CN111297723A

CN111297723A - Preparation method of collagen and preparation method of application thereof

Info

Publication number: CN111297723A
Application number: CN202010218646.2A
Authority: CN
Inventors: 冯幸福
Original assignee: Ningbo Santemuse Biotechnology Co ltd
Current assignee: Ningbo Santemuse Biotechnology Co ltd
Priority date: 2020-03-25
Filing date: 2020-03-25
Publication date: 2020-06-19

Abstract

The present invention relates to a collagen-based, instant-dissolving, cosmetic patch comprising a collagen derivative at a concentration of 0.2% to 10% w/v, said collagen being present in an amount of more than 75% by dry weight of the patch, and one or more cosmetic ingredients, and provides a collagen-based patch for the topical delivery of collagen and optionally one or more cosmetic or other active ingredients to the skin. Cosmetic product ingredients may be included in the patch to improve the appearance of the skin, enhance skin rejuvenation, moisturize the skin, prevent or reduce the formation of wrinkles, whiten the skin, and provide anti-aging care.

Description

Preparation method of collagen and preparation method of application thereof

Technical Field

The invention relates to the technical field of cosmetology, in particular to the technical field of derivatives, and particularly relates to a preparation method of collagen, an instant cosmetic patch based on the collagen and a preparation method of the instant cosmetic patch.

Background

The beauty treatment films are divided into facial masks, pleura, eye masks and the like. Taking a facial mask as an example, commercially available facial masks are classified into an unformed facial mask and a formed facial mask, wherein the unformed facial mask is also classified into a paste facial mask and a powder facial mask.

Disclosure of Invention

The invention aims at the problems and provides an instant cosmetic patch based on collagen, which has the technical scheme that:

an instant cosmetic patch based on collagen, characterized in that: comprises derived collagen and one or more cosmetic ingredients, wherein the derived collagen accounts for more than 75% of the dry weight of the patch, the concentration of the collagen is 0.2-10% w/v,

further, the cosmetic component is at least one moisturizing component or at least one anti-wrinkle component or at least one anti-aging component or at least one whitening component,

further, the cosmetic composition further comprises at least one lipid or at least one oil or at least one yellow or a combination thereof.

Further, the cosmetic composition further comprises hydrolyzed collagen.

Further, the derived collagen is derived bovine collagen or derived porcine collagen or derived human collagen.

In addition, the invention also provides a preparation method of the collagen-based instant cosmetic patch, which is characterized by comprising the following steps: the method comprises the following steps: exposing a solution comprising derivatized collagen and one or more cosmetic ingredients to crosslinking conditions until a film is formed; wherein the crosslinking condition is that a photoinitiator is added in an oxygen-free environment or a common air environment and is exposed in ultraviolet radiation, the radiation time is 10 seconds to 30 minutes, and the wavelength is 254nm under the condition of the ultraviolet radiation.

Further the above method of making further comprises applying the solution to a substrate prior to exposing the solution to crosslinking conditions, the substrate being one of aluminum foil, mylar, non-silicone coating.

Further the above preparation method further comprises spreading the solution on the substrate to a uniform thickness using a film applicator.

Further in the above preparation method: the photoinitiator is riboflavin, sodium persulfate or a combination of the riboflavin and the sodium persulfate, wherein the use concentration of the riboflavin is 0.0001-0.02% w/v, and the concentration of the sodium persulfate is 0.1-2% (w/v).

The invention also provides a preparation method of the collagen, which is characterized by comprising the following steps: the method comprises the following steps:

1-filtration of 200mL of 3mg/mL purified soluble collagen through 0.45um and 0.2um cartridge filters;

2-place the filtered collagen in a 500mL beaker and adjust the pH to 9.0 using 10N and 1N NaOH;

3-after stirring for 5 minutes at room temperature, slowly adding the crushed glutaric anhydride powder to the stirred collagen solution at a concentration equal to 10% of collagen, maintaining the pH of the collagen solution at 9.0 by adding 10n naoh droplets;

the 4-glutaric anhydride reaction was continued for 15-30 minutes, at which time drops of 6N HCl and 1N HCl were added to lower the pH by about 4.5 at the highest to precipitate the derived collagen.

Placing the 5-derived collagen into a 50mL centrifuge tube, and centrifuging at 3500-;

6-dissolving the recovered precipitate by adding 10N NaOH and 1N NaOH drops to adjust the pH to 7.2;

7-monitoring the pH while NaOH is mixed with the derivatized collagen, placing the transparent collagen gel after neutralization into a 50mL centrifuge tube, centrifuging to remove air bubbles, and then storing the collagen gel at refrigerated temperatures, waiting for the preparation of a cosmetic patch containing the active ingredient.

The present invention provides a collagen-based patch for the topical delivery of collagen and optionally one or more cosmetic or other active ingredients to the skin. Cosmetic product ingredients may be included in the patch to improve the appearance of the skin, enhance skin rejuvenation, moisturize the skin, prevent or reduce the formation of wrinkles, whiten the skin, and provide anti-aging care.

Detailed Description

To make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to specific embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The invention provides an instant cosmetic patch based on collagen, which has the technical scheme as follows:

Further, the cosmetic composition further comprises hydrolyzed collagen.

