JPH11106347A - Immunoactivator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine, capable of manifesting the remarkable activities improving and preventing the decrease of immunoactivating activities and immunological function by allowing the medicine to include a rosemary extract. SOLUTION: This medicine includes a rosemary extract. The rosemary extract is the extract of Rosmarinus officinalis of the family Labiatae with water or an organic solvent, and obtained, for example, by stirring and extracting leaves, branches, etc., of the Rosmarinus officinalis with the water or methanol or the like, under heating to 30-70 deg.C for 1-10 hr, filtering the extract, and carrying out the concentration or the like of the filtrate. A formulation amount of the rosemary extract in the medicine is preferably 0.0005-10.0 wt.% as a dried material based on the whole quantity of the medicine. As a result, the objective medicine having immunoactivating activities of the rosemary extract or the improvement and prevention activities for decrease of immunological function by ultraviolet rays and capable of being used in a form of a skin lotion can be provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an immunostimulant or an agent for improving or preventing a decrease in immune function.

[0002]

2. Description of the Related Art The skin is the outermost organ of the living body, and is the organ which is most strongly and directly affected by physical, chemical and biological invasion. It has become clear that it is an organ.

[0003] The skin is composed of keratinocytes of the epidermis, Langerhans cells, dendritic cells of the dermis, vascular endothelial cells, macrophages, etc. Langerhans cells play a central role in the skin immune function due to their ability to process and present antigen. In response to the entry of antigen as a foreign substance from the outside, it immediately contacts and processes it, migrates to the lymph nodes and presents it to T cells, and a series of subsequent immune response reactions Is believed to begin.

[0004]

In recent years, it has been pointed out that in addition to the carcinogenicity of ultraviolet light itself, the possibility of promoting carcinogenesis due to a decrease in skin immune response due to ultraviolet light.
Protecting ultraviolet rays with sunscreen cosmetics, such as sunscreens, is extremely important in preventing ultraviolet ray carcinogenesis, but the immunosuppressive effect may be manifested by continuing to be exposed to ultraviolet rays daily even in the season when sunscreens are not used on a daily basis. There are also concerns about various adverse effects on living organisms other than carcinogenesis.

[0005] Further, it is considered that the skin immune function is lowered by various causes other than ultraviolet rays, such that the skin immune function is lowered by aging.

[0006] For the above reasons, there is an urgent need to develop a drug which can be used on a daily basis and which has an immunostimulating action or an improvement / prevention action for a decrease in immune function.

[0007] The present inventors have studied the preventive effect of various substances on the immunosuppressive action as a solution to these problems. As a result, the rosemary extract improved the remarkable immunostimulatory action and the decrease in the immune function. -It has been found that it has an action of preventing, and the present invention has been completed.

[0008] There have been no reports on the immunostimulatory effect of rosemary extract and the improvement / prevention of immunological decline, etc., and the present invention improves / prevents the immunostimulatory effect of rosemary extract and immunological decline due to ultraviolet rays. This is an invention that has been completed as a result of finding a new effect.

[0009]

That is, the present invention provides an immunostimulant characterized by containing a rosemary extract.

[0010] The present invention also provides an agent for improving or preventing a decrease in immune function, characterized by containing a rosemary extract.

[0011]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The configuration of the present invention will be described below in detail.

The rosemary extract used in the immunostimulant or the immunological impairment ameliorating / preventing agent of the present invention is a perilla plant, Rosmarinus officinalis Linn.
e) an extract of water or an organic solvent, specifically, for example, dried powder or non-dried cuts such as leaves or branches of mannen wax, or seeds or fruits, or roots, or whole plants The product is treated with water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, butanol, chloroform, dichloroethane, carbon tetrachloride, ethyl acetate, ether, etc. or a mixture thereof under heating at 30 to 70 ° C. Extract for 10 hours with stirring, or extract for 1 to 20 days at room temperature,
After filtration, the filtrate is concentrated, and then concentrated under reduced pressure to dryness. In the present invention, the rosemary extract can be used at the stage of a concentrate or at the stage of a dried product.

The amount of the rosemary extract in the immunostimulant or the immune function lowering / preventing agent of the present invention is as follows:
In all amounts of immunostimulants or immune function lowering / preventing agents,
It is 0.0005 to 10.0% by weight, preferably 0.001 to 5.0% by weight as a dry matter. If the amount is less than 0.0005% by weight, the immunostimulant of the present invention or the effect of improving and preventing a decrease in immune function is not sufficiently exhibited, and if it exceeds 10.0% by weight, it is difficult to formulate the preparation, which is not preferable. Also,
Even if the content is 5.0% by weight or more, the effect is not significantly improved.

