FR2894829A1 - Extraction of active principles from plants to increase the rate and to ensure the stabilization of acylphloroglucinol, comprises subjecting the extracts in a suitable pH zone followed by drying in vacuum at low temperature on zeolite - Google Patents

Abstract

Extraction of active principles from plants to increase the rate and to ensure the stabilization of acylphloroglucinol in these extracts, comprises subjecting the extracts in a suitable pH zone, followed by drying by vacuum dehydration at low temperature on zeolite. Independent claims are included for: (1) an extract obtained by the process containing 2-8% of hyperforin in combination with a mineral salt; and (2) compositions containing the extract obtained by the process used for the therapeutic and/or para-pharmaceutical use, comprising the extract (300 mg) with approximately 2% of hyperforin, magnesium element (10 mg) in the form of salts and magnesium (120 mg) as magnesium citrate. ACTIVITY : CNS-Gen.; Gastrointestinal-Gen.; No biological data given. MECHANISM OF ACTION : None given.

Description

A new process for the extraction of active ingredients and the use of

  The invention relates to the field of chemistry and more particularly to the field of pharmacotechnics.

  Elie more particularly relates to a new process for extracting active ingredients from plants rich in flavonoids and diacylphloroglucinols, the oxidability of which presents a major drawback for their storage storage and for their pharmaceutical use.

  The invention more specifically relates to a process for extracting and concentrating active principles in a stable form and enriched with one or more active ingredients, starting from flower buds of St. John's wort (Hypericum perforatum). St. John's wort is indeed a medicinal plant whose tranquillizing and anti-stress properties are becoming better known because of numerous recent scientific works, in particular publications made in various European countries as it is frequent in phytotherapy.

  According to the literature (see in particular USP 6,280,736), the general anti-depressive effect of St. John's Wort can not be reliably attributed to one or more specific components, but it is clear that among these, hyperforins provide a considerable contribution to the establishment of this efficiency (see EP-A-0599 307) probably greater than that of hypericines of formula (I): ## STR2 ##

  These are highly oxidizable and easily labile molecules.

  The crude medicinal drug is formed from the aerial parts of Hypericum perforatum which contain, inter alia, hypericin-type compounds and hyperforin-like compounds (see J. Holzl et al Pharmajentische Zeitung 139 (46) 3959-3977 (1994)). A St. John's Wort extract preparation having a higher hypericin content is described in German Patent DE-1569849 as well as in S. Niesel and H. Schilcher Arch. Pharm. 323 (1990) 755. However, the problem of the conservation of these active principles has been posed by R. Berghofer and J. Holzl in Deutsche Apotheker Zeitung 126 (47) (1987) 2569-2573 who found that hyperforin in St John's wort extracts, was completely degraded after a week, although it should be more stable in extracts obtained from fresh plants. These authors hypothesize that fresh plants contain a stabilizing agent for hyperforin but whose efficacy would be short-lived. This is why the authors conclude that both in the drug and in the conventional extracts of St. John's wort, the Hyperforin content decreases dramatically until the disappearance of this substance within a few months conventional storage (Marsenbacher P. These of Doctorate (1991), Tubingen). These authors advocated the storage of the plant under argon by adding antioxidants (octyldodecanol, BHT, BHA) to improve the stability of the extracts. (I) Already the extractions of St. John's wort by conventional solvents such as water and alcohol, lead to pharmaceutical compositions which contain less than 1% of hyperforin. During storage, this value obviously decreases and can even return to zero depending on storage conditions due to oxidation phenomena that break down hyperforin.

  According to US Pat. No. 6,280,736, this problem could be solved by addition to St. John's wort extracts, antioxidant agents and / or stabilizing agents which fix oxygen or reducing agents. The applicant of this patent also recommends carrying out the extraction under inert atmosphere and / or from light or by extracting with a solvent having a reduced oxygen content.

  Another method of preserving hyperforin is that described by Orth HC, Rentel C and Schmidt PC in J. Pharm. Pharmacol (1999) 51 193-200 which recommend the removal of peroxides at each stage of the extraction. These authors conclude by stating that the conservation of A. 30 C under normal atmospheres and a - C, 4 C and 20 C under nitrogen and again in nitrogen at -196 C did not give different results with respect to the stability of hyperforine and that the preservation method at -70 ° C. under nitrogen provided better results for long-term storage.

