JPS6121527B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an external preparation for treating bedsores, which is in the form of a powder and contains aluminum chlorohydroxyalantonate in an amount of 0.1 to 20% by weight based on the entire preparation. BACKGROUND OF THE INVENTION Various ointments have been known as external preparations for the treatment of lesions and ulcers on the skin and mucous membranes caused by burns and injuries, and some are used for actual treatment. However, in addition to the active ingredients, ointments contain fat, fatty oil, lanolin, petrolatum, paraffin, wax, glycols, higher alcohols, glycerin, surfactants, and the like as an ointment base. Therefore, even though it can be easily applied to areas such as burns and injuries,
During the healing process, it is difficult to absorb exudate from the injured area and dry the affected area, and there has been a real medical need for the development of external preparations that eliminate this drawback. In view of the above-mentioned circumstances, the inventors of the present invention have conducted intensive studies and found that if aluminum chlorohydroxyallantoinate is blended into a powder, it will exhibit an excellent effect of promoting healing of injured areas, etc., and will also have astringent and covering effects. It has been found that it is useful in the treatment of ulcers and ulcers on the skin and mucous membranes. In addition, by using a powder, it also absorbs exudate from the injured area, causing dryness of the affected area, and does not cause the hygroscopic softening seen with conventional ointments, and does not cause the so-called "stickiness" phenomenon. It has been found that it can be treated effectively. Furthermore, for long-term patients, there has been a strong desire for a drug that can treat bed sores that occur due to pressure while bedridden. It was found to be significantly effective in the treatment of animal models of bedsores caused by the disease, and clinical experiments also revealed that it is extremely effective in treating bedsores. As a result, this external preparation was the first to be approved for pharmaceutical manufacturing as an excellent external preparation that also has a bed sore treatment effect. The amount of aluminum chlorohydroxyallantoinate, which is the active ingredient of the external preparation of the present invention, in the powder is not particularly limited;
The amount is 0.1 to 20% by weight, more preferably 2 to 10% by weight based on the total amount of the preparation. Excipients other than aluminum chlorohydroxyallantoinate to be blended into the powder of the present invention include excipients as powder bases, specifically talc, wheat starch, rice starch, corn starch, and potato starch. , zinc stearate, magnesium stearate, zinc oxide, kaolin, precipitated calcium carbonate, magnesium carbonate, bentonite, light anhydrous silicic acid, titanium oxide, dry potassium aluminum sulfate, etc., and these excipients may be used singly or in appropriate combinations. It can be used by Furthermore, a preservative can be added to the powder of the present invention, and specific examples thereof include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate. The powder base compounded in the powder is not limited to the above, and from various viewpoints, it is also possible to add drugs having other characteristics. For example, if the powder is intended to have a bactericidal effect, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, etc. can be added. The method for producing the powder for external use according to the present invention can be carried out by conventional methods for producing powders that are widely used in pharmaceuticals, for example, by mixing the raw materials in a V-type mixer, an S-type mixer, or the like. Next, a method for producing the external preparation of the present invention will be shown in Examples, which are not intended to be particularly limited. Example 1 Aluminum chlorohydroxyallantoinate 60 parts by weight Magnesium carbonate 40 parts by weight Ethyl paraoxybenzoate 2 parts by weight Corn starch Appropriate amount Total 1000 parts by weight Corn starch previously dried at 60°C for 16 hours and each raw material were weighed. The mixture is then mixed in a V-type mixer, further sieved in a sieve (30 mesh), and V-type mixed again to mix the whole mixture uniformly. External powders of Examples 2 to 6 were obtained using the same manufacturing method. Example 2 Aluminum chlorohydroxyallantoinate 60 parts by weight Ethyl paraoxybenzoate 2 parts by weight Corn starch Appropriate amount Total 1000 parts by weight Example 3 Aluminum chlorohydroxyallantoinate 60 parts by weight Dry aluminum hydroxide gel 100 parts by weight Paraoxybenzoic acid Ethyl 2 parts by weight Corn starch Total appropriate amount 1000 parts by weight Example 4 Aluminum chlorohydroxyallantoinate 60 parts by weight Magnesium carbonate 20 parts by weight Dry aluminum hydroxide gel 100 parts Ethyl paraoxybenzoate 2 parts by weight Corn starch Total appropriate amount 1000 Parts by weight Example 5 Aluminum chlorohydroxyallantoinate 60 parts by weight Zinc stearate 50 parts by weight Ethyl paraoxybenzoate 2 parts by weight Corn starch Appropriate amount Total 1000 parts by weight Example 6 Aluminum chlorohydroxyallantoinate 60 parts by weight Magnesium stearate 50 parts by weight Ethyl paraoxybenzoate 2 parts by weight Corn starch Appropriate amount Total: 1000 parts by weight Next, the results of pharmacological tests of the external preparations obtained in the above examples will be described. Among the toxicity tests, the acute toxicity and chronic toxicity are the results obtained when aluminum chlorohydroxyallantoinate itself, which is incorporated into the external preparation of the present invention, was used alone. Toxicity test 1 Acute toxicity (intraperitoneal, oral administration) Aluminum chlorohydroxyallantoinate was administered at each dose of 0.5, 1.0, 2.0, 4.0 g/Kg to mice (intraperitoneal) and rats (intraperitoneal, oral). Death cases were observed after a week. The results are shown in Table 1.

