DE102012101911A1 - Use of collagen hydrolysate such as food addition agent, as an active ingredient for treating and/or preventing cellulite and stretch marks, preferably stretch marks during pregnancy - Google Patents

Abstract

Use of collagen hydrolysate as an active ingredient for treating and/or preventing cellulite, is claimed. ACTIVITY : None given. MECHANISM OF ACTION : None given.

Description

The present invention relates to the use of collagen hydrolyzate for the treatment and / or prevention of cellulite.

Cellulite is an undesirable change in the properties of the skin, which manifests itself externally by the formation of dents on the surface of the skin. Affected are almost exclusively women, of these, however, with increasing age up to 80 to 98%. Cellulite occurs especially in areas of pronounced subcutaneous adipose tissue, i. at the hip, the buttocks, the stomach, the thighs and the upper arms.

The cause of cellulite, according to the research, certain changes in the dermis and the subcutaneous connective tissue, in particular a shortening of collagen fibers formed septa, which connect the reticular dermis with underlying subcutaneous fat tissue muscles. Overall, this leads to a reduction in the elasticity of the skin.

Known therapies for cellulite include in particular physical methods such as lymphatic drainage, ultrasound or vacuum, but these usually bring no or at least no lasting success. The topical application of cosmetics such as creams or ointments does not allow a causal treatment of cellulite, since the upper layers of the epidermis are not directly involved in the phenomenon.

It is already known that oral effects of collagen hydrolyzate can produce beneficial effects on human skin health (see V. Zague: "A new view concerning the effects of collagen hydrolysates intake on skin properties" in Arch. Dermatol. Res. 2008 (9) 479 ). Due to the ability to absorb correspondingly low molecular weight collagen peptides and the good blood circulation of the skin there is a particular accumulation of orally absorbed collagen hydrolyzate, wherein the concentration is highest in the period of about 12 to 24 hours after ingestion (see Watanabe-Kamiyama et al .: "Absorption and effectiveness of orally administered low molecular weight collagen hydrolysates in rats" in J. Agric. Food Chem. 2010 (58) 835 ).

Against this background, the present invention proposes a new approach to the causal treatment and / or prevention of cellulite, which approach is the use of collagen hydrolyzate.

In fact, a clinical study has shown that skin elasticity increases measurably as a result of the administration of collagen hydrolyzate. This effect is particularly pronounced in women over the age of 50 years. A higher skin elasticity means a lower expression of cellulite.

Furthermore, several experiments in vitro demonstrate that the synthesis of extracellular matrix proteins of dermal connective tissue is stimulated by collagen hydrolyzate. These proteins formed by the skin cells (dermal fibroblasts) include collagen (especially type I), elastin and proteoglycans (such as biglycan, versican and decorin). The synthesis of these proteins in sufficient quantities is crucial for the development or regeneration of the extracellular matrix of the skin, which in turn is essential for the properties of the dermis such as elasticity, elasticity and moisture balance.

The collagen hydrolyzate used in the invention advantageously has a relatively low molecular weight. Preferably, at least 90% by weight of the collagen hydrolyzate has a molecular weight of less than 3,500 Da, and more preferably at least 45% by weight has a molecular weight of less than 1,500 Da. It has been shown that more pronounced effects can be achieved by such particularly low molecular weight fractions. The molecular weight distribution of the collagen hydrolyzate, which is based on the corresponding limit values, may be e.g. be determined very accurately and reproducibly by means of gel permeation chromatography using a calibration standard of defined collagen fragments.

The average molecular weight (weight average M _W ) of the collagen hydrolyzate used according to the invention is typically in the range from about 1700 to about 2300 Da.

In a preferred embodiment of the invention, the collagen hydrolyzate comprises at least four characteristic peptides having a molecular weight between 600 and 1200 Da. collagen hydrolysates contain peptides with different chain lengths or molecular weights, which arise during the cleavage of the protein chains of the collagen, wherein the molecular weight distributions of these peptides can differ significantly depending on the preparation conditions of the hydrolyzate. It has surprisingly been found that a collagen hydrolyzate with the abovementioned properties has a particularly advantageous effect on the synthesis of matrix proteins, ie shows significantly better results than collagen hydrolysates which do not contain the characteristic peptides.