  The same problem arises for topical preparations of St John's wort extract, especially in the form of gels as a cicatrizing or anti-viral agent (see US publication 2004/0137 088). The problem of stability of hyperforins has also been envisaged by making synthetic hyperforins described in US Patent (Indena) 6,656,510. Hyperforins correspond to formula (II), hyperforin: R = CH3 adhyperforin: R = CH2-CH3

  and wherein R ~ is an acyl radical or hydrogen.

  They are described as' more stable and more active in anti-depressive action tests. This method of hemisynthesis requires the extraction of hyperforin from St. John's wort by a supercritical gas to obtain a hyperforin-rich oil. However, the esterification yields are particularly low. On the other hand, supercritical fluid extraction is a delicate operation requiring equipment that is resistant to very high pressures and high temperatures.

  Hydrogenation products of the allylic chain of hyperforins have also been described. The resultant hexahydro and octahydrogen cetone compounds are enolated to give metal enolates or enol esters (see PCT Patent No. 03/091191 and 99/64388). Therefore, despite an ever increasing therapeutic interest, St. John's wort extracts have not been used up to now to a corresponding extent due to the easy decomposition of the active ingredients and the resulting loss of progressive activity.

  The process according to the invention aims to improve the processes already described and to lead to more stable and therefore more active St John's Wort extracts. The method according to the invention also aims to obtain extracts richer in hyperforins and depleted in hypericin derivatives.

  More generally, the invention relates to novel processes for the extraction of plants, especially those containing iridoids, quinoline derivatives and especially acylphloroglucinols, flavonoids and naphthodianthrones, as in the case of Hypericum perforatum, which make it possible to obtain stable and pharmaceutically acceptable extracts enriched in hyperforin and, if possible, reduced in hypericin derivatives.

  These extraction processes are mainly characterized by a pH search extraction media where the assets are the most stable and can be obtained after drying by dehydration under vacuum at low temperature on zeolites, also known as zeodration, extracts under the form of a crystalline powder. These methods make it possible to increase the levels of hyperforin in the plant extracts obtained and to maintain or even reduce the levels of pseudohypericin and hypericin. These extracts are preserved either in the form of crystalline powders when the hyperforine is in its salified form with a metal salt, or in amorphous form when it is in base form in the presence or absence of an organic acid such as, for example, citric acid. or still fixed on sugars such as maltodextrin or a similar carrier to have a pharmacotechnically manipulable powder.

  The choice of the new extraction methods is chosen from those described in relation to the desired and necessary levels of hyperforin and hypericin as well as their quantities necessary for the manufacture of pharmaceutical formulations.

  The invention also relates to pharmaceutical or para-pharmaceutical preparations containing these different extracts obtained by the methods of the invention.

  For some products, the pH may be between 1 and 2 or 6.4 and 12 as for St. John's wort depending on the amount of asset to be extracted (between 3 and 5 for the most unfavorable). For others containing iridoids (globular, etc.), the pH should be between 6.5 and 8.

  In all cases, these types of extracts being sensitive to elevations in temperature, oxidation or light, will be dehydrated and dried by dehydration under vacuum at low temperature on zeolites, also known as zeodration.

  It is known that the plant is wet and according to its source contains according to different authors 2 to 4% of hyperforin. This rate continues to decrease as and when. measurement of the different manipulations like the time of maceration before extraction, the concentration of the extracts, the storage time of the extracts, etc ...

  In the arsenal, various means known and used in the face of these instability problems are used by conventional methods such as:

  The nature of the extraction solvents which can be used in pharmacy, the use of antioxidants in acid form, salts or esters in the absence of light, the use of reducing agents, the use of chelating agents The use of inert gas during different manipulations the use of low temperatures during the various manipulations.

  Due to the chemical structure of the phloroglucinic derivatives and more particularly the hydroxyalkyl and cetonic functions of hyperforin, it is normal to think of blocking them to bring about a better stability of the whole molecule.

  This is very well described by Chatterjee et al in US Pat. No. 6,444,662 of September 3, 2002, which describes three methods of preparing salts in suitable solvents according to the metallation types used on the adhyforine and hyperforin mixture, by alcoholates in an anhydrous medium or in the presence of corresponding hydroxides.

  The object of the invention is to provide methods which implement the stability of phloroglucinic derivatives during the extraction process without altering the other constituents of the extract and obtain a pharmaceutically acceptable end product enriched in hyperforin containing 2 at least 5% and containing the other constituents such as flavonoids, naphthodianthrones at the usual levels as for hypericin (less than 0.5%).

