JPH0812586A - Antiplasmin agent - Google Patents

Abstract

PURPOSE:To obtain the subject medicine containing one or more of extracts of Saraca indica, Pnica granatum Mimusops elengi, Eugenia jambolana and Terminalia chebula with a solvent, having high antiplasmin effect, effectively acting on inflammations, being mixed with cosmetics and dentifrice CONSTITUTION:At least one extract of bark, leaf, etc., of Saraca indica, Pnica granatum Mimusops elengi, Eugenia jambolana and Terminalia chebula with a solvent is used as an active ingredient, mixed with a liquid oil such as squalene and jojoba oil, a solid oil such as beeswax and cetyl alcohol, a surfactant such as polyoxyethylene sorbitan monostearate and a humectant such as glycerol and pharmaceutically manufactured to give the objective antiplasmin having high antiplasmin effect, effectively acting on inflammations, being mixed with cosmetics to suppress inflammations in exposure to ultraviolet light and being blended with dentifrice to suppress inflammations of periodontitis and preventing periodontitis, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antiplasmin agent having a high antiplasmin action and effectively acting on inflammation.

[0002]

[Prior Art] Jumbolan, also called purple peach, is a plant belonging to the family Myrtaceae and has a scientific name of Eugenia jambolana. It is an evergreen tree. Fruit juice is made from jumbo lan fruits. In this regard, Japanese Patent Application Laid-Open No. 5-155750 proposes use for cosmetics.

The scientific name of Misakinohana is called Mimusops elengi, which is an evergreen small tree of the Acathaceae family that grows from India in the Taray region of Nepal, and is often planted as a garden tree. The bark is dark gray and cracked, the leaves are oval to oblong, the flowers are axillary and unicellular, or fasciculate, small, astringent yellow and star-shaped, and fragrant. For medicinal uses, bark is astringent and tonic, and is also formulated for heat. The leaves are also used to treat snake bites. Ripe fruit pulp is astringent and is used to treat chronic diarrhea. Seeds are used for bruises and, in some regions, for enema during constipation in children. In addition, JP-A-5
In Japanese Patent No. 124952, it is used for cosmetics.

The scientific name of Saraca Indica is as it is (Saraca
indica), a plant of the legume family, commonly called Muyuju. Muyuju is an evergreen tall tree, which is usually about 4 to 8 meters long and rarely exceeds 20 meters. The bark is thick, grayish reddish brown, and the leaves are pinnate compound. It is distributed in the central to eastern foothills of the Himalayas, eastern Bengal, western Indian Peninsula and northern India, and is partly cultivated. This plant is used as a medicine, leaves are used as a medicine for abdominal pain, bark is a raw material used as a hemostatic agent for the treatment of excessive menstruation, and also for the treatment of hemorrhoids after decoction. In Japanese Patent Laid-Open No. 5-320035,
It is being used for cosmetics.

[0005] Mung bean is a plant of the family Asteraceae, scientific name is Terminalia chebula (Terminalia chebula), and is a dried fruit of the common name Myrobalan tree. Mirobaranoki is native to India and Burma, and it is in Yunnan, Guangdong,
It is a large deciduous tree grown and grown in Guangxi and Tibet. The dried fruit of this matured fruit is called "Ryoko" and is used as an antidiarrheal, hemostasis, antitussive, and is easily available in Japan. Scientific name for the similar plant
There is the Terminalia ballerica. In JP-A-5-331041, use for cosmetics is planned.

Pomegranate is a pomegranate in the pomegranate family, and its scientific name is Punica granatum. Pomegranate is native to Asia Minor and is a deciduous tree that has been cultivated in Japan for medicinal purposes or for appreciation since the Heian period. It is used as a parasite control and mouthwash. In the same manner as Ryoko, Japanese Patent Laid-Open No. 331041/1993 proposes the use for cosmetics.

