WO1998017291A1

WO1998017291A1 - A litholytic medicine

Info

Publication number: WO1998017291A1
Application number: PCT/CN1997/000097
Authority: WO
Inventors: Yuqi Di
Original assignee: Xiang, Wei
Priority date: 1996-10-23
Filing date: 1997-10-05
Publication date: 1998-04-30
Also published as: CN1158740A; AU4548297A

Abstract

The invention relates to a litholytic medicine containing an effective amount of active component extracted from one or more plants selected from dried gentian root, dried flowers of Carthamus tinctoricus, dried fruit of Foeniculum vulgare, dried rhizome of Pinus tabulaeformis, dried cortex of Berberis sargentiana, B. brachypoda or B. dictyophylla. According to the different type of calculus, the medicine may be adjusted to pH 6.3-7.2 by organic acid extracted from plant seed, grain and embryo bud. The medicine can be useful in treating hepatic calculus.

Description

O 98/17291-1-

TECHNICAL FIELD OF THE INVENTION

The invention relates to a medicament having a stone-dissolving effect, in particular to a pharmaceutical preparation prepared by extracting effective ingredients from Chinese herbal medicine. Technical background of the invention

Cholelithiasis is a common and frequently-occurring disease worldwide. The natural incidence of

4.2 to ⁸ %, it seriously endangers the health and life of middle-aged and elderly people. The number of general surgical inpatients with gallstones is second only to those with appendicitis. The traditional treatment of gallstones in Western medicine is surgery, but there are many postoperative complications, and two major problems have not yet been solved. The first is that intrahepatic stones are not easy to remove; the second is the regeneration of residual biliary stones, which has an incidence of 20 to 40% or higher. Cholelithiasis not only causes great pain to patients, but also increases social morbidity and reduces social attendance. As a result, it has caused widespread concern in the medical community and has become one of the hot topics for Chinese and foreign medical experts to explore.

Existing stone-dissolving therapies are generally divided into two categories, one is oral stone-dissolving therapy and the other is direct stone-dissolving therapy. Chenodeoxycholic acid and ursodeoxycholic acid are commonly used drugs for oral stone-dissolving therapy. Practice has proved that this therapy has a long course of treatment, high cost, side effects, and easy to relapse after healing. In addition, this therapy is only effective for cholesterol-type stones, and has little effect on other types of stones.

Direct stone-dissolving therapy is to dissolve the stone by directly contacting the medicinal solution with the stones through the "T" tube or other channels, and it is also a rapidly developing therapy recently. Mono-octane marriage

(mono-octanion) and methyl tert-butyl ether (MTBE) lava. The former has a poor curative effect, and the latter is a recent invention. Its toxicity is high (LD50-1.9072ml / kg), its operation is complicated, and it is only suitable for dissolving gallstones. The above two drugs are developed for the characteristics of cholesterol stones in Europe, America and other countries, but they are not targeted for Chinese patients with cholelithiasis. Patients with cholelithiasis in northern China have the highest number of mixed stones, followed by cholesterol stones. In southern China, patients with bile pigment stones often have more stones. Therefore, it is necessary to develop a new type of high-efficient and low-toxic lysolytic agent suitable for the characteristics of Chinese stone patients. -2-Disclosure of invention

The object of the present invention is to provide a highly effective and low-toxicity stone-holding medicine prepared by using the active ingredients of natural plants obtained from the purification and purification of Tibetan medicine to meet the characteristics of Chinese stone patients.

The medicine of the present invention contains a therapeutically effective amount of a mixture of active ingredients extracted from any one or more of the following plants, which plants include gentian, safflower, fennel, rhizomes and fruits of Pinus tabulaeformis, and three Needle bark; take one or more of the above-mentioned raw medicinal materials, soak in water for 5 to 100 hours, preferably in a ratio of 1:50 to 1: 200, preferably in a ratio of 1:80 to 1: 150, preferably 24 To 72 hours, the soaking solution is filtered, the filtrate is concentrated on a rotary evaporator to remove water, and the concentrated solution is rectified in a rectification tower to collect a fraction of 150 ° C-164 ° C; It was identified as C1 0H16 terpene diene by UV, UV, NMR and mass spectrometry. The above-mentioned plants for extracting an active ingredient are preferably Tibetan medicinal flower Alpine gentian, saffron, Tibetan fennel. The lysolytic agent of the present invention preferably contains the above-mentioned active ingredient mixture in an amount of 2 to 10% by weight. An appropriate amount of a solvent and a solubilizer may be added to the medicine of the present invention, for example, water, soil temperature-80, and the like. In the process of preparing the medicine of the present invention, the pH value is adjusted with organic acids extracted from natural plants to prepare medicines suitable for different types of stones. The organic acid is prepared as follows:

Alpine and hardy plant seeds such as pine nuts, barberry, gentian buds, saffron seeds, grains, and germs are produced in a ratio of 1:50 to 1: 200, preferably 1:80 to 1: 150. Proportion, immerse in water for 5 to 100 hours, preferably for 24 to 72 hours, filter the soaking solution, and extract the filtrate under reduced pressure and concentrate to obtain an organic acid concentrated solution with a concentration of 1% to 40%. The organic acid extract has an oral LD50 of 494 2 mg / kg and is harmless to humans. The preparation method of the lysolytic drug of the present invention is as follows:

Take the terpene diene mixed extract, add Tween 80, mix, and add distilled water to it to prepare an emulsion. Its appearance is white emulsion. Use the above according to the patient's stone composition The prepared organic acid regulates the pH of the emulsion in the range of 6.3 to 7.2, and the medicines with different pH values are directed to different indications.