  Different alkalizing or acidifying agents may be used (sodium hydroxide, magnesium hydroxide and other alkaline agents, etc.) and acids (any mineral or organic acid) in the process according to the invention.

  A qualitative study was carried out from the same batch of plant to evaluate the influence of different extraction media such as a basic medium (soda) or an acidic medium (phosphoric acids and / or citric). The operating modes are identical in all cases and have given the following results.

  Table I pH of EtOH Water NaOH Q: HpF PseudoHpR HpR pH of solvent IN extract 7.74 60 40 0 550 290 250 4.83 12.21 60 40 1 600 280 196 6.04 12.48 60 40 2 750 240 256 6.80 12.55 60 40 3 850 210 320 7.53 12.67 60 40 4 1000 20 200 8.81 12.71 60 40 5 1050 0 160 8.95 pH of EtOH Water H3PO4 Q: HpF PseudoHpR HpR pH of solvent extract 3.11 60 40 0.1% 500 175 80 3.33 pH of EtOH Water Ac. Q: HpF PseudoHpR HpR Citriq solvent pH. Extract 2.66 60 40 4% 550 200 130 4.46 HpF = Hyperforin PseudoHp = PseudoHypericin HpR = Hyperine

  It can be seen that for the same solvent Ethanol / Water 60/40, the extractions differ according to the pH used.

  At acidic pH, the amounts of hyperforin extracted are similar to the amounts extracted by the same solvent in a neutral medium, but pseudo-hypericin and hypericin have greatly decreased. The pH of the extracts is slightly more acidic at the end of the extraction compared with the pH of the neutral extraction, the extractions of which tend to acidify: initial pH 7.74 pH of the extracts 4.83 pH of the solvent H3PO4 3.11 pH of the extracts extracts 3.33 pH sol Ac. Citric 2.66 pH of the extracts 4.46 For extractions in alkaline medium, the quantity of extracts is enriched with hyperforin as a function of the quantity of alkaline agent used, while at the same time the amounts of pseudo-hypericin and of hypericin decrease. This enrichment in hyperforin can reach double whereas the quantities of hypericin derivatives can decrease by half. To better evaluate the operating procedures, the alkaline extractions were compared in the presence of an extraction control without alkaline action and its influence on the wet and / or dried plant was compared as well as the stability of the extracts obtained.

  The procedure described described gives the following results: A TO: 1) two extractions are carried out on 23 g of moist plant (alkaline extraction and neutral extraction).

  2) 150 g of wet plant are dried and then 2 extractions are carried out on the dry product corresponding to 23 g of wet plant.

  3) wet atmosphere is controlled 60 g wet plant. 2535 A T1: 1) 2 extractions were carried out on 23 g of preserved wet plant (alkaline and neutral). 2) 2 extractions are carried out on 23 g of preserved dry plant (alkaline and neutral).

  A total of 4 extractions to TO 10 4 extractions to T 1 month

  This approach has made it possible to evaluate and select a process which may be the alkaline medium when it is desired to increase the level of hyperforin in the extracts and stable, or the acidic medium when it is desired to obtain a standard extract. and stabilizes by decreasing the levels of hypericin derivatives. It is known that in acidic and hydro-alcoholic medium, these derivatives precipitate because of their low solubility at these pH and because of the transformation of pseudo-hypericin to isopseudo hypericin at this pH. The impact of the pH of the extraction medium and especially its effect on the stability of certain extract compounds as well as the transformation of other compounds made it possible to study these extraction possibilities more thoroughly in order to carry out processes. industrial. Description of the methods:

  A first extraction study is carried out in the laboratory from the same batch of plants in order to compare the influence of alkalization on the extraction medium compared to conventional extractions performed with hydro-alcoholic solvents.

  Brief description of the process: The process consists in suspending at room temperature a portion of the dried plant in 10 volumes of a 60% aqueous alcoholic solution in ethyl alcohol for 24 hours.

  After filtration, the solutions are treated and concentrated under vacuum with the exclusion of oxygen and light. The ponding yields in these conditions are close to 20 to 25%.

  The dry extracts obtained are in the form of a fine and crystalline powder in the case of extraction in an alkaline medium and of a very hygroscopic gum in the case of extraction in a neutral medium.

  Comparative analyzes of these two extracts yielded HPLC at the following wavelengths (300 and 590 nm) as shown in FIG.

