Previous Patent: Method of providing sustained analgesia with buprenorphine
Next Patent: Microencapsulated bioactive agents and method of making
Next Patent: Microencapsulated bioactive agents and method of making
Extracts of zanthoxylum bungeanum, and pharmaceutical and cosmetic formulations containing same
Kind Code:
A1
The extract of the pericarp of Zanthoxylum bungeanum, Zanthoxylurn bungeanum,
Representative Image:
Inventors:
Bombardelli, Ezio (Milano, IT)
Gabetta, Bruno (Milano, IT)
Gabetta, Bruno (Milano, IT)
Application Number:
09/749448
Publication Date:
05/31/2001
Filing Date:
12/28/2000
View Patent Images:
Export Citation:
Primary Class:
Other Classes:
424/434, 424/451, 424/400, 424/464, 424/401
International Classes:
(IPC1-7): A61K009/48; A61K009/20
Attorney, Agent or Firm:
PENNIE & EDMONDS LLP (1155 Avenue of the Americas, New York, NY, 10036-2711, US)
Claims:
What is claimed is:
1. An extract of
2. The extract according to claim 1 having an isobutylamide content from 20 to 50% by weight.
3. A pharmaceutical composition in the form of a cream, lotion, foam, gel, capsule, tablet or suppository and containing, as an active ingredient, the extract of claim 1 in an amount sufficient to provide analgesic activity.
4. A cosmetic composition in the form of a cream, lotion, foam, or gel and containing, as an active ingredient, the extract of claim 1 in an amount sufficient to provide analgesic activity.
5. A method of obtaining an extract of
6. The method according to claim 5 wherein the extraction with CO
7. The method according to claim 5 wherein the extraction with CO
8. The method according to claim 5 wherein the extraction is conducted for a time, temperature and pressure sufficient to obtain an extract having an isobutylamide content from 20 to 50% by weight.
9. The extract produced by the method of claim 5.
10. A pharmaceutical composition in the form of a cream, lotion, foam, gel, capsule, tablet or suppository and containing, as an active ingredient, the extract of claim 9 in an amount sufficient to provide analgesic activity.
11. A cosmetic composition in the form of a cream, lotion, foam, or gel and containing, as an active ingredient, the extract of claim 5 in an amount sufficient to provide analgesic activity.
Description:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of the U.S. National Stage designation of co-pending International Patent Application PCT/EP99/02358, filed Jul. 4, 1999 the content of which is expressly incorporated herein by reference thereto.
FIELD OF THE INVENTION
[0002] The present invention relates to a novel extract obtained by extraction of the pericarp of
BACKGROUND OF THE INVENTION
[0003] Pericarp of
[0004] Recently, EP 568001 disclosed the antiviral activity of the skin of this fruit. In U.S. Pat. No. 5,137,912, chelcrythrine extracted from the root bark of
[0005] Despite this, there remains a need for additional anti-inflammatory and analgesic formulations, and the present invention satisfies this need.
SUMMARY OF THE INVENTION
[0006] It has now surprisingly been found that the extract of the pericarp of
[0007] The resulting extract can either be used as it is, after removing the extraction water, or it can further be purified by partitioning it with immiscible solvents such as aliphatic alcohols and aliphatic hydrocarbons, preferably n-hexane or petroleum ether.
[0008] The resulting extracts proved to exert a marked analgesic activity when applied percutaneously to humans; therefore they are valuable for use both in the pharmaceutical and cosmetic fields.
[0009] In the pharmaceutical field, these extracts are useful for alleviating pain resulting from diabetic microangiopathy, hemorrhoids, burns, or due to any other local causes. A further application of the extracts of the invention is in the treatment of itching.
[0010] In the cosmetic field, the extracts according to the invention are useful in depilatory creams, after-sun formulations, shaving lotions and creams, and in all types of skin treatments requiring local analgesic or anti-itching action.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIGURE
DETAILED DESCRIPTION OF THE INVENTION
[0012] The anti-itching activity of the extracts of the invention was evaluated through electrophysiological measurements using the experimental model of the rat ischiatic nerve-musculus extensor digitorum longus (EDL) preparation in vitro.
[0013] Adult Sprague-Dawley rats killed by an intracardial Penthotal overdose were used. The EDL muscle with a long tract of ischiatic nerve was dissected and placed in a container for electrophysiology with a Ringer solution which was substituted every 10 minutes. The tested extracts, preferably added with a surfactant, were dispersed in different concentrations, thereby coming into contact with nerve fibers, neuromuscular junctions and muscle. For the electrophysiological tests, an intracellular microelectrode filled with 3M KCl was placed in muscle cells for recording the electrical phenomena (miniature endplate potentials, endplate potentials, membrane potentials of the muscle cell) both spontaneous and induced by stimulation of the nerve. For this purpose, the nerve was linked to a stimulator and optionally stimulated once a second. The electric events in the muscle cells were detected by a microelectrode linked to a signal amplifier and made visible through a digital oscilloscope.
