A hair improvment combination and composition

Abstract

The subject of the invention is an oral hair improvement combination consisting of at least one proteoglycan and at least one inositol, as well as an oral composition comprising the combination according to the invention and at least one substance selected from the group consisting of an active / nutritional substance, a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient and a pharmaceutically acceptable vehicle. The subject of the invention is the use of the oral combination or the oral composition according to the invention in supporting and enhancing the health and condition of hair in individuals with female pattern hair loss (FPHL) or male pattern hair loss (AGA) as well as in supporting and enhancing the health and condition of hair in individuals before, during and / or after hair transplantation. The invention relates to the field of trichology.

Description

[0001] A HAIR IMPROVMENT COMBINATION AND COMPOSITION

[0002] The present invention relates to the field of trichology. The combination and composition comprising the combination according to the invention will find use in supporting and enhancing the health and condition of hair. In particular, the present invention will find use in non-therapeutic and non-surgical methods of supporting and enhancing hair in female pattern hair loss (FPHL, female pattern hair loss), male pattern hair loss (AGA, androgenetic alopecia) and in people before, during and after hair transplantation.

[0003] Hair health is a rapidly developing field of science and medicine. Initially, much scientists’ and doctors’ attention was focused on women's hair health, especially female pattern hair loss (FPHL, female pattern hair loss). However, more and more attention is now focused on male pattern hair loss (AGA, androgenetic alopecia). AGA, which may be wrongly associated only with men, affects at least 50% of men and at least 40% of women around the age of 50. Recent studies suggest that up to 80% of men will be affected by AGA in their lifetime. The characteristic feature of androgenetic alopecia is a receding frontal hairline in men and a progressive, diffuse hair thinning in women, especially on the frontal-parietal scalp, as these areas are more sensitive to androgens. Interest in the etiology of AGA is also due to the growing popularity of hair transplantation procedures, especially among men.

[0004] The condition of hair is not only directly related to the general state of health (e.g. hormonal balance, skin health) but also has a very significant impact on appearance and well-being. Therefore, in the state of the art, there is a number of solutions intended to affect the condition and health of hair, such as supplements, dermocosmetics, drugs, and even surgical interventions (e.g. hair transplantation). It is also understandable that in the era of heavy pharmacotherapy and treatment, non-pharmacological and non-medicinal methods of supporting hair health are of particular interest. This invention relates to natural, non- pharmacological and non-medicinal solutions supporting the health and condition of hair. Whenever hair is mentioned in this document, it is meant as all types and locations of hair on the body, mainly - but not exclusively - hair of the head, in particular hair of the head, eyebrows, eyelashes and beard. By a hair, in this application, is meant any part of a hair, including its bulb and the surrounding hair follicle. Unless expressly excluded, the present invention relates generally to hair, regardless of age, sex, race or even species. Without departing from the scope of the invention, it can be used to support the condition of the hair and fur of mammals not belonging to the human species. By supporting, improvement and other similar terms is meant all non-therapeutic and non-surgical effects and methods of desired and enhanced influence on hair. Health, condition and other similar terms mean the proper and strengthened condition of a hair, in particular - but not only - its growth (thickness and length), its strength (e.g. physical) and resistance (e.g. to external conditions), as well as - in general - the appearance, dryness / greasiness, brittleness, volume, density and speed of growth of (many) hairs.

[0005] Dermocosmetics containing proteoglycans for application on the skin surface are known in the art. An example of such cosmetic is a multi-component composition in a form of ampoules containing, among others, proteoglycans (Mesoestetic®). However, firstly, this preparation is not intended for the health of hair, but generally appearance of the skin by moisturizing and smoothing wrinkles. Secondly, the preparation is applied (and acts) locally on the skin.

[0006] Proteoglycans typically include: decorin, biglycan, aggrecan, testican, perlecan, betaglycan, agrin, bikunin, neurocan, versican, brevican, lumican and fibromodulin. Unless expressly excluded, proteoglycans in this application are considered to be undifferentiated (unfractionated) proteoglycans. Although proteoglycans can be obtained on a large scale from farm animals such as cattle, due to health and ethical limitations, proteoglycans are not obtained from these sources in favor of fish, in particular from proteoglycan-rich salmon nasal cartilage.

