WO2007010911A1

WO2007010911A1 - Agent for relieving wound and promoting wound recovery

Info

Publication number: WO2007010911A1
Application number: PCT/JP2006/314213
Authority: WO
Inventors: Kinya Takagaki
Original assignee: Toyo Shinyaku Co., Ltd.
Priority date: 2005-07-15
Filing date: 2006-07-12
Publication date: 2007-01-25
Also published as: JPWO2007010911A1

Abstract

It is intended to provide an agent for relieving a wound and promoting wound recovery which contains a pine bark extract. This agent for relieving a wound and promoting wound recovery has an effect of relieving skin injury due to a wound (in particular, a burn wound and a chemical wound) and an effect of promoting the recovery therefrom. Moreover, the agent for relieving a wound and promoting wound recovery thus obtained is usable as a material for oral compositions such as foods and drugs as well as a material for transdermal compositions such as cosmetics.

Description

Description Reduction of trauma and recovery accelerator

The present invention relates to a trauma mitigation and recovery promoter. Background art

Skin damage caused by trauma, especially heat such as burns, chemical burns, and chemicals can occur frequently in daily life or work, but it is known that sequelae such as keloids occur depending on the extent of the damage.

By the way, in recent years, chemical peeling that improves skin spots and acne by treating skin with a drug for cosmetic purposes to remove the skin epidermis and then regenerating normal skin has been widely implemented. However, this chemical peeling may cause burns depending on the chemical peeling agent used, and the inflammation may be prolonged. In addition, there may be side effects on the skin, such as pigmentation and depigmentation.

Currently, chemical peeling agents for the purpose of improving inflammation and side effects have been proposed (for example, JP-A-62-26-262-4, JP-A-2 0 0 0-1 8 6 0 3 6 , And Japanese Patent Laid-Open No. 2 0 0 1— 1 6 3 7 6 1), which are highly safe for the purpose of reducing and promoting recovery from trauma, especially burns and chemical injury. A recovery accelerator is desired. Disclosure of the invention

An object of the present invention is to provide an excellent trauma reduction and recovery promoter with high safety. The present inventor has intensively studied a raw material derived from a natural product having an effect of reducing trauma and promoting recovery. As a result, it has been found that administration of a pine bark extract can provide excellent trauma reduction and recovery promoting effects, and the present invention has been completed.

The trauma alleviation and recovery promoter of the present invention is characterized by containing a pine bark extract.

In one embodiment, the trauma is a burn or a chemical injury.

In one embodiment, the pine bark extract contains 30% by mass or more of oligomeric broanthocyanidin.

The trauma alleviation and recovery promoter of the present invention is also characterized by oral administration. The trauma mitigation and recovery promoter of the present invention reduces the skin damage caused by trauma, particularly burns or chemical injury, by administration in advance, or recovers skin damage by regenerating the epidermis by administration after skin injury. Can be promoted. The trauma mitigation and recovery promoter of the present invention exhibits an excellent trauma mitigation and recovery promoting effect both in oral administration and transdermal administration. BEST MODE FOR CARRYING OUT THE INVENTION

(Pine bark extract)

Examples of pine bark that can be used as a raw material for pine bark extract include French coastal pine (Pinus M artima), larch, black pine, akamatsu, Japanese pine, pine pine, Korean pine, high pine, Ryukyu pine, luck pine, white pine, white pine, Bark such as Aneda from Quebec, Canada is used. Among them, it is preferable to use the bark of French coast pine (Pinus M artima). French coastal pine is a marine pine that grows on the Atlantic coast of southern France. This French coastal pine bark contains proanthocyanidins, organic acids, and other physiologically active ingredients. Proanthocyanidins refer to a group of compounds composed of a condensation polymer having a degree of polymerization of 2 or more, with furan-1-3-ol and furan or furan-1,3-diol as structural units. Proanthocyanidin, which is the main component, is known to have a strong antioxidant action to remove active oxygen.