PH indication

PH = 6. 4-7. 2 cholesterol stones

PH = 6.8-7.2 cholesterol-based mixed stones

PH = 6.8-7.1 mixed stones based on bile pigments

PH-6. 5-7. 0 bile pigment stones

PH = 6. 3-6. 7 liver stones The method of using the medicine of the present invention is as follows:

In clinical treatment, PTCC is instilled by percutaneous puncture of liver tube by infusion. The drip rate is synchronized with the bile and liver juice secretion rates, and the treatment cycle is generally determined by the number of stones. One course is one week. The dosage is 250 ml a day and 1750 ml per course. Best Mode of the Invention

Take the original medicinal material gentian, soak it in water for 72 hours at a ratio of 1: 100, and filter the soaking solution. The filtrate is concentrated on a rotary evaporator to remove water, and the concentrated solution is rectified in a rectification tower to collect 150. C-164. C fraction is a light yellow liquid. The pine nut fruits produced in high mountains and cold-resistant plants were immersed in water for 72 hours at a ratio of 1:50, and the soaking solution was filtered. The filtrate was concentrated under reduced pressure to obtain an organic acid concentrated solution with a concentration of 10%. Take 5 grams of the light yellow liquid prepared above, add 3 grams of Tween-8 0, mix well, slowly add 92 grams of distilled water dropwise, mix well to obtain a white milky liquid, add the organic acid prepared above, and adjust the pH The value is 6.8-7.2, which makes the required drug. Industrial applicability The drug of the present invention has been clinically verified, and not only has a higher efficacy than foreign monooctane

(mono-octanion) is less toxic than foreign methyl tert-butyl ether (MTBE), and it also has the advantages of high efficacy and low toxicity compared with domestic lytic agents. Another advantage of the medicament of the present invention is that it has the effects of incomparable other stone-solving agents to eliminate inflammation of the liver and bile ducts, change bile from turbidity to clear, clear stone lesions, and restore normal organ function. The medicinal product of the present invention has the advantages that it is simple and easy to use and has significant benefits. All kinds of complex and special equipment required for ordinary stone-dissolving therapy can be implemented in ordinary grass-roots factories and medical institutions and family beds. The method is simple and easy to spread. The length of hospital stay reduces the medical expenses of patients, and the social benefits are significant.

Claims

Rights request

1. A lytic stone drug,

It is characterized in that it contains a therapeutically effective amount of a mixture of active ingredients extracted from any one or more of the following plants by the following methods: the plants include gentian, safflower, fennel, rhizomes and fruits of pine And three needle bark; take one or more of the above-mentioned raw medicinal materials, soak in water for 5-100 hours at a ratio of 1:50 to 1: 200, filter the soaking solution, and concentrate the filtrate on a rotary evaporator to remove Water, and the concentrate is rectified in a rectification column to collect a fraction of 150 ° C-164 ° C.

2. The lysolytic drug according to claim 1,

It is characterized in that the plants used for extracting the active ingredients are Tibetan medicinal flower Alpine gentian, saffron and Tibetan fennel.

3-The lysolytic drug according to claim 1,

It is characterized by immersing the original medicinal materials in a ratio of 1: 80-1: 150 and adding water for 24-72 hours.

4-The lysolytic drug according to claim 1,

It is characterized by containing the active ingredient mixture in an amount of 2-10% by weight.

5-The lysolytic drug according to claim 1,

It is characterized by its presence of solvents and solubilizers.

6. The lysolytic drug according to claim 5,

It is characterized in that the solvent is water and the solubilizer is Tween-80.

7. The lysolytic drug according to claim 1,

It is characterized in that its pH is adjusted to 6.3-7.2 with an organic acid.

8-The lysolytic drug according to claim 7,

It is characterized in that the organic acid contained in the lysolytic drug is prepared by the following method: soaking cold-tolerant plant seeds, grains, and germs produced in high mountains at a ratio of 1:50-1: 200 and soaking in water for 5 -100 hours, the soaking solution is filtered, and the filtrate is distilled under reduced pressure Extraction and concentration to obtain a concentrated organic acid solution with a concentration of 1%-40%. 9. The lysolytic drug according to claim 8,

It is characterized in that the organic acid contained in the lysolytic drug is prepared by the following methods: one or more kinds are selected from pine nuts, barley, gentian buds, and saffron seeds, and the ratio is 1: 80-1: 150%, soak in water for 24 to 72 hours, filter the soaking solution, and extract the filtrate under reduced pressure to concentrate it to obtain a concentrated organic acid solution with a concentration of 1%-40 ° /. .