[0007] There are also multi-component dietary supplements containing proteoglycans for consumption in the form of tablets. An example of such supplement is a preparation under the trade name Nourkrin® (containing Marilex® proteoglycan complex isolated from fish). Preparations of this type have complex compositions, which are now abandoned in favor of simpler and clearer ones. What is particularly important, in order to ensure sufficient effects, such preparations require a large proteoglycan content - 300 mg in one tablet taken two or three times a day. This has two serious disadvantages - high price (the extraction process from salmon nasal cartilage is inefficient and expensive) and a specific smell unacceptable to some (especially when using some extraction methods). What is equally important, according to the manufacturer's materials, the mentioned proteoglycan complex consists of specially fractionated lectin proteoglycans (also known as hyalectans). The lectin proteoglycans are specifically: aggrecan, brevican, neurocan and versican. The choice of specific proteoglycan fraction additionally influences the cost of the preparation. At the same time, as it will be discussed in more detail later in the document, the choice of high molecular mass proteoglycans (e.g. aggrecan > 2500 kDa) does not necessarily have a positive effect on the preparation’s effectiveness. Finally, Nourkrin® is indicated for AGA hair loss (and not e.g. FPHL), suggesting effect in this specific condition and absence thereof in others (Thom E. Nourkrin: objective and subjective effects and tolerability in persons with hair loss. J Int Med Res. 2006 Sep-Oct;34(5):514-9).

[0008] In summary, there is still an unmet need to provide a dietary supplement that supports and enhances the health and condition of hair as an alternative or improvement to the solutions currently available on the market. Preferably, such a solution should be relatively universal and address both women’s and men’s hair problems. In particular, it should be helpful in both FPHL and AGA. Furthermore, taking into account the above limitations of the prior art, the invention should offer a more economical and taste / odor- acceptable solution to the problem, but not at the expense of its effectiveness. The above technical problems have been solved by the combination and the composition according to the present invention. Also, the combination according to the invention has unexpectedly proved to have many advantages and benefits over the current state of the art.

[0009] The subject of the present invention is an oral hair improvement combination characterized in that it consists of at least one proteoglycan and at least one inositol. Preferably, the oral combination according to the invention is characterized in that the weight ratio of at least one proteoglycan and at least one inositol is from 1 :600 to 600:1. Unexpectedly, the trichological combination according to the present invention turned out to be more universal than currently available solutions - it is intended in particular to support and strengthen the health and condition of hair in both FPHL and AGA. Proteoglycans find particular application in AGA and are supplemented by the synergistic action of inositol. Inositol, in turn, finds particular use in FPHL and is synergistically supplemented with proteoglycans. The beneficial effect of the combination according to the invention is the effect of the synergy of both components. Inositol has an inhibiting effect on testosterone, which in turn is converted into DHT, reducing the negative impact of DHT on the hair follicle and shortening the anagen (hair growth phase). Proteoglycans affect the production of anagen-stimulating proteins. As a result of the above, it is possible to use less of one component of the combination when used in combination with the other.

[0010] Preferably, the oral combination according to the invention is characterized in that the weight ratio of at least one proteoglycan and at least one inositol is 5.5:1000. As mentioned earlier, particularly preferred fish proteoglycans are expensive and difficult to obtain raw materials. The process of their isolation, especially from salmon nasal cartilage, can have a negative effect on the smell and taste of the obtained proteoglycans. In this regard, the present invention, among others, due to the synergy effect, offers comparable effectiveness without the need to use large amounts of proteoglycans. This has an impact on the price and organoleptic properties of the combination. What is equally important, both components - not intended for simultaneous consumption - can unexpectedly be consumed as a combination according to the present invention. The absorption of inositol is influenced by sugars, therefore it should not be taken with a meal. On the other hand, proteoglycans should be administered with a meal, since their digestion products (e.g. glucosamine and galactosamine) can irritate the gastrointestinal tract. The risk of irritation increases with the amount contained in a single dose, as well as the overall amount ingested during supplementation. However, the combination according to the preferred embodiment containing a lower proportion of proteoglycans to inositol allows the mixture to be taken without the need of full stomach, giving the same effects as preparations with a much higher content of proteoglycans.

