Collagen-containing striae gravidarum repairing film as well as preparation method and application thereof

Abstract

The invention provides a striae gravidarum repairing film containing collagen as well as a preparation method and application thereof. The striae gravidarum repairing film comprises a film carrier and repairing gel loaded on the film carrier, the repairing gel is prepared from the following components: natural fish collagen, sodium hyaluronate, sea buckthron oil, carboxymethyl chitosan and a phosphate buffer solution. The striae gravidarum repairing pasting film has excellent biocompatibility through matched use of the components, the problems of denaturation and activity reduction caused by high temperature, chemical crosslinking or mechanical shearing of collagen in the prior art can be solved, and the striae gravidarum repairing pasting film can also have the remarkable effect of preventing and repairing striae gravidarum.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of daily cosmetics, and particularly relates to a collagen-containing stretch mark repair patch as well as a preparation method and application thereof. BACKGROUND

[0002] Stretch marks (Striae Gravidarum) are a common skin problem during pregnancy in pregnant women, mainly manifested as purple or white striped damage on the skin of the abdomen, chest, hips and other parts. The formation of stretch marks is mainly due to the rapid stretching of the skin during pregnancy, which causes the rupture of collagen fibers and elastic fibers in the dermis, thereby causing damage to the skin structure. Stretch marks not only affect the appearance, but also may be accompanied by skin itching, dryness and other discomfort symptoms, causing psychological and physiological distress to pregnant women.

[0003] The formation mechanism of stretch marks is complex, mainly related to the following factors:

[0004] Hormonal changes: During pregnancy, the hormone levels in pregnant women change significantly, especially the increase in cortisol levels, which inhibits the activity of fibroblasts, reduces the synthesis of collagen and elastin, and leads to decreased skin elasticity.

[0005] Excessive stretching of the skin: As the fetus develops, the abdominal skin of the pregnant woman is rapidly stretched in a short period of time, causing the rupture of collagen fibers and elastic fibers in the dermis, forming striped skin damage.

[0006] Genetic factors: Studies have shown that the occurrence of stretch marks is closely related to genetic factors. If the mother or sister has stretch marks during pregnancy, the probability of the pregnant woman developing stretch marks will also significantly increase.

[0007] Nutrition and metabolic factors: Imbalanced nutrition or metabolic abnormalities during pregnancy can also affect the elasticity and repair ability of the skin, increasing the risk of stretch marks.

[0008] At present, the common stretch mark care products on the market are mainly divided into two categories: preventive and repair. The preventive products mainly contain olive oil, vitamin E, cocoa butter and other ingredients, which can enhance the moisturizing ability and elasticity of the skin to reduce the formation of stretch marks. The repair products mainly contain asiaticoside extract, hyaluronic acid, collagen and other ingredients, aiming to promote skin repair and collagen regeneration. However, the existing products have certain limitations in repair effect, especially for the stretch marks that have already formed, especially the stretch marks that have been formed for a long time, the repair effect is not significant.

[0009] Fish collagen has been widely used in skincare products in recent years due to its high compatibility with human skin and good biological activity. Fish collagen can promote skin cell regeneration and repair, enhance skin elasticity and moisture retention. Studies have shown that small molecule peptides in fish collagen can penetrate the skin through transdermal absorption, promote the proliferation of fibroblasts and the synthesis of collagen, thereby improving skin elasticity and firmness. However, fish collagen itself has poor thermal stability and mechanical properties, which can be easily inactivated or denatured during preparation, limiting its application effect. In addition, the amount and usage of fish collagen added to skincare products also directly affect its efficacy.

[0010] In recent years, with the progress of biotechnology, modified fish collagen has gradually become a research hotspot. Through chemical cross-linking, enzymatic hydrolysis and other technologies, the thermal stability and mechanical properties of fish collagen can be significantly improved, and its biological activity and skin permeability can be enhanced. For example, biphenyl-3,4-diol as a cross-linking agent can covalently bind to the amino and sulfhydryl groups of fish collagen, forming a stable cross-linked structure, thereby improving the stability and anti-degradation ability of fish collagen. In addition, the synergistic effect of modified fish collagen with other active ingredients (such as asiaticoside extract, palmitoyl tripeptide-5, etc.) can further enhance its effect of repairing stretch marks.

[0011] In summary, the existing stretch mark care products have certain limitations in repair effect, especially for the stretch marks that have already formed, the repair effect is not significant. Therefore, the development of an abdominal film based on modified fish collagen, through the synergistic effect of other active ingredients, can effectively prevent and repair stretch marks, and has important application value. SUMMARY

[0012] In view of the shortcomings of the prior art, the present application provides a stretch mark repair film containing collagen and a preparation method and application thereof. The present application solves the industry problem of denaturation of collagen in skincare applications and provides a safe and efficient solution for stretch mark repair.

[0013] To achieve the purpose of the present application, the following technical solutions are adopted:

[0014] In a first aspect, the present application provides a stretch mark repair film containing collagen, which comprises a film carrier and a repair gel loaded on the film carrier.

[0015] The components of the repair gel include natural fish collagen, sodium hyaluronate, sea buckthorn oil, carboxymethyl chitosan and phosphate buffer.