The presence of the characteristic peptides of the collagen hydrolyzate can be determined in particular by means of MALDI mass spectroscopy, the characteristic peptides appearing as peaks in the mass spectrum. Preferably, the at least four characteristic peptides in a molecular weight distribution determined by means of MALDI mass spectroscopy have at least twice the intensity, more preferably at least four times the intensity, in comparison to their surroundings.

In a preferred embodiment of the invention, the collagen hydrolyzate comprises a peptide between 620 and 690 Da, a peptide between 790 and 860 Da, a peptide between 980 and 1050 Da, and a peptide between 1175 and 1245 Da. The collagen hydrolyzate may also have characteristic peptides between 1500 and 3500 Da.

The collagen hydrolyzate preferably has a proportion of hydroxyproline of 12% by weight or more. The amino acid hydroxyproline formed by post-translational hydroxylation of proline occurs exclusively in collagen, so that a high proportion of hydroxyproline in the collagen hydrolyzate represents a measure of the substantial absence of other connective tissue proteins (eg elastin and proteoglycans), the fragments of which depend on the preparation process in certain cases Quantities may also be included in collagen hydrolysates.

It is favorable if the collagen hydrolyzate is produced by enzymatic hydrolysis of gelatin. Gelatin comprises denatured collagen and is recovered from the connective tissue or bones of various animal species by various methods known to those skilled in the art. In the context of the present invention, the gelatin used as starting material for the collagen hydrolyzate is preferably obtained from the skin of mammals, in particular of pigs or cattle, but the use of gelatine from poultry is not excluded. Porcine gelatin is particularly preferred as the starting material, especially pork rind gelatin.

The enzymatic hydrolysis of the gelatin is usually carried out by at least one endoprotease, wherein it is preferred in the invention to use several endoproteases (ie at least two different endoproteases), thereby correspondingly affecting the amino acid profile of the resulting collagen hydrolyzate and the positive effect of the hydrolyzate to increase.

According to a preferred embodiment of the invention, the collagen hydrolyzate is prepared by the sequential action of at least two endoproteases with a different specificity, in particular of at least two different metalloproteases and / or serine proteases, i. Proteases that cleave the amino acid sequence of the collagen molecules in front of or behind specific amino acids. Conveniently, the metalloproteases and / or serine proteases are enzymes from the microorganisms Bacillus subtilis, Bacillus licheniformis, Bacillus amyloliquefaciens, Aspergillus oryzae and Aspergillus melleus.

By selecting suitable endoproteases, not only can the characteristic molecular weight distribution of the collagen hydrolyzate be obtained, but also the nature of the amino acids at the termini of the peptides contained in the hydrolyzate is influenced. In this regard, it is e.g. preferred if at least 50% of the N-terminal amino acids of the collagen hydrolyzate are hydrophobic amino acids, in particular alanine, leucine and isoleucine.

According to a preferred embodiment of the invention, the collagen hydrolyzate is intended for enteral use, in particular in the form of an oral intake. Upon ingestion, a more effective transport of the collagen hydrolyzate through the circulation to the site of action, i. in particular to the dermal fibroblasts, than in a topical application. In addition, this application form for the user is usually associated with a much lower cost.

Since collagen hydrolyzate is obtained from food-approved raw materials, it may be preferred in the context of the present invention for the treatment and / or prevention of cellulite as Dietary supplements are used. Such dietary supplements may be referred to as "nutraceuticals" or "nutricosmetics".

The dietary supplement can be offered in almost any form, e.g. in the form of tablets, capsules, dragees, lozenges, sachets or else a gel or solution (for example in single ampoules or in drinks).

Alternatively, the collagen hydrolyzate may be included in a food or beverage, e.g. in confectionery or in an instant powder for making beverages. The hydrolyzate can be taken in this way by the user without additional effort in the context of normal diet (so-called "functional food"). In this context, it is particularly advantageous if the collagen hydrolyzate is substantially tasteless.