The invention will now be further elucidated by means of specific examples:

example 1: preparation of chemically derived collagen

200mL of 3mg/mL purified soluble collagen (Porcogen, Lot 531131080 or internally prepared bovine collagen made from calf skin) was filtered through 0.45um and 0.2um cartridge filters. The filtered collagen was placed in a 500mL beaker and the pH was adjusted to 9.0 using 10N and 1N NaOH. After stirring for 5 minutes at room temperature, the comminuted glutaric anhydride powder (Sigma, > 95%) was slowly added to the stirred collagen solution at a concentration equal to 10% of the collagen (60 mg). The pH of the collagen solution was maintained at 9.0 by the addition of 10N NaOH droplets. The glutaric anhydride reaction was continued for 15-30 minutes, at which time 6N HCl and 1N HCl drops were added to lower the pH up to about 4.5 to precipitate the derived collagen. The derivatized collagen is then placed into a 50mL centrifuge tube or flask and centrifuged at 10,000rpm to pellet the derivatized collagen. The recovered precipitate was then dissolved by adjusting the pH to 7.2 by adding drops of 10N NaOH and 1N NaOH. The pH was monitored as NaOH was mixed with the derivatized collagen pellets. The neutralized, clear and transparent collagen gel is then placed in a centrifuge tube or vial and centrifuged to remove air bubbles. The transparent, degassed collagen gel is stored at refrigeration temperatures, waiting for the manufacture of a dissolvable, collagen-based cosmeceutical film containing the active ingredient, thereby improving skin appearance and enhancing skin rejuvenation. If desired, the derivatized collagen gel is diluted with a neutral pH solution to reduce concentration and viscosity.

Example 2: fabrication of collagen films that are not exposed to ultraviolet radiation;

the chemically derivatized collagen prepared in example 1 was removed from the refrigerator and warmed to room temperature. Thin films without active ingredients were prepared in glass petri dishes or placed on glass plates to form a thin layer of liquid collagen. The glass petri dish or glass plate was then placed in a laminar flow hood to dry the solution into a thin film. The film was removed from the glass plate, cut to the desired size, measured by caliper, placed in a plastic bag, labeled, and then stored at refrigeration temperatures. The dissolution time of the samples was evaluated by the following method: (1) placing the film on the skin surface and checking the dissolution rate over a period of time; or (2) place the film (dyed with pimcrospirus red) on wet cheesecloth and then place the sample in an oven at 35 ℃. Dissolution was observed when the film melted and the stain penetrated the wet cheesecloth substrate. Dissolution occurred within 30 minutes.

Example 3: preparation of collagen film stabilized by exposure to 254nm ultraviolet radiation in Nitrogen

The chemically derivatized collagen solution (6.7mg/mL) prepared in example 1 was removed from the refrigerator and cast into a thin wet sheet by placing the collagen solution on a polyester support film (Cheever #520) using a micron film. Coater (knife bar) to provide a wet film thickness of 0.05 inches (about 1.3 mm). The wet collagen film was placed in a controlled nitrogen chamber, which was flushed with nitrogen to eliminate oxygen. The uv light in the chamber is activated and the film is exposed to 254nm uv light for 10 to 17 minutes. The resulting stabilized collagen film was removed from the chamber and its solubility and skin moisturization were evaluated by placing a film sample on the skin on the back of the hand. A film exposed to uv radiation for less than 12 minutes provides a collagen film that is moisturized and can be easily rubbed into the skin within 30 minutes. Films exposed to uv radiation for more than 12 minutes are more stable, less moisture-retaining, and "rub" the film into the skin surface with the application of finger pressure and do not dissolve completely.

Example 4: preparation of collagen films stabilized by exposure of photoinitiators to 254nm ultraviolet radiation in an air atmosphere

Three milliliters of 0.3M sodium persulfate was added to the chemically derivatized collagen as prepared in example 1 to make a total volume of 30 mL. An aliquot of this solution was placed in a glass petri dish to cover the bottom surface. The dish lid was removed and the thin layer of collagen was exposed to 254nm UV light for 30 seconds. The hard and moist collagen film was removed and the sections were placed on the back of the hand to assess hand feel and solubility. Within 10 minutes, the wet film shrinks, leaving a small dry film that can be wetted with a drop of water and then rubbed smoothly into the skin by finger movement. The treated part feels comfortable.

Example 5: preparation of collagen films stabilized by exposure to 254nm UV light in nitrogen using the photoinitiator sodium persulfate

The chemically derivatized collagen solution prepared in example 1 was removed from the refrigerator. Sodium persulfate was mixed into the collagen solution prepared according to example 1 at a concentration of 2.5% to 10% (w/v), heated to 28 ℃ or 30 ℃, and the solution was dissolved in an aluminum pot, and then the solution was dispersed into a sheet, and finally cast into a thin wet sheet. The sheet was irradiated with UV light at 254nm in nitrogen for 20 seconds. The resulting film was examined for firmness. The film containing 10% sodium persulfate was very strong, while the film containing 2.5% sodium persulfate did not cure. The membrane exposed to 5% sodium persulfate was firm and slightly wet.

Example 6: preparation of collagen film stabilized by exposure to 254nm UV radiation with photoinitiator riboflavin in nitrogen

The chemically derivatized collagen solution (5.5mg/mL) prepared in example 1 was removed from the refrigerator. The riboflavin solution was mixed into the collagen solution at a concentration of 0.001 to 0.008% and the collagen solution was placed on an aluminum foil and spread into a small film with a pipette (1/2 "x 1-1/2"). The plate was irradiated twice with 254nm UV light in nitrogen at 30 second intervals. All the resulting films cured well except for the lower riboflavin concentration solution (0.001%). Samples containing 0.002% and 0.004% riboflavin provided the best moisturizing and hydrating effect when placed on the skin on the back of the hand.