The pine bark extract is obtained by extracting the pine bark with a solvent (for example, water or an organic solvent). When water is used, warm water or hot water is used. As the organic solvent used for extraction, an organic solvent that is acceptable for the production of foods or drugs is preferably used. For example, methanol, ethanol, 1-propanol, 2-pronolol, 1-butanol, 2-butanol, acetone, hexane, cyclohexane, propylene dalicornole, hydrous ethanol, hydropropylene glycol mononore, Methinoreethinoleketone, Glycerin, Methinole acetate, Ethyl acetate, Jetyl ether, Dichloromethane, Vegetable edible oils, 1, 1, 1, 2-tetrafluoroethane, and 1, 1, 2-Trichloroethene Are listed. These water and organic solvents may be used alone or in combination. In particular, hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.

The extraction method from pine bark is not particularly limited. For example, a warm extraction method or a supercritical fluid extraction method is used.

Supercritical fluid extraction is a method that uses a supercritical fluid, which is a fluid that exceeds the critical point (critical temperature, critical pressure) of a substance's gas-liquid. Carbon dioxide, ethylene, propane, nitrous oxide (laughing gas), etc. are used as supercritical fluids. Carbon dioxide is preferably used.

In the supercritical fluid extraction method, an extraction process that extracts the target component with a supercritical fluid. And a separation step of separating the target component and the supercritical fluid. In the separation step, any one of extraction separation by pressure change, extraction separation by temperature change, or extraction separation using an adsorbent 'absorbent' may be performed.

Alternatively, supercritical fluid extraction may be performed by an entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid. By adding approximately 20 WZV% and performing supercritical fluid extraction with this fluid, the solubility of the target extract such as proanthocyanidins and catechins (described later) in the extraction solvent is dramatically increased. Alternatively, it is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.

The supercritical fluid extraction method can be operated at a relatively low temperature, so it can be applied to substances that are altered and decomposed at high temperatures; the advantage is that the extraction fluid does not remain; and the recycling of the solvent is possible. There is an advantage that the solvent process can be omitted and the process becomes simple.

In addition to the above methods, methods for obtaining an extract from pine bark include a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, and a supercritical carbon dioxide reflux method.

For extraction from pine bark, a plurality of extraction methods may be combined. It is edible to obtain pine bark extracts with various compositions by combining multiple extraction methods.

Considering the administration form (oral administration or transdermal administration) of the trauma mitigation and recovery promoter of the present invention, water or ethanol is used to synthesize a synthetic adsorbent (Diamond (registered trademark) HP-20, Cefadex. (Registered trademark) LH20, ampalite (registered trademark) XAD-4, etc.) and pine bark extract obtained by ultrafiltration are preferable from the viewpoint of safety. As described above, the pine bark extract used in the present invention contains proanthocyanidins. This proanthocyanidin covers a condensation polymer having a degree of polymerization of 2 to 30 (2 to 30 mer), but in the present invention, a large amount of a condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer) is used. It is preferable to include.

In the present specification, the above-mentioned condensation polymer having a degree of polymerization of 2 to 4 is referred to as an oligomeric proanthocyanin (o l i gome r i c p ro a n t o c y a n i din: OPC).

O P c is a kind of polyphenols, a powerful antioxidant produced by plants, and is concentrated in plant leaves, bark, fruit peels or seed parts. Plants containing proanthocyanidins, especially OPCs, are specifically bark of pine, straw, yam, grapes, blueberries, .strawberry, apogado, diseaca, berries or seeds of cowberry, barley, It is contained in wheat, soybeans, black soybeans, cacao, red beans, tochihu hulls, peanut skins, and yew leaves. It is also known that cola nuts in West Africa, Latania roots in Peru, and Japanese green tea contain OPC. Usually, plant extracts obtained by extracting proanthocyanidins from plants to abundantly contain many broanthocyanidins of pentamer or more, but pine bark is one of the proanthocyanidins. Since a plant extract rich in OPC can be obtained efficiently, it is preferably used as a raw material for porcine anthocyanidins. OPC is a substance that cannot be produced in the human body.

