Application of adenine in preparation of medicine for treating diabetic ulcer

Abstract

The invention relates to application of adenine in preparation of a medicine for treating diabetic ulcer. The present disclosure provides an application of a pharmaceutical composition comprising adenine and / or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating diabetic ulcer, which can effectively accelerate and enhance wound healing of diabetic ulcer and can also prevent scar formation.

Description

[0001] This application is a divisional application of the application with application date of April 16, 2021, application number 202110411356.4, and invention name “Application of adenine as a drug for the preparation of drugs for the treatment of diabetic ulcers”. Technical Field

[0002] The present disclosure relates to the use of adenine in preparing a medicine for treating diabetic ulcers, and particularly to the use of adenine in preparing a medicine for treating diabetic foot ulcers. Background Art

[0003] Wound healing is a dynamic tissue remodeling process that involves the formation of a matrix rich in fibrin and fibronectin in the wound area, the infiltration of neutrophils and macrophages, the proliferation of epidermal keratinocytes at the wound edge and their migration through the provisional matrix, the formation of granulation tissue containing new blood vessels, migrating inflammatory cells and fibroblasts, and wound contraction. An ideally healed wound is one that can restore normal anatomical structure, function, and appearance at the cellular, tissue, organ, and organismal levels. If properly treated, wounds typically heal within one to two weeks.

[0004] Currently, there is a significant unmet clinical need for wound care and tissue repair for delayed-healing diabetic ulcers. Diabetic ulcers that fail to heal at the normal or expected rate, such as diabetic foot ulcers, are a major complication of diabetes and can lead to lower limb amputation. They are a growing global problem, severely impacting the quality of life of a large population and even causing death.

[0005] Furthermore, diabetic ulcers can be further differentiated into different degrees of severity based on wound conditions, such as wound depth, extent of wound or tissue necrosis, degree of ischemia, or degree of infection. Different degrees of diabetic ulcer severity require different treatment strategies, and there is a need for effective medications and methods tailored to the severity of diabetic ulcers.

[0006] Therefore, there is still an urgent need in this field for drugs and applications that can solve the above problems. Summary of the Invention

[0007] The present disclosure provides a pharmaceutical composition comprising adenine and / or a pharmaceutically acceptable salt thereof for use as a medicament for treating diabetic ulcers.

[0008] The present disclosure also provides a pharmaceutical composition comprising adenine and / or a pharmaceutically acceptable salt thereof for use in treating diabetic ulcers.

[0009] According to at least one specific embodiment of the present disclosure, the diabetic ulcer belongs to one of grades 1 to 3 in the Wagner-Meggitt ulcer classification system, for example, belongs to grade 1, 2 or 3 in the Wagner-Meggitt ulcer classification system.

[0010] According to at least one specific embodiment of the present disclosure, the diabetic ulcer belongs to grade 1 or 2 in the Wagner-Meggitt ulcer classification system.

[0011] According to at least one specific embodiment of the present disclosure, the diabetic ulcer is located in the skin, oral cavity, gums, corneal epithelial tissue, or any combination of two or more thereof.

[0012] According to at least one specific embodiment of the present disclosure, the area of ​​the diabetic ulcer is 1.5 to 25 square centimeters.

[0013] According to at least one specific embodiment of the present disclosure, the diabetic ulcer is a non-ischemic and non-infected wound, an ischemic but non-infected wound, a non-ischemic but infected wound, or an ischemic and infected wound.

[0014] According to at least one specific embodiment of the present disclosure, the adenine and / or pharmaceutically acceptable salt thereof is the single active ingredient in the pharmaceutical composition.

[0015] According to at least one specific embodiment of the present disclosure, the content of adenine and / or its pharmaceutically acceptable salt in the pharmaceutical composition is 0.0001 wt % to 2 wt %.

[0016] According to at least one embodiment of the present disclosure, the pharmaceutical composition is formulated into a form selected from the group consisting of solution, liniment, lotion, spray, aerosol, ointment, foam, cream, gel, paste, patch, glue, film, oral cream, powder and wound dressing.

[0017] According to at least one specific embodiment of the present disclosure, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.

