DD144719A5 - METHOD FOR OBTAINING A NATURAL POLAR FRACTION WITH ANTIPSORIATIC EFFECTIVENESS - Google Patents

Description

Γ-f-

Method for obtaining a polar fraction with antipsoriatic activity ''

the invention

The invention relates to a method for obtaining a natural polar fraction with antipsoriatic activity by extraction of leaves and roots of various ferns »

Psoriasis and summarized in the expression P.arapsoriasis skin disease are so far from: not covered science loan and therapeutic Port step and it is not a drug "is known which improves the pathological symptoms of the patient or even heals ^/,; Λ.

The knowledge of the disease can be traced back very much and over the course of time countless attempts have been made to heal it, but in practice no noteworthy results can be obtained. In addition, the few remedies with relative efficacy lead to by-effects that bring about serious poling for the patient.

Significantly, 'mari' has lately returned to the well-known methods of healing, which are harmless, and. at least, bring symptomatological relief ¹ , but never the cure or at least, a remarkable improvement6. '

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The problem is constantly increasing as the number of patients with psoriasis is growing steadily. This is due to the assumption that a genetic transfer takes place, whereby the disease appears in the offspring, open or hidden, or at least 'latent, whereby in the latter case the acute form only occurs when certain pathological factors that cause the clinical picture of psoriasis ,,

The disease can manifest itself on any part of the body surface, with the scalp being one of the most frequently affected areas, and psoriasis manifesting itself in dandruff from "dandruff". Often, this manifestation is hardly considered by the patient in the early stages, and initially over a longer period of time only treated locally, which only worsens the problem of the disease. The presence of "dandruff" can be observed in 30% of cases in which psoriasis attacks other skin areas. "Psoriasis not only spares no part of the body surface, but also no age group. The disease can therefore be observed in neonates as well as in sixty or seventy-year-olds. ·

The geographic extent of psoriasis is total and spares no race, although apparently the black race is less vulnerable. "

The most common complication of psoriasis is in the joints, but liver and kidney tissues can also be affected at an advanced stage * ... '..

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In short summary-can be said: psoriasis and parapsoriasis. are diseases that can be diagnosed without • difficulty even if anatomically · mixed pathologic diagnosis is required, "The incidence of the disease is steadily increasing, and according to conservative estimates suffers 1% of the world population have psoriasis _e Currently no v / irksames cure is known and those with psoriasis have only palliative care.

Object of the invention

The aim of the invention is to provide a therapeutic agent for psoriasis, which has no toxic oder'sonstigen'Nebenwirkungen in its application _e

Presentation of the invention

The invention is; the task to win the remedy from natural roots and leaves ·

According to the invention, a polar fraction is obtained from roots and leaves of various fern herbs. "

The process of the present invention enables the extraction of this polar fraction of leaves and roots of various ferns with sufficient industrial production in sufficient quantities for use in the preparation of pharmaceutical preparations. "In order to achieve optimum yield, the leaves should be collected after the young sporangia have already developed "

The method according to the invention comprises the following steps:

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dry

The roots are cut into strips of 2 to 3 cm; the leaves are dried as they were collected. Drying takes place continuously, with the 'material' being incorporated in a conventional dryer, eg a rotating metallic wire cloth about 5 meters wide and about 25 meters long, which is moved within a hot chamber, the temperature not more than 70 ° C. By regulating the speed of the rotating metallic wire mesh, approximately half a ton of wet material can be dried per hour _o

Males

The dried material (residual moisture below 8 $ o) is ground by means of a disc mill, which is adjusted so that particles of 2 mm are obtained.

 Ebctraktion / Verdampfun ^

The extraction can be carried out with any solvent (dielectric constant 1.890 to 9.08), preferably with methanol in a volume ratio of 1: 4. Evaporation takes place until a residue of 1/5 of the initial volume is obtained.

cleaning

The semi-solidified residue of the extraction evaporation is distributed in a system of immiscible solvents of n-hexane / water (10: 4). After leaving in a trap overnight, become lipids and resins; discarded in the hexane phase. ,

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2, the separated and filtered solution is passed through an exchange resin,

3, add Ca (OH p) "until neutralization,

4, The solution is clarified by addition of activated carbon ©

5, This Lö

is quenched to 1/10 of the original volume and precipitated in an anhydrous organic liquid which is miscible with water, ζ »Β _β absolute alcohol,

6. The precipitate is filtered off with suction and gives a first Staubförraige mass, the crystallized water are re-evaporated, and we obtain a second powdered Hasse,

This powder is dried in vacuo until it has a white Parbe ₀ .

The second white, crystalline mass according to the invention is not a defined chemical substance but a composition _e due to the nature of the starting material used and the process of extraction and purification

The presence of D-glycose and D-fructose in a proportion of 70 % in total results from the usual qualitative. Investigations and isolation and complete determination of acetylated derivatives. Furthermore, the presence of acid compounds that only

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are difficult to separate from the sugar, "both by chromatography and conventional spectroscopic methods"

The pharmaceutical compositions according to the invention are prepared by incorporation of the polar fraction into pharmaceutical carriers in accordance with accepted pharmaceutical practice in conventional dosage forms. The resulting pharmaceutical compositions are therefore also the subject of the invention. The active ingredient, d, h. the polar fraction is present in the compositions of the invention in an amount sufficient to exhibit antipsoriatic activity.