[0016] The fish collagen in the stretch mark repair patch of the present application can promote the regeneration and repair of skin cells, and enhance the elasticity and moisturizing capacity of the skin; the carboxymethyl chitosan as a physical crosslinking agent can enhance the mechanical strength of the patch through electrostatic interaction, replace traditional chemical crosslinking (such as diphenyl-3,4-diol), avoid the destruction of the active site of collagen, and the sodium hyaluronate and sea buckthorn oil can not only form a biomimetic extracellular matrix with collagen, but also enhance the moisturizing and antioxidant functions of the product, and the solvent can be used to use a phosphate buffer, which can simulate the environment and maintain the stability of collagen. The product has excellent biocompatibility by using the above components, which can not only solve the problem of denaturation and activity reduction of collagen caused by high temperature, chemical crosslinking or mechanical shearing in the prior art, but also has a significant effect of preventing and repairing stretch marks.

[0017] The sodium hyaluronate and sea buckthorn oil are added to form a biomimetic extracellular matrix, and enhance the moisturizing and antioxidant functions.

[0018] Preferably, the components of the repair gel include 5-15 parts of natural fish collagen, 1-3 parts of sodium hyaluronate, 1-5 parts of sea buckthorn oil, 0.1-2 parts of carboxymethyl chitosan and 55-90 parts of phosphate buffer by weight.

[0019] Preferably, the film carrier includes silica gel.

[0020] Preferably, the components of the repair gel further include any one or a combination of at least two of trehalose, gota kola extract or palmitoyl tripeptide-5.

[0021] Preferably, the components of the repair gel further include trehalose, gota kola extract and palmitoyl tripeptide-5.

[0022] The product of the present application can activate fibroblasts and promote the ordered arrangement of collagen by compounding trehalose, gota kola extract and palmitoyl tripeptide-5, thereby achieving deep repair of stretch marks.

[0023] Preferably, the components of the repair gel include 5-15 parts of natural fish collagen, 1-3 parts of sodium hyaluronate, 1-7 parts of gota kola extract, 1-5 parts of palmitoyl tripeptide-5, 1-5 parts of sea buckthorn oil, 3-8 parts of trehalose, 0.1-2 parts of carboxymethyl chitosan and 55-90 parts of phosphate buffer by weight.

[0024] The amount of the natural fish collagen added in the repair gel of the present application can be 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts or 14 parts, etc.

[0025] The addition amount of the sodium hyaluronate can be 1.1 parts, 1.3 parts, 1.5 parts, 1.8 parts, 2 parts, 2.2 parts, 2.5 parts, 2.7 parts, or 2.9 parts, etc.

[0026] The addition amount of the Centella asiatica extract can be 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, or 6.5 parts, etc.

[0027] The addition amount of the palmitoyl tripeptide-5 can be 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, or 4.5 parts, etc.

[0028] The addition amount of the sea buckthorn oil can be 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, or 4.5 parts, etc.

[0029] The addition amount of the trehalose can be 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, or 7.5 parts, etc.

[0030] The addition amount of the carboxymethyl chitosan can be 0.2 parts, 0.5 parts, 0.8 parts, 1 part, 1.2 parts, 1.5 parts, 1.7 parts, or 1.9 parts, etc.

[0031] The addition amount of the phosphate buffer can be 60 parts, 70 parts, 75 parts, 80 parts, or 85 parts, etc.

[0032] Preferably, the natural fish collagen is prepared by the following method:

[0033] (1) After alkaline washing of fish skin, centrifugal treatment is performed, and then the centrifugate is soaked and washed in water, and the natural fish collagen is obtained after centrifugation;

[0034] (2) The alkaline washed fish skin is extracted in a citric acid solution to obtain an extraction liquor;

[0035] (3) After centrifugation of the extraction liquor, the centrifugate is filtered to collect a filtrate;

[0036] (4) The filtrate is concentrated to obtain the natural fish collagen.

[0037] Preferably, the alkali solution used for the alkaline washing in step (1) is a 0.1-1% (for example, it can be 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, or 0.9%, etc.) NaOH solution.

[0038] Preferably, the temperature during the alkaline washing is 5-10℃ (for example, it can be 6℃, 7℃, 8℃, or 9℃, etc.), and the time is 3-5h (for example, it can be 3.1h, 3.3h, 3.5h, 3.8h, 4h, 4.2h, 4.5h, or 4.8h, etc.).

[0039] Preferably, the material-liquid ratio of the fish skin to the alkali solution is 0.1-0.2 g / mL, for example, it can be 0.11 g / mL, 0.13 g / mL, 0.15 g / mL, 0.17 g / mL or 0.19 g / mL, etc.

[0040] Preferably, the soaking cleaning in step (1) is to pH < 13.

[0041] Preferably, the mass concentration of the citric acid solution in step (2) is 0.5-1%, for example, it can be 0.6%, 0.7%, 0.8% or 0.9%, etc.

[0042] Preferably, the material-liquid ratio of the alkali-washed fish skin to the citric acid solution is 0.05-0.1 g / mL, for example, it can be 0.06 g / mL, 0.07 g / mL, 0.08 g / mL or 0.09 g / mL, etc.

