JPH10120557A - Substance for treating wound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject substance comprising deferoxamine and effective for the therapy of wounds. SOLUTION: This substance for treating wounds comprises deferoxamine of formula I (R' is a group of formula II) or its salt. A wound-treating medicine contains the wound-treating substance in an amount of 10<-5> to 50wt.% as an active ingredient. The compound of formula I is obtained by culturing a deferoxamine-producing strain belonging to the genus Streptomyces or by a synthetic method. The medicine is administered at a daily dose of 10ng to 1g/Kg as the wound-treating substance with one to four portions. Although the wounds of surface tissues are generally refractory, and can sufficiently not be cured with existing medicines, the medicine containing the compound of formula I is highly effective.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound treatment substance comprising a specific compound and a wound treatment agent containing the substance as an active ingredient.

[0002]

BACKGROUND OF THE INVENTION Wounds are damages to surface tissue such as surgical incisions, gastrointestinal ulcers, burns, lacerations, or skin ulcers (such as pressure sores). As a method of treating a wound, it is a common practice to give emergency treatment to the injured part and then wait until the injured part is healed by the natural resilience of the living body. However, it takes a long time to recover, and the pain of the patient, including pain, is not uncommon. Therefore, it is desired to actively and directly promote healing without relying on natural healing. Wound healing generally depends on the formation of new connective tissue and epithelial tissue by cell proliferation, and it is considered that an agent that stimulates or promotes the differentiation and proliferation process of cells involved in wound healing is effective.

[0003] Hitherto, as an agent exhibiting the action of promoting wound healing, calf blood extract (solcoseryl) (applied pharmacology, 2
2, 565-579, 1981) and tocoretinate (orsenone ointment) (Applied Pharmacology, 43, 121-1)
27, 1992).

[0004]

However, the above-mentioned wound (damage to the surface tissue) is generally intractable, and the existing drugs often do not show a sufficient clinical effect.

[0005] In view of the above, an object of the present invention is to provide a highly effective wound treatment substance and a wound treatment agent.

[0006]

Means for Solving the Problems As a result of repeated studies to achieve the above object, the present inventors have found that deferoxamine or a pharmaceutically acceptable salt thereof can be used in wound wounds, as can be seen from the results of pharmacological tests described below. The present inventors have found that the present invention is effective for treatment and completed the present invention.

That is, according to the present invention, deferoxamine represented by the formula (I)

Embedded image Alternatively, a wound treatment substance comprising a pharmaceutically acceptable salt thereof is provided.

According to the present invention, there is also provided a wound healing agent comprising the above wound healing substance as an active ingredient.

[0009] Deferoxamine, which is a wound treatment substance of the present invention, is a known compound. For example, its salt, deferoxamine mesylate, is used for treating iron overload. However, it has never been known that these compounds have a wound treatment effect.

[0010] Deferoxamine is a deferoxamine-producing strain belonging to the genus Streptomyces, such as Streptomyces pirosus.
pirosus, stored as JCM4403 at RIKEN, and in the United States, stored as ATCC19797).
Oleg et al. (Helv, Chim, Acta, 4
5, 31, 1962). In addition, its salt, deferoxamine mesylate, is commercially available as a reagent or pharmaceutical and is available.

[0011] Examples of the pharmaceutically acceptable salts of deferoxamine include conventional non-toxic acid addition salts. More specifically, an inorganic acid addition salt (for example,
Hydrochloride, hydrobromide, sulfate, phosphate, etc.), organic carboxylic acid addition salt or organic sulfonic acid addition salt (eg, formate, acetate, trifluoroacetate, maleate, tartrate, methane) Sulfonate, benzene sulfonate,
p-toluenesulfonate, etc.) and salts with basic or acidic amino acids (eg, arginine, aspartic acid, glutamic acid, etc.).

To formulate the wound healing substance according to the present invention, it is usually in the form of a pharmaceutical composition together with a pharmaceutical carrier. As a carrier, a filler, a disintegrant, a bulking agent, a binder, a coloring agent, a flavoring agent, a pH adjusting agent, a solubilizing agent, a suspending agent, which are generally used for preparing a drug according to a dosage form, Examples thereof include buffers, stabilizers, preservatives, additives, surfactants, lubricants, excipients, antioxidants, dispersants, propellants, solubilizers, and solubilizers. It is also produced by a method in which deferoxamine or a pharmaceutically acceptable salt thereof is dissolved in an appropriate solvent, and deferoxamine or a salt thereof is used as it is to prepare a solution.

