HK1185009A - Formulations containing extracts of echinacea angustifolia and zingiber officinale which are useful in reducing inflammation and peripheral pain - Google Patents

Description

Preparation containing extracts of Echinacea angustifolia and Zingiber officinale for reducing inflammation and peripheral pain

Summary of The Invention

The present invention relates to compositions containing Echinacea (Echinacea) species and lipophilic extracts of ginger (Zingiber officinale) useful for the topical treatment of pruritus, peripheral pain, superficial and deep inflammatory and painful conditions, and pain associated with muscle spasms. The formulations according to the invention are also particularly useful for the treatment of herpetic pain and radiodermatitis caused by radiotherapy of tumors, with or without fungal or bacterial infections.

The formulations can also be used in the cosmetic field for reducing oedema and all types of irritative states.

State of the art

Lipophilic extracts of Echinacea species, preferably those of Echinacea angustifolia (Echinacea angustifolia) described in EP0464298, have anti-inflammatory activity when administered topically or systemically. Their pharmaceutical activity has been shown to be attributed to the isobutanamides (isobutelamides), which are ligands for the CB1 and CB2 cannabinoid receptors.

The isobutylamides have immunostimulatory activity, which characterizes the traditional and pharmaceutical uses of echinacea extracts.

In india and china, the roots and rhizomes of ginger after various treatments are used as spice seasonings. The uses described in traditional medicine include the treatment of dyspepsia, flatulence, diarrhea, cough and other related diseases. Extracts of this plant are particularly considered because of their anti-nausea effect. However, the data reported in controlled clinical trials are contradictory and, due to the lack of convincing data, the US pharmacopoeia recommends a complete examination of the properties possessed by the plant. Some of the conflicting data are due in part to the instability of the active ingredients in the commonly used extracts.

The extract used in the present invention is a lipophilic extract stabilized and prepared with carbon dioxide under well-defined supercritical conditions.

Detailed Description

It has now been surprisingly found that the combination of a lipophilic or partially lipophilic extract of the roots and rhizomes of echinacea species with a lipophilic extract of ginger produces potent analgesic and anti-inflammatory activity which is higher than that obtained with the extracts of echinacea and ginger which are not combined.

The combination according to the invention can be used to treat all types of peripheral pain, from diabetic neuropathy to radiodermatitis, joint and muscle pain of different causes and herpes pain, even in the absence of specific antiviral treatments.

Lipophilic extracts of echinacea species can be obtained by extraction from roots or rhizomes with alcohols, ketones and fatty ethers or preferably with carbon dioxide under supercritical conditions.

The extract of ginger root and rhizome can also be obtained by extracting with carbon dioxide under supercritical conditions.

For the preparation of the extract comprised in the composition of the invention, it is preferred to simultaneously extract with carbon dioxide under supercritical conditions the finely ground echinacea species and the roots and rhizomes of ginger in different proportions, adjusted according to the root value (titre) of the biomass (biomasses) of the active ingredient, in particular according to the isobutyramide content (expressed in pellitorine (pellitorine) or other specific isobutyramides) of echinacea and the gingerol content of ginger. The ratio of the two biomasses can be from 1:1 to 1:0.1, preferably 1: 0.5. The extraction method with supercritical carbon dioxide ensures stability of active ingredient and prevents formation of compounds such as shogaol and other inactive oxidation products.

The finely ground biomass is extracted at a temperature of 40 to 60 ℃, preferably 50 ℃, and a pressure of 200 to 260 bar, preferably 235 bar, for 1-10 hours, preferably 7 hours. The extract was collected in a condenser and, after eliminating water by dissolving the oily residue in ethyl acetate containing ascorbyl palmitate and dehydrating with anhydrous sodium sulfate, it was concentrated to dryness in vacuo at a temperature not exceeding 40 ℃. The extract thus obtained can be diluted directly in oil in the presence of surfactants or phospholipids, or formulated with excipients suitable for administration to animals or humans.

In another embodiment, the present invention provides a composition comprising a lipophilic or partially lipophilic extract of roots and rhizomes of echinacea species as described above in combination with a lipophilic extract of zingiber officinale, together with physiologically compatible carriers and excipients. In a preferred embodiment, the composition is in a form suitable for topical administration.

