mixture). Specifically, the mixture of Larix Europaea wood extract and / or Camellia sinensis leaf extract, glycine, zinc chloride, and sodium metabisulfite, as specified above in terms of quantity, or in an amount ranging from 0.01 to 10% of the active ingredients, preferably 0.1 to 5% and more preferably 0.2 to 3%, can be manufactured as a finished product mixture or, if applicable, purchased commercially. Due to the manufacturing process (Camellia sinensis leaf extract, the INCI name for green tea extract), the mixture may contain caffeine. The caffeine content can range from 0.001 to 5%. Preferred amounts are 0.1 to 1%, preferably 0.2 to 0.5%, possibly also as an additive.Caffeine can be beneficial for improving blood circulation to the hair follicles. This ensures that the hair follicles are supplied with nutrients and the necessary hormones.

[0018] Another suitable additive is, for example, biotin, which can be used in amounts of 0.001% to 5%, preferably 0.01% to 1%.

[0019] Another suitable additive is, for example, the extract of blue honeysuckle (Lonicera caerulea L.). This can be used in amounts of 0.001% to 10%, preferably 0.01% to 1%.

[0020] The aforementioned mixture contains, at a concentration of 1%, a dosage of approximately 50 µg DHQG and / or 5 µg EGCG2.

[0021] Melatonin is used in the composition according to the invention in an amount of 0.0001 to 1%, preferably 0.001 to 0.1%, more preferably 0.005 to 0.05%, and especially about 0.0033%.

[0022] In addition to controlling oxidative stress, controlling a healthy hair growth cycle is important. The human hair growth cycle consists of three phases: the anagen, the catagen, and the telogen phases. The anagen phase is the active growth phase, which can last for several years. The catagen phase is a transitional phase in which the hair follicles gradually detach from their blood supply and shrink. It can last for a few weeks. The telogen phase is the resting phase in which the hair strand no longer grows and is eventually shed. This phase lasts from several weeks to months.

[0023] Age and gender affect the aforementioned A / T ratio. Factors such as hormones, stress, diet, and medical conditions can, as explained above, disrupt the hair cycle. Although genetics plays an important role, the cosmetic composition according to the invention can prolong the anagen phase, reduce hair loss, and improve the appearance and overall quality of the hair.

[0024] The present invention combines the active ingredients dihydroquercetin glucoside and / or epigallocatechin gallate glucoside 2, optionally caffeine and / or biotin, and melatonin, achieving an ideally additive or superior effect compared to the individual active ingredients, and achieving a better consistency and sustainability of the effect than previously expected. The object of the present invention is to optimally supply the hair follicles so that hair growth occurs as quickly and consistently as possible. However, it has now been shown that the combined use of melatonin and DHQG / EGCG2 (the latter in the form of the aforementioned mixture) promotes hair growth, stimulates new hair growth, and promotes it more sustainably compared to the substances alone. In addition to the consistent and sustainable effect, the results are in some cases even surpassed, and advantageous effects on hair growth and / or hair quality are achieved in an unexpected manner.It has also been shown that the cosmetic composition according to the invention is useful for post-hair transplant applications. All of this is surprising and could not have been foreseen. Combinations of the cosmetic composition according to the invention with other measures that promote hair growth

[0025] The cosmetic composition according to the invention can be used in combination with other active ingredients or therapies. A combination with the active ingredient minoxidil is suggested, whereby the application can be carried out simultaneously or at different times (e.g., minoxidil can be administered in the morning and the cosmetic composition according to the invention in the evening), daily, every other day, or weekly. The same applies to the active ingredient finasteride when used in combination with the cosmetic composition according to the invention. A combination of mesotherapy and the application sequence described here with the cosmetic composition according to the invention can also be performed. So-called PRP therapy is also a suitable option in addition to the use of the cosmetic composition according to the invention.It is also conceivable that laser irradiation therapy in combination with the cosmetic composition according to the invention could achieve even better results. Finally, reference is made to the additional intake of hair growth-promoting dietary supplements when the cosmetic composition according to the invention is used after hair transplantation. Other areas of application

[0026] The cosmetic composition according to the invention is also useful for post-operative application after a hair transplant or for preparing for such a procedure. This includes, among other things, preventative and post-operative care. In particular, androgenetic alopecia can progress at the border between the natural and transplanted hairs. This can lead to increasingly larger gaps. The cosmetic composition according to the invention can prevent or avert this. Production of the present cosmetic composition

[0027] To prepare the present cosmetic composition, the components of the aforementioned mixture, preferably 1% to 3%, and melatonin, preferably 0.0033%, are mixed and made up to 100% with an ethanolic solution (ethanol / water 10:90 to 90:10, or 20:80 to 80:20, or 30:70 to 70:30, preferably approximately 30:70). Specifically, the ethanol-water mixture is placed in a mixer, and Larix Europaea wood extract is added first, followed, if desired, by Camellia sinensis leaf extract. The reverse order is also possible. Alternatively, a finished product of the mixture can be used. Finally, the required amount of melatonin is added, followed by menthol, and then any other necessary additives, such as EDTA. The mixture is thoroughly homogenized and filled into application containers.Preferably, the application container is a spray container with a dosing nozzle that can be specifically adjusted and handled to target the scalp area to be moistened with the cosmetic composition according to the invention, so that the dosage is as effective and precise as possible. Application and use

[0028] The cosmetic composition according to the invention is typically used topically on the scalp as a liquid hair care product to stimulate hair growth and combat hair loss and thinning. Approximately 0.1 to 5 ml, preferably 0.5 ml (= 3 pumps) to 2.5 ml (= 14 pumps), of the cosmetic composition is applied once daily to the affected area of ​​the scalp with one or more pumps from a container with an applicator.

