TWI584822B - Use of small-molecule polysaccharides - Google Patents

Description

Use of small molecule polysaccharides

The present invention relates to the use of a small molecule polysaccharide, in particular to the use of a small molecule polysaccharide for the manufacture of a small molecule polysaccharide anhydrous composition for the treatment of a condition caused by or associated with skin or exocrine glands.

The skin is the primary line of defense against damage in the external environment, such as ultraviolet light, pathogens, friction, etc., and the prevention of water loss. The skin consists of an epidermis composed of sebum, horny layer, granular layer, and basal layer, and a dermal layer mainly composed of connective tissue. (dermis), and subcutaneous tissue. As you age, skin becomes aging, such as wrinkles, fine lines, slacks, depressions, and enlarged pores. The formation of these skin aging phenomena is related to many factors, such as hypoaluronic acid (HA) deficiency and collagen deficiency in the dermis. Among them, insufficient hyaluronic acid will reduce the skin moisture content, thereby reducing skin fullness and elasticity.

Hyaluronic acid, also known as hyaluronic acid or uronic acid, is an important component of the intercellular substance. It is mainly distributed in the dermis layer in the skin and has the function of retaining water. This function comes from the high water absorption of hyaluronic acid molecules, and its water retention value can reach 1000ml/g. The hyaluronic acid molecule is a disaccharide polymer whose disaccharide unit is glucuronic acid and acetylglucosamine. The molecular weight of the hyaluronic acid molecule in the human body ranges from about 5 kDa to 10 MDa.

In order to improve the aforementioned hyaluronic acid deficiency and skin water content reduction with age With fewer problems, the medical beauty industry has developed a variety of water-light injection technologies, such as water-light needles, water-light guns, micro-needle water, etc., all of which use invasive methods to inject more than one million molecular weight of hyaluronic acid into the dermis to improve the skin. Water content, to achieve wrinkles, repair skin sag, improve skin firmness and elasticity, reduce pores and enhance skin light. Although these water-light technologies have significant effects, they are accompanied by anesthesia during implementation, and because the needles pierce the skin epidermis during the implementation process, causing trauma to the skin, the skin is prone to redness and swelling, even bruising and bleeding after a period of implementation. In addition, special skin care is required during this period to avoid skin infections, thus affecting lifestyle arrangements.

Compared with the aforementioned invasive skin care methods, the medical beauty industry has recently developed a non-invasive water-light injection technique, such as using high speed generated by high pressure, to break the hyaluronic acid into a keratinocyte gap through the stratum corneum of the skin. A small molecule of hyaluronic acid (about 40-50 nm) is injected into the epidermal layer of the skin to enhance the skin's ability to retain water. Although this method does not cause a wound on the surface of the skin, it still needs to be completed by a professional technician to operate a special instrument, and the cosmetic effect produced by the method can only be maintained for a short period of time compared with the invasive water-light injection technique, that is, if In order to solve the aforementioned skin aging phenomenon, it is necessary to frequently go to a beauty institution for skin care.

Another relatively simple method of skin moisturization is topical application of a commercially available hyaluronic acid moisturizer to the skin. Most of these moisturizing products are aqueous products containing high molecular weight hyaluronic acid with a molecular weight of more than one million. Applying them to the skin can increase the water content of the skin surface and prevent the loss of moisture in the skin to the outside, that is, the effect of "locking water shielding". . Recently, an aqueous moisturizing product containing a small molecular weight hyaluronic acid having a molecular weight of 10 kDa to less than 1 MDa has also appeared on the market in an attempt to increase the skin's absorption of hyaluronic acid, thereby improving the skin's ability to retain water. However, this moisturizing method has limited utility for the following reasons: First, the hyaluronic acid in the hyaluronic acid moisturizing product cannot pass through the stratum corneum of the skin; secondly, the small molecule hyaluronic acid in the hyaluronic acid moisturizing product is mostly prepared by chemical decomposition method, and The produced small molecule hyaluronic acid tends to have inconsistent molecular particle size or destruction of molecular structure, so that the effective concentration of small molecule hyaluronic acid sufficient to penetrate the stratum corneum of the skin is lowered, or the water absorption is deteriorated, thereby affecting the moisturizing effect of the product; Third, moisturizing products containing small molecules of hyaluronic acid are mostly mixed The polymer hyaluronic acid has the function of blocking the water barrier of the polymer hyaluronic acid and the better skin absorption of the small molecule hyaluronic acid. However, due to the attraction between the two molecules, the presence of the polymer hyaluronic acid interferes with the penetration of the small molecule hyaluronic acid. Through the skin stratum corneum; Fourth, the commercially available hyaluronic acid moisturizing products contain water, and the water swelling property of hyaluronic acid enlarges the actual particle size of the small molecule hyaluronic acid, thereby hindering the penetration of the small molecule hyaluronic acid into the stratum corneum of the skin.