[0013] The unit dosage form of the wound healing agent formulated using the wound healing substance of the present invention may be, in addition to the above-mentioned liquid preparations, tablets, pills, drinking liquids, powders, suspensions, emulsions,
Granules, extracts, fine granules, syrups, dips, decoctions,
Eye drops, troches, cataplasms, liniments, lotions, eye ointments, plasters, capsules, suppositories, enemas, injections (solutions, suspensions, etc.), patches, ointments, jellies , Pasta, inhalant, cream, spray,
Examples include nasal drops and aerosols.

The amount of the present invention wound treatment material to be contained in the wound healing agent is particularly limited not extensively appropriately selected, it is preferably from 10 ^-5 to 50 wt% in the wound therapeutic agent .

The wound healing agent obtained from the wound healing substance of the present invention is administered in a manner appropriate for various forms upon use. For example, in the case of an external preparation, it is directly sprayed, affixed or applied to a required site such as skin or mucous membrane, and a tablet,
In the case of pills, drinking solutions, suspensions, emulsions, granules and capsules, it is orally administered, in the case of injections, it is administered intravenously,
It is administered intramuscularly, intradermally, subcutaneously, intraarticularly or intraperitoneally, and in the case of suppositories it is administered rectally.

The dose of the wound healing agent obtained from the wound healing material of the present invention is appropriately selected depending on the purpose of use, symptoms and the like.
It is in the range of about ng to 1 g / kg. Of course, the above pharmaceutical composition may be administered once to four times a day.

[0017]

Next, the effects described above will be demonstrated with reference to examples of the present invention.

Example 1 In order to demonstrate the effect of the wound-treating substance of the present invention, the wound-treating action was examined as follows, using deferoxamine mesylate as an example.

Pharmacological test Action on diabetic mouse skin defect model Deferoxamine mesylate (manufactured by Nacalai Tesque, Inc.)
It was dissolved in physiological saline to a final concentration of 100 mg / ml and used as a test solution.

As a test animal, a female diabetic mouse (db / db) weighing 30 to 45 g was used. The skin on the back of the mouse was shaved using a clipper and a shaver. Three days later, under ether anesthesia, a 16 mm-diameter defect extending across the midline of the back and over the shoulder was created using ophthalmic scissors. 20 μl of a test solution (2 mg of deferoxamine mesylate) was dropped onto the wound surface (2 cm ² ), and covered with a polyurethane film (manufactured by Johnson & Johnson, trade name: Bioclusive) from above. Administration was performed once a day on days 0, 2, and 4, with the defect creation date as day 0. The wound healing effect was measured using a caliper to measure the minor axis and major axis of the defect, determining the area of the defect (minor axis × major axis × 3.14 ÷ 4) assuming the defect as an ellipse, and calculating the initial (0 day) The evaluation was performed by determining the ratio of the area of the defective part on the measurement day to the area of the defective part of the eye) (this is called the area ratio).

As a control, the same procedure as above was performed except that only physiological saline was used instead of deferoxamine mesylate.

This test was carried out using five mice each, and the area of the defect was determined by taking the average of the area of the defect obtained for these mice. Table 1 shows the area ratio on the 14th day of the defect creation in this test.

[0023]

[Table 1]

As can be seen from Table 1, in the group to which deferoxamine mesylate was administered, the area of the defect on the 14th day after the defect creation was significantly reduced as compared with the control group. As described above, it was confirmed that the wound treatment material of the present invention exhibited a remarkable wound healing promoting effect.

[0025]

The constitution of the present invention is as described above. According to the present invention, it is possible to provide a wound treatment substance exhibiting a remarkable wound treatment effect and a wound treatment agent containing the same as an active ingredient.

Claims (2)

[Claims] 1. A compound of the formula (I) A wound healing substance comprising deferoxamine or a pharmaceutically acceptable salt thereof represented by the formula: 2. A wound healing agent comprising the wound healing substance according to claim 1 as an active ingredient.