Example 7: preparation of collagen films prepared from hydrolyzed collagen formulations stabilized by exposure to 254nm ultraviolet light

The hydrolyzed solution (5.5mg/mL) of the chemically derivatized collagen solution prepared in example 1 was prepared by heating the solution to 38 ℃ for 30 minutes. A200. mu.L aliquot was placed on aluminum foil and exposed to 254nm UV light for 30 minutes. Wet collagen films are weak, but can be rubbed against the skin by finger pressure when placed on the back of the hand.

Example 8: preparation of a collagen film prepared from chemically derived collagen containing hydrolyzed collagen and stabilized by exposure to 254nm ultraviolet radiation

The hydrolyzed collagen solution was prepared as described in example 7. Three sets of chemically derived collagen (unhydrolyzed) solutions were prepared with hydrolyzed collagen dissolved: to 1ml of chemically derived collagen was added 3ml of hydrolyzed collagen, to 2ml of chemically derived collagen was added 2ml of hydrolyzed collagen, and to 3ml of chemically derived collagen was added 3ml of hydrolyzed collagen. Films were prepared as described in example 7 and examined for firmness and dorsum manus and moisture retention. None of the centers of the films were completely cured. In subsequent studies, the sample was exposed to 254nm UV light, and 250uL of hydrolyzed collagen was mixed with 1570 uL of the base-derived collagen, and 125uL of hydrolyzed collagen was mixed with 1875uL of the base-derived collagen, forming a firm, wet film.

Example 9: preparation of collagen film prepared from chemically derivatized collagen containing hyaluronic acid and stabilized by exposure to 254nm ultraviolet radiation

The chemically-derived collagen solution (5.5mg/mL) prepared in example 1 was removed from the refrigerator storage and supplemented with hyaluronic acid (LifeCore Biomedical) of different concentrations and molecular weights. Molecular weights include 5,000, 20,000, 100,000 and 500,000 daltons. The concentration of each ranged from 1mL per 6mL of derivatized collagen to 3mL per 6mL of derivatized collagen. Hyaluronic acid of various molecular weights and concentrations was mixed to the basal derived collagen sample, placed on aluminum foil, and irradiated under nitrogen at 254nm uv for 30 minutes. When all samples were placed on the skin on the back of the hand, they cured well, producing a moist, cool feel film. The moisturizing and comfort of samples containing a mixture of high and low molecular weight hyaluronic acids is most desirable.

Example 10: collagen film prepared from chemically derived collagen containing active ingredient with moisturizing, wrinkle preventing or removing, skin whitening and antiaging effects

A: collagen films were prepared by exposure to 254nm uv radiation in nitrogen as described above. The active ingredient was added to the collagen gel before forming the membrane, and then a thin layer was cast on the solid backed aluminum foil. The active ingredients included 250 μ L of nut oil and chia seed oil, 500 μ L of lecithin solution per 5mL of collagen solution. The samples were spread on a solid backing and exposed to uv irradiation at 254nm for 2 minutes to form a film.

B: collagen films were prepared by exposure to 254nm uv radiation in nitrogen as described above. The active ingredient is added to the collagen gel before forming the membrane, and then a thin layer is cast on the solid backing. The ingredients include rosehip oil (2.4-7% in collagen solution) and nut oil (2.4-7% w/v in collagen solution). The samples were placed on an aluminum backing plate and spread onto wet paper using a knife bar set at 0.025 inch (about 0.6 mm). The tablets were placed in a nitrogen chamber and exposed to uv light at 254nm for 10 minutes. All samples formed a slightly whitish film.

Production and testing of various collagen films

Collagen membranes are prepared under a variety of conditions and with a variety of components. In each membrane, a derivatized collagen solution prepared as described in example 1 was used. Unless otherwise stated, crosslinking was carried out in the absence of photoinitiator under nitrogen at a wavelength of 254nm, and the collagen solution was not allowed to dry prior to crosslinking. In each experiment, unless otherwise stated, the collagen solution was heated to room temperature prior to crosslinking. The results of the experiment were judged to be positive (+) or negative (-) depending on the observed properties of the membrane.

Altering collagen concentration and crosslinking time

1: collagen films were prepared by dispensing 1000 μ L of undiluted or diluted derivatized collagen solution to cover a 0.5 inch by 0.5 inch (about 13 mm by 13 mm) square

Aluminum foil, then cross-linked for the time indicated in table 1.

2-collagen films were also prepared by: dispense 500 μ L of derivatized collagen solution to cover a 0.75 inch (about 19mm) diameter

The aluminum foil rings were then cross-linked for the times shown in table 2.

Different film thicknesses

3: collagen films were prepared on Reynolds Wrap aluminum foil substrates and the thickness of the films was varied by setting 0.075 inch (about 1.9 mm) on the left side of the film and 0.0000 inch (0 mm) on the right side of the film. Crosslinking was carried out for 20 minutes. The material at the right 1/3 of the foil is too thin, the material at the left 1/4 of the foil is not covering the foil (dewetting), while the material in the middle of the foil has a good consistency and forms a good film. The ideal thickness appears to be about 0.045 inch (about 1.1mm) according to the experiment. Films at this thickness were observed to have good elasticity and suitable dry humidity.

