JP4575706B2 - Composition for repairing damaged skin - Google Patents

Description

  The present invention relates to a composition for repairing damaged skin comprising a sugar and povidone iodine (polyvinylpyrrolidone-iodo complex, Poly ((2-oxopyrrolidin-1-yl) ethylene) iodine) in which the increase in the consistency of the preparation over time is suppressed. .

Since sugars such as sucrose have wound healing action and granulation action, they are mixed with povidone iodine and used as preparations for treating damaged skin such as pressure ulcers and skin ulcers (for example, Patent Documents 1 and 2, Non-Patent Documents) Literatures 1-2).
However, the composition for repairing damaged skin containing sugar and povidone iodine (hereinafter sometimes referred to as an ointment) occupies most of it with sugar, and therefore has a property of becoming harder with time, which is an inherent property of sugar. It is necessary to use it after spreading it on gauze etc. at the medical site and stirring it until it is softened. Was necessary.

As a method of improving the defect that the consistency increases and hardens over time, a method of blending two or more powdered sugars having different average particle diameters (Patent Document 3), a method of blending a non-volatile solvent and a hydroxy lower alkylamine (Patent Document 4) and the like are known, but are not sufficient.
As another method for reducing the consistency of the composition for repairing damaged skin containing sugar and povidone iodine, it is conceivable to reduce the blending amount of the polymer base or not to blend it, but all of them are over time. The formulation components are separated, which is not preferable.

  Moreover, since the powder form of the preparation is a powder, it is difficult to use it on the affected part, and it is further scattered to cause surrounding dirt.

Therefore, development of a composition for repairing damaged skin containing sugar and povidone iodine that does not increase in consistency and does not become harder over time is required.
Japanese Patent Publication No. 1-32210 Japanese Patent Publication No. 6-17299 JP-A-11-171777 JP-A-11-228421 “Southern Medical Journal”, 1981, Vol. 74, No. 11, p. 1329-1335 “Hospital Pharmacy”, 1984, Vol. 10, No. 5, p. 315-322

  An object of the present invention is to provide a composition for repairing damaged skin, which contains sugar and povidone iodine whose increase in consistency over time is suppressed.

  As a result of intensive studies in view of the above points, the inventors of the present invention surprisingly unexpectedly blended a certain amount of a specific carboxylic acid ester into a system containing sugar, povidone iodine and water over time. The present inventors have found that a composition for repairing damaged skin containing a stable sugar and povidone iodine can be obtained, in which an increase in consistency is suppressed and the stability is good.

  That is, the present invention comprises damaged skin comprising 50 to 90% by weight of sugar, 0.5 to 10% by weight of povidone iodine, 0.1 to 20% by weight of water and 1 to 15% by weight of carboxylic acid mono- or diester. A repair composition is provided.

  The composition for repairing damaged skin containing the sugar and povidone iodine of the present invention is suppressed in the increase in consistency over time, is easy to use, has a softer formulation, and is applicable to deep wounds, granulation surfaces, etc. Excellent.

  The sugar used in the present invention is a non-reducing sugar or a reducing sugar, and examples thereof include sucrose (including purified sucrose), glucose, honey, molasses, and the like, and sucrose is particularly preferable.

  In the present invention, the amount of sugar is 50 to 90% by weight, preferably 60 to 80% by weight, particularly preferably 70% by weight, based on the total amount of the preparation.

  In the present invention, the compounding amount of povidone iodine is 0.5 to 10% by weight, preferably 1 to 7% by weight, particularly preferably 2 to 6% by weight, based on the total amount of the preparation.

  In the present invention, the amount of water is 0.1 to 20% by weight, preferably 0.3 to 15% by weight, particularly preferably 0.5 to 12% by weight, based on the total amount of the preparation.

The carboxylic acid mono- or diester used in the present invention is a carboxylic acid mono- or diester obtained by a dehydration reaction between a carboxylic acid and an alcohol, and is preferably liquid at 25 ° C.
Examples of the carboxylic acid include saturated or unsaturated linear or branched monocarboxylic acid having 1 to 46 carbon atoms, saturated or unsaturated linear or branched dicarboxylic acid having 2 to 18 carbon atoms, and the like. Of these, carboxylic acids having 2 to 18 carbon atoms or dicarboxylic acids having 2 to 10 carbon atoms are preferable, and myristic acid and adipic acid are particularly preferable. Moreover, these carboxylic acids may have a substituent such as a hydroxyl group.
Examples of the alcohol include linear or branched, saturated or unsaturated alcohols having 1 to 24 carbon atoms. Specifically, methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, pentyl alcohol, hexyl alcohol, heptyl alcohol, octyl alcohol, nonyl alcohol, decyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol Oleyl alcohol, behenyl alcohol, 2-octyldodecyl alcohol, benzyl alcohol, glycerin and the like. Of these, those having 3 to 20 carbon atoms are preferred, and isopropanol and 2-octyldodecyl alcohol are particularly preferred.