[0043] Preferably, the extraction in step (2) is: stirring extraction at 20-30°C (for example, it can be 21°C, 23°C, 25°C, 27°C or 29°C, etc.) for 1.5-2.5 h (for example, it can be 1.6 h, 1.8 h, 2 h, 2.2 h or 2.4 h, etc.); then increasing the temperature to 35-45°C (for example, it can be 36°C, 38°C, 40°C, 42°C or 44°C, etc.) and stirring extraction for 45-70 min (for example, it can be 46 min, 48 min, 50 min, 55 min, 60 min or 65 min, etc.).

[0044] Preferably, the stirring speed is 50-150 rpm, for example, it can be 60 rpm, 80 rpm, 100 rpm, 120 rpm or 140 rpm, etc.

[0045] Preferably, the centrifugation in step (3) includes:

[0046] The centrifugate is filtered once using a bag filter with a particle size of 0.4-0.6 μm (for example, it can be 0.42 μm, 0.45 μm, 0.48 μm, 0.5 μm, 0.52 μm, 0.55 μm or 0.58 μm, etc.), the first filtration liquid is collected, then filtered twice using a filter core filter with a particle size of 0.1-0.3 μm (for example, it can be 0.12 μm, 0.15 μm, 0.18 μm, 0.2 μm, 0.22 μm, 0.25 μm or 0.28 μm, etc.), the second filtration liquid is collected, then filtered three times using a membrane filtration system with a particle size of 0.4-0.6 μm (for example, it can be 0.42 μm, 0.45 μm, 0.48 μm, 0.5 μm, 0.52 μm, 0.55 μm or 0.58 μm, etc.), and the third filtration liquid is collected after the filtration is completed.

[0047] Preferably, the concentration in step (4) is ≥5.5% in the concentrated solution, for example, it can be 6%, 8%, 10%, 15%, or 20%, etc.

[0048] Preferably, the conductivity of the concentrated solution is less than 500 μS / cm, for example, it can be 50 μS / cm, 100 μS / cm, 200 μS / cm, 300 μS / cm, 400 μS / cm, or 450 μS / cm, etc.

[0049] Specific point values within the above numerical ranges can be selected, which will not be repeated here.

[0050] In a second aspect, the present application provides a preparation method of the stretch mark repair patch containing collagen as described in the first aspect, the preparation method comprising:

[0051] (a) heating the phosphate buffer and then adding sodium hyaluronate, trehalose, and carboxymethyl chitosan, mixing to obtain a gel matrix;

[0052] (b) cooling the gel matrix, and then sequentially adding natural fish collagen, centella asiatica extract, palmitoyl tripeptide-5, and sea buckthorn oil, mixing and homogenizing to obtain a repair gel;

[0053] (c) coating the repair gel on the film carrier, drying, and sterilizing to obtain the stretch mark repair patch containing collagen.

[0054] Preferably, the heating in step (a) is to 35-40°C, for example, it can be 36°C, 37°C, 38°C, or 39°C, etc.

[0055] Preferably, the mixing in step (a) is carried out by stirring at a speed of 150-250 rpm (for example, it can be 160 rpm, 180 rpm, 200 rpm, 220 rpm, or 240 rpm, etc.) for 10-30 min (for example, it can be 11 min, 13 min, 15 min, 18 min, 20 min, 22 min, 25 min, or 28 min, etc.).

[0056] Preferably, the cooling in step (b) is to 5-12°C, for example, it can be 6°C, 7°C, 8°C, 9°C, 10°C, or 11°C, etc.

[0057] Preferably, the mixing and homogenizing in step (b) is carried out by stirring at a speed of 350-500 rpm (for example, it can be 360 rpm, 380 rpm, 400 rpm, 420 rpm, 450 rpm, or 480 rpm, etc.) for 25-40 min (for example, it can be 26 min, 28 min, 30 min, 32 min, 35 min, or 38 min, etc.).

[0058] Preferably, the thickness of the coating in step (c) is 0.3-0.8mm, for example, it can be 0.4mm, 0.5mm, 0.6mm or 0.7mm, etc.

[0059] Specific point values within the above numerical ranges can be selected, which will not be described here one by one.

[0060] In a third aspect, the present application provides a collagen-containing stretch mark repair patch for use in stretch mark repair.

[0061] Compared with the prior art, the present application has the following beneficial effects:

[0062] The fish collagen in the stretch mark repair patch of the present application can promote the regeneration and repair of skin cells, enhance the elasticity and moisturizing capacity of the skin; the carboxymethyl chitosan as a physical crosslinking agent enhances the mechanical strength of the patch through electrostatic interaction, replaces the traditional chemical crosslinking (such as diphenyl-3, 4-diol), avoids the destruction of the active sites of collagen, and the sodium hyaluronate and sea-buckthorn oil not only can form a biomimetic extracellular matrix with collagen, but also can enhance the moisturizing and antioxidant functions of the product, and at the same time, the solvent uses a phosphate buffer, which can mimic the environment and maintain the stability of collagen. The product has excellent biocompatibility by using the above-mentioned components, not only can solve the problem of denaturation and reduced activity of collagen in the prior art due to high temperature, chemical crosslinking or mechanical shearing, but also has a significant effect of preventing and repairing stretch marks. DETAILED DESCRIPTION

[0063] The technical solutions of the present application will be further described below through specific embodiments. Those skilled in the art should understand that the embodiments are only to help understand the present application and should not be regarded as specific limitations on the present application.

