WO2004078186A1 - Ointment preparation for repairing injured skin - Google Patents

Abstract

It is intended to provide an ointment preparation for repairing injured skin containing sucrose and Popidon Yodo which sustains iodine at a stable constant and is excellent in spreadability and flexibility. An ointment preparation for repairing injured skin which contains from 50 to 90% by weight of sucrose, from 0.5 to 10% by weight of Popidon Yodo, from 0.1 to 20% by weight of water and from 0.01 to 2% by weight of xanthan gum and/or cyclodextrin.

Description

 Ointment preparation for repairing damaged skin

Technical field

 The present invention keeps the iodine content constant, and furthermore has excellent spreadability and flexibility.

The present invention relates to an ointment preparation for repairing damaged skin containing sucrose and povidonodo, whose consistency is hardly changed with time. Fine

Background art

 Hitherto, saccharides have been known to have a granulation-proliferating action and a bacteriostatic action, and povidonodo is a drug commonly used as a fungicide. these

It has already been reported that an excellent skin repair effect was obtained when two drugs, granulated sugar and povidonide preparation, were mixed and applied to various types of damaged skin (Hospital Pharmacy, Vol. 10, No. 3). 1 5—3 2 2 (1 9 8 4)). In addition, damaged skin containing 50 to 90% by weight of sugar, 0.5 to 10% by weight of water, 1 to 20% by weight of water, and a buffer for adjusting the pH of the preparation to 3.5 to 6 Restorative preparations have also been reported (Japanese Patent Publication No. Hei 11-32210), and have been used in clinical practice and have high therapeutic effects. However, ointment-like preparations containing saccharides have a problem that the consistency increases over time after preparation. Increasing the consistency not only deteriorates the usability, but also makes it difficult to apply evenly to the wound. Solutions to reduce the consistency of saccharide-containing ointment formulations include reducing the amount of saccharides and increasing the amount of water, but all of these methods result in separation of the formulation. In addition, there were problems with stability, such as the appearance of spots due to components separated on the surface.

In order to solve this problem, a preparation containing an alkali metal alginate (Japanese Patent Application Laid-Open No. 11-100023), urea, carboxyvinyl polymer, hyaluronic acid Or a salt-containing preparation (JP-A-10-338638), a non-aqueous preparation (JP-A-2002-241287), a preparation containing a solubilizing agent and a shape retaining agent selected from polysaccharides (JP-A-Hei 10-338638). No. 09-40563) have been proposed, but none of them have been described as solving stability problems, such as not mentioning stability or poor stability.

 In addition, a method has been reported to reduce the consistency by including air bubbles in the formulation (Japanese Patent Application Laid-Open No. 2002-193810), but there are problems in terms of cost, such as an increase in the number of steps and the need for special equipment. Have left. As described above, the conventional ointment-form preparations containing saccharides may increase in consistency with time or have a problem in stability. Therefore, a stable formulation that is soft and free of foreign body sensation has been expected. On the other hand, a wound treatment formulation comprising a molded product containing saccharides and odor holes has also been reported (Japanese Patent Application Laid-Open No. 2002-226381). There is a disadvantage that it is difficult. Disclosure of the invention

 The present invention has been made in view of the above, and provides an ointment preparation for repairing damaged skin containing sucrose and povidone chloride which stably retains the iodine content and has excellent spreadability and flexibility. As an issue.

 Under the current situation as described above, the present inventors have conducted intensive studies and as a result, by using xanthone gum and / or cyclodextrin as a base component, the formulation has the required spreadability and flexibility, The present inventors have found that an ointment preparation for repairing damaged skin containing sucrose and povidonide stably retaining a high iodine content can be obtained, and the present invention has been completed.

That is, the present invention comprises 50 to 90% by weight of sucrose, 0.5 to 10% by weight of povidone, 0.1 to 20% by weight of water, and 0.01 to 2% by weight of xanthan gum and / or cyclodextrin. An ointment preparation for repairing damaged skin, characterized in that To provide.

 According to the present invention, there is provided an ointment preparation for repairing wounded skin containing sucrose and povidonide, which has a constant iodine content, is excellent in spreadability and flexibility, and whose consistency is hardly changed with time. be able to. BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in detail.

 As the sucrose in the present invention, purified sucrose described in the Japanese Pharmacopoeia is preferable, and its content is usually 50 to 90% by weight, preferably 60 to 80% by weight based on the total amount of the preparation from the viewpoint of therapeutic effect. And particularly preferably 70% by weight.

 In the present invention, it is preferable to use the povidonide listed in the Japanese Pharmacopoeia, and its content is usually 0-5 to 10% by weight, preferably from 5 to 10% by weight, preferably from the viewpoint of therapeutic effect. The content is 1 to 7% by weight, particularly preferably 2 to 6% by weight. It is preferable to use purified water listed in the Japanese Pharmacopoeia as the water in the present invention, and its content is usually 0.1 to 20% by weight, preferably 0.3 to 15% by weight based on the total amount of the preparation. %, Particularly preferably 0.5 to 12% by weight. It is.