The. Compositions according to the invention preferably contain the active ingredient in a proportion of 10 to 100 mg per unit dosage. The pharmaceutical carrier can be, for example, solid or liquid. Examples of solid carriers are lactose, liagnesium stearate, alba-terra, cane sugar, talc, stearic acid, gelatin, agar, pectin, gum arabic, aerosil and the like. Examples of liquid carriers are alcohols "such as ethanol or propylene glycol, water containing" Solubilizers such as polyethylene glycol, peanut oil, olive oil and the like. The carrier or diluent may contain a retarding agent, such as glyceryl monostearate or glyceryl distearate, alone or with a wax.

A wide range of pharmaceutical forms can be used. Thus, when a solid carrier is used, the preparation may be made into tablets, or may be introduced into hard gelatin capsules in the form of a powder or granules

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a lozenge or Plätzchenform.angepaßt v / ground ₀ The amount of solid carrier may vary widely in a preferably -liegt it between 25 and 300 mg. When a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatin capsules, suspension or liquid solution or in a sterile injectable form for parenteral use, in an ampoule. , .

The pharmaceutical preparations according to the invention in the form of suspensions or liquid solutions comprise - not simple suspensions or liquid solutions of active constituents in common solvents which are not suitable for internal administration in order to produce the desired pharmaceutical activity.

The invention further provides a unit dosage in the form of tablets, capsules, troches, cookies, liquid suspensions or sterile injectable liquids for internal administration to provide antipsoriatic activity containing a pharmaceutical carrier and polar fraction in an amount sufficient to provide said potency to obtain",

Administration may be oral or parenteral, preferably oral. The active ingredient is preferably administered in a daily dosage amount of about 50 to 900 mg, with the range of 100 to 300 mg being especially preferred. It is advantageous to administer equal doses one to four times a day, and if administered as described above, antipsoriatic activity is obtained ₉

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SI ''

Since psoriasis is a chronic, creeping phenomenon with a genetically causative development of the disease, the capsule or tablet is determined. preferred to obtain stable blood concentrations, whereby a continuous influence of the drug is ensured. Undoubtedly, intravenous injection or continuous dropwise delivery into serum can be used to prevent the crisis when serious psoriasis outbreaks caused by other drugs have been treated, such as in the steroid case or by the disease itself.

! It should be noted that the drop shape or emulsion is used in children for obvious reasons, while suppositories may be used in the palate of adults presenting with problems in the upper digestive tract. "

The pharmaceutical compositions are prepared by conventional processing techniques, such as by mixing, granulating and compressing, if necessary, or by dissolving and dissolving the appropriate ingredients for the intended compositions,

It has been found that the natural polar fraction prepared according to the invention consists of roots and leaves of Dryopteris crassir hizom a, Pqlypqdium vulgare, Linn, Ροΐ, γροdium 1euc ο tomos, Phelebodium decumanu m ^ Cyathea taiwaniana and roots of Polypqdium aureuin Linn and Polypo dium triseriale, medicinal efficacy in the treatment of patients of both sexes and

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have arbitrary age who suffer from psoriasis "and Parapsoriasis" This also includes the descendants included: esters, amides etc..Über 300 patients with psoriasis were treated orally daily 5 mg per kg body weight _e treated with a low dose, eg * As a result of the treatment over a period of 3 months, 80 % of the patients showed that the disease had disappeared. In a group of 50 patients, double-blind tests were carried out and it was found that one drug was more equal in comparison with the placebo Size and shape is effective »These fractions and their derivatives have been used in all forms of psoriasis and at various stages of the clinical picture, ...

From a toxicological point of view, no effect was found. During research over a period of 12 years, the blood and bone marrow, liver and liver and urine specimens did not show any signs of change. According to the Food Guidelines and Drug Administration of the United States, and in accordance with the Guidelines for Reproduction Studies for Safety Evaluation of Drugs for Human Use, the compounds do not alter fertility in rats, mice, or dogs, and in four generations of rats and rats Mice and two generations of dogs were not observed to have any birth defects.

A carcinogenic efficacy could not be determined. corresponding studies .. on mice. 24 doses of 1 mg / kg body weight were administered orally for 24 weeks daily. The animals were examined from the 7th week with and without the introduction of glass beads into the bladder.

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The methods used in these studies are described by Juill, J.We in Brit. J. Cancer _f 5, 328 (1951), and the statistical evaluation used is described by Arcos and coworkers in "Chemical Induction of Cancer," S "416" Academic Press Inc., Hew York (1963). ,

The mechanism of action of the polar fraction is via:

a) Increasing permeability through the cell wall for sugars such as glucose, sucrose, fructose and amino-.

¹ acids such as valine, lisin and others to a lesser extent.

b) increase the activity of the carriers of the cell wall.

c) increase the water exchange at the cell wall.

d) Probably in connection with the above, an increase in the activity of the hepatocytes was observed, indicating the large metabolic effects.

e) increase in the activity of growth and maturity of collagen.