In a second set of experiments, different volumes of collagen solution were dispensed into aluminum foil 9.365cm in diameter

Round and cross-linked for 25 minutes.

Altering preheating and crosslinking time of collagen

4-5: the collagen solution was pre-heated by dispensing 500. mu.l to cover a diameter of 0.75 inches (about 19mm)

The collagen film was prepared by aluminum foil winding and then cross-linking for the time shown in table 4.

Sodium persulfate and riboflavin as photoinitiators

6-collagen membranes were prepared using varying amounts of sodium persulfate as the photoinitiator. By dispensing 3.125ml of a collagen solution containing a certain amount of sodium persulfate before crosslinking into 9.365cm diameter pieces

All films were made on aluminum foil circles. All membranes were moisture crosslinked except for the membranes of experiments 12 and 13, which were crosslinked after drying.

7-A second set of experiments was performed using different amounts of riboflavin as photoinitiator. All derivatized collagen solutions were pre-warmed to room temperature and then 8 drops were dispensed and cross-linked for 1 minute on a 0.5 inch by 0.5 inch (about 13 mm by 13 mm) silicone free SuperPolyfoil (TM) (Fisher scientific) square.

Different substrates

Results of crosslinking for 20 minutes

Crosslinking for 30 minutes.

A 0.025 inch thick film (about 0.6 mm) can be made by dispensing a quantity of derivatized collagen solution onto a substrate, spreading the solution to a uniform thickness using a film applicator, and then cross-linking.

It was concluded from these experiments that the best substrates were uv resistant (to avoid collagen solidification onto the substrate) and hydrophilic (to limit moisture reduction). Based on the positive results for films made using Cheever # 520-92 g PET substrate, the substrate was selected for further evaluation. A series of 0.05 inch (about 1.3 mm) thick films were made using different crosslinking times.

Films incorporating other ingredients

Derivatized collagen films are prepared using a variety of different cosmetic ingredients.

In a first set of experiments, 0.015%, 0.045% or 0.09% hyaluronic acid with an average molecular weight of 1M daltons was used

The aluminum foil substrate is made into a collagen film. The membrane was crosslinked for 30 minutes. Each film cured well and was somewhat pasty, but dried to the touch.

In a second set of experiments, collagen films with various compositions were made on a silica-free Super polyfoil (Fisher scientific) matrix using riboflavin as a photoinitiator.

Silicone-free Super polyfoil (Fisher Scientific) matrix, photoinitiator-free.

Collagen films of hyaluronic acid at various concentrations with different molecular weights were prepared on Super polyfoil (FisherScientific) without silicone using riboflavin as a photoinitiator.

Derivatized collagen films of varying concentrations of hyaluronic acid with varying molecular weights were prepared on a silicone-free Super polyfoil (Fisher Scientific) without photoinitiator. All membranes were crosslinked for 30 minutes.

Derivatized collagen films of various blends of hyaluronic acid with different molecular weights were prepared on a silicone-free Super polyfoil (Fisher Scientific) without photoinitiator. All membranes were crosslinked for 30 minutes.

Derivatized collagen films with varying amounts of hydrolyzed collagen were prepared on Super polyfoil (Fisher Scientific) without silicone. All membranes were crosslinked for 30 minutes.

Derivatized collagen films with different compositional content were made on Super polyfoil (Fisher Scientific) without silicon. All membranes were crosslinked for 5 minutes. The film is then transferred to a second substrate.

Derived collagen films with varying amounts of rosehip oil and nut oil were made on Cheever #520 substrates. All membranes were crosslinked for 10 minutes.

Example 11: production of collagen film containing active ingredient for moisturizing and preventing wrinkle

Collagen membranes were prepared as described in examples 3-6. The active ingredient is added to the collagen gel prior to forming the membrane. In one preparation, acetyl hexapeptide-3 (Argireline) was added to the liquefied collagen in an amount of 0.5% prior to film formation. In another preparation, ceramide is added at 0.25% to liquefied collagen prior to forming the membrane. In a third preparation, glycerol and retinol were added to the liquefied collagen at a ratio of 1% before forming the membrane. After film preparation, the samples were examined for skin moisturization and the ability to wipe into the skin after application by placing the film on the back of the hand. After 30 minutes of application, the film can be rubbed into the skin. The skin feels moist.

Example 12: preparation of collagen membrane containing anti-aging active ingredient

Collagen membranes were prepared as described in examples 3-6. The active ingredient is added to the collagen gel prior to forming the membrane. In one formulation, epidermal growth factor was added to liquefied collagen at a ratio of 0.5% prior to film formation. After film preparation, the samples were examined for skin moisturization and the ability to wipe into the skin after application by placing the film on the back of the hand. After 30 minutes of application, the film can be rubbed into the skin. The skin feels moist.

Example 13: preparation of collagen film containing skin whitening active ingredient

Collagen membranes were prepared as described in examples 3-6. The active ingredient is added to the collagen gel prior to forming the membrane. In one preparation, dimethicone was added to the liquefied collagen at 0.5% prior to film formation, or niacinamide was added to the liquefied collagen at 0.5% prior to film formation, or tetrahydrocurcuminoids were added to the liquefied collagen at 0.5% prior to film formation. After film preparation, the samples were examined for skin moisturization and the ability to wipe into the skin after application by placing the film on the back of the hand. After 30 minutes of application, the film can be rubbed into the skin. The skin feels moist.

