JP2012025720A - Ceramide synthesis promoter, cosmetic, skin preparation for external use, quasi drug, drug and method for producing ceramide synthesis promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new technology for promoting the synthesis of ceramide in skin.SOLUTION: A ceramide synthesis promotor has liposome containing sphingomyelin. The liposome has a negative electric charge. Such the liposome can be obtained e.g. by passing through a dissolving process S100 of dissolving the sphingomyelin and negatively charged lipid with an organic solvent to form a solution, a reduced pressure-distilling off process S102 of distilling off the solution to form lipid thin film, and an emulsifying process S104 of adding water to the lipid thin film and emulsifying to obtain the liposome.

Description

  The present invention relates to a technique for promoting ceramide synthesis. The present invention can be suitably applied to fields such as cosmetics, external preparations for skin, quasi drugs, and pharmaceuticals.

  Ceramide, one of the sphingolipids, accounts for more than 50% of the lipid contained in the stratum corneum, the outermost layer of the skin. Ceramide is derived from the lamellar granules produced by the granule layer located below the stratum corneum, and forms a lamellar structure (layered structure) by hydrogen bonding with water molecules in the stratum corneum. It is involved in the holding (moisturizing) function and the barrier function. If the amount of ceramide in the stratum corneum decreases, the skin's moisturizing function and barrier function decrease, and it is thought to cause skin diseases such as dry skin, rough skin, atopic dermatitis, senile psoriasis and psoriasis .

  On the other hand, in recent years, it has been reported that ceramide production in cells induces apoptosis, cell differentiation induction, cell growth inhibition, etc., and ceramide is involved in moisturizing function and barrier function. In addition, it has been found that it functions as an intracellular signaling substance molecule that controls apoptosis, cell differentiation and proliferation, and the like. Therefore, if the production of ceramide is promoted, it is considered that diseases caused by abnormal cell proliferation or differentiation such as inflammatory diseases and malignant tumors can be reduced.

  Ceramide is obtained by hydrolyzing sphingomyelin, so if sphingomyelin can penetrate deep into the skin, the ceramide content in the stratum corneum and the layers below the stratum corneum, the epidermal granule layer, spiny It becomes possible to increase the ceramide content in the layer and the basal layer.

  Therefore, cosmetics containing sphingomyelin have been proposed (for example, Patent Document 1). Patent Document 1 describes that the disclosed cosmetics are excellent in skin permeability of an active ingredient, activate skin cell functions when applied to the skin, and exert a remarkable effect on skin protection and beautification. Yes. However, there is no description as to whether sphingomyelin has penetrated deep into the skin when the cosmetic according to Patent Document 1 is applied to the skin, and there is no description about the change in the amount of ceramide synthesized in the skin. .

  Therefore, a cosmetic containing liposomal sphingomyelin has been proposed, and it is possible to increase the ceramide content in the skin by applying this cosmetic to the skin (for example, Patent Document 2).

Japanese Patent Laid-Open No. 63-211208 International Publication No. 2007/145276

  An object of the present invention is to provide a new technique for promoting the synthesis of ceramide in the skin.

  An example of an embodiment of the present invention includes a ceramide synthesis promoter including a sphingomyelin liposome, wherein the liposome is negatively charged.

  Since the human stratum corneum is weakly acidic from pH 4.5 to around pH 6.5, if the liposome is negatively charged, the liposome can easily penetrate into the stratum corneum, and the sphingomyelin liposome is deeply penetrated into the skin. Can penetrate. Since ceramide is obtained by hydrolyzing sphingomyelin, it penetrates deep into the skin and ceramide in the stratum corneum, the layer below the stratum corneum, the granular layer of the epidermis, the spiny layer, and the basal layer. The synthesis of can be promoted.

  The surface of the liposome may be negatively charged.