[0014] The extracts of the invention, when tested at concentrations ranging from 0.0005 to 0.002%, exerted a strong transitory activating action on the neuromuscular synaptic transmission, evidenced by the increase in the frequency of the miniature endplate potentials and by the appearance of spontaneous endplate potentials. Conversely, the extracts obtained with solvents; having local anesthetic activity, reduced and inhibited the transmission of the nervous impulse.
[0015] The analgesic activity of the tested extracts was evaluated in 10 healthy volunteers through an evaluation study of the skin thermal sensitivity.
[0016] A progressively heated thermal probe was placed on the scapular area of the subject 30 minutes after treatment with the test product or with the corresponding placebo. The value of the temperature considered painful by the subject was measured. 0.5 ml of an emulsion prepared according to Example VII, containing 0.5% of an extract of
TABLE 1 Analgesic activity of tested extract versus placebo Treatment T T Placebo 45.7 ± 1.0 45.3 + 0.4 Extract 46.0 + 0.8 47.2 + 0.4
[0017] The extracts of the invention can be formulated as creams, lotions, foams, or gels for administration to the skin or mucosas, or as soft-gelatin capsules, hard-gelatin capsules, tablets or suppositories. Preferably the extract of the invention is formulated in creams or foams for cutaneous treatment or in soft-gelatin capsules, chewable tablets or suppositories for the systemic route.
[0018] The extract dosages in the formulations range between 5 and 100 mg per dose in the formulations for the systemic use, whereas they vary from 0.05 to 1% in the topical formulations.
EXAMPLES
[0019] The following examples further illustrate the invention without limiting it.
Example I—Preparation of a Zanthoxylum bungeanum Lipophilic Extract
[0020] 10 Kg of pericarp of
[0021] 10 Kg of pericarp mechanically dried after harvesting at a temperature not higher than 60° C. was extruded into cubes and extracted with CO
[0022] temperature: 35° C. in the extractor, 30° C. in the first separator and 20° C. in the second separator;
[0023] pressure: 180 bars in the extractor, 100 bars in the first separator and 50 bars in the second separator.
[0024] The CO
TABLE 2 HPLC analysis results for Example I NUMBER OF TIME WATER ACETONITRILE THE GRADIENT (min.) (%) (%) CURVE 0 60 40 — 20 60 40 6 30 10 90 6 35 60 40 6 40 60 40 6
EXAMPLE II—Preparation of a Zanthoxylum bungeanum Lipophilic Extract
[0025] 10 Kg of pericarp mechanically dried after harvesting at a temperature not higher than 60° C. was extruded into cubes and extracted with CO
[0026] temperature: 40° C. in the extractor, 30° C. in the first separator and 20° C. in the second separator;
[0027] pressure: 205 bars in the extractor, 100 bars in the first separator and 50 bars in the second separator. The CO
EXAMPLE III—Preparation of a Zanthoxylum bungeanum Lipophilic Extract
[0028] 10 Kg of pericarp mechanically dried after harvesting at a temperature not higher than 60° C. was extruded into cubes and extracted with CO
EXAMPLE IV—Preparation of a Purified Lipophilic Extract of Zanthoxylum bungeanum
[0029] 0.5 Kg of lipophilic extract of pericarp of
EXAMPLE V - 100 ml contains: 0.50 g Cyclomethicone 20.00 g Alcohol 100.0 ml EXAMPLE VI- 100 ml contains: 0.50 g PPG-26 Buteth 26 and PEG-40 Hydrogenated Castor Oil 5.00 g Methyl Chloroisothiazolinone and Methyl Isothiazolinone 0.10 g Purified water q.s. to 100.0 ml EXAMPLE VII - 100 g contains: 0.50 g Isohexadecane 5.00 g Glycerin 4.00 g C 2.00 g Cyclomethicone 2.00 g PEG-20 Glyceryl Stearate and Lanolin wax 1.00 g Acrylates/C 0.50 g Cetyl Alcohol 0.50 g Imidazolidinyl urea 0.30 g Phenoxyethanol 0.50 g Methyl paraben 0.20 g Tocopherol 0.10 g Disodium EDTA 0.10 g Water q.s. to 100.0 g EXAMPLE VIII- 100 g contains: 0.50 g PEG-20 Glyceryl Stearate and Glyceryl Stearate 10.00 g C 10.00 g Glycerin 5.00 g Wheat Germ Oil 2.00 g Dimethicone 2.00 g PPG-25 Laureth-25 2.00 g Cetyl Alcohol 1.00 g Hydroxylated Lanolin 0.50 g Imidazolidinyl urea 0.30 g Hectorite (e) Hydroxyethyl 0.50 g Phenoxyethanol and Methylparaben and 0.50 g Ethylparaben and Propylparaben and Butylparaben Tocopherol 0.10 g Water q.s. to 100.0 g
[0030] While the invention has been illustratively described herein with reference to specific aspects, features and embodiments, it will be appreciated that the utility and scope of the invention is not thus limited and that the invention may readily embrace other and differing variations, modifications and other embodiments. The invention therefore is intended to be broadly interpreted and construed, as comprehending all such variations, modifications and alternative embodiments, within the spirit and scope of the ensuing claims.