HK1164743A - Compositions comprising lipophilic extracts of zingiber officinale and echinacea angustifolia for the prevention and treatment of gastro-oesophageal reflux and chemotherapy-induced emesis - Google Patents

Description

composition comprising lipophilic extracts of zingiber officinale and echinacea angustifolia for the prevention and treatment of gastro-esophageal reflux and chemotherapy-induced emesis

Summary of The Invention

The present invention relates to a composition comprising a combination of lipophilic extracts of ginger (Zingiber officinale) and echinacea angustifolia (echinacea angustifolia) for the prevention and treatment of oesophageal reflux and chemotherapy-induced emesis.

Prior Art

Gastrointestinal cancer is the second most common type of cancer and the second most lethal cause in the field. Esophageal cancer and stomach are not very common in developed countries but are very fatal.

Multiple cofactors for these two tumors have been identified, such as alcoholism, often accompanied by smoking, a nitrate-rich diet, and/or products or habits that disrupt the mucous barrier of the stomach and esophagus. The different continental populations were then examined for dietary habits and deficiencies of certain trace elements (pra-wen syndrome and peykok syndrome), trying to prevent gastric and esophageal cancer caused by said co-factors by changing dietary habits and lifestyle and applying drugs or dietary products. Although many of these secondary causes have been eliminated, the incidence worldwide is increasing due to an increasing number of people who suffer from gastro-esophageal reflux and are often accompanied by dietary and/or hiatal hernias, one of the major causes of esophageal neoplasms. Adenocarcinoma is predominantly manifested by mixed columnar epithelia of the terminal portion of the esophagus, with chronic reflux and gastric metaplasia (barrett's esophagus) occurring almost frequently, which is common in obese individuals, and worsened in more than 50% of cases.

Therefore, it is very important to reduce the incidence of this disorder.

Therefore, research has focused primarily on drugs that can reduce reflux, particularly by modifying gastric emptying. In particular, researchers have attempted to develop natural prokinetic drugs that are well tolerated because the underlying drug needs to be taken for many years on a preventive basis, either for long periods of time or intermittently depending on the digestive requirements.

However, many of the drugs used to modify gastric excretion have recently appeared to have serious side effects affecting the CNS or to have carcinogenic effects, and have therefore been or are just about to be withdrawn from the market. Currently gastro-esophageal reflux is treated with mixed drugs such as proton pump inhibitors (ranitidine, -prazole or simple antacids), enzymes, various digestive and prokinetic drugs such as domperidone. However, long-term use of proton pump inhibitors often leads to a number of digestive problems.

Therefore, research is now focused on new therapeutic approaches.

Description of the invention

It has now been found that a combination comprising lipophilic extracts of zingiber officinale and echinacea angustifolia (both prepared by extraction with carbon dioxide under supercritical conditions) has surprising prokinetic and antiemetic activities, leaving the digestive function unaltered and eliminating gastric heaviness and vomiting, which are cofactors of esophageal reflux; it is therefore useful in the prevention and treatment of esophageal reflux and chemotherapy-induced emesis.

Accordingly, the present invention relates to a composition comprising:

a) lipophilic extract of ginger, and

b) lipophilic extract of Echinacea angustifolia (Echinacea angustifolia),

it is used for preventing and treating esophageal reflux and chemotherapy-induced emesis.

More particularly, according to the invention, the lipophilic extract of echinacea angustifolia is prepared by extraction with carbon dioxide under supercritical conditions, as disclosed in patent EP 464298 filed by the applicant. Lipophilic extracts of ginger can also be extracted under the same conditions starting with the crushed roots.

The roots and rhizomes of ginger, treated in various ways, in particular in asia and the middle east, are used as spices and in traditional medicine for the treatment of digestive disorders, flatulence, diarrhoea, cough, and to a lesser extent to protect the mucous membranes, diminish inflammation, treat urinary incontinence, etc.

The active ingredient present in lipophilic extracts of ginger mainly comprises gingerol (generally present in concentrations ranging from 10 to 15%), which has anti-dyspepsia, anti-nausea and anti-vomiting activities and can be used for the treatment of motion sickness, eructation, digestive disorders, colic, vomiting, dyspepsia and stomach and colon pain. However, in view of the well-known chemical instability of gingerol, recent clinical trials have shown that lipophilic extracts of ginger prepared by traditional methods have low activity; thus, the united states pharmacopeia recommends a complete review of plant properties due to the lack of strong evidence. The lipophilic extracts of ginger, prepared by conventional methods, contain gingerol which rapidly decomposes to produce a range of compounds, such as shogaol and other oxidation products, which are not effective. These inconsistent data are due in part to the instability of the active ingredients in the commonly used extracts. However, the extract used in the present invention is a lipophilic extract stabilized and prepared with carbon dioxide under well-defined supercritical conditions.

