JP5756676B2 - Topical skin preparation - Google Patents

Description

  The present invention relates to an external preparation for skin, and particularly to an external preparation for skin effective for prevention of hay fever and reduction of symptoms.

Hay fever is a national disease that is estimated to affect at least 15% of the population. Drugs prescribed for hay fever are oral antiallergic agents that are common to allergic diseases except eye drops, and the most powerful and effective are steroids, but steroids have problems such as side effects and addiction There are many points. Therefore, an increasing number of people are trying to prevent hay fever with health foods.
However, in order to improve allergic diseases with health foods and the like, it is necessary to continue taking the same product over a long period of time, and in general, there are often frustrations due to preference and economic problems.

On the other hand, for example, Patent Document 1 discloses an example in which improvement is made with an external preparation from the viewpoint of stress relaxation, and Patent Document 2 also widely discloses an example in which improvement of allergic diseases is attempted with an external preparation.
Improvement of allergic diseases by external application is known for allergic diseases such as atopic dermatitis, but allergens act directly on mucous membranes such as eyes and nose as in hay fever. There are very few attempts to prevent or alleviate symptoms with external skin preparations.

JP 2001-233723 A JP-A-10-139679

  This invention is made | formed in view of the said subject, The objective is to provide skin external preparations, such as a bath agent, which can aim at prevention of hay fever and symptom reduction.

As a result of intensive studies conducted by the present inventors in order to solve the above-mentioned problems, it has been found that a combination of specific natural ingredients exerts prevention and symptom improvement effects against hay fever, and the present invention has been completed. It was.
That is, the external preparation for skin according to the present invention comprises (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil.

It is preferable to use a bath preparation as the skin external preparation.
In the bathing agent, in the bathing agent for 150 L bath water, (a) perilla extract, (b) whey extract (c) peppermint oil, and (d) tea tree oil may each contain 0.001 to 3.0 g of pure extract. Is preferred.
In the topical skin preparation for topical application, it is preferable that (a) perilla extract, (b) whey extract, (c) peppermint oil and (d) tea tree oil each contain 0.001 to 5.0% as a pure extract. is there.

  According to the external preparation for skin according to the present invention, by blending (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil, it is effective in preventing hay fever and reducing symptoms. Is.

Hereinafter, preferred embodiments of the present invention will be described.
The hay fever that is the subject of the present invention is characterized by symptoms such as seizure / repetitive sneezing, runny nose, nasal congestion, itchy eyes, lacrimation caused by plant pollen contacting the nose and eye mucous membranes. The syndrome that is attached. Therefore, hay fever occurs depending on the time and season when pollen is scattered, so it is a combined syndrome of seasonal allergic rhinitis and seasonal allergic conjunctivitis.

  Pollen allergy is caused by pollen of about 60 kinds of plants such as cypress family (cedar, cypress, etc.), ragweed, pine, gramineous plant (kaya, wheat, etc.) and mugwort. Pollen causes of hay fever vary depending on the country or region. For example, there are many birch pollinosis in Hokkaido, ragweed in the United States, grasses in Europe, and birch in Europe. In Japan, 15% of the population is aware of hay fever, of which 70-80% are cedar and cypress pollinosis.

  Hay fever is representative of immediate type I allergy. On the other hand, atopic dermatitis, which is well-known as an allergic disease, involves type IV allergy related to skin symptoms in addition to type I allergy. When pollen adheres to the mucous membrane of the nose and eyes, it is recognized as a foreign body by macrophages, and then B-type cells, which are one of lymphocytes, are stimulated by pollen allergens, and IgE (an immunoglobulin), an immune antibody, is stimulated. create. Production of IgE is promoted by interleukin 4, which is an intercellular signal transmitter. When a conjugate of IgE and pollen allergen binds to mast cells, release of chemical mediators (mainly histamine) from mast cells becomes active. This stimulates the sensory nerves of the nose and produces sneezing and nasal discharge. On the other hand, the chemical mediator leukotriene stimulates the mucous membrane of the eye, and itching of the eye causes lacrimation. In other words, hay fever and atopic dermatitis are common in that they are type I allergies, and it is effective to suppress IgE production and histamine release. However, the difference between hay fever and atopic dermatitis is that the primary action points of the allergen are the nose and eyes, and that interleukin-4 is involved.

