JP2007126480A - Medicine for treating or preventing angiofibrosis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicine which can prevent and eliminate blood vessel collagen fiberization which is the early stage of arteriosclerosis, and can safely be taken everyday. <P>SOLUTION: The dry powder or extract of a specific portion or whole portions of a plant having been used for foods or galenical, such as Punica granatu, is used as a medicine as such, or as a component for medicinal compositions. Thereby, the medicine of the present invention is safe, and can therefore be taken everyday. Since having an excellent blood vessel fiberization-improving effect, the medicine is useful as a medicine for treating or preventing arteriosclerosis. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a drug capable of treating or preventing vascular collagen fibrosis that causes cardiovascular disease, and a composition for treating or preventing arteriosclerosis comprising the drug as an active ingredient.

  Arteriosclerosis is a disease in which lipid is deposited on the inner wall of the blood vessel, then collagen fiber is formed, and then calcium is deposited, the arterial blood vessel hardens. Eventually, the disease progresses to thrombosis and becomes severe due to rupture of the blood vessel wall, etc. It is a disease that leads to a condition. In recent years, arteriosclerosis is likely to occur due to Westernization of eating habits, overeating, alcohol consumption, lack of exercise, etc., but arteriosclerosis has no subjective symptoms, and symptoms progress unknowingly, One day suddenly causes serious complications such as angina, myocardial infarction, and cerebral infarction. Therefore, regarding arteriosclerosis, it is very important to be aware of its prevention from daily life and to improve it before the symptoms progress.

  By the way, since arteriosclerosis has LDL (so-called bad cholesterol) accumulation as its first stage, a therapeutic agent for hyperlipidemia is used for the treatment.

  However, since therapeutic agents for hyperlipidemia generally have side effects, they should not be used as a prophylactic agent for arteriosclerosis or at a mild stage if administered at a stage where symptoms have progressed. Absent.

  Further, collagen fiberization of coronary arteries and renal blood vessels is considered to be a major cause of cardiovascular diseases (Brilla & Weber, Cardiovascular Res., Vol. 26, 671-679 (1992)). The present condition is that the medicine which can respond to this has not been found yet.

  Under the circumstances as described above, an object of the present invention is to provide a drug that can prevent and eliminate vascular collagen fibrosis, which is an early stage of arteriosclerosis, and can be safely taken every day. .

  Under the above-mentioned problems, the present inventor considers that plants that have been used as food or herbal medicines can be safely used without concern for side effects. We conducted extensive research to find out what has therapeutic effects. As a result, certain plant components not only have preventive and therapeutic effects on vascular fibrosis, but also significantly increase HDL (so-called good cholesterol) effective for arteriosclerosis, The present invention has been completed by finding that it has an excellent effect on prevention of arteriosclerosis by reducing it.

  That is, the therapeutic or prophylactic agent for vascular fibrosis according to the present invention includes fruits of miravalan (Terminaria chebula), fruits of terminaria berylica, and amaroc (scientific name: Emblica officinalis). It consists of a dry powder or extract of the whole plant of the underground part or stem of a plant, pomegranate (Punica granatum) or Takasaburo (Eclipta alba).

  Moreover, the composition for treating or preventing arteriosclerosis according to the present invention is characterized by containing the therapeutic or preventive agent for vascular fibrosis as an active ingredient.

  The therapeutic or prophylactic agent for vascular fibrosis according to the present invention has excellent preventive and resolving action on vascular collagen fibrosis, which is the initial stage of arteriosclerosis, and has been used as a raw material for plants conventionally used as food or herbal medicine Therefore, it is safe and can be taken every day. Therefore, the therapeutic or prophylactic agent for vascular fibrosis according to the present invention is useful as a therapeutic or prophylactic agent for arteriosclerosis and can be used as a component of a pharmaceutical composition.

  The greatest feature enjoyed by the therapeutic agent for vascular fibrosis of the present invention is that it is highly safe and can be taken every day even though it has a high effect on prevention and treatment of vascular collagen fibrosis. is there. That is, in the present invention, since a plant having a high effect of preventing / treating vascular fibrosis has been searched from plants that have been conventionally used as edible or crude drugs, the vascular fibrosis therapeutic agent of the present invention has very few side effects and is very inexpensive. In addition, the convenience of production and formulation is also high.

  Hereinafter, embodiments of the present invention that exhibit such characteristics and effects thereof will be described.

  “Mirobaran (Terminalia chebula)” is a plant belonging to the genus Momotamana, which is 30 m high. The fruit of Myrobalan is used as a raw material for herbal medicine called coconut and is used for chronic diarrhea.

  "Terminalia berylica" is also a raw material plant for herbal medicines and is sometimes used instead of myrobalan. The immature fruit is used to prevent diarrhea and the ripe fruit is used as an antidiarrheal agent.

