JPH10330221A - Enderonic collagen fasciculus remedial agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject agent capable of normalizing enderonic collagen fasciculus developed due to wrinkles, fibrosis, keloid, etc., by including the essence from a plant belonging to the genus Perilla frutescens crispa. SOLUTION: This enderonic collagen fasciculus remedial agent is obtained by including an essence, i.e., a fractionation-purified product (pref. alcohol (e.g. ethanol) extracts and a fractionation-purified product therefrom) which is obtained by separation and column purification of the extracts (concentrate thereof) obtained by subjecting a plant belonging to the genus Perilla frutescens crispa such as thyme, beefsteak plant, archangel, Mentha piperita, piperita japonica, spearmint, CATNIP, melissa, rosemary or sage, or a processed product thereof (e.g. dried, chopped, ground product) to extraction with a solvent such as water, an alcohol, ether, halohydrocarbon, organic acid ester, ketone or hydrocarbon.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a dermal collagen fiber bundle improving agent comprising the essence of a Labiatae plant and a skin external preparation containing the dermal collagen fiber bundle normalizing agent as an active ingredient.

[0002]

2. Description of the Related Art Wrinkles are an aging phenomenon that can be said to be a symbol of aging for human beings, and have many effects on their appearance. Therefore, wrinkles have been taken up as a problem to be solved for cosmetics and external medicine for skin for many years. However, there are various opinions on the mechanism by which wrinkles are formed, and it has not yet been clarified. Therefore, a method of suppressing the formation of wrinkles or returning the formed wrinkles to a state with less wrinkles has not yet been obtained. As with wrinkles, the mechanism of formation of keloids formed in fibroses, scars and burns is not known, and there is still no known method of suppressing their formation or treating these abnormalities. Had not been.

No study has been made on the relationship between the formation of wrinkles, fibroses and keloids and the state of the dermal collagen fiber bundle. Also, it has not been suggested at all that any relationship exists between them.

It is completely known that the essence of the Labiatae plant typified by rosemary and sage has the effect of normalizing the abnormalities of the dermal collagen fiber bundle caused by the formation of wrinkles, fibroses, keloids and the like. I didn't. Therefore, there has been no attempt to improve the structure of dermal collagen fiber bundles by incorporating these essences into cosmetics or external medicines for skin.

[0005]

DISCLOSURE OF THE INVENTION The present invention has been made under such circumstances, and it is an object of the present invention to provide means for normalizing abnormalities of dermal collagen fiber bundles caused by formation of wrinkles, fibroses, keloids and the like. Make it an issue.

[0006]

In view of such a situation,
The present inventors have conducted intensive studies for the formation mechanisms of wrinkles, fibroses, and keloids, and as a result, have found out that wrinkles generated by light irradiation among wrinkles are caused by abnormalities in dermal collagen fiber bundles. As a result of further studies, it has been found that abnormalities in the dermal collagen fiber bundles are also a mechanism during the formation of keloids that occur during healing of fibrosis, burns and wounds. As a result of further research for a drug that normalizes the abnormality of the dermal collagen fiber bundle, the inventors have found such an effect in the essence of Lamiaceae plants represented by rosemary and sage, and have completed the invention. Hereinafter, the present invention will be described in detail focusing on embodiments.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION

(1) Relationship between formation of wrinkles and structure of dermal collagen fiber bundle Relationship between formation of wrinkles and structure of dermal collagen fiber bundle
This will be described using a mouse light irradiation model. From this experimental example, it is understood that the disorder of the structure of the dermal collagen fiber bundle is the mechanism of wrinkle formation by light irradiation. Similarly, the disorder of the structure of the dermal collagen fiber bundle has been observed in fibroses and keloids, suggesting that this is a mechanism.