  1) acylphloroglucinols Table II C10 RT (nm) compound area 9.77 300 458908 Hyperforine I 10.35 300 2964122 Hyperforin II 11.46 300 140894 Hypericine 13.14 300 174313 XXX 11.46 590 290398 Hypericin C11 RT X (nm) compound 9.64 300 272559 Hyperforin I 10.23 300 1923289 Hyperforin II 11.32 300 83330 Hypericine 13.00 300 411835 XXX 10.16 590 149666 Pseudohypericin 11.32 590 173782 Hypericin The results gathered from these two extracts show that the extracts obtained by the alkaline route are twice as concentrated. In hyperforin, however, those produced in acidic medium, whereas the derivatives of hypericin are present in comparable amounts. The pseudo-hypericin encountered in the neutral pH C11 extract was converted to hypericin under alkalinity. The study of the naphthodianthrone profiles is carried out from these two extracts using the analytical method of acid extraction in hexane. This allows to characterize these derivatives.

  Flavonoids can also be characterized and identified for a more in-depth approach to the chromatographic profile of the extracts. - 2) naphthodianthrones determined by HPLC Table III C10 C11 RT Compose RT 8.65 isopseudophypericin 8.70 9.25 flavonoid 9.32 9.86 protopseudohypericin 9.92 10.20 pseudohypericin 10.23 10.82 protohypericin 10.84 11.33 hypericin 11.37 3) flavonoids

  as shown in the chromatograms according to FIG.

  The characterization of a salified form of hyperforin in the presence of other components of the extract was carried out by a return in acidic medium to recover the lipophilic form of the molecule with its low solubilities in an aqueous medium. Table V shows the influence of the alkaline medium on the stability of hyperforin (salification) as well as its inaction on naphthodianthrone derivatives such as hypericin and its derivatives. Table IV hyperforin hypericin pH TR Area TR Area 7.5 9.79 1,812,363 10.9 134 583 6.5 10 1 433 748 11.4 134 503 5.5 10.2 1 371 590 11.5 132 061 4.5 10.5 1 212 085 11.7 136 884 3.5 11.2 1 040 653 11.8 135 194 2.5 13.2 273 355 11.7 137 030 7.5 10 1 089 463 11.3 138 359 These results are also shown in FIG. 4. Example of Degradation of Non-Salified Hyperforin. 10 mg / l solution in an apolar solvent for 3 days. Solution of hyperforin in hexane 10 mg / l Analysis at 0.1 day and 3 days day Hyperforin area 0 231 792 1 3 020 151 3 55 218 Degradation of hyperforin in three days is manifest, giving rise to multiplicity of by-products. All these results show that in soluble alkaline medium and salified powder, extracts containing a higher percentage of hyperforin are much more stable.

  In contrast to the processes described in US Pat. No. 6,444,662, which use chromatographic methods to enrich the hyperforin and adhyperforin extracts and then salify them with different chemical methods in order to obtain stabilized products.

  but practically free of other components (flavonoids, naphthodianthrones, etc.) of the plant, the present method is based on a more pharmaceutical approach since it allows from dried plants to obtain stable extracts whose main criteria in terms of flavonoids, naphthodianthrones and acylglucinols (ie 1 to 8%) are respected and correspond classically to those defined by the methods recognized by the pharmacopees and adapted here to the Hypericum perforatum. Principal steps of the process according to the invention The process according to the invention is characterized mainly by: 1-the use of a hydro-alcoholic extraction solvent of known proportions, or entirely aqueous. 2- the practice of an extraction medium to alkalize or sufficiently acidify so that the pH is always outside the neutrality. 3-the use of a solid / liquid separation carried out in the absence of light and of the oxygen of fair (ex under nitrogen, argon or gas of the same type) 4-evaporation of the extraction solvent during concentration of the dry extract under high vacuum and under inert gas at low temperatures. The use of drying the extract by zeodration which consists in drying the extract in an extreme vacuum drying chamber connected to an adsorption group containing zeolites as dehydrating agent. This technique allows drying at negative temperatures if necessary. 6- By obtaining during the production of metal salts of a crystalline powder very little hygroscopic and easily used in pharmacotechnics. 7- Finally, obtaining such an extract with well-defined chromatographic characteristics is represented by the following chromatogram. (Figure V).

  By an extract which is stored as such or in admixture with formulation excipients such as citric acid or ascorbic acid remains stable using percentages not exceeding 1% to 8% and therefore are pharmaceutically acceptable. To obtain unsalified forms from step 4 the solvent is acidified with the corresponding acid, such as citric acid, and the solution is evaporated in the presence or absence of a sugar such as maltodextrin. to promote a more manipulable form during atomization. The extract thus obtained is dried as in step 5 and stored in sealed sachet or bags with moisture, heat and light.

