DE19859499A1 - Stable ginger extract preparations useful for treating dyspepsia or travel sickness, contain oil, triglyceride or fatty acid or alcohol as stabilizing auxiliary - Google Patents

Abstract

Stable ginger extract preparations (A) contain (as well as the ginger extract) at least one stabilizing galenic auxiliary (I) selected from oils, semi-solid triglycerides, fatty acids and fatty alcohols. Independent claims are included for: (i) the production of (A); and (ii) galenic preparations containing (A) plus further galenic auxiliaries.

Description

The present invention relates to stable ginger extract preparations, the Amount of hot substance (represented by the sum of the amounts of 6-gingerol and 6-Shogaol) decreases by a maximum of 10% over a period of 18 months and a maximum of 20% 6-gingerol can be converted into 6-shogaol. The invention be also writes these galenical accessories containing these ginger extract preparations equations such as solutions and capsules and their use for treatment dyspeptic complaints and the symptoms of motion sickness.

The rootstock of the ginger plant (Zingiber officinalis) has been around for centuries used in Southeast Asia as a spice and medicinal plant. Ginger was there cultivated early; The harvested rhizomes are used unpeeled or ge peels and mostly dried.

Numerous pharmacological effects have been possible in the past few years scientifically proven, in particular the application as Antiemetic and also clinically proven for dyspeptic complaints. (Lite summary: Doctoral thesis Dr. Stefan Germer; Regensburg 1996; Ha gers Handbuch der Pharm. Praxis, 5th edition "Zingiber" p. 837)

Commission E contributed the experience reports and clinical observations of the former Federal Health Office, in 1988 by positi ve published monograph "Zingiberis rhizoma". After that, preparation conditions such as crushed drug, dry extracts etc. used in dyspeptic Complaints as well as to prevent the symptoms of motion sickness, being considered average daily dose of 2-4 g of drug can be prescribed. (Federal Gazette No. 85 from 5.5.1988 or Federal Gazette No. 50 from 13.3.1990)

The described effects - antiemetic, cholagogic, spasmolytic, crate intestinal peristalsis - especially the main lipophilic ingredients, assigned to the essential oil and the spicy substances.

In the monograph of the German Pharmacopoeia (DAB 1997) "Ginger root stock ", a minimum essential oil content of 1.5% is required.

The main ingredients of ginger are:

• - Gingerole, where 6-gingerol is a strong spicy substance, while the longer one 8- and 10-gingerols produce less sharpness.
• - Shogaole, which arise from gingeroles by dehydration and also Are spicy.

Gingerole and Shogaole together are considered the keen principle of the drug. 6-Gingerol is to be regarded as the phytochemical lead substance of the ginger.

• - Essential oil with sesquiterpene and monoterpene hydrocarbons

It also contains amino acids, lipids, carbohydrates, etc. Due to the Lability of gingerols and conversion to shogaole offers the ratio of Concentrations of gingerols and shogaols provide an index to assess the Freshness of ginger and allows a statement about the age and storage stability of the Ginger or a ginger preparation.

Recently, ginger acetone extracts have been used for a number of interesting phar macological results are achieved, in particular the evidence that this extract the serotonin-induced contractions of the smooth Muscles of the ileum reduced. (Dissertation Germer, Regensburg 1996) However these are extracts, which in their native form are a critical stabilizer lity and therefore not directly in galenical preparations and medicines can be used with a reasonable shelf life.

At the moment there is only one single preparation with ginger in Germany Trade, the active ingredient in the form of powdered ginger drug (250 mg / capsule) is present (see formulation A of example 1). This in turn means that for sure the effectiveness of high amounts of active ingredient (2-4 g drug) are required only over an excessive number of dosage units (i.e. at least 10 Capsules per day).

In addition, it can be demonstrated that, as already described, such drug powders Preparations containing a constant conversion of the gingerole to Shogaole ren, so that the active ingredient changes continuously during storage (See also Example 1 and E. Steinegger, K. Stucki Pharm. Acta. Helv. 57, 3, 1982 "Separation and quantitative determination of the main pungents of Zingiberis rhi zoma by means of combined DC / HPLC ").

It is known that ginger extracts made with alcohol / water are also in place the conversion of Gingerol to Shogaol and decrease in the total amount of spicy substances (i.e. the sum of gingerols and shogaoles) show (PhD thesis Germer).

This is illustrated in Figs. 1 and 2.

Fig. 1 shows the breakdown of 6-gingerol when storing a methanolic extract at different storage temperatures. At room temperature, the 6-gingerol content drops by about 40% within 31 weeks; at 60 ° C, 6-gingerol is almost completely broken down after 31 weeks.

Fig. 2 shows the 6-Shogaol content increase during storage under the same conditions.