[0018] According to at least one specific embodiment of the present disclosure, the effective dose of adenine and / or its pharmaceutically acceptable salt is 0.1 mg / kg to 50 mg / kg body weight.

[0019] According to at least one specific embodiment of the present disclosure, the adenine and / or a pharmaceutically acceptable salt thereof is administered to the subject by local administration or systemic administration.

[0020] In addition to wound healing, reducing scar formation during wound healing has long been a primary goal of modern medicine. Research has found that unlike wound healing in adults, wound healing in newborns is less likely to form scars. The difference lies in the activation of cyclooxygenase 2. During wound healing in adults, cyclooxygenase 2 activity is elevated by TGF-β, leading to increased production of prostaglandins at the wound site. Prostaglandins have been shown to promote fibroblast proliferation and collagen formation, both of which contribute to scar formation. Therefore, inhibiting cyclooxygenase 2 activity is believed to be an effective preventative measure for scar formation. The inventors have conducted intensive research and discovered that adenine can inhibit fibroblast growth and reduce cyclooxygenase 2 protein expression. Furthermore, direct administration of adenine to ulcer wounds in diabetic patients not only promotes wound healing but also reduces scar formation. Based on these data, topical administration of adenine can effectively accelerate and enhance wound healing and prevent scar formation in diabetic ulcers.

[0021] According to at least one specific embodiment of the present disclosure, the adenine and / or its pharmaceutically acceptable salt can be used for anti-inflammation, increasing collagen secretion, promoting epithelial cell migration, inhibiting scar formation, inhibiting fibroblast growth, or any combination of two or more thereof. DETAILED DESCRIPTION

[0022] The following embodiments illustrate the present disclosure. Given the details described in the specification, those skilled in the art will readily appreciate the other advantages of the present disclosure. The present disclosure may also be implemented or applied as described in the other specific embodiments. These embodiments may be modified and / or altered to implement the present disclosure for different implementations and applications without departing from the spirit and scope of the present disclosure.

[0023] It should be noted that as used herein, the singular forms "a," "an," and "the" include plural referents unless expressly and unequivocally limited to the singular. The term "or" and the term "and / or" are used interchangeably unless the context clearly indicates otherwise.

[0024] The numerical ranges described herein are inclusive and combinable. Any value within the numerical range described herein can be used as a maximum or minimum value to derive a subrange. For example, the numerical range of "0.0001 wt% to 2 wt%" should be understood to include any subrange between a minimum of 0.0001 wt% and a maximum of 2 wt%, such as subranges of 0.0001 wt% to 1.5 wt%, 0.01 wt% to 2 wt%, and 0.005 wt% to 1 wt%. In addition, multiple numerical endpoints described herein can be optionally used as maximum or minimum values ​​to derive a numerical range. For example, 0.0001, 0.01, or 50 mg / kg body weight can derive a numerical range of 0.0001 to 0.01 mg / kg body weight, 0.0001 to 50 mg / kg body weight, or 0.01 to 50 mg / kg body weight.

[0025] The "diabetes" mentioned herein may be type I diabetes, type II diabetes, gestational diabetes, cystic fibrosis-related diabetes (CFRD), latent autoimmune diabetes in adults (LADA) or monogenic diabetes, but is not limited thereto.

[0026] As used herein, "ulcer" refers to an open lesion (e.g., a wound) on an internal or external body surface that is caused by damage or rupture of the mucous membrane or skin and that does not heal or heals slowly. Ulcers can form on the internal or external surface of the body, such as the mouth, gastrointestinal tract, cornea, or skin, but are not limited thereto. Common ulcers are pit-shaped lesions caused by inflammatory, infectious, malignant conditions, or metabolic disorders. As used herein, "diabetic ulcer" refers to an ulcer caused by a complication of diabetes that usually does not heal within 1 to 3 months. Diabetic ulcers are common in the limbs, especially the legs or feet. As used herein, "diabetic foot ulcer" refers to an ulcer formed on a patient's leg or foot, such as, but not limited to, an ulcer on or around the thigh, groin, knee, calf, shin, ankle, heel, sole, toe, or any combination of two or more thereof.