[0011] Preferably, the oral combination according to the invention is characterized in that the at least one proteoglycan is selected from decorin, versican, biglycan, perlecan and syndecan and the at least one inositol is selected from myo-inositol, scylio-inositol, D-chiro- inositol, L-chiro-inositol, muco-inositol, neo-inositol, allo-inositol, epi-inositol and cis-inositol . More preferably, the oral combination according to the invention is characterized in that it consists of decorin, versican, biglycan, perlecan and syndecan and myo-inositol. Such a combination, in addition to the mentioned advantages, is the most optimal in terms of effectiveness, technology, availability and cost. Preferably, the oral combination according to the invention is characterized in that the average molecular mass of the proteoglycans is less than 1400 kDa. Preferably, the oral combination according to the invention is characterized in that the average molecular mass of the proteoglycans is at least 90 kDa. This way, the content of proteoglycans influencing the hair growth phase (anagen), in particular biglycan (200-350 kDa), perlecan (470 kDa) and decorin (90-140 kDa), is increased. Furthermore, the total amount of proteoglycans can be further reduced, since their amounts are not dominated by high molecular mass proteoglycans. This is an additional unexpected effect, since in the prior art very high molecular mass proteoglycans are additionally preferred (e.g. in EP02455097 and EP2666779B1 ). It has unexpectedly turned out that in the combination according to the present invention, and especially with proteoglycans of lower molecular mass, there is no need to prefer proteoglycans of very high molecular mass (above 1400 kDa). An additional advantage of such a solution is the standardization of the product according to the invention, because the proteoglycans available on the market have a different amount of individual proteoglycans due to the method of obtaining.

[0012] Preferably, the oral combination according to the invention is characterized in that the content of at least one proteoglycan does not exceed 75 mg. Preferably, the oral combination according to the invention is characterized in that the content of at least one proteoglycan is at least 5 mg. Preferably, the oral combination according to the invention is characterized in that the content of at least one inositol is 1000 mg.

[0013] Preferably, the oral combination according to the invention is characterized in that the at least one proteoglycan is a fish-derived proteoglycan. More preferably, the oral combination of the invention is characterized in that the fish-derived proteoglycan is a salmon nasal cartilage proteoglycan.

[0014] The subject of the present invention is also an oral hair improvement composition comprising the oral combination according to the invention and at least one substance selected from a group consisting of an active / nutritional substance, a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient and a pharmaceutically acceptable vehicle. More preferably, the oral composition according to the invention is characterized in that it comprises inulin and nettle extract. Preferably, the oral composition according to the invention is characterized in that it is in the form of a solution, a tablet, a capsule or a powder. More preferably, the oral composition according to the invention is characterized in that it is in the form of a powder. Processing the trichological combination according to the invention into a broadly acceptable form increases the market potential, but also improves the stability.

[0015] Finally, the subject of the present invention is a use of an oral combination according to the invention or the oral composition according to the invention characterized in that the combination or the composition is used in supporting and enhancing the health and condition of hair in individuals with female pattern hair loss (FPHL) or male pattern hair loss (AGA). This is an unexpected advantage of the combination and the composition according to the invention, which - as discussed earlier - is effective in supporting and enhancing the health and condition of hair in general, but is particularly advantageous and optimized towards individuals with female pattern hair loss (FPHL) or male pattern hair loss (AGA). More preferably, the use according to the invention is characterized in that the combination or the composition is used in individuals with hair loss of unknown or mixed etiology to increase the likelihood of success.

[0016] The subject of the invention is also a use of the oral combination according to the invention or the oral composition according to the invention characterized in that the combination or the composition is used in supporting and enhancing the health and condition of hair in individuals before, during and / or after hair transplantation. This is particularly possible due to the versatility of the combination according to the invention, the amount of which - within the weight ratios defined in the invention - can be modified according to the needs of supporting and enhancing the health and condition of hair throughout the process: before, during and / or after hair transplantation.

[0017] Preferably, the use according to the invention is characterized in that the combination or the composition is used regardless of food intake. This allows greater freedom of use and increases acceptability. Example 1

[0018] 0.2 kg of powdered unfractionated (undifferentiated) fish-derived proteoglycans and 120 kg of inositol powder were added to a rotating drum mixer and mixed for 1 hour until a visually homogeneous mixture was obtained. The resulting mixture had satisfactory flowability and bulk density and was manually enclosed in size 00 capsules.

[0019] Similarly, 0.2 kg of powdered inositol and 120 kg of powdered unfractionated (undifferentiated) fish-derived proteoglycans were added to a rotating drum mixer and then mixed for an hour until a visually homogeneous mixture was obtained. The resulting mixture had satisfactory flowability and bulk density and was manually closed in size 00 capsules. Considering that the average density for proteoglycans (1 .51 g / ml) and inositol (1 .75 g / ml) is 1 .63 g / ml, more than 1 .5 g of the combination according to the invention will fit in a size 00 capsule.