The composition according to the invention can be prepared by mixing the extracts obtained separately, thus allowing a ratio between isobutylamides from echinacea species and gingerols from ginger ranging from 1:1 to 1: 0.1. For this purpose, echinacea angustifolia (echinacea angustifolia) extracts described in EP0464298 can be used, as well as lipophilic extracts of ginger prepared by extraction from plant roots and rhizomes with carbon dioxide under supercritical conditions, similar to those just described, by extracting powders from the roots and rhizomes for 1-10 hours, preferably 7 hours, at pressures ranging from 230 to 260 bar, preferably 235 bar, and at temperatures ranging from 40 to 60 ℃, preferably 50 ℃; the extract is collected in a condenser and dehydrated in an inert gas dissolved in n-hexane or heptane containing a lipophilic antioxidant, preferably ascorbyl palmitate or tocopherol, and concentrated in vacuo at a temperature not exceeding 40 ℃.

Echinacea angustifolia root extract typically contains 15 to 45% of isobutylamides, whereas ginger rhizome extract contains 15 to 30% of gingerol and other terpenoids.

The topical composition of the invention typically contains 0.1-1% by weight of the extracts of both plants, in particular 0.2-0.8% of a compound extract of both species, or 0.1-0.3% of ginger extract and 0.2-0.5% of echinacea extract.

Said compositions have proven to be particularly useful for the topical treatment of itching, peripheral pain, superficial and deep inflammatory states and pain states, and pain associated with muscle spasms. The preparation is also particularly useful for the treatment of herpetic pain and radiodermatitis caused by radiotherapy of tumors, with or without fungal or bacterial infections.

The compositions of the present invention may also be used in the cosmetic field for reducing edema and all types of irritative states, including those caused by excessive exposure to sunlight.

The composition may be applied directly to the skin in an oil in which it is dissolved, or incorporated into a cream or ointment suitable for application. Treatment may be carried out 1 to 3 times per day by applying a dose of 0.5-5g of the topical formulation to the body part affected by the pain condition.

The Pharmaceutical or cosmetic compositions according to the invention will be formulated according to conventional techniques such as those described in "Remington's Pharmaceutical Handbook", Mack Publishing co. The following examples further illustrate the invention.

Example 1-oil containing Compound extract of Echinacea angustifolia and ginger

Example 2 oil/Water emulsion containing Compound extract of Echinacea angustifolia and ginger

Example 3 cream containing Compound extract of Echinacea angustifolia and ginger

Example 4 oil containing extracts of Echinacea angustifolia and ginger

EXAMPLE 5 preparation of Compound extract of Echinacea angustifolia and Zingiber officinale

10Kg of a mixture of ginger root (1 part) containing about 3% of gingerol and echinacea angustifolia root (3 parts) containing about 1% of isobutylamides was finely ground and extracted with carbon dioxide under supercritical conditions at 50 ℃ and 235 bar pressure for 7 hours. After extraction, the solvent was removed and the extracted material consisting of an oily residue was recovered in a condenser and taken up in 1.5L of ethyl acetate containing 0.5g of ascorbyl palmitate. The organic solution was washed with Na₂SO₄Dehydrated and concentrated in vacuo at a temperature not exceeding 30 ℃. 110g of a dense, dark yellow oil containing 20% isobutyramide and 12% gingerol were obtained. This extract can be used "as is" in pharmaceutical and cosmetic preparations.

EXAMPLE 6 preparation of lipophilic extract of ginger

10Kg of ginger root containing about 1.2% gingerol was finely ground and extracted with carbon dioxide at 50 ℃ and 235 bar pressure under supercritical conditions for 7 hours. After extraction, the solvent was removed and the extracted material consisting of an oily residue was recovered in a condenser and taken up in 1.5L of hexane containing 0.5g of ascorbyl palmitate. The organic solution was washed with Na₂SO₄Dehydrated and concentrated in vacuo at a temperature not exceeding 40 ℃. 400g of a dense, dark yellow oil containing 20% gingerol were obtained. The extract can be used as it isIn pharmaceutical and cosmetic preparations.