[0027] In at least one embodiment of the present disclosure, diabetic patients with exemplary diabetic ulcers are susceptible to ulcers due to neurological and vascular complications. For example, peripheral neuropathy can lead to altered or complete loss of sensation in the feet and / or legs, potentially leading to loss of sensory perception, failure to notice cuts or injuries to the feet, and loss of the ability to sense sustained pressure injuries. As a result, tissue ischemia and necrosis may occur, leading to ulcers, such as plantar ulcers. Furthermore, microvascular disease is a significant complication in diabetic patients and can also lead to ulcers.

[0028] In order to solve the problems in the prior art, the present disclosure provides a use of adenine and / or its pharmaceutically acceptable salts for preparing a medicament for treating diabetic ulcers.

[0029] There are currently numerous classification systems for diabetic ulcers, with the Wagner-Meggitt ulcer classification system being the most commonly used. This system categorizes ulcers based on wound depth and the extent of tissue necrosis. Specifically, superficial ulcers are classified as Grade 1; deep ulcers (e.g., those invading ligaments, tendons, bones, or joints) are Grade 2; deep ulcers with abscesses or osteomyelitis are Grade 3; ulcers associated with forefoot gangrene are Grade 4; and ulcers with complete foot gangrene are Grade 5. Herein, adenine and / or a pharmaceutically acceptable salt thereof has a significant therapeutic effect when applied to Grade 1 or 2 diabetic ulcers according to the Wagner-Meggitt ulcer classification system, shortening wound healing time and increasing the rate of complete healing.

[0030] In at least one embodiment, the subject of application can be a mammal, such as a human or a mouse. In at least one embodiment, the mammal is a human. In other embodiments, the mammal can be a non-human mammal.

[0031] In at least one embodiment, adenine and / or a pharmaceutically acceptable salt thereof has a significant therapeutic effect when applied to diabetic ulcer wounds with an area of ​​1.5 to 25 square centimeters, wherein the wound area may be about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about 9.5, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 30, about 40, or about 50 square centimeters, but is not limited thereto. In addition, the aforementioned multiple numerical endpoints can be optionally set to maximum or minimum values ​​to derive a numerical range. In at least one embodiment, adenine and / or a pharmaceutically acceptable salt thereof has a significant therapeutic effect when applied to diabetic ulcer wounds with an area of ​​5 to 25 square centimeters, 10 to 25 square centimeters, 15 to 25 square centimeters, or 1.5 to 20 square centimeters.

[0032] In at least one embodiment, adenine and / or a pharmaceutically acceptable salt thereof can be administered to a diabetic ulcer located on the skin, oral cavity, gums, corneal epithelium, or a combination of two or more thereof.

[0033] On the other hand, in addition to the above-mentioned Wagner-Meggitt ulcer classification system for evaluating diabetic ulcers, the University of Texas System is also a commonly used classification method for ulcers. In addition to adopting the depth of the wound, the University of Texas System also evaluates whether the wound is ischemic and infected. Specifically, stage A indicates that the wound has no ischemia or infection; stage B indicates that the wound is infected; stage C indicates that the wound is ischemic; stage D indicates that the wound is ischemic and infected; grade 1 indicates epidermal wounds; grade 2 indicates superficial wounds; grade 3 indicates deep wounds that invade tendons or synovial bursae; grade 4 indicates deep wounds that invade bones or joints. In at least one embodiment of the present disclosure, the diabetic ulcer is a wound without ischemia and infection, a wound with ischemia but no infection, a wound without ischemia but with infection, or a wound with ischemia and infection.

[0034] In at least one embodiment, the subject's ankle brachial pressure index (ABPI) may be about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.0, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, but is not limited thereto. In addition, the aforementioned multiple numerical endpoints can be optionally set as maximum or minimum values ​​to derive a numerical range. In at least one embodiment, the subject's ankle brachial pressure index is 0.4 to 1.8 or 0.4 to 1.5. In at least one embodiment, the subject with an ischemic wound has an ankle brachial pressure index of less than 1 or less than 0.4.