  Most treatments for hay fever are symptomatic treatments, and the only curative treatment is desensitization. Hyposensitization therapy is a method in which pollen allergen is gradually increased in concentration from low to high and injected into a patient to induce immune tolerance in the patient.

However, cedar is the only standardized extract for treatment, and since this treatment takes 1 to 5 years, there are many people who drop out during treatment, and there may be shock symptoms. There is.
The skin external preparation according to the present invention is excellent in preventing hay fever and alleviating various symptoms by blending (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil. Demonstrate the effect.

  The perilla extract (a) used in the present invention is an extract obtained by extraction from perilla (Perilla frutescens Britton var. Acuta Kudo) or its related plant (Labiatae) at room temperature or under heating.

Specifically, the extract is extracted from leaves of perilla or related plants with a solvent such as ethanol and filtered. The perilla extract in the present invention is preferably blended in an amount of 0.001 to 5.0%, particularly preferably 0.005 to 2.0%, as a pure extract in a topical skin external preparation. When the content of perilla extract blended in the external preparation for skin is less than 0.001%, sufficient hay fever prevention and symptom improvement effects cannot be obtained. Moreover, although the content of the perilla extract blended in the external preparation for skin may exceed 5.0%, it is not preferable because the improvement of the effect of the present invention is not so much observed. As the extraction solvent, ethanol is optimal.
In addition, content of the pure extract in this invention was calculated | required by subtracting added components, such as extracts, such as a water | moisture content and alcohol, from all the extracts of extracts, such as perilla.

  The (b) whey extract used in the present invention is preferably obtained by filtering a solution obtained by fermenting a mixed aqueous solution of skim milk powder and glucose with Lactobacillus bulgaricus. If necessary, 1,3-butylene glycol or the like may be added to the filtrate.

  In addition, it can be obtained as a yogurt extract B (70% whey, 1,3-BG 30%; manufactured by Ichimaru Falcos) as a commercial product. The whey extract in the present invention is preferably added in an amount of 0.001 to 5.0%, particularly preferably 0.05 to 3.0%, as a pure extract in the topical skin external preparation. When the content of the whey extract blended in the external preparation for skin is less than 0.001%, sufficient hay fever prevention and symptom improvement effects cannot be obtained. Further, the content of the whey extract to be blended with the external preparation for skin may be contained in excess of 5.0%, but this is not preferable since the effect of the present invention is not so much improved. There are reports that perilla and yogurt are effective for hay fever as health foods (a survey by the Ministry of Health, Labor and Welfare)

  As the mint oil (c) used in the present invention, the oil obtained by steam distillation of the above-ground part of Mentha arvensis Linne var. It is preferable. In recent years, many hay fever countermeasure products (masks, etc.) using menthol, the main ingredient of mint, have been sold. The mint oil in the present invention preferably contains 0.001 to 5.0% of menthol containing 30% by mass or more as a menthol when quantified by the Japanese Pharmacopoeia mint oil method. , 0.005 to 1.0% is particularly preferable. When the content of mint oil blended in the external preparation for skin is less than 0.001%, sufficient hay fever prevention and symptom improvement effects cannot be obtained. Further, the content of mint oil blended in the external preparation for skin may be contained in excess of 5.0%, but the taste may be reduced due to the pungent odor peculiar to mint oil, and the effect of the present invention may be reduced. Since improvement is not so much, it is not preferable.