  Examples of carboxylic acid mono- or diesters include isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, butyl stearate, ethyl oleate, ethyl linoleate, isopropyl linoleate, cetyl caprylate, hexyl laurate, myristine Decyl acid, myristyl myristate, decyl oleate, oleyl oleate, cetyl linoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearyl myristate, octyldodecyl myristate, 2-ethylhexyl palmitate, palmitic acid Isocetyl, isostearyl palmitate, 2-ethylhexyl stearate, isocetyl stearate, isodecyl oleate, octoate oleate Ludodecyl, octyl dodecyl linoleate, ethyl isostearate, isopropyl isostearate, cetyl 2-ethylhexanoate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, octyldodecyl neopentanoate, isocetyl octanoate, Isostearyl octoate, 2-ethylhexyl isoperargonate, hexyldecyl dimethyloctanoate, octyldodecyl dimethyloctanoate, 2-ethylhexyl isopalmitate, isocetyl isostearate, isostearyl isostearate, octyldodecyl isostearate, lauryl lactate, myristyl lactate Cetyl lactate, octyl dodecyl lactate, diisostearyl malate, 2-ethylhexyl hydroxystearate, Hakusanji 2-ethylhexyl, diisopropyl adipate, diisobutyl adipate, dioctyl adipate, glyceryl monooleate, monocaprylate glycerin, Monoundeshiren glyceryl and glycerin monoisostearate.

  Commercially available products include Nikkor BM, Nikkor BS, Nikkor DID, Nikkor ICS-R, Nikkor IOP, Nikkor IPIS, Nikkor IPM-100, Nikkor IPM-EX, Nikkor IPP, Nikkor IPP-EX, Nikkor ISP, Nikkor MM, Nikkor N -SPV, Nikkor ODM-100, Nikkor STO (Nikko Chemicals), Exepar OD-M (Kao), etc.

  Among carboxylic acid mono- or diesters, octyldodecyl myristate and diisopropyl adipate are particularly preferable.

  In the present invention, the carboxylic acid mono- or diester can be used alone or in combination of two or more, and the blending amount is 1 to 15% by weight, preferably 2 to 13% by weight, more preferably 3%, based on the total amount of the preparation. -12% by weight, particularly preferably 5-10% by weight. If the carboxylic acid mono- or diester is less than 1% by weight, a sufficient consistency stabilizing effect cannot be obtained, and if it exceeds 15% by weight, the appearance stability of the preparation is deteriorated.

  The pH of the damaged skin repair composition of the present invention is preferably 3.5 to 6 from the viewpoint of the stability of sugar and povidone iodine. In addition, pH is measured at 25 degreeC with a pH meter (for example, Horiba: F-24), for example, after adding 9 weight part of water to 1 weight part of the composition for repairing damaged skin and shaking well.

  The pH is adjusted using acids and bases such as hydrochloric acid, citric acid, sodium hydroxide, etc., but the preparation may be a pH buffer system, for example, lactate buffer, citrate buffer, phosphate buffer etc. May be used.

  In addition to these components, the composition for repairing damaged skin of the present invention contains various optional components that are acceptable as additives for other drugs and pharmaceuticals, for example, solubilizers, interfaces, etc. The necessary amount of activator, thickener and the like can be appropriately added as desired.

  Examples of other drugs include growth factors such as bFGF, EGF, HGF, and IGF, and proteins such as silk fibroin.

  As the solubilizer, potassium iodide, sodium iodide, glycerin, polyethylene glycol (macrogol) 400, polyethylene glycol (macrogol) 1500, polyethylene glycol (macrogol) 4000, polyethylene glycol (macrogol) 6000, polypropylene glycol , Propylene glycol, dipropylene glycol and the like.

  Surfactants include polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene Ethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene (3) polyoxypropylene ( 17) Glycol, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene hydrogenated castor oil, polysorbate Sorbitan monostearate, and the like.

  Examples of the thickener include pullulan, sodium carboxymethylcellulose, sodium alginate, povidone, carboxyvinyl polymer, methylcellulose, agar, gelatin and the like.

  The composition for repairing damaged skin of the present invention is produced, for example, by mixing the above-mentioned components and heating them as necessary to stir until uniform, thereby forming an ointment.

