The present invention provides a pharmaceutical composition for treating skin disorders, including enhancing the healing of wounds for diabetic patients. Specifically, this invention relates to the use of the extracts of Plectranthus amboinicus and Centella asiatica for improving skin disorders, including enhancing the healing of wounds for diabetic patients, and a pharmaceutical composition comprising the extracts of Plectranthus amboinicus and Centella asiatica as well as a wound dressing comprising the same. The invention also provides a method for preparing the crude extract and extract of Plectranthus amboinicus.

Description of the Invention

FIELD OF THE INVENTION

The present invention relates to Chinese herbal medicine extracts. Specifically, the present invention relates to the use of the extracts of Plectranthus amboinicus Benth and Centella asiatica Urban for treating skin disorders, including enhancing the healing of wounds for diabetic patients.

BACKGROUND OF THE INVENTION

Plectranthus amboinicus Benth (Patchouli), growing in Malaysia and India, is a decorative medicinal herb commonly cultivated by common families. The medicinal part of Plectranthus amboinicus Benth is the epigeal portion. Plectranthus amboinicus Benth is also known as Cuban oregano, Indian borage, Indian mint, Mexican mint, Mexican oregano or Spanish thyme. The Eastern Indians use Plectranthus amboinicus Benth as fabric aromatics, and the English discovered its attractive fragrance when importing shawl fabrics from India in the 1820's. When the Plectranthus amboinicus Benth leaves are put directly with clothing, it not only has an aromatic effect, but also prevents the clothing from being eaten by moths. It is thought to have uses for disinfection, excitement and preventing insect bites. In addition, Plectranthus amboinicus Benth may be used for treating poisonous snake bites, and relieving symptoms such as headache, flatulence, vomiting, diarrhea and fever. Moreover, Plectranthus amboinicus Benth oil is a popular perfume in Asia, and it is used for improving epithelia regeneration, treating acne, and relieving the symptoms of eczema, Athlete's foot and dry cracking skin in aromatherapy. Furthermore, Plectranthus amboinicus Benth is a good tranquilizer and aphrodisiac that can relieve anxiety and enhance sexual desire.

Centella asiatica Urban (pennywort) is a plant naturally growing in the coast area of Madagascar and the Indian Ocean. The medicinal part of Centella asiatica Urban of the Apiaceae family is its dried whole plant. Centella asiatica Urban is also known as European water-marvel, Gotu kola, Kola, Indian pennywort, Indian ginseng, Horse-hoof grass, Pegaga, Mandookaparni, Tiger herbal, Spadeleaf, or Tono. For hundreds of years, Centella asiatica Urban has been thought to be useful in the traditional medicines for improving wound healing in Asian regions. The extracts of Centella asiatica Urban comprise two major compounds: asiaticoside and madecassic acid. The uses of Centella asiatica Urban extracts are in treating burn wounds, trauma, and preventing postoperative adhesion, and the preparation methods of Centella asiatica Urban extracts have been described in some patent applications. For example, U.S. Pat. No. 4,318,906 and CN 1353972A disclose the medical uses of Centella asiatica Urban as the single active ingredient; U.S. Pat. No. 6,475,536, U.S. Pat. No. 6,267,996, CN 1313124A, CN 93110425.4 and CN 1089497A disclose the use of Centella asiatica Urban in combination with other substances for cosmetic formulation, treating burns or making ointment for trauma; and U.S. Pat. No. 5,834,437, U.S. Pat. No. 6,417,349 and CN 1194154A disclose the methods for preparing Centella asiatica Urban extracts.

The functions of skin include protection, excretion, secretion, absorption, heat regulation, storage, sensation and immune process regulation. When a wound occurs on the skin, for example, a wound caused by general trauma or a bedsore, it will cause an adverse effect on the skin and interfere with its normal functions. Diabetes mellitus is a common and chronic worldwide disease. According to the statistical report of the Department of Health, Executive Yuan, Taiwan, R.O.C. published in 2002, mortality due to diabetes increased from 7.9 deaths per 100,000 persons in 1980 to 39.3 deaths per 100,000 persons in 2002. The most common diabetes complications are neuropathy and angiopathy. Autonomic neuropathy causes reduction of sweating and results in dry cracking skin. Sensory neuropathy makes the patient insensitive to pain. Angiopathy causes macro- or micro-vascular obstructions, poor circulation, and atrophy of the skin. Once the wound is infected in a diabetic patient, it is difficult to be treated because not only controlling the bacterial infection but also the healing of the wound must be achieved. The only commercial therapeutic medicine available on the market for healing of wounds for diabetic patients is the gene recombinant product PDGF Regranex Gel (Becaplermin 0.01%) and it is very expensive. Therefore, it is necessary to provide new medicaments for enhancing the healing of wounds for diabetic.