[0029] The container for the cosmetic composition according to the invention is preferably a spray container with a tubular extension at the spray head, which is used to apply the cosmetic composition to the scalp. The container holds approximately 25 to 120 ml of the cosmetic composition according to the invention, preferably 40 to 100 ml and more preferably 75 to 90 ml. Alternatively, ampoules made of plastic (PE or PP) or glass can be used instead of a container with a spray device. These ampoules are preferably designed to allow for convenient application to the scalp. This can be achieved, for example, by means of a tubular extension on the ampoule.

[0030] After application, the cosmetic composition according to the invention is allowed to absorb, which is easily achieved due to the ethanol content. The best time for application is in the evening before bed. The aforementioned amount of the cosmetic composition according to the invention can also be applied at other times of the day. Depending on the extent of hair loss, one course of treatment may require a period of 1, 3, or 6 months, or possibly longer.

[0031] The cosmetic composition according to the invention is provided in an applicator. Adding menthol as a fragrance and penetration aid has proven advantageous. Furthermore, it may contain additives commonly used in the field, such as EDTA. Advantages of the invention

[0032] The surprising effect of the cosmetic composition according to the invention leads to an unexpected improvement in hair growth and the condition of the entire hair follicles in many respects. This may allow for the use of lower overall amounts of active ingredients. The cosmetic composition according to the invention is readily soluble in aqueous ethanol, making it pleasant and convenient to apply. Side effects, if any, are minimal and predictable. The product can be attributed with a universally effective, proven mechanism, thus largely avoiding a more random effect that is heavily dependent on the individual's habitus. The effect is consistent and long-lasting. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited non-patent literature

[0000] Feroze Kaliyadan, “Androgenetic Alopecia - Medical Management” in Clinical Dermatology Review 2022; Vol. 6; pages 75-79; DOI: 10.4103 / cdr.cdr_27_21

[0003] Bae S, Yoon YG, Kim JY, Park IC, An S, Lee JH, 2022. "Melatonin increases growth properties in human dermal papilla spheroids by activating AKT / GSK3β / β-Catenin signaling pathway". PeerJ 10:e13461 http: / / doi.org / 10.7717 / peerj.13461

[0003] Fischer et al. in International Journal of Trichology, 2012, Vol. 4, page 236

[0009]

Claims

[1] Composition, comprising 0.0001 to 1% melatonin, and 1% to 3% dihydroquercitin glucoside (DHQG) or epigallocatechin gallate glucoside 2 (EGCG2), or a mixture thereof, as well as additives and excipients. [2] Composition according to claim 1, comprising Larix Europaea Wood Extract containing 0.01 to 10% DHQG, and / or Camellia Sinensis Leaf Extract containing 0.001 to 1% EGCG2, and the remainder being glycerin and water in a ratio of 2:1 to 1:

2. [3] Composition according to claim 1 or 2, further comprising 0.01 to 10% glycine, 0.001 to 1% zinc chloride and 0.001 to 5% sodium metabisulfite. [4] Composition according to any one of claims 1 to 3 for use as a cosmetic agent to promote hair growth and / or to combat the decline in hair quality and to improve hair quality. [5] Composition according to any one of claims 1 to 3 in combination with a measure selected from the addition of minoxidil, the addition of finasteride, mesotherapy, platelet-rich plasma therapy, laser therapy and the administration of dietary supplements for use as a cosmetic agent to promote hair growth and / or combat hair loss [6] Method for producing a composition according to any one of claims 1 to 3, wherein the plant extracts, namely Larix Europaea Wood Extract and / or Camellia Sinensis Leaf Extract, are dissolved in a solution of glycerin and water in a ratio of 1:2 to 2:1, zinc, glycine and sodium metabisulfite are added, melatonin and excipients are added and everything is mixed homogeneously. [7] Spray container containing a composition according to one of claims 1 to 3, wherein the spray container has a tubular extension at the spray head with which the agent is placed on the scalp. [8] Spray container according to claim 7, wherein the container contains 25 to 100 ml of the composition, preferably 25 to 120 ml of the composition, more preferably about 75 ml to 90 ml of the composition. [9] Spray container according to claim 7 or 8 or composition according to any one of claims 1 to 5 for topical application of the composition to the scalp in the evening before sleep, wherein about 0.5 to 3 ml of composition is applied to the area of ​​the head affected by hair loss in one process. [10] Spray container according to claim 9, wherein an application requires a period of 1, 3 or 6 months and possibly more.

Images