In view of the above-mentioned various skin care methods, there is an urgent need to create a non-invasive skin care method which can effectively increase the moisture content of the skin and can be independently performed by an individual.

The present invention provides a small molecule polysaccharide for use in the manufacture of a small molecule polysaccharide anhydrous composition for treating a condition caused by or associated with a skin or exocrine gland, comprising: (1) cleaning the patient's skin And maintaining the region dry, (2) applying the small molecule polysaccharide anhydrous composition to the region, the small molecule polysaccharide anhydrous composition consisting of at least a small molecule polysaccharide and an anhydrous base, and the small molecule polysaccharide The molecular particle size is about 12-22 nm, and (3) the temperature of the region is raised by an external heating device.

In one embodiment of the present invention, the small molecule polysaccharide is a small molecule hyaluronic acid prepared by hydrolyzing a hyaluronic acid with a hyaluronanase, and has a molecular weight ranging from 4 kDa to 8 kDa.

In a preferred embodiment of the invention, the small molecule hyaluronic acid comprises from 0.5% to 3% w/v of the total amount of the anhydrous composition of the small molecule polysaccharide.

In one embodiment of the invention, the anhydrous base is at least one polyol.

In one embodiment of the invention, the exocrine gland system is a sweat gland.

In one embodiment of the invention, the condition caused by or associated with the skin or exocrine glands is at least one signs of aging selected from the group consisting of: fine lines, wrinkles , skin depression, dark circles, scars and age spots.

In an embodiment of the invention, the external heating device is a heating mask. And the external heating device maintains the heating temperature at least 42 °C.

In an embodiment of the invention, the use may further comprise a step of promoting absorption after the step (3), the step of promoting absorption is to promote absorption by iontophoresis or electromagnetic wave introduction using an introducer.

The use of the small molecule polysaccharide of the present invention directly utilizes a small molecule polysaccharide anhydrous composition containing a small molecule polysaccharide having a molecular particle diameter of about 12-22 nm, which is applied topically to the skin area of the patient, and then the temperature of the area is raised by a heating device. Therefore, the penetration of the small molecule polysaccharide having a moisturizing effect on the epidermal layer of the skin is enhanced, and the skin epidermis is further penetrated to further increase the moisture content of the skin. Therefore, the use of the small molecule polysaccharide of the present invention can effectively prevent or improve the formation of wrinkles on the skin, reduce skin depression, improve skin firmness and elasticity, shrink pores and enhance skin light. In addition, since the use of the use is non-invasive, the skin care area does not need to be anesthetized or wounded, and the use does not require specific equipment and implementation techniques, and can be independently achieved by an individual.

The present invention is characterized in that the anhydrous molecular formula of a small molecule polysaccharide such as small molecule hyaluronic acid and the anhydrous state thereof are used to maintain the original molecular size of the small molecule polysaccharide, thereby effectively penetrating the stratum corneum of the skin, and applying dry type. When heat is applied to the skin and the sweat glands and pores are opened, and sweat is secreted, the polysaccharides themselves enter the skin in a hydrophilic and long-chain manner by virtue of the water absorption of the polysaccharide itself. Multi-channel simultaneous skinning system.

The embodiments of the present invention will be further described with reference to the accompanying drawings. The embodiments of the present invention are intended to illustrate the invention and are not intended to limit the scope of the invention. The definition is subject to change. Any modifications and refinements made by those skilled in the art without departing from the spirit and scope of the invention are intended to be included in the scope of the invention.