  Since the surface of the liposome directly contacts the cells of the stratum corneum, if the surface of the liposome is negatively charged, the liposome can easily penetrate the stratum corneum even if the surface other than the surface of the liposome is not negatively charged. Can do.

  The liposome may be negatively charged by adding a negatively charged lipid. With such a configuration in which a negatively charged lipid is added, the liposome can be easily negatively charged.

  The negatively charged lipid may be a phospholipid. The phospholipid may be dicetyl phosphate or dipalmitoyl phosphatidylglycerol. Since the sphingomyelin that composes the liposome is a phospholipid, the affinity for the sphingomyelin can be increased by using a negatively charged lipid as the phospholipid, and the liposome can be stably charged to a negative charge. It becomes.

  Another embodiment of the present invention is a ceramide synthesis accelerator containing a sphingomyelin liposome, wherein the liposome is a cosmetic containing a negatively charged ceramide synthesis promoter, a ceramide containing a sphingomyelin liposome Synthetic promoters, liposomes are external preparations for skin containing ceramide synthesis promoters with negative charge, ceramide synthesis promoters including sphingomyelin liposomes, and liposomes are for negatively charged ceramide synthesis promotion A quasi-pharmaceutical product containing a ceramide synthesis promoter including a sphingomyelin liposome containing the agent, wherein the liposome includes a ceramide synthesis promoter having a negative charge.

  As described above, if the liposome is negatively charged, the liposome can be easily penetrated into the stratum corneum, and the sphingomyelin can be penetrated deep into the skin, thereby promoting the synthesis of ceramide in the epidermis. is there. Therefore, ceramide synthesis promoters containing sphingomyelin liposomes, which have negatively charged liposomes, can be used in cosmetics and skin for people with reduced skin moisturizing power and skin disease patients. It is extremely promising as an active ingredient for external preparations, quasi drugs, and pharmaceuticals.

  Other embodiments of the present invention include a dissolving step of dissolving sphingomyelin and a negatively charged lipid in an organic solvent to produce a solution, and a reduced pressure by which the solution is distilled off under reduced pressure to produce a lipid thin film. And a method for producing a ceramide synthesis promoter having a distillation step and an emulsification step of adding water to the lipid thin film to emulsify and obtaining liposomes.

  The configurations defined in each claim in the claims are examples of preferred embodiments of the invention.

It is explanatory drawing for demonstrating the manufacturing method of the ceramide synthesis promoter introduced as an Example. It is a figure which shows the structural formula of the lipid used for the manufacturing method of the ceramide synthesis promoter of an Example. It is a figure which shows the surface potential of SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L. It is explanatory drawing for demonstrating the structure of a human three-dimensional cultured epidermis model. It is explanatory drawing for demonstrating the change of the size of the liposome at the time of re-dispersing in PBS or a culture medium, respectively. It is a figure which shows ceramide content when SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L are added from the stratum corneum side of a human three-dimensional cultured epidermis model, respectively. It is a figure which shows ceramide content when SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L are added from the stratum corneum side of a human three-dimensional cultured epidermis model, respectively. It is a figure which shows ceramide content when SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L are added from the basal layer side of the human three-dimensional cultured epidermis model. It is a figure which shows ceramide content when SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L are added from the basal layer side of the human three-dimensional cultured epidermis model.

  Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The dimensions, materials, and other specific numerical values shown in the embodiment are merely examples for facilitating understanding of the invention, and do not limit the present invention unless otherwise specified. In the present specification and drawings, elements having substantially the same function and configuration are denoted by the same reference numerals, and redundant description is omitted, and elements not directly related to the present invention are not illustrated. To do.

<Example: Method for producing ceramide synthesis accelerator>
FIG. 1 is an explanatory diagram for explaining a method for producing a ceramide synthesis accelerator introduced as an example. As shown in FIG. 1, the method for producing a ceramide synthesis accelerator according to this example includes a dissolution step S100, a vacuum distillation step S102, an emulsification step S104, a freeze-thaw step S106, and a size adjustment step S108. Including. Below, the structure of each process is demonstrated in detail.