In addition to the above essential components, the immunostimulating agent or the immunological function improving / preventing agent of the present invention may be any component usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, whitening agents, moisturizing agents, antioxidants , Oily components, ultraviolet absorbers, anti-inflammatory agents, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, and the like can be appropriately compounded as necessary. .

The immunostimulant or the immunological function improving / preventing agent of the present invention can be used, for example, in the form of external preparations for the skin such as ointments, creams, emulsions, lotions, packs, bath preparations and the like. Absent. The immunostimulant or the immunologically impaired improving / preventing agent of the present invention has high utility value as an immunostimulating cosmetic or an immunologically impaired improving / preventing cosmetic.

[0016]

Next, the present invention will be described in more detail by way of examples. Note that the present invention is not limited by this. The compounding amount is% by weight.

The immunostimulatory effect of the rosemary extract and the amelioration / prevention of the immune function decrease by ultraviolet light were evaluated by the intercellular adhesion molecule-1 in Langerhans cells by UV irradiation.
(ICAM-1) It examined from the protective effect with respect to expression suppression.

[Rosemary extract] [0018] The rosemary extract used in the following examples was prepared by extracting a cut piece of Mannenwa flower in 50% ethanol at 50 ° C for 5 hours, followed by filtration. Then, a concentrate obtained by evaporating the solvent of the filtrate was used.

"Test Method and Results: Intercellular adhesion molecule-1 (ICAM) in Langerhans cells by UV irradiation
-1) Protective effect against suppression of expression] Langerhans cells obtained by treating the epidermis of human skin with 0.5% trypsin were irradiated with UVA (5 J / cm ² , BLB lamp), and then irradiated with RPMI 1640/10% FBS. 24 at ° C
Cultivated in a CO ₂ incubator for hours. After culture
After treatment with an FITC-labeled anti-MHC class II antibody (Pharmizen) and a PE-labeled anti-ICAM-1 antibody (Pharmizen), a flow cytometer (XL: Epix)
3) analysis of 3 × 10 ⁴ cells, ICAM of Langerhans cells expressing MHC class II antigen
-1 expression intensity was measured. The result is shown in FIG. FIG.
The vertical axis indicates the ICAM-1 expression rate (%), and the horizontal axis indicates the presence or absence of the rosemary extract (final concentration:% by weight).
From FIG. 1, it can be seen that the addition of the rosemary extract results in the intercellular adhesion molecule-1 in Langerhans cells by UVA.
It can be seen that the (ICAM-1) expression inhibitory effect is clearly protected.

The following examples show the use of the rosemary extract as an immunostimulating agent or an agent for preventing and / or improving immune function.

Example 1 Cream (Formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Rosemary extract 0.01 Paraaminobenzoic acid 0.5 2-Ethylhexyl paramethoxycinnamic acid 5.0 Caustic potash 0.2 Preservatives Appropriate amount Fragrance Appropriate amount Ion-exchanged water residue (Preparation method) Add propylene glycol, rosemary extract and caustic potash to ion-exchanged water and dissolve. Heat to 70 ° C
(Aqueous phase). Mix other ingredients, heat and melt at 70 ° C
(Oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to cause a reaction.
Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 2 Cream (Prescription) Stearic acid 2.0% by weight Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl Alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 2-Ethylhexyl paramethoxycinnamic acid 10.0 Rosemary extract 0.05 Ethylparaben 0.3 Perfume Appropriate amount Ion exchange water Residue (Preparation method) Ion Add propylene glycol to the replacement water,
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsified, homogenized with a homomixer, and cooled to 30 ° C. with good stirring.

Example 3 Cream (Formulation) Solid paraffin 5.0% by weight Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate Ester 2.0 Soap powder 0.1 2-Ethylhexylparamethoxycinnamic acid 1.0 Borax 0.2 Rosemary extract 0.05 Ascorbic acid 2.0 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchange water Residue (Preparation method) Soap powder and borax are added to the exchanged water, and the mixture is dissolved by heating and maintained at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After completion of the reaction, the mixture is uniformly emulsified with a homomixer, and cooled to 30 ° C. while stirring well after emulsification.

Example 4 Emulsion (Formulation) Stearic acid 2.5% by weight Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BFGoodrich Chemical company) Rosemary extract 0.01 Octyl paradimethylaminobenzoate 1.0 Arbutin 3.5 Ethylparaben 0 0.3 Appropriate amount of perfume Residual ion-exchanged water (Preparation method) Dissolve the carboxyvinyl polymer in a small amount of ion-exchanged water (phase A). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is added to the water phase, pre-emulsification is performed, the phase A is added, and the mixture is uniformly emulsified with a homomixer.