Figure 1 is a graph showing changes in skin moisture content of skin coated with different concentrations of small molecule hyaluronic acid anhydrous composition.

2A-B are photographs of a patient's left facial skin before and after performing the present invention.

3A-B are photographs of a patient's full face skin before and after performing the present invention.

In order to specifically describe the use of the small molecule polysaccharide of the present invention, in the following examples, a small molecule hyaluronic acid is used as a representative example of a small molecule polysaccharide, and a small molecule hyaluronic acid and a polyol as a water-free base are first formulated into a specific concentration of small molecule hyaluronic acid without water. Composition. Then, the in vitro transdermal delivery analysis was used to verify that the anhydrous composition of the small molecule hyaluronic acid used in the present invention and the heating step for raising the temperature of the skin can enhance the penetration of the small molecule hyaluronic acid into the epidermal layer of the skin. Secondly, the skin water content test again proves that the present invention can effectively increase the skin moisture content. Finally, in the actual case of the present invention, the use of the small molecule polysaccharide can achieve the effect of reducing wrinkles, increasing skin fullness and the like.

definition

The term "conditions caused by or associated with skin or exocrine glands" as used in the present invention refers to various signs of aging which occur in the skin or secreted glands other than, for example, sweat glands, and the condition and skin moisture content. Insufficient, such as fine lines, wrinkles, sunken skin, dark circles, scars and age spots, so the treatment of these conditions involves skin or exocrine glands.

The "hyaluronic acid" referred to in the present invention is a hyaluronic acid having a molecular weight of about 1 MDa or more and a salt thereof or a derivative thereof, which is also called a hyaluronic acid, which is different from the small molecule hyaluronic acid in the specification of the present invention.

The "small molecule hyaluronic acid" referred to in the present invention is a hyaluronic acid having a molecular weight of about 4 kDa to 8 kDa and a salt thereof or a derivative thereof, unless otherwise specified, and the disaccharide unit contains about 12-22, and its molecular particle The diameter is about 12-22 nm.

The term "polysaccharide" as used in the present invention, also referred to as a polysaccharide, generally refers to a sugar polymerization which is water-absorbing and which is formed by dehydration polymerization of a plurality of monosaccharides, monosaccharide derivatives, disaccharides or disaccharide derivatives. And a salt thereof, wherein the monosaccharide or monosaccharide derivative constituting a single polysaccharide may be one or plural. For example, hyaluronic acid, dextran, aloe polysaccharide, seaweed polysaccharide, tremella polysaccharide, ganoderma lucidum polysaccharide, etc. can be used for the moisturizing function of the polysaccharide.

The "small molecule polysaccharide" referred to in the present invention is the above polysaccharide or a hydrolyzate thereof having a molecular particle diameter of about 12 to 22 nm.

The term "polyol" as used in the present invention generally refers to an alcohol having two or more hydroxyl groups, such as ethanol, glycerol (also known as glycerin), propylene glycol, butanediol, hexahexol (also known as sorbitol), and the like. And the polyol is used in the anhydrous form of the small molecule polysaccharide anhydrous composition used in the present invention.

The term "external heating device" as used in the present invention generally refers to any device, device or design that increases the surface temperature of a user's skin. For example, a heating mask, a heat pad, a baking machine, a hot towel, and the like.

Materials and Methods Small molecule hyaluronic acid anhydrous composition

The small molecule hyaluronic acid contained in the anhydrous composition of the small molecule hyaluronic acid of the following examples was purchased from Bloomage Freda Biopharm (China), and was prepared by hydrolyzing the polymer hyaluronic acid at a neutral pH of 30-50 ° C with hyaluronic acid. Hyaluronic acid, and the micro hyaluronic acid is a small molecule hyaluronic acid dry powder in anhydrous form. Unless otherwise specified, the molecular weight of the small molecule hyaluronic acid in the following examples is about 4 kDa to 8 kDa, and it contains glucuronic acid and acetamidine. The glucosamine disaccharide unit is about 12-22, and its molecular particle size is about 12-22 nm. When preparing the anhydrous composition of small molecule hyaluronic acid, the environment of the normal temperature and the relative humidity of 45%±5% in the temperature below 40 ° C, the small molecule hyaluronic acid dry powder and the anhydrous propylene glycol are first mixed in a vacuum mixer, and then the anhydrous propylene is added. The alcohol was continuously stirred until the powder was completely dissolved, i.e., a small molecular weight hyaluronic acid anhydrous composition having a weight by volume concentration of 2% w/v was prepared, which contained 58% propylene glycol and 40% glycerol. The concentration of the small molecule hyaluronic acid anhydrous composition mentioned in the following examples all represents the weight-volume concentration (w/v) of the small molecule hyaluronic acid in the composition. In order to maintain the anhydrous state of the anhydrous composition of the small molecule hyaluronic acid, all the containers or contactors are kept dry during the preparation, and the prepared small molecule hyaluronic acid anhydrous composition is filled in a vacuum flask with a vacuum filling machine for storage.