[0035] In at least one embodiment of the present disclosure, when adenine and / or a pharmaceutically acceptable salt thereof is applied to a diabetic ulcer wound, the adenine and / or a pharmaceutically acceptable salt thereof can also be used to reduce inflammation in the subject, increase collagen secretion, promote epithelial cell migration, inhibit scar formation, inhibit fibroblast growth, promote matrix deposition, or any combination of two or more thereof, thereby enhancing wound epithelial regeneration and effectively improving and enhancing wound healing of the diabetic ulcer. In some embodiments, the adenine and / or a pharmaceutically acceptable salt thereof can be used to inhibit fibroblast proliferation, thereby preventing scar formation during wound healing of the diabetic ulcer.

[0036] In at least one embodiment of the present disclosure, adenine and / or a pharmaceutically acceptable salt thereof is used to treat wounds of diabetic ulcers in the form of a composition, and in some embodiments, the adenine and / or a pharmaceutically acceptable salt thereof is used as a single active ingredient in the composition. During treatment, the composition can be administered once a day for 7 to 30 days. In some embodiments, the composition can be administered once a day for 14 to 28 days. In other embodiments, the composition can be administered one to four times a day for 1 to 4 months, for example, twice a day for 3 to 4 months.

[0037] In at least one embodiment of the present disclosure, the content of adenine and / or its pharmaceutically acceptable salt as an active ingredient in the composition is 0.0001% to 2% by weight. In at least one embodiment, the amount of adenine and / or its pharmaceutically acceptable salt in the composition may be between 0.0001% to 1% by weight. In some embodiments, the amount of adenine and / or its pharmaceutically acceptable salt in the composition may be between 0.0001% to 0.05% by weight. In some embodiments, the amount of adenine and / or its pharmaceutically acceptable salt in the composition may be between 0.001% to 1% by weight. In some embodiments, the amount of adenine and / or its pharmaceutically acceptable salt in the composition may be between 0.005% to 0.08% by weight. In other embodiments, the amount of adenine and / or its pharmaceutically acceptable salt in the composition may be between 0.005% to 0.02% by weight. In some embodiments, the amount of adenine and / or its pharmaceutically acceptable salt in the composition can be about 0.0001, about 0.001, about 0.005, about 0.01, about 0.05, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1, about 1.2, about 1.5, about 1.8, or about 2% by weight. In addition, the aforementioned multiple numerical endpoints can be optionally set as maximum or minimum values ​​to derive a numerical range.

[0038] In at least one embodiment of the present disclosure, the composition can be formulated into a form selected from the group consisting of solution, liniment, lotion, spray, aerosol, ointment, foam, cream, gel, paste, patch, glue, film, oral cream, powder and wound dressing.

[0039] In at least one embodiment of the present disclosure, the composition may include, but is not limited to, other ingredients such as pharmaceutically acceptable carriers, additives, adjuvants, and / or excipients. For example, the composition may include, but is not limited to, any combination of one or more of the following: a gel former, a solvent, a solubilizer, a stabilizer, a tonicity enhancer, a penetration enhancer, a pH adjuster, a wetting agent, a surfactant, a buffer, a preservative, a viscosity modifier, an emulsifier, a gas propellant, a suspending agent, a flavoring agent, a colorant, and an antibacterial agent.

[0040] In at least one embodiment of the present disclosure, suitable antibacterial agents include, but are not limited to, paraben compounds (e.g., parabens, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, heptyl paraben, benzyl paraben, isobutyl paraben, isopropyl paraben, or pharmaceutically acceptable salts thereof), chlorhexidine acetate, metronidazole, silver ions, sorbic acid, benzalkonium chloride, benzethonium chloride, Chloride), benzyl alcohol, boric acid, ciprofloxacin, cetyltrimethylammonium bromide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethanol, glycerol, hexidine amine, imine urea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and sodium thiothioate. In at least one embodiment of the present disclosure, the antibacterial agent is selected from the group consisting of p-hydroxybenzoic acid esters, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, heptyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate and sodium salts thereof. One or more combinations of any two or more.

[0041] In at least one embodiment of the present disclosure, the content of the antibacterial agent in the composition is from about 0.01% to about 2% by weight, such as, but not limited to, 0.01% to 2% by weight of a paraben compound. In some embodiments, the amount of the antibacterial agent in the composition may be between about 0.05% to about 1% by weight. In some embodiments, the amount of the antibacterial agent in the composition may be between about 0.1% to about 0.5% by weight. In some embodiments, the amount of the antibacterial agent in the composition may be between about 0.1% to about 0.3% by weight. In some embodiments, the amount of bacteriostatic agent in the composition can be about 0.01, about 0.02, about 0.03, about 0.04, about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, about 0.1, about 0.15, about 0.17, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1, about 1.5, or about 2% by weight. In addition, the aforementioned multiple numerical endpoints can be optionally set as maximum or minimum values ​​to derive a numerical range.