The pine bark extract used in the present invention preferably has a high proanthocyanidin content. In the pine bark extract, proanthocyanidins are 30% by mass or more, preferably 50% by mass or more, more preferably 70% by mass or more, more preferably 70% to 99% by mass in terms of dry mass. Is done. Further, OPC is contained in the pine bark extract in terms of dry mass, preferably 30% by mass or more, more preferably 40% by mass or more. Contains 30% by mass or more of OPC Pine bark extract is effective at reducing trauma, especially burns or chemical injury, and promoting recovery even at low concentrations.

The pine bark extract preferably contains catechins together with proanthocyanidins (especially OPC), more preferably contains 5% by mass or more of strength catechins, Furthermore, it is particularly preferable that it is contained in an amount of 10% by mass or more because it has an excellent therapeutic effect on burns or burns. '

Catechin is a general term for polyhydroxyflavan 1-3-ol. (+) -Epicatechin, (+)-Gallocatechin, (1) -Epigallocatechin, Epigalocatechin gallate, Epi force tekin gallate, etc. are known. . From the above pine bark extract, in addition to (+) —force techin, which is said to be a narrow sense of power, galcatechin, affazerekin, and (+) —3-galloyl derivatives of catechin or gallocatechin are isolated.

Catechins have the property of increasing the water solubility in the presence of OPC, and at the same time, activating OPC 1 ", and when ingested with OPC, enhances the action of OPC.

From the viewpoint of improving the solubility and function of OPC, the above pine bark extract particularly preferably contains 0.1 part by mass or more of catechins to 1 part by mass of proanthocyanidins. Better! /.

In particular, 70% by mass or more of proanthocyanidins, 30% by mass or more of OPC, and 10% of catechins. /. The pine bark extract contained above is excellent in reducing and recovering and promoting burns or chemical burns.

(Treatment reduction and recovery accelerator)

The trauma mitigation and recovery promoter of the present invention is characterized by containing the pine bark extract. This trauma alleviation and recovery promoter is administered orally and transdermally. It exhibits excellent trauma mitigation and recovery promoting effects in any administration, and is used, for example, in foods, pharmaceuticals, and quasi drugs.

The content of the pine bark extract in the trauma mitigation and recovery promoter of the present invention is not particularly limited. When used for the purpose of oral administration, the content of the pine bark extract is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, more preferably 0 in terms of dry mass. , 1 mass. / ₀ or more. If you are use for purposes of transdermal administration (e.g., when used as an external preparation), 0 preferably dry weight basis. 0 0 0 1 mass ^_0/0 or more, preferably 0. 0 0 1 mass% or more, more preferably Is 0.01% by mass or more.

The trauma mitigation and recovery promoter of the present invention may contain various additives as required. Such additives include, for example, additives (excipients, extenders, binders, thickeners (eg, agar)), emulsifiers, lubricants, wetting agents, suspensions that are commonly used by those skilled in the art. Suspensions, colorants (pigments), food ingredients (food additives), seasonings, etc.) or additives usually used in quasi-drugs, cosmetics, and toiletries (base materials, animal and plant extracts, etc.) It is done. The above additives may be used alone or in combination. Furthermore, the additive content is arbitrary.

Specific examples of the above food ingredients (food additives) include, for example, royal jelly, propolis, vitamins (A, B group, C, D, E,:, folic acid, pantothenic acid, biotin, derivatives thereof, etc.) Mineral ( Iron, magnesium, calcium, dumbbell, etc.), selenium, chitin 'chitosan, lecithin, polyphenol (hydrolyzed tannins such as gallotannin, ellagitannin, catechins, anthocyanins, flavonoids, isoflavones, derivatives thereof, etc. ), Force rotenoids (lycopene, astaxanthin, zeaxanthin, rutin, etc.), saponins (ginsaneoid, glycyrrhizic acid, etc.), xanthine derivatives (caffeine, etc.), fatty acids, amino acids, proteins (collagen, e) ), Mucopolysaccharides (hyaluronic acid, chondroitin, dermatan, heparan, heparin, ketalan, salts thereof, etc.), amino sugars (gnorecosamine, acetildarcosamine, galactosamine, acetilgalatosamin, no Iramic acid, Acetylneuraminic acid, Hexosamine, salts thereof, etc., Food fiber (Indigestible dextrin, Alginic acid, Gua gum, Pectin, Darcomannan, etc.), Oligosaccharide (Isomaltoligosaccharide, Cyclic oligosaccharide, etc.) ) Phospholipids and their derivatives (phosphatidylcholine), Sphingolipids and their derivatives (sphingomyelin, ceramide, etc.), Sulfur compounds (Alyin, Sepahen, Taurine, Glutathione, Methylsulfonylmethane, etc.), Sugar alcohol, Ki Non-types (such as Coenzyme Q10), monolipoic acid, L-carnitine, and lignans (such as sesamin). Furthermore, animal and plant extracts containing these, root vegetables (turmeric, ginger, etc.), green leaves of gramineous plants such as young wheat leaf powder, green leaves of cruciferous plants such as kale, etc. are also used as the food materials.