[0064] Preparation Example 1

[0065] The present preparation example provides a natural fish collagen, and the preparation method of the natural fish collagen is:

[0066] (1) Fresh fish skin (dab) is stirred with 0.4% NaOH solution at 10℃ for 4 hours, and the solid-liquid ratio is 0.13g / mL; after the alkali washing is completed, the material is extracted into a flat plate centrifuge for centrifugation, and the dried material is transferred into a stirring tank, 200kg of cooling water is added for stirring and soaking for 20min, and then the material is extracted into a flat plate centrifuge for centrifugation to remove water, and the operation is repeated until the pH value of the soaking liquid of the material is 12±0.5;

[0067] (2) The fish skin washed with alkali in step (1) is put into an extraction tank, 0.7% citric acid solution is added, the solid-liquid ratio is 0.07 g / mL, and the extraction is carried out at 30°C for 2 hours, then the temperature is quickly raised to 40°C, and the extraction is continued for 1 hour to obtain the extraction liquid;

[0068] (3) The extraction liquid is pumped into a centrifuge, and low-frequency centrifugation is followed by high-frequency centrifugation;

[0069] (4) The centrifugal liquid is filtered by a 0.5 μm pp bag filter, and then filtered by a 0.2 μm pp folded filter element, the filtrate filtered by the 0.2 μm pp folded filter element is transferred into a 0.5 μm PTFE (polytetrafluoroethylene) membrane filtration system for circulation filtration, and after the filtration is completed, the filtrate is collected by washing the filtrate once with 30 kg of pure water;

[0070] (5) The filtrate is concentrated, 7 times the weight of pure water is added after the concentration is limited, and the concentration is repeated for three to five times, until the solid content of the concentrated liquid is 8% and the conductivity is 450 μS / cm.

[0071] Preparation Example 2

[0072] The preparation example provides a natural fish collagen, and a preparation method of the natural fish collagen is as follows:

[0073] (1) Fresh fish skin (cod) is stirred and washed with 8°C 0.6% NaOH solution for 3.5 hours, and the solid-liquid ratio is 0.15 g / mL; after the alkali washing is completed, the material is pumped into a plate centrifuge for centrifugation, the dried material is transferred into a stirring tank, 200 kg of cooling water is added, and stirring and soaking are carried out for 20 min, then the material is centrifuged to remove water in a plate centrifuge, and the operation is repeated to clean the material until the pH value of the soaking liquid is 11±0.5;

[0074] (2) The fish skin washed with alkali in step (1) is put into an extraction tank, 0.9% citric acid solution is added, the solid-liquid ratio is 0.05 g / mL, and the extraction is carried out at 25°C for 1.5 hours, then the temperature is quickly raised to 38°C, and the extraction is continued for 50 min to obtain the extraction liquid;

[0075] (3) The extraction liquid is pumped into a centrifuge, and low-frequency centrifugation is followed by high-frequency centrifugation;

[0076] (4) The centrifugal liquid is filtered by a 0.6 μm pp bag filter, and then filtered by a 0.1 μm pp folded filter element, the filtrate filtered by the 0.1 μm pp folded filter element is transferred into a 0.4 μm PTFE (polytetrafluoroethylene) membrane filtration system for circulation filtration, and after the filtration is completed, the filtrate is collected by washing the filtrate once with 30 kg of pure water;

[0077] (5) The filtrate is concentrated, and after concentration to the limit, 7 times the weight of pure water is added for continuous concentration. The concentration is repeated for 3 to 5 times, until the solid content of the concentrated solution is 7%, and the conductivity is 480 μS / cm.

[0078] Preparation Example 3

[0079] The present preparation example provides a natural fish collagen, and the preparation method of the natural fish collagen is:

[0080] (1) Fresh fish skin (cod) is stirred with 0.8% NaOH solution at 6°C for 5 hours, and the solid-liquid ratio is 0.18 g / mL. After the alkali washing is completed, the material is extracted into a flat plate centrifuge for centrifugation. The dried material is transferred into a stirring tank, 200 kg of cooling water is added for stirring and soaking for 20 min, and then the material is extracted into a flat plate centrifuge for drying. The washing is repeated until the pH value of the soaking solution of the material is 12±0.5;

[0081] (2) The alkali-washed fish skin in step (1) is put into an extraction tank, and 0.8% citric acid solution is added, with a solid-liquid ratio of 0.09 g / mL. After stirring at 20°C for 2.5 h, the temperature is quickly raised to 43°C for continuous stirring extraction for 70 min, and then an extraction solution is obtained;

[0082] (3) The extraction solution is pumped into a centrifuge for low-frequency centrifugation first and then high-frequency centrifugation;

[0083] (4) The centrifugal solution is filtered with a 0.4 μm pp bag filter, and then filtered with a 0.3 μm pp folding filter element. The filtrate filtered by the 0.3 μm pp folding filter element is transferred into a 0.6 μm PTFE (polytetrafluoroethylene) membrane filtration system for circulation filtration. After the filtration is completed, 30 kg of pure water is added to the filtrate for filtration once, and the filtrate is collected;

[0084] (5) The filtrate is concentrated, and after concentration to the limit, 7 times the weight of pure water is added for continuous concentration. The concentration is repeated for 3 to 5 times, until the solid content of the concentrated solution is 7%, and the conductivity is 480 μS / cm.