(Dissolution step S100)
The dissolution step S100 is a step of dissolving a sphingomyelin and a negatively charged lipid in an organic solvent (for example, chloroform) to generate a solution. In the dissolution step S100, the negatively charged lipid is preferably a phospholipid, and more preferably dicetyl phosphate (hereinafter simply referred to as DCP) or dipalmitoyl phosphatidylglycerol (hereinafter simply DPPG). Called).

  Since sphingomyelin is a phospholipid, the affinity for sphingomyelin can be increased by using a negatively charged lipid as a phospholipid. When a liposome is made with sphingomyelin, the liposome is stably Can be charged.

(Vacuum distillation step S102)
The vacuum distillation step S102 is a step of producing a lipid thin film by vacuum distillation of the solution produced in the dissolution step S100. In the vacuum distillation step S102, the solution produced in the dissolution step S100 is placed in an eggplant-shaped flask, and a lipid thin film is produced by distilling off the organic solvent contained in the solution using a rotary evaporator.

(Emulsification step S104)
The emulsification step S104 is a step of obtaining liposomes by adding water to the lipid thin film produced in the vacuum distillation step S102 to emulsify. In the emulsification step S104 of the present embodiment, PBS (Phosphate Buffered Saline) (pH 7.4) is added to the lipid thin film produced in the vacuum distillation step S102 to emulsify it to obtain liposomes.

(Freeze-thaw step S106)
The freeze-thaw step S106 is a step for freeze-thawing the solution containing the liposome obtained in the emulsification step S104. In the freezing and thawing step S106 of this embodiment, the freezing and thawing is repeated 5 times.

(Size adjustment process S108)
The size adjustment step S108 is a step of adjusting the size of the liposome freeze-thawed in the freeze-thaw step S106. In the size adjustment step S108, a polycarbonate membrane having pores having a pore size of 100 to 400 nm is set in the extruder, and the solution containing the liposomes frozen and thawed in the freeze-thaw step S106 is passed through the pores formed in the polycarbonate membrane. In this example, a polycarbonate membrane having pores with a pore size of 100 nm is set on an extruder, and a solution containing liposomes freeze-thawed in the freeze-thaw step S106 is passed five times.

  Thereafter, the solution containing the liposome is subjected to ultracentrifugation at 250000 g for 15 minutes, for example, to obtain a sphingomyelin liposome (hereinafter simply referred to as a sphingomyelin liposome).

  A ceramide synthesis accelerator can be produced through the dissolution step S100, the vacuum distillation step S102, the emulsification step S104, the freeze-thaw step S106, and the size adjustment step S108 described above.

<Evaluation of ceramide synthesis accelerator>
In order to evaluate the ceramide synthesis promoter produced by the above production method, the amount of increase in ceramide by the ceramide synthesis promoter was measured. Hereinafter, the procedure of the experiment will be described in detail.

(Adjustment of sphingomyelin liposome)
FIG. 2 is a diagram showing the structural formula of lipids used in the method for producing a ceramide synthesis promoter of this example. A sphingomyelin liposome (hereinafter simply referred to as DCP-SPM-L) charged with a negative charge using the DCP shown in FIG. 2 (a) using the above-described method for producing a ceramide synthesis accelerator, and FIG. A sphingomyelin liposome (hereinafter simply referred to as DPPG-SPM-L) charged to a negative charge using DPPG shown in (b) was prepared. As a control, a sphingomyelin liposome prepared using only sphingomyelin (hereinafter simply referred to as SPM-L) was prepared. Furthermore, as a comparison target of DCP-SPM-L and DPPG-SPM-L, a sphingomyelin liposome (hereinafter simply referred to as SA-SPM) charged with a positive charge using stearylamine (Stearyl Amine) shown in FIG. 2 (c). -L). DCP-SPM-L, DPPG-SPM-L, and SA-SPM-L contain 10% molar ratio of each lipid (DCP, DPPG, SA).