Examples of the seasoning include sweeteners such as granulated honey, honey, and sorbit, acidulants such as alcohol, citrate, malic acid, and tartaric acid, and flavors.

When the trauma-relief and recovery-promoting agent of the present invention is used for the purpose of transdermal administration, as an additive, in particular, a base material (glycerol, ethanol, paraben, butylene glycol, etc.), appearance and feeling of use, storage stability For the purpose of further improving the quality, excipients (such as dextrin), fragrances, pigments, preservatives, thickeners (such as silicone polymers, acrylic polymers, carboxyvinyl polymers), chelating agents (such as EDTA), Refreshing agents (such as sucralose, menthol, etc.) and antiseptic / antifungal agents (such as phenoxyethanol) are used.

The form of the trauma mitigation and recovery promoter of the present invention is not particularly limited. For example, when used for oral administration (eg food), hard capsules, soft It can be formed into a capsule, tablet, pill, or the like, or a powder, granule, bowl or the like. These can be eaten as is, or can be taken by dissolving in water, hot water, milk, etc., or can be taken by leaching the ingredients. Furthermore, for example, a beverage having high functionality or high nutritional value can be obtained by adding it to a plant fermented juice, vegetable juice (for example, carrot juice), plant extract, fruit juice or the like.

When used for the purpose of transdermal administration (for example, topical preparations such as cosmetics and toiletries), specifically, lotion, cosmetic cream, emulsion, pack, hair tonic, shampoo, hair rinse, treatment, Body shakes, facial cleansers, stone trials, foundations, lipsticks, hair restorers, ointments, bathing agents, dentifrices, mouthwashes, ships, gels, etc.

The dosage of the trauma alleviation and recovery promoter of the present invention is not particularly limited. When administered orally, the intake of pine bark extract is preferably adult (60 kg) — 0.1 mg / day, more preferably 1 mg / day, more preferably 10 mg / day, most preferably 1 Administer at a rate of 0 O mg or more. Alternatively, it is preferably administered at a rate of preferably not more than 200 mg, more preferably not more than 100 mg, and still more preferably not more than 500 mg per adult day. Example

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

(Example 1)

Use Pro Ant Xia two Jin contain (3 0 mass ⁰ as OPC) 7 0 wt%, a catechin Tsu force 1 0 wt% pine bark extract containing (Toyo new drug) Then, the effect of reducing burns and promoting the recovery were evaluated as follows.

Seven-week-old female SD rats (Nippon Chiarusu 'Ribaichi Co., Ltd.) 10 fed basic feed (MF feed; Oriental Yeast Co., Ltd.) to acclimate for one week, and these rats were divided into two groups. divided.

One group of rats has 1 mass of pine bark extract. /. Water containing water was allowed to drink freely

(As a test group).

On the 8th day from the start of the administration of the aqueous solution containing the pine bark extract, the back hair of the rat was shaved, and then the absorbent cotton soaked with boiling water under anesthesia was applied to the shaved area (3 cm x 4 cm) for 1 minute. Caused burns. Even after the burn, an aqueous solution containing a pine bark extract was allowed to drink freely. On the 1st day (9th day after administration of aqueous solution) and 5th day (4th day after administration of aqueous solution), the skin condition was visually observed, scored according to the criteria shown in Table 1, and the average value was calculated. Asked. The results are shown in Table 2. The larger the value, the higher the damage to the skin.