  The (d) tea tree oil used in the present invention is a natural essential oil obtained by steam distillation of the leaves of a tea tree (English name: Tea Tree scientific name: Melaleuca alternifolia). The well-known medicinal properties of tea tree oil are its strong antibacterial action, which is used in aromatherapy, but it is also used clinically for infections by application. Moreover, the effect | action which regulates an immune function is also known [Aromatherapy Journal Vol. 12 No. 1, P36-42 (2002)] Used for hay fever. When quantified by gas chromatography, the tea tree oil in the present invention preferably contains 0.001 to 5.0% of terpinen-4-ol in a topical external skin preparation containing 30% by mass or more, It is particularly preferable to add 0.005 to 1.0%. When the content of mint oil blended in the external preparation for skin is less than 0.001%, sufficient hay fever prevention and symptom improvement effects cannot be obtained. Moreover, although content of the tea tree oil mix | blended with a skin external preparation may contain 5.0% or more, since the improvement of the effect of this invention is not seen so much, it is unpreferable.

In addition to the above essential components, the external preparation for skin of the present invention can be blended with raw materials usually used for external preparations for skin.
The external preparation for skin of the present invention comprises (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil as essential components, and optionally adds optional components and uniformly with a stirrer. It can be produced by a conventional method such as stirring. The dosage form of the external preparation for skin of the present invention is arbitrary, solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, lotion, cream, gel, Any dosage form such as a mist, a spray, an ointment, a patch for a patch, a mask impregnating agent, etc. may be used.

The external preparation for skin according to the present invention is particularly preferably used as a bath agent.
That is, it is possible to promote volatilization of volatile components with hot water, to directly work on a site where hay fever symptoms are likely to occur, such as the nose or eyes, and to promote the absorption of the active ingredient from the whole body. Further, in the case of elderly people, particularly patients with dementia, topical application of external preparations by the patient himself may be more difficult. Even in such a case, by using the external preparation for skin according to the present invention as a bath agent, it can be easily applied over a wide range by the patient himself / herself, a family other than the patient, and medical personnel. Furthermore, the dosage form of the bath preparation concerning this invention is not specifically limited, It can be set as a powder, a granule, a tablet, a liquid, an emulsified state, etc.
As in the present invention, there are no examples of external preparations for skin, such as a bath preparation in which a volatile component and a water-soluble component effective for hay fever are mixed.

  When the skin external preparation according to the present invention is used as a bath agent, 0% each of (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil in a 150 L dilution bath agent 0.001 to 3.0 g is preferable, and 0.005 to 1.0 g is particularly preferable. When the content of each component blended in the bath agent is less than 0.001 g, sufficient hay fever prevention effect and symptom improvement effect cannot be obtained. Moreover, although content of each component mix | blended with an external preparation for skin may contain 3.0g or more, since the improvement of the effect of this invention is not seen so much, it is unpreferable.

The skin external preparation of the present invention thus obtained has a hay fever preventive effect and a symptom relieving effect by combining (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil. It has excellent usability.
EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the technical scope of the present invention is not limited to these examples.

  First, the present inventors conducted a hay fever prevention test and a symptom reduction test on a composition containing (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil.

  In the following examples, (a) perilla extract, (b) whey extract, (c) peppermint oil, and (d) tea tree oil were respectively Falcolex perilla (35% ethanol extract from Ichimaru Falcos; 0.2%), yogurt extract B (70% 1,3-butylene glycol solution manufactured by Ichimaru Falcos), thin white oil (manufactured by Nagaoka Jitsugyo), and tea tree oil (manufactured by Toyoda Fragrance).

Pollen allergy prevention and symptom reduction effect test The pollen allergy prevention and symptom reduction effect test was conducted as follows.
(1) Target disease Sugi and Hinoki hay fever. `` Sneezing '', `` nasal discharge '', `` nose clogging '', `` eye itch '', `` tears '' in the onset of pollen scatter, onset and non-affected cases, recognized as medical symptoms of hay fever Panelists (patients) are selected from a comprehensive evaluation of these symptoms using as an index whether the increase in various symptoms is noticeable at the time of illness.