Lipophilic extracts of the roots and aerial parts of echinacea angustifolia are characterized by the presence of isobutylamides of polyunsaturated acids with analgesic and anti-inflammatory properties, anti-nausea and anti-vomiting activity, linked to their interaction with cannabinoid receptors. The combination of the present invention has surprisingly significant prokinetic and anti-dyspepsia effects, leaving the digestive function unaltered and eliminating gastric heaviness and vomiting, which are secondary causes of esophageal reflux. Thus, the combination may be used for the prevention and treatment of esophageal reflux and chemotherapy-induced emesis.

The composition of the invention increases gastric emptying, a very effective and totally unexpected effect, since the activity is not demonstrable by the individual components in any patient treated. Indeed, as mentioned above, it was observed that administration of alkylamides of echinacea angustifolia slowed gastric and intestinal excretion, rather than facilitated it.

According to a preferred aspect, the composition of the invention comprises the following two components in the following weight ranges:

a) lipophilic extract of ginger: 1 to 25 mg; and

b) lipophilic extracts of echinacea angustifolia: 1 to 10 mg.

According to a particularly preferred aspect, the composition comprises the following two components by weight:

a) lipophilic extract of ginger: 12.5 mg; and

b) lipophilic extracts of echinacea angustifolia: 5 mg.

According to a preferred aspect, the composition of the invention comprises a lipophilic extract of echinacea angustifolia, prepared according to the process described in EP 464298, characterized by an isobutylamide content ranging from 25 to 50%, in particular dodec-2E, 4E, 8Z, 10Z-tetraenoic isobutylamide.

According to a preferred aspect, the lipophilic extract of ginger and the lipophilic extract of echinacea angustifolia are formulated in a vegetable oil rich in omega 3/omega 6 polyunsaturated fatty acids (e.g. evening primrose oil).

According to a further aspect, the compositions of the invention may be administered with other substances having an effective or complementary activity.

The dosages which prove effective in humans are from 1 to 25mg of lipophilic extract of ginger and from 1 to 10mg of lipophilic extract of echinacea angustifolia per dose; more particularly, 12.5mg of lipophilic extract of ginger and 5mg of lipophilic extract of echinacea angustifolia per dose are taken with each staple food or are suitable for the disorder to be treated.

The compositions of the present invention are formulated according to conventional methods, such as those described in "Remington's pharmaceutical Handbook" Mack Publishing co., n.y., USA. In particular, the compositions of the present invention are formulated according to conventional formulation techniques for lipophilic ingredients for oral administration, primarily as oily sublingual tablets or soft gelatin or cellulose capsules designed to disperse rapidly in the stomach. The lipophilic form employs oils rich in omega-3 fatty acids, which promote rapid absorption of the active ingredient, thereby dispersing the active ingredient. Examples of oral formulations are tablets, lozenges, soft and hard gelatin capsules and cellulose capsules.

The following examples further illustrate the invention.

Example 1 Soft gelatin Capsule

Unit composition:

example 2 hard gelatin Capsule

Unit composition:

Claims (7)

1. Composition comprising the following obtained by extraction with carbon dioxide under supercritical conditions:

a) lipophilic extract of ginger, and

b) lipophilic extract of Echinacea angustifolia.

2. The composition of claim 1, comprising the two components in the following weight ranges:

a) lipophilic extract of ginger: 1 to 25 mg; and

b) lipophilic extracts of echinacea angustifolia: 1 to 10 mg.

3. The composition of claims 1 and 2, comprising the following two components by weight:

a) lipophilic extract of ginger: 12.5 mg; and

b) lipophilic extracts of echinacea angustifolia: 5 mg.

4. Composition according to the preceding claim, comprising a lipophilic extract of Echinacea angustifolia, wherein the content of isobutylamides is comprised between 25 and 50%.

5. The composition of the preceding claims for oral administration.

6. The composition of claim 5, which is in the form of a soft gelatin capsule or a hard gelatin capsule.

7. Obtained by extraction with carbon dioxide under supercritical conditions

a) Lipophilic extract of ginger, and

b) lipophilic extract of Echinacea angustifolia

Use in the manufacture of a composition for increasing gastric emptying, preventing and treating esophageal reflux and chemotherapy-induced emesis.