JP5302526B2 - Artemisia essential oil topical preparation - Google Patents

Description

  The present invention relates to an external preparation containing as an active ingredient an essential oil obtained from mugwort collected at a specific time. The external preparation of the present invention is excellent in the percutaneous and retention properties of the active ingredient, exhibits various medicinal effects such as treatment of dermatitis, and particularly exhibits an excellent therapeutic effect as a skin external preparation for atopic dermatitis. The external preparation of the present invention can be prepared in various dosage forms including ointments.

Steroid ointment is widely used for atopic dermatitis, but side effects are also caused by its inappropriate use. For this reason, an effective crude drug external preparation for atopic dermatitis is desired, and there is an ointment in which various herbal powders are blended into an ointment base such as petrolatum. However, such ointments are not preferable because they are rough and irritate to the skin. Ointments prepared by extracting herbal ingredients by mixing herbal ingredients with petrolatum and heating for a long time, and herbal ointments obtained by extracting herbal ingredients with sesame oil are also commercially available. There is a problem, it is hard to tolerate use, and the therapeutic effect is not obtained. In addition, there are proposals for herbal ointments in which raw materials such as yellow ream, ougon and jaundice are minced, decocted with water and concentrated, and mixed with a hydrophilic petrolatum base, but it is difficult to maintain quality and is familiar to the skin. The therapeutic effect has not been improved.
The present inventor previously used a herbal medicine ointment (Japanese Patent Laid-Open No. 10-236944) using, as an active ingredient, components obtained by extracting various herbal medicines with a non-polar organic solvent, such as bamboo shoots (guinea leaves: collected from May to July). In order to provide a more effective external preparation for the treatment of dermatitis, further research was conducted focusing on mugwort raw materials.

  Artemisia, which has been known for a long time, has a strong aroma, is effective for reducing inflammation and anti-inflammatory effect, and is used for medicinal purposes. Such mugwort is a perennial plant belonging to the family Asteraceae that grows naturally all over Japan. The leaves are green on the upper surface and white on the lower surface, and the cilia are dense. Soft leaves come out around the end of March, and it becomes several tens of centimeters around April. It branches off at the shoot apex in August-September, has a double total inflorescence in September-October, and has a number of extremely small and light brown head flowers consisting of tubular flowers. It will wither and harden in winter. In Japan, the leaves of Artemisia princeps or Artemisia montana are used for medicinal purposes. The prescription name in Kampo is called “Gaiyo”, and the leaves are collected from May to July and sun-dried. The medicinal origin in China is young whole grass or leaves of Artemisia plants. Young whole grass refers to stems and leaves from around May to June. Mogusa (school clan) is mainly dried from spring leaves and exposed to the fur on the back. The persimmon leaves that are widely distributed are also dried products of leaves from May to June. In Kampo, this koji leaf is used exclusively as a hemostatic agent (Kyu Hikijyoto).

  In addition, as a folk medicine, decoction of mugwort leaves and stems in the spring is used, and it is used as an internal medicine with the expectation of an effect especially on abdominal pain and anemia. I have applied it. However, to date, mugwort has not been used in general except for placing young spring leaves in strawberries for food.

  It has been reported that koji leaves have lipid synthesis inhibition, degradation promotion effect, blood coagulation inhibition effect, complement activation effect, interferon induction effect, antipruritic effect and anti-inflammatory effect by water-soluble components. In addition, there are reports that the essential oil contains cineole, tsuyon, etc., but there is no evidence of formulation based on these reports in the clinic.

  In recent years, there are reports that the number of post-adult atopic dermatitis patients is increasing at an accelerating rate. Such patients have suffered from sensitive skin sensations, redness of the skin, and dry symptoms, such as allergic symptoms, itching and pain since adolescence and adulthood. Although transient inflammation can be suppressed with antiallergic drugs and steroid preparations, there is a need for a topical drug that can respond to each of the skin symptoms that may shift depending on the seasons and changes in the living environment. In particular, there are many patients who are sensitive to skin sensation, and there is a demand for a preparation that is easy to use.