[0020] Unfractionated (undifferentiated) proteoglycans typically include: decorin, biglycan, aggrecan, testican, perlecan, betaglycan, agrin, bikunin, neurocan, versican, brevican, lumican and fibromodulin. Inositol may be selected from myo-inositol, scylio-inositol, D- chiro-inositol, L-chiro-inositol, muco-inositol, neo-inositol, allo-inositol, epi-inositol and cis- inositol. In a preferred embodiment of the invention, the combination according to the invention consists of decorin, versican, biglycan, perlecan and syndecan and myo-inositol.

[0021] In this embodiment, fish-derived proteoglycans from salmon nasal cartilage were used due to health, ethical and customer preferences. Other fish proteoglycans tested during the development of the invention were fractionated proteoglycans from fish extract or fractionated proteoglycans from fish bones. Fish extract and fish bones of various origins were examined, i.e. fish (different fish), salmonid fish (according to family) and salmon (according to species). The origin (e.g. from different fish), the location in the fish (e.g. bones) or the method of obtaining did not noticeably affect the critical parameters of the product. Unless otherwise indicated, whenever reference is made in this document to fish- derived proteoglycans, it means any fish and any location of proteoglycans in fish, and particularly proteoglycans from salmon nasal cartilage. Notwithstanding the above, a person skilled in the art understands, without departing from the scope of the invention and without affecting the key features of the combination, fish proteoglycans may be successfully replaced by other sources of proteoglycans, e.g. of bovine origin. The resulting mixture was enclosed in cellulose capsules (HMPC) due to the user preferences. The person skilled in the art understands that without departing from the scope of the invention, the mixture can be enclosed in other capsules, e.g. gelatin. Finally, the purpose of enclosing the mixture in a capsule was to prove the possibility of using the combination according to the invention using technological processes known from the state of the art. The person skilled in the art understands that the essence of the invention is the combination of proteoglycans and inositol in the form of a powder. Subjecting the resulting mixture to further processes of encapsulation, granulation, tableting , palletization depends solely on the user preferences and technological needs.

[0022] For example, the inventors added a binder (2% polyvinylpyrrolidone), a lubricant (1 % magnesium stearate) and an anti-caking / flow agent (0.5% colloidal silica) to the above- mentioned mixture, and then subjected it to tableting in a punch tableting machine, obtaining tablets of about 1220 mg. Inositol as a sugar alcohol is easy to tablet. Therefore, in a particularly preferable embodiment, inositol, in addition to its health-promoting effects, used in a larger proportion than proteoglycans also acts as a carrier and facilitates the tableting process.

[0023] Regardless of the above, the combination can be used as a powder directly consumed in the form of an aqueous solution, or as an additive to food products, e.g. added to yogurt. Solubility tests in water (at room temperature) did not show significant differences between the combination with a dominant ratio of proteoglycans to inositol and vice versa. Both mixtures dissolved completely within 10 seconds with mechanical mixing (using a magnetic stirrer).

[0024] Taking the above into account, in the case of a dominant ratio of inositol to proteoglycans, the tablet form is a particularly preferable version of the invention. Such a beneficial form will find application particularly in supporting the health and condition of hair in people with FHPL. In case of a dominant ratio of proteoglycans to inositol, a particularly preferable version of the invention is the capsule form. Such a beneficial form will find application particularly in supporting the health and condition of hair in people with AGA. Both combinations can be administered in powder form, especially in people who want to control the dose. Such a beneficial form will find application particularly in supporting the health and condition of hair in people before / during / after hair transplantation. More about the beneficial effects of the combinations and compositions according to the invention in Example 5.

[0025] Example 2

[0026] In spite of fully functioning invention and its preferred embodiments above, the authors decided to further optimize the combination according to the invention. For this purpose, particularly preferred embodiments of the invention were developed. The amount of proteoglycans of the combination was selected from three possible amounts: 155 mg, 75 mg and 5 mg. The selected amounts of proteoglycans were mixed according to the example 1 protocol, with 1200 mg, 1100 mg and 1000 mg of inositol, respectively. The main purpose was to provide an effective product supporting and improving the health and condition of hair. Another purpose was to optimize the product cost and improve its quality. The upper limit of the mixture quantity was an effective amount of the combination suitable to be enclosed in a 00 capsule (and therefore convenience of administration).