For the remaining 1 group of rats, the same procedure as in Test Group 1 above was used to promote recovery from burns, except that only water was used instead of an aqueous solution containing 1% by weight of pine bark extract. Evaluated (as control group). The results are shown in Table 2. Table 1 Skin condition score

Redness, dryness 1

Redness, edema, blistering, erosion 2

Redness, blistering, necrosis, ulcer 3

Necrosis, ulcer, dryness, cauterization 4 Table 2

Values are average values

From the results in Table 2, it can be seen that the test group to which pine bark extract was administered reduced the skin damage due to burns compared to the control group to which water alone was administered. Furthermore, on the fifth day after the burn, the difference in the values between the test group and the control group increased, and the recovery from skin damage was promoted by taking pine bark extract. Recognize. These indicate that the trauma mitigation and recovery promoter containing the pine husk extract of the present invention has an excellent burn reduction and recovery promoting effect.

(Example 2)

Pro Ant Xia two gin 7 0 mass ^_0/0 (3 0 mass as OPC ^_0/0) containing, and with have use catechins 1 0 wt% pine bark extract containing (Toyo new drugs), the following In addition, the reduction effect on drug injury and the effect of promoting recovery were evaluated.

Seven-week-old female SD rats (Nippon Chiarus' Lipper Co., Ltd.) 10 fed basic feed (MF feed; Oriental Yeast Co., Ltd.) to acclimate for one week, and divided these rats into two groups It was.

One group of rats was allowed to freely drink an aqueous solution containing 1% by weight of pine bark extract.

(As a test group). On the 8th day from the start of administration of the aqueous solution containing the pine bark extract, the back hair of the rat is trimmed, and 6% sodium hydroxide aqueous solution is soaked under anesthesia into this shaved site (3 cm x 4 cm). Absorbent cotton was applied for 1 minute to cause chemical injury. Even after the chemical injury, the aqueous solution containing the pine bark extract was allowed to drink freely. On the first day (9th day after administration of aqueous solution) and 5th day (4th day after administration of aqueous solution), the skin condition was visually observed, scored according to the criteria shown in Table 1, and the average value was obtained. . The results are shown in Table 3. The larger the value, the higher the damage to the skin.

For the remaining 1 group of rats, the effect of promoting recovery from drug injury was the same as in Test Group 1 except that only water was allowed to drink freely instead of an aqueous solution containing 1% by weight of pine bark extract. Was evaluated (control group). The results are shown in Table 3.

Table 3

Values are average values From the results in Table 3, it can be seen that the test group to which pine bark extract was administered reduced the skin damage caused by chemical injury compared to the control group to which only water was administered. In addition, on day 5 after the drug injury, the difference between the test group and the control group increased, and the recovery from skin damage was promoted by taking pine husk extract. I understand. These indicate that the trauma mitigation and recovery promoter containing the pine bark extract of the present invention has excellent medicinal wound mitigation and recovery promoting effects. (Example 3)

Eight 8-week-old male Wistar rats (Kudo Co., Ltd.) were given MF standard breeding (Oriental Yeast Co., Ltd.) and acclimated for one week.

The hair on the back of each rat was trimmed. A burned 20 g weight was applied to the shaved area under urethane anesthesia for 10 seconds to cause burns. These rats were divided into 2 groups of 4 animals per group, which were used as test and control groups.

The test group contained 0.03 mass of pine bark extract (70 mass% proanthocyanidins, 46 mass% OPC, and 10 mass% force techins, Toyo Shinyaku Co., Ltd.). /. An aqueous solution containing 0.1 mL was applied to the burned area once a day. The burns were visually observed, the number of days required for epithelialization was recorded, and the average value was determined. The results are shown in Table 4. During the period of application of the aqueous solution, rats were given free MF standard feed and water.