  Then, the prepared DCP-SPM-L, DPPG-SPM-L, SPM-L and SA-SPM-L were redispersed in PBS (pH 7.4), respectively, and the prepared DCP-SPM-L, DPPG-SPM-L, SPM-L and SA-SPM-L were re-dispersed in the medium, respectively.

  FIG. 3 is a diagram showing the surface potentials of SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L. In FIG. 3, error bars added to the bar graph indicate standard deviation (S.D.). As shown in FIG. 3, SPM-L is -3.9mV (SD 0.39), SA-SPM-L is + 12.9mV (SD 0.71), DCP-SPM-L is -14.9mV (SD 1.59), DPPG-SPM-L was -14.1mV (SD 1.12). Therefore, it was found that the surface of SPM-L, DCP-SPM-L and DPPG-SPM-L are negatively charged, and that of SA-SPM-L is positively charged.

(Addition of sphingomyelin liposome)
LabCyte EPI-MODEL manufactured by Japan Tissue Engineering Co., Ltd. was used as a cell to which sphingomyelin liposome was added. LabCyte EPI-MODEL is a human three-dimensional cultured epidermis model in which human normal epidermal cells are layered.

FIG. 4 is an explanatory diagram for explaining the structure of a human three-dimensional cultured epidermis model. 200 μL of DCP-SPM-L redispersed in PBS was added from the stratum corneum side of the human three-dimensional cultured epidermis model shown in FIG. 4 and cultured at 37 ° C. under 5% CO ₂ for 7 days. Similarly, 200 μL of DPPG-SPM-L redispersed in PBS, 200 μL of SPM-L redispersed in PBS, and 200 μL of SA-SPM-L redispersed in PBS, It was added from the stratum corneum side of a dimensionally cultured epidermis model and cultured at 37 ° C. and 5% CO ₂ for 7 days.

In addition, 1 ml of DCP-SPM-L re-dispersed in the medium was added from the membrane filter (basal layer) side of the human three-dimensional cultured epidermis model shown in FIG. 4 and added at 37 ° C. under 5% CO _2. Time culture was performed. Similarly, 1 ml of DPPG-SPM-L re-dispersed in the medium, 1 ml of SPM-L re-dispersed in the medium, and 1 ml of SA-SPM-L re-dispersed in the medium, It was added from the basal layer side of the dimensionally cultured epidermis model and cultured at 37 ° C. under 5% CO ₂ for 6 hours.

Thereafter, ascorbic acid-added cornification promoting medium was added to the medium of the human three-dimensional culture epidermis model to which liposome was added from the horny layer side (in this case, PBS) and the medium of the human three-dimensional culture epidermis model added from the basal layer side And cultured at 37 ° C. under 5% CO ₂ for 24 hours.

  FIG. 5 is an explanatory diagram for explaining changes in the size of liposomes when redispersed in PBS or a medium, respectively.

  As shown in FIG. 5 (a), when liposomes were redispersed in PBS and cultured for 7 days, the sizes of DCP-SPM-L, DPPG-SPM-L, SPM-L, and SA-SPM-L Although there was an increase or decrease, there was no significant change in size. In addition, as shown in FIG. 5 (b), when liposomes were redispersed in a medium and cultured for 6 hours, the sizes of DCP-SPM-L, DPPG-SPM-L, SPM-L and SA-SPM-L were Although there was a slight decrease, there was no significant change in size.

  From the above results, it was confirmed that the liposomes exist stably in the medium.

(Ceramide extraction)
The cultured human three-dimensional cultured epidermis model was taken out, and the epidermal tissue was destroyed using probe-type ultrasound in chloroform: methanol (2: 1), and ceramide was extracted from the epidermal tissue. And the epidermis structure | tissue was removed by filtering with a filter and the ceramide extract was obtained. Thereafter, the ceramide extract was dried in a stream of N ₂ and redissolved with 200 μL of chloroform: methanol (2: 1). This was used as a sample in the following experiment.

