WO2001003711A1

WO2001003711A1 - Method for isolating lipophilic materials out of vegetable and/or or animal material

Info

Publication number: WO2001003711A1
Application number: PCT/CH2000/000371
Authority: WO
Inventors: Ingrid Weis
Original assignee: Phyotopharmaka Gmbh
Priority date: 1999-07-08
Filing date: 2000-07-05
Publication date: 2001-01-18
Also published as: AU5385900A

Abstract

The inventive method serves, among other things, to produce and intensify medicaments having a vegetable and purely biological base. This method permits the use of known medicinal plants with the entire range of active substances thereof without their active substances being altered or destroyed by heating, alcoholic extraction, drying or fermentation. In this case, the method is primarily characterized in that a plant material formed from a medicinal plant is disintegrated by a shock-like cooling in liquid nitrogen and is subsequently mixed with a micelle former in order to form a suspension, whereby the released plant constituents are captured by micelles and liposome formed in situ. The micelle/liposome mixture produced in such a manner is absorbed on a supporting material at a temperature of at least 0 °C, preferably ranging from 20 °C to 40 °C, and is converted into an emulsion by agitating. This emulsion is immersed once more into liquid nitrogen, is cooled in the same in a shock-like manner, and is stirred to form a fine powder which can be freeze-dried and poured into medicament capsules.

Description

Process for the isolation of lipophilic active substances from plant and / or animal material

Technical field

The invention relates to a method for isolating lipophilic active substances from plant and / or animal material, namely a method according to the preamble of claim 1.

The method according to the invention is used, for example, to produce and intensify herbal and biological remedies. Known medicinal plants can be treated and digested with the method according to the invention in such a way that the active substances contained therein are neither destroyed nor changed.

Depending on the selected starting material, the method according to the invention can also be used to produce cosmetic preparations or food preparations. Such preparations have the advantage over known preparations of the same type that they are produced in a manner that is gentle, simple and without destroying important pharmaceutical ingredients.

State of the art

European Offenlegungsschrift 0 732 103 describes a process for isolating active substances from fresh medicinal plants in liquid nitrogen using an in situ method. described micelle / liposome mixture. According to this known method, the plants, for example Petroselinum crispum (parsley), are not broken down either by heating or by alcoholic extraction. This method also avoids the disadvantageous drying processes necessary for the production of known medicinal products.

According to this known method, freshly harvested and possibly additionally reduced leaves or flowers of medicinal plants are immersed in liquid nitrogen. Due to the shock-like cooling, the plant cells burst open and release their contents. These are then captured by micelles and liposomes formed in situ, which in turn form from a micelle-forming agent which is additionally added to the digested plant material, for example from the molecules of an added cooking oil.

The digested plant material enriched with micelles and liposomes is then absorbed on a hydrophobic and hydrophilic carrier, such as amorphous silicon dioxide. The resulting free-flowing powder can then be filled into capsules for medicinal or therapeutic agents in a known manner.

The shock-like cooling of the plant material in liquid nitrogen destroys practically all bacteria and fungi, but not the possibly additionally present spores of such microorganisms. With the method known from EP-A-0 732 103 it is therefore not always possible to produce medicinal or therapeutic preparations which have the microbiological purity necessary for therapeutic purposes. Nor can this process be readily applied to other starting materials, which severely limits the scope of the process. Outline of the invention

The present invention is based on the object of improving the method known from EP-A-0 732 103 while maintaining the aforementioned advantages in such a way that it can be used in a much larger area of application. In the production and intensification of herbal remedies, it should also be achieved that the spores of microorganisms that may be present in the starting material are eliminated as completely as possible.

This object is achieved by a method with the characterizing features of claim 1.

The process according to the invention is thus essentially characterized in that a material formed at least in part from animal or vegetable biomass is homogenized, the lipophilic active substances contained in this material are captured by micelles formed in situ and the micelles and liposomes thus produced are absorbed on a carrier material , and that after absorption the material is dispersed in liquid nitrogen and the micelles / liposome mixture contained therein and absorbed on the carrier material mentioned is converted into a solid form by stirring in liquid nitrogen and then freeze-dried.

Advantageous embodiments of the invention emerge from the dependent claims.

For the process according to the invention, all types of plant and animal materials containing lipophilic active substances can be used individually or as a mixture as a raw material. The starting material forming the biomass can therefore be a medicinal plant or consist of a mixture of several medicinal plants. However, the raw material can also have animal origin and can be, for example, milk, meat and / or tissue extract or a glandular fluid, such as a snake secretion.

A plant with microbicidal active ingredients can also be added to the biomass, which in turn inhibit both the growth of microorganisms and the germination of spores of such microbes. Colloidal silver is also suitable as an additional microbicide. Instead of the plant, this can be admixed with microbicidal active ingredients or in addition to one of the biomass serving as raw material in micromolar concentration.

If a biomass formed from plant and / or animal cells or tissue parts is to be used as the starting material, this biomass is immersed in liquid nitrogen for pretreatment and cooled to approximately -190.degree. This shock-like cooling causes the cells to burst open and release their contents, which are then stored in the micelles and liposomes formed in situ.