Example 14: production of collagen films containing nanoparticle active ingredients

Collagen membranes were prepared as described in examples 3-6. Prior to forming the membrane, the active ingredient in the form of nanoparticles is added to the collagen gel prior to forming the membrane. After film preparation, the samples were examined for skin moisturization and the ability to wipe into the skin after application by placing the film on the back of the hand. After 30 minutes of application, the film can be rubbed into the skin. The skin feels moist.

In summary, the following steps: the present invention provides a collagen-based film for the topical delivery of collagen and optionally one or more cosmetic or other active ingredients to the skin. Cosmetic product ingredients may be included in the films of the present invention to improve skin appearance, enhance skin rejuvenation, moisturize skin, prevent or reduce wrinkle formation, whiten skin, and provide anti-aging care.

The present invention also provides a cosmetic product comprising one or more cosmetic films.

The substrate of the beauty product comprises the beauty patch of the invention. The substrate may be any suitable material, for example an aluminium foil or a polymeric film, for example a polyester film cosmetic product may further comprise packaging, for example a sachet, rigid container or box.

The present invention also provides methods for making cosmetic films and cosmetic products.

The present invention also provides methods of delivering collagen and/or one or more cosmetic ingredients to the skin, e.g., the face, of a subject using the cosmetic films and cosmetic products of the present invention.

The present invention provides collagen-based cosmetic films that can be used to deliver one or more ingredients contained in the film to the skin. The cosmetic film of the present invention provides a number of advantages. For example, cosmetic films can be used to deliver cosmetic compositions requiring effective dosages and precise placement. The dosage of the ingredient may be adjusted, for example, by adjusting the concentration of the ingredient in the film and/or by adjusting the size of the film, and the solid nature of the film allows it to be placed anywhere on the body, with the intention of rejuvenating the skin. In addition, the cosmetic film may be rubbed into the skin after it is applied to the skin, such that all or substantially all of the ingredients in the cosmetic film remain on the skin after application. The amount of time the cosmetic film of the present invention needs to be worn before the film can be rubbed into the skin can be adjusted by controlling the amount of cross-linking of the derivatized collagen in the film.

The present invention provides collagen-based cosmetic films that can be used to deliver one or more ingredients contained in the film to the skin. The beauty mask of the present invention has the following advantages. For example, cosmetic films can be used to deliver an effective dose of a cosmetic ingredient to a particular target site. The dosage of the ingredient may be adjusted by adjusting the concentration of the ingredient in the film and/or by adjusting the size of the film, and the solid nature of the film allows it to be placed anywhere on the body, with the desire to rejuvenate the skin. In addition, after the cosmetic film is applied to the skin, it may be rubbed into the skin so that all or substantially all of the ingredients in the cosmetic film remain on the skin after application. The amount of time a cosmetic film of the present invention needs to be worn before the film can be rubbed into the skin can be adjusted by controlling the amount of cross-linking of the derivatized collagen in the film.

The cosmetic film of the present invention comprises a derivatized collagen, one or more cosmetic ingredients. By "derivatized collagen" is meant derivatized soluble collagen. A photoinitiator may also be included for crosslinking of the collagen.

The cosmetic film forms an adherent dry film after being applied to the skin for a period of time, for example, 20 minutes or less, 30 minutes or less, 40 minutes or less, in an environment of room temperature and humidity of 30% or less.

In some embodiments, the film is capable of remaining in contact with dry facial skin of an upright individual for at least 20, 30, or 40 minutes in an environment of room temperature and ≦ 30% humidity, so that the user need not lie down during use.

Ideally, a cosmetic film for cosmetic applications should be strong enough not to tear during application, and the film should be able to transfer from a substrate (e.g., an uncoated aluminum foil substrate) to skin (e.g., facial skin) without tearing.

The cosmetic film may be manufactured to have a size suitable for cosmetic applications. For example, the membrane may be facial shaped such that the membrane may be used as a facial mask. The mask may further include incisions for the eyes, mouth and nose to make the mask more comfortable for the user. These films can be made in different sizes and shapes when intended for use on different skin sites. For example, the membrane for the periphery of the eye may be kidney shaped to match the area around the eye that typically surrounds the crow's feet, while the membrane for the forehead or neck may be rectangular and sized to cover the forehead or neck. Thus, the membranes of the present invention can have a variety of shapes, including facial shapes, rectangular with rounded edges, rectangular without rounded edges, circular, elliptical.

The thickness of the cosmetic film may vary, but is preferably in the range of 0.4mm to 2 mm. In some embodiments, the cosmetic film has a thickness of 0.5mm to 1.5 mm. In other embodiments, the cosmetic film has a thickness of 0.6mm to 1.2 mm. In a preferred embodiment, the thickness of the film is uniform.