Aqueous small molecule hyaluronic acid sample

The aqueous small molecule hyaluronic acid sample of the following examples was prepared by mixing a small hyaluronic acid powder (hyaluronic acid molecular weight of about 4 kDa-8 kDa) purchased from Bloomage Freda Biopharm (China) with secondary water to a water volume concentration of 2% w/v. A small molecule hyaluronic acid sample containing 98% water, similar to a commercially available aqueous hyaluronic acid product having a hyaluronic acid concentration of 1% and a water content of 80% or more. The concentration of the aqueous small molecule hyaluronic acid sample referred to in the following examples represents the weight-volume concentration (w/v) of the small molecule hyaluronic acid in the sample.

In vitro transdermal delivery analysis

First, a penetrating membrane for analysis was prepared, and in this test, the pig ear epidermis was taken. The surface of the pig ear skin was washed with secondary water, and the epidermis of the pig ear was taken with a scalpel, and cut into a penetrating membrane having an area of 1.5×1.5 cm ² and a thickness of 650 μm, and then phosphate buffered saline (phosphate buffered saline, The PBS) solution is wetted to the bag and then frozen for use. Before the experiment, the penetrating membrane was immersed in PBS solution and thawed to room temperature, so that the keratinocyte space returned to the natural state, and then the penetrating membrane was fixed in a Franz type diffusion cell (LOGAN FDC-6, USA; The diffusion area is 0.636 cm ² ). In order to confirm the integrity of the penetrating membrane, the PBS solution was filled in the upper and lower layers of the diffusion tank to remove the bubbles in the lower tank, and the resistance on both sides of the penetrating membrane was measured to be greater than 4 kΩ, indicating that the epidermis slice was intact without damage. For in vitro percutaneous transport analysis, place 1.0 mL of the sample to be tested on the upper application end of the diffusion cell, place the PBS physiological solution on the lower drug receiving end (physical performance: 5.3 mL), and activate the constant temperature water heater (VTC-200). , United States), by magnet stirring, balance the concentration distribution of the sample to be tested in the drug end. At intervals, 50 μL of the drug-end end was sampled and analyzed by high performance liquid chromatography (HPLC), and the same volume of PBS solution was immediately backfilled to ensure that the volume in the drug-receiving end was unchanged. Each experiment was simultaneously measured using 5 diffusion cells, and the average value was taken. The HPLC system consists of TYPE BETA 50 gradient pump (ECOMSRO, Czech Republic), SPD-10Avp ultraviolet light visible light detector (Shimadzu, Japan), DG1310 online defoaming device (Uniflows, Japan) and MetaChem Polaris C18-A 5μm 150x4. Composition of a 6mm column (Agilent Technologies, USA). For sample analysis, equipotential extraction was carried out with a 5 mM sodium dihydrogen phosphate buffer solution (pH 3.0) to set a flow rate of 1.0 mL/min and a detection wavelength of 260 nm. The sample concentration can be calculated against a calibration curve established from an AA2G standard solution having a concentration of 10 ppm to 200 ppm. The concentration of each sample was repeated for the average of 3 detections.