(2) Bath test panel Select 57 persons who are suitable for the symptoms of the target disease as panelists and have them participate in the bath test. 28 out of 57 people participated in a bathing test to verify the prevention effect of hay fever (Group 1), and the other 29 people took a bathing viewpoint to verify the effect of improving symptoms after the onset of hay fever. I had you participate in.

(3) Group distribution The cedar and cypress scattered around Tokyo, the test site, started in mid-February, and hay fever occurred almost simultaneously with the pollen scattering. Therefore, Group 1 panelists conduct a bathing test one month before the onset, that is, from the middle of January for one month. Group 2 panelists will conduct a bathing test for 1 month after the onset is confirmed, that is, from late February.

(4) Bath test method The bath test method is the same for both Group 1 and Group 2.
Panelists take a bath once a day in an ordinary household tub. The temperature of the bath is not particularly limited. The bathing time is about 10 minutes, but is not particularly limited. The test sample is a 30 ml aqueous solution in a bottle. Use one bottle per bath test. Shake the bottle well, put it in the bath just before entering the bath, and stir the bath before bathing.

  If there are two or more panelists in the family, use one bottle per person. There are no restrictions on body washing, hair washing, and showers at the end of bathing. During bathing tests, you should avoid taking medicines and health foods that are used to treat hay fever as much as possible, but if you see signs of worsening symptoms, stop bathing tests and resume taking medicines. To do.

(5) Test sample The active ingredient concentration in one bottle of the test sample is 4% whey extract (70% pure), 4% perilla extract (about 0.2% pure), mint oil 0.2%, tea Tree oil 4%, made up to 30 ml with water. Yogurt extract and perilla extract are water-soluble, but mint oil and tea tree oil are insoluble in water, so they are actually separated into an aqueous phase and an oil phase in the bottle. Therefore, when putting the test sample in the bath water, shake the bottle well.

(6) Manufacture of test sample The test sample was manufactured by preparing a mixed aqueous solution (solution A) of yogurt extract and perilla extract and a mixture of mint oil and tea tree oil (solution B). And solution B are mixed to obtain a desired test sample.

(7) Questionnaire After completion of the bathing test, the panelists will be asked to answer the questionnaire questions. Excluded were no responses.
For both groups 1 and 2, there are two types of questionnaires: a questionnaire that asks about the effect of bathing agents during the bath administration period, and a questionnaire that asks for changes in symptoms after a certain period of time has passed.

  Questionnaire items include five items (improvement, slightly improved, unchanged, slightly different) for hay fever symptoms: “sneeze”, “nasal discharge”, “nasal congestion”, “itching eyes”, and “tears”. There are five choices (good, good) for evaluation as a bathing agent, and four items of “moist feeling”, “smooth feeling”, “how to warm”, and “feel of hot water”. (Slightly good, unchanged, slightly bad, bad) were selected (tested only in group 1).

Test result group 1 Immediately after administration 1 month after completion of administration 2 months after completion of administration a. Number of sneezes 23 people 21 people 22 people decreased 26.1% 19.0% 31.8%
Slightly decreased 21.7% 23.8% 22.7%
No change 52.2% 52.4% 31.8%
Slightly increased 0% 4.8% 13.6%
Increased 0% 0% 0%
b. Nasal discharge 23 people 21 people 22 people decreased 26.1% 23.8% 31.8%
Slightly decreased 21.7% 33.3% 27.3%
No change 52.2% 38.1% 40.9%
Slightly increased 0% 4.8% 0%
Increased 0% 0% 0%
c. Nose clogging 23 people 21 people 22 people Improved 17.4% 23.8% 31.8%
Slightly improved 26.1% 33.3% 40.9%
Unchanged 56.5% 42.9% 27.3%
Slightly worse 0% 0% 0%
0% 0% 0%
d. Itchy eyes 23 people 21 people 22 people improved 21.7% 19.0% 31.8%
Slightly improved 17.4% 33.3% 31.8%
Unchanged 60.9% 38.1% 31.8%
Slightly worse 0% 9.6% 4.6%
0% 0% 0%
e. Tears 23 people 21 people 22 people decreased 26.1% 28.6% 36.4%
Slightly decreased 8.7% 23.8% 31.8%
Unchanged 65.2% 47.6% 27.3%
Slightly increased 0% 0% 4.5%
Increased 0% 0% 0%
f. Moist feeling 23 people Moist 4.3%
Slightly moist 43.5%
Neither 43.5%
Not moist a little 4.3%
Not moist 4.3%
g. Smooth feeling 23 people Smooth 8.7%
Easily smooth 26.1%
60.9%
0%
Not slippery 4.3%
h. How to warm 23 people Warm 21.7%
Slightly warm 30.4%
Unchanged 17.4%
17.4% which does not warm a little
Does not warm 13.1%
i. Hot water feel 22 soft 4.5%
Slightly soft 31.8%
Unchanged 54.6%
Slightly 9.1%
Hard 0%