[0042] In at least one embodiment of the present disclosure, suitable gel-forming agents include, but are not limited to, any combination of one or more of the group consisting of polyacrylic acid, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, chitosan, carboxymethylchitosan, hyaluronic acid, alginic acid, aloe vera gel, guar gum, hydroxypropylguar gum, fenugreek gum, gum arabic, xanthan gum, agar, carageenan, pectin, gelatin, and tragacanth gum. In at least one embodiment of the present disclosure, the gel-forming agent is selected from the group consisting of polyacrylic acid, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, and pharmaceutically acceptable salts thereof.

[0043] In at least one embodiment of the present disclosure, the content of the gel forming agent in the composition is from about 0.3% to about 30% by weight, such as, but not limited to, 0.3% to 30% by weight of carboxymethyl cellulose or its sodium salt. In some embodiments, the amount of the gel forming agent in the composition may be between about 0.5% to about 20% by weight. In some embodiments, the amount of the gel forming agent in the composition may be between about 1% to about 10% by weight. In some embodiments, the amount of the gel forming agent in the composition may be between about 2% to about 5% by weight. In some embodiments, the amount of the gel forming agent in the composition may be about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1, about 1.5, about 2, about 2.5, about 2.9, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25 or about 30% by weight. In addition, the aforementioned numerical endpoints can be optionally set as maximum or minimum values ​​to derive a numerical range.

[0044] In at least one embodiment of the present disclosure, adenine, a pharmaceutically acceptable salt thereof, and / or a composition comprising the same can be administered to a subject by local administration or systemic administration.

[0045] In at least one embodiment of the present disclosure, the effective dose of adenine and / or its pharmaceutically acceptable salt is 0.0001 mg / kg body weight to 50 mg / kg body weight. In at least one embodiment of the present disclosure, the effective dose of adenine and / or its pharmaceutically acceptable salt is 0.0006 mg / kg body weight to 50 mg / kg body weight. In at least one embodiment of the present disclosure, the effective dose of adenine and / or its pharmaceutically acceptable salt is 0.0006 mg / kg body weight to 0.034 mg / kg body weight, which can be used to treat wounds of 1 to 50 square centimeters. In at least one embodiment of the present disclosure, the effective dose of adenine and / or its pharmaceutically acceptable salt is 0.1 mg / kg body weight to 50 mg / kg body weight. In some embodiments, the effective dose of adenine and / or its pharmaceutically acceptable salt is about 0.0001, about 0.0006, about 0.034, about 0.001, about 0.005, about 0.01, about 0.05, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1, about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45 or about 50 mg / kg body weight. In addition, the aforementioned multiple numerical endpoints can be optionally set as maximum or minimum values ​​to derive a numerical range.

[0046] The present disclosure is further described below in conjunction with specific embodiments so that those skilled in the art can better understand the advantages and effects of the present disclosure and implement them. However, the embodiments should not be construed as limiting the present disclosure.

[0047] Preparation Example

[0048] The following method was used to prepare gel compositions containing varying adenine concentrations. First, 6.2 g of sodium chloride, 1.6 g of methylparaben, 0.2 g of propylparaben, and 0.2 g of adenine were dissolved in 1000 mL of distilled water. Then, 30 g of carboxymethylcellulose was added at room temperature to produce a colorless gel containing 0.02% adenine at a low concentration. Separately, a colorless gel containing 2% adenine at a high concentration was prepared using the same method as above, but with the amount of adenine adjusted to 20 g.

[0049] Example 1

[0050] A double-arm, double-blind trial was conducted to evaluate the efficacy of adenine and / or its pharmaceutically acceptable salts disclosed herein as a treatment for diabetic ulcers. The subjects were divided into a 0.02% adenine gel group and a placebo group. The basic information of the subjects is shown in Table 1 below. The wound healing rates analyzed according to the Wagner-Meggitt ulcer classification system and initial wound size are shown in Tables 2 to 4 below, respectively.