EXAMPLES

  Different extracts of St. John's wort were obtained from hydro-alcoholic solvents with varying proportions of alcohol and neutralized by different mineral or organic bases such as mainly sodium hydroxide, calcium hydroxide or magnesium hydroxide, triethanolamine etc. (Ca (OH) 2; TEA) or by acidification as, mainly, with mineral or organic acids such as hydrochloric acid; Sulfuric acid; phosphoric acids, citric, ascorbic acid, etc ... Here are described some tests that have allowed to obtain stable extracts of acylglucinols hyperforine type.

  Example 1 10 kg of finely chopped plant (Hypericum perforatum) are introduced into a 300 liter Colette or Olsa type stainless steel reactor under a nitrogen atmosphere and away from the light. 100 liters of a 60% alcoholic alcoholic solution are introduced. The model is stirred for 5 to 10 minutes at room temperature in order to have a good wettability of the plant. It is basified with 50% sodium hydroxide solution (# 100 mol).

  Still at room temperature, stirring is continued for 24 hours and the solution of extraction of the insoluble material is filtered off.

  The solution thus filtered is concentrated under vacuum at low temperature to remove the alcohol by azeotropy and the residue is dried by zeodration so as not to alter the extract.

  Between 2 and 2.5 kg of dry extract are obtained, the acylphloroglucinols contained therein being in the form of sodium salts. This extract is studied for stability under ICH conditions. It gave the following results in Table V and in Figure 6. Table V Tests To T3 Months A. 4 C T3 Months to 18 C Hypericines 0.25% 0.23% 0.23% Hyperforine 1.90% 1.81% 1.84% Example 2 20 lkg of extract obtained according to the method described in Example 1 is put into a cubic mixer of 10 liters containing 1.73 grams of citric acid and 36.6 grams of ascorbic acid and this by successive elutions. Once the extract is introduced, the mixture is stirred under inert gas in the absence of light until the mixture is homogeneous, ie approximately 2 hours. This extract thus modified is ready for use in pharmacotechnics for the production of pharmaceutical formulations.

  (Ex cps and chromatographic profile) HPLC chromatographic profile of an extract-based tablet of Example 2 in Figure 7. Example 3

  10 kg of finely chopped plant (Hypericum perforatum) are introduced into a 300 liter Colette or Olsa stainless steel reactor under a nitrogen atmosphere and away from the light. 100 liters of a hydroalcoholic solution containing 60% of alcohol are introduced into the reactor. Moderate stirring is carried out for 5 to 10 minutes at room temperature in order to have good wettability of the plant. It is basified with 50% sodium hydroxide solution (# 100 imol).

  Always at room temperature is allowed to stir for 24 hours.

  The solution is neutralized with hydrochloric acid to pH = 6. The extraction solution is separated from the insoluble by filtration. The solution thus filtered is concentrated under vacuum at low temperature to remove the alcohol by azeotropy and the residue is dried by zeodration so as not to alter the extract. This gives about 2 kg of dry extract, the acylphloroglucinols are under basic form. This extract is studied for stability under ICH conditions and gave the results shown in Figure 8 (Figures 8a and 8b).

  This extract can be used as is or in the presence of acids as described in Example 2

Example 4

  Preparation of a Therapeutic Use Formulation with Hypericum Extract p. obtained as in Example 2 Hypericum perforatum extract 31.152 kg Croscarmellose sodium 5.200 kg Microcrystalline cellulose 14.953 kg Glycerol dibehenate 0.676 kg Colloidal silica 0.208 kg 16 The powders are blended and 520 mg tablets containing 300 mg are prepared. crude extract plus 11.11 mg of ascorbic acid and 0.52 mg of citric acid. These tablets can then be dandruffed by agents which will shield them from light and moisture such as stearic acid in the presence of HPMC.