  Regarding group 1, pollen hardly scattered during the bath administration period, but full-scale pollen starts after the bath administration period ends. As a result of the above, the evaluation as a general bathing agent is not necessarily excellent, but it should be noted that the effect persists even after the end of administration, and one month after the end of administration (peak period of pollen scattering) and 2 The questionnaire results at the time of the month showed that alleviation of symptom peculiar to hay fever was recognized.

  The improvement of eye symptoms is particularly remarkable. This may be because the components in the bath water absorbed by the skin contributed to the effect of improving the constitution. (Japan Agricultural Chemistry Society 2010 Conference “Effect of Bifidobacterium G9-1 strain on allergic rhinitis model”)

Group 2 Immediately after administration 1 month after completion of administration a. Number of sneezes 23 people 22 people decreased 39.2% 36.4%
Slightly decreased 30.4% 36.4%
Unchanged 30.4% 27.2%
Slightly increased 0% 0%
Increased 0% 0%
b. Nasal juice 24 people 22 people decreased 37.5% 40.9%
Slightly decreased 29.2% 22.7%
Unchanged 33.3% 36.4%
Slightly increased 0% 0%
Increased 0% 0%
c. Nasal congestion 24 people 22 people improved 33.3% 40.9%
Slightly improved 37.5% 31.8%
Unchanged 29.2% 27.3%
Slightly worse 0% 0%
0% 0%
d. Itchy eyes 23 people 22 people improved 13.0% 13.6%
Slightly improved 30.4% 50.0%
Unchanged 56.6% 36.4%
Slightly worse 0% 0%
0% 0%
e. Tears 22 people 21 people decreased 22.7% 23.8%
Slightly decreased 22.7% 28.6%
Unchanged 54.6% 47.6%
Slightly increased 0% 0%
Increased 0% 0%

  Group 2 was administered (bathing) during the peak period of pollen scattering, and the post-administration data showed an effect of reducing hay fever, and the effect was effective even one month after the end of the administration when pollen scattering was reduced. It lasted.

  From the above, the composition containing (a) perilla extract, (b) whey extract, (c) peppermint oil and (d) tea tree oil is able to obtain an excellent hay fever prevention effect by administration before pollen scattering. In addition, it was found that administration at the time of pollen scattering has a symptom-reducing effect and is excellent in sustainability.

  Although the formulation example of the skin external preparation concerning this invention is given to the following, the technical scope of this invention is not limited at all by this. The obtained external preparation for skin was effective for hay fever and excellent in feeling of use.

Formulation Example 1 Bathing agent (powder type)
Sodium bicarbonate 96.35%
Light white oil 0.10
Tea tree oil 1.00
Monooleic acid polyoxyethylene sorbitan (20E.O.)
0.05
Perilla extract (Falcolex perilla: the same applies below) 0.50
Whey extract (yogurt extract B: Same as below) 0.50
Silica anhydride 0.70

Formulation Example 2 Bathing agent (Bath oil)
Liquid paraffin 83.1
Polyoxyethylene oleyl ether (5EO)
12.0
Light load white oil 0.9
Tea tree oil 1.0
Perilla extract 1.5
Whey extract 1.5