SUMMARY OF THE INVENTION

One of the purposes of the present invention is to provide a pharmaceutical composition for treating skin disorders (including enhancing the healing of wounds for diabetic patients), comprising a therapeutically effective amount of Plectranthus amboinicus Benth crude extracts/extracts and a therapeutically effective amount of Centella asiatica Urban extracts.

Another purpose of the present invention is to provide a use of a combination of Plectranthus amboinicus Benth crude extracts/extracts and Centella asiatica Urban extracts for the manufacture of a medicament for treating skin disorders.

Another purpose of the present invention is to provide a wound dressing comprising the pharmaceutical composition of this invention.

Still another purpose of the present invention is to provide a method for preparing Plectranthus amboinicus Benth crude extracts/extracts.

A further purpose of the present invention is to provide a method for treating a skin disorder comprising administering a pharmacologically effective amount of a pharmaceutical composition of this invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is characterized by using the combination of Plectranthus amboinicus Benth crude extracts/extracts and Centella asiatica Urban extracts for treating skin disorders including enhancing the healing of wounds for diabetic patients.

The present invention herein provides a pharmaceutical composition for treating skin disorder (including enhancing the healing of wounds for diabetic patients), comprising a therapeutically effective amount of Plectranthus amboinicus Benth crude extracts/extracts and a therapeutically effective amount of Centella asiatica Urban extracts. Said pharmaceutical composition can be used for treating disorders including but not limited to wounds and sores. In one preferred embodiment, said disorders are general trauma and bedsores, more preferably a diabetic patient's wound.

The pharmaceutical composition of the present invention can be applied topically to the wounds, and it may be formulated as a spray or non-spray. A spray form includes spray or solution; a non-spray form may be semi-solid or solid, preferably a solid form having a kinematic viscosity greater than water. Suitable formulations include but are not limited to suspensions, emulsions, creams, ointments, liniments and the like. If necessary, it may be sterilized or mixed with any pharmaceutically acceptable carriers, for example, stabilizers, wetting agents and the like. Preferably, the pharmaceutical composition of the invention is formulated as ointments, wherein the preferred pharmaceutically acceptable carriers include but are not limited to higher fatty acids, waxes, lipids, glycerol, higher alcohols or synthetic lipids. The pharmaceutical composition of the present invention, no matter which form it is formulated in, may further comprise emollients, fragrances or colors to increase the acceptability for various uses.

The pharmaceutical composition of the present invention may be conveniently used for manufacturing a wound dressing comprising a therapeutically effective amount of Plectranthus amboinicus Benth crude extracts/extracts and a therapeutically effective amount of Centella asiatica Urban extracts, wherein said wound dressing includes but is not limited to a bandage with adhesive, plaster patch and the like.

The pharmaceutical composition of the present invention may be prepared by persons of ordinary skill in the art using conventional methods. One embodiment of the present invention includes a method of preparing an ointment comprising the following steps: heating the ointment base (BETAMETHASONE ointment base, Sinphar; Taiwan) in a water bath at about 50.degree. C. until softened; adding the softened ointment base in turn into the beaker containing frozen dried Plectranthus amboinicus Benth extracts; adjusting the amount of ointment base and Plectranthus amboinicus Benth extract, the weight ratio being 99.75:0.25, to make the 0.25% Plectranthus amboinicus Benth extract ointment; homogenously mixing 0.25% Plectranthus amboinicus Benth extract ointment and Centella asiatica Urban extracts in a weight ratio of 97:3 to make the 3% Centella asiatica Urban extract+0.25% Plectranthus amboinicus Benth extract ointment; and storing the ointment at 4.degree. C. in a refrigerator.