The present invention has for its object stable stable Ing werextrakt preparations and galenic preparations containing them deliver in which the content in conventional storage at room temperature of sharpness quantities over a very long period of up to 18 months and more remains essentially the same and the least possible conversion of 6-gingerol takes place in 6-shogaol.

This task is characterized by a stable ginger extract preparation by a content of a ginger extract and at least one stabilizing one  galenic excipient selected from the group consisting of oils, semi-fe most triglycerides, fatty acids and fatty alcohols.

Furthermore, the present invention is based on the object of a method for the production of the ginger extract preparations according to the invention, these ent to provide galenical preparations and their use.

These tasks are achieved by the method according to claim 13, a pharmaceutical preparation according to claim 14 and the use according to Claim 16 solved.

The invention is based on the surprising finding that lipophilic concentrated Ginger extracts in the presence of oils or in oily galenic formulations shapes do not experience a change in the amount of sharp substance and in particular the Remodeling of gingerole in Shogaole is pushed back.

According to the present invention, the amount of sharp substance is the sum of To understand the amount of 6-gingerol and 6-shogaol in the extract.

It has been shown that in the ginger extract preparations according to the invention and galenical preparations in conventional storage (i.e. in room temperature perature) the amount of sharpness over a period of 6, 12 or 18 Months and more remains essentially the same, d. H. decreases by a maximum of 10%, based on the initial total amount of sharp substance (i.e. in the sense this invention, the sum of the amounts of 6-gingerol and 6-shogaol) and at the same time a maximum conversion of only 20%, preferably 15% 6- Gingerol takes place in 6-shogaol, based on the initial content of 6- Gingerol.

For the production of the ginger extract preparations and galeni according to the invention Preparations are lipophilic extracts made from ginger sausage zelstock with pure alcohols or high-proof alcohols, such as 70 to 99%, preferably 90 to 98% aqueous methanol, ethanol, propanol, Isopropanol, n-butanol or mixtures thereof, in particular 95 to 98% Ethanol, pure acetone or 70 to 99%, preferably 90 to 98% aq Rigen acetone or mixtures with one or more of the above Alko hole or supercritical carbon dioxide used. This lipophilic, as a rule oily to pasty extracts, are only stabilized with lipophilic pharmaceutical auxiliaries such as oils (e.g. medium-chain triglycerides (definition according to Ph. Eur. = Pharmacopoe Europa = European Pharmacopoeia; also as neutral oil referred), fatty oils such as castor oil, peanut oil, semi-solid triglycerides (e.g. hard fat; definition according to the European Pharmacopoeia) long-chain fatty acids (e.g. linoleic acid, palmitic acid, stearic acid) and long-chain alcohols (e.g. Octyldodecanol; Definition according to the European Pharmacopoeia) processed and in ga lenic forms such as B. oily solutions or oil-filled capsules, such as hard and Brought soft gelatin capsules.

In a preferred embodiment, the acetone ginger extract is included medium-chain triglycerides (i.e. neutral oil according to Ph. Eur.) and hard fat (according to Ph. Eur.) Mixed and filled into a soft gelatin capsule. A particularly be preferred ginger extract preparation and one containing it especially before drawn galenical preparation is described in Example 2.

The mass ratio of ginger extract to stabilizing additives in the Ginger extract preparation is in a range of 1: 0.2 to 1: 3, preferably 1: 0.5 to 1: 2.5.

The invention is illustrated by the following non-limiting examples:

Example 1 (comparative example) Recipe A

Commercial preparation with ground ginger rootstock;

Recipe B

Ginger extract made with 60% ethanol, filled in soft gelatin capsules;

Recipe C

Ginger extract made with 60% ethanol and adsorbed on silica; From filling the powdery material into hard gelatin capsules.

Formulations A to C were stored at room temperature and the content of 6-gingerol and 6-gingerol + 6-shogaol were determined.

Table 1 shows that there is a marked decrease in these 3 recipes of 6-gingerol and to decrease the total amount of spicy substances (6-gingerol + 6- Shogaol) is coming. This effect is particularly strong when transferring the Ingwerex tracts in powder by means of adsorbing galenic additives such as silicon dioxide (Recipe C).

Table 1

6-gingerol or 6-gingerol + 6-shogaol contents when storing various ginger extract preparations and galenic preparations containing them (example 1, recipe A, B, C)

Example 2: Preparation of an extract preparation according to the invention

75 kg of ginger drug were mixed with 520 kg of 98% aqueous acetone at 55 ° C 2 Hours macerated. The drug residue was again with 520 kg 98% extracted aqueous acetone. The combined extract solutions were filtered and freed from the solvent at reduced pressure and a maximum of 50 ° C and after dried in a drying cabinet. The result was 9.3 kg of native extract (6.2% extract te) with 4.65 kg of medium-chain triglycerides (i.e. neutral oil according to Ph. Eur.) were.