(Measurement of ceramide content)
The obtained sample was spotted on an HPTLC (High Performance Thin Layer Chromatography) plate 20 μL at a time and developed twice using chloroform: methanol: acetic acid (190: 9: 1) as a developing solvent. The developed HPTLC plate was sprayed with an 8% aqueous phosphoric acid solution containing 10% copper sulfate, and then baked (heated) for 10 minutes on a 180 ° C. hot plate.

  Then, using a lumino image analyzer system (LAS-1000-plus, manufactured by Fuji Film Co., Ltd.), the HPTLC plate after baking was photographed, and the amount of ceramide was quantified by density.

(result)
6 and 7 show the ceramide content when SPM-L, SA-SPM-L, DCP-SPM-L and DPPG-SPM-L are added from the stratum corneum side of the human three-dimensional cultured epidermis model, respectively. 8 and 9 show ceramides when SPM-L, SA-SPM-L, DCP-SPM-L, and DPPG-SPM-L are added from the basal layer side of the human three-dimensional cultured epidermis model, respectively. It is a figure which shows content. In FIG. 6 to FIG. 9, the error bar added to the bar graph indicates the standard deviation (SD).

As shown in Fig. 6 (a), when liposomes were added from the stratum corneum side of a human three-dimensional cultured epidermis model, the content of ceramide 2 was 1.08 µg / cm ² (SD 0.07) of SPM-L, SA- Compared to 1.13μg / cm ² (SD 0.17) of SPM-L, DCP-SPM-L is 1.27μg / cm ² (SD 0.05) and DPPG-SPM-L is 1.46μg / cm ² (SD 0.15). The content of ceramide 2 was high.

As shown in Fig. 6 (b), when liposomes were added from the stratum corneum side of the human three-dimensional cultured epidermis model, the content of ceramide 3 was 0.03μg / cm ² (SD 0.03) of SPM-L, SA- compared to SPM-L of ^{0.04μg / cm 2 (SD 0.01)} , DCP-SPM-L is ^{0.07μg / cm 2 (SD 0.01)} , next to DPPG-SPM-L is 0.14μg / cm ² (SD 0.08) The content of ceramide 3 was high.

As shown in Fig. 7 (a), when liposomes were added from the stratum corneum side of a human three-dimensional cultured epidermis model, the content of ceramide 5 was 0.37 μg / cm ² (SD 0.02) of SPM-L, SA- Compared to 0.41μg / cm ² (SD 0.07) for SPM-L, DCP-SPM-L is 0.46μg / cm ² (SD 0.08), and DPPG-SPM-L is 0.59μg / cm ² (SD 0.07). The content of ceramide 5 was high.

As shown in Fig. 7 (b), when liposomes were added from the stratum corneum side of a human three-dimensional cultured epidermis model, the content of ceramide 6 was 0.88 µg / cm ² (SD 0.06) of SPM-L, SA- Compared to 0.86μg / cm ² (SD 0.19) of SPM-L, DCP-SPM-L is 1.00μg / cm ² (SD 0.21) and DPPG-SPM-L is 1.35μg / cm ² (SD 0.16). The content of ceramide 6 was high.

  Thus, as shown in FIGS. 6 and 7, when liposomes were added from the stratum corneum side of the human three-dimensional cultured epidermis model, compared to SPM-L and SA-SPM-L, DCP-SPM-L and DPPG-SPM-L contained more ceramide 2, ceramide 3, ceramide 5 and ceramide 6. In particular, DPPG-SPM-L had a high content of ceramide 2, ceramide 3, ceramide 5 and ceramide 6.