 The xanthan gum in the present invention is a polysaccharide in which D-glucose, D-mannose, and D-dalc lanic acid are mainly linked in a chain, and specific commercial products include eco-gum (Dainippon Pharmaceutical, Sanshin), Neosoft (Kohjin), Soaxane (Mitsubishi Rayon), Kuchiichi Digel (Rhone Poulin Japan), Xanthan Gum (San-Ei Gen FFF I, Takeda Pharmaceutical). The content of the xanthan gum should be less than the solubility in water, since the xanthan gum dissolves in water and exerts a thickening effect to obtain an iodine content stabilizing effect and a consistency stabilizing effect. However, it is usually 0.01 to 1% by weight, preferably 0.02 to 0.5% by weight, particularly preferably 0.05 to 0.3% by weight, based on the total amount of the preparation.

The cyclodextrin used in the present invention has a large number of D-dalcopyranos groups. A series of homologous oligosaccharides with excellent crystallinity, having a structure cyclized by 1 → 4 glycosidic bonds. Specific commercial products include Celdex (Nippon Shokuhin Kako) and Lindex-1B (Mershan) , I3-cyclodextrin (Hayashibara) and the like. Further, the cyclodextrin includes α-cyclodextrin, β-cyclodextrin, and Ύ-cyclodextrin, and β-cyclodextrin is particularly preferred. The content of the cyclodextrin is usually from 0.01 to 1% by weight, preferably from 0.02 to 0.5% by weight, particularly preferably from 0.02 to 0.5% by weight, based on the iodine content and the effect of stabilizing the consistency. Is from 0.05 to 0.2% by weight.

 Xansu gum and cyclodextrin may be used alone, but it is particularly preferable to use them in combination from the viewpoint of the effect of stabilizing the iodine content and the consistency. Their content is usually from 0.01 to 2% by weight, preferably from 0.02 to 0.5% by weight, particularly preferably from 0.05 to 0.5% by weight, based on the total amount of the preparation. Since the ointment preparation for repairing damaged skin of the present invention is in the form of an ointment, it can be easily applied to a skin ulcer such as a pressure ulcer, a burn ulcer, and a leg ulcer to treat it. Here, the ointment state means that the consistency (25 ° C.) measured using a texture analyzer is 1 to 900 g, particularly preferably 1 to 500 g. Here, the consistency was measured using a texture analyzer after filling 30 g in a standard bottle (No. 5), storing at 25 ° C-60% RH for 1 hour, and measuring with a texture analyzer. This is the stress (g) when the metal ball adapter was inserted into the formulation at a penetration speed of 60 min Zmin.

 The pH of the preparation of the present invention is preferably in the range of 3.5 to 6. The pH can be measured, for example, by scraping 1 g of an ointment preparation for repairing damaged skin, adding 9 g of water, shaking well, and measuring with a pH meter (H-24, F-24).

As long as the effects of the present invention are not impaired, various optional components that are acceptable as pharmaceutical additives can be added to the preparation of the present invention as desired. Examples of the optional components include a solubilizer, Examples include a surfactant, a thickener, and a pH adjuster. Solubilizing agents include potassium iodide, sodium iodide, glycerin, 1,3-butylene glycol, polyethylene glycol 200, polyethylene glycol 400, polyethylene dalicol 150, polyethylene glycol 400 0, polyethylene glycol 600, polypropylene glycol, propylene glycol and the like.

 Examples of the surfactant include polyoxyethylene lauryl alcohol ester, polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, and the like.

 As thickeners, in addition to xanthan gum, ester gum, arabic gum, carrageenan, tamarind seed gum, guar gum, tragacanth gum, force-doran, dielan gum, pectin, polyisobutylene, pullulan, sodium carboxymethylcellulose, Sodium alginate, methylcellulose, agar, gelatin and the like may be added. '

 Examples of the pH adjuster include sodium hydroxide, citric acid, and acetic acid. The ointment preparation for repairing damaged skin of the present invention can be produced, for example, by mixing the above-mentioned raw materials and stirring until the mixture becomes uniform. Example

 Hereinafter, the present invention will be specifically described with reference to Examples.

