TW202404621A - Use of mangosteen fruit shell extract in the preparation of a medicament for burn wound therapy - Google Patents

Abstract

A use of a composition in preparation of a medicament for burn wound therapy is provided, wherein the composition comprises an effective amount of mangosteen fruit shell extract.

Description

Use of mangosteen husk extract in preparing medicine for treating burns and scald wounds

The present invention relates to the use of a composition for preparing a medicament for treating burns and scald wounds.

The skin is the largest organ of the human body, and there are many types of skin diseases. Skin diseases may be acute (lasting only minutes to hours) or chronic conditions, which may affect an individual for days, months, years or even a lifetime. Skin diseases may It may be a fungal, bacterial, or viral condition, or it may be a non-infectious, immune response, such as an inflammatory reaction with or without allergens, or it may be an idiopathic disease. As a result, symptoms may vary and may range from mild itching, redness and swelling to severe pus and open pain, such as damaging sores, and skin disorders may substantially impact an individual's quality of life.

Burns and scalds are caused by high temperatures, generally dry heat (such as flames), moist heat (such as steam, hot water), radiant heat (such as sunlight), friction, contact with high-temperature objects, electrical appliances, chemicals, etc. The degree of burn is usually determined based on the depth and area of the burn injury. The degree of burn and scald can be divided into five levels.

Most minor burns and scalds (Grade 0-2) can be treated at home, however, for severe burns and scalds, clinical treatment is necessary and includes hydrotherapy, fluids to prevent dehydration, pain relief and anxiety medications, burn and scald creams and ointments, and dressings , debridement and skin grafting, etc. If the area of damage is large, especially if it covers any joints, physical and occupational therapy training may be required.

Mangosteen has been studied in areas such as breast cancer prevention and muscle-related diseases. It has also been developed as nutritional supplements and cosmetics for daily life, and is also used to treat acute hepatitis, liver fibrosis and prevent cirrhosis.

Matsumoto et al. also studied the purification of α-mangostin, β-mangostin, γ-mangostin, and methyl-β-mangostin from mangosteen husks, and studied the effects of these compounds on the cell cycle. The inhibitory effects at each stage show that the compound has anti-cell proliferation and anti-tumor effects (Bioorg. Med. Chem. 2005, 13, 6064-6069).

The present invention provides the use of a composition for preparing a pharmaceutical composition for treating skin diseases.

Specifically, the present invention provides the use of a composition for preparing a medicament for treating burns and scald wounds, wherein the composition contains an effective dose of mangosteen husk extract. The drug may also be used as a topical treatment, medical device or precision therapy.

Mangosteen husks consist of a softer inner husk and a harder outer husk.

In a preferred embodiment, the mangosteen husk is extracted using a solvent, and the extraction solvent is selected from the group consisting of methanol, ethanol, n-propanol, 2-propanol, n-butanol, acetone, ethyl acetate and water. group.

In another preferred embodiment, the mangosteen husk extract includes mangosteen husk water extract and/or mangosteen husk alcohol extract.

In a preferred embodiment, the mangosteen husk extract is a water extract of mangosteen husk.

In another preferred embodiment, the mangosteen husk extract is a mangosteen husk alcohol extract.

In a preferred embodiment, the mangosteen husk includes the outer husk/inner husk of mangosteen husk and/or the whole husk of mangosteen husk.

In another preferred embodiment, the mangosteen husk is the outer husk of the mangosteen husk.

In a preferred embodiment, the composition of the present invention can be an oral or parenteral preparation. The parenteral preparation can be a topical preparation. The topical preparation can be a cream, cream, ointment, gel, lotion, etc. agent or patch.

In a preferred embodiment, the mangosteen husk extract of the present invention contains α-mangostin and γ-mangostin.

In another preferred embodiment, the mangosteen husk aqueous extract of the present invention contains α-mangostin and γ-mangostin.

In another preferred embodiment, the mangosteen husk alcohol extract of the present invention contains α-mangostin and γ-mangostin.

The "effective dose" as used in the present invention refers to a dose that achieves an effective result when administered to an individual, or a dose that possesses the desired activity in vivo or in vitro. In the context of burn wound treatment, effective clinical outcomes include equivalent or better improvement in the degree or severity of burn-related symptoms, and/or prolongation of the individual's lifespan, and/or improvement of the life expectancy of the individual compared with currently used drugs. individual quality of life. The precise amount of compound administered to an individual will depend on the type and severity of the disease or condition, as well as individual characteristics such as the individual's general health, age, gender, weight, and tolerance to the drug. It also depends on the severity and type of the wound. Those skilled in the art will be able to determine appropriate dosages based on these and other factors.