  According to the above experimental results, when the ceramide synthesis promoter containing the negatively charged sphingomyelin liposome produced by the above production method is added from the stratum corneum, the ceramide content in the epidermal tissue containing the stratum corneum is increased. It can be seen that the synthesis of ceramide can be promoted. Since the human stratum corneum is weakly acidic from pH 4.5 to around pH 6.5, the negative charge of the liposome changes the distribution of the liposome into the stratum corneum or the affinity of the liposome for epidermal cells. It is considered that the change in the properties allowed the liposomes to easily penetrate into the stratum corneum, allowing the sphingomyelin liposomes to penetrate deep into the skin.

As shown in Fig. 8 (a), when liposomes were added from the basal layer side of the human three-dimensional cultured epidermis model, the content of ceramide 2 was 0.859μg / cm ² (SD 0.290) of SPM-L, SA- Compared with 0.927μg / cm ² (SD 0.234) of SPM-L, DCP-SPM-L is 1.010μg / cm ² (SD 0.335) and DPPG-SPM-L is 1.132μg / cm ² (SD 0.307). The content of ceramide 2 was high.

As shown in Fig. 8 (b), when liposomes were added from the basal layer side of the human three-dimensional cultured epidermis model, the content of ceramide 3 was 0.267 µg / cm ² (SD 0.029) of SPM-L, SA- Compared to 0.349μg / cm ² (SD 0.102) of SPM-L, DCP-SPM-L is 0.476μg / cm ² (SD 0.072), and DPPG-SPM-L is 0.689μg / cm ² (SD 0.055). The content of ceramide 3 was high.

As shown in FIG. 9 (a), when liposomes were added from the basal layer side of the human three-dimensional cultured epidermis model, the content of ceramide 5 was 0.305 μg / cm ² (SD 0.074) of SPM-L, SA- Compared to 0.311μg / cm ² (SD 0.130) of SPM-L, DCP-SPM-L is 0.437μg / cm ² (SD 0.059) and DPPG-SPM-L is 0.596μg / cm ² (SD 0.047). The content of ceramide 5 was high.

As shown in FIG. 9 (b), when liposomes were added from the basal layer side of the human three-dimensional cultured epidermis model, the content of ceramide 6 was 0.365 μg / cm ² (SD 0.116) of SPM-L, SA- Compared to 0.486μg / cm ² (SD 0.224) of SPM-L, DCP-SPM-L is 0.709μg / cm ² (SD 0.176) and DPPG-SPM-L is 0.992μg / cm ² (SD 0.217) The content of ceramide 6 was high.

  Thus, as shown in FIGS. 8 and 9, when liposomes were added from the basal layer side of the human three-dimensional cultured epidermis model, compared to SPM-L and SA-SPM-L, DCP-SPM-L and DPPG-SPM-L contained more ceramide 2, ceramide 3, ceramide 5 and ceramide 6. In particular, DPPG-SPM-L had a high content of ceramide 2, ceramide 3, ceramide 5 and ceramide 6.

  According to the above experimental results, when the ceramide synthesis promoter containing the negatively charged sphingomyelin liposome produced by the above production method is added from the basal layer side, It can be seen that the ceramide content in the epidermal tissue including the layer can be increased, that is, the synthesis of ceramide can be promoted.

  Therefore, by using a ceramide synthesis promoter containing negatively charged sphingomyelin liposomes, sphingomyelin can penetrate deep into the skin (corner layer, granule layer, spiny layer, basal layer, dermis), It is possible to promote the synthesis of ceramide in the stratum corneum, the layer below the stratum corneum, the granular layer of the epidermis, the spiny layer, and the basal layer.

  In other words, by applying a ceramide synthesis promoter containing negatively charged sphingomyelin liposomes to the stratum corneum of the skin, it is possible to promote the synthesis of ceramide in the epidermal tissue and improve the skin's moisturizing function and barrier function It becomes possible. Therefore, by applying the ceramide synthesis promoter containing the negatively charged sphingomyelin liposome of the present invention to the horny layer of the skin, the skin such as dry skin, rough skin, atopic dermatitis, senile psoriasis and psoriasis It is possible to prevent, ameliorate, or cure the disease.