  "Ammaroc (scientific name: Emblica officinalis, nickname: Phyllantus embrica)" is also called oleum and is a deciduous tree that grows from India to Southeast Asia and southern China. The fruit is used like a lemon, and in China, the dried fruit is called Satsuma Mochi and is used to treat fever, cough, and sore throat associated with a cold.

  “Plants of the genus Salacia” are asteraceae, and examples thereof include Salacia reticulata, S. prinoides, and S. oblonga. These have a postprandial hyperglycemic control action and are known to be effective for constipation.

  Pomegranate (Punica granatum) is a plant belonging to the genus Pomegranate, which has been used for anthelmintic purposes since ancient times due to its anthelmintic components contained in the skin, fruit, bark and root bark. The flower is mainly used as a hemostatic agent in Chinese, Indian, and Arabian medicine, but it has little use in Japan.

  “Eclipta alba” is a plant belonging to the family Asteraceae and grows naturally in paddy fields. Sun-dried products are used as crude drugs and are mainly used as hemostatic agents.

  In the present invention, the above-mentioned plant fruits, underground parts (such as roots and underground stems), trunks, flowers, or the whole plant dry powder or extract are used as active ingredients. In more detail, fruit is used in Myrobalan, Terminaria berylica and Ammarok, underground or stem in Salacia plants, flowers in pomegranate, and whole plant in Takasaburo.

  The method of “drying” is not particularly limited, and examples thereof include sun drying, half sun drying, shade drying, heat drying, room temperature drying, freeze drying, etc., but sun drying, half sun drying, and shade drying conventionally used for manufacturing herbal medicine are preferable. .

  “Powder” means that it can be swallowed orally as it is, and its particle size is not particularly limited. Therefore, the particle size need not be uniform and may be about 1 cm. Furthermore, even if it is generally not possible to say “powder”, it is within the scope of the present invention to become “dry powder” as long as it is granulated.

  The method for extracting the “extract” is not particularly limited. For example, the fruit or the like may be extracted as it is, may be extracted from a ground material, or may be extracted from a once dried product. May be. However, considering the extraction efficiency, it is preferable to extract from a finer one.

  As the solvent for extraction, an aqueous solvent is mainly used. This is in consideration of the convenience of extraction work, safety if it is extracted from an aqueous solvent because it is water-soluble, and safety when the solvent remains. Examples of such aqueous solvents include water; lower alcohols such as methanol, ethanol, isopropanol, and t-butyl alcohol; and mixed solvents of water and lower alcohols.

  The amount of the solvent to be used is generally 2 to 50 times that of the raw material if the extraction material is dry, and 0.5 to 30 times that if it is not dry. The extraction may be performed at room temperature, but it is also effective to increase the extraction efficiency by appropriately heating the solvent.

  The extraction time is not particularly limited, but is preferably 1 hour to 3 days. In addition, the extraction may be left standing or stirred.

  The processing after the completion of extraction follows a conventional method. For example, after filtration, the residue is washed with the solvent used, and after combining with the filtrate, the solvent may be distilled off under reduced pressure or heating.

  The dry powder and extract thus obtained may be drunk as they are, but may be used as a composition for treating or preventing arteriosclerosis by adding other composition components.

  In the present invention, a component having a therapeutic or preventive effect on vascular fibrosis is not specified. However, since the plant used in the present invention has been conventionally used as a herbal medicine or the like, not only one such active ingredient but also a variety of active ingredients interact with each other to provide an excellent therapeutic effect on vascular fibrosis and the like. It is possible to demonstrate. Therefore, it is expected that a further effect is produced by using a plurality of the therapeutic or preventive agents of the present invention in combination.

  The composition for treating or preventing arteriosclerosis according to the present invention may contain the above-mentioned vascular fibrosis therapeutic or preventive agent as an active ingredient and, in addition, those used as constituents of pharmaceutical preparations. Such a component is not particularly limited, and examples thereof include fragrances, preservatives, pigments, and vitamins.

  The present invention is configured as described above, and the vascular fibrosis treatment or prevention agent according to the present invention is safe and can be manufactured at low cost, and also has a very excellent vascular fibrosis improving action. The dose varies depending on whether it is a dry powder or extract, for the purpose of preventing or treating vascular fibrosis, and depending on the symptoms, age and sex of the patient, for example, per day. 0.01 mg / kg to 1 g / kg (preferably 0.1 to 500 mg / kg) is orally administered. However, the dose is merely an example, and can be changed in a timely manner while observing the effects and the like.

  EXAMPLES Examples, test examples, and formulation examples will be shown below to explain the present invention in more detail. However, the scope of the present invention is not limited to these examples.

(Example 1) Preparation of sample The dried product of Myrobalan fruit, Terminaria berylica fruit, Ammarok fruit, Salacia reticulata basement and trunk, pomegranate flower, and Takasaburo whole plant was coarsely pulverized to 50 mesh or less. 20 times the amount of hot water was added, and the mixture was heated and extracted for about 3 hours, filtered, and then the solvent was distilled off under reduced pressure to obtain each dry extract.