It is favorable if a daily intake of about 1.5 to 5 g, preferably about 2 to 3 g, more preferably about 2.3 to 2.7 g of the collagen hydrolyzate is provided. It has been shown that by oral intake of this amount of hydrolyzate already a significant effect can be achieved, which can not be significantly increased by increasing the daily dose.

Within the context of the use according to the invention, the collagen hydrolyzate can be combined with other active substances which have a beneficial effect on the health and in particular on the health of the skin. Such agents are preferably selected from vitamins, minerals, omega-3 fatty acids, omega-6 fatty acids, omega-9 fatty acids, biotin, lutein, lycopene, caffeine, glucosamine, chondroitin, hyaluronic acid, green tea extract, folic acid, amino acids, Ubiquinone-10 and antioxidants.

In a preferred embodiment of the invention, the administration of the collagen hydrolyzate for the treatment and / or prevention of cellulite is particularly intended for women over the age of 50, most of whom are postmenopausal. In this age group, which is generally severely affected by cellulite, the effects are particularly pronounced, as demonstrated by the clinical study described below.

The invention further relates to a method for treating and / or preventing cellulite in a patient, the method comprising administering collagen hydrolyzate to the patient, in particular in the form of an oral administration.

Preferred embodiments of the method, in particular with regard to the properties of the collagen hydrolyzate and the dose to be administered, have already been explained in connection with the use according to the invention.

Furthermore, the invention also relates to the use of collagen hydrolyzate for the treatment and / or prevention of stretch marks, which occur in particular in the form of so-called stretch marks (striae gravidarum) in pregnant women. The cause of these streaks are fine cracks in the subcutaneous connective tissue due to the considerable skin dilation. Similar to cellulite, the occurrence of such cracks can also be counteracted by increasing skin elasticity by administering collagen hydrolyzate.

Another aspect of the invention relates to the use of collagen hydrolyzate for the treatment and / or prevention of local lesions of the skin as a result of bedsores (decubitus), e.g. the development of pressure sores. In this case, the skin is subjected to a pressure load from the outside, the negative consequences of which can also be alleviated by an increase in skin elasticity.

These and other advantages of the invention will be described in more detail with reference to the following examples with reference to the figures. They show in detail:

1A to 1C : Diagrams relating to the stimulation of the synthesis of type I collagen, biglycan and versican, respectively;

2A and 2 B : Charts concerning the increase of skin moisture in hairless mice;

3 : a diagram relating to the stimulation of the synthesis of CE proteins;

4A to 4C : MALDI mass spectra of various collagen hydrolysates; and

5A and 5B : Charts for stimulation of the synthesis of type I collagen, decorin and versican.

Examples

1. Production and Properties of the Collagen Hydrolyzate

For the preparation of a collagen hydrolyzate for the use according to the invention, the starting material used is an aqueous solution of pork skin gelatine (type A, 200 to 250 g Bloom) with a concentration of 20 to 40% by weight (dry matter). The gelatin is enzymatically hydrolysed by the successive action of two different endoproteases of microbial origin at 50 to 60 ° C for 120 to 180 min, using as the first enzyme an endoprotease from Bacillus subtilis or from Bacillus amyloliquefaciens and as second enzyme an endoprotease Bacillus licheniformis. Subsequently, the enzymes are thermally inactivated and the solution spray-dried.