[0027] Unexpectedly, it turned out that even 5 mg of proteoglycans and 1000 mg of inositol gave noticeable effects despite a significantly reduced amount of proteoglycans (for more see: observational study condition, growth and loss of hair in example 5). Such results are further confirmed by in vitro studies of the proteoglycans of the preferred combination according to the invention on cultures of human dermal papilla cells (more in example 5). This, in turn, solves the problem of costs and low acceptability of taste / smell of high content proteoglycan products in the prior art. Finally, unexpectedly, the development of a combination of proteoglycans and inositol in a weight ratio of 5:1000 allowed for a further reduction in the capsule size from 00 to 0 (0.68 ml capacity). For comparison, Nourkrin ® requires administration of two large tablets, and the example 1 embodiments described above use 00 size capsules (0.93 ml capacity). The largest capsule currently available on the market is size 000 (which is 1 .37 ml).

[0028] Accordingly, in a preferred embodiment, the content of the at least one proteoglycan in the combination according to the invention does not exceed 75 mg. More preferably, it is present in an amount at least 5 mg. In another preferred embodiment, the content of the at least one inositol in the combination according to the invention is 1000 mg. Example 3

[0029] In order to further optimize the combination according to the invention, the authors used specially selected proteoglycans and myo-inositol. It unexpectedly turned out, contrary to the teachings of the prior art (e.g. in EP02455097 and EP2666779B1 ), proteoglycans with a lower molecular mass should be preferred over those with a higher molecular mass. The combination according to the invention with a content of proteoglycans with a molecular mass of at least 90 kDa proved to be particularly advantageous. Proteoglycans with a low molecular mass are in particular biglycan (200-350 kDa), perlecan (470 kDa), versican (1000 kDa) and decorin (90-140 kDa) - i.e. proteoglycans influencing the anagenic phase of hair growth (especially decorin and versican). However, due to the proteoglycan fractionation cost-effectiveness, the authors allow a combination according to the invention with a content of proteoglycans with a molecular mass lower than 1400 kDa as a preferred embodiment. Such size turned out to be the most advantageous compromise between improving the effectiveness of the combination and the price / availability of proteoglycan fractionation.

[0030] Accordingly, in a preferred embodiment of the invention the average molecular mass of the proteoglycans in the combination according to the invention is less than 1400 kDa, and more preferably at least 90 kDa.

[0031] Example 4

[0032] The combinations obtained in Examples 1 - 3 were next used to develop compositions comprising, in addition to the above-mentioned preferred embodiments of the invention, at least one substance selected from the group consisting of an active / nutritional substance, a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient and a pharmaceutically acceptable vehicle. Without departing from the scope of the invention, a person skilled in the art will supplement the combination according to the invention with examples of the aforementioned substances available in the art.

[0033] Only on the basis of a non-limiting example, the authors added inulin (300 mg) and nettle extract (165 mg) to the preferred embodiments of the combination according to the invention from examples 1 -3. As a prebiotic, inulin stimulates the intestinal flora and has an additional effect on the intestinal absorption of substances. As a result, it can additionally positively influence the bioavailability of the combination according to the invention. Nettle extract is a natural source of vitamins, additionally increasing the values of the composition. Nettle can also influence reduction of the level of cortisol, the excess of which has a negative effect on the skin and hair. Therefore, the nettle extract provides an additional synergistic effect with the remaining ingredients of the composition according to the invention and has a protective effect.

[0034] In a preferred embodiment, the oral composition according to the invention is in the form of a solution, tablet, capsule or powder. Subjecting the composition of the invention to processing into a widely acceptable form increases the market potential, but also affects stability (enclosing in a coated tablet, capsule or sachet reduces the effects of external factors, especially oxygen, sun and moisture).

[0035] As in Example 1 , the ingredients were mixed for an hour in a rotating drum mixer. The resulting mixture was tested for satisfactory flowability and bulk density. Subjecting the resulting mixture to further processes of encapsulation, granulation, tableting and palletization depends solely on the preferences of the recipients and technological needs. For example, the authors enclosed the resulting mixture in size 000 capsules. In another embodiment, the authors of the invention added a binder (2% polyvinylpyrrolidone), lubricant (1 % magnesium stearate) and an anti-caking / flow agent (0.5% colloidal silica) to the above-mentioned mixture, and then subjected it to tableting in a tableting machine obtaining tablets.