<Experimental example> Examination of changes in skin condition in a photoaging model A hairless mouse (Skh: HR-1, female, 8 weeks old) is irradiated with ultraviolet rays B (Toshiba SE lamp, 60 mJ / cm ² ) every day. Then, skin and skin surface morphological replicas were collected 2, 5 and 10 weeks after the start of irradiation. For the collected skin, the collagen fiber bundle structure was observed by a scanning electron microscope using the NaOH method. FIG. 1 shows the skin surface morphology at 50 × magnification (A: non-irradiated control, B: irradiation 2 weeks, C: irradiation 5 weeks, D: irradiation 10 weeks), and FIG. 2 shows the dermal surface morphology at 50 × magnification (E : Non-irradiated control, F: 2 weeks of irradiation, G: 5 weeks of irradiation, H: 10 weeks of irradiation), FIG. 3 shows the structure of dermal collagen fiber bundle at 500 × magnification (I: non-irradiated control, J: 2 irradiated) Week, K: irradiation 5 weeks, L: irradiation 10 weeks), FIG. 4 shows the structure of the dermal collagen fiber bundle at 2500 × magnification (M: non-irradiation control, N: irradiation 2 weeks,
O: irradiation 5 weeks, P: irradiation 10 weeks). From these figures, when wrinkles are formed, grooves are also formed on the surface of the dermis so as to correspond to them, and the change in the morphology of the skin surface corresponds to the change in the morphology of the dermis surface. It can be seen that the change in the dermis surface reflects a change in the structure of the collagen fiber bundle in the dermis, that is, a decrease in the order of the fiber bundle such that the fiber bundle becomes less clear. Here, the microscope image of FIG. 4 was given a score based on the following criteria. That is, score 0: no fiber bundle structure was observed in the entire observation region, score 1: collapse of the fiber bundle structure or transition to an abnormal structure was observed in the majority region, and score 2: partial collapse of the fiber bundle structure or Degeneration is observed, but an almost normal structure is recognized as a whole. Score 3: This is a criterion that a normal fiber bundle structure is observed over the entire surface and collapse / degeneration is almost not observed. The result is shown in FIG. Regarding the structure of the skin surface, the shadow of wrinkles that could be irradiated with a xenon lamp at an incident angle of 20 degrees on the replica was quantified by image analysis to determine the amount of wrinkles generated. FIG. 6 shows the measurement results. The calculated coefficient of correlation between the amount of wrinkles and the average of the score values was 0.91, and there was a strong relationship between the formation of wrinkles and the disorder (order) of the dermal collagen fiber bundle. It can be seen that turbulence is the mechanism of wrinkle formation.

(2) Agent for Normalizing Dermal Collagen Fiber Bundles of the Present Invention The agent for normalizing dermal collagen fiber bundles of the present invention comprises the essence of a Labiatae plant. Here, the essence referred to in the present invention is a whole plant or a part of the plant itself, a dried, shredded, pulverized processed product of a plant, a plant or its processed product is treated with water, alcohol, ether, halogen. Extract extracted with a solvent consisting of a hydrocarbon, an organic acid ester, a ketone, a hydrocarbon, or a mixture of one or more selected from these, an extract concentrate obtained by removing the solvent from the extract, an extract or It refers to a generic term such as separation of the extract concentrate, fractionated purified product obtained by column purification, and the like. As the essence of the present invention, an alcohol extract and a fractionated purified product thereof are preferable, and among them, a product obtained by extracting a low-polarity portion of the alcohol extract is particularly preferable. Such an extract can be used to remove a plant or its processed product from 1 to 1
Extraction may be performed with a 0-fold amount of alcohol, this extract may be added to a small amount of water to precipitate, and the precipitate may be collected by filtration. Here, as the alcohol that can be used in the present invention, for example, methanol, ethanol, butanol,
Preferred examples include 1,3-butanediol and polyethylene glycol, and particularly preferred is ethanol. The method of extraction is to add an alcohol to the plant
It may be immersed for several days at room temperature or several hours at a temperature near the boiling point. As the Lamiaceae plants, thyme, perilla, perilla, mint, spearmint, catnip, melissa, rosemary and sage are preferred, of which rosemary and sage are preferred, and rosemary is particularly preferred.