On the other hand, plasmin is one of proteolytic enzymes existing in blood. The precursor plasminogen in the blood is cleaved to plasmin by an enzyme called plasminogen activator. An important physiological effect of plasmin is thrombolysis. Plasminogen activator in blood has an affinity for fibrin (fibrin) which is a component of thrombus, and acts on plasminogen in fibrin clot (thrombus) to be activated to plasmin. As a result, the plasmin formed in the fibrin clot dissolves the thrombus from the inside of the clot.

There are several kinds of substances in the blood that inhibit the activity of plasmin, and the plasmin released in the blood is rapidly inactivated,
Nonspecific proteolysis other than fibrin is suppressed. Although plasmin is easily deactivated and cannot be used directly for treating thrombosis, it has been attempted to administer plasminogen activator (urokinase, tissue plasminogen activator (TPA), etc.).

As mentioned above, plasmin, which is one of the proteases, has the action of dissolving fibrin formed in the blood coagulation process, and the factor that antagonizes this action of plasmin is the antiplasmin factor (plasmin inhibitor). , The preparation is called an antiplasmin agent. Tranexamic acid (t-AMCHA) and ε-aminocaproic acid (EACA) are already known as chemically-synthesized plasmin inhibitors, and they are mixed in toothpaste and the like with the expectation of a bleeding-preventing effect.

Plasmin is a lysine binding site (LB) of the kringle structure of plasmin.
S) binds to the thrombus and efficiently decomposes fibrin. With this action, t-AMCHA and EACA bind to LBS to cause steric hindrance, and inhibit fibrin degradation of plasmin. There is a natural plasmin inhibitor called α ₂ plasmin inhibitor in human blood,
It works on the generated plasmin and rapidly deactivates it, suppressing its action. However, the α ₂ plasmin inhibitor binds to LBS and has an inhibitory effect on the plasmin active center. Research and development of a compound having a mechanism similar to that of the natural inhibitor has been actively conducted, and the present invention is one of them.

Anti-plasmin agents also prevent cancer metastasis,
It is said that there is a possibility of application. When cancer cells metastasize, they produce plasmin to melt surrounding tissue, infiltrate,
It is said that it will fly further. Therefore, it is expected that plasmin inhibitors can suppress cancer metastasis.

Irradiation of UVB onto the skin in an amount twice the minimum amount of erythema causes erythema and edema. It has been reported that histamine, serotonin, prostaglandin E ₂ , F ₂ α quinine and the like are involved as chemical mediators in this UV inflammatory reaction.

Further, after UV irradiation, the plasmin activity in rabbit skin tissues is enhanced, the plasmin activity fluctuates in parallel with the degree of swelling of the skin, and the administration of tranexamic acid, an antiplasmin agent, It is known that swelling is severely suppressed. Therefore, this antiplasmin agent is also one of the important chemical mediators in the UV inflammatory response. In addition, this action is of course used as a toothpaste and as a hemostatic agent.

On the other hand, although various substances are known as substances having an antiplasmin action which can be used as a raw material for medicines, toothpaste and cosmetics, synthetic products are safe when applied to human skin for a long period of time. There is no guarantee of the use, and the use is being restricted. On the other hand, many natural products have weak antiplasmin action. However, in terms of safety for human skin, it is a natural product,
For many years, people have eaten it, and it has been required to have a safety assurance and a strong antiplasmin action.

[0015]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide an antiplasmin agent which is safe to be applied to the skin and has a large antiplasmin action.

[0016]

[Means for Solving the Problems] In order to solve the above-mentioned problems, the present inventors have screened and investigated plants that have been used for food for many years and confirmed to be safe for the human body, and have investigated anti-plasmin agents. I examined what is useful as. As a result, they have found that Salaca indica, pomegranate, Misaquinohana, jumbo lan, and licorice are highly effective as raw materials for antiplasmin agents or as quasi drugs.

That is, the present invention is directed to Saraka Indica,
It is an anti-plasmin agent containing solvent extracts of pomegranate, miso hanohana, jumbo lan, and licorice.