The molecular weight distribution of the resulting collagen hydrolyzate can be determined by gel permeation chromatography using the following parameters:

Stationary phase: TSK 2000 SW XL (Tosoh Bioscience GmbH) Mobile phase: 0.4 mol / l sodium dihydrogen phosphate pH 5.3 Flow rate: 0.5 ml / min Calibration Standard:  defined collagen type I fragments (FILK, Freiberg) detection: UV detector Knauer K-2501 at 214 nm

The determination gave a molecular weight distribution for this collagen hydrolyzate (hereinafter referred to as low molecular weight hydrolyzate) according to the following Table 1. For comparison, Table 1 also shows the molecular weight distribution of a commercially available collagen hydrolyzate which was determined by the same method (hereinafter referred to as high molecular weight hydrolyzate designated): Table 1 MW range niedermol. hydrolyzate hochmol. hydrolyzate > 7,500 Da <5% by weight <10% by weight 3,500-7,500 Da about 12-18 wt% about 25-35% by weight 1,500-3,500 Da about 25-31% by weight about 29-35% by weight 500-1,500 Da about 40-46% by weight about 24-30% by weight <500 Da about 5-10% by weight about 2-5 wt%

The hydroxyproline content of this low molecular weight hydrolyzate is about 12 to 13 wt.% And can be determined photometrically after oxidation with chloramine-T and reaction with p-dimethylamino-benzaldehyde. More than 50% of the N-terminal amino acids of the hydrolyzate are hydrophobic amino acids, especially alanine, leucine and isoleucine.

2. Clinical study on the effectiveness of collagen hydrolyzate in cellulite

In a double-blind, randomized, placebo-controlled study, the efficacy of the low molecular weight collagen hydrolyzate prepared according to Example 1 in the treatment and / or prevention of cellulite was investigated. The study participants were 69 healthy women aged 35.3 to 55.4 years, divided into three groups of 23 subjects each. 68 subjects successfully completed the study.

From six weeks before the start of the study, no dermatological therapeutics were allowed to be used. In addition, the subjects were not allowed to change their lifestyle and dietary habits, take any additional dietary supplements or vitamin supplements, and not expose their skin to intense UV radiation before and during the study. On the volar sides of the forearms, where the effects of the collagen hydrolyzate on skin properties were to be investigated, no cosmetics should be used.

Of the three groups, the first received 2.5 g of collagen hydrolyzate daily (every morning) over a period of eight weeks, the second received 5 g of collagen hydrolyzate daily (2.5 g each morning and midday) and the third a placebo. For oral intake, the hydrolyzate could be dissolved in water or a cold drink (except milk).

• – Hautelastizität mit einem Cutometer^® SEM 575 (jeweils Mittelwert aus drei Messungen)
• – transepidermaler Wasserverlust (TEWL) mit einem DermaLab^®-Gerät (jeweils Mittelwert aus drei Messungen)
• – Hautfeuchtigkeit mit einem Corneometer^® CM 825 (jeweils Mittelwert aus zehn Messungen)

Before the first intake, after four weeks and after eight weeks, the following parameters of the skin on the volar side of the left upper arm of the subjects were measured:

• - Skin elasticity with a Cutometer ^® SEM 575 (average of three measurements)
• - transepidermal water loss (TEWL) with a DermaLab ^® device (average of three measurements)
• - Skin moisture with a Corneometer ^® CM 825 (average of ten measurements)

All measurements were made after 30 minutes of acclimatization in an air-conditioned room at a temperature of 21.5 ° C (± 1 ° C) and a relative humidity of 50% (± 5%).

All three parameters were significantly increased in the collagen hydrolyzate-treated groups at both four and eight weeks. The values measured after eight weeks are shown in Table 2 below as a percentage increase over the group treated with the placebo: Table 2 parameter 2.5 g hydrolyzate per day 5 g of hydrolyzate per day skin elasticity about 7% about 9% TEWL about 11% about 14% skin moisture about 6% about 7%

In particular, the increase in skin elasticity demonstrates the effectiveness of the oral administration of collagen hydrolyzate for the treatment and / or prevention of cellulite. The improvement of the TEWL and the skin moisture represent further advantageous effects of the hydrolyzate on the skin's health and in particular lead to an increase in the epidermal barrier function.

In a differentiation of the skin elasticity differentiated by age group, the result shown in Table 3 was found, with women under the age of 50 (mean age 44.1 years) being compared with women over 50 years (mean age 53.0 years): Table 3 skin elasticity 2.5 g hydrolyzate per day 5 g of hydrolyzate per day Women under 50 about 3% about 5% Women over 50 about 14% about 15%

Striking is the particularly marked improvement in skin elasticity in women over the age of 50 years, who thus represent a preferred target group for the inventive use of collagen hydrolyzate.