  As mentioned above, the detail of the manufacturing method of the ceramide synthesis promoter concerning a present Example and the experimental result which proves the effect of the ceramide synthesis promoter manufactured with the manufacturing method were shown. From the experimental results described above, it was shown that the ceramide synthesis promoter in this example has a surprising ceramide synthesis promotion effect. Therefore, the ceramide synthesis accelerator in this example can be used in a wide range of applications such as cosmetics, topical skin preparations, quasi-drugs, and pharmaceuticals. In particular, dry skin, rough skin, atopic dermatitis Application to cosmetics suitable for persons with skin diseases such as senile psoriasis and psoriasis or symptoms similar thereto, or to external skin preparations, quasi drugs, and pharmaceuticals can be expected.

  The ceramide synthesis accelerator according to the present invention is used in cosmetics, skin cosmetics / skin lotions, cosmetic liquids, creams, milky lotions, sunscreens, sunscreens, cleaning agents, shaves, unwanted hair shaves, facial rinses, packs, cosmetic oils. , Body rinse, massage, finishing cosmetics / foundation, makeup base, funny, lipstick, eye makeup, cheek cosmetics, body makeup, body powder, eau de cologne / perfume, bath cosmetics, nail cosmetics, hair cosmetics, Hair styling, hair nourishing, scalp, hair coloring, hair rinsing, hair rinsing, etc. In the case of pharmaceuticals, ointments, liquids for external use, chemical adsorbents, adhesive plasters, plasters, powders, fine granules, granules, tablets , Capsules, pills, glazes, pencils, liquid contents, extracts, suppositories, aerosols, gas agents, ophthalmic agents, injections, etc. .

  As mentioned above, although the suitable Example of this invention was described referring an accompanying drawing, it cannot be overemphasized that this invention is not limited to this Example. It will be apparent to those skilled in the art that various changes and modifications can be made within the scope of the claims, and these are naturally within the technical scope of the present invention. Understood.

  In addition, each process in the manufacturing method of the ceramide synthesis promoter which accelerates | stimulates the synthesis | combination of the ceramide of this specification does not necessarily need to process in time series along the order described as a flowchart, and can also advance in parallel. It is.

S100 ... dissolution process S102 ... vacuum distillation process S104 ... emulsification process S106 ... freeze-thaw process S108 ... size adjustment process

Claims (10)

A ceramide synthesis promoter comprising a sphingomyelin liposome,
A ceramide synthesis promoter, wherein the liposome is negatively charged.   The ceramide synthesis promoter according to claim 1, wherein the surface of the liposome is negatively charged.   The ceramide synthesis promoter according to claim 2, wherein the liposome is negatively charged by adding a negatively charged lipid.   The ceramide synthesis promoter according to claim 3, wherein the negatively charged lipid is a phospholipid.   The ceramide synthesis promoter according to claim 4, wherein the phospholipid is dicetyl phosphate or dipalmitoyl phosphatidylglycerol.   Cosmetics containing the ceramide synthesis promoter of any one of Claim 1 to 5.   A skin external preparation containing the ceramide synthesis promoter according to any one of claims 1 to 5.   A quasi-drug containing the ceramide synthesis promoter according to any one of claims 1 to 5.   A pharmaceutical comprising the ceramide synthesis promoter according to any one of claims 1 to 5. Dissolving a sphingomyelin and a negatively charged lipid in an organic solvent to produce a solution;
Evaporating the solution under reduced pressure to produce a lipid film;
Emulsifying the lipid thin film by adding water to emulsify and obtaining liposomes;
A process for producing a ceramide synthesis accelerator characterized by comprising:

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