As a method of utilizing Saraca indica, pomegranate, Japanese quince, jumbo lan, and koji, extraction is carried out with water or a hydrophilic organic solvent such as ethanol, methanol or acetone. However, it is natural that extraction with water, ethanol, or a mixed solvent thereof is preferable because it is the extraction of the antiplasmin agent raw material.

In some cases, glycerin, 1,
A polyhydric alcohol such as 3-butylene glycol or propylene glycol, or a mixed liquid of polyhydric alcohol and water can also be used for extraction. It is also effective to freeze-dry this solvent extract and use it as a powder depending on the method of use.

This substance is used as a raw material for other cosmetics and pharmaceuticals, for example, liquid oil such as squalane and jojoba oil, solid oil such as beeswax and cetyl alcohol, various active agents, glycerin, 1, and the like.
Anti-plasmin agents of various dosage forms can be prepared by adding moisturizing agents such as 3-butylene glycol and various chemicals. For example, a lotion, a cream, a milky lotion, a pack, or the like may be used depending on the purpose.

[0021]

EXAMPLE An example which is an actual use method will be described below, but the present invention is not limited to this example. The production examples of the extract of Saraka Indica, pomegranate, Misaquinohana, jumbo lan, and licorice used in the present invention are shown below.

Production Example 1 300 g of methanol was added to 10 g of bark (dried product) of jumbo lan, and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 2) To 10 g of jumbo lane bark (dried product) was added 300 ml of 50% methanol, and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 3) To 10 g of bark (dry product) of jumbo lan, 300 ml of purified water was added and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

Production Example 4 Leaf of Misakinohana (dry product)
300 g of 50% methanol was added to 10 g and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 5) Leaf of Misakinohana (dry product)
300 g of purified water is added to 10 g of the above and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Production Example 6) 300 g of methanol was added to 10 g of bark (dried product) of Makinohana and left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 7) To 10 g of bark (dried product) of Makinohana was added 300 ml of 50% ethanol, and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

Production Example 8 To 10 g of bark (dried product) of Makinohana was added 300 ml of 50% methanol, and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 9) To 10 g of bark (dried product) of Makinohana was added 300 ml of purified water and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Production Example 10) 300 g of methanol was added to 10 g of bark (dried product) of Saraca indica and left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 11) To 10 g of bark (dried product) of Salaca indica, 300 ml of purified water was added and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Production Example 12) 300 g of methanol was added to 10 g of mint (dried product), and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 13) 300 g of 50% methanol was added to 10 g of dried sardines and left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 14) 300 g of purified water is added to 10 g of dried sardines and heated for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Production Example 15) 10 stones of garlic root bark (dried product)
300 ml of methanol was added to g and left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 16) 10 stones of garlic root bark (dried product)
300 ml of 50% methanol was added to g and left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Production Example 17) 10 stones of garlic root bark (dried product)
Add 300 ml of purified water to g and heat for 3 hours. This was allowed to cool, then filtered and freeze-dried.

(Production Example 18) 10 stones of garlic peel (dry product)
300 ml of ethanol was added to g and the mixture was left for 5 days with occasional stirring. This was filtered, evaporated and freeze-dried.

(Example 1) Lotion Olive oil 0.5 Extract of Production Example 1 0.5 Polyoxyethylene (20 E.O.) sorbitan monostearate 2.0 Polyoxyethylene (60 E.O.) hydrogenated castor oil 2.0 Ethanol 30.0 1.0% sodium hyaluronate aqueous solution 5.0 Purified water 60.0

(Example 2) Ointment Macrogol 4000 49.8 Macrogol 400 49.8 Extract of Production Example 2 0.4

(Example 3) Example 3 was prepared by replacing the extract of Production Example 1 of Example 1 with the extract of Production Example 3

(Example 4) Example 4 was prepared by replacing the extract of Production Example 2 of Example 2 with the extract of Production Example 4.

(Example 5) Example 5 was prepared by replacing the extract of Production Example 1 of Example 1 with the extract of Production Example 5.