Micelle formers are additionally added to the optionally pretreated biomass if it contains no or only minor amounts of substances capable of forming micelles and liposomes. The same also applies to the absorbent material, which essentially serves to bring the micelle / liposome mixture into a form which allows the mixture to be converted into a solid, stable form with stirring which can be lyophilized and can be filled into capsules in dry form.

Due to the purely biological and gentle process steps, the new process ensures that all active ingredients of the starting material are retained in their natural biological activity and conformation. This applies to the proteins released, which act as enzymes, as well as to the vitamins and medically active substances released.

The isolation of active substances from medicinal plants according to the invention can be divided into two process stages:

In the first stage of the process, the plant material used as biomass is pre-treated as follows:

- A plant material which is at least partially formed from a medicinal plant and optionally additionally cut into small pieces is digested in liquid nitrogen, for example at a temperature of -190 ° C., and mixed with a micelle-forming agent to form a suspension.

- This suspension is then thawed with controlled stirring and preferably heated to 20 ° C to 40 ° C. This means that by unlocking the

Plant ingredients released by the plant are captured by micelles and liposomes formed in situ.

- The micelles thus produced / is then absorbed at least 0 ° C, preferably at 20 ° C to 40 ^C C on a hydrophobic and hydrophilic carrier material liposome mixture, and it is made from the absorbed mixture by stirring an emulsion.

In the second part of the method, which essentially corresponds to the characterizing part of claim 1 finally the prepared emulsion is again immersed in liquid nitrogen, converted into a fine powder by stirring and freeze-dried so that the powdered product thus produced can be filled into medicinal or medicinal capsules.

The renewed shock-like cooling of the biomass not only makes it possible to produce a stable, free-flowing product, but also any microbial microorganisms that may still be present are destroyed, which has an additional advantage.

Since the method according to the invention is a purely biological method and permits gentle treatment of the plant material, it can be used without restriction for all known medicinal plants.

The plant material to be treated can of course also be a mixture of several medicinal plants. A plant with microbicidal active ingredients can also be added to the medicinal plants or the plant material formed therefrom, as has already been mentioned above. Allspice and chilli may be mentioned here as plants with microbicidal properties which can be used according to the invention. These plants can be admixed to the medicinal plant material in optionally comminuted form even before it is digested in liquid nitrogen. However, the plant containing the microbicidal active ingredients and the medicinal plant material to be treated can also be digested separately. In this case, however, the suspension of the separately digested and microbicidally active plant is added to the medicinal plants before the addition of the carrier material, and the mixture thus prepared is then additionally heated to 20 ° C. to 40 ° C., for example to 36 ° C. , A colloidal silane used instead of the microbicidal plant The preparation is also added to the medicinal plants before the carrier material is added, and the mixture thus formed is subsequently heated.

Edible oils, lecithins or polyethylene glycols are suitable as micelle formers for the isolation of herbal active ingredients. The micelle generator can consist, for example, of a mixture of substances dissolved in sterilized water, for example of a dispersion containing sorbic acid, citric acid, vitamin C and lecithin (from soy).

The micelle generator is mixed with the frozen, cut leaves with intensive stirring and subsequent thawing. This process can be repeated 1 - 4 times in order to achieve the most quantitative possible absorption of the active substances in the plant cells into the micelles. This means that in an intermediate step, the suspension consisting of the digested plant material and the micelle-forming agent is mixed with liquid nitrogen at least once more and thereby cooled in a shock-like manner and then thawed again.

The method according to the invention is preferably carried out in at least two different, commercially available containers. Thus, in the isolation of herbal active substances, the plant material formed from the medicinal plant is shock-cooled and finely ground in a first container which has a grinding and / or dispersing agitator and contains liquid nitrogen. The digested and deep-frozen material is then transferred to a second container in which the ground plant material is mixed with the micelle-forming agent to form a micelle / liposome mixture and is absorbed on the carrier material mentioned. The emulsion formed after absorption on the carrier material is then returned to the first container containing the liquid nitrogen. leads and in this to the destruction of any microbial germs that may still be present, is cooled in a shock-like manner and converted into the powder intended for freeze-drying by intensive stirring. The latter is then dried in a known manner in a lyophilizer.

Description of the preferred exemplary embodiments

The method according to the invention is described in more detail below using two examples.

Example 1 - Isolation of Herbal Active Ingredients from Hypericum

The medicinal plant Hypericum to be broken down is introduced into a first Ruhr container containing liquid nitrogen and finely ground at, for example, 18 ^ 000 revolutions per minute (U / mm).

The plant material, which has been cooled and ground to about -190 ° C., is then transferred to a second Ruhr container, in which a solution containing the micelle-forming agent is already specified. The amount of this solution and its composition vary depending on the amount and type of medicinal plant to be treated. A typical solution of a micelle generator can be prepared as follows: Double distilled in 3 liters. Sterilized water, 1.0 g of sorbic acid, 10.0 g of citric acid, 5.0 g of vitamin C and 50 g of lecithm are dispersed and this dispersion is stirred in the second container at room temperature and at 18000 U / mm for about 15 mm.