Skin moisture test

The skin moisture content was measured by a skin moisture meter Corneometer CM 825 (Courage+Khazaka electronic GmbH, Germany). Before the measurement, the subject's skin test area was first cleaned and dried, and then the skin moisture test was performed before and after applying various hyaluronic acid or small molecule hyaluronic acid samples on the skin surface. During the test, the probe connected to the epidermal moisture meter was in contact with the subject's skin test area, and the skin water content of the test area was measured. When the divergent electric field path of the probe surface electrode of the instrument contacts the skin, the capacitance of the electrode is affected by the difference in the water content of the skin layer, so the correlation can be used to define the water content of the skin epidermis. The test results can further calculate the rate of change of skin water content. Due to the outside world Factors such as temperature and humidity have an effect on the water content of the skin. Subjects must first enter the constant temperature and humidity chamber for 20 minutes before testing. The measurement was repeated 3 times for each measurement and the average value was taken. The environmental conditions for this test are relative humidity of 50% ± 10%.

Example 1 Small molecule hyaluronic acid with small molecule hyaluronic acid anhydrous composition has better epidermal penetration rate

In order to verify that the anhydrous formulation of the small molecule hyaluronic acid anhydrous composition used in the present invention allows the small molecule hyaluronic acid to penetrate the stratum corneum and the epidermal layer more effectively than the aqueous formulation of the general aqueous hyaluronic acid product, the present embodiment uses the pig ear epidermis. And the Flanders-type diffusion trough for in vitro transdermal transport analysis, comparing the molecular weight of 4kDa-8kDa in the 2mDa-8kDa small molecule hyaluronic acid and 2% aqueous small molecule hyaluronic acid sample in 2% small molecule hyaluronic acid anhydrous composition at 43 °C The epidermal penetration rate of the small molecule hyaluronic acid. The temperature of this analysis was set to 43 ° C in order to simulate the heating step in the use of the small molecule polysaccharide of the present invention.

After adding the above-mentioned small molecule hyaluronic acid anhydrous composition or aqueous small molecule hyaluronic acid sample to the application end of the diffusion tank, the sampled end is sampled 3 times in one hour and quantified by HPLC, and the quantitative result is divided by the diffusion area of the diffusion tank. That is, the cumulative penetration per unit area of small molecule hyaluronic acid. According to the following formula: J=dQ/dt, the cumulative penetration per unit area (Q in the above formula) is differentiated from the sampling time (t in the above formula), and the epidermal penetration rate of small molecule hyaluronic acid can be calculated (on J) in the formula.

The experimental results show that the epidermal penetration rate of the small molecule hyaluronic acid of the small molecule hyaluronic acid anhydrous composition used in the present invention is 217.86 μg/cm ² . Hr, significantly higher than the small molecule hyaluronic acid in the aqueous small molecule hyaluronic acid sample, the skin penetration rate of 156.02 μg / cm ² . Hr. Therefore, the use of the small molecule hyaluronic acid anhydrous composition in the use of the small molecule polysaccharide of the present invention can more effectively allow the small molecule hyaluronic acid to enter the epidermal layer of the skin. This embodiment also indirectly indicates that the use of the present invention can achieve a better skin moisturizing effect in the case of dry skin.

Example 2 The heating step enhances the epidermal penetration of small molecule hyaluronic acid of small molecule hyaluronic acid anhydrous composition

In order to evaluate the effect of the heating step of increasing the skin temperature in the present invention, the present embodiment uses a porcine ear skin and a flanged diffusion groove for in vitro transdermal delivery analysis, and 2% is measured at 43 ° C and 26 ° C. The epidermal permeability of a small molecule hyaluronic acid having a molecular weight of 4 kDa to 8 kDa in a small molecule hyaluronic acid anhydrous composition.

According to the method of Example 1, the epidermal penetration rate of the small molecule hyaluronic acid in the anhydrous composition of the small molecule hyaluronic acid at different temperatures was calculated. The experimental results show that when the temperature is raised from room temperature of 26 ° C to 43 ° C, the epidermal penetration rate of the small molecule hyaluronic acid of the anhydrous composition of the small molecule hyaluronic acid used in the present invention is from 156.06 μg / cm ² . The hr increased to 212.54 μg/cm ² . Hr, the ratio is about 1:1.34, it is obvious that the use of the small molecule polysaccharide of the invention can further enhance the epidermal penetration of the small molecule hyaluronic acid in the anhydrous composition of the small molecule hyaluronic acid used by the heating step, so that the small molecule hyaluronic acid enters more effectively. Skin epidermis.