[0036] Regardless of the above, the composition compromising the combination according to the invention can be used as a powder directly consumed in the form of an aqueous solution, or as an additive to food products, e.g. added to yoghurt. Similarly to example 1 , the compositions dissolved in water (at room temperature) for up to 10 seconds when mechanically stirred (using a magnetic stirrer).

[0037] In a particularly preferred embodiment, the oral composition according to the invention is in the form of a powder. In that case, the dosage form allows to control the dosage depending on the individual needs. Also the amount of the individual components can be increased accordingly based on the current health needs. For example, the authors have developed a composition with 3000 mg of inulin. Example 5

[0038] The effectiveness of the combination according to the invention and the composition comprising the combination according to the invention, especially according to the preferred embodiments 1 - 4 above, was positively assessed on the basis of observational studies in a group of women (n= 5) and men (n= 3) over 18 years of age, who noticed a significant improvement in the condition of hair and increased growth with simultaneous reduced hair loss. These positive in vivo studies results are additionally confirmed by in vitro studies of the proteoglycans of the preferred combination according to the invention (n= 5). Human dermal papilla cells, incubated for 3 days with the proteoglycans of the combination according to the invention, significantly increased the FGF-7 production (at a concentration of 1 mg / ml) and doubled the amount of culture cells (after the first 24 hours of culture at a concentration of 10 mg / ml). Both of these parameters are associated with the improvement of the hair follicle condition and the hair growth stimulation. Additionally, the oral hair improvement combination consisting of at least one proteoglycan and at least one inositol, and particularly preferably in a weight ratio of 1 :600 to 600:1 , unexpectedly turned out to be more universal than currently available solutions. This is due to the synergistic action of both components, which unexpectedly work well in people with both AGA and FPHL. Inositol reduces the negative effect of DHT on the hair follicle and shortens the anagen (hair growth phase) by reducing testosterone. Proteoglycans affect production of the anagenstimulating proteins. Additionally, the synergistic effect allows reduction of the amount of one component of the combination when used with another.

[0039] This combination is helpful in supporting and enhancing the health and condition of hair in both people with female pattern hair loss (FPHL) and / or male pattern hair loss (AGA). This is an unexpected benefit of the combinations and compositions, which can therefore be used in people with hair loss of unknown or mixed etiology. It makes easier to use the preparations, broadens their scope of action and increases the chance of success.

[0040] Equally important, the widespread belief in the state of the art that to enhance the effects inositol should be administered with choline or D-chiro-inositol did not turn out to be true in this case. Such belief -not only common in trichology, but also in the case of commercially available combinations of inositol and choline, as well as supplementation with inositol and D-chiro-inositol in women with polycystic ovary syndrome (PCOS) - initially suggested to the authors the need to add choline or D-chiro-inositol. The present invention also overcomes this technical problem offering more universal and advantageous solution. A particularly preferred embodiment of the invention is a combination of inositol with proteoglycans, wherein the proteoglycans are present in a smaller amount than inositol. Preferably, the oral combination according to the invention is characterized in that the weight ratio of at least one proteoglycan and at least one inositol is 5.5:1000. Firstly, proteoglycans, especially of fish origin (e.g. from salmon nasal cartilage) are a relatively expensive raw material. Secondly, fish proteoglycans, especially obtained by certain methods known in the art (not being the subject of the invention) have a specific, difficult to accept smell / taste. In connection with the above, the particularly preferred embodiment solves both problems without negatively affecting the effectiveness of the combination.

[0041] Another unexpected effect of the combination of at least one proteoglycan and at least one inositol is the increased absorption of inositol while reducing the irritation of the digestive tract by the proteoglycan digestion products. The technical problem encountered by the authors was the reduced absorption of inositol from the digestive tract when it is administered with food. This is because, among other things, the absorption of inositol is influenced by sugars. Therefore, the optimal time to take inositol is on an empty stomach, before meal or long after it. However, on the other hand, proteoglycans should be administered with food, because their digestion products (e.g. glucosamine and galactosamine) can irritate the digestive tract. The risk of irritation increases with the amount contained in a single dose, as well as the overall amount ingested during supplementation. Unexpectedly, it turned out that the synergistic effect of the combination of at least one proteoglycan and at least one inositol, the specific selection of proteoglycans, and consequently the possibility of reducing the total proteoglycan content reduces the risk of irritation of the digestive tract, enabling the use of combinations and compositions containing them on an empty stomach. This allows increased absorption of inositol while reducing the risk of irritation of the digestive tract without the need to separate these components and increase the dose frequency.