The preparation method for the Centella asiatica Urban extracts, the active component in the pharmaceutical composition of the present invention, is well known to persons of ordinary skill in the art of herbal medicine extraction. The preferred method comprises: extracting Centella asiatica by ethanol reflux extraction for 2 hours, and repeating it 2 to 3 times; condensing the ethanol extract fluids to obtain the extracts; retrieving the ethanol extracts, mixing and dissolving the extracts in water; extracting with petroleum ether, chloroform, ethyl acetate separately, and then extracting with water-saturated n-butanol; retrieving the solvent of n-butanol extracts under reduced pressure to obtain a cream-like substance and dissolving the substance in a small amount of methanol; adding anhydrous acetone, several-fold, to the solution, to precipitate a yellowish crude total glucoside, drying and weighting the sediments; a small amount of methanol is added to dissolve the crude total glucoside, mixing properly with silica gel and drying the mixture; wet column packing with silica gel for chromatography and loading the sample silica gel; eluting with chloroform, methanol and water (16:6:1 homogenous mixture) and collecting 18 components in turn; each component is 50 ml and the components are thin-layer spotting to compare with known controls; combining components 9 to 15, concentrating, and then purifying with column using chloroform, methanol and water (14:6:1 homogenous mixture) for elution; and concentrating the same components and crystallizing with methanol repeatedly to obtain the white aciculate crystalline asiaticoside.

Furthermore, the drug substance containing asiaticoside and madecassic acid, with a purity greater than 70%, is available on the market.

The present invention also provides the preparation methods for Plectranthus amboinicus Benth crude extracts and extracts.

Preparation of Plectranthus amboinicus Benth Crude Extracts

Wash the fresh drug substances of Plectranthus amboinicus Benth with water, then extract the juice with a juice extractor. Freeze-dry the Plectranthus amboinicus Benth juice to obtain dry powders. Use a suitable solvent, for example, chloroform or methanol, to extract the Plectranthus amboinicus Benth crude extracts.

Preparation of Plectranthus amboinicus Benth Extracts

Dip a fixed amount of Plectranthus amboinicus Benth dry materials in a proper amount of high-polarity solvent. After filtration, dip again with a proper amount of high-polarity solvent and concentrate the Plectranthus amboinicus Benth extract solution with a reduced pressure rotary evaporator until its volume is 2-3% of the original volume. Dilute with solvent and separate by column. Optionally, it can be eluted continuously with four different solvents comprising high- to low-polarity solvents (namely high-polarity solvent, sub-high-polarity solvent, medium polarity solvent and low-polarity solvent). According to the present invention, high-polarity solvents include but are not limited to water, methanol, isopropanol, or a mixture of two or more of the preceding solvents. Low-polarity solvents include but not are limited to chloroform, acetone, ethyl acetate, or a mixture of two or more of the preceding solvents. Preferably, column chromatography separation is conducted using methanol-treated DIAION column. For example, dip DIAION, which has the same weight as the dried Plectranthus amboinicus Benth, in methanol, and pack the methanol-treated DIAION into chromatography column. After pack, washing DIAION with methanol (one- to two-fold volume) then wash DIAION with double distilled water (five- to six-fold volume) and the packing is done.
 

Claim 1 of 8 Claims

1. A pharmaceutical composition comprising a therapeutically effective amount of Plectranthus amboinicus Benth crude extracts or Plectranthus amboinicus Benth extracts and a therapeutically effective amount of Centella asiatica Urban extracts, wherein the Plectranthus amboinicus Benth crude extracts and Plectranthus amboinicus Benth extracts are obtained by a method comprising the steps of: (a) extracting juices from whole Plectranthus amboinicus Benth plants directly with alcohol; (b) concentrating the Plectranthus amboinicus Benth juices to obtain Plectranthus amboinicus Benth crude extracts; (c) eluting the Plectranthus amboinicus Benth crude extracts with solvents by column separation; and (d) partially separating the solvent-eluted Plectranthus amboinicus Benth crude extracts to obtain Plectranthus amboinicus Benth extracts; wherein the Plectranthus amboinicus Benth crude extracts have the following HPLC peak of retention time -- see Original Patent.
 

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