JP-A-10-236944

  In view of the above circumstances, the present inventor has continued research on mugwort as a crude drug raw material in order to obtain a crude drug external preparation having a high therapeutic effect. As a result, the present invention was completed with the knowledge that the use of an active ingredient made from mugworts collected at a specific period of time can provide a markedly superior therapeutic effect for various diseases including atopic dermatitis. did. The preparation for external use of the present invention uses mugwort leaves, stems, and flower parts collected from summer to autumn as raw materials for extraction. The mugwort of this period branches at the top of the stem, forms a double gross inflorescence, and attaches many head flowers consisting of tubular flowers. By using mugwort at such a time as a raw material, a remarkable therapeutic effect can be obtained for the symptoms of dermatitis, particularly atopic dermatitis.

  The present invention is an external preparation containing an essential oil contained in mugwort as an active ingredient, and a mugwort essential oil external preparation that is a stem, a leaf attached to the stem, and / or a double inflorescence of the mugwort raw material portion of the essential oil. Is to provide. The external preparation of the present invention has high skin absorption (percutaneous absorption) and moisturizing properties, and exhibits an excellent therapeutic effect. The mugwort can be collected from August to October. The essential oil is preferably obtained from mugwort by non-thermal extraction with an ether solvent or steam distillation. Ointments, lotions, creams, gels, and packs are used as the dosage forms for external preparations. Moreover, an intraoral cleaning agent or a mouthwash is employ | adopted with respect to dryness in a lip | lip or an oral cavity. In the case of an ointment, vegetable oils (olive oil, beeswax, sesame oil, safflower oil), horse oil and honey beeswax are preferably used as the base.

  The external preparation of the present invention has a remarkable effect on dermatitis, particularly atopic dermatitis. Unlike topical preparations using alcohol, skin lipids are not destroyed even after long-term use, and are highly effective compared to conventional preparations using traditional Chinese medicine extracts. The external preparation of the present invention has an effect of improving skin, and no side effects are observed even when used for a long time.

Detailed Disclosure of the Invention

  Artemisia used as a raw material for the external preparation of the present invention can be collected from August to October. The mugwort of this period branches at the top of the stem to form a double total inflorescence, and has many head flowers made of tubular flowers, and the whole plant such as leaves, stems, and spikes is used as an extraction raw material. Mugwort generally used for food is collected in the spring until April, and mugwort used as a traditional Chinese medicine is called gaiyo and is collected from April to July. All of these are before the mugwort blooms appear, and are different from the raw mugwort used in the present invention in the collection time and the properties are as described above, and the essential oil obtained is different.

In order to obtain the essential oil component used in the present invention from the raw mugwort, any of the known methods such as steam distillation and solvent extraction with a nonpolar solvent, which are conventionally used for collecting essential oil from plants, are employed. Although it is good, it is preferable to avoid heating at 250 ° C. or higher.
When performing extraction with a solvent, a nonpolar organic solvent is used unlike water or alcohol such as ethanol, which has been conventionally used for extraction of crude drugs. Typical examples of such solvents include ether solvents such as ether and tetrahydrofuran, petroleum solvents such as petroleum ether, aromatic solvents such as benzene, toluene and xylene, methyl acetate, ethyl acetate and the like. Examples thereof include ester solvents, aliphatic solvents such as hexane and heptane, and halogenated hydrocarbons such as methylene chloride. Of these, ether solvents are preferred, and ethyl ether is particularly preferred.

  In order to extract mugwort with a solvent, it is preferable to first crush the raw mugwort to an appropriate size. The extracted raw material is left in a closed container (soaked) together with 3 to 30 times (weight), preferably 5 to 10 times the amount of solvent. The extraction (soaking) may be slightly heated at 60 ° C. or less, but is preferably performed at room temperature and without heating.

  The immersion time is 6 hours or longer, preferably 12 to 2 days, and generally about one day and night. Care should be taken in changing the hue because of the formation of oxides by immersion for a long time. The suspended matter is removed with filter paper or filter cloth, the immersion liquid is taken, and the solvent is distilled off in a hot water bath using an evaporator. The solvent is distilled off as much as possible so that the essential oil components are not volatilized until the solvent is distilled off. Further, a large amount of raw mugwort may be used, and the extraction operation may be performed a plurality of times by repeatedly replacing with a new solvent. The obtained extract is dissolved in an appropriate oil such as vegetable oil to remove suspended matters, or solid matter is removed by a method such as filtration.

