Title:  Hypertension-treatment and cholesterol-depressant composition comprising extract from mixture of Panax notoginseng and Salvia miltiorrhiza and method of preparing the same

United States Patent:  6,589,572

Issued:  July 8, 2003

Inventors:  Hong; Eun Kyung (Seoul, KR); Chung; Young Shin (Seoul, KR)

Assignee:  Medvill Co., Ltd. (Seoul, KR)

Appl. No.:  880274

Filed:  June 14, 2001

Abstract

A composition for treating hypertension and lowering cholesterol is provided which contains the mixed extract of Panax notoginseng and Salvia miltiorrhiza as an active ingredient thus lowering and maintaining blood pressure substantially constant. Also provided is a method for preparing composition containing the mixed extract of Panax notoginseng and Salvia miltiorrhiza as an active ingredient.

DISCLOSURE OF THE INVENTION

In consideration of the problems inherent in the prior art, it is an object of the present invention to provide a medicinal herb composition for treating hypertension and lowering cholesterol level.

Another object of the invention is to provide a composition for treating hypertension and lowering cholesterol level, in which the plant extract exhibits a significant hypotensive effect with substantially no side effect and regulates the factors responsible for the control of blood pressure to adjust blood pressure within normal range, thereby maintaining the homeostasis of blood pressure, and further to provide a method for preparing same.

BEST MODE FOR CARRYING OUT THE INVENTION

The present inventors have found that the combined use of two kinds of medicinal herbs, i.e. Panax notoginseng and Salvia miltiorrhiza has far greater effect of lowering blood pressure than the independent use of the respective herbal plants and have completed the present invention.

To achieve the above-mentioned purposes of the present invention, a composition for treating hypertension and lowering cholesterol level, which contains the mixed extract of Panax notoginseng and Salvia miltiorrhiza as an active ingredient is provided.

The composition of the present invention can be formulated into the composition selected from the group consisting of tablets, capsules, solutions, suspensions, syrups and edible beverages, by further incorporating a pharmaceutically acceptable excipient.

It is preferred that the mixed medicinal herb extract of the present invention is an aqueous extract or an alcoholic extract.

In the mixture of Panax notoginseng and Salvia miltiorrhiza, the mixing ratio thereof is preferably 5:1 to 1:5, and more preferably 2:1 to 1:2, on the basis of weight. If the mixing ratio is beyond the above-specified range, the synergistic effect derived from the mixed extract is low.

The dosage of the mixed extract of Panax notoginseng and Salvia miltiorrhiza is preferably 10 to 40 mg per 1 kg of the body weight of an adult man.

In addition, the present invention provides a method for preparing the composition for treating hypertension and lowering cholesterol level, which comprises the steps of:

a) mixing Panax notoginseng and Salvia miltiorrhiza and extracting the mixture with water;

b) filtering the extract obtained in the above step a);

c) saturating the filtrate obtained in the above step b) at a temperature of 100 to 140^oC. and under an elevated pressure to produce protein precipitate, which is then removed by centrifuge;

d) extracting the precipitate-removed filtrate of the above step c) with an organic solvent and separating the aqueous layer with removing the oil-soluble materials from the filtrate; and

e) lyophilizing the aqueous layer separated in the above step d).

The method of the present invention further includes the step of preparing the formulation selected from the group consisting of tablets, capsules, solutions, suspensions, syrups and edible beverage by incorporating a pharmaceutically acceptable excipient into the lyophilized mixed extract of Panax notoginseng and Salvia miltiorrhiza as obtained from the above step e).

The amount of water used for extraction in the above step a) is preferably 5 to 10 times, particularly 7 times, greater than the weight of the mixture of Panax notoginseng and Salvia miltiorrhiza.

The organic solvent used in the above step d) is preferably chloroform or hexane.

Alternatively, the present invention also provides a method for preparing the composition for treating hypertension and lowering cholesterol level, which comprises the steps of:

a) extracting the mixture of Panax notoginseng and Salvia miltiorrhiza with one or two kinds of alcohols for 48 to 72 hours at room temperature while stirring;

b) filtering the extract obtained in the above step a) to separate the extract into the residue and the filtrate; and

c) removing alcohol from the filtrate obtained in the above step b) to obtain the extract in the form of powder.