[0051] Table 1: Basic information of subjects

[0052]

[0053]

[0054] Table 2: Analysis of wound healing rates according to the Wagner-Meggitt ulcer classification system

[0055]

[0056] Table 3: Analysis of wound healing rates based on initial wound size

[0057]

[0058] Table 4: Analysis of wound healing rates according to the Wagner-Meggitt ulcer classification system and initial wound size

[0059]

[0060]

[0061] The results in Tables 2 to 4 above demonstrate that the use of adenine and / or a pharmaceutically acceptable salt thereof as a drug for treating diabetic ulcers, when the diabetic ulcers fall within the Wagner-Meggitt ulcer classification system, Grade 1 and / or Grade 2, or when the diabetic ulcers have a wound area of ​​1.5 to 25 cm², is extremely effective in accelerating and enhancing wound healing.

[0062] Example 2

[0063] The double-arm, double-blind trial of Example 1 was also used to evaluate the efficacy of adenine and / or its pharmaceutically acceptable salts as a drug for treating diabetic ulcers. The complete wound healing rates from 0 to 16 weeks were analyzed, as shown in Table 5 below.

[0064] Table 5: Complete healing rates of wounds from 0 to 16 weeks

[0065] week Adenine gel group Placebo group 0 0.00％ 0.00％ 1 0.00％ 0.00％ 2 0.00％ 0.00％ 4 7.32％ 5.00％ 6 12.20％ 5.00％ 8 26.83％ 5.00％ 10 29.27％ 5.00％ 12 43.90％ 10.00％ 14 48.78％ 20.00％ 16 56.10％ 25.00％

[0066] As can be seen from the results in Table 5 above, the wounds treated with adenine and / or its pharmaceutically acceptable salts disclosed herein showed rapid and effective healing after the fourth week.

[0067] The above embodiments are intended to illustrate the principles and effects of the present disclosure and are not intended to limit the present disclosure. Those skilled in the art may modify the above embodiments without departing from the spirit and scope of the present disclosure. Therefore, the scope of protection of the present disclosure shall be as set forth in the claims.

[0068] It should be understood that within the scope of the technical content described in this disclosure, various technical features (such as those described in the specific embodiments) can be freely combined with each other to form new or more preferred technical solutions and applications. For the sake of brevity, they are not described in detail here. In addition, in the numerical range composed of end values ​​described in this disclosure, as long as the value falls between the upper and lower end values, it should be included in the range described in this disclosure, and the sub-range formed by the end value or other values ​​should also be naturally included in the range described in this disclosure.

Claims

1. Use of a pharmaceutical composition comprising adenine and / or a pharmaceutically acceptable salt thereof as a medicament for treating diabetic ulcers, characterized in that: The diabetic ulcer belongs to grade 2 in the Wagner-Meggitt ulcer classification system, The diabetic ulcer has an area of ​​1.5 to 25 square centimeters, and The content of the adenine and / or its pharmaceutically acceptable salt in the pharmaceutical composition is 0.0001 wt% to 2 wt%, and the adenine and / or its pharmaceutically acceptable salt is administered to a subject via topical administration.

2. The use according to claim 1, characterized in that The diabetic ulcer is located in the skin, oral cavity, gums, corneal epithelial tissue or any combination of two or more thereof.

3. The use according to claim 1, characterized in that The diabetic ulcer is a non-ischemic and non-infected wound, an ischemic but non-infected wound, a non-ischemic but infected wound, or an ischemic and infected wound.

4. The use according to claim 1, characterized in that The adenine and / or its pharmaceutically acceptable salt is used for anti-inflammation, increasing collagen secretion, promoting epithelial cell migration, inhibiting scar formation, inhibiting fibroblast growth or any combination of two or more thereof.

5. The use according to claim 1, characterized in that The adenine and / or its pharmaceutically acceptable salt is the single active ingredient in the pharmaceutical composition.

6. The use according to claim 1, characterized in that The effective dose of adenine and / or its pharmaceutically acceptable salt is 0.0001 mg / kg to 50 mg / kg body weight.

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