Skin elasticity was measured again four weeks after the end of the eight-week administration period. There were still about 92 to 98% of the measured after eight weeks increases, suggesting a longer-lasting effect of collagen hydrolyzate.

3. Stimulation of the synthesis of extracellular matrix proteins in vitro

The stimulation of the synthesis of collagen (type I) and the proteoglycans biglycan and versican was investigated in vitro on human dermal fibroblasts (skin cells). For this purpose, the cells were incubated for 24 hours with in each case 0.5 mg / ml of the low molecular weight or of the high molecular weight hydrolyzate and then the expression of collagen RNA, biglycan RNA and versican RNA determined by real-time PCR and semiquantitative (based on a Control without hydrolyzate).

The results are as column charts for type I collagen in the 1A , for Biglykan in the 1B and for Versican in the 1C The graphs each show the mean of at least 18 measurements. On the abscissa, the RNA expression is plotted relative to the control (= 1). The left filled column is for the control, the middle hatched column for the high molecular weight hydrolyzate and the right dotted column for the low molecular weight hydrolyzate.

It turns out that the synthesis of all three matrix proteins is stimulated by both collagen hydrolysates, whereby the positive effect of the low molecular weight hydrolyzate is in each case more pronounced than that of the high molecular weight hydrolyzate. In collagen, which in addition to elastin is mainly responsible for the resilience and elasticity of the skin, as well as the Versican, which plays an important role in the moisture balance of the skin, the enhanced effect of the low molecular weight hydrolyzate is particularly pronounced.

These stimulating properties of the collagen hydrolyzate on the various matrix proteins, in addition to the treatment and / or prevention of cellulite according to the invention, also provide a starting point for diseases such as e.g. Psoriasis in which the natural functionality of the skin is impaired.

4. Increase of the moisture content of the skin in animal experiments

The influence of collagen hydrolyzate on skin moisture was directly investigated on hairless mice. Hairless mice represent an established model system, which is often used in dermatological problems, and the insights gained are in principle transferable to the human skin (see, for example, US Pat T. Fujimura et al .; J. Dermatol. Sci. 2000 (24) 105-111 and Y. Nishimori et al .; J. Invest. Dermatol. 2001 (117) 1458-1463 ).

The animals were fed 150 μg of collagen hydrolyzate per kg of body weight daily for a period of three weeks, the control group receiving BSA instead. At the same time, all animals received a weekly UVB radiation dose of 18 mJ / cm ² skin surface, which negatively affects skin moisture.

The moisture content of the skin was measured after one week and three weeks with a Corneometer CM 825 (manufactured by Courage & Khazaka). The measurement principle is based on the change in the capacitance of a measuring capacitor by the dielectric constant of the bound water in the upper skin layers, which differs significantly from the dielectric constant of most other substances.

The results are as bar graphs for the measurement after a week in the 2A and for the measurement after three weeks in the 2 B The diagrams show the mean value and the standard error from 7 measurements, respectively. On the abscissa the skin moisture is plotted relative to the control (= 1). The left filled column is for the control, the middle hatched column for the high molecular weight hydrolyzate and the right dotted column for the low molecular weight hydrolyzate.

It can be seen that the increase in skin moisture caused by the low-molecular hydrolyzate is greater at one week and three weeks, respectively, than at the high-molecular hydrolyzate.

5. Stimulation of the synthesis of CE proteins in vitro

So-called "cornified envelope" proteins play an important role in the barrier function of the skin against the penetration of pathogenic germs and toxic substances. Synthesis of the CE proteins involucrin, loricrin and filaggrin was determined in hairless mice previously fed daily with 150 μg collagen hydrolyzate per kg body weight for five weeks (as described above). The quantification The protein relative to a control group (feeding with BSA) was by SDS-polyacrylamide gel electrophoresis and Western blot with specific antibodies after extraction of the proteins from the skin.