Example 3: Stable ginger extract preparation according to the invention and this containing galenical preparation (finished product)

From an acetone ginger extract according to Example 2, d. H. with 98% aq extracted acetone, an oily ginger extract preparation was prepared. This was transferred to a soft gelatin capsule. For this, one was per capsule Mixture of 100 mg ginger acetone extract with 100 mg medium chain triglyerides (according to Ph. Eur.) and 140 mg hard fat (according to Ph. Eur.).

Recipe

Ginger acetone extract 100 mg / capsule Medium chain triglycerides 100 mg / capsule Hard fat 140 mg / capsule

Table 2

Influence of storage time on 6-gingerol and 6-gingerol + 6-shogaol content

Table 2 shows that even after 18 months of storage at room temperature in the preparation according to the invention with ginger extract, the content of Sharpness (6-gingerol + 6-shogaol) has changed only slightly Exercise of 6 gingerol to shogaol only occurred to a maximum of 10%. So that's one significant stabilization compared to formulations according to the state of the art Technology recognizable.  

Example 4: Comparative stability of a ginger extract according to the invention preparation with native ginger extract

Native acetone ginger extract made with 98% aqueous acetone as in Example 2, but without the addition of an oily filling and an inventive one Ginger extract preparation consisting of 2 parts acetone ginger extract (Made according to Example 2) and 1 part medium chain triglycerides (i.e. neutral oil according to Ph. Eur.) were compared under stress conditions (40 ° C) over 1 month stored.

Results

While with pure ginger extract 6-gingerol decreases massively and also that Sharp substances are already reduced to 40 ° C. after 4 weeks, this is with fiction according extract preparations pushed back.

Claims (16)

1. Stable ginger extract preparation, characterized by a content of a ginger extract and at least one stabilizing galenic excipient selected from the group consisting of oils, semi-solid triglycerides, fatty acids and fatty alcohols. 2. Stable ginger extract preparation characterized by a content of one Ginger extract and at least one stabilizing galenic excipient selected from the group consisting of oils, semi-solid triglycerides, Fatty acids and fatty alcohols, the amount of hot substance over time within 18 months decreases by a maximum of 10% and a maximum of 20% 6-gingerol being transformed. 3. Stable extract preparation according to claim 1 or 2, wherein the oil is selected is made of medium chain triglycerides Ph. Eur. or fatty oils like castor oil or Peanut oil. 4. Stable extract preparation according to claim 1 or 2, wherein the semi-solid Triglyceride hard fat Ph. Eur. 5. Stable extract preparation according to claim 1 or 2, wherein the fatty acid from is selected from linoleic acid, palmitic acid or stearic acid. 6. Stable extract preparation according to claim 1 or 2, wherein the fatty alcohol is Oc tyldodecanol Ph. Eur. 7. Stable extract preparation according to one of claims 1 to 6, wherein the mas ratio of ginger extract to galenic excipients to be stabilized in ranges from 1: 0.2 to 1: 3. 8. Stable extract preparation according to claim 1 to 6, wherein the ginger extract by extraction with pure or 70-99%, preferably 90 to 98% aqueous acetone, pure or 70-99%, preferably 90 to 98% aqueous alcohols, CO ₂ or other lipophilic solvents or mixtures thereof is produced. 9. Stable extract preparation according to claim 7, wherein the alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol and n-butanol. 10. Stable extract preparation according to claim 7 or 8, wherein the alcohol is out choose from 95-98% aqueous ethanol. 11. Stable extract preparation according to one of claims 1 to 10, containing egg Ginger extract made from 98% aqueous acetone, medium chain Triglyceride Ph. Eur. And Hartfett Ph. Eur. 12. Stable extract preparation according to claim 11, wherein the ginger extract, the medium-chain triglycerides Ph. Eur. and hard fat Ph. Eur. in bulk ratio of 1: 1: 1.4. 13. A method for producing the stable extract preparation according to one of claims 1 to 12, comprising the extraction of the ginger root stock with a solvent selected from the group consisting of pure or 70-99%, preferably 90 to 98% aqueous acetone, pure or 70-99%, preferably 90 to 98% aqueous alcohols, CO ₂ or other lipophilic solvents or mixtures thereof, and addition of at least one stabilizing galenic auxiliary selected from the group consisting of oils, semi-solid triglycerides, fatty acids and fatty alcohols. 14. Galenic preparation containing a stable extract preparation after one of claims 1 to 12 and other pharmaceutical auxiliaries. 15. Galenic preparation according to claim 14, selected from solutions and Capsules such as hard and soft gelatin capsules.   16. Use of a stable extract preparation according to one of claims 1 to 12 as a medicine for the treatment of dyspeptic complaints and the sym ptome of motion sickness.