[0085] Preparation Example 4

[0086] The present preparation example provides a natural fish collagen, and the preparation method of the natural fish collagen is:

[0087] (1) Fresh fish skin (cod) is stirred with 0.8% NaOH solution at 6°C for 5 hours, and the solid-liquid ratio is 0.18 g / mL. After the alkali washing is completed, the material is extracted into a flat plate centrifuge for centrifugation. The dried material is transferred into a stirring tank, 200 kg of cooling water is added for stirring and soaking for 20 min, and then the material is extracted into a flat plate centrifuge for drying. The washing is repeated until the pH value of the soaking solution of the material is 12±0.5;

[0088] (2) The fish skin washed with alkali in step (1) is put into an extraction tank, 0.7% citric acid solution is added, the ratio of material to liquid is 0.07 g / mL, and the extraction is carried out at 30°C for 2 hours, then the temperature is quickly raised to 40°C and the extraction is continued for 1 hour to obtain the extraction liquid;

[0089] (3) The extraction liquid is pumped into a centrifuge and centrifuged at low frequency first and then at high frequency;

[0090] (4) The centrifugal liquid is filtered by a 0.5 μm pp bag filter, then filtered by a 0.2 μm pp folded filter core, and after the filtration is completed, the retained liquid is washed by 30 kg of pure water for filtration once, and the filtered liquid is collected;

[0091] (5) The filtered liquid is concentrated, 7 times the weight of pure water is added after the concentration reaches the limit, and the concentration is repeated for 3 to 5 times, until the solid content of the concentrated liquid is 7% and the conductivity is 460 μS / cm.

[0092] Preparation Example 5

[0093] The present preparation example provides a natural fish collagen, and the preparation method of the natural fish collagen is as follows:

[0094] (1) Fresh fish skin (cod) is stirred and washed with 10°C 0.4% NaOH solution for 4 hours, the ratio of material to liquid is 0.13 g / mL; the material is pumped into a flat plate centrifuge for centrifugation, the dried material is transferred into a stirring tank, 200 kg of cooling water is added for stirring and soaking for 20 min, the material is centrifuged to remove water in a flat plate centrifuge, and the operation is repeated for cleaning until the pH value of the soaking liquid of the material is 12±0.5;

[0095] (2) The fish skin washed with alkali in step (1) is put into an extraction tank, 0.7% citric acid solution is added, the ratio of material to liquid is 0.07 g / mL, and the extraction is carried out at 30°C for 2 hours, then the temperature is quickly raised to 40°C and the extraction is continued for 1 hour to obtain the extraction liquid;

[0096] (3) The extraction liquid is pumped into a centrifuge and centrifuged at low frequency first and then at high frequency;

[0097] (4) The centrifugal liquid is filtered by a 0.5 μm pp bag filter, then filtered by a 0.2 μm pp folded filter core, and after the filtration is completed, the retained liquid is washed by 30 kg of pure water for filtration once, and the filtered liquid is collected;

[0098] (5) The filtered liquid is concentrated, 7 times the weight of pure water is added after the concentration reaches the limit, and the concentration is repeated for 3 to 5 times, until the solid content of the concentrated liquid is 7% and the conductivity is 460 μS / cm.

[0099] Preparation Example 6

[0100] The preparation example provides a natural fish collagen, and a preparation method of the natural fish collagen is as follows:

[0101] (1) fresh fish skin (cod) is stirred with 0.4% NaOH solution at 10°C for 4 hours, and the material-liquid ratio is 0.13 g / mL; after the alkali washing is completed, the material is extracted into a flat plate centrifuge, the dried material is transferred into a stirring tank, 200 kg of cooling water is added, and the material is stirred and soaked for 20 min, then the water is extracted into a flat plate centrifuge, and the material is dried; the washing is repeated until the pH value of the soaking liquid of the material is 12±0.5;

[0102] (2) the alkali-washed fish skin in step (1) is put into an extraction tank, 0.7% citric acid solution is added, the material-liquid ratio is 0.07 g / mL, and stirring extraction is carried out at 30°C for 2 h, then the temperature is quickly increased to 40°C, and stirring extraction is continued for 1 h to obtain an extraction liquid;

[0103] (3) the extraction liquid is extracted into a centrifuge by a pump, and low-frequency centrifugation is followed by high-frequency centrifugation;

[0104] (4) the centrifugal liquid is filtered by a 0.2 μm pp folding filter element, the filtrate filtered by the 0.2 μm pp folding filter element is transferred into a 0.5 μm PTFE (polytetrafluoroethylene) membrane filtration system for circulation filtration, the filtrate is filtered once by adding 30 kg of pure water after the filtration is completed, and the filtered liquid is collected;

[0105] (5) the filtered liquid is concentrated, 7 times the weight of pure water is added after the concentration is limited, and the concentration is repeated for three to five times, until the solid content of the concentrated liquid is 8%, and the conductivity is 450 μS / cm.