  The yield of the extract was 6.5% Salacia reticulata, 28% Myrobalan, 30% Terminaria berylica, 25% Ammarok, 35% pomegranate and 26% Takasaburo.

(Test Example 1)
Diabetes is induced by intravenous injection of 100 mg / kg of male male dd-Y mice having a weight of 35 to 40 g, 12 weeks old, with a group of 10 mice, and Streptozotocin (Sigma) (hereinafter referred to as “STZ”). did. According to findings obtained in recent years, it has been reported that blood vessels are collagenized in such a diabetes model (Mirice et al., Br. J. Pharmacol, 133, 687-694 (1992)). The mouse can be used as a model for vascular collagen fibrosis.

  About the sample prepared by the said Example, the extract of Salacia reticulata was 100 mg / kg, the other sample was administered at a dose of 500 mg / kg, and it was orally administered twice a day for 4 weeks from 3 hours after STZ administration. A non-administration group was also provided as a control group.

  Thirty minutes after the final administration, the mice were anesthetized with ether and then blood was collected, and the blood glucose level, total cholesterol level, neutral lipid level, and HDL cholesterol level were measured using a commercially available measurement kit (Wako Pure Chemical Industries, Ltd.). The results are shown in Table 1.

  According to the result, although the total cholesterol value was not significantly different from that of the control group, the neutral fat value was significantly decreased and the HDL value was significantly increased. Therefore, it has been clarified that if the fibrosis preventing or therapeutic agent according to the present invention is taken, not only can arteriosclerosis be prevented but also the progression thereof can be suppressed.

(Test Example 2)
The heart and kidney were removed from the mouse and fixed with 10% formalin to prepare a tissue specimen. Among these, 200 × and 400 × magnified photographs showing the effect of improving the vascular fibrosis of the pomegranate flower extract are attached as FIG. 1 (heart coronary artery) and FIG. 2 (renal blood vessel).

  Further, 20 fractions were randomly selected from each tissue specimen, and the interstitial fiberized portion was stained with van Gieson, and the collagen fiberization rate was calculated and quantified using the KS400 image system (manufactured by Zeiss). . The results are shown in Table 2.

  According to FIG. 1 and FIG. 2, the fibrosis of coronary arteries and renal blood vessels is clearly progressing by the administration of STZ (the dark colored portion in the figure), but by the administration of the fibrosis treatment or the preventive agent according to the present invention. It can be seen that the collagen fiberized portion of the blood vessel is clearly reduced.

  Further, according to the results shown in Table 2, it can be confirmed that the collagen fiberization rate of the blood vessels is statistically significantly decreased by the administration of the fibrosis treatment or the preventive agent according to the present invention.

  Therefore, it has been clarified that the fibrosis treatment or prophylactic agent according to the present invention has a clear therapeutic effect even on blood vessels once fibrosis has progressed.

(Test Example 3)
Using the same method as in Test Examples 1 and 2 above, an experiment was conducted regarding the combined effect of Terminaria berylica with a particularly high vascular fibrosis improving effect and other samples. Terminaria berylica was administered at 250 mg / kg, Salacia reticulata at 50 mg / kg, and the other extracts at 250 mg / kg. The results are shown in Tables 3 and 4.

  Comparing the results with the results of Test Examples 1 and 2 described above, even when Terminaria berylica and another extract were administered in combination with the dose in Test Example 1 being halved, the blood glucose level, total cholesterol level, Equivalent or higher effects are obtained for both sex fat level and HDL level.

  In addition to these effects, the plant used in the present invention is considered to contain various active ingredients. Therefore, by using in combination with the therapeutic or preventive agent for vascular fibrosis according to the present invention, further addition is possible. It is expected that a positive effect will occur, which can contribute to the maintenance of health.

(Formulation example 1) Granules After sufficiently mixing the powders of the following components, granules are prepared by a known wet granulation method.
Salacia reticulata extract 30mg
Lactose 865mg
Cellulose 5mg
Magnesium stearate 100mg
(Total) 1000mg

  INDUSTRIAL APPLICABILITY The present invention can be applied to a drug capable of treating or preventing vascular collagen fibrosis that causes cardiovascular disease, and a composition for treating or preventing arteriosclerosis containing the drug as an active ingredient. .

The figure showing the improvement effect of coronary artery fibrosis which a pomegranate flower extract shows. The figure showing the improvement effect of renal vascular fibrosis which a pomegranate flower extract shows.

Claims (2)

  A therapeutic or prophylactic agent for vascular fibrosis, comprising a dry powder or extract of pomegranate (Punica granatum) flowers.   A therapeutic or prophylactic agent for vascular fibrosis, comprising a dry powder or extract of a pomegranate (Punica granatum) flower and a dry powder or extract of a fruit of Terminaria berylica.