In one embodiment, the effective dose of the mangosteen husk extract of the present invention is 0.5% (w/w) to 10% (w/w); in a preferred embodiment, the mangosteen husk extract of the present invention The effective dose is 1% (w/w) to 5% (w/w); in the best implementation, the effective dose of the mangosteen husk extract is 1.25% (w/w) to 2.5% (w/ w).

The pharmaceutical composition of the present invention can be formulated into various oral or parenteral preparations. Oral preparations can be formulated into solid preparations, such as powders, granules, tablets, capsules, etc., or into liquid preparations, such as suspensions, emulsions, syrups, etc. Parenteral preparations can be formulated into topical preparations, such as creams, ointments, gels, lotions, patches, etc., or inhalants, aerosols, suppositories, etc.

The pharmaceutical composition of the present invention may contain pharmaceutically acceptable excipients, in particular, may further contain a predetermined solvent or oil, a pH adjuster, and, if necessary, a dispersant.

Examples of solvents used in the present invention include, but are not limited to, water, ethanol, isopropyl alcohol, 1,3-butanediol, propylene glycol, glycerol, etc.

Examples of oils useful in the present invention are selected from the group consisting of corn oil, sesame oil, linseed oil, cottonseed oil, soybean oil, peanut oil, mono-glycerides, di-glycerides, tri-glycerides, mineral oil, and deep-sea fish mackerel. Squalene, jojoba oil, olive oil, evening primrose oil, borage oil, grape seed oil, coconut oil, sunflower oil, shea butter and any combination thereof groups formed, but not limited to this.

Solvents and oils can be used alone or in any combination.

Examples of useful dispersants may include lecithin, organic monoglycerides, sorbitan fatty acid esters, polyoxyethylene fatty acid esters, sorbitan stearate, etc., but are not limited thereto. These raw materials can also be used alone or in any combination.

If desired, the composition may further comprise additional ingredients such as antimicrobial agents or Preservatives.

At the same time, conventional active ingredients can be used simultaneously with the composition, as long as they do not have any adverse effect on the pharmaceutical activity of the composition of the present invention. For example, moisturizers such as ceramide, commonly known as atopic dermatitis agents, or liquid ingredients such as steroids such as hydrocortin, vitamin A derivatives such as vitamin A palmitate and/or Tocopherols and the like can be used with the composition.

When the pharmaceutical composition is used as an external preparation, an appropriate skin external preparation can be used as the basic raw material. Aqueous solutions, non-aqueous solvents, suspensions, emulsions or freeze-dried preparations can be used and sterilized according to common methods.

In the actual administration or administration of the composition of the present invention, the dosage may be determined according to various factors such as the route of administration, age, gender, and weight of the patient, as well as the severity of the disease and the dosage form as the active ingredient.

Where the composition of the present invention may be a food or cosmetic composition, the composition may be prepared by suitably adding at least one food supplement or cosmetically acceptable carrier.

The food composition can be used in or added to, for example, health foods. As used herein, the term "healthy food" means a food containing the composition of the present invention that has enhanced functions compared to ordinary food. Healthy foods can be prepared by adding the composition to general foods, or by encapsulation, powdering or suspension.

The cosmetic composition may be added by itself or together with other cosmetic ingredients, or may be used appropriately according to other conventional methods. Cosmetics include, but are not limited to, aftershaves, lotions, creams, facial masks and makeup.

Cosmetic compositions can be formulated into various composition forms, such as gels, creams, Ointments etc. Compositions in the form of gels, creams and ointments may be suitably prepared according to the form of the composition using known methods by adding conventional softeners, emulsifiers and thickeners or other raw materials known in the art.

Compositions in gel form can be prepared, for example, by adding softeners such as trimethyl alcohol propane, polyethylene glycol and glycerol, solvents such as propylene glycol, ethanol and isocetyl alcohol, and pure water.

Compositions in cream form can be prepared, for example, by adding fatty alcohols, such as stearyl alcohol, myristyl alcohol, behenyl alcohol, arachidyl alcohol, isostearyl alcohol and isocetyl alcohol; emulsifiers, such as lipids , such as lecithin, phosphatidyl choline, phosphatidyl ethanolamine, phospholipid serine, phosphatidylinositol and its derivatives, glyceryl stearate, sorbitol palmitate, sorbitol stearate, etc.; natural fats and oils, such as avocado oil, almond oil, babassu oil, borage oil, camellia oil, etc.; lipid compositions, such as ceramide, cholesterol, fatty acids, phytosphingosine, lecithin, etc.; Solvents, such as propylene glycol, etc.; and pure water.