For the control group, the average number of days required for epithelialization was determined in the same manner as in the test group, except that water was used instead of the aqueous solution containing the pine bark extract. The results are also shown in Table 4. Table 4

From the results shown in Table 4, the group (test group) administered dermally with an aqueous solution containing a pine bark extract had a shorter period of time until the burns were recovered than the group (control group) administered dermally with water alone. You can see it is short. This is due to the dermal administration of pine bark extract. This shows that the effect of promoting the recovery of burns can be obtained. (Example 4)

Eight 8-week-old male Wistar rats (Kudo Co., Ltd.) were fed with MF standard diet (Oriental Yeast Co., Ltd.) and acclimatized for one week. These rats were divided into 2 groups of 4 animals per group and used as the test group and the control group.

In the test group, an aqueous solution containing pine bark extract (containing 46% by mass of OPC, Toyo Shinyaku Co., Ltd.) of 0.02% by mass, and the dose of pine bark extract was 5 mg / kg body weight. As a result, gavage was administered once a day. During the administration period, rats received free MF standard diet and water.

On the second day after administration, the hair on the back of the rat was trimmed, and a heated 20 g weight was applied to the trimmed portion under urethane anesthesia for 10 seconds to cause burns. Even after burns, the above oral administration was continued. The burned part was visually observed, the number of days required for epithelialization was recorded, and the average value was obtained. The results are shown in Table 5. The control group was the same as the test group except that water was used instead of the aqueous solution containing the pine bark extract, and the average number of days required for the subepithelium was obtained. The results are also shown in Table 5. Table 5

From the results in Table 5, the group to which an aqueous solution containing a pine bark extract was orally administered (test group) Compared with the group that received oral administration of water alone (control group), it can be seen that the period until the burn is recovered is shorter. This indicates that oral administration of the pine bark extract has an effect of promoting burn recovery.

(Example 5)

Eight 8-week-old male Wistar rats (Kudo Co., Ltd.) were fed with MF standard diet (Oriental Yeast Co., Ltd.) and acclimatized for one week. These rats were divided into 2 groups of 4 animals per group, and used as the test group and the control group.

The test group contained pine husk extract (70% by mass of proanthocyanidins, 46% by mass of OPC, and 10% by mass of force techins, Toyo Shinyaku Co., Ltd.) An aqueous solution containing mass% was orally administered by gavage once a day so that the dose of pine bark extract was 5 mg / kg body weight. During the administration period, rats were allowed free access to MF standard diet and water.

On day 20 of administration, the rat's dorsal hair was trimmed at three locations, and a 20 g weight of heat was applied to these trimmed sites under urethane anesthesia for 10 seconds to cause burns. It was. Oral administration was continued even after burns.

On day 2 of administration 2 (day 6 after burn), the burned area was visually observed, and the skin condition was scored according to the criteria shown in Table 6 to obtain an average value. The results are shown in Table 7. The higher the score value, the better the skin damage has been recovered.

The test group was the same as the test group except that water was used instead of the aqueous solution containing the pine bark extract, and the skin condition was scored according to the criteria shown in Table 6 to obtain an average value. The results are also shown in Table 7. Table 6

Table 7

Values are average values ± standard deviation From the results in Table 7, the group that received oral administration of an aqueous solution containing pine bark extract (test group) compared to the group that received oral administration of water alone (control group). It can be seen that the time to complete is short. This indicates that oral administration of the pine bark extract has an effect of promoting burn recovery. Industrial applicability

The trauma mitigation and recovery promoter of the present invention contains a pine bark extract. This trauma mitigation and recovery promoter can be pre-administered to reduce skin damage due to trauma, especially burns or chemical injury, or administered after skin injury to restore skin damage by regenerating the epidermis. Can be promoted. This Is useful because it can be used as a raw material for oral compositions such as foods and pharmaceuticals, or as a raw material for transdermal compositions such as cosmetics. .

Claims

The scope of the claims

1. A trauma mitigation and recovery promoter characterized by containing a pine bark extract.

2. The trauma mitigation and recovery promoter according to claim 1, wherein the trauma is a burn or a chemical injury.

3. The traumatic alleviation and recovery promoter according to claim 1 or 2, wherein the pine bark extract contains 30% by mass or more of oligomeric proanthocyanidins.

4. The trauma alleviation and recovery promoter according to any one of claims 1 to 3, which is orally administered.