Acylating agents can be used to change the net charge of collagen from positive to negative and to make derivatized collagen useful in the membranes of the invention. Exemplary acylating agents that can be used to derivatize collagen include acid anhydrides, acid chlorides, sulfonyl chlorides, and sulfonic acids. Exemplary anhydrides include maleic anhydride, succinic anhydride, glutaric anhydride, citraconic anhydride, methylsuccinic anhydride, itaconic anhydride, methylglutaric anhydride, dimethylglutaric anhydride and phthalic anhydride. Exemplary acid chlorides include oxalyl chloride and malonyl chloride. Exemplary sulfonyl chlorides include chlorosulfonyl acetyl chloride, chlorosulfonyl benzoic acid, 4-chloro-3- (chlorosulfonyl) -5-nitrobenzoic acid, and 3- (chlorosulfonyl) -P-anisic acid. An exemplary sulfonic acid is 3-sulfobenzoic acid.

The derived collagen used in the cosmetic film of the present invention may be a single type of derived collagen (e.g., glutaryl collagen or succinylated collagen) or a mixture of multiple types of derived collagen (e.g., a mixture of glutaryl collagen and succinyl). In a preferred embodiment, the derived collagen used in the collagen membrane comprises or consists of glutaryl collagen.

The derived collagen may be made from collagen from any suitable source. For example, the collagen may be bovine collagen, porcine collagen or human collagen. The collagen may be of animal origin (e.g., from bovine or porcine skin) or recombinant (e.g., recombinant human collagen). The derived collagen may consist of collagen from a single species, or may comprise a mixture of collagens from different species. For example, the derived collagen may consist of derived bovine collagen, derived porcine collagen or derived human collagen. As another example, the derived collagen may be a mixture of bovine collagen and porcine collagen.

Although films containing no water are also within the scope of the present invention, the cosmetic film of the present invention preferably comprises water. The concentration of the derivatized collagen in the membrane may vary, with preferred concentrations being 0.2% to 10% w/v. In some embodiments, the concentration of the derivatized collagen in the membrane is 0.2% to 5% w/v, 0.2% to 2% w/v, 0.2% to 1% w/v, 1% to 10% w/v, 1% to 5% w/v, 5% to 10% w/v, or a range defined by any two of the foregoing.

The derived collagen may be the primary non-aqueous component of the collagen membrane. The weight of the derived collagen in the membrane may be greater than any other non-aqueous component. For example, the derived collagen may comprise at least 50% of the dry weight of the membrane. In some embodiments, the derivatized collagen comprises at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 90%, or at least 95%. At least 97% or at least 99% of the dry weight of the film. In some embodiments, the derivatized collagen comprises up to 80%, up to 85%, up to 90%, up to 95%, up to 97%, or up to 99% of the dry weight of the membrane.

Alternatively, the amount of derivatized collagen in the cosmetic film of the invention may be less than the weight of the at least one other non-aqueous component.

The cosmetic film of the present invention preferably comprises one or more cosmetic ingredients. The skin caring component comprises moisture keeping component, anti-wrinkle component, antiaging component and whitening component.

Exemplary moisturizing ingredients that may be included in the cosmetic film include Hyaluronic Acid (HA), hydrolyzed collagen, glycerin, aloe vera juice, lipids (e.g., lecithin), oils (e.g., argan oil, great seed oil, linseed oil), rosehip oil), butter (e.g., almond) and combinations thereof. Exemplary anti-wrinkle ingredients include acetyl hexapeptide-3, HA, glycerol, retinol, ilomastat, ceramide, and combinations thereof. Exemplary anti-aging ingredients include epidermal growth factor, acetyl hexapeptide-3, ceramide, HA, retinol, soluble collagen and combinations thereof. Exemplary skin lightening ingredients include dimethicone, niacinamide, tetrahydrocurcumin, glutathione and combinations thereof. The identification of cosmetic ingredients as moisturizing, anti-wrinkling, anti-aging or skin whitening ingredients herein does not preclude their use for other purposes. The cosmetic ingredient may optionally be included in the cosmetic film in the form of nanoparticles and/or liposomes.

In some embodiments, the cosmetic film comprises HA. HA may comprise up to 15%, up to 10% or up to 5% by weight of the membrane. Alternatively or additionally, HA may comprise at least 0.1%, at least 1% or at least 2% by weight of the membrane. HA having various average molecular weights may be used in cosmetic films. The average molecular weight of HA may range from 1kDa to 4MDa, 1kDa to 5kDa, 5kDa to 50kDa, 50kDa to 100kDa, 100kDa to 500kDa 5kDa to 500kDa, 500kDa to 1MDa, or any range bounded by any two of the above values. In some embodiments, the cosmetic film comprises HA having an average molecular weight of 5kDa, 20kDa, 100kDa, or 500 kDa.

The cosmetic film may be made of a mixture of two or more HA's having different average molecular weights, said average molecular weights being selected from the molecular weight ranges or values determined, for example, in the preceding paragraph. For example, the cosmetic film may comprise a weight ratio of 1: 5 to 5: 1, mixture of two HA populations. In some embodiments, the ratio of the two HA populations is 1: 3 to 3: 1. high average molecular weight HA (e.g., 500kDa) is contained in a low average molecular weight HA (e.g., 5kDa) film. In some embodiments, at least 25%, at least 50% or at least 75% of the HA in the membrane HAs an average molecular weight of at least 100 kDa. In some embodiments, at least 25%, at least 50% or at least 75% of the HA in the membrane HAs an average molecular weight of at least 500 kDa. In some embodiments, at least 25%, at least 50%, or at least 75% of the HA in the film HAs an average molecular weight of at least 1 MDa. In some embodiments, the average molecular weight of the HA in the membrane is at least 100kDa, at least 250kDa, at least 500kDa, or at least 1 MDa. In some embodiments, the average molecular weight of the HA in the film is no more than 4 MDa.