Compositions in the form of ointments can be prepared, for example, by adding softeners, emulsifiers and waxes, such as microcrystalline wax, paraffin, ceresin, beeswax, spermaceti, petroleum jelly and the like.

In another aspect, the present invention provides a method of using the composition to prepare a medicament for the treatment of burn and scald wounds. As used herein, the term "treatment or alleviation" means halting or delaying the course or symptoms of a disease when administered to a patient.

Figure 1 shows the positive control group (existing commercial drug; 1% sulfadiazine cream), 2.5% whole fruit shell extract, 5% whole fruit shell extract and 10% whole fruit shell extract of the present invention on the 12th day. therapeutic effect of the substance. Different letters shown at the top of the histograms indicate significant differences ( p < 0.05 ) from each other.

Figure 2 shows the positive control group (existing commercial drug; 1% sulfadiazine cream), 2.5% whole fruit shell extract, 5% whole fruit shell extract and 10% whole fruit shell extract of the present invention on the 27th day. therapeutic effect. Different letters shown at the top of the histograms indicate significant differences ( p < 0.05 ) from each other.

Figure 3 shows the positive control group (existing commercial drug; 1% sulfadiazine cream), 2.5% whole fruit shell extract, 2.5% inner fruit shell extract, and 2.5% outer fruit shell of the present invention on the 27th day. The therapeutic effects of extract, 5% whole husk extract, 5% inner husk extract and 5% outer husk extract. Different letters shown at the top of the histograms indicate significant differences ( p < 0.05 ) from each other.

Figure 4 shows the therapeutic effects of the present invention on day 12 of the positive control group (existing commercial drug; 1% sulfadiazine cream), 1.25% whole fruit shell extract and 2.5% whole fruit shell extract. Different letters shown at the top of the histograms indicate significant differences ( p < 0.05 ) from each other.

Figure 5 shows the therapeutic effect of the present invention on the 27th day of the positive control group (existing commercial drug; 1% sulfadiazine cream), 1.25% whole fruit shell extract and 2.5% whole fruit shell extract. Different letters shown at the top of the histograms indicate significant differences ( p < 0.05 ) from each other.

The following embodiments are non-limiting and merely represent aspects and features of the invention.

Experimental example

Material

Preparation of test drugs

Take the mangosteen husk, dry the husk to 50%~95%, extract it with a solvent (such as water or 10%~95% alcohol), and concentrate to obtain the mangosteen husk extract.

Separate the outer husk and inner husk of the mangosteen husk, dry the outer husk and inner husk of the mangosteen husk respectively to 50%~95%, and use a solvent (such as water or 10%~95% alcohol) Carry out extraction and concentration to obtain the outer husk extract of mangosteen husk and the inner husk extract of mangosteen husk.

Pastes or ointments of different concentrations are prepared using mangosteen whole fruit shell alcohol extract and water extract, mangosteen fruit outer shell, mangosteen fruit inner shell alcohol extract and water extract as raw materials.

experimental animals

The present invention uses adult (7-8 weeks old) male Sprague ^Dawley® rats with an average body weight of 250-350g. Tail-notch and cage tags are used for animal identification. Animals with the same treatment were housed in polycarbonate cages under the following conditions: temperature maintained at 22 ± 4 °C; humidity maintained at 30%-70%; 12 h/12 h light/dark cycle. Food and water were provided ad libitum throughout the study.

method

Before the start of treatment, 24 rats were randomly divided into specific drug administration groups. These rats were divided into 4 groups, namely: positive control group (given 1% Sulfasil Cream), 2.5% whole fruit shell extract group, 5% whole fruit shell extract group and 10% whole fruit shell extract group .

All rats were treated with 3~4% isoflurane anesthesia, and then, under sterile conditions, the rats were burned with a 92°C brass rod at two different locations on the back of each animal (marked L and R respectively). 12 seconds to form a uniform, 2 cm diameter partial thickness dermal burn wound, and then apply test and control articles daily. 20.29 mg/cm2/day (each wound area is 3.14 cm ² ) of test drug or 1% Sulfasil Cream was applied topically to the burn area once daily.

