SU995700A3 - Process for preparing terpenes having antisporiatic effect - Google Patents

Abstract

A process for extracting antipsoriatic natural terpenes from rhyzomes and leaves of Dryopteris crassirhizoma, Polypodium vulgara Linn, Polypodium leucotomos, Phlebodium decumanun J. Smith, Polypodium decumanum, Cyathea taiwaniana and rhyzomes of Polypodium aureum Linn and Polypodium triseriale comprises solvent extraction of a dry comminuted mass of the plant matter, evaporating off the solvent and purifying the residue.

Description

39 N-hexane with water (10: 4), and after settling, one-tenth of its volume 10-20% potassium hydroxide is added to the n-hexane solution, and after periodic stirring it is left to stand 6 parts of n-Hexane the phase is neutralized by washing with water. After evaporation, the residue is taken up in a threefold volume of 9b-ethanol and left to stand until a complete precipitation takes place, usually CV of an hour at room temperature. The precipitate is filtered through glass filters having an average porosity during absorption, washed with suitable amounts of 9b-ethanol until it becomes almost colorless, and dried under vacuum over potassium hydroxide or concentrated sulfuric acid. The precipitate is dissolved on n-hexane to obtain a 10% by weight solution at room temperature (). The solution is chromatographed depending on the amount of material eluted with n-hexane, eluted in the first 1-liter fraction (relative to 2 L). After evaporation to a concentration of 10, the n-hexane solution is allowed to crystallize spontaneously at room temperature. The crystals are filtered with suction, and the mother liquors are again evaporated, obtaining another crystalline mass. Another method is to use a neutral column on alumina AEgOz (5 x 100 cm |) and elution with n-hexane. In this case, the eluate extracts the enzyme, i.e. active ingredient. Recrystallization occurs in hot absolute ethanol. The pharmaceutical compositions are prepared in the form of conventional dosage forms by the introduction of the enzyme into pharmaceutical carriers. The active ingredient (enzyme) must be present in the compositions in an amount sufficient to provide anti-persoria activity. The compositions preferably contain 1-100 mg of the active ingredient per dosage unit, and the pharmaceutical carrier can be solid or liquid. Try on 12 kg of dry granulated leaves on sieve No. 10 (2.5 mm is extracted with 1.5 hours 10 liters of 96% ethanol at. The extract is filtered and washed with 10 liters of 96% ethanol on the filter. The filtered extract is evaporated to dryness under moderate vacuum (20-30 mm Hg). The residue is taken in mixture of n-hexane and water (15:10 l) and left to stand overnight in a separator. The aqueous phase is removed and the hexane phase is clarified. 10 % potassium hydroxide solution in ethanol (5 L). The hexane phase clarified in this way is neutralized by washing with water and evaporated to dryness. It is dissolved in 500 ml of 96% ethanol with heating, filtered and dried (yield 50 g). Dry, the precipitate is dissolved in 1 l of n-hexane and chromatographed on a column of Geduran S160 (100x10 cm) with elution in portions l N-hexane. The first 1-liter fraction is evaporated and the residue is crystallized in hot hexane, benzene or absolute ethanol (yield 12 g). EXAMPLE 2: 3 kg kg of a dry whole plant granulated on a disc mill to size passing through a No. 10 sieve (2.5 mm), continuously extracted with n-hexane at room temperature, hexane solution p is evaporated to 10 L and clarified in a separator 1 liter of potassium hydroxide in 90% ethanol overnight. The hexane phase is neutralized by washing with water and evaporated to dryness. The residue is taken up in hot benzene in sufficient quantity to obtain a saturated solution (1 l). The precipitate is filtered off, cooled and crystallized in hot benzene or hotter absolute ethanol. The crystalline material is dissolved in H-hexane (500 ml) and chromatographed on a Geduran SI-60 column of 5x50 cm size (Mer-Darmithadt) while elution with half a liter portions. The first two half-liter fractions of the eluate are evaporated and crystallized in hot hexane, hot benzene or hot absolute ethanol (yield 38 g). Example 12 kg of dry rhizome granulated on a disk mill to a size passing through a Vf 10 sieve (2.5 mm) are continuously extracted with dichloromethane at room temperature. Dichloromethane is evaporated to dryness, and the residue is taken in 5 l of n-hexane. The hexane solution was clarified with 1 L of potassium hydroxide in 90% ethanol overnight, and the hexane phase was then neutralized by washing with water and evaporated. The residue is taken in 1 lNhexane and chromatographed on a silica gel-6 (100x10 cm) column using n-hexa. The first two fractions of the eluate are evaporated, and the residue is crystallized in hot n hexane, hot benzene or hot ethanol (yield 25 g). Example. When refluxing for 1 hour, 12 kg of a granulated and dried whole plant (2.5 mm granulometry or If 10 sieve) and extracted with 100 liters of methanol at 70 ° C. The extract is filtered and washed on the filter with 20 liters of methanol. The methanol extract is evaporated, and the residue is taken in a mixture of N-hexane and water (3: 2, i.e. 30–20 l) and left to stand overnight in a separator. The aqueous phase is removed and the hexane phase is clarified with 10 liters of a 20% LIA hydroxide in ethanol, it is neutralized by washing with water and evaporated to dryness. The residue is dissolved in 1 l of hot 90% new ethanol and allowed to stand at rjpM at room temperature for 3 hours. The precipitate is filtered off and dried under vacuum over potassium hydroxide. The dry precipitate is dissolved in 1 ln-hexane and chromatographed on a 50x5 cm neutral aluminum oxide column with elution with ntexan. The first 5 liters are evaporated and the material is crystallized in n-hexane, cyclohexane, hot benzene and hot absolute ethanol (yield 12-13 g). ; Example 5: Use Adt, ml: Fernen 40 Lactose60 The ingredients are mixed, clarified and injected into hard gelatin capsules. The capsule prepared in this manner is administered to the patient three times a day. PRI me R 6. Use mg: fern60 Sucrose, 25 Starch 20 Talc5 Stearic Acid 5 Fernen and sucrose are mixed and granulated with a solution of 10 gelatin. The granules are sieved, dried and then mixed with starch, talc and stearic acid. Then they all sift and turn into tablets. EXAMPLE 7: mg: Fernen 50, Peanut Butter 100 Ingredients are mixed and administered in soft gelatin capsules. The medicinal preparations were called Anapsos and placebo. Example 8. A 37-year-old patient suffered from psoriasis, who developed 8 years, the disease was generalized throughout the body. The patient took Anapsos. 7 months (tOO-600 mg per day), after taking the medication for 2 months, the patient had almost no places affected by psoriasis and now he is completely cured of psoriasis. PRI me R 9. Bopna, 38 years old, with a general lsoriasis developing k g, began taking Anapsos June 27, 1979 G | and after 1 month, the condition of her skin areas affected by psoriasis will improve significantly. In the next hypersubstance of the clinic, a pronounced erythema of the skin was found in her, with Staphylococcusaurea being isolated from the skin areas affected by psoriasis and the adjacent normal areas. The patient continued to take Anapsos together with the antibiotic trimethoprim-sulfamethoxazole (12-13) for 1 week. After such treatment, a rapid improvement in the condition of the affected sites followed. The patient continued to take only Anapsos and, until now, she has not seen a recurrence of the disease with psoriasis. . Example 10. Sick for 25 years, suffered from psoriasis, which developed for 18 years. She took Anapsos in 1968 and the lesions with psoriasis disappeared. After 6 years, the disease resumed, the patient took Anapsos, and again there was remission. She was prescribed a placebo, which she took 5 months. The disease progressed, and Sick began taking Anapsos 1 month. However, the patient further did not return to the clinic and did not receive any treatment for 3 months, as a result her condition worsened. At this time, out of her skin areas affected by psoriasis, and from the adjacent areas of normal skin were excreted 9 | Staphylococcus aurea. The patient took an antibiotic for 5 days, never ceasing to take Anapsos. After 1 month, her condition began to improve, and after two months of taking Anapsos, there were no skin areas left on her body affected by psoriasis. PRI me R 11. A patient 8 years old and 12 years old, suffering from psoriasis for 8 months, began to use Anapsos and