In some embodiments, the cosmetic film comprises hydrolyzed collagen. The hydrolyzed collagen may be included in the membrane at a weight in the range of 0.1% to 2% by weight of the membrane. Preferably, the hydrolyzed collagen comprises less than 1.5% or less than 1% by weight of the film.

In some embodiments, the cosmetic film comprises one or more lipids, one or more oils, one or more butters, or a combination thereof. In some embodiments, the lipid, oil, butter, and combinations thereof may be included in the cosmetic film in an amount of up to 15% w/v, up to 10% w/v, or up to 5% w/v.

Photoinitiators can be used to promote crosslinking of the derivatized collagen in the collagen membrane. Suitable photoinitiators include sodium persulfate and riboflavin. The riboflavin may be included in the cosmetic film in an amount ranging from 0.0001% to 0.02% (w/v). In some embodiments, the amount of riboflavin is 0.001% to 0.01% (w/v). In some embodiments, the amount of riboflavin is 0.001% to 0.008% (w/v). Sodium persulfate may be included in the membrane in an amount ranging from 0.1% to 15%. In some embodiments, the amount of sodium persulfate is from 0.1% to 2% w/v. In some embodiments, the amount of sodium persulfate is from 0.25% to 1%.

The cosmetic film may be formed directly on the substrate or may be transferred to the substrate after formation. The substrate on which the cosmetic film is formed directly is preferably non-reactive during the cross-linking step to avoid cross-linking the derivatized collagen to the substrate. Preferably, the substrate on which the cosmetic film is formed is hydrophilic to avoid dewetting of the substrate surface. Exemplary substrates that may be used in the present cosmetic product include aluminum foil, substrates with non-silicone coatings, substrates with polyester surfaces (e.g., Fisher super polyfoil (TM)), polyester films (e.g., polyethylene terephthalate films), and polypropylene films.

The cosmetic can be further packaged. For example, the cosmetic product may include a pouch or wrapper for containing a cosmetic film, a rigid container for containing one or more films, a box, or a combination thereof.

The cosmetic film may be prepared by drying a solution of the derived collagen (e.g., by "drying" the solution using a laminar flow hood or similar air flow or by circulating the solution by placing it in an oven) and/or subjecting the solution or dried solution to crosslinking conditions to crosslink the derived collagen. The derived collagen solution is not dried prior to crosslinking.

The derivatized collagen solution can optionally be heated to up to 45 ℃ (e.g., to 20 ℃ to 25 ℃, 25 ℃ to 30 ℃, 30 ℃ to 35 ℃, 35 ℃ to 40 ℃, or 40 ℃ to 45 ℃) prior to forming the cosmetic film.

One or more cosmetic ingredients may be included in the derivatized collagen solution prior to drying and/or crosslinking. Alternatively or additionally, one or more cosmetic ingredients may be added to the cosmetic film after drying and/or crosslinking (e.g., by adding one or more cosmetic ingredients to the surface of the cosmetic film). Crosslinking may be performed using Ultraviolet (UV) radiation, preferably using a wavelength of about 254 nm.

Crosslinking may be carried out under normal atmospheric conditions. Alternatively, crosslinking may be carried out in an oxygen-free environment, for example, under nitrogen. The length of the UV radiation may be in the range of, for example, 10 seconds to 30 minutes (e.g., 20 seconds to 5 minutes, 5 minutes to 10 minutes, 10 minutes to 20 minutes, or 20 minutes to 30 minutes). When a photoinitiator is used, a shorter crosslinking time may be used.

The amount of time required for crosslinking can be adjusted depending on the preheating conditions, the collagen concentration, the presence of photoinitiators and the presence, amount and type of different cosmetic ingredients. For example, containing oil-based components, low molecular weight HA or hydrolyzed collagen may require longer cross-linking times (see, e.g., tables 7 and 12 (compare films made without and with oil), table 14 (compare films made) with HA of different molecular weights) and table 17 (compare films made with different amounts of hydrolyzed collagen). On the other hand, using a photoinitiator and preheating the derivatized collagen can shorten the required crosslinking time (see, e.g., table 6 (compare films made with different amounts of sodium persulfate) and tables 4 and 5 (compare films made with different collagens) preheating conditions and crosslinking time)).

Exemplary photoinitiators include riboflavin and sodium persulfate. The riboflavin may be included in the derivatized collagen solution in an amount of 0.0001% to 0.02% (w/v). In some embodiments, the amount of riboflavin is 0.001% to 0.01% (w/v). In some embodiments, the amount of riboflavin is 0.001% to 0.008% (w/v). Sodium persulfate may be included in the derivatized collagen solution in an amount of 0.1% to 15%. In some embodiments, the amount of sodium persulfate is from 0.1% to 2% w/v. In some embodiments, the amount of sodium persulfate is from 0.25% to 1%.

The method of making the present cosmetic film may further comprise forming a solution for making the film by mixing the solution of derivatized collagen with one or more cosmetic ingredients and optionally one or more photoinitiators.