[0106] Preparation example 7

[0107] The preparation example provides a natural fish collagen, and a preparation method of the natural fish collagen is as follows:

[0108] (1) the cod skin is washed with water, and then soaked in a sodium hydroxide solution for 5 hours; the soaked cod skin is washed, mixed with a phosphate buffer solution, ground, and homogenized to obtain a cod skin homogenate;

[0109] (2) the cod skin homogenate is added with pepsin, and then subjected to enzymolysis for 4 h; then, papain and flavor protease are added, and the mixture is subjected to enzymolysis for 3 h to obtain an enzymolysis liquid;

[0110] (3) the enzymolysis liquid is sequentially subjected to ceramic membrane filtration and organic membrane filtration to obtain a filtrate; the filtrate is sequentially subjected to cation exchange resin and anion exchange resin, and then the filtered liquid is collected;

[0111] (4) the filtered liquid is concentrated, 7 times the weight of pure water is added after the concentration is limited, and the concentration is repeated for three to five times, until the solid content of the concentrated liquid is 8%, and the conductivity is 400 μS / cm.

[0112] Example 1-3

[0113] The examples provide three kinds of collagen-containing stretch mark repair patches, which are composed of sterile silica gel and a repair gel loaded on the sterile silica gel, and the preparation raw materials of the repair gel are shown in the following table:

[0114]

[0115] The preparation method of the collagen-containing stretch mark repair patch in Example 1 is as follows:

[0116] (a) After heating the phosphate buffer to 35℃, add sodium hyaluronate, trehalose and carboxymethyl chitosan, stir and mix at a speed of 100 rpm for 20 min to obtain a gel matrix;

[0117] (b) After cooling the gel matrix to 10℃, sequentially add natural fish collagen, centella asiatica extract, palmitoyl tripeptide-5 and sea buckthorn oil, stir and mix at 400 rpm for 30 min, and homogenize to obtain a repair gel;

[0118] (c) Apply the repair gel to the sterile silica gel with a thickness of 0.5 mm, and dry at 25℃ for 48 h, then sterilize by ultraviolet irradiation for 30 min to obtain the collagen-containing stretch mark repair patch.

[0119] Example 4-7

[0120] The examples provide four kinds of collagen-containing stretch mark repair patches, which are different from Example 1 only in that the natural fish collagen of Preparation Example 1 is replaced by an equal amount of natural fish collagen of Preparation Examples 4-7 in the components of the repair gel, and the rest of the components remain unchanged, and the preparation method refers to Example 1.

[0121] Example 8

[0122] The comparative example provides a collagen-containing stretch mark repair patch, which is different from Example 1 only in that the repair gel does not include trehalose, centella asiatica extract and palmitoyl tripeptide-5, and the reduced amount is supplemented by natural fish collagen, and the rest of the components are consistent with Example 1, and the preparation method refers to Example 1.

[0123] Example 9

[0124] The comparative example provides a collagen-containing stretch mark repair patch, which is different from Example 1 only in that the repair gel does not include trehalose, and the reduced amount is distributed to centella asiatica extract and palmitoyl tripeptide-5 in a proportion of parts, and the rest of the components are consistent with Example 1, and the preparation method refers to Example 1.

[0125] Example 10

[0126] The present comparative example provides a stretch mark repair patch containing collagen, which is different from Example 1 only in that the component of the repair gel does not include centella asiatica extract, and the reduced amount is proportionally distributed to trehalose and palmitoyl tripeptide-5, and the remaining components are consistent with Example 1, and the preparation method refers to Example 1.

[0127] Example 11

[0128] The present comparative example provides a stretch mark repair patch containing collagen, which is different from Example 1 only in that the component of the repair gel does not include palmitoyl tripeptide-5, and the reduced amount is proportionally distributed to trehalose and centella asiatica extract, and the remaining components are consistent with Example 1, and the preparation method refers to Example 1.

[0129] Comparative Example 1

[0130] The present comparative example provides a stretch mark repair patch, which is different from Example 1 only in that the component of the repair gel does not include natural fish collagen, and the reduced amount is proportionally distributed to sodium hyaluronate, centella asiatica extract, and palmitoyl tripeptide-5, and the remaining components are consistent with Example 1, and the preparation method refers to Example 1.

[0131] Comparative Example 2

[0132] The present comparative example provides a stretch mark repair patch containing collagen, which is different from Example 1 only in that the component of the repair gel does not include sodium hyaluronate, and the reduced amount is made up by sea buckthorn oil, and the remaining components are consistent with Example 1, and the preparation method refers to Example 1.

[0133] Comparative Example 3

[0134] The present comparative example provides a stretch mark repair patch containing collagen, which is different from Example 1 only in that the component of the repair gel does not include sea buckthorn oil, and the reduced amount is made up by sodium hyaluronate, and the remaining components are consistent with Example 1, and the preparation method refers to Example 1.

[0135] Comparative Example 4

[0136] The present comparative example provides a stretch mark repair patch containing collagen, which is different from Example 1 only in that the component of the repair gel replaces the phosphate buffer with an equal amount of water, and the remaining components are consistent with Example 1, and the preparation method refers to Example 1.

[0137] Test Example 1

[0138] Test condition: The repair gels prepared in Examples 1-11 and Comparative Examples 1-4 were respectively placed in a constant temperature oven at 40℃ and a freezer room at -10℃ for 24h, and then taken out. After the temperature was recovered to room temperature, whether there was delamination or precipitation was observed. The results are shown in Table 1 below.