[0042] Finally, in a preferred embodiment, the average molecular mass of the proteoglycans is less than 1400 kDa, and more preferably, at least 90 kDa. The proteoglycans selected this way, contrary to the teachings of the prior art (e.g. in EP02455097 and EP2666779B1 ), allow to provide the most effective proteoglycans in terms of promoting and strengthening the health and condition of the hair, while at the same time reducing their amount required to achieve the desired effects. In particular, the content of proteoglycans influencing the hair growth phase (anagen) is increased, in particular biglycan (200-350 kDa), perlecan (470 kDa) and decorin (90-140 kDa). Such a combination provides standardisation independently of origin and methods of obtaining proteoglycans. A particularly preferred embodiment is the combination of inositol (especially myo-inositol) with proteoglycans selected from decorin, versican, biglycan, perlecan and syndecan. Such a combination, in addition to the aforementioned advantages, is the most optimal in terms of effectiveness, technology, availability and cost.

[0043] Finally, the advantage is the versatility of the combination according to the invention, the amount of which - within the weight ratios specified in the invention - can be modified by a trichologist or a user, in accordance with the current needs to support and enhance the health and condition of the hair during the process: before, during and / or after hair transplantation.

Claims

Claims :

1. An oral hair improvement combination characterized in that it consists of at least one proteoglycan and at least one inositol.

2. The oral combination according to claim 1 , characterized in that the weight ratio of the at least one proteoglycan and the at least one inositol is from 1 :600 to 600:1 .

3. The oral combination according to any of claims 1 - 2, characterized in that the weight ratio of the at least one proteoglycan and the at least one inositol is 5.5:1000.

4. The oral combination according to any of claims 1 - 3, characterized in that the at least one proteoglycan is selected from decorin, versican, biglycan, perlecan and syndecan and the at least one inositol is selected from myo-inositol, scylio-inositol, D-chiro-inositol, L- chiro-inositol, muco-inositol, neo-inositol, allo-inositol, epi-inositol and cis-inositol.

5. The oral combination according to claim 4, characterized in that it consists of decorin, versican, biglycan, perlecan and syndecan and myo-inositol.

6. The oral combination according to any of claims 1 - 5, characterized in that the average molecular mass of the proteoglycans is less than 1400 kDa.

7. The oral combination according to any of claims 1 - 6, characterized in that the average molecular mass of the proteoglycans is at least 90 kDa.

8. The oral combination according to any of claims 1 - 7, characterized in that the content of at least one proteoglycan does not exceed 75 mg.

9. The oral combination according to any of claims 1 - 8, characterized in that the content of at least one proteoglycan is at least 5 mg.

10. The oral combination according to any of claims 1 - 9, characterized in that the content of at least one inositol is 1000 mg.

11. The oral combination according to any of claims 1 - 10, characterized in that at least one proteoglycan is a fish-derived proteoglycan.

12. The oral combination according to claim 11 , characterized in that the fish-derived proteoglycan is a salmon nasal cartilage proteoglycan.

13. An oral hair improvement composition comprising the oral combination according to any of claims 1 - 12 and at least one substance selected from a group consisting of an active / nutritional substance, a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient and a pharmaceutically acceptable vehicle.

14. The oral composition according to claim 13, characterized in that it comprises inulin and nettle extract.

15. The oral composition according to any of claims 13 - 14, characterized in that it is in the form of a solution, a tablet, a capsule or a powder.

16. The oral composition of claim 15, characterized in that it is in the form of a powder.

17. A use of the oral combination according to any of claims 1 - 12 or the oral composition according to any of claims 13 - 16, characterized in that the combination or the composition is used in supporting and enhancing the health and condition of hair in individuals with female pattern hair loss (FPHL) or male pattern hair loss (AGA).

18. The use according to claim 17, characterized in that the combination or the composition is used in individuals with hair loss of unknown or mixed etiology.

19. The use of the oral combination according to any of claims 1 - 12 or the oral composition according to any of claims 13 - 16, characterized in that the combination or composition is used in supporting and enhancing the health and condition of hair in individuals before, during and / or after hair transplantation.

20. The use according to any of claims 17 - 19, characterized in that the combination or the composition is used regardless of food intake.