Formulation Example 3 Bathing agent (milk type)
Compounding amount (%)
Perilla extract 3.00
Whey extract 5.00
Peppermint oil 0.10
Tea tree oil 0.20
Mineral oil 33.00
Safflower oil 4.00
POE (20) cetyl ether 2.60
Sorbitan palmitate 2.80
Solveste tetraoleate 0.30
Dipropylene glycol 4.10
Diglycerin 6.65
Methylparaben 0.25
Edetate disodium 0.25
Polyethylene glycol 200 0.10
Dipotassium glycyrrhizinate 0.10
Sodium hyaluronate (2) 0.01
Succinyl atelocollagen solution 0.01
Fragrance 0.30
Pure water balance

Formulation Example 4 Lotion
Compounding amount (%)
Perilla extract 1.50
Whey extract 2.00
Peppermint oil 0.05
Tea tree oil 0.20
Alcohol 10.00
POE hydrogenated castor oil 0.50
Glycerin 5.00
Dipropylene glycol 3.00
Sodium hyaluronate 0.05
Succinyl atelocollagen solution 0.20
Methylparaben 0.05
Pure water balance

Formulation Example 5 Latex
Compounding amount (%)
Perilla extract 1.50
Whey extract 5.00
Peppermint oil 0.10
Tea tree oil 0.20
Liquid paraffin 6.50
Stearic acid 1.50
Glycerol monostearate1.00
Cetostearyl alcohol 0.60
POE sorbitan monostearate 0.46
POE sorbitan monooleate 1.36
POE cetyl ether 0.18
Palm oil fatty acid sorbitan 0.50
Dimethicone 0.50
Butylparaben 0.05
Glycerin 2.00
Sodium hyaluronate 0.01
Succinyl atelocollagen solution 0.20
Pure water balance

Formulation Example 6 Cream
Compounding amount (%)
Perilla extract 1.80
Whey extract 0.60
Peppermint oil 0.60
Tea tree oil 0.20
Solid paraffin 11.10
Liquid paraffin 10.10
Cetanol 5.10
White petrolatum 5.00
Stearic acid 3.00
Butylparaben 0.05
Triethanolamine 1.35
Methylparaben 0.05
Sodium hyaluronate 0.01
Succinyl atelocollagen solution 0.20
Pure water balance

Formulation Example 7 Body Soap
Compounding amount (%)
Perilla extract 1.00
Whey extract 1.00
Peppermint oil 0.10
Tea tree oil 0.20
Potassium hydroxide 5.54
Lauric acid 11.10
Myristic acid 4.00
Stearic acid 4.00
Edetate disodium 0.085
Methylparaben 0.20
Sodium chloride 0.70
Palm oil fatty acid monoethanolamide 3.10
Laurolylmethylalanine sodium 1.00
Lauramidopropyl betaine 1.00
Lauryl sulfate triethanolamine 4.50
Glycol distearate 1.90
Glycerin 1.80
Hydroxypropyl methylcellulose 0.50
Fragrance 0.60
Water balance

Formulation Example 8 Ointment
Compounding amount (%)
Perilla extract 3.0
Whey extract 3.0
Peppermint oil 0.5
Tea tree oil 0.3
White petrolatum 25.0
Stearyl alcohol 20.0
Propylene glycol 12.0
POE hydrogenated castor oil 4.2
Glycerol monostearate 1.0
Propylparaben 0.1
Methylparaben 0.1
Pure water balance

Claims (2)

(A) perilla extract,
(B) whey extract;
(C) peppermint oil;
(D) tea tree oil;
Only including, prevention and amelioration agent for pollinosis, characterized by use as a bath additive. In the prevention and amelioration agent for pollinosis according to claim 1, when used as a bathing agent, (a) perilla extract, (b) whey extract, (c) peppermint oil, (d) is tea tree oil, 150L bath water among, prevention and amelioration agent for pollinosis, characterized in that it comprises 0.001~3.0g respectively as pure extract.