Example 3 Comparison of skin water retention capacity of different concentrations of small molecule hyaluronic acid anhydrous composition

In order to evaluate the skin water retention capacity of different concentrations of small molecule hyaluronic acid anhydrous composition, firstly, a small molecule hyaluronic acid anhydrous composition with a molecular weight of 4kDa-8kDa was prepared as a concentration of 0.1%, 0.5%, 1.0%, 2.0%, 3.0%. The compositions contained 59.9%, 59.5%, 59%, 58% or 57% propylene glycol, respectively, and all contained 40% glycerol. Then, at the temperature of 26 ° C, the above five different concentrations of the small molecule hyaluronic acid anhydrous composition were applied to 5 skin regions of the left and right forearms of 5 subjects aged 30 to 45, respectively, each skin area was 4 x 4 cm. ² , the application amount was 3.0 ± 0.1 mg / cm ² , and the skin moisture content of the application area before the application and 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the application was measured by a skin moisture meter.

As shown in Figure 1, the concentration of the anhydrous composition of small molecule hyaluronic acid affects the skin moisture content of the skin in the application area. In Figure 1, the abscissa is time (hours), and the ordinate is the skin water content reading (%). Points represent the average of the skin water readings of the five subjects and are summarized in Table 1. As the concentration of small molecule hyaluronic acid in the anhydrous composition of small molecule hyaluronic acid increased from 0.5% to 2%, the skin moisture content of the skin area of the subject also increased significantly, but when the concentration of the small molecule hyaluronic acid anhydrous composition reached 3% The skin moisture content of the smear area was comparable to that of the 2% small molecule hyaluronic acid anhydrous composition, and no significant increase was observed. The 2% small molecule hyaluronic acid anhydrous composition was sufficient to exhibit the best skin water retention capacity.

Example 4 Heating step promotes skin water retention capacity of small molecule hyaluronic acid anhydrous composition

This example further demonstrates the effect of the heating step of increasing the skin temperature in the present invention on the skin water retention capacity of the small molecule hyaluronic acid anhydrous composition. First, six female subjects aged 25 to 35 washed the skin on the inner side of the forearm with soap and dried the skin area with a paper towel, and then evenly applied a 2% small molecule hyaluronic acid anhydrous composition to the skin area, the area of the skin area. It is 3 x 3 cm ² and the amount applied is 2 mg/cm ² . Thereafter, the subject's left forearm application area was fixedly attached to a thermostatically controlled heat shield, and was heat-applied at 43 ° C for 20 minutes. The subject's right forearm was not treated as a control group, and before and after application. The skin moisture content of the application area was measured by a skin moisture meter for 2 hours.

The experimental results are shown in Table 2. The skin moisture content of the left forearm application area of the subject after hot application is almost twice that of the right forearm application area without hot compress. It can be seen that the heating step of the use of the small molecule polysaccharide of the present invention is promoted. The skin moisturizing effect of the small molecule hyaluronic acid anhydrous composition significantly increases the skin moisture content of the subject.

The following examples are illustrative of the effectiveness of the use of the small molecule polysaccharide of the present invention in the treatment of aging conditions in the skin of a woman's face.

Example 5 Case 1 of the present invention applied to the skin of the face

A female patient first cleans the left side of the skin to be skincare with a facial cleanser. Next, apply 2ml of 2% small molecule hyaluronic acid anhydrous composition on the left face skin (including the eyes), that is, 2g small molecule hyaluronic acid anhydrous composition, and then cover the face with a disposable plastic wrap, avoiding the nostrils and mouth. Thereafter, the temperature-controlled heating mask previously heated for 5 minutes is covered with a hot towel and a dry towel to maintain the temperature of the heating mask, and the combination of the heating mask and the towel covers the face. The temperature of the heating mask is maintained above 42 ° C, and the hot compress time is about 20 minutes, which can be adjusted according to the skin condition of the subject. After the heat application is completed, an iontophoresis device can be further used for facial massage to promote the entry of small molecule hyaluronic acid of the small molecule hyaluronic acid anhydrous composition into the facial skin. Because the small molecule hyaluronic acid is negatively charged, the iontophoresis instrument used is introduced with a probe with a negative electrode, and the small molecule hyaluronic acid is introduced into the skin by the principle of charge homosexual repelling.