The results are shown as a bar chart in the 3 The diagram shows in each case the mean value and the standard error from 7 measurements. On the abscissa, the amount of CE proteins after feeding with the low molecular weight hydrolyzate is plotted relative to the control (= 1). The left column stands for involucrin, the middle column for loricrin and the right column for filaggrin.

It turns out that the synthesis of all three CE proteins stimulated by the oral uptake of collagen hydrolyzate is even more than threefold in the case of involucrin.

6. Analysis of the molecular weight distribution by MALDI-MS

The low molecular weight collagen hydrolyzate prepared according to Example 1, which has an average molecular weight of about 2,000 Da (in the following hydrolyzate A), became two commercially available collagen hydrolysates having an average molecular weight of about 2,100 Da (hereinafter hydrolyzate B) and about 2,900 Since (in the following hydrolyzate C) faced.

The precise molecular weight distributions of these three hydrolyzates were analyzed by MALDI mass spectroscopy (MALDI-MS). For this, the samples were adjusted to a final concentration of 10 μg / μl in 0.1% trifluoroacetic acid and then purified using μC ₁₈ material. The samples were prepared with a HCCA matrix on a MALDI target and the mass spectra determined using an Ultraflex III TOF / TOF mass spectrometer (manufacturer: Bruker Daltonics).

The 4A to 4C show the corresponding mass spectra or molecular weight distributions of the collagen hydrolysates A, B and C, wherein the ordinate is the molecular weight or the mass number and the abscissa on the intensity is plotted. A comparison of the three spectra shows that the hydrolyzate A comprises the following characteristic peptides according to Table 4, wherein the corresponding peaks have a double to fourfold intensity compared to their surroundings: TABLE 4 about 656 da about 825 da about 1,014 Da about 1,211 Da about 1,927 Da about 2.410 Da about 3,433 Da

In particular, the four peptides between 600 and 1500 Da have no equivalents in the two commercial hydrolysates B and C, and thus are particularly characteristic of the hydrolyzate A.

7. Stimulation of the synthesis of extracellular matrix proteins in vitro

The stimulation of the synthesis of collagen (type I) and the proteoglycans Decorin and Versican was investigated in vitro on human dermal fibroblasts (skin cells). For this purpose, the cells were incubated for 24 hours with in each case 0.5 mg / ml of the hydrolyzates A, B or C, and then the expression of collagen RNA, decorin RNA and versican RNA was determined by real-time PCR and evaluated semiquantitatively. Decorin plays an important role in the formation of collagen fibers in the skin.

The results are shown as bar graphs for the hydrolyzate B in the 5A and for the hydrolyzate C in the 5B represented, on the abscissa in each case the RNA expression in the commercial hydrolysates B and C relative to the RNA expression in the hydrolyzate A (= 1) is applied. The left column represents Type I collagen, the center pillar decorin, and the right pillar Versican. The mean value from at least 7 measurements is shown as well as the standard error.

Interestingly, the data show that in all three matrix proteins a significantly lower stimulation of RNA synthesis compared to the hydrolyzate A by the two hydrolysates B and C, the average molecular weight is only slightly higher. The characteristic peptides of hydrolyzate A thus seem to play a crucial role in its beneficial effect.

8. Example formulas for nutritional supplements

In the following, some exemplary formulations for the use according to the invention of the collagen hydrolyzate are given, which of course can be modified in many ways: capsules (food supplements) glycerin 53.67% by weight Collagen hydrolyzate 21.95% by weight gelatin 10.08% by weight guar Gum 6.00% by weight lecithin 5.00% by weight citric acid 2.00% by weight Aroma (Cassis) 0.50% by weight orange oil 0.50% by weight Acesulfame-K 0.30% by weight chocolate cocoa paste 51.0% by weight sucrose 22.4% by weight cocoa butter 16.6% by weight Kollagenhyd rosinate 10.0% by weight drink water 63.00% by weight Aloe Vera Concentrate 31.00% by weight Collagen hydrolyzate 4.00% by weight sucrose 1.50% by weight citric acid 0.26% by weight Flavors and color. 0.24% by weight sucralose 0.0031% by weight