(3) External preparation for skin of the present invention The external preparation for skin of the present invention is characterized by containing one or more selected from the above agents for normalizing dermal collagen fiber bundles. The preferred content of the dermal collagen fiber bundle normalizing agent in the external preparation for skin of the present invention is 0.01 to 10% by weight, more preferably 0.05 to 5% by weight, and still more preferably 0.1 to 5% by weight. 5% by weight. The external preparation for skin of the present invention may contain, in addition to the agent for normalizing dermal collagen fiber bundles, optional components usually used in external preparations for skin. Such optional components include, for example, hydrocarbons such as petrolatum and microcrystalline wax, esters such as jojoba oil and gay wax, triglycerides such as tallow, olive oil, higher alcohols such as cetanol and oleyl alcohol, Fatty acids such as stearic acid and oleic acid, polyhydric alcohols such as glycerin and 1,3-butanediol, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, ethanol, carbopol, etc. Thickeners, preservatives, ultraviolet absorbers, antioxidants, pigments, powders and the like.
The topical skin preparation of the present invention is characterized by being suitably applied to diseases associated with abnormal dermal collagen fiber bundles. Examples of diseases associated with abnormalities of dermal collagen fiber bundles include, for example, abnormal formation of wrinkles, fibrosis, keloid formation at the time of wound or wound healing, etc., among which application to abnormal formation of wrinkles is preferable, and abnormal formation of wrinkles is preferable. Among them, application to abnormal formation of wrinkles caused by long-term irradiation with light is particularly preferable. The external preparation for skin of the present invention can be used as a pharmaceutical or a cosmetic depending on the degree of normalizing action of the collagen fiber bundle. To reduce the effect, the content of the dermal collagen fiber bundle improver to be contained may be reduced, and the content of the dermal collagen fiber bundle improver of the present invention, which is preferable for cosmetics, is 0.001 to 5% by weight. Preferably it is 0.003 to 3% by weight. In particular, when the composition is administered for wrinkle abnormal formation, it is preferable to administer the composition as a cosmetic having a small effect for a long period of time. The external preparation for skin of the present invention not only has a therapeutic effect of normalizing the abnormalities of the dermal collagen fiber bundles that have already occurred, but also has a preventive effect of preventing the abnormalities of the dermal collagen fiber bundles, and further worsens the abnormalities of the dermal collagen fiber bundles. It has a therapeutic prophylactic action to prevent
The dosage form of the external preparation for skin of the present invention can be applied without any particular limitation as long as it is a dosage form usually used in external preparations for skin such as lotions, gel preparations, emulsions, creams, ointments and the like. These can be manufactured according to a generally known method.

[0011]

EXAMPLES The present invention will be described in detail below with reference to examples, but it goes without saying that the present invention is not limited only to these examples.

<Example 1> 10 kg per 1 kg of rosemary
Was refluxed for 2 hours, filtered, and the filtrate was collected. The filtrate was concentrated under reduced pressure to obtain 213 g of dermal collagen fiber bundle improving agent 1. 100 g of the dermal collagen fiber bundle improving agent 1 was dissolved in 600 ml of ethanol, and this was added to 200 ml of water at a stretch, and the precipitated precipitate was collected by filtration and 42 g.
The dermis collagen fiber bundle improving agent 2 was obtained. 100 g of the dermal collagen fiber bundle improving agent 1 was dissolved in 500 ml of normal butanol, and 500 ml of water was added to perform liquid-liquid extraction to obtain a butanol phase. Repeat this work three times,
The butanol phases were combined and concentrated under reduced pressure to obtain 27 g of dermal collagen fiber bundle improving agent 3.

Example 2 10 kg of ethanol was added to 1 kg of sage, refluxed for 2 hours, filtered, the filtrate was collected, and concentrated under reduced pressure to obtain 142 g of dermal collagen fiber bundle improving agent 4. 50 g of dermal collagen fiber bundle improver 4
Was dissolved in 300 ml of ethanol, and
The resulting precipitate was collected by filtration, and 18 g of dermal collagen fiber bundle improver 5 was obtained. 50 g of the dermis collagen fiber bundle improving agent 4 was dissolved in 500 ml of normal butanol, 500 ml of water was added, and liquid-liquid extraction was performed to obtain a butanol phase. This operation is repeated three times, and the butanol phases are combined and concentrated under reduced pressure, and the dermal collagen fiber bundle improving agent 6
14 g was obtained.

<Examples 3 to 8> Using the dermal collagen fiber bundle improving agents 1 to 6 of Examples 1 and 2, lotions 1 to 6 were prepared according to the formulation shown in Table 1. That is, the ingredients were stirred and solubilized at room temperature to obtain lotions 1-6. still,
The numerical values represent parts by weight.