After the plant material has been transferred to the second container, the plant material and micelle formers are thawed to 0 ° C. at reduced Ruhr speed and mixed to form a suspension. This suspension is then stirred at 18,000 U / mm for about 15 minutes and then it becomes this A pimento mixture was added to the mixture, which had also previously been digested and ground in liquid nitrogen. This mixture of medicinal plant and allspice is then slowly heated to 20 ° C. to 40 ° C., for example to 36 ° C., and stirred at 8,000 rpm for about 30 minutes. Then, at 20 ° C to 40 ° C, the micelle / liposome mixture thus formed is added, for example, from the same parts of Aerosil 200 and Aerosil 974 (Degussa AG, GB AC, PO Box 1105 33, D-6000 Frankfurt 11) composed of absorption material. Microfine cellulose can also be added to the mixture if necessary with the absorption material to be supplied in batches. At 18 * 000 rpm and a temperature of, for example, 36 ° C, an emulsion is finally formed from this mixture, which is reintroduced into the cavity of the first container containing the liquid nitrogen and cooled and shock-shocked to destroy any microbial germs that may still be present is then transferred into the dry powder intended for freeze drying by intensive stirring.

After freeze-drying, the powder produced according to the invention has a residual moisture content of about 4-5% and can be filled into hard gelatin capsules in a known manner.

Example 2 - Preparation of an antirid mask from milk

9 liters of whole milk and 14.5 g of lactobacillus are introduced into a first stirred tank and homogenized at room temperature at 1800 stirrer revolutions per minute (rpm). The stirring speed is then increased to 4,000 rpm and the milk is heated to 34-36 ° C. After one hour, the milk treated in this way is left to stand for 48 hours. This process is repeated a second time is dropped at room temperature until the pH of the milk to about 5 at least, preferably 6 minutes to '000 U / min is carried out with a stirring speed of 5 ^Λ 000 U /.

After a cooling period of about 24 hours at 4 ° C, the milk is homogenized, then added dropwise into containers in a liquid nitrogen having second loading and in this a with a stirring speed of approximately 4 'to a curd-like suspension 000 U / ^min' Stirring speed of 7 * 000 U / min stirred intensively. The white precipitate formed is finally lypohilized and transferred to a ready-to-use antiride mask.

With this method, neither additional micelle formers nor an additional absorption material are necessary. Both substance groups are present in sufficient amounts in the starting material in the form of biotin and protein substances so that the micelles and liposomes form in situ during the incubation period taking place in the first container without additives and are absorbed by a suitable absorbent.

Claims

1. A process for isolating lipophilic active substances from biological material, wherein a starting material formed at least in part from animal or vegetable biomass is homogenized, the lipophilic active substances contained therein are captured by micelles formed in situ and the micelles and liposomes thus produced are absorbed on a carrier material, characterized in that after absorption the material is dispersed in liquid nitrogen and the micelle-liposome mixture absorbed on the carrier material is converted into a solid form by stirring and then freeze-dried.

2. The method according to claim 1, characterized in that the animal and / or vegetable biomass is additionally mixed with a plant with microbicidal properties.

3. The method according to claim 1 or 2, characterized in that the animal and / or vegetable biomass is additionally mixed with colloidal silver.

4. The method according to any one of claims 1 to 3, wherein the biomass consists at least partially of plant and / or animal cells or tissue parts, characterized in that the biomass serving as the starting material is broken down by shock-like cooling in liquid nitrogen, with a micelle generator to one The suspension is mixed and then thawed with controlled stirring and preferably heated to 20 ° C to 40 ° C, and that the micelle / liposome mixture thus formed is absorbed on the carrier material at at least 0 ° C, preferably at 20 ° C to 40 ° C.

5. The method according to claim 4, characterized in that the suspension formed from the digested biomass and the micelle-forming agent is mixed with liquid nitrogen at least once more and thereby cooled in a shock-like manner and then thawed again.

6. The method according to any one of claims 4 or 5, characterized in that a mixture consisting of sorbic acid, citric acid, vitamin C and lecithin is used as micelle formers, which is dispersed in distilled, sterilized water.

7. The method according to any one of claims 4 to 6, characterized in that the biomass is broken up in a first container having a grinding and / or dispersing agitator and containing liquid nitrogen and finely ground and then transferred to a second container in which the ground Well mixed with the micelle-forming agent to form the suspension forming the micelle / liposome mixture and this is absorbed on the carrier material mentioned, and that the resulting emulsion is returned to the first container containing liquid nitrogen, cooled in a shock-like manner and then mixed to the powder intended for freeze-drying becomes.

8. The method according to any one of claims 4 to 7, characterized in that at least one medicinal plant is used as biomass.

9. The method according to any one of claims 1 to 3, characterized in that animal milk is used as biomass.