The alcohol used in the above step a) is preferably 70 to 80% alcohol, particularly alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propanol, butanol and pentanol.

The method of the present invention further includes the step of preparing the formulation selected from the group consisting of tablets, capsules, solutions, suspensions, syrups and edible beverage by incorporating a pharmaceutically acceptable excipient into the alcoholic extract of Panax notoginseng and Salvia miltiorrhiza as obtained from the above step c).

The present invention provides a novel pharmaceutical composition containing the extract of the mixture composed of medicinal herbal plants including Panax notoginseng and Salvia miltiorrhiza. The extract has no pathological or physiological influence upon normal tissues and functions thereof, and has an effect of activating the function to maintain the homeostasis of blood pressure by participating in the mechanism of controlling blood pressure. However, the use of only one of Panax notoginseng and Salvia miltiorrhiza provides no expectable hypotensive effect.

The hypotensive effect of the composition according to the present invention could be confirmed by experiments using animals suffering from genetically induced hypertension, namely, spontaneously hypertensive rats (SHR). Currently used antihypertensive agents control hypertension in the manner of symptomatic treatment whereas the composition of the present invention lowers blood pressure by exhibiting CNS inhibitory activity and a potent sedative effect, and at the same time, secondarily inhibiting sympathetic nerve to interfere the entrance of hypertensive substances such as noreinephrine, serotonin and hypertensin into the reservoir. Further, the composition of the present invention also induces the expression of antagonistic substances against hypertensive hormones released from posterior lobe of hypophysis, decreases the resistance of peripheral blood vessel and exhibits activities of increasing new blood flow and relaxing the tension of cerebral blood vessel.

Therefore, the composition of the present invention is characterized in that it provides a superior hypotensive effect but does not decrease the blood pressure to below the normal range, and further that it has no influence upon normal blood pressure and hypotension. In addition, the composition of the present invention does not show any detectable side effect in the course of controlling hypertension but exhibits a progressive and continuous effect of treating hypertension.

In other words, the composition of the present invention, a drug for improving a disorder of blood circulation, has a cardiotonic activity, increases blood flow in coronary artery and reduces oxygen consumption, while at the same time, exhibiting a potent sedative activity.

The composition showing the above-mentioned effects has been developed by the inventors of the present invention through a prolonged experimental study using numerous medicinal herbs related to the controlling of blood pressure, from which it has been confirmed that the novel composition comprising Panax notoginseng and Salvia miltiorrhiza extract exhibits a superior hypotensive activity and has substantially no toxicity and side effects. As a result, we have completed the present invention.

In view of the fact that the pharmacologically active components contained in those herbal plants has an effect of improving abnormal symptoms occurring in cardiac system and blood circulation, we have applied the composition of the present invention to hypertension and observed that the composition of the present invention has no side effect on cardiac system and cerebrovascular system and exhibits an effect of smoothly controlling and improving blood pressure. Further, the inventive composition serves to keep the blood pressure above the normal value, thus preventing any abnormal symptom.

The main components of the composition according to the present invention are saponin and aglycons thereof. However, it has not been identified as yet that the hypotensive effect of the composition of the present invention is induced by these main components. Recently, in China it has been reported that ginseng plants increase the blood flow in coronary artery of animals and exhibit an effect of reducing oxygen consumption by cardiac muscle to reduce the load of heart. In addition, the extract of the present invention is concerned with the endocrine system, and particularly, improves the disorder of blood circulation due to clotting factor. The composition of the present invention makes the function of blood circulatory and cardiovascular systems smooth and can be continuously used with little side effect.

In the composition of the present invention, the mixed extract of Panax notoginseng and Salvia miltiorrhiza is used after removing resins, proteins and fibroid materials therefrom. In case of the aqueous extract, Panax notoginseng and Salvia miltiorrhiza are first macerated or digested in tap water or distilled water and then filtered, and chloroform or hexane is added to the filtrate to remove resins, proteins and fibroid materials. Then, the mixed extract of Panax notoginseng and Salvia miltiorrhiza is purified with addition of talc and then pulverized by lyophilization.