  Results of pilot batches in stability. The results obtained are shown in Table VI below:

  Table VI To T assays: 3 months T: 3 months T: 3 months 25 C / 60% 30 C / 65% 40 C / 70% HR HR HR Hypericine and 0.71 0.67 0.64 0.41 pseudohypericin Hyperforine 5.9 5.8 5.7 5.8 Ascorbic acid 9.7 9.7 9.4 4.5 Example 5

  Preparation of a formulation for therapeutic use with the extract of Hypericum perforatum obtained as in Example 2

  Hypericum.perforatum extract. 30,000 kg Magnesium citrate 12.00 kg Croscarmellose sodium 5.200 kg Microcrystalline cellulose 14.905 kg Glycerol dibehenate 0.676 kg Colloidal silica 0.219 kg Powder is blended and 640 mg tablets are produced containing 300 mg of crude extract plus 11.11 mg of ascorbic acid and 0.52 mg of citric acid. These tablets may then be film coated with agents which will shield them from light and moisture such as stearic acid in the presence of HPMC. Example 6

  Gastro-resistant tablets Preparation of a formula for therapeutic use with the extract obtained according to Example 1 for 100,000 nuclei of 510 mg per unit form

  Hypericum.perforatum extract. 30,000 Kg Croscarmellose Sodium 5,200 Kg to Microcrystalline Cellulose 14,905 Kg Glycerol Dibehenate 0,676 Kg Colloidal Silica 0,219 Kg The kernels are dandruffed by a first layer of Sepifilm LP with a deposit of about 25 mg per core and then a layer of a prepared suspension of Eudragit L30 D55, talc and triethyl citrate for a deposit of about 40 to 45 mg. This gives a finished tablet with an average weight after coating close to 580 mg.

The plant extracts according to the invention may also be supplemented with other active principles and in particular active principles having properties on the gastrointestinal sphere or on the central nephew system. It may be mentioned for this purpose polyunsaturated fatty acids of the type Omega-3 which act on anxiety or mucilages such as pectin or polymethacrylic acid, agents acting on intestinal motricity such as Trimebutine, antispasmodic products such as Tiemonium methylsulfate or anti-diarrheal products such as Formalin Formalin. These additional active ingredients can be contained at doses ranging from 100 mg per unit dose. 18

Claims (7)

  1 - A new process for extracting active ingredients from plants which makes it possible to increase the level of acylphloroglucinols in these extracts and to ensure their stabilization in which the plant extracts are subjected to an appropriate pH zone and then to drying by dehydration under vacuum at low temperature on zeolites. 2 - Process according to claim 1 which makes it possible to increase the level of acylphloroglucinols and to ensure their stabilization in which the plant extract is an extract of Hypericum perforatum. 3 - Process according to claims 1 and 2, the extracts obtained have a concentration of hyperforin which is between 2 and 8%. 4 - Process according to claims 1 to 3 wherein the extracts obtained contain an average of 3 A. 5% hyperforine. 5 - Process according to claims 1 to 3 wherein the stabilization of acylphloroglucinols is obtained by salification of acylphloroglucinols by different alkaline agents and in particular by sodium hydroxide, magnesium hydroxide and calcium hydroxide. 6 - Method according to claims 1 a. 3 and 5 wherein the salification can be carried out by metal salts, triethanolamine and triethylamine. 7 - Process according to claims 1 to 3, 5 and 6 wherein the salt extract is converted into base by controlled acidification of the extraction solutions with a mineral or organic acid such as hydrochloric acid, Sulfuric acid, phosphoric acids, citric acid or ascorbic acid. - Process according to claims 1 to 3 and 5 wherein 1 extract in salified form is isolated and then added citric and / or ascorbic acids or other antioxidants, to improve its physical state. 9 - Process according to the preceding claims in which is added to facilitate the pharmaceutical shaping, dilution additives such as maltodextrins, and / or lubricating agents such as metal stearates, slip agents such as citric acid or silicic acid. 10 - Extract obtained according to the process of claims 1 to 3 containing on average 2 to 8% of hyperforin in combination with a mineral salt 11 - Extract obtained according to the method of rune of claims 1 to 4, wherein it adds citrate of magnesium. 12 - Extract obtained according to the method of rune of claims 1 to 4, containing from 3 to 5% and more particularly 4% of hyperforine. 13 - Compositions based on an extract obtained according to the process of claims 1 to 13 used for therapeutic and / or para-pharmaceutical usecontenant more particularly 300 mg of extract to about 2% of hyperforine and further 10 mg of magnesium element provides in the form of different magnesium salts and 120 mg of magnesium in the form of magnesium citrate. 14 - Compositions based on plant extracts obtained according to the method of claims 1 to 8 wherein is incorporated further active ingredient or active in the gastrointestinal tract and / or the central nervous system .. 15 - Compositions based on plant extracts obtained according to the method of claims 1 to 8 in which one or more active agents acting on the central nervous system, in particular a polyinsaturated fatty acid of the Omega-3 series, is added.