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited non-patent literature

• V. Zague: "A new view concerning the effects of collagen hydrolysates intake on skin properties" in Arch. Dermatol. Res. 2008 (9) 479 [0005]
• Watanabe-Kamiyama et al .: "Absorption and effectiveness of orally administered low molecular weight collagen hydrolysates in rats" in J. Agric. Food Chem. 2010 (58) 835 [0005]
• T. Fujimura et al .; J. Dermatol. Sci. 2000 (24) 105-111 and Y. Nishimori et al .; J. Invest. Dermatol. 2001 (117) 1458-1463 [0055]

Claims (18)

Use of collagen hydrolyzate for the treatment and / or prevention of cellulite. Use according to claim 1, wherein at least 90% by weight of the collagen hydrolyzate has a molecular weight of less than 3,500 Da, and preferably at least 45% by weight of the collagen hydrolyzate has a molecular weight of less than 1,500 Da. Use according to claim 1 or 2, wherein the collagen hydrolyzate comprises at least four characteristic peptides having a molecular weight between 600 and 1200 Da. Use according to claim 3, wherein the at least four characteristic peptides in a molecular weight distribution determined by means of MALDI mass spectroscopy have at least twice the intensity, preferably at least four times the intensity, in comparison to their surroundings. Use according to any one of the preceding claims, wherein the collagen hydrolyzate comprises a peptide between 620 and 690 Da, a peptide between 790 and 860 Da, a peptide between 980 and 1050 Da and a peptide between 1175 and 1245 Da. Use according to any one of the preceding claims, wherein the collagen hydrolyzate comprises further characteristic peptides having a molecular weight of between 1,500 and 3,500 Da. Use according to any one of the preceding claims, wherein the collagen hydrolyzate has a hydroxyproline content of 12% by weight or more. Use according to any one of the preceding claims, wherein the collagen hydrolyzate is prepared by enzymatic hydrolysis of gelatin. Use according to claim 8, wherein the gelatin is a porcine gelatin, especially pork rind gelatin. Use according to claim 8 or 9, wherein the collagen hydrolyzate is prepared by the subsequent action of at least two endoproteases with a different specificity, in particular of at least two different metalloproteases and / or serine proteases. Use according to claim 10, wherein the metalloproteases and / or serine proteases are selected from enzymes of the microorganisms Bacillus subtilis, Bacillus licheniformis, Bacillus amyloliquefaciens, Aspergillus oryzae and Aspergillus melleus. Use according to one of the preceding claims, wherein at least 50% of the N-terminal amino acids of the collagen hydrolyzate are hydrophobic amino acids, in particular alanine, leucine and isoleucine. Use according to any one of the preceding claims, wherein the collagen hydrolyzate is intended for enteral use, in particular by oral administration. Use according to claim 13, wherein the collagen hydrolyzate is a nutritional supplement, and in particular in the form of tablets, capsules, dragees, lozenges, sachets, a gel or a solution. Use according to claim 13 or 14, wherein a daily intake of about 1.5 to 5 g, preferably about 2 to 3 g, more preferably about 2.3 to 2.7 g of the collagen hydrolyzate is provided. Use according to any of the preceding claims, wherein the collagen hydrolyzate is combined with one or more active ingredients selected from vitamins, minerals, omega-3 fatty acids, omega-6 fatty acids, omega-9 fatty acids, biotin, lutein, lycopene, Caffeine, glucosamine, chondroitin, hyaluronic acid, green tea extract, folic acid, amino acids, ubiquinone-10 and antioxidants. Use according to any one of the preceding claims, wherein the collagen hydrolyzate is intended for administration to women over the age of 50 years, in particular to postmenopausal women. Use of collagen hydrolyzate for the treatment and / or prevention of stretch marks, in particular stretch marks.

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