In each example, potassium iodide, citric acid, sodium hydroxide, povidone chloride, xanthan gum (only in Examples 1 to 4), / 3-cyclodextrin (Example 4) were added to a mixed solution of purified water and concentrated dariserin. Only) and dissolved to give Preformulation I, while adding polyethylene (9) lauryl alcohol ester, polyoxyethylene [160] polyoxypropylene [30] glycol to polyethylene glycol 400 After adding and dissolving to obtain Pre-formulation II, sucrose was added to Pre-formulation I, and after kneading, pre-formulation II was added and kneaded in 5 ml. Example 1

 Purified water 8.84 g, concentrated glycerin 1.0 g, polyethylene glycol 400 14.19 g, polyoxyethylene [160] polyoxypropylene [30] glycol 1.3 g, potassium iodide 0.7 g, citrate 0.3 g, 8 mol / L sodium hydroxide aqueous solution 0.31 g, povidone chloride 3.0 g, purified sucrose 70.0 g, polyoxyethylene (9) lauryl alcohol ester 0.5 g, xane Evening Ngam 0.06 g

Example 2

 8.75 g of purified water, 1.0 g of concentrated glycerin, 14.19 g of polyethylene glycol 400, 1.3 g of polyoxyethylene [160] polyoxypropylene [30] glycol, 0.7 g of potassium iodide , Cunic acid 0.3 g, 8 mol / L aqueous sodium hydroxide solution 0.31 g, popidone oxide 3.O g, purified sucrose 70.0 g, polyoxyethylene (9) lauryl alcohol ester 0.5 g, xanthate gum 0 , 1 5 g

Example 3

 8.60 g of purified water, 1.0 g of concentrated glycerin, 14.19 g of polyethylene glycol 400, 1.3 g of polyoxyethylene [160] polyoxypropylene [30] glycol, 0.7 g of potassium iodide, 0.7 g Acid 0.5 g, 8 mol ZL sodium hydroxide aqueous solution 0.31 g, povidonodo 3.0 g, purified sucrose 70.0 g, polyoxyethylene (9) lauryl alcohol ester 0.5 g, xanthate gum 0.30 g

Example 4

Purified water 8.64 g, concentrated glycerin 1.0 g, polyethylene glycol 400 14.19 g, polyoxyethylene [160] polyoxypropylene [30] glycol 1.3 g, potassium iodide 0.7 g, citrate 0.3 lg, 8 mol ZL aqueous sodium hydroxide solution 0.31 g, povidonodo 3.0 g, purified sucrose 70.0 g, polyoxyethylene (9) lauryl alcohol ester 0.5 g, xanthate gum 0.06 g, 3-cyclodextrin 0.2 g

Comparative example

 Purified water 8.90 g, concentrated glycerin 1.0 g, polyethylene glycol 400 14.19 g, polyoxyethylene [160] polyoxypropylene [30] glycol 1.3 g, potassium iodide 0.7 g, citrate 0.3 g, 8 mol / L aqueous sodium hydroxide solution 0.3 1 g, povidone oxide 3. O g, purified sucrose 7 0.0 g, polyoxyethylene (9) lauryl alcohol ester 0.5 g Test 1 (Iodine content)

 After storing the ointment preparations for wound skin repair obtained in Examples 1 to 4 and Comparative Example at 60 ° C. for 7 days, the iodine content in the ointment preparation for wound skin repair (iodine content immediately after production) Was set to 100%). The measurement was performed by precisely weighing about 5 g of an ointment preparation for wound skin repair, adding 40 g of purified water, stirring and dissolving, and using a 1 mol / L sodium thiosulfate solution, a Hiranuma automatic titrator (Hiranuma Sangyo Co., Ltd.) Company: Performed by titration with C0MTITE-900). The results are shown in Table 1.

Test 2 (Sucrose content)

 After the ointment preparations for wound skin repair obtained in Examples 1 to 4 and Comparative Example were stored at 60 ° C for 7 days, purified sucrose in the ointment preparations for wound skin repair was quantified. The measurement was performed by accurately weighing about 0.35 g of an ointment preparation for wound skin repair, adding 10 mL of an internal standard solution and distilled water to make exactly 5 OmL, and preparing a sample solution (d) and a standard solution ( S) 15 L was measured by liquid chromatography according to the Japanese Pharmacopoeia General Test Method.

Test 3 (consistency test)

About 30 g of the ointment preparation for wound skin repair obtained in Examples 1 to 4 and Comparative Example was filled in a standard pin (NO.5) and stored at 60 ° C for 7 days. After one day at room temperature, measurement was performed using a texture analyzer (San Scientific, Sanrometer). The stress was measured when a metal ball adapter with a diameter of 10 was inserted into the preparation at a penetration rate of 60 thigh Zmin.

 table 1

 * 1: After storage, the consistency of Example 3 was 36.3 g after storage and the consistency of Comparative Example was 120 g. As shown in Table 1, the comparative example in which xanthan gum was not used had a remarkably high consistency and was not usable.

 On the other hand, in Examples 1, 2 and 3 in which xansan gum was added at 0.06 g, 0.15 g, and 0.30 g, respectively, the consistency was greatly improved. Further, in Example 4 in which 0.2 g of 3-cyclodextrin was further added to the method of Example 1, the stability and consistency of the iodine content were further improved as compared with Examples 1, 2 and 3. The stability of sucrose was also good. Therefore, satisfactory results were obtained in all aspects of spreadability, flexibility and stability of the active ingredient.

Claims

The scope of the claims  1. An ointment preparation for repairing damaged skin, comprising 50 to 90% by weight of sucrose, 0.5 to: 10% by weight of povidone and 0.1% by weight of water.