When the mixed extract of Panax notoginseng and Salvia miltiorrhiza as obtained according to the present invention is administered to hypertensive rats, a significant hypotensive effect was observed as the amount thereof increases.

Hereinafter, the method for preparing the mixed extract according to the present invention is more specifically explained.

According to the method for extracting the aqueous extract of the present invention, in the first step dried Panax notoginseng and Salvia miltiorrhiza are mixed, ground and then extracted by means of water such as tap water or distilled water as the solvent with heating or heating under saturated vapor pressure (100-140^oC.). The amount of water used for extracting the mixture of Panax notoginseng and Salvia miltiorrhiza is 5 to 7 times, particularly preferably 7 times, as much as the dried material.

Then, in the second step, the extract is centrifuged to remove the precipitate and again boiled under saturated vapor pressure (100-140^oC.) to coagulate the remaining proteins, which is then filtered by centrifuge and removed.

In the third step, the separated filtrate is extracted with an organic solvent such as chloroform, hexane, dichloromethane, cyclohexane, etc., preferably chloroform or hexane, to remove the impurities including resins and fibroid materials, and the aqueous layer is again purified with talc and then lyophilized to obtain the desired aqueous mixed extract.

The alcoholic extract obtained by using an alcohol as the solvent for extraction of the mixture of Panax notoginseng and Salvia miltiorrhiza, which is an alternative method according to the present invention, can provide the same effect of the aqueous extract as defined above. The specific method for obtaining the alcoholic extract is as follows.

The medicinal herbs, Panax notoginseng and Salvia miltiorrhiza, are independently ground, and then mixed together in the ratio of 5:1 to 1:5, preferably in the ratio of 2:1 to 1:2, by weight. The mixture is eluted with one or two kinds of alcohols, preferably 70 to 80% alcohols, at the room temperature for 48 to 72 hours while concomitantly stirring. The eluate is decanted off, and the residue is re-extracted with alcohol having the same concentration according to the same manner as above and the eluate is decanted off and then combined with the first eluate. Talc is added to the eluate, which is remained after recovering alcohol, stirred and then centrifuged. The supernatant is decanted off and then filtered. The filtrate is pulverized after removing alcohols.

The mixed extract (aqueous extract and alcoholic extract) of Panax notoginseng and Salvia miltiorrhiza as obtained according to the above-mentioned methods of the present invention can be effectively used as the pharmacologically valuable composition for lowering blood pressure as described above.

The present inventors have confirmed that the composition of the present invention exhibits a good hypotensive activity and further, demonstrated that the composition of the present invention is a safe drug which has passed through acute toxicity test.

In using the mixed extract of Panax notoginseng and Salvia miltiorrhiza according to the present invention for the clinical purpose, the therapeutically effective amount of the mixed extract can be formulated alone or in combination with a pharmaceutically acceptable carrier into a suitable pharmaceutical preparation according to the conventional method used in the pharmaceutical field, and then, administered according to a conventional manner used in the pharmaceutical field, preferably via oral route. In general, the composition of the present invention can be formulated into the oral dosage form, for example, tablets, capsules, solutions, suspensions or syrups or can be prepared in the form of a beverage.

Although the dosage of the mixed extract of the present invention may vary depending on the severity of diseases to be treated, the sex, age and weight of a patient, the kind of the desired effect, etc., the oral daily dosage for an adult man is generally 5-50 mg, preferably 10-40 mg, per 1 kg of the body weight.

Claim 1 of 6 Claims

What is claimed is:

1. A composition for treating hypertension and lowering cholesterol level, which comprises a mixed extract of Panax notoginseng and Salvia miltiorrhiza as an active ingredient, wherein Panax notoginseng and Salvia miltiorrhiza are mixed in a mixing ratio of 5:1-1:5 by weight of the total composition.

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