[Table] As is clear from the results in the table, aluminum chlorohydroxyallantoinate is highly safe. 2. Subacute Toxicity (Administration at Rat Wound Site) 1 cm ² skin defects were created in three places on the back skin of rats, and the external preparation obtained in Example 1 was administered at 0 (no administration) and 0.04 g/body (in one wound area). ),
0.08g/body (administered to two wound surfaces) and
The drug was administered at a rate of 0.12 g/body (administered to three wound surfaces) twice a day for 14 days from the day of wound creation and observed. Seven rats were used in each experimental group. No deaths were observed in any of the experimental groups, and no effects of drug administration were observed on body weight changes. On the 15th day after administration, histopathological observations of the whole body organs of rats in each experimental group were performed. As a result, no abnormal findings were observed in any organ tissues, except for spontaneous lesions unrelated to drug administration in the lungs. 3. Chronic toxicity (oral administration to rats) Rats were fed feed containing 2.5%, 5%, and 10% aluminum chlorohydroxyallantoinate for 6 months, and no deaths were observed when compared with the control group. Also, organ findings,
No abnormalities were observed in blood findings. Ten%
A tendency to suppress body weight gain was observed only in the treated group (approximately 13 g/Kg in body weight), but no abnormalities that could be attributed to drug administration were found in other test findings. Local Irritation The local irritation effect of the external preparation obtained in Example 1 was observed using the ocular mucosa, healthy skin, and injured skin from which the stratum corneum was removed from rabbits, which are highly sensitive to irritating substances. As a result, in the ocular mucosa, there were cases of slight transient redness of the conjunctiva, but no effect on the cornea was observed. In patch tests on the skin, some cases showed slight redness, but all were temporary, and no bleeding or irritation was observed even on the injured skin. Although Solcoseryl ointment and Fracentin T powder were used as control drugs, only slight redness comparable to that of the external preparation obtained in Example 1 was observed in both control drugs. From the above results, the external preparation obtained in Example 1 does not exhibit any worrying local irritation effects. Pharmacology 1 Effect on wound treatment A circular skin defect was created on the rat dorsal skin.
The external preparation obtained in Example 1 and the base excluding the aluminum chlorohydroxyallantoinate of Example 1 were administered at 0.04 g per 1 cm ² of the wound surface, and as a control drug, Solcoseryl ointment was administered at 0.12 g twice a day.
The effect on wound healing was investigated by spraying or applying the compound twice until healing. Treatment with the external preparation obtained in Example 1 promoted wound healing and showed superior effects in shortening the healing time compared to the control drug. The results are shown in Table 2 and FIG.

[Table] 2. Antibacterial activity The antibacterial activity of aluminum chlorohydroxyallantoinate contained in the external preparation of the present invention was measured by the plate dilution method using SDC medium. The results are shown in Table 3.

[Table] As is clear from the table, the growth of various bacteria and fungi is suppressed at a concentration of 2%. Next, the clinical effects of the external preparation of Example 1 of the present invention will be described. Clinical case: Example 1 for 8 patients with pressure ulcers in long-term treatment.
The external preparation was sprayed once or twice a day. Patients with bedsores were observed for one month after the start of spraying, and the therapeutic effects were evaluated using the following criteria. Significant effects: Significant reduction in ulcer size, granulation, epidermis formation, and exudate reduction, or almost cured condition. Effective: A clear reduction in ulcer size, granulation, epidermis formation, and exudate. Moderately effective: Slight improvement in ulcer, granulation, epidermis formation, or exudate. Unchanged: No improvement or deterioration was observed. Worsening: Increased ulceration. As a result, the following results were obtained in 8 patients with bedsores. Effectiveness Example: Effective in 1 case, Somewhat effective in 3 cases, No change in 2 cases, Worsening in 2 cases - Total of 8 cases.

[Brief explanation of the drawing]

FIG. 1 shows the influence of the external preparation of Example 1 of the present invention on the progress of wound healing in terms of the relationship between the wound area and the number of days for wound healing.

Claims (1)

[Claims] 1. An external preparation for the treatment of bedsores, which is in the form of a powder and contains aluminum chlorohydroxyallantoinate in an amount of 0.1 to 20% by weight based on the entire preparation.