Example 5 Emulsion (Formulation) Microcrystalline wax 1.0 wt% glutathione 1.0 beeswax 2.0 lanolin 20.0 liquid paraffin 10.0 octyl paradimethylaminobenzoate 3.0 2-ethylhexyl Paramethoxycinnamic acid 5.0 squalane 5.0 sorbitan sesquioleate 4.0 polyoxyethylene (20 mol) sorbitan monooleate 1.0 propylene glycol 7.0 rosemary extract 10.0 ascorbic acid phosphate Magnesium 3.0 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchange water residue (Production method) Add propylene glycol to ion-exchange water,
Heat and maintain at 70 ° C. (aqueous phase). The other components are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added thereto, and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C with good stirring.

Example 6 Jelly 95% ethyl alcohol 10.0% by weight dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 (trade name: Carbopol 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Isopropyl paramethoxycinnamate 0.1 2-Ethylhexyl paramethoxycinnamic acid 0.5 Titanium oxide 5.0 Rosemary extract 7.0 2 -Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Ethylenediaminetetraacetate / trisodium / 2 water 0.05 Methylparaben 0.2 Perfume Appropriate amount Ion exchange water Residue (Preparation method) Carbopol 940 is uniformly dissolved in ion exchange water , On the other hand, 95% ethanol Rosemary extract,
Polyoxyethylene (50 mol) oleyl alcohol ether is dissolved and added to the aqueous phase. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Beauty Serum (Formulation) (A phase) Ethyl alcohol (95%) 10.0% by weight Polyoxyethylene (20 mol) octyldodecanol 1.0 Pantothenyl ethyl ether 0.1 Rosemary Extract 1.5 Methyl paraben 0.15 (B phase) Potassium hydroxide 0.1 (C phase) Glycerin 5.0 Dipropylene glycol 10.0 Carboxyvinyl polymer 0.2 (Product name: Carbopol 940, BFGoodrich Chemical company) Purified water residue (Preparation method) Dissolve A phase and C phase uniformly, and add A to C phase
Add phases and solubilize. Next, after adding the phase B, the container is filled.

Example 8 Pack (Formulation) (A phase) Dipropylene glycol 5.0% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) Rosemary extract 0.01 Olive oil 5 2.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Fragrance 0.2 (C phase) Polyvinyl alcohol 13.0 (Saponification degree 90, Degree of polymerization 2,000) Ethanol 7.0 Purified water Residue (Production method) A phase Dissolve B phase and C phase uniformly,
Add phase B to phase and solubilize. Next, this is added to the phase C, and then the container is filled.

Example 9 Solid Foundation (Formulation) Talc 43.1% by weight Kaolin 15.0 Sericite 10.0 Zinc white 7.0 Titanium dioxide 3.8 Yellow iron oxide 2.9 Black iron oxide 0.2 Squalane 8.0 Isostearic acid 4.0 POE sorbitan monooleate 3.0 Isocetyl octanoate 2.0 Rosemary extract 1.0 Preservatives Appropriate amount Perfume Appropriate amount (Production method) Powdery component of talc to black iron oxide is sufficiently blended After mixing and adding the oily components of squalane to isocetyl octanoate, rosemary extract, preservative, and flavor, the mixture is kneaded well, and filled and molded into a container.

Example 10 Emulsion Type Foundation (Cream Type) (Prescription) (Powder Part) Titanium Dioxide 10.3% by Weight Sericite 5.4 Kaolin 3.0 Yellow Iron Oxide 0.8 Bengala 0.3 Black Iron oxide 0.2 (oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (aqueous phase) Purified water 50.0 1,3-butylene glycol 4. 5 Rosemary extract 1.5 Ascorbic acid glucoside 1.0 Sorbitan sesquioleate 3.0 Preservatives Appropriate amount Fragrance Appropriate amount (Production method) Mixer processing. Further, the oil phase mixed by heating is added, and the mixture is treated with a homomixer. Then, a fragrance is added with stirring, and the mixture is cooled to room temperature.

[0031]

According to the present invention, the immunostimulatory effect of rosemary extract or the improvement of immune function reduction by ultraviolet light is improved.
It is possible to provide an excellent immunostimulant or an immunological function improving / preventing agent utilizing the preventive action.

[Brief description of the drawings]

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a diagram showing the suppression of the expression of the intercellular adhesion molecule ICAM-1 in Langerhans cells by UV irradiation and the protective effect of a rosemary extract.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Masato Hatao 1050 Nippa-cho, Kohoku-ku, Yokohama, Kanagawa Prefecture Inside Shiseido Daiichi Research Center Co., Ltd. Address: Shiseido Daiichi Research Center Co., Ltd.

Claims (2)

[Claims] 1. An immunostimulant comprising a rosemary extract. 2. An agent for improving or preventing a decrease in immune function, characterized by containing a rosemary extract.