  Thus, in order to manufacture the skin external preparation in the form of an ointment using the essential oil obtained from mugwort, plant or animal-derived non-mineral oil is used as the base. Preferable bases include vegetable oils such as olive oil, beeswax, camellia oil, sesame oil, safflower oil, horse oil, and white beeswax. Use of such vegetable oils and animal oils is preferable because it has less irritation to the skin than mineral bases such as petrolatum, and also has a therapeutic effect due to the bases themselves.

In the preparation of the ointment, the essential oil extracted from the above mugwort and the ointment base are used, and heating can be avoided as much as possible. When liquid oil is used as a base, a mugwort extract may be added thereto and mixed with stirring. Moreover, when using solid fats and oils, this is heat-melted at melting | fusing point temperature, and after removing a heat source, a crude drug extract is mixed rapidly.
The amount of mugwort extract (essential oil) used in the base is 5 to 100 mg, preferably 10 to 50 mg, based on 100 g of the base.
The formulation of the base may be appropriately changed depending on the temperature and the patient's symptoms. In order to adjust the consistency of the base, it is usually preferable to blend 2 to 3 parts by weight of beeswax and 10 to 15 parts by weight of olive oil with respect to 1 part by weight of horse oil. To increase malleability, it is preferable to reduce beeswax and increase olive oil.

  As an external preparation of the present invention, an ointment, a lotion, a cream using the above-mentioned artemisia essential oil, if necessary, together with a pharmaceutically acceptable known pharmaceutical carrier according to each dosage form, using a conventional production method for formulation. , Gels, packs, mouth washes, gargles and the like. In addition, the external preparation of the present invention may be used in combination with appropriate medicinal components such as other herbal components as long as the purpose is not impaired, and commonly used known components depending on each dosage form such as antioxidants and perfumes. Can be blended as necessary.

Next, the present invention will be described more specifically based on examples and comparative examples.
[Example 1]
50 g of whole mugwort grass (collected in August), which was branched at the top of the stem and formed a double gross inflorescence, with many head flowers consisting of tubular flowers, was weighed and pulverized by a pulverizer. These raw materials were placed in a sealed glass container together with 1 L of ether and allowed to stand at room temperature for 24 hours. Subsequently, the liquid phase was filtered out and the solvent was distilled off with an evaporator (hot water bath 60 ° C.) to obtain a mugwort extract. This was dissolved in vegetable oil (olive oil) to remove suspended matters and then analyzed by mass spectrometry. FIG. 1 shows a chart obtained by searching for the presence of a substance having a mass to charge ratio of 600. This extract was dissolved in 2 L of olive oil. Separately, 500 g of finely ground beeswax and 150 g of horse oil were placed in a container having good heat conductivity, heated and dissolved at about 70 ° C., the heat source was removed, and the mugwort extract mixed with olive oil was added with stirring. Next, the skin ointment was prepared by stirring while rapidly cooling with ice water.

[Example 2]
A mugwort leaf (collected in August) that branches at the shoot apex, forms a biquad inflorescence, and has a large number of head flowers consisting of tubular flowers was processed in the same manner as in Example 1 to obtain an extract (essential oil). This was analyzed by mass spectrometry. The obtained chart is shown in FIG. The obtained extract was treated in the same manner as in Example 1 to prepare an external skin ointment.

[Example 3]
A mugwort stalk (collected in October) that branches at the top of the stalk to form a double gross inflorescence and has many head flowers made of tubular flowers was treated in the same manner as in Example 1 to obtain an extract (essential oil). This was analyzed by mass spectrometry. The obtained chart is shown in FIG. The obtained extract was treated in the same manner as in Example 1 to prepare an external skin ointment.

[Example 4]
Artemisia spikelets (collected in October) with many head flowers were treated in the same manner as in Example 1 to obtain an extract (essential oil). This was analyzed by mass spectrometry. The obtained chart is shown in FIG. The obtained extract was treated in the same manner as in Example 1 to prepare an external skin ointment.

[Comparative Example 1]
A Kampo commercial product (Aoba; sold by Nakajima Seiyaku Co., Ltd.) was treated in the same manner as in Example 1 to obtain an extract. This was analyzed by mass spectrometry. The obtained chart is shown in FIG. The obtained extract was treated in the same manner as in Example 1 to prepare an external skin ointment.