A uniform thickness membrane can be prepared by spreading the derivatized collagen solution on a suitable substrate using a membrane applicator (e.g., Gardco micro membrane applicator) prior to crosslinking or drying. When preparing the cosmetic film of the present invention, the solution may be spread to a desired thickness, for example, a thickness in the range of 0.4mm to 2 mm. In some embodiments, the solution is spread to a thickness of 0.5mm to 1.5 mm. In other embodiments, the cosmetic film is spread to a thickness of 0.6mm to 1.2 mm.

Suitable substrates on which the cosmetic films of the present invention may be formed include aluminum foil, some polyester films and some substrates having non-silicone coatings, such as the Cheever #520 substrate described in the examples. The cosmetic film may optionally be transferred to a second substrate after formation (e.g., from an aluminum foil substrate to a polyester substrate).

Method for delivering derived collagen and/or cosmetic ingredients to skin

The present invention provides a method of delivering collagen and/or one or more cosmetic ingredients to the skin, the method comprising applying the cosmetic film of the present invention to the skin of a subject. The subject is preferably a human, e.g., an adult over the age of 20, 30, 40, 50 or 60 years old. In some embodiments, the subject is a female.

The cosmetic film may be applied to any skin surface where delivery of collagen and/or one or more cosmetic ingredients is desired. For example, the cosmetic film may be applied to the face or one or more portions thereof (e.g., the eyes, the forehead or the area around the nasolabial folds), the neck or anywhere on the body. After the film is applied to the surface for a period of time, e.g., 10 to 60 minutes, 10 to 30 minutes, 10 to 20 minutes, or 20 to 30 minutes, the film may be wiped onto the skin of the subject. In some embodiments, the film may remain on the skin for at least 10 minutes, at least 20 minutes, at least 30 minutes. Preferably, after the film is formed into an adherent dry film, the film is wiped onto the skin. By rubbing the membrane into the skin of the subject, rather than removing the membrane, all or substantially all of the collagen and cosmetic ingredients in the membrane remain on the skin of the subject. Before wiping the film onto the skin, the film may be wetted with water or a liquid cosmetic, such as a lotion, to help disperse the ingredients in the film onto the skin surface.

Finally, it should be noted that: the above-mentioned embodiments are only specific embodiments of the present invention, which are used for illustrating the technical solutions of the present invention and not for limiting the same, and the protection scope of the present invention is not limited thereto, although the present invention is described in detail with reference to the foregoing embodiments, it should be understood by those skilled in the art that: those skilled in the art can still modify or easily conceive of the technical solutions described in the foregoing embodiments or make equivalent substitutions for some technical features within the technical scope of the present disclosure; such modifications, changes or substitutions do not depart from the spirit and scope of the embodiments of the present invention, and they should be construed as being included therein.

Claims

1. An instant cosmetic patch based on collagen, characterized in that: comprises derived collagen and one or more cosmetic ingredients, wherein the derived collagen accounts for more than 75% of the dry weight of the patch, and the concentration of the collagen is 0.2-10% w/v.

2. A collagen-based, instant cosmetic patch as claimed in claim 1, wherein: the cosmetic component is at least one moisturizing component or at least one anti-wrinkle component or at least one anti-aging component or at least one whitening component.

3. A collagen-based, instant cosmetic patch as claimed in claim 2, wherein: the cosmetic composition further comprises at least one lipid or at least one oil or at least one yellow or a combination thereof.

4. A collagen-based, instant cosmetic patch as claimed in claim 1, wherein: the cosmetic composition further comprises hydrolyzed collagen.

5. A collagen-based, instant cosmetic patch as claimed in claim 1, wherein: the derived collagen is derived bovine collagen or derived porcine collagen or derived human collagen.

6. A preparation method of an instant cosmetic patch based on collagen is characterized by comprising the following steps: the method comprises the following steps: exposing a solution comprising derivatized collagen and one or more cosmetic ingredients to crosslinking conditions until a film is formed; wherein the crosslinking condition is that a photoinitiator is added in an oxygen-free environment or a common air environment and is exposed in ultraviolet radiation, the radiation time is 10 seconds to 30 minutes, and the wavelength is 254nm under the condition of the ultraviolet radiation.

7. A process for the preparation of a collagen-based instant cosmetic patch as claimed in claim 6, wherein: comprising applying the solution to a substrate, the substrate being one of an aluminum foil, a mylar, a non-silicone coating, prior to exposing the solution to crosslinking conditions.

8. A method of preparing a collagen-based instant cosmetic patch as claimed in claim 7, wherein: also included is spreading the solution to a uniform thickness on the substrate using a film applicator.

9. A method of manufacturing a collagen-based quick-dissolving cosmetic patch according to claim 8, wherein: the photoinitiator is riboflavin, sodium persulfate or a combination of the riboflavin and the sodium persulfate, wherein the use concentration of the riboflavin is 0.0001-0.02% w/v, and the concentration of the sodium persulfate is 0.1-2% (w/v).

10. The method for preparing collagen according to claim 1, wherein: the method comprises the following steps:

3-after 5 minutes of stirring at room temperature, slowly adding the crushed glutaric anhydride powder to the stirred collagen solution at a concentration equal to 10% of the collagen, maintaining the pH of the collagen solution at 9.0 by adding 10N NaOH drops;

7-while NaOH is mixed with the derivatized collagen, pH is monitored, the transparent collagen gel after neutralization is placed in a 50mL centrifuge tube, air bubbles are removed by centrifugation, and the collagen gel is then stored at refrigerated temperatures awaiting preparation of a cosmetic patch containing the active ingredient.