[0139] Table 1

[0140] Sample 40℃ -10℃ Example 1 No delamination or precipitation No delamination or precipitation Example 2 No delamination or precipitation No delamination or precipitation Example 3 No delamination or precipitation No delamination or precipitation Example 4 No delamination or precipitation No delamination or precipitation Example 5 No delamination or precipitation No delamination or precipitation Example 6 No delamination or precipitation No delamination or precipitation Example 7 No delamination or precipitation No delamination or precipitation Example 8 No delamination or precipitation No delamination or precipitation Example 9 No delamination or precipitation No delamination or precipitation Example 10 No delamination or precipitation No delamination or precipitation Example 11 No delamination or precipitation No delamination or precipitation Comparative Example 1 No delamination or precipitation No delamination or precipitation Comparative Example 2 No delamination or precipitation No delamination or precipitation Comparative Example 3 No delamination or precipitation No delamination or precipitation Comparative Example 4 Delamination Delamination

[0141] From the stability in Table 1, it can be seen that the repair gel samples prepared in the examples of the present application have no oil-water separation, no obvious difference in properties, and stable properties.

[0142] And from Comparative Example 4, it can be seen that the phosphate buffer can provide a biomimetic environment to maintain the stability of collagen and the product.

[0143] Test Example 2: Safety evaluation experiment

[0144] The specific method is as follows: 40 female volunteers aged 18-35 years old without allergy history were selected, and each of the volunteers was applied with the sample prepared in Example 1-11. After the back of the volunteer was cleaned, the patch tester with the sample was attached to the selected position on the back with a non-irritating adhesive tape. After the patch tester was attached, the skin was pressed with fingers to make the patch tester evenly attached to the skin, and the patch tester was kept for 48h. The volunteer kept the patch tester dry within 48h, and avoided intense exercise, scratching the patch tester, long-term sunlight irradiation, etc. After 48h, the patch tester was removed and marked, and after 30min, the pressure marks disappeared, and the determination was performed under sufficient light.

[0145] The skin adverse reaction grading standard is shown in Table 2:

[0146] Table 2

[0147]

[0148] The results are shown in Table 3:

[0149] Table 3

[0150]

[0151]

[0152] From the data in Table 3, it can be seen that after the patch tester was removed, no adverse reaction of the skin was observed in the volunteers, which indicates that the raw materials used in the product of the present application are safe and non-irritating, and have no adverse reaction to the human body, and the safety is high.

[0153] Test Example 3: Repair efficacy test of stretch marks

[0154] 180 women volunteers with striae gravidarum aged between 30-40 years were selected as the test subjects, all the test subjects had similar striae gravidarum (evaluated by using the modified Davey grading standard), and were randomly divided into 15 groups, 12 people in each group. Test method: the test subjects used the products of examples 1-11 and comparative examples 1-4 respectively, the frequency of use was 1 time / day, 2 hours each time, and the continuous use was 150 days.

[0155] The test results were all evaluated by blind evaluation (to avoid subjective bias), first, the modified Davey grading (0-9 points, to evaluate the width, color and skin flatness of the striae) and the patient self-evaluation questionnaire (satisfaction, improvement of itching / tightness, etc.) were used. The improvement level was classified as: no effect (no change, the striae were still obvious), slight improvement (the striae became shallower / narrower, but still had visible marks) and significant improvement (the striae were obviously faded, close to normal skin). The soothing and repairing conditions of the striae gravidarum of the volunteers in each group were counted, and the results are shown in Table 3.

[0156] Table 4

[0157]

[0158]

[0159] According to Table 3, the test group 1 showed the best performance, not only the slight improvement rate reached 41.7%, but also 16.6% of the test subjects showed significant improvement, indicating that the formula might be more effective in promoting the repair of striae gravidarum.

[0160] However, in examples 4-7, when the preparation method of collagen was not the specific method of the present application, no test subject achieved significant improvement;

[0161] As can be seen from examples 8-11, trehalose, asiaticoside extract and palmitoyl tripeptide-5 can synergize with collagen to better enhance the repair effect of the product, and the three components have a synergistic effect on this efficacy;

[0162] In comparative example 1, when collagen was lacking, the effect was the weakest, 66.7% of the test subjects showed no improvement, indicating that the formula might have a weak repair effect on striae gravidarum;

[0163] As can be seen from comparative examples 2-3, the combination of sea buckthorn oil and sodium hyaluronate can better protect collagen, thereby making the repair effect of the product better, and the absence of either of the two will reduce the repair effect of the product.

[0164] The applicant declares that the present application is illustrated by the above-mentioned embodiments of a collagen-containing stretch mark repair patch and its preparation method and application, but the present application is not limited to the above-mentioned embodiments, i.e. it does not mean that the present application must rely on the above-mentioned embodiments to be implemented. It should be understood by those skilled in the art that any improvement of the present application, equivalent replacement of each raw material of the product of the present application, addition of auxiliary ingredients, selection of specific modes, etc. all fall within the protection scope and disclosure scope of the present application.