[Comparative Example 2]
At the flowering time, the leaves of April mugwort at a distant time were collected and treated in the same manner as in Example 1 to obtain an extract (essential oil). This was analyzed by mass spectrometry. The obtained chart is shown in FIG. The obtained extract was treated in the same manner as in Example 1 to prepare an external skin ointment.

[Treatment results]
(Treatment Example 1)
The external ointment obtained in Example 1 and Comparative Example 1 (using a commercially available Artemisia extract) was applied to patients with atopic dermatitis, and the therapeutic effects were compared.
When the ointment of Example 1 is used, the redness of the skin is improved faster than that of the comparative example, and itching and sensation (contact with the wind, clothes and synthetic fibers with hard fibers, and hair contact with the hair) (Feeling) was also consciously or objectively recognized as having a high degree of improvement. The patient did not use steroids or other applied drugs together, and after using the ointment of Example 1, the progress of improvement could be confirmed consciously, and active participation in social life was observed.

(Treatment example 2)
The external ointment for Comparative Example 2 (use of April Artemisia extract) and Examples 1-4 (use of each part of Artemisia collected from August to October) was prepared in accordance with the collection time of the raw Artemisia. These were applied to pediatric patients with atopic dermatitis according to the time of collection of each raw material, and the therapeutic effects were compared.
Compared to the period when Comparative Example 2 (using April Artemisia extract) was applied, the recovery of patients after using Examples 1 and 2 (using Artemisia extract collected in August) was remarkable. In the autumn when 4 (using mugwort collected in October) was applied, the redness of the skin faded and the skin became moist. Until then, pediatric patients who refused to apply due to severe pain when applying the ointment preferred to apply the ointment. Also, ointments prepared after August were particularly excellent. The nurse in charge gave us an evaluation that the scent of the ointment prepared after summer was high, the therapeutic effect was greater, and the improvement of the redness of the skin was quick.

(Treatment Example 3)
The patient had induced contact dermatitis with hair dye. At the time of the rash, he took an antiallergic agent, but the pain on the skin surface was severe, and erythema with no outline spread in various places and it was painful to wear clothes. When the skin external preparation of Example 1 was applied, pain was particularly improved and calming was observed. After partial recovery of inflammation, the skin was darkened, but no improvement with general cosmetics was observed. One year later, the skin feels dry and the whole body spills when the hair is rubbed. Therefore, when an external preparation was applied for daily skin care, the skin preparation of Example 1 using whole mugwort planted in summer (August) was improved and the skin became softer and the skin became softer. .

(Medication: Comparison of improvement)
All were observed in patients (3 cases) with significant systemic symptoms. Evaluation points were 5 points for patients and 5 points for patients, and subjective evaluations were made for 3 months of preparation of each ointment. The state change 3 months after the start of painting was subjectively evaluated. The average value was taken and the number was rounded up after the decimal point.

  The present invention provides an external preparation for skin which is excellent in percutaneous property and retention of an active ingredient, and is highly effective for dermatitis, particularly atopic dermatitis. The external preparation of the present invention can be prepared in various dosage forms including ointments. Also, unlike external preparations using alcohol, there is no destruction of skin lipids even after long-term use, and it is highly effective and has no side effects compared to conventional external preparations using traditional Chinese medicine extracts.

1 is a mass spectrometry spectrum diagram of a mugwort extract used in Example 1. FIG. It is a mass spectrometry spectrum figure of the mugwort extract used for Example 2. FIG. It is a mass spectrometry spectrum figure of the mugwort extract used for Example 3. 6 is a mass spectrometry spectrum diagram of a mugwort extract used in Example 4. FIG. It is a mass spectrometry spectrum figure of the mugwort extract used for the comparative example 1. It is a mass spectrometry spectrum figure of the mugwort extract used for the comparative example 2.

Claims (3)

A topical agent containing essential oil contained in mugwort as an active ingredient, wherein the mugwort raw material portion of the essential oil branches at the shoot apex collected from August to October, forms a multi-growth inflorescence, and has a large number of tubular flowers A topical preparation for atopic dermatitis, which is a mugwort stalk with a head flower, a leaf attached to the stalk, and / or a double gross inflorescence. The external preparation according to claim 1, wherein the essential oil is an essential oil obtained by non-heat extraction with an ether solvent or steam distillation. The external preparation according to claim 1 or 2, wherein the dosage form of the external preparation is an ointment, lotion, cream, gel, pack, oral cleanser or mouthwash.

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