All body weight values were calculated on day 0 (before dosing), days 7, 14, 21, and 27 after dosing, and on days 1, 2, 3, 5, 7, 9, 12, 15, 19, 21, 24 and 27 days calculation Percent wound closure, the reduction in wound area expressed as a percentage of the original wound size. Comparisons between groups were performed by one-way ANOVA, and Duncan's t post hoc tests were used for comparisons between all groups. A p value less than 0.05 was considered statistically significant. The above analysis was completed by using a statistical analysis system (SPSS, Vision 26.0, IBM Inc.) configured for computers.

There were no significant differences in the body weight of each rat recorded during the study.

The wound closes by shrinkage and generation of newly formed epithelial covering. Macroscopic and microscopic assessment of wound closure rate measured wound area by tracing the wound edges on graph paper every two days. The wound closure rate is expressed as the percentage reduction of the wound area on day N compared to the original wound size. The calculation formula is as follows: Wound closure percentage on day N = [(area on day 0 - wound area on day N)/day 0 Wound area]×100.

According to the reference published in Frontier in Bioscience (Diegelmann et al., 2004), a five-stage classification of skin wound healing categories was used:

On days 12 and 27, the wound healing rates (%) and wound healing observation results of the four groups are shown in Table 1 and Figures 1 to 2.

Table 1

The results on the 12th day showed that compared with the positive control group, the wound healing speed of 2.5% whole fruit shell extract, 5% whole fruit shell extract, and 10% whole fruit shell extract was significantly slower than that of the positive control group ( p < 0.05 ), where 5% whole husk extract and 10% whole husk extract healed much slower.

However, on the 27th day, the results of the wound healing rate showed that the 2.5% whole fruit shell extract group and the 5% whole fruit shell extract produced equivalent therapeutic effects to the positive control group, and the 2.5% whole fruit shell extract group The curative effect of retrieval is better.

According to the above results, 2.5% and 5% mangosteen whole husk extract showed better therapeutic effects, so this study further evaluated 2.5% and 5% mangosteen outer husk extract and mangosteen inner husk extract. Efficacy of extracts in the treatment of burn wounds. As shown in Figure 3, the wound healing rate (%) results showed that 2.5% and 5% mangosteen outer shell extract showed better therapeutic effects than other groups on the 27th day.

It is worth noting that all results show that the therapeutic effect of mangosteen husk extract on burns and scald wounds is not dose dependent. On the contrary, lower doses of mangosteen husk extract show better therapeutic effects. Therefore, the present invention The potential of lower doses of mangosteen husk extract to treat burn and scald wounds was further evaluated.

The present invention further compares 1.25% mangosteen husk extract with positive control and 2.5% mangosteen husk extract. The results are shown in Figures 4 and 5. On the 12th day, the efficacy of 1.25% mangosteen husk extract was better than that of 2.5% mangosteen husk extract, and on the 27th day, the efficacy of 1.25% was significantly better than the positive control and 2.5% mangosteen husk extract. Therapeutic effects of extracts.

In addition, 1.25% mangosteen husk extract also showed the best therapeutic effect (not shown in the figure).

While the invention has been described and exemplified in sufficient detail to enable those of ordinary skill in the art to make and practice it, it will be apparent that various substitutions, modifications and improvements can be made without departing from the spirit and scope of the invention. of.

It will be readily understood by those of ordinary skill in the art that the present invention is well adapted to carry out the stated objects and to obtain the objects and advantages mentioned and those inherent therein. Cells, animals, and processes and methods for producing them represent best embodiments only and are illustrative are not intended to limit the scope of the present invention. Modifications and other uses may be conceived by those of ordinary skill in the art, and these modifications are included in the spirit of the invention and are limited by the scope of the patent application.

Claims (10)

A composition is used to prepare a medicament for treating burns and scald wounds, wherein the composition includes an effective dose of mangosteen husk extract. The use as described in claim 1, wherein the mangosteen husk extract contains mangosteen husk water extract and/or mangosteen husk alcohol extract. The use as described in claim 1, wherein the mangosteen husk contains the outer husk of the mangosteen husk and/or the inner husk of the mangosteen husk. The use as described in claim 1, wherein the mangosteen husk is the outer husk of the mangosteen husk. The use as described in claim 1, wherein the mangosteen husk extract contains α-mangostin (α-mangostin) and γ-mangostin (γ-mangostin). The use as claimed in claim 1, wherein the composition is a parenteral preparation. The use as claimed in claim 6, wherein the parenteral preparation is an external preparation. The use as claimed in claim 1, wherein the effective dose is 0.5% w/w to 10% w/w. The use as claimed in claim 1, wherein the effective dose is 1% w/w to 5% w/w. The use as claimed in claim 1, wherein the effective dose is 1.25% w/w to 2.5% w/w.

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