(Example 6) Example 6 was prepared by changing the extract of Production Example 2 of Example 2 into the extract of Production Example 6.

(Example 7) Example 7 was prepared by changing the extract of Production Example 1 of Example 1 into the extract of Production Example 7.

(Example 8) Example 8 was prepared by changing the extract of Production Example 2 of Example 2 into the extract of Production Example 8.

(Example 9) Example 9 was prepared by changing the extract of Production Example 1 of Example 1 into the extract of Production Example 9.

(Example 10) Example 10 was prepared by changing the extract of Production Example 2 of Example 2 into the extract of Production Example 10.

(Example 11) Example 11 was prepared by replacing the extract of Production Example 1 of Example 1 with the extract of Production Example 11.

(Example 12) Example 12 was prepared by replacing the extract of Production Example 2 of Example 2 with the extract of Production Example 12.

(Example 13) Example 13 was prepared by changing the extract of Production Example 1 of Example 1 into the extract of Production Example 13.

(Example 14) Example 14 was prepared by changing the extract of Production Example 2 of Example 2 into the extract of Production Example 14.

(Example 15) Example 15 was prepared by changing the extract of Production Example 1 of Example 1 into the extract of Production Example 15.

(Example 16) Example 16 was prepared by changing the extract of Production Example 2 of Example 2 into the extract of Production Example 16.

(Example 17) Example 17 was prepared by changing the extract of Production Example 1 of Example 1 into the extract of Production Example 17.

(Example 18) Example 18 was prepared by changing the extract of Production Example 2 of Example 2 into the extract of Production Example 18.

(Anti-plasmin test) Test method: A 9 cm Petri dish was charged with 4 ml of a plasminogen-removing fibrinogen type 2-0.6% aqueous solution, 4 ml of 0.1 M phosphate buffer (pH 7.4) was added, and the mixture was stirred. 10 units / ml) 0.1 ml was added dropwise and mixed slowly,
It was left for 30 minutes. Fibrinogen is converted to fibrin by the addition of thrombin, forming a gel.
0.1 ml sample and 0.1 plasmin solution (10 units / ml)
30 μl of the mixed solution was placed on a petri dish gel, and the mixture was left at 37 ° C. for 2 hours. Then, the dissolved area of the fibrin gel was measured. A similar experiment was conducted using water instead of the sample, and the inhibition rate of plasmin activity was calculated by the following formula.

[Equation 1] As a positive control, tranexamic acid and ε-aminocaproic acid were tested.
The amounts were 0 mg / ml and ε-aminocaproic acid 40 mg / ml. Table 1 shows the inhibition rates of the samples of each production example for the samples of 1 mg / ml and the samples of 0.2 mg / ml.

[0059]

[Table 1]

(Usage test) The faces of 6 females were divided into left and right sides, one as an example and the other as a comparative example every day,
A questionnaire was given three months later after having used it at least once.
In addition, in the comparative example, various extracts of the production examples from the examples are replaced with water. (Comparative Examples 1 and 2) 54 people were divided into 9 groups, and experiments were conducted using the following samples. Table 2 shows the experiment numbers and the samples used. The degree of suppression of erythema of skin inflammation after UV irradiation was evaluated according to the following criteria. The total points are shown in Table 3.

The judgment criteria are as follows, and the results of the questionnaire are summarized in Table 2 below. Example is much better 3 Example is much better 2 Example is slightly better 1 No difference 0 Comparative example is slightly better -1 Comparative example is much better -2 Comparative example Is much better -3

[0062]

[Table 2]

[0063]

[Table 3]

[0064]

The antiplasmin agent of the present invention has a large inhibitory effect on plasmin activity, as shown in Examples, and therefore, as a cosmetic composition for suppressing inflammation when exposed to ultraviolet rays, and suppressing inflammation of periodontitis. , Effective in prevention.

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Claims (1)

[Claims] 1. An antiplasmin agent containing at least one selected from the group of solvent extracts of Saraca indica, pomegranate, Misaquinohana, jumbo lan, and licorice.