[0165] The preferred embodiments of the present application are described in detail above, but the present application is not limited to the specific details in the above-mentioned embodiments, and various simple modifications can be made to the technical solutions of the present application within the technical concept scope of the present application, and these simple modifications all belong to the protection scope of the present application.

[0166] In addition, it should be noted that each specific technical feature described in the above-mentioned specific embodiments can be combined in any appropriate manner without contradiction, and in order to avoid unnecessary repetition, the present application will not further describe various possible combination manners.

Claims

1. A stretch mark repairing patch containing collagen, characterized in that: The stretch mark repair patch comprises a membrane carrier and a repair gel loaded on the membrane carrier; The components of the repair gel include natural fish collagen, sodium hyaluronate, sea buckthorn oil, carboxymethyl chitosan and phosphate buffer.

2. The stretch mark repairing patch containing collagen according to claim 1, characterized in that: The components of the repair gel include, by weight, 5-15 parts of natural fish collagen, 1-3 parts of sodium hyaluronate, 1-5 parts of sea buckthorn oil, 0.1-2 parts of carboxymethyl chitosan, and 55-90 parts of phosphate buffer; Preferably, the membrane support comprises silica gel.

3. The stretch mark repairing patch containing collagen according to claim 1 or 2, characterized in that: The components of the repair gel also include any one of trehalose, Centella asiatica extract or palmitoyl tripeptide-5, or a combination of at least two thereof; Preferably, the components of the repair gel also include trehalose, Centella asiatica extract and palmitoyl tripeptide-5; Preferably, the components of the repair gel include, by weight, 5-15 parts of natural fish collagen, 1-3 parts of sodium hyaluronate, 1-7 parts of Centella asiatica extract, 1-5 parts of palmitoyl tripeptide-5, 1-5 parts of sea buckthorn oil, 3-8 parts of trehalose, 0.1-2 parts of carboxymethyl chitosan and 55-90 parts of phosphate buffer.

4. The stretch mark repairing patch containing collagen according to any one of claims 1 to 3, characterized in that: The natural fish collagen is prepared by the following method: (1) the fish skin is alkali-washed and then centrifuged, and the centrifuge is then soaked in water for cleaning, and the alkali-washed fish skin is obtained after centrifugation; (2) extracting the alkali-washed fish skin in a citric acid solution to obtain an extraction liquid; (3) After the extraction liquid is centrifuged, the centrifuged liquid is filtered and the filtrate is collected; (4) Concentrating the filtrate to obtain the natural fish collagen.

5. The stretch mark repairing patch containing collagen according to claim 4, characterized in that: The alkali solution used in the alkali washing in step (1) is a 0.1-1% NaOH solution; Preferably, the alkali washing temperature is 5-10°C and the time is 3-5h; Preferably, the material-liquid ratio of the fish skin to the alkali solution is 0.1-0.2 g / mL; Preferably, the soaking and washing in step (1) is performed until the pH is less than 13.

6. The stretch mark repairing patch containing collagen according to claim 4 or 5, characterized in that: The mass concentration of the citric acid solution in step (2) is 0.5-1%; Preferably, the material-liquid ratio of the alkali-washed fish skin to the citric acid solution is 0.05-0.1 g / mL; Preferably, the extraction step in step (2) is as follows: stirring and extracting at 20-30°C for 1.5-2.5 hours; then heating to 35-45°C and stirring and extracting for 45-70 minutes; Preferably, the stirring speed is 50-150 rpm.

7. The stretch mark repairing patch containing collagen according to any one of claims 4 to 6, characterized in that: The centrifugal step in step (3) comprises: The centrifuge liquid is filtered once using a bag filter with a particle size of 0.4-0.6 μm, the filtrate is collected and then filtered twice using a filter cartridge with a particle size of 0.1-0.3 μm, the secondary filtrate is collected and then filtered three times using a membrane filtration system with a particle size of 0.4-0.6 μm, and the three filtrates are collected after the filtration is completed; Preferably, the step (4) is concentrated to a concentration of ≥5.5% solid content in the concentrate; Preferably, the conductivity of the concentrated liquid is less than 500 μS / cm.

8. A method for preparing a stretch mark repairing patch containing collagen according to any one of claims 1 to 7, characterized in that: The preparation method comprises: (a) heating a phosphate buffer solution, adding sodium hyaluronate, trehalose, and carboxymethyl chitosan, and mixing to obtain a gel matrix; (b) After cooling the gel matrix, natural fish collagen, Centella asiatica extract, palmitoyl tripeptide-5, and sea buckthorn oil are sequentially added and mixed homogenously to obtain a repair gel; (c) coating the repair gel on a film carrier, drying and sterilizing the film to obtain the stretch mark repair film containing collagen.

9. The preparation method according to claim 8, wherein Heating to 35-40° C. in step (a); Preferably, the mixing in step (a) is carried out by stirring at a speed of 150-250 rpm for 10-30 min; Preferably, the temperature in step (b) is lowered to 5-12°C; Preferably, the mixing and homogenizing in step (b) is carried out by stirring at a speed of 350-500 rpm for 25-40 min; Preferably, the coating thickness in step (c) is 0.3-0.8 mm.

10. Use of the stretch mark repairing patch containing collagen according to any one of claims 1 to 7 in pregnancy repair.

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