At 1 month, there was a significant remission of his skin areas affected by psoriasis. After the second month of treatment, there was almost complete remission. Two months later, Staphylococcus aurea was isolated from the places of his skin affected by psoriasis and the pharynx. The patient took the antibiotic for 5 days together with Anapsos, and after 1 month the lesions almost completely disappeared, and at the present time the disease is not progressing.

PRI me R 12 / Sick, aged 59, suffered from psoriasis, developed over two years, began taking Anapsos, and on the same day bacterial cultures were taken from her, and Staphylococcus aurea was isolated. After that, she took an antibiotic for 5 days, but not stop taking Anapsos. After 3 months, there was a clear improvement, and after C months, the patient mostly recovered.

The proposed method provides receiving terpenes with antipsoriatic action. The preparations obtained were applied to 152 patients suffering from psoriasis, with a daily dose of 200 mg, which caused the disappearance of the disease in more than 80 cases within 1-3 months. The resulting pharmaceutical preparations are highly effective, non-toxic and harmless.

invention formula

The method of obtaining terpenes with antipsoriatic action is haracted by the fact that dried at 50-70 ° C are root and leaves Dryopter Js crasslrhizoma, Polypodium vutgara Zinn, Polypod f urn lecotomos, Phlebodium decumanun J. Smith, Polypodium aureum Zinn poly Polytor, Polypodomotrumos J. Smith Smith and the rhizomes of Polypodium aureum Zinn and Polypodium triseriale are extracted with methanol, the solvent is evaporated, the resulting residue is treated with a mixture of N-hexane and water in a ratio of 10: 4, defend and a solution of 10-20% potassium hydroxide in ethanol is added to the solution, evaporated, filtered, the precipitate is washed with ethanol, dissolved n-hexane, chromium They are captured and recrystallized in hot absygne alcohol.

Sources of information taken into account in the examination

1. Hammerman A.F. The course of pharmacognosy. L. ,, Medgiz, I960, p. 125-137.

Claims (1)

Claim A method of producing terpenes having an antipsoriatic effect, characterized in that {dried at 50-70 ° C. rhizomes and leaves of Dryopteris crass! Rhizoma, Polypodium vulgara Zinn, Polypodium lecotomos, Phlebodium decumanun J. Smith, Polypodium aureum Zinn, Polypodium tri serial 1 and the rhizomes of Polypodium aureum Zinn and Polypodium triseriale were extracted with methanol, the solvent was evaporated, the resulting residue was treated with a 10: 4 mixture of K “hexane with water, sedimented, and a solution of 10-20% potassium hydroxide in ethanol was added to the solution, evaporated, filtered, and the precipitate washed with ethanol, dissolved in n-hexane, chromatograph they form and recrystallize in hot absolute alcohol,