[0015]

[Table 1]

<Example 9> Using the above animal model example,
It was investigated how changes in the deterioration of the skin such as wrinkles caused by light irradiation are changed by lotions 1 to 6 which are the skin external preparations of the present invention. Using the above light-irradiated hairless mouse (Skh: HR-1, female, 8 weeks old),
The group was treated with lotions 1 to 6 and the seventh group as a control group, and was administered with ethanol alone in an amount of 0.05 ml each day for 8 weeks every day. The skin of this animal was treated in the same manner as above, and the collagen fiber bundle structure was observed. From this, the collagen fiber bundle score value was calculated and divided by the score value of the control group to calculate the improvement value of the skin condition. Table 2 shows the collagen fiber bundle score value and the improvement value of the skin condition. From this table, it can be seen that lotions 1 to 6, which are external preparations for skin of the present invention, significantly improve the dermal collagen fiber bundle structure.

[0017]

[Table 2]

<Examples 10 to 12> Creams were prepared according to the formulations shown in Table 3 below. That is, knead b,
After dilution with (a), the temperature was adjusted to 80 ° C., to which was gradually added emulsified water having been adjusted to 80 ° C., followed by emulsification, followed by stirring and cooling to obtain a cream. When this was evaluated according to the photoaging screening method described above, the improved value of the dermal collagen fiber bundle structure was as shown in Table 3. These creams were used for 20 months for a group of panelists suffering from wrinkles for 2 months, and the condition of wrinkles was investigated by a questionnaire. These results are also shown in Table 3.
These results indicate that the external preparation for skin of the present invention is excellent in the effect of normalizing the collagen fiber bundle. In addition, the numerical value of a prescription represents a weight part.

[0019]

[Table 3]

<Examples 13 to 17> Ointments were prepared according to the formulation shown in Table 4 below. That is, the ingredients were kneaded with a kneader to obtain an ointment. In all of these, the normalization effect of the dermal collagen fiber bundle (improved value of about 1.4) was observed in the light-irradiated hairless mouse model by electron microscope observation.

[0021]

[Table 4]

<Examples 18 to 22> Liquid preparations were prepared in accordance with the formulation shown in Table 5 below. That is, the ingredients were stirred and solubilized at room temperature to obtain a liquid preparation. In all of these, electron microscopic observation showed a normalizing action (improved value of about 1.5) of the dermal collagen fiber bundle in the light-irradiated hairless mouse model.

[0023]

[Table 5]

[0024]

According to the present invention, it is possible to provide a means for normalizing abnormalities of the dermal collagen fiber bundle caused by the formation of wrinkles, fibroses, keloids and the like.

[Brief description of the drawings]

FIG. 1 is a diagram showing a change in skin surface morphology in a photoaging model.

FIG. 2 is a diagram showing a change in dermal surface morphology in a photoaging model.

FIG. 3 is a diagram showing a collagen fiber bundle structure in a photoaging model. (500 times)

FIG. 4 is a diagram showing a collagen fiber bundle structure in a photoaging model. (2500 times)

FIG. 5 is a diagram showing a wrinkle amount due to light irradiation.

FIG. 6 is a view showing a fiber bundle structure score by light irradiation.

 ──────────────────────────────────────────────────続 き Continued on front page (72) Inventor Mitsuo Kawai 560 Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Pref.

Claims (9)

[Claims] 1. A dermal collagen fiber bundle normalizing agent comprising the essence of a Labiatae plant. 2. The agent for normalizing dermal collagen fiber bundles according to claim 1, wherein the Labiatae plant is thyme, perilla, perilla, mint, mint, spearmint, catnip, melissa, rosemary or sage. 3. The essence of the alcohol-soluble component,
3. The method according to claim 1, wherein the polarity is low.
2. The agent for normalizing dermal collagen fiber bundles according to item 1. 4. A disease associated with abnormal dermal collagen bundles, comprising one or more selected from the dermal collagen fiber bundle normalizing agents according to any one of claims 1 to 3 as an active ingredient. External preparation for skin. 5. The external preparation for skin according to claim 4, wherein the disease associated with dermal collagen fiber bundle abnormality is abnormal formation of wrinkles due to light, fibrosis or keloid. 6. The external preparation for skin according to claim 4, which is a cosmetic. 7. A cosmetic for improving dermal collagen fiber bundles, comprising an essence of a Labiatae plant. 8. The cosmetic composition for improving dermal collagen fiber bundles according to claim 7, wherein the Labiatae plant is thyme, perilla, perilla, mint, mint, spearmint, catnip, melissa, rosemary or sage. 9. The essence of the alcohol soluble component,
The cosmetic for improving dermal collagen fiber bundles according to claim 7 or 8, wherein the cosmetic has low polarity.