The patient's left face skin photo before and after the implementation of the present invention is shown in FIG. 2A and FIG. 2B is shown. Comparing Figure 2A, the skin of the left cheek apple muscle of the patient in Figure 2B is obviously fuller and firmer, the skin is smoother, the facial pattern on the nose is lighter, and the contour of the face is raised upwards. These changes are the skin of the patient's face. Caused by an increase in water volume.

Example 6 Case 2 of the present invention applied to the skin of the face

According to the procedure of Example 5, a female patient performs the present invention on the entire face of the skin. The full-face skin photograph of the patient before and after the application is shown in Figures 3A and 3B. Comparing Fig. 3A, in Fig. 3B, the skin of the cheek apple muscles on both sides of the patient is more full, and the facial pattern on the nose side is also less obvious, indicating that the present invention can effectively improve the skin moisture content of the patient.

It can be seen from the above examples that the small molecule hyaluronic acid anhydrous composition used in the use of the small molecule polysaccharide of the present invention can make the small molecule hyaluronic acid exhibit its ability to penetrate the skin epidermis more than the aqueous small molecule hyaluronic acid sample; and the heating in the present invention The step can further enhance the epidermal penetration rate of the small molecule hyaluronic acid in the anhydrous composition of the small molecule hyaluronic acid, thereby improving the skin water retention capacity of the composition, thereby achieving the effects of increasing the skin firmness, diminishing wrinkles and the like, and treating the skin aging condition.

Regarding the above-mentioned examples, the improvement of skin temperature can promote the absorption of small molecule hyaluronic acid in the small molecule hyaluronic acid anhydrous composition. One possible mechanism is that when the skin temperature rises, the sweat glands in the skin discharge sweat to the skin surface, and attract the skin surface small molecule hyaluronic acid. The small molecule hyaluronic acid in the anhydrous composition enters the epidermal layer and even the dermis layer along the sweat gland duct. This is because the high water absorption of the small molecule hyaluronic acid drives the small molecule hyaluronic acid into the skin via the sweat-filled sweat gland duct. In other words, in the case of an increase in skin temperature, the small molecule hyaluronic acid in the anhydrous composition of small molecule hyaluronic acid can enter the epidermis not only because of its molecular size of 12-22 nm, but also directly through the keratinocyte space (40-50 nm) of the stratum corneum of the skin. The layer can also enter the skin through the sweat gland duct of the skin, thus increasing the skin moisture content.

In summary, the use of the small molecule polysaccharide of the present invention enhances the penetrating power of the small molecule polysaccharide on the skin epidermis by a small molecule polysaccharide anhydrous composition containing a small molecule polysaccharide having a molecular particle diameter of about 12 to 22 nm and a heating step. It penetrates deep into the epidermal layer of the skin, thus increasing the water content of the skin area to be skinned. Therefore, the invention can effectively prevent or improve the formation of wrinkles on the skin, reduce skin depression, improve skin firmness and elasticity, shrink pores and enhance skin light. In addition, since the manner of completion of the use is non-invasive, the skin care area does not need to be anesthetized or wounded, and the use does not require specific equipment and implementation techniques, and can be achieved by an individual.

Claims (5)

A small molecule hyaluronic acid anhydrous composition for use in the manufacture of a composition for moisturizing the skin, wherein the small molecule hyaluronic acid anhydrous composition consists of a small molecule of hyaluronic acid and an anhydrous base, the molecular size of the small molecule hyaluronic acid is about 12 -22 nm and its molecular weight range is from 4 kDa to 8 kDa, and the small molecule hyaluronic acid anhydrous composition is dry heated to a temperature of at least 42 °C. The use of the first aspect of the invention, wherein the small molecule hyaluronic acid is obtained by hydrolyzing a hyaluronic acid with a hyaluronan. The use of claim 1, wherein the small molecule hyaluronic acid comprises from 0.5% to 3% w/v of the total amount of the small molecule hyaluronic acid anhydrous composition. The use of claim 1, wherein the anhydrous base is at least one polyol. The use of claim 1, wherein the dry heating is accomplished by a heating mask.