  The composition for repairing damaged skin of the present invention is preferably used by appropriately spreading on gauze or the like and attaching it to the affected area. Moreover, since it is excellent in water absorption, it has excellent effects such as sucking out exudate.

  EXAMPLES Hereinafter, although this invention is demonstrated concretely using an Example, this invention is not limited to these Examples.

Example 1 Production of Ointment Product of the Invention 1: 9.52 g of purified water, 0.08 g of sodium hydroxide, 0.7 g of potassium iodide, 0.1 g of citric acid, 0.2 g of pullulan, 1 g of concentrated glycerin, 1, 3 -1 g of butylene glycol, 1 g of propylene glycol, 70 g of white sugar and 3 g of povidone iodine were added and kneaded well. Next, 5 g of octyldodecyl myristate (Exepal OD-M: Kao) was added and kneaded well. Further, Macrogol 300 1 g, Macrogol 400 6.3 g, Polyoxyethylene (160) Polyoxypropylene (30) Glycol 1 .1 g was dissolved by heating and kneaded well, followed by stirring until uniform to produce an ointment (Product 1 of the present invention).

  Invention product 2: Invention product 2 was produced using diisopropyl adipate (Nikkor DID: Nikko Chemicals) instead of octyldodecyl myristate of Invention product 1.

  Comparative Product 1: 9.5172 g of purified water, 0.0828 g of sodium hydroxide, 0.7 g of potassium iodide, 0.1 g of citric acid, 0.2 g of pullulan, 1 g of concentrated glycerin, 1 g of 1,3-butylene glycol, 1 g of propylene glycol Then, 70 g of white sugar and 3 g of povidone iodine were added and kneaded well. Next, 1 g of Macrogol 300, 11.3 g of Macrogol 400, and 1.1 g of polyoxyethylene (160) polyoxypropylene (30) glycol were heated and dissolved, kneaded well, and stirred until uniform to ointment. An agent (Comparative product 1) was produced.

About 30 g of the produced ointment was added to a soft glass bottle (plastic inner stopper, metal lid, No. 4 standard (
JIS) bottles) were airtightly filled and stored under room temperature conditions, and changes in consistency, agitation and spreadability over time were examined. The results are shown in Table 1.

(PH)
1 g of the ointment immediately after production was collected and mixed well with 9 g of water, and then measured with a pH meter (F-24: Horiba Seisakusho) at 25 ° C.

(Consistency)
The consistency was measured immediately after production and when stored for 3 months under room temperature conditions.
Using a texture analyzer (TA-XT2i: Stable Micro Systems), a 1 cmφ sphere was allowed to penetrate 2 cm at a speed of 1 mm / s, and the maximum load (g) at the time of penetration was measured.

(Stirability)
Stirability was examined immediately after production and when stored for 3 months at room temperature.
Regarding the stirring ability, the ointment was stirred with a wooden spatula and subjected to sensory evaluation in the following four stages.
A: Very easy to stir and extremely easy to use.
○: Easy to stir and use.
Δ: It is difficult to stir, but it cannot be used.
X: It is very difficult to stir and cannot be used.

(Extensibility)
The spreadability was examined immediately after production and when stored for 3 months under room temperature conditions.
For spreadability, the stirred ointment was spread on gauze with a wooden spatula and subjected to sensory evaluation in the following four stages.
A: Very easy to spread and extremely easy to use.
○: Easy to spread and use.
(Triangle | delta): Although it is hard to spread, it does not have to endure use.
X: It is very difficult to spread and cannot be used.

The inventive products 1 and 2 were extremely easy to use because the increase in consistency was suppressed even after being stored at room temperature for 3 months, and the stirrability and spreadability were good. On the other hand, an ointment (Comparative Product 1) containing sucrose, povidone-iodine and water, but not containing octyldodecyl myristate and diisopropyl adipate carboxylic acid mono- or diester has a marked increase in consistency after being stored at room temperature for 3 months. In addition, the stirring ability also deteriorated.
The sucrose (high performance liquid chromatographic method) and effective iodine (titration method) in the product of the present invention were also stable after storage at room temperature for 3 months.

Claims (3)

Sugar 50 to 90 wt%; povidone iodine 0.5% to 10% by weight; water 0.1 to 20 wt%; and injured skin repair, characterized in that it contains 1-15 wt% octyldodecyl myristate or diisopropyl adipate Composition. Sugar, damaged skin repair composition of claim 1 wherein the sucrose. The composition for repairing damaged skin according to claim 1 or 2 , wherein the pH is 3.5 to 6.