The polar fraction according to the invention does not possess the effectiveness of steroids. It has a pulse-releasing effect similar to the digitalin preparations, probably due to the action on the cell walls of the myocardium.

embodiment

The invention will be explained in more detail by way of examples

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example 1

12 kg dry leaves, granulated by a Hr. 10 sieves (2.5 mm) were extracted with 48 1 95% ethanol at 70 C for one and a half hours.

Evaporation, the residue is taken up with a n-hexane / water mixture (15'.1O 1) and left over laughing in a separator. "The hexane phase is discarded and the aqueous phase is filtered."

The neutralized solution is clarified and evaporated for 48 hours in a moderate vacuum to near dryness (yield: about 150 g). The dried solid is redissolved in methanol and while crystallized at 4 ⁰ C of the IJacht.

36 kg of a dry plant granulated in a disc mill to pass through a Hr ₆ 10 sieve (2.5 mm) was extracted continuously with η-hexane at room temperature. The hexane solution is concentrated and washed with water while stirring a separator introduced »The hexane phase is discarded and evaporated the aqueous phase

The residue is taken up in hot ethanol and allowed to stand during the yacht in a sufficient quantity to form a saturated solution. The solution is filtered and added to the aqueous phase and then passed over an exchanger column. The solution is then neutralized and clarified and evaporated to near dryness

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The solid mass is redissolved in 70% ethanol and crystallized at room temperature during the night. The crystals are discarded and the liquid phase is evaporated (yield: 180 g) and concentrated in vacuo, triturated.

Example 3

12 kg of dry roots granulated in a disc mill to pass through a Sr x 10 sieve (2.5 mm) were extracted continuously with chloroform at room temperature. The solution was concentrated and redissolved in an n-hexane / water mixture , The hexane phase is discarded and the aqueous phase is evaporated.

The residue of the extracted roots is taken up in hot methanol and allowed to stand for 16 hours. The solution is filtered and passed through an exchange column.

The extract is neutralized and clarified and then evaporated and placed overnight in 95% ethanol in a crystallizer. The crystals are discarded and the liquid phase is evaporated and then dried in vacuo (yield: 84 g).

Example 4

Reflux 12 kg of a dried and granulated (Ur.10 sieve, 2.5 mm) plant with 90% methanol at 70 ⁰ C for one and a half hours extracted. The extract is filtered, evaporated and placed in a n-hexane / water mixture (3: 2). The solution is left to stand over IT, the hexane phase is discarded and the aqueous phase is filtered and evaporated. ·

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The residue was taken up in 90% hot ethanol and passed over a "buzzer column".

  "e" "'

The extract is neutralized and evaporated to one tenth of the initial volume and then crystallized in cold, the solution is filtered, the crystals discarded and the aqueous phase dried in vacuo (yield: 24-0-250 g).

The following examples of pharmaceutical preparations should not be construed as limiting but as an illustration of the invention.

at spjlel 1a Ivlengjs component 40 mg 60 rag Polar fraction lactose

The ingredients are mixed, sieved and incorporated into hard gelatin capsules. A capsule prepared according to the procedure described above is administered three times a day

Example 2a

BesjtandtenJ. ·

Polar Fraction Starch IaK Kaolin

Poliviny! Pyrrolidone ·. ,

Amount. mg 60th mg 60 mg .5 mg VJL mg VJI

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The fraction and starch are mixed and granulated with a "solution of 10% gelatin including polyvinylpyrrolidone." The granules are sieved, dried and then mixed with kaolin and talc and formed into tablets.

Claims (2)

-15- 25.ΙΟ.1.979 55 885/18 invention claim · Method of controlling a natural polar fraction with antipsoriatic activity by extraction of roots and leaves of Dryo pteris crassirhizoma, Polypodium vu lgare _{t |} Linn, Polypodium le ucotomos, PhIebq. dium Decumanum J «. Smith , Polypodium d ecurn anumy Cyathea. taiwaniana , and roots of Polypodium aureum Linn and Pol ypod ium tr iseriale , characterized in that , , the roots are cut into 2-3 cm strips and the root strips and leaves are subjected to continuous drying at a temperature not exceeding 70 G, and the dried material is ground to less than 8 % residual moisture to obtain particles of a diameter up to 2 mm and a density between 0.1 and 0.8, an extraction of this material is carried out with a solvent having a dielectric constant between 1.890 and 9.08, the solvent is evaporated and the residue is purified, the ligand esterified The residue is taken up in a n-hexane / Y / water mixture (10: 4), kept in a separator over IT overnight and the aqueous phase is separated off, the aqueous solution is passed through an exchanger resin and Ca (OHP) is added to the mixture Neutralization of the solution is added, proportions of activated carbon are added to clarify the solution, evaporation to 1/10 of the starting solution follows and precipitated with absolute alcohol; the precipitate filtered under suction and the crystallized water is re-evaporated to a second dust-like. Mass to he ™, which is dried in vacuo until a very white solid material remains "- 25.10.1979 55 885/18 2 "polar fraction with antipsoriatic action, characterized in that it is prepared according to the method according to item 1 ·