Example 7 evaluation of analgesic Activity in rats

The analgesic activity of the compositions of the invention was evaluated using the rat tail flick test. Before treatment, 3 basic measurements were taken on the animals to ensure that they were suitable for the treatments and instruments involved. The parameters used were 15V radiant heat and 15 sec power cut (to prevent irreversible damage to the animals) while assessing tail flick. Animals were treated with 0.1ml of oil of the composition described according to example 4, 5cm from the tail. The analgesic effect was measured 15 and 30 minutes after administration. The same experimental model was used to evaluate two individual components of the composition in a formulation containing the same amount of active ingredient as the composition described in example 4. Control animals were treated with 0.1ml of oil (vehicle) to dissolve the two components. The results are shown in table 1 below.

TABLE 1

Example 8 evaluation of analgesic Activity in patients with Knee osteoarthritis

40 patients with knee osteopathy, persistent pain were randomized and treated locally with the oil described in example 1, placebo (consisting of vehicle only) or the individual's (individual) component dissolved in placebo at the same concentration as in the oil described in example 1. Efficacy was assessed by an international simulated pain scale of 0 to 10 points, 10 being the most painful and 0 being the disappearance of pain. The effect was assessed 15 and 60 minutes after treatment.

The results are shown in table 2 below.

TABLE 2

Example 9 Effect on radiation-induced pruritus

10 patients suffering from erythema caused by UV light were treated with a 0.1% olive oil solution of the extract described in example 1 in the amount required to cover the stimulated area. After only 15 minutes of application, the irritation was significantly reduced and the itching disappeared immediately after application. The vector was confirmed to be inactive under the same conditions.

Example 10 Soft gelatin capsules

Unit composition:

example 11 evaluation of analgesic Activity in patients suffering from Knee osteoarthritis

60 patients suffering from knee osteopathy, persistent pain were randomly grouped and treated orally with the capsules described in example 10, with placebo (consisting of vehicle only) or with the individual ingredients dissolved in placebo in the same amounts as in the capsules described in example 10. Efficacy was assessed by an international simulated pain scale of 0 to 10 points, 10 being the most painful and 0 being the disappearance of pain. The effect was assessed after 60 and 120 minutes of treatment.

The results are shown in table 3 below.

TABLE 3

Claims (8)

1. A combination of ginger (Zingiber officinale) and a lipophilic extract of Echinacea angustifolia (Echinacea angustifolia) for use in the treatment of pruritus; peripheral pain; superficial or deep inflammatory disorders and pain disorders; pain associated with muscle spasm; pain due to herpes; radiodermatitis caused by tumor radiotherapy with or without fungal or bacterial infection; edema and irritant skin conditions, including those caused by excessive exposure to sunlight.

2. A combination product as claimed in claim 1, wherein the extracts of both species are obtained by extraction from roots or rhizomes with supercritical carbon dioxide.

3. A combination product as claimed in claims 1-2, which contains isobutyramides from echinacea angustifolia and gingerol from ginger in a weight ratio of 1:1 to 1: 0.1.

4. A combination product as claimed in claim 3, which comprises isobutyramides from echinacea angustifolia and gingerol from ginger in a weight ratio of 1: 0.5.

5. A composition comprising a combination of a lipophilic extract of zingiber officinale and echinacea angustifolia as claimed in claims 1 to 4, together with physiologically compatible carriers and excipients, for use in the treatment of pruritus; peripheral pain; superficial or deep inflammatory disorders and pain disorders; pain associated with muscle spasm; pain due to herpes; radiodermatitis caused by tumor radiotherapy with or without fungal or bacterial infection; edema and irritant skin conditions, including those caused by excessive exposure to sunlight.

6. The composition of claim 5, in a form suitable for topical administration.

7. The composition of claims 5-6, wherein the extract is formulated in an oil in the presence of a surfactant or a phospholipid.

8. Lipophilic extract of ginger obtainable by extraction with carbon dioxide from the roots or rhizomes of said plant under supercritical conditions at a pressure of 230 to 260 bar, at a temperature of 40 to 60 ℃ for 1 to 10 hours.